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Biomedical subjects

P Adhikari

Publications and source records attributed to P Adhikari.

At least 19 recordsLinked to original sources

Portable lead analyzer to locate source of lead.

OBJECTIVE: To investigate the sources of lead in the environment in children with elevated blood, with the help of a Field Portable X-Ray Fluorescence Analyzer. METHODS: One hundred and seven school children were chosen for this study on a random basis, from Mangalore and Karnataka. Their blood lead was analyzed. Of the cases analyzed, 10 students whose blood lead level was more than 40 microg/dl were investigated using a field portable X-Ray Fluorescence Analyzer. This is the first time such a device has been available for this purpose in India. RESULTS: The 'likely' source of lead exposure could be determined in eight cases which was from the immediate environment of the children like 'lead-based' paint on surfaces in the house, on playground and other exterior equipment; lead storage batteries, contaminated dust and soil and other lead-containing substances. CONCLUSION: The use of an X-Ray Fluorescence Analyser appeared to be useful in determining the source of lead.

Child↗

Fine Needle Aspiration cytology versus Fine Needle Sampling without aspiration. A prospective study of 200 cases.

In the present prospective study of 200 patients with superficial swelling of various sites, FNS followed by FNA were performed. Fifteen cases were excluded due to inadequate material. In the 80 lymph node cases, FNS was diagnostic in 85% cases as compared to FNA in 87.5%. The diagnostic accuracy was higher for FNA (87.5%) than for FNS (81.25%). However FNS smears were much superior qualitatively than FNA smears and for the diagnosis of malignant conditions FNS was found to be much better. Regarding the 68 thyroid swellings, FNS obtained a diagnosis in 82.4% cases while FNA got it in 77.9%. The diagnostic accuracy with FNS (89%) was much better compared to FNA (75%). Of the 27 breast cases FNS yielded diagnostic material in 70.38% cases while FNA was diagnostic in 85.19%, thus establishing definite superiority. However FNS seemed to be better for diagnosing malignant lesions while FNA appeared better for diagnosing benign ones. In the 5 salivary gland lesions and 5 miscellaneous lesions both FNS and FNA fared equally well. On the whole FNS technique was much more patient friendly and gave high class "text book" quality smears while FNA smears gave quantitatively more adequate material. Both the techniques therefore would be complementary to each other.

Adolescent↗

Mutational analysis at Asn-41 in peanut agglutinin. A residue critical for the binding of the tumor-associated Thomsen-Friedenreich antigen.

Peanut agglutinin is a clinically important lectin due to its application in the screening of mature and immature thymocytes as well as in the detection of cancerous malignancies. The basis for these applications is the remarkably strong affinity of the lectin for the tumor-associated Thomsen-Friedenreich antigen (T-antigen) and more so due to its ability to distinguish T-antigen from its cryptic forms. The crystal structure of the complex of peanut agglutinin with T-antigen reveals the basis of this specificity. Among the contacts involved in providing this specificity toward T-antigen is the water-mediated interaction between the side chain of Asn-41 and the carbonyl oxygen of the acetamido group of the second hexopyranose ring of the sugar molecule. Site-directed mutational changes were introduced at this residue with the objective of probing the role of this residue in T-antigen binding and possibly engineering an altered species with increased specificity for T-antigen. Of the three mutants tested, i.e. N41A, N41D, and N41Q, the last one shows improved potency for recognition of T-antigen. The affinities of the mutants can be readily explained on the basis of the crystal structure of the complex and simple modeling. In particular, the change of asparagine to glutamine could lead to a direct interaction of the side chain with the sugar while at the same time retaining the water bridge. This study strengthens the theory that in lectins the nonprimary contacts generally made through water bridges are involved in imparting exquisite specificity.

Antigens, Tumor-Associated, Carbohydrate↗

Upstream flanking sequences and transcription of SINEs.

