Spatial dark-soliton stripes and grids in self-defocusing materials.
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Biomedical subjects
Publications and source records attributed to H Yin.
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The fraction of polymerized actin in human blood neutrophils increases after exposure to formyl-methionyl-leucyl-phenylalanine (fmlp), is maximal 10 s after peptide addition, and decreases after 300 s. Most of the gelsolin (85 +/- 11%) in resting ficoll-hypaque (FH)-purified neutrophils is in an EGTA resistant, 1:1 gelsolin-actin complex, and, within 5 s after 10(-7) M fmlp activation, the amount of gelsolin complexed with actin decreases to 42 +/- 12%. Reversal of gelsolin binding to actin occurs concurrently with an increase in F-actin content, and the appearance of barbed-end nucleating activity. The rate of dissociation of EGTA resistant, 1:1 gelsolin-actin complexes is more rapid in cells exposed to 10(-7) M fmlp than in cells exposed to 10(-9) M fmlp, and the extent of dissociation 10 s after activation depends upon the fmlp concentration. Furthermore, 300 s after fmlp activation when F-actin content is decreasing, gelsolin reassociates with actin as evidenced by an increase in the amount of EGTA resistant, 1:1 gelsolin-actin complex. Since fmlp induces barbed end actin polymerization in neutrophils and since in vitro the gelsolin-actin complex caps the barbed ends of actin filaments and blocks their growth, the data suggests that in FH neutrophils fmlp-induced actin polymerization could be initiated by the reversal of gelsolin binding to actin and the uncapping of actin filaments or nuclei. The data shows that formation and dissociation of gelsolin-actin complexes, together with the effects of other actin regulatory proteins, are important steps in the regulation of actin polymerization in neutrophils. Finally, finding increased amounts of gelsolin-actin complex in basal FH cells and dissociation of the complex in fmlp-activated cells suggests a mechanism by which fmlp can cause actin polymerization without an acute increase in cytosolic Ca++.
Histologic examination was made of 1,419 globes from domestic animals (964 dogs, 374 cats, 41 horses, and 40 cattle) with ocular disease; pre-iridal membranes (rubeosis iridis) were found in 98. The membranes originated as endothelial budding from the anterior iridal stroma and seemed to mature into fibrous or fibrovascular membranes that were often followed by hyphema or, occasionally, glaucoma. Pre-existent disease in the 98 affected globes included chronic endophthalmitis (27/98), chronic glaucoma (24/98), anterior uveal melanoma (15/98), ciliary body adenoma (14/98), neoplasms metastatic to the eye (8/98), and chronic retinal detachment (6/98). In terms of likelihood of occurrence, pre-iridal membranes seen in 21% (6/21) of globes with retinal detachment, 19% (14/75) of those with ciliary body adenomas, 14% (24/167) of those with chronic glaucoma, and 10% (15/158) of those with anterior uveal melanoma. They were detected with greatest relative frequency in horses (9/41) followed by dogs (83/964), cats (5/374) and cattle (1/40). These membranes, which are rarely detected by clinical examination, probably form in response to angiogenic factors released by ischemic retina, by neoplasms, or by leukocytes involved in ocular inflammation.
1,351 specimens resected surgically from 100 patients with gastric carcinoma were studied with PAP immunoperoxidase and ultrastructural method. The tumor cells were found positive for gastrin, serotonin, somatostatin and argyrophil particles in 19 patients. Among them the gastrin-secreting tumor cells consisted of 50% of the total in 4 cases, representing a separate new subtype, neuro-endocrine (NE) gastric carcinoma. Of the 100 cases, 16 (32%) contained NE cells among 50 undifferentiated type, while only 3 cases (6%) contained NE cells among the remaining 50 cases, the well-differentiated type. These results suggest that the appearance of NE tumor cells is closely correlated with the degree of differentiation of cancer, and confirms theoretically the heterogenicity of gastric carcinoma, and further supports the concept that exocrine and endocrine type gastric cancer cells are isogenous, i.e., from the endodermal stem cells.
The physical, achievement, and personality characteristics of Chinese schoolchildren are evaluated. The results of two surveys of Chinese schoolchildren, conducted in Beijing and Jilin Province, are presented. In the Beijing sample, the differences between only children and others were small but statistically significant, with the only children having higher scores in achievement and physical size. In the Jilin Province sample, the differences between only children and others were also small but significant. These differences were found entirely in physical characteristics, with only children being smaller, perhaps because the only children in the Jilin sample were much younger than the non-only children. Analyses of the combined sample of Beijing and Jilin schoolchildren indicated that the only-child advantages in achievement were found among children from urban families, not rural peasant families. While significant differences in height and weight were found in all three samples, none of the results indicated a significant difference in the proportion of body fat. None of the analyses indicated that only children had undesirable personalities, as judged by teachers and mothers.
