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Biomedical subjects

K Balakrishnan

Publications and source records attributed to K Balakrishnan.

At least 19 recordsLinked to original sources

Fine needle aspiration cytology in the management of a parotid mass: a two centre retrospective study.

OBJECTIVES: There is a diversity of opinion regarding the role of fine needle aspiration cytology (FNAC) in the pre-operative evaluation of the parotid mass. This study further investigates the role of FNAC from the standpoint of the clinician attempting to resolve one or more clinical issues. METHODS: A retrospective study conducted at two UK Hospitals with no overlap of cytopathologists or surgeons. Patients undergoing parotidectomy at each institution were identified from Pathology department databases. The definitive histopathological diagnosis was compared with any pre-operative FNAC diagnosis. Cytology results were classified as suggestive, non-diagnostic, sampling error, or misleading. SETTING: The study was conducted in a District General Hospital and a University Teaching Hospital providing secondary care for each community. RESULTS: For the University Teaching Hospital the sensitivity in distinguishing malignant from benign disease was 79% (95% CI 61-97%) with a specificity 84% (95% CI 73-95%). However, three of eight patients with a primary parotid salivary gland malignancy were reported as having benign disease on FNAC. For the participating District General Hospital the sensitivity in distinguishing malignant from benign disease was 38% (95% CI 13-63%) and specificity 95% (95% CI 73-95%). CONCLUSIONS: Fine needle aspiration cytology does not reliably distinguish a benign from a malignant primary salivary gland neoplasm in the participating institutions. Where clinical teams use FNAC in an attempt to resolve this clinical problem, the results should be interpreted with caution and an ongoing audit of performance is required.

Biopsy, Fine-Needle↗

Identification of virulent isolates of the entomopathogenic fungus Nomuraea rileyi (F) Samson for the management of Helicoverpa armigera and Spodoptera litura (identification of virulent isolates of N. rileyi).

Eleven geographical isolates of the entomopathogenic fungus Nomuraea rileyi (Farlow) Samson of Helicoverpa armigera (Hubner)/Spodoptera litura (Fabricius) origin were studied for efficacy against the two host insects. Laboratory bioassays at a concentration of 2 x 10(8) conidia ml(-1) indicated that N. rileyi isolates of S. litura origin were better in terms of time taken for mycosis and mortality in both the test larvae: S. litura (77-80% mortality in 7 days) and H. armigera (79-85% in 8 days). Among the isolates of S. litura origin, geographical isolates from Hyderabad and Karimnagar were superior in terms of high percent kill as well as 100% germination of conidia within 48 h. Fastest germination was observed with Karimnagar isolate followed by Hyderabad isolate. Conidial yield was highest on barley-carrot extract-yeast extract medium. However in terms of material cost, barley-yeast extract medium was the lowest. The Karimnagar isolate of S. litura origin gave the highest conidial yield on barley-yeast extract medium. Chitinolytic enzyme profiles of different isolates revealed polymorphism in all the isolates from S. litura origin. Overall among the parameters studied the best traits were found in the Karimnagar isolate of S. litura origin.

Animals↗

HLA-DRB1*, -DQB1* in Piramalai Kallars and Yadhavas, two Dravidian-speaking castes of Tamil Nadu, South India.

Two Dravidian-speaking castes of Tamil Nadu, Piramalai Kallars (PKs, n = 205) and Yadhavas (YDs, n = 239) and a random panel (84) were studied for HLA-DRB1* and -DQB1* polymorphisms by DNA-SSOP typing methods. XI and XII International Histocompatibility primers and non-radioactive-labelled oligo probes were employed to identify the alleles. Results revealed that PKs possessed >0.1 allele frequencies of HLA-DRB1*15011, 0301, -DQB1*0201, 0501 and 0601; YDs, HLA-DRB1*0301, 0401, 07 and -DQB1*0601; and the random panel, DRB1*15021, 0401, 07, -DQB1 0201, 0301, 0302 and 0501. The highest frequency of DRB1*1501 in the world (GF = 0.225) was found in PKs. The most frequent two-locus haplotype (>500/10,000) in all the study samples was DRB1*10-DQB1*0501, while 1501-0601 was frequent in PKs and YDs. Comparison of the HLA-DRB1* data with Eastern European and South-East Asian populations suggested migration as the prime cause of the observed diversity in DRB1* allele frequencies. Nonetheless, the heterozygocity test and Watterson's homozygosity test indicated that balancing selection still operates on HLA-DRB1* locus, in this endemic region of various infectious diseases. This and spatial autocorrelation analysis support the view that selection may be a cause of "generating" new variants and allelic diversity in different ancient settlements. The study suggested that South Indian, inbred, endogamous, sympatrically isolated castes or similar well-defined breeding isolates around the world, living under the same milieu-epidemiology, may be ideal models to test the immunogenetic basis of disease susceptibility.

