Efficacy of biorhythmic transdermal combined hormone treatment in relieving climacteric symptoms: a pilot study.

Objective: To evaluate the efficacy of a combination of bioidentical combined 17β-estradiol and progesterone transdermal delivery system (lipophilic emulsion-type base) to relieve climacteric symptoms. The hormonal replacement was given during a period of 6 months at four different cyclic doses to mimic the normal ovary secretory pattern.

Design: An open, randomized, comparative, between-patient trial conducted over 6 months in 29 menopausal women with climacteric symptoms assessed with the Kupperman index at baseline and during treatments.

Oral contraceptive pill use and abnormal menstrual cycles in women with severe condylar resorption: a case for low serum 17beta-estradiol as a major factor in progressive condylar resorption.

Introduction: Progressive condylar resorption has been described for many years. Because condylar resorption favors women over men, many have thought that a prominent systemic factor for the pathogenesis of this disease might be related to sex hormones.

Methods: Over a 3-year period, 27 women without autoimmune disease came to our office for orthognathic surgical correction of their skeletal deformity secondary to severe condylar resorption.

Lactate-sensitive response elements in genes involved in hyaluronan catabolism.

Tissue anoxia occurs early in wound healing. This is accompanied by production of lactate followed by increased hyaluronan and CD44 expression, suggesting a cause and effect relationship. Fibroblasts increased hyaluronan and CD44 when lactate was added to cultures.

Developmental expression of the type I diabetes related antigen sulfatide and sulfated lactosylceramide in mammalian pancreas.

Previous studies have shown that sulfatide is present and functionally involved in beta cells, and that anti-sulfatide antibodies (ASA) exist during development of type I diabetes mellitus. To further explore the possible role of sulfatide in type I diabetes, developmental expression was examined in human pancreas and in pancreas of the type I diabetes models BB rat and NOD mouse compared to Lewis rat and BALB/c mouse, respectively. Sulfatide was not only expressed in adult pancreas, but also in human fetal and rodent neonatal pancreas, i.

Hyaluronidase reduces human breast cancer xenografts in SCID mice.

A hyaluronan-rich environment often correlate with tumor progression. and may be one mechanism for the invasive behavior of malignancies. Eradication of hyaluronan by hyaluronidase administration could reduce tumor aggressiveness and would provide, therefore, a new anti-cancer strategy.

Lactate stimulates fibroblast expression of hyaluronan and CD44: the Warburg effect revisited.

Hyaluronan, a high-molecular-weight glycosaminoglycan of the extracellular matrix, is prominent during rapid tissue growth and repair. It stimulates cell motility and hydrates tissue, providing an environment that facilitates cell movement. Markedly enhanced levels of hyaluronan also occur in the stroma surrounding human cancers, thus providing an environment that promotes spread of cancer cells.

Progesterone induces apoptosis in malignant mesothelioma cells.

Progesterone has been used in the treatment of patients with recurrent or metastatic progesterone receptor-positive endometrial carcinoma and breast cancer. In vitro study using a breast cancer cell line, T47D, demonstrated an increase in p53 gene expression and induction of apoptosis by the administration of progesterone. Therefore, we investigated the effect of progesterone administration on the proliferation and apoptosis in a mesothelioma cell line, 211H.

Hyaluronidase can modulate expression of CD44.

CD44 is a family of transmembrane glycoproteins with multiple isoforms generated by alternative exon splicing of a single gene. CD44 and its variants are expressed on a wide variety of cells including cancer cells. The mechanisms by which splice variant exons are selected are unknown.

Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: inhibition of cell growth and induction of apoptosis.

Progesterone inhibits the proliferation of normal breast epithelial cells in vivo, as well as breast cancer cells in vitro. But the biologic mechanism of this inhibition remains to be determined. We explored the possibility that an antiproliferative activity of progesterone in breast cancer cell lines is due to its ability to induce apoptosis.

Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53.

Progesterone inhibits the proliferation of normal breast epithelial cells in vivo, as well as breast cancer cells in vitro. But the biologic mechanism of this inhibition remains to be determined. We explored the possibility that an antiproliferative activity of progesterone in breast cancer cell lines is due to its ability to induce apoptosis.

