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 mechanism and characteristics of intestinal absorption of arachidonic acid were studied in vitro using everted intestinal sacs of the rat. Arachidonic acid absorption was studied at concentrations of 5 micron to 8.36 mM. The plot of absorption rate vs. concentration fitted best to a rectangular hyperbola at low micron concentrations and to a straight linear relationship in the mM range of concentrations. Metabolic inhibitors and uncouplers did not change absorption in either range of concentrations. The absorption of arachidonic acid increased with thinning of the unstirred water-layer, decrease in the pH, or the substitution of sodium taurocholate by Pluronic F 68 OR Tween 80. Absorption decreased following the equimolar additions of oleic, linoleic, and linolenic acids. Absorption rate did not change when the taurocholate concentration was varied from 5-15 mM or following the additions of butyric or glutamic acids, leucine, lysine, or dextrose. It was concluded that arachidonic acid is absorbed by a concentration-dependent dual mechanism of transport which is not energy dependent. At the low micron range of concentrations, facilitated diffusion is predominant, while at mM concentrations, simple diffusion is the dominant mechanism of absorption. Changes in the intestinal fluid composition, flow rate, and pH can modify the rate of absorption of arachidonic acid.
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PMID:Arachidonic acid intestinal absorption: mechanism of transport and influence of luminal factors of absorption in vitro. 71 12

The effects of systemic cortisol treatment on the biophysical and biochemical properties of skin were investigated. Rats were injected sc with cortisol for 14, 60 and 120 days and samples of lumbar skin were studied. Corticosteroids exert a biphasic effect on the strength of skin: 1) a relatively fast increase in the strength and stability, caused by an increased collagen cross-linking and 2) an inhibited collagen synthesis which ultimately results in a thinning of the skin and a decrease of collagen content consistent with clinical observations. The thermal stability is increased indicating an increased proportion of thermostable cross-links in skin collagen. No changes are observed in the percentage type III collagen with respect to type I collagen. Increased amounts of glucose attached to the epsilon-amino group of lysine residues in the collagen are found after long-term treatments, an alteration which may play a role in hampering the tissue functions.
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PMID:Changes in mechanical properties, thermal stability, reducible cross-links and glycosyl-lysines in rat skin induced by corticosteroid treatment. 681 40

Monilethrix is a rare dominant hair disease characterized by beaded or moniliform hair which results from the periodic thinning of the hair shaft and shows a high propensity to excess weathering and fracturing. Several cases of monilethrix have been linked to the type II keratin gene cluster on chromosome 12q13 and causative heterozygous mutations of a highly conserved glutamic acid residue (Glu 410 Lys and Glu 410 Asp) in the helix termination motif of the type II hair keratin hHb6 have recently been identified in monilethrix patients of two unrelated families. In the present study, we have investigated two further unrelated monilethrix families as well as a single case. Affected members of one family and the single patient exhibited the prevalent hHb6 Glu 410 Lys mutation. In the second family, we identified in affected individuals a lysine substitution of the corresponding glutamic acid residue, Glu 403, in the type II hair keratin hHb1, suggesting that this site represents a mutational hotspot in these highly related type II hair keratins. Both hHb1 and hHb6 are largely coexpressed in cortical trichocytes of the hair shaft. This indicates that monilethrix is a disease of the hair cortex.
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PMID:A new mutation in the type II hair cortex keratin hHb1 involved in the inherited hair disorder monilethrix. 940 62

Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair due to periodic thinning of the shaft. The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. Mutations of the helix-encoding region in two hair-specific keratins (hHb1 and hHb6) have been identified. We have now investigated two unrelated monilethrix patients and identified two different novel heterozygous point mutations of the same codon in exon 7 of the hHb6 gene. Dystrophic hair samples obtained from both patients showed the typical beaded appearance by scanning electron microscopy. Both mutations affected the first base of codon 402 (glutamic acid). In patient A, a G to C transition occurred causing a glutamine substitution (GAG to CAG: E402Q) whereas in patient B, the transition was G to A yielding a lysine substitution (GAG to AAG: E402K). The sequence of the 1A helical regions of hHb1 and hHb6 as well as the 2B helical region of hHb1, were normal. Unaffected relatives did not have the hHb6 mutation and this codon was found to be highly conserved showing no alteration in the normal population (100 alleles examined). Both mutations disrupted a Taq I restriction site and restriction fragment length polymorphism analysis showed that a diagnostic 361 bp fragment could confirm the mutation. Thus, two new point mutations of the hair-specific keratin gene hHb6 have been identified in this genetic disease.
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PMID:Two different mutations in the same codon of a type II hair keratin (hHb6) in patients with monilethrix. 1059 61

