Vibrio cholerae hemagglutinin/protease inactivates CTXphi.

Pathogenic strains of Vibrio cholerae are lysogens of the filamentous phage CTXphi, which carries the genes for cholera toxin (ctxAB). We found that the titers of infective CTXphi in culture supernatants of El Tor CTXphi lysogens increased rapidly during exponential growth but dropped to undetectable levels late in stationary-phase growth. When CTXphi transducing particles were mixed with stationary-phase culture supernatants of El Tor strains, CTXphi infectivity was destroyed.

Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation.

Patients requiring reintubation after failed extubation have a poor prognosis, with hospital mortality exceeding 30 to 40%, though the reason remains unclear. To examine the impact of etiology of extubation failure and time to reintubation on hospital outcome, we performed a post hoc analysis of prospectively gathered data on 74 MICU patients (47 men, 27 women), 64 +/- 2 yr of age who required reintubation within 72 h of extubation. Cause for reintubation was classified as airway (upper airway obstruction, 11; aspiration/excess pulmonary secretions, 12) or nonairway (respiratory failure, 21; congestive heart failure, 17; encephalopathy, 7; other, 6).

Systemic alpha-MSH suppresses LPS fever via central melanocortin receptors independently of its suppression of corticosterone and IL-6 release.

Systemically administered alpha-melanocyte-stimulating hormone (alpha-MSH) inhibits endotoxin (lipopolysaccharide; LPS)- or interleukin (IL)-1-induced fever and adrenocortical activation, but the sites of these actions and the mechanisms involved are unknown. The aims of this study were, first, to determine whether melanocortin receptors (MCR) located within the central nervous system mediate the suppressive effects of peripherally administered alpha-MSH on LPS-induced fever and activation of the pituitary-adrenal axis and, second, to determine whether systemic alpha-MSH suppresses the LPS-induced rise in plasma IL-6 levels, potentially contributing to its antipyretic effect. Male rats received Escherichia coli LPS (25 microg/kg ip).

Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group.

Background: The risk of acquiring Lyme disease is high in areas in which the disease is endemic, and the development of a safe and effective vaccine is therefore important.

Methods: We conducted a multicenter, double-blind, randomized trial involving 10,936 subjects who lived in areas of the United States in which Lyme disease is endemic. Participants received an injection of either recombinant Borrelia burgdorferi outer-surface lipoprotein A (OspA) with adjuvant or placebo at enrollment and 1 and 12 months later.

Interferon treatment for chronic hepatitis B or C infection: costs and effectiveness.

Introduction: With recognition that resources are limited, health care payers and policy makers have increasingly turned toward economic analyses to determine whether particular therapies are an efficient use of economic resources. Both chronic hepatitis B and C infections can progress to cirrhosis or hepatocellular carcinoma over time. Interferon treatment has been shown to eradicate viremia, but only does so in a proportion of treated patients.

Upregulation of xanthine oxidase by lipopolysaccharide, interleukin-1, and hypoxia. Role in acute lung injury.

LPS and selected cytokines upregulate xanthine dehydrogenase/xanthine oxidase (XDH/XO) in cellular systems. However, the effect of these factors on in vivo XDH/XO expression, and their contribution to lung injury, are poorly understood. Rats were exposed to normoxia or hypoxia for 24 h after treatment with LPS (1 mg/kg) and IL-1beta (100 microg/kg) or sterile saline.

The arcuate nucleus is the major source for neuropeptide Y-innervation of thyrotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus.

Neuropeptide Y (NPY) immunoreactive (-ir) nerve fibers densely innervate hypophysiotropic TRH perikarya and dendrites in the hypothalamic paraventricular nucleus (PVN). To evaluate the contribution of the arcuate nucleus (Arc) to this innervation, the effect of Arc ablation by neonatal monosodium glutamate (MSG) treatment on the density of NPY-fibers contacting TRH neurons in the PVN was investigated. After the lesioned animals and vehicle-treated controls reached adulthood, the number of contacts between NPY-ir boutons and TRH-ir perikarya in the PVN was determined in double-immunostained sections.

Growth factor activation of the estrogen receptor in vascular cells occurs via a mitogen-activated protein kinase-independent pathway.

The classical estrogen receptor ERalpha mediates many of the known cardiovascular effects of estrogen and is expressed in male and female vascular cells. Estrogen-independent activation of ERalpha is known to occur in cells from reproductive tissues, but has not been investigated previously in vascular cells. In this study, transient transfection assays in human saphenous vein smooth muscle cells (HSVSMC) and pulmonary vein endothelial cells (PVEC) demonstrated ERalpha-dependent activation of estrogen response element-based, and vascular endothelial growth factor-based reporter plasmids by both estrogen-deficient FBS (ED-FBS) and EGF.

