A major ingredient of green tea rescues mice from lethal sepsis partly by inhibiting HMGB1.

Background: The pathogenesis of sepsis is mediated in part by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release early (e.g., TNF, IL-1, and IFN-gamma) and late (e.

Association between maternal smoking and increased symptom severity in Tourette's syndrome.

Objective: Substantial evidence suggests that both environmental and genetic factors contribute to the development and clinical expression of Tourette's syndrome. Although genetic studies of Tourette's syndrome are common, studies of environmental factors are relatively few and have not identified consistent risk factors across studies. This study examines in a large cohort of subjects (N=180) the relationship between prenatal/perinatal adverse events with Tourette's syndrome severity as determined by tic severity and rates of commonly comorbid disorders such as obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and self-injurious behavior.

Potential role of high mobility group box 1 in viral infectious diseases.

A nuclear protein, high mobility group box 1 (HMGB1), is released passively by necrotic cells and actively by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli. After binding to the receptor for advanced glycation end products (RAGE), or Toll-like receptor 4 (TLR4), HMGB1 activates macrophages/monocytes to express proinflammatory cytokines, chemokines, and adhesion molecules. Pharmacological suppression of its activities or release is protective against lethal endotoxemia and sepsis, establishing HMGB1 as a critical mediator of lethal systemic inflammation.

Effect of triiodothyronine on gene transcription during cardiopulmonary bypass in infants with ventricular septal defect.

We tested the hypothesis that triiodothyronine (T3) supplementation alters gene transcription in the left ventricular myocardium of infants undergoing cardiopulmonary bypass for ventricular septal defect repair. To our knowledge, a novel heteronuclear assay demonstrated for the first time in human heart that rapid change in T3 levels altered the adenine nucleotide translocase-1 transcription rate during cardiopulmonary bypass.

Posttranscriptional regulation of myosin heavy chain expression in the heart by triiodothyronine.

Triiodothyronine (T3) regulates cardiac contractility in part by regulating the expression of several important cardiac myocyte genes. In the rat, the T3-mediated induction of alpha-myosin heavy chain (MHC) transcription in hypothyroid hearts is rapid, exhibiting zero-order kinetics, whereas the repression of beta-MHC in these same hearts is much slower. To elucidate the mechanism for T3 transcriptional as well as posttranscriptional regulation of both MHC gene isoforms, we used an RT-PCR-based transcription assay and the RNA polymerase II inhibitor actinomycin D in an in vivo model to simultaneously measure specific alpha- and beta-MHC heterogeneous nuclear RNA (hnRNA), mRNA kinetics, and MHC antisense RNA.

Topical treatments for pain.

Topical analgesics exert their analgesic benefit locally and without significant systemic absorption. The mechanism of the topical analgesic is unique to the specific medication. Key differences between topical and transdermal analgesics are discussed in this article.

Extracellular HMGB1 as a proinflammatory cytokine.

High mobility group box-1 protein (HMGB1, formerly known as HMG-1), a highly conserved ubiquitous protein, has been for a long time described as a nuclear DNA-binding protein involved in nucleosome stabilization and gene transcription. Recent discoveries indicate that HMGB1 is released from activated innate immune cells or necrotic cells and functions as an important mediator of endotoxemia, sepsis, arthritis, and local inflammation. Therapeutic agents that inhibit HMGB1 release or action confer significant protection against endotoxemia, sepsis, and arthritis in animal models and thus hold potential for the clinical management of various inflammatory diseases.

Seminal lead concentrations negatively affect outcomes of artificial insemination.

Objective: To determine the relationships among seminal lead levels, acrosome status, and artificial insemination cycle fecundity (AI f) in semen donors.

Design: Longitudinal analysis of seminal lead levels, sperm function testing, and fecundity.

Setting: University medical center andrology and research laboratories.

Triiodothyronine-mediated myosin heavy chain gene transcription in the heart.

We developed an RT-PCR assay to study both the time course and the mechanism for the triiodothyronine (T(3))-induced transcription of the alpha- and beta-myosin heavy chain (MHC) genes in vivo on the basis of the quantity of specific heterogeneous nuclear RNA (hnRNA). The temporal relationship of changes in transcriptional activity to the amount of alpha-MHC mRNA and the coordinated regulation of transcription of more than one gene in response to T(3) are demonstrated here for the first time. Quantitation of alpha-MHC hnRNA demonstrated that T(3) induced alpha-MHC transcription in hypothyroid rats within 30 min of a single injection of T(3) (0.

Small Bowel Diverticulosis: An Overlooked Entity.

Small bowel diverticulosis (SBD) is a rare entity. Most cases of diverticulosis are asymptomatic. SBD is often discovered incidentally during contrast studies and endoscopy.

Multicenter evaluation of the performance characteristics of the NucliSens HIV-1 QT assay used for quantitation of human immunodeficiency virus type 1 RNA.

The analytical performance of the NucliSens HIV-1 QT assay, a highly sensitive test based on nucleic acid sequence-based amplification technology, was evaluated in a multicenter trial. Assay specificity was evaluated with 502 plasma (EDTA) specimens from human immunodeficiency virus type 1 (HIV-1)-seronegative volunteer donors. No HIV-1 RNA was reported in any of the donor specimens.

