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Biomedical subjects

M Wang

Publications and source records attributed to M Wang.

At least 955 records · Page 53Linked to original sources

Effects of ritanserin on aversive classical conditioning in humans.

According to one formulation of the behavioural functions of 5HT, aversive conditioned stimuli mediate their behavioural and emotional effects through activation of 5HT projections from dorsal raphe nucleus to receptors of the 5HT2 family in amygdala and elsewhere. To test this theory in humans, groups of ten normal volunteers received placebo, the 5HT2 lc antagonist ritanserin (10 mg PO) and no pill. Ritanserin had no effect on skin conductance level, variability (spontaneous fluctuations) or habituation to a sequence of ten neutral tones. After a conditioning trial in which tone 11 was followed by an aversive white noise, skin conductance responses to a further ten tones were enhanced. This effect was abolished by ritanserin. The results indicate a selective involvement of 5HT2/lc receptors in modulating aversively conditioned skin conductance responses.

Adult↗

Characterization of a psychophysiological model of classical fear conditioning in healthy volunteers: influence of gender, instruction, personality and placebo.

Two experiments are described which evaluate the role of associative mechanisms and placebo effects on aversively conditioned skin conductance responses in groups of healthy volunteers. In both experiments, skin conductance level (SCL), variability (spontaneous fluctuations, SF) and amplitude (SCR) were recorded during a sequence of tone stimuli (80 dB, 1 s, 360 Hz). All the variables habituated during the first ten presentations of the tones. Tone 11 was immediately followed by a loud (100 dB) aversive brief (1 s) white noise UCS. The conditioning trial significantly enhanced SCRs to a further ten presentations of the tones and increased SCL and variability (SF). No enhancement of SCRs occurred when tone 11 was omitted and the UCS occurred in temporal isolation (experiment 1). Thus enhanced SCRs to tones following paired tone-noise presentation involves an associative mechanism. Increased "spontaneous" variability was shown to involve both conditioning and sensitization following the UCS. In both experiments females showed greater conditioned SCRs than males. In experiment 2 no effect of "anxiolytic" placebo could be discerned and there were no general relationships between questionnaires scores of extraversion or neuroticism with skin conductance measures in a group of 40 volunteers. The results question the role of conditionability and autonomic lability as major determinants of extraversion and neuroticism. These studies validate the use of the psychophysiological model of aversive conditioning in pharmacological studies of the mechanisms of habituation, conditioning and sensitization.

Adult↗

Isolation and characterization of PC-3 human prostatic tumor sublines which preferentially metastasize to select organs in S.C.I.D. mice.

We have developed and partially characterized a mouse model system for studying human prostate tumor cell metastases in vivo. To develop this model we have selected highly invasive (3 x I.) and non-invasive (3 x N.I.) PC-3 human prostatic tumor sublines based on enhanced and diminished capacities to migrate across a reconstituted basement membrane barrier (Matrigel) in Boyden chamber chemotactic assays. When the 3 x I. cells were injected intravenously (i.v.) in the tail vein of severe combined immune deficient (scid) mice, the cells initially metastasized to a wide variety of tissues as demonstrated by using [125I] IUdR labeled cells and histology. Four distinct sublines were eventually isolated which preferentially metastasized at approximately 80% efficiency to the lumbar vertebrae (PC-3 ML), the mandibular region of the right cheek (PC-3 MC), the rib cartilage (PC-3 MR), and the right front knee bone (PC-3 MK), respectively. Implantation experiments at different sites indicated that organ metastases may somehow be conferred on the tumor subclones by the host tissue.

Animals↗

Arm abscesses caused by Clostridium botulinum.

Wound botulism is an uncommon disorder that continues to be rarely reported in the United States. A 34-year-old intravenous heroin user was admitted to the Loma Linda, Calif., Veterans Administration hospital with multiple abscesses on his forearms. His clinical course was compatible with botulism, and his culture and serum were positive for Clostridium botulinum toxin type A. Early culture and/or serum identification can lead to prompt diagnosis, treatment, and improvement in the morbidity and mortality rates of this disease.

Abscess↗

Ascorbic acid concentration in amniotic fluid in late pregnancy.

