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Biomedical subjects

M S Halpern

Publications and source records attributed to M S Halpern.

At least 37 records · Page 2Linked to original sources
PubMed1986

Viral antigen expression in the pancreas of DHBV-infected embryos and young ducks.

The time course of appearance of viral antigen-positive pancreatic cells was examined in both congenitally duck hepatitis B virus (DHBV)-infected duck embryos and experimentally DHBV-infected posthatch ducks. In the embryos, the earliest detectable viral antigen-positive pancreatic cells were localized to islets and identifiable as endocrine on the basis of hormone expression. Non-islet-associated, viral antigen-positive cells appeared at a late stage of embryogenesis, following the onset of chymotrypsinogen production by exocrine tissue; a number of these viral antigen-positive cells were directly identifiable as exocrine on the basis of chymotrypsinogen expression. By contrast, in the pancreas of experimentally infected posthatch ducks, the appearance of viral antigen-positive exocrine cells (chymotrypsinogen-positive) predated the appearance of antigen-positive islet cells. These results are consistent with the possibility that viral antigen expression in exocrine tissue is dependent on the state of cell maturation.

Animals↗
PubMed1986

Expression of endogenous retroviral envelope glycoprotein as a determinant of immunity to Rous sarcoma.

To analyze the effect of the expression of endogenous retroviral envelope glycoprotein on tumor immunity, patterns of sarcoma growth were compared in inbred FP line chickens infected with either of two strains of avian sarcoma virus, Pr-B (subgroup B) or cl.85 (subgroup G). These viruses were chosen for analysis because the envelope glycoprotein of Pr-B, but not of cl.85, is antigenically cross-reactive with the endogenous retroviral envelope glycoprotein expressed in the FP line. Inoculation of 1-day-old hatchmates with either virus yielded a significant percentage of chickens with distal sarcomas localized to visceral organs. By contrast, a marked difference in the percentage of chickens bearing distal sarcomas was noted when sarcoma tissue excised from virus-inoculated donors was implanted in 1-day-old recipients; a high proportion of the recipients of Pr-B-induced sarcoma tissue (Pr-B-sarcoma recipients), but only a low proportion of the cl.85-sarcoma recipients, exhibited distal sarcomas. At 3 weeks posthatch, a significantly higher percentage of donor-derived cells was detected in the primary tumors of the cl.85- versus the Pr-B-sarcoma recipients. A model of immune control, premised on the tolerogenicity of endogenous viral glycoprotein, is proposed to rationalize these results.

Animals↗
PubMed1985

Ablation of humoral immunity in 15I5 x 72 chickens is not predisposing to the formation of subgroup G virus-induced distal sarcomas.

Clone (cl.) 85 infection of 15I5 x 72 chickens at 4 weeks posthatch results in a lower frequency of distal sarcomas than does Prague (Pr)-B infection. As higher titers of virus-neutralizing antibody are generated in the cl.85-infected chickens, the possibility was addressed in the present study that the low frequency of cl.85-induced distal sarcomas is a direct consequence of the strong neutralizing response. Our observations indicate that ablation of humoral immunity by embryonic bursectomy does not serve to increase this frequency, implying that the antiviral humoral response is not required to limit formation of cl.85-induced distal sarcomas.

Animals↗
PubMed1985

Duck hepatitis B virus is tropic for exocrine cells of the pancreas.

Earlier observations had established that duck hepatitis B virus (DHBV) is tropic for pancreatic endocrine cells, including cells localized to islets and to acini. Because cells identifiable as endocrine represented only a minor fraction of the total acinar-associated, infected subpopulation, the possibility was addressed in the present study that this subpopulation also comprises exocrine cells. Fixed preparations of cells from pancreas of congenitally DHBV-infected young ducks were reacted in double immunofluorescence assay with anti-virus serum and either anti-avian pancreatic polypeptide (APP) serum, a probe for a major subclass of acinar-associated endocrine cells, or anti-chymotrypsin serum, a probe for exocrine cells. Approximately 2-5% of the cells in these preparations were viral antigen-positive, comprising a minor fraction positive for APP and a much larger fraction positive for chymotrypsinogen. The detection of the latter establishes that DHBV is tropic for exocrine cells.

Animals↗
PubMed1984

Sarcoma growth in 15I5 x 7(2) chickens infected with avian sarcoma viruses of subgroup B or G.

