Different mechanisms by which anti-DNA MoAbs bind to human endothelial cells and glomerular mesangial cells.

The mechanisms by which anti-DNA MoAbs derived from MRL-lpr/lpr mice, bind to human umbilical vein endothelial cells (HUVEC) and glomerular mesangial cells were studied using a cellular ELISA. DNAse-treatment of either the MoAb or HUVEC followed by reconstitution with DNA and/or histones was performed to determine whether DNA and histones mediated such binding. It was found that MoAb410 bound to HUVEC and mesangial cells in the form of preformed DNA/anti-DNA immune complex, and such binding was facilitated by histones. In contrast, MoAb 152 bound directly to cell membrane-associated DNA, and adding DNA to MoAb 152 reduced its cellular binding. DNA binds endothelial cell surface and histones enhance the binding of both MoAb 410 and MoAb 152 to HUVEC by increasing cell membrane-associated DNA. Finally, the degree of MoAb binding to HUVEC is critically influenced by the relative concentrations of antibody, DNA, and histones.     

Motility initiation in herring sperm is regulated by reverse sodium-calcium exchange

Sperm of the Pacific herring, Clupea pallasi, are unique in that they are immotile upon spawning in the environment. Herring sperm have evolved to remain motionless for up to several days after spawning, yet are still capable of fertilizing eggs. An egg chorion ligand termed "sperm motility initiation factor" (SMIF) induces motility in herring sperm and is required for fertilization. In this study, we show that SMIF induces calcium influx, sodium efflux, and a membrane depolarization in herring sperm. Sperm motility initiation by SMIF depended on decreased extracellular sodium (<350 mM) and could be induced in the absence of SMIF in very low sodium seawater. Motility initiation depended on > or =1 mM extracellular calcium. Calcium influx caused by SMIF involved both the opening of voltage-gated calcium channels and reverse sodium-calcium (Na(+)/Ca(2+)) exchange. Membrane depolarization was slightly inhibited by a calcium channel blocker and markedly inhibited by a Na(+)/Ca(2+) exchange inhibitor. Sodium efflux caused by SMIF-initiated motility was observed when using both extracellular and intracellular sodium probes. A Na(+)/Ca(2+) exchange antigen was shown to be present on the surface of the sperm, primarily over the midpiece, by using an antibody to the canine Na(+)/Ca(2+) exchanger. This antibody recognized a 120-kDa protein that comigrated with the canine myocyte Na(+)/Ca(2+) exchanger. Sperm of Pacific herring are now shown to use reverse Na(+)/Ca(2+) exchange in motility initiation. This mechanism of regulation of motility initiation may have evolved for both maintenance of immotility after spawning as well as ligand-induced motility initiation.     

Hemodynamic monitoring and management in patients undergoing high risk surgery: a survey among North American and European anesthesiologists

Introduction  

Several studies have demonstrated that perioperative hemodynamic optimization has the ability to improve postoperative outcome in high-risk surgical patients. All of these studies aimed at optimizing cardiac output and/or oxygen delivery in the perioperative period. We conducted a survey with the American Society of Anesthesiologists (ASA) and the European Society of Anaesthesiology (ESA) to assess current hemodynamic management practices in patients undergoing high-risk surgery in Europe and in the United States.     

Effects of alcohol and oxidative stress on liver pathology: the role of the mitochondrion

This article represents the proceedings of a symposium at the 2001 Research Society on Alcoholism meeting in Montreal, Canada. The chairs were Alan Cahill and Carol C. Cunningham. The presentations were (1) Mitochondrial regulation of ethanol-induced hepatocyte apoptosis: possible involvement of proapoptotic Bcl-2 family protein Bax, by Masayuki Adachi and Hiromasa Ishii; (2) Effects of ethanol on mitochondrial reactive oxygen species production and oxidative protein modification, by Shannon M. Bailey; (3) Acute ethanol binges elicit widespread oxidative mitochondrial DNA damage and depletion: protective effects of antioxidants and inhibitors of ethanol metabolism, by Bernard Fromenty; and (4) Effects of chronic ethanol consumption upon hepatic mtDNA oxidative modification and depletion, by Alan Cahill and Adrian Davies.     

