Immunological changes in lymphadenopathy virus positive and negative symptomless male homosexuals: two years of observation.
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Deltaretrovirus↗
Biomedical subjects
K Schwartz
Publications and source records attributed to K Schwartz.
Effects of atrial natriuretic factor, sodium nitroprusside, and acetylcholine on cyclic GMP levels and relaxation in rat aorta.
The purpose of this study was to investigate the mechanisms whereby an endothelium-dependent vasodilator, acetylcholine, a nitrovasodilator, sodium nitroprusside and atrial natriuretic factor (atriopeptin II), elevate cyclic GMP levels and induce relaxation in rat thoracic aorta. Methylene blue inhibited the elevated cyclic GMP levels and relaxation due to sodium nitroprusside and acetylcholine, but not those to atriopeptin II. Cyanide inhibited relaxations to all three vasodilators, but inhibited the elevated cyclic GMP levels in response to only nitroprusside and acetylcholine. The reducing agents sodium borohydride, dithiothreitol, sucrose and isoproterenol all inhibited the elevated cyclic GMP levels due to nitroprusside and acetylcholine, while the increased cyclic GMP levels with atriopeptin II were unaffected by sodium borohydride, sucrose and isoproterenol. The effects of the reducing agents on relaxation induced by the vasodilators were difficult to interpret due to their nonspecific contractile and relaxant properties. Agents and procedures known to inhibit the Na+, K+-pump and relaxation to endothelium-dependent vasodilators and nitroprusside, including ouabain, K+-free, Mg2+-free and low Na+ Krebs-Ringer bicarbonate solution, all partially inhibited relaxations to atriopeptin II. Relaxations to atriopeptin II were also inhibited in tissues contracted with KCl. The present results suggest that the mechanism of atrial natriuretic factor-induced increased cyclic GMP levels, in contrast to that of nitroprusside and acetylcholine, does not involve the formation of free radicals, a reducible species or interaction with heme. Furthermore, the cyclic GMP formed in response to nitroprusside, acetylcholine and atrial natriuretic factor mediates relaxation through a common mechanism that may be functionally antagonized by agents and procedures which result in membrane depolarization.
Acetylcholine↗
Effects of Na+,K+-pump inhibitors and membrane depolarizing agents on acetylcholine-induced endothelium-dependent relaxation and cyclic GMP accumulation in rat aorta.
The purpose of this study was to investigate the effects of inhibitors of the Na+,K+-pump and membrane depolarizing agents on endothelium-dependent relaxation and elevated cyclic GMP levels induced by acetylcholine in rat thoracic aorta. Ouabain or exposure to K+-free or Mg2+-free Krebs-Ringer bicarbonate solution, agents and procedures known to inhibit the Na+,K+-pump, inhibited acetylcholine-induced relaxation and the associated increased levels of cyclic GMP. However, the inhibitory effect of ouabain on cyclic GMP levels was abolished in the absence of norepinephrine or in the presence of norepinephrine and the alpha-adrenergic receptor antagonist phentolamine. The membrane depolarizing agents KCl and tetraethylammonium also inhibited the acetylcholine-induced relaxation and the elevated cyclic GMP levels. Exposure to norepinephrine reduced the increased levels of cyclic GMP due to acetylcholine as compared to rested controls. This effect was inhibited by prior exposure to phentolamine, but not by the beta-adrenergic receptor antagonist, propranolol. These results suggest that increased activity of the Na+,K+-pump may mediate, in part, endothelium-dependent relaxation; inhibition of relaxation may be due to membrane depolarization; the endothelium-dependent increased levels of cyclic GMP may increase Na+,K+-pump activity; a complex interaction exists between membrane polarization, the Na+,K+-pump and alpha-adrenergic stimulation in regulation of cyclic GMP accumulation and relaxation.
Acetylcholine↗
Distinct atrial natriuretic factor receptor sites on cultured bovine aortic smooth muscle and endothelial cells.
