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Biomedical subjects

R Ahmed

Publications and source records attributed to R Ahmed.

At least 19 recordsLinked to original sources
PubMed1992

Effective vaccination against papilloma development by immunization with L1 or L2 structural protein of cottontail rabbit papillomavirus.

Immunization of rabbits with either L1, the major structural protein, or L2, a minor structural protein of cottontail rabbit papillomavirus (CRPV), protected against challenge with the virus. Neutralizing antibodies were elicited by both the L1 and L2 trpE fusion proteins. Neutralization with anti-L1 serum, however, was more efficient than with anti-L2 serum. In contrast, when tested on Western blots the immune response to L2 was stronger than to L1. Rabbits were also protected against CRPV infection by immunization with L1 expressing recombinant vaccinia virus. Sera from two of three rabbits immunized with recombinant vaccinia virus were negative on Western blots but all three were positive in ELISA's with nondenatured fusion protein or in immunoprecipitations. The results suggest that both the viral structural proteins, L1 and L2, merit consideration in the development of a vaccine against papillomavirus.

Animals↗
PubMed1992

Multiple typing techniques applied to a Clostridium perfringens food poisoning outbreak.

Twenty-one stool specimens obtained from persons implicated in two food poisoning outbreaks at the same institution in Smith Falls, Ontario, were examined for Clostridium perfringens. Ninety-two colonies of Cl. perfringens (3-5 per stool specimen) were typed with antisera, bacteriocins and by plasmid analysis. They were also tested for the in vitro production of bacteriocin and enterotoxin. Sixteen of the 21 stool specimens were tested directly for enterotoxin. This was detected in 13, five of which were from individuals listed as 'asymptomatic' food handlers. The predominant strain isolated from 15 of the 21 stool samples produced bacteriocin and enterotoxin in vitro, contained no plasmids, and was of a common bacteriocin type and serotype.

Bacterial Typing Techniques↗
PubMed1992

Viral infection of the thymus.

We have examined infection of the thymus during congenitally acquired chronic lymphocytic choriomeningitis virus (LCMV) infection of mice, a classic model of antigen-specific T-cell tolerance. Our results show that (i) infection starts at the fetal stage and is maintained throughout adulthood, and (ii) this chronic infection of the thymus can be eliminated by transfer of virus-specific cytotoxic T lymphocytes (CTL) that infiltrate the thymus and clear all viral products from both medullary and cortical regions. Elimination of virus from the thymus results in abrogation of tolerance. During the fetal stage, the predominant cell type infected is the earliest precursor of T cells with a surface phenotype of Thy1+ CD4- CD8- J11d+. In the adult thymus, infection is confined primarily to the cortisone-resistant thymocytes present in the medullary region. The infected cells are CD4+ and J11d+. The presence of J11d, a marker usually associated with immature thymocytes, on infected single positive CD4+ "mature" thymocytes is intriguing and suggests that infection by this noncytolytic virus may affect development of T cells. There is minimal infection of the CD8+ medullary thymocytes or of the double positive (CD4+ CD8+) cells present in the cortex. Infection within the cortex is confined to the stromal cells. Interestingly, there is infection of the double negative (CD4- CD8-) thymocytes in the adult thymus, showing that even during adulthood the newly developing T cells are susceptible to infection by LCMV. Virus can be eliminated from the thymuses of these carrier mice by adoptive transfer of medullary region first and then from the thymic cortex. This result clearly shows the need to reevaluate the widely held notion that mature T cells are unable to reenter the thymus. In fact, in our experiments the donor T cells made up to 20 to 30% of the total cells in the thymus at 5 to 7 days after the transfer. The number of donor T cells declined as virus was eliminated from the thymus, and at 1 month posttransfer, the donor T cells were hardly detectable. The results of this study examining the dynamics of viral infection and clearance from the thymus, the primary site of T-cell development, have implications for understanding tolerance induction in chronic viral infections.

Aging↗
PubMed1992

Immunological memory against viruses.

Viral infections often result in long-term immunological memory. This article reviews the phenotypic changes seen in memory T cells and suggests a re-evaluation of the current dogma that T cell memory is maintained by persistence of antigen.

Animals↗
PubMed1991

Abrogation of tolerance to a chronic viral infection.

