Polymyositis: a cause of acute renal failure.
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Acute Kidney Injury↗
Biomedical subjects
S Carr
Publications and source records attributed to S Carr.
Bryostatin 1 activates splenic lymphocytes and induces sustained depletion of splenocyte protein kinase C activity in vivo after a single intravenous administration.
Bryostatin 1 activates and subsequently down-regulates protein kinase C (PKC) in vitro and has potential use as an immunomodulator and as an anti-cancer agent. Despite extensive examination of its activities in vitro and anti-tumor effects in vivo, previous studies have failed to document that bryostatin 1 modulates total cellular PKC activity in tumor or normal tissues when administered in vivo. After a single bolus injection of bryostatin 1 (1.0 microgram) in normal C57BI/6 mice, blood was drawn at various intervals and assayed for bryostatin 1 levels. In addition, spleens from bryostatin-treated mice were harvested 10 min to 10 days after treatment, weighed and analyzed for cell numbers, PKC activity and cell surface phenotypes. Bryostatin 1 levels in plasma rose rapidly, reaching peak levels of 56.5 nM less than 1 min after injection, and then declined to undetectable levels by 1 h. A similar pattern was observed when bryostatin 1 was incubated with leukemia cells in vitro, raising the possibility that the rapid fall in plasma levels results from intracellular uptake and binding. Bryostatin 1 induced marked depletion of total splenocyte PKC activity (as much as 69% relative to control values) at 24-96 h after drug administration, but not at earlier times (i.e. 1 h). A single injection of bryostatin 1 also induced expression of the T cell activation marker CD69, leading to positivity in 53% of cells at 3-24 h versus 11% in control mice, and resulted in marked splenomegaly, associated with increased numbers of nucleated cells at 48-96 h. Together, these studies demonstrate that despite rapid disappearance of the drug from plasma, a single i.v. dose of bryostatin 1 exhibits significant and sustained effects on normal murine spleen cells, including early lymphocyte activation, prolonged depletion of PKC activity, splenocyte proliferation and splenomegaly. These findings may have implications for attempts to understand the in vivo effects of bryostatin 1 in normal host tissues.
Animals↗
Activation of phospholipase A2 by the human endothelin receptor in Chinese hamster ovary cells involves Gi protein-mediated calcium influx.
The signalling pathways used by the human endothelin A receptor to activate phospholipase A2 in Chinese hamster ovary cells were investigated. Pertussis toxin caused a partial but significant reduction in endothelin-1-induced arachidonic acid release although cAMP-dependent kinase inhibitors did not mimic its action. Extracellular calcium and its entry into the cell was essential for activation of phospholipase A2 as its removal from media or incubation with an intracellular calcium chelator-reduced activation. Nifedipine had no effect on endothelin-1-induced arachidonic acid release while divalent cations caused a significant reduction indicating the possible role of CRAC. Thapsigargin caused an increase in arachidonic acid release which was completely inhibited by pertussis toxin treatment. This further supports the involvement of CRAC in calcium influx and activation of phospholipase A2 by the human endothelin A receptor.
Animals↗
Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins.
Human interleukin 5 (hIL5) and soluble forms of its receptor alpha subunit were expressed in Drosophila cells and purified to homogeneity, allowing a detailed structural and functional analysis. B cell proliferation confirmed that the hIL5 was biologically active. Deglycosylated hIL5 remained active, while similarly deglycosylated receptor alpha subunit lost activity. The crystal structure of the deglycosylated hIL5 was determined to 2.6-A resolution and found to be similar to that of the protein produced in Escherichia coli. Human IL5 was shown by analytical ultracentrifugation to form a 1:1 complex with the soluble domain of the hIL5 receptor alpha subunit (shIL5R alpha). Additionally, the relative abundance of ligand and receptor in the hIL5.shIL5R alpha complex was determined to be 1:1 by both titration calorimetry and SDS-polyacrylamide gel electrophoresis analysis of dissolved cocrystals of the complex. Titration microcalorimetry yielded equilibrium dissociation constants of 3.1 and 2.0 nM, respectively, for the binding of hIL5 to shIL5R alpha and to a chimeric form of the receptor containing shIL5R alpha fused to the immunoglobulin Fc domain (shIL5R alpha-Fc). Analysis of the binding thermodynamics of IL5 and its soluble receptor indicates that conformational changes are coupled to the binding reaction. Kinetic analysis using surface plasmon resonance yielded data consistent with the Kd values from calorimetry and also with the possibility of conformational isomerization in the interaction of hIL5 with the receptor alpha subunit. Using a radioligand binding assay, the affinity of hIL5 with full-length hIL5R alpha in Drosophila membranes was found to be 6 nM, in accord with the affinities measured for the soluble receptor forms. Hence, most of the binding energy of the alpha receptor is supplied by the soluble domain. Taken with other aspects of hIL5 structure and biological activity, the data obtained allow a prediction for how 1:1 stoichiometry and conformational change can lead to the formation of hIL5.receptor alpha beta complex and signal transduction.
