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Biomedical subjects

M Wang

Publications and source records attributed to M Wang.

At least 703 records · Page 39Linked to original sources

Effects of increasing dialysis dose on serum albumin and mortality in hemodialysis patients.

Dialysis dose and malnutrition have a great impact on the clinical out come of chronic hemodialysis patients. The interrelationships between them, however, remain undefined. Thus, we performed a study to determine the effects of increasing the dialysis dose on serum albumin concentrations and mortality in hemodialysis patients. We examined urea kinetic modeling, biochemical nutritional indices, comorbid conditions, patient survival time, and annual mortality rate. Dialysis dose, measured by Kt/V, significantly increased from 1.3 +/- 0.3 in 1987 to 1.5 +/- 0.4 in 1990 and to 1.7 +/- 0.4 in 1993. Serum albumin level also increased from 3.8 +/- 0.4 g/dL in 1987 to 4.0 +/- 0.4 in 1990 and to 1.7 +/- 0.4 in 1993. In 1993, 76% of patients had Kt/V > or = 1.50 compared with 45% in 1990 and 28% in 1987, whereas 82% of patients had a serum albumin level > or 4.0 g/dL in 1993 compared with 58% in 1990 and 29% in 1987. Protein catabolic rate and hematocrit also increased from 1987 to 1993, but not serum cholesterol or triglyceride. The annual mortality rate declined from 16.1% in 1987 to 13.2% in 1990 and to 8.0% in 1993. The decrease in mortality appeared to be unrelated to differences in patient selection or comorbid conditions. Serum albumin levels, hematocrit, Kt/V, and protein catabolic rate were significantly related to patient survival after age, sex, and diabetic status had been adjusted. Furthermore, there was a positive correlation between Kt/Vs and serum albumin concentration (r = 0.216, P < 0.001). Thus it appears that increasing the dose of dialysis improves serum albumin levels and perhaps survival rate in hemodialysis patients as well.

Adult↗

Cloning and heterologous expression of a second (+)-delta-cadinene synthase from Gossypium arboreum.

Screening of a Gossypium arboreum L. cv. Nanking cDNA library resulted in the identification and cloning of a second (+)-delta-cadinene synthase. A probe for the screens was prepared by PCR using primers based on conserved sequences in farnesyl diphosphate cyclases and genomic DNA as a template. This second cDNA clone encodes a protein that is 80% identical to the recently described (+)-delta-cadinene synthases CAD1-C1 and C14 from G. arboreum and maintains a significant degree of homology to the other known mono-, sesqui-, and diterpene synthases. As in the case of CAD1-C1 (+)-delta-cadinene synthase from cultured cotton cells, the synthesis of the second CAD1-A mRNA was induced by treatment of cotton cell suspension cultures with a partially purified elicitor preparation from the phytopathogenic fungus Verticillium dahliae. Expression of CAD1-A mRNA was quantitated with reverse transcription PCR and showed that CAD1-A mRNA was maximally increased 8-fold, 6 h after addition of elicitor. Heterologous expression of this second cDNA produced a 64 kD protein that catalyzed the cyclization of farnesyl diphosphate to (+)-delta-cadinene, the identical product produced by CAD1-C1. The steady-state kinetic parameters of CAD1-A were similar to CAD1-C, showing a Km of 7 mM farnesyl diphosphate and kcat of 0.039 s-1 at 30 degrees C. However, the optimal pH and Mg2+ concentration for CAD1-A activity were significantly higher than those observed for CAD1-C.

Amino Acid Sequence↗

Bacterial artificial chromosome cloning and mapping of a 630-kb human extrachromosomal structure.

