Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined whether hormones would modify the carcinogenic action of aflatoxin B1 (AFB1). Four groups of inbred Fischer rats received AFB1, 125 mug per animal, weekly per os. In three of the groups, certain hormones were administered simultaneously: One group received 1 U growth hormone (GH) sc weekly, another was given 4 U adrenocorticotropin (ACTH) weekly, and a third received 0.5 U insulin weekly sc. AFB1, ACTH, and insulin were given for 20 weeks; GH was given for only 10 weeks. The control group did not receive hormone adjuvant. In each group, 4 animals were killed at 7, 14, 21, 28, and 35 weeks; the remaining rats were killed at 77 weeks. Their livers were carefully examined and samples prepared for light and electron microscopy. Animals receiving AFB1 and ACTH failed to exhibit hepatocellular carcinoma. On the other hand, malignant lymphoma appeared at 56 weeks in 3 of the 6 surviving males on this regime. AFB1, alone or when given with insulin or GH, caused hepatocellular carcinoma in all animals; in these, lymphoma was not observed. Lymphoma comprised two cell types, each with similar neclear characteristics but differing in their nucleocytoplasmic ratios and in the amount and distribution of cytoplasmic organelles. Alterations leading to hepatocellular carcinoma were examined at various stages of development. "Basophilic hyperplasia" reflected an increase in free ribosomes. "Hyperplastic nodules" were composed of hepatocyte aggregates with characteristics similar to those encountered in the earlier stage. Both the "neoplastic nodules" and hepatocellular carcinomas were formed by cells containing large, "smooth fingerprints" and free ribosomal aggregates. These features supported the concept that AFB1 impairs ribosomal binding to endoplasmic reticulum membranes. The failure of ACTH-treated animals to develop hepatocellular carcinoma was ascribed to the effect of adrenal cortical stimulation upon membrane-polysome binding.
 ...
PMID:Inhibition of hepatocarcinogenesis by adrenocorticotropin in aflatoxin B1-treated rats. 18 49

The activation of human granulocytes and invertebrate immunocytes was found to be suppressed by corticotropin (ACTH) and melanotropin (MSH). In spontaneously active granulocytes both neuropeptides caused significant conformational changes indicative of inactivity plus a reduction in their locomotion. Significant inactivation of human granulocytes by ACTH required 2 hr, that by MSH only 20 min. The addition to the incubation medium of phosphoramidon, a specific inhibitor of neutral endopeptidase 24.11, blocked inactivation of granulocytes by ACTH. Radioimmunoassay for MSH of supernatant fluids from granulocytes incubated with ACTH demonstrated a time-dependent increase in MSH. These data strongly indicate that the effect of ACTH is largely due to its conversion to MSH by granulocyte-associated neutral endopeptidase. Parallel experiments with immunocytes from the mollusc Mytilus edulis gave similar results, indicating the universality of this phenomenon. Our finding that the human immunodeficiency virus, among several viruses, induces ACTH and MSH production in H9 T-lymphoma cells suggests an important role of these neuropeptides in the immunosuppression characteristic of such infections.
 ...
PMID:Immunosuppressive effects of corticotropin and melanotropin and their possible significance in human immunodeficiency virus infection. 130 58

In a randomized, double-blind, placebo-controlled pilot study, we examined the effect of Org 2766--a corticotropin (4-9) analogue--on neurotoxicity in 28 patients with lymphoma who were treated with combination chemotherapy containing Vinca alkaloids (vincristine and vinblastine). The patients received a total dose of 12 mg of vincristine in the case of non-Hodgkin's lymphoma and a total dose of 16 mg of vincristine in the case of Hodgkin's disease. Moreover, the patients with Hodgkin's disease received a mean total dose of 84 mg of vinblastine. Subcutaneous injections of 2 mg of Org 2766 or placebo were administered to patients with non-Hodgkin's lymphoma on days 1 and 10 of each chemotherapy course and to patients with Hodgkin's disease on days 1 and 8 of each chemotherapy course. The first injection was always given before the administration of vincristine. Assessment of neurologic symptoms and signs and measurement of sensory thresholds (vibration sense and temperature sense) were performed on day 1 of the first, fourth, and sixth (or eighth) courses and 6 weeks after cessation of chemotherapy. Thirteen patients (mean age, 44.7 years) received Org 2766 and 15 patients (mean age, 54.7 years) received placebo. More symptoms occurred in the placebo group, but only numbness and autonomic complaints occurred significantly more often in the placebo group. Motor deficit and sensory disturbances were more severe and also occurred significantly more often in the placebo group. There was no difference with respect to reflex examination findings and sensory thresholds.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A pilot study on the influence of a corticotropin (4-9) analogue on Vinca alkaloid-induced neuropathy. 132 97