A comparative study was made of sarcoma growth in 15I5 x 7(2) chickens infected in the wing web at 4 weeks of age with strains of subgroup B or G avian sarcoma viruses. Infection with sarcoma viruses of either subgroup B or G resulted in the formation of progressive wing web sarcomas at the site of inoculation. The survival times of the subgroup G virus-infected chickens were generally at least twice as great as the survival times of the subgroup B virus-infected chickens, which averaged 6-9 weeks postinoculation. At 5 weeks postinfection, a significantly higher titer of virus neutralizing antibody was detected in the subgroup G virus-infected chickens. Necropsy indicated that a high percentage of subgroup B virus-infected chickens exhibited fibrosarcomas at sites distal to the primary wing web sarcomas, whereas only a small percentage of subgroup G virus-infected chickens exhibited distal sarcomas. The results further indicated that the viral env gene is a determinant of the pattern of distal sarcoma formation.

Animals↗
PubMed1984

Efficacy of amiodarone during long-term treatment of malignant ventricular arrhythmias in patients with chronic chagasic myocarditis.

Oral amiodarone was administered to 24 patients with chronic chagasic myocarditis (CCM) and malignant ventricular arrhythmias. Control 24-hour Holter recordings revealed frequent ventricular premature beats (VPBs) (157 to 2572/hr; mean 714 +/- 125), multiform VPBs, and countless numbers of ventricular couplets in all patients, R-on-T phenomenon in 17 patients, and ventricular tachycardia in 21 patients. Amiodarone caused total and persistent suppression of ventricular couplets and tachycardia and greater than 93% reduction of VPB number in 22 patients, during a follow-up of 26.6 months (range 2 to 55 months). In 1 patient, ventricular couplets and tachycardia persisted despite the fact that a 98.2% reduction of VPB number was achieved. This latter patient was the only one in the whole group who experienced sudden death. The maximal antiarrhythmic effect was attained gradually after 3 to 26 weeks (mean 7.4). In four patients in whom treatment was discontinued after 3 to 12 months, the antiarrhythmic protection lasted 4 to 9 weeks. In nine patients the dose of amiodarone was 600 to 800 mg/day. In 15 patients the dose had to be increased to 800 to 1000 mg/day. Despite the presence of congestive heart failure in seven patients and intraventricular block in 17 patients, no limiting side effects were observed. Amiodarone proved to be extremely effective and safe against the most malignant ventricular arrhythmias of CCM.

Adult↗
PubMed1984

Individual cells in tissues of DHBV-infected ducks express antigens crossreactive with those on virus surface antigen particles and immature viral cores.

Double immunofluorescence assays of fixed sections of tissues from Pekin ducks congenitally infected with duck hepatitis B virus were carried out to score cells reactive to antiserum elicited either to viral DNA synthesis complexes (immature cores) purified from liver of infected ducks or to viral surface antigen particles and virions purified from sera of viremic ducks. Subpopulations of doubly fluorescent cells were detectable in liver (hepatocytes and bile duct epithelia), in kidney (proximal tubular epithelia), and in pancreas (acinar-associated cells and endocrine alpha and beta cells); all cells reactive with one antiserum were reactive with the second antiserum. Competition assays established that the cell-associated antigens recognized by the two antisera were mutually non-crossreactive. The cell-associated antigen recognized by the antiserum elicited to the purified immature cores appears to be crossreactive with a 35,000-Da polypeptide fraction associated with immature cores.

Animals↗
PubMed1984

Individual ev loci determine characteristic patterns of endogenous retroviral envelope antigen expression during lymphocyte maturation.

A comparative study of the expression of retroviral envelope antigen by T and B lymphocytes at different maturational stages was made with chickens typed for genomic ev loci. All lymphocyte subclasses from chf(-) chickens were negative for expression of retroviral envelope antigen. By contrast, cells of the lymphocyte lineage from all the chf(+) lines examined were positive for expression, with the levels of envelope antigen in the lymphoblasts exceeding the levels in the immature and resting cells. This pattern of lymphocyte expression was found in lines of chickens in which the expression of chf in fibroblasts was encoded by the ev 3, ev 6, or ev 9 loci. Plasma cells from those chf(+) lines possessing ev 6 expressed higher levels of envelope antigen than the lymphoblasts, an effect not observed with the chf(+) lines lacking ev 6.

Animals↗
PubMed1984

Viral antigen in endocrine cells of the pancreatic islets and adrenal cortex of Pekin ducks infected with duck hepatitis B virus.

Endocrine cells in the pancreas and adrenal glands of duck hepatitis B virus-infected ducks were examined for the presence of viral antigen. Analysis of pancreas tissue was based on double immunofluorescence assays in which anti-duck hepatitis B virus serum was used to detect viral antigen, and anti-glucagon and anti-insulin serum were used, respectively, to identify endocrine alpha and beta cells. Assays of pancreas from infected ducks ranging in age from 3 to 20 weeks indicated that subpopulations of both alpha and beta cells expressed viral antigen. A higher percentage of viral antigen-positive cells was observed in alpha-islets than in beta-islets. As assayed by immunofluorescence and immunoperoxidase staining with anti-viral serum, small clusters of viral antigen-positive cells were detected in the adrenal glands of young infected ducks. These cells were identified as cortical cells on the basis of histologic criteria.

