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Biomedical subjects

M T Wang

Publications and source records attributed to M T Wang.

At least 19 recordsLinked to original sources

Human LBP-32/MGR is a repressor of the P450scc in human choriocarcinoma cell line JEG-3.

Steroid hormones regulate a wide range of physiologic functions in humans. The cholesterol side-chain cleavage enzyme P450scc regulates the initial step of biosynthesis of all steroid hormones. We investigated the expression of P450scc by studying a potential regulator of P450scc, LBP-32/MGR. Using a Northern blot, we found that LBP-32/MGR mRNA was expressed mainly in the human placenta. Using radiation hybrid mapping, we identified LBP-32/MGR on human chromosome 2p25. Recombinant LBP-32/MGR protein bound preferentially to a DNA fragment from the promoter of P450scc in vitro and exhibited clear nuclear localization in transfected cells. Luciferase reporter gene assays showed that LBP-32/MGR specifically repressed transcriptional activation of the human P450scc promoter. Because placental P450scc expression is essential for pregnancy and steroid biosynthesis, the placental expression and transcriptional repressor activity of LBP-32/MGR in JEG-3 cells suggest it has a role as a transcriptional modulator of steroid biosynthesis.

Cell Line, Transformed↗

Stability of 4-DMAP in solution.

A stability-indicating reversed-phase performance liquid chromatographic method was developed for the detection of 4-(N,N-dimethylamino)phenol (4-DMAP) and its degradation products under accelerated degradation conditions. The degradation kinetics of 4-DMAP in aqueous solution over a pH range of 1.12-6.05 and its stability in solutions based on propylene glycol or polyethylene glycol 400 were investigated. The observed rate constants were shown to follow, apparent first-order kinetics in all cases. The pH rate profile shows that maximum stability of 4-DMAP was observed in the pH range 2.0 to 3.0. Acid/base catalysis of 4-DMAP was not affected by systems of various ionic strengths. Incorporation of nonaqueous propylene glycol or polyethylene glycol 400 in the pH 3.05 solution of 4-DMAP showed an increase in the stability at 55 degrees C +/- 0.5 degrees C.

4-Aminopyridine↗

Effects of hypoxia on granulocytic-monocytic progenitors in rats. Role of bone marrow stroma.

Hemorrhagic shock leads to hypoxia and is associated with bone marrow (BM) failure. Hemorrhagic shock is also a predisposing factor in immune dysregulation. Since the BM is the major organ of immune cells in the adult, its failure following hemorrhagic shock may explain the increased susceptibility to infection. The in vitro evidence indicates that hypoxia mediates altered functions in BM stroma. Since similar hematopoietic alterations are reported in hypoxia and hemorrhagic shock, hypoxia alone could be a representative model to study BM responses during hemorrhagic shock. In this study, we use an animal model to dissect the hematopoietic effects of hypoxia. We subjected rats to hypoxia, and at days 1 and 5 post-hypoxia we determined the numbers of granulocytic-monocytic progenitors (CFU-GM) in the BM. We found significant increase (P < 0.05) in CFU-GM at day 1 and a downward trend by day 5. Enhanced BM cellularity could not explain the increase in CFU-GM by day 1. BM stromal cells mediated most of the stimulatory effects by hypoxia. CFU-GM was inversely proportional to bioactive TGF-beta and directly proportional to IL-1. Compared to normoxic rats, IL-6 production was suppressed in BM cells from hypoxic rats. The results show that hypoxia alone initiate a stimulatory response in CFU-GM progenitors. These effects are at least partially mediated through the BM stroma. In the absence of a second insult, CFU-GM reverts to baseline. The data also suggest that hypoxia mediates complex responses that include cytokine production. These results add to the current understanding of hematopoietic responses by hypoxia and adds to the mechanisms of immune dysfunctions following hemorrhagic shock.

Animals↗

Formulation optimization of controlled-release pellets of metoclopramide hydrochloride using dissolution fit factor approach.

