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  • 1
    Keywords: CANCER ; EXPRESSION ; microenvironment ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; CLINICAL-SIGNIFICANCE ; DISEASE PROGRESSION ; PD-1 ; CHRONIC VIRAL-INFECTION ; SUB-POPULATIONS ; EXHAUSTION
    Abstract: T-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Emu-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3(+)CD8(+) T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1(+) T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8(+) T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity.
    Type of Publication: Journal article published
    PubMed ID: 25979947
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  • 2
    ISSN: 0309-1651
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1106
    Keywords: Memory: visual recognition or working memory ; Medial temporal lobe ; Perirhinal cortex ; Hippocampal formation ; Monkey ; Single unit recording
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recordings of the activity of 2705 single neurones were made in entorhinal and perirhinal cortex, area TG of the temporal lobe, and the inferior temporal cortex both during monkeys' performance of a serial recognition memory task using complex pictures and when monkeys were shown objects. Responses of 120 (9.7%) of the visually responsive neurones recorded were significantly smaller to the second than to the first presentations of unfamiliar stimuli. The incidence of such responses was highest in perirhinal cortex plus areas TE1 and TE2 of the temporal lobe, intermediate in lateral entorhinal cortex and areas TE3 and TG, and lowest in other parts of entorhinal and inferior temporal cortex. Response decrements were maintained across 20 or more intervening presentations of other stimuli for the majority of the neurones tested. Responses of 43 (14.4%) of the visually responsive neurones tested were significantly greater to unfamiliar than to highly familiar stimuli. Such differential responses were found only in lateral entorhinal and perirhinal cortex plus areas TG, TE1, TE2 and TE3. For 6 neurones the response difference was significant even when the familiar stimuli had not been seen for more than 24 h: such neurones demonstrate access to information stored in long-term memory for more than 24 h. Seven familiarity neurones signalled information concerning the relative familiarity of stimuli but not information concerning how recently they were last seen; 58 recency neurones signalled information concerning the recency of presentation of stimuli, but not their relative familiarity. Thus certain neurones demonstrate the separable encoding of recency and familiarity information. Neurones signalling information of use for recognition memory are found in cortex close to the rhinal sulcus where lesions result in major deficits in the performance of recognition memory tasks. The conjunction of these findings provides strong evidence for the importance of these neurones and this cortex for processes (recency and familiarity discrimination) necessary for recognition and working memory. The possible relation of the neuronal responses to priming memory is also discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Clinically normal skin from patients being treated for dermatitis herpetiformis was examined with the electron microscope.Cytoplasmic processes from the basal epidermal cells penetrated the dermis through discontinuities in the basal lamina which otherwise was normal in structure and thickness. The fibrous network of the dermis consisting of collagen, small reticular fibrils, anchoring fibrils and elastin, appeared normal.In patients receiving only dapsone, membrane-bound‘vacuoles’were found just below the basal lamina. They contained a fibrillar material of low electron density and were often associated with cell processes or complete cells, the classification of which was difficult. It is suggested that these vacuoles may be implicated in the reaction between reticulin and immunological complexes.In two specimens, early blister formation was also seen in the dermal papillae. The basal lamina remained applied to the stratum basale and was only absent where basal cell processes projected into the blister space which contained fibrin deposits. Vesiculated structures observed in the region of the blisters are interpreted as abnormal sensory nerve endings.This evidence supports the view that disruption of the basal lamina and blister formation in dermatitis herpetiformis are secondary to an earlier reaction.