A retrospective analysis of the efficacy and safety of metformin in the African-American patient.

A retrospective analysis was conducted to determine the effects of metformin on glycosylated hemoglobin (HbA1c), body weight, and adverse events in an African-American population. Thirty-six patients who were receiving combination therapy with metformin and either a sulfonylurea or insulin were identified from a hospital pharmacy database. Nineteen patients met the criteria for efficacy analysis. The combination of metformin with either a sulfonylurea or insulin resulted in a decrease of the average HbA1c from a baseline of 10.07% to 7.92% (delta = 2.15%). The effect of combination therapy on weight was variable; however, twice as many patients lost weight compared with those who gained weight. Metformin appeared to be well-tolerated, with gastrointestinal symptoms being the most commonly reported adverse events.     

Association of a 70-kDa tyrosine phosphoprotein with the CD16:ζ:γ complex expressed in human natural killer cells

The CD16: ζ: γ receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fcγ domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of ζ and γ are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the ζ subunit and the phospholipase C γ-1 and γ-2 isoforms. Here we show that CD 16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16:ζ:γ receptor complex, results in the tyrosine phosphorylation of a 70 kDa ζ-associated protein (pp70). Similarly, a 70-kDa ζ-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa ζ-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16:ζ:γ complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation.     

A genetic and environmental time series analysis of blood pressure in male twins

Systolic and diastolic blood pressures were measured on 254 monozygotic (MZ) and 260 dizygotic (DZ) male twin pairs, during middle age (average age 48 years) and at two later age points. Genetic and environmental components of covariation were modeled by time series. For both measures, shared environmental influences were absent and specific environmental influences were largely time-specific. Although heritability was about 0.5 at each time point, genetic variation present at middle age contributed only about 60% to that present 9 years later, the remaining 40% being new. Fifteen years later, at the third time point, no new genetic variation was evident, variation in individual differences being entirely attributable to genetic differences laid down at the two earlier ages. © 1993 Wiley-Liss, Inc.     

Osteoinductive ability of confluent Saos-2 cells correlates with enhanced expression of bone morphogenetic proteins

Implants of defatted, freeze-dried Saos-2 human osteosarcoma cells grown to confluency induce de novo bone formation in athymic mice. These cells are also richly endowed with bone morphogenetic proteins and express mRNA for bone morphogenetic proteins 1, 2, 3, 4, and 6, as well as for transforming growth factor-β1. Our aim was to study whether the ability to induce bone formation is related to the level of expression of bone morphogenetic protein. We studied the osteoinductive abilities and levels of expression of bone morphogenetic protein of Saos-2 cells both during the growth phase and after confluency was reached. Subconfluent cells were at least 70% less effective in their osteoinductive ability than confluent cells. Comparison of bone morphogenetic protein mRNA expression in confluent and subconfluent cells revealed that the latter had lower expression of all the mRNAs studied. The expression of bone morphogenetic protein-1, bone morphogenetic protein-2, and bone morphogenetic protein-6 mRNAs was 2, 3, and 6 to 10-fold lower, respectively, in subconfluent cells. These results suggest that the ability of Saos-2 cells to induce de novo bone formation may be correlated with the relative expression of these proteins; the expression of bone morpho-genetic proteins in Saos-2 cells also may be dependent on the cell cycle.     

Bovine colostrum immunoglobulin concentrate for cryptosporidiosis in AIDS.

Lactobin-R is a commercial hyperimmune bovine colostrum with potent anticryptosporidial activity. It was administered to a 4 year old child with AIDS and severe diarrhoea associated with cryptosporidiosis. There was significant clinical improvement in the diarrhoea and permanent elimination of the parasite from the gut as assessed through serial jejunal biopsy and stool specimens.     

Extracorporeal membrane oxygenation for pediatric cardiopulmonary failure

Extracorporeal membrane oxygenation is now standard treatment of severe respiratory failure in newborn infants in our center (200 cases) and worldwide (over 2500 cases), but there are few reports of such trials in older children. We reviewed our experience with extracorporeal membrane oxygenation in 33 children aged 1 week to 18 years between 1971 and 1989. The modality was used when all other treatment failed. Extracorporeal membrane oxygenation provided excellent cardiopulmonary support for 1 to 25 days (average 7 1/2 days). The survival rate was 25% for cardiac support patients and 47% for respiratory failure patients (36% overall survival). Mechanical complications included membrane lung failure, tubing rupture, and pump failure, all managed without mortality. Physiologic complications included bleeding, pneumothorax, cardiac arrest, renal failure, hepatic failure, and brain injury. The major cause of death was irreversible injury to lung, heart, or brain. Extracorporeal life support is a reasonable approach for children with serious but reversible cardiopulmonary failure.     

Comparison of the use of bulk to micro culture of cell preparations for lymphokine-activated cytotoxicity assays.

Different assay systems have been used to quantitate lymphokine-induced natural cytotoxic activity as a measure of immune status. This study compares the effects of inducing cytotoxicity in a bulk culture system, where effector cells are transferred to a micro culture well for assay, to a micro culture system where the effector cells are not transferred. The effector/target ratio for both the bulk and micro culture systems was calculated using the number of viable effector cells present at the time of target cell addition. After overnight incubation with interleukin-2 (IL-2), the lytic activity of murine spleen cells to targets using a micro culture system was increased two-fold over the bulk culture method. This increase was amplified further after 5 days of activation with IL-2, in that the micro culture system resulted in a four-fold increase in cytotoxic activity. The loss of some adherent cells in the bulk culture system did not explain the overall decrease in recovered cytotoxicity. The difference appeared to be related to cell loss during centrifugation. Therefore, the E/T ratios are different in the two systems if not corrected for the number of viable cells.     

Immunopathology of glomerulonephritis associated with chronic woodchuck hepatitis virus infection in woodchucks (Marmota monax).

Retrospective analysis of necropsy findings of 705 woodchucks was performed to determine the prevalence and morphology of immune-mediated glomerulonephritis, its relationship to woodchuck hepatitis virus (WHV) infection, and the presence of major WHV antigens. Twenty-six woodchucks had glomerular lesions. Renal tissue of the 26 animals was evaluated histologically and immunohistochemically for immune-mediated glomerulonephritis. Of these 26 animals, immune-mediated glomerulonephritis was diagnosed in six, all of which were chronic WHV carriers. Membranous glomerulonephritis was identified in three animals, two of which also had mesangial proliferation. Host immunoglobulin was present within the mesangium and along capillary loops in all three. Woodchuck hepatitis virus core antigen (WHcAg) was present along capillary loops of two of these animals, one membranous and one mixed, and in the mesangium of all three. Woodchuck hepatitis virus surface antigen (WHsAg) deposition was similar to WHcAg deposition but was only present along capillaries in those animals with mixed nephritis. The remaining three animals had mesangial proliferation. WHsAg and host immunoglobulin deposition were predominately mesangial; WHcAg was not detected. Transmission electron microscopy showed thickening of the capillary loop basement membranes and subepithelial electron-dense deposits in animal one, and deposits in the mesangium in animal six.