Biomedical subjects

R Raghupathy

Publications and source records attributed to R Raghupathy.

At least 19 recordsLinked to original sources

PubMed2003

Pro-inflammatory maternal cytokine profile in preterm delivery.

PROBLEM: The objective of this study was to determine the levels of cytokines produced by maternal peripheral blood mononuclear cells (PBMC) upon stimulation with a mitogen, with autologous placental cells and with a trophoblast antigen extract. METHOD OF STUDY: Peripheral blood mononuclear cells from 54 women with a history of successful pregnancy and 30 women undergoing preterm delivery (PTD) were stimulated with the mitogen and antigens, and the cytokine levels in mitogen-stimulated culture supernatants assessed. RESULTS: Significantly higher levels of the type 1 cytokines, interferon (IFN)-gamma and interleukin (IL)-2, were produced by the PTD group than by the normal pregnancy group, which on the contrary showed significantly greater production of the type 2 cytokines, IL-4, IL-5 and IL-10. A comparison of the ratios of type 2 to type 1 cytokines is indicative of a type 1 cytokine bias in PTD. CONCLUSIONS: These data are suggestive of a maternal type 1 cytokine bias in PTD.

Cytokines↗

PubMed2002

Quality of paper boards from arecanut leaf sheath.

A study was carried on utilizing arecanut leaf sheath for making paper boards. Paper boards were made with various combinations of arecanut leaf sheath with waste paper, 1:1, 1:2, 1:3, 3:1, 2:1, control (100% areca leaf sheath) and the qualities of these paper boards were tested as per the Bureau of Indian Standards (IS: 1060 (part-I)-1966). The paper boards made with more arecanut sheath materials had more resistance to water absorption. The addition of paper increased the substance weight of the paper boards. The 2:1 and 3:1 combinations of arecanut leaf sheath and waste paper had best tear strength, tensile strength, bursting strength and water resistance with minimum substance weight.

Absorption↗

PubMed2001

Pregnancy: success and failure within the Th1/Th2/Th3 paradigm.

Evidence from studies on murine and human pregnancy points to a strong association between maternal Th2-type immunity and successful pregnancy on the one hand and between Th1-type immune reactivity and pregnancy loss on the other. While there is a paucity of data from human pregnancy indicating that Th1-type immune effectors actually lead to pregnancy, it is difficult to ignore the compelling evidence linking inappropriate Th1-type immunity to pregnancy loss. Th2-type immunity and TGF beta secreted by Th3 cells may play protective roles during pregnancy, hence the nexus between a Th2/Th3 shift and successful pregnancy. This paper examines these associations and discusses possible mechanisms underlying immunologically mediated pregnancy failure.

Abortion, Habitual↗

PubMed2001

Cytokine patterns in maternal blood after premature rupture of membranes.

OBJECTIVE: To compare two types of cytokines, type 1, which activate cell-mediated reactions and are important in cytotoxic and delayed-type hypersensitivity reactions, and type 2, which encourage vigorous antibody production and are commonly found in association with humoral immune responses, in blood of women with premature rupture of membranes (PROM). METHODS: Forty-four women with histories of at least three successful pregnancies and who currently delivered normally served as controls. The PROM group consisted of 30 women with spontaneous rupture of fetal membranes at term. Peripheral blood mononuclear cells were stimulated separately with a mitogen, placental cells, and a trophoblast antigen extract, and the supernatants examined for type 1 and type 2 cytokines. RESULTS: Mitogen-stimulated blood cells produced significantly higher levels of type 1 cytokines in PROM women than in normal controls. Higher levels of the type 1 cytokine interferon-gamma were produced by PROM samples stimulated with autologous placental cells and with trophoblast antigens. Ratios of type 1 to type 2 cytokines were higher in PROM compared with normal pregnancy, and in some cases as much as 25-fold higher. CONCLUSION: Women in the PROM group had a stronger type 1 reactivity whereas normal women were more predisposed to type 2 immunity; thus, PROM appears to be associated with a maternal type 1 bias.

Adult↗

PubMed2001

Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions.

