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Biomedical subjects

D Reed

Publications and source records attributed to D Reed.

At least 91 records · Page 5Linked to original sources

Prediction of outcome after mitral valve replacement in patients with symptomatic chronic mitral regurgitation. The importance of left atrial size.

BACKGROUND: The ability to predict outcome after mitral valve replacement remains limited in patients with symptomatic chronic mitral regurgitation. The aims of this study were to determine the preoperative predictors of postoperative cardiac-related mortality and to assess the additive prognostic value of tests performed in such patients. METHODS AND RESULTS: Accordingly, 176 patients (mean age, 57 +/- 14 years) who underwent mitral valve replacement were followed up for 3.8 +/- 0.5 years. Four categories of variables were analyzed to predict postoperative cardiac-related mortality: clinical, laboratory, two-dimensional echocardiographic (2DE), and cardiac catheterization. There were 39 cardiac-related deaths (29 due to congestive heart failure and 10 sudden). When the four categories were analyzed separately, two clinical, one laboratory, two 2DE, and one catheterization variable best predicted postoperative death. When these six variables were examined simultaneously, only three (one clinical and two 2DE) remained significant predictors of cardiac-related mortality: presence of pulmonary rales, left atrial size, and the ratio of left ventricular wall thickness to left ventricular cavity dimension in end systole. A model based on these three variables may predict cardiac-related death with considerable accuracy. Laboratory data did not add to clinical information for predicting death. 2DE variables provided significant additional information in this regard (p less than 0.001). Further addition of catheterization variables was not useful. Prognostic value did not change significantly when 50 patients with prior mitral valve surgery or 49 patients undergoing concomitant aortic valve replacement or coronary artery bypass surgery were excluded from analysis. CONCLUSIONS: We conclude that 1) measures of both left ventricular systolic function and left atrial size are equally important in predicting postoperative cardiac-related mortality in patients with symptomatic chronic mitral regurgitation undergoing mitral valve replacement; 2) left atrial size may be important because it reflects the "history" (severity and duration) of mitral regurgitation; 3) 2DE assessment of left atrial size and left ventricular function provides prognostic information that is significantly greater than that obtained from clinical and laboratory parameters alone; the addition of catheterization variables does not increase the prognostic value of the clinical and 2DE data.

Atrial Function, Left↗

Does cigarette smoking have an independent effect on coronary heart disease incidence in the elderly?

In order to evaluate the effects of cigarette smoking on coronary heart disease (CHD) in elderly persons in the Honolulu Heart Program, 1,394 men between ages 65 and 74 were followed during an average 12-year period for new cases of nonfatal myocardial infarction and fatal CHD. Incidence rates increased progressively in individuals classified at baseline as never, former, and current smokers, respectively. The absolute excess risk associated with cigarette smoking was nearly twice as high in elderly compared with middle-aged men.

Aged↗

Sequence of rat alpha 1-macroglobulin, a broad-range proteinase inhibitor from the alpha-macroglobulin-complement family.

The alpha-macroglobulin-complement family of plasma proteins includes at least three different alpha-macroglobulins in rats, alpha 2-macroglobulin (alpha 2M), alpha 1 inhibitor III (alpha 1I3), and alpha 1-macroglobulin (alpha 1M). These high molecular weight polypeptides (Mr 160,000 to 200,000) are broad-range proteinase inhibitors. They utilize an internal thiolester function to trap proteinases that cleave their bait regions. The amino acid sequences of alpha 2M and two variants of alpha 1I3 are known. The isolation of alpha 1M cDNA clones and the determination of their cDNA and derived amino acid sequences are reported here. Alpha 1M shares 57.2% and 53.0% overall amino acid sequence identity with alpha 2M and alpha 1I3, respectively, but differs significantly from both in its bait region, suggesting that each inhibitor addresses a different spectrum of proteinases. The disulfide bridge structure of alpha 1M was deduced from its sequence and showed extensive similarities with the experimentally determined structures of other alpha-macroglobulins, suggesting similar overall tertiary structures. Alpha 1M mRNA was detected in 13 different rat tissues tested, whereas alpha 2M and alpha 1I3 mRNAs showed a far more restricted tissue distribution. While alpha 2M and alpha 1I3 mRNA and protein concentrations are significantly altered during acute and chronic inflammations, alpha 1M plasma concentrations are changed only twofold. Thus, in contrast with alpha 2M and alpha 1I3, the functions provided by alpha 1M may be ubiquitously and constitutively required in a broad range of tissues.

Amino Acid Sequence↗

Physicians' prognoses about the quality of life for infants with intraventricular hemorrhage.

