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  • 1
    ISSN: 1573-7322
    Keywords: hypertrophy ; pacing ; hemodynamics ; review ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ventricular hypertrophy due to genetic mutations of sarcomeric proteins or that associated with long-standing hypertension typically yields a cavity with hyperdynamic ejection, elevated diastolic pressures, and limited filling volumes. The net result is reduced reserve capacity, dyspnea with exertional intolerance, and chest discomfort despite normal appearing coronary vessels. In addition to pharmacologic therapy by agents having negative inotropic effects, recent studies have examined the potential of ventricular pacing using right apical pre-excitation as a treatment for these disorders. This form of pacing can increase end-systolic volume and reduce cavity obliteration in both forms of the disease, yet has no demonstrable acute benefit on diastolic function. Chronic therapy trials have yielded mixed results, with more favorable responses observed in older patients particularly those with hypertensive hypertrophic disease. These data have also highlighted the importance of enhancing systolic reserve rather than diastolic function as a key therapeutic effect from pacing therapy. This review discusses the mechanisms by which pacing with ventricular pre-excitation acutely influences ventricular function, and summarizes results of recent clinical trials, putting the data into perspective regarding the relative role of systolic versus diastolic effects in these patients.
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  • 2
    ISSN: 1573-7330
    Keywords: Apoptosis ; CD44 ; human ; hyaluronic acid ; granulosa cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: This study was designed to examine whether hyaluronicacid (HA) inhibits apoptosis in cumulus and muralgranulosa cells and to examine whether this effect of HAwas mediated through CD44. Methods: Mural and cumulus granulosa cells were obtainedfrom in vitro fertilization patients. The cells were culturedwith various concentrations of HA or HA plus variousconcentrations of anti-CD44 antibody without serum supplement.After 24 hr of culture, the cells were fixed and stainedwith Hoechst 33258. One thousand granulosa cells of eachconditions were observed by fluorescence microscopy. Results: HA inhibited apoptosis in both kinds of granulosacells, and anti-CD44 antibody prevented this effect of HA.Conclusions: The incidence of apoptotic granulosa cellswith fragmented condensed nuclei was reduced by HA viaCD44.
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  • 3
    ISSN: 1573-742X
    Keywords: osteonectin ; acute myocardial infarction ; thrombolysis ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Osteonectin is a phosphoglycoprotein exclusively located in bone and platelet α-granules. Human platelet-derived osteonectin is released into plasma after thrombin-induced activation. Recognizing the unique distribution of the osteonectin pool, we first sought to investigate whether osteonectin could serve as a sensitive marker of platelet activity, and identify patients with acute myocardial infarction (AMI). The second objective was to define the effects of thrombolytic therapy in these patients on the plasma concentrations of osteonectin at prespecified time points following attempted reperfusion. Osteonectin levels by ELISA were determined in AMI patients before thrombolysis and at 3, 6, 12, and 24 hours thereafter and compared with 12 healthy controls. At baseline, soluble osteonectin plasma levels were similar between controls (447.7±20.6 ng/ml) and AMI patients (425.7±43.3 ng/mL; p=NS). A significant increase of the soluble osteonectin was observed at 3 hours after thrombolysis (519.4±26.9 ng/mL; p=0.03), and was followed by a decrease to baseline levels at 6 hours after attempted reperfusion. Contrary to expectations, the plasma osteonectin level in our pilot study was not a sensitive marker distinguishing patients with AMI. The early peak of soluble osteonectin at 3 hours after thrombolytic therapy is most likely not related to coronary thrombolysis per se but rather to the phasic changes of platelet activity during myocardial ischemia-reperfusion. The unquestionable platelet origin of this protein and the lack of elevated plasma levels of this α-granule constituent, challenge the postulate of uniform platelet activation in AMI patients.
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  • 4
    ISSN: 1573-7276
    Keywords: bone metastasis ; breast carcinoma ; histomorphometry ; human ; immunohistochemistry ; MMP ; TIMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Matrix metalloproteinases (MMPs) are essential in several stages of the metastatic process, and in normal bone development and remodeling. We explored whether the interaction between tumor cells and bone leads to changes in MMP and tissue inhibitor of MMP (TIMP) expression thus affecting osteolysis in metastatic bone disease. Using immunohistochemistry we have investigated the MMP/TIMP expression in tumor cells, fibroblasts, osteoblasts and osteoclasts. Thirty one specimens of bone metastasis from breast carcinoma were stained for MMP-1, -2, -9, MT1-MMP and TIMP- 1, and -2 and compared with staining in normal breast tissue, primary breast carcinoma and normal bone. Specimens came from patients in three clinical scenarios: from open biopsies without or with pathological fracture, or bone marrow biopsies containing tumor from patients with pancytopenia but without clinical evidence of osteolysis. By bone histomorphometry the latter group showed a heavy tumor load not different from the open biopsy groups but displayed little active bone resorption and low numbers of osteoclasts. Cell type-specific MMP/TIMP expression was observed and the staining patterns were comparable between the three groups of patients. Though no major differences in the MMP/TIMP staining of tumor cells and fibroblasts were observed between bone metastasis and primary tumor, we showed that tumor cells do express MMPs capable of degrading bone matrix collagen. The number and activity of osteoclasts and osteoblasts was increased dramatically in bone metastases, their MMP/TIMP profiles, however, were not different from normal bone, suggesting that the mechanism of bone degradation by osteoclasts is not different from normal bone remodelling.
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  • 5
    ISSN: 1573-7322
    Keywords: heart failure ; human ; cytoskeleton ; contractile dysfunction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In addition to functional alterations, heart failure has a structural basis as well. This concerns all components of the cardiac myocytes as well as the extracellular space. Proteins of the cardiomyocyte can be subdivided in 5 different categories: 1) Contractile proteins including myosin, actin, tropomyosin and the troponins. 2) Sarcomeric skeleton: titin, myosin binding protein C, α-actinin, myomesin, and M-protein. 3) True ‘cytoskeletal’ proteins: tubulin, desmin and actin. 4) Membrane-associated proteins: dystrophin, spectrin, talin, vinculin, ankyrin and others. 5) Proteins of the intercalated disc: desmosomes consisting of desmoplakin, desmocollin, desmoglein and desmin; adherens junctions with N-cadherin, the catenins and vinculin, and gap junctions with connexin. Failing myocardium obtained from patients undergoing cardiac transplantation exhibits ultrastuctural degeneration and an altered nucleus/cytoplasm relationship. The contractile proteins and those of the sarcomeric skeleton, especially titin, are downregulated, the cytoskeletal proteins desmin and tubulin and membrane-associated proteins such as vinculin and dystrophin are upregulated and those of the intercalated disc are irregularly arranged. Elevation of cytoskeletal proteins correlates well with diastolic and contractile dysfunction in these patients. The enlarged interstitial space contains fibrosis, i.e. accumulations of fibroblasts and extracellular matrix components, in addition to macrophages and microvascular elements. Loss of the contractile machinery and related proteins such as titin and α-actinin may be the first and decisive event initiating an adaptive increase in cytoskeleton and membrane associated components. Fibrosis may be stimulated by subcellular degeneration. The hypothesis is put forward that all proteins of the different myocardial compartments contribute to the deterioration of cardiac function in heart failure.
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  • 6
    ISSN: 1573-8221
    Keywords: human ; embryogenesis ; blood vessels ; encephalon ; electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract It was found that intracerebral blood vessels in human embryo telencephalon first appear on the 7th week of prenatal development as capillaries with poorly differentiated walls and signs of functional immaturity. The formation of the basal capillary membrane consisting of laminin and type IV collagen starts immediately after the formation of primary capillary network.
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  • 7
    ISSN: 1573-8221
    Keywords: human ; Body surface area
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A novel universal mathematical model for calculation of human body surface area with maximum accuracy is proposed.
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  • 8
    ISSN: 1573-742X
    Keywords: alcohol ; platelets ; acute myocardial infarction ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Moderate alcohol consumption (MAC) and platelet inhibition have been independently associated with a reduced risk for the development of acute myocardial infarction (AMI). The effects of MAC on the initial platelet status in patients presenting with AMI are not elucidated. Here we sought to define the effects of MAC on platelet characteristics in AMI patients before applying any reperfusion strategies. The study was designed as an analysis within the cohort study in 23 patients with AMI enrolled in the GUSTO-III. Platelets were investigated by different techniques, including aggregometry, flow cytometry, and ELISA. MAC patients exhibited mild, but consistent, inhibition of platelet aggregability, surface receptor expression, and released substances as compared to non-alcohol consuming patients. These differences were significant for 5 µM ADP (p = 0.04), 10 µM ADP-induced aggregation (p = 0.02); P-selectin (p = 0.01), and PECAM-1 (p = 0.02) platelet-bound expression. Our study confirms that moderate alcohol consumption is associated with diminished platelet activation in patients presenting with AMI. The ability of MAC to favorably modulate the pre-reperfusion platelet status in such patients is of clinical importance, and further investigation in large-scale clinical trials seem warranted.