Evidence has accumulated that human peripheral blood mononuclear cells (PBMC) may release adrenocorticotropic hormone (ACTH) and endorphin-like peptides into the culture medium when stimulated with different substances such as Newcastle disease virus and the lipopolysaccharide of Escherichia coli. However, to our knowledge, no quantitative assessment of ACTH-LIR (like-immunoreactivity) in human PBMC has been reported. We thus utilized a radioimmunoassay for ACTH to find a median of 30 pg of ACTH-LIR in 10(7) PBMC of 11 normal subjects. ACTH-LIR was also detected in 7 different cell lines derived from patients with lymphoid and myeloid malignancies, two of them, JM and U937, showed values of 135 and 108 pg/10(7) cells respectively. Stimulation with IL-1 beta at the concentration of 1000 U/mL induced, after 48 h, a significant increase of intralymphocytic ACTH levels when compared to basal and 24 h values. The chromatographic characterization of this ACTH-LIR showed, at least, three molecular forms of immunoreactive ACTH; molecular weights were 31 kD POMC, 22 kD ACTH and 4.5 kD ACTH. We used northern blotting with human genomic DNA probe for POMC gene to evidence specific mRNA in PBMC; mRNA was also observed in a T lymphocyte cell line derived from a patient with lymphoma. We conclude that PBMC produce ACTH-LIR which may act as a paracrine immunomodulator similar to lymphokine and/or may signal the adrenal gland to secrete glucocorticoids.
 ...
PMID:[ACTH of lymphocytic origin under normal and pathological conditions]. 166 15

Using Northern blotting with a human genomic DNA probe for the pro-opiomelanocortin (POMC) gene, we have shown specific mRNA in normal human peripheral mononuclear cells (PBMC); the presence of specific mRNA was also observed in a T lymphocyte cell line derived from a patient with lymphoma. We then demonstrated that PBMC translate the message into protein. Thus, using a radioimmunoassay with an antibody for ACTH, a median of 29 pg of ACTH-like immunoreactivity (ACTH-LIR) was found in 10(7) PBMC. ACTH-LIR was also detected in seven different cell lines derived from patients with lymphoid and myeloid malignancies, two of them JM and U937 showing the highest values 135 and 108 pg/10(7) cells, respectively. The chromatographic characterization of this ACTH-LIR showed, at least, three molecular forms of immunoreactive ACTH with molecular weights of the order of 31,000 POMC, 22,000 ACTH, and 4,500 ACTH, in addition to high-molecular-weight material (greater than 43,000). We conclude that PBMC produce ACTH-LIR which may act as a paracrine immunomodulator in a similar way to lymphokines and/or may signal the adrenal gland to secrete glucocorticoids.
 ...
PMID:Expression of pro-opiomelanocortin gene and quantification of adrenocorticotropic hormone-like immunoreactivity in human normal peripheral mononuclear cells and lymphoid and myeloid malignancies. 253 7

The role of adrenocorticotropin, cortisol, and corticosterone on chemical carcinogenesis was investigated using the rat aflatoxin B1 hepatocarcinoma model. The animals were divided into untreated controls and various experimental groups receiving the carcinogen alone or the carcinogen with a hormone. Animals lost during the treatment period died mostly of massive hepatic necrosis. The results following 65 weeks of observation show that: (1) hormones decrease the toxicity of aflatoxin B1; (2) adrenocorticotropin possibly exerts its influence on aflatoxin B1 hepatocarcinogenesis through adrenal stimulation, and (3) in aflatoxin B1-adrenocorticotropin treated animals, hepatocellular carcinoma, cholangiocarcinoma, and malignant lymphoma may be observed.
 ...
PMID:Hormonal influences on chemical carcinogenesis: studies with the aflatoxin B1 hepatocarcinoma model in the rat. 625 37

