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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Silicone, previously thought to be a biologically inert and harmless material, has now been reported to elicit antibody response and to be responsible for adjuvant disease in humans. The present study was designed to evaluate the immune function of forty individuals who had undergone silicone breast augmentation for a period of longer than ten years and who were compared with 40 sex and age-matched controls. The following immunological functions were studied: lymphocyte subset analysis, lymphocyte mitogenic response, NK cytotoxic activity and markers for autoimmunity such as ANA, rheumatoid factor immune complexes such as smooth muscle, myelin, and thyroid, and tissue antibodies. Results of lymphocyte subpopulation analysis showed significantly elevated T helper/suppressor ratio in 60% and significantly decreased T helper/suppressor ratio in 7.5% of the silicone implant group, while the control group showed increased helper/suppressor ratio only in 10% of tested individuals and no significant decrease in the T helper/suppressor ratio. There was 20% inhibition in T cell mitogenic responses in the silicone implant group, which is significant when compared to the controls. When NK cytotoxic activity was compared between the two groups, significant inhibition in the ability of lymphocytes to kill tumor target cells was observed in the silicone implant group. This inability of target cell lysis was attributed to the demonstrated lack of granularity of NK cells from the silicone implant group. There was significant increase in: immune complexes, anti-nuclear antibodies, anti-thyroid antibodies, anti-striated muscle cell antibody, and anti-myelin basic protein antibodies. These immunological abnormalities in individuals who underwent silicone breast augmentation indicate a mechanism of tissue injury to these patients, causing autoimmune diseases or syndromes. Since autoimmunity in some other conditions is associated with abnormalities in the HLA serotyping system, and since some collagen vascular diseases have been associated with a higher incidence of the HLA serotyping system, it is recommended that HLA studies be included in future investigations of immune-mediated abnormalities associated with silicone breast augmentation. Our findings here show definite abnormalities of the T helper/suppressor ratio, increased autoimmunity, as well as increased production of immune complexes. Silicone implants have been used in cosmetic and reconstructive surgery more than 30 years (Brown et al., 1960). The gel used in the implant is produced from silicone, which is then related with methyl chloride and polymerized to form stable polydimethylsiloxane (Brown, et al., 1960). There have been a number of reports describing the occurrence of connective tissue disease in patients after the implantation of silicone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immune functional impairment in patients with clinical abnormalities and silicone breast implants. 757 Jun 22

Nonenzymatic glycation of body proteins and subsequent advanced glycation reactions have been implicated in the aging process, while caloric restriction (CR) in rodents results in an increase in both mean and maximum life span. We have evaluated the effect of chronic (25 months) CR on glycation of blood proteins and accumulation of advanced glycation and oxidation (glycoxidation) products, N epsilon-(carboxymethyl)lysine (CML), and pentosidine, in skin collagen. Brown-Norway rats, fed ad libitum (AL) from birth, were divided into two equal groups at 4 months of age and placed on AL or CR diets (CR = 60% of AL diet). Cohorts of animals were sacrificed at 7, 13, and 25 months after the initiation of CR. At necropsy glycated hemoglobin was measured by affinity HPLC and glycated plasma protein by the fructosamine assay; extracts of skin collagen were analyzed by gas chromatography-mass spectrometry for CML and by reversed-phase HPLC for pentosidine. Glycation of hemoglobin, plasma proteins, and skin collagen was decreased significantly (18-33%) by CR. Concentrations of CML and pentosidine increased significantly with age in skin collagen in both AL and CR animals; however, CR significantly reduced levels of CML (25%), pentosidine (50%), and fluorescence (15%) in collagen in the oldest rats. We conclude that CR reduces the extent of glycation of blood and tissue proteins and the age-related accumulation of glycoxidation products in skin collagen.
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PMID:Caloric restriction decreases age-dependent accumulation of the glycoxidation products, N epsilon-(carboxymethyl)lysine and pentosidine, in rat skin collagen. 758 89