Amino Acid Sequence↗
Intrauterine therapy for homozygous alpha-thalassemia.
BACKGROUND: Alpha-thalassemia is one of the most common genetic disorders in the world and is becoming more common in the United States with the increase in immigration of susceptible populations. This disease has been stated previously to be incompatible with extrauterine life. CASE: A Filipino woman with a prior loss due to hemoglobin Bart's underwent prenatal diagnosis that confirmed recurrence in the index pregnancy. Intravascular intrauterine exchange transfusions maintained appropriate fetal growth. A cesarean delivery yielded a 2190-g male infant with minor malformations. The postnatal course was characterized by mild respiratory insufficiency. Postnatal chronic transfusion therapy is underway pending consideration for bone marrow transplantation. CONCLUSION: Antenatal diagnosis and therapy of homozygous alpha-thalassemia can prevent the prenatal consequences of hydrops and fetal death. New technologies such as stem cell transplantation may help to avert both prenatal and postnatal consequences.
Abnormalities, Multiple↗
A comparison of chamba (marijuana) abusers and general psychiatric admissions in Malawi.
The study aimed to provide the first general description of chamba-related admissions to Zomba Mental Hospital, the major psychiatric facility in Malawi, and to analyse the distinctiveness of this patient group from other admissions. A questionnaire was verbally administered to 50 chamba abusers and 50 other patients matched by gender, age, and admission date. The typical chamba abusing patient is: 27, male, a subsistence farmer, takes the drug because it is the cheapest form of intoxication, reports 'seeing things clearly' (immediate effect), and general apathy (long-term); and compared to other patients is more likely to originate from a chamba-growing area, less likely to have been raised by his natural parents, and has had more schooling.
Adolescent↗
TMD support for doctors and patients.
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Consumer Organizations↗
The impact of caring upon the health of older women.
Much community care relies upon the provision of unpaid care by family members. The short- and longer-term effects of providing care upon older women were researched in an interview survey of 286 women aged over 50 in urban and rural areas of Queensland. The findings were validated by reports from the women's general practitioners. The results suggest that providing care has both short- and long-term negative effects upon the physical health and emotional wellbeing of older women. The major predictor of a range of self-reported health problems was the level of self-reported stress. Implications are drawn for both community care policy, which needs to focus upon the impact on the carer of continuing to provide care at home, and for health research relating to older women, which has ignored the demands of caring among older people.
Activities of Daily Living↗
Fetal tissue.
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Fetal Tissue Transplantation↗
Association of anticholinergic activity of prescribed medications with postoperative delirium.
In a prior study, delirium and plasma anticholinergic drug levels were significantly correlated in 9 of 25 surgical intensive care patients. The present study, using cumulative anticholinergic effects of parent compounds of these patients' medications, found that delirious patients' medication combinations had significantly higher cumulative anticholinergic effects than those of nondelirious patients.
Adult↗
Patient rules, OK?
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Organizational Culture↗
Factors affecting parents' perceptions of temperament in early infancy.
Parents' perceptions of temperament in their three-month-old infants were examined in relation to prenatally measured parental characteristics and to objective indices of infant behavior at three months. Infant behavior and parental characteristics appear to make independent contributions to parents' perceptions in early infancy.
Attitude↗
Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium.
