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Biomedical subjects

C M Smith

Publications and source records attributed to C M Smith.

At least 217 records · Page 12Linked to original sources

Sequence of bronchoalveolar lavage and histopathologic findings in rat lungs early in inhalation asbestos exposure.

To assess the early cellular inflammatory response of the lungs, 7 rats per group were exposed nose-only to 13 mg/m3 of chrysotile asbestos, 7 h/day for 2, 4, or 6 wk. Lung histopathology and bronchoalveolar lavage (BAL) were analyzed. In exposed animals, dose-related bronchiolitis and fibrosis were found that were not seen in control rats (p less than 0.001). In exposed rats, total BAL cells were increased six-to sevenfold over matched controls, and more cells were retrieved with longer exposure (p less than 0.001). In the BAL, counts of macrophages, lymphocytes, and polymorphonuclear cells (PMNs) were each elevated in the exposed rats (each p less than 0.001). PMNs seen histologically and in the BAL may be related to the time period examined. PMNs and lymphocytes observed throughout this 6-wk study support the idea that these cells may have an important role in the early events of asbestos lung injury.

Administration, Inhalation↗

Influence of focal growth conditions on the pathogenesis of toxic shock syndrome.

Patients with toxic shock syndrome (TSS) had sequestered focal sites colonized or infected with Staphylococcus aureus significantly more frequently than did patients with scalded skin syndrome. Growth conditions within the infected foci of four patients with TSS included nearly physiological levels of pH, pO2, pCO2, protein, calcium, and magnesium. Two strains of S. aureus had typical TSS phenotypes (production of TSS toxin-1 [TSST-1] and protease), which were optimally expressed in vitro under conditions similar to those documented in vivo (6% CO2, pH 7.0, aerobic, high levels of protein). Altering any one of these growth factors significantly decreased production of TSST-1. In protein-containing media, depletion of divalent cations had a less-profound effect on organism growth and TSST-1 production. The unique in vivo environment in patients with non-menstrual TSS is similar to conditions associated with tampon use during menstruation. Growth conditions may play an important role in the expression of S. aureus phenotype and the pathogenesis of TSS.

Bacterial Toxins↗

Effects of acute and chronic ethanol ingestion on pantothenate and CoA status of rats.

Total coenzyme A (CoA) and pantothenate levels in tissues were compared in three studies in which rats were fed Lieber-DeCarli formula diet with either 5% ethanol or maltose-dextrin (controls) for 19-36 d. The heart pantothenate levels of ethanol-fed rats were 51-78% of that in controls. The heart total CoA levels of ethanol-fed rats were 78-90% of that in controls. Liver total CoA and pantothenate levels were lower in ethanol-fed rats than in controls in one and two studies, respectively. Differences were diminished in rats fasted for 24 h. Control and chronic ethanol-treated rats given no ethanol for 24 h were intubated with [1-14C]pantothenate. Accumulation of radioactive pantothenate in hearts of ethanol-treated rats was 58% and accumulation in livers was 75% of that in controls. An acute effect of ethanol on pantothenate conversion to CoA in liver was found in naive rats intubated with 0.5-2.5 g ethanol/kg body weight and given [1-14C]pantothenate by intubation or intraperitoneal injection. In ethanol-treated rats, conversion of [1-14C]pantothenate to CoA was 4-28% of that in controls. These studies demonstrated an effect of chronic ethanol ingestion on pantothenate and total CoA contents of heart and possibly other tissues and an acute effect of ethanol ingestion on [1-14C]pantothenate conversion to CoA in liver.

Animals↗

Possible role of acetyl-CoA in the inhibition of CoA biosynthesis by ethanol in rats.

Ethanol, both administered to rats in vivo and added to cultured hepatocyte incubations, inhibits the conversion of [14C]pantothenate to coenzyme A (CoA). Data suggesting that the inhibition by ethanol involves its oxidation to acetate were obtained with rat hepatocytes maintained in primary culture. Ethanol, acetaldehyde and acetate were approximately equally effective inhibitors of [14C]pantothenate conversion to CoA (46-71%) and had no effect on uptake of [14C]pantothenate by hepatocytes. In the presence of saturating levels of acetate, acetaldehyde had no additional inhibitory effect. Cyanamide and diethyldithiocarbamate decreased the inhibition by acetaldehyde at the same concentration (10 microM), which saturated their ability to inhibit acetaldehyde oxidation. Studies with an isolated pantothenate kinase preparation showed that, of the ethanol metabolites, only acetyl-CoA was an effective inhibitor. Acetate and butyrate, which were both inhibitors of [14C]pantothenate conversion to CoA, increased the acetyl-CoA and decreased the free, unacylated CoA (CoASH) content of the cultured hepatocytes. The data were consistent with a mechanism for the inhibitory effect of ethanol that involves inhibition of pantothenate kinase by acetyl-CoA, but did not exclude a possible role of additional regulatory factors.

Acetaldehyde↗

Encephalomyelitis in two sisters who died suddenly at home.

