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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 19 recordsLinked to original sources

Antibody-enhanced binding of dengue-2 virus to human platelets.

The mechanisms underlying severe thrombocytopenia in dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are not completely understood. We present here the first evidence that dengue type 2 virus binds to human platelets only in the presence of virus-specific antibody, supporting a role for immune-mediated clearance of platelets in the pathogenesis of thrombocytopenia in DHF/DSS. Antibody-enhanced binding of virus of platelets was also demonstrated with a panel of eight murine monoclonal antibodies specific for the dengue E protein. The degree of binding was dependent on the antibody used but not on the antibody IgG subclass, indicating that factors other than the platelet Fc receptor are involved in binding of virus-antibody complexes to the platelet surface. Confirmation that antibody-dependent virus binding to platelets is not primarily mediated by the platelet Fc receptor was obtained by demonstrating good binding even when platelets were pretreated with the Fc gamma RII-specific antibody IV.3.

Animals

On the mechanism of skin wound "contraction": a granulation tissue "knockout" with a normal phenotype.

This report explores the mechanism of spontaneous closure of full-thickness skin wounds. The domestic pig, often used as a human analogue for skin wound repair studies, closes these wounds with kinetics similar to those in the guinea pig (mobile skin), even though the porcine dermis on the back is thick and nearly immobile. In the domestic pig, as in the guinea pig, daily full-thickness excisions of the central granulation tissue up to but not including the wound edges in both back and flank wounds do not alter the rate or completeness of wound closure or the final pattern of the scar. A purse-string mechanism of closure was precluded by showing that surgical interruption of wound edge continuity does not alter closure kinetics or wound shape. We conclude that "tightness" of skin is not a key factor nor is the central granulation tissue required for normal wound closure. These data imply that in vitro models such as contraction of isolated granulation tissue or of the cell-populated collagen lattice may not be relevant for understanding the cell biology of in vivo wound closure. Implications for the mechanism for wound closure are discussed.

Animals

Failure of high-dose oral acyclovir to suppress CMV viruria or induce ganciclovir-resistant CMV in HIV antibody positive patients.

Ninety-three symptomatic HIV antibody positive patients were randomized to receive zidovudine (ZDV) 600 mg/day and acyclovir (ACV) 4,800 mg orally per day versus ZDV 600 mg/day plus placebo. Urine was obtained at 3-month intervals and cultured for cytomegalovirus (CMV) in diploid fibroblast cells. The percent of urine specimens positive for CMV was 7.1% in the ZDV group and 5.8% in the ZDV plus ACV group (p = 0.55); 27% of patients had at least one urine culture positive for CMV while taking ZDV, versus 20% of patients taking the combination of ZDV plus ACV (p = 0.52). We conclude that ACV at a dosage of 4,800 mg/day does not suppress CMV excretion in urine of symptomatic HIV antibody positive patients taking concurrent ZDV. Use of ACV did not appear to induce resistance of CMV to ganciclovir since the ID50 of isolates from the two treatment groups did not differ.

Acyclovir

Antibodies that block virus attachment to Vero cells are a major component of the human neutralizing antibody response against dengue virus type 2.

Epidemiological data strongly implicate a role for the host humoral immune response in both protection against and exacerbation of dengue virus-caused disease. In an effort to characterize elements of the normal human immune response against dengue virus we have addressed the issue of antibody-mediated neutralization of dengue virus. We show here the ability of both mouse monoclonal antibody 3H5 and human anti-dengue neutralizing sera to block binding of dengue-2 virus to monkey kidney (Vero) cells. Since Vero cells possess virus receptors but not Fc receptors we conclude that the major effect of host neutralizing antibodies is to block virus attachment to Vero cell dengue virus receptors. Analysis of 61 patient antisera yielded good correlation (Pearson's coefficient = 0.90; P < 0.001) between neutralizing activity and ability to block virus-cell attachment suggesting that antibody-mediated neutralization of dengue virus occurs primarily extracellularly and less by a postattachment mechanism as has been described for certain other viruses.

Adolescent

Plasma levels of beta-carotene are inversely correlated with circulating neutrophil counts in young male cigarette smokers.

Relationships between plasma levels of beta-carotene (BC) and the numbers and oxidant-generating activities of circulating neutrophils have been investigated in a group of asymptomatic young male cigarette smokers (N = 40) and in a group of nonsmoking control subjects. Plasma BC levels were measured using HPLC, while oxidant generation was measured using a phorbol myristate acetate (PMA) activated whole blood luminol-enhanced chemiluminescence (LECL) method. Relative to nonsmokers, the numbers of circulating neutrophils, as well as the LECL responses of these cells, were increased by 41% (p = 0.0001) and 47% (p = 0.004), respectively, while plasma BC levels were decreased by 24% (p = 0.01). In cigarette smokers, but not in nonsmokers, the numbers of circulating neutrophils, as well as the LECL responses of these cells, were significantly and inversely correlated with plasma BC levels (r = -0.36, p = 0.02; and r = -0.33, P = 0.04 respectively). Diminished plasma levels of BC in cigarette smokers probably reflect the increased numbers and prooxidative activities of circulating neutrophils. Intake of this antioxidant nutrient may be a determinant of susceptibility to smoking-related pulmonary dysfunction mediated by oxidants derived from smoke-activated phagocytes.

