Biomedical subjects
Publications and source records attributed to J Wagner.
Emphysematous cystitis is a rare complication of lower urinary tract infection, occurring almost exclusively in diabetic women. The prognosis, usually good, depends on early diagnosis and prompt treatment which consists of urinary drainage, antibiotic therapy and strict blood glucose control. The authors report a case of emphysematous cystitis diagnosed on laparotomy for acute abdomen. Death occurred despite treatment.
Protein meals and infusion of amino acids cause an increase of glomerular filtration rate in humans and animals with normal renal function despite the circulating renin concentration remaining unchanged. The renal hemodynamic response is not altered by angiotensin converting enzyme inhibitors, but it is obliterated by cyclooxygenase inhibitors. By contrast, chronic exposure to high protein diets raises circulating renin and increases messenger RNA of renin (but not of angiotensinogen) in kidney tissue. Chronically high protein intake raises the glomerular filtration rate and reduces glomerular permselectivity; the reverse is seen with low protein intake. In patients with renal failure, acute amino acid infusion or protein meals cause a paradoxical drop in glomerular filtration rate which is not influenced by converting enzyme inhibitors.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Cocaethylene is a pharmacologically active cocaine metabolite that is formed in the presence of ethanol by the activity of liver enzymes. The pharmacology of cocaethylene has not been extensively investigated and its acute toxicity is unknown. The acute toxicity of cocaethylene was compared to cocaine in Swiss-Webster mice. The LD50 of cocaethylene was 60.7 mg/kg and 63.8 mg/kg in female and male mice, respectively. In comparison, the LD50 of cocaine was 93.0 mg/kg in both female and male mice. These studies demonstrate that the cocaine-alcohol metabolite, cocathylene, is more potent in mediating lethality than the parent drug.
Cytogenetic evaluation of patients after bone marrow transplantation (BMT) has provided a standard method of documentation of hematopoietic engraftment. More recently, recombinant DNA technology has also been applied to determine engraftment status. In order to establish the relative utility of these methods in clinical practice we have directly compared the data from cytogenetic and recombinant DNA methods, evaluating engraftment status in 68 BMT recipients. Patients were evaluated pre-transplant, 30, 60, 90, and 180 days after BMT, and yearly thereafter for 1) the presence or absence of the Y chromosome in sex-mismatched allogeneic transplant recipients, 2) the presence or absence of the Philadelphia chromosome [t(9;22)] in patients transplanted for chronic myelogenous leukemia (CML), 3) restriction fragment length polymorphism (RFLP) profiles, and/or 4) clonal rearrangement of the bcr gene. Cytogenetic examination of unstimulated bone marrow and recombinant DNA tests of nucleated peripheral blood or bone marrow cells produce qualitatively similar data in the identification of patient and donor cells and/or normal and tumor cells. Differences in the results obtained by the two analytic methods were most often due to the restricted cell populations evaluable by cytogenetic studies of PHA-stimulated peripheral blood specimens. DNA analyses could frequently be applied at earlier intervals after transplantation and, in cases of graft rejection, when cell counts were low. Although recombinant DNA methods required fewer cells and demonstrated greater sensitivity in detection of minor cell populations in the majority of instances, the cytogenetic evaluation may complement the DNA studies and allow detection of additional chromosomal anomalies.
The alpha-tocopherol analogue 3,4-dihydro-6-hydroxy-N,N,N,2,5,7,8- heptamethyl-2H-1-benzopyran-2-ethanaminium 4-methylbenzenesulfonate (1a, MDL 73404) and its O-acetate 1b (MDL 74270) were synthesized. Compound 1a was found to be hydrophilic (log P = -0.60) and to prevent lipid autoxidation in rat brain homogenate with an IC50 of 1.7 +/- 0.9 microM. Tissue distribution studies with [14C]-1b in rats (1 mg/kg iv) showed that radioactivity accumulates in the heart (ratio 20:1 vs blood after 1 h). Infusion of 1 mg/kg per h of 1b bromide reduced infarct size by 54% in rats subjected to coronary artery occlusion for 60 min followed by reperfusion for 30 min, compared to saline-infused controls. By comparison, the tertiary amine analogue 5 was found not to accumulate in heart tissue, to be an equally effective free-radical scavenger in vitro, but to require a higher dose to reduce infarct size in rats. This shows that the cardioselectivity of compound 1 contributes to its potency in salvaging myocardial tissue in rats after ischemia and reperfusion.
The different parts of the lumbar pedicle were identified on an anteroposterior (AP) radiograph to determine reliable reference points to be used to quantify vertebral rotation. Standard AP radiographs were taken of dry lumbar vertebrae with 5 degrees increments in rotation in the transverse plane, ranging from 0 degrees to 30 degrees both to left and right. Identical sets of radiographs were taken with radiopaque markers around the middle and in the anterior and posterior parts of the pedicles. The anatomic center of the pedicle was found to lie slightly more lateral than the center of the pedicle halo. The inferior edge of the pedicle corresponded with the anterior part of the pedicle and the superior edge, with the posterior part.
