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Biomedical subjects

V Wang

Publications and source records attributed to V Wang.

At least 19 recordsLinked to original sources
PubMed2001

Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers.

DNA mismatch repair is of considerable scientific and medical importance because of its essential role in maintaining genomic integrity, and its association with hereditary non-polyposis colon cancer (HNPCC). Germline mutations in five mismatch repair genes (MLH1, MSH2, PMS1, PMS2, and MSH6) have been associated with HNPCC susceptibility. Our laboratory recently identified MLH3, a novel DNA mismatch repair gene. We screened the MLH3 coding sequence in 60 probands with increased genetic risk factors for colorectal cancer susceptibility and no mutations in the other candidate genes. No definite MLH3 germline mutations were found. We subsequently screened 36 colon tumors, and discovered an appreciable frequency of somatic MLH3 coding mutations in MSI-H tumors (25%). In four of six tumors, evidence of biallelic inactivation was noted. Furthermore, MLH3 nonsense mutations were identified in two of 12 microsatellite stable (MSS) tumors with 14q24 loss of heterozygosity. While our analyses do not exclude the existence of germline MLH3 mutations in patients with increased genetic risk factors for colorectal cancer susceptibility, they suggest such mutations are uncommon in this patient population. The finding of an appreciable frequency of somatic MLH3 mutations is consistent with a possible role for this gene in the progression of colorectal cancer tumorigenesis. Hum Mutat 17:389-396, 2001. Published 2001 Wiley-Liss, Inc.

Adaptor Proteins, Signal Transducing↗
PubMed2001

An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial.

OBJECTIVE: To examine in overweight humans the short-term safety and efficacy for weight loss of an herbal supplement containing Ma Huang, Guarana and other ingredients. DESIGN: An 8 week randomized, double-blind placebo controlled study of a herbal dietary supplement (72 mg/day ephedrine alkaloids and 240 mg/day caffeine). SUBJECTS: Overweight men and women (body mass index, > or =29 and < or =35 kg/m2). MEASUREMENTS: The primary outcome variable was body weight change. Secondary variables included anthropometric, metabolic and cardiovascular changes. RESULTS: Sixty-seven subjects were randomized to either placebo (n=32) or active Ma Huang/Guarana (n=35). Twenty-four subjects in each group completed the study. Active treatment produced significantly (P<0.006) greater loss of weight (X+/-s.d.,-4.0+/-3.4 kg) and fat (-2.1+/-3.0% fat) over the 8-week treatment period than did placebo (-0.8+/-2.4 kg and 0.2+/-2.3% fat). Active treatment also produced greater reductions in hip circumference and serum triglyceride levels. Eight of the 35 actively treated subjects (23%) and none of the 32 placebo-treated control subjects withdrew from the protocol because of potential treatment-related effects. Dry mouth, insomnia and headache were the adverse symptoms reported most frequently by the herbal vs placebo group at the final evaluation visit. CONCLUSIONS: This herbal mixture of Ma Huang and Guarana effectively promoted short-term weight and fat loss. Safety with long-term use requires further investigation.

Adult↗
PubMed2000

Dysregulated expression of androgen-responsive and nonresponsive genes in the androgen-independent prostate cancer xenograft model CWR22-R1.

