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Biomedical subjects

S Huang

Publications and source records attributed to S Huang.

At least 487 records · Page 27Linked to original sources

Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure.

To determine whether additional hypertrophy would be beneficial or maladaptive in cardiac failure, the effects of insulin-like growth factor (IGF-1) were investigated in rats with left ventricular (LV) dysfunction. In normal rats, 3 mg/kg per d of recombinant human IGF-1 for 14 d augmented LV wt (32%) and increased LV/body wt ratio (P < 0.01). 2 d after coronary occlusion, rats were randomized to IGF-1 (3 mg/kg per d) or placebo. After 2 wk, IGF-1-treated rats showed significant increases in LV wt (13%) and LV wt/tibial length ratio, but LV/body wt ratio was unchanged. By microangiography, compared with controls (n = 12) IGF-1-treated rats (n = 16) showed increased LV end-diastolic volume (19%) and stroke volume (31%) (both significant normalized to tibial length, but not to body wt). Average infarct size did not differ between groups. The LV ejection fraction (EF) was not significantly different between groups, but estimated cardiac output was higher in treated rats; there was a significant interaction for the EF between infarct size and treatment (P = 0.029) and a trend for EF to be higher in treated rats with large infarctions (EF 33.4 vs 25.1% in controls). Myocyte cross-sectional areas in noninfarcted LV zones tended to be larger in treated rats (232.1 vs 205.4 microns 2; P = 0.10), but there was no difference in capillary density and collagen content did not differ between groups. In conclusion, IGF-1 administration caused hypertrophy of the normal heart in vivo. When stimulated by IGF-1, the severely dysfunctional heart in evolving myocardial infarction is capable of undergoing additional hypertrophy with evidence of improved function, suggesting a beneficial effect. Further investigation of the potential role of growth factor therapy in heart failure appears warranted.

Animals↗

Molecular mechanisms of an inborn error of methionine pathway. Methionine adenosyltransferase deficiency.

Methionine adenosyltransferase (MAT) is a key enzyme in transmethylation, transsulfuration, and the biosynthesis of polyamines. Genetic deficiency of alpha/beta-MAT causes isolated persistent hypermethioninemia and, in some cases, unusual breath odor or neural demyelination. However, the molecular mechanism(s) underlying this deficiency has not been clearly defined. In this study, we characterized the human alpha/beta-MAT transcription unit and identified several mutations in the gene of patients with enzymatically confirmed diagnosis of MAT deficiency. Site-directed mutagenesis and transient expression assays demonstrated that these mutations partially inactivate MAT activity. These results establish the molecular basis of this disorder and allow for the development of DNA-based methodologies to investigate and diagnose hypermethioninemic individuals suspected of having abnormalities at this locus.

Amino Acid Metabolism, Inborn Errors↗

Rakicidins, new cytotoxic lipopeptides from Micromonospora sp. fermentation, isolation and characterization.

The new cytotoxic agents rakicidins A and B were isolated from cultured broth of a Micromonospora sp. Spectroscopic and amino acid analysis has shown that rakicidin A is a new cyclic lipopeptide, consisting of 4-amino-penta-2,4-dienoic acid, 3-hydroxy-2,4,16-trimethyl-heptadecanoic acid, sarcosine, and 3-hydroxyasparagine. Rakicidin B differs by one methylene group in the lipid side chain. These compounds exhibited cytotoxicity against the M109 cell line.

Animals↗

Bacillaene, a novel inhibitor of procaryotic protein synthesis produced by Bacillus subtilis: production, taxonomy, isolation, physico-chemical characterization and biological activity.

Bacillaene, a novel polyene antibiotic, was discovered and isolated from fermentation broths of a strain of Bacillus subtilis. The novel antibiotic has a nominal molecular weight of 580 and an empirical formula of C35H48O7. Bacillaene is active against a broad spectrum of bacteria in agar-plate diffusion assays. Studies in vitro indicate that the antibiotic inhibits prokaryotic protein synthesis but not eukaryotic protein synthesis. Cell survival studies performed with strains of Escherichia coli indicate that the antibiotic is a bacteriostatic agent.

Anti-Bacterial Agents↗

Role of interferon-gamma in interleukin 12-induced pathology in mice.

