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Biomedical subjects

W Sha

Publications and source records attributed to W Sha.

18 recordsLinked to original sources

[Biofeedback for urinary bladder dysfunctions in childhood. Indications, practice and the results of therapy].

In children, abnormal behavior during micturition, i.e. detrusor/sphincter dyscoordination, causes persistent voiding problems, urinary incontinence and/or recurrent urinary tract infections in up to 15% of cases. Contractions of the external urethral sphincter during micturition lead to functional subvesical obstruction. Nowadays, biofeedback training is the most suitable therapy. Biofeedback training for children is based on the assumption that relaxation and contraction of the urinary external sphincter is a habitual phenomenon and can be restored. With specially developed, computer-assisted biofeedback programs, sphincter contraction and relaxation can be transformed into acoustic or visual signals. Acoustic or optical feedback indicates relaxation and contraction control to the patient. The residual urine volume should subsequently be assessed. The results should be reviewed after each micturition. Poor compliance sometimes makes biofeedback training impossible. Further biofeedback training at home is a reasonable suggestion. Good results-a response rate of up to 90%-demonstrates that biofeedback training is successful in the treatment of detrusor-sphincter dyscoordination. After effective therapy, associated urinary tract infections and vesicoureterorenal reflux may disappear.

Biofeedback, Psychology↗

In situ high temperature microscopy study of the surface oxidation and phase transformations in titanium alloys.

Two popular commercial titanium alloys, Ti-6Al-4V and Ti-6Al-2Sn-4Zr-2Mo-0.08Si, were used for in situ high temperature microscopy study. The experiments were performed on an optical microscope equipped with high temperature stage using both normal and florescence lights. Two kinds of experiments were performed, at continuous heating/cooling with different rates and in isothermal conditions at different temperatures. The changes taking place on the sample surface during the experiments were monitored. The morphology of the alpha ==> beta ==> alpha phase transformation was recorded at different heat treatment conditions using the effect of thermal etching. An effect of sample surface oxidation and deoxidation was observed during continuous heating. The appearance and disappearance of ordered titanium oxides Ti3O and Ti2O are discussed based on the phase equilibrium diagram. The kinetics of the surface oxidation was monitored in both isothermal and continuous cooling conditions.

Microscopy↗

[Effect of octreotide on intragastric pH in patients with duodenal ulcer bleeding].

OBJECTIVE: To evaluate the effect of octreotide on the intragastric pH of patients with duodenal ulcer bleeding during the period of 24 hours and to observe if it can advance the effect of hemostasis by endoscopic injection of epinephrine. METHODS: Twenty-four patients with duodenal ulcer bleeding were randomly divided into three groups, eight in each. Patients in group 1 received an intravenous injection of 0.1 mg of octreotide followed by continuous intravenous drip of octreotide at a constant speed of 25 microg/h for 24 hours. The patients in group 2 received an intravenous injection of 0.1 mg of octreotide followed by continuous intravenous drip of octreotide at a constant speed of 42 microg/h for 24 hours. The patients in group 3 received an intravenous injection of 40 mg of omeprazole followed by continuous intravenous drip of omeprazole at a constant speed of 8 mg/h for 24 hours. Intragastric pH was continuously recorded with a pH meter. The patients with active ulcer bleeding was treated with injection of epinephrine via endoscope and then received intravenous drip of octreotide (with the same dosage as in group 1, n = 42) or omeprazole (with the same dosage as in group 3, n = 54) for 72 hours and were given omeprazole (20 mg Bid). RESULTS: The mean and median intragastric pH values among the patients in group 2 treated by a larger dosage of octreotide (6.7 +/- 0.5 and 6.9 +/- 0.4) were similar to those in the group 3 treated by omeprazole (6.8 +/- 0.4 and 7.0 +/- 0.4). There was no statistically significant difference between these two groups in percentage of intragastric pH above 4, 6, and 7 The mean and median of intragastric pH among the patients in group 1 treated by a smaller dosage of octreotide were statistically significantly smaller (5.2 +/- 0.5 and 5.4 +/- 0.4) than those in the omeprazole group. There was no statistically significant difference between octreotide treatment and omeprazole treatment in terms of volume of blood transfusion (0.7 +/- 0.5 vs. 0.6 +/- 0.4 L), rebleeding rate (11.6% vs. 12.9%), emergency operation rate (7.1% vs. 3.7%), and mortality (2.3% vs. 3.7%). CONCLUSION: Octreotide effectively inhibits the secretion of gastric acid. However, the dosage in common use clinically fails to increase the intragastric pH to the best situation needed for effective hemostasis. Only a large dosage (1.10 mg/d) works.

