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Biomedical subjects

C Wang

Publications and source records attributed to C Wang.

At least 1,279 records · Page 71Linked to original sources

Simultaneous visualization of vascular permeability change and leukocyte egress in the central nervous system during autoimmune encephalomyelitis.

An unresolved issue in the study of demyelinating disease is whether blood-brain barrier damage is dependent upon the migration of inflammatory cells into the central nervous system (CNS). In a study of experimental autoimmune encephalomyelitis (EAE) in rabbits, a freeze-dried, paraffin-embedded tissue technique was exploited to enable (1) the immobilization of intravenously injected sodium fluorescein tracer, as an index of vascular permeability; and (2) an effective labeling by monoclonal antibodies of both T-lymphocytes and mononuclear phagocytes in "unfixed" neural tissue. Using these newly combined methods, evidence was found that increased vascular permeability in the CNS during EAE occurs concomitantly with, and not prior to, infiltration by mononuclear phagocytes.

Animals↗

Symptomatic hypothalamic-pituitary dysfunction in nasopharyngeal carcinoma patients following radiation therapy: a retrospective study.

Endocrine assessment was performed in 32 relapse-free southern Chinese patients (21 males and 11 females, aged 27-50 years at the time of assessment) 5-17 years following radiation therapy (RT) alone for early nasopharyngeal carcinoma (NPC). Initial screening was done using questionnaires emphasizing on impaired sexual function and menstrual disturbance plus measurement of serum levels of thyroxine, free thyroxine index, thyrotropic hormone, prolactin, and additionally testosterone for males only. Those showing abnormalities were subjected to detailed pituitary function tests. Hypothalamic-pituitary dysfunction was found in 7 female patients and only 1 male patient. A delayed TSH response to thyrotropin releasing hormone suggesting a hypothalamic disorder was seen in 6 of the affected female patients, and hyperprolactinaemia in also 6. None of the patients had evidence of diabetes insipidus. Hypopituitarism became symptomatic 2-5 years after RT with a mean latent interval of 3.8 years. A practical protocol for regular endocrine assessment for NPC patients after RT has been proposed. Multiple linear regression analysis of the radiotherapeutic data from the 11 female patients indicates that the likelihood of late occurrence of symptomatic hypothalamic-pituitary dysfunction following RT is dependent on the TDF of the target dose to the nasopharyngeal region and the height of the upper margin of the opposed lateral facial fields above the diaphragma sellae (coefficient of multiple correlation = 0.9025). Except when the sphenoid sinus or the middle cranial fossa is involved, it is advisable to set the height of the upper margin of the lateral facial field at a level no higher than the diaphragma sellae. The hypothalamus and possibly the pituitary stalk as well may sustain permanent damage by doses of radiation within the conventional radiotherapeutic range for carcinomas.

Adult↗

Long-term treatment of hyperprolactinaemia with bromocriptine: effect of drug withdrawal.

Fifty-one patients with hyperprolactinaemia (23 with macroadenoma, 23 with microadenoma, and five with idiopathic hyperprolactinaemia) were treated with bromocriptine for 2-12 years (4.9 +/- 2.9 years, mean +/- SD). During therapy, the serum PRL levels were suppressed into the normal range in all but five patients. In these five patients, despite the high circulating PRL, gonadal function returned to normal in three, while in the other two gonadotrophin reserve was impaired even before therapy. Gel chromatography showed that one of these patients had a high proportion of a large molecular weight form of PRL. Twenty-four patients received bromocriptine as the sole method of treatment for over 2 years (3.4 +/- 2.3 years). In five out of the 24 subjects (21%), serum PRL remained normal with no clinical symptoms after prolonged drug withdrawal (1-4 years). Twenty-one patients received radiotherapy in conjunction with bromocriptine therapy. Of these 11 had prior surgery. After a follow-up of 6.0 +/- 3.0 years after radiotherapy, serum PRL remained within the normal range in 6 out of 21 subjects (29%), 1-4 years after bromocriptine withdrawal. One of the patients had impaired GH response to insulin hypoglycaemia developing after radiotherapy. We conclude that prolonged bromocriptine treatment is an effective treatment for prolactinomas.

Adenoma↗

Prevention of hypoglycaemia in a patient with pancreatic microadenomatosis by a long-acting somatostatin analogue SMS 201-995.

Acute suppression of insulin secretion from pancreatic insulinomas by long-acting somatostatin analogue SMS 201-995 has been documented. We report the chronic use of the drug in a patient with persistent hypoglycaemia due to benign pancreatic microadenomatosis with satisfactory control of plasma glucose level and reduction of insulin production. There was no tachyphylaxis or untoward side-effect noted during the 6-month treatment period.