Amniotic fluid and venous blood specimens were obtained from 34 pregnant women and analyzed for the ascorbic acid concentration. The mean amniotic ascorbic acid concentration of smoking pregnant women was less than 50% of that of non-smoking women. Pregnant women who smoked had a significantly lower serum and amniotic fluid ascorbic acid concentration than those who did not smoke. No differences were observed between the groups with or without premature rupture of the fetal membrane. The results suggest that ascorbic acid in the amniotic fluid reflects the ascorbic acid status in the blood of pregnant women and smoking had a greater effect in decreasing the ascorbic acid concentration in amniotic fluid than in serum.

Adult↗

Oral clofilium produces sustained lowering of defibrillation energy requirements in a canine model.

The effect of long-term oral administration of antiarrhythmic drugs on defibrillation energy requirements is not well understood. We examined the effect of clofilium, a drug that prolongs cardiac action potential duration without slowing cardiac conduction, on defibrillation energy requirements and ventricular effective refractory periods in a canine model during a 3-week period. Epicardial patch electrodes were implanted in 12 dogs, and baseline testing was conducted under fentanyl anesthesia on day 7. An oral clofilium (100 mg/day) regimen was started on day 8. Six clofilium-treated and six control dogs underwent repeated testing on days 14, 21, and 28 after surgery. Truncated trapezoidal shocks were given repeatedly at various stored energies in random order; delivered current and impedance were measured; and delivered energy was calculated. The energy and current for 50% success in defibrillation (E50 and I50, respectively) were determined. For control animals, E50 increased by a mean 34 +/- 78%, 60 +/- 83%, and 69 +/- 122% compared with baseline (day 7) on days 14, 21, and 28, respectively. In contrast, E50 in clofilium-treated dogs decreased by 39 +/- 62%, 24 +/- 33%, and 32 +/- 15% on days 14, 21, and 28, respectively. Mean current requirements (I50) remained relatively stable compared with baseline in control animals (-7 +/- 39%, +25 +/- 36%, +40 +/- 75% on days 14, 21, and 28, respectively). After clofilium administration I50 decreased by 36 +/- 22%, 32 +/- 17%, and 33 +/- 17% on days 14, 21, and 28, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes.

We report the cloning of cDNAs encoding two different human nonmuscle myosin heavy chains designated NMMHC-A and NMMHC-B. The mRNAs encoding NMMHC-A and NMMHC-B are both 7.5 kb in size but are shown to be the products of different genes, which are localized to chromosome 22q11.2 and chromosome 17q13, respectively. In aggreement with previously reported results using avian tissues, we show that the mRNAs encoding the two myosin heavy chain isoforms are differentially expressed in rat nonmuscle and muscle tissues as well as in a number of human cell lines. The cDNA sequence encoding the 5' portion of the NMMHC-A isoform completes the previously published 3' cDNA sequence encoding a human myosin heavy chain, thus providing the cDNA sequence encoding the entire NMMHC-A amino acid sequence. Comparison of this sequence to cDNA clones encoding the amino-terminal one third of the NMMHC-B sequence (amino acids 58-718) shows them to be 89% identical at the amino acid level and 74% identical at the nucleotide level.

Amino Acid Sequence↗

3 alpha-androstanediol glucuronide in virilizing congenital adrenal hyperplasia: a useful serum metabolic marker of integrated adrenal androgen secretion.

To determine whether serum 3 alpha-androstanediol glucuronide (3AG) reflects the overall effect of integrated adrenal androgen secretion in the virilizing form of congenital adrenal hyperplasia (CVAH), circadian levels (0800, 1200, 1600, and 2000 h) of serum 3AG and 17-hydroxyprogesterone (17OHP) or 11-deoxycortisol (S), androstenedione (A), testosterone (T), and 24-h urinary 17-ketosteroids (17KS) were examined in seven patients (pts) with classical 21-hydroxylase deficiency (21OHD) and one pt with classical 11 beta-hydroxylase deficiency (11 beta OHD). Hormonal studies were conducted during the second day of dexamethasone (Dex) administration (2 mg/day). In five poorly controlled CVAH pts, including the 11 beta OHD pt, highly elevated baseline morning (AM) serum 17OHP or S as well as A levels, and elevated AM T levels in three pts decreased markedly in the evening (PM), while elevated serum 3AG showed no significant circadian changes; 17KS levels were markedly elevated for age. During Dex, moderately or slightly elevated AM 17OHP, A, or T in two to four pts with 21OHD decreased to the normal range in the PM. In the pt with 11 beta OHD, S, A, and T levels were suppressed. 3AG levels were modestly elevated or normal, without circadian changes, in these pts; 17KS levels were elevated or normal. In two other 21OHD pts, modestly elevated AM baseline 17OHP and A levels decreased in the PM; elevated AM T decreased in one pt in the PM; modestly elevated 3AG levels showed no circadian changes; 17KS levels were modestly elevated. During Dex, normal or slightly elevated serum steroids and 17KS levels were associated with normal or high normal 3AG levels without circadian changes. In one postpubertal female with 21OHD, modestly elevated AM baseline 17OHP levels decreased at 2000 h; normal A and T levels throughout the day and low normal 17KS were associated with slightly low 3AG levels, without circadian variation. During Dex treatment, normal 17OHP, A, T, and low 17KS levels were associated with low 3AG levels without circadian variation. In all pts as a group, an excellent correlation (r = 0.9) was found between either 0800 h or mean, or 2000 h serum 3AG levels and 17KS. In addition, AM and PM serum 3AG levels in five normal women were similar. We conclude that the high correlation between serum 3AG and urinary 17KS and the absence of a significant circadian variation in 3AG indicate that serum 3AG, regardless of sample time, is a useful metabolic index of integrated adrenal androgen secretion in CVAH.

