Lymphocytes expressing Fc gamma receptors suppress antigen-induced proliferation in cells from guinea pigs infected with virulent Mycobacterium tuberculosis.

The immunomodulatory role of T lymphocytes expressing receptors for the Fc portion of IgG (T gamma cells) in BCG-vaccinated guinea pigs following pulmonary infection with a low dose of virulent Mycobacterium tuberculosis H37Rv was studied. Compared to uninfected animals, guinea pigs infected 2 or 4 weeks previously harbored significantly increased percentages of T gamma cells in the peripheral blood (twofold increase) and the spleen (50% increase), and at 4 weeks had nearly fourfold increases in T gamma cells in bronchotracheal lymph nodes draining the infected lungs. Removal of T gamma cells by panning on plastic dishes coated with a monoclonal antibody specific for guinea pig Fc gamma R resulted in significant increases in proliferative responses of splenocytes to Con A and PPD in vitro.

Antiuveitis and inhibition of fibroblast-like corneal and conjunctival cell cultures by interleukin-1 blockers, CK 125, CK 126 and CK 128.

Three new interleukin-1 (IL-1) blockers, CK 125, CK 126 and CK 128, were studied for their effects on IL-1-induced uveitis in rat eyes. They were more potent (at 3-10 mg/kg t.i.

Spontaneous oligomerization of a staphylococcal alpha-hemolysin conformationally constrained by removal of residues that form the transmembrane beta-barrel.

Staphylococcal alpha-hemolysin is a water soluble, monomeric, bacterial exotoxin, which forms heptameric pores in membranes. The rate determining step in assembly is the conversion of a heptameric prepore to the fully assembled pore in which the central glycine-rich domain of each subunit inserts into the membrane to form a 14 strand beta barrel. Barrel formation is accompanied by a conformational change in which each N terminus latches onto an adjacent subunit.

Mosaic structure of the smpB-nrdE intergenic region of Salmonella enterica.

The Salmonella enterica smpB-nrdE intergenic region contains about 45 kb of DNA that is not present in Escherichia coli. This DNA region was not introduced by a single horizontal transfer event, but was generated by multiple insertions and/or deletions that gave rise to a mosaic structure in this area of the chromosome.

Circadian rhythm of brain-derived neurotrophic factor in the rat suprachiasmatic nucleus.

This study was conducted to determine whether the rat suprachiasmatic nucleus (SCN) is characterized by circadian expression of brain-derived neurotrophic factor (BDNF). In constant darkness, SCN content of both BDNF mRNA and protein oscillated in a circadian fashion. BDNF mRNA and protein levels in the SCN reached peak values during the early subjective day and during the subjective night, respectively.

VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells.

Vascular endothelial growth factor (VEGF) is an endothelium-specific secreted protein that potently stimulates vasodilation, microvascular hyperpermeability, and angiogenesis. Nitric oxide (NO) is also reported to modulate vascular tone, permeability, and capillary growth. Therefore, we hypothesized that VEGF might regulate endothelial production of NO.

BiP maintains the permeability barrier of the ER membrane by sealing the lumenal end of the translocon pore before and early in translocation.

Secretory proteins are cotranslationally translocated across the mammalian ER membrane through an aqueous pore in the translocon while the permeability barrier is maintained by a tight ribosome-membrane junction. The lumenal end of the pore is also blocked early in translocation. Extraction of soluble lumenal proteins from microsomes and reconstitution with purified proteins demonstrate, by fluorescence collisional quenching, that BiP seals the lumenal end of this pore.

Ethanol inhibition of NMDA currents in acutely dissociated medial septum/diagonal band neurons from ethanol dependent rats.

The effect of acutely applied ethanol and the impact of chronic ethanol treatment, sufficient to induce tolerance and physical dependence, on N-methyl-D-aspartate (NMDA) receptor function were studied in acutely isolated neurons from the medial septum/diagonal band (MS/DB) of adult rats using whole cell, patch-clamp electrophysiology. There was a small positive correlation for capacitance and current amplitude activated by 100 microM NMDA for all groups. Also, cell membrane capacitance was significantly smaller for Ethanol Dependent (approximately 80-84%) than either Naive or Control cells.

