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Biomedical subjects

A Mathur

Publications and source records attributed to A Mathur.

At least 145 records · Page 8Linked to original sources

Immunoglobulin (Fc) receptors on murine T- and B-lymphocytes: investigations using tumor models.

Lymphoid tumors are productive experimental models for the study of lymphocyte immunoglobulin receptors. Investigations with Fc receptor expressing lymphoid tumor cells have generated much useful information about: (a) the developmental expression of the different classes of Fc receptors on lymphoid cells of the T- and B-lineages; (b) the biochemical steps involved in the regulation of Fc receptor expression on lymphoid cells; (c) the structures of lymphoid cell Fc receptors and their genes; (d) the signals that induce alterations in the expression of Fc receptors on lymphoid cells; and (e) the molecular specificity of the binding of immunoglobulin to lymphoid cells Fc receptors. In addition, tumors that secrete immunoglobulins are providing useful models for analysis of the mechanisms by which B-cells influence Fc receptor expression and function on T-cells. An interesting, bi-directional immunoregulatory circuit involving Fc epsilon R+ host T-cells and IgE-secreting hybridoma cells has been identified that could prove useful in the analysis of the regulation of epsilon heavy chain expression. The studies discussed in this article and elsewhere in this volume serve to emphasize that, in addition to being clonal sources of key molecules such as Fc receptors and their messenger RNAs, lymphoid tumor cells that express Fc receptors are powerful and unique experimental models for investigating the developmental biology, regulation and function of lymphocyte Fc receptors.

Animals

Experimental evaluation of the antibiotic carrying capacity of a muscle flap into a fibrotic cavity.

A study was undertaken to determine the antibiotic carrying capacity of a transferred muscle flap into a fibrotic cavity using a tissue cage model in rabbits. Blood and chamber fluid antibiotic levels were determined after intramuscular hindlimb gentamicin injection up to 56 days following muscle transfer. This study suggests that muscle flaps increase the concentration of antibiotics that can be achieved within a fibrotic cavity. The measurable peak level decreases with time, probably due to increased scarring around the muscle. This model should enable the study of many different classes of antibiotics with different protein binding and other administration schedules using multiple timed doses or a combination of agents.

Animals

Japanese encephalitis--an important cause of acute childhood encephalopathy in Lucknow, India.

Eighty-six randomly selected children between 6 months and 12 years of age admitted with acute unexplained encephalopathy over a one year period were examined for evidence of Japanese encephalitis. One or more indicators of the infection were present in 36 (41.8%). Viral isolation from brain tissue was possible in 2 of 12 patients and from cerebrospinal fluid in 19 out of 62 patients. Serological evidence of probable Japanese encephalitis was found in 21 out of 36 patients. Japanese encephalitis is an important cause of acute childhood encephalopathy in the Lucknow area, where it is probably endemic.

Brain

Immunomodulation of intradermal mammary carcinoma using staphage lysate in a rat model.

Staphage lysate (SPL), a preparation of Staphylococcus aureus obtained by bacteriophage lysis, is an interferon-inducer and stimulator of T and B lymphocytes. Does SPL, as an immunopotentiator, have an effect on the growth and metastases of an intradermal mammary carcinoma? To answer this question, a study using SPL in female Fischer rats injected with 7 x 10(6) viable 13762 mammary tumor cells on the midback were used. Four groups were created with 10 animals in each group. Group I was the control group. They received no treatment. Group II received 0.3 ml of medium in which SPL was carried on alternate days. Group III received 0.3 ml SPL on alternate days. Group IV were sensitized with dead staphylococcal organisms prior to SPL treatment as in Group III. Tumor diameters were recorded on days 10, 13, 17, and 21, and autopsies were performed to determine the extent of metastases. Histologic examination and serum antibody measurements were performed. The mean tumor diameters on day 21 were: Group I: 4.1 +/- 0.2 cm; Group II: 3.80 +/- 0.19 cm; Group III: 3.04 +/- 0.13 cm; and Group IV: 2.97 +/- 0.14 cm. Rats receiving SPL treatment in Groups III and IV had significantly smaller tumors (P less than .001). The incidence of axillary lymph node involvement was: Group I: 100%; Group II: 87.5%; Group III: 62.5%; and Group IV: 40%. Lung metastases were seen in all groups. Groups I and II had 100% incidence of grossly visible nodules, whereas Groups III and IV had 75% and 70% involvement. Gross findings were confirmed by microscopic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Experimental pretransfer expansion of free-flap donor sites: II. Physiology, histology, and clinical correlation.

