Tyrosine kinases: modular signaling enzymes with tunable specificities

Cytoplasmic tyrosine kinases are composed of modular domains; one (SH1) has catalytic activity, the other two (SH2 and SH3) do not. Kinase specificity is largely determined by the binding preferences of the SH2 domain. Attaching the SH1 domain to a new SH2 domain, via protein-protein association or mutation, can thus dramatically change kinase function.     

COPD: using nutrition to prevent respiratory function decline

Close to three-fourths of patients with chronic obstructive pulmonary disease (COPD) suffer from weight loss. Identifying a single cause for this is difficult, as several factors-including chronic mouth breathing, dyspnea, aerophagia, certain medications, and depression-often act in concert. Malnutrition can exacerbate symptoms of COPD by decreasing ventilatory muscle strength, exercise tolerance, and immunocompetence, and by increasing the risk of depression and anxiety. Goals of nutrition intervention are to prevent or reverse malnutrition without worsening the disease process and to improve respiratory function, thereby reducing morbidity and delaying mortality. Recommendations for intake of fats, carbohydrates, protein, and water must be individualized.     

Familial jejunal atresia with renal dysplasia

Although jejunal atresia occasionally may occur with a familial pattern, an association with renal disease has not been described. The authors report on three family members treated over two generations, all of whom had both proximal jejunal atresia and renal dysplasia. This association was most likely inherited as an autosomal dominant trait.     

Enhanced antibody response in Venezuelan infants immunized with Haemophilus influenzae type b-tetanus toxoid conjugate vaccine

The safety and immunogenicity of primary immunization at 2, 4 and 6 months of age with Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid (PRP-T; Act-HIB) were evaluated in infants in Valencia, Venezuela. In order better to assess reactions to PRP-T, subjects received their initial PRP-T vaccine a mean of 6.5 days after their initial diphtheria-tetanus-pertussis (DTP) vaccine. The PRP-T vaccine was well tolerated. Serum was obtained at ages 2 and 7 months (before the first and 1 month after the third PRP-T dose). Antibody responses were compared with those from Nashville infants who had received PRP-T and DTP simultaneously in a previous trial. The preimmunization titers in the Venezuelan and Nashville infants did not differ. The geometric mean postimmunization titer in the Venezuelan infants was 37.9 micrograms/ml, as compared with 3.63 micrograms/ml in the Nashville infants (P < 0.00001). Possible explanations for the exceptional antibody response of these Venezuelan infants to PRP-T include carrier priming caused by prior DTP immunization, synergy associated with the specific DTP vaccine used, preimmunization immunologic experience that differed from their United States counterparts and genetic differences that altered response to the vaccines. Further studies are proposed to evaluate these possibilities.     

Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) are present in the peripheral blood and liver of chronically infected patients. The current study was performed to study the relationship between the strength of the CTL response, liver disease severity, and viral load. The results may be summarized as follows: first, using CTL precursor frequency (CTLpf) analysis to quantitate the peripheral blood CTL response, chronically infected patients were less strongly sensitized to a panel of well-defined HCV epitopes than they were to an epitope within the influenza matrix protein. Second, HCV-specific CTLpf did not correlate with disease activity or viral load in the majority of patients on a cross-sectional basis, although it did increase in three patients concomitant with sharp increases in liver disease. Finally, interferon therapy did not enhance the CTLpf against the HCV epitopes studied in these patients, indicating that its antiviral effect is independent of the CTL response. Since the HCV-specific CTLpf in the blood is actually quite low, the CTL may contribute to ongoing liver disease in these patients while being quantitatively inadequate to destroy all of the infected hepatocytes, thereby facilitating HCV persistence and contributing to chronic liver disease.