Interleukin 12 (IL-12) activates natural killer (NK) and T cells with the secondary synthesis and release of interferon-gamma (IFN-gamma) and other cytokines. IL-12-induced organ alterations are reported for mice and the pathogenetic role of IFN-gamma is investigated by the use of mice deficient in the IFN-gamma receptor (IFN-gamma R-/-). IL-12 caused a rapid infiltration of liver and splenic red pulp with activated macrophages; this and increased NK cells resulted in a fivefold increase of splenic weight in wild-type mice. Splenomegaly was associated with myelosuppression and decreasing peripheral leukocyte counts. IL-12-induced changes in wild-type mice were associated with markedly increased IFN-gamma serum levels and up-regulation of major histocompatibility complex (MHC) class I and II expression in various epithelia. IL-12 induced a qualitatively similar macrophage infiltration in IFN-gamma R-/- mice, less marked splenomegaly (to 2 x normal), and no MHC upregulation. Strikingly increased vascular endothelial intercellular adhesion molecule-1 expression was apparent in both IFN-gamma R-/- and IFN-gamma R+/+ mice. Restricted to mutant mice was a severe, invariably lethal, interstitial, and perivascular pulmonary macrophage infiltration with diffuse pulmonary edema. Extensive quantitative reverse transcriptase polymerase chain reaction analysis revealed an increase of only IL-6 and IL-10 pulmonary gene transcripts in IFN-gamma R-/- mice compared with wild-type mice. IL-12-induced myelosuppression is due to IFN-gamma-release from NK cells and T cells, and is associated with macrophage activation and distinct MHC class I and II antigen upregulation. The pulmonary pathology in IFN-gamma R-/- mice, however, reveals a toxic potential for IL-12 and suggests that endogenous IFN-gamma plays a protective role in preventing fatal pulmonary disease in these mice.

Animals↗

[Amplification of proto-oncogenes C-myc, C-N-ras, C-Ki-ras, C-erbB2 in ovarian carcinoma].

OBJECTIVE: To observe the amplification rate of C-myc, C-N-ras, C-Ki-ras, C-erbB2 in human ovarian carcinoma. METHODS: Southern blot hybridization of DNA was employed, pathological diagnosis was made from fresh tissues. The beta-globin gene was used as an internal control. RESULTS: The amplification rate of C-myc, C-N-ras, C-Ki-ras and C-erbB2 in ovarian carcinoma was 50%, 44%, 31% and 25% respectively. The amplification rates of C-myc, C-erbB2 in stage III and IV were all significantly greater than that in stage I (P < 0.01). The amplification rate of C-N-ras in stage I was also significantly greater than that in stage III (P < 0.01). The amplification rate of C-Ki-ras in stage I was significantly greater than that in stage III or IV (P < 0.01). CONCLUSIONS: The amplification of C-Ki-ras and C-N-ras took place chiefly in cases of the early stages and in cases with good differentiation. The amplification of C-N-ras was also found in cases of advanced stages. The amplifications of C-myc and C-erbB2 were chiefly found in cases above stage III and in cases with poor differentiation, 83% of the patients who died were found to have amplifications of more than 2 proto-oncogenes, with the amplification of C-erbB2 involved in all of them.

Blotting, Southern↗

[Analysis of short tandem repeats polymorphism in the phenylalanine hydroxylase gene and its application to prenatal gene diagnosis of phenylketonuria].

There is a polymorphic tetranucleotide short tandem repeats (STR) sequence in the intron 3 of the phenylalanine hydroxylase (PAH) gene. The polymorphism of this STR sequence in Chinese was analysed on 36 normal individuals and 16 PKU families. After PCR amplification, the DNA fragments were separated on polyacrylamide sequencing gel and visualized by silver-staining. Seven alleles were identified with frequencies of 0.028, 0.042, 0.014, 0.138, 0.542, 0.208 and 0.028 in normal populations, and 0.016, 0.078, 0.047, 0.312, 0.375, 0.156 and 0.016 in PKU families, and PICs of 0.585 and 0.693, respectively. This polymorphic marker is very useful in quick prenatal gene diagnosis in PKU families, and prenatal gene diagnosis was performed by linkage analysis in two pregnancies at risk.

Alleles↗

Serum levels of transforming growth factor alpha in gastrointestinal cancer patients.

Transforming growth factor alpha (TGF alpha), a polypeptide growth-stimulating factor, has been implicated to play a role in the progression of gastrointestinal (GI) cancer. It has been suggested that TGF alpha expression in tumors or TGF alpha in the biological fluids of cancer patients may have tumor marker value. The serum levels of TGF alpha in GI cancer patients have not been reported. In this study, the serum TGF alpha levels of 100 GI cancer patients, as well as 74 healthy individuals, were determined by a TGF alpha-specific RIA kit. All of the cancer patient sera and 67% of the normal sera had detectable levels of TGF alpha. The TGF alpha concentrations in GI cancer patients ranged from 119 to 760 pg/ml, with a mean value of 269 +/- 102 pg/ml. Fifty normal individuals had detectable levels of TGF alpha, and their levels ranged from 120 to 207 pg/ml, with a mean value of 147 +/- 18 pg/ml. Differences in serum TGF alpha concentration between cancer patients and healthy individuals were found to be statistically significant, as evaluated by Mann-Whitney and Student's t tests. Serum TGF alpha levels were found to be significantly elevated in all disease stages of gastric, pancreas, colon, and rectal cancers, and only in the late stages of esophageal cancer. Serum carcinoembryonic antigen levels were significantly elevated only in the late stages of these diseases. The potential of serum TGF alpha as a tumor marker for GI malignancy, therefore, warrants further investigation.

