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

Hemorrhagic diathesis was observed in patients with renal insufficiency after carbenicillin at serum levels greater than 300 mug/ml. Normal coagulation factors (F. I, II, V, VII, VIII, X), normal PTT, normal platelet counts, negative ethanol gelation test (fibrin monomers) were found as well as a prolongation of thromboplastin time (Quick), thrombin time, reptilase time and thrombin coagulase time. Platelet function was disturbed. In addition, the plasmatic system was involved: inhibition of fibrinogen-fibrin conversion (Belitser assay) and enhanced antithrombin III activity; in vivo the latter was ascribed to a heparin-like activity. In vitro, abnormal III was seen: however an enhanced antithrombin III activity in vitro was not found with carbenicillin and various penicillin derivatives. This study demonstrates that carbenicillin, in addition to its known effect on platelet function, also disturbs the plasmatic coagulation system. This additional effect of carbenicillin is clinically important since protamin chloride effectively blocks bleeding without interfering with antibacterial activity. Both penicillin and penicillin derivatives have been shown to interfere with hemostasis and to cause clinically manifest hemorrhagic diathesis (Fleming and Fish 1947, Lurie et al. 1970a, b, McClure et al. 1970, Yudis et al. 1972, Demos 1971, Waisbren et al. 1971). Carbenicillin interferes with ADP-, collagen- or thrombin-induced platelet aggregation and with the release reaction both in vivo (McClure et al. 1970, Cazenae et al. 1973) and in vitro (McClure et al. 1970, Cazenave et al. 1973). In addition Lurie and colleagues (1970b) concluded that an inhibition of the conversion of fibrinogen to fibrin is involved although no experimental details were given. Later Brown and colleagues (1974) concluded that carbenicillin at usual dose levels "only affects the platelet component of hemostasis and has little effect on fibrin formation or other phases of coagulation in patients with normal renal function".
 ...
PMID:Bleeding in uremic patients after carbenicillin. 103

The target antigen, a 54-kD glycoprotein (gp54), reactive with sera from patients with anti-tubular basement membrane (anti-TBM) nephritis, was isolated from collagenase-digested (CD) bovine TBM. The purified gp54 was shown to be non-collagenous by amino acid analysis, and to be a unique basement membrane component by amino-terminal sequencing. The nephritogenicity of gp54 was demonstrated by immunizing strain XIII guineapigs with purified gp54, and producing anti-gp54 antibody and tubulo-interstitial nephritis. Anti-gp54 antibody, affinity-purified from sera of patients with anti-TBM nephritis, bound by immunoblotting to 54-kD and, to a lesser extent, 48-kD components of partially purified human CD-TBM. Indirect immunofluorescence showed that gp54 was present in the basement membrane of proximal tubules of the kidneys of normal human, cow, rabbit, guineapig and Brown-Norway rat but not in Lewis rat. Immunoelectron microscopy revealed localization of gp54 along the interstitial side of the TBM and its association with interstitial collagen fibres. These results indicate that gp54 is the nephritogenic antigen involved in tubulo-interstitial nephritis, and is unique in chemical characteristics and localization in the kidney.
 ...
PMID:Isolation and characterization of the tubular basement membrane antigen associated with human tubulo-interstitial nephritis. 142 91

Two antibody probes were used to characterize the putative renal antigens of HgCl2-induced antiglomerular basement membrane renal disease in Brown Norway (BN) rat. The first probe was the linear immunofluorescence imparting, in vivo bound, nephritogenic antiglomerular-basement-membrane autoantibody (anti-GBM-Ab). The second probe was a rat monoclonal antibody to the B subunit of laminin that was obtained from fusion of spleen cells of HgCl2 injected BN rat. By enzyme-linked immunosorbent assay (ELISA) the anti-GBM-Ab reacted with laminin, type IV collagen, collagenase-resistant noncollagenous portion of glomerular basement membrane (GBM), saline soluble proteins of kidney cortex homogenate and fibronectin. Western blot analysis of laminin indicated that the reactive epitopes detected by both probes were on the B chain subunit but not the A subunit. In nonreduced collagenase-digested GBM the epitopes were present on 27 kD and 42 to 48 kD polypeptides. A similar pattern was seen on collagenase-digested human GBM. On rat and human GBM the patterns obtained with rat autoantibody and autoantibody from a patient with Goodpasture syndrome were similar, suggesting that some of the in vivo bound anti-GBM autoantibodies in HgCl2-induced disease in rat are directed against epitopes which are similar to the Goodpasture antigen of human. Reactive epitopes were also detected on saline soluble proteins of kidney cortex homogenate with the predominant antigen being a 31 kD polypeptide. In the saline soluble proteins the reactive polypeptides including the major 31 kD polypeptide did not originate from laminin, type IV collagen, or the collagenase-resistant noncollagenous part of GBM. The precise structural origin of soluble proteins was not defined.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Renal antigens in mercuric chloride induced, anti-GBM autoantibody glomerular disease. 168 61

