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Biomedical subjects

W Lee

Publications and source records attributed to W Lee.

At least 379 records · Page 21Linked to original sources

Arterial intimal embrittlement. A possible factor in atherogenesis.

Sections of aorta, coronary artery, basilar artery and vena cava were collected at autopsy. Macroscopically normal intimal specimens were removed by stripping. Intimal collagen was measured as hydroxyproline. Intimal film embrittlement was measured in vitro by a bursting volume distensibility test developed in our laboratory. There was an average increase of over 100% in the collagen content of apparently lesion-free human arterial intima on aging over a fifty-year period. This includes an increase of 113% for aortic intima, 49% increase for coronary artery intima, and an increase of 158% in collagen in basilar artery intima. In contrast the collagen level in the vena caval intima decreases on aging, by 42% in fifty years. The large increase in collagen in arterial intima is accompanied by a large increase in intimal embrittlement. The decreasing collagen content of the venous intima on aging results in increased distensibility. Increased aortic intimal film embrittlement (lower distensibility) correlates with age (R = 0.699), but even better with intimal collagen (R = 0.911), suggesting that aortic intimal collagen level is a more important determinant of intimal embrittlement than age. Men, older than 55, have significantly higher aortic intimal collagen levels than women. Embrittlement of arterial intima should make it more susceptible to injury under the pulsatile pressure of the blood. Decreased venous intimal collagen and greater distensibility on aging could be factors in the development of venous valvular insufficiency and varicose veins. However, our study of veins was performed primarily as a control in this instance. Fundamental elements in the atherogenic process are increased intimal collagen, increased intimal brittleness, endothelial injury, followed by intimal cell proliferation. In the vena caval intima on aging there is decreased collagen, increased intimal distensibility, no injury due to increased pulse or blood pressure, and, therefore, no cell proliferation and no intimal lesion.

Adolescent↗

A scanning electron-microscopic study of the muscle layer of the canine gallbladder.

A connective tissue digestion and removal technique utilizing collagenase and hyaluronidase incubation followed by treatment with 8 N hydrochloric acid successfully revealed the muscular components within the gallbladder wall of the dog, allowing three-dimensional visualization with the scanning electron microscope. The muscle adjacent to the serosa appeared as a homogeneous layer with few discontinuities. In contrast to this were the more superficial muscle layers which were arranged as a meshwork of interlacing smooth muscle bundles of various size, the interstices of which were filled with cellular connective tissue. These gaps in the muscle layer varied in size, becoming larger as the muscle bundles tapered out just below the mucosal aspect of the gallbladder wall.

Animals↗

Arrhythmia susceptibility and myocardial composition in diabetes. Influence of physical conditioning.

Abnormal myocardial composition in diabetes mellitus has been described, but the effects on ventricular vulnerability have not been defined. We have assessed the susceptibility to arrhythmias in a canine model after 1 yr of mild diabetes induced by alloxan. Since physical conditioning can affect metabolic abnormalities in diabetes, this intervention has also been evaluated. Group 1 served as controls and groups 3 and 4 were diabetic. Animals in the latter group as well as nondiabetic controls of group 2 were exercised on a treadmill for the last 8 mo of the experiment. After 1 yr, anesthesia was induced with chloralose for vulnerability studies. The ventricular fibrillation threshold of 24.4 +/- 1.9 mA in group 3 was significantly less than in normals (45.1 +/- 2.2). Spontaneous arrhythmias were also more prevalent in diabetics during acute ischemia (group 3-A). Increased ventricular vulnerability after epinephrine infusion was present in the sedentary diabetes despite normal ventricular function responsiveness. In a superfused preparation of myocardium, resting membrane potential and action potential amplitude were normal in diabetics, and beta-adrenergic stimulation shortened repolarization more than in controls. Myocardial collagen concentrations, which included an interfibrillar distribution on morphologic examination, were increased in group 3. In the trained diabetics of group 4 the basal vulnerability thresholds and responses to epinephrine were normal. While myocardial collagen levels were normal, cholesterol and triglyceride increments persisted. Thus, in mild experimental diabetes, enhanced susceptibility to arrhythmias exists; this susceptibility may be based on a combination of nonhomogenous collagen accumulation affecting local conduction and increased electrophysiologic sensitivity to catecholamines.

