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Biomedical subjects

M Venkataraman

Publications and source records attributed to M Venkataraman.

At least 19 recordsLinked to original sources
PubMed1997

Effects of cryopreservation of immune responses. XI. Heightened secretion of tumor necrosis factor-alpha by frozen human peripheral blood mononuclear cells.

In view of the wide usage of frozen PBMCs as stem cell support following high-dose chemo- and/or radiotherapy, and the pleiotropic activities of tumor necrosis factor-alpha (TNF-alpha), the influences of freezing and radiation on LPS-induced TNF-alpha production by human peripheral blood mononuclear cells (PBMCs) were studied. Frozen PBMCs secreted significantly larger quantities of TNF-alpha than fresh cells. Blocking of endogenous IL-10 by neutralization with anti-IL-10 monoclonal antibody resulted in further augmented and prolonged secretion of TNF-alpha by both the fresh and frozen cells. In contrast, addition of exogenous IL-10 to LPS-stimulated cultures inhibited TNF-alpha secretion. In vitro irradiation had an inconsistent effect on TNF-alpha production by the fresh PBMCs. Taken together, these results suggest that the endogenously hypersecreted TNF-alpha is indirectly responsible for the previously reported elevated IL-1-, IL-6-, and IL-10-secreting capabilities of frozen PBMCs. They also indicate that the TNF-alpha induced IL-10 and then down-regulates the monocytes from further TNF-alpha secretion. Considering the vital role played by TNF-alpha in antimicrobial and antitumor activities, in the immune system, and in the pathogenesis of many acute and chronic diseases, the abilities of frozen cells to produce large quantities of TNF-alpha in response to infectious agents could have profound impact on patients receiving such frozen PBMCs as stem cell support following myeloablative therapies.

Antibodies, Blocking↗
PubMed1996

Effects of cryopreservation on immune responses. X. Decrease in interleukin-12 production by frozen human peripheral blood mononuclear cells is mediated by the endogenously hypersecreted interleukin-10.

The contrasting effects of freezing and radiation on lipopolysaccharide (LPS)-induced interleukin (IL)-10 production by human peripheral blood mononuclear cells (PBMCs) have recently been reported. In view of the potent inhibitory properties of IL-10 on IL-12 secretion and the central role played by IL-12 in the immune system, the influences of freezing and radiation on LPS-induced IL-12 production by PBMCs were studied. Frozen PBMCs secreted significantly smaller amounts of IL-12 than fresh cells. In contrast, the in vitro-irradiated PBMCs produced significantly larger amounts of IL-12. Culture of frozen cells in the presence of exogenous anti-IL-10 antibody resulted in the production of significantly larger amounts of IL-12. These results suggest that the endogenously hyperscreted IL-10 is primarily responsible for the observed decrease in IL-12 released by the frozen cells. They further suggest that the increased amounts of IL-12 secreted by the irradiated PBMCs could account for the previously reported increase in IL-2 and interferon (IFN)-gamma release by the irradiated PBMCs and the radiation-induced immunopotentiation and tumor regression. Considering the pivotal role played by IL-12 in the immune system, and in antimicrobial and antitumor activities, production of only 10% of the normal levels by the frozen cells could have profound impact on patients receiving such frozen PBMCs as stem cell support following myeloablative therapy. Administration of exogenous IL-12 at the time of frozen PBMC transplantations might have a therapeutic value in these patients.

Cells, Cultured↗
PubMed1996

Effects of cryopreservation on immune responses: IX. Stimulus-mediated dichotomy in IL-10 production by frozen human peripheral blood mononuclear cells.

The effects of freezing on phytohemagglutinin (PHA) and lipopolysaccharide (LPS)-induced interleukin-10 (IL-10) production by human peripheral blood mononuclear cells (PBMC) were studied. The freezing process had a divergent effect on the production of IL-10 by PBMC. Frozen PBMC produced significantly smaller amounts of IL-10 in response to PHA stimulation while secreting significantly larger quantities in response to LPS activation. In vitro irradiated PBMC produced significantly smaller amounts of IL-10 in response to both PHA and LPS stimulation. The results indicate that the functional inactivation of a naturally occurring subset of cryosensitive and radiosensitive immunodownregulatory cells is responsible for the observed divergence. They further suggest that, in addition to other mechanisms, a reduction in the secretion of this cytokine synthesis inhibitory factor by the frozen PHA-activated cells could have contributed to the previously reported, augmented IL-2 and IFN-gamma-secreting capabilities of frozen PBMC. The significance of this freezing-induced deviation in IL-10 secretion by PBMC in relation to cancer therapy is discussed.