There is a statistically significant increase in blood flow into expanded cutaneous and myocutaneous flaps in a pig model over controls. The vascular trees within flaps enlarge following expansion, and pronounced neovascularization is seen in the papillary dermis and capsular layers. Experimentally, there is differential thinning of all tissue layers except the epidermis. A successful clinical application of this technique, by free-tissue transfer of an expanded fasciocutaneous scapular flap, is described. The technique is applicable when altered flap size or contour is desired.

Adipose Tissue

Immunological memory in latent Japanese encephalitis virus infection.

Long term B-cell memory to Japanese encephalitis virus (JEV) in latently infected mice was investigated by adoptive cell transfer. Both IgM and IgG memory were elicited by antigen challenge or cyclophosphamide induced reactivation of virus. A weak antigen-specific IgM response for a brief period and a strong IgG response were detected in Swiss albino mice exposed to secondary infection. A correlation between the secondary IgM antibody and protection against JEV challenge was observed in adoptive transfer experiments. This was abrogated by pretreatment of the serum with 2-mercaptoethanol. Similarly secondary immune splenic T-cells up to day 5 post-reactivation provided protection. These results suggest that a long term antigen-specific IgM and IgG memory was induced by JEV challenge in latently infected mice. Further, the role of IgM antibody and T-cells in the response of mice to secondary JEV infection has been shown.

Animals

Immunopathological study of spleen during Japanese encephalitis virus infection in mice.

Following intraperitoneal inoculation, Japanese encephalitis virus replicated in peritoneal macrophages, appeared on day 3 in the splenic macrophages of the perifollicular region and later in cells of the periarteriolar lymphoid sheath (PALS) as shown by indirect immunofluorescence. Productive JEV infection was observed both in macrophages and T-cells. Morphological study of spleen during JEV infection revealed proliferative changes, with increased number of macrophages from day 3 p.i. in the perifollicular region followed by accumulation of polymorphonuclear leucocytes which reached a maximum on day 9 p.i. The T dependent areas were considerably enlarged by day 9 and gradually reduced in size by week 3. At later periods germinal centres appeared in the T independent area and were prominent by day 15. The cells containing virus antigen disappeared with the appearance of germinal centres, thus indicating the role of the latter also in virus clearance.

Animals

Thymus-dependent in vivo suppression of IgE synthesis in a murine IgE-secreting hybridoma.

In previous studies we demonstrated that BALB/c mice bearing ascitic tumors of the IgE-secreting hybridoma B53 (epsilon, kappa, anti-dinitrophenyl) developed large numbers of Lyt-1-2+ Fc epsilon R(+) T lymphocytes (T cells with membrane Fc receptors) in response to the elevated serum IgE concentration. The development of Fc epsilon R(+) T lymphocytes was followed by a progressive decrease in the levels of serum IgE in spite of continued proliferation of the hybridoma cells. This sequence of events suggested that the IgE-secreting hybridoma triggered a suppressive immunoregulatory circuit of the host that inhibited IgE expression by the hybridoma cells. The present studies were undertaken to investigate the basis for the subsequent decline in serum IgE levels in mice with B53 tumors and to identify host factors that might be involved in this process. We observed that ascitic B53 cells recovered at increasing time points from BALB/c mice exhibited a selective decline in steady state levels and rates of synthesis of epsilon-heavy chain protein and mRNA. The expression of kappa-light chain protein and mRNA appeared relatively unchanged. The decrease in epsilon-heavy chain gene expression did not occur when B53 tumors were passaged in nu+/nu+ mice or in BALB/c mice depleted of Lyt-2+ cells (suppressor/cytotoxic cell lineage), but did occur in nu+/nu+ mice reconstituted with neonatal BALB/c thymus and in BALB/c mice depleted of L3T4+ cells (helper/inducer cell lineage). That Fc epsilon R(+) T lymphocytes were directly involved in the inhibition of IgE expression was supported by the earlier and more pronounced inhibition of B53 IgE in mice infused with Fc epsilon R(+) T lymphocytes. We conclude from these findings that: 1) the decline in serum IgE levels that occurs toward the end of each generation of in vivo passage of the B53 hybridoma is due to decreased production of IgE by the hybridoma cells, 2) the decreased production of IgE is due to a selective loss of epsilon mRNA expression, 3) the decrease production of IgE by B53 cells is dependent on the presence of Lyt-2+ cells, and 4) Fc epsilon R(+) T lymphocytes participate in the mechanism by which IgE production is suppressed.

Animals

Memory suppressor T cells in latent Japanese encephalitis virus infection.