Vascular smooth muscle cells (SMCs) produce the bulk of the connective tissue of major arteries, including collagen types I, III, and V. Recently, we have shown, they also have the capacity to synthesize the alpha 1 chain of type XI, a collagen related to type V (Brown, K., Lawrence, R., and Sonenshein, G. (1991) J. Biol. Chem. 266, 23268-23273). Furthermore, expression of types V and XI collagen were coordinately regulated with respect to serum deprivation and cell density in a fashion distinct from that for types I and III. To begin to determine the factors that influence vascular SMC production of types V/XI collagen, we have examined the effects of transforming growth factor (TGF)-beta 1, a major modulator of connective tissue expression. In serum-deprived confluent cultures of bovine pulmonary artery SMCs, TGF-beta 1 treatment increased the steady-state levels of the mRNAs of collagen types V and XI, as well as of types I and III, elastin and fibronectin. The largest increase was seen for alpha 2(V) procollagen. The increase in alpha 2(V) mRNA was detectable by 12 h after addition of 2 ng/ml TGF-beta 1, and concentrations as little as 0.5 ng/ml were effective. A similar increase in alpha 2(V) mRNA levels was observed with SMCs derived from the aortic arch and carotid artery. Type V collagen protein was found to be elevated by TGF-beta 1 treatment in both the conditioned media and the cell layer associated fraction of pulse-labeled cultures. A slight decrease in SMC proliferation as judged by DNA content, [3H]thymidine incorporation, and steady-state levels of histone H3.2 mRNA resulted from TGF-beta 1 treatment. These results suggest that the elevated levels of TGF-beta 1 in the vessel wall during atherosclerosis may be, in part, responsible for the increase in type V collagen that typifies advanced fibrotic lesions.
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PMID:Transforming growth factor beta 1 stimulates type V collagen expression in bovine vascular smooth muscle cells. 814 47

Microscopic aneurysmal-like structures (ALS) develop spontaneously in the convoluted rat testicular artery and have been previously proposed as a model relevant to cerebral aneurysms. The effect of defects in connective tissue fibres on ALS formation was investigated by microscopy using two approaches: (i) the study of the effect of beta-aminopropionitrile (BAPN), an inhibitor of the cross-linking of elastic and collagen fibres, on the incidence, size and morphology of ALS in spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). The straight spermatic artery was studied for comparison. (ii) The determination of the incidence of spontaneous ALS in Brown Norway (BN) and Long Evans (LE) rats which are highly susceptible (BN) or resistant (LE) to the spontaneous rupture of the arterial internal elastic lamina. (i) BAPN increased the number and size of ALS in SHR and WKY rats and had no effect on the straight spermatic artery and (ii) ALS were more numerous and of greater size in BN than in LE rats. Taken together, these results show that defective connective tissue fibres may favour the formation and induce the enlargement of aneurysmal-like structures. By analogy, these data suggest that a lack of connective tissue fibre integrity may be of importance in cerebral aneurysm formation and development.
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PMID:Effect of defective connective tissue on the formation of aneurysmal-like structures in the rat testicular artery. 876 63

Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndrome in Brown-Norway (BN) rats characterized by a humoral response, tissue injury with an accumulation of CD8+ and CD4+ T cells, and an increase in tissue IL-4 mRNA and serum IgE suggesting Th2 cell activation. In other models of autoimmune disease, CD8+ cells act in both anti- and pro-inflammatory capacities, suggesting that functionally distinct CD8+ populations exist in vivo. The effect of treatment with OX8, a depleting anti-CD8 MoAb, on the initiation of HgCl2-induced autoimmunity was assessed in two experiments in a total of 20 BN rats, and compared with 20 animals treated with a control MoAb or PBS. OX8 significantly depleted peripheral blood CD8+ lymphocytes, had no effect on HgCl2-induced anti-collagen or myeloperoxidase antibodies, nor on the incidence or severity of caecal vasculitis. The severity of HgCl2-induced arthritis was significantly reduced in OX8-treated animals; median peak score reduced from 7.5 to 3.0 (experiment 1) and from 7.0 to 4 (experiment 2) (P = 0.009, Mann-Whitney U-test). OX8 treatment also exacerbated the early rise in HgCl2-induced IgE and induced a significant rise in plasma interferon-gamma (IFN-gamma), suggesting that CD8+ cells may have a regulatory influence on Th cell populations. These data provide direct evidence that CD8+ cells may act in a proinflammatory capacity in both this model of autoimmunity and the pathogenesis of inflammatory arthritis.
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PMID:Anti-CD8 treatment reduces the severity of inflammatory arthritis, but not vasculitis, in mercuric chloride-induced autoimmunity. 891 74