BACKGROUND: This study compared Th1-Th2 cytokine profiles in a subgroup of recurrent aborters who had an abortion with those in a subgroup of recurrent aborters who had a successful pregnancy. METHODS: Fifty-four women with a history of at least three normal pregnancies, 24 women with a history of recurrent spontaneous abortion (RSA) followed by abortion (RSA-->A) and 39 women with a history of RSA followed by normal pregnancy (RSA-->N) were studied. Blood samples and placentas were obtained at the time of delivery or abortion; peripheral blood mononuclear cells were stimulated separately with phytohaemagglutinin and with autologous placental cells, and the secreted cytokines estimated. RESULTS: Peripheral blood mononuclear cells from the RSA-->N subgroup secreted higher concentrations of Th1-type cytokines as compared with normal pregnant women, indicating a higher Th1 bias in these women. However, women in the RSA-->N subgroup had significantly higher concentrations of Th2 cytokines as compared with women in the RSA-->A subgroup. A comparison of Th1:Th2 cytokine ratios indicated a higher Th2 bias in RSA-->N women as compared with RSA-->A women. CONCLUSIONS: We conclude that abortion-prone women who proceed to have successful pregnancy are more Th2-biased than abortion-prone women who abort, and that recurrent aborters who undergo spontaneous abortion have a stronger Th1 bias than aborters who have normal pregnancy.

Abortion, Habitual↗

PubMed2000

Tumor necrosis factor-alpha is undetectable in the plasma of SS patients with elevated Hb F.

Steady-state sickle cell disease (SCD) patients may have increased plasma levels of acute phase reactants and pro-inflammatory cytokines because of subclinical inflammation. We have estimated TNF-alpha levels in the plasma and in supernatants following peripheral blood mononuclear cell (PBMC) activation with phytohemagglutinin (PHA) in a group of Kuwaiti SCD patients using ELISA. The group consisted of 28 SS, 8 Sbeta-thal, and 2 SD patients all in steady state; 5 SS patients were studied during 7 episodes of painful crisis. The subjects were aged 2 to 16 years, with a mean of 7.3 +/- 3.5 years. The beta(S)-globin gene cluster haplotype, alpha-tha1 status, and spleen function were determined in the SS group using standard techniques. Most (82%) were homozygous for the Saudi Arabia/India haplotype and had elevated Hb F levels ranging from 15% to 35%. There were 24 controls (Hb AA or AS), of whom 14 were healthy and 10 were acutely ill at the time of the study. None of the children with SCD (either in steady state or crisis) had detectable plasma TNF-alpha, but four controls (3 acutely ill and one healthy) had levels ranging from 61.7 to 249.8 pg/mL. Following PHA stimulation most subjects responded with high levels of TNF-alpha, with the median level among the steady-state SS patients being significantly higher than that in the controls (both the acutely ill or healthy). It therefore appears that because of the mild disease among our Arab SS children, TNF-alpha is not detectable in their plasma in steady state; these children, however, had a significantly higher response than controls following PBMC activation.

Adolescent↗

PubMed2000

The use of flow cytometry for the detection of CMV-specific antigen (pp65) in leukocytes of kidney recipients.

Flow cytometric assay (FCA) was used to detect a cytomegalovirus (CMV) specific antigen (pp65) in CMV-infected fibroblast cells and in leukocytes of kidney recipients. FCA distinguished clearly between the infected and non-infected fibroblast cells. Regarding transplant patients, the FCA was positive when the number of antigenemia assay (AA) positive cells was five or more per 5 x 10(4). Moreover, the percentage of antigenemia-positive cells by FCA correlated well with symptomatic CMV infections.

Adolescent↗

PubMed2000

Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion.

It has been proposed that successful pregnancy is a T helper 2-type phenomenon, and that T helper (Th)1-type reactivity is deleterious to pregnancy. The objective of this study was to compare the concentrations of Th1 and Th2 cytokines produced by peripheral blood mononuclear cells from women undergoing unexplained recurrent spontaneous abortion (RSA) with those produced during normal pregnancy at a similar gestational stage. The control group consisted of 24 women with a history of successful pregnancies and the abortion group comprised of 23 women with a history of unexplained RSA. Blood from the control group was obtained at the end of the first trimester as gestational age controls for the abortion group from whom blood was collected at the time of abortion. Phytohaemagglutinin-stimulated peripheral blood cell culture supernatants were analysed for concentrations of cytokines. Significantly higher concentrations of Th2 cytokines were produced by the first trimester normal group than by the RSA group, while significantly higher concentrations of Th1 cytokines were produced by the abortion group as compared to first trimester normal pregnancy, indicating a distinct Th2-bias in normal pregnancy and a Th1-bias in unexplained RSA.