We have cloned and mapped a circular 630-kb human extrachromosomal structure (termed amplisome) using the bacterial artificial chromosome (BAC) cloning system. Twenty-one BACs were isolated from an amplisome-enriched library by colony hybridization. The insert sizes range from 25 to 143 kb, with an average size of 82 kb. The coverage of the amplisome in clones is approximately 2.7-fold. To construct a physical map of the amplisome, we used three different but complementary methods: hybridization, STS content mapping, and fingerprinting. In addition, we compared the advantages and the drawbacks of these techniques in mapping the amplisomal BACs. The 21 BACs were grouped into two contigs and the two small gaps (3.5 and 26.5 kb) were filled by screening of a human genomic BAC library. The organization of the amplisome revealed by the BAC-based physical map is consistent with the long-range restriction map reported previously. Our results demonstrate that a 630-kb region can be rapidly cloned and mapped into contigs by use of the BAC system. Because of the low frequency (<0.1%) of chimerism and rearrangement, these BAC clones are ready for DNA sequencing and functional analysis.

Chromosome Mapping↗

An optimized index of human cardiovascular adaptation to simulated weightlessness.

Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

Adaptation, Physiological↗

Double mutant fibrillin-1 (FBN1) allele in a patient with neonatal Marfan syndrome.

It is now well established that defects in fibrillin-1 (FBN1) cause the variable and pleiotropic features of Marfan syndrome (MFS) and, at the most severe end of its clinical spectrum, neonatal Marfan syndrome (nMFS). Patients with nMFS have mitral and tricuspid valve involvement and aortic root dilatation, and die of congestive heart failure, often in the first year of life. Although mutations in classical MFS have been observed along the entire length of the FBN1 mRNA, mutations in nMFS appear to cluster in a relatively small region of FBN1, approximately between exons 24 and 34. Here we describe the appearance of two FBN1 mutations in a single allele of an infant with nMFS. The changes were within six bases of each other in exon 26. One was a T3212G transversion resulting in an I1071S amino acid substitution and the second was an A3219T transversion resulting in an E1073D amino acid substitution. This is the first reported double mutant allele in FBN1.

Alleles↗

Comparison of three inhaled non-steroidal anti-inflammatory drugs on the airway response to sodium metabisulphite and adenosine 5'-monophosphate challenge in asthma.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are used to assess the role of prostaglandins in asthma but their effects on bronchoconstrictor challenges have been inconsistent. The effects of three nebulised nonsteroidal anti-inflammatory drugs on the airway response to inhaled sodium metabisulphite (MBS) and adenosine 5'-monophosphate (AMP) were compared in the same asthmatic subjects to see whether contractile prostaglandins were involved in MBS or AMP induced bronchoconstriction. A possible protective effect of the osmolarity or pH of the inhaled solutions was also assessed. METHODS: Two double blind placebo controlled studies were carried out. In study 1, 15 non-aspirin sensitive patients with mild asthma attended on four occasions and inhaled 5 ml of lysine aspirin (L-aspirin) 900 mg, indomethacin 50 mg, sodium salicylate 800 mg, or saline 20 minutes before an inhaled MBS challenge. On four further occasions 14 of the patients inhaled the same solutions followed by an inhaled AMP challenge. In study 2, 10 of the patients attended on four additional occasions and inhaled 5 ml of 0.9%, 3%, 10%, or 9.5% saline with indomethacin 50 mg 20 minutes before an inhaled MBS challenge. RESULTS: In study 1 inhaled lysine aspirin had a similar effect on MBS and AMP induced bronchoconstriction, increasing the provocative dose causing a 20% fall in FEV1 (PD20) by 1.29 (95% CI 0.54 to 2.03) and 1.23 (95% CI 0.53 to 1.93) doubling doses, respectively. Indomethacin increased the MBS PD20 and AMP PD20 by 0.64 (95% CI -0.1 to 1.38) and 0.99 (95% CI 0.29 to 1.69) doubling doses, respectively. Sodium salicylate had no significant effect on either challenge. The two solutions causing most inhibition were the most acidic and the most alkaline. In study 2 inhaled 9.5% saline with indomethacin (osmolarity 3005 mOsm/kg) increased the MBS PD20 by 1.1 doubling doses (95% CI 0.2 to 2.0) compared with only 0.09 (95% CI -0.83 to 1.0) and 0.04 (95% CI -0.88 to 0.95) doubling doses with 3% saline (918 mOsm/kg) and 10% saline (2994 mOsm/ kg), respectively. CONCLUSIONS: Inhaled L-aspirin and indomethacin have broadly similar protective effects against MBS and AMP induced bronchoconstriction in the doses given, although the effect of indomethacin on MBS was not quite statistically significant. The osmolarity and pH of the solutions did not appear to be important determinants of the response. The effect of L-aspirin and indomethacin is likely to be the result of cyclooxygenase inhibition reducing the production of contractile prostaglandins during MBS and AMP challenge.