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Apolipoprotein B-100 (ApoB) is the principal structural and functional protein of the pro-atherogenic lipoproteins. Elevated plasma apoB is an independent risk factor for coronary artery disease. In the present study we aimed to assess the factors that determine the kinetics of apoB in the very low-density lipoprotein (VLDL) in healthy men.2. We studied 17 non-obese men who were consuming an ad libitum diet and had the following characteristics: mean (± SD) age 45.5 ± 9.7 years, body mass index (BMI) 25.1 ± 1.4 kg/m2, waist: hip ratio 0.91 ± 0.04, serum cholesterol 5.2 ± 0.6 mmol/L, triglycerides 1.08 ± 0.53 mmol/L and high-density lipoprotein-cholesterol 1.24 ± 0.31 mmol/L. Daily dietary intake was as follows: total fat 76 ± 26 g, carbohydrate 238 ± 67 g, protein 103 ± 33 g and alcohol 20 ± 16 g.3. The kinetics of VLDL ApoB were studied using a primed, constant infusion (1 mg/kg per h) of l-[13C]-leucine over 8 h with measurement of isotopic enrichment of ApoB using gas chroma-tography/mass spectrometry. The fractional turnover rate of VLDL ApoB was estimated using a monoexponential function. The mean (± SD) absolute hepatic secretion rate (ASR) of ApoB was 8.5 ± 4.6 mg/kg per day and the fractional catabolic rate (FCR) was 7.9 ± 5.6 pools/day. The ASR was significantly correlated with the waist: hip ratio (r= 0.60; P= 0.04), but not with age, BMI, weight or nutrient intake. The FCR was significantly and inversely correlated with plasma triglycerides (r =—0.53; P= 0.03) and alcohol intake (r = -0.48; P= 0.05).4. In conclusion, the hepatic secretion of VLDL ApoB in non-obese, healthy men is primarily determined by the waist: hip ratio, a measure of visceral fat. This is consistent with the hypothesis that the rate of lipid substrate supply to the liver regulates the output of ApoB. The fractional catabolism of VLDL ApoB may, however, be inversely related to alcohol intake and appears to determine the plasma concentration of triglycerides.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 109 (1983), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The distribution of carbohydrates containing 1,2-glycol groups at the basement membrane zones of the dermo-epidermal junction and dermal blood vessels was investigated using the periodic acid-thiosemicarbazide-silvcr proteinate technique. Controls included pre-incubation with dimedone, dimedone treatment both before and after periodate oxidation, and dimedone treatment followed by thiosemicarbazide and silver proteinate.At the dermo-epidermal junction the anchoring fibrils were stained selectively after both short (45 min) and long (71 h) thiosemicarbazide incubation periods, there being no staining of the lamina densa; however, the lamina densa surrounding blood vessels was labelled. After prolonged treatment with thiosemicarbazide, fibrils were observed traversing the lamina lucida at the dermo-epidermal junction, and collagen fibres were stained faintly. Pre-incubation with dimedone to block aldehyde groups did not affect the staining. However, when periodic acid treatment was omitted, or when sections were incubated with dimedone both before and after periodate oxidation, only melanin granules and the cytoplasm of fibroblasts were stained.Thus, anchoring fibrils are rich in carbohydrates containing 1,2-glycol groups susceptible to periodate oxidation, and correspond to the periodic acid Schiff-positive layer seen at the dermo-epidermal junction. Furthermore, the basement membrane zones of dermal blood vessels and the dermo-epidermal junction differ in their carbohydrate distribution.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0014-4827
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Die Wirkung von Kaninchen-anti-Maus-Lymphozytenserum auf das Wachstum von Tumorallotransplantaten kann in kleineren Tiergruppen leicht bestimmt werden, indem man das immunosuppressive Potential verschiedener Serumsätze prüft. Ein gutes Verhältnis zwischen dem durchschnittlichen Durchmesser von Tumortransplantaten am 14. Tag nach dem Implantat und die entsprechende, durchschnittliche, prozentuale Zunahme der Überlebenszeit der Hauttransplantate wird demonstriert.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Microwave irradiation of EAT cells caused an increase in length and number of surface microvilli. The tumor cells tend to form large aggregates by means of extensive interdigitation of surface microvilli. On the other hand, heat hyperthermia caused a decrease of surface microvilli but an increase of surface blebs. Hence the surface morphology of EAT cells after in vitro exposure to microwave irradiation differs markedly from that after heat hyperthermia.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pest science 34 (1961), S. 192-192 
    ISSN: 1612-4766
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Type of Medium: Electronic Resource
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