Adult↗

Total synthesis of 17-isoLevuglandin E4 and the structure of C22-PGF4alpha.

The isolevuglandin 17-isoLGE4 (10-acetyl-11-formyl-14-hydroxynonadeca-4(Z),7(Z),12(E),16(Z)-tetr aenoic acid) is a levulinaldehyde derivative that is expected to be generated during the free radical-induced oxidation of docosahexaenoic acid. A total synthesis was executed to facilitate detection and identification of 17-isoLGE4 in biological samples. Conjugate addition of a higher order vinyl cyanocuprate to a gamma-alkoxy enone achieved the final carbon-carbon bond formation to complete a convergent elaboration of the 17-isoLGE4 carbon skeleton. Attempted construction of the requisite vinyl nucleophile synthon using hydrostannylation of an alkyne was foiled by tri-n-butylstannyl radical-promoted isomerization of a cis to a trans double bond. Derivatization of 17-isoLGE4 with methoxylamine under anhydrous or wet conditions generated bismethoximes of 17-isoLGE4 or the isomerized delta11-17-isoLGE4 respectively. Analysis of the mass spectrum of a bismethoxime-pentafluorobenzyl ester-trimethylsilyl ether derivative of 17-isoLGE4 provided presumptive evidence that an incorrect structure was proposed earlier for C22-PGF4alpha, the only F4-isoprostane which is produced enzymatically. We conclude that the 22-carbon analogue of PGF2alpha, produced from docosahexaenoic acid by a cyclooxygenase from trout gill, does not have the same side chains as 17-isoLGE4. Furthermore, we now propose that mass spectral data reported for "C22-PGF4alpha" support a 14-PGF4alpha structure rather than the 17-PGF4alpha structure suggested previously.

Hydrolysis↗

Effect of intragastric pH on control of peptic ulcer bleeding.

BACKGROUND: We have performed series studies to investigate the effect of intragastric pH on control of peptic ulcer bleeding. In laboratory and animal studies, both platelet aggregation and gastric mucosal bleeding time were shown to be extremely sensitive to different pH levels. Platelet aggregation decreased significantly at pH > or = 6.8 and gastric mucosal bleeding time fell significantly at pH > or = 6.4. In a prospective clinical trial, primed infusions of different dosages of omeprazole (8 or 4 mg/h) after a bolus (40 mg) produced consistently high intragastric pH values in patients with bleeding duodenal ulcer. These results were not significantly different from that obtained from omeprazole 40 mg bolus treatment every 12 h (P > 0.05). However, primed injection with cimetidine (800 mg/12 h) was less effective (P < 0.05). METHODS: In a retrospective analysis, 303 patients with bleeding peptic ulcer who were treated with cimetidine and 326 patients who were treated with omeprazole were compared. RESULTS: The emergency surgery (4.91%) and mortality rates (1.84%) in the omeprazole group were not significantly different (P > 0.05) from those (7.28 and 1.99%) in the cimetidine group. However, the standardized emergency surgery rate of the omeprazole group (3.28%) was significantly lower than that (9.28%) of the cimetidine group (P < 0.05). CONCLUSION: We conclude that increased intragastric pH to at least 6.4 with omeprazole is helpful in controlling peptic ulcer bleeding. Chinese patients require a lower dose of omeprazole than their Western counterparts to control ulcer bleeding.