Adenosine Monophosphate↗

Involvement of annexin II in exocytosis of lamellar bodies from alveolar epithelial type II cells.

Annexins are a family of Ca(2+)- and phospholipid-binding proteins that have been implicated in exocytosis. In the present study, we investigated the participation of selected annexins in exocytosis of lamellar bodies by examining their liposome aggregation property and ability to reconstitute surfactant secretion from permeabilized rat lung alveolar type II cells. Annexins I, II, III, and VI were demonstrated in type II cells by immunoblot analysis, but annexin IV and V were not found. Annexins I-IV mediated liposome aggregation in the presence of 1 mM Ca2+. However, only annexin II tetramer had aggregation activity at 10 microM Ca2+. Annexins V and VI had negligible aggregation activity at any Ca2+ concentrations (up to 1 mM Ca2+). To study reconstitution of secretion by annexins, isolated type II cells were permeabilized with 40 microM beta-escin. Under these conditions, the permeabilized cells released approximately 30-40% lactic acid dehydrogenase into the medium. An underestimated fraction of cellular annexin content was lost during permeabilization. However, lamellar bodies in the permeabilized type II cells stained appropriately with the fluorescent dyes Nile red and quinacrine, indicating that they were intact. These permeabilized cells were secretion competent, since phosphatidylcholine (PC) secretion was stimulated by 0.2-1.0 microM Ca2+. Addition of an exogenous annexin mixture enhanced PC secretion from the permeabilized type II cells with maximal stimulation at 0.5 microM Ca2+. Of six purified annexins (I-VI) tested for their ability to reconstitute secretion from permeabilized cells, only annexin II was effective. Our results suggest that annexin II is not necessary for exocytosis of lamellar bodies.

Animals↗

Artificial neural network to assist psychiatric diagnosis.

BACKGROUND: Artificial Neural Network (ANN), as a potential powerful classifier, was explored to assist psychiatric diagnosis of the Composite International Diagnostic Interview (CIDI). METHOD: Both Back-Propagation (BP) and Kohonen networks were developed to fit psychiatric diagnosis and programmed (using 60 cases) to classify neurosis, schizophrenia and normal people. The programmed networks were cross-tested using another 222 cases. All subjects were randomly selected from two mental hospitals in Beijing. RESULTS: Compared to ICD-10 diagnosis by psychiatrists, the overall kappa of BP network was 0.94 and that of Kohonen was 0.88 (both P < 0.01). In classifying patients who were difficult to diagnose, the kappa of BP was 0.69 (P < 0.01). ANN-assisted CIDI was compared with expert system assisted CIDI (kappa = 0.72-0.76); ANN was more powerful than a traditional expert system. CONCLUSION: ANN might be used to improve psychiatric diagnosis.

Adult↗

Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one.

The relationship between symptoms of premenstrual syndrome (PMS) and serum levels of pregnenolone (Pe), pregnenolone sulfate (PS), 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha- pregnan-20-one (5 alpha-THP), LH, 17 beta-estradiol (E2), and progesterone (P) was investigated during 2 consecutive menstrual cycles in 12 patients using daily measurements. Corresponding hormones were also measured during 1 cycle in 8 control women. Pe, PS, 5 alpha-DHP, and 5 alpha-THP showed a significant cyclicity within menstrual cycles and a high rate of correlation with P variation in both PMS patients and controls. No significant difference was found between PMS patients and controls in average serum concentrations of Pe, PS, 5 alpha-DHP, 5 alpha-THP, and LH during the luteal phase, whereas a significantly higher level of E2 and a lower level of P were observed in PMS patients. The variation in symptom scores was compared with that in hormone levels within each woman. The symptom peak showed a delay of 3-4 days after the serum P, Pe, 5 alpha-DHP, and 5 alpha-THP peaks. However, the plasma PS peak appeared on the same day or only 1 day before the symptom peak in PMS patients. When comparing the 2 cycles studied, more negative symptoms occurred in cycles with higher luteal phase E2, Pe, and PS concentrations, whereas higher luteal phase 5 alpha-DHP and 5 alpha-THP concentrations were associated with improved symptom ratings in PMS patients. These results suggest that the mentioned steroids are related to the severity of distressing symptoms in PMS patients.

