The potential of incretin-based therapies in type 1 diabetes.

Finding a cure for type 1 diabetes (T1D) has been elusive. Incretin-based therapies, since their approval, have demonstrated their clinical utilities in type 2 diabetes (T2D). Yet, their potential clinical benefits in T1D remain to be appraised.

Enhancement of proteasomal function protects against cardiac proteinopathy and ischemia/reperfusion injury in mice.

The ubiquitin-proteasome system degrades most intracellular proteins, including misfolded proteins. Proteasome functional insufficiency (PFI) has been observed in proteinopathies, such as desmin-related cardiomyopathy, and implicated in many common diseases, including dilated cardiomyopathy and ischemic heart disease. However, the pathogenic role of PFI has not been established.

Identification of Rgg binding sites in the Streptococcus pyogenes chromosome.

Streptococcus pyogenes Rgg is a regulatory protein that controls the transcription of 588 genes in strain NZ131 during the post-exponential phase of growth, including the virulence-associated genes encoding the extracellular SpeB protease, pullulanase A (PulA), and two extracellular nucleases (SdaB and Spd-3). Rgg binds to DNA proximally to the speB promoter (PspeB) to activate transcription; however, it is not known if Rgg binds to the promoters of other genes to influence expression, or if the perturbation of other global regulons accounts for the genome-wide changes in expression associated with the mutant. To address this issue, chromatin immunoprecipitation followed by DNA microarray analysis (ChIP-chip) was used to identify the DNA binding sites of Rgg.

Alcohol use and problem severity: associations with dual systems of self-control.

Objective: The current study tested the associations between a dual-systems model of self-control and alcohol use and problem severity.

Method: The sample consisted of 491 college students (77.0% women) from a rural state university.

Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases D1 receptor expression in carotid bodies, PVN and striatum of hamsters.

Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)-induced hypothyroidismin hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.

An uncommon etiology for a common problem: hirsutism.

Hirsutism is a common problem affecting women that is usually the result of a benign etiology. However, sudden onset or rapidly progressive hirsutism, especially when accompanied by virilizing signs, is suspicious for androgen-producing neoplasms of the ovaries or adrenals. A 28-year-old female presented with the rapid onset of hirsutism and virilizing signs, accompanied by a markedly elevated serum testosterone.

Autophagy and p62 in cardiac proteinopathy.

Rationale: Recent studies suggest an important role of autophagy in protection against αB-crystallin-based (CryAB(R120G)) desmin-related cardiomyopathies (DRC), but this has not been demonstrated in a different model of cardiac proteinopathy. Mechanisms underlying the response of cardiomyocytes to proteotoxic stress remain incompletely understood.

Objective: Our first objective was to determine whether and how the autophagic activity is changed in a mouse model of desminopathy.

Estrogens and selective estrogen receptor modulators regulate gene and protein expression in the mesenteric arteries.

Estrogen has both beneficial and detrimental effects on the cardiovascular system. Selective estrogen receptor modulators (SERMs) exhibit partial estrogen agonist/antagonist activity in estrogen target tissues. Gene targets of estrogen and SERMs in the vasculature are not well-known.

Antiprogestin mifepristone inhibits the growth of cancer cells of reproductive and non-reproductive origin regardless of progesterone receptor expression.

Background: Mifepristone (MF) has been largely used in reproductive medicine due to its capacity to modulate the progesterone receptor (PR). The study of MF has been expanded to the field of oncology; yet it remains unclear whether the expression of PR is required for MF to act as an anti-cancer agent. Our laboratory has shown that MF is a potent inhibitor of ovarian cancer cell growth.

Aortoesophageal fistula secondary to aortic dissection: case report and review.

Aortoesophageal fistula (AEF) formation nearly always results in catastrophic consequences. As a result of its development being extremely rare, many may never consider it in their differential. Although prognosis is extremely grim, early diagnosis and intervention is considered the optimal means to enhance one's prognosis.

Three-dimensional ultrasound to detect Apert syndrome and improve patient understanding.

Standard two-dimensional ultrasound has been used to aid prenatal visualization and detection of anomalies for the past 60 years. Three-dimensional ultrasound, introduced in the 1980s, provides the additional capability of examining the in utero environment from a variety of different angles. Use of this technology in conjunction with standard two-dimensional ultrasound can lead to a more thorough evaluation of structural defects and a greater patient understanding of genetic conditions.

Alcohol-related infractions among college students: associations with subsequent drinking as a function of sensitivity to punishment.

Problematic alcohol use on college campuses is a significant concern. Violations of campus alcohol policies can lead to disciplinary action from the university. These and other alcohol-related legal infractions may be a sign of significant alcohol-related problems.

CUG-binding protein represses translation of p27Kip1 mRNA through its internal ribosomal entry site.

