FoxP3 maintains Treg unresponsiveness by selectively inhibiting the promoter DNA-binding activity of AP-1.

Regulatory T cells (Tregs) have been shown to play a crucial role in maintaining self-tolerance and suppressing autoimmunity. The forkhead transcription factor, FoxP3, is a key molecule necessary and sufficient for Tregs development and function. However, the molecular mechanisms by which FoxP3 regulates the phenotypic (anergic) and the functional (suppressive) characteristics of Tregs are not well defined.

Selective serotonin reuptake inhibitor treatment of post-traumatic Klüver-Bucy syndrome.

Two cases of Klüver-Bucy syndrome following severe traumatic brain injury (TBI), are described during the period of recovery from acute TBI. These patients posed significant management problems, until successfully managed with selective serotonin reuptake inhibitors (SSRIs). These cases support the benefit of SSRIs in treating associated Klüver-Bucy syndrome.

Cloning, expression, and characterization of a novel guanylate-binding protein, GBP3 in murine erythroid progenitor cells.

We report the molecular cloning of a novel guanylate-binding protein (GBP), termed mouse GBP3 (mGBP3) in Friend virus-induced mouse erythroid progenitor (FVA) cells. The 71-kDa mGBP3 belongs to a family of known GBPs that contain the first two consensus motifs, GXXXXGK(S/T) and DXXG, but lack the third element, (N/T)KXD, found in typical GTP-binding proteins. Recombinant mGBP3 protein, expressed using a baculovirus expression system, binds to agarose-immobilized guanine nucleotides (GTP, GDP and GMP).

Newly diagnosed hepatitis C. Lack of symptoms doesn't mean lack of progression.

Hepatitis C is the most common liver disease currently seen in clinical practice. Many patients remain asymptomatic until decompensation occurs. Lack of symptoms and minor liver enzyme elevations are typical of HCV infection and cannot be taken as evidence of lack of progression.

Vaccines for hepatitis A and B. The latest recommendations on safe and extended protection.

Hepatitis A vaccines (Havrix and Vaqta), administered in two doses, provide long-term protection. Target groups include international travelers, children in high-risk communities, homosexually active men, injecting drug users, persons who work with nonhuman primates, patients with chronic hepatitis, and recipients of clotting factors. The place of hepatitis A vaccination in the childhood-immunization schedule has not been determined.

Is routine screening for colorectal cancer justifiable? These gastroenterologists say YES!

While methods of screening for colorectal cancer undoubtedly will be refined and new techniques developed, there is ample evidence to support use of the currently employed protocol: annual fecal occult blood testing and periodic flexible sigmoidoscopy. Aggressive attempts to educate physicians and patients on the importance of such screening are needed. Primary care physicians can play an important role in ensuring patient compliance and reducing the incidence of this serious public health problem.

Glucocorticoid effects on the skeletal muscle differentiation program: analysis of clonal proliferation, morphological differentiation and the expression of muscle-specific and regulatory genes.

We examined the effect of glucocorticoids on the proliferation and differentiation of skeletal muscle cells using the C2C12 cell line. We found that treatment with glucocorticoids enhanced muscle cell differentiation but had only minor effects on the clonal growth rate of C2C12 cells. The stimulatory effect of glucocorticoids on myogenic differentiation was reflected in the increased expression of muscle-specific genes, creatine kinase (CK) and acetylcholine receptor gamma subunit (AChR).

Faculty attitudes and opinions about problem-based learning.

Background: Systematic research on faculty attitudes toward problem-based learning (PBL) has focused exclusively on the opinions of tutors. The purpose of the present study was to examine the attitudes of faculty at a single medical school who either (1) did not participate in the first year of a new PBL curriculum or (2) participated in ways other than as PBL tutors.

Method: In 1993-94, at the end of the first year of a new PBL curriculum, a questionnaire used in an earlier, larger study of PBL tutors was sent to all 494 faculty at the University of Missouri-Columbia School of Medicine.

Insulin receptor structural requirements for the formation of a ternary complex with IRS-1 and PI 3-kinase.

Insulin receptor substrate-1 (IRS-1) is a major substrate of the insulin receptor tyrosine kinase and is an intermediate in insulin signaling. Phosphotyrosyl-IRS-1 binds to other signaling proteins including phosphatidylinositol 3-kinase (PI 3-kinase). We examined the role of three insulin receptor tyrosine autophosphorylation domains in association of the receptor with IRS-1.

Regulation of changes in cytosolic Ca2+ and Na+ concentrations in rat submandibular gland acini exposed to carbachol and ATP.

The relationship between cytosolic concentrations of Ca2+ (Ca2i) and Na+ (Na+i) were studied in preparations of rat submandibular and pancreatic acini loaded with the Ca(2+)-sensitive dye Fura-2 or the Na(+)-sensitive dye SBFI. Pancreatic acini showed no changes in Na+i during either transient or persistent changes in Ca2+i. Increases in Ca2+i produced by exposure of submandibular gland acini to carbachol, a muscarinic cholinergic agonist, were followed by an increase in Na+i after a delay of 5-10 s.

Combination of insulinomimetic agents H2O2 and vanadate enhances insulin receptor mediated tyrosine phosphorylation of IRS-1 leading to IRS-1 association with the phosphatidylinositol 3-kinase.

