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)

Methyl n-butyl ketone (MBK) is known to produce a giant axonal neuropathy in man and experimental animals characterized pathologically by a gradual increase in the number of neurofilaments which become associated with focal areas of axonal swelling and thinning of the myelin sheath. Fast axoplasmic transport was studied in rats exposed to MBK. In 10 severely paralyzed rats exposed to MBK there was a significant impediment of fast axoplasmic transport following dorsal root ganglion injections (x +/- S.D. = 283.2 +/- 20.34 mm/day) compared to normal controls (417.6 +/- 23.78 mm/day). In rats undergoing injections into the ventral horn of the spinal cord there was a gradual impairment of the mean down flow rate for transport of [3H]leucine which correlated with the severity of the MBK induced neuropathy. Quantitative morphological determinations showed that the total number of neurotubules per unit cross-sectional myelin area and the number of neurotubules associated with mitochondria in swollen axons was unchanged from normal. The total number of mitochondria in randomly sampled axons varied significantly from controls but the absolute number of mitochondria associated with neurotubules was unchanged from normal. The results of these studies suggest that the impediment of fast axoplasmic transport may be related to the increased neurofilaments producing focal areas of axonal blockage.
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PMID:Alterations of fast axoplasmic transport in experimental methyl n-butyl ketone neuropathy. 7 Nov 85

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 retinal changes of a mutant strain of goldfish with megalophthalmia were studied by histology, electron microscopy and biochemistry. Changes in the morphology of the pigment epithelium, decrease in number of photoreceptors, thinning out of retinal layers and the existence of spaces in the retina were all features as the eyes grew in size. Invasion of macrophages was also evident in the retina. A decrease in leucine uptake per milligram of retina was also detected as the eye grew beyond 0.8 millilitre in volume. These changes, although related to volume changes (i.e., growth) of the eyes, were found to have little relationship with increase of intraocular pressure as intraocular pressures in the growing eyes of the mutant strain did not change much. Goldfish from a control strain with similar eye volumes and sizes (ages) were used for comparison and similar changes as in the mutant were not apparent.
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PMID:Retinal changes in a mutant form of goldfish with megalophthalmia. 194 41

We report a patient with hyperkeratosis lenticularis perstans (HLP) manifesting as multiple reddish-brown hyperkeratotic papules on the lower extremities. Typical histologic features of HLP include hyperkeratosis, thinning or absence of the granular layer and a band-like infiltrate in the upper dermis underlying an atrophic epidermis. In order to determine the cellular composition of the infiltrate, skin biopsy specimens were studied immunohistochemically using a series of commercially available monoclonal antibodies. The dermal infiltrate consists predominantly of helper/inducer T cells (Leu-4+, Leu-3a+). Suppressor/cytotoxic T cells (Leu-2a+) were fewer at the periphery of the infiltrate. The majority of T cells were activated as they expressed HLA-DR-antigen. Large numbers of Leu-6+ Langerhans' cells were observed at the dermo-epidermal interface. Few natural killer cells (Leu-11b+) were noted within the dermal infiltrate. These findings support the hypothesis than an active cellular immune reaction involving the epidermis is of pathogenic importance for HLP.
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PMID:Hyperkeratosis lenticularis perstans (Flegel's disease). In situ characterization of T cell subsets and Langerhans' cells. 245 81

Transplacental exposure to the DNA alkylating agent N-methyl-N-nitrosourea on day 16 of gestation in CD-1 albino mice induces a degeneration of the retina, the severity of which depends upon the dosage level of the drug. A 1 mg kg-1 dose provokes a progressive retinal degeneration in the offspring which begins at about 4-6 weeks of age and is characterized by gradual thinning of the retinal layers. A 15 mg kg-1 dosage of MNU provokes severe retinal dysplasia characterized morphologically by rosettes in the outer nuclear layer and loss of rod outer segments (ROS). In the present biochemical experiments, retinal protein synthesis was examined in mice 2-, 4-, and 6 weeks of age exposed to 1 mg kg-1 MNU and 2- and 5 weeks of age exposed to 15 mg kg-1 MNU. Phospholipid synthesis was examined in mice 2-, 4-, 6- and 12 weeks of age exposed to 1 mg kg-1 MNU and at 2 weeks in mice exposed to 15 mg kg-1 MNU. Retinas were incubated for 2 hr at 37 degrees C in media supplemented with either [3H]leucine for protein synthesis studies or [3H]glycerol for phospholipid synthesis experiments. Aliquots of crude ROS and the retinal debris were taken for protein determination, scintillation counting, SDS-PAGE separation of labeled opsin, phosphorus determination and TLC separation of phospholipids. Results indicated that mice exposed to 1 mg kg-1 MNU did not differ significantly from age-matched controls in these measurements, whereas mice exposed to 15 mg kg-1 MNU were significantly different from controls. These results suggest that even as early as 2 weeks of age protein and lipid metabolism are adversely affected in mice exposed to the higher dose of the alkylating agent at a critical time in retinal development, but general protein and lipid synthesis is not affected in animals exposed to 1 mg kg-1 MNU at least up to 12 weeks of age. These studies suggest further investigation of more subtle derangement in the retinal function in animals exposed to low levels of MNU.
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PMID:Biochemical characterization of retinal protein and phospholipid synthesis in mice exposed transplacentally to N-methyl-N-nitrosourea. 319 72

