Completion rates of hospital-based tuberculosis treatment.
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Humans↗
Biomedical subjects
R Ramasamy
Publications and source records attributed to R Ramasamy.
Eliminating inappropriate classroom behavior using a DRO schedule: a preliminary study.
The purpose of this study was to eliminate out-of-seat behavior of a 14-yr.-old boy with learning disabilities using a single-subject design. Based on functional analysis, a Differential Reinforcement of Other Behavior interval schedule was used to eliminate an inappropriate behavior. During baseline, an average of 15 out-of-seat behavior problems were recorded. After 4 wk. of intervention, the inappropriate out-of-seat behavior was eliminated and on-task behavior improved.
Adolescent↗
Isotypes of naturally acquired antibodies to a repetitive & non-repetitive epitope on Plasmodium falciparum surface proteins in an endemic area of Sri Lanka.
Isotypes of antibodies in adults and 7-15 yr old children living in a malaria endemic area of Sri Lanka were measured by radioimmunoassay against synthetic target antigens derived from two Plasmodium falciparum surface proteins. Greater than 50 per cent of the sample population possessed IgM antibodies while < or = 13 per cent developed each of the IgG antibody isotypes against a repetitive epitope present on the circumsporozoite protein (CS repeat). A more even distribution of IgM, IgG1, IgG2, IgG3 and IgG4 antibodies was seen against a non-repetitive epitope (P103) on a 45 kDa merozoite surface protein. This difference is attributed to a T-independent antibody response against the CS repeat.
Adolescent↗
The design of macrocyclic ligands for monitoring magnesium in tissue by 31P NMR.
A series of ligands based upon 1,4,7-triazacyclononane, containing variable numbers of acetate vs methylenephosphonate ester or methylenephosphonate sidechains, has been synthesized and characterized as possible 31P NMR probes for monitoring [Mg2+]free. The diacetate monophosphonate and diacetate monophosphonate ester mixed ligands proved to have conditional (dissociation) constants at pH 7.4 in an appropriate range for measuring typical levels of intracellular [Mg2+]free, and binding selectivities for Mg2+ over Ca2+ that ranged from 1.4 to 6.8. The 31P resonances of these ligands were well downfield of typical tissue phosphate metabolite resonances, and addition of Mg2+ to any one of these ligands resulted in well-resolved resonances for HL and MgL (where L = ligand), in slow chemical exchange. The chemical shift differences between the HL and MgL species varied from 2.1 to 2.6 ppm for three different ligands. The conditional Mg(2+)-L binding constants were sensitive to pH in the physiological range, due to protonation of a single macrocyclic nitrogen at high pH (log K1 values ranged from 10 to 12). However, given conditions that allow an independent assessment of pH (i.e., from the 31P chemical shift of Pi), we show that accurate KD values can be estimated from the known thermodynamic stability constants (KMgL) and ligand protonation constants (Ki). This makes these ligands potentially useful for monitoring [Mg2+]free by 31P NMR over a variety of solution conditions, even during conditions when the pH may be changing.
Chelating Agents↗
Antibody and clinical responses in volunteers to immunization with malaria peptide-diptheria toxoid conjugates.
Twenty residue peptides from the 185-200-kD and 45-kD merozoite surface antigens of the malaria parasite Plasmodium falciparum were covalently linked to diphtheria toxoid as a carrier and used to immunize human volunteers with aluminium hydroxide as an adjuvant. Significant antibody levels were elicited by two boosting injections. The antibodies reacted with acetone-methanol fixed merozoite membranes in an immunofluorescence assay, but no inhibition of merozoite reinvasion could be detected in in vitro cultures containing the antibodies. Antibody levels against the immunizing peptides declined markedly within 77 days after the third injection. No hypersensitivity was observed against the peptides. However, the volunteers developed hypersensitivity against diphteria toxoid, and in particular a pronounced type III (Arthus) hypersensitivity after three injections with the toxoid. This effect might appear to limit the use of peptide-diphtheria toxoid conjugates for human immunization. Several biochemical, haematological and immunological tests done on the volunteers showed no other adverse effects from the immunizations.
Adolescent↗
Antibodies to Anopheles midgut reduce vector competence for Plasmodium vivax malaria.
Anopheles tessellatus mosquitoes ingested Plasmodium vivax gametocytes in human erythrocytes suspended in rabbit sera with and without anti-mosquito midgut antibodies. When the mosquito bloodmeal contained anti-midgut antibodies, fewer oocysts of P.vivax developed on the mosquito midgut and the proportion of mosquitoes becoming infected was significantly reduced. Complement inactivated serum also reduced the infection rate and load. A second bloodmeal containing anti-midgut antibodies, given 48 or 72 h later, did not enhance the transmission-blocking effect. IgG purified from anti-midgut sera was shown to mediate the transmission-blocking effect.