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In the Tsukamoto-French model, ethanol causes an important 10-20-fold induction of ethanol-inducible cytochrome P4502E1 (CYP2E1), mediated through enzyme stabilization and increased rate of gene transcription. The CYP2E1 induction results in a pronounced increase in the rate of NADPH-dependent microsomal lipid peroxidation, an elevation which is not seen after simultaneous administration of the CYP2E1 inhibitor diallylsulfide. Increased amounts of lipid peroxides are seen in plasma and red blood cells of both rats and humans during high ethanol intake. A mechanism for ethanol-dependent liver damage is proposed which involves the CYP2E1-dependent lipid peroxide formation, either directly by its capability to induce NADPH-dependent peroxidation in the microsomal membranes or indirectly by a hypoxia-mediated transformation of xanthine dehydrogenase to xanthine oxidase, in activation of Ito cells and Kupffer cells to yield cytokine and collagen production. The CYP2E1 gene is polymorphic among Caucasians. Four different unrelated or partially linked polymorphisms have been observed. One polymorphism in the 5'-flanking region has been described to be associated with altered enzyme expression in vitro, and the rare allele was found to be less frequent among Swedish patients having lung cancer when compared to two different control groups. Another polymorphism, detectable with Dra I restriction endonuclease fragment length polymorphism (RFLP), was localized to intron 6, and the rare allele was less common among Italian alcoholics with clinical signs of liver cirrhosis, as compared to controls. Several other mutations in the CYP2E1 gene were found to be associated with this allele. However, further research is needed to relate the CYP2E1 gene polymorphism with incidence of liver cirrhosis.
The chlorofluorocarbon substitute 1,2-dichloro-1,1-difluoroethane (HCFC-132b) undergoes oxidative metabolism in rats to give a range of metabolites, including chlorodifluoroacetaldehyde [Harris and Anders (1991) Chem. Res. Toxicol. 4, 180]. The present experiments were undertaken after studies to characterize an unidentified metabolite of HCFC-132b revealed that chlorodifluoroacetaldehyde was toxic in vivo: rats given chlorodifluoroacetaldehyde died showing signs of cholinergic stimulation. Because some fluoroketones are known inhibitors of hydrolases, including acetylcholinesterase, the inhibitory effects of chlorodifluoroacetaldehyde on acetylcholinesterase (electric eel and human erythrocyte), on pseudocholinesterase (horse serum), on carboxylesterase (pig liver), and on alpha-chymotrypsin (bovine pancreas) were studied. In aqueous solution, the ratio chlorodifluoroacetaldehyde:chlorodifluroacetaldehyde hydrate, as determined by 1H nuclear magnetic resonance spectroscopy, was 1:157. Chlorodifluoroacetaldehyde was a slow-binding inhibitor of both acetylcholinesterases, of pseudocholinesterase, and of carboxylesterase; the Ki values, corrected for the aldehyde:hydrate ratio, were 150 nM, 1.7 nM, 3.7 nM, and 23 pM, respectively, as determined by final velocity of the progress curves; the kon values were 9.1 x 10(4), 1.1 x 10(5), 3.2 x 10(4), and 9.2 x 10(5) M-1 min-1, respectively. Chlorodifluoroacetaldehyde did not inhibit alpha-chymotrypsin. Acetaldehyde and trichloroacetaldehyde were classical competitive inhibitors of acetylcholinesterase. These results show that hydrochlorofluorocarbon metabolites may exert significant biological effects.