We have studied the effect of chronic intracerebroventricular (i.c.v.) infusion of different opioid peptides on natural killer (NK) cell mediated cytotoxicity in vivo in the spontaneously hypertensive rat (SHR). The in vivo NK cell activity was measured as the clearance of 51Cr-labelled YAC-l lymphoma cells from the lung tissues. Further, the phenotype of lymphocytes in spleen and peripheral blood was analysed by flow cytometry (FACS). All opioid drugs were administered i.c.v. for 6 days with osmotic minipumps releasing 1.0 microliter/h. beta-Endorphin (10 or 20 micrograms/rat per day) significantly increased NK cell cytotoxicity in vivo. The opioid receptor antagonist naloxone (10 mg/kg, i.p.) given immediately before the injection of YAC-lymphoma cells, completely abolished the effects of i.c.v. administered beta-endorphin. Corresponding doses of beta-endorphin administered subcutaneously (s.c.) with minipumps for 6 days did not significantly affect NK cell cytotoxicity. Neither Leu- or Met-enkephalin (20 micrograms/rat per day) nor dynorphin (20 micrograms/rat per day) administered i.c.v. had any significant effects on NK cell activity. In beta-endorphin treated SHR, the percentage of cells with NK cell phenotype (OX52+/CD5-) in peripheral blood was not significantly different from that of controls, while the percentage of cells with T cell phenotype (CD5+/OX52-) was significantly decreased. The percentage of splenic NK cells (OX52+/CD5-) and T cells (CD5+/OX52-) was also unchanged by beta-endorphin treatment i.c.v. These results suggest that of the opioid peptides administered i.c.v., only beta-endorphin augments in vivo NK cell mediated cytotoxicity. We thus conclude that these effects most probably are centrally and opioid receptor mediated effects, since beta-endorphin in the same dose administered peripherally does not influence in vivo NK cell cytotoxicity.
 ...
PMID:Chronic intracerebroventricular administration of beta-endorphin augments natural killer cell cytotoxicity in rats. 879 73

Hypothalamic corticotropin-releasing hormone (CRH) is the principal regulator of the hypothalamus-pituitary-adrenal axis in mammals. In addition, immunoreactive CRH is also present at peripheral sites, where it is thought to act as a proinflammatory peptide. However, the source of peripheral CRH has remained obscure. Human lymphocytes were shown to produce immunoreactive CRH, yet the data on CRH mRNA expression in these cells are equivocal. More recently, Vaughan et al. discovered a new member of the CRH family, termed urocortin. Urocortin was shown to act through the same receptors as CRH. The current study was designed to investigate both mRNA and protein expression of CRH and urocortin in human lymphocytes. Using a commercial CRH(1-41) radioimmunoassay, we demonstrate that normal human lymphocytes and Jurkat T lymphoma cells produce significant amounts of immunoreactive peptide. However, no CRH mRNA was detectable by RT-PCR in these cells. In contrast, a band of the correct size and sequence was amplified with urocortin-specific primers. Immunocytochemical analysis of human lymphocytes using antibodies that could distinguish between CRH and urocortin revealed significant expression of urocortin but not of CRH, consistent with our RT-PCR data. We conclude that human lymphocytes produce urocortin, but not CRH.
 ...
PMID:Human lymphocytes produce urocortin, but not corticotropin-releasing hormone. 946 98

Disruption of the linkage among the immune, nervous, and endocrine systems may contribute to the pathology and symptoms of acquired immunodeficiency syndrome (AIDS). We investigated the role of human immunodeficiency virus (HIV) in altering these linkages via induction of corticotropin (ACTH) by lymphocytes. Cultured T lymphocytes (H9 cell line) were infected with HIV-1, after which ACTH production was measured and characterized at various time intervals by immunofluorescence and Western blotting. We report a coordinate expression of ACTH and p24 HIV core protein in H9 cells. Also, the kinetics of HIV-induced ACTH production by H9 T lymphoma cells are demonstrated using three different strains of HIV as well as UV-inactivated HIV. ACTH production corresponded with the appearance of p24 antigen and was maximal 35 days after infection. UV-inactivated HIV and the viral envelope protein, gp120, were also able to induce ACTH production in these cells, indicating that viral replication was not required for the ACTH induction. The HIV-induced ACTH was synthesized de novo and had the size and biological activity of pituitary ACTH. Inhibition of ACTH in HIV-infected lymphocyte cultures by anti-ACTH antiserum enhanced viral p24 expression. The significance of lymphocyte ACTH in AIDS is not clear, but these results suggest that it may restrict HIV replication and possibly infection.
 ...
PMID:Human immunodeficiency virus induction of corticotropin in lymphoid cells. 985 80