This study documents failure of peripheral tolerance mechanisms in a chronic viral infection and shows that T cell tolerance to a viral Ag seen as self from fetal life can be broken despite the presence of this Ag in extrathymic tissues. Congenital infection of mice with lymphocytic choriomeningitis virus (LCMV) results in T cell tolerance to the virus. Such mice become carriers for life harboring virus in many tissues including the thymus and exhibit no LCMV-specific CTL responses. Our previous studies have documented the curing of this congenitally acquired chronic infection after adoptive transfer of CD8+ T cells from LCMV-immune mice and the presence of host-derived, LCMV-specific CTL in these "cured" carriers. In this study we have examined the mechanism by which these carriers acquired T cell competence and show that these CTL differentiated from the bone marrow after elimination of viral Ag from the thymus. These results demonstrate that even when a chronic infection has been established in utero, the adult thymus retains the ability to restore immunocompetence to the host and to provide protection against reinfection. Surprisingly, these LCMV specific CTL were acquired at a time when infectious virus and intracellular viral Ag, although cleared from the thymus, were readily detectable in organs such as the kidney, testes, and brain. In fact, active viral replication in peripheral tissues was ongoing when these mice acquired new virus-specific T cells. These results show that clearance of virus form the thymus was sufficient to abrogate tolerance to a congenitally acquired chronic infection and that Ag in peripheral tissues did not tolerize newly developing T cells. These findings suggest that mechanisms that operate on immature cells within the thymus to silence self-reactive T cells are effective in induction of tolerance to viruses, but mechanisms of tolerizing mature T cells are likely to breakdown. This has implications for virus-induced autoimmunity and for treatment of chronic infections.

Animals↗
PubMed1991

T-cell tolerance to viruses.

T-cell tolerance to self antigens is maintained by events that occur within the thymus and in the periphery. Mechanisms that operate on immature T cells within the thymus are effective in induction of tolerance to viruses, but mechanisms of tolerizing mature T cells are likely to break down. This failure of peripheral mechanisms to induce T-cell tolerance to viruses has implications for autoimmunity and for treatment of chronic viral infections.

Animals↗
PubMed1991

Role of viral strains and host genes in determining levels of immune complexes in a model system: implications for HIV infection.

Virus-antibody immune complexes form during infection with most RNA and DNA viruses, including those with human immunodeficiency virus (HIV). Yet a subset of individuals so infected apparently does not mount such responses. To understand the principles involved, we studied the formation and deposition of virus-antibody immune complexes in the circulation in a model system utilizing mice persistently infected with lymphocytic choriomeningitis virus (LCMV). Although mice of several genetic haplotypes could be persistently infected with LCMV, mount anti-LCMV antibody responses, and form immune complexes levels varied among murine strains. Earlier, genetic analysis of high and low immune complex formers, their F1 crosses, and appropriately selected recombinant inbred strains located the ability to mount heightened immune responses in genes within the MHC. Further, variations among LCMV strains in the capacity to incite high levels of immune complex formation were found. Persistent infection with LCMV Armstrong (ARM) strain was associated with high levels of complexes in the circulation and marked deposits in the glomeruli of high-responder SWR/J mice. In contrast, persistent infection of SWR/J mice with LCMV Traub strain led to very low levels of circulating complexes and minimal immune complex deposition in tissues. The amount of virus carried during both infections was roughly equivalent indicating that the genetics of both the host and the virus play essential roles in whether or not immune complexes develop. Antibody responses in SWR/J mice persistently infected with LCMV ARM were 5- to 10-fold higher than responses of age- and sex-matched mice infected with LCMV Traub.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Arrhythmogenic properties of the ventricular myocardium in cardiomyopathic Syrian hamster, BIO 14.6 strain.

STUDY OBJECTIVE: Incidence of spontaneous cardiac arrhythmias and inducibility of ventricular arrhythmias in the cardiomyopathic hamster, BIO 14.6 strain, were examined. DESIGN: A 3 min electrocardiogram (ECG) was recorded weekly to 50 weeks of age. Programmed ventricular stimulation was then performed with single and double ventricular premature stimuli during both sinus rhythm and ventricular pacing, and with brief bursts of ventricular pacing to induce ventricular arrhythmias. EXPERIMENTAL MATERIAL: 19 male cardiomyopathic and 10 age matched normal hamsters from 16 to 50 weeks were used for recording the 3 min ECG; 11 cardiomyopathic and 10 normal hamsters aged 50 to 55 weeks were used for the induction of ventricular arrhythmias. MEASUREMENTS AND MAIN RESULTS: Spontaneous and sporadic ventricular premature contractions were documented in 8.3% of 218 ECGs from the cardiomyopathic hamsters between the ages of 30 and 46 weeks, whereas no ventricular arrhythmia was recorded in normal hamsters throughout the entire follow up period. Non-sustained ventricular tachycardia (NSVT) was induced in 7/11 cardiomyopathic hamsters by single ventricular premature stimulus. Either NSVT or ventricular fibrillation was induced in all cardiomyopathic hamsters with a significantly prolonged intraventricular conduction delay and refractory period. In contrast, neither NSVT nor ventricular fibrillation was induced in normal hamsters. CONCLUSION: This study provides the first evidence of the high arrhythmogenicity of the ventricles in cardiomyopathic hamsters.

