Pituitary tumour transforming gene: a novel factor in pituitary tumour formation.

Although pituitary tumours are common monoclonal neoplasms, they rarely metastasize outside the pituitary fossa, even though they cause considerable morbidity and mortality. Many molecular events underlying pituitary tumourigenesis have been elucidated in recent years, but no clear tumour marker has emerged that assists clinical decision-making with regard to appropriate therapy. Activating mutations and a loss of inactivating mutations, together with hypothalamic hormones, circulating hormones, growth factors and cytokines, co-operatively ensure the inexorable expansion of the initial mutated pituitary cell clone.

Leptin regulation of aromatase activity in adipose stromal cells from regularly cycling women.

Objectives And Design: Leptin, a product of adipocytes, is a cytokine with multiple effects on the reproductive axis. Leptin causes the activation of STAT proteins within target cells. The aromatase gene promoter in adipose stromal cells contains a functional STAT binding region, leading to the hypothesis that leptin may regulate aromatase activity in fat tissue.

Mutation and expression analysis of the cyclin-dependent kinase inhibitor gene p27/Kip1 in pituitary tumors.

By regulating cyclin-cyclin-dependent kinase (CDK) complex activity, individual CDK inhibitors (CDKIs) are potential tumor suppressors. One of the CDKIs, p27/Kip1, binds to a variety of CDK-cyclin complexes. A link between loss of p27/Kip1 function and development of pituitary tumors was suggested by the formation of pituitary tumors in almost all mice with germline deletion of the p27/Kip1 gene.

Pituitary corticotroph SOCS-3: novel intracellular regulation of leukemia-inhibitory factor-mediated proopiomelanocortin gene expression and adrenocorticotropin secretion.

As pituitary leukemia-inhibitory factor (LIF) mediates neuroimmune signals to the hypothalamo-pituitary-adrenal axis, we tested the role of intracellular SOCS-3 in corticotroph function. SOCS-3, a cytokine-inducible protein of the suppressor of cytokine signaling (SOCS) family, is expressed in the murine pituitary in vivo. After i.

Leukemia inhibitory factor regulates proopiomelanocortin transcription.

Leukemia inhibitory factor (LIF), a pleiotropic cytokine, is expressed in both fetal and adult pituitary tissue, and LIF immunoreactivity is found in functional human pituitary tumors. LIF induces basal, and augments CRH-induced, POMC mRNA and ACTH secretion from AtT20 cells. Therefore, we examined LIF signaling and LIF regulation of POMC expression in AtT20 cells.

Treatment of severe liver failure with a bioartificial liver.

Orthotopic liver transplantation (OLT) is the definitive therapy for severe liver failure. However, many patients die before an organ becomes available, mostly from cerebral edema. To provide temporary liver support, we developed a bioartificial liver (BAL) based on porcine hepatocytes and a charcoal column.

C/EBP-epsilon: chromosomal mapping and mutational analysis of the gene in leukemia and preleukemia.

We and others have cloned a novel human gene CCAAT/enhancer-binding protein epsilon (C/EBP-epsilon) encoding a member of the C/EBP gene family. It is exclusively expressed in myeloid and T-lymphoid cells and appears to have an important role in inducing expression of several myeloid-specific genes. We used a polymerase chain reaction (PCR)-based technique to examine DNA from 93 hamster/human radiation hybrid clones in order chromosomally to map C/EBP-epsilon to 14q11.

Structure and function of somatostatin receptors in growth hormone control.

This new generation of SRIF analogs offer exciting opportunities to improve hormone hypersecretion in patients with GH- and TSH-secreting pituitary adenomas and possibly even in patients harboring prolactinomas and non-functioning tumors. Future development of novel analogs with improved affinity for both SSTR2 and SSTR5 may have even greater potency to suppress pituitary hormone hypersecretion and block adenoma growth.

Inhibition of proliferation of prostate cancer cells by a 19-nor-hexafluoride vitamin D3 analogue involves the induction of p21waf1, p27kip1 and E-cadherin.

We have synthesized and studied the ability of a series of seven novel 1 alpha,25(OH)2 vitamin D3 analogues to inhibit clonal growth of prostate cancer cells (LNCaP, PC-3 and DU-145). Addition of double and triple bonds to the C/D ring (C-16) and side chain (C-22 and C-23) as well as lengthening of the side chain were important for enhanced activity against LNCaP and PC-3. Reorientation of the side chain in the 20-epi configuration resulted in analogues that were extremely potent only against LNCaP (ED50 approximately 5 x 10(-11) M).

Effects of retinoid X receptor-selective ligands on proliferation of prostate cancer cells.

Background: Management of prostate cancer that either is detectable by prostate specific antigen (PSA) measurements after curative intent or has spread outside of its capsule is a serious problem. Innovative, nontoxic approaches to the disease are required. One approach might be therapy with retinoids.

Cytomegalovirus infection induces anti-endothelial cell antibodies in cardiac and renal allograft recipients.

Cytomegalovirus (CMV) infection represents a significant morbidity factor for transplant recipients. CMV infection has an association with the development of allograft rejection (AR) through graft endothelial cell (EC) damage, but the mechanisms are not yet clear. There are few reports addressing the role of humoral immunity in vascular EC injury mediated by CMV infection whereas many reports are available regarding the mechanism(s) of CMV-associated allograft EC injury mediated by cellular immunity.

