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1.
A nonionic RNA analogue of the sequence r(USO2GSO2ASO2C) has been synthesized where each bridging phosphate diester is replaced by a dimethylene sulfone unit (rSNA). The rSNA was synthesized in solution from 3',5'-bishomo-beta-ribonucleoside derivatives as building blocks. Full experimental procedures are provided, and the product and all synthetic intermediates are fully characterized. The tetramer is nonionic but highly dipolar due to multiple hydrogen bonding opportunities. It is freely soluble in water only at higher pH's, permitting it to be radiolabeled by exchange of the acidic protons alpha to the sulfones with tritiated water. The tritiated molecule was administered intravenously into the tail vein (2.6 mg/kg) of mice, and its distribution was monitored over 48 h. The rSNA was widely distributed in the biological tissues, including the brain, and excreted in both the feces and the urine. The accumulation of radioactivity was significantly higher in liver and kidney than in other tissues. Radiolabel was recovered from the urine, analyzed by HPLC, and shown to be intact oligonucleotide sulfone. This is the first bioavailability study on a short nonionic oligonucleotide analogue, a class of molecules with potential biomedical applications.  相似文献   

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Relatively little is known about the effects of chronic transection on human peripheral nerves. In this study intraoperative biopsies were obtained from proximal and distal nerve stumps and intervening neuromas resected before peripheral nerve reconstruction. Biopsies were collected from ten patients following differing types of nerve injury, with delays to repair ranging from 8 to 53 months. Nerves were examined by light and electron microscopy. In general, reinnervation was poor, although even following the most severe injuries, all of the distal stumps contained some regrowing axons, which were always associated with Schwann cells. Denervated Schwann cells, arranged in typical bands of Büngner were consistently present in each distal stump. Our findings confirm that the morphology of chronically denervated human peripheral nerves is essentially similar to that described in experimental models.  相似文献   

4.
A serological survey detected antibodies against Babesia ovis in mouflon sheep (Ovis musimon) from two different reserves located in Catalonia in northeastern Spain. An indirect fluorescent antibody test (IFAT) was developed using a B. ovis isolate of ovine origin as the antigen. Of 50 sera tested, six (12%) showed titres between 1:160 and 1:640 and were considered positive. These results indicate that exposure of mouflon to Babesia ovis is common in this region.  相似文献   

5.
This paper describes the detection of 13 lymphocyte antigens in sheep. The results obtained from family studies are consistent with the hypothesis that at least 12 antigens are under the control of a single genetic system. The distribution of antigens in the population suggests that the system contains two loci. The 13 antigens were compared with those previously reported. Only one additional specificity was found.  相似文献   

6.
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) can be used to determine number- and weight-average molecular weights of narrow polydispersity polymers. In this work, several possible sources of error in determining molecular weights of polymers with narrow polydispersity by MALDI-TOFMS are rigorously examined. These include the change in polymer distribution function, broadening or narrowing of the overall distribution, and the truncation of selected oligomer peaks within a distribution (i.e., the oligomer peaks at the high- and low-mass tails expected to be observed are not detected). These variations could be brought about by a limited detection sensitivity, background interference, and/or mass discrimination of oligomer analysis in MALDI-TOFMS. For narrow polydispersity polystyrenes, it is shown that by using an appropriate MALDI matrix and sample preparation protocol and a sensitive ion detection instrument, no systematic errors from these possible variations were detected within the experimental precision (0.5% relative standard deviation) of the MALDI method. It is concluded that MALDI mass spectrometry can provide accurate molecular weight and molecular weight distribution information for narrow polydispersity polymers, at least for polystyrenes examined in this work. The implications of this finding for polymer analysis are discussed.  相似文献   

7.
Oestrus ovis is a very common parasite of sheep and goats in many countries. Its pathological effects are often underestimated because owners and veterinarians are used to seeing the infection. The study of natural and experimental infections has provided information about the evolution of the disease and its pathophysiology. Hypersensitivity is involved; the numbers of mast cells and eosinophils increase but changes in IgE have only recently been examined. Little is known about the development of immunity but it is possible that some animals are immunodeficient.  相似文献   