Abortion, Habitual↗

PubMed2000

Circulating cytokines and CD30 in normal human pregnancy and recurrent spontaneous abortions.

Concentrations of the T-helper (Th) 1 cytokines interleukin (IL)-2, tumour necrosis factor (TNF) -alpha, TNF-beta and interferon-gamma, Th2 cytokines IL-4, IL-5, IL-6, IL-10 as well as those of soluble CD30 in sera have been examined during the three trimesters of gestation, at delivery in normal pregnancy, and at the time of spontaneous abortion in women with a history of unexplained recurrent spontaneous abortion (RSA). Significantly higher concentrations of the Th2 cytokines IL-6 and IL-10 were found at normal delivery than in women with RSA, and conversely significantly increased concentrations of the Th1-type cytokine TNF-alpha were found in RSA as compared with successful pregnancy. In abortion-prone women who had a successful pregnancy, significantly higher concentrations of IL-6 and significantly lower concentrations of TNF-alpha were found as compared with abortion-prone women who had another abortion, supporting the notion that Th2- and Th1-bias are associated with successful and unsuccessful pregnancy respectively. Serum CD30 concentrations did not correlate with the outcome of pregnancy. These findings support observations drawn from experiments on the cytokine secretion profiles of peripheral blood mononuclear cells and decidual lymphocytes which suggest that normal pregnancy is Th2-biased and that unexplained RSA is associated with Th1-type reactivity.

Abortion, Habitual↗

PubMed2000

GM-CSF in sickle cell anemia patients with elevated Hb F.

We estimated plasma GM-CSF levels in a group of 28 steady-state sickle cell anemia (SS) patients in Kuwait, using an ELISA technique. There were 24 age-matched Hb AA controls, 14 of whom were healthy while 10 were acutely ill at the time of the study. Five SS patients were also studied during 6 episodes of painful crisis. Among the SS patients, 82.1% were homozygous for the Saudi Arabia/India (SAI) haplotype with Hb F ranging from 15 to 35% and total Hb from 8.5 to 11 g/dl. Three patients (siblings) were SAI/Benin compound heterozygotes with Hb F of 9-23% and total Hb >10 g/dl. One patient each was homozygous for the Benin or the Bantu haplotype; they had Hb F <2% and total Hb of 6.6 and 7.2 g/dl, respectively. Four (14. 3%) steady-state SS patients had detectable plasma GM-CSF ranging from 75 to 1,817.6 pg/ml. These included the 2 patients with Hb F <2. 0% and 2 with the SAI/Benin compound heterozygotes with Hb F of 11 and 9%, respectively. Four (66.7%) SS patients in crisis, 6 (42.9%) healthy controls and 6 (60%) acutely ill controls had detectable plasma GM-CSF. A clearcut association of GM-CSF with Hb F level or degree of anemia in steady-state SS patients could not be established. The appearance of GM-CSF in the plasma of patients in crisis and also among control subjects raises the possibility that other factors are involved in the production of this cytokine in the subjects studied.

Adolescent↗

PubMed2000

Th1 and Th2 cytokine profiles in sickle cell disease.

We have investigated the levels of Th1 (IL-2 and IFN-gamma) and Th2 (IL-4) cytokines in the plasma and supernatants following peripheral blood mononuclear cell culture and mitogen stimulation in a group of 39 patients with sickle cell disease (SCD) made up of 29 SS, 8 Sbeta-thal and 2 Hb SD in steady state. Five SS patients were studied during 7 episodes of vaso-occlusive crisis. Twenty-four control (3 Hb AS and 21 Hb AA) were also studied; 10 were acutely ill while 14 were healthy at the time of the study. The plasma levels of IL-2 and IFN-gamma were similar in the patients and the controls. However, plasma IL-4 was significantly higher among the steady-state SS patients than in the controls. While there was no significant difference in cytokine levels following mitogen stimulation in the different groups, plasma IL-2 to IL-4 and IFN-gamma to IL-4 ratios were significantly lower among the steady-state SS patients, indicating a possible Th2 bias in our sickle cell patients and suggesting a possible mechanism to explain the predisposition of SCD patients to bacterial infections. However, SS patients with good splenic function showed a relative Th1 bias, which may be an additional explanation for the protection against bacterial infections in such patients.