Adult

Contribution of visceral fat mass to the insulin resistance of aging.

Recent studies have shown that central obesity (increased waist to hip ratio [WHR]) is related to insulin resistance and aging. Furthermore, in central-obesity states, the intraabdominal fat (IAF) depot has been postulated to contribute most to the development of insulin resistance. Therefore, the observed insulin resistance of aging may be related more to changes in body composition than to aging per se. The purpose of this study was to explore the association of IAF with age and insulin sensitivity (SI) after controlling for obesity. We examined 60 healthy nondiabetic subjects (normal 75-g oral glucose tolerance test, aged 23 to 83, 15 men and 45 women). We chose subjects so that those < or = 125% and greater than 125% of ideal body weight were equally represented in each age decade. We quantified total and subcutaneous abdominal fat and IAF at the umbilicus using a validated magnetic resonance imaging (MRI) scanning technique and determined SI using a modified minimal model. IAF correlated significantly with age (r = .49, P = .0001) in the group as a whole, as well as in men (r = .58, P = .022) and women (r = .48, P = .0008) separately. In all subjects, SI was significantly related to IAF (r = -.50, P < .0001) but was not related to age (r = .00, P = .98). In multivariate analysis for various combinations of age, sex, and measures of fat distribution, WHR accounted for 28% and IAF for 51% of the variance in SI, whereas age, sex, and interactions of age and sex accounted for only 1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Development of a guinea pig model to assess immunogenicity of Haemophilus influenzae type b capsular polysaccharide conjugate vaccines.

There is currently no animal model which reliably predicts the immunogenicity of Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines in human infants. We evaluated various Hib vaccines in guinea pigs using techniques similar to the United States potency test for adsorbed diphtheria and tetanus toxoids with a view to developing a method for evaluating the potency of a combined adsorbed tetanus, diphtheria, pertussis and Hib conjugate vaccine. Groups of 6-8 guinea pigs received 1.5 single human doses of vaccine at 0 and at 6 or 8 weeks and were bled at 6 weeks and 2 weeks after the booster injection. Total antibodies to polyribosylribitolphosphate (PRP), the Hib capsular polysaccharide, were measured in individual animals and in serum pools by radioimmunoassay. The relative antibody responses of guinea pigs to Hib conjugate vaccines qualitatively resembled those of human infants. Unconjugated polysaccharide was not immunogenic; PRP-D produced a low antibody response, HbOC, PRP-T (Merieux) and Hib-T (MPMBL) produced a low response to the first dose and a strong anamnestic response to the booster (geometric mean anti PRP > 1 micrograms ml-1). PRP-OMP uniquely produced a strong response after the first dose which was further boosted by the second dose. Experimental Hib-T vaccine lots with low levels of conjugation were poorly immunogenic in guinea pigs. Combinations of DTP and Hib-T vaccines showed equivalent or greater immunogenicity than Hib-T alone. We propose that the guinea pig model may be useful to verify the immunogenicity of PRP conjugate vaccines and for pre-clinical evaluations of DTP-Hib combination vaccines containing PRP conjugates.

Animals

Vitamin E, pulmonary functions, and phagocyte-mediated oxidative stress in smokers and nonsmokers.

Relationships among the plasma levels of vitamin E (VE), the numbers and prooxidative activities of circulating phagocytes, serum alpha-1-protease inhibitor (API), and pulmonary functions were investigated in 83 asymptomatic male cigarette smokers and 65 nonsmoking controls. Plasma levels of VE, of cholesterol, and of API were measured using high performance liquid chromatography, spectrophotometry, and nephelometry, respectively, whereas reactive oxidant (ROS) generation by activated blood phagocytes was measured using a whole blood luciginen-enhanced chemiluminescence method. Smoking was associated with significantly increased circulating neutrophil counts (p 0.0001), serum API (p 0.0001) and phagocyte-derived ROS-generation (p 0.0001), and decreased spirometric values (FEV1: p 0.0138 and FEF25-75: p 0.0654). Plasma VE and cholesterol levels were not significantly different between smokers and nonsmokers. However, in smokers both plasma VE and cholesterol correlated significantly and positively with serum API (r 0.24, p 0.03 and r 0.30, p 0.005, respectively), neutrophil counts (r 0.24, p 0.03 and r 0.25, p 0.03, respectively), and phagocyte-derived ROS-generation (r 0.32, p 0.003 and r 0.32, p 0.003, respectively), and significantly and inversely with FEV1 (r -0.23, p 0.03 and r -0.22, p 0.04, respectively) and FEF25-75 (r -0.32, p 0.003 and r -0.26, p 0.02, respectively). In nonsmokers plasma VE, but not cholesterol, was positively correlated with FEV1 (r 0.34, p 0.007) and FEF25-75 (r 0.40, p 0.001). The results suggest that VE protects the lungs of both smokers and nonsmokers and may act as a mobilizable antioxidant in response to smoking-induced oxidative stress.

