Fatty Liver Disease, Women, and Aldosterone: Finding a Link in the Jackson Heart Study.

Context: Fatty liver disease is one of the most common forms of chronic liver disease. The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of fatty liver.

Objective: Determine the relationship between fatty liver and aldosterone in a large cohort study.

Care of the Athlete With Type 1 Diabetes Mellitus: A Clinical Review.

Context: Type 1 diabetes mellitus (T1DM) results from a highly specific immune-mediated destruction of pancreatic β cells, resulting in chronic hyperglycemia. For many years, one of the mainstays of therapy for patients with T1DM has been exercise balanced with appropriate medications and medical nutrition. Compared to healthy peers, athletes with T1DM experience nearly all the same health-related benefits from exercise.

Top 10 Facts to Know About Inpatient Glycemic Control.

Uncontrolled hyperglycemia in hospitalized patients with or without a previous diagnosis of diabetes is associated with adverse outcomes and longer lengths of hospital stay. It is estimated that one-third of hospitalized patients will experience significant hyperglycemia, and the cost associated with hospitalization for patients with diabetes accounts for half of all health care expenditures for this disease. Optimizing glycemic control should be a priority for all health care providers in the inpatient setting.

Diagnosis and management of hyperglycemic emergencies.

This article is aimed at providing a practical up-to-date review of the precipitating factors, diagnosis, management and secondary prevention of hyperglycemic emergencies (diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) to assist critical care physicians and hospitalists caring for these patients. Limitations of various guidelines include implementation in settings with an infrastructure different from that specified in the guidelines of a respective country, state, region or community. Appropriate individualized acute management of these conditions typically results in satisfactory clinical outcomes and may decrease the mortality rate from up to 20% in type 2 diabetics with hyperglycemic hyperosmolar state vs less than 2% in patients with DKA.

The effect of oncoprotein v-erbA on thyroid hormone-regulated genes in hepatocytes and their potential role in hepatocellular carcinoma.

Mutant forms of thyroid hormone receptor (TR) with dominant negative activity are frequently found in human hepatocellular carcinoma (HCC). Interestingly, the v-erbA oncogene, known to exert a dominant-negative effect on the expression of thyroid hormone (T3)-responsive genes, led to the development of HCC in a transgenic mouse model. Thus it is possible that the oncogenic activity of v-erbA in hepatocytes may be mediated by its dominant negative activity on T3-responsive genes.

RACK1 downregulates levels of the pro-apoptotic protein Fem1b in apoptosis-resistant colon cancer cells.

Evasion of apoptosis plays an important role in colon cancer progression. Following loss of the Apc tumor suppressor gene in mice, the gene encoding Fem1b is upregulated early in neoplastic intestinal epithelium. Fem1b is a pro-apoptotic protein that interacts with Fas, TNFR1 and Apaf-1, and increased expression of Fem1b induces apoptosis of cancer cells.

Clustering of sebaceous gland carcinoma, papillary thyroid carcinoma and breast cancer in a woman as a new cancer susceptibility disorder: a case report.

Introduction: Multiple distinct tumors arising in a single individual or within members of a family raise the suspicion of a genetic susceptibility disorder.

Case Presentation: We present the case of a 52-year-old Caucasian woman diagnosed with sebaceous gland carcinoma of the eyelid, followed several years later with subsequent diagnoses of breast cancer and papillary carcinoma of the thyroid. Although the patient was also exposed to radiation from a pipe used in the oil field industry, the constellation of neoplasms in this patient suggests the manifestation of a known hereditary susceptibility cancer syndrome.

Modulation of expression of RA-regulated genes by the oncoprotein v-erbA.

Retinoic acid (RA) modulates the expression of genes involved in embryogenesis, development and differentiation processes in vertebrates. The v-erbA oncogene is known to exert a dominant-negative effect on the expression of RA-responsive genes. v-erbA belongs to a superfamily of transcription factors called nuclear receptors, which includes the retinoic acid receptors (RARs) responsible for mediating the effects of retinoic acid.

Retinoic acid responsive genes in the murine hepatocyte cell line AML 12.