Adrenal Cortex↗
PubMed1983

The influence of the ev 3 locus on the inducibility of serum antibody reactivity for envelope glycoprotein group-specific determinants.

Chickens segregating for the ev 3 locus were bred by backcross matings of line 6(3) to line 15B. Analysis of RAV-1-infected segregants indicated that inducibility of antibody reactivity for envelope glycoprotein group-specific determinants correlated with the absence of ev 3, whereas noninducibility correlated with the presence of ev 3. Since the ev 3(+) and ev 3(-) segregants possessed similar genetic backgrounds, these results provide direct evidence that the ev 3 locus determines the phenotype of noninducibility.

Animals↗
PubMed1983

Differential reactivity of serum antibody from tumor-bearing 15I5 X 7(2) chickens for cross-reactive species of endogenous retroviral envelope glycoprotein.

Experiments were undertaken to determine if the sera of avian sarcoma virus-infected 15I5 X 7(2) chickens exhibit antibody reactivity for species of endogenous retroviral envelope glycoprotein expressed in 15I5 X 7(2) fibroblasts. Two viruses were used for infection of the 15I5 X 7(2) chickens, Pr-A and cl. 85; the envelope glycoprotein of Pr-A, but not of cl. 85, is antigenically cross-reactive with 15I5 X 7(2) endogenous retroviral envelope glycoprotein. Both the Pr-A and cl. 85-infected 15I5 X 7(2) chickens exhibited serum antibody reactivity for the envelope glycoprotein of the endogenous retrovirus RAV-O. In contrast, neither group of infected chickens exhibited detectable serum antibody reactivity for a distinct species of endogenous retroviral envelope glycoprotein, one which though antigenically cross-reactive with the envelope glycoprotein of RAV-O is expressed to much higher levels in 15I5 X 7(2) fibroblasts. Possible mechanisms to account for the observed pattern of antibody reactivity are discussed.

Animals↗
PubMed1983

Experimental transmission of duck hepatitis B virus.

Susceptibility to experimental infection with duck hepatitis B virus (DHBV) was explored, with the objective of defining procedures that were both rapid and reproducible. For the purpose of these experiments, a small flock of DHBV-free breeders was established as a source of susceptible eggs and ducklings, since ca. 10% of the ducks (all ages) from commercial flocks were DHBV infected. Intravenous inoculation of DHBV into 15-day duck embryos from the DHBV-free flock produced a persistent infection, with a high-titer viremia, in at least 80% of the injected animals. The tissue tropism of DHBV in these experimentally infected animals was similar to that associated with natural, congenital infections from viremic ducks to their progeny. Virus antigen was found not only in hepatocytes and bile duct epithelium of liver, but also in cells associated with exocrine and endocrine pancreas, and in proximal convoluted tubular epithelium of kidney. Infection of embryonic liver was rapid, as evidenced by active synthesis of DHBV-DNA by reverse-transcription of RNA by 24 hr postinjection. During this latter analysis, formation of supercoiled viral DNA appeared to precede the reverse-transcription phase of viral DNA synthesis, suggesting that this species may be important in initiation of infection.

Animals↗
PubMed1983

Viral nucleic acid synthesis and antigen accumulation in pancreas and kidney of Pekin ducks infected with duck hepatitis B virus.

Liver, pancreas, and kidney from Pekin ducks infected with duck hepatitis B virus (DHBV) were assayed for the presence of both viral antigen and replication-specific forms of viral nucleic acid. In young congenitally infected ducks, antigen was detectable in hepatocytes and bile duct epithelia, in kidney glomeruli and tubular epithelia, and in cells localized to pancreatic acini. In older experimentally infected ducks, antigen was detectable in hepatocytes, in glomeruli and tubular epithelia, and in cells localized to presumptive pancreatic alpha-islets. All but the glomeruli-associated viral antigen appeared to be localized to the cytoplasm of antigen-positive cells. Much of the glomeruli-associated antigen appeared to be extracellular and was detected in glomeruli that were positive for the accumulation of immunoglobulin, observations suggestive of the deposition of viral antigen-antibody complexes. As analyzed with bulk tissue, replication-specific forms of viral nucleic acid were detectable in liver and pancreas from the young congenitally infected ducks and in liver and kidney from the older experimentally infected ducks.

Animals↗
PubMed1983

Increased endogenous retroviral gene expression is a consequence of lymphocyte activation.

