Search PubMed⌕ Search

Biomedical subjects

J Pool

Publications and source records attributed to J Pool.

At least 19 recordsLinked to original sources
PubMed1995

Interindividual conservation of T-cell receptor beta chain variable regions by minor histocompatibility antigen-specific HLA-A*0201-restricted cytotoxic T-cell clones.

Minor histocompatibility antigens (mHags) are involved in the induction of graft-versus-host disease (GVHD) after HLA-identical bone marrow transplantation. Previously, we isolated a series of HLA-A*0201-restricted cytotoxic T-cell (CTL) clones specific for the same mHag HA-1 from peripheral blood of three unrelated patients who were suffering from GVHD. We have now analyzed the composition of the T-cell receptor (TCR) V regions of 12 of these mHag HA-1-specific HLA-A*0201-restricted CTL clones by DNA sequencing of the alpha and beta chains. Of these 12 clones, derived from three unrelated individuals, five independent TCR alpha V- and beta V-region sequences were established. The TCR alpha chains were composed of varying TCR alpha V and TCR alpha J genes with no obvious similarities in structure in the N regions. However, the TCR beta chains all used the TCR beta V6S9 gene segment, and showed remarkable similarities within the N-D-N regions; ie, three independent beta-chain sequences (originating from donors Ha and Gy) shared a leucine/valine amino acid pair, whereas the other two (originating from donors Ha and Wi) shared a serine/threonine pair, all at positions 99 and 100 of the TCR beta V region. In conclusion, the TCR analysis of HA-1 mHag-specific CTL clones has shown that the HA-1 mHag/HLA-A*0201 complex selects for highly similar TCR beta V regions.

Amino Acid Sequence↗
PubMed1995

ST segment and T wave characteristics as indicators of coronary heart disease risk: the Zutphen Study.

OBJECTIVES: This study evaluated the predictive value of T wave amplitude and ST segment level on lead I for angina pectoris, a first myocardial infarction, sudden death and coronary heart disease death in middle-aged and elderly men. BACKGROUND: Certain ST-T wave characteristics may reflect favorable autonomic cardiac control. Slight ST segment elevation has been reported to indicate a low risk of coronary heart disease mortality. METHODS: A total of 876 men, born between 1900 and 1920, participated in periodic medical examinations and were followed up with respect to morbidity and mortality from 1960 to 1985. In 1985, the remaining cohort was extended to 836 elderly men from the same birth cohort who were followed up until 1990. Relative risks in categories of T wave amplitude and ST segment level were estimated by survival analysis. RESULTS: Both middle-aged and elderly men with T wave amplitudes > or = 0.15 mV had a lower risk of myocardial infarction, coronary heart disease death and sudden death than men with T wave amplitudes 0.05 to 0.15 mV. The adjusted relative risk of coronary heart disease death was 0.5 (95% confidence interval [CI] 0.2 to 1.0); in men with T wave amplitude < or = 0.05 mV, relative risk was 2.0 (95% CI 1.3 to 3.1). Slight ST segment elevation was also associated with decreased risk: relative risk 0.5 (95% CI 0.3 to 1.0) compared with the isoelectric ST segment level. In men with ST segment depression, relative risk was 2.2 (95% CI 1.4 to 3.4). The association of T wave amplitude and ST segment level were independent of each other. CONCLUSIONS: In addition to the elevated risk of coronary heart disease that is associated with ST-T wave abnormalities, we observed that normal variations in repolarization characteristics are predictive of future heart disease.

Aged↗
PubMed1992

Well shaped ST segment and risk of cardiovascular mortality.

OBJECTIVE: To investigate the prognostic value of frequently occurring slight variations in the ST segment for cardiovascular mortality in healthy subjects. DESIGN: Follow up study of mortality in relation to variations in ST segment level in a cohort over the 28 years from 1953 to 1981. A case-cohort sampling design was applied to limit the number of electrocardiograms that had to be coded by hand. SETTING: General health examination carried out in 1953 of civil servants in Amsterdam and assessment of subsequent mortality. SUBJECTS: Apparently healthy civil servants aged 40 to 65 years: 1583 men and 1508 women. MAIN OUTCOME MEASURES: Relative risk of variations in ST segment level for mortality from all causes, cardiovascular disease, and coronary heart disease. RESULTS: In men the multivariate relative risks of 15 year mortality from cardiovascular disease and coronary heart disease of slight ST elevation at 80 ms past the J point (compared with isoelectric ST segment) were 0.5 (95% confidence interval 0.3 to 0.9) and 0.4 (0.2 to 0.8), respectively. As expected, ST segment depression (greater than 0.25 mm) was associated with increased risk: 1.9 (1.1 to 3.0) and 2.2 (1.2 to 3.9), respectively. In women associations were weaker. The full 28 year period showed a similar pattern of somewhat weaker associations for men; among women, however, no predictive value was apparent. CONCLUSION: These results are empirical evidence for the intuitive opinion among doctors that a curved, upward sloping ST segment, resulting in slight ST elevation at 80 ms, indicates low risk compared with the isoelectric flat, stretched ST segment.

