Prospective study of human herpesvirus 6, human herpesvirus 7, and cytomegalovirus infections in human immunodeficiency virus-positive patients

Blood samples from human immunodeficiency virus (HIV)-positive patients were monitored for cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and HHV-7 by PCR. We detected CMV in 17% of the patients, HHV-6 in 6%, and HHV-7 in 3%. The viral loads of CMV were significantly higher than those of HHV-6 (P = 0.007) or HHV-7 (P = 0.01). Detection of CMV and HHV-6 was associated with low and high CD4 counts, respectively.     

Pretreatment of astrocytes with interferon-alpha/beta impairs interferon-gamma induction of nitric oxide synthase

Excessive nitric oxide/peroxynitrite generation has been implicated in the pathogenesis of multiple sclerosis, and the demonstration of increased astrocytic nitric oxide synthase activity in the postmortem brain of multiple sclerosis patients supports this hypothesis. Exposure of astrocytes, in primary culture, to interferon-gamma results in stimulation of nitric oxide synthase activity and increased nitric oxide release. In contrast to interferon-gamma, interferon-alpha/beta had a minimal effect on astrocytic nitric oxide formation. Furthermore, pretreatment of astrocytes with interferon-alpha/beta inhibited (approximately 65%) stimulation by interferon-gamma of nitric oxide synthase activity and nitric oxide release. Treatment with interferon-alpha/beta at a concentration as low as 10 U/ml caused inhibition of mitochondrial cytochrome c oxidase. Furthermore, the damage to cytochrome c oxidase was prevented by the putative interferon-alpha/beta receptor antagonist oxyphenylbutazone. In view of these observations, our current hypothesis is that the mitochondrial damage caused by exposure to interferon-alpha/beta may impair the ability of astrocytes to induce nitric oxide synthase activity on subsequent interferon-gamma exposure. These results may have implications for our understanding of the mechanisms responsible for the therapeutic effects of interferon-alpha/beta preparations in multiple sclerosis.     

The copper chaperone for superoxide dismutase

Copper is distributed to distinct localizations in the cell through diverse pathways. We demonstrate here that the delivery of copper to copper/zinc superoxide dismutase (SOD1) is mediated through a soluble factor identified as Saccharomyces cerevisiae LYS7 and human CCS (copper chaperone for SOD). This factor is specific for SOD1 and does not deliver copper to proteins in the mitochondria, nucleus, or secretory pathway. Yeast cells containing a lys7Delta null mutation have normal levels of SOD1 protein, but fail to incorporate copper into SOD1, which is therefore devoid of superoxide scavenging activity. LYS7 and CCS specifically restore the biosynthesis of holoSOD1 in vivo. Elucidation of the CCS copper delivery pathway may permit development of novel therapeutic approaches to human diseases that involve SOD1, including amyotrophic lateral sclerosis.     

Comparison of mitochondrial respiratory chain enzyme activities in rodent astrocytes and neurones and a human astrocytoma cell line

This study has found that mitochondrial NADH-CoQ1 reductase (complex I) activity is significantly lower in C57 mice astrocytes compared with Wistar and Sprague-Dawley rat astrocytes, and a human astrocytoma cell line. In addition, complex I activity is 4-fold greater in Sprague-Dawley neurones when compared to Wistar or C57 neurones. These findings have important implications for mitochondrial studies involving rodent or human cell line systems, and in particular, indicate the importance of choosing an appropriate model when investigating the mitochondrial respiratory chain.     

Analysis of the interdependent localization of vimentin and microtubules in neoplastic myoepithelial cells

Certain biological differences between men and women are relevant to the problem of AAA, and are widely accepted. Women unequivocally have smaller aortas. The size difference correlates with a variety of anthropomorphic measurements, but is most strongly associated with body surface area. In women the compliance of the aorta decreases in linear fashion with age, whereas in men the decrease in compliance is exponential with age. Women appear to be underrepresented in AAA surgical series (typically 18% to 20% of operative cases) compared with autopsy studies (29% to 32%), ultrasound screening studies (19% to 25%), and mortality studies (34% of the 14,982 deaths due to AAA in the US in 1988). Several lines of evidence suggest that women with AAA are less likely than men to be referred for surgery, and that, when referred, they have higher mortality rates. The reasons for these differences are unclear. The very factors that allow increased longevity in women may have an adverse effect on the ability to tolerate a major surgical stress. Wenger et al have suggested that psychosocial and economic factors may affect women's decisions to seek care, or their choice of therapeutic options. Lack of knowledge among practitioners of gender-related aortic size differences and overreliance on simplistic clinical paradigms that dictate operations for 5-cm diameter aneurysms and watchful waiting for 4- to 5-cm AAAs may result in unintended bias in patient selection. It may be that a 5-cm diameter AAA in a woman with a predicted normal aortic size of 1.4 cm represents a more advanced stage of disease than a 5-cm diameter AAA in a man with a normal aortic diameter of 2.5 cm. More precise and detailed algorithms are needed to permit clinicians to tailor decisions to patients' size, sex, and risk factors. Development of such algorithms requires expansion of clinical and epidemiological studies to include enough women to make precise risk estimates.     