Adult

An epidemiologic analysis of Mycobacterium avium complex disease in homosexual men infected with human immunodeficiency virus type 1.

Cofactors associated with the Mycobacterium avium complex (MAC) disease and its prognosis in incident cases of AIDS in homosexuals were studied. We compared 51 men in whom MAC disease developed as the initial AIDS-defining illness (termed AIDS illness hereafter); 157 men who had MAC disease subsequent to another AIDS illness; and 884 men who had only non-MAC AIDS illnesses. MAC disease was the initially diagnosed AIDS illness more often in Baltimore (6.9%) and Los Angeles (5.6%) than in Chicago (2.6%) and Pittsburgh (0) (P < .01). MAC disease also was a more common subsequent AIDS illness in Baltimore (14.3%) and Los Angeles (22.4%) than in Chicago (8.5%) and Pittsburgh (6.5%) (P < .0001). Prophylaxis for Pneumocystis carinii infection increased the occurrence of MAC disease as the initial AIDS illness (from 2.3% to 12.5%; P < .0001). A low white blood cell (WBC) count was slightly more predictive of MAC disease than was a low CD4+ cell count. At 0-6, 7-12, and 13-18 months before diagnosis, the WBC cell counts of 75.0%, 61.1%, and 50.0%, respectively, of those with MAC disease as the initial AIDS illness were < or = 3,400/microL. Men in whom cytomegalovirus disease developed were at higher risk for subsequent MAC disease (relative hazard = 2.65; P < .0001). MAC disease also increased the risk for subsequent cytomegalovirus disease (relative hazard = 3.96; P < .0001).

AIDS-Related Opportunistic Infections

Glucosyl diglyceride lipid structures in Deinococcus radiodurans.

The structures of two lipids from the radiation-resistant bacterium Deinococcus radiodurans are reported here: 1,2-diacyl-3-alpha-glucopyranosyl-glycerol and 3-O-[6'-O-(1",2"-diacyl- 3"-phosphoglycerol)-alpha-glucopyranosyl]-1,2-diacylglycerol. These lipids are strikingly different from previously characterized polar lipids from this organism, in that they are not unique to the genus Deinococcus and indeed have counterparts in both gram-negative and gram-positive bacteria. Moreover, as examples of glucose-containing lipids, they further illustrate the diversity of carbohydrate-containing lipids in D. radiodurans, from which lipids containing galactose and N-acetylglucosamine have already been structurally characterized.

Carbon Isotopes

Neutralization of respiratory syncytial virus after cell attachment.

Little is known about the mechanisms of antibody-mediated neutralization of respiratory syncytial virus (RSV) which causes recurrent infections in human despite the virtually universal presence of neutralizing serum antibodies. Human serum neutralization titers showed strong correlation with post-cell-attachment neutralizing titers for both RSV-convalescent sera and control sera but showed less strong correlation with cell-attachment blocking titers. Neutralization was effective for the first 60 min of infection, indicating that immune serum-mediated neutralization of RSV infection largely involves inhibition of early events following cell attachment.

Adhesiveness

Role of social class in excess black stroke mortality.

BACKGROUND AND PURPOSE: It has been suggested that a substantial proportion of the excess stroke mortality among black Americans may be attributable to relatively lower socioeconomic status (SES) in this group. In this report we provide the first quantitative estimates of the proportion of excess black stroke mortality attributable to SES for a large population-based cohort. METHODS: We used data from the National Longitudinal Mortality Study for persons 45 years and older (73,400 white men, 87,528 white women, 6522 black men, and 8816 black women). Sex-specific proportional hazards model were used to estimate excess black stroke mortality with and without adjustment for education and income (measures of SES). The contribution of SES to the excess black stroke risk was estimated from the difference in regression coefficients for race in these models. RESULTS: In men, low SES was associated with increased stroke mortality (P < or = .0001) and accounted for 14% to 46% of the excess black stroke risk (P < .05). However, we could find no association between SES and stroke mortality in women, and SES did not account for a significant proportion of the excess stroke mortality in black women. CONCLUSIONS: Although SES proved to account for a statistically significant proportion of excess male black stroke mortality, overall SES explained less than one quarter of the observed excess between ages 45 and 65. In women, SES did not significantly reduce the estimated excess black stroke mortality. Although SES may be playing a role in excess black stroke mortality, a substantial proportion of the excess appears attributable to other sources, including cerebrovascular risk factors that are unrelated to SES, unmeasured lifestyle influences, social resources, and genetic factors.

Black or African American

Anterior tibial tendon rupture.

Twelve patients with rupture of the anterior tibial tendon are presented. Nine patients were aware of an acute event prior to their symptom onset and three were not aware of any acute event. Complete rupture of the tendon was noted in 10 patients and incomplete rupture was seen in two patients. Treatment was individualized based on age, etiology, preinjury function, patient health, and personal considerations. Five patients were treated without surgery. Three preferred no orthotic devices, and two believed their function was improved with an ankle-foot orthosis. Seven patients were treated operatively using a variety of individualized reconstructive techniques. All operatively treated patients demonstrated increased function and strength. Based on our findings, operative reconstruction is recommended in appropriate patients.

Adolescent