Two sudden infant deaths of female siblings occurring at the ages of six and 5 1/2 months are reported. The temporal separation of their deaths was 14 months. Both showed virtually identical pathological findings within the central nervous system, consistent with encephalomyelitis. No causative agent, metabolic defect or common predisposing factor was identified and no evidence of a relationship to immunisation could be established.

Encephalomyelitis↗

Development of a broth medium for Bacteroides forsythus.

Bacteriodes forsythus has been implicated as a possible pathogen in certain destructive periodontal diseases. This species has been extremely difficult to grow in broth, thus hampering its characterization and identification. A broth medium was developed consisting of 30 g of phytone, 10 g of NaCl, and 1 g of filter-sterilized L-cysteine per liter. The medium supported the growth of 23 fresh isolates of B. forsythus from six subjects to optical densities averaging 0.71 +/- 0.20 (standard deviation) at 550 nm after 48 to 72 h of anaerobic incubation.

Bacteroides↗

Pluronic F-68 reduces the endothelial adherence and improves the rheology of liganded sickle erythrocytes.

A perfluorochemical blood substitute emulsified with Pluronic F-68 has been shown to improve the filterability of deoxygenated sickle red cells. We questioned whether some of the effect was independent of oxygen loading and studied the influence of Fluosol DA (Green Cross, Osaka, Japan) and Pluronic on the rheology and adhesion of sickle red cells saturated with oxygen and carbon monoxide. A 5-vol/vol% concentration of Fluosol or equivalent concentration of Pluronic was equally effective at improving the filtration of washed sickle cells through 5-micron-diameter pores at wall shear stresses approximating 1,000 dyne/cm2. The same concentration of Pluronic reduced the extensional static rigidity of irreversibly sickled cells (ISC) by 25% and also abolished the adherence of gravity-sedimented sickle cells to endothelial monolayers in the presence of saline or plasma. The inhibition of adherence was not reversible by washing and was accomplished with equal ease by isolated treatment of sickle cells or endothelium. Pluronic had no effect on the rheology or adhesion of normal adult red cells. Neither Fluosol nor Pluronic changed sickle or normal cell shape, mean cell volume, mean cell density, or cell density distribution. A lubricating effect of Pluronic on cell surfaces could explain all of the rheological observations and offers another direction of inquiry in the search for therapy for sickle cell disease.

Adult↗

Size and filterability of human and hamster pulmonary macrophages exposed to cigarette smoke.

Pulmonary alveolar macrophages (PAM) obtained from healthy human cigarette smokers generated greater pressure in filtration through small cylindrical pores than PAM from nonsmoking controls. A well standardized hamster smoking model was employed to study the structural basis for the impaired PAM filtration accompanying cigarette smoke exposure. Hamsters also demonstrated increased PAM filtration pressure through cylindrical pores less than half a cell diameter in size after inhalation of cigarette smoke, but not after exposure to vapor phase smoke that had been strained through a particle filter. Cigarette smoker PAM were equally filterable as control through larger diameter channels, and showed comparable improvements in filterability with cytochalasin B treatment. Altered PAM filtration was associated with the formation of characteristic cytoplasmic smoker inclusions, an increase in cell size, and loss of redundant, ruffled surface membrane. The study of smoker and control PAM separated into different sizes on the basis of variations in cell density suggested that discrepancies in cell size were insufficient to explain the filtration disparity. A loss of availability of surface membrane for deformation appeared to be the most important factor responsible for the impaired filtration.

Animals↗

Hyperosmolarity as the stimulus to asthma induced by hyperventilation?

Hyperosmolarity of the epithelial fluid of the large airways caused by evaporative water loss (wloss) has been proposed as the stimulus to exercise-induced asthma. The aim of this study was to compare the wloss during hyperpnea with a theoretical wloss from a known hypertonic stimulus in order to determine whether comparable volumes of wloss will induce the same response. Since wloss also occurs during isocapnic hyperventilation (ISH), we decided to compare the airway response to ISH with the response obtained after inhaling 4.5% NaCl aerosol. Changes in FEV1 were measured in 17 subjects with asthma in response to increasing rates of ventilation (ISH) and increasing doses of 4.5% NaCl aerosol. For ISH, wloss was calculated at 29 mg/L of expired air and for 4.5% NaCl, at 4.0 ml/l ml of aerosol inhaled, as this is the volume of water that will bring the periciliary fluid to normal tonicity. Two dose-response curves were drawn for each subject. These curves were similar both in position (PD20) and in shape (i.e., the slope of the curve as estimated by the ratio of wloss for maximum recorded percent fall in FEV1 [PDmax] to PD20). There was no significant difference in the PD20 (ISH, 10.3 ml, 95% confidence limits 7.5 and 13.9; 4.5% NaCl, 12.3 ml, 95% confidence limits 8.9 and 17.1) or between the ratio of log PDmax:log PD20 (ISH, 1.19 +/- 1 SD, 0.14; 4.5% NaCl, 1.17 +/- 1 SD, 1.17; p = not significant). These findings support the concept that airway hyperosmolarity may be the mechanism for ISH and exercise-induced asthma.

Adolescent↗

The effects of osmotic tissue dehydration and air drying on morphology and energy transfer in two species of porphyra.

