Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The surface pH of rat distal colonic mucosa and human rectal mucosa was measured in vitro using first a small pH electrode with a flattened tip. In buffer with pH 7.56 the mean rat colonic surface pH was 6.72. Lowering the buffer pH in steps resulted in a small fall in surface pH, the values being buffer pH 7.06 surface pH 6.64, buffer pH 6.58 surface pH 6.61 and finally buffer pH 6.09 surface pH 6.39. Similar results were obtained with a buffer where butyrate, 30 mmol/l replaced chloride and when a CO2/bicarbonate buffer was used. During the time taken for the study transmural potential difference only changed by 1-2 mV. Serosal surface pH changed with buffer pH, suggesting that the maintained surface pH is a property of the mucosal surface only. The surface pH of human rectal mucosa was similar to that of rat distal colonic mucosa. As buffer pH fell from pH 7.51 to 5.96 mucosal surface pH only fell from pH 6.80 to 6.26. The values obtained in ulcerative proctitis did not differ from normal mucosa. Secondly pH microelectrodes were used to measure the juxta mucosal pH and the pH-microclimate thickness when luminal pH was controlled. The microclimate had a pH 6.63 adjacent to the mucosa with a thickness of 840 micron. The importance of mucus in maintaining the microclimate was shown by n-acetyl cysteine thinning and prostaglandin E2 thickening the layer. These results describe a surface microclimate in the large intestine of appreciable thickness and a constant juxta mucosal pH. Luminal pH changes produce only a small change in microclimate pH.
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PMID:Mucosal surface pH of the large intestine of the rat and of normal and inflamed large intestine in man. 362 17

Endothelial perfusions of preswollen rabbit corneal preparations with S-methyl glutathione at levels of 2 x 10(-4)M and 10(-3)M achieve about 70% to 100%, respectively, of the stromal thinning attained with 10(-4)M oxidized glutathione (GSSG). S-methyl cysteine at 10(-4)M is without effect and, at 10(-4)M, inhibits the fluid pump. The results are interpreted to signify that thiol-disulfide exchanges with GSSG probably are not an obligatory part of the endothelial pump mechanism. Contrary to the frequently inhibitory effect of high levels of GSSG on various enzyme systems, increasing the concentration of GSSG from 10(-4)M to 10(-2)M stimulates the first hour rate of stromal thinning 33%. Neither the total amount nor the duration of thinning, however, is significantly affected.
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PMID:Effects of S-methyl glutathione, S-methyl cysteine, and the concentration of oxidized glutathione on transendothelial fluid transport. 738 Jun 26

The lindane embryotoxicity and associated changes in cysteine (CYS) and glutathione (GSH) status have been investigated in the early organogenesis-stage rat conceptus utilizing whole embryo culture techniques. Direct exposure of gestational day 10 (GD 10) conceptuses to lindane (50, 100, 200, 300, and 400 microM) in the culture medium resulted in a dose- and time-dependent increase in mortality (88% at 400 microM), frequency, and severity of malformations and in decreased growth parameters. Protein and DNA contents of embryo and visceral yolk sac (VYS), likewise decreased significantly as lindane concentrations increased. Lindane exposures greater than 100 microM produced abnormal axial rotation, pooled blood on lateral cephalic surfaces, cephalic edema, and decreased VYS vasculature. Histologic sections showed a variety of abnormalities, including distended anterior cardinal veins, thinning of the neuroepithelium in forebrain and hindbrain regions, and abnormal branchial arch development. CYS and GSH levels in the VYS were not significantly affected by 100 microM lindane exposure during a 5-h incubation period on GD 10 and GD 11. In contrast, CYS and GSH levels in lindane-exposed embryos remained unchanged while control levels continued to increase with gestational age. At 5 h, treated embryos showed a significant depletion of CYS (GD 10, 22%; GD 11, 35%) and GSH (GD 10, 41%; GD 11, 24%) relative to controls. Selective lindane-induced depletion of embryonic GSH suggests involvement of the glutathione redox cycle in lindane embryotoxicity.
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PMID:Lindane embryotoxicity and differential alteration of cysteine and glutathione levels in rat embryos and visceral yolk sacs. 752 28

The amount of human growth hormone (HGH) decreases significantly after the age of 30. This decrease has been implicated as one of the major causes in the signs of aging, such as thinning of the skin and bones, a decrease in lean muscle mass and an increase in adipose tissue. Supplementing the body's dwindling supply with recombinant human growth hormone (rHGH) has been shown to reverse the signs and symptoms of aging. However, drawbacks in rHGH replacement therapy include prohibitively high cost, the need for repeated injection and side effects such as carpel tunnel syndrome, gynecomastia and insulin resistance. The purpose of this study was to establish an in vitro model using genetically-engineered keratinocytes to screen natural compounds for the ability to stimulate HGH secretion. We now report that a combination of equal amounts of L-arginine and L-lysine, aged garlic extract (Kyolic), S-allyl cysteine and Pycnogenol significantly increased secretion of HGH in this in vitro model. The data indicate that this in vitro model may be used to screen for other secretagogues.
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PMID:Kyolic and Pycnogenol increase human growth hormone secretion in genetically-engineered keratinocytes. 1212