Plasma cells of line 151(5) chickens have been shown to express elevated levels of endogenous retroviral envelope glycoprotein (VEG), measured relative to levels expressed by both immature B cells and resting peripheral B lymphocytes. In this study we analyzed the relationship between peripheral blood lymphocyte (PBL) maturation and the level of VEG expression. A culture system was developed that would support maturation of pokeweed mitogen-activated peripheral B lymphocytes. As analyzed by cytofluorometry, both Ig+ and Ig- lymphoblasts present in the pokeweed mitogen-stimulated cultures expressed detectable levels of VEG in contrast to bursacytes and PBL. Similarly, Ig- blasts, which were present in concanavalin A-stimulated cultures of PBL and presumed to represent activated T cells, were also positive for the expression of VEG. Immature T cells, i.e., thymocytes, although negative by immunofluorescence analysis, expressed VEG at levels that were detectable by radioimmunochemical techniques. These results indicate that T cells as well as B cells constitutively express VEG, and that mitogenic activation of the resting lymphocyte induces an increase in VEG expression.

Animals↗
PubMed1982

Electrocardiographic changes evoked by ajmaline in chronic Chagas' disease with manifest myocarditis.

Conversion from Chagas' infection to chagasic myocarditis occurs slowly and the earliest signs of myocardial involvement are hard to define. To obtain new information on this difficult clinical problem, ajmaline was administered (1 mg/kg body weight intravenously) to 101 patients with Chagas' infection and to 46 patients without such infection (control group). In 3 patients in the control group left anterior hemiblock alone occurred whereas in the group with Chagas' infection, ajmaline caused the occurrence of right bundle branch block, left anterior hemiblock, or both, in 32 patients (31.6 percent), ventricular extrasystoles in 8 (7.9 percent) and ischemic ST-T changes in 7 (6.9 percent). Ajmaline may thus evoke the most typical electrocardiographic changes of chronic chagasic myocarditis in patients without signs of myocardial involvement or only minor nonspecific signs. A positive ajmaline test, defined in the present context as the occurrence of a fascicular block, ventricular arrhythmias or ischemic ST-T changes, may indicate the existence of localized areas of injured myocardial tissue, not enough to alter the electrocardiogram by itself, but able to give rise to severe abnormalities after exposure to the drug. The test may therefore be used as a nonspecific detector of myocardial damage, and thus may have a much broader scope of clinical application. In chronic Chagas' infection, the ajmaline test is a relatively simple and apparently safe procedure that may serve to unveil the earliest signs of chagasic myocarditis.

Adolescent↗
PubMed1982

Usefulness of the ajmaline test in patients with latent bundle branch block.

Twelve patients were studied with intermittent bundle branch block whose conduction disturbance disappeared completely and could no longer be recorded even after provoked changes in heart rate. Premature atrial stimulation and atrial pacing at rapid rates were performed in nine patients; in none of these nine were these procedures able to evoke the complete bundle branch block pattern that all patients exhibited before the spontaneous normalization of conduction. In marked contrast, the administration of ajmaline (1 mg/kg body weight, intravenously in 90 seconds) caused the bundle branch block pattern to reappear in 10 (83.3 percent) of the 12 patients 30 to 120 seconds after the end of the injection, and in 11 patients (91.6 percent) when additional atrial stimulation was performed in 1 of the 2 "failures." This pharmacologic test was much more rapid and simple than electrophysiologic testing and it was noninvasive. Results of this study suggest that some form of subclinical fascicular injury was present (or had persisted) at a time when intraventricular conduction was persistently normal even though no significant physiologic alteration could be demonstrated by the atrial stimulation techniques. The ajmaline test may become a valuable tool for uncovering cases of latent bundle branch block and furthering our knowledge of the early natural history of intraventricular block.

Adult↗
PubMed1982

Malignant ventricular arrhythmias in chronic chagasic myocarditis.

We studied 28 cases of chronic chagasic myocarditis (CCM) with frequent ventricular arrhythmias. Two-hundred and three conventional ECGs recorded during 3 months showed ventricular extrasystoles (VE) ranging between 0.2 and 6 per ten beats in 100%; multiform VE in 97.04%; couplets in 79.31%; ventricular tachycardia (VT) in 42.85%; and R on T in 21.67%. A 24-hour continuous recording showed that VE ranged between 3780 and 61733 (mean 16618 +/- 2627); multiform VE and couplets were present in 100% of patients, and VT was present in 78.5%. In 16 patients (group I) the frequency of VE was persistently high, without diurnal variation; 11 patients showed sustained reduction during sleeping hours and only one showed an increase during night sleep (group II). Even in group II, VE never disappeared for periods longer than 10 minutes. In five patients, four 24-hour recordings were obtained at weekly intervals, and in five other patients a second 24-hour recording was performed 10 to 24 months later. The remarkable frequency, persistence and low variability of ventricular arrhythmias in CCM suggest that such arrhythmias can be used as a most stable, reliable, but highly demanding model for testing the efficacy of antiarrhythmic drugs.

Adult↗