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Biomedical subjects

R Gilbert

Publications and source records attributed to R Gilbert.

At least 127 records · Page 7Linked to original sources

Approaches to prevention of asbestos-induced lung disease using polyethylene glycol (PEG)-conjugated catalase.

Asbestos-associated damage to cells of the respiratory tract in vitro can be prevented by the simultaneous addition of scavengers of active oxygen species to cultures. To determine if administration of scavenger enzymes to animals and humans is a plausible approach to the prevention of asbestos-induced lung disease, osmotic pumps were filled with various concentrations of PEG-coupled catalase and implanted subcutaneously into Fischer 344 rats over a 28-day period. At 3, 14, and 28 days after implantation of the pumps, the animals were evaluated for levels of catalase in serum and lung. In addition, lung tissue and lavage fluids were examined at 28 days for biochemical and morphologic indications of cell injury, inflammation, and fibrotic lung disease. At all time points examined, the administration of PEG-catalase caused a dosage-dependent increase in serum levels of catalase. The levels of lung catalase were evaluated at 28 days but not at earlier time periods. In comparison to control rats, the amounts of enzymes (lactic dehydrogenase, alkaline phosphatase), protein, and cells in lavage fluids from treated animals were unaltered. Moreover, the lungs showed no evidence of inflammation or fibrotic disease as determined by differential cell counts in lavage and measurement of hydroxyproline. These studies suggest that administration of PEG-catalase does not cause injury or other alterations in lung tissue and can be pursued as a feasible approach to prevention of asbestosis.

Animals↗

Effect of high-fat diet on cholesterol distribution in plasma lipoproteins, cholesterol esterifying activity in leucocytes, and erythrocyte membrane components studied: importance of body weight.

Effects of isocaloric changes in dietary fat on plasma lipoproteins and lipids and enzymes of erythrocytes and leucocytes were assessed. Subjects with a higher Brocca index showed increase in total and LDL cholesterol, significant reduction in HDL cholesterol, and increased total cholesterol:HDL cholesterol ratio after high-fat diet consumption. Due to high-fat diet feeding, erythrocyte membrane and leucocyte cholesterol and phospholipid contents were increased, cholesterol:phospholipid molar ratio was elevated, and erythrocyte enzymes (G6PD and 6PGD) and leucocyte enzymes (CEH and CES) were elevated. Erythrocyte membrane glycoprotein components showed marked increase, indicating possible alterations of membrane surfaces. The metabolic alterations were reversed slowly after resumption of the normal (low-fat) diet. Body weight plays an important role in the alterations in major lipoprotein cholesterol contents in response to changes in dietary fat composition. Cellular changes indicate alterations in structure and function of blood cells due to high-fat diet feeding.

Adult↗

Comparison of two rapid latex agglutination methods for detection of group A streptococcal pharyngitis.

Throat swabs from 404 patients with suspected pharyngitis were collected using duplicate swabs. Both swabs were used to inoculate 5% sheep blood agar plates, which were incubated in an anaerobic atmosphere for the isolation of Group A streptococci. The throat swabs were tested for the presence of Group A antigen using the Culturette Brand 10-Minute Group A Strep ID kit (Marion Scientific, Kansas City, MO), and the Direct Antigen Identification D.A.I. Strep A Test (Difco Laboratories, Inc., Detroit, MI). We found that 77 of the 404 specimens were culture positive for Group A streptococci. The Strep ID kit had a sensitivity of 83.7% and a specificity of 91.6%. The positive and negative predictive values were 72% and 95.6%, respectively. The D.A.I. test had a sensitivity of 80.2% and a specificity of 100%. The positive and negative predictive values were 100% and 94.5%, respectively. There was not a significant difference in the sensitivity of the two kits (P less than 0.1), but there was a significant difference in the specificity (P less than 0.01).

Humans↗

What is a 'restrictive' defect?

We studied 211 sets of pulmonary function data to evaluate spirographic findings in patients with restrictive defects, and to determine the significance of the spirographic interpretation of restriction. A combination of clinical and body plethysmographic data was used as the standard for the diagnosis of restriction. Restriction was diagnosed spirographically when forced vital capacity (FVC) was low and the ratio of one-second forced expiratory volume (FEV1) to FVC (FEV1/FVC%) was normal. With these criteria, using 70% as the lower limit of normal for FEV1/FVC%, the spirogram had a 93% sensitivity and an 82% specificity for the detection or exclusion of a restrictive defect. Ten percent of patients with pure obstructive defects by clinical and plethysmographic criteria showed a restrictive defect on the spirogram. Combined obstructive and restrictive defects were rare; in these cases the spirogram showed a restrictive defect but missed the obstructive component.