Effects of potent vitamin D3 analogs on clonal proliferation of human prostate cancer cell lines.

Background: Management of prostate cancer that has spread outside of the prostate capsule is a difficult problem. Innovative, non-toxic approaches to the disease are required. New, relatively non-toxic vitamin D3 analogs have recently been synthesized.

Frequent loss of heterozygosity in the region of the D7S523 locus in advanced ovarian cancer.

Loss of heterozygosity (LOH) of the long arm of chromosome 7 occurs frequently in many types of primary cancers. We analyzed 22 primary ovarian cancers for LOH of chromosome arm 7q using a set of 16 microsatellite markers in order to determine the location of a putative tumor suppressor gene (TSG). Eleven samples (50%) showed LOH at least at one locus on chromosome arm 7q.

Pituitary cytokine and growth factor expression and action.

The complex range of pituitary regulatory mechanisms reviewed here underlies the critical function of the pituitary in sustaining all higher life forms. Thus, the ultimate net secretion of pituitary hormones is determined by signal integration from all three tiers of pituitary control. It is clear from our current knowledge that the trophic hormone cells of the anterior pituitary are uniquely specialized to respond to these signals.

Immunohistochemical detection of schwannomin and neurofibromin in vestibular schwannomas, ependymomas and meningiomas.

In addition to schwannomas, patients with neurofibromatosis type 2 (NF2) frequently develop meningiomas and occasionally, ependymomas. Using DNA and protein analyses, we have shown NF2 gene mutations and lack of the gene product schwannomin in 29 schwannomas, 10 meningiomas, and in 7 ependymomas. We have raised antibodies (ABs) to peptides from the C-terminal (5990-AB) and N-terminal (5991-AB) domains of schwannomin.

Ontogeny of steroidogenic enzyme gene expression in ovarian theca-interstitial cells in the rat: regulation by a paracrine theca-differentiating factor prior to achieving luteinizing hormone responsiveness.

The theca cells (TC) first become identifiable in preantral follicles after the granulosa cells (GC) begin to divide. It remains unknown when the TC first respond to LH and acquire the capacity to produce androgens. The signal initiating TC differentiation is also unknown since pre-theca cells do not contain LH receptors.

Molecular analysis of the adenomatous polyposis coli gene in sarcomas, hematological malignancies and noncolonic, neoplastic tissues.

Somatic mutations of the adenomatous polyposis coli (APC) gene have been frequently found in sporadic colorectal tumors, and the frequency of such mutations remain constant as tumors progress from benign adenomas to malignant cancers. Thus the mutations of the APC gene may have a major role in the early development of sporadic colorectal tumors. Whether inactivation of the APC gene accounts for other types of primary tumors is still being investigated.

Direct intraovarian effects of leptin: impairment of the synergistic action of insulin-like growth factor-I on follicle-stimulating hormone-dependent estradiol-17 beta production by rat ovarian granulosa cells.

The Ob gene product, leptin, is secreted by adipocytes and is required for fertility in the mouse. Leptin-deficient mice are obese and infertile, symptoms reminiscent of polycystic ovary syndrome (PCOS). Prior studies have shown that serum leptin levels are elevated in a significant sub-population of anovulatory women with PCOS, suggesting that elevated leptin levels may adversely affect ovarian function.

Morbidity and mortality of recurrent hepatitis C infection after orthotopic liver transplantation.

Through molecular virological testing it is now clear that HCV reinfection of the allograft is virtually universal in liver transplant recipients. Although histopathological recurrence of hepatitis C occurs in the majority of patients, it is absent in a substantial minority. To date, no prognostic factors, other than genotype 1b, have been identified that accurately predict these dissimilar outcomes.

Reducing length of stay for patients hospitalized with exacerbation of COPD by using a practice guideline.

Unlabelled: Clinical practice guidelines have been promoted as an effective way of reducing costs while maintaining quality care.

Objective: To study a practice guideline to shorten length of stay for patients hospitalized with exacerbation of COPD.

Methods: We retrospectively studied a practice guideline to identify patients who were at low risk of complications from their exacerbation of COPD and hence potentially suitable for early hospital discharge.

Leukemia inhibitory factor (LIF) induces acute adrenocorticotrophic hormone (ACTH) secretion in fetal rhesus macaque primates: a novel dynamic test of pituitary function.

Leukemia Inhibitory Factor (LIF), a pituitary cytokine, and LIF receptors are expressed in human fetal and adult adenohypophyseal cells. LIF induces adrenocorticotropin hormone (ACTH) secretion in vitro and potently synergizes with both corticotropin-releasing hormone (CRH) and cAMP-induced pro-opiomelanocortin (POMC) transcription. We therefore investigated the effects of intra-carotid administration of recombinant human LIF to chronically catheterized fetal non-human primates.

Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome.

Recent data in the mouse demonstrate that leptin, a protein hormone produced by fat cells, is required for fertility. In the absence of leptin the mice become obese, diabetic and infertile. Polycystic ovary syndrome (PCOS), a common cause of infertility in women, is associated with obesity and insulin resistance.