The cyclin dependent kinase inhibitor p27 (Kip1) plays an important role in controlling the eukaryotic cell cycle. The 5'-untranslated region of the p27 mRNA harbors an internal ribosome entry site (IRES) which may facilitate synthesis of p27 in certain conditions. In this study, the RNA-associated protein CUGBP1 was shown to interact with the human p27 5'-untranslated region.

Uterine pleomorphic rhabdomyosarcoma: a case report and review of literature.

Primary pleomorphic rhabdomyosarcoma of the uterus is a very rare neoplasm. We describe a 65-year old female with this diagnosis, who underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy and lymph node dissection. Also included is a discussion on the different types of rhabdomyosarcoma with reviews of their histological features, epidemiology and common sites of origin.

Mucin 13: structure, function, and potential roles in cancer pathogenesis.

Mucin 13 (MUC13) is a high-molecular-weight transmembrane glycoprotein that is frequently and aberrantly expressed in a variety of epithelial carcinomas, including gastric, colorectal, and ovarian cancers. On the basis of the high expression of MUC13 in cancer cells as well as recent laboratory findings suggesting a malignant phenotype of MUC13-transfected cell lines, the oncogenic potential of MUC13 has emerged. The various functional domains of MUC13 may confer oncogenic potential to MUC13.

Growth inhibition induced by antiprogestins RU-38486, ORG-31710, and CDB-2914 in ovarian cancer cells involves inhibition of cyclin dependent kinase 2.

Antiprogestins have been largely utilized in reproductive medicine, yet their repositioning for oncologic use is rapidly emerging. In this study we investigated the molecular mediators of the anti-ovarian cancer activity of the structurally related antiprogestins RU-38486, ORG-31710 and CDB-2914. We studied the responses of wt p53 OV2008 and p53 null SK-OV-3 cells to varying doses of RU-38486, ORG-31710 and CDB-2914.

Phosphorylation at serine 482 affects stability of NF90 and its functional role in mitosis.

Objectives: NF90 is a multifunctional double-strand RNA binding protein with documented roles in transcription, mRNA stability, translation, RNA processing and transport, and mitosis. It is a phosphoprotein that interacts with, and is a substrate for, several protein kinases. The study described here was initiated to gain better understanding of specific NF90 phosphorylation sites and their relationship to mechanisms by which NF90 performs its various functions.

Anxiety states induced by post-weaning social isolation are mediated by CRF receptors in the dorsal raphe nucleus.

Post-weaning social isolation of rats is utilized as a model of early life stress. We have previously demonstrated that rats exposed to post-weaning social isolation exhibit greater anxiety-like behaviors as adults. Furthermore, these rats exhibit greater density of corticotropin-releasing factor (CRF) type 2 receptors in the dorsal raphe nucleus.

Cytoplasmic ATM protein kinase: an emerging therapeutic target for diabetes, cancer and neuronal degeneration.

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia and oculocutaneous telangiectasias. The gene mutated in this disease, Atm (A-T mutated), encodes a serine/threonine protein kinase that has been traditionally considered to be a nuclear protein controlling cell-cycle progression. However, many of the growth abnormalities observed in patients with A-T, including neuronal degeneration and insulin resistance, remain difficult to explain with nuclear localization of ATM.

Rational screening strategies.

Screening for disease can significantly improve both individual and public health. Many different screening interventions have been proposed for a wide range of conditions. This article reviews the elements that make up an effective clinical screening test and discusses what it means to effectively detect and treat a condition, risks and benefits of screening and the measurement of outcomes from screening.

Ovarian small cell carcinoma, hypercalcemic type exhibiting a response to high-dose chemotherapy.

A gravida 2, para 2 25-year-old woman three months post-partum presented to her primary physician with abdominal pain and bloating; a 20-cm complex cystic pelvic mass was identified by ultrasound. No ovarian masses were noted during ultrasound exam at the prior pregnancy, less than one year earlier. Her labs included hypercalcemia (11.

Enhancement of proteasome function by PA28α overexpression protects against oxidative stress.

The principal function of the proteasome is targeted degradation of intracellular proteins. Proteasome dysfunction has been observed in experimental cardiomyopathies and implicated in human congestive heart failure. Measures to enhance proteasome proteolytic function are currently lacking but would be beneficial in testing the pathogenic role of proteasome dysfunction and could have significant therapeutic potential.

Perturbation of cullin deneddylation via conditional Csn8 ablation impairs the ubiquitin-proteasome system and causes cardiomyocyte necrosis and dilated cardiomyopathy in mice.

Rationale: Ubiquitin-proteasome system (UPS) dysfunction has been implicated in cardiac pathogenesis. Understanding how cardiac UPS function is regulated will facilitate delineating the pathophysiological significance of UPS dysfunction and developing new therapeutic strategies. The COP9 (constitutive photomorphogenesis mutant 9) signalosome (CSN) may regulate the UPS, but this has not been tested in a critical vertebrate organ.