The purpose of this study was to optimize the formulation variables for the preparation of ethyl cellulose-coated nonpareils loaded with metoclopramide hydrochloride (MCL). The approach to evaluate the effectiveness of formulation parameters was monitored by release rate testing using dissolution fit factors as a tool. The content of ethyl cellulose used in the formulation was based on the drug-loaded weight. The interrelationship of each developed formulation and the reference formulation Gastro-Timelets and their respective dissolution curves were evaluated using Moore's equation: [equation: see text]. The relationship between the ethyl cellulose content in the formulation and the dissolution fit factor f2 can be described as the following regression equation: Y = -0.054X2 + 3.347X - 1.915 (r2 = 0.99). The optimum ethyl cellulose content obtained from the equation was 30.8%. The type and content of plasticizer used in the formulation to achieve the greatest f2 were determined to be Myvacet 9-40 at the concentration of 25%. Results indicated that using the release rate testing approach with the dissolution fit factor as a tool could provide valuable information for formulation optimization.

Cellulose↗

Percutaneous transport of diclofenac sodium from mixtures of fatty alcohol (or fatty acid) and propylene glycol through the rabbit abdominal skin.

Diclofenac sodium is a nonsteroidal anti-inflammatory drug with analgesic, antipyretic, and anti-inflammatory activity. When used in a topical application, diclofenac can diffuse through the skin and into the subcutaneous tissue to effect the anti-inflammatory action. In this study, in vitro evaluations of the percutaneous transport of diclofenac sodium in various bases containing fatty alcohols/propylene glycol or fatty acid/propylene glycol mixtures through the abdominal skin of the rabbit were investigated. Results show that the transdermal flux of diclofenac sodium in the fatty alcohol/propylene glycol bases of the same ratio is affected by the chain length of the fatty alcohol, and its effect is in the order of C10 > C12 > C14 > C18. However, the transdermal flux of diclofenac sodium in the fatty acid/propylene glycol bases of the same ratio is also affected by the chain length of the fatty acid, but no absolute relationship was found. For the same chain length of fatty acid and fatty alcohol used in the formulation base that was otherwise the same, the transdermal flux of diclofenac sodium is higher in the formula containing fatty alcohol than that containing fatty acid.

Abdomen↗

Dermatoses in cement workers in southern Taiwan.

Construction workers are known to have occupational dermatoses. The prevalence of such dermatoses was unknown in Taiwanese construction workers. The objective of this study was to determine the work exposure, prevalence of skin manifestations, and sensitivity to common contact allergens in cement workers of southern Taiwan. A total of 1147 current regular cement workers were telephone-interviewed about skin problems during the past 12 months, work exposure, and personal protection. Among those interviewed, 166 were examined and patch tested with common contact allergens. A high % of cement workers reported skin problems in the past 12 months. More men (13.9%) reported skin problems possibly related to work than women (5.4%). Prevalence was associated with lower use of gloves, duration of work as cement worker, and more time in jobs involving direct manual handling of cement, especially tiling. A high % of dermatitis was noted in the 166 workers examined, which correlated with reported skin problems. On patch testing, construction workers had a high frequency of sensitivity to chromate. Sensitivity to chromate or cobalt was associated with reported skin problems, or dorsal hand dermatitis on examination. These workers' dermatitis was under-diagnosed and inadequately managed. It is concluded that cement workers in southern Taiwan had a high prevalence of skin problems related to cement use. Protective measures, work practice, and physician education should be improved to prevent or manage such problems.

Adult↗

Preliminary study of dose equivalent evaluation for residents in radioactivity contaminated rebar buildings.

It has recently been found that several resident and office buildings in Taiwan were constructed with 60Co-contaminated reinforcing steel bar (rebar). Both governmental officials and the residents of such buildings have been concerned about this finding. In order to respond to the situation, the government has adopted a number of remedial measures, including full-scale radiation survey, dose evaluation and physical examinations of residents. This article presents three methods for evaluating the dose equivalents of the residents living in the contaminated rebar buildings by means of gamma-ray survey, necklace-type thermoluminescence dosimeters (TLDs) and the human lymphocyte chromosome aberration analyses. The results reveal that the dose evaluation by gamma-ray survey is rather conservative. Generally for the residents whose annual dose equivalents are greater than 5 mSv (0.5 rem) by gamma-ray survey, the dose equivalents from necklace-type TLDs are only within the range of 20 to 50% of the evaluated values mentioned above. For chromosome analyses, at least 500 lymphocyte cells were scored and analyzed for each resident. Most of the chromosome analysis data show that the dose equivalents received by residents are lower than the detection limit of the method (100 mSv) and quite different from the estimated dose obtained from either gamma-ray survey or necklace-type TLD measurements.