Adolescent↗

Protein adducts of iso[4]levuglandin E2, a product of the isoprostane pathway, in oxidized low density lipoprotein.

Levuglandin (LG) E2, a cytotoxic seco prostanoic acid co-generated with prostaglandins by nonenzymatic rearrangements of the cyclooxygenase-derived endoperoxide, prostaglandin H2, avidly binds to proteins. That LGE2-protein adducts can also be generated nonenzymatically is demonstrated by their production during free radical-induced oxidation of low density lipoprotein (LDL). Like oxidized LDL, LGE2-LDL, but not native LDL, undergoes receptor-mediated uptake and impaired processing by macrophage cells. Since radical-induced lipid oxidation produces isomers of prostaglandins, isoprostanes (isoPs), via endoperoxide intermediates, we postulated previously that a similar family of LG isomers, isoLGs, is cogenerated with isoPs. Now iso[4]LGE2-protein epitopes produced by radical-induced oxidation of arachidonic acid in the presence of protein were detected with an enzyme-linked immunosorbent assay. Iso[4]LGE2-protein epitopes are also generated during free radical-induced oxidation of LDL. All of the LGE2 isomers generated upon oxidation of LDL are efficiently sequestered by covalent adduction with LDL-based amino groups. The potent electrophilic reactivity of iso-LGs can be anticipated to have biological consequences beyond their obvious potential as markers for specific arachidonate-derived protein modifications that may be of value for the quantitative assessment of oxidative injury.

Antibody Specificity↗

Colloidal bismuth pectin: an alternative to bismuth subcitrate for the treatment of Helicobacter pylori--positive duodenal ulcer.

BACKGROUND: Bismuth triple therapy provides consistently good results in Helicobacter pylori eradication worldwide, whereas quadruple therapy using a combination of omeprazole and bismuth triple regimen has produced cure rates in excess of 90%. The prevalence of metronidazole-resistant strains was 26.8% in our area. Colloidal bismuth pectin (CBP) is a new, lower-priced bismuth salt made in China. The purpose of this study was to investigate the efficacy and safety of CBP triple and quadruple regimens in the treatment of H. pylori-positive duodenal ulcer. MATERIALS AND METHODS: In this prospective trial, 205 patients with H. pylori-positive duodenal ulcer were allocated randomly to receive one of four regimens: metronidazole, 200 mg; amoxicillin, 250 mg; and colloidal bismuth subcitrate (CBS), 120 mg (group 1), or CBP, 100 mg qid (group 2) for 2 weeks, then continued CBS, 240 mg, or CBP, 200 mg bid for a further 2 weeks. A quadruple regimen using a combination of omeprazole, 20 mg bid, and CBS triple therapy (group 3) or CBP triple therapy (group 4), respectively, was given to patients for 1 week, followed by omeprazole, 20 mg once daily for a further 3 weeks. Further endoscopy was performed at least 4 weeks after cessation of the treatment. H. pylori status was determined by histology, a 14C urea breath test, and a urease test. RESULTS: The per-protocol H. pylori cure rates were 85% (22 of 26 patients), 90% (35 of 39), 96% (46 of 48), and 95% (75 of 79) for groups 1 through 4. In the intention-to-treat analysis, cure rates were 79% (22 of 28), 83% (35 of 42), 90% (46 of 51), and 89% (75 of 84), respectively. The cure rates of quadruple therapy were higher than those of triple therapy; an 8.2% difference was not statistically significant (95% confidence interval [CI], 2.3-18.7%). The ulcer-healing rates were 88%, 87%, 98%, and 97%, respectively, for groups 1 through 4. The ulcer pain was relieved more rapidly in quadruple- than in triple-therapy regimens. Two patients discontinued treatment prematurely owing to drug-related side effects. CONCLUSION: One-week quadruple therapy is highly effective and safe in H. pylori eradication in Chinese patients. CBP is as effective as CBS.

Adolescent↗

B lymphocytes differentially use the Rel and nuclear factor kappaB1 (NF-kappaB1) transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogen-activated cells.