Variation at NOD2/CARD15 in familial and sporadic cases of Crohn's disease in the Ashkenazi Jewish population.

Objective: Recent reports indicate that allelic variants in NOD2/CARD15 are associated with Crohn's disease (CD) susceptibility, and that homozygosity or compound heterozygosity at this locus for any of three recently defined sequence variants confers a greatly increased risk of CD. These sequence changes include two missense mutations, R702W and G908R, and a frameshift insertion, 1007insC. The aim of this study was to determine the frequency of these NOD2/CARD15 variants in familial and sporadic CD patients in the Ashkenazi population and to determine their effects on disease susceptibility and age of disease onset (AOO).

Globin attenuates the innate immune response to endotoxin.

Hemoglobin is an endotoxin (lipopolysaccharide; LPS)-binding protein that synergistically increases the release of proinflammatory cytokines from the innate immune system in response to LPS. It has been suggested that this activity of hemoglobin facilitates the recognition of Gram-negative bacteria in a wound, thereby maximizing immune efficiency. This synergy may be important to the pathogenesis of a broad spectrum of clinical conditions because elevated hemoglobin levels frequently are observed in patients after the transfusion of red cells, trauma, cardiopulmonary bypass surgery, hemolysis, in addition to other disorders.

Return of fertility after autologous stem cell transplantation.

Objective: To study cases where bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT)-induced menopause was entirely reversed.

Design: Retrospective analysis.

Setting: An inpatient BMT unit and an ambulatory fertility center in a university hospital.

In vitro fertilization-intracytoplasmic sperm injection split: an insemination method to prevent fertilization failure.

Objective: To determine whether the performance of intracytoplasmic sperm injection (ICSI) in cases of unexplained infertility and of borderline semen parameters can prevent fertilization failure.

Design: Prospective cohort study.

Setting: Hospital-based assisted reproductive technology program.

Human immunodeficiency virus gag and pol-specific CD8 T cells in perinatal HIV infection.

Background: Binding of fluorochrome-conjugated MHC class I tetramers is a powerful means to detect antigen-specific CD8 T lymphocytes. In human immunodeficiency virus (HIV) infection, cellular immune response is essential in curtailing HIV disease progression but gaps persist in our understanding of HIV-specific cells during the disease course. In this study, we evaluated tetramer binding HIV-specific CD8 T cells in HIV-infected children.

Pulmonary adenocarcinoma simulating malignant mesothelioma.

Adenocarcinoma of the lung with pleural involvement frequently resembles pleural epithelioid mesothelioma clinically as well as macro- and microscopically. Special stains, immunohistochemical studies, and electron microscopic studies are needed to differentiate these 2 tumors. We report a case of pleural involvement by adenocarcinoma, mimicking in the hematoxylin-eosin stain an epithelioid mesothelioma, correctly identified only after immunohistochemical and electron microscopic examinations.

Chemokine receptor CCR5 Delta 32 genetic analysis using multiple specimen types and the NucliSens Basic Kit.

Resistance to HIV-1 infection and delayed disease progression have been associated with a 32-bp deletion (Delta32) in the gene encoding the CCR5 chemokine receptor. In the present study we describe the modification of a nucleic acid sequence-based amplification (NASBA)-based CCR5 genotyping assay for a NucliSens Basic Kit (Organon Teknika, Durham, N.C.

Treatment of aggressive non-Hodgkin's lymphoma in elderly patients with thiotepa, Novantrone (mitoxantrone), vincristine, prednisone (TNOP).

The aging of the population and the increased incidence of non-Hodgkin's lymphoma will result in a large number of elderly patients with this disorder. Newer therapies will be required for this group of patients. This article reports a new therapy for elderly patients with diffuse aggressive non-Hodgkin's lymphoma.

Origin of cardiac mucosa: ontogenic consideration.

The origin and histology of the cardiac mucosa remains controversial. The classical concept that the cardiac mucosa is of gastric origin has been challenged by those who advocate that the cardiac mucosa results from a metaplastic esophageal process. Some regard cardiac mucosa as consisting solely of pure mucous glands, whereas others accept the presence of isolated parietal cells within the mucous gland (mixed glands).

Interleukin-2 therapy in HIV infection.

Immune cells secrete a variety of cytokines that have a profoundly significant influence on the immune system. For example, cytokines secreted by T-helper cells have a role in cellular immune response (Th1 cytokines) and in antibody production (Th2 cytokines). Interleukin 2 (IL-2) is used therapeutically for immune modulation, most specifically in cancer therapy.

The IBD1 locus for susceptibility to Crohn's disease has a greater impact in Ashkenazi Jews with early onset disease.

Objective: Recent studies have suggested that a susceptibility gene located on chromosome 16 and designated IBD1 may contribute to the development of Crohn's disease (CD). However, these findings were observed in predominantly non-Jewish populations; in the three studies where Ashkenazi Jews were included for analysis, the results have been widely divergent. Because Ashkenazi Jews are known to have a higher incidence of the disease than non-Jews, we sought to determine whether this previously reported linkage could be extended to the Ashkenazi population.

Recombinant human erythropoietin use in hemolytic anemia due to prosthetic heart valves: a promising treatment.

Two patients are reported with hemolytic anemia due to red blood cell fragmentation in association with prosthetic heart vales. They were treated with erythropoietin which eliminated the need for packed red blood cell transfusion.