8.
The immunological response of lambs to Brucella ovis before and after birth was investigated. The establishment of indwelling cannulas in the efferent prescapular lymphatic ducts of foetal lambs allowed continual monitoring of the immune response of a single lymph node. Foetal lambs in the last trimester of pregnancy were shown to mount a strong cell-mediated immune response to B. ovis. Lymphocytes from the challenged lymph node stimulated with B. ovis in vitro usually first reacted significantly and had highest [3H]-thymidine incorporation between 4 and 6 days after primary and secondary challenge, whereas, lymphocytes from the unchallenged node did not exhibit significant [3H]-thymidine incorporation until some 24 h later. Lymphocytes from these lambs challenged as foetuses still exhibited significant [3H]-thymidine incorporation in response to B. ovis for 4 to 5 months after birth. The proportion of surface immunoglobulin-positive cells in efferent prescapular lymph of unchallenged lambs ranged from 0.5 to 2.0% but after B. ovis challenge this proportion ranged from 2.7 to 8.7% between 4 to 6 days after challenge. By 9 to 12 days after challenge, the proportion had declined to pre-challenge values.  相似文献   

9.
Clinical, clinico-pathological and serological studies were performed in sheep experimentally infected with Babesia ovis. Acute babesiosis occurred in all the lambs infested with adult Rhipicephalus bursa ticks and in one lamb infested with the larvae. The rate of parasitaemia and the degree of anaemia were not correlated. Decrease in the packed-cell volume ranged from 30 to 40%. Parasitized erythrocytes were not observed to block capillaries in the brain, which explained the absence of nervous symptoms in acute babesiosis. The kidneys were the most severely affected organs, exhibiting acute glomerulonephritis. The lesions observed were suggestive of vascular alteration and vascular stasis, leading to anoxia of the tissues. A disseminated intravascular coagulation (DIC) syndrome was recorded in sheep infected with babesiosis. A marked increase in the enzymes of the transaminase groups, mainly aspartate aminotransferase (AST), was observed. Enzymatic changes (increases in AST, alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) and decreases in sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP) and malic enzyme (MEZ)), decreases in total proteins and albumin, and increases in urea and creatinine might reflect the degree of severity of the damage to the liver and kidney tissues. Most of the lambs (85%) that were infested with larvae, and all lambs infested with adult R. bursa ticks, reacted serologically to B. ovis antigen. The serological reactions following infestation with the larvae occurred much later than those following infestation with the adult stage. The lambs which were infested with larvae showed mild clinical reactions when challenged by infected R. bursa adults, as compared with the reactions to the challenge in naive control animals. The serological findings, in addition to the fact that one splenectomized lamb reacted to larval infestation with acute ovine babesiosis, show that the preimaginal stages of R. bursa can transmit B. ovis, usually causing a sub-clinical disease. It is suggested that infections derived from preimaginal ticks in the winter can preimmunize sheep for the subsequent more severe infections derived from adult ticks in the summer. Furthermore, in the absence of a reliable vaccine against B. ovis, grazing flocks in the enzootic regions should be exposed to the preimaginal stages during their activity period (October-February) before exposure to the adult ticks in spring and summer (April-July).  相似文献   

10.
The antibody responses to experimental Nairobi sheep disease vaccines have been assayed. The responses to an inactivated methanol precipitated vaccine were comperable with those following infection with virulent virus. The responses to attenuated vaccines were inadequate to protect against challenge with virulent virus.  相似文献   

11.
The aim of the present study was to validate an in vitro assay for quantifying resistant starch (RS) in foods against an in vivo model. The amount of starch escaping digestion in the small intestine of ileostomates was compared with that observed by using the in vitro assay. Subjects with ileostomies were fed five foods containing different types and amounts of RS (baked beans, pearl barley, cornflakes, and whole and ground rice). The total amount of starch escaping digestion and recovered in the effluent (ranging from 5.7% in baked beans to 0.7% in ground rice) was compared with results obtained by using the in vitro assay with an incubation time of 6 h. The assay was found to be a good qualitative predictor (r = 0.90, P < 0.05), but a poor quantitative predictor of RS amounts. Increasing the duration of incubation with alpha-amylase and amyloglucosidase to 15 h resulted in a very close agreement between results from the in vitro technique and the in vivo model. These data indicate that for a variety of foods the in vitro assay produced an excellent estimate of starch escaping digestion in the small intestine of humans.  相似文献   