We have used fluorescence quenching of tryptophan-containing trans-membrane peptides by bromine-containing phospholipids to study the specificity of peptide-lipid interactions. We have synthesized peptides Ac-K2GLm WLnK2A-amide where m = 7 and n = 9 (L16) and m = 10 and n = 12 (L22). Binding constants of L22 for dioleoylphosphatidylserine [di(C18 : 1)PS] or dioleoylphosphatidic acid [di(C18 : 1)PA] relative to dieoleoylphosphatidylcholine [di(C18 : 1)PC] were close to 1. However, for L16, whilst the bulk of the di(C18 : 1)PA molecules bound with a binding constant relative to di(C18 : 1)PC close to 1, a small number of di(C18 : 1)PA molecules bound much more strongly. Assuming just one high affinity binding site on L16 for anionic lipid, the affinity of the site for di(C18 : 1)PS was calculated to be ca. 8 times that for di (C18 : 1)PC. The relative binding constant was little affected by ionic strength and close contact between the anionic headgroup of di(C18 : 1)PS and a lysine residue on the peptide was suggested. The relative binding constant for di(C18 : 1)PS at this high affinity site was less than for di(C18 : 1)PA. Cholesterol interacts with L22 with an affinity about 0.7 of that of di(C18 : 1)PC. The structure of the peptide itself is important. The peptide Ac-KKGYL6WL8YKKA-amide (Y2L14) incorporated into bilayers of dinervonylphosphatidylcholine [di(C24 : 1)PC] whereas L16 did not incorporate into this lipid. It is suggested that thinning of a lipid bilayer around a peptide to give optimal hydrophobic matching is less energetically unfavourable when a Tyr residue is located in the lipid/water interfacial region.
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PMID:Lipid-protein interactions in the membrane: studies with model peptides. 1082 5

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

Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair resulting from periodic thinning of the shaft (MIM 158000). The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. Mutations of the helix-encoded region in two hair-specific keratins (hHb1 and hHb6) have been identified as responsible for this disorder. We investigated two unrelated families from Russia and Colombia with monilethrix and found two missense mutations in hHb6. In the Russian family, we found a G to A transition at the first base of codon 402, resulting in a lysine substitution (GAG to AAG), designated E402K. In the Colombian family, affected patients carried a missense mutation of codon 413, involving a transition from G to A causing a lysine substitution (GAG to AAG), designated E413K. These two mutations have been identified in other monilethrix families from Europe. Our findings extend the body of evidence implicating recurrent hHb6 and hHb1 mutations in monilethrix families from around the world.
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PMID:Recurrent missense mutations in the hair keratin gene hHb6 in monilethrix. 1265 15

Aging of skin is a continuous process that may be enhanced by sun exposure. Photoaging may provoke changes different from aging. Epidermal changes involve thinning of stratum spinosum and flattening of the dermo-epidermal junction. The senescent keratinocytes becomes resistant to apoptosis and may survive for a long time giving time for DNA and protein damage to accumulate with possible implication for carcinogenesis. The numbers of melanocytes decrease with age with dysregulation of melanocyte density resulting in freckles, guttate hypo-melanosis, lentigines and nevi. The number of dendritic Langerhans cells also decreases with age and the cells get less dendrites and have reduced antigen-trapping capacity. Aging involves dermal changes such as damage to elastic and collagen fibers giving thickened, tangled, and degraded non-functional fibers. Collagen intermolecular cross-links are stable and essential for stability and tensile strength. Cross-links increase with age converting divalent cross-links into mature trivalent cross-links of, e.g. histidinohydroxylysinonorleucine. Two mechanisms are involved; an enzyme-controlled process of maturation and a non-enzymatic glycosylation, the Maillard reaction leading to cross-links in proteins such as in collagen between arginine and lysine. Such may be seen with age and in diabetes mellitus. However, autofluorescence studies have shown that UVR reduces collagen cross-links. Natural photoprotection involves thickening of stratum corneum by sunlight and increased pigmentation. This leads to a factor 2 increase in photoprotection from spring until after-summer. The constitutive pigmentation is independent of age and thickness of stratum corneum is likewise independent of age. The minimal erythema dose is thus the same through life, when corrected for pigmentation or measured in areas with constitutive pigmentation.
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PMID:Skin aging and natural photoprotection. 1503 73

