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Biomedical subjects

S M Smith

Publications and source records attributed to S M Smith.

At least 271 records · Page 15Linked to original sources
PubMed1990

Nephrotic syndrome and rapid renal failure in autosomal dominant polycystic kidney disease.

A 44-year-old man, with autosomal dominant polycystic kidney disease and hypertension under satisfactory control, developed nephrotic syndrome with negative serology. Open renal biopsy revealed focal glomerular sclerosis. Prior to the appearance of heavy proteinuria, serum creatinine was 1.7 mg/dl. After the nephrotic syndrome had been established, renal function deteriorated rapidly and hemodialysis was started within 2.6 years. In patients with autosomal dominant polycystic kidney disease, the appearance of nephrotic range proteinuria along with a rapid decline in renal function indicates the presence of a glomerular lesion, which needs to be investigated by renal biopsy.

Adult↗
PubMed1990

Bioavailability of clindamycin during peritoneal dialysis.

Clindamycin phosphate becomes biologically active only with cleavage of the phosphate ester bond. A rat model was used to examine the amount of biologically active clindamycin attainable in the dialysate and in the blood during peritoneal dialysis. Intravenous administration of 10 mg/kg clindamycin phosphate alone without peritoneal dialysis produced peak blood levels of 15-20 micrograms/ml. With peritoneal dialysis, blood levels of less than 5 micrograms/ml were achieved. When clindamycin phosphate was added to the dialysis fluid at an initial concentration of 10 mg/ml, less than 5 micrograms/ml of the active antibiotic can be detected in the dialysis return fluids. Even in rats with induced peritonitis, less than 15 micrograms/ml could be found in the dialysis returns. With or without peritonitis, less than 5 micrograms/ml of active clindamycin was attained in blood from peritoneal installation alone. The conversion of the ester to the active compound appears to be the major problem. It is recommended that in those clinical situations in which the patient requires peritoneal dialysis, an alternate antimicrobial agent be used in place of clindamycin to avoid infections in the abdominal cavity or the blood while under therapy.

Animals↗
PubMed1990

Rat tracheal epithelial cells produce granulocyte/macrophage colony-stimulating factor.

It is unknown whether local resident cells of the upper airway are able to regulate the number and function of phagocytic cells by the secretion of cytokines. We undertook to determine if tracheal epithelial cells (TEC) produce the potent cytokine granulocyte/macrophage colony-stimulating factor (GM-CSF) and how TEC-derived GM-CSF might be regulated. Conditioned media (TEC-CM) from 7- to 21-day-old primary cultures of rat TEC contained material with bioactivity similar to GM-CSF. This bioactivity was increased in conditioned medium from lipopolysaccharide (LPS)-treated (1 microgram/ml) TEC. Molecular characterization of bioactivity revealed a molecular weight of 27 to 44 kD by gel-filtration high performance liquid chromatography (HPLC), and elution at 44 to 50% acetonitrile by reverse-phase HPLC, similar to that of authentic GM-CSF. The biologic activity of TEC-CM was completely blocked by a goat polyclonal anti-GM-CSF antibody. With in situ hybridization using a murine GM-CSF cDNA probe, more than 95% of the adherent TEC population expressed GM-CSF transcripts, and the number of transcripts was significantly increased by LPS (1 microgram/ml, 48 h). TEC appear to produce a cytokine that is functionally, biochemically, and antigenically indistinguishable from GM-CSF. The ability of TEC to produce GM-CSF suggests that these cells may play a role in modulating the inflammatory response in the airway.

Animals↗
PubMed1990

Alcohol abuse-related mesangial glomerulonephritis: immunoelectron microscopy.