CTXphi immunity: application in the development of cholera vaccines.

CTXphi is a filamentous bacteriophage that encodes cholera toxin, the principal virulence factor of Vibrio cholerae. CTXphi is unusual among filamentous phages because it encodes a repressor and forms lysogens. CTXphi can infect the existing live-attenuated V.

Calpain regulates actin remodeling during cell spreading.

Previous studies suggest that the Ca2+-dependent proteases, calpains, participate in remodeling of the actin cytoskeleton during wound healing and are active during cell migration. To directly test the role that calpains play in cell spreading, several NIH-3T3- derived clonal cell lines were isolated that overexpress the biological inhibitor of calpains, calpastatin. These cells stably overexpress calpastatin two- to eightfold relative to controls and differ from both parental and control cell lines in morphology, spreading, cytoskeletal structure, and biochemical characteristics.

Minor modifications of a cholecystokinin-B/gastrin receptor non-peptide antagonist confer a broad spectrum of functional properties.

The development of non-peptide agonists for peptide hormone receptors would markedly expand the treatment options for a large number of diseases. However, difficulty in identifying non-peptide molecules which possess intrinsic activity has been a major obstacle in achieving this goal. At present, most of the known non-peptide ligands for peptide hormone receptors appear in standard functional assays to be antagonists.

Both C3a and C3a(desArg) regulate interleukin-6 synthesis in human peripheral blood mononuclear cells.

Synthesis of complement components is part of the acute-phase response. Interleukin-6 (IL-6) is a critical mediator of the acute-phase response during infections and injuries. Plasma levels of C3a and IL-6 have been proposed as prognostic indicators in sepsis and trauma.

Superoxide as an intermediate signal for serotonin-induced mitogenesis.

Serotonin (5-HT) stimulates tyrosine phosphorylation and proliferation of bovine pulmonary artery smooth muscle cells (SMC) through its active transport (Lee et al, 1991). The present studies show that 5-HT also rapidly elevates O2.- formation by these cells within 10 minutes as measured by a lucigenin-enhanced chemiluminescence assay.

Acute lung injury in the medical ICU: comorbid conditions, age, etiology, and hospital outcome.

The independent effects of chronic disease, age, severity of illness, lung injury score (LIS) and etiology, and preceding nonpulmonary organ-system dysfunction (OSD) on the outcome of acute lung injury (ALI) have not been examined in an exclusively medical-intensive-care-unit (MICU) population. Therefore, 107 consecutive MICU patients with ALI (76% with acute respiratory distress syndrome [ARDS]) were prospectively investigated. The impact of comorbidities, age > 65 yr, acute physiology score (APS), LIS, etiology of ALI, and OSD on hospital survival were studied.

The basic helix-loop-helix protein BETA2 interacts with p300 to coordinate differentiation of secretin-expressing enteroendocrine cells.

The major epithelial cell types lining the intestine comprise a perpetually self-renewing population of cells that differentiate continuously from a stem cell in the intestinal crypts. Secretin-producing enteroendocrine cells represent a nondividing subpopulation of intestinal epithelial cells, suggesting that expression of the hormone is coordinated with cell cycle arrest during the differentiation of this cell lineage. Here we report that the basic helix-loop-helix protein BETA2 associates functionally with the coactivator, p300 to activate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor p21.

Efficacy of quinolone prophylaxis in neutropenic cancer patients: a meta-analysis.

Purpose: To perform a meta-analysis to estimate the efficacy of quinolone antibiotics in preventing infections, fevers, and deaths among cancer patients neutropenic following chemotherapy.

Methods: We searched MEDLINE to identify randomized trials of quinolone prophylaxis, controlled either with no prophylaxis or trimethoprim/sulfamethoxazole (TMS) prophylaxis. We pooled relative risks for outcomes using a random-effects model.

Specific matrix metalloproteinase profiles in the cerebrospinal fluid correlated with the presence of malignant astrocytomas, brain metastases, and carcinomatous meningitis.

Background: Detection in tumor tissue of specific matrix metalloproteinases (MMPs), particularly gelatinases A and B, correlates with the grade and aggressiveness of primary and metastatic brain tumors. The ability to detect these enzymes in the cerebrospinal fluid (CSF) would be a minimally invasive method of evaluating brain tumors.

Methods: CSF from 66 patients with white blood cell counts of < or = 5 microL were analyzed for the presence of gelatinolytic activity by zymography.

