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H Chahal

Publications and source records attributed to H Chahal.

13 recordsLinked to original sources
PubMed2006

Dissociation of caspase-mediated events and programmed cell death induced via HLA-DR in follicular lymphoma.

Human leukocyte antigens (HLA) class II antigen-mediated apoptosis has been documented in antigen-presenting cells and B lymphoproliferations. Characteristics of the apoptosis include rapidity and selectivity for mature cells. Follicular lymphomas are particularly refractory to apoptosis. The B-cell lymphoma Ramos shares characteristics of this subgroup and is insensitive to apoptosis via simple HLA-DR engagement. However, oligomerization of HLA-DR antigens induced caspase activation followed by phosphatidylserine externalization, activation of PKC-delta and cleavage of nuclear lamin B. Mitochondrial injury was also detected. However, inhibition of caspase activation simply delayed the apoptotic phenotype but neither protected against cell death nor prevented mitochondrial injury. The data in this report demonstrate that the requirements for the initiating signal (oligomerization versus engagement) as well as the molecular pathways varies between different B lymphoproliferations despite their common expression of HLA-DR. Finally, blockade of caspase activation in parallel with HLA-DR mAb stimulation could provide a potent autovaccination stimulus by leading to necrotic death of B-cell lymphomas.

Antibodies, Monoclonal↗
PubMed2003

Effect of age on susceptibility to post-traumatic infection in the elderly.

Previous work has demonstrated an age-related decline in neutrophil function, including a decline in phagocytic capacity, with age in healthy individuals. This decline in function may contribute to increased susceptibility to bacterial infections in the elderly population. The present study has investigated the effects of age on susceptibility to infection and neutrophil function in elderly humans following mild trauma. Specifically, we have measured neutrophil function in 44 patients, all of whom had no significant co-morbidity, were over 65 years old (mean age 82.5 years) and had sustained a fractured neck of femur. We obtained neutrophils and examined the process of microbial engulfment by phagocytosis and the bactericidal mechanism of superoxide production. In the 5-week period after trauma, almost half of the elderly trauma patients succumbed to bacterial or fungal infection, with a predominance of chest and urinary tract infections. When examining neutrophil function, a decline in superoxide production was observed in neutrophils from the elderly trauma group at the time of hip fracture when compared with those from healthy elderly controls, and this was maintained 5 weeks after trauma. This was accompanied by an age-related reduction in phagocytic function during this period. We propose that trauma and an age-related decline in neutrophil function combine to decrease the immune response to bacteria in the elderly.

Adult↗
PubMed2001

Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans.

Elderly humans are more susceptible to bacterial infections because of declining immune status. We have investigated the effect of aging on neutrophil bactericidal responses, comparing neutrophil function in healthy, young (23-35 years) and elderly (>65 years) volunteers. Superoxide generation in response to fMLP was slightly increased in neutrophils from elderly donors, and serum from the elderly was able to opsonize E. coli efficiently. In contrast, phagocytic index was significantly lower in neutrophils from the elderly, compared with young donors (P<0.005). CD11a and CD11b expression was not affected by age, but CD16 was significantly reduced in neutrophils from elderly donors (P<0.0001). CD16 expression and phagocytic index were measured in the same neutrophils using FITC-labeled E. coli, PE-conjugated anti-CD16 antibody, and CD16 expression correlated with phagocytic index (r=0.83; P<0.05). In elderly patients with bacterial infection, CD16 expression remained low. We propose that reduced neutrophil CD16 expression and phagocytosis contribute to human immunesenescence.

Adult↗
PubMed1998

Modulation by magnesium of N-methyl-D-aspartate receptors in developing human brain.

AIM: To investigate age related alterations in glutamate N-methyl-D-aspartate (NMDA) receptor binding produced by the modulatory compounds glutamate, glycine, and magnesium (Mg2+) sulphate. METHODS: The effects produced by glutamate plus glycine, and Mg2+ on the binding of [3H]MK-801, a ligand for the N-methyl-D-aspartate ion channel phencyclidine site, were measured in membrane preparations made from prefrontal cortex from human neonate (n = 5), infant (n = 6), and adult (n = 6) necropsy brains. RESULTS: Neonatal brains had the least [3H]MK-801 binding, suggesting either a low density of NMDA receptors or a more restricted access of [3H]MK-801 to cation channel sites. Infant brains had the most [3H]MK-801 binding which was stimulated to a greater extent by L-glutamate (100 microM) and glycine (10 microM) than in neonatal and adult brains. MG2+ invariably inhibited [3H]MK-801 binding. However, the Mg2+ IC50 value was higher in neonatal brain (3.6 mM) than infant (1.4 mM) and adult (0.87 mM) brains. CONCLUSION: Infant brain may have excess NMDA receptors which are hyper responsive to glutamate and glycine. The lower potency of Mg2+ to inhibit [3H]MK-801 binding in neonatal cortex may be because newborn babies have NMDA receptors without the normal complement of Mg2+ sites. The findings suggest that therapeutic NMDA receptor block in neonates requires higher concentrations of magnesium sulphate in brain tissue.