SINEs, short interspersed repeated DNA elements, undergo amplification through retroposition and subsequent integration into a new location in the genome. Each new SINE insertion will be located in a new chromosomal environment, with different flanking sequences. Modulation of transcription by different flanking sequences may play an important role in determining which SINE elements are preferentially active in a genome. We evaluated the ability of upstream flanking sequences to regulate the transcription of three different SINEs (Alu, B2 and ID) by constructing chimeric constructs with known 5' flanking sequences of RNA polymerase III-transcribed genes. Upstream sequences from the 7SL RNA gene, U6 RNA gene, vault RNA gene, and BC1 gene increase transcription of Alu, B2 and BC1 in transient transfections of NIH3T3, HeLa, Neuro2a and C6 glioma cell lines. The 7SL sequence proved most efficient in increasing SINE transcription. The 7SL upstream fused to the BC1 RNA gene (an ID element) was used to create a transgenic mouse line. In contrast to the tissue-specific endogenous BC1 transcription, BC1 transgene transcripts were detected in all tissues tested. However, expression was much higher in those tissues that express the endogenous gene, demonstrating both transcriptional and post-transcriptional regulation. The BC1 RNA was detected in a similar ribonucleoprotein complex in the different tissues.

Alu Elements↗

Recurrent malaria--an enigma?

Management of recurrent malaria has to be individualised. A careful history, details of the drugs received, family history, laboratory evaluation will definitely help us in arriving at a reasonable diagnosis. For the future, genotyping, PCR testing and gamma interfiron levels may help us in identifying causes for recurrences.

Chronic Disease↗

Serotype 1a O-antigen modification: molecular characterization of the genes involved and their novel organization in the Shigella flexneri chromosome.

The factors responsible for serotype 1a O-antigen modification in Shigella flexneri were localized to a 5.8-kb chromosomal HindIII fragment of serotype 1a strain Y53. The entire 5.8-kb fragment and regions up- and downstream of it (10.6-kb total) were sequenced. A putative three-gene operon, which showed homology with other serotype conversion genes, was identified and shown to confer serotype 1a O-antigen modification. The serotype conversion genes were flanked on either side by phage DNA. Multiple insertion sequence (IS) elements were located within and upstream of the phage DNA in a composite transposon-like structure. Host DNA homologous to the dsdC and the thrW proA genes was located upstream of the IS elements and downstream of the phage DNA, respectively. The sequence analysis indicates that the organization of the 10.6-kb region of the Y53 chromosome is unique and suggests that the serotype conversion genes were originally brought into the host by a bacteriophage. Several features of this region are also characteristic of pathogenicity islands.

Chromosomes, Bacterial↗

Experience with quinine in falciparum malaria.

During a period of 1 year from July 95 to June 96, 60 patients with falciparum malaria were treated with quinine at Kasturba Medical College Hospital, Mangalore. Of these, 24 patients developed adverse effects to quinine. They were cinchonism (15) cardiotoxicity (10) hypoglycemia (9) hyperventilation (3) hypersensitivity reactions (3) and hypokalemia (1). Cardiotoxicity was noted in 4 of the 7 patients who received intravenous quinine and all four had renal and hepatic failure and prolonged Q-Tc on electrocardiogram. All 4 died of cardiac arrhythmias, 2 had broad QRS tachycardia and 2 had sinus bradycardia. We conclude that: 1. Quinine should be used cautiously in patients with impaired hepatic or renal function and in those with prolonged QTc as it can lead to cardiotoxicity in the form of I0 AV block, prolonged Q-Tc, broad QRS tachycardai or fatal bradyarrhythmia. Dosage reduction to 5 mg/kg body weight in the patients seem to be safer. 2. Hypoglycemia is a very frequent complication of quinine therapy and special care and frequent blood sugar estimations are required especially if the patient has vomiting. 3. Parenteral quinine is more likely to cause toxicity than oral quinine as earlier described.

Administration, Oral↗

Safety and efficacy of Hartone in stable angina pectoris--an open comparative trial.

OBJECTIVES: To evaluate the safety and efficacy of 'Hartone'--a proprietary herbal product primarily containing Terminalia arjuna in stable angina pectoris patients. PATIENTS AND METHODS: Ten patients with stable angina pectoris were given Hartone 2 caps twice daily for 6 weeks and 1 cap twice daily for the next 6 weeks. Haematological and biochemical investigations to assess safety were carried out on day 0, day 42 and day 84. Serum lipid profile was done before and after therapy. Efficacy was assessed by considering the reduction in the number of anginal episodes and improvement in stress test. The results were compared with 10 patients of stable angina pectoris on isosorbide mononitrate (ISMN) 20 mg twice daily. RESULTS: Hartone afforded symptomatic relief in 80% of patients and ISMN in 70%. The number of anginal attacks were reduced from 79/wk to 24/wk by Hartone and from 26/wk to 7/wk by ISMN. Although patients of both groups showed improvement in several stress test parameters compared to base line, the difference was not statistically significant. Hartone improved BP response to stress test in two patients and ejection fraction in one. Hartone was better tolerated than ISMN and showed no evidence of hepatic or renal impairment. Its effects on lipid profile was not consistent. CONCLUSION: Hartone is a safe and effective anti-anginal agent comparable to ISMN and is better tolerated. Large scale, randomised, double blind trials are needed to prove its efficacy.