12.
The efficacy of ivermectin administered orally at a dosage rate of 0.2 mg/kg liveweight against naturally acquired larval infestations of Oestrus ovis in sheep was 100% in a field trial. Ten sheep were free from infestation by first, second and third instar larvae of O. ovis 12 days post treatment, whereas 10 control sheep harboured 37.7 larvae on average, most of them first stage.  相似文献   

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OBJECTIVE: This article reports the results of segmental reversal of the small bowel on parenteral nutrition dependency in patients with very short bowel syndrome. SUMMARY BACKGROUND DATA: Segmental reversal of the small bowel could be seen as an acceptable alternative to intestinal transplantation in patients with very short bowel syndrome deemed to be dependent on home parenteral nutrition. METHODS: Eight patients with short bowel syndrome underwent, at the time of intestinal continuity restoration, a segmental reversal of the distal (n = 7) or proximal (n = 1) small bowel. The median length of the remnant small bowel was 40 cm (range, 25 to 70 cm), including a median length of reversed segment of 12 cm (range, 8 to 15 cm). Five patients presented with jejunotransverse anastomosis, and one each with jejunorectal, jejuno left colonic, or jejunocaecal anastomosis with left colostomy. RESULTS: There were no postoperative deaths. Three patients were reoperated early for wound dehiscence, acute cholecystitis, and sepsis of unknown origin. Three patients experienced transient intestinal obstruction, which was treated conservatively. Median follow-up was 35 months (range, 2 to 108 months). One patient died of pulmonary embolism 7 months postoperatively. By the end of follow-up, three patients were on 100% oral nutrition, one had fluid and electrolyte infusions only, and, in the four other patients, parenteral nutrition regimen was reduced to four (range of 3 to 5) cyclic nocturnal infusions per week. Parenteral nutrition cessation was obtained in 3 of 5 patients at 1 years and in 3 of 3 patients at 4 years. CONCLUSION: Segmental reversal of the small bowel could be proposed as an alternative to intestinal transplantation in patients with short bowel syndrome before the possible occurrence of parenteral nutrition-related complications, because weaning for parenteral nutrition (four patients) or reduction of the frequency of infusions (four patients) was observed in the current study.  相似文献   

15.
Cattle, sheep and rats were infected orally with gamma-irradiated (4 krad) metacercariae of fasciola hepatica, or with normal metacercariae. The antibody response was monitored in each host to metacercarial tegument (T0), juvenile tegument (T1), adult tegument (T2) and gut antigens. The response was examined at weekly intervals for cattle and sheep throughout 15 weeks of infection and four weeks after infection in rats, using an indirect fluorescent antibody labelling technique. It was found that the irradiated metacercariae engendered a normal humoral response to T0, T1 and gut antigens in all three hosts although the antibody levels were somewhat reduced due to an early death or stunting of the flukes. T0 and T1 appeared to be antigenically similar. Antibodies against T2 appeared late in the animals infected with gamma-irradiated metacercariae and the titres attained were considerably lower than in the controls. the T2 antigen stimulus in the animals given gamma-irradiated metacercariae was probably provided by flukes which 'broke through' the developmental barrier imposed by irradiation and which were found alive at autopsy.  相似文献   

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1. The dermal wheal response to bradykinin is increased by drugs which inhibit angiotensin-converting enzyme, and thus provides a measure of angiotensin-converting enzyme activity at the tissue level. An insertion/deletion polymorphism of the angiotensin-converting enzyme gene predicts serum angiotensin-converting enzyme activity, but its relation to angiotensin-converting enzyme activity in tissue is unclear. 2. The relations between angiotensin-converting enzyme genotype and wheal responses to intradermal bradykinin were studied in 105 healthy subjects: 30 of genotype DD, 51 of genotype ID and 24 of genotype II. Dermal wheal area was measured by digitized planimetry and the angiotensin-converting enzyme genotype by polymerase chain reaction. 3. Bradykinin produced significant linear log dose-wheal area responses. The potency of bradykinin by parallel line bioassay did not differ significantly between the genotypes; the potency in the II subjects relative to DD subjects was 1.25 (95% confidence interval: 0.83-1.88). 4. Although the angiotensin-converting enzyme gene polymorphism is a consistent and powerful predictor of serum angiotensin-converting enzyme activity, it does not appear to predict tissue angiotensin-converting enzyme activity as measured by dermal responses to bradykinin.  相似文献   

