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Biomedical subjects

H G Fein

Publications and source records attributed to H G Fein.

27 records · Page 2Linked to original sources

Optimization of the production of hCG beta-like material by CaSki human cervical carcinoma cells in roller bottle culture.

This study was aimed at optimizing large-scale roller bottle culture conditions for CaSki human cervical carcinoma cells, to produce ectopic hCG beta-like material in quantities sufficient for subsequent characterization studies. Several cell culture techniques contributed to the achievement of this goal: (1) use of serum-free culture medium; (2) use of intermittent recovery periods in presence of serum; and (3) ultrafiltration of the serum-free medium pool for initial concentration of 100-fold.

Carcinoma, Squamous Cell↗

A distinctive form of human chorionic gonadotropin beta-subunit-like material produced by cervical carcinoma cells.

The DoT and CaSki human cervical carcinoma cell lines ectopically produce material immunologically similar to the beta-subunit of human chorionic gonadotropin (hCG beta). Culture fluids were analyzed by gel filtration chromatography and radioimmunoassay (RIA) using (a) antiserum directed to conformation-specific (core-directed) determinants not involving the carboxyl-terminal peptide (CTP) in hCG beta purified from urinary hCG (i.e., standard hCG beta) or (b) antiserum directed to the CTP in standard hCG beta. CTP-directed RIA recognized a peak of hCG beta-like immunoreactive material that eluted in the same position as standard hCG beta. However, core-directed RIA recognized additional hCG beta-like material (i.e., ectopic beta-II), most of which eluted before standard hCG beta. CaSki cells were incubated with [3H]mannose, [3H]proline, and [3H] leucine, and the spent medium was immunoprecipitated and analyzed by gel electrophoresis. Several labeled peaks were detected in the lane from the anti-hCG beta X Sepharose immunoprecipitate, one of which corresponded in mobility to standard hCG beta, with two more intense components migrating at higher apparent molecular weights. Carboxypeptidase Y digestion released only 0.2 mol equivalents each of [3H]proline and [3H]leucine from the labeled CaSki material immunoprecipitated with anti-hCG beta X Sepharose, compared to 1 mol equivalent each in similar analysis of standard hCG beta. These findings were consistent with the absence of the 4-carboxy-terminal amino acids from 80% of the hCG beta-like immunoreactive material secreted by CaSki cells. The affinity purified ectopic beta-II failed to combine with standard hCG alpha under conditions in which combination of standard hCG beta with standard hCG alpha was essentially complete. Neither aggregation nor proteolytic degradation was the cause of failure of ectopic beta-II to combine with hCG alpha. We conclude that both the DoT and CaSki cervical carcinoma cell lines secrete a distinctive form of hCG beta-like material, ectopic beta-II. Lack of recognition by CTP-directed antisera and amino acid analysis suggest that ectopic beta-II may lack the CTP, despite its apparent larger size relative to standard hCG beta.

Amino Acids↗

Goitrous Hashimoto's thyroiditis. Lack of association with HLA antigens.

We studied HLA antigen frequency in 54 carefully selected patients with goitrous Hashimoto's thyroiditis. All had an appropriate clinical course, positive family history, antithyroid antibodies and/or a needle biopsy indicating chronic lymphocytic thyroiditis. We found no statistically significant association with any HLA-A, -B, -C or DR specificity.

Female↗

Postpartum lymphocytic thyroiditis in American women: a spectrum of thyroid dysfunction.

Six episodes of primary hypothyroidism followed pregnancy in five women. Within 6 months post partum, all were clinically hypothyroid, with a diffuse goiter of two or three times normal size, altered thyroid function tests (average thyroxine [T4] = 2.6 micrograms/dl, thyroid-stimulating hormone [TSH] = 58.2 microunits/ml), and elevated antithyroid antibodies. (All had antimicrosomal antibody titers of 1:6,400 or more.) After 5 more months, all patients had a decrease in antibody titer, resolution of symptoms, and recovery of thyroid hormone levels (average T4 = 7.3 micrograms/dl), although two patients had compensated hypothyroidism (their average TSH = 9.3 microunits/ml). Four patients had lymphocytic thyroiditis diagnosed by fine-needle aspiration biopsy. Despite the apparent transience of postpartum hypothyroidism, all five patients have chronic thyroid dysfunction: three women have persistent goiters (all less than twice normal size) and two have compensated hypothyroidism; one patient had previous Graves' hyperthyroidism, and two had recurrent transient hypothyroidism (at 21 months postpartum in one patient, and 5 months after another pregnancy in the other). Three women had transient, painless hyperthyroidism (average T4 = 16.1) before becoming hypothyroid: two patients within 8 weeks post partum, and the third patient at 20 months (preceding an episode of recurrent hypothyroidism). Previous reports of postpartum hypothyroidism have come from scattered locales abroad, and it is unclear whether local environmental factors are pathogenic. Nevertheless, this syndrome may, in general, have gone unrecognized and may be a significant cause of illness in postpartum women.

Adult↗

Increased glycosylation of serum human chorionic gonadotropin and subunits from eutopic and ectopic sources: comparison with placental and urinary forms.