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  • 9
    ISSN: 1573-4919
    Keywords: apolipoprotein C-III ; hepatic plasma membranes ; specific binding ; human ; mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Apo C-III plays an important role in the metabolism of plasma triglyceride, which can delay the catabolism of triglyceride-rich lipoproteins by interfering with apo E-mediated receptor clearance of remnant particles from plasma. The mechanism of the interference has not yet been defined. To further explore the role of apo C-III, we first injected mice with 125I-apo C-III. The measurement of radioactivity showed that liver took up 3.3-10 fold as much radioactivity as other organs such as heart, spleen, lung, kidney, stomach, large intestine, small intestine, and muscle. This was confirmed by incubating the tissue homogenates of the organs with 125I-apo C-III that the radiolabeled apo C-III specifically bound to only hepatic homogenate. To investigate which subcellular part or parts of hepatic cells play the role of binding to apo C-III, hepatic cell components of nucleus, mitochondria, microsomes and plasma membranes were then incubated with 125I-apo C-III. The radiolabeled apo C-III could specifically bind to only hepatic plasma membranes. Finally hepatic plasma membranes were purified to study the characteristics of the specific binding with apo C-III. Addition of increasing concentration of 125I-apo C-III to human hepatic plasma membranes revealed saturable binding to membranes with a Kd of 0.31±0.07 μmol/l. The maximum specific binding capacity was 1.74±0.45 μ apo C-III/mg membrane protein. In competition studies using unlabeled apo C-III and isolated lipoproteins HDL, LDL and VLDL, only apo C-III and VLDL effectively competed with 125I-apo C-III for membrane binding. The binding of 125I-apo C-III to human liver plasma membranes was Ca2+-independent, and was abolished when plasma membranes were treated with trypsin. The characteristics of 125I-apo C-III binding to mouse liver plasma membranes were similar to those of human liver plasma membranes with the exception of a binding maximum of 1.52±0.39 μapo C-III/mg membrane protein. We conclude that apo C-III exhibits high-affinity binding to hepatic plasma membranes, which is saturable, reverse and specific.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Biogerontology 1 (2000), S. 103-121 
    ISSN: 1573-6768
    Keywords: human ; immortalization ; senescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Following a limited number of population doublings(PD), human diploid somatic cells enter the terminalproliferation arrest state of senescence. This is anintrinsic mechanism which involves p53- andpRB/p16INK4-mediated pathways. The mostpopular candidate for the counting mechanism whichmeasures the age of a cell in PD is telomereshortening. Recent studies have shown that senescencecan also be induced independently of a PD levelby various factors; this premature senescence alsoappears to involve the activity of p53 and/orp16INK4. Immortalization of cells requiresabrogation of p53 and pRB-mediated terminalproliferation arrest and/or activation of a telomeremaintenance mechanism. The central role of telomeresin human cell senescence and immortalization hasreceived much attention; however there is evidencethat senescence can occur independently of telomerelength and that genes that are not necessarily involved in telomere maintenance are involved in immortalization.
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  • 11
    ISSN: 1573-675X
    Keywords: Apoptosis ; differential display ; human ; placenta.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Placenta is a transient feto-maternal association that develops during mammalian pregnancies. Human placental tissue during the first trimester of pregnancy is an actively dividing and differentiating tissue, while near term, it represents a fully differentiated unit performing many life-sustaining functions for the fetus. Previous studies have demonstrated that the percentage of placental cells that undergo apoptosis is greater at full term as compared to the first trimester of pregnancy. In this study, we undertook a study aimed at gaining an insight into the kind of genes expressed in the two developmentally distinct stages of gestation ie, the first trimester and term using Differential Display RT-PCR. Cloning and sequencing of one of the differentially expressed cDNAs from term placental tissue revealed that it is a novel gene, referred to as T-18 in the text. In this study, we also examined the regulation of this gene during apoptosis in the human placenta. A model for analysis of placental apoptosis was established by incubating placental villi in serum-free culture medium. It was observed that apoptosis occurred rapidly following incubation of placental villi without tropic support, and the proposed free-radical scavenger, superoxide dismutase (SOD) suppressed apoptosis in the placenta. Interestingly, the levels of T-18 mRNA increased significantly during spontaneous induction of apoptosis and decreased when apoptosis was blocked by SOD. These data clearly suggest that there is a strong correlation between the expression of T-18 and placental apoptosis and that T-18, may play a significant role in this process. Furthermore, the establishment of a defined in vitro explant culture model should facilitate elucidation of factors, which regulate apoptosis in human placenta.
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  • 12
    ISSN: 1573-6792
    Keywords: conductivity ; skull ; human ; inhomogeneity ; spongiosum ; compact layer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study, electrical conductivities of compact, spongiosum, and bulk layers of cadaver skull were determined at varying electric fields at room temperature. Current was applied and withdrawn over the top and bottom surfaces of each sample and potential drop across different layers was measured using the four-electrode method. We developed a model, which considers of variations in skull thicknesses, to determine the conductivity of the tri-layer skull and its individual anatomical structures. The results indicate that the spongiform and the two compact layers of the skull have significantly different and inhomogeneous conductivities ranging from 0.76 ∓ .14 to 11.5 ∓ 1.8 milliS/m.
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  • 13
    ISSN: 1573-6903
    Keywords: Isoprostanes ; thromboxanes ; norepinephrine ; human ; iris-ciliary body
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Isoprostanes (IsoP's) are prostaglandin-like compounds that are derived from free-radical catalyzed peroxidation of arachidonic acid independent of the cyclcooxygenase enzyme. In the present study, we investigated the effect of IsoP's on norepinephrine (NE) release from human isolated iris-ciliary bodies. Isolated human iris-ciliary bodies were prepared for studies of [3H]NE release using the superfusion method. Both 8-iso-prostaglandin F2α (F2-IsoP) and the thromboxane (Tx) receptor agonist, U46619 enhanced field-stimulated [3H]NE release from isolated, superfused human iris-ciliary bodies without affecting basal tritium efflux. On the other hand, an equimolar concentration (10 μM) of 8-iso-prostaglandin E2 (E2-IsoP) inhibited evoked [3H]NE overflow. The Tx-receptor antagonist, SQ 29548 blocked the enhancements of electrically-evoked [3H]NE release induced by F2-IsoP and U46619. However, the inhibitory responses elicited by E2-IsoP was not antagonized by SQ 29548. We conclude that IsoP's can produce both excitatory and inhibitory effects on sympathetic neurotransmission in human isolated iris-ciliary bodies. The stimulatory effects of IsoP' on NE release may be mediated by Tx-receptors.
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  • 14
    ISSN: 1573-2568
    Keywords: growth hormone ; intestinal absorption ; intestinal secretions ; human ; jejunum ; intestinal perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies in rats showed that the administration of recombinant human growth hormone markedly increased intestinal absorption of electrolytes and water and suggested that growth hormone would be a useful antidiarrheal agent. We therefore examined the effect of recombinant human growth hormone on the human jejunum in vivo, using a triple lumen nonabsorbable marker technique. Healthy subjects were studied on two different test days, one as a control and a second where recombinant human growth hormone was injected subcutaneously in a dose of 100 μg/kg. With this dose we achieved equal or higher growth hormone serum levels than in previous rat studies. However the administration of recombinant human growth hormone did not stimulate absorption or inhibit secretion of water and electrolytes in the human jejunum in vivo. We believe that the discrepancy between humans and rats is most likely due to the species difference rather than to differences in methods that were used. Therefore recombinant human growth hormone cannot be considered a useful proabsorptive antidiarrheal agent in humans.
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  • 15
    ISSN: 1573-2592
    Keywords: IL-18 ; sepsis ; human ; endotoxemia ; cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interleukin-18 (IL-18) is a recently identified immunoregulatory cytokine that shares biochemical features with IL-1β and acts in part by inducing interferon-gamma (IFN-γ). Endotoxic bacterial lipopolysaccharide (LPS) (1 or 2 ng/kg) was insufficient to increase plasma IL-18 in five healthy adults measured 3, 12, and 24 hr following challenge. In contrast, in the first 96 hr of admission to the surgical intensive care unit, mean maximal serum IL-18 was elevated (1122 ± 259 pg/ml) in nine septic patients compared to six healthy adults (191 ± 42 pg/ml), P 〈 0.01). Serum IL-18 concentrations in septic patients did not correlate with other measured inflammatory mediators: tumor necrosis factor, IL-6, IL-10, or secretory leukocyte protease inhibitor. Therefore, IL-18 circulates in healthy adults and is a component of the human systemic inflammatory response. Further, stimuli other than LPS may induce IL-18 production in vivo in human sepsis.
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  • 16
    ISSN: 1573-2622
    Keywords: diabetes ; ERG ; glucose ; human ; photopic ; retina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Circulating glucose was manipulated in young human volunteers with clinically normal vision. Fasting achieved a concentration range of 45-91 mg/dl. And sugar loading produced a range of 79-108 mg/dl. Glucose increased in all subjects. A nonparametric ANOVA provided a p=0.0005 for the significance of the concentration differences between group glucose concentrations under the two conditions in the sample. Each volunteer participated in each condition of the repeated-measures design. Clinical tests were completed before electroretinograms were recorded under photopic and scotopic adaptation conditions. Measures were made from 12 eyes. Only photopic adaptation conditions with maximal stimuli produced significant results. Inter-individual differences were robust and constrained to reduced implicit times for b-wave peaks and 30 Hz flicker implicit times. Under the elevated glucose conditions. Other variables showed very strong trends. These results confirm and extend other human indications of photopic retinal sensitivity to variations within the normal range of circulating glucose concentrations.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Annals of clinical psychiatry 12 (2000), S. 171-173 
    ISSN: 1573-3238
    Keywords: serotonin uptake inhibitors ; pharmacology ; testosterone ; metabolism ; human ; antidepressive agents ; adverse effects ; case report ; paraphilia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report on a patient with a low testosterone level which occurred during treatment with venlafaxine. The testosterone level increased when the medication was discontinued. Possible clinical correlation with amelioration of paraphilia is discussed.