The extracellular matrix of the optic nerve head is altered in both human glaucoma and in experimental primate models of this disease. However, the relationship of this change to glaucomatous optic nerve degeneration is unknown. This report describes similar matrix alterations in rats with unilateral elevated intraocular pressure. Brown Norway rats received episcleral vein injections of hypertonic saline to produce prolonged elevations of intraocular pressure. After up to 6 months of pressure elevation, optic nerve head sections from the rats were evaluated by light microscopic immunohistochemistry using antibodies to collagens I, III, IV and VI, laminin, elastin and chondroitin and dermatan sulfate proteoglycans. In experimental eyes with 11 days or more of pressure elevation, depositions of collagen IV, collagen VI and laminin were found within regions of the optic nerve head that, in normal eyes, are occupied solely by nerve bundles. Collagen I and III deposition appeared to be more dependent on the level and duration of the pressure rise. Eyes with lower mean intraocular pressures showed deposits of interstitial collagens primarily at the level of the sclera, while eyes with higher mean pressure elevations had depositions in the neck regions as well. Chondroitin and dermatan sulfate proteoglycans were deposited in a pattern similar to that of collagen I. No extracellular matrix deposition was seen in the orbital optic nerve in any experimental eye. These extracellular matrix changes in rats replicate previous findings in human glaucomatous eyes and monkey eyes with experimentally elevated pressures. They also suggest a sequence of extracellular matrix protein deposition in response to pressure elevation. The optic nerve head deposition of matrix materials in response to elevated intraocular pressures may affect the susceptibility of remaining axons to pressure by changing the physical properties of their support tissues, by affecting the support functions of astrocytes and by changing the microenvironment of injured axons. This model may be useful for studying these and other aspects of the process of axonal injury resulting from elevated intraocular pressure.
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PMID:The effect of chronically elevated intraocular pressure on the rat optic nerve head extracellular matrix. 898 48

We have previously characterized two normotensive strains of rats which differ markedly in their susceptibility to spontaneous rupture of the internal elastic lamina (IEL), the Brown Norway (BN) being very susceptible and the Long Evans (LE) being resistant. Here we quantified biochemically the elastin and collagen content of aortae from adult male BN and LE rats aged 12, 18 and 22 weeks and showed that the elastin content was lower and the collagen content higher in the BN strain than in the LE strain, resulting in a markedly lower elastin/collagen ratio in the former strain. These modifications were present both in the thoracic aorta, which is devoid of IEL ruptures, and in the abdominal segment where ruptures frequently occur in the BN rat, suggesting that they could represent a predisposing factor in the presence of other local factors. Quantifications of relevant mRNAs in aortae of younger male BN and LE rats by Northern blot showed that there are lower tropoelastin transcript levels in the BN rat at 6 weeks in both thoracic and abdominal segments than in the age-matched LE rat. In contrast there was no consistent interstrain difference in alpha 1 type I collagen transcripts and alpha 1 type III collagen transcripts were higher in the BN aorta only at 6 weeks in the abdominal segment. We conclude that the BN rat presents an aortic elastin deficit which appears to be in part explained by a decreased elastin synthesis in young, growing rats and may be genetically determined. However, a direct relation of this elastin deficit with susceptibility to rupture of the IEL cannot be concluded from this study.
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PMID:Aortic elastin and collagen content and synthesis in two strains of rats with different susceptibilities to rupture of the internal elastic lamina. 916 45

The strong association of anti-neutrophil cytoplasmic antibodies with various forms of systemic vasculitis suggests a role for these autoantibodies in the pathophysiology of systemic vasculitis. In the present study, we tested the hypothesis that release of neutrophil lysosomal enzymes in the presence of an anti-myeloperoxidase (anti-MPO) immune response may underlie the development of systemic vasculitis. Brown Norway rats were immunized with MPO in complete Freund's adjuvant or complete Freund's adjuvant alone. Two weeks after immunization, rats bad developed antibodies to human and rat MPO as measured by enzyme-linked immunosorbent assay. Next, rats were intravenously infused with 400 micrograms of a human neutrophil lysosomal extract containing 200 micrograms of MPO followed by 0.5 ml of a 1 mmol/L solution of H2O2 through a cannula inserted into the right jugular vein. Rats were sacrificed at 4 hours, 24 hours, 7 days, or 14 days, and several organs (lungs, heart, liver, spleen, gut, and kidneys) were examined for vasculitic lesions and inflammatory cell infiltrates. Macroscopically, patchy hemorrhagic spots were observed in the lungs and gut of MPO-immunized rats at days 7 and 14 after systemic infection of the neutrophil lysosomal extract and H2O2. Such changes were not observed at earlier time points or in control immunized rats. Histologically, the lungs of MPO-immunized rats sacrificed at days 7 and 14 showed patchy inflammatory cell infiltrates associated with vasculitis, granuloma formation, giant cells, and foci of hemorrhage. At 14 days, early signs of fibrosis were found with deposition of collagen and proliferation of fibroblasts. Furthermore, a prominent leukocytoclastic vasculitis was found in the small intestine of these rats characterized by fibrinoid necrosis and an extensive neutrophilic infiltrate. No inflammatory changes were found in the other organs studied (heart, liver, spleen, and kidneys). Control immunized rats, sacrificed at days 7 and 14 showed only some small foci of inflammatory infiltrates in the lungs whereas no inflammatory changes were found in the gastrointestinal tract. These studies show that release of products from activated neutrophils in the presence of anti-MPO autoantibodies may be relevant to the pathogenesis of anti-MPO-associated vasculitides.
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PMID:Systemic injection of products of activated neutrophils and H2O2 in myeloperoxidase-immunized rats leads to necrotizing vasculitis in the lungs and gut. 921 39