Air Pollution, Indoor↗

Differential effects of acute hypoxia and endotoxin on the secretion and expression of bone marrow interleukin-1 and interleukin-6.

Hemorrhagic shock induces tissue hypoxia and has been demonstrated to alter the myelopoietic response to bacterial lipopolysaccharide (LPS). Interleukin-1 and interleukin-6 are important mediators of immunologic events after hemorrhagic shock. Bone marrow stroma release inflammatory cytokines, which may play a role in the regulation of myelopoiesis after injury. The aim of this study was to correlate cytokine gene expression with protein release and myelopoiesis by total bone marrow cells. The role of bone marrow stroma after exposure to hypoxia and lipopolysaccharide was also examined. BALB/c mice were designated as normoxia or hypoxia and total bone marrow cells were harvested. Hypoxia mice were exposed to 2 h of 5% O2/95% N2, and then returned to room air. Additional groups of mice were given LPS intraperitoneally. Bone marrow stroma, from BALB/c mice, was similarly designated. Myelopoiesis was assessed by growth of granulocyte-macrophage progenitor cells (CFU-GM). Interleukin-1 and interleukin-6 protein activity was assessed by bioassay. RNA was extracted from both total bone marrow cells and bone marrow stroma. By day 5, LPS alone resulted in a 93% increase in CFU-GM versus normoxia. Hypoxia and LPS exposure significantly decreased CFU-GM on days 1, 3, and 5. LPS alone induced an increase in interleukin-6. At 2, 6, and 24 h, hypoxia blunted interleukin-6 release in response to LPS. Hypoxia alone could not induce interleukin-6. However, hypoxia did induce interleukin-1 mRNA without the release of bioactive protein. In the remainder of groups, interleukin-1 protein levels and mRNA levels were correlated. Bone marrow stroma interleukin-1 and interleukin-6 protein activity was consistently correlated with that of total bone marrow. These data demonstrate that bone marrow cytokine production is differentially regulated by hypoxia. Hypoxia impairs interleukin-6 protein and mRNA in response to LPS, which may play a role in the suppression of myelopoiesis after shock. Also, bone marrow stroma plays an integral role in regulating myelopoiesis.

Animals↗

Hemorrhagic shock abolishes the myelopoietic response to turpentine-induced soft tissue injury.

Hemorrhagic shock has been shown to alter bone marrow (BM) myelopoiesis. Isolated hemorrhagic shock is uncommon after trauma and the combined effect of tissue injury and shock on myelopoiesis is unknown. We studied the growth of BM granulocyte-macrophage colony forming units (CFU-GM) following shock and soft tissue injury. Rats were anesthetized and allocated into one of four groups: CONTROL, sham neck dissection; SHOCK, rats were bled to a mean BP of 45 mmHG for 45 min and resuscitated with shed blood and saline; TURP, soft tissue injury was induced by turpentine 0.5 ml/100 g SQ into the hindquarter; SHOCK + TURP, rats received TURP just before SHOCK as described above. Groups (n = 6) were sacrificed 1, 3, and 5 days after treatment. BM cells plated for CFU-GM and splenic macrophages were cultured for IL-1 production. Unstimulated splenic macrophage production of IL-1 alpha was not different for any group except Day 5 turpentine animals. TURP induced a significant increase in CFU-GM on Day 1 compared to that in control (47 +/- 22 vs 21 +/- 11; P < 0.05). SHOCK completely abolished this response to TURP. Both the SHOCK and TURP alone increased CFU-GM on Day 5 compared to that in CONTROL but there was no additive effect in the SHOCK + TURP group. These data show that the BM response to combined soft tissue injury and shock (TURP + SHOCK) appears similar to that of SHOCK alone and that hemorrhagic shock appears to be a significant immunosuppressive factor in the regulation of myelopoiesis following injury.

Animals↗

Toward a physical map of human chromosome 10: isolation of 183 YACs representing 80 loci and regional assignment of 94 YACs by fluorescence in situ hybridization.

