Cell-mediated immunity in rheumatic disease

Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis are the three most common systemic rheumatic diseases in which disordered immune function is thought to play a pathogenetic role. Each disease has different and characteristic abnormalities of the cellular immune system. In rheumatoid arthritis the identified abnormalities of immunoregulation are largely limited to specific antigens: Epstein-Barr virus and collagen. Systemic lupus erythematosus is characterized by exuberant B-cell activity with exaggerated humoral response, a diversity of autoantibodies, non-antigen-specific loss of suppressor cell function, and general suppression of cell-mediated immunity. In systemic sclerosis systemic defects of cellular and humoral immune function are mild, but the release of lymphokines and monokines at sites of inflammatory lesions is thought to be important in the pathogenesis of the disease. Similar immune cell-connetive tissue cell interactions are probably important in the propagation of rheumatoid synovitis. Thus, despite the many shared clinical and serologic features of these diseases as well as the presence of many patients who have clinically overlapping features of more than one of these entities, the immune defects and the immunopathogenesis of these disorders appear to be distinct.     

Fanconi's anemia treated by allogeneic marrow transplantation

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647- 3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.     

Sephadex-gel filtration (SGF) in infant and adult Gunn rats

SGF was compared in infant and adult homozygous Gunn rats. Without any drug application, the test was negative in the adult animals, whereas a remarkable percentage of positive SGF was obtained in 5-7-day-old rats, especially in those undernourished and/or intensely icteric. Unexpectedly, in infant rats the rate of positive SGF after sulfadimethoxine injection was lower than in the untreated control group. Moreover, in 9-10-day-old animals who had positive SGF before the injection, the test became negative 15-20 min after sulfadimethoxine application in vivo. No convincing explanation could be given, but drug interference with the binding capacities of the Sephadex column could be excluded by appropriate in vitro tests.     

Systematic screening for mutations in the human necdin gene (NDN): identification of two naturally occurring polymorphisms and association analysis in body weight regulation.

BACKGROUND: NDN, which codes for the human necdin protein, is a candidate gene for Prader-Willi syndrome (PWS). One feature of this neurogenetic disorder is hyperphagia resulting in extreme obesity observed later in development. OBJECTIVE AND DESIGN: In this study we have used single-strand conformation polymorphism (SSCP) analysis to identify sequence variants at the human necdin gene. Furthermore we tested whether these variants were associated with obesity in extremely obese German children and adolescents. RESULTS: Two gene variants could be identified: a g.1352T-->C polymorphism in the putative promotor region and a silent g.2311C-->T polymorphism in the coding region. Genotype and allele frequency distribution of both of the polymorphisms were not significantly different between lower and higher body mass index (BMI) subjects. CONCLUSIONS: Hence, it is unlikely that these polymorphisms play a major role in the emergence of juvenile onset human obesity.     

Gender Differences in Deviance and Health Risk Behaviors Among Young-Adults Undergraduate Students

Background: Deviant and health risk behaviors among young-adults are associated with many adverse outcomes. Objectives: This study aims to evaluate a broad variety of behaviors by gender differences and their contribution to predicting cannabis use in undergraduate students. Method: This research is based on a structured, self-reported anonymous questionnaire distributed to 1,432 young adult undergraduate students at an Israeli University, 533 males and 899 females (mean age 27.4; SD 6.01).

Results: The findings demonstrate a significant proportion of sampled young adults reported to be involved in deviant and health risk behaviors and that all risky behaviors were more frequently significant in males than in females. Among drivers 72% reported speeding, 60% reported failure to keep distance, 44% reported being involved at a car accident as a driver, 40% reported not stopping at a stop sign, and quarter reported driving after drinking alcohol. These findings also expand how certain risk behaviors contribute to predicting cannabis use. Conclusions: The relatively high prevalence of some of these risky behaviors among normative young adults suggests that risky behaviors are considered as normative behavior for this group, especially among man, and therefore, policymakers need to consider prevention and harm reduction interventions relevant to this risk group.     

Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes

Adrenergic activation of L-type Ca²⁺ and various K⁺ currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca²⁺ and K⁺ currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I _Ca, I _Ks, and I _Kr, while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I _Ca and I _Ks and moderate stimulation of I _Kr. The ISO-induced plateau shift and I _Ca increase developed faster than the shortening of APD and stimulation of I _Ks and I _Kr. Blockade of β₁-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of β₂-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I _Ca is turned on faster than the stimulation of I _Ks and I _Kr in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization.     

Hydroalcoholic extract and fractions of Davilla rugosa Poiret: effects on spontaneous motor activity and elevated plus-maze behavior

Davilla rugosa Poiret is commonly used in Brazilian folk medicine. The use as stimulant induced us to study the effects on motor activity and anxiety using an open-field and an elevated plus-maze, respectively. The hydroalcoholic extract of the stems (HE) was fractionated with chloroform (CF), chloroform/ethyl acetate (CAF), ethyl acetate (AF), ethyl acetate/ethanol (AEF), ethanol (EF) and ethanol/water (EWF). Rats were treated orally with HE (7.5, 15, 30 or 60 mg/kg) or fractions (15 mg/kg). In the open-field, HE (15 mg/kg), AEF, EF and EWF increased locomotion frequency and decreased immobility time; the contrary was observed with 30 and 60 mg/kg of HE. These doses also increased defecation. No effects were observed with 7.5 mg/kg of HE, CF, CAF or AF, except for an increase in defecation induced by AF. In the elevated plus-maze, total entries and number of entries into the open and closed arms and the time spent in the open arms and its percentage were increased only with 15 mg/kg of HE. The open-field results suggest that the drug increases motor activity (stimulant effect) and that the active components are in the three more polar fractions. An anxiolytic effect was observed only with the HE.     

The association between high plasma homocysteine levels and lower bone mineral density in Slovak women: the impact of vegetarian diet

Background  

A long-term vegetarian diet is generally poor in vitamin B group. The lack of vitamin B₁₂ together with vitamin B₆ and folate deficiency is closely related to homocysteine metabolism. Hyperhomocysteinemia was found to be associated with increased bone turnover markers and increased fracture risk. Thus, hyperhomocysteinemia, vitamin B₁₂ and folate deficiency may be regarded as novel risk factors for micronutrient deficiency-related osteoporosis.     

Pr?vention der nosokomialen übertragung von humanem Immunschw?chevirus (HIV) durch HIV-positive Mitarbeiterinnen und Mitarbeiter im Gesundheitswesen

To the best of our knowledge, the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V. are the first in Europe to provide precise recommendations for the management of health care workers (HCWs) who are infected with human immunodeficiency virus (HIV). Requirements for HIV-infected HCWs need to be clearly defined. With a permanent viral burden of less than or equal to 50 copies/mL, HIV-positive HCWs are allowed to perform any surgery and any invasive procedure, as long as the infected HCW uses double-gloving, undergoes follow-up routinely by occupational medicine professionals, undergoes a quarterly examination of viral burden, and has a regular medical examination by a physician who has expertise in the management of HIV. Unrestricted professional activity is only possible with a strict compliance to take antiretroviral therapy and if the HIV-infected HCW strictly adheres to the recommended infection control procedures. Complete compliance with the recommendation almost certainly leads to no HIV transmission risk in patient care.