Adult↗

The Eurasian heartland: a continental perspective on Y-chromosome diversity.

The nonrecombining portion of the human Y chromosome has proven to be a valuable tool for the study of population history. The maintenance of extended haplotypes characteristic of particular geographic regions, despite extensive admixture, allows complex demographic events to be deconstructed. In this study we report the frequencies of 23 Y-chromosome biallelic polymorphism haplotypes in 1,935 men from 49 Eurasian populations, with a particular focus on Central Asia. These haplotypes reveal traces of historical migrations, and provide an insight into the earliest patterns of settlement of anatomically modern humans on the Eurasian continent. Central Asia is revealed to be an important reservoir of genetic diversity, and the source of at least three major waves of migration leading into Europe, the Americas, and India. The genetic results are interpreted in the context of Eurasian linguistic patterns.

Adult↗

A major susceptibility locus for leprosy in India maps to chromosome 10p13.

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is prevalent in India, where about half of the world's estimated 800,000 cases occur. A role for the genetics of the host in variable susceptibility to leprosy has been indicated by familial clustering, twin studies, complex segregation analyses and human leukocyte antigen (HLA) association studies. We report here a genetic linkage scan of the genomes of 224 families from South India, containing 245 independent affected sibpairs with leprosy, mainly of the paucibacillary type. In a two-stage genome screen using 396 microsatellite markers, we found significant linkage (maximum lod score (MLS) = 4.09, P < 2x10-5) on chromosome 10p13 for a series of neighboring microsatellite markers, providing evidence for a major locus for this prevalent infectious disease. Thus, despite the polygenic nature of infectious disease susceptibility, some major, non-HLA-linked loci exist that may be mapped through obtainable numbers of affected sibling pairs.

Chromosome Mapping↗

The course of putrescine immunocytochemical appearance in neurons, astroglia and microglia in rat brain cultures.

Putrescine, the diamine precursor for polyamine biosynthesis, is a ubiquitous molecule normally present at low concentration in quiescent cells. During development, or after traumatic stress, putrescine concentrations are greatly increased. Here we describe the localization of putrescine by fluorescence immunocytochemistry in primary cultures of embryonic rat brain using specific antibodies. Antibodies against putrescine conjugated to keyhole limpet hemocyanin (KLH) were produced in rabbits. The antisera were adsorbed on KLH affinity columns and the specificity of the antibodies was assessed by inhibition enzyme-linked immunoassays (ELISA). The cellular localization paralleled the temporal sequence of appearance and disappearance of the different cell types in these mixed cultures. During the first 3 days after plating the antibodies were localized mainly in neurons. As the neurons disappeared the localization was mainly in the growing astroglia, and then, as astroglia reached confluence between 10 and 14 days in vitro, labeled astroglia were diminished in numbers while the number of labeled microglia was greatly increased. The subcellular localization was prominent in the perinuclear region of the cytoplasm. The results indicate that antibodies to KLH-conjugated putrescine can be used for immunocytochemical studies of changes in putrescine concentrations during development and after traumatic injuries.

Animals↗

Associations of HLA-DRB1, DQB1 and DPB1 alleles with pulmonary tuberculosis in south India.

SETTING: Tuberculosis is endemic in south India: sputum positive pulmonary tuberculosis is predisposed by HLA-DR2 in south India and few other populations of the world. OBJECTIVE: To study HLA-DRB1, DQB1, DQA1 and DPB1 allelic polymorphism in pulmonary tuberculosis patients and endemic controls from south India. DESIGN: One hundred and twenty-six, sputum positive pulmonary tuberculosis patients and 87, endemic controls, from Madurai were studied for MHC class II allelic polymorphism by PCR-SSOP method. XI IHWC primers and probes and non-radioactive probing methods were employed. RESULTS: HLA DRB1*1501 and DQB1*0601 predisposed for pulmonary tuberculosis (DRB1*1501: odds ratio (OR) = 2.68, 95% confidence interval (CI) = 1.30-5.89, P value (P) = 0.013, aetiological fraction (EF) = 0.17; DQB1*0601: OR = 2.32, CI = 1.29-4.27, P = 0.008, EF = 0.26). Haplotype DRB1*1501-DQB1*0601 was higher in patients (1324 per 10,000, X2 = 27.07) than controls (F = 404/10,000, X2 = 8.84). In a subset of 63 caste matched samples, DPB1*04 was preventive (OR = 0.45, CI = 0.21-0.95, P = 0.036, PF = 0.26): the distributions of DRB1*1501-DQB1*0601-DPB1*04 phenotypes were different between patients and controls (P = 0.0092). These alleles were predominant in patients and controls of T5SU caste. CONCLUSION: HLA-DRB1*1501 and DQB1*0601 predisposed to sputum positive pulmonary tuberculosis, and DPB1*04 was preventive and epistatic to this risk. Caste T5SU is an ideal model to study immunology of tuberculosis.

