Identification of an early endosomal protein regulated by phosphatidylinositol 3-kinase

Phosphatidylinositol 3-kinases (PI 3-kinases) have been implicated in membrane trafficking in the secretory and endocytic pathways of yeast and mammalian cells, but the molecular mechanisms by which these lipid kinases operate are not known. Here we identify a protein of 170 kDa that is rapidly released from cell membranes in response to wortmannin, a potent inhibitor of mammalian PI 3-kinases. The amino acid sequence of peptides from p170 reveal its identity to early endosomal antigen (EEA) 1, an endosomal antigen with homology to several yeast proteins genetically implicated in membrane trafficking. Immunofluorescence analysis of 3T3-L1 adipocytes with antisera against p170/EEA1 reveal a punctate peripheral pattern that becomes diffuse in response to wortmannin. In vitro, p170/EEA1 binds specifically to liposomes containing PIns(3)P, suggesting that the effect of wortmannin on cells is due to inhibition of PIns(3)P production. Thus, p170/EEA1 may define a family of proteins that mediate the regulatory effects of 3′-phosphoinositides on membrane trafficking in yeast and mammalian cells.     

Carcinoid associated encephalitis successfully treated with tryptophan.

This case report describes the rare phenomenon of encephalopathy associated with massive carcinoid tumor. Extensive investigation failed to reveal an obvious cause but a presumptive diagnosis of tryptophan deficiency was made and she was commenced on tryptophan dietary supplements. A rapid and complete response resulted. This case report discusses this unusual case and reviews the literature regarding carcinoid associated encephalopathy.     

Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings

The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain.     

Über die Störungen des Kohlenhydratstoffwechsels bei der experimentellen Diphtherievergiftung

Ohne ZusammenfassungMit 1 Kurve.     

Laparoscopic Versus Open Renal Procurement for Pediatric Recipients of Living Donor Renal Transplantation

Despite reports demonstrating the safety of laparoscopic donor nephrectomy (LDN) for pediatric recipients of renal transplants, recent evidence has challenged using LDN for recipients 5 years of age or younger. We retrospectively reviewed the records of all pediatric recipients of living donor renal transplants from September 2000 through August 2004. We compared those who received allografts recovered by LDN (n = 34) with those recovered by open donor nephrectomy (ODN, n = 26). Outcomes of interest included operative complications, postoperative renal function, the incidence of delayed graft function or episodes of acute rejection and long-term graft function. Donor and recipient demographic data were similar for the LDN and ODN groups. Serum creatinine and calculated creatinine clearance were not significantly different between groups both in the early postoperative period and at long-term follow-up (p > 0.142). Rates of delayed graft function and acute rejection did not differ between groups. Among recipients aged 5 years old or younger stratified by donor technique (9 LDN, 5 ODN recipients), no difference was noted in graft outcomes both early and long-term (p > 0.079). At our center, pediatric LDN recipients have graft outcomes comparable to those of ODN recipients. At experienced centers, we recommend continued use of LDN for pediatric recipients of all ages.     

Diabetes mellitus-associated diffuse autonomic dysfunction causing debilitating hypotension manifested after rapid weight loss in a morbidly obese patient: case report and review of the literature.

The association between weight and blood pressure is well established, especially the paradigm of obesity-related hypertension. The relationship between diffuse autonomic dysfunction and orthostatic hypotension in patients with long-term diabetes mellitus is also well known. We report on a 57-year-old morbidly obese male with a long medical history of hypertension, myocardial infarction, type 2 diabetes mellitus, and hypothyroidism. After a loss of 147 pounds (representing a percent excess weight loss of 76%) within 6 months after gastric bypass surgery, the patient developed worsening orthostatic hypotension and near-syncopal episodes requiring medication. The subsequent diagnosis and treatment, as well as a literature review, are presented.