Animals↗
Effects of glycogen depletion on ischemic injury in isolated rat hearts: insights into preconditioning.
Limitation of myocardial injury and infarction has been demonstrated by interventions such as ischemic preconditioning or the use of pyruvate as a substrate, which reduces glycogen content before, and acidosis during, ischemia. An isolated perfused rat heart model of global ischemia was employed to test the hypothesis that glycogen depletion reduces ischemic injury as measured by creatine kinase release. 31P-nuclear magnetic resonance spectroscopy was used to measure high-energy phosphates (ATP and phosphocreatine), phosphomonoesters (PME), and intracellular pH. Compared with control glucose-perfused hearts with normal glycogen content (1.49 +/- 0.13 mg Glc/g wet wt), glycogen-depleted pyruvate, ischemic preconditioned, and glycogen-depleted glucose hearts all had reduced glycogen content before ischemia (0.62 +/- 0.16, 0.81 +/- 0.10, and 0.67 +/- 0.12 mg Glc/g wet wt, respectively; P = 0.003) and significantly higher pH at the end of ischemia (5.85 +/- 0.02, 6.33 +/- 0.06, 6.24 +/- 0.04, and 6.12 +/- 0.02 in control, glycogen-depleted pyruvate, preconditioned, and glycogen-depleted glucose-perfused hearts, respectively; P < 0.01), although acidification during the initial phase of ischemia was differentially affected by the three interventions. Glycogen-depleted pyruvate and preconditioned hearts had reduced PME accumulation, greater recovery of function and phosphocreatine, and lower creatine kinase release on reperfusion, whereas glycogen-depleted glucose-perfused hearts were similar to control hearts. In summary, glycogen depletion by these three methods limits the fall in pH during global ischemia, although glycogen depletion in the absence of preconditioning does not limit ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Ischemic preconditioning stimulates sodium and proton transport in isolated rat hearts.
One or more brief periods of ischemia, termed preconditioning, dramatically limits infarct size and reduces intracellular acidosis during subsequent ischemia, potentially via enhanced sarcolemmal proton efflux mechanisms. To test the hypothesis that preconditioning increases the functional activity of sodium-dependent proton efflux pathways, isolated rat hearts were subjected to 30 min of global ischemia with or without preconditioning. Intracellular sodium (Nai) was assessed using 23Na magnetic resonance spectroscopy, and the activity of the Na-H exchanger and Na-K-2Cl cotransporter was measured by transiently exposing the hearts to an acid load (NH4Cl washout). Creatine kinase release was reduced by greater than 60% in the preconditioned hearts (P < 0.05) and was associated with improved functional recovery on reperfusion. Preconditioning increased Nai by 6.24 +/- 2.04 U, resulting in a significantly higher level of Nai before ischemia than in the control hearts. Nai increased significantly at the onset of ischemia (8.48 +/- 1.21 vs. 2.57 +/- 0.81 U, preconditioned vs. control hearts; P < 0.01). Preconditioning did not reduce Nai accumulation during ischemia, but the decline in Nai during the first 5 min of reperfusion was significantly greater in the preconditioned than in the control hearts (13.48 +/- 1.73 vs. 2.54 +/- 0.41 U; P < 0.001). Exposure of preconditioned hearts to ethylisopropylamiloride or bumetanide in the last reperfusion period limited in the increase in Nai during ischemia and reduced the beneficial effects of preconditioning. After the NH4Cl prepulse, preconditioned hearts acidified significantly more than control hearts and had significantly more rapid recovery of pH (preconditioned, delta pH = 0.35 +/- 0.04 U over 5 min; control, delta pH = 0.15 +/- 0.02 U over 5 min). This rapid pH recovery was not affected by inhibition of the Na-K-2Cl cotransporter but was abolished by inhibition of the Na-H exchanger. These results demonstrate that preconditioning alters the kinetics of Nai accumulation during global ischemia as well as proton transport after NH4Cl washout. These observations are consistent with stimulation of the Na-K-2Cl cotransporter and Na-H exchanger by preconditioning.
Ammonium Chloride↗
Dynamics of natural antibody responses to malaria parasite surface proteins in the intermediate rainfall zone of Sri Lanka.
