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Biomedical subjects

P Band

Publications and source records attributed to P Band.

At least 37 records · Page 2Linked to original sources
PubMed1983

Somatostatin enhances binding of [3H]estradiol to a cytosolic protein in rat pancreas. Possible role of oligopeptide coligands in secretion.

The cytosol fraction of rat pancrease can bind [3H] estradiol specifically and extensively. In contrast to the rat uterus, the binding protein in pancreas requires an accessory factor as a coligand in the steroid-binding reaction. Removal of this accessory factor by passage of the cytosol through CM Affi-Gel blue columns renders eluate fractions virtually incompetent with respect to binding of [3H]estradiol (10 nM). Certain synthetic oligopeptides such as N-benzoyl-L-argininyl-p-nitroanilide, as well as an endogenous accessory factor, can reactivate binding of [3H]estradiol. Thus, localization of the protein that binds [3H]estradiol following chromatography with CM Affi-Gel blue columns can be determined readily by assaying eluate fractions in the absence and presence of either accessory factor or N-benzoyl-L-argininyl-p-nitroanilide. Addition of somatostatin (tetradecapeptide referred to as SRIF14; somatotropin release inhibiting factor) to the activatable, but incompetent, eluate fractions, also enhanced binding of [3H]estradiol. The effect of SRIF14 was biphasic. The threshold concentration required for activation of [3H]estradiol binding was about 1 microM, and maximal stimulation occurred at 25 microM. At higher concentrations of SRIF14, binding declined and reached basal levels at about 75 microM. The concentrations of somatostatin required for activation of binding of [3H]estradiol in vivo may be lower than those indicated above since 1) preparations containing [3H]estradiol-binding protein also contained an SRIF14 peptidase. Following incubation of [125I-Tyr1]SRIF14 with these preparations there was loss of binding of radiolabeled peptide with SRIF14 antiserum. 2) The biphasic nature of SRIF14 activation may reflect feedback inhibition of [3H]estradiol binding by a degradation product of SRIF14. Since SRIF14 has been identified in the delta- (or D-) islet cells of the pancreas, and in concentrations that may be in the microM range, the possibility is raised that these cells serve a paracrine function with respect to acinar cell secretion.

Animals↗
PubMed1983

Role of steroids in secretion--modulating effect of triamcinolone and estradiol on protein synthesis and secretion from the rat exocrine pancreas.

Following adrenalectomy of male rats, or adrenalectomy and ovariectomy of females, there was marked depletion of zymogen granules in acinar cells of the pancreas. Within 9 h after treatment with either triamcinolone or 17 beta-estradiol, complete restoration of these secretory vesicles was observed. This repletion was not inhibited by actinomycin-D. Supernatant fractions (100,000 g, 60 min) of rat pancreas, from both normal and surgically altered animals, contained proteins that bound [3H]-triamcinolone and [3H]-estradiol, suggesting that the action of these hormones is exerted directly on the pancreas. Binding of both steroid hormones required the presence of an additional coligand referred to as accessory factor. In addition, the binding proteins for [3H]-triamcinolone and [3H]-estradiol eluted in similar positions after Sephadex G-200 and CM Affi-gel Blue chromatography. It is uncertain, however, whether a single protein binds both steroid hormones since they had different binding isotherms. Scatchard analysis of binding of [3H]-estradiol yielded a single straight line of negative slope from which it was calculated that there were about 4.4 pmol of binding sites per mg protein, having an average apparent Kd of about 5 X 10(-8) M. Similar analysis of the data for [3H]-triamcinolone yielded a straight line of zero slope indicating nonsaturable binding of hormone at concentrations as high as 10 microM. Since both [14C]-L-leucine incorporation into protein and amylase secretion were affected markedly by the steroid-hormonal status of the animal, it is presumed that steroid-bound complexes in acinar cells of the pancreas modulate synthesis and secretion of protein.

Adrenalectomy↗
PubMed1983

Analysis of binding of [3H]Estradiol to the cytosol fraction of rat pancreas: comparison with sites in the cytosol of uterus.