Adult↗

[Osteoarthritis: clinical and epidemiological investigation].

A population study of 1,722 adults in Chenghai city, Guangdong province showed that the prevalence of osteoarthritis (OA) was 8.3% and there was no significant difference between male and female. The prevalence of OA increased after the age of 40 and reached a peak at 50-55 years. The prevalence of osteoporosis (OP) in OA patients of this population survey and in patients in our clinic was around 30%. OA accompanying OP was more frequently seen in female than male, especially in postmenopausal women. The results of CT screen of lumbar spine in 66 OA patients showed: 89.4% (59 cases) was associated with the protrusion of intervertebrale disc, occurring frequently at L4 and L5. MR imaging of 20 knee joints in 10 cases of OA patients with knee involvement showed: all of the patients were associated with one or all of the following conditions: chondropathies, degeneration or injury of semilunar plate, bursitis and synovitis. It is suggested that OA is a heterogeneous disorder and must be treated with different ways.

Adult↗

Cardiac sarcoidosis: an unforeseen cause of sudden death.

Sudden death occurring in a male with established coronary artery disease is inevitably assumed to result from the atherosclerotic process, and an autopsy is rarely requested to confirm the cause. On occasions, however, an autopsy reveals the unexpected, such as cardiac sarcoidosis.

Autopsy↗

Amplifications of proto-oncogenes in ovarian carcinoma.

Thirty-two cases of ovarian carcinoma, two of normal ovaries, four of benign epithelial ovarian tumor, and three of borderline epithelial ovarian tumor were studied using Southern blot hybridization of DNA. In 15 of the 32 cases of ovarian carcinoma, peripheral lymphocytes were also studied. The amplification rate of C-myc, C-N-ras, C-Ki-ras and C-erbB-2 in ovarian carcinoma were 50%, 44%, 31% and 25% respectively. The amplification of C-Ki-ras and C-N-ras took place chiefly in cases of early stage and those of good differentiation. The amplification of C-N-ras was also found in cases of advanced stage. The amplifications of C-myc and C-erbB-2 were chiefly found in cases above stage III and those of poor differentiation. A total of 83% of the patients who died were found to have amplifications of more than 2 proto-oncogenes, with which the amplification of C-erbB-2 was involved.

Adenocarcinoma, Clear Cell↗

[Effects of gestrinone on experimental endometriosis in rabbits].

OBJECTIVE: To study the therapeutic effects of gestrinone on experimental endometriosis in rabbits. METHODS: Mature female rabbits were laparotomized under sterile condition and three or four segments of endometrium (7 mm x 7 mm) were sutured to the mesentery of uterus. Seven weeks after operation these animals were divided into 5 groups: control; treated with danazol 20mg/kg; gestrinone 0.06, 0.12, 0.24 mg/kg for 4 weeks respectively. At the end treatment they were laparotomized again. The ectopic endometrial implants were weighted and their morphologic features were analysed quantitatively by semi-automatic image analysis system, meanwhile serum follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P) concentrations were determined by radioimmunoassay. RESULTS: Decreased weight and atrophy of ectopic endometrial implants were shown in all experimental groups, except for control and 0.06 mg/kg gestrinone treated-group. In 0.12, 0.24 mg/kg gestrinone treated-group, except for P serum FSH, LH and E2, concentrations decreased significantly. The degree of inhibition on ectopic lesions of 0.12 mg gestrinone group was similar to that of danazol group. CONCLUSIONS: Gestrinone inhibits the growth of ectopic endometrial implants in a dose-dependent manner and showed a significant therapeutic effects on experimental endometriosis in rabbits.

Animals↗

Studies on high salt tolerance of transgenic tobacco.

With E. coli mtlD gene (encoding mannitol 1-phosphate dehydrogenase) and gutD gene (encoding glucitol 6-phosphate dehydrogenase) cloned, plant expression vector pBIGM had been obtained by inserting mtlD and gutD genes into binary vector pBin438. Tobacco was transformed with A. tumefaciens LBA4404 containing pBIGM. Results of molecular hybridization of transformed plants indicated that mtlD and gutD genes had integrated into the genomic DNA of tobacco plants. Experiments of salt tolerance and analysis of sugar alcohols showed that the accumulation of different sugar alcohols in transgenic tobacco plants had increased salt tolerance of tobacco.

Blotting, Southern↗