Rel and nuclear factor (NF)-kappaB1, two members of the Rel/NF-kappaB transcription factor family, are essential for mitogen-induced B cell proliferation. Using mice with inactivated Rel or NF-kappaB1 genes, we show that these transcription factors differentially regulate cell cycle progression and apoptosis in B lymphocytes. Consistent with an increased rate of mature B cell turnover in naive nfkb1-/- mice, the level of apoptosis in cultures of quiescent nfkb1-/-, but not c-rel-/-, B cells is higher. The failure of c-rel-/- or nfkb1-/- B cells to proliferate in response to particular mitogens coincides with a cell cycle block early in G1 and elevated cell death. Expression of a bcl-2 transgene prevents apoptosis in resting and activated c-rel-/- and nfkb1-/- B cells, but does not overcome the block in cell cycle progression, suggesting that the impaired proliferation is not simply a consequence of apoptosis and that Rel/NF-kappaB proteins regulate cell survival and cell cycle control through independent mechanisms. In contrast to certain B lymphoma cell lines in which mitogen-induced cell death can result from Rel/NF-kappaB-dependent downregulation of c-myc, expression of c-myc is normal in resting and stimulated c-rel-/- B cells, indicating that target gene(s) regulated by Rel that are important for preventing apoptosis may differ in normal and immortalized B cells. Collectively, these results are the first to demonstrate that in normal B cells, NF-kappaB1 regulates survival of cells in G0, whereas mitogenic activation induced by distinct stimuli requires different Rel/NF-kappaB factors to control cell cycle progression and prevent apoptosis.

Animals↗

Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density lipoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo.

Entry of monocytes into the vessel wall is an important event in atherogenesis. Previous studies from our laboratory suggest that oxidized arachidonic acid-containing phospholipids present in mildly oxidized low density lipoproteins (MM-LDL) can activate endothelial cells to bind monocytes. In this study, biologically active oxidized arachidonic acid-containing phospholipids were produced by autoxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (Ox-PAPC) and analyzed by liquid chromatography and electrospray ionization mass spectrometry in conjuction with biochemical derivatization techniques. We have now determined the molecular structure of two of three molecules present in MM-LDL and Ox-PAPC that induce monocyte-endothelial interactions. These lipids were identified as 1-palmitoyl-2-(5-oxovaleryl)-sn-glycero-3-phosphocholine (m/z 594.3) and 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (m/z 610.2). These two molecules were produced by unambiguous total synthesis and found to be identical by analytical techniques and bioactivity assays to those present in MM-LDL and Ox-PAPC. Evidence for the importance of all three oxidized phospholipids in vivo was suggested by their presence in fatty streak lesions from cholesterol-fed rabbits and by their immunoreactivity with natural antibodies present in ApoE null mice. Overall, these studies suggest that specific oxidized derivatives of arachidonic acid-containing phospholipids may be important initiators of atherogenesis.

Animals↗

Pneumococcal cell wall activates NF-kappa B in human monocytes: aspects distinct from endotoxin.

The transcription factor NF-kappa B plays a central role in inflammation by controlling the transcription of multiple genes which participate in the acute phase response. Mice with a targeted disruption of the p50 subunit of NF-kappa B are hyper-susceptible to challenge with pneumococci but not endotoxin. We sought to clarify the role of NF-kappa B in the host response to the critical inflammatory component of pneumococci, the cell wall. Activation of NF-kappa B was monitored by expression of luciferase from cells transfected with an NF-kappa B dependent luciferase reporter construct. 70Z/3 murine pre-B cells and U937 human monocytes failed to produce luciferase in response to 10(7) pneumococci or 10 mu g cell wall; strong responses were obtained with lO mu g of LPS. In contrast, THP-1 human monocytes showed strong luciferase production with all three stimuli: LPS, intact pneumococci and cell wall. The response was time and dose dependent. Cell wall activity was retained despite alteration of the choline of the teichoic acid or protease treatment suggesting the glycopeptide backbone to be a critical determinant of bioactivity. We conclude that activation of NF-kappa B by pneumococci is restricted to certain cells and that this proinflammatory activity may be a specific feature of the pneumococcal cell wall glycopeptide backbone.

