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  • Articles  (26)
  • DKFZ Publication Database
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  • 2000-2004  (26)
  • 1
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    German Medical Science; Düsseldorf, Köln
    In:  GMS Current Topics in Otorhinolaryngology - Head and Neck Surgery; VOL: 3; DOC06 /20041228/
    Publication Date: 2004-12-29
    Description: Hearing loss from occupational and leisure noise numbers amongst the most frequent causes of an acquired sensorineural hearing loss. Here we present a review of up-to-date findings on the pathophysiology of acoustic injury to the inner ear, with special attention being paid to its molecular-biological and genetic aspects. Epidemiological aspects shall also be dealt with, as shall the roles of lacking recovery from occupational noise due to additional exposure by leisure noise and the combined exposure of noise and chemicals. Based on the epidemiological and pathophysiological findings and against the background of published animal-experimental, pre-clinical and clinical findings, the various approaches for prevention, protection and therapeutic intervention with acoustic trauma are discussed. Pharmacological strategies involving anti-oxidative, anti-excitotoxic and anti-apoptotic substances as well as non-pharmacological strategies like "sound conditioning" are given attention. Furthermore, systemic and local substance application as well as the therapy of acute acoustic trauma and chronic hearing problems (including modern therapy forms for comorbidities such as tinnitus) shall be delved into.
    Keywords: acute acoustic trauma ; noise-induced hearing loss ; recreational ; leisure noise ; occupational ; prevention ; protection ; therapy ; animal ; human ; ddc: 610
    Language: English
    Type: article
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  • 2
    ISSN: 1573-904X
    Keywords: methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    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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  • 7
    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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  • 8
    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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  • 9
    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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  • 10
    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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  • 11
    ISSN: 1573-4943
    Keywords: Creatine kinase ; human ; expression ; brain ; muscle ; purification ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We report the expression of the human muscle (CK-MM) and brain (CK-BB) creatine kinases in Escherichia coli. The proteins have been purified to apparent homogeneity and several of their physical and kinetic properties investigated. In the process, we have conclusively verified the correct DNA sequence of the genes encoding the respective isozymes, and determined the correct primary structure and mass of the gene products. Alignment of the primary sequences of these two enzymes shows 81% sequence identity with each other, and no obvious gross structural differences. However, Western blot analyses demonstrated the general lack of antigenic cross-reactivity between these isozymes. Preliminary kinetic analyses show the K m and k cat values for the creatine and MgATP substrates are similar to values reported for other isozymes from various tissues and organisms. The human muscle and brain CKs do not, however, exhibit the synergism of substrate binding that is observed, for example, in rabbit muscle creatine kinase.
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  • 12
    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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  • 13
    ISSN: 1572-8773
    Keywords: Al ; human ; lymphocytes ; urine concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The purpose of this study was to examine whether oral exposure to aluminum (Al) can affect the human immune system. Eighteen healthy volunteers (mean age 42, 28–57 yr) were divided into a test group (9 females, 4 males) and a referent group (3 females, 2 males). Over 6 weeks, the test subjects ingested 10 ml of antacid (aluminum hydroxide, 59 mg Al/ml) three times daily. Aluminum was analyzed in urine before and during the exposure period (ICP-MS). Blood samples were used for analysis of lymphocyte subpopulations, mitogen-induced lymphocyte proliferation and in vitro production and circulating plasma concentrations of immunoglobulin (Ig) A, IgG, IgM, interleukin (IL) -2 and IL-4. Urinary Al concentration in the test subjects was approximately 10- to 20-fold higher than in the referent group during exposure. This indicates that ingestion of an Al-containing antacid is associated with an Al absorption far above that originating from food and drinking water. In both referents and test subjects the lymphocyte subpopulations, lymphocyte proliferation and the in vitro Ig and IL production showed similar, time-dependent changes before as well as during the exposure period. No major differences were seen between the referent and test groups regarding the immune parameters, except for a slightly smaller CD8+CD45R0+ population (primed cytotoxic T-cells), in the exposed individuals as compared to the referents. The results also show that subjects on antacid therapy may constitute a suitable population for studying biological effects of high-dose oral exposure to Al.