The role of carbohydrate in the heterogeneity of hCG and its subunits is unclear. To study this question, we chromatographed over Sephadex G-100 an extract of term placenta as well as sera from a woman in the first and third trimesters of pregnancy and sera from two patients with nontrophoblastic malignancies. Samples were cochromatographed with radiolabeled urinary standards. hCG from first trimester pregnancy serum showed multiple peaks on G-100. The dominant peak eluted with an apparent molecular weight (72,000) higher than that of hCG from third trimester serum (63,000), urine (6),000), and placenta (59,000). hCG from both malignancy sera eluted with an apparent molecular weight (62,000) similar to that of hCG from third trimester and urinary hCG. Free hCG alpha from all sera eluted with a similar apparent molecular weight (29,000), which was higher than that of placental and urinary free alpha-subunit (22,000) and the alpha-subunit dissociated from intact hCG from all sources (22,000--23,000). The subunits were dissociated in the denaturing medium of 6 M guanidine-HCl, pH 3.0, and chromatographed in this medium over Sepharose CL-6B. This eliminated all of the differences in apparent molecular weight among corresponding forms that were found on G-100. All forms of hCG alpha coeluted with a chemically identified 80% deglycosylated hCG alpha. hCG and free alpha-subunits were incubated with mixed exoglycosidases which lacked detectable protease activity and were then rechromatographed on G-100. After deglycosylation, hCG from different sources eluted with a considerable heterogeneity (mol wt range, 40,000--50,000) not present in the native forms. Despite the heterogeneity of native free alpha-subunit from various sources, deglycosylation produced a common species with apparent molecular weights of 11,000--12,000, close to the chemically determined molecular weight of the polypeptide chain (10,400). These studies suggest that1) ectopic serum hCG and free alpha-subunit are similar to corresponding eutopic forms; 2) serum hCG and free alpha-subunit from all sources are more glycosylated than placental or urinary forms; 3) first trimester hCG is more glycosylated than other forms of hCG; and 4) serum free alpha-subunit is more glycosylated than the alpha-subunit which combines with hCG beta to form intact hCG.

Carcinoid Tumor↗

Anemia in thyroid diseases.

Thyroid hormones generally stimulate erythropoiesis. These agents also increase erythrocyte 2,3-DPG concentrations, which serve to enhance the delivery of oxygen to tissues. In the absence of thyroid hormones, anemia frequently develops and may be normocytic, hypochromic-microcytic, or macrocytic. Anemia is an uncommon finding in hyperthyroidism but when present may be morphologically similar to that observed in hypothyroidism. Pernicious anemia has been strongly associated with hypothyroidism, hyperthyroidism, and thyroiditis. Complete correction of anemia often requires restoration of thyroid function as well as specific hematinic therapy. Continued attention to hematologic status is essential in the management of patients with thyroid diseases.

Anemia↗

Effects of soman on neuroendocrine and immune function.

We have previously reported that plasma growth hormone (GH) and prolactin levels were markedly decreased in rats two weeks following a single dose (100 micrograms/kg, SC) of soman. We have now conducted additional experiments to attempt to determine whether neuroendocrine responses to physiological or pharmacological challenge are altered in rat survivors of soman exposure, and whether immune function, which can be affected by circulating hormones, is altered in the soman-exposed rats. In the present study, basal prolactin levels were not significantly lower in the soman-treated rats although prolactin increases in response to physiological or pharmacological challenge were attenuated. Also, basal growth hormone levels in soman survivors were similar to control levels in 2 of 3 experiments in the present report. In the third experiment, growth hormone levels were lower in soman-treated animals. Endocrine abnormalities appeared to be related to the severity of soman insult as assessed by changes in body weight following exposure. Both ACTH and prolactin responses to stress were impaired in a severely affected subpopulation of soman survivors. The thymus, an important immune organ, was decreased in weight in severely affected soman survivors, but other tests of immune function did not show differences between control and soman-exposed rats.

Adrenocorticotropic Hormone↗

A hypocaloric high-protein diet as primary therapy for adults with obesity-related diabetes: effective long-term use in a community hospital.

The use of reducing diets as the sole therapy for the long-term management of obese diabetic patients has been generally unsuccessful. Most previous attempts took place with a few patients in university hospital clinical research centers. We placed 36 such patients on a hypocaloric high-protein food diet, consisting of 1.7-2.0 g protein/kg ideal body wt, during admission to a community hospital. After beginning this diet, patients could be weaned from sliding-scale regular insulin in an average of 1.9 days. Patients remained on this diet after discharge (mean hospital stay = 4.3 days), and complex carbohydrates were gradually added up to 80 g daily. Outpatient long-term management consisted of alternating biweekly visits to a sole nurse practitioner or physician or to a group discussion meeting. Follow-up averaged 41 wk, during which eight patients (22%) had sustained weight loss throughout and remained euglycemic. Twenty patients (56%) initially lost weight (average: 23% of ideal body weight), then plateaued weight, but have also remained euglycemic. Only eight patients, (22%) required insulin. Side effects of the diet were not serious in any patient; no one had myocardial irritability or serum potassium less than 2.9 meq/L. This hypocaloric high-protein diet thus appears to be a generally successful means of weaning obese diabetic adult patients from insulin. This can be done rapidly, safely, and permanently in the community. Such diet therapy appears to require minimal laboratory and hospital resources that are available to all health care providers.

Adult↗