Nitric oxide prevents human platelet adhesion to fiber membranes in whole blood

During cardiopulmonary bypass or long-term extracorporeal life support, foreign surface induced platelet deposition in the oxygenator causes deterioration of gas exchange. In this study, the authors evaluated the effectiveness of nitric oxide (NO) in reducing the adhesion of platelets in whole blood to the surface of hollow fiber membranes. For this purpose, a test chamber was designed consisting of a gas exchanger with ten mitsubishi multi-layered composite hollow fibers (MHF: 257 mm OD; 203 mm ID; 70 mm length) and a polypropylene tube (16 mm OD; 100 mm length). Pure N2 (control) or nitric oxide (NO) (100 ppm, 200 ppm in N2) were delivered into the test chamber previously filled with 13 ml human whole blood. Platelet counts and platelet factor 4 (PF4), as a measure of platelet activation, were measured before and after either 1 or 2 hr of testing, and fibers were observed under scanning electron microscopic study (SEM) after each experiment. In the control and 100 ppm NO groups, platelet counts decreased and the level of PF4 increased during the 1 hr period. In the 200 ppm NO group, almost no platelet deposition could be observed on the surface of fibers under SEM. In conclusion, NO flow through hollow fiber membranes can markedly reduce platelet adhesion. Additional quantitative studies should define the optimal concentration for this effect and determine if this finding could improve oxygenator function, especially under conditions of long-term support.     

Arabidopsis NPH1: a flavoprotein with the properties of a photoreceptor for phototropism

The NPH1 gene of Arabidopsis thaliana encodes a 120-kilodalton serine-threonine protein kinase hypothesized to function as a photoreceptor for phototropism. When expressed in insect cells, the NPH1 protein is phosphorylated in response to blue light irradiation. The biochemical and photochemical properties of the photosensitive protein reflect those of the native protein in microsomal membranes. Recombinant NPH1 noncovalently binds flavin mononucleotide, a likely chromophore for light-dependent autophosphorylation. The fluorescence excitation spectrum of the recombinant protein is similar to the action spectrum for phototropism, consistent with the conclusion that NPH1 is an autophosphorylating flavoprotein photoreceptor mediating phototropic responses in higher plants.     

Familial influences on gambling behavior: an analysis of 3359 twin pairs

BACKGROUND: Pathological gambling is becoming an increasing problem in the United States as the number of legalized gambling establishments grows. To examine vulnerability to pathological gambling, we estimated the familial contributions (i.e. inherited factors and/or experiences shared by twin siblings during childhood) to DSM-III-R pathological gambling symptoms and disorder. METHODS: Data were obtained from a telephone interview performed in 1991-92 utilizing the Diagnostic Interview Schedule Version III-Revised. Interviews were administered to 6718 members of the nationally distributed Vietnam Era Twin Registry of male-male monozygotic and dizygotic twin pairs who served in the military during the Vietnam era. RESULTS: Inherited factors explain between 35% (95% CI: 28%, 42%) and 54% (95% CI: 39%, 67%) of the liability for the five individual symptoms of pathological gambling behavior that could be estimated statistically. In addition, familial factors explain 56% (95% CI: 36%, 71%) of the report of three or more symptoms of pathological gambling and 62% (95% CI: 40%, 79%) of the diagnosis of pathological gambling disorder (four or more symptoms). CONCLUSIONS: Familial factors have an important influence on risk for pathological gambling behavior. The increasing access to legalized gambling is likely to result in a higher prevalence of pathological gambling behavior among individuals who are more vulnerable because of familial factors.     

Changes in corneal epithelial barrier function after excimer laser photorefractive keratectomy

PURPOSE: To use fluorophotometry to measure corneal epithelial barrier function after excimer laser photorefractive keratectomy (PRK). SETTING: Seoul National University Hospital, Seoul, Korea. METHODS: Twenty-five eyes of 21 patients (13 women, 8 men) had PRK to correct myopia. Corneal epithelial healing time was measured and corneal epithelial permeability to sodium fluorescein evaluated by fluorophotometry 1, 2, and 3 weeks after surgery. RESULTS: Epithelial permeability showed a statistically significant increase 1 week after surgery and returned to its preoperative level 1 week later. Comparative studies according to epithelial healing day and corrected diopter showed results that were not statistically significant (P > .05). CONCLUSION: These results suggest that PRK delays complete reconstruction of corneal epithelial barrier function. In humans, the corneal epithelium regained its normal barrier function 2 weeks after PRK. Thus, at least during these weeks, care should be taken to minimize further epithelial trauma.     

