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Biomedical subjects

Y Schwarz

Publications and source records attributed to Y Schwarz.

10 recordsLinked to original sources

Replication-deficient adenovirus induces expression of interleukin-8 by airway epithelial cells in vitro.

Preclinical studies with first-generation adenovirus (Ad) vectors administered in vivo to the respiratory tract have demonstrated a nonspecific host response consisting, in part, of parenchymal neutrophil accumulation followed by mononuclear cell and macrophage accumulation. We hypothesized that the mechanism for this host response might be the elaboration of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) from the airway epithelium following the exposure to Ad. To evaluate this hypothesis, we infected A549 cells (a human-derived lung epithelial cell line) in vitro with an adenovirus type 5 (Ad5)-based vector expressing a nuclear targeted beta-galactosidase enzyme (Av1LacZ4). We found that cellular transduction was efficient, resulting in gene delivery to 85.5% +/- 3.9% of the cell monolayer after 96 hr. Importantly, IL-8 mRNA transcript levels in Av1LacZ4-transduced cells were significantly higher than uninfected controls by 24 hr and remained elevated for 96 hr. IL-8 protein secretion from Av1LacZ4-transduced cells was increased for the same period. The Av1LacZ4-transduced A549 cells also showed a neutrophil chemoattractant activity higher than control cells, measurable at 24 hr, and persisting for 96 hr. The chemoattractant activity could be neutralized by a specific monoclonal antibody to IL-8. Whereas Av1LacZ4 transduction induced IL-8 gene expression, there was a lack of expression of MCP-1 by A549 cells. These observations demonstrate that the gene delivery to the airway epithelium using the Ad5-based expression vector results in IL-8 gene activation in these cells, which may contribute to the described inflammatory host response.

Adenoviruses, Human

Changes in sensitivity to methacholine after inhalation with distilled water: the role of the bronchoconstrictive response.

The inhalation of distilled water can induce bronchoconstriction and a transient increase in sensitivity to methacholine in asthmatics. The purpose of this study was to determine the role of the induced bronchoconstriction in the increased sensitivity to methacholine which follows the challenge with distilled water. Eighteen asthmatic children (age 9-17 yrs) were challenged by inhalation of distilled water. Bronchial responsiveness, the provocative concentration of methacholine producing a 20% decrease in forced expiratory volume in one second (PC20), was determined before inhalation of distilled water, and 1.5 and 24 h thereafter. Following inhalation of distilled water, eight patients (Group I) had a greater than 15% decrease in FEV1 (mean 23%); whereas, in the remaining 10 (Group II) the decrease was less than 7% (mean 1%). PC20 to methacholine, geometric mean and 95% confidence interval (CI), decreased transiently only at 1.5 h following inhalation of distilled water. The decrease was from 0.78 mg.ml-1 (95% CI 0.11-5.54 mg.ml-1) at baseline to 0.25 mg.ml-1 (95% CI 0.03-2.14 mg.ml-1) after challenge in Group I; and from 2.67 mg.ml-1 (95% CI 0.35-20.34 mg.ml-1) at baseline to 0.72 mg.ml-1 (95% CI 0.18-14.87 mg.ml-1) after challenge in Group II. The transient increase in sensitivity to methacholine observed following inhalation of distilled water occurred independently of the bronchoconstrictive response. This finding may have important clinical implications when hypo-osmolar solutions are used for delivery of drugs.

Adolescent

Meiosis-dependent tyrosine phosphorylation of a yeast protein related to the mouse p51ferT.

The FER locus of the mouse encodes two mRNA species: one is constitutively transcribed, giving rise to a 94 kDa tyrosine kinase (p94ferT); the second is a meiosis-specific RNA that gives rise to a 51 kDa tyrosine kinase (p51ferT). The p51ferT RNA and protein accumulate in primary spermatocytes that are in prophase of the first meiotic division. By using polyclonal antibodies directed against synthetic peptides derived from the unique amino-terminus of the mouse p51ferT, a 51 kDa phosphotyrosyl protein --p51y-- was identified in Saccharomyces cerevisiae. The p51y protein is constitutively expressed in yeast, but in meiotic cells, concomitantly with commitment to meiotic recombination, its level of phosphorylation on tyrosine residues is increased. A different pattern of phosphorylation is observed on serine residues: at early meiotic times the level is decreased, while in later meiotic time the level increases, reaching the vegetative level. When p51ferT is ectopically expressed in yeast, it is active, leading to preferential phosphorylation of an approx. 65 kDa protein. A similar pattern of phosphorylation by p51ferT is seen in mammalian cells.

Animals

Evaluation of asymptomatic subjects with low forced expiratory ratios (FEV1/VC).

BACKGROUND: Heightened bronchial hyperreactivity is frequently associated with airflow limitation, atopy, or cigarette smoking. The purpose of this study was to evaluate healthy subjects with significantly low values of forced expiratory volume in one second/vital capacity % (FEV1/VC%) by measuring their airway response to exercise and methacholine challenge, compared with a control group with normal spirometric values. METHODS: Eighty four healthy subjects with significantly low flow rates (group A, FEV1/VC% < 2 SD% predicted) were evaluated and compared with 37 subjects with normal flow rates (group B). Static lung volumes, spirometric tests, exercise, and methacholine challenges were performed. RESULTS: Lung volumes were normal for both groups. Mean FEV1/VC% was 69% for group A and 82% for the control group. Salbutamol improved baseline FEV1 in eight subjects in group A (mean 15%), while methacholine induced a drop in FEV1 in 12 subjects. The dose-response curve to methacholine reached a plateau in all the responders. None of the subjects in the control group improved their baseline FEV1/VC% to salbutamol, but three showed bronchial hyperreactivity similar to those in group A. CONCLUSIONS: Bronchial hyperreactivity does not occur more often in asymptomatic subjects with mildly low FEV1/VC% so these subjects do not require special investigations for airway disease.

