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41.
In a series of recent studies on 'lethargic' mice, a neurological mutation of the mouse, significant abnormalities were discovered in the thymus and its dependent regions in the lymph nodes and spleen. The present study was made as an approach toward finding the possible causes for these abnormalities. Serum IgG1 levels were stldied in 'lethargic' mutants at the age when severe deficiency of the thymus-dependent lymphoid system is known to occur in the animal. Using the radial immunodiffusion method, it was found that serum IgG1 levels are always significantly higher in 'lethargic' mice than in their normal littermates. Possible causes of the higher IgG1 in the serum of 'lethargic' mice are discussed. The authors note the similarities of other mouse mutations to that of the 'lethargic' mouse and propose the possibility that a common mechanism may account for immunologic deficiencies in several types of mutant mice. 相似文献
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Dudal S Krzywkowski P Paquette J Morissette C Lacombe D Tremblay P Gervais F 《Neurobiology of aging》2004,25(7):861-871
Alzheimer's disease (AD) is characterized by a progressive cognitive decline leading to dementia and involves the deposition of amyloid-beta (Abeta) peptides into senile plaques. Other neuropathological features that accompany progression of the disease include a decrease in synaptic density, neurofibrillary tangles, dystrophic neurites, inflammation, and neuronal cell loss. In this study, we report the early kinetics of brain amyloid deposition and its associated inflammation in an early onset transgenic mouse model of AD (TgCRND8) harboring the human amyloid precursor protein gene with the Indiana and Swedish mutations. Both diffuse and compact plaques were detected as early as 9-10 weeks of age. Abeta-immunoreactive (Abeta-IR) plaques (4G8-positive) appeared first in the neocortex and amygdala, then in the hippocampal formation, and lastly in the thalamus. Compact plaques (ThioS-positive) with an amyloid core were observed as early as diffuse plaques were detected, but in lower numbers. Amyloid deposition increased progressively with age. The formation of plaques was concurrent with the appearance of activated microglial cells and shortly followed by the clustering of activated astrocytes around plaques at 13-14 weeks of age. This TgCRND8 mouse model allows for a rapid, time-dependent study of the relationship between the fibrillogenic process and the inflammatory response during the brain amyloidogenic process. 相似文献
44.
Brian R Lawson Stanley M Belkowski John F Whitesides Paul Davis John W Lawson 《BMC complementary and alternative medicine》2007,7(1):20
Background
Rheumatoid arthritis (RA) and its accepted animal model, murine collagen-induced arthritis (CIA), are classic autoimmune inflammatory diseases which require proinflammatory cytokine production for pathogenesis. We and others have previously used N, N-dimethylglycine (DMG) and extracts from the New Zealand green-lipped mussel Perna canaliculus (Perna) as potent immunomodulators to modify ongoing immune and/or inflammatory responses. 相似文献45.
46.
Dean E. Brenner Sherri Galloway John Cooper Richard Noone Kenneth R. Hande 《Cancer chemotherapy and pharmacology》1985,14(2):139-145
Summary We compared doxorubicin and metabolite pharmacokinetic data obtained from thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) assay of plasma samples from six patients who had been treated with doxorubicin. Duplicate 1-ml samples were extracted with chloroform: isopropanol (1:1) and assayed using a sensitive HPLC system incorporating a dual pump gradient with tetrahydrofuran as the mobile phase and fluorescence detection. Duplicate 1-ml samples from the same specimens were assayed using a modification of a previously described TLC assay. Areas under the curve for doxorubicin by HPLC (3.36±2.30 M · h) and TLC (4.16±2.50 M · h) were not significantly different (P=0.5). Terminal half-life of doxorubicin by HPLC (28.0±6.98 h) and TLC (23.2±7.8) (P=0.29) and the calculated total-body clearances by HPLC (0.55±0.29 l/min) and TLC (0.45±0.23) (P=0.55) were not significantly different. Areas under the curve for doxorubicinol by HPLC (2.75±1.4 M · h) and TLC (2.53±7.1 M · h) (P=0.73) showed no significant differences. HPLC detected a mixed 7-deoxydoxorubicinol aglycone-doxorubicin aglycone peak, 7-deoxydoxorubicin aglycone, and two nonpolar, unidentified metabolites. TLC detected the following aglycone metabolites: doxorubicin aglycone, doxorubicinol aglycone, 7-deoxydoxorubicinol aglycone, an unidentified polar metabolite, and several unidentified nonpolar metabolites. From these data we conclude that HPLC and TLC detect concentrations of doxorubicin and doxorubicinol from human plasma equally well to concentrations of 7.0 nM (4 pmol injected doxorubicin). Aglycones do circulate in human plasma at concentrations above the detection limits of both assays. Doxorubicinol aglycone, which is detected by TLC but not by HPLC, may be formed from artifactual breakdown of doxorubicinol during TLC development. Unidentified nonpolar compounds seen on HPLC and TLC may represent further doxorubicin metabolism than previously described. 相似文献
47.
Rats were trained to press a bar for sucrose reward on a random-interval (RI) schedule and footshock punishment was then introduced for 3-min intrusion periods (signalled by a tone) on an independent RI schedule. Shock intensity was individually adjusted to produce stable intermediate levels of response suppression during the tone for each animal. Groups of animals were then allocated to a number of separate experiments in which they were systemically injected with anxiolytics (chlordiazepoxide HCl or sodium amylobarbitone), GABA antagonists (picrotoxin or bicuculline), the GABAA agonist muscimol, the GABAB agonist baclofen, an antagonist (RO 15-1788) at the benzodiazepine receptor and, an inverse agonist (FG 7142) at this receptor. The results showed that the alleviation of punishment-induced suppression of barpressing produced by chlordiazepoxide was blocked or partially blocked by RO 15-1788, picrotoxin and bicuculline but not by FG 7142; that picrotoxin (but not FG 7142) increased the suppression of responding by punishment; that neither muscimol nor baclofen affected responding on their own, but their combination weakly but reliably released punished responding from suppression; and that the anti-punishment effect of amylobarbitone was unaffected by either picrotoxin or bicuculline, though the barbiturate reversed the punishment-enhancing effect of picrotoxin. These results are discussed in the light of the hypothesis that anxiolytic behavioural effects are due to increased GABAergic inhibition. 相似文献
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Graham C. Smith Michael H. Winterborn Christopher M. Taylor Nigel Lawson Mark Guy 《Pediatric nephrology (Berlin, Germany)》1994,8(2):148-150
Retinol-binding protein (RBP) is a low molecular weight protein freely filtered at the glomerulus. The fractional tubular reabsorption of RBP is 99.97% and increased excretion is therefore a sensitive marker of tubular dysfunction. We obtained early-morning urine specimens from 151 well children, from newborn to 16 years of age. RBP was measured using an enzyme-linked immunosorbent assay, albumin by a radioimmunoassay and creatinine by a modified Jaffé reaction. Protein excretion was assessed by calculating the protein: creatinine ratio for early-morning urine samples. We found a fall in both RBP and albumin excretion with increasing age, particularly in the 1st year of life, with a much wider variation in values from the infants studied. The mean excretion of RBP for children aged 0–6 months [51.4 (0.6–4,719) g/mmol] was significantly higher (P<0.001) than the mean for children aged 6 months to 16-years [15.0 (3.8–60) g/mmol]. It has been shown that measurement of tubular proteinuria using the RBP: creatinine ratio is useful in the assessment of children with renal disease and we propose a value two standard deviations above the geometric mean for the age of the patient as an upper limit of normal. 相似文献