Action Potentials↗

Quantitative analysis of cellular glutathione by flow cytometry utilizing monochlorobimane: some applications to radiation and drug resistance in vitro and in vivo.

An assay using a bimane derivative has been developed to detect free glutathione (GSH) in individual viable cells by flow cytometry. Monochlorobimane [syn-(ClCH2CH3)-1,5-diazabicycla[3.30]acta-3,6-diene-2,8-dio ne], itself nonfluorescent, reacts with GSH to form a highly fluorescent derivative. High pressure liquid chromatography analysis showed that, using specific staining conditions, the only low molecular weight fluorescent derivative formed in Chinese hamster ovary cells was that formed with GSH. Very little reaction with protein sulfhydryls was observed. Rates of GSH depletion in Chinese hamster ovary cells exposed to diethylmaleate were essentially the same, whether measured by relative fluorescence intensity, by flow cytometry or by enzymatic assay on cellular extracts. This method was shown to be useful for measurement of GSH resynthesis, uptake, and depletion by prolonged hypoxia and misonidazole treatment. Since measurements are made on individual cells, cell-to-cell variation and populational heterogeneity in GSH content are revealed by flow cytometry. Although under most conditions in vitro GSH content is relatively homogeneous, under certain circumstances, such as release from hypoxia, heterogeneity in populational GSH levels was observed. The significance of this heterogeneity is discussed in regard to the induction of gene amplification and drug resistance by transient hypoxia. Numerous subclones of Chinese hamster ovary cells selected by growth in Adriamycin or methotrexate-containing medium express elevated levels of GSH per cell. The method was extended to quantitate the GSH content of cells excised from EMT-6/SF mouse tumors that had been treated in vivo with L-buthionine-S-R-sulfoximine, an inhibitor of GSH synthesis. The bivariate analysis (forward angle light scatter versus monochlorobimane fluorescence) of cells derived from these tumors gave excellent resolution of normal and tumor cells and demonstrated extensive heterogeneity in the tumor cell population with respect to GSH content per cell.

Animals↗

Outbreak of systemic Candida albicans in intensive care unit caused by cross infection.

The first documented outbreak of systemic candidosis shown to be due to cross infection with a particular strain of Candida albicans is reported. Over nine months in an intensive care unit 13 patients developed definite and one probable systemic candidosis. Twenty five further patients had superficial candidal infections. The strain that caused the outbreak (serotype A, morphotype A1, biotype 0/(1)5 5/7) was responsible for all the cases of systemic candidosis acquired in the intensive care unit, 11 (44%) of the superficial candidal infections in the unit, and 17% of candidal infections outside the unit but in the same hospital. The strain was also isolated from oral swabs taken from four nurses working in the unit and the hands of one of these nurses. Two out of 17 nurses were shown to have acquired the strain on their hands when examined immediately after nursing systemically infected patients. No environmental source could be identified. The strain also showed enhanced survival in handwashing experiments and was relatively resistant to Hibiscrub. Management of patients with systemic candidosis might include measures to prevent cross infection and handwashing with disinfectants that are active against candida.

Adult↗

Reactions during hemodialysis caused by allergy to ethylene oxide gas sterilization.

In patients receiving long-term hemodialysis (HD), we have examined the presence of IgE-dependent sensitization to ethylene oxide (EO) gas, which is used for sterilization of disposable medical products including dialyzers. Serum was obtained from 25 patients who experienced acute allergic reactions during HD, five patients receiving HD with isolated eosinophilia, and 37 unselected patients receiving HD. Sera from 22 of 25 of the allergic reaction group and from five of 35 of the unselected group were demonstrated to contain IgE antibodies with specificity for EO. Corresponding IgG antibodies were also present. No such antibodies were detected in serum from normal controls or ragweed-allergic patients. The serum from one patient with isolated eosinophilia had a borderline elevated IgE antibody level. These results demonstrate a close relationship between the presence of IgE antibodies to EO and HD-related allergic reactions in this patient population.