Immunoelectron microscopy, using post-embedding immunohistochemistry with colloidal gold, was performed on renal samples from forensic autopsies. We confirmed that electron-dense deposits seen in alcohol abuse-related mesangial nephritis correspond to immunoglobulins, as has been shown previously by others in idiopathic cases. We investigated seven control samples and 13 specimens from individuals with evidence of alcohol abuse, six of whom had mesangial nephritis with IgA deposition. We found concentration of the gold particles over large electron-dense deposits in four of six cases of mesangial nephritis, confirming that they correspond to the IgA shown by immunofluorescence. Furthermore, a similar concentration of gold particles was not observed in control cases or in alcoholics without mesangial glomerulonephritis (4/6 vs 0/14; p = 0.005). IgM, seen as small aggregates, was confirmed in only two of six of the same cases. This is the first time that immunoelectron microscopy is performed on tissues obtained post mortem.

Ethanol↗
PubMed1990

An evaluation of external cause-of-injury codes using hospital records from the Indian Health Service, 1985.

To evaluate the usefulness of International Classification of Diseases external cause-of-injury and poisoning codes (E codes) for public health surveillance of nonfatal injuries, we analyzed E codes from Indian Health Service (IHS) hospital records. E codes for unknown or unspecified causes were used for 25 percent of records. At two hospitals, 63 percent of E codes assigned by independent coders agreed; another 18 percent matched on general cause-of-injury groups. With uniform guidelines and increased training, E coding could provide a valuable, cost-effective method of quantifying and characterizing severe, nonfatal injuries.

Health Services Administration↗
PubMed1990

Effects of iron repletion and correction of anemia on norepinephrine turnover and thyroid metabolism in iron deficiency.

The reversibility of the alterations in norepinephrine (NE) content and turnover in interscapular brown adipose tissue and heart of iron-deficient rats has not been demonstrated. We therefore examined NE metabolism in age-matched male Sprague-Dawley rats depleted of iron by dietary means and after repletion with iron dextran. Heart NE content was 58, 61, and 85% of controls at 0, 3, and 7 days after repletion, whereas interscapular brown adipose tissue-NE content was 87, 103, and 104% of controls. Fractional heart NE turnover was 225% greater in iron-deficient anemics than controls but normalized within 3 days. Interscapular brown adipose tissue NE turnover was 58%, 46%, and 20% above controls in iron-deficient rats after 0, 3, or 7 days of iron repletion. Hematocrit returned to 80% of normal in 7 days. Liver triiodothyronine production also increased to 80% of control in this period. A second experiment used isovolemic exchange transfusion to examine the influence of anemia per se on these alterations in organ NE turnover. Acute correction of anemia in iron deficiency did not alter brown fat NE turnover. Heart NE turnover was significantly lower in anemic animals regardless of iron status. Defects in heart and brown fat NE metabolism are reversible within 7 days of iron treatment as are alterations in triiodothyronine production. Anemia per se has little effect on brown fat NE metabolism but does dramatically decrease heart NE content.

Adipose Tissue, Brown↗
PubMed1990

Hospital image and the positioning of service centers: an application in market analysis and strategy development.

The research confirms the coexistence of different images for hospitals, service centers within the same hospitals, and service programs offered by each of the service centers. The images of individual service centers are found not to be tied to the image of the host facility. Further, service centers and host facilities have differential rankings on the same service decision attributes. Managerial recommendations are offered for "image differentiation" between a hospital and its care centers.

Adult↗
PubMed1990

IgA nephropathy in alcohol abuse. An animal model.

In search of an animal model for alcohol abuse related IgA nephropathy, we investigated the Tsukamoto-French alcoholic rat. Continuous intoxication was induced by gastric infusion of a liquid diet with up to 47% ethanol in Wistar rats designated "alcoholic". Control animals received the same calorie count in the form of glucose. Animals were sacrificed after 6 or 10 weeks. IgA nephropathy was observed in 67% (10 of 15) of alcoholic rats and in none of 14 controls (p less than 0.0002). Alcohol abuse related renal changes, similar to those described in humans were present. These included mild mesangial expansion and intense IgA deposition. Foot process effacement was observed in alcoholic animals; severe proteinuria was found in half the animals with IgA nephropathy. This is the first report of chronic ethanol ingestion induced mesangial IgA nephropathy in an animal model.

Alcoholism↗
PubMed1990

Environmental context-dependent homophone spelling.