Adult↗
PubMed1995

Effects of cryopreservation on immune responses. VIII. Enhanced secretion of interferon-gamma by frozen human peripheral blood mononuclear cells.

The effect of freezing on phytohemagglutinin-induced interferon-gamma (IFN-gamma) production by human peripheral blood mononuclear cells (PBMCs) was studied. The possible mechanisms responsible for the observed effects were also analyzed. Frozen PBMCs produced significantly larger quantities of IFN-gamma than fresh cells. Like the frozen cells, the monocyte- and natural killer cell-eliminated populations of fresh PBMCs also secreted significantly larger quantities of IFN-gamma. In contrast, the freezing process had no enhancing effect on IFN-gamma production by monocyte-depleted PBMCs. Irradiated PBMCs also secreted larger quantities of IFN-gamma. The results suggest that functional inactivation of a subset of cryosensitive suppressor monocytes is associated with an increase in IFN-gamma production by the T lymphocytes. The results provide further evidence that monocytes mediate their suppressive effect through the activation of a subset of radiosensitive, immuno-down-regulatory T cells. The ability of frozen cells to produce larger quantities of IFN-gamma should be of clinical importance. For instance, cancer patients receiving frozen PBMCs as stem cell support (after myeloablative radio/chemotherapy) should benefit from the increased IFN-gamma secretion because of its potent immunoregulatory, microbicidal, and antitumor activities.

Blood Preservation↗
PubMed1994

Effects of cryopreservation on immune responses: VII. Freezing induced enhancement of IL-6 production in human peripheral blood mononuclear cells.

To better understand the effects of freezing on various immunocompetent cell functions, the interleukin-6 (IL-6)-producing activities of frozen peripheral blood mononuclear cells (PBMCs) from healthy subjects were determined. Frozen, lipopolysaccharide (LPS)-activated PBMCs produced significantly larger quantities of IL-6 than fresh cells. Although elimination of radiosensitive, CD8+ suppressor T cells had no significant effect on PHA-induced IL-6 production by T cells, elimination of CD4+ Leu-8+ suppressor T cell subsets resulted in a significantly enhanced IL-6 secretion. Exogenous addition of prostaglandin E-2 to frozen PBMCs and monocytes inhibited LPS-induced IL-6 production. The results suggest that functional inactivation of a subset of cryosensitive, PGE-2-secreting monocytes is associated with an increase in IL-6 production by the other subset. They also indicate that a subset of CD4+ Leu-8+ T cells might be involved in feedback inhibition of PHA-induced T cell-mediated IL-6 production. The results provide further evidence that the presence of larger quantities of IL-6 in conjunction with increased amounts of IL-1 and IL-2 secreted by the frozen cells may be responsible for the previously reported enhanced immunoglobulin-producing abilities of frozen cells from clinically healthy subjects and from patients with lung cancer.

Antilymphocyte Serum↗
PubMed1994

Cystic fibrosis in children from ethnic minorities in the West Midlands.

BACKGROUND: We have observed that Doctors often perceive that cystic fibrosis (CF) is exceptionally rare in non-whites, and that this bias has repeatedly resulted in diagnostic delay. We therefore compared the age at diagnosis, genetic features and relative prevalence of CF in non-whites and white patients in the West Midlands. METHODS: Analysis of data on all CF patients diagnosed in childhood and stored in the West Midlands CF register. RESULTS: Sixteen of the 514 children on the register were not of white European extraction, comprising 13 patients whose families originated from the Indian subcontinent, two of mixed AfroCaribbean/white European extraction and one of mixed Pakistani/white European extraction. The median age of diagnosis was similar in the white European and non-white patients (0.42 vs. 0.33 years, 95% CI for the difference of the medians -0.15, 0.37). However, in five cases with typical clinical features the diagnosis appears to have been delayed because of the child's racial origin (median age of diagnosis 3.87 years), and in five others the diagnosis was obvious (two siblings with CF, three had meconium ileus). There was a degree of consanguinity in nine cases. Five patients were homozygous or heterozygous for the delta F508 mutation, but no mutation could be identified in the remaining 11 patients. CONCLUSIONS: The possibility of CF needs to be considered in any patient with relevant clinical problems, regardless of racial origin. These findings need to be considered when planning any mass population screening programme for CF.

