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Biomedical subjects

A Menon

Publications and source records attributed to A Menon.

At least 73 records · Page 4Linked to original sources

Presence of a non-HLA B cell antigen in rheumatic fever patients and their families as defined by a monoclonal antibody.

Numerous investigators have suspected that there is a genetic predisposition to rheumatic fever (RF). In this context we have recently produced a series of monoclonal antibodies directed against B cells obtained from RF patients one of which, labeled D8/17, identifies a B cell antigen present in 100% of all RF patients studied. While the highest percentage of positive cells were exhibited by RF probands (33.5% +/- SE), the percentage of cells in unaffected siblings and parents was 14.6 and 13%, respectively. The percentage of positive cells in APSGN probands, unaffected siblings, and parents was 2.96, 3.86, and 2.8%, respectively. A low level of B cells (5-7%) bearing the D8/17 marker was seen in control patients. The segregation pattern of the phenotypes defined by the percentage of D8/17 positive cells within HLA-typed RF families are consistent with an autosomal recessive mode of inheritance not associated with the human MHC system. We postulate that these phenotypes indicate the presence of at least one necessary genetic factor for susceptibility to RF.

Analysis of Variance↗

Flanking markers for the gene causing von Recklinghausen neurofibromatosis (NF1).

The defective gene causing von Recklinghausen neurofibromatosis (NF1), one of the most common inherited disorders affecting the human nervous system, was recently mapped to chromosome 17. We have used additional DNA markers to further narrow and bracket the NF1 defect. A multipoint linkage analysis suggests that the NF1 gene is flanked by D17Z1 on the centromeric side and by EW 207 on the telomeric side of the long arm of chromosome 17. The identification of closely linked flanking markers should allow us to develop a reliable prenatal and presymptomatic diagnostic test for this serious neurological disorder and provides the basis for applying chromosome-specific cloning techniques for the isolation and characterization of the mutant gene.

Chromosome Mapping↗

Differential non-responsiveness in humans of candidate Plasmodium falciparum vaccine antigens.

Synthetic subunit vaccines to sporozoites, merozoites, and gametes are being developed for malaria. The vaccine strategy assumes that the population to be immunized will respond favorably to these vaccine antigens. Using sera of 35 adults and 50 children from the The Gambia, West Africa, where Plasmodium falciparum is highly endemic, we examined the humoral immune response to candidate malaria vaccine antigens from sporozoites, merozoites, and gametes. We observed widespread restricted immunogenicity to defined parasite antigens in children and adults. HLA typing of adult lymphocytes demonstrated a marked diversity in HLA haplotypes in this population. Our results and those from our studies in mice suggest that genetic factors may partly explain the immunological non-responsiveness. This may necessitate re-evaluation of the malaria vaccine strategy.

Adult↗

Immunity to malaria in young Gambian children after a two-year period of chemoprophylaxis.

A cohort of 48 Gambian children was protected against malaria by fortnightly administration of Maloprim (pyrimethamine and dapsone) for 2 years between their 3 and 5 birthdays. A matched cohort of 47 children received placebo. During the year following the termination of prophylaxis there was no increase in the frequency of clinical attacks of malaria in the protected children compared with the control children. Antibody levels to circumsporozoite protein were measured by a radioimmunoassay and that to blood-stage antigens by a variety of techniques including an ELISA to whole blood-stage Plasmodium falciparum antigen, immunofluorescent assays (IFAT) to acetone fixed, glutaraldehyde fixed and unfixed parasites, a merozoite inhibition test and an opsonizing assay. Antibody levels were, in general, lower in protected than in control children and several differences between the two groups were statistically significant. When antibody levels were measured by ELISA and IFAT at the end of the following rainy season, when malaria transmission was intense, those in protected children had increased to comparable levels to those found in control children. Our findings suggest that chemoprophylaxis given for 2 years lowers malaria antibody levels but that it does not interfere with the development of protective immunity.

Animals↗

An ELISA test for detecting chloroquine in urine.

Two ELISA tests for detecting chloroquine in urine have been developed using polyclonal and monoclonal antibodies which react with the 7-chloro-4-amino-quinoline part of the chloroquine molecule and thus recognize chloroquine, its metabolites, and amodiaquine. The ELISAs were sensitive and specific and did not cross-react with other commonly used antimalarials. In a field trial the chloroquine ELISA performed better than the Dill Glazko or Haskins colorimetric tests. A small proportion of urines gave an apparently false positive reaction when tested at a dilution of 1:10, but not when tested at higher dilution.

Aminoquinolines↗

Human T-cell recognition of the circumsporozoite protein of Plasmodium falciparum: immunodominant T-cell domains map to the polymorphic regions of the molecule.

The definition of human T-cell antigenic sites is important for subunit vaccine development of a peptide immunogen if the goal is to allow antibody boosting during infection or to stimulate antibody-independent T-cell immunity. To identify such sites on the circumsporozoite (CS) protein of Plasmodium falciparum, 29 overlapping synthetic peptides spanning the entire CS protein were made and tested for their ability to stimulate peripheral blood lymphocytes from 35 adults living in a P. falciparum malaria-endemic region of West Africa. Three immunodominant domains were located outside the repetitive region. These domains, however, occurred in the polymorphic regions of the molecule, suggesting that parasite mutation and selection has occurred in response to immune pressure from T cells. Such polymorphism may impose an obstacle for vaccine development.

