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Biomedical subjects

M Li

Publications and source records attributed to M Li.

1,183 records · Page 66Linked to original sources

Decline of serum levels of free testosterone in aging healthy Chinese men.

OBJECTIVE: To investigate the age-related change of serum androgen levels in healthy men and to define a cut-off value of serum testosterone for the diagnosis of androgen deficiency in the aging male. METHOD: 1080 healthy men aged 20 to 70 years old were enrolled in Beijing, Shanghai, Xian and Chongqing. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T), calculated free testosterone (cFT), sex hormone binding globulin (SHBG), 17beta-oestradiol (E2), the T/LH ratio, and T/SHBG as a free testosterone index (FTI) were all determined. RESULTS: Serum total T did not significantly decline, but the cFT, T/LH and FTI progressively decreased with aging. To determine androgen deficiency, the 10th percentile value of men < 40 years was defined as the lower cut-off value for cFT, T/LH or FTI, which were 0.3 nmol/L, 2.8 nmol/IU, and 0.4 nmol/IU respectively. With the median value of cFT of men aged between 20 and 49 years as the criterion, the level of cFT was lower in 2.82% of men from 40 to 49 years, in 19.53% from 50 to 59 years, in 22.57% from 60 to 69 years, and in 33.19% of men > or = 70 years. Taking the above value of cFT as the cut-off point, the prevalence of androgen deficiency in men 40-49 years was 13.0%, 31.8% in men 50-59 years, 30.1% in men 60 to 69 years, and 46.7% in men > 70 years. CONCLUSIONS: (i). While serum total T values do not decline with aging, the levels of cFT gradually decline with aging; (ii) when using the value of cFT of the 10th percentile of men aged 20 to 39 years as the cut-off point, the prevalence of androgen deficiency was < 15% before the age of 50 years, and about 30% thereafter, approaching 45% after the age of 70 years; and (iii) in this study the values of T/LH paralleled those of cFT closely; therefore, T/LH could serve as a surrogate for cFT.

Adult↗

Immune response against 3LL Lewis lung carcinoma potentiates the therapeutic efficacy of endostatin.

The ability of the antitumor immune response to potentiate the therapeutic efficacy of the antiangiogenic agent endostatin was investigated. The antitumor effects of endostatin were tested against weakly immunogenic 3LL Lewis lung carcinoma and its highly immunogenic variant 3LL-C75. Using in vivo Matrigel assay, it was found that the recombinant endostatin produced in the authors' laboratory has a potent antiangiogenic effect. Endostatin manifested a more potent antitumor effect against highly immunogenic 3LL-C75 than weakly immunogenic 3LL tumor. Endostatin induced regression of immunogenic 3LL-C75 tumor in 40% of C57BL/6 mice, whereas partial inhibition and no regression were found in mice bearing weakly immunogenic 3LL tumor. 3LL and 3LL-C75 cells produced similar amounts of Vascular Endothelial Growth Factor, and immunohistochemical analysis revealed that endostatin treatment reduced microvessel density in both 3LL and 3LL-C75 tumors. However, infiltration of T lymphocytes was observed in 3LL-C75 but not in 3LL tumors. These results suggest that the host's immune response may potentiate the antitumor effects of antiangiogenic agents. This possibility was further supported by findings that the antitumor activity of endostatin against 3LL-C75 tumor was lower in immunodeficient than in immunocompetent mice. Stimulation of immune response against 3LL tumor by vaccination with highly immunogenic 3LL-C75 cells substantially increased the antitumor effect of endostatain, resulting in a complete and permanent regression of 3LL tumor in 50% of mice. Tumor vaccination or endostatin treatment applied separately inhibited but did not induce regression of 3LL tumor. These results suggest that the combined attack against tumor cells and the tumor vascular system using antitumor immune mechanisms and antiangiogenic drugs can be a promising strategy for cancer treatment.

Angiogenesis Inhibitors↗

No difference in the proportion of insulin receptor exon 11 +/- isoform mRNA in the liver of rats after development of hypertension.

1. There are two functionally different isoforms of the insulin receptor in humans and rats. We hypothesized that a change in their relative proportion could be of relevance to insulin resistance in hypertension. 2. A reverse-transcriptase polymerase chain reaction technique was established for the detection of mRNA for the exon 11+ and exon 11- isoforms and the proportion of each was determined in 3, 6, 9 and 12 week old spontaneously hypertensive rats and Wistar-Kyoto rats, as well as adrenocorticotrophin (ACTH)-induced hypertensive rats and controls. 3. The proportion of the exon 11+ form (approximately 95%) and exon 11- form (approximately 5%) was similar in the liver of all rats studied. 4. We conclude that there is no change in insulin receptor isoform expression in the liver in the models of hypertension studied.

Adrenocorticotropic Hormone↗

Hypotensive effects of peptide T in conscious rats.

