Sequence analysis of cDNAs for the human and bovine ATP synthase β subunit: mitochondrial DNA genes sustain seventeen times more mutations

We have cloned and sequenced human and bovine cDNAs for the subunit of the ATP synthase (ATP-synß), a nuclear DNA (nDNA) encoded oxidative phosphorylation (OXPHOS) gene. The two cDNAs were found to share 99% amino acid homology and 94% nucleotide homology. The evolutionary rate of ATPsynß was then compared with that of two mitochondrial DNA (mtDNA) ATP synthase genes (ATPase 6 and 8), seven other mtDNA OXPHOS genes, and a number of nuclear genes. The synonymous substitution rate for ATPsynß proved to be 1.9 × 10^–9 substitutions per site per year (substitutions × site^–1 × year^–1) (SSY). This is less than 1/2 that of the average nDNA gene, 1/12 the rate of ATPase 6 and 8, and 1/17 the rate of the average mtDNA gene. The synonymous and replacement substitution rates were used to calculate a new parameter, the selective constraint ratio. This revealed that even the most variable mtDNA protein was more constrained than the average nDNA protein. Thus, the high substitution mutation rate and strong selective constraints of mammalian mtDNA proteins suggest that mtDNA mutations may result in a disproportionately large number of human hereditary diseases of OXPHOS.     

LFA-1-dependent OKT3-driven T cell clusters in common variable immunodeficiency.

The triggering of the TCR/CD3 complex by anti-CD3 (OKT3) antibody leads to the formation of T cell clusters. In cultures of T lymphocytes from most normal individuals, the peak of cluster formation occurs at 24 h, but with cells from patients with common variable immunodeficiency (CVI) it was seen earlier at 4-9 h; in addition, the clusters were larger than normal, particularly at 9 h. Cluster formation by CVI and normal cells was dependent on temperature and divalent cations, but did not require Fc receptors. Since OKT3 clustering is known to be dependent on the LFA-1/ICAM-1 adhesion system, the effect of monoclonal antibodies directed against these molecules was tested. A potent inhibitor was the antibody against the common beta chain of the integrin family (CD18), but of four MoAbs against the alpha chains (CD11), three inhibited and one stimulated T cell aggregate formation. Increased expression of LFA-1 or ICAM-1 on CVI patients' T cells could not be demonstrated. The accelerated clustering was therefore probably due to an increase in the proportion of cells carrying the activated form of LFA-1. The formation of large numbers of homotypic lymphocyte clusters might reduce the effective interaction between B and T cells, thus contributing to the depression of immunoglobulin synthesis observed in this disease.     

A differential effect of C5a and C5a des Arg in the induction of pulmonary inflammation.

Earlier studies have shown that C5 fragments induce an inflammatory reaction when instilled into the rabbit lung. Because C5a is rapidly converted to C5a des Arg in vivo, experiments were performed to determine which fragment was most effective in producing pulmonary inflammation in this animal model. C5a des Arg consistently produced marked inflammation. This was characterized by neutrophil accumulation, edema, hemorrhage, fibrin formation, and damage to alveolar epithelium. The time course of the inflammatory reaction initiated by C5a des Arg showed pulmonary vascular sequestration of neutrophils with no intra-alveolar migration at 30 minutes after injection. By 2 hours, interstitial and alveolar neutrophils were numerous, with the accumulation of neutrophils in the alveoli increasing to a maximum at 6 hours. At 24 and 48 hours, the predominant cells were mononuclear (macrophages). By 120 hours, the lesions were resolving. In contrast, at all doses examined, a similar instillation of C5a induced either no inflammation or a milder, more focal response than C5a des Arg. This inability of C5a to initiate inflammation was not apparently due to the generation of inhibitors, since mixtures of C5a and C5a des Arg were phlogistic. A prolonged, intrapulmonary infusion of C5a (20 minutes), in contrast to a bolus instillation (1 minute), did initiate an inflammatory response, which may reflect the conversion of the C5a to C5a des Arg in the lung. This study points out the inflammatory potential of products of complement activation, particularly of the C5 fragment C5a des Arg, when applied to the airway side of the lungs. This inflammatory response raises the possibility that cleavage of intrapulmonary C5 may play an important role in the initiation of pulmonary inflammation.     

