PubMed HealthSearch

Biomedical subjects

V Wu

Publications and source records attributed to V Wu.

18 recordsLinked to original sources

Prevention of unexplained recurrent spontaneous abortion using intravenous immunoglobulin: a prospective, randomized, double-blinded, placebo-controlled trial.

PROBLEM: The efficacy of intravenous immunoglobulin (IVIG) for treatment of unexplained recurrent spontaneous abortion was assessed in a prospective, randomized, double-blinded, and placebo-controlled study. METHOD OF STUDY: The study took place in a provincial recurrent pregnancy loss clinic, located in a tertiary/quaternary care academic center. The study subjects were women with a history of two or more documented consecutive spontaneous pregnancy losses under 20 weeks of gestation, excluding any associated with aneuploidy by karyotype analysis, and with no evidence of genetic, endocrine, infectious, anatomic, or autoimmune factors associated with a history of recurrent spontaneous abortion. The subjects were randomized to receive either intravenous immunoglobulin (Gamimune N) as treatment or normal saline as placebo. Randomization was stratified for primary, secondary, and unclassified unexplained recurrent spontaneous abortion. Success was defined as an ongoing pregnancy beyond 20 weeks of gestation. RESULTS: Sixty-two subjects enrolled in the trial. There were 37 index pregnancies and 6 cross-over pregnancies. There was no clinically significant difference between the treatment arm and the placebo arm in terms of subsequent pregnancy success. There seemed to be a higher success rate with the stratified analysis of couples with secondary unexplained recurrent spontaneous abortion, but the trial did not have sufficient power to confirm this. CONCLUSIONS: Based on this trial and three similar trials in the literature, a multicentered trial is needed to determine conclusively whether IVIG is effective in the treatment of unexplained recurrent spontaneous abortion.

Abortion, Habitual

First intracellular loop of the human cholecystokinin-A receptor is essential for cyclic AMP signaling in transfected HEK-293 cells.

Cholecystokinin (CCK)-A and CCK-B receptors are highly homologous members of the seven transmembrane domain G-protein-coupled receptor superfamily. Genes of both receptors contain five exons and share a similar exon-intron organization. To determine the structural basis of CCK-A receptor (CCK-AR) functionally coupled to Gs, a series of chimeric mutants were constructed by replacing exons of human CCK-B receptor (CCK-BR), from the second to the fifth (last) exon, with human CCK-AR counterparts. Binding and signal transduction properties of wild-type and chimeric receptors were examined in stably transfected HEK-293 cells. Chimeric receptors that maintained high affinity binding to CCK exhibited dose-dependent increases in intracellular calcium mobilization similar to both wild-type receptors. However, only the wild-type CCK-AR and chimeric mutants containing the second exon of CCK-AR were able to mediate significantly greater increases in intracellular cAMP content and adenylyl cyclase activity compared with wild-type CCK-BR. A CCK-BR mutant was further constructed by replacing five amino acids, Gly-Leu-Ser-Arg-(Arg)-Leu, in the first intracellular loop with the corresponding five CCK-AR specific amino acids, Ile-Arg-Asn-Lys-(Arg)-Met. The resultant receptor maintained high affinity binding to both CCK and gastrin and dose-dependent calcium responses similar to wild-type CCK-BR. However, this first intracellular loop mutant also gained positive cAMP responses to both sulfated CCK-8 and gastrin-17 with EC50 values of 8.5 +/- 1 nM and 23 +/- 7 nM, respectively. These data suggest that the first intracellular loop of CCK-AR is essential for coupling to Gs and activation of adenylyl cyclase signal transduction cascade.

Adenylyl Cyclases

A simplified protocol for pessary management.