Adenoma↗

TEST-egg yolk buffer storage increases the capacity of human sperm to penetrate hamster eggs in vitro.

A total of 85 semen samples from infertility clinic patients were examined to study the effect of storage at 4 degrees C in TES-Tris (TEST)-egg yolk buffer for 24 h on the penetrating capacity of sperm in the zona-free hamster egg penetration assay (HEPA). The mean sperm penetration rate and the fertilization index increased significantly after storage in TEST-egg yolk buffer. Only five out of the 85 samples (5.9%) failed to show any improvement in sperm penetration rate after cold storage. The sperm penetration rate before cold storage showed no significant correlations with routine semen characteristics, semen ATP concentration or the functional integrity of sperm membranes as measured by the hypo-osmotic swelling technique. Significant but low correlations were observed between sperm penetration rate after cold storage and the following semen parameters: sperm count, % motility, total number of motile sperm, % normal sperm morphology, total number of normal sperm, semen ATP concentration and sperm penetration rate before cold storage. Partial correlation analysis revealed that the positive correlation between semen ATP concentration and sperm penetration rate after cold storage was not a direct relationship but was due to the correlation with sperm count. The combination of sperm penetration rate before cold storage, sperm count and % normal sperm morphology accounted for 26.2% of the variation in sperm penetration rate after cold storage by stepwise multiple regression analysis, while sperm penetration rate before cold storage alone explained 13.5% of the variation. The results indicate that TEST-egg yolk buffer treatment can enhance sperm penetration rate in vitro and may be useful in the treatment of impaired sperm fertility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Genetically determined regulators acting on the blast cells of acute myeloblastic leukemia.

Regulatory mechanisms affecting the growth of leukemic cells are attractive targets for new treatments. The blast cells of acute myeloblastic leukemia (AML) may be considered as a lineage; a minority are stem cells capable of both self-renewal and determination followed by terminal divisions ending in proliferatively inert cells retaining blast morphology. Two cell culture methods are available for the study of blasts. The first is a clonogenic assay. Blast stem cells form colonies in methylcellulose, containing proliferatively inert blast cells, together with a small number of new progenitors. Growth factor(s) are usually required. These may be supplied by media conditioned by the continuous bladder carcinoma cell line HTB9 (HTB9-CM). The recombinant growth factors GM-CSF and G-CSF are also active, and in many instances are synergistic. Blast progenitors will also grow in suspension, provided the cell density is high and growth factors are provided. In these cultures, blast progenitors increase in number, reflecting their self-renewal capacity. Evidence is also available that specific genes may be involved in the self-renewal process. Thus, three forms of growth regulation, similar to those encoded by proto-oncogenes, can be shown to be operative in AML blast cell cultures.

Antimetabolites, Antineoplastic↗

Estrogens, progestogens, and androgens enhance the follicle-stimulating hormone-stimulated plasminogen activator production by cultured rat granulosa cells.

We have previously shown that FSH caused a dose-dependent increase in plasminogen activator (PA) production by cultured rat granulosa cells. PA production was assayed by culturing granulosa cells, obtained from immature diethylstilbestrol-treated rats, on [125I]fibrin plates and determining the extent of fibrinolysis after the addition of the specific substrate plasminogen. To study the effect of ovarian steroids on FSH-stimulated PA production, concomitant treatment with FSH and estradiol [(E2) 10(-7) M], progesterone [(P) 10(-6) M], testosterone [(T) 10(-7) M] or 5 alpha-dihydrotestosterone [(DHT) 10(-7) M] were tested in these cultures. Treatment with E2 significantly enhanced the FSH-stimulated PA production by 35-210% over the whole range of the FSH dose response curve. The augmentation of FSH-stimulated PA production by E2 was not affected by the concomitant treatment with the antiprogestin RU 486 (10(-6) M). Similarly, P significantly enhanced the FSH-stimulated PA production by 34 to 90%. The stimulating action of P on FSH-dependent PA production was blocked by the simultaneous treatment with RU 486. Concomitant treatment with T significantly increased the FSH-induced PA production by 22-60%. That the effect of T was not due to the aromatization to E2 was evidenced by the augmentation by DHT of FSH-stimulated PA production. DHT caused a significant 20-39% enhancement in the responsiveness of the granulosa cells to FSH by further increasing PA production. The enhancement of PA production by androgen is decreased partially by concomitant treatment with the antiandrogen flutamide (10(-5) M) and the antiprogestin RU 486. These in vitro data demonstrated the importance of estrogens, progestogens, and androgens in modulating the stimulating effect of FSH on PA production by immature rat granulosa cells.