Animals↗
PubMed1991

Dual chamber pacing aborts vasovagal syncope induced by head-up 60 degrees tilt.

To determine if pacing might prevent syncope in cardioinhibitory 'Malignant Vasovagal Syndrome' (also known as 'Neurally-Mediated Bradycardia/Hypotension'), a study of dual chamber pacing during head-up 60 degrees tilt was undertaken. Paired invasive tilts were performed in 10 patients who had a history of recurrent syncope, normal routine investigations including electrophysiological study and prior tilt-induced vasovagal syncope. Vasovagal reactions of identical severity were produced by prolonged 60 degrees head-up tilt on consecutive days in seven out of 10 patients. On day 2, without pacing, seven patients had tilt-induced vasovagal reactions and six became syncopal during the reaction. On day 3, with temporary DVI pacing with rate hysteresis, seven patients had tilt-induced vasovagal reactions and 1 patient was syncopal. Syncope was aborted in the other five patients. DVI pacing significantly improved cardiac index (CI) (one +/- 0.2 to 1.6 +/- 0.3 L/min/m2, P less than 0.01) and mean arterial blood pressure (MABP) (30 +/- 11 to 48 +/- 12 mmHg, P less than 0.01) during vasovagal reactions on day 3 compared with day 2. The mean period of time that patients could tolerate in the tilted position after the onset of the tilt-induced vasovagal reaction was significantly prolonged by pacing from 0.9 +/- 1.2 to 3.2 +/- 1.6 min (P less than 0.01). Dual chamber pacing may abort syncope in 85% of patients with cardioinhibitory malignant vasovagal syndrome. Pacing may prolong consciousness sufficiently during a vasovagal reaction to allow injury to be avoided.

Adult↗
PubMed1991

Molecular basis of organ-specific selection of viral variants during chronic infection.

Viral variants of different phenotypes are present in the central nervous system (CNS) and lymphoid tissues of carrier mice infected at birth with the Armstrong strain of lymphocytic choriomeningitis virus. The CNS isolates are similar to the parental virus and cause acute infections in adult mice, whereas the lymphoid isolates cause chronic infections associated with suppressed T-cell responses. In this study, we provide a molecular basis for this organ-specific selection and identify a single amino acid change in the viral glycoprotein that correlates with the tissue specific selection and the persistent and immunosuppressive phenotype of the variants. This phenylalanine (F)-to-leucine (L) change at position 260 of the viral glycoprotein was seen in the vast majority (43 of 47) of the lymphoid isolates, and variants with L at this residue were selected in spleens of persistently infected mice. In striking contrast, isolates with the parental sequence (F at residue 260) predominated (48 of 59 isolates) in the CNS of the same carrier mice. Complete nucleotide sequence analysis of the major structural genes of several independently derived (from different mice) spleen isolates showed that these variants were greater than 99.8% identical to the parental virus. In fact, the only common change among these spleen isolates was the F----L mutation at residue 260 of the glycoprotein. These results show that an RNA virus can exhibit minimal genetic drift during chronic infection in its natural host, and yet a single or few mutations can result in the organ-specific selection of variants that are markedly different from the parental virus.

Amino Acid Sequence↗
PubMed1991

A camera that directly measures physical parameters.