Adult↗

Alloantigen gene therapy for squamous cell carcinoma of the head and neck: results of a phase-1 trial.

OBJECTIVE: To determine the safety and efficacy of an immunogenic gene therapy using a drug designed to produce expression of a foreign class I major histocompatibility complex protein in patients with head and neck cancer. DESIGN: Phase 1 prospective clinical trial. SETTING: Academic medical setting. PATIENTS: Nine patients with advanced head and neck squamous cell carcinoma who had failed conventional therapy and did not express HLA-B7, a class I major histocompatibility complex protein. INTERVENTION: Patients were treated with Allovectin-7 (Vical Inc, San Diego, Calif) by direct intratumoral injection. Allovectin-7 contains a plasmid complementary DNA complexed with a cationic lipid, which results in expression of HLA-B7. MAIN OUTCOME MEASURES: Patients were assessed for any toxic effects and for any change in tumor volume. Biopsy specimens obtained before and after therapy were evaluated by immunohistochemistry to detect HLA-B7 expression and with the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay to detect any induction of apoptosis. RESULTS: There were no toxic effects of the gene therapy. In 4 of these 9 patients there was a partial response to treatment, evidenced by a gradual reduction in tumor size. One patient has remained alive for more than 17 months since commencing treatment, with no clinical evidence of disease but with persistent histological evidence of cancer. Analysis of the biopsy specimens from 2 of the patients who responded to therapy demonstrated HLA-B7 expression. The TUNEL assay demonstrated extensive apoptosis in both of these patients, suggesting that this may be the mechanism of tumor reduction. CONCLUSIONS: These data demonstrate the potential efficacy and lack of toxicity of this form of alloantigen gene therapy. A multi-institutional study has been initiated to expand on these findings.

Adult↗

Genetic and immunologic studies of patients on procainamide.

Forty (40) patients with cardiac arrhythmias receiving procainamide (PA) therapy and 24 patients who were receiving other drugs for their cardiac disorders were investigated for class II HLA phenotypes and their DRB1*04 and DQB1*03 subtypes. Other genetic marker evaluations in the PA patients included: 1) class III MHC C4A and C4B null alleles of complement; and, 2) acetylation phenotype. Twenty (20) of the PA patients were also tested for the ability of their stimulated cells to secrete Interleukin-1 (IL-1 beta) and tumor necrosis factor (TNF alpha). We also examined the spontaneous production of these cytokines by peripheral blood leukocytes (PBL) from patients who were receiving chronic PA treatment. The results revealed no association of acetylation phenotypes with the class II HLA phenotypes nor class III MHC C4 allotypes in these patients. The results did show a significant increase in class III C4 complement allotypes in the PA patients when compared to the controls. The results also showed a significant increase in autoantibodies and DQw3 phenotypes in the PA patient group when compared to control populations. Results of spontaneous IL-1 and TNF production suggested there may be an association of select class II HLA phenotypes in some patients and this may be relevant to host responsiveness to PA treatment.

Acetylation↗

Is the hippocampus a Kalman filter?

Based on a large body of neurophysiological, neuroanatomical, and behavioral data, it has been suggested that the hippocampal formation serves as a spatial learning and localization system. This spatial representation is metric in nature and arises as a result of associations between sensory inputs and dead-reckoning information generated by the animal. However, despite the fact that these two information streams provide uncertain information (e.g., recognition errors, dead-reckoning drifts, etc.), the hippocampal computational models suggested to date have not explicitly addressed information fusion from erroneous sources. In this paper we develop a computational model of hippocampal spatial learning and relate its functioning to a probabilistic tool used for uncertain sensory fusion in robots: the Kalman filter. This parallel allows us to derive statistically optimal update expressions for the localization performed by our computational model.

