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Biomedical subjects

E Hill

Publications and source records attributed to E Hill.

At least 55 records · Page 3Linked to original sources
PubMed1997

A novel approach for the quantitative kinetic study of reactions at solid/liquid interfaces in the presence of power ultrasound.

A novel cell and procedure is described which permits the quantitative mechanistic study of ultrasonically enhanced reactions which occur at solid/liquid interfaces. A model of a controlled and calculable time-average rate of mass transport to and from the interface is used in order to compare experimental results with theoretical predictions based on mechanistic reaction schemes. In this way concentrations of mechanistically significant species near the interface can be related to those in bulk solution and hence the sonochemical effects of ultrasound dissected from those arising purely from mass transport. The effect of ultrasound is demonstrated for the reaction dissolution of p-chloranil in the presence of aqueous base and for the reaction of the same substrate with the aromatic amine, N,N-dimethyl-phenylenediamine, both systems which have been studied previously in the absence of ultrasound. Complementary atomic force microscopy images are also reported.

Journal Article↗
PubMed1997

Diagnosis and assessment of depression and suicidality using the NIMH Diagnostic Interview Schedule for Children (DISC-2.3).

The diagnostic Interview Schedule for Children (DISC-2.3) was studied in a sample of 265 adolescent inpatients to determine type and concurrent validity of depressive symptoms and depressive disorder diagnoses for different DISC-2.3 informants (parent, adolescent, both). The Children's Depression Rating Scale--Revised, Reynolds Adolescent Depression Scale (RADS), Suicide Ideation Questionnaire--Junior, Spectrum of Suicide Behavior Scale, and clinical consensus diagnoses were used to assess concurrent validity. Results indicated that (1) parents, compared to adolescents, reported a higher prevalence of all depressive symptoms with the exception of weight change; (2) DISC-2.3 depressive and suicidality symptoms were related positively to independent validating criteria for all informant conditions, suggesting good concurrent validity; (3) the DISC-2.3 both informant condition correctly identified the most depressive disorders; and (4) the parent, but not the adolescent, DISC-2.3 Informant condition contributed to the prediction of clinical consensus diagnoses of depression after taking into account RADS scores.

Adolescent↗
PubMed1996

Immune regulation in Cushing's syndrome: relationship to hypothalamic-pituitary-adrenal axis hormones.

Hormones of the hypothalamic-pituitary-adrenal (HPA) axis are connected closely with immune measures. To investigate whether Cushing's syndrome (CS) is associated with immune dysregulation, we compared the percentage of specific lymphocyte subsets as well as natural cell activity (NKCA) in 48 patients with Cushing's syndrome and 48 age- and sex-matched normal controls. Lymphocyte subset analysis included the percentage of lymphocytes expressing CD3 (total T), CD4 (T helper/inducer), CD8 (T suppressor/cytotoxic) and CD56 (NK cell) antigens. Baseline plasma concentrations of cortisol, ACTH and beta-endorphin as well as 24 h urinary-free cortisol (UFC) levels also were determined. Results indicated a decrease in the percentage of CD4+ cells (p < 0.05), an increase in percentage of CD8+ cells (p < 0.05), a decrease in CD4/CD8 ratios (p < 0.01), and a reduction in NKCA (p < 0.05) in patients with CS compared to matched controls. We also found significant negative correlations between NKCA on the one hand and 24 h UFC (p < 0.05) and plasma beta-endorphin (p < 0.05) on the other. These results indicate there is immune dysregulation in CS patients which can be explained in part by an increase in HPA-axis hormones.

Adrenocorticotropic Hormone↗
PubMed1996

Predictors of comorbid alcohol and substance abuse in depressed adolescents.

OBJECTIVE: To identify clinical profiles discriminating depressed adolescents on the basis of comorbid alcohol/substance use disorders and to determine whether or not profiles with high predictive power are gender-specific. METHOD: One hundred three adolescent inpatients with major depression (65 girls, 38 boys) participated in a comprehensive diagnostic evaluation. Independent assessments of depression, suicidality, and psychosocial adjustment were conducted using well-validated instruments. RESULTS: Gender-specific clinical profiles were identified that predicted alcohol/substance abuse in depressed adolescents with high levels of sensitivity (90%). The significant discriminant function for depressed girls included the following predictors: longer depressive episodes, more conduct problems and psychosocial impairment, and more active involvement in relationships with boys. The significant discriminant function for depressed boys included conduct disorder, older age, and schoolwork problems. These profiles correctly identified most depressed adolescents with comorbid alcohol/substance abuse. CONCLUSIONS: Given that alcohol abuse and depression are associated with highly impaired social functioning and increased risk of self-harm, sensitivity in case identification is critical. Clinicians should conduct comprehensive assessments of alcohol/substance abuse in depressed adolescents with the identified clinical profiles.