OBJECTIVE: To evaluate a simplified protocol for pessary management. METHODS: Women with symptomatic pelvic organ prolapse who opted for pessaries were enrolled in a prospective simplified protocol for pessary management. After the initial pessary fitting, they were seen at 2 weeks for reexamination and thereafter at 3- to 6-month intervals. RESULTS: One hundred ten women (mean age 65 years) were enrolled, and 81 (74%) of them were fitted successfully with a pessary. Life-table analysis showed that 66% of those who used a pessary for more than 1 month were still users after 12 months and 53% were still users after 36 months. The severity of pelvic prolapse did not predict the likelihood of pessary failure except in cases of complete vaginal eversion. Patients complaining of stress incontinence were less likely to have a successful pessary fitting and more likely to opt for surgery. Current hormone use and substantial perineal support do not predict greater likelihood of pessary fitting success. No serious complications from using the pessary were observed in the study sample. CONCLUSION: Stringent guidelines calling for frequent pelvic examinations during pessary use can be relaxed safely. Pessaries can be offered as a safe long-term option for the management of pelvic prolapse.

Adult

Induction failure in de novo acute myelogenous leukemia is associated with expression of high levels of CD34 antigen by the leukemic blasts.

The prognostic significance of CD34 antigen expression in acute myelogenous leukemia (AML) is controversial. Most studies to date have reported on CD34 positivity and not the level of antigen present. In this study of 62 patients with de novo AML, 48 (77%) patients were CD34+ in varying levels (0-85 mean channels of fluorescence (MCF)). Forty seven of 62 were treated with combination chemotherapy and 39 (83%) of them achieved complete remission (CR). Patients with CD34- blasts were more likely to achieve CR; however, this trend was not statistically significant (p = .11). On the other hand, patients with higher levels of CD34 antigen on the blasts were less likely to attain CR (p < 0.001, multivariate analysis). The patients who achieved CR expressed lower levels of CD34 (0-57; median 9 MCF) as compared to those who did not achieve CR (15-85; median 30 MCF). Of the other antigens tested, partial or complete absence of CD33 (CD33 absent in > or =25% blasts) correlated with failure to achieve CR (p = 0.0029). These results are in keeping with the hypothesis that more primitive AML blasts with high levels of CD34 are chemoresistant.

Adult

Predictive factors for early menarche in Taiwan.

The rapid increase of breast cancer in Taiwan has prompted the authors to evaluate the predictive factors of early menarche among contemporary Taiwanese girls. A total of 895 four-grade girls from eight elementary schools in Taipei City and County were identified as a closed cohort from the first semester of 1993. Data were collected from self-administered questionnaires and school records. A total of 799 girls who had not menstruated in the first year remained in the group through 1994. The effects of potential predictive factors were assessed by logistic regression. Among the 799 girls followed, 69 (8.6%) had first menstruation between the fourth and fifth grades. Height, weight, body mass index and maternal early onset of menarche were positively related to the onset of menarche within the preceding year. Energy consumption during exercise showed only moderate association after being adjusted for age and weight. Calorie intake from junk food was not associated with early menarche within the preceding year. Poor interpersonal family relationships and stressful life events also showed a moderate association with early menarche. The data obtained supported the hypothesis that height, weight, body mass index and maternal early menarche are positive predictive factors of early menarche. The effects of exercise and childhood stress are less prominent.

Age of Onset

Myeloma Ig heavy chain V region sequences reveal prior antigenic selection and marked somatic mutation but no intraclonal diversity.

The lg VH region sequence in 48 patients with multiple myeloma (MM) was analyzed to characterize the malignant cell of origin. The sequences were obtained after amplification of bone marrow cDNA by using VH family-specific and CH primers, then compared with either directly sequenced patient germ-line or published VH gen sequences to assay for somatic mutation. Because somatic hypermutation of the VH gene occurs late in B cell development, its presence has been helpful in determining the cell of origin in other B cell malignancies. Overall, a median of 8.2% of the nucleotides had evidence of substitution within each VH gene sequence (range=2.7% to 16.5%), which is more prevalent than in any other reported tumor type. Strong evidence of prior antigenic selection pressure was also evident. The ratio of nucleotide substitutions that resulted in amino acid replacement was significantly higher in the complementarity-determining region than in the framework region (3.25 vs 1.56, respectively; p < 0.00005). No VH gene intraclonal diversity was noted, despite sequencing multiple clones (3-16) from each patient, nor was there evidence of further VH gene somatic mutation over the course of three patients' disease. These findings strongly imply that the malignant clone in MM evolves from a cell late in B cell development.