Studies were conducted to document the effects on morphology and energy transfer in photosynthesis of severe tissue dehydration induced either by air-drying or by immersing the tissues of two Porphyra species in hyperosmotic solutions. These studies showed that the dehydration-tolerant intertidal alga, Porphyra perforata J.Ag., was almost unaffected by either of these treatments, while the dehydration-sensitive Porphyra nereocystis Anders. was damaged similary by both treatments. Damage to that sensitive species was characterized by ruptured organelles as seen by interference microscopy as well as by increased fluorescence emission at 682 nanometers emanating from allophycocyanin. These results suggest that a disruption of energy transfer between allophycocyanin and chlorophyll a occurs because of the damage to membranes following tissue dehydration, and that the increase in the yield of phycobilin fluorescence is a good indicator of these phenomena. Thus, air-drying and osmotic-dehydration appear to have similar physiological consequences in a dehydration-sensitive alga but almost no effect in a tolerant species.

Journal Article↗

Assessing intellectual deterioration.

Twenty patients fulfilling the clinical criteria of Alzheimer-type dementia were assessed on the Wechsler Adult Intelligence Scale (WAIS), the Schonell Graded Word Reading Test (SGWRT) and the National Adult Reading Test (NART). Fifteen normal elderly control subjects were administered the WAIS and the NART. The regression equations of Nelson & McKenna (1975) and the tables of Nelson (1982) were used to estimate premorbid Full Scale IQ on the basis of WAIS Vocabulary subtest score and performance on each of the reading tests. The data were analysed in order to assess the relative utility of these methods, and of WAIS Verbal-Performance IQ discrepancy, in the assessment of intellectual deterioration. The data suggested that performance on the NART was the best indicator of premorbid level of functioning in terms of the size of predicted-obtained discrepancies.

Aged↗

Intrusion errors in Alzheimer's disease.

The Kendrick Object Learning Test (OLT) was used to study the incidence of intrusion errors in patients with Alzheimer's disease (AD). Although such errors constituted a higher proportion of the responses made by patients than by controls, suggestions in the literature that patients with AD show a propensity for prior-list intrusion errors were not supported.

Aged↗

Micropipette aspiration of human platelets: influence of rewarming on deformability of chilled cells.

Recent studies using micropipette elastimetry have shown that the circumferential microtubule supporting the discoid form of resting platelets has a direct influence on the resistance of the cell to deformation. However, the findings did not resolve whether the mere presence of microtubules, their organization into coils, or location under the cell wall was responsible for resistance to aspiration into micropipettes. In the present study platelets were cooled to 2 degrees to 4 degrees C to remove microtubules completely. The chilled cells were then rewarmed to 37 degrees C, and the influence of microtubule reassembly on resistance to deformation in micropipettes measured at intervals up to 1 hour. Chilled platelets without microtubules were aspirated more than twice as far as control platelets at all negative pressures from 1 to 10 cm H2O (tensions 4 to 41 X 10(-2) dynes/cm). At negative tensions beyond 32.5 X 10(-2) dynes/cm (8 cm H2O), the aspirated lengths of control platelets plateaued until the cells finally fragmented. Aspirated segments of chilled platelets continued to increase in length on exposure to greater negative pressure. Twenty minutes after rewarming at 37 degrees C, chilled cells began to return toward normal resistance to aspiration when only 6% had recovered discoid shape. The range of deformability at this time was narrow, indicating that partial recovery was not caused by development of two cell populations, one with and one without microtubules. The return toward normal resistance continued at 30 minutes when 75% of platelets were discoid, and was identical to that in control platelets after 1 hour at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

The mechanism of pantothenate transport by rat liver parenchymal cells in primary culture.

The mechanism of pantothenate transport across the plasma membrane was investigated with initial velocity studies of [14C]pantothenate uptake and efflux in rat liver parenchymal cells maintained in primary culture. At 116 mM sodium, double-reciprocal plots of the initial velocity of uptake versus [pantothenate] were linear from 0.3 to 36.5 microM pantothenate and gave an apparent Km,pant of 11 +/- 2 microM. The rate of pantothenate uptake at 0 [sodium] was about 14% of the rate at 116 mM sodium, and the reciprocal of the apparent Km,pant was a linear function of [sodium]. Vmax obtained by extrapolation to infinite [pantothenate] was independent of [sodium]. Ouabain, gramicidin D, cyanide, azide, and 2,4-dinitrophenol inhibited uptake, but preloading cells with pantothenate did not. Pantothenate derivatives or carboxylic acids were only weak inhibitors of uptake. Efflux was measured in cells preloaded with [14C]pantothenate. The apparent Km for efflux was 85 +/- 29 microM, and the rate of efflux was unaffected by addition of pantothenate, sodium, ouabain, gramicidin D, or 2,4-dinitrophenol to the external medium. These features are consistent with a mechanism for pantothenate transport in which sodium and pantothenate are cotransported in a 1:1 ratio on a carrier highly specific for pantothenate; sodium decreases the apparent Km for pantothenate, and a sodium-carrier complex forms only on the intracellular side of the membrane.

Animals↗