Adolescent↗

PubMed2000

Th1-type cytokines production is decreased in kidney transplant recipients with active cytomegalovirus infection.

Cytomegalovirus (CMV) infection is a major complication after kidney transplantation. Despite antiviral therapy the infection contributes significantly to high morbidity. The present study was aimed at determining: (a) the stimulation index (S.I.) of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) and (b) the levels of Th1- and Th2- related cytokines in kidney transplant recipients with and without active CMV infection. Thirty-five patients with, and 44 without active CMV infections, as diagnosed by a CMV antigenemia assay, were inducted into this study. After PHA stimulation of PBMC from patients, stimulation index (S.I.) was determined by radioactive thymidine uptake while the production of Th1-type cytokines (interleukin-2 [IL-2], interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) and Th2-type cytokines (IL-4, IL-10) were measured by enzyme-linked immunosorbent assay. PBMC of patients with active CMV infection showed significantly lower S.I. values than patients without an ongoing CMV infection (P <.0001). Levels of Th2-type cytokines in CMV-infected and uninfected kidney recipients were similar; however, the levels of the Th1-type cytokines were significantly lower in CMV-infected patients. Low levels of Th1-type cytokines seem to correlate well with active CMV infection in kidney recipients.

Adult↗

PubMed1999

Maternal Th1- and Th2-type reactivity to placental antigens in normal human pregnancy and unexplained recurrent spontaneous abortions.

Spontaneous abortion is the most common complication of pregnancy, but the etiology of a significant proportion of abortions is still unknown. We have examined the production of Th1- and Th2-type cytokines by women with unexplained recurrent spontaneous abortion (RSA) since it appears that successful murine pregnancy occurs in a Th2-dominant situation and that Th1-type immunity is associated with pregnancy failure. We have compared maternal reactivity toward placental antigens in women with a history of successful pregnancy with that in women with a history of RSA. This was done by coculturing maternal peripheral blood mononuclear cells (PBMC) with autologous placental cells and also by stimulating maternal PBMC with antigens from a choriocarcinoma cell line of trophoblastic origin. We detected significantly greater levels of the Th2 cytokines IL-6 and IL-10 in normal pregnancy compared to unexplained RSA and significantly higher levels of the Th1 cytokine IFN-gamma in RSA compared to normal pregnancy. These results suggest that women with normal pregnancy have a higher Th2 bias, while women with a history of RSA evince a bias toward Th1-type reactivity.

Abortion, Habitual↗

PubMed1999

Prior immunity to a carrier enhances antibody responses to hCG in recipients of an hCG-carrier conjugate vaccine.

Pre-sensitization with carrier often leads to epitopic suppression of subsequent anti-hapten antibody responses. To ascertain whether epitopic suppression occurs in humans, we examined the effect of pre-existing anti-carrier immunity on antibody responses to hCG in volunteers of a clinical trial of an hCG-based conjugate birth-control vaccine. When we studied the correlation between pre-vaccination anti-carrier immunity and post-vaccination anti-hCG responses, we found that prior immunity to the carriers did not lead to epitopic suppression of anti-hCG responses. On the contrary, it was found that prior immunity to TT, one of the two carriers used in this vaccine, led to enhancement of anti-hCG responses. Our data indicates that prior immunity to the carriers may not be detrimental to the performance of conjugate vaccines, and may actually be beneficial in some cases.

Adult↗

PubMed1999

Sequential production of cytokines by dengue virus-infected human peripheral blood leukocyte cultures.

The study was undertaken to elucidate the sequence of appearance of T helper (Th)1- and Th2-type cytokines in human peripheral blood leucocyte cultures infected in vitro with dengue type 2 virus. Commercial sandwich enzyme-linked immunosorbent assay kits were used to assay the levels of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-5, IL-6, and IL-10 in culture supernatants. Culture supernatants were also screened for the cytotoxic factor and the dengue virus titres determined. The cytokines that appeared in the culture supernatants on the first day post-infection (p.i.) were cytotoxic factor, TNF-alpha, IL-2, and IL-6; their levels were highest on the second day p.i. IFN-gamma appeared on the second day with a peak on the third day p.i. The levels of these cytokines declined quickly, except for human cytotoxic factor (hCF) and IL-2. The cytokines that appeared later were IL-10 and IL-5 on the fourth day and IL-4 on the sixth day p.i. Dengue virus replicated in the peripheral blood leucocyte (PBL) cultures and was present throughout the course of the study. The findings of the present study show that dengue virus induced a predominant Th1-type cytokine response during the first 3 days of infection of PBL cultures that was replaced by a Th2-type response later.

