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Biomedical subjects

A G Fazekas

Publications and source records attributed to A G Fazekas.

At least 19 recordsLinked to original sources
PubMed1988

Progesterone receptors regulate gallbladder motility.

The increased incidence of gallstones in multiparous women may be related to hormonal effects on the gallbladder and its contractility. The occurrence of estrogen and progesterone receptors were studied in the gallbladders of three groups of female guinea pigs (normals, oophorectomized, and oophorectomized treated with estrogen + progesterone for 14 days). Gallbladder contractile response in vivo to cholecystokinin (CCK) was related to the presence of these receptors. The gallbladders from normal females showed low progesterone and estrogen binding activity (4.9 +/- 2.0 and 2.4 +/- 0.8 fmoles/mg cytosol protein). Oophorectomized females had no detectable progesterone or estrogen receptors, but after treating oophorectomized females for 14 days with estrogen + progesterone, gallbladder concentrations of progesterone receptors increased significantly to 14.7 +/- 5.9 fmoles/mg and estrogen binding activity was minimally detectable at 1.4 +/- 0.8 fmoles/mg. The gallbladder contractile response to CCK was inversely related to the concentration of progesterone receptors in the gallbladder wall. These data suggest that the gallbladder contains progesterone receptors which are susceptible to circulating hormonal conditions and which have a regulatory effect on gallbladder contractility.

Animals↗
PubMed1988

Relationship between gallbladder contraction and progesterone receptors in patients with gallstones.

Stasis of bile within the gallbladder has long been suspected of having an important role in the pathogenesis of gallstone disease. We postulated that the female preponderance of gallstone disease might partly be related to the effects of progesterone, a known smooth muscle relaxant, on specific receptors in the gallbladder wall, leading to stasis of bile. A total of 42 patients with gallstone disease and 28 control subjects underwent radionuclide scan imaging and their gallbladder ejection fractions were calculated in response to intravenous infusion of cholecystokinin octapeptide. Patients then underwent cholecystectomy and a piece of gallbladder fundus was assayed for the presence of progesterone receptors. Receptors were present in 60 percent of patients. As a group, gallstone patients had a decreased ejection fraction compared with control subjects. The presence of progesterone receptors in the gallbladder wall was associated with a decreased percentage of ejection compared with both healthy control subjects and patients whose gallbladders were receptor-negative. We conclude that progesterone receptors are present in the gallbladder wall of gallstone patients and that their presence correlates with impaired gallbladder emptying.

Adult↗
PubMed1980

Studies on estrogen receptors and regression in human breast cancer.

Estradiol receptors were studied both qualitatively and quantitatively in 650 cases of breast cancer to obtain information on molecular forms and relationship with response to endocrine therapy. Cytosol estradiol receptor (ERC) was assayed by a charcoal method following incubations with 3H-estradiol and also by chromatography on Sephacryl columns. Results were classified as positive (10 fmoles/mg P and up), borderline (3-10 fmoles) and negative (0-3 fmoles). It was found that 44.6% of tumors were positive, 14.15% were borderline, and 41.2% were negative. Qualitatively, two major molecular forms of ERC were identified with molecular weights 31,000 and approximately 250,000. ERC level and response to endocrine therapy were correlated in a group of 52 patients. Response rate to hormonal therapy only was 59% in the ERC-positive, 28% in the borderline, and 9% in the ERC-negative group. Combination therapy, including endocrine manipulation, chemotherapy, and/or radiation improved response rates to 66% in the ERC-positive, 40% in the borderline, and 33% in the ERC-negative group. Defects in the translocation of the cytosol estradiol receptor (ERC)-estradiol complex to the nucleus could partly explain the failure of endocrine therapy in 40% of patients with significant ERC. To examine this possibility, 98 cases of breast cancer were examined for both ERC and nuclear translocation of estradiol (ERN). Nuclei were isolated from the low speed sediment and incubated with the ERC-3H-estradiol complex in the presence and absence of an estrogen competitor. After incubation, ERN was extracted from the nuclei and expressed as specifically bound estradiol, fmoles/mg DNA. Of 44 cases with significant ERC, nine had no ERN (20%). In the borderline group of 23 cases, eight had no ERN (34%), and of the 31 cases with zero or negligible ERC 27 had no ERN (87%). Results indicate that ERC-negative cases should be excluded from hormonal therapy and appear to benefit most from chemo- and/or radiation therapy. The absence of ERN in a significant proportion of ERC-positive cases probably contributes to the failure of hormonal manipulation in such patients. The results indicate that the determination of both ERC and ERN could improve the selection of patients for endocrine therapy.

Breast Neoplasms↗
PubMed1977

Cortisol in human breast cancer tissue.

Endogenous cortisol levels were measured by radioimmunoassay in 140 primary and 31 metastatic human breast cancer specimens. The adjacent normal breast was assayed in 15 cases. Mean values for normal breast were 17.3 ng/g tissue. Significantly higher levels were found in cancer tissue. Primary lesions contained 26 ng/g and metastases 32.5 ng/g cortisol. These results lend support to our previous data on increased cortisol binding activity in human breast cancer.

Breast Neoplasms↗
PubMed1977

Macromolecular binding of glucocorticoids in human mammary carcinoma.

The presence of glucocorticoid receptors was examined in 100 primary and 22 metastatic human breast cancer lesions. Aliquots of cytosol were incubated in vitro with tritiated cortisol and dexamethasone with and without competing steroids. Two different types of glucocorticoid receptors were detected. One is similar to transcortin; it sediments at 4 S in the ultracentrifuge, has a dissociation constant in the same range (10(-8) M), and does not bind fluorinated corticosteroids. While every tumor showed cortisol binding, very high activity (greater than 1000 fmoles/g tissue) was detected in 38% of primaries and in 59% of metastases. Plasma transcortin could be excluded as the source of binding activity. The other receptor binds both natural and fluorinated corticosteroids, has a higher affinity (Kd 10(-9) M), and sediments at 8 S. It was present in 23% of tumors and its quantity (26 to 995 fmoles/g) was much less than that of cortisol binder (50 to 6000 fmoles/g). While there was no correlation between the two glucocorticoid receptors, 80% of dexamethasone receptor-positive cases also had estrogen receptor. The results indicate that a significant proportion of these tumors could be subject to glucocorticoid influence.

Adrenal Cortex Hormones↗