Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreaticoduodenal (PD) allografts (Brown Norway-alloxan-diabetic rats, n = 190) were treated with cyclosporin A (Cy-A) 10 mg/kg/daily and compared with nondiabetics with Cy-A treatment (n = 55), diabetics (n = 50), and diabetics with Cy-A treatment (n = 45). Body weight, blood sugar, blood insulin, blood urea nitrogen (BUN), and creatinine were monitored periodically; there were marked elevations of BUN and creatinine levels, indicating probably nephrotoxicity of Cy-A at this dosage. Some islet cell atrophy in the PD allografts was noted at the conclusion of the study. With respect to the immunosuppressive effect of Cy-A in alloxan diabetic rats, Brown Norway PD transplants into Lewis rats were successful and free of rejection for as long as 15 months post-transplantation. The body weight of these PD transplanted rats, however, never approached values representative of the nondiabetic rats. In our experience, the PD allograft model is acceptable in the clinical situation, particularly in children if the microsurgical technique is mastered and if the Cy-A regimen is used in combination with other immunosuppressant(s).
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PMID:Long-term studies of pancreas allotransplantation in experimental diabetes mellitus. 305 15

Nephrotoxicity has limited the effectiveness of cyclosporine in transplantation therapy and has precipitated the need to develop a new immunosuppressive agent that lacks this nephrotoxicity or has a higher therapeutic index. Prior studies have suggested that cyclosporin G may be equally effective immunosuppressively, but less nephrotoxic than cyclosporine. To compare the immunosuppressive effects of the two agents, graft survival was analyzed in Lewis-Brown Norway rats, which received heterotopic ACl heart allografts and were treated orally with cyclosporin G or cyclosporine at 5 and 10 mg/kg/day. To compare nephrotoxicity the group of rats that had transplantations and an additional group of surgically intact Lewis-Brown Norway rats, treated orally with cyclosporin G or cyclosporine at dosages ranging from 10 to 50 mg/kg/day and for durations ranging from 50 to 180 days, were analyzed in terms of kidney morphology (fibrosis, glomerular damage, interstitial infiltrate, and tubular dilation) and kidney function (blood urea nitrogen and serum creatinine levels) in this model cyclosporin G was significantly less effective than cyclosporine in prolonging graft survival at 5 mg/kg/day but equally effective at 10 mg/kg/day. In addition, cyclosporin G was substantially less nephrotoxic both morphologically and functionally at low (10 mg/kg/day) and high (50 mg/kg/day) dosages. Further studies are indicated to determine the therapeutic index of cyclosporin G and to evaluate its use in combination with other immunosuppressive agents.
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PMID:Analysis of the immunosuppressive and nephrotoxic effects of cyclosporin G. 328 81

Results of extended x-ray absorption fine structure (EXAFS) studies of the iron atom in deoxygenated hemoglobin are reviewed. It is shown that the iron-porphinato nitrogen distance has been determined to be 2.06 +/- 0.01 A by two independent investigations [Eisenberger, P.M., Shulman, R.G., Kincaid, B. M., Brown, G. S. & Ogawa, S. (1978) Nature (London) 274, 30-34 and Perutz, M.F., Hasnain, S.S., Duke, P.J., Sessler, J.L. & Hahn, J.E. (1982) Nature (London) 295, 535-538]. Difficulties experienced by Perutz et al. in using this distance to calculate the iron's distance above the plane by triangulation are shown to be due to ignoring differences between ferrous and ferric hemes. It is concluded that the iron is 0.2 +/- 0.1 0.2 A above the plane of the nitrogens as originally shown by Eisenberger et al.
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PMID:On extended x-ray absorption fine structure studies of hemoglobin. 346 53