Bangladesh↗
PubMed1992

Cryopreservation-induced enhancement of interleukin-2 production in human peripheral blood mononuclear cells.

To better understand the effects of cryopreservation on various immunocompetent cell functions, we have examined the interleukin-2 (IL-2)-producing activities of frozen mononuclear cells (MNCs) from healthy subjects. The mechanisms responsible for the observed effects were also analyzed. Both the unfractionated and monocyte-depleted, frozen MNCs produced significantly larger quantities of IL-2 than fresh cells. Similar to freezing, L-leucine methyl ester (Leu-OMe) treatment (to eliminate IL-1 and prostaglandin E-2 (PGE-2)-secreting cells) also increased the IL-2-producing activities of fresh cells, but freezing no longer enhanced the production of IL-2 by Leu-OMe-treated cells, suggesting that (1) both the freezing process and Leu-OMe treatment have similar effects on IL-2 production, (2) the increased IL-2 secretion by frozen MNCs is independent of IL-1, and (3) inactivation of PGE-2-secreting cells during the freezing procedure is responsible for increased IL-2 secretion. Elimination of CD8+ T cells (putative suppressor cells) from MNCs has also resulted in the production of increased amounts of IL-2 by fresh cells, and again, freezing did not further enhance the IL-2-secreting activities of MNCs, that are devoid of CD8+ T cells. This confirms that the increased IL-2 production is due to the inactivation of immuno-down-regulatory cells. The results provide further evidence that the lack of active, suppressor T cells, monocytes, and increased IL-1 and -2 production may be responsible for the previously reported enhanced immunoglobulin-producing abilities of cryopreserved cells from healthy subjects and from patients with lung cancer.

CD8 Antigens↗
PubMed1992

Effects of cryopreservation on immune responses: VI. An inexpensive method for freezing human peripheral blood mononuclear cells.

To determine the true usefulness of the commercially available inexpensive freezing unit (Mr Frosty) for cryopreservation of peripheral blood mononuclear cells (PBMCs), functional assays were carried out on cells that were frozen in this unit. The responses of these cells were compared with those of controlled rate frozen and fresh cells. Cell viability, recovery, proliferative responses to both phytohemagglutinin (PHA) and pokeweed mitogen (PWM), as well as interleukin (IL)-1 secreting activities of cells frozen in this container were closely comparable to controlled rate frozen cells. Although, the mean immunoglobulin (Ig) and IL-2 secreting abilities of these frozen cells were lower than the controlled rate frozen cells, these responses were still comparable to fresh cells in several of the individuals. Based on these results and considering the cost involved in controlled rate freezing method, we recommend this inexpensive unit for freezing PBMCs for subsequent immunological studies.

Adult↗
PubMed1992

Functional studies on long-term cryopreserved peripheral blood mononuclear cells from patients with lung cancer and from healthy subjects.

To determine the functional abilities of long-term cryopreserved peripheral blood mononuclear cells (PBMCs) from patients with lung cancer and from healthy subjects, we assayed the proliferative and plaque-forming cell (PFC) responses of cells from these individuals after the cells had been cryopreserved for up to 31 months. The stability of these cells for B and T cell quantitative assays was also determined by using their respective monoclonal antibodies. The patients' results were compared with those in healthy subjects to ascertain whether the conclusions derived from the assay of cryopreserved cells are consistent with our earlier studies on fresh cells from similar patients. The results show that proliferative and PFC responses of the frozen cells were not significantly affected by further storage, despite an initial, irreversible functional loss in some subsets of T lymphocytes and monocytes during the process of freezing. They also demonstrate that cryopreserved PBMCs from both patients and controls can be successfully utilized for B and T cell quantitative assays. The conclusions derived from the assay of cryopreserved cells are also consistent with our earlier observations on fresh cells from patients with lung cancer; those studies indicated a B cell functional abnormality caused in part by increased suppressor T cell and monocyte activity.