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  • 18
    ISSN: 1435-1463
    Keywords: Keywords: Mouse ; cat ; human ; rat ; striatum ; adenosine A2A receptors ; 6-OH-dopamine.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Adenosine A2A receptors are present on enkephalinergic medium sized striatal neurons in the rat and have an important function in the modulation of striatal output. In order to establish more accurately whether adenosine transmission is a generalized phenomenon in mammalian striatum we compared the A2A R expression in the mouse, rat, cat and human striatum. Secondly we compared the modulation of enkephalin gene expression and A2A receptor gene expression in rat striatal neurons after 6-OH-dopamine lesion of the substantia nigra. Hybridization histochemistry was performed with a 35S-labelled radioactive oligonucleotide probe. The results showed high expression of A2A adenosine receptor genes only in the medium-sized cells of the striatum in all examined species. In the rat striatum, expression of A2A receptors was not significantly altered after lesion of the dopaminergic pathways with 6-OH-dopamine even though enkephalin gene expression was up-regulated. The absence of a change in A2A receptor gene expression after 6-OH-dopamine treatment speaks against a dependency on dopaminergic innervation. The maintained inhibitory function of A2A R on motor activity in spite of dopamine depletion could be partly responsible for the depression of locomotor activity observed in basal ganglia disorders such as Parkinson's disease.
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  • 19
    ISSN: 1432-0428
    Keywords: Keywords Islets ; pig ; xenograft ; human ; lymphocytes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The intensity and mechanisms of cell-mediated rejection of pig islet cells were studied in 49 Type I diabetic and 34 healthy subjects. Human peripheral mononuclear cells proliferated strongly in response to pig islet cells (p 〈 0.001), though with notable interindividual variations (stimulation index 2 to 215). The variance of stimulation index was higher in diabetic than healthy subjects (p 〈 0.0001). The response to islet cells was stronger (p 〈 0.01) than that to pig splenocytes. Proliferation in response to islet cells was strongly decreased (p 〈 0.01) when CD4 + T cells were blocked with monoclonal antibodies, whereas the blocking of CD8 + cells or NK cells gave less pronounced effects. The response to islet cells was decreased (p 〈 0.01), but not abolished, after antigen-presenting cells were removed. Purified CD4 + cells alone did not proliferate in response to islet cells but recovered their proliferative ability when mixed with antigen-presenting cells, whereas CD8 + cells alone proliferated in the presence of interleukin-2 in response to islet cells. Proliferation was blocked (p 〈 0.01) by anti-DR monoclonal antibodies. During proliferation in response to islet cells, interleukin-10 increased 43-fold (p 〈 0.01) but interferon-γ increased only slightly. No statistical differences were detected between diabetic and control subjects with respect to lymphocyte subsets and the recognition mechanisms or to interferon-γ / interleukin-10 production in response to islet cells. These results provide the first detailed information on human cell-mediated xenoreaction to pig islet cells. This situation involves a dominant CD4 class II-restricted Th2 response, with an indirect recognition pathway, as well as a CD8 T-cell response resulting from direct recognition. This strong reaction constitutes a serious obstacle which may vary in degree among subjects. [Diabetologia (1999) 42: 330–335]
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  • 20
    ISSN: 1573-899X
    Keywords: Thalamus ; human ; ventrolateral nucelus ; single and network neuron activity ; voluntary movement ; rhythmic spike processes ; Parkinson's tremor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The responses of neurons in the ventrolateral nucleus (VL) of the thalamus were studied in humans during performance of voluntary motor tests; recordings were made with microelectrodes during stereotaxic operations in patients with Parkinson's disease. Two previously classified types of polyvalent neurons (A, B) were found to show different patterns of responses during the functional stages of carrying out a voluntary movement (preparation, initiation, performance). A and B neurons showed concordant changes in the dynamics of ongoing network activity in the form of linked (activation-inhibition) and synergic (activation) response patterns, correlating with the preparation-trigger and performance phases of movements. It is suggested that the simultaneous activity of both types of neuron, with their common functional nature, reflects integrative processes occurring in the ventrolateral nucleus and associated with programming and processing of general signal parameters but not with the performance of any particular movement. The anterior (Voa nucleus) and posterior (Vop) parts of the ventrolateral nucleus were found to have different roles in organizing voluntary movements, associated with differences in their cellular organization and mechanisms of transmitting motor signals. It is suggested that the concordant changes in the activities of the two types of neurons in these areas seen during the performance of voluntary movements gives the ventrolateral nucleus a key role in the motor control system in humans.
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  • 21
    ISSN: 1573-7217
    Keywords: α2‐adrenergic agonists ; α2‐adrenergic antagonists ; α2‐adrenoceptor ; breast cancer ; catecholamines ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract (-)Epinephrine (Epi) and –Norepinephrine (NEpi) significantly stimulated tritiated Thymidine incorporation in MCF‐7 cells at concentrations 10–30 pM to 10 nM, with an EC50 of 10 pM for Epi and 14.2 pM for NEpi. To characterize this action, cells were incubated in the presence of NEpi or Epi and different antagonists. The β‐adrenergic antagonist Propanolol showed no effect on the agonist's stimulation, whereas the α‐adrenergic antagonist Phentolamine, reverted it completely at high concentrations (100 μM). The α1‐adrenergic antagonist Prazosin (Pra) acted only at high concentrations, while the α2‐adrenergic antagonist Yohimbine (Yo) reverted the stimulation at an EC50 of 0.11μM. Likewise, when the cells were incubated in the presence of the specific α2‐adrenergic agonist Clonidine (Clo), Thymidine incorporation was significantly stimulated at an EC50 of 0.298 pM. Again, the incubation of the cells in the presence of the α1‐adrenergic antagonist Pra exerted its action at high concentrations, whereas the α2‐adrenergic antagonist Yo showed a clear reversal of the agonist's enhancement at an EC50 of 0.136 μM. Moreover, Clo caused a clear and significant inhibition of stimulated cAMP levels both in the intracellular and the extracellular fractions. Yo showed a complete reversion of cAMP levels to control values in the presence of Clo, while Pra had the opposite effect. These data suggest that the stimulation provoked in Thymidine incorporation by the agonists Epi, NEpi, and Clo is, at least in part, due to an α2‐adrenergic mechanism directly on tumoral cells, and that the effect is coupled with inhibition of cAMP levels, as described for this kind of receptors.
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  • 22
    ISSN: 1573-7330
    Keywords: human ; medium ; ICSI ; embryo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Our purpose wax to evaluate the efficiency of a medium, devoid of any human or animal compound and specially designed for early embryo development (from the zygote to the eight-cell stage), SMART2, in intracytoplasmic sperm injection (ICSI) and to compare it with a medium containing human serum albumin (EllioStep2). Methods: Oocytes from 50 ICSI attempts were randomly placed, after sperm injection, into either SMART2 or EllioStep2. After a 48-hr incubation, the embryos were examined for quality scoring before transfer or freezing. Results: The percentage of normally fertilized oocytes per intact oocytes was slightly higher using SMART2 (139/199 vs. 135/224, respectively, for SMART2 and EllioStep2: P 〈 0.05). The distribution of embryo scores and the percentage of embryos with a fair morphology (71/143 vs. 72/148, respectively, for SMART2 and EllioStep2; not significant) were identical in both media. Conclusions: These data show that SMART2 medium can be successfully used for early embryo growth and, because it is devoid of any human or animal compound, offers better safety for patients than conventional media.
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  • 23
    Electronic Resource
    Electronic Resource
    Springer
    Sepsis 3 (1999), S. 335-344 
    ISSN: 1573-7411
    Keywords: human ; inflammation ; bacterial infections ; peritonitis ; immunology ; genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Normal peritoneal response to microorganisms is characterized by hyperemia, exudation of protein-rich fluid into the peritoneal cavity and marked influx of neutrophils, universally known as peritonitis. Under favorable circumstances for the host, peritoneal and systemic defense mechanism can remove infection from peritoneal cavity (resolution) or at least manage to contain infection (intra-abdominal abscess). Normal peritoneal response to infection may be altered by local peritoneal and systemic factors resulting in a non-efficient mechanism that interfere with the ability of the host to eradicate infection from the peritoneal cavity or further damage the peritoneal interface.
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  • 24
    Electronic Resource
    Electronic Resource
    Springer
    Neurochemical research 24 (1999), S. 1385-1395 
    ISSN: 1573-6903
    Keywords: Epilepsy ; human ; amino acids ; glutamate ; GABA ; polyamines ; phosphoinositol ; metabotropic glutamate receptors ; microdialysis ; nuclear magnetic resonance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies of neuroactive amino acids and their regulatory enzymes in surgically excised focally epileptic human brain are reviewed. Concentrations of glutamate, aspartate and glycine are significantly increased in epileptogenic cerebral cortex. The activities of the enzymes, glutamate dehydrogenase and aspartate aminotransferase, involved in glutamate and aspartate metabolism are also increased. Polyamine synthesis is enhanced in epileptogenic cortex and may contribute to the activation of N-methyl-D-aspartate (NMDA) receptors. Nuclear magnetic resonance spectroscopy (NMRS) reveals that patients with poorly controlled complex partial seizures have a significant diminution in occipital lobe gamma aminobutyric acid (GABA) concentration. The activity of the enzyme GABA-aminotransaminase (GABA-T) which catalyzes GABA degredation is not altered in epileptogenic cortex. NMRS studies show that vigabatrin, a GABA-T inhibitor and effective antiepileptic, significantly increases brain GABA. Glutamate decarboxylase (GAD), responsible for GABA synthesis, is diminished in interneurons in discrete regions of epileptogenic cortex and hippocampus. In vivo microdialysis performed in epilepsy surgery patients provides measurements of extracellular amino acid levels during spontaneous seizures. Glutamate concentrations are higher in epileptic hippocampi and increase before seizure onset reaching potentially excitotoxic levels. Frontal or temporal cortical epileptogenic foci also release aspartate, glutamate and serine particularly during intense seizures or status epilepticus. GABA in contrast, exhibits a delayed and feeble rise in the epileptic hippocampus possibly due to a reduction in the number and/or efficiency of GABA transporters.