Two experiments provided evidence of environmental context-dependent memory using a homophone spelling test (e.g., Jacoby & Witherspoon, 1982), an implicit, indirect measure of memory (Richardson-Klavehn & Bjork, 1988). Context reinstatement significantly increased priming in both experiments. The finding of environmental context reinstatement effects with this implicit memory test and others (Garberg & Radtke, 1986; Graf, 1988) indicates that the effect can be found reliably using a test that does not encourage subjects to generate their own context cues from memory.

Attention↗
PubMed1989

Activity and deletion analysis of recombinant human cathepsin L expressed in Escherichia coli.

A cDNA clone encoding the human cysteine protease cathepsin L was expressed at high levels in Escherichia coli in a T7 expression system. The insoluble recombinant enzyme was solubilized in urea and refolded at alkaline pH. 38-kDa procathepsin L was purified by gel filtration at pH 8.0, and a 29-kDa form of the enzyme was purified by gel filtration after autoprocessing of the proenzyme at pH 6.5. The kinetic properties of the 29-kDa species of recombinant cathepsin L were similar to those published for the human liver enzyme (Mason, R. W., Green, G. D. J., and Barrett, A.J. (1985) Biochem. J. 226, 233-241), using benzyloxycarbonyl-Phe-Arg-7-(4-methyl)coumarylamide as substrate. However, the stability of the recombinant enzyme, and its pH optimum for this substrate was shifted to a higher pH. Structure-function studies of cathepsin L were performed by constructing mutations in either the propeptide portion or the carboxyl-terminal light chain portion of the protein. These constructions were expressed in the E. coli system, and enzymatic activities were assayed following solubilization, renaturation, and gel filtration chromatography of the mutated proteins. Deletions of increasing size in the propeptide resulted in large proportional losses of activity, indicating that the propeptide is essential for proper enzyme folding and/or processing in this renaturation system. Deletion of part of the light chain containing a disulfide-forming cysteine residue or a single amino acid substitution of alanine for this cysteine residue resulted in almost complete loss of activity. These data suggest that the disulfide bond joining the heavy and light chains of cathepsin L is essential for enzymatic activity.

Amino Acid Sequence↗
PubMed1989

Field efficacy of ivermectin, fenbendazole and pyrantel embonate paste anthelmintics in horses.

Three anthelmintic pastes were compared in terms of their ability to suppress the output of parasite eggs in the faeces of 108 grazing horses at four sites in Britain; the horses were treated once with either ivermectin, fenbendazole or pyrantel. At each site, the horses grazed together throughout the trials which took place during the summers of 1985 and 1986. The median periods before parasite eggs reappeared in faeces were 70 days for ivermectin, 14 days for fenbendazole and 39 days for pyrantel embonate. Geometric mean faecal egg counts in the groups treated with ivermectin and pyrantel were significantly less (P less than 0.05) than in the fenbendazole group on days 21, 28, 35 and 42 after treatment. On days 49, 56, 63 and 70 the mean egg counts in the ivermectin group were significantly lower (P less than 0.05) than those in either of the other groups. The results indicated that in order to ensure minimal contamination of pastures, grazing horses treated with ivermectin paste would have required a second treatment approximately 10 weeks after the first, and to achieve similar control with fenbendazole or pyrantel embonate, a second treatment would have been required after approximately two weeks and six weeks, respectively.

Animals↗
PubMed1989

Geographic distribution of heat-related deaths among elderly persons. Use of county-level dot maps for injury surveillance and epidemiologic research.

Mapping is a useful tool for initiating data analysis of relatively infrequent injury events and can lead to interesting hypotheses that can then be tested in further epidemiologic studies. From national death certificate data for the years 1979 through 1985, we made dot maps of fatalities due to excessive heat (International Classification of Diseases code E900) among persons 65 years or older. The maps show clusterings of deaths, particularly in the central, south central, and southeastern sections of the United States, to an extent not fully explained by the population density or temperature extremes. The counties principally affected were highly urbanized and, for races other than white, were relatively poor. Our maps identify counties in which heat-related health problems in the elderly are particularly severe. Public health officials in high-risk areas should undertake heat-wave contingency planning and physicians practicing in such areas should familiarize themselves with the treatment of the spectrum of heat-related illnesses.

