Search PubMed⌕ Search

Biomedical subjects

M Venkataraman

Publications and source records attributed to M Venkataraman.

At least 37 records · Page 2Linked to original sources
PubMed1989

The functional deficiency of B lymphocytes in patients with lung cancer is due to inadequate T-cell help and excessive suppression by T and non-T cells.

The proliferative and plaque-forming cell (PFC) responses of unseparated mononuclear cells (MNC) and B- and T-cell-enriched populations of cells were analyzed in 15 patients with lung cancer to determine the mechanisms involved in the functional abnormality of their B cells. The PFC responses of the MNC of the patient group were significantly lower than those of normal controls. In addition, the enriched B cells of several patients showed a further decrease in their PFC responses after coculture with autologous T cells compared with their respective MNC responses. The proliferative response against phytohemagglutinin (PHA) was also lower in many of the patients after similar cocultures. Cocultures of patients' B cells with T cells from normal controls significantly enhanced the PFC responses in 7 patients. In most of the normal controls, B lymphocytes showed a significant decrease in their PFC responses after coculture with the patients' T cells. Although the percentages of total T cells, T-helper, and B cells were within the normal range, the number of suppressor T cells was significantly higher in the patient group. These results indicate that a combination of insufficient T-cell help, excessive suppression by both T and non-T cells, and a possible intrinsic B-cell abnormality are responsible for the B-cell functional deficiency observed in patients with lung cancer.

Aged↗
PubMed1987

Effects of cryopreservation on the mononuclear cells of patients with lung cancer and normal controls.

Studies were carried out to determine the effects of cryopreservation on the mitogen-induced proliferative and immunoglobulin-producing abilities of peripheral blood mononuclear cells (MNC) of patients with lung cancer and normal controls. One-half of each sample of cells was tested fresh, while the other half was frozen, thawed immediately, and cultured at the same time. The responses of each sample of cryopreserved cells were compared to the responses of fresh cells from the same individual in simultaneous assays. The cryopreserved mononuclear cells of most of the lung cancer patients showed significantly enhanced plaque-forming cell (PFC) responses after stimulation with pokeweed mitogen (PWM). No such significant differences were observed between the proliferative responses of cryopreserved and fresh cells against phytohemagglutinin (PHA) or PWM stimulation. The cryopreserved MNC of some of the normal controls also showed a similar increase in the PFC responses, although to a lesser extent. Coculture of cryopreserved B cell-enriched populations of cells with fresh T cell-enriched fractions obtained from these patients also resulted in the generation of a higher number of PFCs as compared to the number of PFCs observed after coculture of fresh B and T cell-enriched populations. The results indicate that the suppressor activities of monocytes/macrophages and other non-T cells (NK cells) are sensitive to cryopreservation. The results also show that the MNC of patients with lung cancer can be cryopreserved and used for subsequent B and T cell assays.

Adult↗
PubMed1986

Susceptibility of human T cells, T-cell subsets, and B cells to cryopreservation.

We have studied the number of viable and functionally active T and B lymphocytes obtainable after cryopreservation to determine the best and most practical way to recover the maximal number of viable and functionally active cells. Assays were done on purified populations of human T and B cells recovered after cryopreservation. The results were compared to those obtained from similar types of cells fractionated from fresh and from cryopreserved mononuclear cells. The number of viable T cells recovered after cryopreservation was significantly lower than the number of viable T cells obtained from either fresh or cryopreserved mononuclear cells. The residual viable T cells recovered after cryopreservation showed significantly reduced blastogenic activity in response to pokeweed mitogen (PWM) stimulation. This occurred despite their normal blastogenic response to phytohemagglutinin and their normal ability to help B cells in the production of immunoglobulins following PWM stimulation. The reduction in the blastogenic responses of these T cells to PWM stimulation is attributed to the loss of a portion of the PWM responding subset of T cells. The loss in this subset of T cells was related to the exposure of cells to ammonium chloride prior to cryopreservation. The viability and functional abilities of B cells were not affected regardless of whether purification was done before or after cryopreservation. These findings indicate that extrinsic membrane damage to T cells induced prior to cryopreservation can affect the viability and responsiveness of a certain population of normal T cells. The damage can be minimized by reversing the sequence of T-cell isolation and freezing so that isolation of T cells is done after, rather than before, freezing. These results could be important in the study of T cells from patients with T-cell abnormalities, since the patients' cells could have an intrinsic membrane defect which would make them sensitive to freezing similar to that induced by extrinsic damage.

B-Lymphocytes↗
PubMed1985

B-cell changes occur in patients with sickle cell anemia.

