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M Suresh

Publications and source records attributed to M Suresh.

53 records · Page 3Linked to original sources
PubMed1998

Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection.

Viral infections induce extensive T cell proliferation in vivo, but the specificity of the majority of the responding T cells has not been defined. To address this issue we used tetramers of MHC class I molecules containing viral peptides to directly visualize antigen-specific CD8 T cells during acute LCMV infection of mice. Based on tetramer binding and two sensitive assays measuring interferon-gamma production at the single-cell level, we found that 50%-70% of the activated CD8 T cells were LCMV specific [2 x 10(7) virus-specific cells/spleen]. Following viral clearance, antigen-specific CD8 T cell numbers dropped to 10(6) per spleen and were maintained at this level for the life of the mouse. Upon rechallenge with LCMV, there was rapid expansion of memory T cells, but after infection with the heterologous vaccinia virus there was no detectable change in the numbers of LCMV-specific memory CTL. Therefore, much of the CD8 T cell expansion seen during viral infection represents antigen-specific cells and warrants a revision of our current thinking on the size of the antiviral response.

Animals↗
PubMed1998

Long-term CD4 Th1 and Th2 memory following acute lymphocytic choriomeningitis virus infection.

CD4 T cells play a central role in viral immunity. They provide help for B cells and CD8 T cells and can act as effectors themselves. Despite their importance, relatively little is known about the magnitude and duration of virus-specific CD4 T-cell responses. In particular, it is not known whether both CD4 Th1 memory and CD4 Th2 memory can be induced by viral infections. To address these issues, we quantitated virus-specific CD4 Th1 (interleukin 2 [IL-2] and gamma-interferon) and Th2 (IL-4) responses in mice acutely infected with lymphocytic choriomeningitis virus (LCMV). Using two sensitive assays (enzyme-linked immunospot assay and intracellular stain) to measure cytokine production at the single-cell level, we found that both CD4 Th1 and Th2 responses were induced during primary LCMV infection. At the peak (day 8) of the response, the frequency of LCMV-specific CD4 Th1 cells was 1/35 to 1/160 CD4 T cells, and the frequency of Th2 cells was 1/400. After viral clearance, the numbers of virus-specific CD4 T cells dropped to 1/260 to 1/3,700 and then were maintained at this level indefinitely. Upon rechallenge with LCMV, both CD4 Th1 and Th2 memory cells made an anamnestic response in vivo. These results show that unlike some microbial infections in which only Th1 or Th2 responses are seen, an acute viral infection can induce a mixed CD4 T-cell response with long-term memory.

Animals↗
PubMed1996

Effects of estradiol-17 beta and progesterone on isolated human omental artery from premenopausal nonpregnant women and from normotensive and preeclamptic pregnant women.

OBJECTIVE: Our purpose was to study the direct vascular effects of estradiol-17 beta and progesterone on isolated omental artery from premenopausal nonpregnant women and from normotensive and preeclamptic pregnant women. STUDY DESIGN: Omental artery rings from normotensive premenopausal nonpregnant women and from normal and preeclamptic pregnant women were mounted in Krebs-bicarbonate solution in organ baths for isometric tension recording. The endothelium was removed from some of the rings, and all were contracted with potassium chloride (60 mmol/L) and then exposed to cumulative concentrations of estradiol-17 beta and progesterone. Concentration response curves were constructed and relaxation was expressed as percent change from the reference 60 mmol/L potassium chloride contraction. Data analysis was by repeated-measures analysis of variance, Newman-Keuls test, and the unpaired Student t test as appropriate. A two-tailed p < 0.05 was considered statistically significant. RESULTS: Both hormones studied caused vasorelaxation in omental arteries from all three groups of patients. Of the two, estradiol-17 beta was more effective, regardless of the presence or absence of endothelium. Removal of the endothelium shifted the estradiol-17 beta concentration-response curve to the right in the normal pregnant artery but not in nonpregnant or preeclamptic vessels. Removal of the endothelium shifted the progesterone concentration-response curve to the left in arteries from preeclamptic patients. CONCLUSIONS: Estradiol-17 beta and progesterone have direct in vitro vasodilator activity that appears to be linked, in part, to the endothelium in human omental artery from normal and hypertensive women in different hormonal states.