18.
The characterization of T cell reactivities that are prone to down-modulation by filarial parasites is central to understanding how these nematodes can survive for long periods of time within their human host and to design appropriate immunoprophylactic measures. In the present study, TCRBV gene usage was analyzed in response to filarial antigens by PCR using a panel of TCRBV gene segment family-specific oligonucleotide primers. Analysis of individuals highly responsive to Brugia malayi adult worm antigen (BmA) (n = 4) indicated that following stimulation with BmA a maximum of four TCRBV gene families were over-represented in each subject. Those were TCRBV2, 9, 19 and 23 in subject 1; TCRBV8, 9 and 16 in subject 2; TCRBV2, 8, 9 and 11 in subject 3; and TCRBV13 and 23 in subject 4. The analysis of one subject who was unresponsive to BmA before but regained responsiveness after diethylcarbamazine treatment revealed that there was no overexpression of a particular TCRBV gene family before chemotherapy, whereas after chemotherapy three TCRBV gene families (TCRBV8, 16 and 19) were found to be overexpressed. Complementarity determining region 3 size analysis of a selection of the overexpressed TCRBV genes displayed oligoclonality in some of the observed expansions. Together these observations show that limited T cell subpopulations are clonally amplified in BmA-stimulated peripheral blood mononuclear cells of filarial responder subjects, possibly driven by a restricted number of antigens.  相似文献   

19.
Endogenous allantoin derives from the breakdown of tissue nucleic acids. This study examined the effect of changes in protein supply on endogenous allantoin excretion by sheep. The animals were nourished by infusions of volatile fatty acids into the rumen and casein into the abomasum, thus avoiding ruminal microbial fermentation (i.e., no supply of exogenous nucleic acids). While a constant energy supply was maintained, the protein supply was altered in one of two ways: 1) changed from 0 to 3000 mg casein-N/kg metabolic weight (W0.75) per day in progressive steps; or 2) completely removed from an initial constant level [500 mg N/(kg W0.75.d)]. With the first alteration, endogenous allantoin excretion was not directly affected by the daily N input or N retention, but was linearly correlated with the cumulative N retention. With the second alteration, allantoin excretion increased (35-145%) on the first day after removal of the protein supply and then fell to a level equivalent to, or lower than, that before protein removal. The results suggest that the changes in endogenous allantoin excretion may reflect remodeling of the metabolic state of the animal during periods when protein supply fluctuates.  相似文献   

20.
A mycobacterial etiology has been proposed in Crohn's disease (CD). We have sought evidence of increased or modified T lymphocyte immune responses to Mycobacterium tuberculosis and Myco, paratuberculosis in patients with CD (n = 13), compared with ulcerative colitis (UC; n = 17) and controls (n = 17). Peripheral blood cells were cultured with phytohaemagglutinin (positive mitogen control), mycobacterial purified protein derivative (PPD) preparations, lysates, column fractions and whole, heat-killed bacteria. Responses of T cells and T cell subsets were assessed by expression of activation markers (CD25, CD69), coupled with blastogenesis assays (3H-thymidine uptake) and estimates of proliferation. Virtually all patients responded to Myco. paratuberculosis and Myco. tuberculosis antigens. There were no significant differences between patient groups, although there was a very high overall correlation (r = 0.95; P < 0.0001) between responses to the two mycobacterial species. Most of the activation and proliferative responses resided in the CD4+ (T helper) subset. Although up to 15% of CD8+ (suppressor/cytotoxic) cells also became activated, the CD8+ cells did not proliferate subsequently. Cells expressing the alternate gamma delta form of the T cell receptor (TCR gamma delta+) did not activate or proliferate in response to mycobacterial antigens. There were no differences in any of these parameters between patient groups. We conclude that there is no specific increase or alteration in cell-mediated anti-mycobacterial immunity in inflammatory bowel disease (IBD). Thus our data do not support a mycobacterial etiopathology of Crohn's disease.  相似文献   

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