To analyze the mechanism of action of the insulinomimetic agents H2O2, vanadate, and pervanadate (H2O2 and vanadate), CHO cells or CHO cells that overexpress wild-type or mutant insulin receptor and/or the insulin receptor substrate (IRS-1) were used. H2O2 or vanadate treatment alone had little or no effect on tyrosine phosphorylation of cellular proteins; however, pervanadate treatment dramatically enhanced tyrosine phosphorylation of a number of proteins including the insulin receptor and IRS-1. However, the insulin receptor and IRS-1 coimmunoprecipitate from insulin-treated but not from pervanadate-treated cells.

Effect of phosphotyrosyl-IRS-1 level and insulin receptor tyrosine kinase activity on insulin-stimulated phosphatidylinositol 3, MAP, and S6 kinase activities.

The role of tyrosine phosphorylation of the insulin receptor substrate 1 (IRS-1) was studied utilizing parental CHO cells or CHO cells that overexpress IRS-1, the insulin receptor, or both IRS-1 and the insulin receptor. Insulin stimulation of these four cell lines led to progressive levels of IRS-1 tyrosine phosphorylation of one, two, four, and tenfold. Maximal insulin-stimulated IRS-1 associated PtdIns 3'-kinase activit in these cells was 1-, 1.

The measurement of community benefit: issues, options, and questions for further research.

Community benefit from a conceptual perspective can be traced to the philanthropic and humanitarian spirit that dominated the earliest foundations of the hospital as a social institution. However, the measurement of community benefit is a recent development and one rarely addressed in the literature in any detail. This article outlines the various concepts integral to community benefit measurement that must be taken into account for a program to demonstrate community accountability in an era where hospitals and health care institutions are increasingly required to evaluate and document their value to society.

Seasonal variations of capillary hydraulic conductivity and volume status.

The purpose of this study was to determine whether circulating plasma protein concentration, capillary hydraulic conductivity (Lp), and overall volume status in frogs were correlated and whether these correlations varied with season. Individual vessel Lp was thus examined on a monthly basis and correlated with changes in protein content in three body compartments (blood, lymph, and body cavity) over a 10-yr period. The frogs were anesthetized, blood and fluid samples collected, Lp assessed, and samples assayed for overall protein content.

Acute prenatal ethanol exposure and luteinizing hormone-releasing hormone messenger RNA expression in the fetal mouse brain.

Ethanol exposure during critical periods of development results in alterations of central nervous system morphology and function. In this study, the effects of acute ethanol exposure on the number of neurons expressing luteinizing hormone-releasing hormone (LHRH) messenger RNA (mRNA) has been analyzed. Also, the expression of LHRH mRNA in the diagonal band of Broca/preoptic area (DBB/POA) was determined.

Inhibition of adenylyl cyclase in rat striatal homogenates by combinations of dopamine and ferric iron compounds.

The adenylyl cyclase activity of homogenates of striatal tissue from rat brain has been used as a model to test the hypothesis that the products of the reaction of polyphenols with ferric iron compounds are toxic. Dopamine (DA), at levels that stimulate adenylyl cyclase, inhibited the activity in the presence of 2 mol of potassium ferricyanide (FC), methemoglobin or ferricytochrome c per mol of DA. Combinations of potassium ferrocyanide and DA were not inhibitory.

CRIES: a new neonatal postoperative pain measurement score. Initial testing of validity and reliability.

We have developed a neonatal pain assessment tool CRIES. The tool is a ten point scale similar to the APGAR score (Apgar 1953). It is an acronym of five physiological and behavioural variables previously shown to be associated with neonatal pain.

Intrathecal morphine (ITM) for postoperative pain control in children: a comparison with nalbuphine patient controlled analgesia (PCA).

This is a retrospective study covering the ten-year period 1984-1993. Single shot spinal morphine (ITM) is compared with PCA nalbuphine for postoperative pain relief in children having abdominal or thoracic procedures. The records of 52 patients meeting selection criteria were examined.

Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons.

In our previous experiments, evidence of free radical formation has been demonstrated in gerbil brain after kainic acid (KA) administration. In the present study, the mechanisms involved in KA-induced free radical formation and subsequent cell degeneration were investigated using high density cortical neuron cultures. A free radical trapping agent, alpha-phenyl-N-tert- butyl-nitrone (PBN), as well as the combined action of superoxide dismutase and catalase attenuated KA neurotoxic effect.

Proliferation of immature T cells within the splenocytes of athymic mice by Pseudomonas exotoxin A.

Pseudomonas aeruginosa exotoxin A has been shown to stimulate splenocytes from athymic nude mice. The present studies were performed to characterize the exotoxin A-responsive cells within the splenocytes of athymic nude mice. The results of these studies indicate that exotoxin A-responsive cells were represented in the nylon wool-adherent cell population and in the Ig-depleted splenocyte population (IgNA).

Health care reform in the states.

Challenged by relentless increases in health care spending, state governments have been forced to experiment with health care system reform. Medicaid has been expanded by Congress, forcing states to provide a broader array of health benefits to more recipients. As states consider reform, federal limitations mandated by Medicaid and by the Employee Retirement Income Security Act (ERISA) of 1974 on state activity pose significant obstacles.

Health care reform. The 1993-1994 evolution.

Health care costs in the United States continue to increase, as does the number of individuals who lack health care coverage. The magnitude of these critical problems assures that health reform of the health care system will continue to be debated over the next decade. Increasing health care costs are associated with increased complexity of services and a greater number of health care providers.