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Biomedical subjects

C Wang

Publications and source records attributed to C Wang.

At least 1,261 records · Page 70Linked to original sources

Multivariate discriminant analysis of the relationship between the hypo-osmotic swelling test and the in-vitro fertilizing capacity of human sperm.

Multivariate discriminant analysis was used to evaluate the usefulness of routine semen parameters and the hypo-osmotic swelling test (HOST) as predictors of the in-vitro fertilizing capacity of human sperm as assessed by the zona-free hamster egg penetration assay (HEPA). Eighty-eight semen samples from untreated patients attending an infertility clinic were analysed. Semen samples were classified into the following three groups before statistical analysis: group 1--positive sperm penetration (greater than or equal to 10%, n = 39); group 2--borderline penetration rates for HEPA (greater than 0% but less than 10%, n = 39) and group 3--negative sperm penetration (0%, n = 10). The percentage of sperm with normal morphology and sperm count were found to be significant in discriminating between semen samples exhibiting different in-vitro fertilizing capacity. These two discriminating variables in combination gave an overall correct classification rate of 45.5%. The multivariate discriminant analysis was also performed after excluding the data of group 2 semen samples (n = 39), which exhibited borderline sperm penetration rates. As a result, three discriminating variables including semen volume, sperm count and the percentage of sperm with normal morphology were selected. These three variables in combination could accurately predict whether a semen sample would exhibit positive sperm penetration (group 1) or negative sperm penetration (group 3) with an overall accuracy of 75.5%. The percentage of swollen sperm after hypo-osmotic treatment was not related to the HEPA result, as determined by linear correlation and multiple regression analyses, and did not give additional information about the in-vitro fertilizing capacity of sperm as evaluated by multivariate discriminant analysis.

Female↗

Recovery of sperm production following the cessation of gossypol treatment: a two-centre study in China.

A number of variables were investigated in 46 men who had stopped taking gossypol for their predictive association with the degree and time of recovery of spermatogenesis. Thirty-nine (87%) of the men were azoospermic at cessation of gossypol treatment. In those with sperm present the geometric mean concentration and total sperm count were 8.3 X 10(6)/ml and 30.7 X 10(6), respectively. Twenty-eight men (61%) recovered to a defined threshold of spermatogenic function (sperm concentration greater than or equal to 20 X 10(6)/ml), with a median recovery time of 1.1 years. However, 18 men (39%) had not recovered to this degree of spermatogenic function after a median follow-up of 1.9 years and, of these, 10 (22%) remained azoospermic. The influence of individual baseline variables on the time to defined recovery was examined using Kaplan-Meier curves for groups and their joint effect by Cox's regression model. The failure of recovery was strongly associated with longer treatment, greater total dose of gossypol, smaller testicular volume, elevated FSH concentrations and, to a lesser extent, with greater body weight.

China↗

Temporal lobe and hypothalamic-pituitary dysfunctions after radiotherapy for nasopharyngeal carcinoma: a distinct clinical syndrome.

Eleven patients with combined neurological and endocrine complications after external radiotherapy for nasopharyngeal carcinoma are described. Neurologically, memory disturbance, complex partial seizures and hypodense areas in one or both temporal lobes on CT were typical features. Endocrinologically, hypopituitarism was the prominent manifestation. This constellation of clinical features in a patient with previous radiotherapy to the nasopharynx characterises radiation injury to the inferomedial aspects of the temporal lobes and the hypothalamic-pituitary axis. While the parenchymal brain lesions may mimic metastases or glioma on CT, the associated endocrine disturbance would betray the correct diagnosis. The importance of recognising the hypopituitarism which may be clinically asymptomatic and which is amenable to therapy is emphasised, as is the need for a proper fractionation of the radiation dose to minimise the incidence of these disabling complications.

Adult↗

Glomerulonephropathy of Laurence-Moon-Biedl syndrome.

A patient with Laurence-Moon-Biedl syndrome and nephrotic range proteinuria is presented. Radiological investigation of the urinary tract revealed clubbed calyces but no evidence of obstruction or vesicoureteric reflux. Renal biopsy revealed occasional sclerotic glomeruli, extensive foot-process fusion and segmental glomerular basement membrane abnormalities with negative immunofluorescence for immunoglobulins and complement. Nephrotic proteinuria responded to steroid therapy but mild proteinuria persisted. The findings were consistent with minimal change nephropathy superimposed on the glomerular lesions of Lawrence-Moon-Biedl syndrome.