Vpx is required for dissemination and pathogenesis of SIV(SM) PBj: evidence of macrophage-dependent viral amplification

The viral accessory protein Vpx is required for productive in vitro infection of macrophages by simian immunodeficiency virus from sooty mangabey monkeys (SIV(SM)). To evaluate the roles of Vpx and macrophage infection in vivo, we inoculated pigtailed macaques intravenously or intrarectally with the molecularly cloned, macrophage tropic, acutely pathogenic virus SIV(SM) PBj 6.6, or accessory gene deletion mutants (deltaVpr or deltaVpx) of this virus. Both wild-type and SIV(SM) PBj deltaVpx viruses were readily transmitted across the rectal mucosa. A subsequent 'stepwise' process of local amplification of infection and dissemination was observed for wild-type virus, but not for SIV(SM) PBj deltaVpx, which also showed considerable impairment of the overall kinetics and extent of its replication. In animals co-inoculated with equivalent amounts of wild-type and SIV(SM) Pbj deltaVpx intravenously or intrarectally, the deltaVpx mutant was at a strong competitive disadvantage. Vpx-dependent viral amplification at local sites of initial infection, perhaps through a macrophage-dependent mechanism, may be a prerequisite for efficient dissemination of infection and pathogenic consequences after exposure through either mucosal or intravenous routes.     

An epidemic of Malassezia pachydermatis in an intensive care nursery associated with colonization of health care workers' pet dogs

BACKGROUND: Malassezia species are lipophilic yeasts that are emerging as nosocomial pathogens, particularly in low-birth-weight neonates who receive lipid emulsions. When a cluster of patients with Malassezia pachydermatis infection was identified in an intensive care nursery, we initiated an investigation. METHODS: A case patient was defined as any infant in the intensive care nursery who had a positive culture for M. pachydermatis between October 17, 1993, and January 18, 1995. We conducted a cohort study to identify risk factors for colonization and infection with M. pachydermatis. We collected cultures from the infants and the health care workers and from the health care workers' pets, since this organism has been associated with otitis externa in dogs. RESULTS: Fifteen infants met the case definition: eight with bloodstream infections, two with urinary tract infections, one with meningitis, and four with asymptomatic colonization. The case patients were significantly more likely than the other infants to weigh 1300 g or less (15 of 65 vs. 0 of 419, P<0.001). In a multivariate analysis of infants weighing 1300 g or less, the independent risk factors for colonization or infection with M. pachydermatis were a greater severity of concomitant illness (odds ratio, 19.7; P=0.001), arterial catheterization for nine or more days (odds ratio, 29.5; P=0.027), and exposure to Nurse A (odds ratio, 74.7; P=0.004). In a point-prevalence survey, 9 additional infants, 1 health care worker, and 12 of the health care workers' pet dogs had positive cultures for M. pachydermatis. The isolates from all 15 case patients, the 9 additional colonized infants, 1 health care worker, and 3 of the 12 dogs had identical patterns of restriction-fragment-length polymorphisms. CONCLUSIONS: In this outbreak, it is likely that M. pachydermatis was introduced into the intensive care nursery on health care workers' hands after being colonized from pet dogs at home. The organism persisted in the nursery through patient-to-patient transmission.     

Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara

The dynamics of plasma viremia were explored in a group of 12 simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) that had received prior immunization with either nonrecombinant or trivalent (gag-pol, env) SIV-recombinant vaccinia viruses. Three distinct patterns of viral replication observed during and following primary viremia accounted for significant differences in survival times. High-level primary plasma viremia with subsequently increasing viremia was associated with rapid progression to AIDS (n = 2). A high-level primary plasma virus load with a transient decline and subsequent progressive increase in viremia in the post-acute phase of infection was associated with progression to AIDS within a year (n = 6). Low levels of primary plasma viremia followed by sustained restriction of virus replication were associated with maintenance of normal lymphocyte subsets and intact lymphoid architecture (n = 4), reminiscent of the profile observed in human immunodeficiency virus type 1-infected long-term nonprogressors. Three of four macaques that showed this pattern had been immunized with an SIV recombinant derived from the attenuated vaccinia virus, modified vaccinia virus Ankara. These data link the dynamics and extent of virus replication to disease course and suggest that sustained suppression of virus promotes long-term, asymptomatic survival of SIV-infected macaques. These findings also suggest that vaccine modulation of host immunity may have profound beneficial effects on the subsequent disease course, even if sterilizing immunity is not achieved.