Treatment of metastatic prostate cancer with androgen-ablation often elicits dramatic tumor regressions, but the response is rarely complete, making clinical recurrence inevitable with time. To gain insight into therapy-related progression, changes in gene expression that occurred following androgen-deprivation of an androgen-dependent prostate tumor xenograft, CWR22, and the emergence of an androgen-independent tumor, CWR22-R, were monitored using microarray analysis. Androgen-deprivation resulted in growth arrest of CWR22 cells, as evidenced by decreased expression of genes encoding cell cycle components and basal cell metabolism, respiration and transcription, and the induced expression of putative negative regulatory genes that may act to sustain cells in a nonproliferative state. Evolution of androgen-independent growth and proliferation, represented by CWR22-R, was associated with a reentry into active cell cycle and the up-regulation of several genes that were expressed at low levels or absent in the androgen-dependent tumor. Androgen repletion to mice bearing androgen-independent CWR22-R tumors induced, augmented, or repressed the expression of a number of genes. Expression of two of these genes, the calcium-binding protein S100P and the FK-506-binding protein FKBP51, was decreased following androgen-deprivation, subsequently reexpressed in CWR22-R at levels comparable with CWR22, and elevated further upon treatment with androgens. The dysregulated behavior of these genes is analogous to other androgen-dependent genes, e.g., prostate-specific antigen and human kallikrein 2, which are commonly reexpressed in androgen-independent disease in the absence of androgens. Other androgen-responsive genes whose expression decreased during androgen-deprivation and whose expression remained decreased in CWR22 were also identified in CWR22-R. These results imply that evolution to androgen-independence is due, in part, to reactivation of the androgen-response pathway in the absence of androgens, but that this reactivation is probably incomplete.

Androgens↗
PubMed2000

Comparison of particulate mass, chemical species for urban, suburban and rural areas in central Taiwan, Taichung.

Aerosol samples for PM2.5, PM(2.5-10) and TSP were collected from June to September 1998 and from February to March 1999 in central Taiwan. Ion chromatography was used to analyze the acidic anions: sulfate, nitrate and chloride in the Universal samples. The ratios of fine particle concentrations to coarse particle concentrations displayed that the fine particle concentrations are almost greater than that of coarse particle concentrations in Taichung area. The average concentrations of PM2.5, PM(2.5-10) and TSP in urban sites are higher than in suburban and rural sites at both daytime and night-time. Chloride dominated in the coarse mode in daytime and in fine mode in night-time. Nitrate can be found in both the coarse and fine modes. Sulfate dominated in fine mode in both daytime and night-time.

Air Pollutants↗
PubMed2000

The study of TSP, PM(2.5-10) and PM2.5 during Taiwan Chi-Chi Earthquake in the traffic site of central Taiwan, Taichung.

Ambient particle concentration was taken on the traffic sampling site over the Chung-Chi Road over bridge (CCROB) in front of Hungkuang Institute of Technology (HKIT). The sampling time was from August 1999 to December 1999. During the sampling period, Taiwan's biggest earthquake in more than a century registered 7.3 on the Richter scale (Taiwan Chi-Chi Earthquake). Besides, there were more than 20,000 aftershocks that followed the Taiwan Chi-Chi Earthquake within three months. Thus, the PM2.5, PM(2.5-10) particle concentrations were also collected then and compared with total suspended particle (TSP) in this study. The average PM(2.5-10), PM2.5 and TSP concentrations are 24.6, 58.0 and 106 microg/m3, respectively, after the Taiwan Chi-Chi Earthquake. The average TSP concentrations before and after Taiwan Chi-Chi Earthquake were 70 and 127 microg/m3, respectively. It is clearly shown that the average concentration of TSP after Taiwan Chi-Chi Earthquake was about 1.8 times as that of TSP concentration before Taiwan Chi-Chi Earthquake in the traffic site of central Taiwan. And the ratios of PM2.5/PM(2.5-10), PM2.5/PM10 and PM2.5/TSP are 2.2%, 67.2%, 38.9%, respectively. The results also indicated about Chi-Chi fine particle concentration (PM25) and the TSP increases in the traffic site of central Taiwan after Taiwan Chi-Chi Earthquake.

Air Pollutants↗
PubMed2000

The study of fine and coarse particles, and metallic elements for the daytime and night-time in a suburban area of central Taiwan, Taichung.