There is an absence of definitive information concerning the long-term outcome of children born with intraventricular hemorrhage (IVH). Physicians, however, are called on to prognosticate about the future quality of life of these children. Our study examined pediatricians' and neonatologists' prognoses for infants with grade I- and grade-IV IVH and the impact of those prognoses on recommendations for treatment. A national random survey of 289 pediatricians and 283 neonatologists found that both groups expected infants with grade-I IVH to have slight impairments to future development, whereas infants with grade-IV IVH were expected to have severe impairments. Physicians prognosticated that infants with grade-IV IVH would function at a moderate to severe level of mental retardation, incapable of any employment, and residing in an institution. Furthermore, physicians would encourage parents to seek medical treatment of respiratory distress for the infant with grade-I IVH but were neutral or would discourage parents from seeking treatment for the infant with grade-IV IVH. Lastly, physicians' prognoses were significantly related to their recommendations for treatment. Several differences in physicians' prognoses and recommendations were found to be related to their discipline and training.

Adult↗

Characterization of ovarian follicular fluids of sheep, pigs and cows using proton nuclear magnetic resonance spectroscopy.

Proton NMR spectra were produced for Graafian follicular fluids obtained by aspiration from sheep, pig and cow ovaries. The following low molecular mass, non-protein-bound metabolites were detected at concentrations exceeding 0.1 mM: acetate, alanine, creatinine/creatine, glycine, D-3-hydroxybutyrate, lactate, valine. Glucose was difficult to quantify and N-acetyl sugars gave a broad resonance at 2.06 ppm, presumably representing side-chains of glycoproteins. Ethanol was detected at up to millimolar concentrations in some specimens, though the physiological significance of this finding was not clear. The concentrations of all metabolites were comparable to those of plasma. These results have therefore shown that NMR spectroscopy is useful for gaining a broad and semiquantitative impression of the more abundant metabolites in the fluids of preovulatory Graafian follicles.

3-Hydroxybutyric Acid↗

Is elevated serum cholesterol level a risk factor for coronary heart disease in the elderly?

Since serum cholesterol is a major component in the causal pathway of atherosclerosis, a pathological process that usually progresses with age, we have evaluated reported findings of a diminished association between serum cholesterol level and coronary heart disease in the elderly. In the Honolulu (Hawaii) Heart Program, 1480 men aged 65 years and older and free of coronary heart disease were followed up for an average of 12 years. Incidence rates of coronary heart disease increased progressively from the lowest to the highest quartile of serum cholesterol level. The independent role of serum cholesterol level as a predictor of coronary heart disease risk was evaluated with other major risk factors using a Cox multivariate regression model. The upper-lower quartile relative risk for serum cholesterol level was 1.64 (95% confidence interval, 1.14 to 2.36). The relative risk for middle-aged men was also 1.64. The results suggest that serum cholesterol level is an independent predictor of coronary heart disease, even among men older than 65 years. Thus, an elevated serum cholesterol level in the elderly should be regarded, as in middle-aged men, to be an indicator for further evaluation of lipoprotein levels and possible intervention.

Aged↗

Antibodies to Aujeszky's disease virus in pigs immunized with purified virus glycoproteins.

Antibodies to Aujeszky's disease virus (ADV) glycoproteins gII, gIII, and gp50 were compared using four in vitro tests. Antibodies generated by vaccination with a modified-live vaccine (MLV) were also compared. The serological assays employed were: serum neutralization test (SNT), complement facilitated serum neutralization test (C'SNT), complement-mediated cytolysis and antibody dependent cellular cytotoxicity (ADCC). Pigs were immunized with single glycoproteins twice 14 days apart, or once with the modified-live vaccine. Fourteen days after the second immunization, sera were collected. Virus neutralizing activity (SNT) was demonstrated in the sera from all pigs immunized with gp50 and in one out of three immunized with gIII. Sera from the MLV group all had neutralization titers higher than animals immunized with single glycoproteins. Addition of guinea pig complement to the serum neutralization test (i.e., C'SNT) produced an enhancement of antibody titers in all groups except the pigs immunized with gIII. The complement-mediated cytolysis test rendered antibody titers similar in magnitude for all pigs immunized with single glycoproteins, but slightly lower than values for MLV vaccinated pigs. ADCC activity was clearly displayed in sera from pigs immunized with gIII or vaccinated with MLV, whereas sera from pigs immunized with gII or gp50 had a minimal response. The results indicate that the relative efficiency of antibodies against ADV glycoproteins in protection should be considered for selecting or producing gene-deleted strains for use in vaccine production.

Animals↗

Molecular similarity of Drosophila melanogaster alcohol dehydrogenase thermostable alleles from populations on different continents.

Allele specific oligonucleotide probes have been used to show that DNA, amplified by the polymerase chain reaction, from eleven thermostable Adh alleles extracted from populations on different continents contains the triplet TCC, which distinguishes AdhFChD (Fast Chateau Douglas) from AdhF (Fast). The molecular similarity of Adh thermostable alleles suggests that they had a common origin, and it is argued that the mutation probably occurred in China where high frequencies of AdhFChD are found.

