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Biomedical subjects

D K Miller

Publications and source records attributed to D K Miller.

At least 109 records · Page 6Linked to original sources

Identification and isolation of medicarpin and a substituted benzofuran as potent leukotriene inhibitors in an anti-inflammatory Chinese herb.

In a search for new inhibitors of leukotriene formation, a methylene chloride extract of the plant Dalbergia odorifera (Jiangxiang) was found to be a potent inhibitor of LTC4 formation in AB-CXBG Mct-1 mastocytoma cells. Following LH-20 and reverse phase HPLC chromatography, two compounds were isolated that had potent LTC4 inhibitory activity: medicarpin and 6-hydroxy-2-(2-hydroxy-4-methoxyphenyl) benzofuran (IV) with IC50s of 0.5 and 0.05 microM respectively. IV was shown to be a specific inhibitor of 5-lipoxygenase with an IC50 against the soluble rat enzyme of 0.08 microM, whereas it was inactive against cyclooxygenase. In neutrophils IV inhibited LTB4 production at comparable concentrations but had no effect on neutrophil degranulation or adhesion.

Animals↗

Auto anti-M. Clinical and serologic findings of seven patients from one hospital and review of the literature.

Auto-anti-M antibodies are not commonly documented serologically. A review of the literature reveals only ten cases with no consistent clinical or laboratory findings. In their institution, over a 12-year period, the authors have identified this autoantibody in seven patients, suggesting that it may not be such a rare entity but rather may be underdiagnosed. In this article the authors describe the pertinent clinical and serologic findings in their seven patients, as well as review the salient features of the previously reported cases.

Adult↗

[Treatment of morbid obesity by gastric bypass. Apropos of 1158 cases treated surgically].

After defining pathological obesity and describing the technical methods used for gastric bypass, a series of 1158 surgical cases is analysed. Discussion, supported by a review of the literature, involved post-operative mortality and morbidity, mid-term results and patient selection criteria. In the light of the results obtained, it would no longer appear justified to offer this type of surgical procedure.

Adolescent↗

Graphical aid for determining power of clinical trials involving two groups.

Physicians need to evaluate clinical research critically, and determining the power of a study is an essential component of research evaluation. This report presents a graphical aid that permits rapid power determination for clinical trials with two groups. Power curves were developed for dichotomous outcomes by setting two tail alpha at 0.05 and varying the sample size, the control group response rate, and the clinically important difference between control and experimental groups as defined by the user. Use of the graphical aid was demonstrated to a group of 18 medical students, residents, fellows, and faculty in a 15 minute session. Evaluation of the trainees' application of the aid showed a small average bias of -0.0003 and an average variance of 0.006. Ninety percent of power estimates were within 0.05 of the true value determined by formula. This graphical aid is recommended as a rapid and accurate method for determining power in the critical appraisal of clinical research.

Clinical Trials as Topic↗

Development of a high capacity microassay for measurement of neutrophil adhesion.

A high capacity semiautomated assay for neutrophil adhesion was developed utilizing the 96 well microtiter plate format. Optimal adhesion occurred with about 150 microliters/well of neutrophils at 5 X 10(6) cells/ml in tissue culture plates that had been precoated with 5% serum. Optimal incubation times were 10 min for f-Met-Leu-Phe-treated cells and 20 min for A23187 or phorbol myristate acetate stimulation. Optimal washing occurred after three washes with a Cetus Pro/pette pump. Adhesion could be effectively blocked by the inhibitors of cellular protein kinase C, an enzyme known to be necessary for the occurrence of neutrophil adhesion.

Alkaloids↗

Cyclic AMP-dependent regulation of lipid mediators in white cells. A unifying concept for explaining the efficacy of theophylline in asthma.

Activation of white cells, including the neutrophil, eosinophil, basophil, and mast cell, has long been known to be suppressed by high, nonphysiological levels of E-prostaglandins (PGE). In contrast, PGE at levels consistent with an interaction with the PGE receptor (5 X 10(-9) M) have recently been shown to suppress leukotriene (LT) and prostaglandin (PG) production by neutrophils and eosinophils. This occurs by cyclic AMP-dependent inhibition of release of substrate arachidonic acid (AA) from phospholipid pools. The additional observation that indomethacin (10(-9) M) enhances release of eicosanoids by suppressing endogenous PGE2 acting to increase cAMP levels in these cells. Theophylline and other phosphodiesterase inhibitors precisely duplicate the action of PGE2, and the combined effects of such phosphodiesterase inhibitors and adenylate cyclase stimulators are synergistic. The mechanism of action of theophylline in asthma is not know, although it is generally agreed that its effect is a direct one on the bronchial smooth muscle. The findings described in this report now permit the bronchial smooth muscle, but is primarily one of suppressing mediator release from relevant white cells by inhibition of cAMP phosphodiesterase, an action that is enhanced by the presence of inflammatory prostaglandins in the lung.

Animals↗

Pregnancy after gastric bypass for morbid obesity.

There has been only one previous report on pregnancies following gastric bypass for the treatment of morbid obesity. In this study 57 such pregnancies were compared to a group of control pregnancies occurring in morbidly obese women before their bypass surgery. There was a significantly lower incidence of hypertension and large-for-gestational-age infants in the postoperative pregnancies. There was no significant difference in a number of other pregnancy complications studied.

Birth Weight↗

Further characterization of the glycoproteins and glycosaminoglycans released from TA3 murine adenocarcinoma cells in culture.