Matrix metalloproteinases in the cerebrospinal fluid of patients with Lyme neuroborreliosis.

Neurologic manifestations of Lyme disease include meningitis, encephalopathy, and cranial and peripheral neuropathy. There are no sensitive markers for neuroborreliosis, and diagnosis is often based on clinical presentation and cerebrospinal fluid (CSF) abnormalities, including intrathecal antibody production. Matrix metalloproteinase (MMP) activity in CSF was compared in patients with neuroborreliosis, patients with diverse neurologic disorders, and healthy controls.

ToxR-independent expression of cholera toxin from the replicative form of CTXphi.

The ctxAB operon, which encodes cholera toxin, resides in the genome of CTXphi, a filamentous bacteriophage. Within Vibrio cholerae cells, the CTXphi genome can exist either as a replicating plasmid or as a prophage integrated into the chromosome. Previous work established that ToxR is required for chromosomal ctxAB expression.

Isolation, cloning, and expression of a 70-kilodalton plasminogen binding protein of Borrelia burgdorferi.

Surface receptors for plasminogen are expressed by many gram-positive and gram-negative bacteria and may play a role in the dissemination of organisms by binding plasminogen, which upon conversion to plasmin can digest extracellular matrix proteins. Two plasminogen binding proteins have been identified for Borrelia burgdorferi, outer surface protein A and a 70-kDa protein (BPBP). We purified BPBP by plasminogen affinity chromatography and obtained its amino acid sequence by Edman degradation of a tryptic digest.

A phase II multicenter trial of high-dose sequential chemotherapy and peripheral blood stem cell transplantation as initial therapy for patients with high-risk non-Hodgkin's lymphoma.

The purpose of this study was to evaluate the safety and feasibility of front-line high-dose sequential (HDS) chemotherapy with peripheral blood stem cell (PBSC) transplantation in patients with newly diagnosed high-risk non-Hodgkin's lymphoma (NHL). Thirty-two patients with high-risk NHL (defined by the age-adjusted international index) underwent HDS chemotherapy followed by PBSC transplantation and consolidative radiotherapy. Twenty-eight patients (88%) had intermediate/high grade NHL and four patients (12%) had small noncleaved or lymphoblastic lymphoma.

Host-pathogen interactions in the immunopathogenesis of Lyme disease.

The immunopathogenesis of Lyme disease is complicated and requires a thorough understanding of the interaction among the causative organism, Borrelia burgdorferi, its tick vector, and its mammalian hosts. In vitro, animal and human studies have shown that the organism is capable of adapting to and utilizing elements from its environment to establish infection and persist despite a inducing a strong immune response. Indeed, the immune response may be responsible for many of the symptoms associated with Lyme disease.

Inter- and intraspecies polymorphisms in the cholecystokinin-B/gastrin receptor alter drug efficacy.

The brain cholecystokinin-B/gastrin receptor (CCK-BR) is a major target for drug development because of its postulated role in modulating anxiety, memory, and the perception of pain. Drug discovery efforts have resulted in the identification of small synthetic molecules that can selectively activate this receptor subtype. These drugs include the peptide-derived compound PD135,158 as well as the nonpeptide benzodiazepine-based ligand, L-740,093 (S enantiomer).

Evaluation of microbiological diagnostic techniques in postoperative endophthalmitis in the Endophthalmitis Vitrectomy Study.

Objective: To analyze the data for cultures and Gram stains prospectively collected by protocol in the Endophthalmitis Vitrectomy Study.

Design: Cultures of aqueous, undiluted vitreous, and (for patients who underwent vitrectomy) vitrectomy cassette fluid obtained from 420 patients were prepared on chocolate agar, in thioglycolate broth, and on Sabouraud dextrose agar; Gram stains of the aqueous and undiluted vitreous were made. Criteria were devised to distinguish true pathogens (confirmed positive cultures) from contaminants.

Glucocorticoids inhibit stress-induced phosphorylation of CREB in corticotropin-releasing hormone neurons of the hypothalamic paraventricular nucleus.

The corticotropin-releasing hormone (CRH) gene contains a perfect palindromic motif in its promoter region that allows binding of the cyclic adenosine monophosphate response element binding protein, CREB. Since previous studies suggest that the CRH gene can be activated by cyclic adenosine monophosphate, we determined whether stress and feedback inhibition by glucocorticoids in CRH-producing neurons in the hypothalamic paraventricular nucleus could be mediated by changes in the phosphorylation of CREB. Antisera to CREB and phospho-CREB Ser133 (PCREB), the active phosphorylated form of CREB, were used for immunohistochemical studies on rat brain.