Amino Acid Sequence

Standardization of flow cytometric crossmatch (FCXM) for investigation of unexplained habitual abortion.

PROBLEM: To define a positive flow cytometric crossmatch (FCXM), in terms of channel shift, for maternal IgG and IgM (n = 28) against paternal T and B lymphocytes. METHOD: A reference range study. Mononuclear cells were obtained from 28 healthy volunteers using density gradient separation of heparinized blood, followed by pre-incubation with goat immunoglobulin. A total of twelve tubes were prepared for each volunteer. Primary incubation was with negative control serum, positive control sera (either IgG or IgM) and individual AB sera. Secondary incubation was with four combinations of fluorochromes: CD3 PE/IgG-Fc F(ab')2FITC, CD3 PE/IgM F(ab')2FITC, CD20 PE/IgG-Fc F(ab')2FITC and CD20 PE/IgM F(ab')2FITC. The cells were then analyzed with an EPICS Profile flow cytometer, using 256-channels and a four decade log scale. RESULTS: The linear mean channel fluorescence of the negative control serum was subtracted from the individual AB sera (channel shift) for each of the four combinations of fluorochromes. By determining the 95% one-sided upper reference limits of the negative control serum for each of the four trimmed data sets, we clinically defined a positive FCXM for bound IgG or IgM to T lymphocytes as a shift of 10 or more channels, and for bound IgG or IgM to B lymphocytes as a shift of 25 or more channels, above the linear mean channel shift of the negative control serum. CONCLUSION: Positive FCXMs were defined for maternal IgG and IgM against T and B lymphocytes, in terms of channel shift above the linear mean channel fluorescence of the negative control serum. By standardizing the dual-color FCXM methodology, the clinical significance of alloantibodies in the maintenance of pregnancy could be addressed in a collaborative manner.

Abortion, Habitual

Cognitive deficit and depressive symptoms in a community group of elderly people: a preliminary study.

Since the number and proportion of old people increases worldwide, health professionals and systems should be made aware and prepared to deal with their problems. Cognitive deficit and symptoms of depression are common among the elderly, and may occur in relation to various risk factors such as health conditions and psychosocial variables. In order to study cognitive deficit and the presence of signs and symptoms of depression, 62 elderly community subjects enrolled at a Community Health Unit in Porto Alegre, southern Brazil, were interviewed. They were evaluated by means of the Mini Mental State Exam, the Montgomery-Asberg Depression rating scale, and a questionnaire on health conditions, living arrangements and social variables. Higher levels of symptoms of depression were observed among subjects exposed to major risk factors for cerebrovascular diseases (diabetes and coronary disease), while impaired cognitive performance was seen among individuals who could not count on the presence of a confidant (social network variable). The results suggest that the early identification of major risk groups among old people can help to prevent institutionalization and keep individuals in the community.

Activities of Daily Living

Effect of histamine on rat gastric H(+)-K(+)-ATPase alpha-subunit expression.

The H(+)-K(+)-adenosinetriphosphatase (ATPase) is expressed in the parietal cell and is responsible for acid secretion by the stomach. Histamine binds to an H2 receptor and activates adenylate cyclase and intracellular calcium concentration ([Ca2+]i) elevation, stimulating acid secretion. It has been shown that omeprazole administered to rats increases serum gastrin and transiently increases the level of mRNA for the alpha-subunit of the pump, but this increase is blocked by the presence of the H2-receptor antagonist, famotidine [A. Tari, G. Yamamoto, K. Sumii, M. Sumii, Y. Takehara, K. Haruma, G. Kajiyama, V. Wu, G. Sachs, and J. H. Walsh. Am. J. Physiol. 265 (Gastrointest. Liver Physiol. 28): G752-G758, 1993]. These observations suggest that the release of histamine induced by gastrin is essential for the increase of the expression of mRNA induced by omeprazole. Infusion of histamine at 15 mumol.kg-1.h-1 i.v. for 1 h increased the alpha-subunit mRNA level by 144 +/- 2.4% and induced a stimulated morphological appearance of the parietal cell. These changes were inhibited completely by the competitive H2-receptor antagonist famotidine, which elevated gastric pH and serum gastrin. Famotidine also reduced the level of H(+)-K(+)-ATPase mRNA compared with control animals. No change in the expression of beta-actin mRNA was observed in any group of animals. These data provide direct evidence for histamine stimulation of H(+)-K(+)-ATPase alpha-subunit gene expression by activation of the H2 receptor.