IroN, a novel outer membrane siderophore receptor characteristic of Salmonella enterica.

Speciation in enterobacteria involved horizontal gene transfer. Therefore, analysis of genes acquired by horizontal transfer that are present in one species but not its close relatives is expected to give insights into how new bacterial species were formed. In this study we characterize iroN, a gene located downstream of the iroBC operon in the iroA locus of Salmonella enterica serotype Typhi.

Effective treatment of experimental uveitis with interleukin-1 blockers, CK 123 and CK 124.

Interleukin-1 (IL-1) blockers are known to inhibit IL-1-induced uveitis. CK 123 and CK 124 are new IL-1 blockers which showed potent anti-uveitis actions that are more potent than the classic corticosteroid, prednisolone. In addition to anti-inflammation, CK 123 and CK 124 were also found to inhibit proliferation of fibroblast-like corneal and conjunctival cells, indicating that these compounds could be used not only as anti-uveitis agents but also as useful agents to prolong the functional period of aqueous humor outflow after trabeculectomy.

Protein deficiency induces alterations in the distribution of T-cell subsets in experimental pulmonary tuberculosis.

Previous research has suggested that dietary protein deficiency alters resistance to experimental pulmonary tuberculosis, in part, by affecting the distribution and trafficking of antigen-reactive T cells. In this study, guinea pigs were maintained on either a protein-deficient (10% ovalbumin) or control (30% ovalbumin) diet and infected 4 to 6 weeks later with a low dose of virulent Mycobacterium tuberculosis H37Rv by the respiratory route. Monoclonal antibodies directed against the CD4 or CD8 markers on guinea pig lymphocytes were used in a flow cytofluorometric assay to determine the proportion of each subset in the peripheral circulation, spleen, and bronchotracheal lymph nodes at 4 weeks after infection.

Relative contributions of G protein, channel, and receptor to voltage-dependent inhibition of neuronal N-type and P/Q-type calcium channels in HEK 293 cell lines.

The voltage-dependent modulation of neuronal voltage-gated calcium channels by heterotrimeric G protein-coupled receptors potentially provides a means for activity-dependent modulation of synaptic efficacy. Recent attention has focused upon the molecular mechanisms by which such G proteins influence the biophysical properties of calcium channels. We have used an HEK 293-based heterologous system which stably expresses human neuronal calcium channels to address the relative contributions of receptor, G protein, and channel to voltage-dependent inhibition.

Arginase modulates nitric oxide production in activated macrophages.

In macrophages and many other cell types, L-arginine is used as a substrate by both nitric oxide synthase (NOS) and arginase to produce nitric oxide (NO) and urea, respectively. Because the availability of L-arginine is a major determinant for NO synthesis in the activated macrophage, we hypothesized that NO production may be reduced by arginase via depleting the common substrate in this cell type. To test this hypothesis, we investigated the effect of an arginase inhibitor, L-norvaline, on NO production in J774A.

Immunochemical visualization and identification of rat liver proteins adducted by 2,6-di-tert-butyl-4-methylphenol (BHT).

Several alkylphenols (e.g., 2,6-di-tert-butyl-4-methylphenol, BHT) form reactive quinone methide intermediates (e.

Energetics of polar side-chain interactions in helical peptides: salt effects on ion pairs and hydrogen bonds.

The energetics of the interaction between the polar side chains of glutamate or aspartate with lysine and glutamate with histidine have been determined using a model alanine-based peptide helix. An evaluation of the effects of NaCl and pH on the interactions between these acidic and basic residues in several different orientations and spacings in an alpha-helical peptide has been made. For many of the peptides, we find a considerable interaction between the polar side chains.

Neonatal alcohol and nicotine exposure limits brain growth and depletes cerebellar Purkinje cells.

The present study examined the effects of coexposure of alcohol and nicotine during the brain growth spurt period on brain weights and cerebellar Purkinje cell numbers. Sprague-Dawley rat pups were randomly assigned into five groups (four artificially reared groups and one suckle control). Artificially reared pups were given alcohol (0 or 4 g/kg/day) and/or nicotine (0 or 6 mg/kg/day) daily from postnatal days (PDs) 4 to 9, and the suckle controls received no experimental treatments.