Animals↗

PubMed1999

A placenta-derived suppressor factor with a T-cell bias.

PROBLEM: Functional and mechanistic aspects of immunosuppression by murine placental supernatants (MPS) were investigated. METHOD OF STUDY: MPS and a low molecular weight fraction of the supernatant (MPSf) were tested for suppressive action on T-cell reactivity in vitro and in vivo, on B-cell responses and on T-cell activation events. RESULTS: MPS and MPSf suppress mitogen-induced proliferation and mixed lymphocyte reactions of human and murine lymphocytes, antigen-induced proliferation of T cells in vitro and in vivo, proliferation of CD8+ lymphocytes, proliferation induced by cross-linking of surface CD3 and the in vivo response of mice to allogeneic stimuli. MPSf affects cell cycling of activated T cells and blocks interleukin (IL)-2 production. MPSf does not affect antibody production or the induction of MHC class II expression on B cells. CONCLUSIONS: MPSf is a potent inhibitor of T-cell responses in vitro and in vivo, with no demonstrable effect on B-cell function.

Animals↗

PubMed1999

Mitogen-induced cytokine responses of maternal peripheral blood lymphocytes indicate a differential Th-type bias in normal pregnancy and pregnancy failure.

PROBLEM: Profiles of Th1- and Th2-type cytokines were studied in women with a history of successful pregnancy and in women with a history of unexplained recurrent spontaneous abortions (RSA) with the objective of elucidating Th1- and Th2-type bias in normal pregnancy and pregnancy failure. METHOD OF STUDY: Peripheral blood mononuclear cells (PBMCs) from 54 women with a history of normal pregnancy and 23 women with a history of unexplained RSA, obtained at delivery or on the day of abortion, respectively, were stimulated with phytohemagglutinin (PHA), followed by the estimation of four Th2 cytokines and four Th1 cytokines. RESULTS: Significantly greater levels of Th2 cytokines were produced by the normal group than by the RSA group. On the other hand, significantly higher levels of Th1 cytokines were produced by the RSA group than by the normal pregnancy group. CONCLUSIONS: These data support the concept that unexplained recurrent spontaneous abortion is associated with an increase in Th1-type reactivity, while Th2 dominance is a feature of successful pregnancy.

Abortion, Habitual↗

PubMed1998

Elevated levels of IL-8 in dengue hemorrhagic fever.

Dengue virus causes dengue fever, a mild febrile illness, and at times dengue hemorrhagic fever (DHF), a severe illness the pathogenesis of which is not fully understood. Given the crucial roles played by interleukin-8 (IL-8) as a chemoattractant cytokine and in inflammatory processes, levels of circulating IL-8 in the sera and IL-8 mRNA in the peripheral blood mononuclear cells (PBMC) were measured in 99 patients of a recent dengue epidemic that occurred in India in 1996 and in 21 normal healthy controls. Twenty-six of the patients had dengue fever (DF) and the remaining 73 were diagnosed as having different grades of DHF. All the control normal sera were negative for IL-8, so were their PBMC for IL-8 mRNA. Increased levels of IL-8 in the sera and IL-8 mRNA in their PBMC were observed in patients with severe illness of DHF grades III and IV. Only two out of 26 patients of DF and one out of 10 DHF grade I patient were positive for IL-8 and all three deteriorated to DHF grade IV within 24 hr. All six patients of DHF grade IV who died had higher serum level of IL-8 above 200 pg/ml, the highest being 5,568 pg/ml in one patient; the presence of mRNA for IL-8 was very high in all patients. A striking correlation was observed between increased levels of IL-8 and severe DHF, with greater levels in patients with increased grade of the disease and death. These results suggest that IL-8 may have an important role and may be an indicator of increasing severity of the disease and death.

Adolescent↗