Angina Pectoris↗

Molecular basis of recognition by Gal/GalNAc specific legume lectins: influence of Glu 129 on the specificity of peanut agglutinin (PNA) towards C2-substituents of galactose.

The ability to discriminate between galactose and N- acetylgalactosamine, observed in some lectins, is crucial for their biological activity as well as their usefulness as tools in biology and medicine. However, the molecular basis of differential binding of lectins to these two sugars is poorly understood. Peanut agglutinin (PNA) is one of the few galactose-specific legume lectins which does not bind N- acetylgalactosamine at all and is, therefore, ideal for the study of the basis of specificity towards C-2 substituted derivatives of galactopyranosides. Examination of the three-dimensional structure of PNA in complex with lactose revealed the presence of both a longer loop and bulkier residues in the region surrounding the C-2 hydroxyl of the galactopyranoside ring, which can sterically prevent the accommodation of a bulky substituent in this position. One such residue, is a glutamic acid at position 129 which protrudes into the binding site and perhaps directly obstructs any substitution at the C-2 position. Two mutants in bacterially expressed PNA were therefore constructed. These were E129D and E129A, in which Glu129 was replaced by Asp and Ala, respectively. The specificity of the mutants for galactose, galactosamine, and N- acetylgalactosamine was examined through observing the inhibition of hemagglutination and binding of the lectin to immobilized asialofetuin. The results showed that the affinity of E129A and E129D for C-2-substituted derivatives of the galactose varies. The mutant E129D showed significant binding towards N- acetylgalactosamine, suggesting that the residue Glu 129 is crucial in imparting exclusive galactose-specificity upon PNA. This study not only attempts to provide an explanation for the inability of PNA to accommodate C-2-substituted derivatives at its primary subsite, but also seeks to present a basis for engineering lectins with altered specificities.

Acetylgalactosamine↗

FNAC diagnosis of tuberculosis--an eight years study at Mangalore.

1. FNAC is a very useful adjunct in the diagnosis of tuberculosis: 2. Diagnosis of tuberculosis can be made by the demonstration of epithelioid granulomas with or without caseation even in the absence of AFB. 3. Necrotic features whether acellular or accompanied by neutrophilic infiltrate are usually misdiagnosed as suppurative abscesses. Such smears however show high AFB positivity and thus the diagnosis of tuberculosis is still possible even in the absence of epithelioid granulomas. 4. Therefore all smears obtained by FNAC of suspected tuberculous lesions should be subjected to ZN staining for AFB.

Adolescent↗

The fbpABC locus of Neisseria gonorrhoeae functions in the periplasm-to-cytosol transport of iron.

We have determined that the DNA sequence downstream of the well-characterized gonococcal fbp gene contains two open reading frames: one designated fbpB, which encodes a protein proposed to function as a cytoplasmic permease, and one designated fbpC, which encodes a protein proposed to function as a nucleotide-binding protein. The fpbABC operon composes an iron transport system that is homologous to the sfu and hit operons previously reported for Serratia marcescens and Haemophilus influenzae, respectively, and displays elements characteristic of ATP binding cassette transporters. The fpbABC operon differs from these loci in that it is lethal when overexpressed in Escherichia coli.

Amino Acid Sequence↗

Evaluation of safety and efficacy of azithromycin in lower respiratory tract infections (LRTI)

Azithromycin was given to 55 cases of lower respiratory tract infections in the doses of 500 mg on day 1, followed by 250 mg on days 2-5. It produced bacteriological cure in 70.8% patients and clinical cure or improvement in 69.09% of patients. 4.27% of patients had throat colonisation with new organisms, of which 9.09% needed a second antibiotic. The drug was well tolerated and minor side effects were noted. Gastrointestinal disturbances (16.36%) headache and giddiness (14.55%), rash (3.64%) were the noted side effects. Reduction of platelet count by 50% occurred in 12.29% of the cases compared to 0.2% reported earlier. But this thrombocytopenia was clinically not significant, as it did not cause any symptoms.