Anticholinergic effects of the 25 drugs most commonly prescribed for the elderly were measured by radioreceptor assay. Fourteen had detectable anticholinergic drug levels; 10 of these had levels that have been associated with impairments in memory and attention in normal elderly subjects. These data indicate that patients taking multiple medications may be at increased risk for side effects from psychotropic drugs, most of which have anticholinergic effects.
Age Factors↗
Long-term care administration and liability issues.
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Health Facility Administrators↗
Increase in glomerular filtration rate in patients with insulin-dependent diabetes and elevated erythrocyte sodium-lithium countertransport.
Increased sodium-lithium countertransport in erythrocytes is found in patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy. To determine whether such an increase precedes the onset of nephropathy and, if so, whether it is associated with changes in renal function, we measured erythrocyte sodium-lithium countertransport in 52 patients with IDDM but not nephropathy or hypertension and in 32 control subjects. Seventeen of the 52 patients with IDDM (33 percent) had sodium-lithium countertransport activity that exceeded the maximal activity in the control subjects (0.39 mmol of lithium per hour per liter of cells). Eighteen of the 52 patients with IDDM were studied in more detail. The 7 patients with raised sodium-lithium countertransport values had glomerular filtration rates (median, 159 ml per minute per 1.73 m2 of body-surface area; range, 134 to 197) that were significantly higher (P less than 0.01) than those in the remaining 11 patients with IDDM and normal sodium-lithium countertransport (median, 126 ml per minute per 1.73 m2; range, 110 to 176) or in the 10 control subjects (median, 128 ml per minute per 1.73 m2; range, 93 to 151). In the seven patients with elevated sodium-lithium countertransport, the filtration fraction (median, 0.27; range, 0.22 to 0.37) was also greater (P less than 0.01) than that in control subjects (median, 0.22; range, 0.18 to 0.28). There were no differences in renal function between the patients with IDDM and normal sodium-lithium countertransport and the control subjects. We conclude that sodium-lithium countertransport is increased in patients with IDDM before the onset of nephropathy and is associated with hyperfiltration. Thus, elevated sodium-lithium countertransport activity may be an early marker of diabetic nephropathy.
Adult↗
Disseminated zygomycosis and systemic lupus erythematosus.
A young woman with long-standing systemic lupus erythematosus and rheumatic fever presented with deteriorating renal function. She had severe gastritis treated with cimetidine and received methylprednisolone when her blood cultures were repeatedly negative. She developed spontaneous bruising and bleeding from venepuncture sites, leading to clotting studies and a diagnosis of thrombotic thrombocytopenic purpura. At post-mortem, extensive evidence of disseminated zygomycosis was found. The likely portal of entry was the gastric route.
Adult↗
Regulation of particulate guanylate cyclase by Escherichia coli heat-stable enterotoxin: receptor binding and enzyme kinetics.
1. Escherichia coli heat-stable enterotoxin (ST) induces a secretory diarrhea by binding to receptors on brush borders of intestinal villus cells, activating particulate guanylate cyclase and increasing intracellular concentrations of guanosine 3',5'-cyclic monophosphate (cyclic GMP). 2. However, little is known concerning coupling of receptor-ligand interaction to enzyme activation. 3. This study compares the kinetics of toxin-receptor binding and enzyme activation to better understand this transmembrane signal cascade. 4. Toxin receptor binding was linear and saturable with 50% of maximum displacement of [125I]ST by unlabeled toxin observed at 1.1 x 10(-7) M. ST increased the maximum velocity (Vmax) of guanylate cyclase with magnesium or manganese as the cation substrate without altering the affinity of the enzyme for its substrate or its positive cooperativity. 5. The concentration of toxin yielding half-maximum stimulation of guanylate cyclase was 1.2 x 10(-6) M, 10-fold higher than the affinity of the ligand for its receptor. 6. These data are consistent with the suggestion that ST-receptor interaction is coupled to activation of particulate guanylate cyclase. 7. However, the discrepancy between the affinity of ST for its receptor and its efficacy in activating the enzyme suggests that this coupling is complex. 8. Possible mechanisms underlying this coupling are discussed.
Animals↗
Congress challenges medical schools on progress in minority representation.
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Health Workforce↗