Aged↗
PubMed1989

Head injury-associated deaths in the United States from 1979 to 1986.

Review of US mortality data from 1979 to 1986 identified 315,328 deaths associated with head injury, which represented 2% of all deaths, 26% of injury deaths, and an annualized head injury-associated death rate of 16.9 per 100,000 residents. Motor vehicles (57%), firearms (14%), and falls (12%) were the most frequent causes. Death rates peaked at 15 to 24 years of age and at 75 years or older, with the younger group most affected by motor vehicles (77%) and the older group by falls (43%). Although blacks and whites had similar death rates overall, age- and cause-specific rates varied considerably. The rate of head injury-associated death for males was three times that of females. Rates for head injury-associated death plateaued after declining in the early 1980s. Physicians can play an important role in primary prevention of head injury through careful prescribing of medications, patient counseling, and advocacy of proved interventions such as motor vehicle-occupant restraints. use, we observed 9827 children riding bicycles at sites in high-, middle-, and

Accidental Falls↗
PubMed1989

Glycosylation of procathepsin L does not account for species molecular-mass differences and is not required for proteolytic activity.

Cathepsin L is a major lysosomal cysteine proteinase in mouse and human cells. Despite similar predicted molecular masses, procathepsin L in these two species migrates on SDS/polyacrylamide gels with apparent molecular masses of 39 kDa and 42 kDa respectively. To determine if glycosylation differences account for this discrepancy, and to ascertain whether glycosylation is essential for enzymic activity, mouse and human procathepsins L were expressed at high concentrations in mouse NIH 3T3 cells or in human A431 cells after DNA-mediated transfection of cloned DNAs for these enzymes. In pulse-chase studies, human procathepsin L transfectants synthesized and secreted large amounts of enzymically active 42 kDa proenzyme and processed it into 34 kDa and 26 kDa intracellular peptides, a pattern of secretion and processing similar to that seen with endogenous or transfected mouse procathepsin L. Both translation of cloned procathepsin L cDNAs in vitro and Endoglycosidase H treatment of 39 kDa mouse and 42 kDa human procathepsin L resulted in non-glycosylated proteins 2 kDa lower in molecular mass than the untreated proteins for both species. This suggests that glycosylation differences are not responsible for the molecular-mass disparity between the two species. Moreover, Endoglycosidase H-treated mouse enzyme retained full proteolytic activity, indicating that glycosylation of cathepsin L is not essential for enzymic function.

Acetylglucosaminidase↗
PubMed1989

1-(2-Pyrimidinyl)piperazine antagonizes GABA-activated currents in cultured spinal neurones of the rat.

Buspirone is an anxiolytic drug with an unknown mechanism of action. We have addressed the proposal that its therapeutic effect is due to a metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), increasing the open probability of gamma-aminobutyric acid (GABA)-activated channels. By making whole-cell recordings from cultured spinal neurones we demonstrated that 1-PP, in contrast to flurazepam, actually antagonizes GABA- and glycine-activated currents. These observations are inconsistent with this proposed mechanism of action for buspirone.

Animals↗
PubMed1989

Characterization of a helper T lymphocyte defect in vitamin A-deficient mice.

Vitamin A-deficient mice exhibited sharply decreased IgG1 responses to protein Ag in vivo and in vitro. We traced the cellular basis for these impaired responses to a functional defect in A-deficient Th. Ag-presenting cells and B cells from A-deficient mice showed no functional defects. The A-deficient T cells proliferated normally in response to Ag but failed to provide the B cell stimulus for Ag-specific IgG1 responses. The A-deficient mice had fewer Th by limiting dilution analysis, and retinyl acetate supplementation in vitro restored Th frequency to control levels. Because added retinyl acetate reversed the Th functional block, these vitamin A-deficient T cells must be primarily defective in activation, not in establishment of immunologic memory.

Animals↗