Comparison of the abilities of proteins from Bartonella bacilliformis and Bartonella henselae to deform red cell membranes and to bind to red cell ghost proteins.

Infections in humans by Bartonella bacilliformis, but not Bartonella henselae, are characterized by invasion of red cells. Supernatants of culture medium from B. bacilliformis and B.

Fetal alcohol exposure and temporal vulnerability regional differences in alcohol-induced microencephaly as a function of the timing of binge-like alcohol exposure during rat brain development.

In humans, microcephaly (small head for body size) is a common feature of fetal alcohol syndrome. An analogous measure, termed microencephaly (small brain for body size), can be used for evaluating the detrimental effects of the differential timing of alcohol exposure on brain development in animal model systems. Timed-pregnant rats were exposed to binge-like alcohol during either the first 10 days (first trimester equivalent) or second 10 days of gestation (second trimester equivalent), or the combination of first and second trimesters equivalent for prenatal treatments.

Glial-derived neurotrophic factor rescues calbindin-D28k-immunoreactive neurons in alcohol-treated cerebellar explant cultures.

Ethanol exposure during development leads to alterations in neuronal differentiation and profound neuronal loss in multiple regions of the developing brain. Although differentiating Purkinje cells of the cerebellum are particularly vulnerable to ethanol exposure, the mechanisms that ameliorate ethanol-induced Purkinje cell loss have not been well defined. Previous research indicates that glial-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta family, promotes the survival of several neuronal populations, including cerebellar Purkinje cells.

Moderate alcohol consumption does not augment bone density in ovariectomized rats.

Moderate levels of alcohol consumption have been reported to have a beneficial effect on bone mineral density in postmenopausal women. The objective of this study was to examine the effect of a moderate level of alcohol consumption on bone density in a rigorously controlled animal model of osteoporosis. Ovariectomized and nonovariectomized rats were placed on standard lab pellets with free access to deionized water ad libitum.

The alpha4beta1 integrin can mediate leukocyte adhesion to casein and denatured protein substrates.

An understanding of the binding specificity of leukocyte integrins is important to determine the range of ligands that interact with these receptors during inflammatory processes. In this study we show that the alpha4beta1 integrin can interact with casein and denatured albumin and promote leukocyte adhesion through these interactions. This was demonstrated with the use of blocking antibodies directed to alpha4beta1 and peptide adhesion competitors containing the alpha4beta1 binding tripeptide, Leu-Asp-Val (LDV).

Developmental regulation of DNA replication: replication fork barriers and programmed gene amplification in Tetrahymena thermophila.

The palindromic Tetrahymena ribosomal DNA (rDNA) minichromosome is amplified 10,000-fold during development. Subsequent vegetative replication is cell cycle regulated. rDNA replication differs fundamentally in cycling vegetative and nondividing amplifying cells.

Alcohol consumption by young actively growing rats: a study of cortical bone histomorphometry and mechanical properties.

Alcohol consumption by young actively growing rats has been previously demonstrated to decrease cortical and cancellous bone density, to reduce trabecular bone volume, and to inhibit bone growth at the epiphyseal growth plate. This study addresses the action of alcohol on cortical bone growth using histomorphometric techniques and on mechanical properties by three-point bending. Four-week-old, female Sprague-Dawley rats were divided into three groups.

The record of horizontal gene transfer in Salmonella.

The evolution of virulence in Salmonella is driven by horizontal gene transfer. This has given rise to highly flexible pathogens that are able to colonize new niches and extend their host range. Tracing the record of horizontal gene transfer can provide clues to the virulence factors that contribute to the formation of new pathovars.

Type I elements mediate replication fork pausing at conserved upstream sites in the Tetrahymena thermophila ribosomal DNA minichromosome.

Two-dimensional gel electrophoresis was used to study replication of the Tetrahymena thermophila ribosomal DNA (rDNA) minichromosome. During vegetative growth, the rDNA is replicated exclusively from origins in the 5' nontranscribed spacer (NTS). Whereas replication fork movement through the rest of the chromosome appears to be continuous, movement through the 5' NTS is not.