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  • 25
    ISSN: 1573-7233
    Keywords: melanoma ; skin ; reconstructs ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Melanoma develops from a series of architectural and phenotypically distinct stages and becomes progressively aggressive. Considerable progress has been made in understanding the biological, pathological, and immunological aspects of human melanoma. Genetic and cytogenetic studies have revealed broad chromosomal abnormalities and wide mutational spectra. Precise biological and molecular determinants responsible for melanoma progression are not yet known. This is in part due to lack of experimental models that mimic human melanomas. Experimental models in melanoma should not only identify cause and origin of malignancy, but also should represent the ordered progression steps that culminate in metastasis to distant organs. Currently, there are several mouse and other vertebrate melanoma models under investigation; several of them promise to shed light on mechanisms of melanomagenesis. However, many of them suffer from lack of context to human skin architecture and hence, are of basic interest. The lack of appropriate models impeded the efforts to understand origin, etiology, progression and ultimately therapeutic benefits to humans. Development of human skin–mouse chimeric models has appeal because it mimics human diseases. In addition, human artificial skin constructs in vitro promises to be a versatile and efficient model to study not only origin and mechanisms of melanoma, but also progression. This review will focus on the recent progress in establishing tumor models in melanoma in general and their relevance to human melanoma as molecular determinants of tumor progression.
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  • 26
    ISSN: 1573-7330
    Keywords: calcium signaling ; preimplantation development ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Cell cycle-related calcium signals, bearing some similarity to those previously described in other animal species, have also been observed in human preimplantation embryos. These signals follow those occurring in both gametes during the period preceding fertilization and those induced by the fertilizing spermatozoon in the oocyte after gamete fusion. Even though the signals occurring during each of these distinct developmetal periods have different temporal and spatial characteristics, there may be a relationship between them; in fact, abnormalities of calcium signals occurring in an earlier developmental period may be at the origin of abnormal signals during later developmental periods. Methods: Possible mechanisms by which inadequate or truncated calcium signals can impair embryo development are discussed. Results: These mechanisms include complete failure of the second meiotic division, leading to triploidy; incomplete failure of the second meiotic division, leading to de novo chromosomal numerical abnormalities; abnormal pronuclear development and function; abnormalities of the blastomere cell cycle, possibly leading to embryo cleavage arrest; and problems with blastomere allocation to embryonic cell lineages, leading to disproportionate development of the inner cell mass and trophectoderm derivatives, which can be the origin of implantation failure or miscarriage. Conclusions: Future research should make it possible to decipher the nature of normal developmental signals, to determine the key checkpoints at which these signals are required to prevent the switch to apoptosis, and to examine the possibilities of therapeutic action at these checkpoints to rescue the endangered embryo for normal development.
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  • 27
    Electronic Resource
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    Springer
    Molecular and cellular biochemistry 191 (1999), S. 21-28 
    ISSN: 1573-4919
    Keywords: protein kinase CK2 ; intersubunit contact ; holoenzyme structure ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Chemical crosslinking and analysis of CNBr-digested fusion products by immunoblotting with sequence-specific antibodies identifies an interaction between positions 55-70 of subunit β (β55-70) and 65-80 of subunit α (α65-80). This has been supported by crosslinking of subunits with peptides α65-80 and β55-70, by binding of subunits to immobilized peptides, and by the hindrance of coprecipitation with peptide-raised antibodies (anti-α65-80; anti-β55-70). Functionally, β55-70 is a negative regulatory region for the kinase activity of subunit α. The opposite, stimulatory property of subunit β has been assigned to its C-terminal part. Subdivision of peptide β155-181, that has stimulatory effect, into overlapping peptides and assaying for a binding and binding competition revealed a tight physical contact at β162-175. This region, however, is non-stimulatory indicating binding a necessary but not sufficient quality for stimulation. A contact might exist to regions surrounding C147 and/or C220 at subunit a as indicated by crosslinking and peptide competition. The crosslinking data also confirm a β-β contact in CK2 holoenzyme. Effects by non-ionic detergents show hydrophobic interactions to play an important role in catalytic activity adjustment.
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  • 28
    ISSN: 1573-4919
    Keywords: protein kinase CK2 ; gene structure and organization ; gene promotor activation ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Two CK2α loci are present in the human genome. First, locus 20p13, that contains the CK2α coding gene. It spans around 70 kb, is composed of 13 exons and shows homology to the respective gene in the nematode Caenorhabditis elegans. The translation start site is located in the second exon, the stop codon in exon 13. Two transcription start sites were identified, the further 5′ located site defines position 1 of the gene, the second site is located at position 50, respectively. The promoter region shows characteristics of a so-called house keeping gene: A high GC content, lack of a TATA-box and presence of several GC-boxes. By reporter gene assays, the promoter region of the CK2α gene could be located between position -256 and 144 relative to the first transcription start site. In the 3′ noncoding region of the CK2α gene, six polyadenylation signals were identified. As indicated by Northern blot analysis and by comparison with expressed sequence tags from the EMBL databank, the most 3′ located, active polyadenylation signal seems to be the fourth defining the end of the CK2α gene. The second CK2α locus is at 11p15. It contains a processed pseudogene, which shows all typical features of a processed sequence, such as absence of introns, short poly-A tail and direct flanking repeats. Interestingly, it contains a complete open reading frame and has potential promoter elements in its 5′ region. Nevertheless, no promoter activity could be detected in reporter gene assays.
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  • 29
    ISSN: 1573-0743
    Keywords: body height ; body weight ; cardiac output ; gender ; heart mass ; human ; stroke volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To obtain normal values of left ventricular (LV) end-diastolic volume (EDV), stroke volume (SV), cardiac output (CO) and LV mass, in relation to gender, weight (W), length (L) and body surface area (BSA). Methods: Sixty-one healthy volunteers (32 male, 22.4 ± 2.2 years) were examined, weight was 70.9 ± 12.2 kg, length was 1.78 ± 0.09 m, BSA was 1.88 ± 0.19 m2. Segmented k-space breathhold cine MRI was used to obtain a stack of parallel short-axis images, from which LV volumes and end-diastolic mass were derived by slice summation. Four different body size indices were studied: W, L, L2 and BSA. Results: After indexing for L, L2 and BSA, the gender differences in all LV parameters are still persisting. After indexing for W, gender differences persist for EDV and EDM, but are no longer observed for SV and CO. Separate regression analyses for males and females were performed. EDV, SV, CO and EDM correlated significantly with each body size index, both in males and in females. L or BSA were in general better predictors for LV parameters than W. Linear regression equations of EDV (ml) vs. L(m) were for males: EDV = 275 × L − 359 and for females: EDV = 190 × L − 215. Equations of SV(ml) vs. L were for males: SV = 186 × L − 237 and for females: SV = 118 × L − 121. Equations of LV mass(g) vs. L were for males: Mass = 175 × L − 179 and for females: Mass = 65.8 × L − 10.9. Conclusion: Most gender differences in LV parameters remain even after correction for body size indices. Normal reference values for LV parameters are given in relation to body size indices, by calculating regression coefficients separately for males and females. These normal values serve to obtain more accurate reference values for a patient with given gender, weight and length, and thus to improve the differentiation between normal and abnormal LV parameters.
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  • 30
    ISSN: 1573-0778
    Keywords: alpha-2-macroglobulin ; α2M ; bait region ; CHO cells ; human ; lysyl endopeptidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Alpha 2-macroglobulin (α2M), a plasma glycoprotein produced in the liver, inhibits a variety of proteinases and thus considered to play important homeostatic roles in the body. This broad inhibitory spectrum has been explained by the trapping theory by which a proteinase recognizes a region of 25–30 amino acid peptide in α2M called bait region and cleaves it, leading to the conformational change of α2M, and to the subsequent entrapment and inhibition of the proteinase. We constructed α2M cDNAs with mutated DNA sequences in the bait region, and obtained recombinant CHO cell lines producing either wild type α2M, or mutant α2Ms, i.e., α2M/K692 and α2M/K696, each with substitution of Arg with Lys at codons 692 and 696, respectively. We tested if lysyl endopeptidase is not inhibited by wild type α2M, but could be inhibited by these engineered mutant α2Ms. Thus, recombinant α2M/K696 protein successfully inhibited lysyl endopeptidase activity, while recombinant α2M/K692 protein was not sensitive to lysyl endopeptidase, suggesting that not all bait region peptide bonds can equally be accessible and susceptible to proteinases. The present results not only provided the trapping theory with additional supportive evidence, but the first experimental evidence for the value of engineered α2M-derived proteinase inhibitor with an artificial proteinase inhibitory spectrum of potential industrial and/or therapeutic usefulness.