The generation of secondary suppressor T (Ts) cells has been studied during latent Japanese encephalitis virus (JEV) infection of mice. The mice infected with JEV 27 weeks earlier, on challenge with the homologous virus, showed accelerated generation of secondary Ts cells; these appeared on Day 6, with peak activity on Day 8, and lasted for 27 days. The secondary Ts cells were Thy1.2+, Ly1-2+, antigen-specific, and acted in a dose-dependent manner. The secondary Ts cells could also be generated by reactivation of the JEV in latently infected mice. The findings thus show the presence of memory suppressor T cells in mice latently infected with JEV that can be stimulated to produce secondary Ts cells by exogenous or endogenous virus challenge. This phenomenon could help to persistence of the virus.

Animals

Induction of secondary immune response by reactivated Japanese encephalitis virus in latently infected mice.

Development of secondary immune response has been studied following reactivation of latent Japanese encephalitis virus (JEV) infection in mice. The virus could be reactivated in 43% of the latently infected mice at 27 weeks p.i. by treatment with cyclophosphamide. The reactivated virus induced delayed-type hypersensitivity (DTH) and leucocyte migration inhibition (LMI) responses in mice, with peak activity on Day 5 post-reactivation (p.r.). The DTH persisted at low levels for long periods. Humoral immunity measured by haemagglutination-inhibiting antibody showed a four-fold rise in antibody titres. DTH was transferable by immune spleen cells for 5 days p.r. only. It is, therefore, concluded that JEV reactivation generates a quick and short-lived secondary immune response.

Animals

Variable effects of dengue virus-induced cytotoxic factors on different subpopulations of macrophages.

Dengue virus (DV) induces T lymphocytes of the spleen to produce a cytotoxic factor (CF) that induces a subpopulation of macrophages (M phi) to produce a soluble cytotoxin (CF2). Both these factors kill normal lymphoid cells and M phi. The present study was undertaken to investigate the effects of these factors on the I-A-positive and I-A-negative subpopulations of mouse peritoneal M phi. It was observed that CF kills I-A-negative M phi and induces I-A-positive M phi to produce the CF2 that kills both types of cells. However, even when combined together, CF and CF2 do not kill 100% of the M phi. The two-step mechanism involving co-operation between T cells and M phi appears to be biologically economical for maintaining the cytotoxic pathway.

Animals

Macrophage functions during dengue virus infection: antigenic stimulation of B cells.

This study was undertaken to investigate the function of dengue type 2 virus (DV)-infected mouse peritoneal macrophages (M phi) regarding the antigenic stimulation of B lymphocytes of the spleen. It was observed that a variable proportion of M luminal diameter show DV-specific immunofluorescent antigen, which depended upon the route of administration of the virus, being higher in i.p.-inoculated mice and in vitro-infected M luminal diameter monolayers. The DV-infected M luminal diameter presented the DV antigen to B cells in vitro and in vivo, leading to their clonal expansion as shown by counting the virus-specific IgM antibody plaque-forming cells (PFC). The PFC response depended upon the number of DV-infected M luminal diameter. The antigen was presented equally well both by I-A-negative and I-A-positive M luminal diameter. Superimposition of a heterologous antigen (Coxsackie B4 virus) in a Mackaness type of experiment depressed the capacity of M luminal diameter to present both the homologous as well as heterologous antigen.

Animals

Increased T epsilon cells in BALB/c mice with an IgE-secreting hybridoma.

Since it has been proposed that T cells with receptors for the Fc portion of IgE (T epsilon) in rats, mice and humans are IgE-specific regulatory cells, it was investigated whether mice with an IgE-secreting hybridoma might be a source of large numbers of T epsilon cells. BALB/c mice with ascitic tumors of the IgE hybridoma B53 (epsilon, kappa, anti-DNP) developed high serum concns of monoclonal IgE which was followed by the appearance of large numbers of Lyt1-2+ L3T4- T epsilon cells. In contrast, mice bearing a non-IgE producing variant of B53 failed to develop T epsilon cells. Mice infused with cell-free ascites fluid (containing high levels of monoclonal IgE) from the IgE-secreting B53 hybridoma developed high serum IgE levels and also developed high numbers of T epsilon cells. Mice infused with cell-free ascites obtained from the non-IgE-secreting variant ENP-1 (containing very low amounts of IgE) did not develop either high serum IgE levels or T epsilon cells. These findings suggest that high serum IgE concns induce large numbers of T cells that express phenotypic markers of suppressor cells and have surface IgE-Fc receptors. These studies extend to IgE the principle that hybridomas and plasmacytomas induce large numbers of immunoregulatory T cells that express Fc receptors specific for the heavy chain class of the secreted monoclonal immunoglobulin. Since T epsilon cells are normally present only in small numbers, their marked increase in mice with IgE-secreting hybridomas identifies a ready source of large numbers of T epsilon cells that can be used to investigate their regulatory properties.

Animals