Adult↗
PubMed1996

Effects of selected vasoconstrictor agonists on isolated omental artery from premenopausal nonpregnant women and from normal and preeclamptic pregnant women.

OBJECTIVE: Our purpose was to compare the responsiveness of omental resistance arteries from nonpregnant women and from normotensive and preeclamptic pregnant women to selected contractile agonists. STUDY DESIGN: Omental artery rings with intact endothelium from normotensive premenopausal nonpregnant women and from normal and preeclamptic pregnant women were mounted in Krebs-bicarbonate solution in organ baths for isometric tension recording. After the presence of endothelium was confirmed, cumulative concentrations of norepinephrine, serotonin, U46619, and endothelin-1 were added. Concentration-response curves were constructed and expressed as percentage of a reference 60 mmol/L potassium chloride contraction. Data analysis was by repeated-measures analysis of variance. Newman-Keuls test, and paired or unpaired Student t test, as appropriate. Statistical significance was by two-tailed p<0.05. RESULTS: Endothelin-1 and U46619 increased tension similarly in all three groups. Norepinephrine increased tension in nonpregnant vessels to a greater extent than in either preeclamptic or pregnant vessels (nonpregnant 114.3 +/- 5.42% vs pregnant 65.2 +/- 10.5%, p<0.05). Nonpregnant omental artery developed significantly greater tension than did pregnant tissue at three concentrations of norepinephrine (10(-5) mol/L, 3 x 10(-5) mol/L, 10(-4) mol/L), and preeclamptic vessels developed more tension than that from normal pregnant vessels at 3 x 10(-6) mol/L (p=0.06) and 10(-5) mol/L (p<0.05). There was a negligible change in tension with increasing concentrations of serotonin in the vessels from nonpregnant women; serotonin-induced contraction in the omental arteries from normotensive pregnant women and preeclamptic patients was <6% of the potassium chloride reference contraction, but this was significantly (p<0.05) different from that of the nonpregnant women. CONCLUSIONS: Omental artery segments from nonpregnant, normotensive pregnant and preeclamptic women contract similarly to endothelin-1 and U46619 but exhibit variable responses to norepinephrine and serotonin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Antigen-specific lymphoproliferative responses to tetanus toxoid: a means for the evaluation of Marek's disease virus-induced immunosuppression in chickens.

Antigen-specific lymphoproliferative responses were examined in chickens following immunization with tetanus toxoid (Ttx). The immune competence of chickens was assessed by mitogen assay utilizing phytohemagglutinin (PHA)-stimulation and Ttx-specific antigen proliferation assay (Ttx-APA). Immune spleen cells but not peripheral blood leucocytes demonstrated specific proliferation following stimulation in vitro in a Ttx-APA. In this study, we examined firstly the effects of Marek's disease (MD)-associated immunosuppression on specific immune responses. The humoral and cell-mediated immune responses were monitored by enzyme-linked immunosorbent assay (ELISA) and Ttx-APA, respectively. Secondly, we examined if vaccination against MD using a conventional herpesvirus of turkeys (HVT) vaccine and two recombinant HVT (rHVT) vaccines would affect the development of Ttx-specific immune responses. The rHVT vaccines used in this study included two constructs: one expressing both Newcastle disease virus (NDV) and MD virus (MDV) genes (HVT/NDV/MDV), and another expressing only MDV genes (HVT/MDV). The mitogenic responses of spleen cells of the vaccinated chickens were inconsistent allowing no definitive conclusions about vaccinal immunosuppression. The results of the Ttx-APA indicated that Ttx-specific lymphoproliferative responses provide a meaningful measure of immunosuppression. The MDV-induced immunosuppression resulted in the inhibition of Ttx-specific lymphoproliferation in vitro. Both HVT and rHVT vaccines were not immunosuppressive as indicated by the development of normal Ttx-specific lymphoproliferative responses in chickens. These results indicate that vaccination against MD results not only in the prevention of tumor formation but also protection from possible virus-induced immunosuppression.

Animals↗
PubMed1996

Pathogenesis of type II avian adenovirus infection in turkeys: in vivo immune cell tropism and tissue distribution of the virus.