Animals↗

A clinical study on TCM differentiation of symptoms and signs in pregnancy hypertension syndrome.

An epidemiological investigation was made into the diagnostic types of 457 cases of pregnancy classified according to differentiation of symptoms and signs by traditional Chinese medicine (TCM) with the aim of finding out its relationship with pregnancy hypertension syndrome (PHS). The total occurrence rate of PHS was 36.8%. In early pregnancy, 65.9% of patients with deficiency of yin of the liver had a high rate of developing PHS, while in the intermediate stage, 61.6% of patients with deficiency of the spleen and exuberance of the liver were most liable to develop it. In 50 cases diagnosed and treated on the basis of TCM differentiation of symptoms and signs the incidence was reduced to be 20%. The changes of such biochemical indices as ACh, AChE, cholic acid and gastrin in different diagnostic types during pregnancy, as well as the effect of spleen-invigorating therapy on these indices in pregnancy with deficiency of the spleen were also observed.

Adult↗

The level of CD8 expression can determine the outcome of thymic selection.

During thymic development, thymocytes that can recognize major histocompatability complex (MHC) molecules on thymic epithelial cells are selected to survive and mature (positive selection), whereas thymocytes that recognize MHC on hematopoietic cells are destroyed (negative selection). It is not known how MHC recognition can mediate both death and survival. One model to explain this paradox proposes that thymocytes whose T cell antigen receptors (TCRs) recognize MHC with high affinity are eliminated by negative selection, whereas low affinity TCR-MHC interactions are sufficient to mediate positive selection. Here we report that, while the expression of a 2C TCR transgene leads to positive selection of thymocytes in H-2b mice, expression of both a CD8 transgene and a 2C TCR transgene causes negative selection. This observation indicates that quantitative differences in TCR-MHC recognition are a critical determinant of T cell fate, a finding predicted by the affinity model for thymic selection.

Animals↗

T-cell receptor beta-chain expression: dependence on relatively few variable region genes.

Fifteen independently isolated complementary DNA clones that contain T-cell receptor (TCR) V beta genes were sequenced and found to represent 11 different V beta genes. When compared with known sequences, 14 different V beta genes could be defined from a total of 25 complementary DNA's; 11 clones therefore involved repeated usage of previously identified V beta's. Based on these data, we calculate a maximum likelihood estimate of the number of expressed germline V beta genes to be 18 with an upper 95 percent confidence bound of 30 genes. Southern blot analysis has shown that most of these genes belong to single element subfamilies which show very limited interstrain polymorphism. The TCR beta-chain diversity appears to be generated from a limited V beta gene pool primarily by extensive variability at the variable-diversity-joining (V-D-J) junctional site, with no evidence for the involvement of somatic hypermutation.

Alleles↗

Immunochemical evidence supporting 2-pentylpyrrole formation on proteins exposed to 4-hydroxy-2-nonenal.

Previous model studies suggested the formation of lysine-based 2-pentylpyrroles as novel late adduction products formed upon exposure of proteins to the lipid peroxidation product 4-hydroxy-2-nonenal (HNE). Two 2-pentylpyrrole immunogens were prepared, one by treating keyhole limpet hemocyanin (KLH) directly with 4-oxononanal and the other by preformation of 6-(2-pentylpyrrol-1-yl)hexanoic acid from 6-aminocaproic acid and 4-oxononanal, followed by carbodiimide coupling to KLH. Pyrrole content and lysine modification in KLH were assayed independently. Following immunization of rabbits, antibody titer increased and plateaued over a 4 month period. The structural specificity of the IgG fractions of the antisera was evaluated through comprehensive competitive ELISA studies. These antibodies were used to verify the time-dependent appearance of the 2-pentylpyrrole epitope in protein exposed to HNE. Potential advantages of antibodies recognizing "advanced lipid peroxidation end products" over those recognizing "early" HNE adduction products are discussed.

Aldehydes↗