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Biomedical subjects

R H Tomar

Publications and source records attributed to R H Tomar.

At least 19 recordsLinked to original sources
PubMed1999

Guidelines for clinical and laboratory evaluation patients with monoclonal gammopathies.

This guideline provides the recommendations of an expert panel for the clinical and laboratory evaluation of patients suspected of having a clinical condition that produces a monoclonal protein in serum or urine. The recommendations describe the clinical conditions in which a monoclonal protein should be sought, the optimal sequence of testing to diagnose and monitor these patients, and the most effective laboratory procedures.

Evaluation Studies as Topic↗
PubMed1998

Development and application of a model to estimate the impact of type 1 diabetes on health-related quality of life.

OBJECTIVE: To develop a simulation model to assess the impact of type 1 diabetes and its associated complications on health-related quality of life of a population. RESEARCH DESIGN AND METHODS: The methodology builds upon 1) an existing population model of type 1 diabetes progression, 2) an empirical study designed to measure state- and age-specific health statuses of type 1 diabetes, and 3) existing literature to quantify quality of life of the corresponding health status. Health statuses were measured in a group of type 1 diabetic patients using the Medical Outcomes Study short form 36 (SF-36). A published empirical regression equation was then used to predict corresponding Quality of Well-Being Index (QWB) scores from these assessments. The QWB scores were incorporated into a previously developed type 1 diabetes progression and cost simulation model. Sensitivity analyses on key parameters were performed, and the model was found to be robust. RESULTS: The augmented model can estimate quality-adjusted life years (QALYs) as well as costs associated with type 1 diabetes on any population of interest over any period of time. The model is used to compare intensive versus conventional treatment strategies using a simplified set of assumptions regarding the relative effects of these alternative treatments. With these assumptions, intensive strategy produces more QALYs than does conventional strategy and is cost-beneficial after 5 years. CONCLUSIONS: The model enables health planners to perform cost-effectiveness analyses to compare alternative treatment strategies for type 1 diabetes and support subsequent decision making.

Adult↗
PubMed1998

Disease progression and cost of insulin dependent diabetes mellitus: development and application of a simulation model.

This paper presents the development and application of a Markov model that simulates the onset and progression of insulin dependent diabetes mellitus (IDDM) and its sequelae. The model estimates direct medical costs resulting from different patterns of health states during the course of the disease. The model is user-friendly and allows for changes in the input variables to be specified, thereby providing a frame-work for sensitivity analysis. The Markov process moves a cohort of individuals through six different health states: Healthy, IDDM without chronic microvascular complications, IDDM with retinopathy alone, IDDM with neuropathy alone or with retinopathy, IDDM with nephropathy, and death. Epidemiologic data were obtained from governmental sources as well as the medical literature. Transition probabilities were estimated using data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Direct medical costs were estimated from actual charges from a local health maintenance organization in Wisconsin. The validity of the model was tested in several ways including a comparison with an independent cost estimate made by the Wisconsin Department of Health and Family Services. The model appears to be useful in estimating the progression and associated costs of IDDM for any large population over any period of time and in allowing changes in the inputs to evaluate their impact thus providing pertinent information to healthcare decision-makers and health planners.

Age Factors↗
PubMed1997

Introduction to diagnostic laboratory immunology.

Assays performed in the diagnostic immunology laboratory support the diagnosis and management of a wide spectrum of clinical conditions. This chapter reviews immunologic principles as they apply to diagnostic laboratory assays. Most of the determinations are based on well-established principles of antigen-antibody reactions. Some of the specific areas discussed include flow cytometric analyses, critical in the care of patients with hematologic malignancies, with the acquired immunodeficiency syndrome, or undergoing transplantation, and protein electrophoretic assays to identify the presence of monoclonal gammopathies. We also discuss the use of molecular techniques in the diagnosis of hematologic malignancies and primary immunodeficiencies, characterization of the major histocompatibility complex, and enumeration of viral burden.

Allergy and Immunology↗
PubMed1995

Reversal of immunosuppression of lymphocyte proliferation caused by sera from persons with AIDS.

Sera from persons with AIDS contain inhibitors of lymphocyte proliferation. Inhibitory activity can be detected before the development of AIDS in humans. There appear to be at least three distinct suppressive moieties, one of which is prostaglandin E2. We and others had previously shown that serum samples from subjects with AIDS contained antibody to the cell line HUT 102B2. We attempted to remove this antibody and to determine if that action would also remove the inhibitory activity present in human immunodeficiency virus-positive sera. We incubated sera from subjects with AIDS with HUT 102B2 cells and tested the resultant supernatants for inhibition of cell proliferation. We found that this procedure significantly reversed inhibition by serum. Other cells and cell lines were similarly tested, but only HUT 102B2 cells absorbed the inhibitory product(s). However, we determined that secretory material from another cell line, MLA 144, also reversed inhibition. The physical characteristics of the supernatant were investigated. Thus, two procedures and likely separate products, possibly cytokines, reverse immunosuppression by sera from persons with AIDS.

