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Pathogen research abs 1 || Pathogen research abs 2 || Pathogen research abs 3 || Pathogen research abs 4 || Pathogen research abs 5 || Hormone and endocrine research abs 1 || Hormone and endocrine research abs 2 || Hormone and endocrine research abs 3 || Hormone and endocrine research abs 4 || Hormone and endocrine research abs 5

Am J Pathol. 2002 Jun;160(6):2081-93.
Latent transforming growth factor-beta activation in mammary gland: regulation by ovarian hormones affects ductal and alveolar proliferation.

Ewan KB, Shyamala G, Ravani SA, Tang Y, Akhurst R, Wakefield L, Barcellos-Hoff MH.

Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA.

Transforming growth factor-beta1 (TGF-beta 1) is a pluripotent cytokine that can inhibit epithelial proliferation and induce apoptosis, but is also widely implicated in breast cancer progression. Understanding its biological action in mammary development is critical for understanding its role in cancer. TGF-beta 1 is produced as a latent complex that requires extracellular activation before receptor binding. To better understand the spatial and temporal regulation of its action during mammary gland development, we examined the pattern of activation in situ using antibodies selected to distinguish between latent and active TGF-beta. Activation was highly restricted. TGF-beta 1 activation was localized primarily to the epithelium, and within the epithelium it was restricted to luminal epithelial cells but absent from either cap or myoepithelial cells. Within the luminal epithelium, we noted a further restriction. During periods of proliferation (ie, puberty, estrus and pregnancy), which are stimulated by ovarian hormones, TGF-beta 1 activation decreased in some cells, consistent with preparation for proliferation. Paradoxically, other cells simultaneously increase TGF-beta 1 immunoreactivity, which suggests that TGF-beta 1 differentially restrains epithelial subpopulations from responding to hormonal signals to proliferate. These data suggest that endogenous TGF-beta 1 activation and thus activity are regulated by ovarian hormones. To determine the specific consequences of TGF-beta 1 activity, we manipulated TGF-beta 1 levels in vivo using Tgfbeta 1 knockout mice and undertook tissue recombination experiments with heterozygous tissue. In Tgfbeta 1 heterozygous mice, which have <10% wild-type levels of TGF-beta1, ductal development during puberty and alveolar development during pregnancy were accelerated, consistent with its role as a growth inhibitor. The proliferative index of Tgfbeta 1+/- epithelium was increased approximately twofold in quiescent tissue and fourfold in proliferating tissue but both ducts and alveoli were grossly and histologically normal. To test whether epithelial TGF-beta1 was critical to the proliferative phenotype, Tgfbeta 1+/+ and +/- epithelium were transplanted into +/+ mammary stroma. The outgrowth of Tgfbeta 1+/- epithelium was accelerated in wild-type hosts, indicating that the phenotype was intrinsic to the epithelium. Moreover, proliferation was 15-fold greater in Tgfbeta 1+/- than wild-type mice after ovariectomy and treatment with estrogen and progesterone, suggesting that TGF-beta 1 acts in an autocrine or juxtacrine manner to regulate epithelial proliferation. Together these data indicate that ovarian hormones regulate TGF-beta 1 activation, which in turn restricts proliferative response to hormone signaling.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12057913&dopt=Abstract

Am J Pathol. 2002 Jun;160(6):2259-65.
Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model.

Shimokawa I, Higami Y, Utsuyama M, Tuchiya T, Komatsu T, Chiba T, Yamaza H.

Department of Respiratory and Digestive Medicine, Division of Experimental Medicine, Pathology, and Gerontology, Nagasaki University School of Medicine, Nagasaki City, Japan. shimet.nagasaki-u.ac.jp

The longer life span in dwarf mice suggests that a reduction in the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis retards aging and extends the life span in mammals. We tested this hypothesis in a transgenic strain of rats whose GH gene was suppressed by an anti-sense GH transgene. Male rats homozygous for the transgene (tg/tg) had a reduced number of pituitary GH cells, a lower plasma concentration of IGF-1, and a dwarf phenotype. Heterozygous rats (tg/-) had an intermediate phenotype in plasma IGF-1, food intake, and body weight between tg/tg and control (-/-) rats. The life span of tg/tg rats was 5 to 10% shorter than -/- rats. In contrast, the life span of tg/- rats was 7 to 10% longer than -/- rats. Pathological analysis suggested that neoplasms caused earlier death in tg/tg rats; in contrast, tg/- rats had reduced nonneoplastic diseases and a prolonged life span. Immunological analysis revealed a smaller population and lower activity of splenic natural killer cells in tg/tg rats. The results of the present study support the hypothesis, but suggest that there is an optimal level of the GH-IGF-1 axis to maximize survival in mammals.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12057928&dopt=Abstract

Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2000;32(5):490-494.
Effects of Divalent Cations and Disulfide Bond Reducing Agents on Specific Binding of Growth Hormone to Liver Membrane Receptors from Snakehead Fish (Ophiocephalus argus, Cantor).

Sun X, Zhang XN, Zhu SQ, Zheng HQ.