Alcohol Dehydrogenase↗

Bovine serological response to a recombinant BPV-1 major capsid protein vaccine.

Four of five groups of Holestine by Angus calves (5 calves/group) were immunized with different formulations of a recombinant BPV-1 DNA vaccine using a BPV-1 major capsid:B-galactosidase fusion protein as the immunogen. Group 5 was not vaccinated. Vaccinated calves received the vaccine on days 0 and 21 of the trial, and calves from all five groups were challenged intradermally with 10(10) BPV-1 particles at each of two different sites on day 56. All calves were bled on days 3, 24, 55, 77, and 104 of the trial, and the sera were tested for reactivity with intact and disrupted BPV-1 particles by ELISA. At the time of challenge with BPV-1 virions (day 56), 19 of 20 vaccinated calves were seropositive for disrupted BPV-1 particles; sera from 3 of 20 calves reacted with intact BPV-1 virions. By day 77, 11 of 19 vaccinated calves had developed antibody titers to intact BPV-1 virions; only 1 calf in group 5 developed antibodies (transiently) against BPV-1 capsid epitopes. After challenge, 24 of 25 calves from the five groups developed intradermal fibromas, the biological end point of this study. Fibromas appeared to increase in size in group 5 (unvaccinated, inoculated controls), whereas most tumors from the four vaccinated groups (1-4) stabilized or decreased in size. Although the calves developed fibromas, 90% of calves (in groups 1-4) developed antibodies against disrupted BPV-1 capsid proteins whereas 58% developed antibodies that reacted with intact virions. The immunologic response of vaccinated calves to intact and disrupted BPV-1 particles appeared to be determined in large part by the various formulations of the vaccine, particularly the adjuvant.

Animals↗

Response bias in the Honolulu Heart Program.

The 14-year incidence rates (1969-1982) for coronary heart disease, cerebrovascular disease (stroke), total mortality, and cause-specific mortality were compared between 8,006 examined and 3,130 nonexamined men of the Honolulu Heart Program using identical surveillance procedures. There was a significant decrease in examination participation with increasing age. Examined men smoked less, weighed more, had a higher level of education, and had a lower percentage of never-married status than did nonexamined men. Total mortality rates, cancer mortality rates, and coronary heart disease incidence rates were higher in nonexamined men, while there were no differences in stroke rates. The average annual response error for total mortality and coronary heart disease rates was underestimated at 8.7% and 5.4%, respectively. The differences in rates were greatest during the first half of the follow-up period and converged during the second half. By the end of 10 years, there were no differences between nonexamined and examined men for any of the endpoints studied. The pattern of convergence of rates suggests a diminishing healthy participant advantage over time. In conclusion, a response bias did occur in this study, but the effect was small and did not alter any of the earlier findings concerning the relative incidence of cardiovascular disease. Because the degree of response bias can vary widely depending on when during follow-up a particular analysis is undertaken, it is recommended that prospective studies monitor, insofar as possible, a sample of nonparticipants in order to ensure valid results.

Aged↗

Nostoc commune UTEX 584 gene expressing indole phosphate hydrolase activity in Escherichia coli.

A gene encoding an enzyme capable of hydrolyzing indole phosphate was isolated from a recombinant gene library of Nostoc commune UTEX 584 DNA in lambda gt10. The gene (designated iph) is located on a 2.9-kilobase EcoRI restriction fragment and is present in a single copy in the genome of N. commune UTEX 584. The iph gene was expressed when the purified 2.9-kilobase DNA fragment, free of any vector sequences, was added to a cell-free coupled transcription-translation system. A polypeptide with an Mr of 74,000 was synthesized when the iph gene or different iph-vector DNA templates were expressed in vitro. When carried by different multicopy plasmids and phagemids (pMP005, pBH6, pB8) the cyanobacterial iph gene conferred an Iph+ phenotype upon various strains of Escherichia coli, including a phoA mutant. Hydrolysis of 5-bromo-4-chloro-3-indolyl phosphate was detected in recombinant E. coli strains grown in phosphate-rich medium, and the activity persisted in assay buffers that contained phosphate. In contrast, indole phosphate hydrolase activity only developed in cells of N. commune UTEX 584, when they were partially depleted of phosphorus, and the activity associated with these cells was suppressed partially by the addition of phosphate to assay buffers. Indole phosphate hydrolase activity was detected in periplasmic extracts from E. coli (Iph+) transformants.

Cyanobacteria↗

Association of human immunodeficiency virus (HIV) p24 antigenemia with decrease in CD4+ lymphocytes and onset of acquired immunodeficiency syndrome during the early phase of HIV infection.