Androgens↗

Early effects of cranial irradiation on hypothalamic-pituitary function.

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.

Adult↗

Serum bioactive follicle-stimulating hormone in men with idiopathic azoospermia and oligospermia.

Using an in vitro granulosa cell aromatase bioassay (GAB), serum bioactive FSH (bio-FSH) levels were measured in 20 fertile men and 74 men with idiopathic azoospermia or oligospermia. The serum bio-FSH levels measured by the GAB assay and the immunoreactive FSH (immuno-FSH) levels measured by RIA were positively correlated (r = 0.93). Compared to normal men, serum bio-FSH and immuno-FSH levels were elevated in patients with idiopathic azoospermia associated with severe germinal epithelium damage; the bioactive to immunoreactive ratio (B:I ratio) of FSH in these men [mean, 1.5 +/- 0.5 (+/- SD)] was significantly lower than that in fertile men (2.7 +/- 0.8). Similarly, in men with moderate and severe oligospermia, the B:I ratios of FSH were decreased (1.4 +/- 0.4 and 1.7 +/- 0.3, respectively). Although serum immuno-FSH levels correlated weakly with mean sperm concentrations in the normal and oligospermic men (r = -0.35), no relationship was found between serum bio-FSH and sperm concentrations. The B:I ratio of FSH correlated weakly with sperm concentration (r = 0.46). These findings suggest that the B:I ratio of FSH measured by the GAB assay decreases in patients with low sperm concentrations and germinal cell failure.

Adult↗

Strong association between HLA DRw9 and Hashimoto's thyroiditis in southern Chinese.

The distribution of HLA-A, -B, and -DR antigens in 53 Southern Chinese patients with Hashimoto's thyroiditis including 33 with goitre and 20 without goitre was compared with the distribution in 100 Southern Chinese controls. There was a significantly increased prevalence of HLA Bw46 in the nongoiterous patients and of HLA DRw9 in both groups of patients, but only for HLA DRw9 in the goiterous group was the increase significant after adjustment for the number of antigens studied. Based on these findings and those in other autoimmune diseases it is considered that the haplotype Bw46, DRw9 in Chinese takes the place of B8, DR3 in Caucasians in carrying genes which predispose to the development of auto-immune disease.

Adolescent↗

Sensitivity to 5-azacytidine of blast progenitors in acute myeloblastic leukemia.

In a previous study, we showed that the blast stem cells of acute myeloblastic leukemia (AML) were more sensitive to cytosine arabinoside (ara-C) when growing in suspension culture than during colony formation in methylcellulose. We suggested that the difference might be explained by considering the cellular mechanisms responsible for growth in suspension and colony formation. In the former, the clonogenic cells increase in number (self-renewal); in the latter, most of the divisions are terminal. The increased sensitivity to ara-C in suspension might then be attributed to its ability to inhibit self-renewal to a greater degree than cell division generally. A test of this hypothesis would be to compare the survival curves in suspension and in methylcellulose using a drug that spared or stimulated self-renewal. Such an agent is 5-azacytidine (5-aza) and has the additional advantage that its analogue, 6-azacytidine (6-aza) has no effect on self renewal. The data supported the hypothesis, since clonogenic AML blasts were much less sensitive to 5-aza in suspension than in methylcellulose. The effect of 6-aza, while qualitatively similar, was much less marked. Controls showed that the difference in survival curves could not be explained on a kinetic basis or by the secretion of growth factors by 5-aza-treated cells. We suggest that a comparison of the effects of drugs in suspension and in methylcellulose may be useful in preclinical screening of putative anti-AML compounds.

Azacitidine↗

The effects of dauricine and verapamil as calcium channel blockers on the plasma concentration of 6-keto-prostaglandin F1 alpha and thromboxane B2 during cardiopulmonary bypass.

Three groups of ten dogs underwent 80 minutes cardiopulmonary bypass. Two of the three groups were administered dauricine, as a new calcium channel blocker, and verapamil, as a generally recognized calcium channel blocker, respectively, from 15 minutes pre-bypass to the end of the bypass procedure (a period of 95 minutes). By means of radioimmunoassay plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2) as the stable metabolites of prostacyclin and thromboxane A2 were surveyed. During the aortic clamping the hemodynamic changes were recorded. The dauricine and verapamil groups showed markedly inhibited generation of excessive 6-keto-PGF1 and TxB2, a narrowed ratio of TxB2 to 6-keto-PGF1 alpha, as well as a reduced total systemic peripheral resistance within the perfusion period. These results suggest that dauricine and verapamil have a salutary effect in extracorporeal circulation. The possible mechanisms are discussed.