Trihaloacetaldehydes are used as sedatives, are key intermediates in the metabolism of 1,1,1,2-tetrahaloethanes, some of which are chlorofluorocarbon substitutes, and are metabolites of trihaloethanols, which are intestinal and bone marrow toxins. In the present study, trifluoroacetaldehyde was used as a model to examine the reactions of trihaloacetaldehydes with cellular nucleophiles, including amino acids, nucleotides, and lipid components. Reaction of trifluoroacetaldehyde hydrate (10 mM) with amino acids (100 mM) in buffer at pH 7.0 and 30 degrees C showed that only L-cysteine formed stable adducts, which were identified as (2R,4R)- and (2S,4R)-2-(trifluoromethyl)thiazolidine-4-carboxylic acid. The absolute stereochemistry of (2R,4R)- and (2S,4R)-2-(trifluoromethyl)thiazolidine-4-carboxylic acid was determined by homonuclear Overhauser effect experiments. The diastereoisomers were formed in a 2.8:1 ratio at 37 degrees C and in a 1:4.0 ratio at 80 degrees C. Trifluoroacetaldehyde also reacted with L-cysteine methyl ester and 2-mercaptoethylamine to form stable thiazolidine derivatives, but did not react with N-acetyl-L-cysteine. The reaction of trifluoroacetaldehyde with the amino groups of ATP, GMP, CMP, L-citrulline, and urea resulted in the formation of stable imines. TMP, which lacks an exocyclic amino group, did not react. Glutathione reacted with trifluoroacetaldehyde to form (2R,5R)- and (2S,5R)-5-amino-6-[carboxymethyl)imino]-2-(trifluoromethyl)-1,3- oxathiane, whose formation was accompanied by simultaneous cleavage of the glutamyl moiety. The reactivity of nucleophilic groups with trifluoroacetaldehyde follows the order SH > NH2 > OH. The results of the present study indicate that trifluoroacetaldehyde covalently modifies cellular nucleophiles. The biological significance of these reactions warrants further investigation. The reaction of trifluoroacetaldehyde with L-cysteine and glutathione may afford routes for the stereoselective synthesis of cysteine prodrugs and five- or six-membered heterocyclic compounds.
1,2-Dichloro-1-fluoroethane (HCFC-141) and 1,1,2-trichloro-2-fluoroethane (HCFC-131) were chosen as models to study the regioselectivity of halogenated alkane metabolism. Metabolites in the urine of rats given HCFC-131 ip were the following: inorganic fluoride, chlorofluoroacetic acid, dichloroacetic acid, N-(2-hydroxyethyl)chlorofluoroacetamide, and three unidentified minor metabolites. In vitro incubation of HCFC-131 with either rat liver microsomes from pyridine-treated rats or expressed human cytochrome P450 2E1 isozyme in the presence of NADPH gave fluoride, chlorofluoroacetic acid, and dichloroacetic acid as metabolites. HCFC-141 was biotransformed in rats to inorganic fluoride, chlorofluoroacetic acid, 2-chloro-2-fluoroethanol, and 2-chloro-2-fluoroethyl glucuronide, which were detected in urine. Incubation of HCFC-141 with NADPH-fortified liver microsomes from pyridine-induced rats or expressed human cytochrome P450 2E1 afforded fluoride, chlorofluoroacetaldehyde hydrate, and chloroacetic acid as products. The metabolites identified were consistent with a cytochrome P450-dependent oxidation mechanism. The data also indicated that phosphatidylethanolamine may be a cellular target for chlorofluoroacetyl chloride, a reactive intermediate generated from HCFC-131 by cytochrome P450-dependent oxidation. Chlorofluoroacetic acid given to rats ip was largely recovered in the rat urine, although the formation of inorganic fluoride as a metabolite was observed. The mechanism of defluorination of chlorofluoroacetic acid is not clear. Regioselective oxidation by cytochrome P450 was observed between the two potential oxidizable sites in HCFC-141 and in HCFC-131. Comparison of the observed ratio of oxidation at different sites in in vitro experiments with the calculated activation energies for hydrogen-atom abstraction from these sites indicated that electronic factors are the primary determinant of regioselectivity. In vivo regioselectivity could not be compared with theory since this ratio does not reflect the true regioselectivity due to differences in excretion, reabsorption, secondary metabolism (e.g., fluoride generation from chlorofluoroacetic acid), other routes of fluoride formation, and limitation of the method of detection.
An analysis of 121 cases of cervical spondylotic myelopathy treated by anterior excision of the disc and fusion was undertaken. All patients were followed at least six months, and follow-up averaged 22 months. Results showed that 97.5% of patients had no aggravation of symptoms, 90.9% were improved, and 72.6% were able to resume normal activity. Surgical intervention can greatly improve the prospects of patients with severe cervical spondylotic myelopathy, and its use should not be lightly ruled out. Autografts yield higher fusion rates and better overall results than homografts. Selection of the number and level of discs to be excised depends upon clinical and roentgenographic indications, as well as the myelogram and the amount of fluid injected into the discs.