We present a method for solving the governing equations from our anisotropic biphasic theory of tissue-equivalent mechanics (Barocas and Tranquillo, 1997) for axisymmetric problems. A mixed finite element method is used for discretization of the spatial derivatives, and the DASPK subroutine (Brown et al., 1994) is used to solve the resulting differential-algebraic equation system. The preconditioned GMRES algorithm, using a preconditioner based on an extension of Dembo's (1994) adaptation of the Uzawa algorithm for viscous flows, provides an efficient and scaleable solution method, with the finite element method discretization being first-order accurate in space. In the cylindrical isometric cell traction assay, the chosen test problem, a cylindrical tissue equivalent is adherent at either end to fixed circular platens. As the cells exert traction on the collagen fibrils, the force required to maintain constant sample length, or load, is measured. However, radial compaction occurs during the course of the assay, so that the cell and network concentrations increase and collagen fibrils become aligned along the axis of the cylinder, leading to cell alignment along the axis. Our simulations predict that cell contact guidance leads to an increase in the load measured in the assay, but this effect is diminished by the tendency of contact guidance to inhibit radial compaction of the sample, which in turn reduces concentrations and hence the measured load.
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PMID:A finite element solution for the anisotropic biphasic theory of tissue-equivalent mechanics: the effect of contact guidance on isometric cell traction measurement. 928 39

Spontaneous rupture of the internal elastic lamina (IEL) occurs in some arteries of the rat during growth and aging. Inbred, normotensive, Brown Norway (BN) rats are particularly susceptible to rupture of the IEL, especially in the abdominal aorta (AA). Preliminary experiments showed that different angiotensin-converting enzyme (ACE) inhibitors protect against rupture of the IEL in the BN rat to a greater extent than hydralazine, suggesting a role of the renin-angiotensin system (RAS) in this phenomenon. To explore this possibility, we have treated male BN rats from 4.5 to 14 weeks of age with either enalapril or losartan (both at 1, 3, and 10 mg x kg(-1) x d(-1)) or with the calcium antagonists mibefradil (at 3, 10, 30, and 45 mg x kg(-1) x d(-1)) and amlodipine (at 30 mg x kg(-1) x d(-1)). Systolic blood pressure (SBP) was measured weekly, and at the end of treatment we (1) recorded body and heart weights, (2) measured various parameters of the RAS in plasma, (3) quantified interruptions in the IEL on "en face" preparations of AA, and (4) quantified elastin, collagen, and cell proteins in the media of the thoracic aorta. Results showed that enalapril and losartan similarly decrease SBP and rupture of the IEL in the AA, suggesting that enalapril inhibits the latter via a decrease in the production of angiotensin II (Ang II) and not via another effect on ACE. The decrease in IEL rupture and in SBP, as well as the modifications in the parameters of the RAS, were all dose dependent. Mibefradil had little effect on the RAS and, at the highest doses, decreased SBP to an extent similar to that for enalapril at 3 mg x kg(-1) x d(-1) but did not significantly inhibit IEL rupture. Amlodipine decreased SBP, increased plasma renin concentration, and was without effect on IEL rupture. All treatments at the highest doses had a hypotrophic effect on the aortic media but differed in their effects on the heart, with enalapril and losartan decreasing and mibefradil and amlodipine increasing heart weight, suggesting that the inhibition of IEL rupture may be related to a cardiac hypotrophic effect. All these results, taken together, suggest that Ang II plays a role in the rupture of the IEL that is, in part, independent of SBP.
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PMID:Protection of the arterial internal elastic lamina by inhibition of the renin-angiotensin system in the rat. 957 7


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