Antibodies against repetitive epitopes on Plasmodium falciparum and P. vivax circumsporozoite (CS) proteins and epitopes on the 45 kDa and 185-200 kDa P. falciparum merozoite surface proteins were measured by radioimmunoassay in a two year longitudinal study in Nikawehera village located in the intermediate rainfall zone of Sri Lanka. The prevalence and concentrations of specific antibodies were in many, but not all instances, greater in adults than in children who were aged 7-15 yr at the beginning of the study. The concentrations and prevalence of antibodies were associated with malaria transmission levels previously determined from entomological and hospital admission data in the area. Antibody responses to epitopes on different P. falciparum antigens, two different epitopes within the 185-200 kDa merozoite surface protein and between the P. falciparum and P. vivax CS repeats were significantly correlated. Antibody concentrations against a conserved epitope in the 185-200 kDa protein were significantly higher in P. falciparum infected individuals than in non-parasitaemic subjects. Antibody concentration and prevalences in Nikawehera were lower than at Weheragala, a site located 70 km away in the dry zone of Sri Lanka. It is postulated that lower levels of immunity in the population in areas such as Nikawehera, that are adjacent to more highly malaria endemic areas, may promote epidemics when conditions favour transmission.
Adolescent↗
The intermediate rainfall zone as a source of malaria epidemics in Sri Lanka.
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Humans↗
Cycle DNA sequencing with [alpha-35S]dATP demonstrates polymorphism of a surface antigen in malaria parasites from Sri Lankan patients.
Structural diversity in a 45 kDa surface antigen on Plasmodium falciparum merozoites (termed GYMSSA, MSP-2 or MSA-2) and other candidate molecules for developing a malaria vaccine need to be investigated in parasites obtained directly from patients in different malaria endemic countries. A double-stranded DNA sequencing method suitable for this purpose, and also for studying diversity in genes of other haploid cells, is described. A first round polymerase chain reaction (PCR) on DNA isolated from blood was carried out with a primer containing the GCN4 binding site to amplify and subsequently purify the coding region of the MSA-2 gene on GCN4 coated tubes. A second round PCR with more internal primers incorporating M13 forward and reverse primer sequences was then performed. Cycle sequencing was done with unlabelled M13 primers and [alpha-35S]dATP by the dideoxynucleotide procedure. Two different allelic forms of MSA-2 were identified in samples of Plasmodium falciparum from patients in Sri Lanka.
Amino Acid Sequence↗
Competition between Li+ and Mg2+ for the phosphate groups in the human erythrocyte membrane and ATP: an NMR and fluorescence study.
We investigated the mechanism of competition between Li+ and Mg2+ in Li(+)-loaded human red blood cells (RBCs) by making 7Li and 31P NMR and fluorescence measurements. We used 7Li NMR relaxation times to probe Li+ binding to the human RBC membrane and ATP; an increase in Mg2+ concentration caused an increase in both 7Li T1 and T2 values in packed Li(+)-loaded RBCs, in suspensions of Li(+)-loaded RBC ghosts, in suspensions of Li(+)-containing RBC membrane, and in aqueous solutions of ATP, indicating competition between Li+ and Mg2+ for binding sites in the membrane and ATP. We found that increasing concentrations of either Li+ or Mg2+ in the presence of human RBC membrane caused an increase in the 31P NMR chemical shift anisotropy parameter, which describes the observed axially symmetric powder pattern, indicating metal ion binding to the phosphate groups in the membrane. Competition between Li+ and Mg2+ for phosphate groups in ATP and in the RBC membrane was also observed by both fluorescence measurements and 31P NMR spectroscopy at low temperature. The ratio of the stoichiometric binding constants of Mg2+ to Li+ to the RBC membrane was approximately 20; the ratio of the conditional binding constants in the presence of a free intracellular ATP concentration of 0.2 mM was approximately 4, indicating that Li+ competes for approximately 20% of the Mg(2+)-binding sites in the RBC membrane. Our results indicate that, regardless of the spectroscopic method used, Li+ competes with Mg2+ for phosphate groups in both ATP and the RBC membrane; the extent of metal ion competition for the phosphate head groups of the phospholipids in the RBC membrane is enhanced by the presence of ATP. Competition between Li+ and Mg2+ for anionic phospholipids or Mg(2+)-activated proteins present in cell membranes may constitute the basis of a general molecular mechanism for Li+ action in human tissues.
Adenosine Triphosphate↗
Is malaria linked to the absence of alpha-galactosyl epitopes in Old World primates?
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Animals↗
Population dynamics of anthropophilic mosquitoes during the northeast monsoon season in the malaria epidemic zone of Sri Lanka.