TA3 murine ascites adenocarcinoma cells were compared for their ability to release radioactive glucosamine and 35SO4-labeled glycoproteins and glycosaminoglycans into the culture medium. Both TA3-Ha and TA3-St cells contained cell-surface heparan sulfate that was released into culture, but not chondroitin sulfate. Both cells released a membranous aggregate of labeled components from the cell surface and hyaluronic acid from inside the cells that fractionated in the void volume of Sepharose CL-4B. This void-volume fraction from the TA3-Ha cells contained glucosamine-labeled epiglycanin at a higher concentration relative to other glucosamine-labeled components than that found on plasma membranes. Glycoproteins associated with epiglycanin found on the cell surface, as well as released into culture medium, contained sulfate that could not be removed by chondroitinase ABC, heparinase, or keratinase. Kinetic analysis of the glucosamine-labeled material released from TA3-Ha cells indicated that hyaluronic acid was released rapidly with a 45-min half-life, whereas the other membranous components were released much more slowly.

Adenocarcinoma↗

Gastric tuberculosis: a manifestation of acquired immunodeficiency syndrome.

A Haitian man with acquired immunodeficiency syndrome (AIDS), fever, malaise, and diarrhea is described. A computed tomographic (CT) scan showed a retrogastric mass with an associated ulcer. An upper gastrointestinal tract study showed an ulcer with both benign and malignant features. Endoscopy revealed a malignant-appearing ulcer, but cultures and histologic examinations of surgical biopsy specimens indicated gastric tuberculosis. The relationship between tuberculosis and AIDS is discussed.

Acquired Immunodeficiency Syndrome↗

Further assessment of the reliability and validity of a Nutritional Risk Index: analysis of a three-wave panel study of elderly adults.

This paper reports on the further assessment of the reliability and validity of a short (16-item), portable method for assessing nutritional risk which is easily administered in the typical social survey setting. Data were obtained from a three-wave panel study of 401 randomly selected, noninstitutionalized elderly persons (age 65 and over) in St. Louis. Reliability was assessed by both internal consistency and test-retest methods. Reliability coefficients (internal consistency) of .603, .544, and .515 were obtained at T-1, T-2, and T-3, respectively. Cross-panel intercorrelations (test-retest) ranged between .67 and .71. Validity was assessed using factor analysis and various outcome measure comparisons for those at risk versus those not at risk. A five-factor orthogonally rotated solution explained 47.9 percent of the variance in the 16 items. Individuals with higher risk scores had significantly poorer health as measured by other standard indexes, and used significantly more health services than those with lower risk scores. These results underscore the potential of the Nutritional Risk Index (NRI) as a screening device for use among the elderly.

Activities of Daily Living↗

Development of enzyme-linked immunosorbent assays for measurement of leukotrienes and prostaglandins.

Enzyme-linked immunosorbent assays (ELISAs) were developed for the leukotrienes LTC4 and LTB4 and the prostaglandins 6-keto PGF1 alpha and thromboxane (TxB2). In an indirect assay procedure for all 4 eicosanoids a BSA conjugate of the leukotrienes or an ovalbumin conjugate of the prostaglandins was absorbed to polystyrene microtiter plates. Samples containing the respective eicosanoids were incubated in the coated wells with specific rabbit antisera. The wells were then incubated successively with a goat anti-rabbit antibody linked to fluorescein and a rabbit anti-fluorescein antibody linked to alkaline phosphatase. The resultant assays for LTC4, LTB4, 6-keto PGF1 alpha, and TxB2, gave steep, sensitive inhibition curves; IC50s were 0.2, 10, 1, and 0.4 pmol respectively with minimal cross-reactivity to other eicosanoids. The sensitivities and specificities were comparable to those found in the RIA, and the levels determined in this assay correlate well with those determined in non-immunological assays.

6-Ketoprostaglandin F1 alpha↗

Endothelial cell prostacyclin production induced by activated neutrophils.

A bovine aortic endothelial cell (EC) line released prostacyclin (greater than 1 pmol/10(+5) EC cells) when incubated with fMet-Leu-Phe (FMLP)-stimulated rat and human neutrophils (PMNs). This prostaglandin (PG) I2 was shown to come from the ECs and not from the PMNs by radioactive, high-performance liquid chromatography, and immunochemical criteria. Both FMLP-stimulated rat peritoneal and human peripheral PMNs as well as their stimulated cell-free supernatants and unstimulated sonicates could elicit the release of PGI2 from ECs. Since phorbol myristate acetate stimulated PMN adherence but elicited little PGI2 release from ECs, the PGI2 stimulation in ECs is unrelated to PMN adhesion. The addition of catalase and superoxide dismutase to FMLP-stimulated PMNs enhanced rather than reduced PGI2 formation, indicating that activated oxygen products of the PMN are not responsible for the induction of PGI2. Incubation of ECs with leukotriene (LT) B4, LTC4, or LTD4 did not trigger PGI2 release nor did aspirin pretreatment of the PMNs reduce the PGI2 induction. These data suggest that arachidonic acid metabolites of the PMNs were not responsible for the PGI2 induction. Available data indicates that the PMN factor that stimulates PGI2 from ECs is either released concomitantly with the azurophilic granules or is closely related to this event.

Animals↗

Correlates of change in subjective well-being among the elderly.

This study examines two related issues concerning the subjective well-being of elderly adults: change over time and correlates of that change. Data come from a three-wave panel study of 401 elderly residents in St. Louis. Residualized change score regression analyses indicate: there is change in subjective well-being over 4-5 months and over 12 months; the 4-5 month and 12 month changes are remarkably similar; the effect of subjective well-being over time indicates regression to the mean; and, only socioeconomic status is a significant predictor of change in subjective well-being (net of the effects of subjective well-being itself). The implications of these results for our understanding of subjective well-being in the elderly are discussed, as are the policy implications of the positive effect of socioeconomic status on changes in the subjective well-being of the elderly.

Aged↗