Asthma↗

Effect of aging on the hepatobiliary transport of dimeric immunoglobulin A in the male Fischer rat.

Recent studies have suggested that the hepatobiliary transport of serum dimeric immunoglobulin A constitutes an important secretory route for this ligand. However, the information that is currently available has been accumulated from studies in young animals or in patients with liver disease. Aging is known to result in (a) reduced hepatobiliary function(s), (b) an increased incidence of gastrointestinal infectious diseases, and (c) a marked decline in the immune response. We evaluated the effect of aging on the in vivo hepatic capacity to transport dimeric immunoglobulin A from blood to bile. Young adult rats (3-4 mo) secreted 125I-labeled dimeric immunoglobulin A into the bile at a rate sixfold greater than that measured in either mature (12 mo) or senescent (24-25 mo) animals. This age-related decline appears to be relatively independent of bile flow and bile acid secretion. Quantitative light and electron microscopic autoradiographic evidence suggests that aging may impair the rate at which this ligand is translocated across the hepatocytes to the bile canaliculi.

Aging↗

The extracellular matrix of normal chick embryo fibroblasts: its effect on transformed chick fibroblasts and its proteolytic degradation by the transformants.

Extracellular matrix (ECM), prepared from chick embryo fibroblasts, contains fibronectin as the major structural protein along with collagen and other polypeptides as less abundant protein components. When Rous sarcoma virus-transformed chick embryo fibroblasts are cultured on the ECM in the presence of the tumor promoter tetradecanoyl phorbol acetate, the transformed cells lose their characteristic rounded morphology and align on and within the ECM fibrillar network. This restrictive aspect of ECM is only temporary, however, and with time (24-72 h) the transformed cells progressively degrade the ECM fibers and resume their rounded appearance. The matrix degradation can be monitored by employing biosynthetically radiolabeled ECM. The addition of purified chicken plasminogen to the Rous sarcoma virus-transformed chick embryo fibroblast cultures enhances the rate and extent of ECM degradation, due to the elevated levels in the transformed cultures of plasminogen activator. Plasminogen-dependent and -independent degradation of ECM has been characterized with regard to sensitivity to various natural and synthetic protease inhibitors and to the requirement of cell/ECM contact. Plasminogen-dependent degradation of ECM occurs rapidly when ECM and cells are in contact or separated, whereas plasminogen-independent degradation is greatly reduced when ECM and cells are separated, which suggests that cell surface-associated proteolytic enzymes are involved. A possible role in ECM degradation has been indicated for cysteine proteases, metallo enzymes, and plasminogen activator, the latter as both a zymogen activator and a direct catalytic mediator.

Animals↗

The interpretation of the spirogram. How accurate is it for 'obstruction'?

The accuracy of the spirogram in detecting or excluding airway obstruction based on airflow limitation was assessed prospectively in 200 subjects, 74 with obstruction and 126 without it. The diagnosis of airway obstruction was based on a combination of clinical and body plethysmographic data. The ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC %) had a sensitivity of 0.82 and a specificity of 0.98. A fixed lower limit seemed better than a lower limit based on prediction formulas. Because specificity is so much higher than sensitivity, less precise clinical information is required to confirm the presence of obstruction if FEV1/FVC % is abnormal than is needed to exclude obstruction if FEV1/FVC % is normal. Using a combination of FEV1/FVC % and the ratio of forced expiratory flow (FEF) at 50% of FVC gave a higher sensitivity with a comparable specificity when compared with FEV1/FVC % used alone. A normal value for FEF between 25% and 75% of FVC virtually ruled out obstruction, but low values had poor specificity.

Adult↗

Patterns of alliances in nondistressed and multiproblem families.

The goal of this study was empirically to investigate differences between distressed and nondistressed families in the strength, patterning, and cross-situational consistency of alliances. Audiotapes were made of 12 distressed and 12 nondistressed families in two observational situations. The resultant interaction was then coded for family alliances by trained observers. Distressed families were characterized by low overall levels of alliance behavior, weakness in the marital alliance relative to other family alliances, and discrepancies in parental alliances with the target child. There were generally no differences between groups in the cross-situational variability of alliance strength or patterning. The results are discussed in relation to the predictions of structural models of family process.

Adolescent↗

Hyperactive children: a study of the content analysis of their speech.

A group of hyperactive boys with attention deficit disorder (DSM-III) (n = 13) was compared to a group of normative, nonhyperactive boys (n = 16) with respect to Gottschalk-Gleser scores derived from 5-min speech samples they produced in response to standardized and purposely ambiguous instructions. The hyperactive boys had significantly higher mean scores than the normative boys for cognitive impairment, social alienation-personal disorganization, and total depression. Of the eight depression subscales, the hyperactive boys had significantly elevated scores on hopelessness, self-accusation (a cluster composed of shame, guilt, and hostility inwards), and psychomotor retardation. Problems with the classification of the hyperactive syndrome, which is equated with the attention deficit disorder, are briefly discussed. The present study gives some support to the concept, as adjudged from the content analysis of verbal behavior, that hyperactivity, at least in boys, may be associated with cognitive impairment, increased general psychiatric morbidity, and depression. Whether single or multiple etiological factors are involved in this disorder cannot be ascertained from this study.

