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Biomedical subjects

J Adams

Publications and source records attributed to J Adams.

At least 307 records · Page 17Linked to original sources

Relation between hospital experience and in-hospital mortality for patients with AIDS-related Pneumocystis carinii pneumonia: experience from 3,126 cases in New York City in 1987.

There is marked debate about whether outcomes of care, particularly mortality, vary as a function of hospital and physician experience with a disease. This issue is especially important with respect to AIDS because greater than 200,000 individuals have now been diagnosed with this disease. We analyzed discharge data for 3,126 persons with AIDS who had Pneumocystis carinii pneumonia and who were treated at one of 73 New York City hospitals in 1987. In-hospital mortality was 25%. Factors associated with higher chances of short-term death were older age, being black, not having private health insurance, and being severely ill. A logistic regression model indicated that after controlling for differences in patient and hospital characteristics, the chances of death decreased when care was given at hospitals with higher caseloads of patients with Pneumocystis carinii pneumonia. Our findings suggest that hospital experience may decrease mortality in this subset of patients with human immunodeficiency virus disease, although it is unknown whether this is due to differences in quality of care.

Acquired Immunodeficiency Syndrome↗

Morphologic and physiologic effects of artificial tear formulations on corneal epithelial derived cells.

The biological effects of four commercially available artificial tear formulations were evaluated using sensitive in vitro techniques. Two of the formulations contained ingredients implicated in cell damage; the other two products were not chemically preserved, and their components have not been reported to damage corneal tissue. We assayed the effects of these formulations on viability, morphology, and physiology in corneal cell (SIRC) cultures. Their effect on the hydration of excised rabbit corneas was also determined. In all formulations, cell viability declined with time relative to control cells, but the time course varied significantly. Viability remained at 100% for 6 h in an unpreserved carboxymethylcellulose-based product (CMC-U), and decreased to 50% after greater than 16 hours. Viability decreased to 50% in 3 h for the other unpreserved, polyvinyl alcohol-based product (PVA-U), and in 1 h for a hydroxypropylmethylcellulose formulation (HPMC-P) that contains edetate disodium (EDTA). Cells in a preserved formulation (PVA-P), using polyvinyl alcohol as the polymer and containing EDTA and benzalkonium chloride (BAK), failed to survive even 15 min of treatment. Overall, cells treated with the unpreserved products were nearly indistinguishable from those in the control solution with respect to morphology, electrophysiology, and corneal hydration. Also, the relative ranking from least to most deleterious (control less than CMC-U less than PVA-U less than HPMC-P less than PVA-P) was consistent across several measures. Of the preserved formulations, HPMC-P, which contains the chelating agent EDTA as an additive, was less damaging than was PVA-P, which contains two chemicals, EDTA and BAK, that reportedly damage cells.

Animals↗

Characterization of the binding site for nevirapine (BI-RG-587), a nonnucleoside inhibitor of human immunodeficiency virus type-1 reverse transcriptase.

Nevirapine (BI-RG-587) is a potent and specific non-nucleoside inhibitor of human immunodeficiency virus type-1 reverse transcriptase. The compound is non-competitive with respect to template, primer, and nucleoside triphosphates indicating that BI-RG-587 does not act directly at the catalytic site. The binding site for this inhibitor was investigated by employing an azido photoaffinity analogue, BI-RJ-70, to covalently label the enzyme. The resulting photoadduct was subjected to enzymatic digestion by trypsin and endoproteinase lys-C and a single, highly labeled peptide was identified as residues 174-199. Sequencing of this peptide identified Tyr-181 and Tyr-188 as labeled residues.

Affinity Labels↗

Role of nitric oxide in lysis of tumor cells by cytokine-activated endothelial cells.

The purpose of these studies was to determine whether nitric oxide produced by cytokine-activated murine lung vascular endothelial cells plays a role in their lytic destruction of M-5076 reticulum cell sarcoma. Vascular endothelial cells harvested from perfused lungs of mice were adapted to grow in culture. Cloned lines ascertained to be of endothelial origin were incubated in vitro with interferon gamma and tumor necrosis factor. Lysis of radiolabeled tumor cells and accumulation of nitrite in the culture medium were determined at several time points. The concentration of nitrite in the culture medium directly correlated with endothelial cell-mediated tumor cell lysis. Endothelial cells cultured in L-arginine-free medium did not produce significant tumor cell lysis nor accumulation of nitrite in the medium. Both tumor cell lysis and nitrite accumulation were observed when the deficient medium was reconstituted with L-arginine, suggesting that endothelial cell-mediated tumor lysis was dependent on L-arginine, a precursor of nitric oxide. Moreover, specific inhibition of nitric oxide synthesis by NG-methyl-L-arginine resulted in complete inhibition of endothelial cell-mediated lysis of the M-5076 reticulum cell sarcoma. Similarly, treatment of cytokine-activated endothelial cells with dexamethasone inhibited both target cell lysis and production of nitrite. Collectively, these results suggest that nitric oxide plays a major role in the lysis of tumor cells mediated by cytokine-activated endothelial cells.