The effects of helium pressure and of general anaesthetics were studied on the responses of the isolated superior cervical ganglion of the rat, to determine how far these reflected the pressure reversal of anaesthesia seen in vivo. The method of Brown & Marsh (1974) for extracellular recording of surface potentials was adapted for use in a high-pressure chamber. Helium alone, at 130 atm, did not alter the responses of the ganglion to gamma-aminobutyric acid (GABA) but significantly depressed the depolarizing and hyperpolarizing components of the nicotinic responses, and the muscarinic responses. The potentiation of the responses to GABA caused by pentobarbitone was not altered by the application of helium, at 130 atm. This pressure also decreased further the nicotinic responses which were depressed by pentobarbitone. Nitrogen, at 34 atm (the anaesthetic ED50 in vivo) and at 68 atm, significantly decreased the nicotinic responses of the ganglia, and the addition of helium to a total of 130 atm further increased this depression. At pressures of 3.3-68 atm, nitrogen caused small decreases in the responses to GABA. Nitrous oxide at 1.5 atm (the ED50 for loss of righting reflex in mice) and at 3 atm, significantly depressed the responses to GABA and to the nicotinic agonist, but did not alter the responses to methylfurmethide. The effects of nitrous oxide were unaltered when helium was added to a total of 130 atm, although this pressure of helium added alone significantly depressed the cholinergic responses. A mixture of 50% nitrous oxide and 50% oxygen, when added to the pressure chamber, at normal atmospheric pressure, caused transient increases in the responses to GABA. The effects of temperature on GABA responses and on nicotinic responses were very different from those of pressure. Preliminary evidence suggested that raising the temperature may decrease the extent of potentiation of GABA responses by pentobarbitone. The results are discussed in relation to the pressure reversal of anaesthesia in vivo. It was concluded that there was no evidence that the basis of this interaction lay in the potentiation of GABA responses by general anaesthetics, or the depression of cholinergic responses, although the changes seen were not in all cases simply additive. It was considered that effects of general anaesthetics such as the potentiation of GABA may contribute to the effects used to measure general anaesthesia in vivo, such as loss of righting reflex, but may not be related to the non-specific actions which cause anaesthesia.
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PMID:The effects of anaesthetics and high pressure on the responses of the rat superior cervical ganglion in vitro. 374 96

Rat renal allograft survival was enhanced by active immunization with donor strain RT1.B (Ia) antigens. Lewis (LEW) rats (16) were immunized with Brown Norway (BN) lymphocyte extracts containing RT1.B, but not RT1.A antigens, prior to receiving (LEW X BN)F1 renal allografts. Group 1 (8 rats) was immunized with lymphocyte membrane fragments group 2(8 rats) was primed with lymphocyte supernatant extract. Longterm survivors (greater than 60 days; 12 animals) had a mean blood urea nitrogen of 75 +/- 31 mg% and serum creatinine of 2.0 +/- 0.8 mg% at one month. Death occurred in 90% of control allograft recipients within 10 days. Anti-BN RT1.B but not RT1.A antibodies were detected in sera from actively enhanced rats following immunization and at day 7 posttransplantation. We conclude that preimmunization with cell extracts containing donor RT1.B antigens has a protective effect on the allograft, and that the phenomenon of active immunologic enhancement can be produced without immunization to RT1.A antigens.
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PMID:Long-term renal allograft survival in rats preimmunized with donor strain RT1.B antigens. 622 Apr 93

Studies of teratogenic steroidal alkaloids from Veratrum and Solanum have shown that those bearing a basic nitrogen atom in ring F, shared or unshared with ring E, with bonding capabilities alpha to the steroid plane may be suspect as teratogens. Examples of steroidal alkaloids which produce terata but, until recently, have been of uncertain structure include muldamine and the isomeric 3, N-diformylsolasodines. The correlation of their structures with the structure-terata relationship developed by Keeler and Brown is discussed. A brief introduction to teratogenicity is presented.
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PMID:Structure and stereochemistry of steroidal amine teratogens. 638 62

Six recessive second chromosomal mutants of Drosophila melanogaster exhibiting larval hypersensitivity to methyl methanesulfonate have been identified and assigned to six complementation groups. The strains have been analyzed for their sensitivities to UV, X-ray, nitrogen mustard and formaldehyde. Two classes of mutants not previously observed in Drosophila have been identified. The mus 204A1 and mus 205A1 mutants exhibit sensitivity to MMS and UV but not X-ray or nitrogen mustard, while the mus 206A1 and mus 207A1 mutants display sensitivity to MMS, UV, and nitrogen mustard. Four of the seven strains exhibit poor female fertility and two of these are shown to have a weak meiotic disjunctional defect. Biochemical studies of the mus 205A1 mutant suggest a defect in DNA synthetic ability associated with excision and postreplication repair performed on UV and alkylation-damaged templates (Boyd and Harris 1981; Brown and Boyd 1981 b; R.L. Dusenbery, manuscript in preparation).
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PMID:Mutagen sensitivity of Drosophila melanogaster. V. Identification of second chromosomal mutagen sensitive strains. 681 27