Adolescent

The association of perennial rhinitis with Trichophyton infection.

Trichophyton was recently reported to be the cause of respiratory allergy in patients with severe bronchial asthma. We describe eight patients with perennial rhinitis in combination with skin or toe-nail infection, in whom Type I hypersensitivity reaction to Trichophyton was confirmed by skin test, RAST and nasal provocation. When treated with oral fungicidal therapy, there was significant improvement in both their skin and nasal symptoms. Local therapy produced only a mild, transient improvement. We emphasize the need for thorough evaluations in patients with respiratory allergies and negative routine skin tests.

Administration, Oral

Effects of glucose on nitrogen balance during high nitrogen intake in malnourished patients.

1. The effects of increasing glucose intake on nitrogen balance, energy expenditure and fuel utilization were measured in 12 malnourished adult patients receiving parenteral nutrition with constant, very high nitrogen intake (500 mg of N/kg), high (105 kJ/kg) or low (30 kJ/kg) glucose intake and constant fat intake (7 kJ/kg). Each patient received each diet for 8-day periods in random order. 2. Energy balance and nitrogen balance were determined daily. Blood samples, taken at admission, during 5% (w/v) dextrose (D-glucose) infusion and at the end of days 7 and 8 of each diet, were analysed for urea, glucose, lactate, triacylglycerols, fatty acids, glycerol, 3-hydroxybutyrate, insulin and glucagon. 3. The effect of increasing glucose intake was to increase nitrogen balance by 0.60 +/- 0.25 (SEM) mg/kJ. At zero energy balance, nitrogen balance was 48 mg day-1 kg-1. This confirms findings of previous studies: that the effects of glucose on nitrogen balance are greater at high than at low nitrogen intakes, and that, in malnourished patients, unlike in normal adults, markedly positive nitrogen balance can be achieved at zero or negative energy balances. 4. Changes in nitrogen balance were due almost entirely to changes in urea excretion. 5. The high nitrogen intake markedly increased plasma insulin and glucagon concentrations and reduced glycerol, fatty acid and 3-hydroxybutyrate concentrations, independent of any glucose effect. Glucagon concentrations were significantly decreased by added glucose intake, an effect not previously seen at low nitrogen intakes. At this high nitrogen intake, the effects of added glucose appear to be mediated by both insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid

Energy measurements and requirements of critically ill patients.

The energy expenditure of the critically ill patient is influenced by many factors, thus making it difficult to predict. Measurement of energy expenditure in mechanically ventilated patients receiving elevated oxygen concentrations requires a good understanding of the measurement technique and its limitations, whether it be the gas exchange or Fick method. More investigation is needed to better understand the determinants of energy expenditure, as well as the total energy requirements of the critically ill patient.

Critical Care

Effects of increasing nitrogen intake on nitrogen balance and energy expenditure in nutritionally depleted adult patients receiving parenteral nutrition.

The effects of increasing nitrogen intake were studied in 10 nutritionally depleted patients receiving total parenteral nutrition. After 1 to 2 days on 5% dextrose, the patients received, in random order, intravenous diets containing either a low (180 mg/kg . day) or high (364 mg/kg . day) nitrogen content. Equicaloric amounts of glucose and fat emulsion were given. Total energy intake averaged 33.0 kcal/kg . day corresponding to 1.31 X resting energy expenditure or 1.08 X total energy expenditure. Nitrogen and energy balances were measured daily. Concentrations of glucose, glycerol, fatty acids, triglycerides, urea, insulin and glucagon in plasma, and of beta-hydroxybutyrate in whole blood were measured during the last 2 days of each diet period. An increase in plasma urea was the only change in hormone or substrate concentrations identified. Resting energy expenditure increased approximately 10%, going from 5% dextrose to the low and from the low to the high N diet. Nitrogen balances were 0.21 and 0.61 mg N/kg . day on the low and high N diets. Nitrogen retention of 21% of the increment in intake, three times that seen in normal adult subjects, indicates that the malnourished patients in this study responded in a manner similar to growing organisms. Attainment of markedly positive N balance at, or close to, zero energy balance indicates that lean body mass can be restored without excessive energy intakes which may often be undesirable.

Adaptation, Physiological

Production of egg yolk coloring material by a fermentation process.

Rhodotorula mucilaginosa was cultivated in a yeast propagator, for the production of biomass and carotenoids. A spray-dried preparation of the yeast was incorporated into the diets of laying chickens for the promotion of egg yolk color. Several aspects of the effect of media on growth and carotenogenesis of pigmented yeast were examined. Addition of 1 to 2% of Rhodotorula yeast to the feeding mixture considerably improved egg yolk color. The possibility of using carotenogenic yeasts as a feed supplement is suggested.

Animals