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  • 31
    ISSN: 1573-6903
    Keywords: Calmodulin ; human ; localization ; phosphodiesterase ; brain ; cAMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The amplification of cyclic nucleotide ‘second messenger’ signals within neurons is controlled by phosphodiesterases which are responsible for their degradation. Calmodulin-dependent phosphodiesterase (CaMPDE) is an abundant enzyme in brain which carries out this function. For the first time, we have localized CaMPDE in the normal human brain at various ages, using a monoclonal antibody designated A6. This antibody was generated using standard techniques, purified, and applied to tissue sections. Autopsy specimens of human brain with no neuropathological abnormalities were selected representing a range of pre- and postnatal ages. Sections of various brain regions were evaluated for immunoreactivity, graded as nil, equivocal, or definite. We demonstrated definite CaMPDE immunohistochemical staining in neocortex, especially in neurons in layers 2 and 5. There was definite neuronal immunoreactivity in the hippocampus, and in the subiculum. The striatum had definite patchy neuronal staining. Definite terminal staining in the globus pallidus externa and substantia nigra pars reticulata outlined resident neurons, interpreted as axonal terminal staining. Cerebellar Purkinje cells showed definite immunoreactivity. In the developing brain, definite immunohistochemical staining was seen in the cerebellar external granular layer. The expression of CaMPDE in specific subsets of neurons suggests they may correlate with cells having dopaminergic innervation and/or high levels of neuronal integration.
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  • 32
    ISSN: 1573-2614
    Keywords: Compliance ; human ; lung ; mechanical ventilation ; mechanics ; resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Medicine
    Notes: Abstract Objective. To evaluate and further develop a method for determination and mathematical characterisation of the elastic pressure-volume (Pel-V) relationship in mechanically ventilated human subjects during one single modified insufflation with simultaneous determination of resistance of the respiratory system. Subjects. Eight adult non-smoking human subjects without heart, lung, or thoracic cage disease scheduled for non-thoracic surgery. The study was performed in anaesthetised and muscle-relaxed subjects. Measurements and Main Results. The Pel-V curve was determined with a computer-controlled Servo Ventilator 900C during a modified insufflation with either constant or sinusoidally varying flow. Pressure and flow were measured with the built-in sensors of the ventilator. Tracheal pressure (Ptr) was calculated by subtracting the pressure drop over the tracheal tube. The elastic recoil pressure in the peripheral lung, Pel, was obtained from the calculated Ptr by subtracting the pressure drop over the airways. Ptr was also directly measured through a catheter. The calculated Ptr gave similar results as the directly measured Ptr, thus indicating the reliability of the signal originating from the ventilator sensor for computation of downstream pressures. The inflection points of the sigmoidal Pel-V curve and the compliance of the linear segment were determined with high reproducibility. Conclusions. Using one single modified insufflation allows a fast and accurate determination of respiratory mechanics. The Pel-V curves were determined with high reproducibility and were adequately described by a three-segment model of the curve incorporating a linear segment between two asymmetrical non-linear segments.
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  • 33
    ISSN: 1573-2614
    Keywords: occlusion pressure ; P0.1 ; monitor ; human ; automatic measurement ; mechanical load ; software
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Medicine
    Notes: Abstract Objective. To design and evaluate a clinical monitor of respiratory drive (P0.1) and other respiratory variables in a simple way, using a commercial ventilator. Methods. Nine healthy males were studied as they were breathing spontaneously in a Servo 900C Ventilator, at rest and during light exercise (50 W). The ventilator was slightly modified to improve its mechanical performance during spontaneous breathing, and was used as a measuring instrument. All the relevant information was retrieved, calculated and monitored by a PC. Respiratory drive was assessed as occlusion pressures from the inspiratory airway pressure signal. The equipment was compared with a two-way non-rebreathing laboratory system. Furthermore, negative and positive inspiratory pressures were applied from the ventilator, to study respiratory responses to mechanical loads. Results. At rest, the ventilator introduced a minor influence on inspiratory time and P0.1, but not in ventilatio n, tidal volume, expiratory duration and respiratory frequency. During exercise, the influence was more evident. This effect could also be noticed in the coefficients of variation. The responses to mechanical loads were easily recorded and can be used as a simple test of central load-compensating mechanisms. Conclusions. The ventilator, with limitations, may be an alternative to conventional techniques, especially in clinical studies of the central inspiratory activity with and without respiratory loading.
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  • 34
    ISSN: 1435-1463
    Keywords: Keywords: Aromatic L-amino acid decarboxylase ; brain ; colocalization ; GTP cyclohydrolase I ; human ; immunohistochemistry ; tetrahydrobiopterin ; tyrosine hydroxylase.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Guanosine triphosphate (GTP) cyclohydrolase I (GCH) is the first and rate-limiting enzyme for biosynthesis of tetrahydrobiopterin, the cofactor of tyrosine hydroxylase (TH). Our previous study reported the presence of GCH in several neuronal groups in animal brains using a newly raised anti-GCH antibody. The present study aims at elucidating whether GCH and TH coexist in the same neurons of the human brain with the aid of immunohistochemical dual labeling. GCH-immunoreactivity was observed in the cell bodies and fibers of monoaminergic neurons of the human brain. Neurons which contain both enzymes are seen in the human substantia nigra, ventral tegmental area, locus coeruleus, dorsal raphe, and zona incerta. In these regions, almost all the cells also show immunoreactivity for aromatic L-amino acid decarboxylase (AADC), the second step enzyme for catecholamine synthesis, indicating that these neurons are catecholaminergic. However, some neurons in the dorsal and dorsomedial hypothalamic nuclei are stained only for GCH or TH. They appear to constitute an independent cell group in the human brain. The present observation suggests that L-dopa is not produced in the cells immunoreactive for TH but not for GCH, and that TH in these cells which lack GCH may have an unidentified role other than dopa synthesis.
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  • 35
    ISSN: 1435-5604
    Keywords: Key words: alendronate ; bisphosphonate ; human ; osteoclasts ; morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Alendronate is a powerful therapeutic agent for the treatment of hypercalcemia in malignancy and osteoporosis and has recently been developed as a treatment for hypercalcemia of malignancy. In this study, time-lapse cinemicrography was used to investigate the effects of this agent on the morphology and the motility of human osteoclast-like multinucleated cells (MNCs) from human bone marrow. Alendronate at 10−5 M induced contraction of the cells starting 7.5 h after its addition. contraction was markedly induced immediately after alendronate removal. However, contraction almost disappeared 18 h after removal, and osteoclast-like MNCs recovered their original sizes and shape. There was only partial recovery from contraction after alendronate treatment at 10−4 M. In contrast, untreated control cells did not change their morphology after washing with culture medium. Motility analysis showed that osteoclast-like MNCs treated with 10−5 M alendronate moved actively after washing, but at 10−4 M the motility locus was very narrow. At 10−4 M, the actin ring in the cells began to break down, beginning 6 h after addition. The effects of alendronate on human osteoclast-like MNCs morphology and motility were reversible at 10−5 M, suggesting that alendronate dose not cause any cellular damages in human osteoclasts up to 10−5 M, which is an effective dose for bone resorption.
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  • 36
    ISSN: 1432-0428
    Keywords: Keywords Dietary fibre ; thiamine ; thiamine deficiency ; glucose tolerance test ; sex ; insulin resistance ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epidemiologic studies have shown an association between the intake of dietary fibres and 2-h glucose values. Food rich in dietary fibres is often also rich in thiamine. Animal studies have shown that thiamine deficiency can induce glucose intolerance. Our aim was to investigate the association between fibre consumption and thiamine intake on the one hand and glucose tolerance on the other hand. We used data from the Hoorn Study, a study of glucose tolerance among 1008 men and 1188 women, aged 50–75 years, without diabetes. In linear regression analyses, fibre intake was inversely associated with fasting glucose. There was also an inverse association between fibre intake and 2-h glucose but it disappeared for the greater part after adjustment for fasting glucose. Fibre intake appeared to be strongly correlated with thiamine intake, and this correlation explained the remaining part of the association between fibre intake and 2-h glucose. Thiamine intake appeared to have a strong and relevant association with 2-h glucose, which was independent of fibre intake and fasting glucose. This association was borderline after adjustment for potential confounders. In women, but not in men, the effect of thiamine intake on 2-h glucose seemed to be modified by fibre intake, independent of potential confounders. In conclusion, part of the association between fibre intake and glucose tolerance is possibly attributable to concomitant thiamine intake. [Diabetologia (1998) 41: 1168–1175]
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  • 37
    Electronic Resource
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    Angiogenesis 2 (1998), S. 287-294 
    ISSN: 1573-7209
    Keywords: angiogenesis ; capillary ; endometrium ; endothelial cell ; human ; VEGF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract As a tissue that exhibits rapid cyclical growth and shedding throughout the reproductive life of the female, the human endometrium provides a good model for the study of normal physiological angiogenesis. This paper will review current information on the timing of angiogenesis during the menstrual cycle, the mechanisms involved in endometrial capillary formation, and current information on angiogenesis factors and inhibitors. Based on endothelial cell proliferation studies, the timing of angiogenesis during the menstrual cycle remains unclear. The major mechanism by which endometrial capillaries are formed is probably a mixture of elongation and intussusception, with minimal evidence currently available for sprouting. Numerous angiogenesis factors have been identified in endometrium, the most well studied of which is VEGF. However, to date there is no evidence supporting a relationship between the expression of any given angiogenic factor and the occurrence of angiogenesis in the endometrium. Very limited studies have been undertaken to date on endometrial angiogenesis inhibitors, although the precursors to many of the known proteolytic fragments which act as inhibitors exist in the endometrium. In conclusion, neither the timing of vascular growth during the menstrual cycle nor the mechanisms by which endometrial vessels are formed are currently understood, thus placing major limitations on our understanding of how angiogenesis promoters and inhibitors may act in human endometrium.