Adult↗
PubMed1992

Immunogenetics of human minor histocompatibility antigens: their polymorphism and immunodominance.

Minor Histocompatibility (mH) antigens are polymorphic endogenously synthesized products that can be recognized by alloreactive T cells in the context of major histocompatibility complex molecules. In transplant situations where tissue donor and recipient are matched for HLA, mH antigens may trigger strong cellular immune responses. To gain insight into the polymorphism of mH antigens we studied their frequencies in the healthy population. Five HLA class I restricted mH antigens recognized by distinct cytotoxic T-cell (CTL) clones were used in the population genetic analysis consisting of a panel (N = 100) of HLA typed target cells. Three mH antigens showed phenotype frequencies of 69% or higher, this contrasted the frequencies of two other mH antigens with 16 and 7% respectively. To gain insight into the "functional" polymorphism of the T-cell response to mH antigens, we analyzed the specificity of CTL clones within individuals. Three out of five individuals investigated shared a CTL response to one single HLA-A2 restricted mH antigen. These results indicate limited allelic polymorphism for some mH antigens in the healthy population and are suggestive of the existence of immunodominant human mH antigens.

Alleles↗
PubMed1992

Maternal and fetal cardiovascular responses to strenuous bicycle exercise.

In a longitudinal study we investigated some cardiovascular responses to strenuous bicycle exercise in 33 healthy women during pregnancy and the postpartum period. The exercise electrocardiogram demonstrated depression of the ST segment in 12% of women in the absence of clinical signs of ischemia, and the incidence of these changes was unaffected by pregnancy. In spite of slightly different blood pressures at rest during the first and second trimesters of pregnancy, the blood pressure response to exercise at approximately 75% Vo2max was virtually unaffected by pregnancy. After a maximal bicycle test, the fetal heart rate was increased by an average of 4 beats/min, without a change in pattern. Tocodynamometry suggested a transient increase in uterine activity after maximal exercise in 6% of the tests. These findings support the view that strenuous exercise of limited duration is not harmful to the healthy mother and fetus.

Bicycling↗
PubMed1992

Prehospital thrombolysis with alteplase (rt-PA) in acute myocardial infarction.

The improvement in survival in patients undergoing thrombolytic therapy in myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPerfusion in Acute Infarction Rotterdam (REPAIR) study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, 'Actilyse'). A small portable ECG computer system is used to confirm the presence of a large myocardial infarction (at least 1.0 mV ST-deviation) 'on the spot'. Between 22 June 1988 and 1 January 1991, 226 patients were treated by the ambulance service after the evaluation of 9052 patients complaining of chest pain. Therapy could be initiated within an average of 100 +/- 56 min (SD) after the onset of symptoms, and within 22 +/- 9 min after ambulance arrival. Three patients were defibrillated during transportation. Six patients (3%) died after arrival in the hospital. The time gained by prehospital treatment was 47 min (95% confidence limits 44-51 min) in comparison with 220 patients who did not meet the criteria for prehospital thrombolysis, but received thrombolytic therapy as soon as possible after hospital admission. The developed procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician. The observed low mortality supports the concept that prehospital thrombolytic therapy is indeed beneficial to the patient.

Adult↗
PubMed1991

Hering-Breuer reflex in young asthmatic children.

The aim of this study was to assess if the Hering-Breuer reflex could be provoked in young children. Thirty asthmatic children with a mean age of 5.3 years and 18 healthy children with a mean age of 7.0 years were studied. The presence of the reflex was indicated by prolongation of the spontaneous expiratory time following application of continuous positive airways pressure (CPAP). The occurrence of the reflex was then related to age, compliance of the respiratory system (Crs) measured by weighted spirometry, functional residual capacity (FRC) determined by helium gas dilution, and the change in lung volume resulting from the application of CPAP. The asthmatic children in whom the Hering-Breuer reflex was observed tended to be younger (P less than 0.01) and the reflex was present in those children of both groups who had more compliant lungs (P less than 0.05). The FRC was not different in asthmatic children with and without the Hering-Breuer reflex, but healthy children in whom the reflex was present tended to have smaller lung volumes. The change in lung volume resulting from application of CPAP was significantly greater in those children of both groups in whom the reflex was present (P less than 0.01 asthmatics, P less than 0.02 healthy children). We conclude that the Hering-Breuer reflex may be provoked in young children.