5-alpha-Dihydroprogesterone↗

Novel mutations in the estrogen receptor messenger RNA in human breast cancers.

One mechanism that has been suggested to play a role in the progression of human breast cancer from hormone dependence to independence is the expression or altered expression of mutant and/or variant forms of estrogen receptor (ER). Two major types of variant ER messenger (m)RNA have been identified in human breast biopsy samples so far: truncated transcripts and exon deleted transcripts. In this study we provide data indicating the existence of a novel type of abnormal ER mRNA. These transcripts were identified as larger than wild-type ER mRNA RT-PCR products in 9.4% of 212 human breast tumors analyzed. The data suggest nucleotide insertions are present in ER mRNA of some breast tumors. Cloning and sequencing of the larger RT-PCR products showed three different types: a complete duplication of exon 6 occurring in 7.5% of tumors; a complete duplication of both exons 3 and 4 occurring in 1 tumor; and a 69 nucleotide insertion between exons 5 and 6 occurring in 3 tumors. Open reading frame analysis suggested that exon 6 duplicated transcripts encoded a 51.4 kDa ER-like protein truncated just after exon 6 sequences; the exon 3 and 4 duplicated transcript encoded a 83.3 kDa protein containing duplication of ER amino acid residues encoded by exons 3 and 4; the 69 nucleotide insertion was inframe, adding 23 novel amino acid residues between residues 412 and 413 of the normal ER protein to produce a 68.8 kDa protein. It is unknown if these novel ER-like mRNAs are stably translated in vivo. Any resulting protein would be structurally altered, however, possibly resulting in altered function.

Base Sequence↗

Activation of amylin gene transcription by LIM domain homeobox gene isl-1.

The amylin (IAPP) and insulin genes are coexpressed in the pancreatic beta-cell and share related promoter elements that may bind similar islet transcription factors. The observation that these promoter elements contain AT-rich subdomains suggests that homeobox proteins may be important for the regulation of both insulin and amylin gene transcription. We show here that the LIM domain homeobox protein isl-1 activates the rat amylin promoter in both fibroblast and islet cell lines. Mutation of the rAMY promoter TAAT motifs was associated with a marked reduction in both basal and isl-1 -dependent transcriptional activity. The isl-1 homeodomain binds to the AT-rich AMY element (-156 to -137) in the human amylin (hAMY) gene promoter, and electrophoretic mobility shift assay experiments using isl-1 specific antiserum detected the formation of an hAMY-isl-1 complex using nuclear extract from InR1 -G9 islet cells. Although isl-1 binds to both the insulin and amylin gene promoter elements in vitro, these sequences display marked differences in their relative transcriptional properties when ligated adjacent to a heterologous promoter and transfected into InR1 -G9 islet cells. The insulin gene E2 sequence that binds isl-1 (-230 to -208) functions as a negative element, whereas the hAMY sequence activates the thymidine kinase promoter in islet, but not nonislet, cell lines. Transfection of isl-1-depleted isl-1 (AS)InR1 -G9 cell lines demonstrated that the E2 element continued to repress thymidine kinase promoter activity, whereas the positive transcriptional activity mediated by the AMY element was considerably reduced in isl-1 (AS)-InR1-G9 cell lines. These dat2 demonstrate that highly similar elements in islet hormone gene promoters display differential functional properties and support a role for the isl-1 homeodomain protein in the regulation of amylin, but not insulin, gene transcription.

Amyloid↗