Rupture of the internal elastic lamina may occur spontaneously with age in certain arteries of the rat and to various extents in different strains. This phenomenon may have some bearing on certain aspects of arterial pathology. For this study, we investigated biochemically the mechanisms of formation of interruptions in the internal elastic lamina (IIEL) by comparing aortas of Brown Norway (BN) rats, which develop numerous IIEL in the abdominal aorta, with those of Long-Evans (LE) rats, which develop none. We isolated aortic elastin from BN and LE rats and determined its amino acid composition and its susceptibility to different elastases. No differences were found between the two strains, but the quantity of elastin isolated per aorta was lower in the BN than in the LE rats. Elastase-like activity (ELA) of whole aortic extracts, measured with Suc(Ala)3NA as a substrate, was greater in the BN rats than in the LE rats of both sexes. The assay of ELA in endothelium, media, and adventitia extracted separately showed very low levels in the media compared to the endothelium and adventitia. The endothelium accounts for about one-half of the total aortic ELA, but a difference between the two strains was detected only in the adventitia. With 3H-insoluble elastins prepared from BN and LE aortas as substrates, elastinolytic activity (EA) was detected only in extracts of endothelium after prior exposure to trypsin. Extracts from BN endothelium on BN elastin were more active than were those from LE endothelium on LE elastin. The assay of lysyl oxidase activity in aortic extracts from the two strains with 3H-collagen from chick embryo calvaria as the substrate showed a lower activity in the BN than in the LE rats. Taken together, these results suggest that increased elastase activity and decreased lysyl oxidase activity may be involved in the formation of IIEL.
 ...
PMID:Role of elastase and lysyl oxidase activity in spontaneous rupture of internal elastic lamina in rats. 197 75

The spontaneous rupture of the internal elastic lamina (IEL) in various arteries occurs to different extents in different rat strains. We have quantified this phenomenon in the caudal and renal arteries and abdominal aorta in two normotensive inbred strains: the Brown Norway (BN) and Long Evans (LE) strains. At 5 weeks of age, BN rats of both sexes exhibited small numbers of interruptions in the IEL of the caudal artery, whereas LE rats did not. Postpubertal male and female BN rats presented large numbers of IEL interruptions in the caudal artery and significant numbers in the renal artery and abdominal aorta, whereas LE rats showed few in the caudal artery and none in the other arteries. Treatment with beta-aminopropionitrile (BAPN, an inhibitor of lysyl oxidase, the enzyme involved in the formation of cross-links in elastin and collagen) increased the formation of IEL ruptures in both strains in the caudal and renal artery and in the abdominal aorta in BN rats, but not in the abdominal aorta of LE rats. Apart from IEL ruptures, which were more prevalent in BN rats, no differences were observed in the ultrastructure of the aortic elastic fibers between the two strains, either in controls or in BAPN-treated rats. When male rats of both strains were made hypertensive by unilateral nephrectomy and administration of deoxycorticosterone and salt, mortality was more precocious in the BN strain although blood pressure was significantly higher in the BN strain at only one time point. The incidence of cerebrovascular hemorrhage was 48% in BN rats and 0% in LE rats. Hypertension increased the formation of ruptures in the IEL in some arteries - to a greater extent in the BN than in the LE rats. These results raise the possibility that the propensity to spontaneous rupture of the IEL, which is in part genetically determined, may reflect a latent form of vascular fragility which becomes significant in hypertension, resulting in poor survival and susceptibility to cerebrovascular accidents.
 ...
PMID:Spontaneous rupture of the internal elastic lamina in the rat: the manifestation of a genetically determined factor which may be linked to vascular fragility. 257 18

Neuronal responses to extracellular matrix (ECM) constituents are likely to play an important role in nervous system development and regeneration. We have studied the interactions of a neuron-like rat pheochromocytoma cell line, PC12, with ECM protein-coated substrates. Using a quantitative cell attachment assay, PC12 cells were shown to adhere readily to laminin (LN) or collagen IV (Col IV) but poorly to fibronectin (FN). The specificity of attachment to these ECM proteins was demonstrated using ligand-specific antibodies and synthetic peptides. To identify PC12 cell surface proteins that mediate interactions with LN, Col IV, and FN, two different antisera to putative ECM receptors purified from mammalian cells were tested for their effects on PC12 cell adhesion and neuritic process outgrowth. Antibodies to a 140-kD FN receptor heterodimer purified from Chinese hamster ovarian cells (anti-FNR; Brown, P. J., and R. L. Juliano, 1986, J. Cell Biol., 103:1595-1603) inhibited attachment to LN and FN but not to Col IV. Antibodies to an ECM receptor preparation purified from baby hamster kidney fibroblastic cells (anti-ECMR; Knudsen, K. A., P. E. Rao, C. H. Damsky, and C. A. Buck, 1981, Proc. Natl. Acad. Sci. USA., 78:6071-6075) inhibited attachment to LN, FN, and Col IV, but did not prevent attachment to other adhesive substrates. In addition to its effects on adhesion, the anti-ECMR serum inhibited both PC12 cell and sympathetic neuronal process outgrowth on LN substrates. Immunoprecipitation of surface-iodinated or [3H]glucosamine-labeled PC12 cells with either the anti-FNR or anti-ECMR serum identified three prominent cell surface glycoproteins of 120, 140, and 180 kD under nonreducing conditions. The 120-kD glycoprotein, which could be labeled with 32P-orthophosphate and appeared to be noncovalently associated with the 140- and 180-kD proteins, cross reacted with antibodies to the beta-subunit (band 3) of the avian integrin complex, itself a receptor or receptors for the ECM constituents LN, FN, and some collagens.
 ...
PMID:Interactions of a neuronal cell line (PC12) with laminin, collagen IV, and fibronectin: identification of integrin-related glycoproteins involved in attachment and process outgrowth. 350 Jan 75