Hemorrhagic enteritis virus (HEV), a type II avian adenovirus, causes intestinal hemorrhages and immunosuppression in turkeys. In this study, we exposed turkeys to virulent HEV and examined fractionated spleen cells for the presence of viral DNA by in situ hybridization and amplification of DNA extracted from virus-infected cells by PCR. HEV replication was detected only in the immunoglobulin M-bearing B lymphocytes and macrophage-like cells but not in the CD4+ or CD8+ T lymphocytes. The inability to infect T cells distinguishes type II avian adenoviruses from lymphotropic mammalian adenoviruses which infect and replicate in T cells. Furthermore, these data suggested that HEV-induced immunosuppression in turkeys may be due to the effect of the virus on B lymphocytes and macrophages. We also examined tissue tropism of HEV by in situ hybridization conducted on sections of lymphoid and nonlymphoid tissues. Large numbers of HEV-positive cells were detected in spleen and cecal tonsils. Diminutive viral activity was present in the intestines, the principal site of HEV-induced pathology. Thus, intestinal pathology was not associated with local cytopathic viral replication. This result and our previous observation that cyclosporin A abrogated intestinal hemorrhaging in HEV-infected turkeys strongly suggested that intestinal lesion induced by this virus may be immune system mediated.

Adenoviridae Infections↗
PubMed1995

The effect of lipid peroxides on isolated human umbilical artery contraction.

OBJECTIVE: Our purpose was to determine the effect of oxidized lipids on the contractile activity of isolated human umbilical arteries. STUDY DESIGN: Umbilical artery rings were prepared for isometric tension recording and exposed to cumulative concentrations of oxidized and nonoxidized lipid and control solutions. Rings were also incubated with the lipid or control solutions and then contracted with cumulative concentrations of U46619. A final set of rings in Ca(++)-free depolarized solution was incubated with the agents above, and then the Ca++ concentration was increased cumulatively. RESULTS: The lipids had no direct contractile effect. Both lipids inhibited the response to U46619 and Ca++, with the oxidized lipids having the most significant effect. CONCLUSION: Oxidized lipids lack a direct contractile effect on isolated human umbilical arteries and inhibit the contractile response to thromboxane and calcium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Human umbilical vessels: responses to agents frequently used in obstetric patients.

OBJECTIVE: Our purpose was to study the effects of some drugs frequently used in pregnant women on isolated human umbilical artery and vein segments. STUDY DESIGN: Umbilical artery and vein rings from normal term pregnancies were mounted in Krebs-bicarbonate solution in organ baths for isometric tension recording. Rings were contracted with potassium chloride (60 mmol/L) or U46619 (10(-8) mol/L) and then exposed to cumulative concentrations of nimodipine, nifedipine, nicardipine, phenytoin, magnesium sulfate, and hydralazine. Concentration-response curves were constructed by means of the difference in the percent relaxation between test and control vessels. Data analysis was by repeated measures analysis of variance, Newman-Keuls test, and the unpaired Student t test as appropriate. A value of p < 0.05 was considered statistically significant. RESULTS: All the agents studied were effective umbilical vasodilators, except for hydralazine, which had minimal effect. The dihydropyridine calcium antagonists were more potent vasodilators than were the other agents studied. Nifedipine was the most potent calcium blocker and was the only dihydropyridine that relaxed the umbilical vein to a greater extent than the umbilical artery. CONCLUSION: The most commonly used drugs in preeclampsia have variable effects on the umbilical vessels.

Analysis of Variance↗
PubMed1995

Hemorrhagic enteritis virus induced changes in the lymphocyte subpopulations in turkeys and the effect of experimental immunodeficiency on viral pathogenesis.

We examined the changes in the lymphocyte subpopulations in the spleen and peripheral blood of turkeys and the effects of experimental immunodeficiency in the B and T cell compartments on the pathogenesis of hemorrhagic enteritis (HE) in turkeys. Inoculation of turkeys with hemorrhagic enteritis virus (HEV) induced a drop in the relative proportions of IgM bearing cells on Day 2, 3, and 9 post-infection and an elevation in the relative proportions of CD4+ cells on Day 4 and 6 post-infection. Elevated levels of CD8+ cells were observed in the infected turkeys only on Day 16 after infection. Marked depletion of IgM+ cells may play a role in immunodepression caused by HEV. Cyclophosphamide (CY) treatment induced B cell deficiency in turkeys severely impaired HEV replication in the spleen suggesting that B lymphocytes are important for viral replication. Cyclosporin A (CsA) selectively impaired T cell mitogenesis and protected the turkeys against HEV-induced intestinal hemorrhages. CsA did not prevent viral replication in the spleen or the associated splenomegaly. This result suggested that T cell immunity may be important for intestinal hemorrhaging induced by HEV.

