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Biomedical subjects

J Weil

Publications and source records attributed to J Weil.

At least 127 records · Page 7Linked to original sources
PubMed1983

A unique set of polypeptides is induced by gamma interferon in addition to those induced in common with alpha and beta interferons.

Human immune interferon (IFN-gamma) differs from leukocyte interferon (IFN-alpha) and fibroblast interferon (IFN-beta) in cell origin, inducing agents, physical and biological properties and amino acid sequence. These differences have led to interest in possible differences in the biological properties of IFN-gamma compared with IFN-alpha and IFN-beta. IFN-gamma has the same broad range of biochemical and biological actions as do IFN-alpha and IFN-beta, although relative potencies vary depending on the cell type and function investigated. There has so far been no direct evidence that IFN-gamma alters normal cell functions differently from other interferons. We report here striking qualitative and quantitative differences in the intracellular response of human fibroblasts to IFN-gamma compared with IFN-alpha and IFN-beta. Two-dimensional gel electrophoresis demonstrates, in addition to the induction of a common group of polypeptides, the existence of a set of polypeptides whose synthesis is uniquely induced by IFN-gamma.

Cell Line↗
PubMed1983

Interferon induction of (2'-5') oligoisoadenylate synthetase in diploid and trisomy 21 human fibroblasts: relation to dosage of the interferon receptor gene (IRFC).

Trisomy 21 human fibroblasts are more sensitive to human interferon-alpha (IFN-alpha) than are diploid controls, consistent with the location of the gene (IFRC) which codes for the IFN-alpha receptor on chromosome 21. When compared in the antiviral assay, the difference in sensitivity is five- to tenfold, much greater than the 50% difference in IFRC gene dosage. An understanding of the mechanism by which this amplification of gene dosage occurs is relevant to the specific pathology of Down's syndrome and as a model system for studying the pathogenic effects of chromosomal aneuploidy. The enzyme (2'-5') oligoisoadenylate synthetase (2-5A synthetase), which is believed to be central to the interferon-induced antiviral response, is induced 50% more in trisomy 21 fibroblasts than in diploid controls. Thus the amplification in response occurs subsequent to the binding of IFN-alpha to its receptor and the triggering of the first set of intracellular events, the latter exemplified by the induction of 2-5A synthetase. Similar results were obtained with IFN-gamma, consistent with other evidence which indicates that a gene coding for a separate IFN-gamma receptor is also located on chromosome 21.

Diploidy↗
PubMed1983

Computer-assisted analysis demonstrates that polypeptides induced by natural and recombinant human interferon-alpha are the same and that some have related primary structures.

The biological effects on diploid and trisomy 21 human fibroblasts of pure human interferon IFLrA, a single IFN-alpha species produced from cloned DNA, were compared with those of partially purified natural IFN-alpha. Twelve interferon-induced polypeptides were visualized by two-dimensional gel electrophoresis and autoradiography. Seven of these were shown to have related primary structures and are therefore products of related genes or are related through post-translational modification. Qualitative visual comparisons and computer-aided quantitation of autoradiograms revealed no differences in the patterns of polypeptide induction following treatment with the two types of IFN-alpha, and the two interferons also induced (2'-5') oligoisoadenylate synthetase equally. By these criteria, the activities of the two interferons are qualitatively and quantitatively indistinguishable. In addition, the effects of trisomy 21 on IFLrA-induced polypeptide synthesis and on antiviral response were similar to those previously demonstrated with natural IFN-alpha.

Computers↗
PubMed1983

Chronic treatment and tolerance with high doses of isosorbide dinitrate in a slow release form in patients with angina pectoris.

Nine men with angiographically proven coronary sclerosis and a reproducible ischemic response on the exercise ECG were treated for 9 weeks with a dose of 180-240 mg isosorbide dinitrate slow release (ISDN sr) daily. In the week before the beginning of the treatment (week 1) and in the week after its conclusion (week 10), exercise tests were carried out before and 1 and 3 h after administration of 60 mg ISDN sr or placebo. This part of the investigation was double-blind, cross-over and randomized. In an open study carried out during the 2nd-9th weeks, exercise tests were carried out weekly before and 1 and 3 h after the usual morning dose of 60 mg ISDN sr. The interval between the morning exercise and the last evening dose was 8-10 h. Exercise duration and required level of exertion remained constant during the entire study. The sum of ischemic ST-segment depression during and after exercise, heart rate (ECG) and blood pressure (RR) were all measured. Both before and after the period of treatment 60 mg ISDN sr produced a significant reduction in ST-segment depression after 1 and 3 h. During the treatment phase no significant improvement in comparison to controls could be observed from the 7th week onward. However, even in controls the ST-segment depression was less in the 8th and 9th weeks than during the first few weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1982

Bradycardia during sleep apnea. Characteristics and mechanism.