6-Ketoprostaglandin F1 alpha↗

Response to 5-azacytidine of leukemic blast cells in suspension: a biological parameter associated with response to chemotherapy.

Sensitivities to drugs acting on cells in culture can be measured as dose-response curves, provided a quantitative assay is available for a relevant cell function. We have used two such assays in the study of the blast cells of acute myeloblastic leukemia. Colony formation in culture with methylcellulose detects principally terminal divisions, while growth of clonogenic cells in suspension reflects self-renewal. In a previous study different cytosine arabinoside and 5-azacytidine dose-response curves were obtained with the two assays. For the former the slope of the dose-response curve measured in suspension was steeper than that obtained using the clonogenic assay. For the latter, 5-azacytidine, the relationship between sensitivity in suspension and in methylcellulose was reversed. Further, for cytosine arabinoside, sensitivity in suspension but not in methylcellulose was associated with successful remission-induction. In this article we report an association between 5-azacytidine sensitivity in suspension and successful remission induction, for patients treated only with high-dose cytosine arabinoside. There was no correlation between the 5-azacytidine dose-response curve in methyl-cellulose and clinical outcome. A model is presented that may explain these findings, based on the hypothesis that there are genetic mechanisms responsible for blast cell renewal.

Adult↗

Intramuscular imipenem/cilastatin in the treatment of mild and moderate infections.

Imipenem/cilastatin is the combination of a broad spectrum beta-lactam antibiotic with dehydropeptidase I--an inhibitor of the metabolism of imipenem. Clinical trials have shown that imipenem/cilastatin given intravenously is effective in the treatment of mild, moderate or severe infections. A new milled form of imipenem has been developed for intramuscular use as a suspension with cilastatin, which provides a longer effective half-life of three to four hours with lower peak concentrations of imipenem. A multicenter clinical trial was instituted in the treatment of mild and moderate infections with 500 mg b.i.d. and 500 mg t.i.d. or 750 mg b.i.d., respectively. All 500 mg doses were suspended in saline while the 750 mg doses were in 1% lidocaine. A total of 346 (126 on 500 mg b.i.d., 70 on 500 mg t.i.d. and 128 on 750 mg b.i.d.) were entered. Another 22 patients received a combination of the two regimens. Of the total 346 patients entered, 286 were considered evaluable for efficacy. Skin and soft tissue infections were the most common followed by intra-abdominal, respiratory and urinary tract infections. Overall favorable outcomes were demonstrated in 98.7% with a range of 92 to 100%. All patients were included in the safety analysis. Clinical adverse experiences (AEs) were reported in 3.2% of patients with two AEs considered drug related. Both were pain at the injection site with 500 mg doses. No injection site pain was reported as AEs with the 750 mg doses. Laboratory AEs were reported in 17% and considered drug related in 7% (primarily liver enzymes changes).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

Correlation between semen adenosine triphosphate and sperm fertilizing capacity.

The concentration of ATP was determined in a large number of semen samples from fertile men and infertility clinic patients. Results were correlated with routine semen characteristics, in vitro sperm fertilizing capacity, and functional integrity of the sperm membrane. The results confirm the findings of Comhaire et al. and Irvine and Aitken that there are positive correlations between semen ATP concentration and sperm count and sperm motility. In routine laboratory examination of semen specimen, the results agree with those of Irvine and Aitken that semen ATP determination does not appear to be useful as a biochemical marker for sperm fertilizing capacity, as assessed by the in vitro zona-free HEPA.

Adenosine Triphosphate↗

Preliminary studies of the complement fixation test to confirm the diagnosis of bovine ephemeral fever.

A strain of bovine ephemeral fever (BEF) virus isolated in China in 1976 was adapted to growth in tissue cultures. A baby hamster kidney complement fixing (CF) antigen, stable at -20 degrees C for at least 120 days, was prepared from the BEF virus grown in tissue culture and used to test bovine sera for antibodies to that virus. CF antibodies were detected in all of 31 cattle after convalescence from experimental infection with BEF virus, in 208 (98%) of 213 cattle observed to have shown clinical ephemeral fever in an epidemic, in 96 cattle in these herds which did not show clinical signs of ephemeral fever and 16 cattle from herds in northern China outside the epidemic area. The CF antibodies to BEF virus were found to persist in 34 (89%) of 38 cattle which were bled 6 years after natural exposure to ephemeral fever. The CF antigen is economical to prepare and is suitable to differentiate ephemeral fever from other viral infections with which it could possibly be confused on clinical appearance.

Animals↗