Cultured bovine aortic smooth muscle and endothelial cells each display distinct specific binding sites for radiolabeled atrial natriuretic peptide (ANF). 125I-pro-rANF (103-126)I binding to both cell types is rapid, reversible and competitive. Scatchard plots of the binding data show Bmax values of 5.5 and 0.1 - 2.1 X 10(5) sites/cell and Kd values of 2.1 and 0.3 nM for smooth muscle and endothelial cells, respectively. In addition, ANF elevates levels of cGMP substantially in both cell types at concentrations of ANF close to its Kd and Ki for binding. Sodium nitroprusside, however, has essentially no effect on cGMP levels in either cell type. These results show that distinct functionally active receptor sites for ANF exist on both vascular smooth muscle and endothelial cells.
Animals↗
Microtubules and desmin filaments during the onset of heart growth in the rat.
Microtubules and intermediate desmin filaments were visualized in rat cardiomyocytes during the onset of heart growth by double immunolabelling of isolated myocytes, with specific antibodies raised against tubulin and desmin. Heart growth was stimulated either by mechanical overloading induced by aortic stenosis, or by injection of thyroxine into hypothyroid rats. In both experimental models, alterations in the microtubule pattern were observed soon after stimulation of growth whereas desmin filament organization remained unchanged. Microtubules were redistributed in arrays parallel to the long axis of the myocytes and were more numerous around the nuclei. Microtubules therefore appeared to be involved in the cellular events occurring during stimulated heart growth irrespective of the nature of the stimulus.
Animals↗
Effect of sodium-potassium pump inhibitors and membrane-depolarizing agents on sodium nitroprusside-induced relaxation and cyclic guanosine monophosphate accumulation in rat aorta.
The purpose of this study was to investigate the relationship between sodium nitroprusside-induced relaxation, inhibition of the sodium-potassium pump, and cyclic guanosine monophosphate. Exposure of rat thoracic aorta to ouabain, or potassium- or magnesium-free Krebs-Ringer bicarbonate solution, procedures which presumably inhibit the sodium-potassium pump, or to potassium chloride or tetraethylammonium, membrane-depolarizing agents, inhibited relaxation to nitroprusside. These conditions had little or no effect on the elevated cyclic guanosine monophosphate levels at a concentration of nitroprusside (0.1 microM) that relaxed norepinephrine contracted tissues by 80%. However, at a maximum relaxant concentration of nitroprusside (1.0 microM), these conditions decreased the elevation of cyclic guanosine monophosphate. The inhibition of elevated cyclic guanosine monophosphate levels was independent of the endothelium, extracellular calcium, and the cyclic guanosine monophosphate phosphodiesterase inhibitor, M&B 22,948. The inhibitory effects of ouabain and of potassium- and magnesium-free solution on the increased levels of cyclic guanosine monophosphate caused by 1.0 microM nitroprusside were abolished when tissues were incubated without norepinephrine, or with norepinephrine in the presence of the alpha-adrenergic blocker, phentolamine. In contrast, a beta-adrenergic blocker, propranolol, had no effect on the ouabain-induced inhibition of elevated cyclic guanosine monophosphate levels, with norepinephrine present. These results are consistent with the hypothesis that membrane events regulate cyclic guanosine monophosphate synthesis. At nitroprusside concentrations greater than 0.1 microM, the formation of cyclic guanosine monophosphate appears to be coupled to the status of the smooth muscle cell membrane and integrity of the sodium-potassium pump.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Decreased contractility after myocardial hypertrophy: cardiac failure or successful adaptation?
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Adaptation, Physiological↗
The relation of cytomegalovirus and Epstein-Barr virus antibodies to T-cell subsets in homosexually active men.
Eighty-nine homosexual men participated in a study of sexual practices, T-cell subsets, and antibody titers to cytomegalovirus (CMV) and Epstein-Barr virus (EBV). The prevalence of antibody to CMV was 96% and to EBV, 94%. Titers to CMV were higher in those practicing receptive anal intercourse. The CMV antibody titers were positively correlated with the T-helper/suppressor ratio, number of partners and venereal disease episodes, number of T-suppressor cells, and EBV titers. Twelve percent of the participants had a low ratio only, 18% T-suppressor augmentation, and 3% T-helper deficiency. The CMV titer and prevalence of receptive anal intercourse were higher in those with a low ratio only, T-suppressor augmentation, and T-helper deficiency. These results suggest that CMV infection is acquired through receptive anal intercourse and is associated with an increase in T-suppressor cells and, in some persons, a decrease in T-helper cells.