Absorption↗
PubMed1994

Breaking the asymptomatic phase of HIV-1 infection.

AIDS typically consists of three phases: (1) an acute, infectious mononucleosis-like syndrome followed by (2) a prolonged asymptomatic stage ending in (3) the appearance of frank AIDS. The asymptomatic phase may last for years and its presence suggests a persistent conflagration between the virus and the host's immune response. There is considerable evidence that an immune response develops but the response is ultimately inadequate. From the work of others as well as our own, we have constructed a hypothesis which attempts to explain some aspects of the immune response. We propose that HIV-1 preferentially infects a subset of CD4+ lymphocytes which are then either destroyed or altered in their biological functions. Further, we suggest that this subset represents the CD4+ TH1 lymphocyte population. By decreasing the quantity of IL-2 and interferon-gamma produced by TH1 lymphocytes, the production of cytokines by TH2 cells is increased. One of the cytokines produced by TH2 lymphocytes is IL-10, a polypeptide with significant inhibitory properties towards lymphocytes. Sera from patients with frank AIDS have significant lymphocyte inhibitory activities some of which operate through IL-10. Thus, a gradual shift to a TH2-type response and release of increasing amounts of inhibitors eventually prevents the host from replacing destroyed cells or mounting new and appropriate immune responses.

CD4-Positive T-Lymphocytes↗
PubMed1993

Serum inhibitors precede the development of SAIDS.

Rhesus macaque monkeys infected with the simian immunodeficiency virus develop a syndrome mimicking AIDS in humans. We have demonstrated previously that sera from individuals infected with human immunodeficiency virus type 1 inhibit the proliferation of lymphocytes from healthy noninfected subjects and that this phenomenon is associated with the development of clinical AIDS. We have also shown that sera from monkeys infected with SIV also have such inhibitors. In this body of work, we attempted to document the onset of these inhibitors in relation to the time of SIV infection. Twenty rhesus macaques were injected with one of two tissue strains of SIV or media. Blood was drawn on a set schedule and the serum samples frozen at -70 degrees C. The animals were monitored and observed for up to 42 weeks. All test animals were autopsied. Sera from all the draws were assayed against the same populations of human peripheral blood mononuclear cells in the same experiment using suboptimal amounts of phytohemagglutinin (PHA). Sera from those animals that subsequently developed SAIDS were more likely to demonstrate serum inhibition. This inhibition could be seen as early as 8-10 weeks after infection. By week 14, the assay could differentiate animals into SAIDS or healthy groups with a sensitivity of 67% and a specificity of 89%.

Analysis of Variance↗
PubMed1992

Sera from simian immunodeficiency virus-infected rhesus macaques inhibit lymphocyte proliferation.

Rhesus macaque monkeys infected with the simian immunodeficiency virus (SIV) develop a syndrome mimicking acquired immunodeficiency syndrome (AIDS) in humans. We had demonstrated previously that sera from individuals infected with human immunodeficiency virus (HIV) inhibit the proliferation of lymphocytes from healthy noninfected subjects and that this phenomenon was associated with the development of clinical AIDS. Thus, we sought to determine whether sera from SIV-infected monkeys would also inhibit lymphocytes from healthy humans and SIV-negative rhesus monkeys. Sera from SIV-infected monkeys were compared with sera from uninfected animals and cultured with cells from healthy human volunteers or SIV-negative monkeys in the presence or absence of phytohemagglutinin (PHA). Cell proliferation was determined by measuring the incorporation of radiolabeled thymidine into cellular DNA. Sera from SIV-infected monkeys suppressed the proliferation of human and non-human primate lymphocytes. This activity appears to be similar to that described for sera from HIV-1-infected humans. Therefore, rhesus macaques infected with SIV provide a model for the study of serum inhibitory factors previously reported in AIDS patients.

Animals↗
PubMed1991

A streptococcal erythrogenic toxin preparation augments natural killer activity of peripheral blood mononuclear cells.