Mosquito-borne diseases are a major health problem in Sri Lanka. Human biting mosquitoes were collected during the night (18.00-06.00 hours) at Nikawehera village, in the malaria endemic intermediate rainfall zone of the country. Collections were made at monthly intervals in the period October 1991 to April 1992, which included the main rainy season due to the northeast monsoon (October-January). Thirteen Anopheles, eleven Culex, three Aedes, three Mansonia and one Armigeres species were identified, including known vectors of malaria, Bancroftian filariasis, Japanese encephalitis and dengue fever. Mosquito human-biting rates were highest in December. The main malaria vector Anopheles culicifacies showed peak biting between 18.00 and 23.00 hours whereas the predominant culicines Culex fuscocephala and Cx quinquefasciatus preferred to bite after midnight. In 1991-92 the prevalence of some species of anophelines at Nikawehera differed markedly from that observed in 1990-91 and the possible reasons are discussed.
Animals↗
Antibodies to epitopes on merozoite and sporozoite surface antigens as serologic markers of malaria transmission: studies at a site in the dry zone of Sri Lanka.
Antibodies against repetitive epitopes on Plasmodium falciparum and P. vivax circumsporozoite (CS) proteins and epitopes on the 45-kD and 185-200-kD P. falciparum merozoite surface antigens were measured by radioimmunoassay in Weheragala, a malaria-endemic site in the dry zone of Sri Lanka. Antibodies were measured in sera collected in February at the end of the main malaria transmission season and three months later in May during the low transmission period. Ninety-seven percent of the sample population had antibodies to the P. falciparum CS repeat in February and a significant proportion possessed antibodies directed against all epitopes tested. Concentrations and prevalence of antibodies to the CS repeats decreased with time after the end of malaria transmission in adults and children. Similar temporal changes were observed with antibodies to the epitopes on merozoite surface antigens. Children 7-15 years of age had lower antibody concentrations against most epitopes than adults. Antibody concentrations to two different epitopes within the same merozoite surface antigen showed significant association as did antibody levels against the P. falciparum CS repeat and the predominant P. vivax CS repeat. However, antibody concentrations did not correlate with the presence of blood-stage malaria infections.
Adolescent↗
Influence of N-terminal amino acids & conjugation position to carrier on specificities of antibodies elicited by malaria peptides.
The specificity of murine antibodies raised against structurally related peptides derived from a malaria parasite membrane protein was studied. The peptides were conjugated to bovine serum albumin (BSA) with 6-maleimido caproic acyl N-hydroxysuccinimide ester before immunization. Conjugation to BSA through a C-terminal or an internal cysteine residue elicited antibodies with noticeably different specificities. An N-terminal tripeptide sequence arginine-asparagine-asparagine had a dominant influence on the immunogenicity of the peptides. Such factors need to be taken into consideration while designing peptide-based immunogens.
Amino Acid Sequence↗
Fecundity of Anopheles tessellatus reduced by the ingestion of murine anti-mosquito antibodies.
High titres of antibodies to antigens derived from head/thorax, midgut or abdomen of Anopheles tessellatus were produced in inbred mice. These antibodies, when ingested in a bloodmeal, reduced the fecundity of An. tessellatus by up to 29% in different experiments. It is postulated that antibodies directed against antigens shared between the head/thorax, abdomen and midgut tissues are involved in the reduction of fecundity.
Animals↗
Effect of lidocaine on contracture, intracellular sodium, and pH in ischemic rat hearts.
The relationships among intracellular Na concentration ([Na+]i), intracellular pH, [ATP], and contracture during global ischemia were studied in isolated, perfused rat hearts. Intracellular Na was monitored by 23Na nuclear magnetic resonance (NMR) spectroscopy using thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonate) (TmDOTP5-) as the paramagnetic shift reagent. High-energy phosphates and pH were monitored under the same conditions using 31P-NMR spectroscopy. Lidocaine (130 microM), a class IB fast Na channel blocker known to protect ischemic myocardium, prolonged the time to contracture in both unpaced and paced hearts (240 beats/min). After 10 min of global ischemia in paced hearts, [Na+]i was lower in the lidocaine-treated group compared with untreated hearts. The addition of lidocaine also significantly attenuated the depletion of ATP as well as development of intracellular acidosis. At the time of contracture, however, there was no difference in [Na+]i or pH between the two groups. Interestingly, the effect of lidocaine on Na+i accumulation during ischemia was manifested during the first 5-10 min of ischemia, while its effect on pH occurred after 9 min. This finding suggests that a mechanism other than the Na-H exchanger may play a role in the accumulation of Na+i early in the course of ischemia.
Animals↗