To determine the characteristics of and mechanisms causing the bradycardia during sleep apnea (SA), both patients with SA and normals were studied. Evaluation of six consecutive SA patients demonstrated that bradycardia occurred during 95% of all apneas (central, obstructive, and mixed) and became marked with increased apnea length (P less than 0.01) and increased oxyhemoglobin desaturation (P less than 0.01). Heart rate slowed 9.5 beats per minute (bpm) during apneas of 10-19 s in duration, 11.4 bpm during 20-39s apneas, and 16.6 bpm during 40-59-s apneas. Sleep stage had no effect unexplained by apnea length or degree of desaturation. Oxygen administration to four SA patients completely prevented the bradycardia although apneas lengthened (P less than 0.05) in three. Sleeping normal subjects did not develop bradycardia during hypoxic hyperpnea but, instead, HR increased with hypoxia in all sleep stages, although the increase in HR was not as great as that which occurred while awake. Breath holding in awake normals did not result in bradycardia during hyperoxia (SaO2 = 99%), but was consistently (P less than 0.01) associated with heart rate slowing during room air breath-holds (-6 bpm) at SaO2 = 93%, with more striking slowing (-20 bpm) during hypoxic breath-holds (P less than 0.01) at SaO2 = 78%. Breath holding during hyperoxic hypercapnia had no significant effect on rate. Breath holding in awake SA subjects demonstrated similar findings. We conclude that the bradycardia of SA is a consistent feature of apnea and results from the combined effect of cessation of breathing plus hypoxemia.

Adult↗
PubMed1980

Synthesis of interferon-induced polypeptides in normal and chromosome 21-aneuploid human fibroblasts: relationship to relative sensitivities in antiviral assays.

Localization of the gene for the species specific response to interferon (IFRC) to human chromosome 21 has stimulated interest in the effect of aneuploidy for chromosome 21 on cell sensitivity to interferon. Previous reports have shown that the relative sensitivities of trisomy 21, diploid and monosomy 21 human fibroblasts as measured in an antiviral assay are greater than the ratio 0.67 : 1.0 : 2 predicted on the basis of gene dosage for IFRC. As an alternative test for sensitivity, we have investigated the synthesis of interferon-induced polypeptides visualized by 2-dimensional gel electrophoresis and autoradiography. Of 10 such polypeptides identified, 3 were measured quantitatively in 2 diploid, 2 trisomic, and one monosomic fibroblast strains. In contrast to the antiviral response, the relative responses in this test correspond closely to expected gene dosage relationships over a range of interferon concentrations from 0.5 to 5000 units/ml. These results are compatible with the conclusion that the number of IFRC gene products (presumed to be the interferon receptor) per cell is proportional to the number of IFRC genes. Thus, the amplified effect of aneuploidy as measured in the antiviral response appears to result from some step subsequent to synthesis of interferon receptors and formation of interferon-receptor complexes.

Autoradiography↗
PubMed1980

Treatment of anorchia with oral testosterone undecanoate: pharmacodynamics and clinical effectiveness.

The pharmacodynamics of plasma testosterone (T) and androstenedione (A) levels were studied in ten hypogonadal boys after oral administration of testosterone undecanoate (TU). Plasma T and A levels were measured by specific radioimmunoassays. Six hours after a single dose of 120 mg TU, there was a significant increase (P < 0.005) in plasma T and A with a median T peak level of 940 ng/100 ml. Furthermore, twelve agonadal boys treated with a mean dose of 60 mg TU/day were examined over a period of 18-24 months. During this therapy, plasma T and A levels were significantly higher than before (P < 0.005), whereas plasma levels of LH and FSH did not decrease significantly. With the exception of one anorchic boy, all patients showed signs of sexual maturation, such as growth of pubic and axillary hair, and steady development of bone age during oral TU treatment.