Adult↗
PubMed1996

Antibodies against Mycobacterium paratuberculosis in Crohn's disease.

Until recently the investigation of serological responses to mycobacteria in patients with Crohn's disease has been hindered by the considerable degree of cross-reactivity between antigens of M. paratuberculosis, and other mycobacterial subspecies. We evaluated the serological response of Crohn's disease patients to a recently identified species-specific 18 kDa protease-resistant antigen corresponding to M. paratuberculosis bacterioferritin. The 18 kDa antigen was purified from M. paratuberculosis as previously described. Serum was obtained from 40 patients with Crohn's disease, 15 with ulcerative colitis, 25 coeliac patients, and 21 normal blood donors. Antibody levels were measured by enzyme-linked immunosorbent assay (ELISA), with anti-human IgA and IgG alkaline phosphatase conjugate. Antibody titres were expressed as the dilution giving 1/3 of the plateau binding value of a standard positive serum (MT/3). Disease activity of the Crohn's disease cases was assessed using the Harvey-Bradshaw index. There was no statistically significant elevation of the mean IgG or IgA MT/3 titres of Crohn's disease patients over controls. No patients had antibody titres greater than two standard deviations above the mean control MT/3 titres, and there was no significant correlation between Crohn's disease activity and level of antibody titres. These findings make it unlikely that M. paratuberculosis is of primary pathogenic importance in Crohn's disease.

Antibodies, Bacterial↗
PubMed1992

Mucosal cell-mediated immunity to mycobacterial, enterobacterial and other microbial antigens in inflammatory bowel disease.

Culture studies have suggested that Mycobacterium paratuberculosis may play a role in the aetiology of Crohn's disease. However, evidence of sensitization to mycobacterial antigens amongst patients with Crohn's disease has not yet been adequately demonstrated. Previous studies of cell-mediated immunity (CMI) in Crohn's disease were restricted to responses of peripheral blood mononuclear cells (PBMC) to mycobacterial antigens. In this study we have investigated the proliferative responses of both PBMC and mesenteric lymph node mononuclear cells (MLNMC) to a range of mycobacterial and non-mycobacterial antigens. There was no evidence of specific sensitization in the responses of MLNMC and PBMC from patients with inflammatory bowel disease (IBD) to the mycobacterial antigens. However, anergy to M. paratuberculosis could not be excluded. IBD MLNMC responses to most antigens were generally greater than those of PBMC, which were often undetectable. When compared with controls, there was evidence of increased CMI to a range of non-mycobacterial antigens, especially Yersinia enterocolitica, amongst both MLNMC and PBMC from patients with Crohn's disease and ulcerative colitis (UC). These results do not provide support to the proposed role of mycobacteria in the pathogenesis of Crohn's disease, but indicate that further investigation may determine a role for bacterial-specific T cell-mediated responses in the pathogenesis of IBD.

Antigens, Bacterial↗
PubMed1988

Gram-negative bacteria, HLA-B27 and inflammatory bowel disease.

Lymphocytes from 48 IBD patients including nine with HLA-B27 were examined for their capacity to absorb Y.enterocolitica 0:9 antiserum. They possessed a range of absorption ability which was unconnected with HLA-B27 status. Samples of lymphocytes from 28 AS patients, 10 RA patients and 28 normal control subjects were included for comparison. The significance of the findings is discussed.

Arthritis, Rheumatoid↗
PubMed1988

Cross-reactivity studies on bacteria believed to be associated with inflammatory bowel disease (IBD), ankylosing spondylitis (AS) and reactive arthritis (ReA).

Six bacteria believed to be associated with IBD and/or AS and ReA were investigated for antigenic cross-reactivity using an ELISA. Considerable degrees of cross-reactivity were detected and it is suggested that if bacterial antigens are involved aetiologically in the diseases, no specific bacterium is concerned.

Antigens, Bacterial↗
PubMed1980

The isolation and characterisation of guinea-pig polymorphonuclear leucocyte actin and myosin.

The contractile proteins actin and myosin have been isolated from the soluble phase of guinea-pig polymorphonuclear leucocytes and partially characterised. Two forms of actin have been identified, designated 'Mg-actin' and 'KCl-actin'. They have different polymerising properties but their propensity to form synthetic homologous and heterologous actomyosins and to inhibit DNAase-1 does not significantly differ. Both show beta and gamma isoelectric forms in focusing gels and the Mg-actin accounts for about 5% of the soluble-phase protein and te KCl-actin around 2%. Leucocyte myosin has been isolated by affinity chromatography on N6-ADP-Sepharose with a good enrichment of both Ca2+-ATPase and the ATPase activity measured in the absence of Ca2+ or Mg2+ and in the presence of EDTA. This protein, too, has the capacity to form synthetic homologous and hybrid actomyosins with enhancement of the basal Mg2+-ATPase activity. The ratio of actin to myosin in the leucocyte calculated on a molar basis is well in excess of 100, a figure consistent with the findings from other non-muscle cells.

Actins↗