Adolescent↗

Biochemical characterization of a Haemophilus influenzae periplasmic iron transport operon.

Bacterial iron transport is critical for growth of pathogens in the host environment, where iron is limited as a form of nonspecific immunity. For Gram-negative bacteria such as Haemophilus influenzae, iron first must be transported across the outer membrane and into the periplasmic space, then from the periplasm to the cytosol. H. influenzae express a periplasmic iron-binding protein encoded by the hitA gene. This gene is organized as the first of a three-gene operon purported to encode a classic high affinity iron acquisition system that includes hitA, a cytoplasmic permease (hitB), and a nucleotide binding protein (hitC). In this study we describe the cloning, overexpression, and purification of the H. influenzae hitA gene product. The function of this protein is unambiguously assigned by demonstrating its ability to compete for iron bound to the chemical iron chelator 2,2'-dipyridyl, both in vitro and within the periplasmic space of a siderophore-deficient strain of Escherichia coli. Finally, the importance of a functional hitABC operon for iron acquisition is demonstrated by complementation of this siderophore-deficient E. coli to growth on dipyridyl-containing medium. These studies represent a detailed genetic, biochemical, and physiologic description of an active transport system that has evolved to efficiently transport iron and consequently is widely distributed among Gram-negative pathogenic bacteria.

Bacterial Proteins↗

The 1993 epidemic of dengue fever in Mangalore, Karnataka state, India.

An epidemic of febrile illness with hemorrhagic manifestations occurred in certain parts of Mangalore city, Karnataka state, India, from the last week of July 1993. The epidemic reached its peak by mid-August and then started declining. Sporadic cases, however, continued to occur till early December. About 200 cases were reported covering all age groups and both sexes. The cases presented with pyrexia, myalgia, arthralgia and headache. Palatal petechiae, magenta colored tongue with central coating, maculopapular rash and facial flush were observed as classical signs. The tourniquet test was positive in 12% of the cases. Hemorrhage was observed in the form of epistaxis (2 cases), subconjunctival hemorrhage (2 cases) or purpura (3 cases). There were no deaths which were attributable to the epidemic. Five strains of dengue (DEN-2) virus were recovered from the acute-phase sera. Dengue virus-specific IgM type of antibodies were detected in 29/116 (25%) sera. Breeding of Aedes aegypti was observed in some of the areas where cases had occurred. No virus was isolated from any of the field-caught Ae. aegypti mosquitos.

Acute Disease↗

Prevalence of bancroftian filariasis in Burdwan district, West Bengal: II. Vector and microfilariae density in colliery and non-colliery areas.

The paper reports the density of Culex quinquefasciatus, infection and infectivity rates, microfilariae(mf)- density and microfilaraemic persons in the colliery and non-colliery areas of Burdwan district, West Bengal. The numbers C. quinquefasciatus were significantly higher in colliery areas, as compared to non-colliery areas. The infection rate and infectivity rates of the vector were found to be higher in colliery areas. The higher vector density in colliery area is one of the major reasons of higher prevalence of filariasis in that area. However, other environmental factors like exposure of the host to the coal might influence the pathogenesis of filariasis in the colliery area.

Animals↗

Prevalence of Bancroftian filariasis in Burdwan District, west Bengal: a comparative study between colliery and non-colliery areas.

The present study reports results of a survey of bancroftian filariasis in Burdwan district West Bengal. 85,974 persons were examined of which 46,221 were inhabitants of the colliery areas of the district and rest 39,753 were from non-Colliery areas, including urban and rural areas of the district. The clinicopositivity, endemicity, microfilaria(mf)-positivity, mf-clinicopositivity, and mf-density were determined. It was found that all these epidemiological and parasitological parameters were significantly higher in the colliery area as compared to non-colliery area. The high vector density in the colliery area may account for such significantly higher prevalence of filariasis in this area. From a differential count of neutrophils, eosinophils and lymphocytes in the mf-positive cases, it was revealed that neutrophil percentage was significantly (P < 0.01) decreased while eosinophils and Lymphocytes increased. The decrease of neutrophils was correlated ((Correlation co-efficient, r = -0.78) with the increase of lymphocytes, indicating an imbalance in the immune-system of the infected persons. The geographical and geological factors resulting in high vector density are considered responsible for the significantly higher rate of bancroftian filariasis in the Colliery area.

Adolescent↗