Brief ischemia was reported to protect retinal cells against injury induced by subsequent ischemia-reperfusion with de novo protein synthesis, and this phenomenon is known as late ischemic preconditioning. The aims of the present study were to determine whether nitric oxide synthase (NOS) was involved in the mechanism of late ischemic preconditioning in rat retina using pharmacological tools. Under anesthesia with pentobarbital sodium, male Sprague-Dawley rats were subjected to 60 min of retinal ischemia by raising intraocular pressure to 130 mm Hg. Ischemic preconditioning was achieved by applying 5 min of ischemia 24 hrs before 60 min of ischemia. Retinal sections sliced into 5 microm thick were examined 7 days after ischemia. Additional groups of rats received NG-nitro-L-arginine and NG-monomethyl-L-arginin, non-selective NO synthase inhibitors, 7-nitroindazole, a neuronal NOS inhibitor, and aminoguanidine and L-N6-(1-iminoethyl) lysine, inducible NO synthase (iNOS) inhibitors before preconditioning, and were subjected to 60 min of ischemia. In the non-preconditioned group, cell loss in the ganglion cell layer and thinning of the inner plexiform and inner nuclear layer were observed 7 days after 60 min of ischemia. Ischemic preconditioning for 5 min completely protected against the histological damage induced by 60 min of ischemia applied 24 hrs thereafter. Treatment of rats with aminoguanidine and L-N6-(1-iminoethyl) lysine, but not NG-nitro-L-arginine, NG-monomethyl-L-arginine or 7-nitroindazole, wiped off the protective effect of ischemic preconditioning. The inhibitory effect of aminoguanidine was abolished by L-arginine, but not D-arginine. The results in the present study suggest that NO synthesized by iNOS is involved in the histological protection by late ischemic preconditioning in rat retina.
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PMID:Inducible nitric oxide synthase inhibitors abolished histological protection by late ischemic preconditioning in rat retina. 1619 35

Keratoconus is an ocular condition that causes corneal thinning, cone formation and scarring. In view of a hypothesis that activated MMP-2 may initiate or facilitate disease progression, the MMP-2/TIMP systems of stromal cells derived from normal and keratoconic corneas have been compared. To achieve this, stromal cell cultures were established from normal, clear keratoconic (KCS-1) and scarred keratoconic (KCS-2) corneas. The secreted MMP-2 was assayed using [(3)H]Type IV collagen and analysed by zymography. Optimally maintained and nutrient deprived cells were subsequently incubated with [(3)H]lysine. The secreted radiolabelled macromolecules were separated and quantified. The results obtained indicated that optimally maintained KCS-1 stromal cells produced more MMP-2 than normal stromal cells but not TIMP. Nutrient deprivation induced MMP-2 activation and cell death. Surviving cells upregulated TIMP-1 synthesis and in this respect became similar to the KCS-2 stromal cells that did not excessively generate activated MMP-2 or die as a consequence of nutrient deprivation. From these results, it was concluded that KCS-1 stromal cells over-expressed MMP-2 without increasing TIMP production. This may facilitate MMP-2 activation in vivo and hence advance the keratoconic condition. KCS-2 cultures over-expressed both MMP-2 and TIMP-1. Because TIMP-1 inhibits MMP-2 activity and protects against cell death it may be of significance in initiating repair processes and curtailing keratoconus.
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PMID:Keratoconus: matrix metalloproteinase-2 activation and TIMP modulation. 1651 44


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