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Biomedical subjects

W Su

Publications and source records attributed to W Su.

At least 109 records · Page 6Linked to original sources

[Ultrastructural study of the extraocular muscles from congenital nystagmus].

OBJECTIVE: To study the pathogenesis of congenital nystagmus. METHODS: We observed the ultrastructure of extraocular muscles from congenital nystagmus patients with transmission electron microscope. RESULTS: As to extraocular muscle in congenital nystagmus of jerky type, there wre myofibrillae perpendicular to axes of myocytes within the myocytes in the quick phase side. This kind of myofibrillae had the structure of sarcomeres. In slow phase side, there were perpendicular myofibrillae in the periphery of myocytes and the adjacent nuclear region. There was dense nuclear matrix within myocytes and the membrane of nucleus was intact. With regard to pendular type of congenital nystagmus, there was no perpendicular myofibrillae within myocytes. The myofibrillae parallel to the axes of myocytes were arranged disorderly. The length of sarcomeres in different myofibrillar was not identical. Within myocytes of different types of congenital nystagmus, there was a large amount of mitochondria, in which the inner crest was arranged disorderly and there was vacuole formation. CONCLUSION: This study demonstrates that congenital nystagmus has the pathological basis of ultrastructural changes.

Adolescent↗

Denaturant unfolding of the ferric enterobactin receptor and ligand-induced stabilization studied by site-directed spin labeling.

FepA is an integral outer membrane protein that is the specific receptor for the siderophore, ferric enterobactin, and is thus primarily responsible for iron uptake in many Gram-negative bacteria. A site-specific mutant of FepA, containing a single introduced cysteine in the ligand-binding domain, was spin labeled and used to examine the denaturant-induced unfolding of this receptor with guanidine hydrochloride (Gdn-HCl) and urea. Electron spin resonance (ESR) spectra showed conversion of the spin label from a motionally-restricted, immobilized environment to a freely-accessible, rotationally-mobile state upon denaturation. Unfolding was also followed by nondenaturing polyacrylamide gel electrophoresis (PAGE), which is sensitive to loss of the putative transmembrane beta-structure, and displayed a similar concentration dependence. Unfolding occurred over relatively narrow ranges of denaturant concentration, indicating a high degree of cooperativity. Unfolding was fully reversible under the conditions employed. Rapid, spontaneous refolding occurred in the presence of Triton X-100 and did not require exogenous lipids. Refolding could be induced by either dialysis, dilution to low denaturant concentration, or ethanol precipitation. At ambient temperature the free energy of unfolding extrapolated to zero denaturant concentration (delta GU zero) was 6.24 +/- 0.63 kcal/mol. Values of delta GU zero obtained with Gdn-HCl and urea were in good agreement, as were values obtained from linear extrapolation and nonlinear regression fitting to a two-state equilibrium. This is the first report of a quantitative evaluation of the free energy of unfolding for an integral membrane protein.

Bacterial Outer Membrane Proteins↗

Association of Polyomavirus middle tumor antigen with phospholipase C-gamma 1.

Middle tumor antigen (MT) is the primary transforming protein of murine Polyomavirus. MT transforms by associating with and modulating the activities of cellular proteins involved in control of cell proliferation. MT binds to and is phosphorylated by cellular tyrosine kinases. The phosphorylated tyrosines become docking sites for SH2 (Src homology 2) domain-containing molecules. Tyrosine 322 of MT is known to be phosphorylated but has no known binding protein. We have found that phospholipase C-gamma 1 (PLC-gamma 1), a SH2 domain-containing protein, coimmunoprecipitates with MT. Tyrosine phosphorylation of PLC-gamma 1 is elevated in cells expressing MT, suggesting activation of this enzyme by MT. A Tyr-322-->Phe mutation in MT renders it defective in MT-PLC-gamma 1 interaction and in transformation. From the correlation between transformation and MT-PLC-gamma 1 interaction, we suggest that PLC-gamma 1 may play a role in transformation.