Animals↗
PubMed1995

Increased tumor necrosis factor-alpha and interleukin-1 beta expression in the lungs of calves with experimental pneumonic pasteurellosis.

We used a well characterized pneumonic pasteurellosis model in calves to determine whether increased proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) expression and secretion were associated with pneumonic lesions. Bronchoalveolar lavage fluids, lavage cells consisting of alveolar macrophages and neutrophils with degenerative changes, and lung tissues were analyzed for the presence of TNF-alpha and IL-1 beta approximately 48 h following endobronchial inoculation of logarithmic phase Pasteurella haemolytica 12296 organisms. Levels of TNF-alpha and IL-1 beta mRNA were significantly increased in lavage cells of P. haemolytica-infected animals but not in cells from phosphate buffered saline (PBS) inoculated controls based on in situ hybridization analysis. Significantly increased levels of TNF-alpha, and IL-1 beta mRNA were also expressed within the pneumonic lesions from P. haemolytica-infected calves. In contrast, lung tissues from PBS-inoculated control calves had cytokine mRNAs expressed at extremely low levels. Increased levels of bioactive IL-1 and immunoreactive (not bioactive) TNF-alpha were found in lavage fluids from P. haemolytica-infected calves compared with lavage fluids from PBS-inoculated calves. These findings indicate that the proinflammatory cytokines TNF-alpha and IL-1, may be associated with pathogenesis of lung injury in bovine pneumonic pasteurellosis.

Animals↗
PubMed1995

Molecular cloning and sequence analysis of the penton base genes of type II avian adenoviruses.

We describe here the identification of the penton base gene of hemorrhagic enteritis virus (HEV), a type II avian adenovirus, in a 2477-base pair (bp)-EcoRI fragment of the viral DNA by sequence analysis. Identification is based on an extensive amino acid homology between the HEV-open reading frame and the penton base of a fowl adenovirus (FAV-10) and various human adenoviruses. The 1344 bp-penton base gene of HEV encodes a 448-amino acid polypeptide of molecular weight of 50,843 Da. The nucleotide sequences of penton base genes of HEV and marble spleen disease virus (MSDV) are identical. The HEV penton base lacks the RGD motif, present in most human adenoviruses (Ad2, Ad3, Ad4, and Ad 12) suggesting that HEV may not use alpha v integrins to gain entry into host cells. Further sequence analysis revealed the presence of a Leu-Asp-Val (LDV) motif in the HEV penton base amino acid sequence similar to most of the human adenoviruses. LDV motif on the fibronectin has been shown to interact with the alpha 4 beta 1 integrins on cells, which includes lymphocytes and monocytes. The presence of LDV motif in the penton base of HEV implicates the involvement of alpha 4 beta 1 integrins in the viral internalization into host cells.

Amino Acid Sequence↗
PubMed1995

Molecular and functional characterization of turkey interferon.

The turkey interferon (TkIFN) gene encodes a signal peptide and a mature protein of 30 and 162 amino acids, respectively. TkIFN mRNA expression was induced by reoviral double-stranded RNA in fibroblasts. The recombinant TkIFN protein possessed species-specific antiviral activity and in synergy with lipopolysaccharide (LPS) induced bone marrow macrophages to produce nitric oxide (NO). LPS or TkIFN alone did not induce bone marrow macrophages to produce significant amounts of NO, which showed that TkIFN provided one of the two signals necessary to induce NO production in turkey macrophages. Unlike the anti-inflammatory nature of mammalian alpha/beta IFNs, TkIFN augmented the LPS-induced expression of interleukin-8, a proinflammatory cytokine. This finding suggests a role for TkIFN in inflammatory conditions.

Amino Acid Sequence↗
PubMed1989

Oligonucleotide gene probes may detect enterotoxigenic Escherichia coli directly in fecal smears.