Animals↗

T-cell receptor V beta gene segment expression in diisocyanate-induced occupational asthma.

BACKGROUND: Diisocyanates are the most common cause of occupational asthma induced by low-molecular-weight chemicals. The disease appears to be immunologically mediated but is independent of IgE antibody synthesis. An underlying genetic susceptibility is suggested by the fact that the disease only develops in approximately 5% to 10% of exposed workers. OBJECTIVE: The study was designed to determine whether disease susceptibility is influenced by HLA and T-cell receptor V beta gene segment usage. METHODS: T-cell receptor V beta repertoires were quantitated by using primer pairs specific for V beta gene segments in conjunction with a common C beta region primer. One group of workers with diisocyanate-induced occupational asthma produced diisocyanate-specific IgG and IgE antibodies, whereas the other group did not produce specific antibodies. Occupational asthma was previously confirmed by either workplace challenge or laboratory specific diisocyanate bronchoprovocation. Control groups consisted of diisocyanate-exposed workers who were free of symptoms, patients with nonoccupational asthma, and unexposed subjects who were free of symptoms. RESULTS: Lymphocytes from workers with diisocyanate-induced occupational asthma had significantly decreased V beta 1 and V beta 5 gene segment expression before in vitro exposure to diisocyanates, compared with control groups. Percent V beta 1 and V beta 5 gene segment expression was selectively increased when peripheral blood mononuclear cells were stimulated in vitro with diisocyanate-conjugated proteins. Low-resolution HLA class II phenotyping revealed no significant differences in the distribution of HLA-DR or HLA-DQ alleles between diisocyanate-induced occupational asthma and control groups. CONCLUSIONS: These findings are consistent with a hypothesis that antigen-specific T-cell subpopulations may be sequestered in the lungs of workers with diisocyanate-induced occupational asthma and clonally expand after further exposure to diisocyanates.

Asthma↗

Sociobiology and HLA genetic polymorphism in hill tribes, the Irula of the Nilgiri hills and the Malayali of the Shevroy hills, south India.

Two endogamous tribes of Tamil Nadu, South India, the Irula of the Nilgiri hills and the Malayali of the Shevroy hills, were studied for their sociobiology and HLA polymorphism. For sociobiological studies 166 marriages in the Irula and 368 marriages in the Malayali were recorded. The number and spatial distribution of patrilineal clans and their marriageable range (number of clans from which the brides came) were studied. Eight clans in the Irula and 16 clans in the Malayali were identified. Of these the Kuppar of the Irula and the Malayan of Malayali were the largest clans, and both of them had the greatest marriageable range. The numerical strength and the resultant spatial distribution correlated well with the marriageable range. HLA-A, B, and DR polymorphism was studied on 191 Irula and 42 Malayali following standard procedures. HLA typing revealed high frequencies (> 10%) of alleles HLA-A2, A9, A11, B17, B35, B40, DR2, and DR7 in both tribes, but the Irula had elevated HLA-A10, B8, and DR8 frequencies and the Malayali had elevated HLA-A31, B7, DR4, and DR5 frequencies. Two-locus haplotypes A10-B8 and A2-B5 were identified in both tribes, but A11-B40 and A2-B53 were present only in the Irula and A33-B44 and B15-DR6 were present only in the Malayali. The sociobiology of the Irula was correlated to the HLA genetic profile. The Irula sample was stratified based on clan and HLA data; The Kuppar clan was closer to the Kalkatti, the second largest clan, than to the Pungar and the Sambar clans. Thus the numerical strength and spatial distribution of various exogamous clans, presumably a result of migration during different periods of history, is reflected in the marriageable range and thus in the genetic distance. In studying HLA or any other genetic polymorphism of an endogamous tribe or caste, one needs to consider the social structure, spatial distribution, and marriageable range.

Emigration and Immigration↗

Growth and cyclosporin A production by an indigenously isolated strain of Tolypocladium inflatum.

A fungal culture isolated from a local soil sample which showed antifungal activity and produced cyclosporin A, was identified as Tolypocladium inflatum. The culture grew best in a medium containing 1% maltose (pH 5-6) when inoculated with a one-day-old inoculum at 2% (V/V) concentration. Under batch fermentation conditions, growth and cyclosporin A production were better in complex media (24.6 g biomass and 205 mg cyclosporin A per liter) in comparison with synthetic media (6.84 g biomass and 35 mg cyclosporin A per liter). While addition of peptone increased culture growth (high biomass yield), supplementation with casein acid hydrolyzate favored cyclosporin A production.

Culture Media↗