Oligomycin-resistant mitochondrial ATPase from mouse fibroblasts

Fourteen oligomycin-resistant LM(TK^–) clones were isolated following the mutagenesis of minicells. In the absence of oligomycin, the mutants grew with population doubling times similar to that of the wild type (1 day). In 3 or 5 g oligomycin/ml the doubling times of the mutants were 1.2–2.5 days. Both stable and unstable classes were represented among the oligomycin-resistant mutants. Mitochondrial ATPase activities of the mutants were 1.3–1130 times more resistant to oligomycin than the wild type. The mitochondrial ATPase of OLI 14 was found to be bound firmly to the mitochondrial membrane, showed no alteration in the pH optimum compared to wild-type, and exhibited increased resistance to DCCD and venturicidin. These results are consistent with the conclusion that oligomycin resistance in these mutants results from altered mitochondrial ATPase.     

Surveillance of the genetic variation in incident HIV, HCV, and HBV infections in blood and plasma donors: implications for blood safety, diagnostics, treatment, and molecular epidemiology

Surveillance for molecular variants in blood donors is vital to assuring that blood screening and supplemental assays are sensitive to circulating strains of blood-borne viruses. Blood screening and diagnostic assays licensed in the United States are largely based on prototype viral strains. Documentation of divergent viral strains in the donor pool can lead to accelerated development and licensure of robust serologic and nucleic acid amplification (NAT) assays for donor screening and diagnostic applications. In addition, surveillance for viral variants among donors has implications for assessing the prevalence of drug and vaccine escape mutants and for detecting and monitoring rare variants that may be newly introduced or increasing in the United States donor population. Combined NAT and serologic screening, supplemented by novel serologic testing strategies, can be used to identify donors with incident infections, which are of particular interest with respect to blood safety and public health implications. A systematic program is proposed for the genetic characterization of viral genomes in donors with incident HIV, HCV, or HBV infections.     

Multiple Dimensions of Stigma and Health Related Factors Among Young Black Men Who Have Sex with Men

This study is among the first to examine the association between multiple domains of HIV-related stigma and health-related correlates including viral load and medication adherence among young Black men who have sex with men (N = 92). Individual logistic regressions were done to examine the hypothesized relationships between HIV-related stigma and various health and psychosocial outcomes. In addition to examining total stigma, we also examined four domains of HIV stigma. Findings revealed the various domains of stigma had differential effects on health-related outcomes. Individuals who reported higher levels of total stigma and personalized stigma were less likely to be virally suppressed (OR 0.96, 95 % CI 0.91–1.00 and OR 0.50, 95 % CI 0.25–1.02, respectively). Concerns about public attitudes toward HIV were positively related to medication adherence (OR 2.18, 95 % CI 1.20–3.94) and psychological distress (OR 5.02, 95 % CI 1.54–16.34). The various domains of HIV stigma differentially affected health and psychosocial outcomes, and our findings suggest that some forms of HIV stigma may significantly affect viral load and medication adherence among this population. Stigma-informed approaches to care and treatment are needed, along with incorporated psychological and social supports.     

The "patellar ratio" in hemophilia and juvenile rheumatoid arthritis.

The ratio of patellar length to width was analyzed in comparison with subjective examination using radiographs of the affected knees in patients with hemophilia, juvenile rheumatoid arthritis (JRA), and controls to determine the usefulness of this measurement in differentiating the two diseases. A statistically significant difference was found between the proportion of JRA patients, controls, and patients with hemophiliac arthritis involving the knee. It was difficult to distinguish hemophilia from JRA by subjective analysis of the appearance of the knee using standard criteria. The patellar ratio is a more objective criterion which should be helpful in the radiological differentiation of JRA from hemophilia affecting the knee.     