Adult↗

Bioassays of follicle stimulating hormone.

With the availability of these highly sensitive in vitro assays, measurement of bio-FSH in serum and urine becomes possible. Clinical studies have been done to investigate the role of bioactive FSH in different physiological and pathological conditions. There are however problems with these assays. All the assays required cell-culture facility and technique. In general they are technically demanding, expensive, and cumbersome. Both the GAB and SAB will take 5 working days for a technician to process 15-20 samples at multiple dilutions. Both assays rely on primary cultures of cells. Different pituitary FSH standards had been used for the validation of these biological assays. It had been previously demonstrated that pituitary and urinary gonadotropin preparations and standards exhibit different B/I ratios because of the marked heterogeneity of the gonadotropins. Comparing samples with standards of varying B/I ratios and bio-FSH activity makes the data difficult to interpret. In addition, in the GAB, rat FSH (FSH-I-6) and ovine FSH (NIH-S-15) are equipotent, but in the in vivo Steelman-Pohley assay, rat FSH is 5 times more potent than the ovine preparation. Similarly for the SAB, the NIH-hFSH-3 preparation was more potent than the NIH-hFSH-2 preparation, although the reverse was the case when biopotencies were stimulated by the Steelman-Pohley assays. This clearly demonstrates that both the GAB and SAB are in vitro bioassays and do not fully reflect in vivo activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aromatase↗

Long term pulsatile growth hormone (GH)-releasing hormone therapy in children with GH deficiency.

We treated seven GH-deficient children with 3-hourly 1 microgram/kg sc pulses of GHRH-(1-44) for 6 months and 2 micrograms/kg.pulse for another 6 months. Four patients had a serum GH response to iv GHRH before treatment, and an additional patient responded to iv GHRH after 1 month of pulsatile sc GHRH administration. The mean cumulative growth velocity increased from a pretreatment mean of 2.7 +/- 0.2 (+/- SE) to 8.4 +/- 2.5 and 5.4 +/- 0.7 cm/yr after 2 months and 1 yr of treatment, respectively. Low dose pulsatile GHRH therapy was effective in promoting growth in five of seven children, with height gain ranging from 4.4-7.5 cm at the end of 1 yr's therapy. Only one of the two patients who did not respond to GHRH had an improvement in linear growth when they were subsequently treated with synthetic GH. The other patient, a 16.5-yr-old pubertal girl who had both satisfactory GH and somatomedin-C responses during GHRH therapy, did not respond to either GHRH or, later, synthetic GH. The pretreatment serum GH response to iv GHRH, the serum somatomedin-C concentrations, and the peak serum GH response during sc GHRH therapy were not reliable predictors of clinical response.

Adolescent↗

The use of glucagon challenge tests in the diagnostic evaluation of hypoglycemia due to hepatoma and insulinoma.

We previously found that patients with hypoglycemia due to chronic renal and liver disease had anomalous metabolic responses to glucose and glucagon stimulation. In this study we evaluated the use of glucagon (2 mg, iv) tests in the diagnosis of spontaneous hypoglycemia secondary to hepatocellular carcinoma (HCC) and insulinoma. Twenty-one normal subjects, 45 patients with HCC (11 with hypoglycemia), and 14 patients with insulinoma (all with hypoglycemia) were studied. The fasting blood glucose level was low in all patients with hypoglycemia. The fasting plasma insulin and C-peptide concentrations were high in patients with insulinoma and low in patients with HCC and hypoglycemia. The blood glucose responses to glucagon administration were less than normal in patients with HCC and hypoglycemia and within normal limits in patients with insulinoma. The insulinoma patients had increased plasma insulin and C-peptide responses to glucagon despite having low blood glucose levels. Compared with the HCC patients without hypoglycemia, HCC patients with hypoglycemia had impaired plasma insulin and C-peptide responses. The fasting hypoglycemia, hypoinsulinemia, and impaired insulin/C-peptide responses to glucagon in patients with hepatoma and hypoglycemia presumably reflect the production of insulin-like substances by the hepatoma. We conclude that glucagon administration results in characteristic responses in these groups of patients and can be of use in the diagnosis of spontaneous hypoglycemia secondary to hepatoma or insulinoma.