We reviewed the clinical features, essential laboratory data, pituitary imaging findings (computerized tomography and magnetic resonance imaging), management, and outcome of 353 consecutive patients with the presumptive diagnosis of pituitary tumor investigated from January 1984 through December 1997 at University Hospital, Lausanne, Switzerland. In 18 cases primary empty sella turcica was diagnosed, and in 13 cases of pseudacromegaly there were no endocrine abnormalities. The remaining 322 patients disclosed abnormal pituitary masses, including 275 pituitary adenomas, 18 craniopharyngiomas, 6 cases of primary pituitary hyperplasia, 6 intrasellar meningiomas, 6 cases of distant metastases, 4 intrasellar cysts, 2 chordomas, 1 primary lymphoma, and 1 astrocytoma. Biologic data and immunohistochemical analysis of the excised tissues demonstrated that prolactinomas and nonsecreting adenomas (NSAs) were the most frequent pituitary tumors (40% and 39%, respectively), followed by somatotropic adenomas with acromegaly (11%) and Cushing disease (6%). In contrast with the vast majority of NSAs, which significantly expressed glycoprotein hormones in tissue without secreting them, there was a small group of glycoprotein hormone-secreting adenomas (2%), which had a more severe clinical course after surgery. Thirty-eight pituitary masses were incidentally discovered, most of them NSAs. The expansion of pituitary adenomas into the right cavernous sinus was twice as frequent as to the left cavernous sinus. For the differential diagnosis of hyperprolactinemia, basal prolactin (PRL) levels above 85 micrograms/L, in the absence of renal failure and PRL-enhancing drugs, and a PRL increment of less than 30% after thyrotropin-releasing hormone (TRH) accurately ruled out functional hyperprolactinemia due to NSA, and were typical of prolactinomas. For screening and follow-up of acromegaly, basal growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, as well as the paradoxical GH response to TRH (present in 2/3 acromegalic patients), could be used as convenient tools, but the most accurate test for diagnosis and prediction of outcome after therapy was GH (lack of) suppression during oral glucose tolerance test. In Cushing disease, single evening plasma cortisol was as good as the overnight dexamethasone suppression test for screening, and a combined dexamethasoneovine corticotropin-releasing hormone (oCRH) test was as accurate as the long dexamethasone suppression test to confirm the diagnosis. Bilateral inferior petrosal sinus catheterization coupled with oCRH test confirmed the pituitary origin of excess adrenocorticotropic hormone (ACTH) in all patients, including those with normal pituitary on magnetic resonance imaging (50% of the cases). However, this procedure failed to predict tumor localization correctly within the pituitary in 21% of patients. Pituitary cysts, meningiomas, and craniopharyngiomas with an intrasellar component were correctly diagnosed based on pituitary imaging in 75%, 67%, and 44% of cases, respectively. The remainder, as well as the cases of pituitary hyperplasia, metastases, and other less frequent pathologies, were initially diagnosed as NSAs or as masses of unknown nature. When surgery was indicated, pituitary adenomas and other intrasellar masses were operated on by the transsphenoidal route, with the exception of 100% of meningiomas, 83% of craniopharyngiomas, and 10% of NSAs, which were operated on by the transcranial route. Favorable late surgical outcome of prolactinomas could be predicted by a restored PRL response to TRH. However, dopamine agonist (DA) therapy, usually resulting in satisfactory control of PRL levels and in tumor shrinkage, progressively displaced surgery as primary treatment for prolactinomas throughout the study period. After full-term pregnancy, the size of prolactinoma decreased in 7 of 9 patients, and PRL was normal in 2. Surgery was the first treatment for NSAs, with a tumor rela
 ...
PMID:Diagnosis, treatment, and outcome of pituitary tumors and other abnormal intrasellar masses. Retrospective analysis of 353 patients. 1042 6


1 2 Next >>