Animals↗

A novel dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a nonsubstrate binding site.

A novel dipyridodiazepinone, 6,11-dihydro-11-cyclopropyl-4-methyldipyrido[2,3-b:2',3'-e]- [1,4]diazepin-6-one (BI-RG-587), is a selective noncompetitive inhibitor of HIV-1 reverse transcriptase (RT-1). An azido photoaffinity analogue of BI-RG-587 was synthesized and found to irreversibly inhibit the enzyme upon UV irradiation. BI-RG-587 and close structural analogues competitively protected RT-1 from inactivation by the photoaffinity label. A thiobenzimidazolone (TIBO) derivative, a nonnucleoside inhibitor of RT-1, also protected the enzyme from photoinactivation, which suggests a common binding site for these compounds. Substrates dGTP, template-primer, and tRNA afforded no protection from enzyme inactivation. A tritiated photoaffinity probe was found to stoichiometrically and selectively label p66 such that 1 mol of probe inactivates 1 mol of RT-1.

Affinity Labels↗

A catalytic antibody uses a multistep kinetic sequence.

Antibody NPN43C9 catalyses the hydrolysis of a p-nitrophenyl ester and p-nitroanilide. Kinetic investigations show that hydrolysis of the ester involves at least two steps whose relative importance changes with pH. We propose that the reaction proceeds via formation of an acyl intermediate that deacylates through attack by hydroxide. The rate-limiting step changes from product release at high pH to hydroxide ion-mediated hydrolysis at low pH. This multistep pathway shares similarities with that used by serine proteases.

Antibodies↗

Plasmid macro-evolution: selection of deletions during adaptation in a nutrient-limited environment.

Under conditions where plasmid-carriage is deleterious to the cell, evolutionary changes may be expected which result in an attenuation of the deleterious effect of the plasmid. During long-term growth in glucose-limited continuous culture, initiated with a single clone of Escherichia coli containing a derivative of the plasmid pBR322, a structural change arose in the plasmid and predominated in the plasmid-containing sector of the population. This variant possessed a 2.25 kb deletion encompassing the tetracycline resistance operon as well as a region of about 1.5 kb upstream from this operon. Competition experiments involving strains carrying the plasmid with the spontaneous deletion, and strains carrying plasmids with artificially constructed deletions, revealed that deletion of this region of the plasmid, involving loss of tetracycline resistance, resulted in an increment in fitness of between 10 and 20%. From the magnitude of the growth advantage, we conclude that the attenuation of the deleterious effect of the plasmid was mainly due to a reduction in the plasmid mediated interference in the metabolism of the cell caused by a deletion of the tetracycline resistance gene.

Adaptation, Physiological↗

Screening for vertebral osteoporosis using individual risk factors. The Multicentre Vertebral Fracture Study Group.

Osteoporosis is a major cause of ill health in postmenopausal women. Several risk factors for osteoporosis have been identified, and they have been widely recommended as a means of identifying subgroups of postmenopausal women who might benefit from prophylaxis and therapy. Evidence to support this use of risk factors is currently lacking, however. We have constructed and evaluated a profile of putative risk factors as a means of identifying women attending general practitioners who have sustained vertebral fractures. The overall prevalence of vertebral fractures in the 1012 women (mean age 64.4 years) studied was 7.8%. Women who had sustained vertebral fractures in this population were significantly (p less than 0.05) older and shorter than those without fractures. They reported a significantly (p less than 0.05) earlier menopause, lower parity and a greater prevalence of hyperthyroidism. However, the best screening instrument devised was not sufficiently predictive to warrant widespread use.

Aged↗

Cysteine usage increases the need for acetate in neonates who receive total parenteral nutrition.

The addition of cysteine (as cysteine HCl) to a total parenteral nutrition (TPN) solution enhances calcium and phosphate solubility because cysteine lowers the pH of the solution. To determine whether adding cysteine to TPN solutions affected the acid-base homeostasis of infants and increased their need for acetate to obviate acidosis, we studied two groups of neonates--those receiving TPN before (group C) and after (group NC) the addition of cysteine. Measurements were made before and during the first 2 wk of TPN administration. We measured the pH of our standard TPN solution with and without the addition of cysteine. Serum carbon dioxide was significantly lower in group C despite a significantly greater intake of acetate in group NC. In the in vitro study the addition of cysteine to the TPN solution lowered the pH from 5.5 to 5.1. Newborns who received TPN solutions to which cysteine was added had lower serum carbon dioxide values and a greater need to receive acetate than did newborns who received TPN solutions without cysteine.

Acetates↗

Inhibition of human immunodeficiency virus type 1 (HIV-1) replication by the dipyridodiazepinone BI-RG-587.

