From the periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy

Nephropathy is a major complication of diabetes. Alterations of mesangial cells have traditionally been the focus of research in deciphering molecular mechanisms of diabetic nephropathy. Injury of podocytes, if recognized at all, has been considered a late consequence caused by increasing proteinuria rather than an event inciting diabetic nephropathy. However, recent biopsy studies in humans have provided evidence that podocytes are functionally and structurally injured very early in the natural history of diabetic nephropathy. The diabetic milieu, represented by hyperglycemia, nonenzymatically glycated proteins, and mechanical stress associated with hypertension, causes downregulation of nephrin, an important protein of the slit diaphragm with antiapoptotic signaling properties. The loss of nephrin leads to foot process effacement of podocytes and increased proteinuria. A key mediator of nephrin suppression is angiotensin II (ANG II), which can activate other cytokine pathways such as transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) systems. TGF-beta1 causes an increase in mesangial matrix deposition and glomerular basement membrane (GBM) thickening and may promote podocyte apoptosis or detachment. As a result, the denuded GBM adheres to Bowman's capsule, initiating the development of glomerulosclerosis. VEGF is both produced by and acts upon the podocyte in an autocrine manner to modulate podocyte function, including the synthesis of GBM components. Through its effects on podocyte biology, glomerular hemodynamics, and capillary endothelial permeability, VEGF likely plays an important role in diabetic albuminuria. The mainstays of therapy, glycemic control and inhibition of ANG II, are key measures to prevent early podocyte injury and the subsequent development of diabetic nephropathy.     

Methods of constraint-induced movement therapy for children with hemiplegic cerebral palsy: development of a child-friendly intervention for improving upper-extremity function

We delineate the methodology for constraint-induced movement therapy (CIMT) modified for children with hemiplegic cerebral palsy (CP) and describe important considerations that need to be made when testing this intervention in children. The resulting intervention evolved from piloting and testing it with 38 children with hemiplegic CP who were between the ages of 4 and 14 years. Thirty-seven successfully completed the treatment protocol. The intervention retains the 2 major elements of the adult CIMT (repetitive practice, shaping) and was constructed to be as child-friendly as possible. It involves restraining the noninvolved extremity with a sling and having the child engage in unimanual activities with the involved extremity 6 hours a day for 10 days (60 h). Specific activities are selected by considering joint movements with pronounced deficits and improvement of which interventionists believe have greatest potential. The activities are chosen to elicit repetitive practice and shaping. The intervention is conducted in groups of 2 to 3 children to provide social interaction, modeling, and encouragement. Each child is assigned to an interventionist to maintain at least a 1:1 ratio. CIMT can be modified to be child-friendly while maintaining all practice elements of the adult CIMT. The modified therapy is tolerated by most children. Further modifications will likely be required to hone in on the specific components of the intervention that are most effective before applying them to children who are most likely to benefit.     

Ein Einmaloxygenator zur Selbstanfertigung für Kleintiere

Zusammenfassung Es wird die Arbeitsanweisung zur Anfertigung eines Schaumoxygenators für Zeitvolumina bis 400 ml/min gegeben. Die Sauerstoffsättigung des oxygenierten Blutes beträgt im Mittel 98%. Die Hämolyserate ist gering. Materialkosten und Zeitaufwand für die Anfertigung sind sehr niedrig.Die Untersuchungen wurden durch eine Sachbeihilfe der Deutschen Forschungsgemeinschaft in dankenswerter Weise unterstützt.     

Rosette inhibition test: A multicentre investigation of early pregnancy factor in humans

The rosette inhibition test for the detection of early pregnancy factor is described in detail. The extended methodology presented here represents the cumulative experience of three independent laboratories. Special reference is made to the effect on the assay of varying the conditions of rosette formation between lymphocytes and sheep red blood cells. Antilymphocyte sera prepared for use in the rosette inhibition test fell into three catagories: (i) with no rosette inhibiting activity, (ii) with rosette inhibiting activity which is not affected by the presence of EPF, and (iii) rosette inhibiting activity which is significantly increased in the presence of EPF. To date, this third reaction has been found to be a specific indication of the presence in serum of early pregnancy factor.     

The B-L (Ia-like) antigens of the chicken. Lymphocyte plasma membrane distribution and tissue localization

Specific antisera reacting with B-L (Ia-like) antigens were prepared by reciprocal immunization of animals from the congeneic lines CB and CC. The resulting antisera were tested either in direct or indirect immunofluorescence tests and stained 10-16% of peripheral blood cells (PBL). Of the B-L+ cells, 90% were B cells and 8% were T cells. After in vitro stimulation of PBL with ConA, 58% were B-L+ and 91% of these were T cells. B and T cells were defined by means of rabbit antisera raised against bursa and thymus cells made specific by absorption with the relevant tissues. Antigens determined by anti-B-L antisera, rabbit anti-bursa (ABS) and rabbit anti-thymus (ATS) sera showed an independent distribution on the membrane of PBL. The tissue distribution of B-L+ cells, defined by means of allo-antisera and monoclonal antibodies, was studied by direct and indirect immunofluorescence on sections of skin, liver, kidney and brain. In all organs, in addition to B cells and a small number of, presumably activated, T cells, macrophages and dendritic cells were positive. Notably, glia cells in the brain were also shown to express B-L antigen.