Studies were carried out on the chemical composition of the muscles/m. gracilis, m. longissimus dorsi, caput longum of m. triceps brachii, as well as the muscles of the neck between the 5th and 7th neck vertebrae and livers from 16 spontaneously ill with osteoarthrosis degenerative calves, meant for fattening, of the breed "Bulgarian Brown Cattle." The studies were carried out with regard to the contents of general, extractive and protein nitrogen, ashes, as well as the quantity of the aminoacids tryptophan and hydroxyproline. The contents of adequate and inadequate proteins was determined, as well as the relative nourishing value of the proteins from the samples under investigation. A tendency was accounted for towards a reduction of the nourishing quantitites of the samples studied, taken from the sick calves, as compared with the data about the healthy animals, but this tendency was very slightly pronounced and in most cases was statistically ensured (P greater than 0.05).
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PMID:[Chemical makeup of the musculature and liver of fattening calves having degenerative osteoarthrosis]. 721 Apr 92

Lewis rat recipients of long-term, surviving, orthotopic Brown-Norway rat intestinal allografts, initially treated with cyclosporin A (CyA) or FK 506, were evaluated for their functional capacity and morphology over 1 year after the immunosuppressive therapy had been discontinued. Functional parameters such as nitrogen and fat balances, maltose absorption, blood chemistry, hematologic studies, and the weight gained by the allografted animals did not differ from those of syngeneically grafted or age-matched normal animals. Immunohistochemical studies showed that the lamina propria of the allografts was repopulated with recipient MHC class II+ mononuclear cells and that a normal distribution of T helper, T suppressor/killer, and IgA+ plasma cells had occurred. However, fibrous replacement of the mesenteric lymph nodes and Peyer's patches were detected in all, and an inflammatory obliterative arteriolopathy developed in the mesenteric vasculature of half of the allografted animals. No such findings were observed in recipients of syngeneic grafts. These results demonstrate that the limited use of potent immunosuppressive agents immediately after transplantation averts rejection and is followed by recipient-type mucosal lymphocytic repopulation. Simultaneously, a clinically not recognizable chronic rejection evolves. This suggests that the timely diagnosis of chronic rejection may not be possible with the use of standard tests of gut function and random mucosal biopsies alone.
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PMID:Mucosal recipient-type mononuclear repopulation and low-grade chronic rejection occur simultaneously in indefinitely surviving recipients of small bowel allografts. 751 99

It has recently been shown in several species that lung tissue resistance increases after administration of exogenous bronchoconstrictors. This finding suggests the possibility that lung parenchymal tissues could be involved in the pathophysiology of pulmonary allergic responses. To test this hypothesis, we sensitized Brown Norway rats with ovalbumin (OA) and performed experiments in anesthetized, open-chested, mechanically ventilated (respiratory frequency [f] = 1 Hz, tidal volume [VT] = 9 ml/kg, positive end-expiratory pressure [PEEP] = 3 cm H2O) animals. We affixed alveolar capsules to the lungs to measure alveolar pressure and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) under control conditions and after aerosol administration of saline (S) (n = 10) or OA (n = 14). To assess lung morphometry during the late response, the lungs of six S and six OA animals were frozen with liquid nitrogen (PEEP = 3 cm H2O) and processed via freeze substitution. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed airway (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), an atelectasis index (ATI) derived by calculating the ratio of tissue/airspace, and the standard deviation (SD) of Lm and ATI. In the OA group, all animals demonstrated an early response (ER; RL, Rti, Raw = 183.5 +/- 7.7, 159.7 +/- 9.9, 232.5 +/- 17.2% baseline, respectively) and 11 animals showed a late response (LR; RL, Rti, Raw = 178.9 +/- 5.1, 191.3 +/- 11.5, 176.6 +/- 17.3% baseline, respectively). Neither ER nor LR were observed in the saline group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Airway and tissue responses to antigen challenge in sensitized brown Norway rats. 802 52


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