The dipyridodiazepinone human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitor BI-RG-587 was tested for its ability to inhibit HIV-1 replication in both acutely and chronically infected cell lines. The ability of BI-RG-587 to inhibit steps in the virus replicative cycle other than reverse transcription was also assessed. BI-RG-587 was found to be a potent inhibitor of HIV-1 replication in acutely infected cells (50% inhibitory concentration [IC50] = 37.2 nM), and the sensitivity and kinetics of that inhibition was similar to the known RT inhibitor zidovudine (AZT). Even at 100x IC50, BI-RG-587 had no effect on gp120/CD4 interaction, syncytia formation, or envelope glycoprotein processing. In addition, no inhibition of viral replication or protein production was noted in a chronically infected cell line that produces viral products in an RT-independent manner. Finally, no inhibition of acute HIV-2 replication was noted, even with very high (2500x IC50 for HIV-1) concentrations of BI-RG-587. These results demonstrate that BI-RG-587 is a potent inhibitor of HIV-1 replication and that this inhibition occurs at the point of reverse transcription.

Antiviral Agents↗

Identification of adaptive changes in an evolving population of Escherichia coli: the role of changes with regulatory and highly pleiotropic effects.

A population of Escherichia coli initiated with a single clone developed extensive morphological and physiological polymorphism after being maintained for 773 generations in glucose-limited continuous culture. To understand the mechanisms of adaptation to this environment, total protein patterns of four adaptive clones and of the parent strains were examined by two-dimensional gel electrophoresis. Approximately 20% of the proteins (approximately 160 in absolute numbers) showed significantly different levels of expression in pairwise comparisons of parent and adapted clones. The extent of these changes points to the importance of mutations with regulatory and/or highly pleiotropic effects in the adaptive process. The four evolved clones all expressed fewer proteins than did the parent strain, supporting the hypothesis of energy conservation during evolutionary change. Forty-two proteins that could be assigned to known cellular functions were identified. The changes in some of them indicated that the evolved clones developed different adaptive mechanisms to glucose-limited environment. Changes were observed in the expression levels of proteins associated with translation, membrane composition, shock response, and active transport. A fraction of the changes could not be either explained or predicted from a consideration of the nature of the environment in which the clones evolved.

Adaptation, Biological↗

Juvenile spring eruption of the ears: a probable variant of polymorphic light eruption.

We report 18 cases in which a pruritic, erythematous, papular and vesicular eruption developed on the ears following sun exposure. Four of these patients had, on other occasions, suffered from typical polymorphic light eruption. The clinical features, histological changes, and results of phototesting suggest that juvenile spring eruption of the ears is a localized form of polymorphic light eruption.

Adolescent↗

Life events, depression, and perceived problem solving alternatives in adolescents.

The association between negative life events and depression may be mediated by adolescents' sense of competency in solving problems. This study investigated (a) the relationship between troublesome life events and level of depression and (b) the association between level of depression and adolescents' perceived problem solving alternatives, in 135 tenth graders. The specific life events of "unemployment of a family member", "starting at a new school", and "breaking up with a boy/girlfriend", were associated with higher levels of depression. In addition, higher levels of depression were associated most consistently with the perceived alternatives of getting intoxicated and of isolating oneself in response to a variety of problems. Further research is needed to clarify both the extent to which depression influences adolescents' responses to negative life events and leads to poorer problem solving choices, and the degree to which negative life events and the lack of constructive problem solving alternatives increase the risk of depression.

Adaptation, Psychological↗

Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age.

An investigation as to whether any particular subgroup of patients with Hodgkin's disease was particularly likely to be Epstein-Barr virus (EBV) genome positive was made on samples from 95 patients. These were grouped according to age and Hodgkin's disease subtype, and analysed using Southern blot analysis. Most samples from children or adults aged 50 years or over contained detectable EBV genomes; samples from young adults were only rarely positive. The differences in EBV positivity by age were highly significant, but there was no significant association between EBV and histological subtype after allowing for the effect of age. The results support the hypothesis that Hodgkin's disease in different age groups may have different aetiologies, and suggest that EBV does have a pathogenetic role in Hodgkin's disease in children and older age groups.

Adolescent↗

Operation, formulary decision-making activities of a P & T Committee in a managed care setting.

Managing drug benefits in a Health Maintenance Organization (HMO) is perhaps best accomplished through a formulary, as demonstrated by Kaiser Permanente of Colorado. According to Dr. Jim Adams and Ms. Jackie Richardson, the Chairman and Secretary, respectively, of Kaiser Permanente's P & T Committee, since the advent of their formulary only a few years ago, the cost of drugs has been kept well under control, without jeopardizing the quality of care. Both physician and patient education are critical to the success of a formulary in a managed care system--both monumental tasks for Kaiser Permanente of Colorado considering that prescribers exceed 300 and the number of patients they treat approaches 250,000. What is clear in this exclusive Hospital Formulary interview is that HMOs--long recognized for their ability to control costs--can also provide quality health care for patients who use their facilities.

Colorado↗