B- and T-lymphocytes were studied in patients with sickle cell anemia. Samples were analyzed during asymptomatic periods and during vasocclusive pain crises to assess a possible relationship to these periods. Assays of B-cell function and quantitation of B- and T-lymphocytes and their subsets were carried out. During crises, six of the eight patients showed a significant decrease in the number of immunoglobulin-producing cells, together with normal or enhanced blastogenic responses. The total number of T-lymphocytes was normal when measured by the monoclonal antibody OKT3 in contrast to the significantly lower level observed in some patients, as determined by the E-rosette technic. There were no significant changes in the percentage of either helper or suppressor T-cells or in the percentage of B-cells. The results show that changes in in vitro B-cell function occur during vasocclusive pain crises in patients with sickle cell anemia. These may be clinically important in these patients.

Adult↗
PubMed1985

Suppression of B-lymphocyte function by T-lymphocytes in patients with advanced lung cancer.

The ability of B-lymphocytes to produce immunoglobulins in response to pokeweek mitogen stimulation was studied in 21 untreated stage III lung cancer patients by culture of their mononuclear cells in vitro. The number of immunoglobulin-producing cells was significantly lower in 20 of the 21 patients when compared to responses shown by normal control subjects. In contrast, the proliferative responses of many of the patients were within the normal range. When the T-lymphocytes of these patients were irradiated with 1,250 rad to eliminate the suppressor T-cell activity and then cultured with autologous B-cells, the number of immunoglobulin-producing cells was enhanced to the normal range in 7 of the 18 patients. These results indicate that B-cell function is impaired in most patients with advanced lung cancer. They also suggest that, in addition to suppression by radiosensitive suppressor T-cells, other mechanisms are involved in the observed B-cell functional abnormality.

Adult↗
PubMed1984

B lymphocyte changes in homosexual men with generalized lymphadenopathy.

Studies of B and T lymphocytes were done on homosexual men with generalized lymphadenopathy, homosexuals without any clinical symptoms, and on normal heterosexual controls. In vitro proliferative responses induced by pokeweed mitogen (PWM) and phytohemagglutinin (PHA) were determined, as was the polyclonal plaque-forming cell (PFC) response to PWM. A decreased proliferative response to PWM and PHA was observed in mononuclear cells from patients with generalized lymphadenopathy and in some of the asymptomatic individuals. In addition, the mononuclear cells of these groups showed a reduced PFC response to PWM, which was not due to a kinetic difference. Serum immunoglobulins, particularly IgG, were elevated in most of the patients with generalized lymphadenopathy. T cell changes including reduced T helper/suppressor ratios were observed in most of the symptomatic and in some of the asymptomatic homosexuals. The reduced proliferative and differentiative responses of mononuclear cells to PWM may be compatible with a B cell abnormality, in addition to a previously described T cell dysfunction.

Adult↗
PubMed1983

Subpopulation of human helper and suppressor T lymphocytes.

Mitogen driven differentiation of normal human mononuclear cells is a well-established model for the study of antibody synthesis in man. In certain rare individuals who are clinically normal, unfractionated mononuclear cells or a mixture of purified B plus T lymphocytes differentiate into immunoglobulin producing cells in response to purified protein derivative of tuberculin (PPD) but not in response to pokeweed mitogen (PWM). To evaluate this observation we have irradiated T cells from such individuals to eliminate naturally occurring suppressor T cell activity and then added the irradiated T cells back to autologous B cells before culture. The B cells then responded to PWM. The original PPD responses of cells from these individuals were now significantly reduced. Although, there was no difference between PWM nonresponders and responders in the number of OKT-8 positive cells, elimination of OKT-8 positive cells in the PWM nonresponders with OKT-8 monoclonal antibody and complement resulted in a significantly increased response to PWM. This study indicates that there are suppressor T cells which specifically inhibit B cell response to PWM without affecting the PPD response. These results also show that the helper T cells involved in the PWM response are radioresistant and those involved in the PPD response are radiosensitive.

Antibodies, Monoclonal↗
PubMed1980

Cellular events in tolerance. VIII. Analysis of the proliferative capacity of antigen-binding cells isolated from normal or tolerant spleens.

Previous studies in our laboratory have demonstrated that hapten-binding lymphocytes (ABC) can be isolated from the spleens of mice rendered tolerant to the hapten. These cells are reduced in PFC precursor frequency when stimulated with either specific antigen or mitogen (Reference 6). In the present studies, we have combined antigen-specific cell isolation and an analysis of thymidine uptake by purified B cells to determine whether hapten-binding B cells in tolerant mice can be stimulated to proliferate in response to specific antigen. Compared with normal ABC, "tolerant" ABC showed a significantly reduced thymidine incorporation responsiveness in vitro. This suggests that unresponsiveness in adult mice can result in an impairment of clonal proliferation. Hence, these "tolerant" ABC appear to be functionally though not physically, deleted.