The toxic effects of i.v. administration of N-acetyl-l-cysteine (NAC), a component of parenteral nutrition solutions, on fertility and embryonic development were investigated in SD male and female rats at doses of 100, 300, and 1000 mg kg-1 day-1. Infertility was observed in females in the 1000-mg/kg group throughout the period from before mating to embryogenesis. No effect of NAC on the reproductive ability of the male rats was seen. The oocytes and embryos were assessed morphologically to clarify the cause of the effects of NAC. The unfertilized oocytes (UO) recovered from the ampullae of the uterine tubes and Gestational Day (GD) 1 and 2 embryos recovered from the oviducts or uterus of the rats that received NAC i.v. at a dosage of 1000 mg kg-1 day-1 for more than 1 wk before mating were assessed morphologically by stereomicroscopy. In addition, the thickness of the zona pellucida (ZP) was calculated by morphometric evaluation of the UO. Fewer UO were collected in the NAC group than in the control (nontreatment) group. Interestingly, ZP-lacking or partially ZP-lacking oocytes were observed in the NAC group, and the morphometric evaluation of the UO showed thinning of the ZP. The number of embryos in each animal was markedly decreased on GD1, and no embryos were recovered on GD2 in the NAC group. The oocytes that had ZP affected by NAC treatment were abnormal or nonviable. The findings of the present study suggest that changes in the ZP are related to the infertility associated with NAC.
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PMID:Infertility observed in reproductive toxicity study of N-acetyl-L-cysteine in rats. 1262 Sep 35

We previously reported infertility in female rats that received N-acetyl-L-cysteine (NAC) intravenously at a dosage of 1000 mg/kg/day. Unfertilized oocytes and gestation day 1 and 2 embryos were assessed morphologically, and the results suggested that absence or thinning of the zona pellucida (ZP) is related to infertility. However, the morphological characteristics of oocytes before ovulation and recovery from the effects of NAC were not clarified. In the present study, the ovarian follicles were histopathologically examined and the recovery of reproductive function was evaluated to investigate the effects of NAC. Female Sprague-Dawley rats at 10 weeks of age received NAC intravenously at 1000 mg/kg/day for more than 1 week. Thinning of the ZP was observed in the ovarian follicles in all stages of growth by light microscopy. Outflow of the components of the ZP between the corona radiata and disarrangement of the corona radiata were more pronounced in growing follicles than in large secondary follicles. Similar findings were observed by electron microscopy, and the effects of NAC were limited to the ZP. Infertility and thinning of the ZP were observed in the no-recovery NAC group, but not in the recovery NAC group, in which animals recovered within four estrous cycles after NAC administration. It has been reported that the ZP is expressed by oocytes or by both oocytes and granulosa cells, but no changes were noted in these cells. The present findings suggest that NAC affects the ZP directly and that reproductive function may recover from the effects of NAC.
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PMID:Infertility observed in female rats treated with N-acetyl-L-cysteine: Histopathological examination of ovarian follicles and recovery of fertility. 1468 66

Between 1998 and 1999 we suggested a role for cysteine proteases, particularly cathepsins S and K, in atherosclerosis and abdominal aortic aneurysm (AAA) formation. We also demonstrated the presence and activity of cathepsins S, K, and L in atherosclerotic and aneurysmal lesions in humans. Features unique to this family of extracellular enzymes indicate its likely participation in these vascular diseases. As very potent elastolytic enzymes, cathepsins are strong candidates as key participants in aneurysm development. Importantly, cathepsins express very high elastolytic activity in AAA due to reciprocal correlation with cystatin C, their most abundant endogenous inhibitor. Two opposite processes coexist in aneurysmal tissue: overexpression of elastolytic cathepsins, and severe suppression of cystatin C, probably due to differentially regulated expression and secretion of cathepsins and their inhibitors in response to inflammatory cytokines. Involvement of cathepsins in microvessel formation, a pathophysiological marker of human AAA, and programmed cell death (apoptosis), increases the likelihood of cathepsin participation in AAA formation and growth. We also summarize here results obtained in our and other laboratories that demonstrated reduced atherosclerosis and AAA in in vivo models using mice lacking different cathepsins. Deficiency of cysteine protease inhibitor cystatin C in atherosclerosis-prone ApoE-null mice leads to the development of specific features of AAA such as thinning of the tunica media and aortic dilatation. Taken together, such findings in humans in vitro with different cell types and in vivo in genetically altered mice demonstrate the importance of cysteine protease/protease inhibitor balance in dysregulated arterial integrity and remodeling during atherosclerosis and aortic aneurysm formation.
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PMID:Do cathepsins play a role in abdominal aortic aneurysm pathogenesis? 1718 32