Adult↗
Comparison of the tryptic digestion pattern of subfragments 1 from V1 and V3 rat cardiac isomyosins.
The limited tryptic digestion patterns of the chymotryptic subfragment 1 (S1) of the two rat ventricular isomyosins V1 and V3, were compared under several conditions. Pure S1V1 was obtained from 3-week-old rats and pure S1V3 from adult rats 6 weeks after hypophysectomy. To localize the sites of trypsin susceptibility and to determine the distribution of the peptides along the S1 molecule, we used, as a probe, antibodies raised against a pig cardiac 29-kDa peptide. We demonstrate that this peptide contains the N-acetyl group located on the N-terminal part of the cardiac myosin molecule. In S1V1 we observed two major sites of proteolysis, independently of the digestion conditions: they are located at 27kDa and 80kDa from the N terminus as in skeletal muscle S1.S1V3 appears much more sensitive to the proteolysis conditions: at least two additional sites of cleavage are present in the 50-kDa peptide when digested at pH 8.0. Decrease in the pH from 8.0 to 7.0 or the presence of Mg-ATP have no effect on the digestion of S1V1 while these ambient factors protect the 50-kDa peptide of S1V3 from breakdown. We conclude that the 50-kDa peptide is a variable portion of the myosin molecule, the conformation of which is sensitive to ambient factors such as the pH or the presence of nucleotides.
Amino Acids↗
Isozymes of myosin in growing and regenerating rat muscles.
Native myosin isozymes of rat muscles have been isolated by electrophoreses in non-dissociating conditions. Their mobilities were measured, using taenia coli myosin as an internal standard and their relative concentrations were determined by computer planimetry of the electrophoretograms. Three isozymes were observed in extensor digitorum longus (EDL), two in soleus (SOL), four in neonatal muscles three days before birth. Regenerates of minced EDL or SOL muscles in adult animals had no native myosin the third day after surgery; they were similar to neonatal muscles 15 days after surgery and to adult muscles 60 days after surgery.
Animals↗
Quantitative changes in T helper or T suppressor/cytotoxic lymphocyte subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders.
Quantitative measurements of the immune cell subgroups, T helper (Leu 3+/OKT4+) cells and T suppressor/cytotoxic (Leu 2+/OKT8+) cells, were made in patients having acquired immune deficiency syndrome (AIDS) with Kaposi's sarcoma and in patients with AIDS and opportunistic infection, as well as in three other relevant populations. These included patients with lymphadenopathy syndrome, e.g., homosexually active males with lymphadenopathy who sought medical care for additional symptoms, and healthy male homosexuals, as well as a control population. Decrease in the number of T helper cells is characteristic of AIDS with Kaposi's sarcoma or opportunistic infection. Augmentation of the T suppressor/cytotoxic cell population is rare in AIDS with Kaposi's sarcoma but is more frequent in AIDS with opportunistic infection. Augmentation of the T suppressor/cytotoxic cell population, however, may occur in a variety of circumstances, including cytomegalovirus and other viral infections, in healthy, homosexually active males, and in otherwise healthy hemophiliac subjects receiving factor VIII treatment. Reduced T helper:T suppressor/cytotoxic cell ratio can be caused by either decrease in the number of T helper cells or augmentation of the T suppressor/cytotoxic cell population. Lowered T helper:T suppressor/cytotoxic cell ratio does not, by itself, help to distinguish between AIDS and other causes of reduced ratios. Quantitative measurements are needed to define the T subset changes. AIDS is characterized by decrease in the number of T helper cells and reduced T helper:T suppressor/cytotoxic cell ratio. The T helper (Leu 3+) and T suppressor/cytotoxic (Leu 2+) cell subpopulations can change independently. Identification of decrease in the number of T helper cells as an alteration that occurs independently of numerical change in other lymphoid subpopulations, such as T suppressor/cytotoxic cells and B cells, and the close association of the decrease in the number of T helper cells with AIDS are consistent with a distinct pathogenesis (and cause) for AIDS.
Acquired Immunodeficiency Syndrome↗
Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle.
