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Biomedical subjects

K Balakrishnan

Publications and source records attributed to K Balakrishnan.

At least 37 records · Page 2Linked to original sources
PubMed1996

HLA affinities of Iyers, a Brahmin population of Tamil Nadu, South India.

Seventy-four randomly sampled Iyers, a Brahmin population of Tamil Nadu and preachers and followers of the Advaita philosophy, living in Madurai, were studied for their HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, C4A, C4B, and BF polymorphisms and compared with other populations. HLA alleles A1, A11.1, A24, A33, B35, B44, B51, B52, B57, Cw4, Cw6, Cw7, DR4, DR7, DR8, DR10, DR11, DR15, and DQ1 and C4A*3, C4A*4, C4A*6, C4A*Q0, C4B*1, and BF*S were represented in 15% of the samples studied. HLA alleles A25, A69, Cw3, Cw8, B45, B14, B39, B18, B50, and B56 were not identified. Various populations of Tamil Nadu were compared, but the Iyers of Madurai formed a separate cluster with Sourashtrans of Madurai and major group 4 (various Brahmin populations of Tamil Nadu); hill tribes (Irulas, Malayalis, and Badagas) and caste groups in the plains (Kallars and Nadars) formed distinct clusters. Comparison of the Iyers with other Indian and world populations revealed that Iyers form a distinct branch of the Indo-European and Central Asian tree. The Bhargavas of Lucknow, another Brahmin caste group from Uttar Pradesh, did not cluster with the Iyers but clustered with Central Asian populations. The Punjabis of Delhi clustered with European and Middle Eastern populations. Studies on two-locus haplotypes of Iyers revealed unique haplotypes in them (A26-B8, A33-B44, A33-Cw7, A1-B57, B8-DR3, B44-DR7, DR7-DQ2, C4A*32-C4B*Q0, and C4A*6-C4B*2), most of which were not identified in the Bhargavas of Lucknow and the Punjabis of Delhi. Thus it is possible that various Brahmin populations of India differ in their origin, migration, and settlement, although all of them adopted Hinduism in ancient times. A comparison of haplotypes in Iyers with the world population reveals a sharing of haplotypes with Southeast Asian populations. This implies that the ancestors of the Iyers of Madurai, who originated in the Eurasian steppes or Central Asia, might have migrated to India through Southeast Asia, thus developing the prevalent haplotypes en route.

Adolescent↗
PubMed1994

Red cell enzymes and serum protein polymorphisms in three population groups of south India.

Blood and serum samples from random individuals of three populations in south India, the first being an endogamous group from the Nilgiri hills (Tamil Nadu), the second from the Shevroy hills (Tamil Nadu), and the third from a semi-urban area of Tamil Nadu, were screened for ESD, GLO1 and Hp polymorphisms. The allelic frequencies for these markers have been estimated. High GLO1*1 (0.379) frequency was observed in the tribal Malayalis, in contrast with other Indian population groups.

Alleles↗
PubMed1994

Prevalence of sickle cells in Irula, Kurumba, Paniya & Mullukurumba tribes of Nilgiris (Tamil Nadu, India).

A total of 1377 tribals, comprising Irulas (536), Paniyas (196), Kurumbas (87), Mullukrurumbas (156) and Soligas (402), living in the Nilgiris, Tamil Nadu, India were studied for sickle cell trait between 1981-85. Patients attending various tribal clinics at Arayure, Kozhikarai, Kothagiri and Biligiri Rengan hills for various ailments were screened at random by solubility test and by acetate paper electrophoresis, if required. HbAS carrier frequency was 30-37.8 per cent in all the tribals studied except Kurumbas (19.5%). The frequency of carriers were more (37.8%) on the western part of Nilgiris (Nedungode, Kappala and adjoining regions) than the eastern part (30%). Further, the prevalence of carriers was higher (47-49%) in the 10-19 yr age group amongst Paniyas and Mullukurumbas living in the western part of Nilgiris. An episodic, epidemic of malaria so rampant during the early part of this century in the western parts of Nilgiris might have eliminated many children with HbAA and hence the higher frequency of HbAS in this particular age group.

Adolescent↗
PubMed1993

Genetic, immunologic and biotransformation studies of patients on procainamide.