A comparison of two anti-neuraminidase monoclonal antibodies by complement activation

The specificities of two anti-neuraminidase monoclonal antibodies have been compared by their ability to fix complement. They were found to differ to some extent in their reactivity with a range of N2 influenza viruses. Thus, as in the case of anti-hemagglutinin antibodies, anti-neuraminidase monoclonal antibodies are able to detect subtle structural changes in the viral antigen. Although both monoclonal antibodies fixed complement with intact virus, neither one fixed complement when complexed with isolated neuraminidase “heads”.     

HIV infection and associated risks among young men who have sex with men in a Florida resort community

OBJECTIVE: Several recent studies have reported high rates of sexual risk-taking and HIV infection among young men who have sex with men (MSM). Most of these studies used samples of convenience. The authors obtained population-based data on young MSM living in South Beach (Miami Beach, Florida), a resort community where some of the highest AIDS rates in the United States have been reported. METHODS: A household probability sample was drawn to survey unmarried 18- to 29-year-old MSM living in South Beach. Subjects were interviewed, completed self-administered questionnaires, and provided oral specimens for HIV antibody testing. RESULTS: From the 2,622 screened residential units, 100 mostly white and Hispanic MSM (92.6% of eligible participants) were enrolled in the study. Fifteen percent of the sample tested positive for antibodies to HIV. White and Hispanic MSM had similar rates. Forty-five percent of the sample reported engaging in unprotected anal intercourse (UAI) in the prior 12 months, and 31% reported UAI with a nonprimary partner. The estimated annual incidence of HIV infection was 6.3%. CONCLUSION: The high prevalences of UAI and HIV infection in South Beach attest to a previously undocumented public health concern. The extremely high estimated incidence for young MSM in South Beach highlights the urgent need for more effective risk-reduction interventions and further epidemiological research on resort areas.     

Evaluation of encephalic ventricular volume from the magnetic resonance imaging scans of thirty-eight human subjects

Summary Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for normal subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm³, while that for males was 16.3 cm³ and that for females was 18.0 cm³. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age.

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Evaluation du volume des ventricules cérébraux à partir des images obtenues en résonance magnétique nucléaire chez 38 sujets humains

Résumé La détermination exacte du volume des ventricules cérébraux est importante en clinique comme par exemple dans la démence présénile d'Alzheimer, la schizophrénie et l'hypertension intracrânienne bénigne. Des études antérieures ont étudié la fiabilité de la résonance magnétique nucléaire en pratique clinique pour évaluer le volume des ventricules cérébraux. Toutefois une évaluation correcte dans les conditions pathologiques implique une bonne connaissance des données morphométriques du sujet normal. Pour établir ces données sur « le sujet normal », nous avons étudié les coupes obtenues en IRM chez 38 sujets apparemment indemnes de toute pathologie; nous avons calculé le volume ventriculaire dans chaque cas en utilisant des méthodes mises au point auparavant dans notre laboratoire. Les résultats ont été ensuite comparés avec ceux obtenus par d'autres études utilisant soit des moules ventriculaires, soit des coupes tomographiques computérisées. Le volume ventriculaire total moyen chez 38 sujets est de 17,4 cm³, mais il est chez les sujets masculins de 16,3 cm³ et chez les sujets de sexe féminin de 18 cm³. Une corrélation faible mais significative a été trouvée entre l'âge du sujet et le volume ventriculaire, étant entendu que la taille du ventricule augmente avec l'âge.

     

Assessment of Self-Reward Strategies for Maintenance of Breast Self-Examination

This study examined the relative impact of different self-reward strategies on maintenance of breast self-examination (BSE) practice among 1649 women trained to do BSE. Training groups were randomized into four conditions: (a) self-reward instructions and materials delivered at the end of the BSE training session; (b) self-reward suggestions delivered through the mail each month, contingent upon the BSE performance; (c) external monetary rewards and self-reward suggestions delivered through the mail each month on an intermittent schedule, contingent upon BSE practice; and (d) a no-reward control condition. Follow-up assessments 12 months following training revealed a pattern of evidence in support of the benefits of external monetary rewards and self-reward prompts on BSE frequency and quality; however, it is likely that the value of that condition lies in the external reward component.