Animals

Effects of postnatal methylmalonate administration on neurobehavioral development of rats.

Administration of methylmalonic acid in rats has been used as a model for methylmalonicacidemia in humans. Nestling Wistar rats of both sexes received 5 injections daily at 3-h intervals (starting at 7:30 a.m.) of saline or methylmalonic acid (MMA, 10 mg/ml) in a volume of 9 microliters/g body weight per injection subcutaneously in the lumbar region from the 5th to the 9th day of life and 11 microliters/g from day 10 to 14. Growth and neuromotor development were assessed by monitoring the following parameters daily in 54 rats: body weight, ear unfolding, incisor eruption, eye opening, righting, palmar grasp, negative geotaxis, cliff avoidance, free-fall righting and startle reflex. The only statistically significant effects of MMA administration were on the day of appearance of the free-fall righting reflex: MMA, 12.44 +/- 1.55 vs 11.0 +/- 0.39 days for saline control (P < 0.05, by two-way ANOVA) and a significant decrease in weight (P < 0.05, by ANOVA with repeated measures). The results suggest that chronic MMA administration to rats has a selective effect on neuromotor development.

Animals

Distribution and abundance of neutral endopeptidase (EC 3.4.24.11) in the alimentary tract of the rat.

The distribution of neutral endopeptidase (NEP; EC 3.4.24.11) was examined in the alimentary tract of the rat. Immunoreactive NEP and NEP mRNA were localized to epithelial cells of the small intestine and to muscle cells in the stomach, small intestine, and colon by immunohistochemistry and in situ hybridization histochemistry. NEP antisera recognized a protein on Western blots of membranes from gastric, jejunal, and colonic mucosa and gastric muscle with an electrophoretic mobility identical to that of recombinant human NEP (approximately 95 kDa). An antisense cRNA probe to NEP hybridized to RNA of approximately 3.5 kb and approximately 6.5 kb, corresponding to the primary transcripts of rat NEP, on Northern blots of total RNA from the jejunal mucosa. NEP message was detected in mRNA from jejunal and colonic mucosa and gastric, jejunal, and colonic muscle using a ribonuclease protection assay. NEP enzymatic activity, assessed by DL-thiorphan-inhibitable degradation of glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine, was highest in homogenates of jejunal mucosa (868 +/- 98 pmol.h-1 x micrograms protein-1) and was between 49- and 413-fold lower in other gastrointestinal tissues. The cellular origin of NEP in the gastric and colonic mucosa could not be determined.

Animals

Role of histamine2 receptor in increased expression of rat gastric H(+)-K(+)-ATPase alpha-subunit induced by omeprazole.