Administration, Oral↗
PubMed1979

Comparison of two tests for heterozygosity in congenital adrenal hyperplasia (CAH).

The increase of plasma cortisol (F), androstenedione (A), 17 alpha-hydroxy-progesterone (17-OH-P) and testosterone (T) was measured after iv administration of ACTH in heterozygotes for CAH and in controls under two different conditions: Test 1: ACTH stimulation was performed without any particular preparation. Test 2: 1.5 mg of dexamethasone (dex.) was given the evening before the ACTH stimulation. Plasma F, A, 17-OH-P and T were measured by specific radioimmunoassays (RIA). Following ACTH stimulation, the increase of 17-OH-P was significantly higher in CAH-heterozygotes than in controls in both tests (P less than 0.0005). Heterozygotes were characterized by a 17-OH-P increase after ACTH stimulation exceeding the + 2 SD limit of the 17-OH-P increase found in controls. The detection of female heterozygotes was considerably improved by the administration of dex. before testing (test 2). In males, however, a better identification of heterozygotes was obtained without previous administration of dex. (test 1). By these tests, 100% of female (test 2) and 79% of male (test 1) CAH heterozygotes could be correctly identified. There were no significant differences in the levels of F, A and T between heterozygotes and controls except for decreased T levels in test 1 (2P less than 0.01) in most male heterozygotes after ACTH stimulation.

Adrenal Cortex Function Tests↗
PubMed1979

The effect of trisomy 21 on the patterns of polypeptide synthesis in human fibroblasts.

In addition to direct gene dosage effects, the deleterious phenotypic consequences of aneuploidy may result from secondary regulatory effects on the production and degradation of gene products coded for by other chromosomes. In an initial test of the hypothesis that extensive secondary effects play an important role in the phenotypic consequences of aneuploidy, we have used two-dimensional gel electrophoresis with radioautography to look for such secondary effects among the polypeptides synthesized by human fibroblasts grown in vitro. The polypeptide patterns of fibroblast strains from four trisomy 21 subjects and one trisomy 21/normal mosaic were compared to those from five matched normal subjects. Of approximately 850 polypeptides visualized, only four show a pattern of variation which may be related to trisomy 21. Additional differences in polypeptide concentrations were found among the strains, attributable to genetic heterogeneity between donor individuals and differences in tissue of origin. These results indicate that, at least in fibroblasts in vitro, trisomy 21 does not cause major regulatory changes in the rates of production and degradation of a large number of polypeptides.

Adult↗
PubMed1978

[Tuberculosis of the oesophagus (author's transl)].

Two cases of tuberculosis of the oesophagus serve as an opportunity to review the clinical and radiological features of this rare condition. Generally situated at the junction of the upper and middle third of the oesophagus, the lesion is found opposite the invaded inter-tracheobronchial mediastinal nodes which may give rise to a fistula. Confirmed by oesophagoscopy, direct bacteriological examination, oesophageal tuberculosis is usually cured without sequelae by antituberculous therapy.

Adult↗
PubMed1978

Hypoventilation in obstructive lung disease. The role of familial factors.

To determine the role of familial factors in the hypoventilation of chronic obstructive lung disease we measured chemical drives to breathe in normal offspring of two groups of patients with an equal degree of obstruction. One group of five patients had repeatedly normal arterial carbon dioxide tension (PaCO2), whereas PaCO2's were elevated in the other group of six. Two adult offspring of each patient were studied. Drives were measured as the ventilatory response to isocapnic hypoxia, and the slopes of the ventilation/PCO2 relation (the hypercapnic ventilatory response). The mean response to isocapnic hypoxia was lower (P less than 0.01) in offspring of patients with high PaCO2's than in the offspring of patients with normal levels (71 +/- 7.8 [S.E.M.] vs. 113 +/- 10.3); one offspring of each patient with high PaCO2 had a response below the range found in offspring of all patients with normal PaCO2. Lower hypercapnic ventilatory responses (P less than 0.05) were also found in the offspring of patients with high PaCO2. Familial factors in the control of breathing may be an important determinant of ventilation in chronic obstructive lung disease.

Adult↗