Differential leptin responses to acute and chronic biliary obstruction in rats.

Background/aims: Recently leptin, a protein released from adipocytes, has been identified as a potent circulating satiety factor. We therefore undertook this series of experiments to examine leptin's role in the anorexia associated with biliary obstruction.

Methods: Rats underwent either surgical bile duct resection (BDR) or sham resection (sham).

Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice.

Background & Aims: CD1d is a major histocompatibility complex class I-like molecule that presents glycolipid antigens to a subset of natural killer (NK)1.1(+) T cells. These NK T cells exhibit important immunoregulatory functions in several autoimmune disease models.

Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis: lack of CC chemokine receptor 5 expression results in a NK1.1+ lymphocyte-associated Th2-type immune response in the intestine.

The chemokine receptors CCR2 and CCR5 and their respective ligands regulate leukocyte chemotaxis and activation. To determine the role of these chemokine receptors in the regulation of the intestinal immune response, we induced colitis in CCR2- and CCR5-deficient mice by continuous oral administration of dextran sodium sulfate (DSS). Both CCR2- and CCR5-deficient mice were susceptible to DSS-induced intestinal inflammation.

Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy.

Helicobacter pylori is causally associated with gastritis and gastric cancer. Some developing countries with a high prevalence of infection have high gastric cancer rates, whereas in others, these rates are low. The progression of helicobacter-induced gastritis and gastric atrophy mediated by type 1 T-helper cells may be modulated by concurrent parasitic infection.

Oral 5-aminosalicylic acid for maintaining remission in ulcerative colitis.

Objectives: To assess the efficacy, dose-responsiveness and safety of the newer release formulations of 5-aminosalicylic acid (5-ASA) compared to placebo or sulfasalazine (SASP) in the maintenance of remission in ulcerative colitis.

Search Strategy: A computer-assisted literature search for relevant studies (1981-1998) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease Trials Register, and Science Citation Index, followed by a manual search of reference lists from previously retrieved articles, review articles, symposia proceedings, and abstracts from major gastrointestinal conferences.

Selection Criteria: Studies were accepted for analysis if they were prospective, randomized, double-blinded, and placebo- or SASP-controlled clinical trials of parallel design with treatment duration of at least six months.

Oral 5-aminosalicylic acid for inducing remission in ulcerative colitis.

Objectives: To assess the efficacy, dose-responsiveness and safety of the newer release formulations of 5-aminosalicylic acid (5-ASA) compared to placebo or sulfasalazine (SASP) for the induction of remission in active ulcerative colitis.

Search Strategy: A computer-assisted literature search for relevant studies (1981-1998) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register and the Science Citation Index, followed by a manual search of reference lists from previously retrieved articles, review articles, symposia proceedings, and abstracts from major gastrointestinal conferences.

Selection Criteria: Studies were accepted for analysis if they were randomized, double-blinded, and controlled clinical trials of parallel design, with treatment durations of a minimum of four weeks.

Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors.

LPS elicits several immediate proinflammatoy responses in peripheral blood leukocytes via a recently described pathway including CD14, Toll-like receptors (TLR), serine-threonine kinases, and NF-kappaB transcription factor. However, the functional responses of intestinal epithelial cells (IEC) to stimulation with LPS are unknown. Expression of mRNA and protein for CD14 and TLRs were assessed by RT-PCR, immunoblotting, and immunohistochemistry in mouse and human IEC lines.

A paradoxical reduction in susceptibility to colonic injury upon targeted transgenic ablation of goblet cells.

Goblet cells are the major mucus-producing cells of the intestine and are presumed to play an important role in mucosal protection. However, their functional role has not been directly assessed in vivo. In initial studies, a 5' flanking sequence of the murine intestinal trefoil factor (ITF) gene was found to confer goblet cell-specific expression of a transgene.

Gamma-hydroxybutyrate is a weak agonist at recombinant GABA(B) receptors.