17-Ketosteroids↗

Evidence that estramustine binds MAP-1A to inhibit type IV collagenase secretion.

Estramustine is a novel anti-microtubule drug shown to bind MAP-1 and MAP-2 (microtubule-associated proteins) in vitro. In this paper we have shown that estramustine specifically binds MAP-1A in Du 145a cells, resulting in disruption of MAP-1A microtubules and inhibition of type IV collagenase secretion. Immunofluorescence studies revealed that at 30 microM levels estramustine blocked type IV collagenase secretion by partial disruption of the MAP-1A microtubule networks. Immunoprecipitation studies with polyclonal antibodies provided quantitative evidence that 30-60 microM estramustine blocked secretion of a 105 x 10(3) Mr type IV collagenase. Pulse-labeling experiments confirmed that the effect was not a result of inhibition of either protein synthesis or altered rates of type IV collagenase turnover. Finally, drug uptake studies with [3H]estramustine, scintillation counting and fluorography demonstrated that the principal target of the drug was MAP-1A. For the first time we have shown that the drug blocks secretion by binding MAP-1A and causing incomplete disruption of the microtubule networks.

Cell Line↗

Photodynamic therapy for 50 patients with skin cancers or precancerous lesions.

Hematoporphyrin photodynamic therapy (HpD-PDT) was used to treat 50 patients (51 lesions) with skin cancers or precancerous lesions. The preliminary results were satisfactory, with 44 cases (45 lesions) obtaining excellent results, 4 cases good, 1 case fair, and 1 case poor. The effective rate was 98%, the significant remission rate 96%, and the complete remission rate 88.2%. Exposure to sunlight should be avoided after HpD injection, since it produces photosensitivity. A follow-up for 1 to 3 years confirmed that HpD-PDT is a good new adjuvant therapy for selected cases. It brings a hopeful future to the treatment of skin cancers.

Adult↗

Functional analysis of the CPS I upstream sequences with a cat assay.

Expression plasmids (pKCPS-CAT) containing carbamyl phosphate synthetase (CPS I) upstream sequences of different lengths were constructed, and the function and characteristics of the sequences were studied with the CAT assay. Results showed that the CPS I upstream sequences exerted highly tissue-specific control on CPS I gene expression, and the -113 approximately -38 bp region relative to the cap site was found to be indispensable for CPS I gene transcription. The -1700 approximately -161 bp region contains sequences which confer an enhancing effect on CPS I gene transcription. Dexamethasone and thioproline (a differentiation inducer) showed enhancing effects on CPS I gene transcription in hepatoma cells. These results would have significance in studies on the gene regulation of CPS I associated with the mechanism of hepatocyte differentiation and carcinogenesis.

Antineoplastic Agents↗

Aetiologic study on an influenza-like epidemic in horses in China.

About thirty thousands horses were affected and hundreds of them died in an epidemic caused by equine 2 influenza virus (H3N8) in China. The estimated morbidity and mortality accounted for 81% and 2%, respectively. The viral protein and RNA electrophoresis patterns revealed that the new isolates were antigenically different from the prototype strain influenza A/eq/Miami/1/63(H3N8). Therefore, the representative strain of the equine 2 subtype of influenza A virus recommended for producing reference reagents, vaccines, and for serological diagnosis must have been altered by antigenic drift.