One hundred eighty-three YACs carrying human chromosome 10 sequences were isolated from multigenome equivalent libraries by PCR-based screening for the presence of 80 different chromosome 10-specific STSs. Ninety-four of the isolated YACs, representing 52 genes and DNA segments, were mapped to regions of chromosome 10 by fluorescence in situ hybridization. The results localized 26 DNA segments to cytogenetic bands for the first time. About 37% (35/94) of the YACs hybridized to more than one chromosomal location: 31 to other chromosomes in addition to chromosome 10 and 4 to 2 distinct locations on chromosome 10. These results are consistent with the number of chimeric YACs expected from these libraries but may also reflect the presence of 2 or more YACs within a single clone or the presence of low copy repeated elements within the genome. This STS anchor screening effort resulted in the identification of 69 contigs, with 7 contigs consisting of 2 anchors each and 1 contig consisting of 5 anchors. All linked STSs were multiply linked by at least 2 independent YACs. These anchored YACs span the entire chromosome and appear to cover 15% of chromosome 10.

Chromosome Mapping↗

Development of 124 sequence-tagged sites and cytogenetic localization of 217 cosmids for human chromosome 10.

A total of 124 new chromosome 10-specific sequence-tagged sites (STSs) were derived from two sources: (1) DNA sequences obtained from anonymous clones in new libraries enriched for human chromosome 10 inserts, and (2) published sequences of genes and other loci already known to map to chromosome 10. Libraries were constructed from a somatic cell hybrid carrying human chromosomes 10 and Y. A cosmid library was made from total DNA of the hybrid and probed with labeled total human DNA to identify clones with human DNA inserts. Two hundred seventeen cosmids were mapped to regions of human chromosome 10 by fluorescence in situ hybridization. Twenty-five cosmids represent probes that have been placed on the genetic map previously. One hundred ninety-two cosmids represent new probes that have not been mapped previously. Cosmids carrying inserts with CA repeats were identified by hybridization with a labeled poly(dC-dA)-poly(dG-dT) probe and subcloned to yield microsatellite STS markers. Two small insert plasmid libraries were made, the first by subcloning inserts from a chromosome 10-enriched lambda phage library (LL10NS01) and the second by cloning Alu element-mediated PCR products amplified from hybrid DNA. STSs were generated from the DNA sequences of clone inserts. Chromosome 10-specific STSs were distinguished from Y chromosome STSs by one or both of the following criteria: (1) successful PCR amplification from a template consisting of DNA from another chromosome 10-containing cell line, NA10926B, or (2) FISH localization to chromosome 10 of the source cosmid or of YACs isolated by PCR screening with the STS. These libraries were the source of 90 new chromosome 10-specific STSs, 42 of which contain CA repeats.

Base Sequence↗

Clinical significance of multiple hypothalamic-pituitary functions assessment in patients with Turner's syndrome.

Hypothalamic-pituitary functions in 26 cases of Turner syndrome were assessed with a combined stimulation test. The results showed that the peak GH levels of 12 cases were less than 10 micrograms/L; 3 patients were demonstrated as having an even TSH response, while another one with a delayed TSH peak, and other 4 had high basal values and consistent exaggerated TSH responses to TRH; all patients showed increased basal and peak LH and FSH levels but 5, whose LH and FSH secretion patterns were similar to normal. 12 cases have been treated with individualized protocols and followed up for 12 months or more, of them the growth velocity all increased, especially those with hypothyroidism or with a BA less than 13. It is suggested that multiple functions of hypothalamic-pituitary axis in Turner patients be evaluated as early as possible, in order that proper treatment could be adopted and their growth and development improved.

Adolescent↗

Excess cancer mortality among children and adolescents in residential districts polluted by petrochemical manufacturing plants in Taiwan.

We have collected data on the cancer deaths of children and adolescents 0-19 yr old living in a residential area near 3 large petroleum and petrochemical complexes in and near Kaohsiung city (petrochemical industrial districts, PIDs) in the period of 1971-1990 and compared these with the cancer deaths of children and adolescents 0-19 yr old among the entire population of Taiwan (national reference) and among the residents of 26 administrative districts, comprising all of Kaohsiung city and Kaohsiung county (local reference), except for 8 sparsely populated, rural districts. Having scrutinized all cancer death certificates, we have identified various statistically significant excess deaths, as compared with the national and local reference, due to cancers at all sites. Cancer of the bone, brain, and bladder in boys and girls 0-9 yr and 10-19 yr of age in the 1981-1990 decade that followed the establishment of petrochemical production in the PIDs was studied. However, excess cancer deaths seemed to have clustered in the 10-19 yr age group, who had been potentially exposed to the petrochemical pollutants for the longest period of time from the youngest age. Almost all bone, brain, and bladder cancer deaths registered were within 3 km of the 3 complexes. Bone and brain cancers in particular occurred in girls in the PIDs more frequently than in boys, even though these are believed to occur more in males than females elsewhere.