Adenoma, Islet Cell↗

Stem cell renewal and differentiation in acute myeloblastic leukaemia.

The defining properties of stem cells are capacities for self-renewal and, after determination, a limited number of terminal divisions. The blast cells of acute myeloblastic leukaemia (AML) are maintained by stem cells with these two properties. Since renewal and differentiation can be assessed separately in cultures of AML blasts, these cancer cells provide a useful model for examining stem regulation; such studies have practical importance for future developments in the treatment of AML. This paper considers three aspects of blast cell biology. First, evidence is presented that self-renewal and differentiation are regulated by specific genes; further, the DNA encoding these genes has structural features that affect the chemosensitivity of self-renewal. This sensitivity varies from patient-to-patient and is an important attribute contributing to variation in treatment efficacy. Second, the effects of myelopoietic growth factors on blast stem cells are presented and discussed, as these bear on the regulation of the balance between renewal and differentiation. Finally, models of leukaemic haemopoiesis are considered in light of the experimental findings. The suggestion is advanced that leukaemia can be explained better by abnormalities of gene expression than by blocked differentiation.

Antineoplastic Agents↗

Evaluation of the infertile couple.

The evaluation of the infertile couple is usually a lengthy investigation in which all possible etiologic factors in both partners have to be considered. Optimal and cost-effective investigation requires adequate recognition of significant historical data and physical findings. Males without stigmata of endocrinopathies or general medical illnesses require an analysis of their semen as the minimum initial step of evaluation. Those suspected of deficient androgen production and/or action and those with abnormal sperm counts, motility, and/or morphology need assessment of their serum concentrations of selected reproductive hormones. When these initial investigations are negative and there are no demonstrable etiologic female factors underlying the state of infertility, specialized sperm function and sperm allergy testing needs to be performed. The initial investigation of the female partner is best served by assessing the frequency of ovulation and adequacy of corpus luteum function. Women without ovulatory defects should be assessed for the presence of the hostile cervical mucus and structural anomalies of the reproductive tract. Investigations of patients with menstrual dysfunctions should be based upon the presence or absence of hirsutism, changes in body weight, and evidence of other endocrinopathies or medical illnesses. Following the identification and normalization of causes of anovulation, further work-up of patients who remain infertile is similar to those with regular menstrual cycles. The diagnosis of idiopathic infertility is essentially by exclusion of all other causes. Algorithms for the diagnostic evaluation of most infertile couples are provided.

Female↗

Heterogeneity in acute myeloblastic leukemia.

Morphological-identified blast populations are the hallmark of the malignant clones that dominate hemopoiesis in acute myeloblastic leukemia (AML). Marked heterogenity is characteristic of AML blasts. Patient-to-patient variation is seen in their biological properties but is particularly evident in the response to treatment. Intraclonal variation is generated during clonal expansion, particularly as blast stem cells either undergo self-renewal or enter into a series of terminal divisions. These two alternative activities can be monitored in cell culture using a clonogenic assay and a suspension assay. The balance between renewal and differentiation can be altered by exposing blast populations to various growth factors in culture. Further, certain drugs, particularly ara-C, appear to be more toxic for self-renewing divisions than cell-cycle events generally. We suggest that both drugs and growth factors should be assessed for their effects on self-renewal as part of preclinical testing.

Antineoplastic Agents↗

Circulatory effects of anisodamine on cardiopulmonary bypass.

Anisodamine, a new M-cholinergic blocker discovered in China, was employed in experimental dogs on cardiopulmonary bypass (CPB) with a view to observing its hypotensive activities. Before bypass an intravenous bolus injection of anisodamine 5 mg/kg caused a transient fall of about 20 mmHg in arterial blood pressure for 10 to 15 minutes, with an increase of about 10 mmHg in pulse pressure, indicating lowering afterload. During bypass, a continuous intravenous drip of anisodamine brought about 27 to 37 mmHg fall in perfusion pressure (compared with the control group) while the perfusion flow rate was kept constant. Beneficial effects of anisodamine were manifested, post-bypass, by enhancement of cardiac output, lack of elevation of pulmonary arterial pressure, a speedy recovery of the ST segment to normal, and a decrease of the rate-pressure product, as results of circulatory improvement and myocardial protection.

Animals↗

Structure and expression of genes of GM-CSF and G-CSF in blast cells from patients with acute myeloblastic leukemia.