Adolescent↗
PubMed1996

Effects of disulfiram on positron emission tomography and neuropsychological studies in severe chronic alcoholism.

Disulfiram is an aldehyde dehydrogenase inhibitor that is widely used as an adjunctive agent in the treatment of patients with severe chronic alcoholism. Recent positron emission tomography (PET) studies of local cerebral metabolic rates for glucose (ICMRglc) and benzodiazepine receptor binding in alcoholic patients have shown regional cerebral abnormalities; however, some of the patients were studied while receiving disulfiram, which could influence the biochemical processes under investigation. In a retrospective investigation, we examined the influence of disulfiram administration on the results of PET studies of ICMRglc and benzodiazepine receptor binding and neuropsychological tests of cognition and executive function in patients with severe chronic alcoholism. [18F]Fluorodeoxyglucose was used to measure ICMRglc in 48 male patients, including 11 receiving and 37 not receiving disulfiram in therapeutic doses. [11C]Flumazenil was used to measure benzodiazepine receptor binding in 17 male patients, including 3 receiving and 14 not receiving disulfiram. All patients studied with FMZ were also examined with fluorodeoxyglucose. PET studies of ICMRglc revealed significantly decreased global values in the patients receiving disulfiram compared with those not receiving disulfiram. PET studies of benzodiazepine receptor binding revealed decreased flumazenil influx and distribution volume in patients receiving disulfiram. The neuropsychological tests demonstrated no differences between the two groups of subjects. The findings suggest that disulfiram may influence the results of PET studies of glucose metabolism and benzodiazepine receptor binding.

Adult↗
PubMed1996

A conceptual model of Army nursing practice.

This conceptual model of Army nursing incorporates all of the components of nursing practice to include research, education and administration. The pyramid of clinical practice emphasizes that Army nursing maximizes the clinical expertise and graduate education of advanced practice nurses while depending on the foundation of traditional nursing.

Clinical Competence↗
PubMed1995

Analysis and quantitation of splicing variants of the TPA-inducible PGHS-1 mRNA in rat tracheal epithelial cells.

Previously we reported that 12-myristate 13-acetate diester (TPA) and dexamethasone regulate the expression of a putative prostaglandin G/H synthase-1 (PGHS-1) gene in a transformed, immortalized rat tracheal epithelial cell line (EGV-6). Here we report the cloning and sequencing of the cDNA for this gene. Two transcripts of similar size but differing in their 5' ends were detected. One transcript contains the complete 5' coding and noncoding regions, while the other form has an apparently intronic sequence in place of these regions. This aberrantly spliced form lacks codons 1-36. Northern analysis and quantitative PCR indicated that more than 90% of the PGHS-1 mRNA in EGV-6 cells has the aberrantly spliced 5' end. TPA treatment increases the expression of only the complete PGHS-1 mRNA, elevating it to 50% of the total PGHS-1 transcript pool. Levels of the aberrant mRNA are not affected by TPA treatment. A comparison among EGV-6 cells, primary rat tracheal epithelial (RTE) cultures, and rat fibroblasts showed that all three cell lines have similar levels of the aberrantly spliced PGHS-1 mRNA. RTE cells and fibroblasts, unlike EGV-6 cells, also contain properly spliced PGHS-1 mRNA, at levels 100-fold higher than the level of aberrant PGHS-1 mRNA. TPA does not regulate either of the PGHS-1 transcripts in RTE or rat fibroblast cells. These results confirm the induction of functional PGHS-1 mRNA by TPA only in EGV-6 cells.

Amino Acid Sequence↗
PubMed1995

Multivariate discriminant function analysis of neurologic, pain, and psychiatric patients with the MMPI.

The ability of the MMPI to classify five well-defined patient groups was investigated (N = 394; control, neurologic, psychiatric, chronic pain, and random). Clinical inspection and discriminant function analyses of basic clinical and research scales could not classify groups correctly, but discriminant function analyses of 37 variables loaded with CNS items (Cripe Neurologic Symptom items) correctly classified the groups with 78% overall accuracy (70% of neurologic, 62% of psychiatric, 81% of pain, 84% of controls, and 100% random). Results indicate that differential diagnosis is not possible with clinical inspection of scales, but complex statistical analysis of the MMPI is potentially useful in diagnosis and decision making. A method for applying the discriminant function analysis to individual cases is provided.

Activities of Daily Living↗
PubMed1994

Eosinophil 15-lipoxygenase is a leukotriene A4 synthase.