Enhanced binding of low-affinity antibodies interacting simultaneously with targeted cell surface molecules and Fc receptor

The possibility that different forms of class I molecules might be expressed on the cell surface of lymphocytes has been investigated periodically over the past several decades. A series of major histocompatibility complex (MHC) class I-specific monoclonal antibodies, including the commonly used antibodies 64-3-7 and 25-D1.16, bind B cells differentially, suggesting the existence of differentially expressed class I-associated cell surface determinants on B lymphocytes. However, the ability of antibodies to bind cells is determined by the sum of interactions between the antibodies and the molecules expressed on the cell surface. The interactions of class I-specific antibodies with B cells were dissected, revealing dual specificity of the antibodies for the targeted class I molecules, as well as to Fc receptors preferentially expressed by B cells. We demonstrate that antibodies simultaneously bind targeted class I molecules and Fc receptors expressed on the surface of B cells. Simultaneous binding to two cell surface structures significantly enhances the class I-specific binding pattern of certain antibodies by increasing their avidity, leading to apparent cell-specific differences in MHC expression patterns. We conclude that no differences in MHC structures need be postulated to account for the observed binding patterns.     

Gastric emptying using three different formulas in infants with gastroesophageal reflux.

The role of delayed gastric emptying (GE) in the pathogenesis of gastroesophageal reflux (GER) in infants is controversial at present. GE has been shown to be altered by the composition and osmolality of the feedings. This prospective study was undertaken to assess the changes in the GE and the percentage of time GER was detected by scintigraphy using three different formulas on consecutive days in infants with GER. Twenty-eight infants under 1 year of age diagnosed to have GER by extended intraesophageal pH monitoring (pH being less than 4.0 for greater than 5% of the duration of the test), underwent scintigraphy on three consecutive days using the same volume per single feeding of a casein-predominant, soy, or a whey-hydrolysate formula in a randomized order. The formulas were isocaloric. Gastric emptying and percentage of GER into the esophagus were estimated for 60 min following these feedings. Mean GER percent during the study was 20.39, 17.68, and 16.34 on casein-predominant, soy, and whey-hydrolysate formulas, respectively, and was not significantly different. Mean values of GE were 39.7%, 44.6%, and 48.5% on casein, soy, and whey formula, respectively. No significant difference in GE was also observed between casein-predominant and soy formula. However, a significant difference was observed (p less than 0.05) on GE between casein-predominant and whey-hydrolysate feedings. Our data suggest that formula selection may be important in the treatment of conditions associated with delayed gastric emptying.     

Relationship of phenotypic expression of blood group H to changes in growth kinetics of cultured primary and transformed epithelioid cells

Population studies of continuously cultured primary amnion cells from appropriate donors and of HeLa cells have established that the H- cell behaves as a stem cell which commonly divides into a like cell and a differentiated H+ type. Exfoliated H+ cells, anucleate or with small or pyknotic nuclei and impaired membrane function, constitute the terminal cell in this process. Stem and differentiated populations have been identified and enumerated a) during the phase of exponential growth in monolayer culture, b) in the course of serial transfers of established and primary cultures, c) in chemically synchronized cells and d) in nutritionally deprived cells. Under the experimental conditions, the rate of phenotypic expression of group H was essentially the same in primary amnion cells from group O donors and in HeLa cells during the phase of exponential growth. The quantitative experiments on H+/H- cell populations suggested that the phenotypic expression of blood group H was adversely affected by altered cell growth which came about by limiting the potential of H- stem cells for differentiation. This occurred following multiple passages of primary cell cultures, or under conditions of nutritional inadequacy in HeLa cells. Studies on chemically synchronized cells indicated that following exposure to excessive thymidine, the predominant cell doubling pattern was reflected as mixed H+/H- progeny. Limitations imposed upon the ability of stem cells to differentiate are probably expressed either as slowly cycling, noncycling or nonviable cells and compensation by surviving stem cells may be provided for by changes in the cell doubling pattern. Since L-fucose is the immunodeterminant sugar for blood group H, it is proposed that a portion of the cellular DNA codes for a fucosyl transferase enzyme responsible for attaching this sugar to a membrane acceptor molecule. Disturbances of cell growth may interrupt this pathway at one or more points.     

Ultrasonography of the annular ligament partial tear and recurrent “pulled elbow”

A 2-year-old boy had multiple episodes of radial head subluxation, recurrent pulled elbow. On initial ultrasonography, there was subluxation of the radial head in relation to the capitellum, and the annular ligament was partially disrupted. Following brace treatment, subluxation of the radial head was corrected and annular ligament disruption healed. As shown by ultrasonography, these findings correlated well with the clinical course and can be utilized to guide treatment.