Natural killer (NK) activity in peripheral blood mononuclear cells is augmented by products released by two different strains of streptococci. This property is due at least in part to an erythrogenic toxin (ET). A preparation of physiologically active ET from strain NY5 group A beta-hemolytic streptococci and streptococcal products (SP) derived from the culture supernatants of ATCC strain 19165 group A streptococci were both potent inducers of NK activity. An anti-serum to ET reacted with two polypeptides in SP, one of which comigrated with ET when analyzed by SDS-PAGE. Using an affinity column with an antiserum to ET known to neutralize its mitogenic properties, the NK-enhancing activity of ET and SP was partly absorbed and was recovered upon elution. These findings suggest that immunologically related ETs in different streptococcal strains play a role in the activation of NK cells. This novel property of streptococci may feature in the pathogenesis of streptococcal infections and their protean manifestations.

Adsorption↗
PubMed1990

Serum factors in the progression of human immunodeficiency virus type 1 infection to AIDS.

We studied the prevalence of four serum factors in individuals at different stages of human immunodeficiency virus-1 (HIV-1) infection. Soluble interleukin-2 receptors (sIL-2R) were elevated in all antibody-positive groups compared with high-risk, antibody-negative controls. Paraproteins, usually of the IgG-kappa isotype, were found in the sera of a significant number of HIV-1-infected individuals as were antibodies to lymphocytes (ALAs). Serum factors that inhibit proliferation of peripheral blood mononuclear cells from healthy donors appear late in the course of infection and were associated with increasing clinical severity. Measurement of these factors may prove to be useful in defining the stages of infection and in predicting the appearance or exacerbation of symptoms. They may also play a role in the development of the HIV-1-induced immune defects that lead to the expression of clinical acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Peripheral blood mononuclear cells from AIDS patients release but do not respond to antigen-stimulated NK-activating lymphokines.

We have previously shown that streptococcal product (SP) extracted from the culture supernatants of Streptococcus pyogenes ATCC 19615 augments NK activity, partly by inducing the release of soluble factors from mononuclear cells. In this study we use SP as an NK stimulant to investigate the mechanism of NK depression in AIDS. We demonstrate that the NK activity of AIDS patients is lower than normal controls and can be significantly enhanced with SP, although not to control levels. The decreased cytotoxicity in AIDS is not due to a depletion of NK cells, nor to the depletion of lymphokines from CD4 cells that are directly involved in NK cell activation. PBMCs from patients with AIDS respond to SP, producing normal levels of NK-enhancing substances in their supernatants. However, upon examining the ability of SP-induced supernatants from control cells to augment the NK activity of cells from AIDS patients, we find significantly less activity in AIDS cells than in control cells, suggesting an intrinsic effector dysfunction of NK cells in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Preferential homing of tumor-infiltrating lymphocytes in tumor-bearing mice.

In view of the current interest in the use of lymphoid cells in adoptive immunotherapy of patients with advanced cancer, we have studied the homing patterns of various lymphoid effector cells in mammary-tumor-bearing mice. Single-cell suspensions of total splenocytes, natural killer (NK) cells, and lymphokine-activated killer (LAK) cells were prepared from the spleens of C3H/OuJ mice. Tumor-infiltrating lymphocytes (TIL) were isolated from mammary adenocarcinomas excised from retired breeder females of the same substrain. Effector cells were labeled with indium-111 and injected via a tail vein into female C3H/OuJ mice bearing one or more mammary tumors. Twenty-four hours after administration, total splenocytes, NK cells, and LAK cells distributed themselves evenly between normal mammary tissue and mammary adenocarcinomas. Only TIL had a higher concentration in tumors than in corresponding normal mammary tissue. The ability of the different lymphocyte preparations to lyse YAC-1 cells was determined by means of a 4-h 51Cr-release cytotoxicity assay. Cells harvested from LAK cell cultures and further enriched by centrifugation through a discontinuous Percoll gradient and interleukin-2 (IL-2)-stimulated TIL demonstrated the highest levels of cytotoxicity, while total splenocytes and fresh TIL were characterized by the lowest levels. Since IL-2-stimulated TIL were highly cytotoxic and exhibited better tumor localization than both NK cells and LAK cells in this system, they may be the lymphoid effectors of choice for adoptive immunotherapy of advanced cancer.

Adenocarcinoma↗
PubMed1988

Human T-lymphotropic virus type I-associated benign transient immature T-cell lymphocytosis.