Gamma-hydroxybutyrate (GHB) is a neuromodulator with high affinity binding sites in the mammalian brain. However, the receptor for GHB has not yet been identified. There are indications that GHB and gamma-aminobutyric acid (GABA) mediate their effects via the same receptor.

Human parvovirus B19 infection in acute fulminant liver failure.

We previously reported detection of human parvovirus B19 DNA in livers from patients requiring transplantation for acute fulminant liver failure. In this study, we used immune adherence PCR (IA-PCR) to bind B19 virions in recipient native liver onto solid phase with specific monoclonal antibodies followed by PCR amplification of virion DNA. IA-PCR had sensitivity and specificity similar to conventional PCR.

Cortical connections of the dorsomedial visual area in old world macaque monkeys.

The connections of a wedge of densely myelinated cortex along the dorsomedial border of V2 were determined by injecting tracers into this region in macaque monkeys. According to previous descriptions, this cortex would constitute parts of dorsal V3 and V3A, or a dorsomedial visual area, DM, homologous to the DM described in prosimians and New World monkeys. Injections of wheat germ agglutinin conjugated to horseradish peroxidase or various fluorescent tracers demonstrated connections with architectonically defined V1, V2, and the middle temporal area, as well as regions of visual areas known as the ventral posterior parietal area, the rostral dorsolateral area or rostral V4, ventral posterior cortex and more rostral cortex in the ventral temporal lobe, and medial and dorsointermediate areas.

Selectin blockade prevents antigen-induced late bronchial responses and airway hyperresponsiveness in allergic sheep.

Antigen challenge can elicit an allergic inflammatory response in the airways that involves eosinophils, basophils, and neutrophils and that is expressed physiologically as a late airway response (LAR) and airway hyperresponsiveness (AHR). Although previous studies have suggested that E-selectin participates in these allergic airway responses, there is little information concerning the role of L-selectin. To address this question, we examined the effects of administering an L-selectin-specific monoclonal antibody, DU1-29, as well as three small molecule selectin binding inhibitors, on the development of early airway responses (EAR), LAR and AHR in allergic sheep undergoing airway challenge with Ascaris suum antigen.

Growth factors in inflammatory bowel disease.

The pathogenesis of both ulcerative colitis and Crohn's disease is unknown but these forms of inflammatory bowel disease (IBD) may be associated with an inability of the intestinal mucosa to protect itself from luminal challenges and/or inappropriate repair following intestinal injury. Numerous cell populations regulate these broad processes through the expression of a complex array of peptides and other agents. Growth factors can be distinguished by their actions regulating cell proliferation.

Inhibition of L-selectin-mediated leukocyte rolling by synthetic glycoprotein mimics.

Synthetic carbohydrate and glycoprotein mimics displaying sulfated saccharide residues have been assayed for their L-selectin inhibitory properties under static and flow conditions. Polymers displaying the L-selectin recognition epitopes 3',6-disulfo Lewis x(Glc) (3-O-SO3-Galbeta1alpha4(Fucalpha1alpha3)-6-O-SO3-Glcbeta+ ++-OR) and 3',6'-disulfo Lewis x(Glc) (3, 6-di-O-SO3-Galbeta1alpha4(Fucalpha1alpha3)Glcbeta-OR) both inhibit L-selectin binding to heparin under static, cell-free binding conditions with similar efficacies. Under conditions of shear flow, however, only the polymer displaying 3',6-disulfo Lewis x(Glc) inhibits the rolling of L-selectin-transfected cells on the glycoprotein ligand GlyCAM-1.

GABA(B)-receptor subtypes assemble into functional heteromeric complexes.

B-type receptors for the neurotransmitter GABA (gamma-aminobutyric acid) inhibit neuronal activity through G-protein-coupled second-messenger systems, which regulate the release of neurotransmitters and the activity of ion channels and adenylyl cyclase. Physiological and biochemical studies show that there are differences in drug efficiencies at different GABA(B) receptors, so it is expected that GABA(B)-receptor (GABA(B)R) subtypes exist. Two GABA(B)-receptor splice variants have been cloned (GABA(B)R1a and GABA(B)R1b), but native GABA(B) receptors and recombinant receptors showed unexplained differences in agonist-binding potencies.