Daily average concentrations of fine and coarse particulates, and TSP samples have been measured simultaneously at daytime and night-time periods by using Universal and PS-1 sampler in a suburban area of central Taiwan from June to August 1998. The samples were analyzed by atomic absorption spectrometry to determine the fine and coarse particulate concentrations of metallic elements (Ca, Fe, Mn, Pb, Cu, Zn and Cr). The concentration of PM2.5 and TSP showed a decreased trend for the daytime period. The fine particle concentrations were about two times as that of coarse particulate concentrations. The averaged fine particulate concentrations at daytime are higher than at night-time. Ca and Fe were mostly in the coarse particulate mode. The correlation coefficients were 0.63 and 0.69 for elements Ca and Fe in the coarse particle mode for day and night periods. Pb showed a similar distribution ratio with Mn for the fine to coarse particle ratios at both day and night period. Pb and Mn are highly correlated for the day (R = 0.78) and night period (R = 0.61) at particle size <2.5 microm. Cu and Zn were mainly in fine particles at both day and night period. Fe and Ca consist of the major parts of all the elements. Elemental Mn is the lowest among the rest of the heavy metals.

Air Pollutants↗
PubMed2000

Transient spinal cord ischemia in rat: the time course of spinal FOS protein expression and the effect of intraischemic hypothermia (27 degrees C).

1. In the present study, we characterize the time course of spinal FOS protein expression after transient noninjurious (6-min) or injurious (12-min) spinal ischemia induced by inflation of a balloon catheter placed into the descending thoracic aorta. In addition, this work examined the effects of spinal hypothermia on FOS expression induced either by ischemia or by potassium-evoked depolarization (intrathecal KCl). 2. Short-lasting (6-min) spinal ischemia evoked a transient FOS protein expression. The peak expression was seen 2 hr after reperfusion in all laminar levels in lumbosacral segments. At 4 hr of reperfusion, more selective FOS expression in spinal interneurons localized in the central part of laminae V-VII was seen. At 24 hr no significant increase in FOS protein was detected. 3. After 12 min of ischemia and 2 hr of reflow, nonspecific FOS expression was seen in both white and gray matter, predominantly in nonneuronal elements. Intrathecal KCl-induced FOS expression in spinal neurons in the dorsal horn and in the intermediate zone. Spinal hypothermia (27 degrees C) significantly suppressed FOS expression after 6 or 12 min of ischemia but not after KCl-evoked depolarization. 4. Data from the present study show that an injurious (but not noninjurious) interval of spinal ischemia evokes spinal FOS protein expression in glial cells 2 hr after reflow. The lack of neuronal FOS expression corresponds with extensive neuronal degeneration seen in this region 24 hr after reflow. Noninjurious (6-min) ischemia induced a transient, but typically neuronal FOS expression. The significant blocking effect of hypothermia (27 degrees C) on the FOS induction after ischemia but not after potassium-evoked depolarization also suggests that simple neuronal depolarization is a key trigger in FOS induction.

Animals↗
PubMed2000

MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability.

DNA mismatch repair is important because of its role in maintaining genomic integrity and its association with hereditary non-polyposis colon cancer (HNPCC). To identify new human mismatch repair proteins, we probed nuclear extracts with the conserved carboxy-terminal MLH1 interaction domain. Here we describe the cloning and complete genomic sequence of MLH3, which encodes a new DNA mismatch repair protein that interacts with MLH1. MLH3 is more similar to mismatch repair proteins from yeast, plants, worms and bacteria than to any known mammalian protein, suggesting that its conserved sequence may confer unique functions in mice and humans. Cells in culture stably expressing a dominant-negative MLH3 protein exhibit microsatellite instability. Mlh3 is highly expressed in gastrointestinal epithelium and physically maps to the mouse complex trait locus colon cancer susceptibility I (Ccs1). Although we were unable to identify a mutation in the protein-coding region of Mlh3 in the susceptible mouse strain, colon tumours from congenic Ccs1 mice exhibit microsatellite instability. Functional redundancy among Mlh3, Pms1 and Pms2 may explain why neither Pms1 nor Pms2 mutant mice develop colon cancer, and why PMS1 and PMS2 mutations are only rarely found in HNPCC families.

Amino Acid Sequence↗
PubMed1999

A YAC-based physical map of the mouse genome.

A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.

Animals↗
PubMed1999

Usefulness of molecular testing in Huntington's disease.