Human immunodeficiency virus (HIV) p24 antigenemia was assessed in a longitudinal study of 52 homosexual men who developed serum antibody to HIV. Antibody seroconversion to HIV as defined by a positive HIV enzyme immunoassay (EIA) confirmed by Western (immuno-) blot was associated with three major patterns of HIV antigenemia. In the first pattern, a transient antigenemia was noted 6 (six subjects) and 12 (one subject) months prior to detection of antibody by HIV EIA and Western blot in 7 (13.5%) of the 52 men. Use of an EIA employing a recombinant envelope protein (ENV9) was able to detect antibody in four of these seven men at the time of this early antigenemia. In the second pattern, HIV p24 antigenemia occurred in 8 (15.4%) of the 52 subjects within the first 12 months after HIV antibody seroconversion. No p24 antigen was detected in the 37 (71.1%) remaining subjects. CD4+ cell numbers were lower in antigen-positive men before and after antibody seroconversion. Development of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was strongly associated with evidence of persistent p24 antigenemia during the early, postseroconversion period. HIV p24 antigenemia may be of value in determining appropriate cohorts for drug therapy trials for subjects with early-phase HIV infection.

AIDS-Related Complex↗

The nineteen-year trends in CHD in the Honolulu Heart Program.

Accumulated data from the Honolulu Heart Program cohort of men of Japanese ancestry were analysed for 19-year trends in coronary heart disease (CHD) mortality and incidence rates, case-fatality ratios, and changes in risk factor levels. From 1966 to 1984, there was an estimated average annual decline of 2.7% for CHD mortality rates for the population from which the cohort was drawn. This decline was similar to that of US white males of the same age distribution. Within the examined cohort of men who were free of prevalent CHD at entry into the study, the temporal pattern of incidence rates of definite CHD was quite similar to the pattern of CHD mortality rates. Thus, for the examined cohort, mortality rates were an accurate indication of incidence rates. There was no evidence that the decline in CHD mortality rates was due to reductions in case-fatality ratios. There were, however, significant decreases in the percentages of men who smoked cigarettes, in blood pressure level among treated hypertensives and in the intake of dietary cholesterol. These changes, and a drop in coronary artery atherosclerosis measured during the same time period, are all compatible with the concept that the decline of CHD mortality among Japanese men in Hawaii reflects primary prevention of new disease.

Aged↗

HIV-1-specific production of IFN-gamma and modulation by recombinant IL-2 during early HIV-1 infection.

Specific cellular immune responses to human immunodeficiency virus type 1 (HIV-1) were assessed in mononuclear leukocyte cultures from homosexual men with documented, early phase HIV-1 infection. Cell cultures from men with a mean duration of 1.3 yr (range, 0.3 to 2.2 yr) of HIV-1 infection were treated with UV-inactivated, whole, purified HIV-1 Ag together with various concentrations of rIL-2. Cell supernatants were harvested after 5-day incubation and assayed for IFN activity against encephalomyocarditis virus in human WISH cells. IFN subtypes were characterized by neutralization of antiviral activity with antiserum specific for human IFN-gamma and IFN-alpha. Results showed that cultures from 68% (17 of 25) of the HIV-1-seropositive subjects produced "immune" IFN-gamma in response to whole HIV-1 Ag plus rIL-2. IFN-gamma was induced in only 20% (5 of 25) of cultures treated with HIV-1 Ag alone. Enhancement of HIV-1-specific IFN-gamma production by rIL-2 was synergistic rather than additive in that titers induced by the mixture were consistently higher than the sum of IFN titers induced by HIV-1 or rIL-2 alone. This effect was not demonstrable in cultures from 18 HIV-1-seronegative men. Similarly, HIV-1-immune specific augmentation of IFN-gamma production by rIL-2 was noted for PENV9, a recombinant HIV-1 envelope glycoprotein gp41 and gp120 fragment. Production of IFN-gamma may be an important, HIV-1-immune specific parameter in the host response to this retrovirus.

Acquired Immunodeficiency Syndrome↗

Recombinant human tumor necrosis factor increases granulocyte cell-surface complement receptor number.

Exposure of human buffy-coat granulocytes to tumor necrosis factor (TNF) produced cellular activation as indicated by an increase in the neutrophil and monocyte cell-surface number of C3b receptors (measured by indirect immunofluorescence). The degree of receptor increase depended on the dose of TNF from 25 to 1250 pg/mL. Results of kinetic analysis confirmed this response: TNF, 250 pg/mL, caused an increase in the C3b receptor number within ten minutes. Purified neutrophils exhibited a similar increase in cell-surface C3b receptors dependent on the concentration of TNF. Tumor necrosis factor could be a mediator of granulocyte activation in patients.

Granulocytes↗