5-Lipoxygenase is the first committed enzyme in the leukotriene biosynthetic pathway and is known to catalyze not only the first oxygenation of arachidonate to form 5(S)-hydroperoxyeicosatetraenoic acid (5(S)-HPETE), but also dehydration of this intermediate into leukotriene A4 (LTA4) by an activity termed leukotriene A4 synthase. Inhibition of cytosolic 5-lipoxygenase prepared from human blood granulocytes with zileuton (100 microM) was virtually complete, but LTA4 synthase activity was only inhibited by 47%. Structural characterization of eicosanoids synthesized in these preparations revealed an abundance of 15-lipoxygenase metabolites including 15-HETE when arachidonate was used as substrate and 5(S),15(S)-dihydroxy-6,8,11,13(E,E,Z,Z)-eicosatetraenoic acid when 5(S)-HPETE was used as substrate. When neutrophils were prepared that contained less than 1% eosinophil contamination, zileuton was found to almost completely inhibit all 5-lipoxygenase, as well as LTA4 synthase products. Immunochemical analysis of the supernatants from purified neutrophils and eosinophils confirmed the previous observation that neutrophils do not express 15-lipoxygenase. Incubation of 5(S)-HPETE with recombinant mammalian 15-lipoxygenase resulted in the formation of 6-trans-LTB4 and 6-trans-12-epi-LTB4 as LTA4 products, as well as the 12-lipoxygenase product 5(S),12(S)-diHPETE. The mechanism of action of 15-lipoxygenase acting as an LTA4 synthase is proposed to involve removing the pro-R hydrogen atom at carbon-10 of 5(S)-HPETE, which is antarafacial to the hydroperoxy group to yield LTA4.

Arachidonate 15-Lipoxygenase↗
PubMed1993

Potential for combined therapy with 348U87, a ribonucleotide reductase inhibitor, and acyclovir as treatment for acyclovir-resistant herpes simplex virus infection.

Inhibitors of the ribonucleotide reductase of herpes simplex viruses (HSV) potentiate the activity of acyclovir in vitro and in animal studies. In addition, the combination of the ribonucleotide reductase inhibitor 348U87 and acyclovir has synergistic therapeutic effects against infections in mice due to thymidine kinase-deficient, thymidine kinase-altered, and DNA polymerase mutants of HSV. We performed a pilot study of topical combination therapy with 348U87 (3%) and acyclovir (5%) cream for acyclovir-resistant, anogenital HSV infections in ten human immunodeficiency virus (HIV)-infected patients. Our results, with lack of complete reepitheliazation of lesions in all patients and poor virologic response, suggest that this therapy is unlikely to be useful for this indication.

Acyclovir↗
PubMed1993

Immune function in alcoholism: a controlled study.

Several studies have shown an increased risk for infection and cancer in alcoholic patients. The mechanisms for such observations remain largely unknown. In an effort to investigate the possibility of immunological dysfunction in alcoholism, we studied three immune parameters in 47 hospitalized chronic alcoholic patients and 47 age- and sex-matched normal controls. The immune measures were: (1) lymphocyte phenotyping, with estimates of percentages of T cells, B cells, T helpers, T suppressors, natural killer (NK) cells, and cells carrying the activation markers IL2R1 and I2; (2) NK cell activity; and (3) lymphokine-activated killer cell activity. Results indicate a significant increase in the IL2R and I2 lymphocyte markers in alcoholic patients compared with matched controls. We also found a nonsignificant trend for a decrease in the percentage of suppressor T cells in the alcoholic group, as well as a trend for a negative correlation between the percentage of T suppressor cells and age. There were no significant differences in either NK or lymphokine-activated killer cell activities between the two groups. Furthermore, there were no significant associations between duration and intensity of alcohol consumption and any of the immune measures. These results suggest subtle alterations in immune regulation in alcoholic patients that cannot be explained solely on the basis of duration and/or amount of alcohol consumed.

Adult↗
PubMed1993

Topical treatment of infection with acyclovir-resistant mucocutaneous herpes simplex virus with the ribonucleotide reductase inhibitor 348U87 in combination with acyclovir.

The thiocarbonohydrazone 348U87 inactivates herpes simplex virus ribonucleotide reductase and potentiates the activity of acyclovir against wild-type and acyclovir-resistant strains of herpes simplex virus. We treated 10 human immunodeficiency virus-infected patients with acyclovir-resistant anogenital herpes simplex virus infection with a topical preparation of 348U87 (3%) in combination with acyclovir (5%) in an open-labelled study. Transient improvement with combination therapy occurred frequently; however, target lesions reepithelialized completely in only 1 of 10 patients. Termination of study drug therapy was most often due to cessation of therapeutic effect before complete resolution of lesions. As currently formulated, topical 348U87 offers little therapeutic benefit for this indication.

Acyclovir↗
PubMed1992

Reversible membrane association of neutrophil 5-lipoxygenase is accompanied by retention of activity and a change in substrate specificity.