BACKGROUND: Uncertainty in diagnosing Huntington's disease (HD) may occur in the absence of a family history or typical movement disorders. HD is characterized by a progressive disturbance of typical movement disorders (i.e., chorea, athetosis), psychiatric symptoms (i.e., depression, insomnia, anxiety, suspiciousness), and cognitive deterioration, in the absence of a dominant family history of similar disorders. Often, some of these symptoms are missing, which makes the diagnosis difficult. In recent years molecular testing has become the gold standard for diagnosing HD. Diagnostic accuracy for HD on genetic screening of patients and their families is important. We evaluated a polymerase chain reaction (PCR) technique for the detection of CAG trinucleotide repeats in the Huntington IT15 gene on chromosome 4 for the diagnosis of HD. METHODS: A segment of the Huntington gene was amplified by PCR using the primers HD-1 and HD-3 flanking the CAG repeat sequence. Genomic PCR was performed on DNA extracted from the peripheral leukocytes of 12 patients from three unrelated families. One family had no documented history of movement or mental disorders, while the other two did. These two, therefore, required pre-symptomatic testing and exclusion of diagnosis in a seemingly symptomatic case. RESULTS: We successfully identified four subjects with expansion of CAG trinucleotide repeats in Huntington gene IT15 on chromosome 4. Movement disorder was present in three of these subjects. One was the sister of subject 4, who was asymptomatic. A sister of subject 9 was ruled out from having HD by PCR despite having depression symptoms, which are frequently seen in HD patients. CONCLUSIONS: Genetic testing is of prime importance in the establishment of an accurate diagnosis of Huntington's disease, especially in "sporadic" cases and presymptomatic family members, and for the exclusion of HD in family members with equivocal symptoms.

Adult↗
PubMed1998

Genetic polymorphism and Parkinson's disease in Taiwan: study of debrisoquine 4-hydroxylase (CYP2D6).

Debrisoquine 4-hydroxylase (CYP2D6) is one of the cytochrome P450 enzyme families that catalyze the breakdown of a variety of exogenous and endogenous compounds. Previous reports have suggested that genetic polymorphisms of debrisoquine 4-hydroxylase are associated with susceptibility to Parkinson's disease (PD) in Caucasians. To determine if CYP2D6 also confers susceptibility to PD in Chinese patients, we carried out a study of genetic association using three polymorphic markers of the CYP2D6 gene, 188C/T, 1934G/A (mutant B), and 4268G/C. No differences of allele or genotype frequencies of these three polymorphisms were detected upon comparison of primary PD patients (n=53) with normal controls (n=94). The 1934A allele (mutant B), which accounts for the majority of poor metabolizers in Caucasians, is extremely rare in Chinese. Our data do not support the suggestion that the CYP2D6 gene is related to PD susceptibility in Chinese.

Adult↗
PubMed1995

Isolated lateropulsion of the trunk in cerebellar infarct.

MRI in a 63-year-old male with isolated lateropulsion of the trunk disclosed an infarct in the inferior portion of the right cerebellar hemisphere, suggesting an end-zone type infarct in the lateral branch of the right posterior inferior cerebellar artery (1PICA) or a borderzone infarct between 1PICA and superior cerebellar artery. A close clinico-topographical relationship between isolated lateropulsion of the trunk and lesion in the territory of 1PICA was demonstrated.

Cerebellum↗
PubMed1994

Evaluation of cervical radiculopathy by cervical root stimulation.

For precise evaluation of cervical radiculopathy, cervical root stimulation (CRS), conventional electromyographic (EMG) studies, nerve conduction velocity (NCV) studies and F responses were done in 32 patients with clinical symptoms and signs of cervical radiculopathy. While performing CRS, a monopolar needle was inserted into the paraspinal muscles, and the compound muscle action potentials (CMAPs) in the biceps, triceps and abductor digiti minimi muscles were recorded. Conventional EMG was abnormal in 18 (56.2%), whereas CRS was abnormal in 25 (78.1%). Among the 25 patients with positive CRS tests, 13 received surgical decompression for cervical root compression caused either by a cervical disc or by foramen narrowing due to spondylosis. Only 10 out of 13 (76.9%) had abnormal conventional EMG findings. CRS provides a sensitive method for making a direct evaluation of proximal root conduction and is a good aid for pre-surgical evaluation of cervical radiculopathy.