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  • 38
    ISSN: 1573-7209
    Keywords: Angiogenesis ; endothelial cells ; fibrin degradation ; human ; in vitro
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fibrin is a temporary matrix which not only covers a wound, but also provides a structure for invading cells during healing. Changes in the polymerization conditions before gelation of the clot affect the structure of fibrin and thus might influence the interaction with invading cells. Therefore we tested whether changes in the fibrin structure influence the formation of capillary-like tubular structures by human microvascular endothelial cells (hMVEC) in an in vitro angiogenesis model. Opaque [125I]fibrin structures prepared at pH 7.0, fibrin matrices at pH 7.4 and transparent [125I]fibrin structures prepared at pH 7.8 were neutralized (pH 7.4) before seeding hMVEC on top of them in confluent density. Endothelial cells were stimulated with a growth factor [basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF)165] and a cytokine [tumor necrosis factor (TNF)-α] to induce the u-PA/u-PA receptor-dependent formation of capillary-like tubular structures. The formation of these structures was quantified by determining the length of the invasive structures by image analysis and by measuring the accompanying [125I]fibrin degradation. Ingrowth of tubular structures proceeded at a faster rate in opaque matrices consisting of thick fibrin fibers as compared to transparent gels with fine fibrin fibers. The more rapid ingrowth of tubular structures in opaque fibrin gels induced by bFGF/TNF-α or VEGF165/TNF-α was accompanied by a larger extent of fibrin degradation. Both processes were inhibited by aprotinin and ∈-aminocaproic acid indicating the involvement of plasmin. They were also inhibited by anti-u-PA or anti-u-PA receptor IgG, but not by anti-t-PA IgG, suggesting the involvement of cell-bound u-PA activity. However, in the opaque fibrin gels, the tubular structures dissolved upon prolonged incubation due to excessive fibrin degradation. Simulation of hMVEC with bFGF alone did not induce tubular structures, but ca used a high degree of t-PA- and plasmin-dependent fibrin lysis, and, after several days, a partial detachment of sheets of cells. Gradual inhibition of the excessive fibrin degradation by a series of aprotinin concentrations did not lead to tube formation in bFGF-treated cells. These data indicate that the formation and stability of tubular structures by hMVEC in fibrin is accompanied by controlled fibrinolysis and depends critically not only on cell-bound u-PA-dependent plasminogen activation, but also on the fibrin structure. Because the fibrin structure is largely influenced by the conditions in which fibrin has been polymerized, these conditions may have considerable impact on angiogenesis during wound healing and vascularization of tumour stroma.
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  • 39
    ISSN: 1573-7322
    Keywords: angiotensin receptors ; fibroblasts ; human ; collagen ; osteopontin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Angiotensin (Ang) II contributes to myocardial hypertrophy by modulating fibroblast function. In the nonhypertrophied adult rat, rabbit, monkey and human heart, both angiotensin receptor subtypes, AT1 and AT2, are expressed. AT1 seems to be present on almost all myocardial cells, whereas AT2 has so far been localized to coronary endothelial cells and to fibroblasts. AT1 signaling in fibroblasts resembles in many aspects growth factor and cytokine signaling. It includes Ca2+ influx, protein kinase C activation, tyrosine phosphorylation of a number of proteins, activation of the JAK–STAT pathway, and protooncogene induction. Effects of Ang II on the cellular level include proliferation, migration, activation of paracrine–autocrine loops via TGF-β1 and other mediators, stimulation of cell–cell interaction, and synthesis of matrix proteins, i.e., collagens I and III and fibronectin. Ang II stimulation induces an increase in osteopontin, which then engages to the αvβ3 integrin receptor on the cell surface of the fibroblasts. These events appear necessary for increased DNA synthesis and collagen gel contractions. Several modulators of fibroblast function interfere with the effects of Ang II, including prostaglandins, which interact with matrix synthesis; nitric oxide, which modulates proliferation at the level of cell cycle regulation; and endothelin, which transmits Ang II-induced proliferation signals. Mechanical loading of intact hearts also affects isolated fibroblast function, and therefore, isolated fibroblasts from pressure- and volume-loaded animals exhibit specific features that interfere with matrix synthesis and calcium handling. Fibroblasts from explanted human hearts respond to Ang II and to Ang (1–7) by DNA and protein synthesis. So far, binding assays to identify angiotensin receptor subtypes have been inconclusive. PCR has consistently revealed the presence of AT1. It is possible that AT2 receptors are also present on human cardiac fibroblasts in vivo, but their number is downregulated by growth factors in cell culture. The question concerning the conditions under which Ang II stimulates collagen formation in human cardiac fibroblasts cannot yet be conclusively answered.
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  • 40
    ISSN: 1573-7276
    Keywords: ovarian cancer ; human ; RMG-1 ; tumor-associated galactosyltransferase (GAT) ; orthotopic implantation ; nude mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinically relevant animal models of human cancer are important for studies of cancer biology, invasion and metastasis, and for investigating new forms of prognostic diagnosis and therapy. An ovarian tumor line (RMG-1: human clear cell carcinoma of the ovary) previously grown subcutaneously was implanted ortho-topically as intact tissue into the ovarian capsule of 22 nude mice. The tumors showed progressive growth at the orthotopic site in all animals. Tumor-associated serum galactosyltransferase (GAT) tended to be posi-tive in all nude -mice. The tumors invaded or metastasized to the contralateral ovary, retroperitoneum, mesentery and peritoneum, and omentum, and metastasized to the subcutaneous tissue, lymph nodes and distant organs including the liver, kidney, pancreas, and diaphragm. In striking contrast, subcutaneous trans-plantation of this tumor resulted in growth in only 2 of 5 animals with local lymph node and kidney involve-ment but no retroperitoneal or peritoneal involvement. These findings suggest that orthotopic implantation provides a suitable micro-environment in which ovarian cancer can express its intrinsic clinically-relevant properties. This approach is relevant to the clinical features of ovarian cancer and is thought to be a useful model for studies of therapy for this cancer.© Kluwer Academic Publishers 1998
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  • 41
    ISSN: 1573-7330
    Keywords: embryo ; human ; hyperstimulation ; in vitro maturation ; oocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Our purpose was to examine the rate of immature oocyte recovery and their potential for in vitro maturation from canceled human menopausal gonadotropin cycles due to the risk of having ovarian hyperstimulation syndrome develop. Methods: Patients underwent ultrasound-guided immature oocyte pickup. The number of oocytes recovered from these patients was recorded, and then cultured in vitro. Cumulus expansion and the stage of nuclear maturation were observed after 24 and 48 hr, respectively. Results: Seventeen patients underwent 20 immature oocyte recoveries. A total of 162 oocytes (8.1 oocytes/patient) was obtained. All of the oocytes were enclosed in dense layers of cumulus cells. Among them, 78.4% showed cumulus expansion after 24 hr and 66% completed meiotic maturation to metaphase II after 48 hr in culture. There was only one immature oocyte pickup in which no oocytes were recovered (95% recovery rate). None of the patients had ovarian hyperstimulation syndrome develop. Conclusions: Immature oocytes can be recovered from canceled human menopausal gonadotmpin cycles in patients who are at potential risk for severe hyperstimulation syndrome. These oocytes can be matured in vitro and can be used for clinical and research purposes as well.
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  • 42
    ISSN: 1573-742X
    Keywords: platelets ; glycoprotein Ib ; glycoprotein IIIa ; glycoprotein IIb/IIIa ; flow cytometry ; human ; swine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Swine platelets are very similar to those of humans and are therefore relevant to cardiovascular research. The swine coronary circulation mimics the human circulation and is large enough to obtain multiple blood samples in survival experiments. In swine regional ischemia similar to the human condition is easily obtainable, which makes the porcine model an ideal choice to study coronary artery disease. However, little is known about the similarity between swine and human platelet surface antigens. We tested the hypothesis that certain swine platelet antigens could crossreact with antihuman antibodies. Using FITC-conjugated monoclonal murine antihuman platelet antibodies, surface antigen expression was determined for human and Yorkshire swine platelets. Expression of CD9 (p24), CD42B (Ib), CD41b (IIb), CD61 (IIIa), CD41a (IIb/IIIa), CD49b (VLA-2), CD62p, (P selectin), CD31 (PECAM-1), and CD51/CD61 (vitronectin) was measured by flow cytometry. Significant crossreactivity with human platelets was observed consistently for swine platelet GP Ib and GP IIIa. Crossreactivity of the swine GPIb and GP IIIa with the human receptors is evidence of receptor similarity between human and swine platelets. The implications of significant crossreactivity of these antigens and the lack of recognition of IIb/IIIa needs to be understood in cardiovascular research. Determining commercially available antihuman GP Ib and GP IIIa, rather than GP IIb/IIIa, would contribute to better elucidation of the effects of von Willebrand factor and the booming family of platelet inhibitors in the swine model of ischemia-reperfusion.
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  • 43
    ISSN: 1573-7233
    Keywords: human ; cancer ; nitric oxide ; angiogenesis ; invasion ; inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Varied cellular expression and localisation of nitric oxide synthase (NOS) isoforms has been shown in human cancers, including tumours of the breast, ovary, stomach, cervix and central nervous system. Mapping of NOS expression within tumour tissue from breast and gastric cancers shows inducible NOS (iNOS) is expressed predominantly in stromal (macrophage and endothelial) cells, although the level of NOS activity is at least 1–2 orders of magnitude lower than the enzyme activity associated with cytotoxicity and apoptosis. There is evidence that the intratumoural environment may provide chemoattractant signals for monocyte-macrophage recruitment and their subsequent activation via expression of interleukin-4, IgE, and CD23. Such signals lead to induction of iNOS in human macrophages in vitro. The correlation between NOS activity and grade for breast cancer suggests that NO may provide a positive growth signal within the tumour microenvironment. In vivo studies showing increased growth rate, vascular density and invasiveness of a human tumour cell line transfected to constitutively express iNOS support this. Furthermore, in vivo administration of a highly selective inhibitor of iNOS limited invasion and growth rate of iNOS transfected tumours and other murine tumours expressing this isoform. Inhibition of NO generation in the intratumoural microenvironment may prove a useful cancer therapy by preventing angiogenesis, invasion and metastasis.