Diarrhoeal stools from 86 Indian children were examined for the presence of enterotoxigenic Escherichia coli (ETEC) by DNA hybridization on bacterial colonies as well as directly on fecal smears. Colony hybridization showed that 8 of the samples contained ETEC. Only in three of these specimens were all the colonies tested positive for ETEC. These samples were correctly identified by the stool smear hybridization assay. The remaining 5 specimens produced enterotoxigenic as well as nonenterotoxigenic colonies. These samples were all negative by the stool smear hybridization technique. Methodological improvements of the stool smear assay may provide a substantially simplified method for the otherwise cumbersome identification of ETEC.

Diarrhea↗
PubMed1984

The effects of intravenous cimetidine and metoclopramide on gastric volume and pH.

The effects on gastric pH and volume of intravenous administration of cimetidine and metoclopramide before induction of anesthesia were studied. Sixty ASA Class I patients scheduled for elective surgery were randomly divided into four groups of 15 each, and the study was double-blinded. Group I received normal saline only; Group II received 4 mg/kg of cimetidine only; Group III received 0.15 mg/kg of metoclopramide only; and Group IV received 4 mg/kg of cimetidine and 0.15 mg/kg of metoclopramide. All drugs were given intravenously 30 min before induction of anesthesia. Gastric aspirates were collected during anesthesia, 30 min and 60 min after administration of the drugs. Metoclopramide reduced gastric volume significantly when administered alone (P = 0.0001), but cimetidine did not (P = 0.10). Cimetidine increased the gastric fluid pH significantly (P = 0.0001) as did metoclopramide (P = 0.0023). The effects of cimetidine and metoclopramide on gastric fluid pH were additive when administered together. The combination of cimetidine and metoclopramide when given intravenously before anesthesia provides greater protection against aspiration pneumonitis in patients at risk than does either drug alone.

Adolescent↗
PubMedDate not supplied

Studies on lymphocyte subpopulations and the effect of age on immune competence in turkeys.

We characterized the lymphocyte subpopulations and investigated the effect of age on cellular and humoral immunity, development of lymphoid organs, and the relative proportions of CD4+ and CD8+ cells in turkeys. The mitogenic responses of peripheral T cells were poorly developed at hatch but developed rapidly after hatch and reached adult levels by 2 weeks-of-age. The average percentage of CD4+ cells was 45, 29.8, and 26.3 in the thymi, peripheral blood, and spleens, respectively, in turkeys. The mean percentage of CD8+ cells in the thymi, peripheral blood, and spleens of turkeys was 53.8, 13.6, and 15.5, respectively. Age did not influence the relative proportions of CD4+ and CD8+ T cells in the spleens and peripheral blood of turkeys. The mean percentages of IgM+ cells in the bursae and spleens were 78.5 and 26.8, respectively. Day-old turkeys did not develop detectable antibodies to either thymus dependent or independent antigens. However, 2 week or older turkeys showed good humoral responses. Inoculation of BSA at hatch induced tolerance, whereas injection of SRBC did not. Analysis of relative organ weights of turkey lymphoid organs showed that spleens and thymi developed rapidly during the first week-of-age.

Aging↗
PubMedDate not supplied

A simple and efficient method for radiolabeling of preformed liposomes.

A simple and efficient method for radiolabeling preformed liposomes was developed using hepatobiliary imaging agent (99m)Tc-diisopropyl iminodiacetic acid ((99m)Tc-DISIDA). Chloroform extraction of (99m)Tc-DISIDA from aqueous solutions results in 80% radioactivity in the organic phase due to its lipophilic properties. However, with the presence of reduced glutathione (gamma-Glu-Cys-Gly), chloroform extraction results in only 30% of label in the organic phase because the (99m)Tc-DISIDA complex undergoes reduction decomposition to more hydrophilic species by reaction with glutathione. The incorporation efficiency of the (99m)Tc-DISIDA into the liposomes containing reduced glutathione was greater than 90%. The labeled liposomes were stable up to 24 h in saline and 90% FBS after preparation. Biodistribution studies in mice showed that (99m)Tc labeled liposomes accumulated in liver and spleen at 24 h postinjection, unlike (99m)Tc-DISIDA. Compared to hexamethylpropyleneamine oxime (HMPAO), the (99m)Tc-DISIDA compound is much cheaper and has a longer shelf life when used for liposome labeling. The labeling technique described here could be used for monitoring pharmacokinetic and pharmacodynamic changes of liposomes, and tumor or infection imaging when coupled with targeting antibodies.

Animals↗