Animals↗

[Effects of gossypol and GnRHa on the prostaglandins contents of endometriotic cell and in situ].

In order to study a direct effect of some traditional and western medicine on the prostaglandins (PGs) of endometriosis, endometriotic cell and endometrial cell in situ were cultured in vitro. 6-keto-PGF1 alpha and thromboxane (TXB2) were measured in the above cells using the RIA from the superfusates. These PGs changes after gossypol acetate, progesterone, danazol and gonadotrophin releasing hormone agonist (GnRHa) treatment were studied. High PGs levels were observed in endometriotic cell, and higher in endometrial cell in situ of patients than in endometrial cell of healthy persons (P less than 0.01). After treatment with drug (but not GnRHa), the prostacyclin (PGI2) and TXB2 content were reduced in endometriotic cell, and the TXB2 contents were reduced in endometrial cell in situ (P less than 0.01). These results indicate that endometriotic cell and endometrial cell in situ can produce more PGI2 and TXB2--at least in vitro, which perhaps may provide an explanation for the puzzling clinical phenomenon of endometriosis. Gossypol acetate, progesterone and danazol inhibit PGI2 and TXB2 content in endometrial cell of patients with endometriosis. It is pertinent to ask whether these drugs can be used to improve endometriosis-associated infertility or dysmenorrhea as well.

6-Ketoprostaglandin F1 alpha↗

[Inhibition by polyamine biosynthesis inhibitor DFMO of the growth of transplanted human colon cancer in nude mice].

A human colon cancer cell line Hce-8693 was heterotransplanted in nude mice. polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) showed a marked reproducible inhibition in this model. The size and weight of transplanted tumor in DFMO group were smaller than those of the control group and the average inhibition rate was 72.8% (P less than 0.001). DFMO showed higher tumor inhibitory rate than 5-Fu (35.4%) (P less than 0.001). Furthermore, DFMO demonstrated less severe bone marrow inhibition in the nude mice than 5-Fu (20.0% vs 53.2%, P less than 0.001). There was no synergistic action in these two drugs at the experimental doses. The concentration of putrescine and spermidine in the serum and tumor tissue in the DFMO group were 70% lower than those of the control group (P less than 0.001). These results indicate that the anti-tumor effect of DFMO might be explained by the inhibition of polyamine biosynthesis and this study provides an experimental basis for future clinical application of DFMO.

Animals↗

[The value of residual volume testing in determining degree of emphysema in patients with pneumoconiosis].

A comparative study of chest roentgenograms and the value of RV/TLC% in determining degree of emphysema of patients with pneumoconiosis and workers exposed to dust was made in 400 cases. Accordance rate of RV/TLC% with roentgenograms in determining emphysema in the same subjects was 61.1% and that in the patients group, 67.7%. Moreover, the accordance rate increased with grade of pneumoconiosis diagnosed. The results showed that RV/TLC% was valuable in determining emphysema of patients with pneumoconiosis. The classes of degree of emphysema were proposed according to the testing value of RV/TLC%.

Adult↗

[Study on thixotropic parameters of whole blood from healthy children].

With low shear-30 rheometer, the authors used a modified protocol to measure thixotropic parameters of whole blood from 200 healthy newborns and children, so as to suggest the normal range of blood thixotropic parameters in four age groups, namely, the newborns, 1 year- group, 5 year- and 10-15 year group. The results demonstrated that the thixotropic parameters in the newborn group were higher than those in other three groups. However, these thixotropic parameters in the group 1-10 years were lower than those in the 10-15 year group. No significant sex differences were noted among the fore three groups, but sex differences appeared obviously in the 10-15 year group. It implied that the changes relying on the age is consistent with children's growth, development and physiologic activities.

Adolescent↗

[Study of lipid peroxidation in patients with chronic renal failure].

The levels of lipid peroxide in plasma and erythrocyte membrane, the contents of blood superoxide dismutase and copper, zinc, iron in plasma, and erythrocyte membrane fluidity were investigated in patients with chronic renal failure (CRF). In comparison with the health subjects the levels of lipid peroxide in plasma and erythrocyte membrane were significantly higher, the contents of blood superoxide dismutase were significantly lower in the patients with CRF. The plasma copper increased and plasma zinc decreased, but plasma iron remained unchanges in the patients of CRF. We found that rises of lipid peroxide in erythrocyte membrane were closely related to changes of microviscosity in them.

Adult↗