Omeprazole is a specific inhibitor in vivo of the functioning gastric acid pump, the H(+)-K(+)-adenosinetriphosphatase (ATPase), in the secretory canaliculus of the parietal cell. It has been shown previously that omeprazole in rats led to an increase in the mRNA for the alpha-subunit of the H(+)-K(+)-ATPase. Omeprazole causes a marked increase in circulating gastrin in this species, which in turn stimulates release of histamine from the enterochromaffin-like cell. The possible role of this pathway was investigated by the in vivo administration of famotidine, a potent H2 receptor antagonist. A single intraperitoneal dose of famotidine, 200 mg/kg, produced a transient hypergastrinemia peaking at 3 h and normalizing at 12 h, inhibition of secretion that lasted for 12 h, but no change in the level of the alpha-subunit mRNA or of beta-actin mRNA. In contrast, a single dose of omeprazole, 100 mg/kg, inhibited acid secretion and produced hypergastrinemia, peaking at 12 h, both effects lasting for the 24-h observation period. Omeprazole elevated the alpha-subunit mRNA transiently by more than threefold at 3 h, with normal levels being restored at 24 h. The administration of famotidine 1 h after omeprazole did not change the effects of omeprazole on acid secretion but elevated the gastrin levels further. There was now no elevation of the alpha-subunit mRNA for the first 6 h, but a small increase at 12 h and a further increase to approximately 2.5-fold at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Regulation of rat gastric H+/K(+)-ATPase alpha-subunit mRNA by omeprazole.

The H+/K(+)-ATPase is the dimeric enzyme responsible for H+ secretion by the gastric parietal cells. The present study examined the response of rat fundic mRNA levels of H+/K(+)-ATPase alpha-subunit and somatostatin to the inhibition of H+/K(+)-ATPase enzyme activity and gastric pH elevation by oral omeprazole administration. Omeprazole inhibits the alpha-subunit of H+/K(+)-ATPase covalently and stabilizes stimulated morphology of the parietal cell. After a single administration of omeprazole (100 mg/kg), H+/K(+)-ATPase alpha-subunit mRNA levels increased significantly by 57% at 3 h and remained elevated for 6 h, returning to the basal level by 24 h. After multiple administrations of omeprazole (100 mg/kg per day, every 24 h for 3 days), H+/K(+)-ATPase alpha-subunit mRNA levels were already elevated at the time of the last dose, reached maximum at 6 h (95% increase above control), and returned to the pre-treatment level after 36 h. Nuclear run-on assay indicated H+/K(+)-ATPase gene transcription was significantly increased by omeprazole pretreatment in vivo. In contrast, a significant decrease in fundic somatostatin mRNA occurred at 12 h after a single dose, and the inhibition was more pronounced and lasted longer after multiple doses of omeprazole. These data indicate that omeprazole, while effectively inhibiting H+/K(+)-ATPase activity, induces H+/K(+)-ATPase gene expression in the parietal cells. An inverse relationship exists between the regulation of somatostatin gene expression in fundic D-cells and H+/K(+)-ATPase gene expression. The increase in H+/K(+)-ATPase alpha-subunit mRNA could be due to alterations in extracellular gastrin/somatostatin ratios or could be induced by intracellular effects of omeprazole.

Actins

Regulation of rat antral gastrin and somatostatin gene expression during starvation and after refeeding.

Antral gastrin and somatostatin gene expression during starvation and after refeeding with liquid meals of varying composition were studied. Northern and slot-blot hybridization analyses showed that starvation caused a marked decrease in antral gastrin messenger RNA (mRNA) level by 12 hours associated with an increase in somatostatin mRNA. After 48 hours of fasting, antral gastrin mRNA was 26% and somatostatin mRNA was 136% of their prefasting levels. Refeeding caused increased 2-hour integrated gastrin mRNA levels after liquid peptone (+45%), phenylalanine (+31%), and olive oil (+13%), but no changes were observed with glucose or saline solutions. Integrated 2-hour immunoreactive antral gastrin content was increased after peptone (+106%), phenylalanine (+68%), and olive oil (+32%) meals but was not increased after glucose (-11%) or saline (-10%). In some cases, both gastrin mRNA and peptide responses could be measured as early as 15 minutes. The same nutrients that increased gastrin mRNA levels caused decreased 2-hour integrated somatostatin mRNA levels; peptone (-30%), phenylalanine (-28%), and olive oil (-21%), but neither glucose nor saline, altered somatostatin mRNA levels. These results suggest that antral gastrin and somatostatin genes were regulated in opposite directions, in a coordinate manner, by specific gastric nutrients that stimulate gastrin release.

Animals

Somatostatin monoclonal antibody immunoneutralization increases gastrin and gastric acid secretion in urethane-anesthetized rats.