The ultrastructure of rat brown adipose tissue (BAT) and of adipocytes cultured from BAT were studied by scanning electron microscopy (SEM). Brown adipocytes in the intact tissue were arranged in lobules with bundles of collagen among them; within each lobule 20- to 40-microns-large adipocytes were packed together. Fibers of reticular collagen enveloped each adipocyte and also connected each cell to vessels and nerves. At the adipocyte surface rounded protrusions were present, which corresponded to the BAT-typical multivacuolar lipid depot. Gradual digestion of the stroma with collagenase disclosed a more delicate, felt-like cover surrounding each adipocyte, probably representing the external lamina of the cell. Complete digestion of the stroma showed a smooth plasmalemma with occasional roundish blebs which varied in size. Cultured (24 h) brown adipocytes from the stromal-vascular fraction of BAT were elongated or polygonal in shape, with a flattened, central nucleus and a number of spherical cytoplasmatic inclusions which have the same dimension and location as lipid droplets. These inclusions were arranged either at cellular poles or around the nucleus; this suggests that brown adipocytes with mature features were present in the culture. Pictures suggesting the detachment of lipid droplets from the cell body were also visible. Lipid droplet extrusion could be a complementary mechanism which might explain the rapid delipidation of brown adipocytes in culture.
 ...
PMID:Brown adipose tissue: a scanning electron microscopic study of tissue and cultured adipocytes. 354 2

Brown Norway rats injected with mercuric chloride (HgCl2) develop autoantibodies which immunolocalize along the glomerular basement membrane at first in a linear pattern and then in a granular pattern. The aim of this study was to characterize the specificity of these antibodies and to investigate the mechanisms responsible for the formation of granular immune deposits in the subepithelial zone of the glomerular basement membrane. The rats were found to develop circulating anti-laminin, anti-type IV collagen, anti-heparan sulfate proteoglycan, and anti-entactin antibodies. Antibodies against laminin and type IV collagen were found in relatively high titers in the sera and were specifically concentrated in the nephritic kidneys. Antibodies eluted from the nephritic kidneys with either linear or granular deposits reacted with basement membrane antigens synthesized and secreted by cultured rat glomerular visceral epithelial cells. Thus, in this model, the interaction of anti-laminin and type IV collagen antibodies with antigens secreted by glomerular visceral epithelial cells might, together with other mechanisms, contribute to the formation of granular immune deposits in the subepithelial part of the glomerular basement membrane.
 ...
PMID:Studies on the formation of glomerular immune deposits in brown Norway rats injected with mercuric chloride. 362 83

Monoclonal anti-glomerular basement membrane (GBM) antibodies were obtained by fusing spleen cells from Brown-Norway (BN) rats injected with mercuric chloride with IR 983 F, a nonsecreting rat myeloma cell line. These antibodies showed the same pattern of fixation on renal basement membranes by indirect immunofluorescence. One of them was developed. It reacted both in vivo and in vitro with GBM but failed to react with collagenase-digested GBM, laminin, and collagen IV. This monoclonal antibody which resembles the kidney acid eluate obtained from BN rats injected with mercuric chloride induced a weak and transient proteinuria when intravenously injected into normal BN rats.
 ...
PMID:Production of monoclonal anti-glomerular basement membrane antibodies during autoimmune glomerulonephritis. 638 29

Age-related increases in basement membrane thickness have been noted in many tissues, including the testis. The current investigation examined the morphology of the basement membrane in the aged Brown Norway rat and sought to determine whether the accumulation of basement membrane was the result of an increase in the expression of the basement membrane genes. The aged testis was characterized by atrophy of the seminiferous tubules. Closer examination of the degenerated tubules revealed that the seminiferous epithelium was completely devoid of germ cells and that the basement membrane of these tubules was thickened and highly convoluted. In some animals, there was a measurable increase in basement membrane thickness in tubules of normal diameter together with an apparently normal epithelium, suggesting that the thickening is not solely due to a shrinkage of the tubules. To determine whether an increase in basement membrane synthesis was responsible for the thickening, the expression of the genes for laminin, collagen IV, heparan sulfate proteoglycan, and fibronectin was analyzed by Northern blot. There were no changes in the expression of the genes for the laminin B1 and B2 chains, heparan sulfate proteoglycan, or fibronectin that could be correlated with increasing age. Surprisingly, however, the levels of mRNA for the laminin A chain and collagen IV decreased with age.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effects of aging on basement membrane in the testis. 755 41


1 2 3 4 5 6 7 8 Next >>