Asthma↗
PubMed1991

A 2-year longitudinal study of lung hyperinflation in young asthmatics.

Functional residual capacity (FRC) was measured at 6-monthly intervals for at least 2 years in 42 young asthmatic children. Over the 2-year period FRC decreased in the 42 children from a median of 136% to 117% of that predicted for height (P less than 0.05). These changes in FRC were associated with a reduction in the number of children receiving no regular treatment (ten at recruitment, 0 at 2 years), P less than 0.05, and an increase in the number of children receiving inhaled steroids (ten at recruitment and 29 at 2 years), P less than 0.01. Twenty-five children were hyperinflated at recruitment (FRC greater than 120% of that predicted for height) with median FRC 152% compared to only 16 children at 2 years median FRC 117%, P less than 0.01. We conclude that FRC decreases as asthmatic children get older but some children, worryingly and despite increased use of prophylactic therapy, remain chronically overdistended which may put them at serious risk of chronic obstructive airways disease in later life.

Anti-Inflammatory Agents↗
PubMed1991

The effects of nisoldipine on the total ischaemic burden: the results of the ROCKET study.

This study was designed to examine the effects of nisoldipine (relative to placebo), a new dihydropyridine calcium entry blocking agent, in the treatment of silent ischaemia in conventional doses. A total of 409 patients with proven coronary artery disease were screened and of this 64 had at least six episodes or a total duration of 30 min of ST segment depression (1 mm lasting at least 1 min) over 48 h. Fifty-two patients ultimately completed a randomized double-blind cross-over study comparing nisoldipine 5 mg twice a day, nisoldipine 10 mg daily and placebo. There was a reduction in the ST segment integral and number of episodes of ST segment depression when compared to placebo on treatment with nisoldipine 5 mg twice a day and nisoldipine 10 mg daily. However, the confidence limits were wide and crossed the no-treatment effect line. In addition, the nisoldipine doses neither affected the circadian distribution of ischaemic episodes nor caused an alteration of the workload achieved either at peak exercise or at 1 mm ST segment depression measured 24 h after nisoldipine 10 mg or 12 h after nisoldipine 5 mg. We conclude that frequent silent ischaemia in patients with proven coronary artery disease is relatively uncommon; it accounts for approximately 16% of patients with positive exercise. In these patients nisoldipine, given as 5 mg twice a day and 10 mg daily, showed no significant therapeutic effects, either on the frequency or severity of silent ischaemia. New formulations of slow release nisoldipine are consequently being developed so that a fuller 24 h therapeutic profile may be obtained.

Coronary Disease↗
PubMed1991

Month-related variability in immunological test results; implications for immunological follow-up studies.

This longitudinal study was originally designed to detect changes in the in vitro immune response of healthy subjects as a result of a psychological intervention. In this study a significant proportion, about 70%, of the immunological variability in the test results was accounted for by the differences in immunological response levels of the subjects. Apart from this between-subject-effect, a significant proportion of the variability in test results was related to the month of data sampling. The month-effect was computed in such a way that the between-subject variation was taken into account. This resulted in a more accurate estimation of the month-effect. Even after correction for the intervention, i.e. the defence of the PhD thesis, the effect of month of data sampling remains significant for mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, percentage of CD4 and CD8 cells, and for the response to the mitogens phytohaemagglutinin, pokeweed mitogen and concanavalin A as well as the results for the mixed lymphocyte culture for one pool out of three. In contrast, no significant month-effect was observed for the whole blood cell counts, for the differential white blood cell counts as determined by monoclonal antibody staining for cell surface markers CD3, CD16, TAC and OKM1, nor for the immunoglobulin IgM and IgG serum levels. Likewise the cell-mediated lympholysis activities measured against three pools of stimulator cells remained unaltered. We discuss the implications for future immunological follow-up studies of the observation that a significant proportion of the variability in immunological test results is related to differences between subjects and to the month of data sampling.

Adult↗
PubMed1991

Relation between nocturnal symptoms and changes in lung function on lying down in asthmatic children.