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  • 44
    ISSN: 1573-7330
    Keywords: embryo ; fertilization ; human ; in vitro fertilization ; reduced insemination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Recent studies showed a beneficial effect of reducing the time of sperm–oocyte interaction on fertilization, division, and implantation rates of the oocytes obtained from randomized patients. In the present study, the effects of reduced insemination time on fertilization and embryo development were evaluated by using sibling oocytes from the same patient. Methods: A total of 464 oocytes from 36 patients was randomly allocated to be inseminated for either 1 hr (reduced) or 18 hr (regular). Results: Fertilization rates were not significantly different between reduced (135/229; 59%) and regular (150/235; 64%) groups. Cleavage rates and embryo quality were similar in both groups. A total of 135 embryos (73 from the reduced and 62 from the regular group) was transferred to 36 patients. Thirty-four embryos implanted in 18 patients (25.2% implantation and 50.0% pregnancy rates). Conclusions: Fertilization, cleavage, and embryo development from 1-hr insemination is comparable, not superior, to those from an 18-hr insemination time, which is commonly used in in vitro fertilization programs. These data suggest that reduced insemination time can be used during in vitro fertilization to avoid unnecessarily longer exposure to spermatozoa.
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  • 45
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    Theoretical medicine and bioethics 19 (1998), S. 337-352 
    ISSN: 1573-1200
    Keywords: communication ; dialogue ; dignity ; dying ; human ; humane ; individual ; proper ; worth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Philosophy
    Notes: Abstract The word “dignity” is frequently used both in clinical and philosophical discourse when referring to and describing the ideal conditions of the patient's treatment, particularly the dying patient. An exploration of the variety of meanings associated with the word dignity will note dignity's ambiguous usage and reveal instrumental concepts needed to better understand the discourse of the dying. When applied to a critique of recent and contemporary criticisms of the medical community's handling of the dying, such concepts might provide a more coherent notion of dignity. Rather than a separate construct, a death with dignity might be viewed as an interactive process among the dying and their caretakers. Together, this interdependent amalgam engages in humanizing communication aimed toward understanding the final needs and wants of the patient.
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  • 46
    ISSN: 0730-2312
    Keywords: cartilage ; aging ; osteoarthritis ; programmed cell death ; cell culture ; human ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The regulation of chondrocyte apoptosis in articular cartilage may underlay age-associated changes in cartilage and the development of osteoarthritis. Here we demonstrate the importance of Bcl-2 in regulating articular chondrocyte apoptosis in response to both serum withdrawal and retinoic acid treatment. Both stimuli induced apoptosis of primary human articular chondrocytes and a rat chondrocyte cell line as evidenced by the formation of DNA ladders. Apoptosis was accompanied by decreased expression of aggrecan, a chondrocyte specific matrix protein. The expression of Bcl-2 was downregulated by both agents based on Northern and Western analysis, while the level of Bax expression remained unchanged compared to control cells. The importance of Bcl-2 in regulating chondrocyte apoptosis was confirmed by creating cell lines overexpressing sense and antisense Bcl-2 mRNA. Multiple cell lines expressing antisense Bcl-2 displayed increased apoptosis even in the presence of 10% serum as compared to wild-type cells. In contrast, chondrocytes overexpressing Bcl-2 were resistant to apoptosis induced by both serum withdrawal and retinoic acid treatment. Finally, the expression of Bcl-2 did not block the decreased aggrecan expression in IRC cells treated with retinoic acid. We conclude that Bcl-2 plays an important role in the maintenance of articular chondrocyte survival and that retinoic acid inhibits aggrecan expression independent of the apoptotic process. J. Cell. Biochem. 71:302-309, 1998. © 1998 Wiley-Liss, Inc.
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  • 47
    ISSN: 0730-2312
    Keywords: bone marrow stroma ; human ; differentiation ; TGF-β ; BMP-2 ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Osteoprogenitor cells in the human bone marrow stroma can be induced to differentiate into osteoblasts under stimulation with hormonal and local factors. We previously showed that human bone marrow stromal (HBMS) cells respond to dexamethasone and vitamin D by expressing several osteoblastic markers. In this study, we investigated the effects and interactions of local factors (BMP-2 and TGF-β2) on HBMS cell proliferation and differentiation in short-term and long-term cultures. We found that rhTGF-β2 increased DNA content and stimulated type I collagen synthesis, but inhibited ALP activity and mRNA levels, osteocalcin production, and mineralization of the matrix formed by HBMS cells. In contrast, rhBMP-2 increased ALP activity and mRNA levels, osteocalcin levels and calcium deposition in the extracellular matrix without affecting type I collagen synthesis and mRNA levels, showing that rhBMP-2 and rhTGF-β2 regulate differentially HBMS cells. Co-treatment with rhBMP-2 and rhTGF-β2 led to intermediate effects on HBMS cell proliferation and differentiation markers. rhTGF-β2 attenuated the stimulatory effect of rhBMP-2 on osteocalcin levels, and ALP activity and mRNA levels, whereas rhBMP-2 reduced the rhTGF-β2-enhanced DNA synthesis and type I collagen synthesis. We also investigated the effects of sequential treatments with rhBMP-2 and rhTGF-β2 on HBMS cell differentiation in long-term culture. A transient (9 days) treatment with rhBMP-2 abolished the rhTGF-β2 response of HBMS cells on ALP activity. In contrast, a transient (10 days) treatment with rhTGF-β2 did not influence the subsequent rhBMP-2 action on HBMS cell differentiation. The data show that TGF-β2 acts by increasing HBMS cell proliferation and type I collagen synthesis whereas BMP-2 acts by promoting HBMS cell differentiation. These observations suggest that TGF-β2 and BMP-2 may act in a sequential manner at different stages to promote human bone marrow stromal cell differentiation towards the osteoblast phenotype. J. Cell. Biochem. 68:411-426, 1998. © 1998 Wiley-Liss, Inc.
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  • 48
    ISSN: 0952-3499
    Keywords: substance P ; endopeptidase ; spinal cord ; cerebrospinal fluid ; human ; purification ; characterization ; ÄKTATM ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: An enzyme activity capable of hydrolysing the neuroactive undecapeptide substance P (SP) between its Phe7-Phe8 residues was purified from the membrane-bound fraction of human spinal cords. The enzyme preparation yielded was compared with a previously described SP-hydrolysing enzyme from human cerebrospinal fluid (CSF) with regard to inhibition profile, protein chemical properties and kinetics. In addition, the results were compared with those of bovine pancreatic chymotrypsin (a serine protease that cleaves the carboxy-terminal side preferentially at hydrophobic amino acids). The SP peptidase activity was extracted from human spinal cords with 1% Triton X-100 in 20 mM Tris-HCl pH 7.8. After ion exchange chromatography (DEAE-Sepharose) where the enzyme activity was separated from other proteins by gradient elution, the pooled enzyme fraction was further purified by molecular sieving (Sephadex G-50). The enzyme activity was finally recovered by HPLC molecular sieving (Superdex® 75 HR 10/30) using a new preparative system, ÄKTATM-purifier, controlled by UNICORN® software version 2.20. Copyright © 1998 John Wiley & Sons, Ltd.
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  • 49
    ISSN: 1572-8633
    Keywords: heart attacks ; coronary heart disease ; social construction ; medical knowledge ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Philosophy
    Notes: Abstract There has been a modern epidemic of heart attacks in the western world, and this paper is concerned with this ‘new’ medical condition and how it arose. Two competing theories are commonly proposed, relating either to conventional accounts of medical science, or to social construction. Whilst recognising that aspects of both theories have some validity, it is claimed that neither is wholly adequate. This issue has particular relevance for heart attacks and is explored in some detail, but it also points to some more general conclusions. First that medical knowledge cannot be separated into ‘scientific’ and ‘social’ compartments but is united by its human aspect; and second that although medical knowledge has a special dimension, when understood in this way, it may also resonate with a more general re-examination of the relationship between scientific and human knowledge.
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  • 50
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    Springer
    Journal of medical systems 22 (1998), S. 225-236 
    ISSN: 1573-689X
    Keywords: patients ; dependency ; information ; systems ; hospitals ; nursing ; human ; resources ; management
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract One of the most challenging decisions in resource allocations in hospitals is: how to allocate nursing duties on the basis of patients' needs? Patient Dependency Systems, in different forms, can be used to provide information for staffing decisions and budgetary developments. That is why Patient Dependency Systems are emerging as powerful tools in hospital management. It is anticipated that their use will grow, as hospitals everywhere come under pressure to reduce cost and improve the delivery and quality of health care to patients. Experience has shown that manual Patient Dependency Systems lack the ability to process and provide information fast enough to handle crisis situations. In addition, manual calculations are inefficient and are not free from human errors. However, the utilization of current advances in computing technology can overcome these disadvantages. Patient Dependency Systems are suitable for automation since their essence is too complex to handle manually. Furthermore, it is essential to automate the Patient Dependency Systems because of their critical role and their inherent complexity. In this paper, the automation of Patient Dependency Systems is presented. The development of Patient Dependency Automated Systems is shown to provide reliable and valid methods for evaluating the needs of patients in terms of the nursing effort required.