3T3 Cells↗

Demonstration of kappa 3-opioid receptors in the SH-SY5Y human neuroblastoma cell line.

In addition to the mu- and delta-opioid receptors previously reported, the SH-SY5Y human neuroblastoma cell line has high levels of kappa 3 receptors, accounting for 40% of total opioid binding, as measured with [3H]-diprenorphine binding. Competition studies reveal binding profiles for all three receptor classes that are similar to those observed in brain membranes. Differentiation with retinoic acid increases the levels of opioid receptor binding in the cell line, with the largest elevations in kappa 3 binding. Fully 75% of the increased binding corresponds to kappa 3 sites, which represent 50% of total opioid receptor binding in differentiated cells. Morphine inhibits forskolin-stimulated cyclic AMP accumulation, and this effect is readily blocked by the mu antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). Naloxone benzoylhydrazone, a kappa 3 agonist, inhibits forskolin-stimulated cyclic AMP accumulation more potently than morphine and is not reversed by CTAP. These studies indicate that SH-SY5Y cells contain high levels of functional kappa 3 receptors.

Binding Sites↗

Antisense oligodeoxynucleotides to the cloned delta receptor DOR-1: uptake, stability, and regulation of gene expression.

Phosphodiester antisense oligodeoxynucleotides (ODNs) directed against various domains of the cloned mouse delta receptor DOR-1 reduce delta-opioid receptor binding in vivo and in vitro. The present study examines the stability of an antisense ODN (275 nM) directed against the delta-opioid receptor and its effect on DOR-1 mRNA in cultured neuroblastoma cells and in vivo. When added to NG108-15 cells, much of the antisense ODN is degraded. However, > 1% is intact, associated with cells, and stable for at least 72 h. Northern blot analysis demonstrates that treatment of NG108-15 cells with the antisense ODN reduces the levels of a species of DOR-1 mRNA by approximately 25%. Similarly, intrathecal administration of the antisense ODN results in the accumulation of intact ODN within the spinal cord, which is stable for at least 72 h, although the levels of accumulation in vivo are lower than in vitro after either 4 or 72 h. Antisense ODN treatment lowers DOR-1 mRNA levels by approximately 25%. The loss of mRNA both in vivo and in vitro corresponds quite well to the decreases in receptor binding previously observed by our laboratory and is consistent with reduction of delta-opioid receptor protein in vitro as determined by western blot with a monoclonal antibody selective for the delta-opioid receptor. In conclusion, these studies indicate that a small, but significant, proportion of ODN is taken up by cells and remains intact for up to 72 h. This appears to be sufficient to down-regulate mRNA levels of delta-opioid receptors and their expression.

Animals↗

Polyoma middle tumor antigen interacts with SHC protein via the NPTY (Asn-Pro-Thr-Tyr) motif in middle tumor antigen.

Polyomavirus middle tumor antigen (MT) transforms a large number of cell types by binding to and modulating the activities of cellular proteins. Previous genetic analysis defined in MT an independent motif, NPTY (Asn-Pro-Thr-Tyr), required for transformation. This report demonstrates that NPTY is required for interaction between MT and SHC protein, a Src homology 2 (SH2)-containing protooncogene product implicated in activating Ras via association with GRB2 protein. SHC is phosphorylated on tyrosine and associates with GRB2 in MT-transformed cells. These effects require an intact NPTY motif in MT. SHC immunoprecipitates from MT-transformed cells possess kinase activity that phosphorylates not only SHC and MT but also the 85-kDa subunit of phosphatidylinositol 3-kinase. This result suggests that a complex exists that contains, at a minimum, MT, Src family tyrosine kinases, phosphatidylinositol 3-kinase, and SHC.

3T3 Cells↗

Mechanisms of Weight Loss following Intestinal Bypass Surgery.