Contribution of T cells to the development of autoimmune diabetes in the NOD mouse model.

The nonobese diabetic (NOD) mouse spontaneously develops an autoimmune diabetes that shares many immunogenetic features with human insulin-dependent diabetes mellitus (IDDM), type 1 diabetes. The mononuclear cell infiltrates in the islet, which results in the development of insulitis (a prerequisite step for the development of diabetes) are primarily composed of T cells. It is now well accepted that these T cells play important roles in initiating and propagating an autoimmune process, which in turn destroys insulin-producing islet beta cells in the pancreas.

Phosphorylation stabilizes alternatively spliced CD44 mRNA transcripts in breast cancer cells: inhibition by antisense complementary to casein kinase II mRNA.

CD44, the predominant vertebrate cell surface receptor for hyaluronan, exists in a variety of isoforms resulting from alternative splicing of a single gene. Particular spliced variants of CD44 correlate with increased cell motility, and with poor clinical prognosis in several kinds of carcinomas. Combinations of 9 variant exons that confer this enhanced motility on tumor cells are inserted into a single site in the middle of the extracellular domain of CD44.

Expression of CD44 isoforms in cultured human trabecular meshwork cells.

Purpose: To determine the expression of CD44 isoforms in cultured human trabecular meshwork (HTM) and to discuss their possible relationship with outflow facility.

Methods: CD44 isoform expression in cultured HTM was qualitatively examined using immunohistochemistry and RT-PCR analysis.

Results: Immunohistochemistry of cultured HTM showed intense staining with a CD44s antibody, and with antibodies against CD44 exon 7, exon 11-12 and exon 14.

Hyaluronan is a prerequisite for ductal branching morphogenesis.

Hyaluronan, a macromolecular carbohydrate polymer of the extracellular matrix is prominent early in embryogenesis, coinciding with rapid tissue growth. CD44, the predominant receptor for hyaluronan on vertebrate cells, is a variably expressed transmembrane glycoprotein. Mouse anterior prostate glands obtained at various postnatal time points were examined for the expression of hyaluronan and CD44.

Effect of 5-alpha dihydrotestosterone on T-cell proliferation of the female nonobese diabetic mouse.

Nonobese diabetic (NOD) mice develop type I diabetes spontaneously and have been utilized as a model for human autoimmune insulin-dependent diabetes. The disease is caused by the destruction of insulin-producing beta cells in the pancreatic islet of Langerhans by infiltrating inflammatory cells, which are primarily T lymphocytes. The incidence of diabetes in NOD mice is increased in females compared with males, suggesting that sex steroid hormones play an important role in the development of the disease.

Immunologic response in pregnancy. Its role in endocrine disorders of pregnancy and influence on the course of maternal autoimmune diseases.

During gestation, the immune system is challenged with establishing tolerance to the partial allograft represented by the paternal contribution to the fetal genome. That fact that cell-mediated immunity is decreased while T-cell-dependent immunoglobin production remains intact or is increased is generally accepted. This latter phenomenon can be placed in teleological perspective in terms of providing passive immunity to the fetus.

Association of an androgen-responsive T cell phenotype with murine diabetes and Idd2.

T cells are involved in the induction and suppression of autoimmune diabetes in nonobese diabetic (NOD) mice. Because the incidence of diabetes is 13-fold greater in NOD/Smrf females, we searched for T cell phenotypes that showed sexual dimorphism and associated with diabetes in backcross segregants. The percentage of CD4+PBL was higher in NOD/Smrf females than males, was intermediate in [NOD X NON] F1 mice and approximated a 1:1 distribution in F1 mice backcrossed to either NOD or NON parental strains, suggesting primary control of the phenotype by an incompletely dominant gene, but not excluding additional effects by other genes.

In situ islet cytokine gene expression during development of type I diabetes in the non-obese diabetic mouse.