Retinoic acid (RA) exerts profound effects on multiple aspects of vertebrate development, homeostasis and cellular differentiation. Although the liver is a major target organ for RA, no data exist on global expression of RA-responsive genes in hepatocytes. Therefore, the aim of this study was to characterize RA-responsive genes in a simple system, by using a non-transformed hepatic cell line that is able to express sufficient amounts of endogenous retinoic acid receptors (RARs).

Thyroid hormone responsive genes in the murine hepatocyte cell line AML 12.

Thyroid hormone (T3) plays an important role in gene regulation in the liver. Previous studies have been done in complex systems such as animal models, or in transformed malignant hepatic cell lines in which thyroid hormone receptor (TR) was over-expressed by co-transfection. Therefore, the aim of this study was to characterize T3-responsive genes in a simple system, by using a non-transformed hepatic cell line that is able to express sufficient amounts of endogenous TRs.

FEM1A is a candidate gene for polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, and is characterized by infertility, hyperandrogenism and insulin resistance in skeletal muscle. There is evidence for a PCOS gene localized to chromosome 19p13.3.

The Fem1a gene is downregulated in Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue neoplasm of children, and those metastatic at presentation have a poor prognosis. RMS development is related to defective skeletal muscle differentiation, involving a variety of cell signaling and transcriptional control pathways, including aberrant hedgehog signaling. Here we evaluate Fem1a, a gene highly expressed in skeletal muscle, as a candidate for involvement in RMS.

Abnormal glucose homeostasis and pancreatic islet function in mice with inactivation of the Fem1b gene.

Type 2 diabetes mellitus is a disorder of glucose homeostasis involving complex gene and environmental interactions that are incompletely understood. Mammalian homologs of nematode sex determination genes have recently been implicated in glucose homeostasis and type 2 diabetes mellitus. These are the Hedgehog receptor Patched and Calpain-10, which have homology to the nematode tra-2 and tra-3 sex determination genes, respectively.

V-erba homodimers mediate the potent dominant negative activity of v-erba on everted repeats.

The oncoprotein v-erbA is a mutated form of TRalpha1 that is unable to bind thyroid hormone (T3). V-erbA homodimerizes or heterodimerizes with retinoid X receptor (RXR) on core motifs arranged as direct, everted, or inverted repeats (DRs, ERs, or IRs). We created a series of v-erbA mutants in order to obtain a better understanding of the role of v-erbA homodimers versus v-erbA-RXR heterodimers in the dominant negative activity of v-erbA on ERs (the most potent v-erbA response elements).

The myosin binding protein is a novel mineralocorticoid receptor binding partner.

The mineralocorticoid receptor (MR) plays a role in congestive heart failure; however, the molecular mechanism(s) remains undefined. We hypothesized that interaction of the MR with a cardiac protein modulates the transcriptional activation function of the MR within the heart. We used the yeast two-hybrid technique to screen a human heart library and found an aldosterone-dependent interaction between the hMR and the cardiac myosin binding protein (cMBP-c).

Sequences required for the transition from monomeric to homodimeric forms of thyroid hormone receptor alpha and v-erbA.

Thyroid hormone receptor alpha (TRalpha) and the oncoprotein v-erbA (a mutated form of TRalpha incapable of binding T3) bind as heterodimers with retinoid X receptor (RXR) to DNA sequences with different orientations of AGGTCA half sites. v-erbA can also form homodimers, whereas, TRalpha1 homodimerizes poorly. Therefore, in order to obtain a better understanding for the distinct homodimerization properties between TRalpha1 and v-erbA, we created chimeras between these two receptors and tested their abilities to homodimerize on direct and everted repeats (DRs, ERs).

Dimerization of v-erbA on inverted repeats.

Thyroid hormone receptors (TRs) and the oncoprotein v-erbA can heterodimerize with retinoid X receptor (RXR) on core motifs arranged as inverted repeats (IR0) which contain the consensus sequence AGGTCA. On this core motif, v-erbA can also form homodimers whereas TRs homodimerize very poorly. Therefore to obtain a better understanding of distinct homodimerization properties of TR alpha 1 as compared to those of v-erbA, we created chimeras between these two receptors and tested their abilities to homodimerize on IR0.