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  • 51
    ISSN: 1573-7217
    Keywords: mammary tumor ; human ; mouse ; retinoids ; tamoxifen ; RU-486 ; apoptosis ; proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Retinoids constitute a very promising class of agents for the chemoprevention or treatment of breast cancer. These retinoids exert their biological activity through two distinct classes of retinoic acid (RA) receptors (R), the RAR isotypes (α, β, and γ) and the three RXR isotypes (α, β, and γ) and their numerous isoforms which bind as RXR/RAR heterodimers to the polymorphic cis-acting response elements of RA target genes. With respect to these numerous receptor sub-types, the retinoid-induced effects at the biological level include marked modifications with respect to both cell proliferation and cell death (apoptosis), and also in the induction of differentiation processes. The present study aims to characterize the effect which four retinoids (TTNPB, 9-cis-RA, LGD 1069, 4-HPR) with distinct RAR/RXR binding properties induced on various in vitro and in vivo mouse and human breast cancer models. The experiments with the retinoids were carried out in comparison with the anti-estrogen tamoxifen and the anti-progestagen RU-486 compounds. The results show that the 6 compounds under study were markedly more efficient in terms of growth inhibition in the human T-47D cell line when maintained under anchorage-independent culture conditions than when maintained under anchorage-dependent ones. While RU-486 exhibited a weak statistically significant (p 〈 0.05) influence on the growth of the T-47D stem cells, tamoxifen had a marked inhibitory influence on the growth of these cells. Of the four retinoids, 4-HPR was the least effective since the lowest doses tested (1 and 0.1 nM) exhibited no statistically (p 〉 0.05) significant influence on the growth of the stem cells. The most efficient retinoid was TTNPB. It was only at the highest dose (10 μM) that tamoxifen and RU-486 showed a weak inhibitory influence on the growth of the T-47D non-stem cells while all 4 retinoids exerted a significant inhibitory influence on the growth of these non-stem cells, with 4-HPR being the most efficient (P 〈 0.001) at the highest dose, but ineffective (P 〉 0.05) at the lowest. Tamoxifen and TTNPB were tested in vivo on hormone-senstive (HS) and hormone-insensitive (HI) strains of the MXT murine mammary carcin oma. While TTNPB appeared to be equally efficient in terms of growth inhibition in both MXT-HS and MXT-HI models, tamoxifen had only a marginal inhibitory influence on the growth of the MXT-HI strain but did inhibit growth in the case of the MXT-HS one. TTNPB was markedly more efficient than tamoxifen in terms of both inhibiting the cell proliferation level (measured by means of computer-assisted microscopy applied to Feulgen-stained nuclei, a method which enables the percentage of cells in the S phase of the cell cycle to be determined) and triggering cell death (measured by means of the determination of the transglutaminase activity) in both the MXT-HI and MXT-HS models. The very significant TTNPB-induced inhibition of the macroscopic MXT-HS growth rate relates to the triggering of cell death (apoptosis) rather than to an inhibition of cell proliferation. All these results clearly indicate that retinoids are very efficient agents against breast cancer, at least as efficient as tamoxifen.
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  • 52
    ISSN: 1573-2622
    Keywords: electrophysiology ; human ; texture segregation ; VEP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract ‘Texture segregation’ results from parallel processing in the visual cortex. It occurs when the stimulus contains spatial gradients within a visual dimension. We here present an introductory overview of the field, concentrating on electrophysiological correlates in the human EEG (‘tsVEPs’) of the neuronal processes underlying texture segregation. We describe the isolation of the tsVEP from the background EEG, give examples of the correlation between saliency and tsVEP amplitude and compare texture segregation between visual dimensions.
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  • 53
    ISSN: 1573-2622
    Keywords: development ; electroretinogram ; human ; infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to determine how responses in the normal human electroretinogram (ERG) change with subject age. We studied 62 children, 10 days to 15 years old, and 30 subjects 15–37 years old, using the standard protocol established by the International Society for Clinical Electrophysiology of Vision, with Burian-Allen bipolar contact-lens electrodes. We measured rod response, maximal response, oscillatory potentials (OPs), cone response, flicker response, and b-wave amplitude/log intensity (V/log I) curve. A logistic growth curve was used to describe the developmental changes. Dark- and light-adapted ERG a- and b-wave amplitudes reached adult levels by three to five years of age, although b-wave amplitudes of scotopic rod-mediated responses were slower to reach maturity than mixed rod-cone mediated responses. In early infancy OPs were the most immature of the ERG responses, although the rate of development thereafter exceeded that of the other responses such that OP amplitudes were within adult levels by two years of age. Amplitudes of the ERG responses in 21 children sedated with chloral hydrate did not differ significantly from 21 who had not been sedated. ERG responses developed at varying rates, reflecting different developmental stages in photoreceptors, middle retinal layers and more proximal retina.
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  • 54
    ISSN: 1573-2592
    Keywords: Complement ; human ; lyonization ; oligomerization ; X chromosome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three properdin deficiency phenotypes have been reported—complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin protein (type III)—all associated with increased susceptibility to meningococcal disease. Expression of properdin by monocytes was examined in type I deficiency and in two unrelated cases with type II deficiency, one from a Swedish and one from a Danish family. The properdin gene in the Danish family contained a point mutation in exon 8 causing a Gln316→Arg substitution, distinct from a point mutation in exon 4 previously found in the Swedish family. Both genes coded for physicochemically abnormal properdin molecules with changed hydrophilicity. Monocytes from all the properdin-deficient individuals produced properdin mRNA in a normal fashion. In type I deficiency no intracellular or secreted properdin was found, indicating rapid intracellular degradation. Monocytes from the males with type II deficiency expressed and secreted properdin normally. Properdin in sera with type II deficiency showed abnormal oligomerization with a relative decrease in properdin trimers and tetramers. Our findings suggest that the low concentration of circulating properdin in type II deficiency is caused by increased extracellular catabolism. Analysis of properdin expression by mono-cytes in a female carrier in the family with properdin deficiency type I provided direct evidence of lyonization at the cellular level.
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  • 55
    ISSN: 1573-2592
    Keywords: Apoptosis ; T lymphocytes ; human ; intestinal lamina propria ; regional immunity ; HIV ; gp120
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intestinal mucosa represents an important portal of entry of HIV and a site of virus reservoir and active replication. Recently, in HIV patients, an early depletion of intestinal lamina propria T lymphocytes (LPT) has been described. HIV-1 gp120 has been demonstrated to promote apoptosis in noninfected isolated peripheral blood T cells, therefore we investigated whether gp120 modulates apoptosis of normal human intestinal lamina propria T cells. Purified T cells were obtained by immunomagnetic negative selection from human lamina propria mononuclear cells isolated from surgical specimens by enzymatic procedure. Cells were incubated with or without recombinant gp120 (10 μg/ml) and cultured either in the absence of any stimulus or in the presence of plate-bound anti-CD3 Ab (OKT3) or soluble anti-CD2 Ab (T112 + T113). Apoptosis was assessed by flow cytometric analysis after propidium iodide staining. We demonstrated that preincubation of normal LPT cells with HIV-1 gp120 accelerates the apoptosis observed during CD2-pathway stimulation of LPT cells. This process is mediated by Fas/Fas ligand interaction and related to an increased induction of Fas ligand mRNA by gp120. Therefore HIV-1 gp120 could contribute to the depletion of noninfected LPT cells inducing a premature cell death.
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  • 56
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    Archives of sexual behavior 27 (1998), S. 561-580 
    ISSN: 1573-2800
    Keywords: SEXUAL HARASSMENT ; RISK ; SEXISM ; ATTRACTIVENESS ; SEXROLE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract A new model of the etiology of sexual harassment,the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model,and the sexrole spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sexrole). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures.
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  • 57
    ISSN: 0263-6484
    Keywords: hepatocyte ; protein kinase ; insulin ; glucagon ; MAPK ; EGF ; epidermal growth factor ; rat ; human ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Many hepatocellular activities may be proximally regulated by intracellular signalling proteins including mitogen-activated protein kinases (MAPK). In this study, signalling events from epidermal growth factor (EGF) and insulin were examined in primary cultured human and rat hepatocytes. Using Western immunoblots, rat and human hepatocytes were found to produce a rapid tyrosine phosphorylation of the EGF receptor and MAPK following 0·5-1 min exposure to EGF. Phosphorylation of p42 and p44 MAPK was observed following 2·5 min exposure to EGF. Insulin treatment produced phosphorylation of the insulin receptor β subunit; shc phosphorylation was not observed. MAPK phosphorylation corresponded with a shift in molecular weight and an increase in kinase activity. Insulin-dependent activation of MAPK was unequivocally observed only in human hepatocytes, though a slight activation was detected in rat. Co-treatment with insulin and EGF produced phosphorylation and complete electrophoretic shift in molecular weight of MAPK, with an additive or synergistic increase in enzyme activity in rat but not human hepatocytes; human hepatocyte MAPK was maximally stimulated by EGF alone. Glucagon pretreatment blocked phosphorylation, gel mobility shift and kinase activity of MAPK induced by insulin but only partially blocked EGF-induced MAPK activation in human hepatocytes. Glucagon also reduced the activation of MAPK by EGF in rat hepatocytes. Pre-treatments with forskolin or cyclic AMP analogues diminished in the insulin-, EGF- and insulin plus EGF-dependent activation of MAPK in rat hepatocytes without effecting phosphorylation of receptors or MAPK. These results indicate that although EGF and insulin may both signal through the MAPK/ras/raf/MAPK pathway, the response for MAPK differs between these ligands and between species. Further, in both rat and human, glucagon exerts its effects through a cyclic AMP-dependent mechanism at a level in the insulin and EGF signal transduction pathways downstream of MAPK but promixal to MAPK. The partial inhibition of EGF-induced MAPK phosphorylation by glucagon in human hepatocytes provides further evidence for a raf-1-independent pathway for activation of MAPK. © 1998 John Wiley & Sons, Ltd.
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