Accurate measurement of physical parameters is essential for the practice of modern medicine and ophthalmology in particular. A measuring device is presented that combines a single lens reflex (SLR) camera body incorporating two aligned in-camera grids with a calibrated macrozoom attachment. The device has multiple applications wherever accurate measurements are required. The ability to measure and record physical parameters in both health and disease is essential to modern medical practice. This is particularly so in ophthalmology. Despite the relative accessibility of external structures, the clinician's measuring equipment often takes the form of a clear plastic ruler with the ever present possibility of inaccuracy from parallax and perspective. Indeed, even in the hands of expert observers, the results from the commercially produced Hertel exophthalmometer are prone to significant variation. Various photographic methods of measurement have been described using a fixed focal length lens system, and recently evaluated. These, however, require processing of the photographs before measurements can be taken. We present a simple, relatively inexpensive multi-purpose device which can measure physical parameters directly and record photographic evidence of these measurements. In essence, the device consists of a single lens reflex (SLR) camera fitted with two carefully aligned grids, linked to a calibrated macrozoom lens.

Anthropometry↗
PubMed1990

Genetic basis of viral persistence: single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice.

This study has identified a single amino acid change in the viral glycoprotein that profoundly affects the ability of lymphocytic choriomeningitis virus (LCMV) to persist in its natural host. Adult immunocompetent mice infected with a variant of the Armstrong strain, spleen isolate clone 13 (svA/svA), harbor virus for several months and exhibit suppressed T cell responses. In contrast, adult mice infected with a reassortant virus (svA/wtA) that contains the L segment of the spleen variant and the S segment of the parental wt Armstrong, make potent LCMV-specific CTL responses and clear the infection within 2-4 wk. These two viruses, spleen variant clone 13 and the reassortant svA/wtA, are identical in their noncoding regions and show no amino acid changes in any of their viral genes except for one substitution in the glycoprotein. The reassortant virus svA/wtA has a phenylalanine at amino acid residue 260 of the glycoprotein, whereas the spleen variant clone 13 has a leucine at this position. This study constitutes one of the first reports defining the genetic basis of viral persistence at the whole animal level, and identifying a single mutation that markedly increases the ability of a virus to persist in its natural host.

Amino Acid Sequence↗
PubMed1990

Viruses as therapeutic agents. II. Viral reassortants map prevention of insulin-dependent diabetes mellitus to the small RNA of lymphocytic choriomeningitis virus.

Nonobese diabetic (NOD) mice are the experimental prototype of type 1 insulin-dependent diabetes mellitus (IDDM). These mice develop a characteristic autoimmune lesion in the pancreatic islets of Langerhans, where infiltrating lymphocytes destroy beta cells, resulting in hypoinsulinemia, hyperglycemia, ketoacidosis, and death. This IDDM, which closely resembles that in humans, is prevented by infecting NOD mice with particular strains of lymphocytic choriomeningitis virus (LCMV), including Armstrong 53b, Traub, WE, and Pasteur. In contrast, the LCMV Armstrong 53b variant, Clone 13, fails to abort IDDM. Hence, although Clone 13 establishes a persistent infection that endures throughout the life spans of NOD mice, their hyperglycemia, hypoinsulinemia, and lymphocytic infiltration into the islets of Langerhans still occur. Genetic reassortant viruses generated between the IDDM therapeutic strain of LCMV Pasteur and the nontherapeutic variant, LCMV Clone 13, were used to treat NOD mice. By using such reassortants and both parental strains of virus to infect NOD mice, the prevention of IDDM was mapped to the S RNA segment of LCMV Pasteur.

Amino Acid Sequence↗
PubMed1990

In vivo selection of lymphocyte-tropic and macrophage-tropic variants of lymphocytic choriomeningitis virus during persistent infection.

This study demonstrates cell-specific selection of viral variants during persistent lymphocytic choriomeningitis virus infection in its natural host. We have analyzed viral isolates obtained from CD4+ T cells and macrophages of congenitally infected carrier mice and found that three types of variants are present in individual carrier mice: (i) macrophage-tropic, (ii) lymphotropic, and (iii) amphotropic. The majority of the isolates were amphotropic and exhibited enhanced growth in both lymphocytes and macrophages. However, some of the lymphocyte-derived isolates grew well in lymphocytes but poorly in macrophages, and a macrophage-derived isolate replicated well in macrophages but not in lymphocytes. In striking contrast, the original wild-type (wt) Armstrong strain of lymphocytic choriomeningitis virus that was used to initiate the chronic infection and from which the variants are derived grew poorly in both lymphocytes and macrophages. These three types of variants also differed from the parental virus in their ability to establish a chronic infection in immunocompetent hosts. Adult mice infected with the wt Armstrong strain cleared the infection within 2 weeks, whereas adult mice infected with the variants harbored virus for several months. These results suggest that the ability of the variants to persist in adult mice is due to enhanced replication in macrophages and/or lymphocytes. This conclusion is further strengthened by the finding that the variants and the parental wt virus grew equally well in mouse fibroblasts and that the observed growth differences were specific for cells of the immune system.