Dramatic weight loss has been observed following intestinal bypass surgery. Initially, malabsorption was recognized as the major cause of weight loss. Only in recent years have investigators noted that the intestinal bypass could significantly reduce caloric intake, which largely or almost fully explains the weight loss following this procedure. The reduced energy intake as well as malabsorption are probably the major causes of weight loss after intestinal bypass surgery. Increased energy output has been proposed as a factor for weight loss, and more recently, it has been suggested that certain hormonal changes may play a role in regulating satiety and metabolic processes. This article examines these proposed factors that may impact on weight loss following intestinal bypass surgery.

Journal Article↗

Joint risks in a case-control study of esophageal cancer in Shanxi Province, People's Republic of China.

A multifactorial analysis on the etiology of esophageal cancer was conducted based on a case-control study conducted in Shanxi. The study analyzed the data of 326 cases and 396 controls. The joint risks of two factors were calculated from dichotomous distributions. Three models of factor combinations were assessed: (1) two risk-enhancing factors, (2) two risk-reducing factors, and (3) a risk-enhancing and a risk-reducing factor. The observed joint risks were in the neighborhood of the multiplicative products of single acting risks of individual factors. This was a uniform pattern across three models.

Adult↗

Biochemical and pharmacological characterization of mu, delta and kappa 3 opioid receptors expressed in BE(2)-C neuroblastoma cells.

Total opioid binding in the human neuroblastoma cell line BE(2)-C has a density similar to that found in brain, with a Bmax value of 383 +/- 60 fmol/mg protein and a KD of 0.4 +/- 0.07 nM for the nonselective opioid antagonist 3H-diprenorphine. Selective assays reveal a binding distribution of mu (38%), delta (16%) and kappa 3 (43%) opioid receptors. There is no observable kappa 1 or kappa 2 binding. The sum of the Bmax values in the selective binding assays (370 +/- 39 fmol/mg protein) approximates closely that observed with 3H-diprenorphine, suggesting that mu, delta and kappa 3 sites account for most of the binding. The binding selectivities of various opiates and opioid peptides in the BE(2)-C cells are similar to those in rat brain. Delta and mu binding are defined easily by traditional selective ligands. The binding profiles also distinguish clearly mu from kappa 3 binding. The selective mu ligand DAMGO competes with mu binding over 35-fold more potently than kappa 3 binding, whereas morphine shows a 10-fold selectivity. Functionally, selective mu, delta and kappa 3 agonists inhibit forskolin-stimulated cAMP accumulation through distinct receptor mechanisms that are pertussis toxin-sensitive. In addition to demonstrating that BE(2)-C cells provide a useful model system for studying mu, kappa 3 and delta receptors, these studies confirm that kappa 3 receptors represent a pharmacologically distinct receptor class in this cell line.

Animals↗

The influence of hydration on the conformation of lysozyme studied by solid-state 13C-NMR spectroscopy.

13C proton decoupled cross-polarization magic-angle spinning nmr spectra of lysozyme are reported as a function of hydration. Increases in hydration level enhance the resolution of the spectra, particularly in the aliphatic region, but has no significant effect on either the rotating frame proton spin-lattice relaxation time or the cross-relaxation time. The enhancement in spectral resolution with hydration is attributed to a decrease in the distribution of isotropic chemical shifts, which reflects a decrease in the distribution of conformational states sampled by the protein. Changes in the distribution of isotropic chemical shifts occur after the addition of water to the charged groups as coverage of the polar side chains and peptide groups takes place. The onset of this behavior occurs at a hydration level of about 0.1-0.2 g water/g protein and is largely complete at about 0.3 g water/g protein, the same hydration range where changes in the heat capacity are observed. That hydrogen exchange of buried protons can occur at hydration levels significantly lower than those at which changes in the distribution of conformational states are first observed suggests that some motions that mediate exchange are already present in the dry protein. The preservation of efficient dipolar coupling indicates that the conformational rearrangements that do occur on hydration are small and do not involve any significant overall expansion of free volume or weakening of interactions that would increase the reorientational freedom of protein groups.