Action Potentials↗
PubMed1993

Reversible motor neuron disease.

We investigated a 69-year-old male with a clinical syndrome resembling amyotrophic lateral sclerosis characterized by fasciculation, wasting of the limb muscles and increased deep tendon reflexes in the lower limbs. Electromyographic (EMG) studies showed abundant positive sharp waves and fibrillation potentials with decreased recruitment in the limbs and paraspinal muscles. The patient recovered almost completely in approximately 1.5 years, and follow-up EMG studies showed no positive sharp waves or fibrillation potentials in the limb muscles except for some polyphasic motor units in the bilateral intrinsic hand muscles. No known systemic disease, malignancy or heavy metal intoxication was found during the course of his illness. So far, there are only few cases reported with spontaneous remission of motor neuron disease; however, the possibility should always be considered.

Aged↗
PubMed1993

Immunosuppressive treatment in lower motor neuron syndrome with autoantibodies against GM1 ganglioside.

We report the results of immunosuppressive treatment with intravenous cyclophosphamide in 12 patients with lower motor neuron syndrome and elevated titers of serum autoantibodies to GM1 ganglioside. All patients had lower motor neuron dysfunction including proximal or distal weakness, fasciculation and muscle atrophy, but no upper motor neuron dysfunction such as hyperreflexia, spasticity or Babinski's sign. Electrophysiological studies revealed no evidence of conduction block, but EMG findings of acute or chronic denervation in the limbs were present. Serum biochemistry and immunological studies were negative for M protein. After a 6-month follow-up, despite a fall in antibody titer, there was no significant clinical improvement in any of the patients.

Aged↗
PubMed1993

Myokymia and neuromyotonia of the tongue: a case report of complication of irradiation.

A 51-year-old man has suffered from progressive dysarthria since 1989. He himself noted slight weakness and tightness of the tongue, so that he was unable to perform motor tasks in a normal fashion. He was diagnosed as having nasopharyngeal carcinoma and had irradiation 70 Gy in 32 divided doses in 1979. Neurological examination revealed left-sided tongue atrophy and myokymia sparing of facial muscles involvement. Electrical discharges of myokymia and neuromyotonia were observed in the tongue muscles, suggesting hypoglossal nerve lesion with hyperexcitability of the axon membrance. Computed tomogram of brain did not show any evidence of recurrence of tumor; indicating that irradiation was the pathologic basis. Our report revealed that myokymia and neuromyotonia of the tongue was an unusual complication of irradiation.

Cranial Nerve Diseases↗
PubMed1976

Muscle growth in two genetically different lines of swine.

Skeletal muscle growth in two genetic lines of pigs that differed in total muscle content was studied at live weights of 23, 45, 68, 91, 104, 118 kg. Total physically separable muscle and cross-sectional area of the longissimus dorsi muscle were greater in the muscular than in the obese genetic lines. Above 45 kg, animals in the muscular genetic line had less total separable fat than animals in the obese line, but the two lines did not differ in total physically separable fat at 23 and 45 kg live weight. Hence, these two genetic lines may differ in weight at which maturity is reached as much as in inherent propensity for obesity. Longissimus muscle form the muscular line had more water, less protein, and less lipid than longissimus from the obese line. DNA and RNA concentration, total DNA and RNA content, and RNA/DNA ratio of the pituitary and liver did not differ between the two genetic lines. Above 68 kg, longissimus from the muscular line had higher DNA and RNA concentrations than longissimus from the obese line; this difference did not exist between 23 and 68 kg. RNA/DNA ratio of the longissimus muscle was greater and protein-to-DNA and protein-to-RNA ratios in longissimus were lower in the muscular than in the obese line. Total DNA content of physically separable muscle increased 2.0 (obese) to 2.7 (muscular)-fold between 23 and 118 kg; hence, number of muscle nuclei increases during growth. Total DNA content of physically separable muscle was greater in the muscular than in the obese line and was the measurement most highly related to total muscle content.

Animals↗