Expression of cytokine genes in the islets of non-obese diabetic (NOD) female mice was examined. RNA samples were prepared from the islets and spleens of NOD mice at different time points at prediabetic stages during the natural disease process. Cytofluorometric analyses showed that the majority of lymphocyte infiltrates in the islets at 14 weeks of age consisted of T cells (68%).

Maternal hyperglycemia is not the only cause of macrosomia: lessons learned from the nonobese diabetic mouse.

Maternal hyperglycemia has been implicated as the major cause of neonatal macrosomia, yet clinicians frequently report the birth of large-for-gestational-age infants in normoglycemic pregnancies. We examined the relationship between birthweight, maternal blood glucose (BG), glycosylated hemoglobin (GHb) levels, litter size, maternal age, gestational duration, and parity using the non-obese diabetic (NOD) mouse model. We observed 133 litters and analyzed the birthweight in relation to BG, GHb, litter size, maternal age, gestational duration, and parity.

Voluntary exercise improves glycemia in non-obese diabetic (NOD) mice.

The non-obese diabetic (NOD) mouse was used to investigate the effects of voluntary wheel running exercise on blood glucose levels, glycosylated hemoglobin, and longevity in Type 1 diabetes mellitus. In Experiment 1, diabetic and normoglycemic mice exercised 5 h/day, 5 days/week for 3 weeks matched with non-exercising controls. In diabetic animals a positive correlation was found between blood glucose and the number of revolutions performed (P < or = 0.

T cell vaccination against autoimmune diabetes in nonobese diabetic mice.

The diabetogenic autoimmune process was accelerated in 23 days nonirradiated postnatal nonobese diabetic (NOD) female mice by adoptive transfer of pathogenic, polyclonal CD4+ 8- T cells isolated from diabetic spleens. Recipient mice developed hyperglycemia 15 days after transfer of pathogenic immune cells with typical histological signs of pancreatic infiltration. The CD4+V beta 8+ T cells isolated from diabetic spleens and activated by surface-immobilized anti-TCRV beta 8 monoclonal antibody (mAb, clone F23.

Adhesion and costimulation of proliferative responses of human gamma delta T cells by interaction of VLA-4 and VLA-5 with fibronectin.

The very late antigens, VLA-4 and VLA-5 belong to the beta 1 subfamily of integrins and have been identified as receptors for different binding regions of fibronectin (FN). We have detected VLA-4 and VLA-5, but not VLA-3 and VLA-6 expressed on human CD3+CD4-CD8- gamma delta TCR T cells by flow cytometry. Binding assays, performed on FN-coated plates, showed that activated CD25high (IL-2 receptor) but not resting CD25low gamma delta T cells specifically adhere to FN.

In situ islet T cell receptor variable region gene usage in the nonobese diabetic mouse.

Several features of the genetics and immunopathology of diabetes in the nonobese diabetic (NOD) mouse, which spontaneously develops type I diabetes, are shared with the human disease. Immunohistochemical studies support the concept that T lymphocytes are the major components of inflammatory cells in the pancreatic islets and these cells may play a critical role in the destruction of the beta cells leading to diabetes. Therefore, we examined whether particular TCR-beta variable region genes were utilized by in situ islet T cells at different stages (4 - 5, 7, 14 - 15 and 16 weeks of age) of the disease process.

Quantitative and functional analyses of spleen and in situ islet immune cells before and after diabetes onset in the NOD mouse.

Cytofluorometric analysis using specific monoclonal antibodies directed against the T cell antigens Thy-1.2, CD4, CD8, CD4V beta(8.1 + 8.

Exogenous administration of IL-1 alpha inhibits active and adoptive transfer autoimmune diabetes in NOD mice.

Diabetes susceptibility in non-obese diabetic (NOD) mice may involve immune dysregulation resulting from cytokine deficiencies. The cytokine IL-1 plays a role in various immune as well as endocrine responses and may be hypoexpressed in NOD mice. Treatment with low levels of exogenous IL-1 alpha for 22 weeks prevented the naturally occurring insulitis and diabetogenic process in NOD mice during and at least 33 weeks after cessation of IL-1 alpha treatment.