Animals↗

The influence of hydration on the conformation of bovine serum albumin studied by solid-state 13C-NMR spectroscopy.

13C proton-decoupled cross-polarization magic-angle spinning nmr spectra of bovine serum albumin are reported as a function of hydration. Increases in hydration level enhance the resolution of the peak centered at about 40 ppm but has little or no effect on the other spectral peaks. Hydration has little effect on either the rotating frame proton spin-lattice relaxation time or the cross-relaxation time for any of the peaks, suggesting that the efficiency of dipolar coupling is largely preserved on hydration of the protein. Resolution enhancement of the peak at 40 ppm is not understood, but possible sources of the behavior include a decrease in the line width of contributing resonances from lysine epsilon carbons due to increased motional averaging on hydration, reordering of disulfide bridges, and titration shifts induced by hydration. Hydration of bovine serum albumin appears to have little effect on the distribution of conformations sampled by the protein so that the broad distribution of conformations observed in the dry state is also observed in the fully hydrated state. This is in contrast to lysozyme where significant ordering of the conformation is seen on hydration.

Animals↗

Dietary fatty acid composition influences energy accretion in rats.

To study the influence of dietary fatty acid composition on energy metabolism, forty male rats were fed elemental diets containing 42% of energy as fish oil, safflower oil, olive oil or beef tallow for 12 wk. Food intakes and body weights were measured daily. Energy expenditure and body composition were determined using doubly labeled water on the final 2 d. Pooled fecal energy losses differed in response to dietary manipulation, with losses greatest in rats fed beef tallow and least in those fed olive oil. Higher lean body mass gains and lower fat mass gains were observed in rats fed diets containing fish oil, compared with rats fed olive oil or beef tallow. Total energy gains in rats fed olive oil (3632 +/- 145 kJ) and beef tallow (3850 +/- 136 kJ) were higher than those in rats fed fish oil (2905 +/- 196 kJ). Energy efficiency in both the olive oil and beef tallow groups was also higher than that in the fish oil group. There were no differences in energy expenditure measured by doubly labeled water technique among the four groups. The data suggest that dietary fatty acid composition alters the efficiency of energy substrate accretion in rats.

Adipose Tissue↗

Methyl jasmonate inhibition of root growth and induction of a leaf protein are decreased in an Arabidopsis thaliana mutant.

Jasmonic acid and its methyl ester, methyl jasmonate (MeJA), are plant signaling molecules that affect plant growth and gene expression. Primary root growth of wild-type Arabidopsis thaliana seedlings was inhibited 50% when seedlings were grown on agar medium containing 0.1 M MeJA. An ethyl methanesulfonate mutant (jar1) with decreased sensitivity to MeJA inhibition of root elongation was isolated and characterized. Genetic data indicated the trait was recessive and controlled by a single Mendelian factor. MeJA-induced polypeptides were detected in Arabidopsis leaves by antiserum to a MeJA-inducible vegetative storage protein from soybean. The induction of these proteins by MeJA in the mutant was at least 4-fold less in jar1 compared to wild type. In contrast, seeds of jar1 plants were more sensitive than wild type to inhibition of germination by abscisic acid. These results suggest that the defect in jar1 affects a general jasmonate response pathway, which may regulate multiple genes in different plant organs.

Journal Article↗

Esophageal cancer in Shanxi Province, People's Republic of China: a case-control study in high and moderate risk areas.