The mammalian embryo is encased in a glycoproteinaceous coat, the zona pellucida (ZP) during preimplantation development. Prior to implantation, the blastocyst must undergo 'hatching' or ZP escape. In hamsters, there is a thinning of the ZP followed by a focal lysis and a complete dissolution of the ZP during blastocyst hatching. Earlier studies from our laboratory have indicated a role for cysteine proteases in the hatching phenomenon. In this study, we tested the effect of specific inhibitors of the three classes of cysteine protease on blastocyst hatching. Cystatin, an endogenous cathepsin inhibitor, blocked blastocyst hatching. Similarly, Fmoc-Tyr-Ala-diazomethane, a synthetic cathepsin inhibitor, blocked hatching. Both showed dose-dependent and temporal inhibition of hatching. However, Z-Val-Ala-Asp-fluoromethylketone, a synthetic caspase inhibitor, and calpastatin, an endogenous calpain inhibitor, had no effect on hatching. The cathepsins were localized to blastocyst cells. Exogenous addition of cathepsins L, P or B to cultured 8-cell embryos caused a complete ZP dissolution. The expression of mRNA and protein of cathepsins L and P was observed in peri-hatching blastocysts. Cathepsins L and P were detected in trophectodermal projections and in the ZP of peri-hatching blastocysts. These data provide the first evidence that blastocyst-derived cathepsins are functionally involved as zonalytic factors in the hatching of blastocysts in the golden hamster.
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PMID:Role of cathepsins in blastocyst hatching in the golden hamster. 1846 58

Missense mutations in the cone opsins have been identified as a relatively common cause of red/green color vision defects, with the most frequent mutation being the substitution of arginine for cysteine at position 203 (C203R). When the corresponding cysteine is mutated in rhodopsin, it disrupts proper folding of the pigment, causing severe, early onset retinitis pigmentosa. While the C203R mutation has been associated with loss of cone function in color vision deficiency, it is not known what happens to cones expressing this mutant opsin. Here, we used high-resolution retinal imaging to examine the cone mosaic in two individuals with genes encoding a middle-wavelength sensitive (M) pigment with the C203R mutation. We found a significant reduction in cone density compared to normal and color-deficient controls, accompanying disruption in the cone mosaic in both individuals, and thinning of the outer nuclear layer. The C203R mosaics were different from that produced by another mutation (LIAVA) previously shown to disrupt the cone mosaic. Comparison of these mosaics provides insight into the timing and degree of cone disruption and has implications for the prospects for restoration of vision loss associated with various cone opsin mutations.
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PMID:Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin. 1993 58

The Neuromutagenesis Facility at the Jackson Laboratory generated a mouse model of retinal vasculopathy, nmf223, which is characterized clinically by vitreal fibroplasia and vessel tortuosity. nmf223 homozygotes also have reduced electroretinogram responses, which are coupled histologically with a thinning of the inner nuclear layer. The nmf223 locus was mapped to chromosome 17, and a missense mutation was identified in Lama1 that leads to the substitution of cysteine for a tyrosine at amino acid 265 of laminin alpha1, a basement membrane protein. Despite normal localization of laminin alpha1 and other components of the inner limiting membrane, a reduced integrity of this structure was suggested by ectopic cells and blood vessels within the vitreous. Immunohistochemical characterization of nmf223 homozygous retinas demonstrated the abnormal migration of retinal astrocytes into the vitreous along with the persistence of hyaloid vasculature. The Y265C mutation significantly reduced laminin N-terminal domain (LN) interactions in a bacterial two-hybrid system. Therefore, this mutation could affect interactions between laminin alpha1 and other laminin chains. To expand upon these findings, a Lama1 null mutant, Lama1(tm1.1Olf), was generated that exhibits a similar but more severe retinal phenotype than that seen in nmf223 homozygotes. The increased severity of the Lama1 null mutant phenotype is probably due to the complete loss of the inner limiting membrane in these mice. This first report of viable Lama1 mouse mutants emphasizes the importance of this gene in retinal development. The data presented herein suggest that hypomorphic mutations in human LAMA1 could lead to retinal disease.
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PMID:Mutations in Lama1 disrupt retinal vascular development and inner limiting membrane formation. 2004 58


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