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Biomedical subjects

W B Panko

Publications and source records attributed to W B Panko.

At least 37 records · Page 2Linked to original sources
PubMed1982

Estrogen binding sites in the nucleus of normal and malignant human tissue: characteristics of the multiple nuclear binding sites.

The studies presented here describe the effects of the nonionic detergent, Tween 80 and the reducing agent, dithiothreitol (5 mM), on the quantitation of specific nuclear estrogen binding sites, both estrogen receptors (ER) and type II estrogen binding sites (EBS), in human breast cancer. Neither of these agents had any significant effect on the apparent Kd of the amount of ER measured; however, both had a dramatic effect on the amount of type II EBS measured. Two antiestrogens, tamoxifen and nafoxidine, were also tested for their ability to bind to ER and type II EBS in human breast tumors. Both of the antiestrogens were capable of competing with estradiol for ER and type II EBS. We also present a series of 25 individual human breast cancer specimens which were analyzed for cytoplasmic ER and progesterone receptor by sucrose density gradient centrifugation and for nuclear ER and type II EBS by the sucrose pad assay. Sixty-four % (16 of 25) of the tumors contained nuclear ER and type II EBS when analyzed by the sucrose pad assay. The concentration of type II EBS was strongly correlated to the concentration of cytoplasmic progesterone receptor.

Breast Neoplasms↗
PubMed1981

Glucocorticoid receptors: documentation in the rat uterus.

The question of the presence of specific glucocorticoid receptors in the rat uterus was reassessed. A high speed supernatant obtained from uteri of ovariectomized or intact 45-day old rats was incubated 18 h at 4 c in the presence of [3H]triamcinolone acetonide ([3H]TA) with or without excess dexamethasone, followed by a 10 min exposure to dextran-coated charcoal. A specific uterine glucocorticoid receptor was detected with a Kd=5.1 nM and the number of binding sites equal to 1.1 pmol/uterus. [3H]dexamethasone was observed to underestimate the number of specific receptor sites, probably due to the instability of the dexamethasone-receptor complex during treatment with charcoal. In addition, unlabeled TA was unsatisfactory for determining nonspecific binding because of the cross-reactivity with the progesterone receptor also present in uterine cytosol. The uterine glucocorticoid receptor exhibited the appropriate steroid specificity. Sucrose density gradient analysis of uterine cytosol revealed peaks of dexamethasone-competable [3H]TA binding at 7.2S and 5.75 in low salt and at 4S in 0.4M KCL. Similar components were observed in cytosol and nuclear fractions, respectively, 20 min after in vivo injection of 25 mu Cl [3H]TA. The physical characteristics of the specific glucocorticoid receptor were consistent with those determined for other receptor proteins. The documentation of the presence of glucocorticoid receptors in the rat uterus is important physiologically because of numerous reports of glucocorticoid effects on this reproductive tissue. If receptors could not be demonstrated, extensive studies of the mechanism of these effects would be necessary for a full understanding of uterine endocrinology.

Adrenalectomy↗
PubMed1979

Effect of prostaglandin F2 alpha on endocrine-ovarian function in the domestic cat.

The effect of prostaglandin F2 alpha (PGF2 alpha) on endocrine and ovarian function during the early luteal phase of the domestic cat was investigated. Queens were induced to ovulate and then injected subcutaneously with 0.5-5.0 mg PGF2 alpha/kg body weight. The greatest dose was found to approach toxicity. Concentrations of progesterone were similar in cats following treatment with PGF2 alpha compared to values of controls. Development and regression of corpora lutea as determined by serial laparoscopy were similar in all groups. These data indicate that PGF2 alpha at the tested dosages, given during the early luteal phase is not luteolytic in this species and suggest that these regimens would be ineffective for the premature termination of pseudopregnancy.

Animals↗
PubMed1979

The effects of vasectomy on testicular metabolism in the guinea-pig.

The effects of vasectomy on testicular DNA production were studied in guinea-pigs at 2 weeks and 2 and 6 months after surgery. By 6 months, vasectomy had resulted in lower testicular weight and absolute DNA, RNA and protein contents, although RNA and DNA concentrations/protein were unchanged. Incorporation of thymidine into the testis had decreased by 2 weeks after vasectomy, and continued to do so unless the ductal system subsequently ruptured and formed a granuloma when thymidine incorporation returned to normal control levels. It is suggested that in the guinea=pig vasectomy alters spermatogenesis by reducing testicular DNA synthesis.