Ionophore activation of the human polymorphonuclear neutrophil results in eicosanoid synthesis and the accumulation of inactive 5-lipoxygenase in a membrane compartment. We report here that inhibition of self-inactivation of 5-lipoxygenase in ionophore-treated neutrophils with the reversible inhibitor zileuton, results in the accumulation of active 5-lipoxygenase in the membrane fraction. In zileuton plus ionophore-treated cells, 77% of the specific activity of the cytosolic enzyme from resting cells was diverted to the membrane fraction compared to 22% of the activity translocated when ionophore alone was used to activate the neutrophils. Accumulation of active membrane-associated 5-lipoxygenase was inhibited and reversed by the 5-lipoxygenase translocation inhibitor MK-886. The membrane-associated 5-lipoxygenase was two times more efficient in the production of leukotriene A4 from arachidonate-derived 5-hydroperoxyeicosatetraenoic acid than the cytosolic enzyme. Unlike the cytosolic enzyme, membrane-associated 5-lipoxygenase could metabolize 12(S)- and 15(S)-hydroxyeicosatetraenoic acid to 5(S),12(S)- and 5(S),15(S)-dihydroxyeicosatetraenoic acid, respectively. The ability to metabolize hydroxy fatty acids was dependent upon 5-lipoxygenase-activating protein association, but was lost if 5-lipoxygenase was eluted from the membrane by MK-886. These studies reveal for the first time that significant quantities of active 5-lipoxygenase can be detected in the membrane fraction of activated neutrophils and show that membrane association can alter the substrate specificity of 5-lipoxygenase which is further evidence for the role of the membrane-associated enzyme in the synthesis of 5-lipoxygenase metabolites.

Arachidonate 5-Lipoxygenase↗
PubMed1992

Quantitation of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) produced by human polymorphonuclear leukocytes using electron capture ionization gas chromatography/mass spectrometry.

Arachidonic acid can be enzymatically oxidized at the terminal methyl group by the cytochrome P450 system found in several tissues and cells, including the human polymorphonuclear leukocyte. The omega-hydroxy metabolite, 20- hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) has recently been found to have interesting and diverse biological activities. Accurate measurement of quantities of this metabolite using physical chemical methods has not been previously described, but is necessary to assess biosynthesis of this eicosanoid from endogenous arachidonic acid. A procedure is described to quantitate 20-HETE produced by the human polymorphonuclear leukocyte following physiological stimulation using (18O2)carboxy-20-HETE as internal standard. Since the human neutrophil produces relatively small amounts of this eicosanoid, such a study required substantial sensitivity in the quantitative assay. Following stimulation of the neutrophil, cell extracts and supernatants were purified by reverse-phase high-performance liquid chromatography, catalytically reduced then derivatized to the pentafluorobenzyl ester, trimethylsilyl ethers before electron capture ionization gas chromatography/mass spectrometry. Using selected ion monitoring, the amount of 20-HETE present in a biological extract could be detected when as little as 60 pg per sample were available. Following stimulation of the human neutrophil with formyl-methionyl-leucyl-phenylalanine (0.1 microM), platelet activating factor (0.1 microM) as well as with the calcium ionophore A23187 (2 microM), 20-HETE was generated from endogenous arachidonate in concentrations of 1.2, 1.3 and 5.7 pg per 10(6) cells, respectively.

Gas Chromatography-Mass Spectrometry↗
PubMed1992

Biological activity and metabolism of 20-hydroxyeicosatetraenoic acid in the human platelet.

1. The cytochrome P-450 metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE), was found to be a potent, dose-dependent inhibitor of platelet aggregation and inhibitor of thromboxane biosynthesis induced by arachidonic acid (IC50 5.2 +/- 1.5 microM), A23187 (IC50 16.2 +/- 5.4 microM), and U46619 (IC50 7.8 +/- 2.4 microM). 20-HETE did not inhibit thrombin-induced aggregation. 2. The human platelet metabolized 20-HETE to a series of novel metabolites formed by cyclo-oxygenase as well as lipoxygenase pathways. The structures of the metabolites were identified by mass spectrometry as 20-hydroxy-thromboxane B2, 12,17-dihydroxyheptadecatrienoic acid, 12,20-dihydroxyeicosatetraenoic acid, and 11,20-dihydroxyeicosatetraenoic acid. 3. The identification of the 11-hydroxy metabolite of 20-HETE suggests that 20-HETE is less efficiently cyclized to an endoperoxide intermediate by cyclo-oxygenase than is arachidonate. 4. Although some biological activity of 20-HETE may be related to competition with endogenous arachidonate for cyclo-oxygenase metabolism, the predominant mechanism of action of 20-HETE appears to be through antagonism of the prostaglandin H2/thromboxane A2 receptor.

Adult↗