The acute cardiovascular effects of pregnanolone emulsion, a new steroid preparation for intravenous anaesthesia, were investigated in artificially ventilated dogs. The anaesthetic was administered as repeated intravenous bolus injections, doubling the dosage with each injection. The plasma concentration of pregnanolone, and the haemodynamic, respiratory and metabolic variables were determined after each injection. Cardiac output and heart rate increased from the first bolus dose of the anaesthetic (0.5 mg/kg), which produced anaesthesia lasting 10 to 15 min. Both continued to increase after administration of 1.0, 2.0 and 4 mg/kg, whereas reductions of systemic arterial pressure and estimated myocardial contractility were observed only at the two highest dosages. A decrease in vascular resistance was calculated in the systemic circulation, whereas vascular resistance increased in the pulmonary circulation. A state of circulatory shock followed administration 8, 16 and 32 mg/kg of the anaesthetic.
We investigated the recognition of the conserved 5-bp repeated motif NGAAN, which occurs in heat shock gene promoters of Drosophila melanogaster and other eukaryotic organisms, by human heat shock transcription factor (HSF). Extended heat shock element mutants of the human HSP70 gene promoter, containing additional NGAAN blocks flanking the original element, showed significantly higher affinity than the wild-type promoter element for human HSF in vitro. Protein-DNA contact positions were identified by hydroxyl radical protection, diethyl pyrocarbonate interference, and DNase I footprinting. New contacts in the mutant HSE constructs corresponded to the locations of additional NGAAN motifs. The pattern of binding indicated the occurrence of multiple DNA binding modes for HSF with the various constructs and was consistent with an oligomeric, possibly trimeric, structure of the protein. In contrast to the improved binding, the extended heat shock element mutant constructs did not exhibit dramatically increased heat-inducible transcription in transient expression assays with HeLa cells.
Homeless mothers and their children have become a highly politicized issue. This article presented a study comparing the stressors and coping behaviors of homeless women with their domiciled counterparts, low-income and poor mothers. The results of the study indicated that although homeless, poor, and low-income mothers cope in a similar manner, homeless mothers were considerably more disadvantaged in terms of education, family size, and work history, and were besieged by many more stressors. These results suggest that CHNs must design interventions that are not only interdisciplinary in nature and use the expertise of many professional groups but also influence the communities' political and decision-making bodies.
1. The disposition of [14C]-labelled benazepril HCl, an ACE-inhibitor, was studied in four normal adult volunteers after a single oral dose of 20 mg and after repeated doses of 20 mg once daily for 5 days. Radioactivity was measured in plasma, urine and faeces. The prodrug ester benazepril and the pharmacologically active metabolite benazeprilat were determined quantitatively in plasma and urine by a g.c.-m.s. method. The pattern of metabolites in urine was analysed semiquantitatively by h.p.l.c.-radiometry. 2. After a single oral dose at least 37% was absorbed, as indicated by urinary recovery. The peak plasma concentration of benazepril (0.58 +/- 0.13 nmol/g (SD] was observed at 0.5h after dose, indicating rapid absorption. Peak concentrations of radioactivity (1.88 +/- 0.48 nmol/g) and of active benazeprilat (0.84 +/- 0.25 nmol/g) were observed at 1 h after dose, demonstrating rapid bioactivation. 3. The area under the plasma curve (AUC0-96 h) of total radioactivity amounted to 9.7 +/- 1.1 (nmol/g)h, 5% of which was accounted for by benazepril and about 50% by benazeprilat. 4. Over 9 days 96.8 +/- 0.5% of the dose was excreted in urine and faeces. Urinary excretion accounted for 37.0 +/- 6.0% of the dose, 80% of which was recovered in the first 8 h after dosing. 5. In urine, only 0.4% of the dose (1% of the radioactivity) was excreted as unchanged benazepril, indicating that the compound was extensively metabolized. Benazeprilat accounted for 17% of the dose (about half of the radioactivity; 0-96 h). Glucuronide conjugates of benazepril and benazeprilat constituting approximately 11% and 22% of the radioactivity (about 4% and 8% of the dose; 0-48 h) were tentatively identified. 6. Repeated oral treatment with benazepril HCl did not influence the pharmacologically relevant kinetics and disposition parameters.
Thiol titrations of bovine brain calcineurin, phosphatase with Ellman's reagent revealed the presence of 5 exposed sulfhydryl groups on the native protein, and 10 sulfhydryl groups on the denatured protein. Attempts were made to identify the location of the free thiols within the catalytic and regulatory domains of the enzyme. Our data indicates that free sulfhydryl groups are absent from the vicinity of the Mg2+ and calmodulin binding sites as well as from the active site of the enzyme. However, the fact that the number of free thiols decreased in the presence of Ca2+ and Mn2+, to 4 and 2 respectively, possibly indicates that either free thiols are at or near these domains or become inaccessible as a consequence of conformational changes induced by the metal ions. The Ca2+ and Ca2+/Mg2+ stimulated activities of calcineurin were monitored during modification with Ellman's reagent, iodoacetate and iodoacetamide. Upon modification of 1-2 of the free thiols the activity of the enzyme increased 1.3 to 10.5-fold depending on the thiol reagent and the stimulatory metal ions employed. Modification of the remainder of the free thiols resulted in a decrease in activity. These results suggest that 1-2 thiols are essential for the full expression of calcineurin activity.