Nocturnal symptoms are common in young asthmatic children. Such symptoms may be caused by increased impairment of lung function when they adopt the supine posture. Thirty one children aged 2.8-8.3 years were studied, of whom 20 had asthma (10 with frequent nocturnal symptoms) and 11 had no respiratory problems (control subjects). Peak expiratory flow (PEF) was measured with a Wright's peak flow meter and functional residual capacity (FRC) by a helium gas dilution technique after 30 minutes of lying supine; the values were compared with FRC measured sitting and PEF standing. Peak flow fell significantly on adoption of the supine posture in the asthmatic children, but there was no difference in this fall between the asthmatic children with and without nocturnal symptoms. FRC also fell on adoption of the supine posture, but the decrease in FRC was significant only in the control children and the asthmatic children without nocturnal symptoms. The failure to find a greater fall in PEF or a greater change in FRC on adoption of the supine posture among asthmatic children with nocturnal symptoms suggests that mechanisms other than increased impairment of lung function are responsible for nocturnal asthma.

Asthma↗
PubMed1991

Maximal aerobic exercise in pregnant women: heart rate, O2 consumption, CO2 production, and ventilation.

This study was to determine whether pregnancy affects maximal aerobic power. We measured heart rate, O2 uptake (VO2), CO2 production (VCO2), and ventilation at rest and during bicycle (BE) and treadmill exercise (TE) tests with rapidly increasing exercise intensities at 16, 25, and 35 wk gestation and 7 wk after delivery. Maximal heart rate was slightly lower throughout pregnancy compared with the nonpregnant state during both BE [174 +/- 2 vs. 178 +/- 2 (SE) beats/min] and TE (178 +/- 2 vs. 183 +/- 2 beats/min). Maximal VO2 was unaffected by pregnancy during BE and TE (2.20 +/- 0.08, 2.16 +/- 0.08, 2.15 +/- 0.08, and 2.19 +/- 0.08 l/min for BE and 2.45 +/- 0.08, 2.38 +/- 0.09, 2.33 +/- 0.09, and 2.39 +/- 0.08 l/min for TE at 16, 25, and 35 wk gestation and 7 wk postpartum, respectively). As a result of increased VO2 at rest, the amount of O2 available for exercise (exercise minus rest) tended to decrease with advancing gestation, reaching statistical significance only during TE at 35 wk gestation (1.99 +/- 0.08 l/min vs. 2.10 +/- 0.08 l/min postpartum). Power showed a positive linear correlation with O2 availability during BE as well as TE, and the relationship was unaffected by pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobiosis↗
PubMed1991

QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest.

BACKGROUND: QTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance. METHODS AND RESULTS: In the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventricular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazett's formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction less than 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compared with a QTc of 440 msec or less (95% confidence interval: 1.4, 3.9). In contrast, in patients with evidence of cardiac dysfunction, the relative risk of QTc prolongation was 1.0 (0.5, 1.9). Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks. CONCLUSIONS: These data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death.

Death, Sudden↗
PubMed1991

QT interval prolongation predicts cardiovascular mortality in an apparently healthy population.

BACKGROUND: In myocardial infarction patients, heart rate-adjusted QT interval (QTc), an electrocardiographic indicator of sympathetic balance, is prognostic for survival. METHODS AND RESULTS: In a 28-year follow-up, the association between QTc and all-cause, cardiovascular, and ischemic heart disease mortality was studied in a population of 3,091 apparently healthy Dutch civil servants and their spouses, aged 40-65 years, who participated in a medical examination during 1953-1954. Moderate (QTc, 420-440 msec) and extensive (QTc, more than 440 msec) QTc prolongations significantly predict all-cause mortality during the first 15 years among men (adjusted respective relative risks [RRs], 1.5 and 1.7) and among women (RRs, 1.7 and 1.6). In men, cardiovascular (RRs, 1.6 and 1.8) and ischemic heart disease mortality (RRs, 1.8 and 2.1) mainly account for this association. In women, the association cannot be attributed specifically to cardiovascular and ischemic heart disease mortality. RRs for a subpopulation without any sign of heart disease at baseline are similar. The same is observed for QTc prolongation after light exercise, although in this situation most associations are not statistically significant, probably because of smaller numbers in the QTc prolongation categories. CONCLUSIONS: Our results suggest that QTc contributes independently to cardiovascular risk. If autonomic imbalance is an important mechanism, it might be speculated that changes in life-style (e.g., with regard to physical exercise and smoking) may have a preventive impact.

Autonomic Nervous System↗