Attention Deficit Disorder with Hyperactivity↗

Pharmacologic identification, activation and antagonism of two muscarine receptor subtypes in the lower esophageal sphincter.

Lower esophageal sphincter pressures were monitored with water-filled catheters in anesthetized opossums. Muscarinic agonists McN-A-343 and bethanechol were administered in the arterial supply of the sphincter. McN-A-343 caused relaxation after a brief contraction of the sphincter. Bethanechol caused a dose-dependent contraction. Tetrodotoxin antagonized the inhibitory effect of McN-A-343 but did not antagonized sphincter contraction caused by McN-A-343 or bethanechol. The mean ED50 values were 6.9 nmol/kg i.a. for McN-A-343-induced relaxation, 10.5 nmol/kg i.a. for McN-A-343-induced contraction and 0.4 nmol/kg i.a. for bethanechol-induced contraction. Atropine caused a dose-dependent rightward shift in the dose-response curves of inhibitory and excitatory effects of the two muscarinic agonists. Pirenzepine caused a dose-dependent rightward shift in the dose-response curves of McN-A-343-induced relaxation. Pirenzepine did not modify sphincter contraction caused by the muscarinic agonists. 4-Diphenylacetoxy-N-methylpiperidine methiodide, on the other hand, did not modify McN-A-343-induced sphincter relaxation but caused dose-dependent rightward shifts in the dose-response curves of sphincter contraction caused by McN-A-343 or bethanechol. These studies suggest that there are two distinct types of muscarine receptors in the opossum lower esophageal sphincter. The M1 muscarine receptors are present on the inhibitory neurons and participate in the synaptic transmission between vagal preganglionic and intramural postganglionic inhibitory neurons. They are activated by McN-A-343 and antagonized by pirenzepine. The M2 muscarine receptors are located directly on the sphincter muscle. They are also activated by McN-A-343, but are selectively activated by bethanechol and are antagonized by 4-diphenylacetoxy-N-methylpiperidine methiodide.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

The presence of a receptor for complement on T lymphocytes. Restriction of the complement receptor to Fc-receptor-bearing T lymphocytes.

Using rhodaminated guinea pig anti-ovalbumin:ovalbumin:complement complexes, a fluoresceinated monoclonal anti-Thy 1 antibody and a FACS-II equipped with dual fluorescence detection channels, we find that 25-30% of Thy 1+ splenocytes express a receptor for complement. That a receptor for complement is involved in binding the guinea-pig AgAb:C' complexes is supported by the observations that: a) guinea-pig complexes, which were not treated with a serum source of complement or which were treated with either fresh serum in the presence of EDTA or with heat-inactivated serum, do not bind to the T lymphocytes, and b) heat-aggregated human gamma globulin, which effectively inhibits binding of mouse AgAb complexes to the aFcR gamma, has no effect on the binding of guinea-pig AgAb:C' complexes to the T lymphocytes. By analyzing cell subpopulations isolated by cell sorting, it is demonstrated that the C'R-positive T lymphocyte clearly delineates a major subpopulation of aFcR gamma-positive T lymphocytes, whereas no cells are found bearing a C'R, while lacking the aFcR gamma. The implications of the presence of a C'R in immunoregulation are discussed.

Animals↗

Correlation of amylase and lecithin sphingomyelin ratios in amniotic fluid samples.

The use of amniotic fluid amylase (AF amylase) has been proposed as a screening test to determine fetal maturity. We reviewed data from 944 amniotic fluid samples analyzed by our laboratory for amylase and lecithin sphingomyelin (L/S) ratio between 1975 and 1980. AF amylase shows poor overall correlation with L/S ratios (r = 0.256). Retrospective analysis of AF amylase as a screen to determine the need for L/S ratios showed an overall sensitivity of 57%, and an overall specificity of 86% for AF amylase. Three groups were studied: a low amylase group (amylase less than 200 U/L), a middle group (amylase 200-300 U/L), and a high amylase group (amylase greater than 300 U/L). Only 55% of the low amylase group had an immature L/S ratio. The high amylase group had the best correlation between AF amylase and L/S ratio, but 13% of these samples had an immature or borderline L/S ratio. We conclude that AF amylase cannot be used as a screening test to determine the need to perform L/S ratios.

Amniotic Fluid↗