Prevalence of, and risk factors for, hepatitis C virus infection among recent initiates to injecting in London and Glasgow: cross sectional analysis

Our aim was to compare the prevalence of antibody to hepatitis C virus (anti-HCV) among recently initiated injecting drug users (IDUs) in London and Glasgow, and to identify risk factors which could explain differences in prevalence between the cities. Complementary studies of community recruited IDUs who had initiated injection drug use since 1996 were conducted during 2001-2002. Data on HCV risk behaviours were gathered using structured questionnaires with identical core questions and respondents were asked to provide an oral fluid specimen which was tested anonymously for anti-HCV but was linked to the questionnaire. Sensitivities of the anti-HCV assays for oral fluid were 92-96%. Prevalence of anti-HCV was 35% (122/354) in London and 57% (207/366) in Glasgow (P < 0.001). Multifactorially, factors significantly associated with raised odds of anti-HCV positivity were increasing length of injecting career, daily injection, polydrug use, having had a needlestick injury, and having served a prison sentence. In addition lower odds of anti-HCV positivity were associated with non-injection use of crack cocaine and recruitment from drug agencies. After adjustment for these factors, the increased odds of anti-HCV associated with being a Glasgow IDU were diminished but remained significant. HCV continues to be transmitted among the IDU population of both cities at high rates despite the availability of syringe exchange and methadone maintenance. Effectiveness of harm reduction interventions may be compromised by inadequate coverage and failure to reduce sufficiently the frequency of sharing different types of injecting equipment, as well as the high background prevalence of HCV, and its high infectivity. Comprehensive action is urgently required to reduce the incidence of HCV among injectors.     

The causes of musculoskeletal chest pain in patients admitted to hospital with suspected myocardial infarction

BACKGROUND: We wished to investigate the causes and characteristics of musculoskeletal chest pain leading to acute medical admission. METHODS: We studied patients admitted to Queen Elizabeth Hospital, Gateshead, over a 10-week period. Patients with chest pain for which no acute cardiorespiratory cause was evident were identified and only included if they were tender on anteroposterior chest compression, thoracic spine rotation or firm sternal pressure. A detailed clinical history, anxiety and depression scale and a focussed physical examination were done to define the nature of musculoskeletal disease and their therapeutic requirements. RESULTS: Fifty patients satisfying the inclusion criteria were admitted in the 10-week period and comprised 54% females with a mean age of 57 years (S.D.=13.48). Chest pain lasted for 1 h or less in 24 patients and was mostly anterior. Three distinct groups of patients were identified. Twelve patients had evidence of inflammatory joint disease, thirteen had fibromyalgia and half had regional syndromes with pain arising from the shoulder, neck, thoracic spine or sternocostal areas. Visual analogue scores were highest in fibromyalgia for pain, and highest in inflammatory arthritis for impaired mobility. Anxiety and depression scores were highest in fibromyalgia and lowest among patients with regional syndromes. CONCLUSIONS: Musculoskeletal causes for acute chest pain are common and varied. Most patients have an identifiable cause of pain, but accurate diagnosis is needed to select the most appropriate intervention. Anxiety and depression are frequent, with much self-reported pain and dysfunction. However, all patients in this study had a disorder that was amenable to treatment and diagnosis. Management needs to be actively pursued in all patients.     

Vasculitis in the geriatric population

Vasculitis represents an uncommon but important group of disease entities that may affect older patients. The most common systemic vasculitic disease in humans is giant cell arteritis, a disease process seen almost exclusively in patients over the age of 50. Vasculitic disease in geriatric patients presents unique challenges with regard to diagnosis and treatment. A thorough understanding of the vasculitic disease entities that may affect older patients as well as their diagnosis and management is essential in minimizing disease and treatment related morbidity and mortality.