We describe a case of human T-lymphotropic virus type I (HTLV-I)-associated transient benign immature T-cell lymphocytosis in a black female patient, which over the course of several months underwent spontaneous complete remission. The patient presented with a white blood cell count of 20,000/microliter and a T4/T8 ratio of 1.7:1. The majority of cells appeared to be lymphoid in origin, and cell marker analyses established that the circulating lymphocytes were predominantly immature T-cells. HTLV-I was detected at this time by a p19 indirect immunofluorescent slide assay. Over a 1-month period of time the patient's clinical status evolved into a mature T-lymphocytosis with a T4/T8 ratio of 4.5:1. HTLV-I was detected by anti-p19 immunofluorescence by cell sorter analyses and by dot-bloc nucleic acid hybridization. Serological testing demonstrated that the patient had anti-HTLV-I antibodies and antimembrane antibodies specific for an HTLV-I producing cell line. In a competitive HTLV-I ELISA assay only HTLV-I proteins could effectively compete out the seroreactivity. The patient also had a high serum level of soluble interleukin-2 (IL-2) receptors, which is associated with HTLV-I infection. This is the first reported case of immature T-lymphocytosis in a patient infected with HTLV-I. The patient's HTLV-I markers disappeared with time, and her lymphocytosis subsequently spontaneously resolved. She remains disease free and virus negative after 2 years of follow-up study.

Antibodies, Viral↗
PubMed1988

HIV-1 infection abolishes CD4 biosynthesis but not CD4 mRNA.

In order to improve understanding of how HIV-1 infection down-modulates cell surface membrane expression of CD4, we have measured several parameters of CD4 expression in the human tumor T-cell lines CEM and MOLT-4 at different times after infection. Three independent HIV-1 isolates were used including one that encodes a truncated nef protein and another that appeared to be noncytolytic against CEM. The level of CD4 mRNA, the rate of biosynthesis of CD4 protein, and the percentage of CD4-positive cells were measured. With each viral isolate it was found that infection led to a specific and almost complete inhibition of CD4 protein biosynthesis. This substantially exceeded, at every time point after infection, a concomitant reduction in CD4 mRNA. Hence an inhibition of translation probably accounts for much of the decline in the rate of CD4 biosynthesis. This implicates a novel selective translational inhibition of host gene expression by HIV-1 as a factor in the disappearance of surface membrane CD4 from infected cultures.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Migratory patterns of different indium-111 labeled leukocyte populations (chiefly lymphocytes) from control and thymectomized rats.

The blood clearance and 24-hr organ distribution of five lymphocyte-rich suspensions harvested from different source organs were compared in the Wistar rat, after labeling with [111In]tropolone and intravenous injection. Peripheral blood lymphocytes (chiefly T cells) had the highest levels in the blood and lymph nodes, a relatively higher level in intestine and a lower level in the spleen than other suspensions. Thymocytes cleared promptly from the blood, accumulated markedly in the liver, moderately in the spleen, but very poorly in other organs, including the thymus. Splenic cells (rich in B cells) sequestered predominantly in the spleen and liver. Splenic cells nonadherent to nylon wool (T-cell enriched) had a relatively high uptake in lymph nodes and marrow. Splenic cells from thymectomized rats (NK cell enriched) localized predominantly in the liver and spleen, and poorly in lymph nodes. We conclude that the source organ for harvesting rat lymphocytes is an important determinant in their localization, as well as other factors such as the techniques of isolation, the toxicity and stability of the radioactive label and the cell radiation dose from internalized radioactivity.

Animals↗
PubMed1987

Lysis of fresh murine mammary tumor cells by syngeneic natural killer cells and lymphokine-activated killer cells.

We have compared the ability of natural killer (NK) cells from two substrains of C3H mice that differ with respect to their susceptibility to the development of mammary adenocarcinomas to lyse fresh syngeneic mammary tumor cells. Single cell suspensions of mammary tumors from retired breeder females were used as targets in 22-h 51Cr-release cytotoxicity assays with syngeneic NK cells. Tumor cell suspensions were prepared by enzymatic digestion of finely minced tissue followed by centrifugation through a discontinuous Percoll gradient. Effector cells were prepared by passing spleen cells over nylon wool followed by centrifugation through Percoll fraction 7. Syngeneic NK cells had significant levels of lysis against 5/8 tumors studied. NK cells from low risk animals (C3Heb/FeJ) consistently demonstrated greater cytotoxicity against tumor cell preparations than did effectors from the high tumor substrain (C3H/OuJ). Study of cytocentrifuge preparations stained with Wright-Giemsa revealed that the two substrains were identical with respect to the number of azurophilic granules present in the cytoplasm of their NK cells. We have also shown that lymphokine-activated killer (LAK) cells can be generated from splenocytes in C3H mice. While LAK cells from both substrains were capable of lysing fresh syngeneic mammary tumor cells in vitro, LAK cells from the animals at high risk for the formation of mammary adenocarcinomas had greater cytotoxicity against tumor cell suspensions than LAK cells from the low tumor substrain.

Adenocarcinoma↗