The hematopoietic growth factors granulocyte/macrophage colony-stimulating factor (GM-CSF) and G-CSF, available as recombinant products, stimulate the growth in culture of blasts from patients with acute myeloblastic leukemia (AML). We used cDNA probes for each gene to study the genomic organization in blast cells of 22 patients and expression in the blast cells of 18 patients. Alteration in the structure of G-CSF (two instances) and GM-CSF (two instances) was found. In two patients in whom it was possible to study DNA from bone marrow obtained at remission, the new bands detected in the leukemic cells were not found. Fifteen of 18 patients showed no RNA expression of either growth factor. Both patients with GM-CSF abnormalities as seen by Southern analysis expressed an abnormally large GM-CSF message but no G-CSF messages. One patient with an abnormal Southern pattern with G-CSF expressed normal-sized G-CSF and GM-CSF messages. The biologic significance of these findings remains to be determined. Nonetheless, the abnormal Southern patterns may prove to be useful clonal markers in the study of AML.

Adolescent↗

Radioimmunoassay for etorphine in horses with a 125I analog of etorphine.

To improve the sensitivity and specificity of screening for etorphine in horses, an 125I-labeled etorphine analog was synthesized and an antibody to etorphine was raised in rabbits. A radioimmunoassay (RIA) for etorphine was developed, using these reagents. Bound and free 125I-labeled etorphine was separated by a double-antibody method that reduced interference from materials associated with equine urine. The 125I-labeled etorphine binding was rarely greater than 250 pg of background etorphine equivalents/ml in raw urine and was 100 pg/ml in hydrolyzed urine. The 125I-RIA was capable of detecting etorphine equivalents in urine above these background values. Etorphine equivalents were detected in equine urine samples for about 7 days after 4 mares were dosed with 0.22 microgram of etorphine/kg of body weight, IV. The stability of etorphine in urine from these mares was evaluated. Urine from these dosed mares was held in constant -20 C storage, and aliquots were repeatedly frozen and thawed. When analyzed for etorphine equivalents using an 125I-RIA, etorphine and its metabolites in urine samples were stable for less than or equal to 38 days if continuously frozen and also were resistant to repeated freezing and thawing.

Animals↗

The D-glucose transporter is tissue-specific. Skeletal muscle and adipose tissue have a unique form of glucose transporter.

Using isotopic equilibration with [3H]D-glucose and measurement of D-glucose inhibitable cytochalasin B binding, I show that the erythrocytes of embryonic and newborn rats contain D-glucose transporters. On the basis of cytochalasin B binding and the time course of isotopic exchange, the number of transporters in rat embryonic erythrocytes is only 5% of that in human erythrocytes. Antibodies raised against the human erythrocyte glucose transporter were used as a probe to investigate the structural similarity between transporters. On this basis, the polypeptides of the glucose transporter of human erythrocytes and of embryonic rat erythrocytes are similar but not identical; in addition, certain antibodies showed similar reactivity toward the transporter of rat embryonic erythrocytes and that of rat brain. These antibodies, however, react with brain transporters 5 to 10 times better than with those of skeletal muscle and adipocytes suggesting that insulin responsive tissues may have a different type of glucose transporter. The cellular location of glucose transporters in skeletal muscle, determined by immunofluorescence, is on the plasma membrane or very close to the plasma membrane.

Adipose Tissue↗

Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV40 T antigen.

We have purified a 52 kd protein, AP-2, that binds to enhancer regions of SV40 and human metallothionein IIA (hMT IIA) and stimulates RNA synthesis from these promoters in vitro. Surprisingly, AP-2 also binds to two SV40 early promoter regions recognized by Sp1 and T antigen. Juxtaposed binding sites for AP-2 and Sp1 in the 21 bp repeats may facilitate productive interactions between the two factors. In contrast, sequence-specific binding of AP-2 to SV40 and hMT IIA DNA is inhibited by the viral repressor protein T antigen. Furthermore, T antigen inhibits AP-2-dependent transcriptional activation of the hMT IIA promoter in vitro. The inhibition is neither a direct nor an indirect result of T antigen binding to DNA, because the hMT IIA promoter lacks T antigen binding sites. Instead, sedimentation studies suggest that protein-protein interactions between AP-2 and T antigen block AP-2 binding to DNA. These findings suggest novel mechanisms for mediating positive and negative regulation of transcription.

Antigens, Polyomavirus Transforming↗