Animals↗
PubMed1989

T cell memory. Long-term persistence of virus-specific cytotoxic T cells.

This study documents that virus-specific CTL can persist indefinitely in vivo. This was accomplished by transferring Thy-1.1 T cells into Thy-1.2 recipient mice to specifically identify the donor T cell population and to characterize its antigenic specificity and function by using a virus-specific CTL assay. Thy-1.1+ T cells from mice previously immunized with lymphocytic choriomeningitis virus (LCMV) were transferred into Thy-1.2 mice persistently infected with LCMV. The transferred LCMV-specific CTL (Thy-1.1+ CD8+) eliminate virus from the chronically infected carriers and persist in the recipient mice in small numbers, comprising only a minor fraction of the total T cells. Upon re-exposure to virus, these long-lived "resting" CD8+ T cells proliferate in vivo to become the predominant cell population. These donor CD8+ T cells can be recovered up to a year post-transfer and still retain antigenic specificity and biological function. They kill LCMV infected H-2-matched cells in vitro and can eliminate virus upon transfer into a second infected host. In addition, these long-lived CD8+ T cells appear not to be dependent on help from CD4+ T cells, since depletion of CD4+ T cells has minimal or no effect on their biological properties (proliferation, CTL response, viral clearance). These donor CTL also exhibit an immunodominance over the host-derived LCMV-specific CTL response. When both host and donor T cells are present, the donor CTL response is dominant over the potential CTL response of the cured carrier host. Taken together, these results suggest that virus-specific CTL can persist for the life span of the host as memory cells.

Animals↗
PubMed1989

Changes in T wave morphology during hypercalcemia and its relation to the severity of hypercalcemia.

The effect of hypercalcemia on T wave morphology, polarity, and amplitude was studied in 14 patients with a primary diagnosis of malignant lymphoma (8 patients), adult T-cell leukemia (5 patients), and Hodgkin's disease (1 patient). Hypercalcemia was severe to extreme in 11 (14.9-22.8 mg/dl), moderate in 1 (13.4 mg/dl), and mild in 2 (11.8 and 12.2 mg/dl) patients. Ten of the 11 patients (91%) with severe hypercalcemia showed inverted, biphasic, and notched T waves, mainly in the chest leads. Notched T waves were observed in all 10 of these patients in anterior to lateral, mid to lateral, or lateral chest leads. Biphasic and/or inverted T waves in anterior or anterior to midchest leads were present in 4 of these 10 patients who had extreme hypercalcemia (greater than 16 mg/dl). Changes in T wave morphology were not observed in moderate or mild hypercalcemia. T wave amplitude showed significant inverse correlation with serum calcium (T mV vs Ca, r = -0.60, p less than 0.001; T/R ratio vs Ca, r = -0.68, p less than 0.001; n = 35). Decrease in T wave amplitude was marked in severe hypercalcemia (p less than 0.0001) and moderate hypercalcemia, but there was no change in mild hypercalcemia. Changes in T wave morphology, polarity, and amplitude either appeared with development of hypercalcemia or disappeared with normalization of serum calcium level. It was concluded that in addition to shortening the QT interval, severe to extreme hypercalcemia can cause development of inverted, biphasic, or notched T wave with a marked decrease in amplitude of T waves.

Adult↗
PubMed1989

Results of hepatobiliary imaging using Tc-99m EHIDA.

Tc-99m labelled 2,6-diethylphenylcarbamoylmethyliminodiacetic acid (EHIDA) is a non-toxic radiopharmaceutical that was found to undergo rapid biliary excretion in a normal human, with accumulation of radioactivity in the gall bladder and intestine. Images in normal subjects and nonjaundiced patients showed rapid concentration of tracer by the liver and the passage of the same into the intestine within 15 to 40 minutes, with or without visualization of the gall bladder. In the jaundiced patient, the tracer blood clearance was delayed and urinary excretion was increased. Tc-99m EHIDA has been extensively investigated in 1634 patients to evaluate its performance in the diagnosis of hepatobiliary disorders.

Abdomen↗