Shanghai Institute of Biochemistry,the Chinese Academy of Sciences, Shanghai 200031,China. zhusunm.shcnc.ac.cn

Divalent cations, Ca(2 ), Mg(2 ) and Mn(2 ) enhance the binding of bream growth hormone (brGH) to snakehead fish liver membrane, and their optimum concentration was found to be 8 12 mmol/L, at which Ca(2 ), Mg(2 ) and Mn(2 ) could increase, respectively, the specific binding to 230%, 180%, and 200%, compared with the binding in the absence of ions. The Eadie-Scatchard plot was used for the dynamic analysis of the Ca(2 ) binding site. A low affinity Ca(2 ) binding site was found in the GH-receptor complex with K(m)=0.384 mmol/L, and the affinity constant (K(a)) was increased from 1.045x10(9) L.mol(-1) to 1.295x10(9) L.mol(-1) by the addition of 10 mmol/L CaCl(2). The effects of disulfide bond reducing agents, DTT and ME, on (125)I-brGH binding to growth hormone receptor (GHR) on snakehead fish liver memebrane were also analyzed. The addition of 0.1 20 mmol/L DTT or 0.01% 1% ME to the radioreceptor assay system caused a significant dose dependent increase in the specific binding for (125)I-brGH. In the presence of 0.8 mmol/L DTT or 0.08% ME, the specific binding of (125)I-brGH was increased from 10.2% to 15.5% and 13.2% respectively, and the affinity constant was also increased from 1.265x10(9) L.mol(-1) to 2.185x10(9) L.mol(-1) and 1.625x10(9) L.mol(-1), respectively but no changes in the binding capacity were observed. Further studies showed that the effects of reductants on the specific binding of brGH were due in part to the ligand itself and in part to GHR. In addition, it was observed that one of the three disulfide bonds of brGH could be reduced by 0.8 mmol/L DTT.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12058197&dopt=Abstract [PubMed - as supplied by publisher]

Bone Marrow Transplant. 2002 May;29(10):861-6.
Factors affecting progression-free survival in hormone-dependent metastatic breast cancer patients receiving high-dose chemotherapy and hematopoietic progenitor cell transplantation: role of maintenance endocrine therapy.

Montemurro F, Rondon G, Ueno NT, Munsell M, Gajewski JL, Champlin RE.

Department of Oncology and Hematology, Institute for Cancer Research and Treatment, Candiolo, Torino, Italy.

We retrospectively analyzed the effect of maintenance endocrine therapy (MET) after high-dose chemotherapy with hematopoietic progenitor cell transplant (HDCT) on the progression-free survival (PFS) of patients with hormone-dependent metastatic breast cancer (MBC). One hundred and nine consecutive patients with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive MBC, who were progression free for at least 4 months after HDCT with cyclophosphamide, carmustine and thiotepa (CBT), were analyzed. Of these, 55 were non-randomly submitted to MET. After a median follow-up of 34.4 months (17.1-91.0), univariate analysis showed that MET was significantly associated with improved median PFS (31.1 vs 19.2 months, P = 0.022). Complete response to HDCT, pattern of metastatic spread, extent of the disease, single vs multiple metastatic sites, prior endocrine therapy for metastatic disease and prior exposure to any hormonal therapy (adjuvant and/or for the advanced disease) were also associated with PFS at univariate analysis. A multivariate Cox proportional hazard model was fitted to the data in order to correct the effect of MET for the other significant covariates. After correcting for these covariates, MET was still significant, predicting improved PFS (hazard ratio (HR) 0.580, 95% CI; 0.362-0.931). Administration of MET after optimal cytoreduction might result in increased efficacy of HDCT in hormone-dependent metastatic breast cancer.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12058236&dopt=Abstract

Zentralbl Chir. 2002 May;127(5):443-7.
[Patient selection criteria for single-sided or minimal invasive operative procedures in primary hyperparathyroidism (pHPT)]

[Article in German]

Timm S, Hamelmann W, Luster M, Reiners C, Geling M, Thiede A, Timmermann W.

Chirurgische Universitatsklinik Wurzburg, Germany.

In 56 postoperative patients with primary hyperparathyroidism we analysed retrospectively whether a single-sided or minimal invasive operative procedure could have been utilized. Additionally the sensitivity of (99m)TC-Sestamibiscintiscanning and ultrasound of the neck region was assessed. Single gland disease was found in 49 patients, 6 patients had primary multiglandular disease and one patient revealed a double adenoma. The overall sensitivity of (99m)TC-Sestamibiscintiscanning and ultrasound was found to be 78 % and 53 % respectively. In 46 patients the operation would have been started minimal invasive, in 7 of these patients a conversion to bilateral exploration would have been necessary because of four gland hyperplasia, double adenoma or misleading preoperative localisation. In 39 patients a successful minimal invasive procedure would have been possible. A primary bilateral exploration would have been necessary in 10 patients because of either coexisting goiter or questionable localisation of the pathological altered gland. Since sensitivity of localisation diagnostics is low with regard to multiglandular disease, parathyroid hormone should be monitored intraoperatively whenever minimal invasive operative procedures are performed.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12058306&dopt=Abstract

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