This report represents follow-up observations of a unique long-term study of patients on procainamide (PA) for various cardiac arrhythmias. Serologic and clinical evaluations associated with drug-related autoimmunity were assessed and patients were characterized for factors postulated to influence susceptibility to autoimmunity, including acetylator phenotype, oxidative metabolism of PA, HLA class profile, and production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Fifty-two percent had IgM and 70% IgG antibodies to total histones; 67% had IgG antibodies to histone H2A/H2B. Patients were equally divided between fast and slow acetylators. N-oxidative metabolism of PA was indicated by the presence of urinary nitroprocainamide, which correlated with elevated titers of antihistone antibodies. There was a significant incidence of the DQw7 split of DQw3 in PA patients when compared to controls, and the frequency of antibodies to total histones and H2A/H2B was significantly increased in the DQw7 patients. C4A*QO and C4B*QO alleles were more frequent in the PA patients than in controls. IL-1 and TNF production was not different in patients compared to controls. These data suggest that certain genetic factors may serve as markers for PA-related autoimmunity.

Aged↗
PubMed1992

Evaluation of flowcytometric crossmatching in renal allograft recipients.

Forty-four cadaver renal allograft recipients who had flowcytometric cross-match (FCXM) testing and sequential quadruple immunosuppression were studied with respect to the number of rejection episodes and the functional viability of the graft in the first year after transplantation. Fourteen of these patients had antibodies to donor T cells by FCXM. All were negative by conventional crossmatch. Multiple-regression analysis with HLA mismatches, panel-reactive antibody (PRA) percentage, flowcytometric channel shifts and transplant number as independent variables revealed that transplant number and high PRA (> 50%) impacted (p < 0.05) on serum creatinine at 1 month and 1 year, and graft survival at 1 year. In first transplants, a positive FCXM had no impact on 1-year graft survival rates; however, in retransplants, a positive FCXM and/or high PRA had a significant negative impact on 1-year graft survival. This study indicates that the FCXM should be utilized for retransplant patients, and in patients with a high PRA, in an attempt to improve graft survival for these high-risk recipients.

Antilymphocyte Serum↗
PubMed1992

Flow cytometric evaluation of cytotoxic peripheral blood lymphocytes in acute renal graft rejection.

The presence of the S6F1+ epitope on the surface of CD8+ lymphocytes is believed to be uniquely representative of cytotoxic subpopulations. A preliminary study was conducted to evaluate the CD8+ S6F1+ peripheral lymphocytes by flow cytometry in patients undergoing renal allograft biopsy for allograft dysfunction. Lymphocytes, obtained at the time of biopsy, were analyzed by flow cytometry with CD8-FITC/S6F1-RD1 as the test monoclonal antibody and MsIgG-RD1/MsIgG-FITC as internal control. A 100% increase in S6F1+ cells over internal control was considered to be positive result. The results were correlated with the histopathologic findings in 14 instances of allograft dysfunction occurring 26.5 +/- 11.6 days posttransplantation. The histopathologic diagnosis was acute cellular rejection in eight cases, acute tubular necrosis in four, and cyclosporine nephrotoxicity in two. Flow cytometric detection of an increase in S6F1+ cells yielded a sensitivity of 87.5% and a specificity of 83.3% for the diagnosis of acute rejection. It would appear that the use of a monoclonal antibody to detect increases in the number of CD8+ S6F1+ peripheral lymphocytes is a valuable test for the detection of acute allograft rejection in the initial period after transplantation.

Acute Disease↗
PubMed1991

Spectrum of immune reactivity to mycobacterial (BCG) antigens in healthy hospital contacts in south India.

In an effort to study the immunological responses to antigens of tubercle bacilli, 49 tuberculin positive and 41 tuberculin negative hospital contacts aged 20-29 years (staff nurses and students working in Government Rajaji Hospital, Madurai, South India) were studied for serum antibodies (IgG, IgM and IgA classes) to BCG by ELISA and diameter of induration to PPD by Mantoux procedures. The two immunological parameters were correlated in regression analysis. The results have revealed higher anti-BCG serum antibody levels in hospital contacts than in non-contacts, significantly higher antibodies in tuberculin negative hospital contacts than in tuberculin positive hospital contacts, an inverse correlation of tuberculin reactivity and antibodies and a bimodal decline (regression) of antibodies against the increase in skin test induration. This study has thus suggested the existence of an immunological spectrum in hospital contacts from south India; persons at one pole of the spectrum were tuberculin negative and possessed significantly elevated antibody levels and those at the other pole of the spectrum were tuberculin positive and possessed low antibody levels. Thus the spectrum of immune reactivity may be due to an inherent susceptibility/resistance of an individual to Mycobacterium tuberculosis.