A 26 amino acid synthetic peptide fragment of atrial natriuretic factor (ANF) relaxed isolated rabbit aortic segments in which the endothelium was either intact or functionally destroyed. The relaxations were temporally associated with increases in levels of cGMP with no change in the levels of cAMP. The ANF-induced increases in cGMP were also observed in aortic segments pretreated with calcium-free buffer or the cGMP phosphodiesterase inhibitor M&B 22,948. Qualitatively similar results were obtained for sodium nitroprusside. ANF selectively activated particulate guanylate cyclase, having no effect on the soluble form of the enzyme. Thus, the direct (endothelium-independent) vasodilator effect of ANF may be mediated via increased tissue levels of cGMP. ANF appears to increase vascular cGMP levels by activation of particulate guanylate cyclase.
Animals↗
Messenger RNA content and complexity in normal and overloaded rat heart: a preliminary report.
Cardiac overload is associated with two different changes in gene expression: an increase in overall protein synthesis leading to hypertrophy, and at least two isoenzymic redistributions affecting myosin and creatine kinase. This preliminary report was an attempt to study the cardiac genome in this model. Total RNA (ribonucleic acid) was prepared by a combination of the guanidine-ethanol and phenol procedures. A DNA (deoxyribonucleic acid)-, t(transfer)-RNA-free preparation containing non-degraded 28 and 18 S rRNA and 3% poly A+-m (messenger) RNA was obtained. The poly A+mRNA isolated on an oligo (dT) cellulose column had an average nucleotide length of 1300 to 1800 and its c (complementary) DNA was 600 to 1400 base pairs. The first analysis of the kinetics of hybridation revealed a complex pattern which could be described by division into three components. Northern blot and dot blot using a recombinant cDNA plasmid complementary to myosin heavy chain or to actin mRNA (a gift from A. Weydert and M. Buckingham) indicated the presence of these two mRNA, with the former being frequently degraded. After aortic stenosis, both the content and the concentration of total RNA and poly A+mRNA increased in parallel and peaked by the 4th day at +35%. This is the first suggestion that the control of gene expression is transcriptional in this model.
Animals↗
Isomyosins, microtubules and desmin during the onset of cardiac hypertrophy in the rat.
Chronic overloading of the rat heart induces a cascade of adaptational events which compensate for the increase in work. Two of these have been extensively described: a qualitative event with an isomyosin change leading to an improved efficiency and a quantitative event resulting in cardiac hypertrophy. By means of immunofluorescence, we investigated if elements of the cytoskeleton, i.e. microtubules and intermediate filaments, could be triggers for these adaptational mechanisms. Studies of overloaded heart were performed in young rats with aortic stenosis or adult rats with aortic insufficiency. Cardiac myocytes were isolated and labelled by immunofluorescence with antibodies raised against V1 or V3 isomyosin, desmin or tubulin. The aim of the work was to visualize: when and where the shift in the expression of isomyosins occurs within the myocytes; the eventual changes in the pattern of intermediate filaments of desmin and/or of microtubules during the adaptation of myocytes to overload. We observed: that the shift from the high (V1) to low (V3) ATPase isomyosin occurred in a population of myocytes soon after stenosis; that changes in the pattern of microtubules occurred soon after induction of hypertrophy; no changes in the distribution or intensity of the staining of desmin.
Adenosine Triphosphatases↗
Left ventricular isomyosins in normal and hypertrophied rat and human hearts.
Regulation of rat cardiac contractility by changes in the expression of a particular form of myosin (V1-V3) has been demonstrated with a pressure overload. Previous reports of the effect of a volume overload have been controversial. Therefore, we measured the isomyosin composition and mechanical function in the same papillary muscles from rat hearts subjected to a chronic volume overload (aortic insufficiency, AI). A marked change in isomyosin composition from V1 to V3 occurred. Contractility, as assessed by shortening velocity Vmax, was also significantly decreased, and this decrease was correlated with the isomyosin transformation. The changes in isomyosin composition and speed of contraction with AI are thus similar to changes induced by aortic stenosis. Little experimental evidence exists for involvement of such changes in the regulation of human cardiac contractility. Using immunoglobulins highly specific for V1 and V3 in autopsy samples we have observed that the human left ventricle is mostly composed of a V3 isoform (HV3) and that small amounts (1 to 15%) of a V1 type (HV1) are present in foetal and some adult hearts. This HV1 is absent from the left ventricles of patients with valvular disease, assessed at the time of valve replacement (N = 30, samples provided by Dr P. Menasché). Myosin Ca2+-stimulated ATPase activities were not significantly different between normal and hypertrophied hearts. These data demonstrate the heterogeneity of human ventricular myosin, which is composed of V1 and V3 isomyosins, as in other mammalian species. Isomyosin shifts from V1 to V3 are possible in man, but they are quantitatively small and without noticeable influence on overall ATPase activities.