Animals↗
PubMed1979

B-cell subsets responsive to fluorescein-conjugated antigens. III. Differential effect of E. Coli lipopolysaccharide on T-dependent and T-independent responses in vivo.

The effect of E. coli lipopolysaccharide (LPS) on the induction of both hapten-specific immunity and tolerance was studied in an in vivo system utilizing putative T-cell dependent (TD) or T-cell independent (TI) challenge antigens. The administration of LPS 1 day prior to challenge preempted the response of C3D2 mice to a TD antigen (FL-KLH) but had little effect on the response to FL-Ficoll, a TI antigen. LPS did not affect the responsiveness of C3H/HeJ mice, an LPS-unresponsive strain, to either antigen. The reduction of the response to a putative T-dependent antigen by LPS pre-treatment was only temporary since mice challenged 7 days after LPS responded normally in vivo. We also confirmed that LPS administered shortly after a tolerogen prevented FL-specific IgG tolerence induction and produced B-cell priming to a subsequent T-dependent antigenic challenge. LPS, however, did not significantly interfere with tolerance induction in terms of the IgM responce to either challenge antigen. These results suggest that LPS acts either directly or indirectly on a subpopulation of B cells responsive to a TD antigen. Our data further reflect the heterogeneity of B-cell subpopulations responsive to various polyclonal activators.

Animals↗
PubMed1977

Cellular events in tolerance. VI. Neonatal vs adult B cell tolerance: differences in antigen-binding cell patterns and lipopolysaccharide stimulation.

The numbers and fate of antigen-binding cells (ABC) in neonatal and adult mice rendered tolerant to fluorescein (FL)-labeled heterologous gamma-globulins were studied. Similar numbers of FL-ABC were observed 1 day after tolerogen in both adult and neonatal mouse spleens: by 7 days after tolerization, no FL-ABC were observed in either case. Reinjection with FL-tolerogen at 7 days led to the detection of normal numbers of ABC in adult mice but significantly reduced numbers in neonates. This suggests that neonatal ABC either have been deleted or have failed to resynthesize surface receptors. Two weeks after tolerance induction, spleen cells from these tolerant mice were cultured with Escherichia coli lipopolysaccharide (LPS), a polyclonal B cell mitogen, or with specific antigen. Tolerant adult spleen cells made an equivalent anti-FL response to that of the uninjected controls when stimulated with LPS, but were unresponsive to specific antigenic triggering. In contrast, spleen cells from neonatally tolerized mice were unresponsive to either specific or nonspecific (LPS) stimulation. Thus, these neonatally tolerized spleen cells lose sensitivity to polyclonal-stimulating agents (along with their receptors), or more simply, are deleted.

Aging↗
PubMed1974

Immunological study of typhoid: immunoglobulins, C3, antibodies, and leukocyte migration inhibition in patients with typhoid fever and TAB-vaccinated individuals.

The development of humoral and cell-mediated immune responses to Salmonella typhi antigens and immunoglobulin and C(3) levels were determined in patients suffering from typhoid fever, TAB-vaccinated individuals, and appropriate controls. In 45 patients with typhoid, a significant elevation of immunoglobulin M (IgM) level was noted from the first week of illness onwards. Eighteen TAB-vaccinated persons also showed a significant elevation of IgM levels. In typhoid sera, the anti-O and anti-H antibodies were mostly 2-mercaptoethanol (2-ME) sensitive. The rise of IgM level correlated well with the 2-ME-sensitive anti-O and anti-H antibodies seen in typhoid patients. The anti-O antibodies in the TAB-vaccinated group were almost entirely 2-ME sensitive, but both 2-ME-sensitive and -resistant anti-H antibodies were detected in the TAB group. A marked increas in C(3) level was also noted in patients with typhoid. The cell-mediated immunity (CMI), as measured by leukocyte migration inhibition tests, was demonstrable in 15 of 22 patients with typhoid. On the other hand, only 8 of the 20 normal subjects, 5 of the 16 fever control cases, and 6 of the 18 TAB-vaccinated individuals gave a positive CMI. The latter three groups were comparable with each other but were significantly different from the typhoid patients. It was concluded that TAB-vaccination did not induce CMI even though it induced the development of antibodies, the latter being comparable with those of the patients with typhoid. The significance of these findings is discussed.

Agglutination Tests↗