Adult↗
PubMed1991

The sensitivity of antibody detection testing using pooled versus unpooled reagent red cells.

Evaluation of paternity (alleged father, mother, and child) can range from a straightforward resolution to a complex problem that cannot be resolved without family studies. We present a case of disputed paternity in which tests for crossreactive groups (CREcS) and antigen subtypes (splits) within the human leukocyte antigen (HLA) system could not be used confidently to prove or disprove paternity. Further analysis, red cell enzyme tests, enabled a final verdict and confirmed the current reliability of HLA antisera defining splits.

Journal Article↗
PubMed1991

HLA-DQA1*0101 haplotypes and disease outcome in early onset pauciarticular juvenile rheumatoid arthritis.

To further investigate a clinical impression that patients with early onset pauciarticular juvenile rheumatoid arthritis (EOPA-JRA) who carry HLA-DQw1 have more severe arthritis, we subtyped HLA-DQw1 in American midwestern patients with EOPA-JRA. The HLA-DQA1*0101 subtype was present in 10 of 19 patients who developed persistent polyarticular erosive disease compared with 18 of 92 healthy controls (chi 2 = 9.13, p = 0.003, RR = 4.6), and occurred more frequently in this polyarticular group than in patients without polyarticular erosive disease (chi 2 = 4.11, p = 0.040, RR = 3.0). The presence of HLA-DQA1*0101 was significantly lower in patients with chronic iridocyclitis than in patients without chronic iridocyclitis (chi 2 = 7.07, p = 0.008, RR = 0.21). In HLA-DQA1*0101 positive patients, DNA sequences of the beta-1 domain of the HLA-DQ alpha and HLA-DQ beta genes (HLA-DQA1*0101, HLA-DQB1*0501 and HLA-DQB1*0503) were identical to those in controls. In this midwestern EOPA-JRA population, HLA-DQA1*0101 or genes in linkage disequilibrium with it, are associated with a cohort of patients with EOPA-JRA with distinct clinical characteristics.

Alleles↗
PubMed1990

HLA and Kaposi's sarcoma in solid organ transplantation.

Of 188 cases of Kaposi's sarcoma arising de novo after transplantation, HLA-A, -B typing was available for 135 and HLA-DR typing available for 67. Compared to the reported HLA phenotype frequencies of renal transplant recipients in the Southeast Organ Procurement Foundation (SEOPF), there is a significantly decreased frequency of HLA-A1 and HLA-B7, and increased frequency of HLA-B5, -B8, -B18, and -DR5. The most striking characteristic of the Kaposi's sarcoma group was its ethnic background. Fifty-six percent of patients were Italian, Greek, Jewish, or Arabic. When this ethnic background is considered, the expected HLA phenotype frequencies are almost exactly the same as in the Kaposi's sarcoma population. The quality of donor-recipient HLA match was evaluable for 106 patients. Only 22% had four or more mismatches, and 59% had at least two antigens matched. This argues against poor donor-recipient matching as a risk factor for developing Kaposi's sarcoma after transplantation.

HLA Antigens↗
PubMed1990

Uniparental isodisomy 6 associated with deficiency of the fourth component of complement.

We identified an extremely rare condition, isolated complete deficiency of the fourth component of complement, in a child with systemic lupus erythematosus. The genes for C4 are located within the major histocompatibility complex (MHC) on the short arm of chromosome 6. The patient expressed only paternal phenotypes for proteins encoded by the MHC (HLA and GLO), yet was 46XX with no detectable 6p deletion. Genomic DNA from patient, parents, and sibling was digested with restriction enzymes, and blots were probed for five chromosome 6 markers. At all loci, maternal and paternal RFLPs could be distinguished, and the patient showed only paternal bands. RFLP analysis of markers from four other chromosomes showed maternal and paternal contribution. The data are consistent with uniparental isodisomy 6 (inheritance of two identical chromosome 6 haplotypes from the father and none from the mother). Direct analysis of genetic material from both parents, as well as detection of multiple protein polymorphisms encoded on chromosome 6, clearly demonstrates this novel mechanism for the expression of a recessive genetic condition.

Blotting, Southern↗
PubMed1988

HLA and altered sex ratios in juvenile rheumatoid arthritis sibships.