Animals↗
PubMed1978

Effect of obstruction of renal metabolism. Renal tissue metabolite concentration after alpha-ketoglutarate infusion.

beta-Hydroxybutyrate and/or alpha-ketoglutarate were infused into awake, resing dogs after varying periods of unilateral ureteral obstruction. The animals were then anesthetized, and the kidneys rapidly excised and frozen in liquid nitrogen. While maintained at temperatures below -60 C, the frozen kidneys were separated into cortical and medullary fractions. The concentrations of alpha-ketoglutarate, glutamate, lactate, pyruvate, citrate, and malate were determined in both cortical and medullary renal tissue. The induction of reversible renal damage by 2 weeks of obstruction was associated with decreased ability to accumulate alpha-ketoglutarate after alpha-ketoglutarate and/or beta-hydroxybutyrate infusion. The induction of irreversible renal damage by 6 weeks of obstruction was associated with the inability to produce or accumulate (i) alpha-ketoglutarate, (ii) lactate, (iii) citrate, or (iv) malate after infusion of alpha-ketoglutarate and/or beta-hydroxybutyrate. The metabolic changes induced by unilateral ureteral obstruction indicatr that aerobic metabolism is inhibited with the virtual elimination of many aerobic reacions in the irreversibly damaged kidney. The reversibly damaged kidney is capable carrying on certain aerobic reactions but usually at a diminished rate. Differences in the extent and character of the metabolic changes induced by ureteral obstruction may make it possible to predict the degree of renal damage and, therefore, recoverability.

Aerobiosis↗
PubMed1978

Uncharged nuclear receptors for estrogen in breast cancers.

This study was undertaken to define the incidence and concentration of uncharged nuclear estrogen receptors (RN) in human breast cancer. The concentrations of RN and cytoplasmic uncharged receptor were determined on sucrose gradients following a 4-hr incubation at 4 degrees with 1.6 nM 17 beta-[3H]estradiol in 139 tumor specimens from 137 patients. RN was extracted from washed nuclear pellets in buffer containing 0.4 M KCl. The receptor molecule extracted had a high affinity for 17 beta-[3H]estradiol (Kd = 0.9 to 7.6 nM) and was specific for estrogen. The possibility of artifact due cytoplasmic contamination of the nuclear fraction or high-ionic-strength-induced exchange of charged nuclear receptors was rendered unlikely by validation experiments performed with pooled tumor tissue. Significant amounts of cytoplasmic uncharged receptor (greater than 7 fmol/mg protein) were found in 63.3% of the tumors. Similar significant amounts of RN were found in 29.5% of the tumors. Significant amounts of RN in the presence of undetectable cytoplasmic uncharged receptor were found in 2.9% of the tumors. The percentage of tumors that contain significant amounts of RN is approximately the same percentage of estrogen receptor-positive tumors that do not respond to ablative therapy.

Adult↗
PubMed1977

Effects of ureteral obstruction on the renal metabolism of alpha-ketoglutarate and other substrates in vivo.

The renal metabolims of alpha-ketoglutarate, glutamate, oxygen, carbon dioxide, and citrate during the infusion of beta-hydroxybutyrate and/or alpha-ketoglutarate was evaluated in vivo in the awake, resting dog after varying periods of unilateral ureteral obstruction. The induction of reversible renal damage by 2 weeks of obstruction was associated with (i) decreased utilization of alpha-ketoglutarate and oxygen; (ii) decreased production of carbon dioxide; (iii) elevated respiratory quotient; and (iv) nearly complete lack of citrate production. The induction of irreversible renal damage by 6 weeks of obstruction was associated with (i) a nearly total absence of alpha-ketoglutarate utilization; (ii) a markedly decreased amount of oxygen utilization and carbon dioxide production; (iii) a normal respiratory quotient; and (iv) a nearly total absence of citrate production. The metabolic changes observed after obstruction indicate that aerobic metabolism is inhibited by either reversible or irreversible renal damage. However, certain anaerobic reactions continued in the reversibly damaged kidney. Differences in the extent and character of metabolic changes may make it possible to predict the degree of renal damage.

Anaerobiosis↗
PubMed1977

Progesterone production by an ovarian granulosa cell carcinoma.

A patient with a progesterone-producing granulosa cell carcinoma is the basis of this report. Seven years after initial surgical therapy pelvic masses were palpated. At laparotomy the recurrence of tumor was confirmed, and many nonresectable metastases were discovered on the surface of the liver and on the mesentery of the bowel. An exceedingly high plasma progesterone level of 6270 pg/ml was obtained in the postoperative period. During 12 months of single agent chemotherapy with melphalan, serial plasma progesterone assays declined to 310 pg/ml. Complete tumor regression was subsequently confirmed by laparoscopy. Evaluation of progesterone levels in patients with granulosa cell tumors is recommended to determine the incidence of this finding and to further assess its value in following response to therapy.

Aged↗