The effect of dietary thiamin deficiency has been studied on intestinal functions and chemical composition of brush border membranes in rats. Intestinal uptake of glucose, glycine, alanine, and leucine was significantly stimulated in thiamin deficiency compared to pair-fed control group. Studies with glucose and glycine revealed that stimulation of the absorption process occurs only in the presence of Na+ but not in its absence. Km measured in the presence of 140 mM Na+ for glucose and glycine uptakes was reduced by 56 and 41%, respectively, but Vmax remained unaltered in vitamin deficiency. There was no change in these parameters in Na+-free medium (Km = 31.3 and 23.3 mM; Vmax = 17.2 to 19.7 and 13.5 to 16.4 mumol/10 min/g wet tissue, respectively) under these conditions. The activities of brush border sucrase, lactase, maltase, alkaline phosphatase, and leucine aminopeptidase were reduced by 42 to 66% in thiamin deficiency, compared to pair-fed controls. Kinetic studies with sucrase and alkaline phosphatase evinced that a decrease in Vmax (61 and 64%, respectively) with no change in Km (33.8 and 4.3 mM, respectively) was responsible for observed impairment in the enzyme activities in thiamin deficiency. Microvillus membrane proteins expressed on dry membrane basis were reduced by 20% in thiamin-deficient intestine. There was no difference in membrane sialic acid, cholesterol, phospholipids, and triglycerides fractions under these conditions. It is suggested that thinning of the microvillus membrane may be implicated in observed aberrations of intestinal functions in thiamin-deprived animals.
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PMID:Effect of dietary thiamin deficiency on intestinal functions in rats. 646 54

Decorin (dcn) and biglycan (bgn), two members of the family of small leucine-rich proteoglycans (SLRPs), are the predominant proteoglycans expressed in skin and bone, respectively. Targeted disruption of the dcn gene results in skin laxity and fragility, whereas disruption of the bgn gene results in reduced skeletal growth and bone mass leading to generalized osteopenia, particularly in older animals. Here, we report that bgn deficiency leads to structural abnormality in collagen fibrils in bone, dermis, and tendon, and to a "subclinical" cutaneous phenotype with thinning of the dermis but without overt skin fragility. A comparative ultrastructural study of different tissues from bgn- and dcn-deficient mice revealed that bgn and dcn deficiency have similar effects on collagen fibril structure in the dermis but not in bone. Ultrastructural and phenotypic analysis of newly generated bgn/dcn double-knockout (KO) mice revealed that the effects of dcn and bgn deficiency are additive in the dermis and synergistic in bone. Severe skin fragility and marked osteopenia characterize the phenotype of double-KO animals in which progeroid changes are observed also in the skin. Ultrastructural analysis of bone collagen fibrils in bone of double-KO mice reveals a complete loss of the basic fibril geometry with the emergence of marked "serrated fibril" morphology. The phenotype of the double-KO animal mimics directly the rare progeroid variant of human Ehlers-Danlos syndrome (EDS), in which skin fragility, progeroid changes in the skin (reduced hypodermis), and osteopenia concur as a result of impaired glycosaminoglycan (GAG) linking to bgn and dcn core proteins. Our data show that changes in collagen fibril morphology reminiscent of those occurring in the varied spectrum of human EDS are induced by both bgn deficiency and den deficiency in mice. The effects of an individual SLRP deficiency are tissue specific, and the expression of a gross phenotype depends on multiple variables including level of expression of individual SLRPs in different tissues and synergisms between different SLRPs (and likely other macromolecules) in determining matrix structure and functional properties.
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PMID:Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues. 1210 52

