The association of Schistosomiasis mansoni and proteinuria in an endemic area. A preliminary report.

The association of Schistosoma mansoni infection and proteinuria was investigated by measuring quantitative urinary protein in a defined population in an endemic area in northeastern Brazil. Persons with schistosomiasis had higher mean urinary protein than those without. Two of 162 persons with schistosomiasis had clear evidence of renal disease (pathologic proteinuria, abnormal urinary sediment). These results seemed to be related neither to the intensity of S. mansoni infection as measured by fecal egg excretion nor to the presence of hepatic and splenic enlargement in schistosomiasis.     

Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3

We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.     

Treatment of arrhythmias in chronic cardiac insufficiency

Arrhythmias are frequent and associated with a poor prognosis, especially when they arise from the ventricle. Although the correction of predisposing factors and improvement of hemodynamic conditions are essential, the use of antiarrhythmic drugs in this context poses problems. The treatment of even complex ventricular extrasystoles has not been shown to effectively prevent the serious arrhythmias responsible for sudden death. Depression of left ventricular function and: Or proarrhythmic effects of antiarrhythmic therapy in some patients, probably offset the benefits observed in others. The treatment of atrial arrhythmias remains traditional: reduction by drugs or electrotherapy and prevention of recurrences, or simply slowing the ventricular response. Sustained ventricular tachycardia and resuscitated ventricular fibrillation should be managed more aggressively, not by empirical antiarrhythmic treatment but by medical therapy guided by the results of electrophysiological studies, and, when this fails, by non-medical treatment: fulguration, implantable defibrillator, antiarrhythmic surgery, or even cardiac transplantation.     

Mitochondrial DNA mutations activate the mitochondrial apoptotic pathway and cause dilated cardiomyopathy

OBJECTIVE: To determine whether low frequency mitochondrial DNA (mtDNA) mutations are pathogenic. METHODS: We studied mice that express a proofreading-deficient mitochondrial DNA polymerase in the heart and develop cardiac mtDNA mutations. RESULTS: At 4 weeks of age, when point mutation levels had risen to on average two per mitochondrial genome, these mice developed severe dilated cardiomyopathy. Interstitial fibrosis first became apparent at 4 weeks of age and progressed with age. Sporadic myocytic death occurred in all regions of the heart, apparently due to apoptosis as assessed by histological analysis and TUNEL staining. The frequency of TUNEL-positive cells peaked at 4-5 weeks of age and then gradually declined. While mitochondrial respiratory function, ultrastructure, and number remained normal, cytochrome c was released from mitochondria, a known apoptotic signal. CONCLUSION: mtDNA mutations therefore are pathogenic, and seem to trigger apoptosis through the mitochondrial pathway.     

Hospital and medical care use by nursing home patients: the effect of patient care plans

Although there has been increasing attention to the ethical and legal issues involved in the patient's right to have treatment or hospitalization withheld, there have been few empirical evaluations of programs designed to accomplish that end. Over a 7-year period, a medical group cared for 110 patients in a skilled nursing facility. After assessing the patients' wishes and the opinions of the personal physicians and nurses, care plans were made specifying whether each one was to receive maximum, intermediate, or comfort care. The hospitalization rate was found to be 79% lower for the patients receiving comfort care. Multiple admissions were unusual. Those patients made no use of outpatient consultants or major diagnostic procedures and had only 14% as many roentgenograms as the patients receiving maximum care. Whereas acute medical and surgical problems and related physician visits were more frequent for the comfort care groups, specific treatment of those problems was withheld far more often. Mortality was twice as great among the comfort care patients, and nearly all of these deaths occurred in the nursing home. It was concluded that the patient's decision to avoid active management can be honored by specific patient plans carefully communicated to all physicians sharing responsibility for that person's care.     

B lymphoblastoid cell lines with normal and defective O-glycosylation established from an individual with blood group Tn

Individuals with the Tn blood group contain terminal serine/threonine- linked N-acetylgalactosamine residues in their blood cells. This is due to lack of UDP-D-galactose: D-N-acetyl galactosamine beta-D-galactosyl transferase from part of their red cells and probably from their leukocytes. We have established B lymphoblastoid cell lines from such an individual by in vitro infection of his lymphocytes with Epstein- Barr virus. The original line contained a mixture of cells reactive and nonreactive with Helix pomatia lectin (Hp). These cells were subcloned after staining with fluorescent Hp by a fluorescence-activated cell sorter (FACS) into homogeneous, phenotypically stable lines of Hp- positive (Hp+) and Hp-negative (Hp-) cells. The molecular differences between the membrane glycoproteins were characterized by carbohydrate- specific surface labeling techniques, Hp affinity chromatography, polyacrylamide slab gel electrophoresis and glycopeptide/oligosaccharide analysis. The major O-glycosidic membrane glycoprotein (GP105) was retained on Hp-Sepharose columns only from Hp+ cells, whereas the common leukocyte antigen (GP160-200) was partially retained on Hp columns from both lines. These proteins were isolated by immune precipitation with monoclonal antibodies and characterized. The results show that the GP105 glycoprotein from Hp+ cells contains terminal N-acetylgalactosamine residues but also more complex oligosaccharides. The common leukocyte antigen showed different electrophoretic mobilities in Hp+ and Hp- cells. UDP-galactose D-N- acetyl galactosamine beta-galactosyl transferase was almost absent in the Hp+ cells. These cell lines are useful for studies on the functional role and regulation of the biosynthesis of O-glycosidic carbohydrates.     

In vitro stretch injury induces time- and severity-dependent alterations of STEP phosphorylation and proteolysis in neurons

Striatal-enriched tyrosine phosphatase (STEP) has been identified as a component of physiological and pathophysiological signaling pathways mediated by N-methyl-d-aspartate (NMDA) receptor/calcineurin/calpain activation. Activation of these pathways produces a subsequent change in STEP isoform expression or activation via dephosphorylation. In this study, we evaluated changes in STEP phosphorylation and proteolysis in dissociated cortical neurons after sublethal and lethal mechanical injury using an in vitro stretch injury device. Sublethal stretch injury produces minimal changes in STEP phosphorylation at early time points, and increased STEP phosphorylation at 24 h that is blocked by the NMDA-receptor antagonist APV, the calcineurin-inhibitor FK506, and the sodium channel blocker tetrodotoxin. Lethal stretch injury produces rapid STEP dephosphorylation via NR2B-containing NMDA receptors, but not calcineurin, and a subsequent biphasic phosphorylation pattern. STEP(61) expression progressively increases after sublethal stretch with no change in calpain-mediated STEP(33) formation, while lethal stretch injury results in STEP(33) formation via a NR2B-containing NMDA receptor pathway within 1 h of injury. Blocking calpain activation in the initial 30 min after stretch injury increases the ratio of active STEP in cells and blocks STEP(33) formation, suggesting that STEP is an early substrate of calpain after mechanical injury. There is a strong correlation between the amount of STEP(33) formed and the degree of cell death observed after lethal stretch injury. In summary, these data demonstrate that previously characterized pathways of STEP regulation via the NMDA receptor are generally conserved in mechanical injury, and suggest that calpain-mediated cleavage of STEP(33) should be further examined as an early marker of neuronal fate after stretch injury.