Ethylene Oxide↗

The effects of diclofenac sodium on arachidonic acid metabolism.

Evidence has been presented that inhibition by diclofenac sodium of the production of leukotrienes by cells participating in the inflammatory process is due to a decreased availability of intracellular arachidonic acid which results from enhanced uptake of the substrate into triglyceride pools. The diminished leukotriene production does not result from direct inhibition of 5-lipoxygenase or phospholipase A2. Reduced availability of arachidonic acid would also limit production of prostaglandins, although in this case manifestation is obscured by the potent inhibitory effect of diclofenac sodium on cyclooxygenase. This recently discovered action of diclofenac sodium, which has been characterized by studies on isolated leukocytes, appears to be operative in vivo. Consistent with this mechanism, and not explainable by classical cyclooxygenase inhibition, diclofenac sodium inhibited leukotriene production in whole blood from drug-treated animals and also suppressed leukocyte infiltration of subcutaneously implanted sponges. The latter effect contrasts with increased infiltration frequently obtained with other NSAIDs and thought to reflect enhanced production of leukotrienes. In conclusion, the findings suggest that patient acceptance or preference for diclofenac sodium is not merely subjective but has a logical scientific basis.

6-Ketoprostaglandin F1 alpha↗

Comparison of chemical analyses of hollow-fiber dialyzer extracts.

Hollow-fiber hemodialyzers containing cellulose-based membranes have been shown to produce positive results with the Limulus amebocyte lysate (LAL) test. This study was undertaken to determine whether endotoxin was causing the reaction. Rinses from 45 parallel-plate and hollow-fiber dialyzers from eight different manufacturers were tested using three lysates and four LAL methods. In addition, four in vitro cellular methods--human leukocytic pyrogen, lymphocytic activating factor, peritoneal macrophage, and arginase release--were used to evaluate endotoxin activity. The substance causing the reaction was identified using chromatographic methods. Results indicate that the LAL-reactive material is cellulose derived and is not pyrogenic.

Arginase↗

Allergy to ethylene oxide in chronic hemodialysis patients.

Almost a decade ago, a single chronic hemodialysis patient in Hamilton, Ontario, Canada, who was experiencing recurrent acute reactions during hemodialysis was found to have become allergic to ethylene oxide gas (EO). This observation recently provided a stimulus to examine the possibility that others exhibiting acute allergic-type reactions during hemodialysis might be similarly sensitized. Serum was obtained from 27 reacting patients and tested in a radioallergosorbent test (RAST) for antibodies to EO. The test was positive for 22 of these sera. EO-related specificity of the antibodies was confirmed. However, EO sensitization was not found in other hemodialysis patients with isolated eosinophilia. In a survey of the current Hamilton chronic hemodialysis population for EO-related antibodies, 9% had a positive allergy skin test and 12% had a positive RAST. The sensitized individuals had no distinctive symptoms. The lesser sensitivity of the skin test contrasts with usual findings in allergic individuals; however, the use of histamine and codeine in chronic hemodialysis and peritoneal dialysis patients might well explain a reduced sensitivity of the EO-related allergy skin test. Chronic peritoneal dialysis could not be invoked as a source of sensitization. None of these patients had a positive skin test or RAST for EO-related antibodies that could be attributed to peritoneal dialysis.

Antibodies↗

Characterization of Limulus amoebocyte lysate-reactive material from hollow-fiber dialyzers.

Hollow-fiber hemodialyzers containing cellulose-based membranes have been shown to produce positive results with the Limulus amoebocyte lysate test. This study was undertaken to determine whether endotoxin was causing the reaction. Rinses from 45 parallel-plate and hollow-fiber dialyzers from eight different manufacturers were tested before and after treatment with cellulase, using three lysates and four Limulus amoebocyte lysate methods. In addition, four in vitro cellular methods--human leukocytic pyrogen, lymphocytic activating factor, peritoneal macrophage, and arginase release--were used to evaluate endotoxin activity. The substance causing the reaction was identified by chromatographic methods. Results indicate that the Limulus amoebocyte lysate reactive material is cellulose derived and not pyrogenic.

Cellulose↗