The clinical features and course of cardiac involvement in a patient with maternally inherited diabetes and deafness associated with the mitochondrial DNA 3243 mutation are reported. A 45-year-old woman with maternally transmitted diabetes mellitus and deafness presented with congestive heart failure. The patient showed a short P-R interval on electrocardiogram (ECG) and had developed progression from left ventricular hypertrophy to a hypokinetic cardiomyopathy pattern over the course of 10 months. Rapid cardiac change was accompanied by left ventricular remodeling, as shown by wall thinning on echocardiogram and decrease in QRS voltages on ECG. Coronary arteriography revealed no significant stenosis. In the endomyocardial biopsy specimens, light microscopy showed nonspecific cardiomyopathic changes. Genetic testing for mitochondrial DNA mutations in peripheral blood lymphocytes revealed an adenine (A)-to-guanine (G) substitution at nucleotide 3243 in the mitochondrial DNA encoding the transfer RNA for leucine (tRNA Leu (UUR)). The proportion of mutant mitochondrial DNA was 25%. Two of the patient's daughters, aged 13 and 21 years, who were symptom free, were found to carry the same point mutation. A short P-R interval on ECG in the younger of them was the sole manifestation of the mutation. Unfortunately, 6 months after diagnosis, the patient died suddenly at home. Accelerated cardiomyopathy can occur as a mitochondria-related complication in patients with maternally inherited diabetes and deafness associated with the 3243 mutation.
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PMID:Accelerated cardiomyopathy in maternally inherited diabetes and deafness. 1557 73

Gly-Leu-Phe (GLF), an immunostimulating peptide derived from alpha-lactalbumin, prevented alopecia induced by an anticancer agent etoposide in a neonatal rat model after intraperitoneal injection at a dose of 100 mg/kg for 4 d or oral administration at a dose of 300 mg/kg for 6 d. By microscopic analysis of skin sections, GLF proved to inhibit etoposide-induced loss of hair, thickening of the epidermis, and thinning of the adipocyte layer. The anti-alopecia effect of GLF was inhibited by pyrilamine, a histamine H1 receptor antagonist, suggesting that the anti-alopecia effect is mediated by histamine release.
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PMID:Anti-alopecia effect of Gly-Leu-Phe, an immunostimulating peptide derived from alpha-lactalbumin. 1611

Peptidyl-glycine-leucine-carboxyamide (PGLa), isolated from granular skin glands of Xenopus laevis, is practically devoid of secondary structure in aqueous solution and in the presence of zwitterionic phospholipids, when added exogenously, but adopts an alpha-helix in the presence of anionic lipids. The peptide was shown to exhibit antifungal activity and to have antimicrobial activity towards both Gram-negative and Gram-positive bacteria. As a broad variety of peptides is found in the secretions of amphibian skin combinatorial treatment of PGLa and magainin 2 was studied showing enhanced activity by a heterodimer formation. Thus production of mutually recognizing peptides seems to be an effective way in nature to increase selective membrane activity. Biophysical studies on membrane mimics demonstrated that PGLa can discriminate between different lipid species, preferentially interacting with negatively charged lipids, which are major components of bacterial but not mammalian cell membranes. This emphasizes the role of electrostatic interactions as a major determinant to trigger the affinity of antimicrobial peptides towards bacterial membranes. PGLa induced the formation of a quasi-interdigitated phase in phosphatidylglycerol bilayers below their chain melting transition, which is due to the creation of voids below the peptide being aligned parallel to the membrane surface. In the fluid phase of phosphatidylglycerol the peptide inserts perpendicularly into the bilayer above a threshold concentration, which results in a hydrophobic mismatch of the peptide length and bilayer core for lipids< or =C16. This mismatch is compensated by stretching of the acyl chains and in turn thickening of the bilayer demonstrating that membrane thinning cannot be taken generally as the hallmark of pore formation by antimicrobial peptides. Furthermore, PGLa was shown to affect membrane curvature strain of phosphatidylethanolamine, another main lipid component of bacterial membranes, where a cubic phase coexists with the fluid bilayer phase. Investigations on living Escherichia coli showed distinct changes in cell envelope morphology, when treated with the peptide. In a first stage loss of surface stiffness and consequently of topographic features was observed, followed in a second stage by permeabilization of the outer membrane and rupture of the inner (cytoplasmic) membrane supposedly by the mechanism(s) derived from model studies.
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PMID:Biological activity and structural aspects of PGLa interaction with membrane mimetic systems. 1948 33


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