The role of endogenous somatostatin in mediating urethane anesthesia-induced inhibition of gastric acid secretion was investigated using measurement of somatostatin messenger RNA concentrations in the antrum and the influence of somatostatin monoclonal antibody CURE.S6 on acid secretion in rats anesthetized with urethane and acutely implanted with gastric fistulas. Fifteen minutes after injection of urethane, somatostatin messenger RNA concentrations were increased by 128% compared with those in nontreated rats. The significant elevation of somatostatin messenger RNA was maintained for 2 hours after injection. Somatostatin monoclonal antibody injected intravenously (2 mg) completely reversed the inhibitory effect of somatostatin (20 micrograms/kg.h) on pentagastrin (24 micrograms/kg.h)-stimulated gastric acid secretion. The somatostatin monoclonal antibody dose dependently increased basal gastric acid secretion in urethane-anesthetized rats. Peak acid response to the somatostatin monoclonal antibody (2 mg) was observed 20 minutes after antibody injection (preinjection, 1.4 +/- 1.2 mumol/10 min; postinjection, 10.6 +/- 0.6 mumol/10 min); meanwhile, levels of plasma gastrin increased from 27 +/- 6 pg/mL to 75 +/- 8 pg/mL and were maintained elevated for the 2-hour experimental period. When gastrin monoclonal antibody 28.2 was injected together with somatostatin monoclonal antibody, the stimulatory effect of the somatostatin antibody was inhibited by 82%. A control monoclonal antibody 109-21 directed against the biologically inactive glycine-extended fragment 66-72 of progastrin did not alter basal gastric acid secretion or the inhibitory effect of somatostatin. These results indicate that one mechanism by which urethane induced low basal gastric acid secretion involved increased synthesis and release of endogenous somatostatin and associated inhibition of gastrin secretion.

Anesthetics

Colicin A receptor: role of two Escherichia coli outer membrane proteins (OmpF protein and btuB gene product) and lipopolysaccharide.

ompF cells were completely resistant to colicin A, whereas btuB cells were partially resistant. The OmpF protein, in the presence of added lipopolysaccharide, inactivated colicin A. This inactivation was enhanced by added btuB gene product, btuB gene product with lipopolysaccharide did not inactivate colicin A. These data, together with the observation that vitamin B12 protected btuB+ cells from the killing effect of colicin A, suggest that the colicin A receptor in Escherichia coli K-12 is composed of the OmpF protein, the btuB gene product, and lipopolysaccharide.

Adsorption

An automated method for vacuum testing pharmaceutical vials.

A new automated vacuum tester which applies a high voltage, high frequency electric field and a stroboscopic flash to conveyorized vials was found to yield zero percent false rejections of lyophilized vials with internal pressures of less than 62 Torr. The hand-held testing device used until now was found to produce, on extended contact with vials containing sensitive protein product, excessively high numbers of particulates upon drug reconstitution. In the automated machine operating at rates between 150 and 30 vials per minute, each vial is exposed for only 0.3 to 1.4 seconds and sensitive products emerge undamaged.

Automation

Microprocessor-base system for ultrasonic tissue characterization.

A microprocessor-based ultrasonic data acquisiton and analysis system has been developed for measuring acoustic parameters of biologic media in a controlled environment. The system consists of commercially available pulse-echo electronics and both minicomputers and microcomputers. Measurements were made on various biologic tissues, both freshly excised and formalin fixed. Propagation velocity measurements were made using the substitution technique. Peak amplitude and log power spectra difference methods were used for attenuation measurements. Measured results indicate that propagation velocity in the soft tissues was in the range of 1530-1580 m/sec at 20 degrees C. Velocity variation among tissues at any given frequency was less than 2%; dispersion in the frequency range 1-10 MHz was approximately 1.5%. Attenuation coefficients showed a marked dependence on frequency increasing in a linear fashion. The slope of the attenuation frequency curve varied with tissue type and could be used for tissue characterization.

Acoustics