Complex segregation analysis of leprosy in southern Vietnam

To investigate the nature of the genetic component controlling susceptibility to leprosy and its subtypes, 402 nuclear families were ascertained through a leprosy patient followed at the Dermatology Hospital in Ho Chi Minh City, Vietnam; 285 families were of Vietnamese origin and 117 were of Chinese origin with a higher proportion of lepromatous forms among Chinese patients. Segregation analyses were conducted using the model developed by Abel and Bonney [(1990) Genet Epidemiol 7:391-407], which accounted for variable age of onset and time-dependent covariates. Three phenotypes were considered: leprosy per se (all forms of leprosy together), nonlepromatous leprosy, and lepromatous leprosy. For each of this phenotype, analyses were performed on the whole sample and separately on the Vietnamese and the Chinese families. The results showed that a single Mendelian gene could not account for the familial distributions of leprosy per se and its two subtypes in the whole sample. However, these results were different according to the ethnic origin of the families. In the Vietnamese subsample, there was evidence for a codominant major gene with residual familial dependences for the leprosy per se phenotype, and borderline rejection of the Mendelian transmission hypothesis for the nonlepromatous phenotype. In Chinese families, strong rejection of Mendelian transmission was obtained in the analysis of leprosy per se, and no evidence for a familial component in the distribution of the nonlepromatous phenotype was observed. For the lepromatous phenotype, the discrimination between models was poor, and no definitive conclusion could be reached. Referring to immunological data, we suggest that these results could be explained by a heterogeneity in the definition of the lepromatous phenotype. It is likely that progress in the understanding of the genetic components involved in the expression of leprosy will come from a better definition of the phenotype under study, and immunological studies are ongoing in this population to investigate this hypothesis.     

Adolescent sexuality: Part 4. The practitioner''s role

As no systematic study has been done to get an accurate estimate of the incidence of return to oestrus after first insemination in sows in the Netherlands, the objectives of this investigation were: 1) to obtain an estimate of the incidence of return to oestrus after insemination at the herd level; 2) to investigate the association between incidence of return to oestrus after first insemination and reproduction characteristics in order to get an impression of the economic importance of reproductive failure. These objectives were investigated by using the reproduction results of 240 swine breeding herds in the Southern Netherlands in 1987. This information was obtained from CBK plus computerized herd management records. The average incidence rate of return to oestrus after first insemination at a herd level was 16.9 per 100 first inseminations. The occurrence of return to oestrus after first insemination was distinctly higher in the insemination months July and August compared to the rest of the year. An increased incidence, with 10 returns per 100 first inseminations corrected for confounders in a multiple linear regression model, was associated with a decrease of approximately 0.3 live born piglets/sow/year. A prospective longitudinal study was started in 1988 and 1989 in 37 sow herds. Individual sows were monitored from weaning to first insemination, to the occurrence of return to oestrus, or not, after first insemination, and to farrowing. The investigation focused in particular on the relationship between return to oestrus after first insemination and seroconversion against porcine parvovirus (PPV) and Leptospira interrogans serovar bratislava (L. bratislava).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the inducible nitric oxide synthase inhibitors aminoguanidine and L-N6-(1-iminoethyl)lysine on zymosan-induced plasma extravasation in rat skin

The effect of nitric oxide synthase (NOS) inhibitors on plasma extravasation in a rat model of zymosan-induced inflammation has been investigated. Plasma extravasation was determined in response to intradermal test agents over 0 to 45 min or 0 to 4 h by the accumulation of i.v. injected 125I-labeled human serum albumin. Zymosan (1-100 microg/site) produced a dose- and time-dependent plasma extravasation. N(G)-nitro-L-arginine methyl ester (30-300 nmol/site), but not aminoguanidine (AG; 10-300 nmol/site) or L-N6-(1-iminoethyl)lysine (L-NIL; 10-300 nmol/site), significantly (p < 0.01) inhibited zymosan-induced (10 microg/site) plasma extravasation over 0 to 45 min. However, both AG and L-NIL produced significant (p < 0.05) inhibition over 0 to 4 h. The inhibition produced by AG was reversed by i.v. L-arginine or by coinjection of the vasodilator, calcitonin gene-related peptide. Zymosan (10-100 microg/site) induced an increase in dermal blood flow (laser-Doppler flowmetry) and this was inhibited by AG. Neutrophils were depleted selectively with antiserum, but this did not affect plasma extravasation except at the highest dose of zymosan (100 microg/site). Furthermore, zymosan-induced edema was not modified at either time point by pretreatment with the cyclooxygenase inhibitor indomethacin (30 micromol/kg, s.c., -30 min). In conclusion, in this model of dermal inflammation, it is suggested that inducible NOS inhibitors selectively remove an inducible NOS component that, at least in part, acts to increase microvascular blood flow and thus the edema formation observed during 0 to 4 h. There is no evidence of a contributory role for neutrophils or cyclooxygenase products in this model.