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Primary cultures of rat mesangial cells were exposed to glomerulopathic light chain produced alterations in Ca2+ homeostasis to determine the effects of immunoglobulins on the mechanisms cellular homeostasis. Pretreatment of primary cultures of rat mesangial cells with glumerulopathic light chain reduced calcium transients in response to surface receptor agonists. Furthermore, the effects of monoclonal light chains on intracellular calcium homeostasis involved the inhibition of calcium influx and calcium release from intracellular stores.

Hypertension is a well-recognized complication of obesity. However, the mechanisms for the development of obesity hypertension are not known. One mechanism proposed is that the hyperinsulinemia present in obese hypertensive patients causes hypertension via sodium retaining and/or sympathetic nervous system stimulatory effects. However, numerous studies in dogs have revealed no evidence for such chronic pressor actions of hyperinsulinemia. This is in close agreement with studies in human insulinoma patients that show marked hyperinsulinemia and normal blood pressure. The appropriateness of the dog as an experimental model is strengthened by reports from our laboratory and others that inducing obesity in dogs reproduces many of the characteristics of obesity in humans, including insulin resistance, hyperinsulinemia, sodium retention, hypertriglyceridemia and hypertension. Recent studies in obese dogs have indicated that significant increases in renal medullary cellularity and intercellular matrix deposition could contribute to the sodium retention and hypertension. Additional evidence suggests that sympathetic nervous system stimulation also may contribute to the elevated blood pressure. However, the mechanisms through which obesity induces these changes and the temporal relationship between these factors and the development of the hypertension remain to be determined. INDEXING KEY WORDS: obesity; hypertension; sympathetic nervous system; insulin; kidney

Supplementation of diet with vitamin A may decrease the number of deaths among children with measles, whether hospitalized or still in the community. Vitamin A deficiency is common among children in many developing countries. A survey of the medical literature found that supplementation with vitamin A decreased the number of deaths among children hospitalized with measles. Supplementation with vitamin A had a protective effect against death from a respiratory infections among these children. The protective effect of vitamin A was greater in children under two years old than in older children, and in higher-risk areas. Supplementation with vitamin A also decreased the number of deaths among children in the community. The protective effect of Vitamin A was slightly higher in younger children than in older children in the community. Vitamin A should be given to all children suffering from measles regardless of whether they have a vitamin A deficiency.

Germline mutations in the tumor-suppressor gene p53 may be common among sarcoma patients who have a personal or family history of cancer, but not among those who do not. Of 196 sarcoma patients whose DNA was analyzed, eight germline mutations in the p53 gene were found. Five mutations were found in patients who had had multiple types of cancer or with a known family history of cancer. Three mutations were found in patients with no personal or known family history of cancer. Two of these mutations were considered to be new with the patient. Four mutations changed the amino acid composition of the protein for which the gene encodes, and four resulted in an abrupt termination of protein synthesis. None of these mutations were found among 200 healthy individuals. Individuals who have inherited mutations in tumor-suppressor genes may be more likely to develop cancer than other individuals. Identification of these mutations allows for genetic counseling of individuals who have inherited them.

Context.--Lesions associated with monoclonal light and heavy chains display a variety of glomerular, tubular interstitial, and vascular manifestations. While some of the entities are well recognized, including light and heavy chain deposition diseases, AL (light chain) and AH (heavy chain) amyloidosis, and light chain ('myeloma') cast nephropathy, other lesions centered on proximal tubules are much less accurately identified, properly diagnosed, and adequately understood in terms of pathogenesis and molecular mechanisms involved. These proximal tubule-centered lesions are typically associated with monoclonal light chains and have not been reported in patients with circulating monoclonal heavy chains. Objective.--To determine the incidence of proximal tubulopathies in a series of patients with monoclonal light chain-related renal lesions and characterize them with an emphasis on clinical correlations and elucidation of molecular mechanisms involved in their pathogenesis. Design.--A study of 5410 renal biopsies with careful evaluation of light microscopic, immunofluorescence, and electron microscopic findings was conducted to identify these monoclonal light/heavy chain-related lesions. In selected cases, ultrastructural immunolabeling was performed to better illustrate and understand molecular mechanisms involved or to resolve specific diagnostic difficulties. Results.--In all, 2.5% of the biopsies were diagnosed as demonstrating renal pathology associated with monoclonal light or heavy chains. Of these, approximately 46% were classified as proximal tubule-centered lesions, also referred to as monoclonal light chain-associated proximal tubulopathies. These proximal tubulopathies were divided into 4 groups defined by characteristic immunomorphologic manifestations associated with specific clinical settings. Conclusions.--These are important lesions whose recognition in the different clinical settings is extremely important for patients' clinical management, therapeutic purposes, and prognosis. These entities have been segregated into 4 distinct variants, conceptualized morphologically and clinically. Specific mechanisms involved in their pathogenesis are proposed. (Arch Pathol Lab Med. 2014; 138:1365-1380; doi: 10.5858/arpa.2013-0493-OA), Our understanding of renal lesions occurring in patients with plasma cell dyscrasias has advanced considerably in the last 2 decades. These lesions are classified into specific entities (1-6) that have [...]