1. The present study investigated the effects of peptide T on mean arterial blood pressure (MAP) in conscious normotensive Sprague-Dawley (SD) rats, spontaneously hypertensive rats (SHR) and two-kidney one-clip (2K1C) hypertensive rats. 2. Peptide T was infused via the left jugular vein at a rate of 1 mg/kg per h in SD, SHR and 2K1C rats and then at doses of 0.1, 0.25, 0.5, 1 and 5 mg/kg per h in SHR, with 0.9% saline as a sham control in SHR and 2K1C. Mean arterial pressure was measured directly before, during and after infusion. 3. Peptide T (1 mg/kg per h) decreased blood pressure in both SHR (P < 0.01) and 2K1C (P < 0.05). In normotensive SD rats the fall in MAP approached statistical significance (P = 0.06). The effect of peptide T was not significantly different in normotensive compared with hypertensive rats. Saline infusion had no effect. The blood pressure lowering effect of peptide T appeared to be dose-dependent in SHR.

Animals↗

Dexamethasone-induced hypertension in the rat: effects of L-arginine.

1. The effects of L-arginine treatment on dexamethasone-induced hypertension were examined in the Sprague-Dawley rat. Seventy rats were randomly divided into the following eight groups: sham, dexamethasone (5 and 10 micrograms/day, L-arginine (100 and 500 mg/kg per day), L-arginine (100 or 500 mg/kg per day) + dexamethasone (10 micrograms/day), L-arginine (520-797 mg/kg per day in food) + dexamethasone (5 micrograms/day). Systolic blood pressure (SBP), bodyweight and plasma nitrate/nitrite concentration were measured. 2. Dexamethasone (5 and 10 micrograms/day) increased SBP in both sham and L-arginine-treated rats. Dexamethasone at 10 micrograms/day decreased bodyweight, but did not alter plasma nitrate/nitrite concentrations. 3. L-Arginine (500 mg/kg per day, i.p.) increased plasma nitrate/nitrite concentrations in 10 micrograms/day dexamethasone-treated rats. L-Arginine did not alter blood pressure in either sham or dexamethasone-treated rats. 4. Dexamethasone-induced hypertension differs from adrenocorticotropic hormone (ACTH)-induced hypertension in the rat in that it is not modified by L-arginine. Thus, ACTH-induced hypertension cannot be explained simply in terms of glucocorticoid activity.

Animals↗

Co-localization of histamine and dopamine-beta-hydroxylase in sympathetic ganglion and release of histamine from cardiac sympathetic terminals of guinea-pig.

1. The aim of this study was to investigate the co-localization of histamine and dopamine-beta-hydroxylase in the superior cervical ganglion of guinea-pig and release of histamine from cardiac sympathetic terminals in guinea-pig isolated atrium. 2. Histidine decarboxylase (a histamine-synthesizing enzyme) mRNA signals were detected in the neurones of superior cervical ganglion of guinea-pig by in situ hybridization. The results of double-labelled immunofluorescence further confirmed the co-localization of histamine and dopamine-beta-hydroxylase in the large principle neurons and small intensely fluorescent cells in the superior cervical ganglion. The immunoreactivities of both histamine and dopamine-beta-hydroxylase were significantly attenuated after 6-hydroxydopamine-induced lesion of sympathetic nerves. 3. The refractory electrical field stimulation caused the release of histamine from cardiac sympathetic terminals of guinea-pig isolated atria (112.14 +/- 40.34 ng x ml(-1)), which was significantly attenuated to 35 +/- 15.57 ng x ml(-1) by reserpine pretreatment. Following administering compound 48/80, a mast cell degranulator, electrical field stimulation induced a dramatic increase of endogenous histamine release from isolated atria (303.57 +/-72.93 ng x ml(-1)). When compound 48/80 was added to the reserpine-treated atria, the release of histamine induced by field stimulation was decreased to 207.14 +/- 76.39 ng x ml(-1). 4 These results provide novel evidence that histamine co-exists with noradrenaline in sympathetic nerves and might act as a neurotransmitter to modulate sympathetic neurotransmission.

Animals↗

Effects of protein malnutrition and endotoxin on the intestinal mucosal barrier to the translocation of indigenous flora in mice.

Since protein malnourished or endotoxemic patients are at increased risk of developing nosocomial infections with enteric organisms, we investigated the effects of these risk factors alone and in combination on the intestinal mucosal barrier to bacteria. Protein malnutrition resulted in severe ileal atrophy that was directly related to the length of time the mice were protein malnourished. Although protein malnutrition did not promote bacterial translocation from the gut to systemic organs, the protein-malnourished mice were more susceptible to endotoxin-induced bacterial translocation than normally nourished mice (p less than 0.01). Since the gross epithelial damage documented after endotoxin administration in normally nourished mice was diminished after protein malnutrition, there was no correlation between the gross appearance of the epithelial mucosal barrier and the extent of endotoxin-induced bacterial translocation. These results suggest that the synergistic effect of endotoxin plus protein malnutrition on bacterial translocation is not primarily related to failure of the gut mucosal barrier. Nonetheless, it appears that protein-malnourished mice are less able to clear translocating bacteria than normally nourished mice.