The cytosol fraction of rat pancreas [100,000 X g (for 1 h) supernatant] demonstrated specific but nonsaturable binding of [3H]estradiol in the concentration range of 2-50 X 10(-9) M. Scatchard analysis of specifically bound [3H]estradiol, determined by the isotope dilution technique (competition with excess unlabeled estradiol), indicated a single class of binding sites (approximately 4.4 pmol/mg protein) with an apparent Kd of 5 X 10(-8) M. Such cytosol fractions, prepared from homogenates that contained protease inhibitors, when prelabeled with [3H]estradiol, demonstrated a single sharp eluate peak of radioactivity after Sephadex G-200 chromatography that corresponded to a molecular weight of 120,000. When protease inhibitors were omitted, [3H]estradiol was associated with material of considerably lower molecular weight. Routinely, the protease inhibitors leupeptin (1 mM), phenylsulfonyl fluoride (0.5 mM), and tosylphenylalanylchloromethyl ketone (0.05 mM) were included in the buffer used for homogenizing both the pancreas and uterus. The protein that binds [3H]estradiol in uterus differed from that in pancreas in a number of ways: 1) in the range of 10-20 X 10(-9) M [3H]estradiol, specific binding of the hormone to uterine sites was saturable, and Scatchard analysis indicated a single class of binding sites, (approximately 0.5 pmol/mg protein) having an apparent Kd of 3 X 10(-10) M; 2) the rate constants of dissociation of the [3H] estradiol-bound complexes in pancreas and uterus were 3.1 X 10(-4) sec-1 (t1/2, 37 min) and 8.7 X 10(-5) sec-1 (t1/2, 134 min), respectively; 3) the molecular weight of the estrogen-binding protein in freshly prepared uterine supernatant fractions appeared to be at least 240,000; this was unaltered regardless of whether protease inhibitors were present during initial homogenization of the tissue; and 4) when uterine supernatants prepared in the absence of protease inhibitors were kept at 8 C for 24 h and then analyzed by Sephadex G-200 chromatography, a second peak of [3H]estradiol-binding activity appeared at the same eluate volume as the low molecular weight binding fractions of pancreas. These data suggest that although the binding proteins in pancreas and uterus are different, there may be some common features at the hormone-binding locus.

Animals↗
PubMed1981

Requirement for an accessory factor for binding of [3H]estradiol to protein in the cytosol fraction of rat pancreas.

Supernatant fractions from rat pancreas bind approximately 300 fmol of [3H]estradiol per mg of protein when incubated with 5 nM [3H]estradiol for 1 hr at room temperature. Passage through gel filtration columns reduces binding in the eluate to approximately 1% of its initial activity. Extracts of the supernatant contain a factor that reactivates binding in gel filtrates. Addition of accessory factor to fractional eluates gives one sharp peak of activity. Since fractions that cannot be reactivated contain as much or more protein as fractions that can be reactivated, it is concluded that interaction of accessory factor and [3H]estradiol-binding protein is specific. Peptides such as antipain [(1-carboxy-2-phenylethyl)carbamoyl-L-arginyl-L-valyl-L-argininal] and, especially, N-benzoyl-L-phenylalanyl-L-valyl-L-arginine-p-nitroanilide also enhanced binding of [3H]estradiol. Accessory factor is water soluble, dialyzable, and heat stable. Although as currently purified, it contains several substances, the data suggest that at least one component of accessory factor is an oligopeptide.

Animals↗
PubMed1981

[Cancerous Peutz-Jeghers syndrome with disseminated metastases].

This report of a patient with Peutz-Jeghers syndrome is unusual in a number of ways: the patient, a 49-year-old woman, was first seen with deep thrombophlebitis of the leg which appeared to be part of a paraneoplastic syndrome. The patient had an adenocarcinoma originating in a hamartoma of the terminal ileum, with ovarian and lymph-node metastases. During the course of the disease the patient was found to have metastatic disease in the cervical lymph nodes which responded, temporarily, to chemotherapy. The authors review the literature on metastatic Peutz-Jeghers syndrome. Although the rate of metastatic disease is low, they believe that all patients with Peutz-Jeghers syndrome deserve a close long-term follow-up.

Adenocarcinoma↗
PubMed1980

Potentiation of cigarette smoking and radiation: evidence from a sputum cytology survey among uranium miners and controls.

To assess the effect of cigarette smoking and of exposure to radon daughters, a prospective survey consisting of periodic sputum cytology evaluation was initiated among 249 underground uranium miners and 123 male controls. Sputum cytology specimens showing moderate atypia, marked atypia, or cancer cells were classified as abnormal. As compared to control smokers, miners who smoke had a significantly higher incidence of abnormal cytology (P = .025). For miner smokers, the observed frequencies of abnormal cytology were linearly related to cumulative exposure to radon daughters and to the number of years of uranium mining. A statistical model relating the probability of abnormal cytology to the risk factors was investigated using a binary logistic regression. The estimated frequency of abnormal cytology was significantly dependent, for controls, on the duration of cigarette smoking, and for miners, on the duration of cigarette smoking and of uranium mining.

Adult↗
PubMed1977

Chemotherapy of disseminated breast cancer. Current status and prospects.

Chemotherapy once relegated to end stage patients has markedly improved with the use of combinations. Response rates with single agents have improved from 15 to 35%, to 50 to 70%, using combinations with an increase in complete response rates to about 25%. A series of four studies completed by the Eastern Cooperative Oncology Group over the past eight years typifies the improvement in response rates achieved by combinations as compared to single agents. Survival gain can be demonstrated for responders vs non-responders; however with current combinations, there is an apparent plateau in response rates (55 to 60%), durations of response (eight months) and survival for responders (18-22 months) as compared to survival of non-responders (six to eight months). Further improvement in response rates may occur by searching for new agents, combining hormonal and immunostimulation with chemotherapy or by sequencing non-crossresistant combinations. However, since most patients with breast cancer present with local or regional disease but go on to die of disseminated cancer, major improvements in survival are most likely to occur by treating this neoplasm as a systemic disease through cobmining effective local therapy with systemic treatments.

Antineoplastic Agents↗