Adenosine Triphosphatases↗
Preparation of venous allografts. A comparison of techniques.
In order to evaluate alternate techniques of preparing veins for use as homografts, 102 femoral veins were harvested from adult mongrel dogs. The veins were treated in four different ways, then transplanted into recipient animals bypassing their ligated femoral arteries. Group I--24 veins (6 cm each) were harvested and immediately transplanted. Group II--24 veins were stored in 15% dimethyl sulfoxide (DMSO) solution at -120 C for 21 days prior to transplantation. Group III--26 veins were stored for 21 days in plasminate solution at -60 C prior to use as allografts. Group IV--28 veins were stored in 0.5% gluteraldehyde solution for 21 days prior to implantation. Animals were randomly sacrificed at 1-month, 2-month, 6-month, and 12-month intervals. Patency of the transplant was determined weekly by ultrasound. Specimens were sent for light and scanning electron microscopy at the time of harvest, prior to implantation, and at sacrifice. Endothelial damage was graded on a scale of 0-16. Veins in Group II had a significantly higher patency rate (68% at 1 year) than Group III (35%) and Group IV (11%) (p less than 0.05). The intimal layer of all patent vessels was replaced by an organized mural thrombus. Partial endothelialization of the luminal surface was most prevalent in Group II. Intimal damage related to storage technique was significant in Group III (p less than 0.01). At sacrifice, severe endothelial damage was present in all groups (p less than 0.01). In conclusion, veins stored in 15% dimethylsulphoxide (DMSO) solution at -120 C have immunologic and physical characteristics that yield patency rates acceptable for clinical use when autogenous tissue is not available.
Animals↗
Myosin types in the human heart. An immunofluorescence study of normal and hypertrophied atrial and ventricular myocardium.
Two distinct myosin heavy chain isoforms, referred to as alpha and beta, were identified in the human heart with specific antimyosin antibodies. By indirect immunofluorescence, myosin heavy chain alpha was found to be a major component of atrial myosin and a minor component of ventricular myosin, while heavy chain beta was found to be a major component of ventricular myosin and a minor component of atrial myosin. In the normal heart, there was marked individual variability in the proportion of ventricular myocytes reactive for heavy chain alpha. Atrial myocytes staining for heavy chain beta were rare in the left atrium and more numerous in the right atrium, especially in the crista terminalis and in the interatrial septum. Surgical and autoptic specimens from hypertrophied left ventricles of patients with mitral regurgitation showed a myosin immunoreactivity pattern similar to that of normal specimens. Very rare muscle cells reactive for heavy chain alpha were seen in the hypertrophied left ventricles of subjects with hypertension and in the hypertrophied right ventricles of subjects with tetralogy of Fallot. A dramatic transformation of myosin heavy chain composition was observed in hypertrophied left atria of patients with mitral stenosis, with a shift to heavy chain beta in a large proportion of atrial myocytes. The findings indicate that chronic exposure to hemodynamic overload can induce marked changes in the myosin heavy chain composition of human atria, whereas it affects only slightly that of the ventricles.
Adult↗
[Characterization of total RNA, messenger poly(A)+ RNA and homologous complementary DNA in experimental cardiac hypertrophy].
Two biological modifications are observed during adaptation of cardiac tissue to work overload: an increase in total protein synthesis and a redistribution of myosin isoenzymes. These modifications suggest that changes in DNA transcription are involved in the early response of cardiac tissue to overload. Results are reported in this paper that show a parallel increase in total and polyadenylated RNA content and concentration in cardiac overloaded tissue in the rat. The characterization of cardiac poly (A)+ mRNA by mRNA X cDNA hybridization and the identification of specific mRNAs with recombinant plasmid cDNAs are given in this report as preliminary results.
Animals↗