Animals↗

[Tobacco etch virus proteinase: crystal structure of the active enzyme and its inactive mutant].

Tobacco Etch Virus Protease (TEV protease) is widely used as a tool for separation of recombinant target proteins from their fusion partners. The crystal structures of two mutants of TEV protease, active autolysis-resistant mutant TEV-S219D in complex with the proteolysis product, and inactive mutant TEV-C151A in complex with a substrate, have been determined at 1.8 and 2.2 A resolution, respectively. The active sites of both mutants, including their oxyanion holes, have identical structures. The C-terminal residues 217-221 of the enzyme are involved in formation of the binding pockets S3-S6. This indicates that the autolysis of the peptide bond Met218-Ser219 exerts a strong effect on the fine-tuning of the substrate in the enzyme active site, which results in considerable decrease in the enzymatic activity.

Binding Sites↗

Inspection for gastric occult blood at regular intervals is the optimum program for the screening of esophageal-gastric cancer.

Gastric occult blood screening has been performed for 242296 persons from 1986 to 1993. 30227 persons had positive reactions to the occult blood reagent. Among them, 17915 persons were asked to accept gastroscopy exam, and 638 esophageal-gastric cancers were found. The cancer detection rates were 3.56%. 4774 persons were asked to accept screening twice and 203 persons were asked to accept screening three times. After follow-up, the cancer detection rates were 2.11% for occult blood positive group if the screening was conducted once a year. The missing case was 0.77% for negative group and it was 0.05% in the same group if the screening was performed twice. Lastly, the missing case would be decreased to 0% when the patients undergone the exam, for three times in continuity. Two thirds of patients still belonged to the early-middle stage of cancer. The 5-year survival rates were 95.2%. The missing case of cancer would be reduced to 0% if the screening was conducted for three years in continuity. The death rates were deducted as well. It is certified that this method is the most effective and reliable way for reducing the death rate of cancer and screening of the upper digestive tract cancer.

Adolescent↗

Induction of experimental SLE in naive mice by immunization with human polyclonal anti-DNA antibody carrying the 16/6 idiotype.

Recently, the induction of SLE in naive mice employing monoclonal anti-DNA antibodies (anti-DNA Ab) carrying the pathogenic idiotype 16/6 (16/6 Id) has been reported. In the current study we report on the induction of experimental SLE by polyclonal IgG anti-DNA Ab derived from a patient with active SLE and carrying the 16/6 Id. Two different experiments were conducted in which BALB/c mice were immunized in the footpads with 1 microgram/ml or 5 micrograms/ml of anti-DNA Ab. The first experiment showed the appearance in the immunized mice of high titre anti-DNA Ab together with antinuclear antibodies, alopecia and proteinuria. In the second experiment we compared, as immunizing agents, 16/6 positive anti-DNA Ab and 16/6 negative anti-tetanus toxoid antibodies (anti-TT Ab) obtained from the serum of the same patients. Our results show that only mice immunized with 16/6 positive antibodies produced anti-DNA Ab, while mice immunized with anti-TT Ab did not show any DNA-binding activity but, surprisingly, developed high titre anti-cardiolipin antibodies.

Alopecia↗

Determination of menthol in honey by gas chromatography.

A gas chromatographic method was developed for the determination of L-menthol in honey at levels as low as 0.1 ppm. The method includes steam distillation and hexane extraction with an internal standard (2,6-dimethylphenol). Beehives treated to control Acarapis woodi over 21 days with 30-60 g L-menthol contained L-menthol residues in honey and beeswax. L-Menthol was found only in treated portions of the hive and not later transferred to added honey supers. The highest levels of residues in honey (18 ppm) and beeswax (2790 ppm) were found when pure L-menthol was adsorbed into foam strips placed on top of the hives. L-Menthol residues in honey were not reduced by storage in open containers at room temperature for up to 55 days. Untrained panelists could not detect L-menthol in honey until the levels approached 36 ppm.

Chromatography, Gas↗

Tumor inhibitory activity of anti-ras ribozymes delivered by retroviral gene transfer.

This study reports the successful introduction into tumor cells of a ribozyme directed against an oncogene using a retroviral gene delivery system. A hammerhead ribozyme that selectively targets and cleaves the activated Ha-ras (V12Ras) oncogene was delivered using a retroviral vector and expressed under the control of a transfer RNA promoter in V12Ras-transformed 3T3 murine fibroblast and rat colon epithelial cells. The expression of V12Ras messenger RNA and V12Ras P21 protein was reduced by up to 100% and 75%, respectively, in cells transduced with functional ribozyme. Reductions in V12Ras expression correlated with the stable expression of the functional ribozyme in vivo and decreased tumorigenicity in nude mice. Ribozyme constructs containing identical antisense flanking regions, but a mutant catalytic center, did not attenuate V12Ras expression or decrease the tumorigenicity of transduced tumor cells. These data support the potential therapeutic role of antioncogene ribozymes.

3T3 Cells↗