Dietary, smoking, and drinking habits, as well as sociopsychological factors and familial history, were investigated in a case-control study on the etiology of esophageal cancer (EC) in two areas of Shanxi (Yangcheng and Linfen), north central China. Data were analyzed from 326 cases and 396 controls. We identified several factors associated with high or low risk; some were common across the areas and others were area-specific. Consumption of millet gruel was associated positively with EC, in a dose-response relationship. An increase in EC risk was seen for consumption of millet soup with noodles, and also with certain sociopsychological factors, in both areas. A large increase in risk was found with consumption of boiled vegetables in Linfen, with a dose-response relationship. EC risk tended to become greater with the increasing intake of moldy foods and of pickled vegetable juice. A positive association between EC risk and family history of EC was observed only in Yangcheng. Soybean consumption was found to be associated with reduced risk. Dental hygiene (brushing teeth) was associated with reduced risk in Linfen. There was a suggestion of increased risk associated with heavy tobacco smoking, but it was not significant in either area. Alcohol consumption had a marginally significant association with risk in the high risk area, but not in Linfen.

Adult↗

A Single Genetic Locus, Ckr1, Defines Arabidopsis Mutants in which Root Growth Is Resistant to Low Concentrations of Cytokinin.

Arabidopsis mutants resistant to cytokinin (benzyladenine [BA]) have been isolated with the intent to find plants defective in cytokinin perception or response. At low concentrations, BA produces a "cytokinin root syndrome" in which primary root elongation is inhibited, but root hair elongation is stimulated. Five independent mutants that did not express this syndrome in the presence of BA were selected. All five mutants were recessive, and crosses between them indicated that they were in the same complementation group. The genetic locus represented by these mutations has been designated ckr1 and mapped to chromosome 5.

Journal Article↗

The study of G6PD in erythrocyte and lens in senile and presenile cataract.

The G6PD activity of erythrocytes in 113 male patients with senile and presenile cataract and 86 controls, and G6PD activity of lens in 30 patients with senile cataract and 42 controls were reported. The cataractous group had higher frequency of G6PD deficiency and lower average G6PD level in erythrocytes and lenses, but without statistical significance. The frequency of G6PD deficiency of erythrocytes in presenile cataractous group was higher than that of senile cataractous group but with no statistical significance too. However, the average G6PD level of erythrocytes in presenile cataractous group was lower than that of senile cataractous group and with statistical significance (P < 0.05). The G6PD activity of lenses only presenile in the cortex and have a positive correlation with that of erythrocytes. There was a case with deficiency of G6PD both of erythrocytes and cataractous lenses in both eyes. The results indicate that the deficiency of G6PD might be one of the cataractous pathogenetic factor for presenile cataract. Measurement of G6PD activity of erythrocytes among population might be of significance in finding the risk factor for cataract.

Adult↗

[Roles of T cell subsets in the protective immunity of mice against Plasmodium yoelii].

BALB/c mice which had developed protective immunity against Plasmodium yoelii (P. y.) challenge were injected with anti-CD4 or anti-CD8 monoclonal antibody, and were then challenged again with P. yoelli. No impairment of protection was observed. CD8+T cells obtained from spleens of these mice were transferred to BALB/c nude mice and induced partial protection, while transfer of CD4+T cells did not so. In P. yoelli-mouse model, the parasites invaded reticulocytes in the early infection, and the infected reticulocytes could be recognized and attacked by sensitized CD8+T cells. In late infection when P. yoelli also invaded mature erythrocytes, the protective effect of CD8+T cells decreased and the main role of protection was played by antibodies.

Animals↗

Changes in hemorrheology in urticaria.

Hemorrheology was studied in 41 cases of urticaria, and platelet aggregation function in 37 cases. The whole blood viscosity in low shearing stress, plasma viscosity, fibrinogen level and platelet aggregation were found to be markedly increased (P less than 0.05 - P less than 0.005). The cause of high blood viscosity is discussed. It is considered as the results of high plasma viscosity and increased RBC aggregation. The hemorrheological changes coincided with the hemodynamic changes seen in cutaneous microcirculation: slow granular blood stream, and aggregation of erythrocytes.

Adult↗