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  • 14
    ISSN: 1573-6849
    Keywords: chimpanzee ; chromatin condensation ; human ; mouse ; XY body
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We used multicolour fluorescence in-situ hybridization on air-dried pachytene nuclei to analyse the structural and functional domains of the sex vesicle (SV) in human, chimpanzee and mouse. The same technology associated with 3-dimensional analysis was then performed on human and mouse pachytene nuclei from cytospin preparations and tissue cryosections. The human and the chimpanzee SVs were very similar, with a consistently small size and a high degree of condensation. The mouse SV was most often seen to be large and poorly condensed, although it did undergo progressive condensation during pachynema. These results suggest that the condensation of the sex chromosomes is not a prerequisite for the formation of the mouse SV, and that a different specific mechanism could be responsible for its formation. We also found that the X and Y chromosomes are organized into two separate and non-entangled chromatin domains in the SV of the three species. In each species, telomeres of the X and Y chromosomes remain clustered in a small area of the SV, even those without a pseudoautosomal region. The possible mechanisms involved in the organization of the sex chromosomes and in SV formation are discussed.
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  • 15
    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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  • 16
    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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  • 17
    ISSN: 1573-6849
    Keywords: gene mapping ; human ; R-banding ; river buffalo ; sheep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 18
    ISSN: 1573-6849
    Keywords: cat ; chromosome painting ; comparative mapping ; dog ; evolution ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Domestic cats and dogs are important companion animals and model animals in biomedical research. The cat has a highly conserved karyotype, closely resembling the ancestral karyotype of mammals, while the dog has one of the most extensively rearranged mammalian karyotypes investigated so far. We have constructed the first detailed comparative chromosome map of the domestic dog and cat by reciprocal chromosome painting. Dog paints specific for the 38 autosomes and the X chromosomes delineated 68 conserved chromosomal segments in the cat, while reverse painting of cat probes onto red fox and dog chromosomes revealed 65 conserved segments. Most conserved segments on cat chromosomes also show a high degree of conservation in G-banding patterns compared with their canine counterparts. At least 47 chromosomal fissions (breaks), 25 fusions and one inversion are needed to convert the cat karyotype to that of the dog, confirming that extensive chromosome rearrangements differentiate the karyotypes of the cat and dog. Comparative analysis of the distribution patterns of conserved segments defined by dog paints on cat and human chromosomes has refined the human/cat comparative genome map and, most importantly, has revealed 15 cryptic inversions in seven large chromosomal regions of conserved synteny between humans and cats.
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  • 19
    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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  • 20
    ISSN: 1573-6849
    Keywords: autoantibodies ; cell cycle ; DNA replication ; human ; MCP1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Metaphase chromosome protein 1 (MCP1) is a nuclear autoantigen that is associated with condensed chromosomes throughout mitosis. During interphase, this antigen shows a speckle distribution in the nucleus, excluding the nucleolus. Additionally, MCP1 binds tightly to the scaffold/matrix component of nuclei and isolated chromosomes. In order to determine the in-vivo localization of the antigen, we have expressed MCP1 fused to EGFP in tissue culture cells. The results demonstrate that MCP1 is located in the nucleus during interphase and during mitosis associates tightly to condensed chromosomes. Furthermore, microinjection of specific antibody confirms these results. We have used a specific monoclonal antibody (mAb 402) against MCP1 to assess the function of this antigen during cell cycle progression. HeLa and Ptk-2 cells that were microinjected into the nucleus and/or cytoplasm at G1/S and very early S phase were not able to progress and complete DNA replication. However, injection of mAb 402 at mid or late S phase does not prevent completion of DNA replication and subsequent progression into mitosis. Microinjection of mAb 402 in Ptk-2 cells synchronized in mitosis did not interfere with progression of mitosis and cells divided. Our results suggest that MCP1 is required at the G1/S transition and during early S phase.
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  • 21
    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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  • 22
    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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  • 23
    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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  • 24
    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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  • 25
    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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  • 26
    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.
    Type of Medium: Electronic Resource
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