Adult↗

Maternal administration of chloroquine: an unexplored aspect of malaria control.

A health education package, designed to teach women to perceive and treat episodes of malaria, was tried in a rural area of The Gambia with no tradition of home based antimalarial therapy and a poor working knowledge of malaria. During the course of the rainy season, after a period of health education, 67.9% of the study mothers dispensed complete courses of chloroquine as instructed. Mothers were interviewed either weekly, monthly, halfway through or at the end of the 6 month study. Mothers interviewed weekly gave 65% more chloroquine than mothers interviewed less frequently. The implications of morbidity surveillance on chloroquine consumption, and of the study as a whole for Primary Health Care programmes are discussed.

Adult↗

Binding of nuclear factors to an upstream region of the human A gamma globin gene.

Two regions in the 5' flanking sequence of the human A gamma globin gene have been identified which bind nuclear factors. One of these regions is located between nucleotides -299 and -140 while the other lies between nucleotides -140 and -60. The former sequence is of interest as this region contains several mutations associated with non-deletion HPFHs. It is possible that factors responsible for the formation of these complexes are involved in developmental regulation of this gene. At the present time it is unknown whether this protein binds at or near the site of the mutations associated with HPFH. It is possible that a protein normally binds to this region in adult erythroid cells and represses expression of the gamma globin genes. When this sequence is altered the factor can not bind and expression of gamma globin genes in adult cells occurs. This could explain the continued production of fetal hemoglobin into adult life. In this model the sites of DNA-factor interaction include the nucleotides at -202, -198, -196 etc. such that nucleotide changes at these positions directly affect factor binding. Alternatively, the sites of DNA factor interaction may be sufficiently proximal to the -202 and -196 region such that single base change at -202, -198, and -196 cause perturbations in the DNA that indirectly effect the DNA-factor interaction. Careful footprinting must be carried out to define the exact binding site. The assay described here provides the basis for the purification of this factor and a study of its interaction with DNA.

Base Sequence↗

Pelvic tuberculosis: an uncommon gynaecological problem in Malaysia.

Tuberculosis of the genital tract was diagnosed in only 12 patients during the 17 year period from March 1968 to February 1985 at the University Hospital, Kuala Lumpur, which serves as a major referral centre in Malaysia. The incidence was 0.31 per 1000 gynaecological admissions and the peak age incidence was in the age group 26 to 35 years. The surgical management was mainly conservative as infertility was the most frequent mode of presentation (50%). Evidence of previous pulmonary tuberculosis was present in only five cases. Adnexal adhesions were the commonest pelvic finding; the fallopian tubes and endometrium were affected with equal frequency. Positive cultures for Mycobacterium tuberculosis were obtained in only five of the 12 patients. All patients received combination anti-tuberculosis drugs with satisfactory response.

Adult↗

Pulmonary protective mechanisms in human infants.

The flow of oral and nasal secretions into the pharynx is a recognized source of pulmonary aspiration during sleep in infants and adults alike. Such aspiration probably accounts for many cases of bacterial pneumonia. In infants, swallowing occurs frequently in sleep, and the rate of swallowing appears to be far greater than that of the sleeping adult. Such swallowing during sleep appears to be the major mechanism whereby oral and nasal secretions are transported to the digestive tract. Certain aspects of those swallows, such as "swallow-breaths" and their coordination with the respiratory cycle, have been documented. A brief period of airway closure is always seen during such nonfeeding swallows. Nonfeeding swallows are usually seen during mixed and obstructive apneic spells in preterm infants. The underlying reflex mechanisms responsible for such swallows during apnea are unclear. During ordinary postfeeding regurgitation, upper airway closure and swallowing occur in close temporal sequence. These events appear to be major mechanisms of airway protection during regurgitation. In certain infants, regurgitation and prolonged apnea often occur simultaneously. The mechanism underlying their association is unclear but may involve laryngeal chemoreceptors.

Apnea↗

Interferences with potentiometry of CO2 in the Ektachem 400 Analyzer.

We have investigated the Kodak Ektachem 400 Analyzer procedure for CO2 for interferences from benzyl alcohol, benzoic acid, and several compounds structurally similar to benzoic acid. Benzoic acid in plasma, at concentrations found in neonates intoxicated with benzyl alcohol, caused a large increase in the results for CO2, as did substantially above-normal concentrations of certain fatty acids and keto-acids, and toxic concentrations of aspirin. We observed a correlation between increasing benzoic acid concentrations (up to 17 mmol/L) and falsely increasing CO2 values (greater than 47 mmol/L) obtained with the Ektachem Analyzer for samples from a neonate in the intensive-care unit, who was receiving benzyl alcohol-preserved saline solutions. Although the Ektachem CO2 procedure is simple and rapid, and in most cases accurate, questionable results are occasionally encountered, as indicated by a low anion gap or a measured CO2 exceeding that calculated from blood gas measurements. Such results require the use of another method for verification.

Benzoates↗

Giant 'cryptococcoma' of the lung.

A case is described of cryptococcosis presenting as a large round intrathoracic lesion with superior vena caval obstruction and clubbing of the fingers. The patient was satisfactorily treated by lobectomy under cover of amphotericin B therapy.

Amphotericin B↗