The utility of endoscopy in the management of patients with gastroesophageal reflux symptoms.

Objective: The utility of endoscopy in the management of patients with symptoms of gastroesophageal reflux disease (GERD) is unclear. The purpose of this prospective study was to assess the impact of endoscopy on the subsequent management of patients with uncomplicated reflux symptoms.

Methods: A total of 742 patients underwent endoscopy for symptoms of GERD.

Augmented interleukin-1beta-induced depression of locomotor activity in cholestatic rats.

"Sickness behaviors" such as lethargy, fatigue, and malaise occur commonly in patients with cholestatic liver diseases and contribute significantly to the morbidity associated with these diseases. However, the cause of these symptoms is unknown. Interleukin-1beta (IL-1beta) released within the brain has been implicated in the genesis of a number of "sickness behaviors," including malaise and lethargy.

[Intravascular lymphomatosis (angiotrophic large-cell lymphoma), a rare differential diagnosis in painful swelling of the leg with treatment-resistant fever].

History And Clinical Findings: For one month a 69-year-old woman had been suffering from increasingly painful and reddened swelling of both legs and induration of the skin of the left thigh, about 15 cm in diameter. In addition she had fever and rigors. Antibiotic treatment, begun because erysipelas was suspected, was ineffective and she was hospitalized.

Cortical connections of the dorsomedial visual area in new world owl monkeys (Aotus trivirgatus) and squirrel monkeys (Saimiri sciureus).

The dorsomedial visual area (DM) is an extrastriate area that was originally described in owl monkeys as a complete representation of the visual hemifield in a heavily myelinated wedge of cortex just rostral to dorsomedial visual area V2. More recently, connections of DM in owl monkeys have been described (Krubitzer and Kaas [1993] J. Comp.

The influence of reperitonization on the induction of formation of intraperitoneal adhesions by a polypropylene mesh prosthesis. An experimental study in rats.

The correction of groin hernias has increasingly been performed by transperitoneal videolaparoscopic methods, using a polypropylene mesh. This could lead to an increased incidence of adhesion formation. The incidence of adhesions induced by mesh placement and the influence of reperitonization was observed on 40 male adult Wistar rats.

Cortical connections of the dorsomedial visual area in prosimian primates.

The dorsomedial visual area (DM) was originally identified in New World owl monkeys as an area rostral to dorsomedial visual area 2 (V2) that is heavily myelinated, contains a complete representation of the visual field, and has a unique distribution of connections with other visual areas. A DM homologue has been proposed in prosimian galagos on the basis of physiological mapping. We determined the pattern of connections of the proposed DM with other cortical visual areas in galagos by placing injections of several different neuroanatomical tracers into DM and locating the resulting label in relation to areal boundaries and modules by using architecture from cytochrome oxidase and myelin preparations.

Thalamic connections of the dorsomedial visual area in primates.

The dorsomedial visual area (DM) of owl monkeys is a cortical area that has been described recently in a range of primate species. To study the thalamic connections of this area, injections of several distinguishable neuroanatomical tracers were placed into DM in galagos, owl monkeys, squirrel monkeys, and macaque monkeys. The distribution of label was remarkably consistent across these diverse primate species.

Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D- mannopyranosyloxy)phenyl]hexane (TBC1269).

Reports of a high-affinity ligand for E-selectin, sialyl di-Lewis(x) (sLe(x)Le(x), 1), motivated us to incorporate modifications to previously reported biphenyl-based inhibitors that would provide additional interactions with the protein. These compounds were assayed for the ability to inhibit the binding of sialyl Lewis(x) (sLe(x), 2) bearing HL-60 cells to E-, P-, and L-selectin fusion proteins. We report that dimeric or trimeric compounds containing multiple components of simple nonoligosaccharide selectin antagonists inhibit sLe(x)-dependent binding with significantly enhanced potency over the monomeric compound.