Analysis of sex ratio in 301 siblings of 150 patients with early-onset pauciarticular juvenile rheumatoid arthritis revealed a male-to-female ratio of 1:2.00 in sibships with an HLA-B44+ proband, compared with a ratio of 1:1.05 in other sibships (G2 = 6.07, df = 1, p = 0.014). The siblings had a sex ratio of 1:0.8, when the HLA-B44 antigen was present in either parent but not transmitted to the proband. The capacity to distort the sex ratio was limited therefore to disease-associated HLA-B44 haplotypes.

Adolescent↗
PubMed1986

Major-histocompatibility-complex extended haplotypes in membranoproliferative glomerulonephritis.

Membranoproliferative glomerulonephritis is often associated with evidence of immune derangement, especially hypocomplementemia. We studied genetic markers for membranoproliferative glomerulonephritis within the major histocompatibility complex in 34 patients and their families and in 29 normal families. We examined the frequencies of extended haplotypes (combinations of alleles that tend to occur together) in patients and controls. The extended haplotype HLA-B8,DR3,SC01,GLO2(glyoxalase I 2) was observed in 9 of 68 disease-associated haplotypes (13 percent), but in only 3 of 205 controls (1 percent) (relative risk, 14.79; P less than 0.001). An extended haplotype similar except for a different glyoxalase allotype (B8,DR3,SC01,GLO1) did not occur with increased frequency, nor did any other extended haplotypes. Patients with the extended haplotype B8,DR3,SC01,GLO2 had a higher incidence of renal insufficiency than those without it (P less than 0.01). The data support the hypothesis that a specific extended haplotype of the major histocompatibility complex is associated with susceptibility to membranoproliferative glomerulonephritis, and that patients with glomerulonephritis who have this extended haplotype have a poorer prognosis for kidney survival than those without the haplotype.

Alleles↗
PubMed1986

Effect of blood transfusions on macrophage-lymphocyte interaction in an animal model.

Blood transfusions have been reported over the last 2 decades to decrease allograft rejection, to increase the rate of tumor growth, and to increase susceptibility to infectious complications. The effect of transfusions on macrophages, specifically on their regulation of lymphocyte proliferation, was investigated. Both macrophages and their supernatants obtained from transfused rats impaired lymphocyte blastogenesis to a greater degree than those from nontransfused rats. This effect was greatest when the lymphocytes were subjected to mitogen stimulation. The immunosuppression was seen with macrophages from both allogeneically and syngeneically transfused rats. Blood transfusions exert their immunosuppressive effect at least in part by increasing macrophage suppression of lymphocyte response to stimuli.

Animals↗
PubMed1985

Recurrence of diabetic nodular glomerulosclerosis in a renal transplant.

A 36-year-old woman with a 26-year history of insulin-dependent diabetes mellitus developed chronic renal failure in 1974 and was started on dialysis. She received a kidney transplant from her HLA-identical brother. Her HLA typing showed the following antigens: A1, A28, B8, B12 (44), BW4, BW6 DR3, and DR4. Nephrectomy performed prior to transplantation showed advanced diffuse diabetic glomerulosclerosis. Her postoperative course was relatively uncomplicated, but within the next seven years she gradually developed symptoms of deteriorating renal function and hypertension. Two years later, a renal arteriogram showed 90% stenosis of the main renal artery. Biopsy of the kidney was obtained during surgical repair of this lesion and showed diffuse nodular diabetic glomerulosclerosis. Since the B8/DR3 form of diabetes is reported to have a predilection for diabetic microangiopathy and vascular complications, we are speculating that the patient's antigenic composition might have enhanced the recurrence of the diabetic lesions in the transplanted kidney.

Adult↗
PubMed1984

Donor-specific blood transfusions with stored and fresh blood in a rat heart allograft model.

Donor-specific transfusions ( DSTs ) using stored and fresh blood were investigated in a rat heart allograft model. Lewis rats were recipients of preoperative DSTs and cardiac allografts from ACI donors. Blood was stored for 0, 1, 2, 3, 4, and 5 weeks prior to transfusion. Allograft survival and recipient sensitization were recorded. In all DST groups, allograft survival was superior to nontransfused controls (P less than 0.05). Stored blood was equal or better than fresh blood, and a 2-week storage was optimal (P less than 0.05). Storage of 2 weeks or greater resulted in decreased sensitization compared to storage for 1 week or less (P less than 0.05). This study supports the use of stored blood to enhance allograft survival and reduce recipient sensitization.

Animals↗