Aged↗
PubMed1990

Cryopreservation enhances interleukin-1 production in human mononuclear cells.

The effects of cryopreservation on bacterial lipopolysaccharide (LPS)-induced interleukin-1 (IL-1) production by unfractionated mononuclear cells (MNCs), adherent cells (ACs), and nonadherent cells (NACs) were studied. Culture supernatants from cryopreserved cells contained significantly larger concentrations of IL-1 [MNCs, 211 +/- 50; ACs, 640 +/- 41; NACs, 116 +/- 19 U/ml (mean +/- SEM)] as compared with supernatants from fresh cells (69 +/- 22, 427 +/- 69, and 72 +/- 33 U/ml, respectively). In addition, supernatants obtained from cocultures of autologous fresh and frozen cells contained much less than the expected quantities of IL-1 (78 +/- 8%), indicating that suppressor cells in the fresh population are responsible for the decreased IL-1 content. The studies suggest that functional inactivation of cryosensitive suppressor monocytes is associated with an increase in IL-1 production by the other subset. The results provide further evidence that lack of active suppressor monocytes and increased IL-1 production may be responsible for the previously reported enhanced plaque-forming cell responses of cryopreserved cells from normal controls and from patients with lung cancer.

Adult↗
PubMed1990

Radiation causes increased production and decreased utilization of IL-2 in human mononuclear cells.

The effects of radiation on the kinetics of Interleukin-2 (IL-2) production and utilization by mononuclear cells (MNCs) were studied. Mononuclear cells from normal, healthy individuals were subjected to various doses of radiation ranging from 0 to 2,000 rad and cultured in the presence of PHA. Supernatants from these cultures were harvested at various periods and their IL-2 contents determined by both the standard bioassay and ELISA. A radiation dose of 800 rad and higher had a marked effect on both IL-2 production and consumption. Although the supernatants from both the irradiated and non-irradiated MNCs contained maximal concentrations of IL-2 between 8 and 24 h of culture, the former had three times as much IL-2 as the latter. An increase in IL-2-mRNA levels was also noticed in irradiated, PHA-stimulated cells. Moreover, the supernatants from irradiated MNCs collected as late as 72 h after the initiation of culture contained more than 30% of the total IL-2 produced compared to less than 8% in supernatants from non-irradiated cells. Supernatants from non-irradiated cells incubated further with irradiated cells contained relatively higher quantities of IL-2 than those incubated continuously with non-irradiated cells. Supernatants from co-cultures of irradiated and non-irradiated MNCs contained less than expected amounts of IL-2 in two of the three subjects. Despite a difference in both the production and consumption of IL-2 between the irradiated and non-irradiated cells, there was no difference in their ability to generate IL-2 receptors. The results indicate that inactivation of radiosensitive suppressor T cells is associated with superinduction of IL-2 mRNA, increased production and decreased consumption of IL-2 by MNCs, thereby resulting in increased accumulation of IL-2.

Cell Survival↗
PubMed1990

Coexistent double gammopathy, myeloproliferative disorder, and malignant lymphoma.

The authors report a patient with coexistent double gammopathy, a Philadelphia chromosome-negative, bcr rearrangement-negative myeloproliferative disease resembling chronic myelocytic leukemia and a malignant lymphoma of B-cell origin. The double gammopathy consisted of IgM (kappa) and IgG (kappa). Peripheral blood, spleen, and marrow lymphocytes had primarily an IgG (kappa) isotype, whereas lymph node lymphocytes had predominantly an IgM (kappa) surface isotype. Increased numbers of marrow lymphocytes stained doubly for both IgM (kappa) and IgG (kappa). The results suggest that doubly isotypic as well as single isotypic lymphocytes contributed to the double gammopathy. Organ localization differed for lymphocytes with different antibody isotypes. This cluster of findings has not been described previously.

Aged↗