Adolescent↗

Continuous infusion of cefazolin is superior to intermittent dosing in decreasing infection after hemorrhagic shock.

Standard doses of antibiotic administered by intermittent infusions after hemorrhagic shock have decreased efficacy in combating infection. This study compared identical quantities of cefazolin administered after shock as intermittent doses or as continuous infusions in a subcutaneous abscess model. One hour after resuscitation from shock, rats were inoculated with 2 x 10(8) Staphylococcus aureus subcutaneously on the dorsum and divided into three groups: (1) control rats, which received no drug treatment; (2) rats in the intermittent group, which received cefazolin at either 30 or 60 mg/kg intraperitoneally, 30 minutes prior to inoculation, then every 8 hours for three doses, and (3) rats in the continuous infusion group, which received cefazolin at either 30 or 60 mg/kg intraperitoneally, 30 minutes prior to inoculation, followed by cefazolin, 90 or 180 mg/kg, intraperitoneally by continuous infusion more than 24 hours after inoculation. Seven days after the inoculation, abscess number, diameter, and weight were measured. Rats that received either dosage of cefazolin intermittently had the same abscess rate after shock as control rats. Rats that received a continuous infusion of cefazolin at either dose had 56% fewer abscesses than control rats. Abscess diameter and weight decreased with increasing quantities of cefazolin, and abscesses were always smaller in rats receiving the continuous infusion. There were no differences in peak subcutaneous cefazolin levels between the intermittent and continuous groups. Continuous infusion provided significantly more cefazolin to the tissue than an equivalent quantity of cefazolin delivered as intermittent doses. These data demonstrate that continuous infusion of cefazolin provided more antibiotic to the tissue and was superior to intermittent injection in reducing infection after hemorrhagic shock.

Abscess↗

Detection of dengue virus antigens in cultured cells by using protein A-gold-silver staining (pAgs) method.

A protein A-gold-silver (pAgs) staining was developed to detect dengue virus antigens in cultured cells. The method can be carried out in either newly-subcultured or monolayered cells. Dengue virus-inoculated C6/36 clone of Aedes albopictus cells and human endothelial cells appeared brown-yellowish color on the peripheral membrane of the infected cells. In many cases, the infected C6/36 cells appeared darker than that of the infected endothelial cells. The positive results from the inoculated C6/36 cells usually appeared as early as 2 days post-inoculation for types 1, 2, and 4 of dengue viruses and 3 days for the dengue 3 virus. The same batch of specimens detected by direct immunofluorescence antibody test (DFA) showed positive 4 days post-inoculation for the types 2, 3, and 4 of dengue viruses and 6 days for the dengue 1 virus. The result also showed that all pAgs-positive specimens were also DFA-positive, but not vice versa. It suggested that pAgs is not only sensitive but also specific for dengue virus detection from inoculated cultured cells.

Aedes↗

Study on blackfoot disease: with special reference to evaluating its cutaneous microcirculatory status.

We evaluated the microcirculatory status of blackfoot disease by skin temperature measurement, laser Doppler flowmetry and capillary microscopy. The results of these assessments revealed a good correlation between the disease stage and the microcirculatory status. No effective therapy other than surgical amputation was recommended before. In this study, we treated this endemic disease with prostaglandin E1 (PGE1) infusion therapy. PGE1 was most effective in the erythematous stage and some minor ulcer with an improvement of microcirculatory status. However, PGE1 had no effect in severe ulcerative (ulcer > 0.5 cm) and gangrenous stages. These microcirculatory improvements foreshadowed the improvement of clinical manifestations. The microcirculatory status after PGE1 treatment demonstrated the effectiveness of the therapy.

Aged↗