Do human leukocyte antigens have a role to play in differential manifestation of multibacillary leprosy: A study on multibacillary leprosy patients from North India

118 multibacillary leprosy patients with differential manifestations were studied for the antigens they expressed at MHC loci to investigate the role of human leukocyte antigens in the differential response to the same causative agent. While the lepromatous leprosy (LL) patients showed a significant increase of Bw60, DR2, DRw8 and DQw1, borderline lepromatous (BL) patients had Bw52, DR9 and DQw7 significantly more often as compared to the normal controls. A comparison of LL, BL and mid-borderline (BB) patients showed a significantly higher frequency of Bw60 in LL patients as compared to the BL. However, Bw52, Bw53, DR9 and DQw7 were found significantly more often in the BL patients as compared to the LL patients but the difference failed to reach significance after pc. A comparison of HLA antigens in BB patients with those of either the LL or BL patients did not show any significant differences.     

Effect of aerosol challenge with sensitising antigen on the permeability of the surface of the rat trachea in life.

A rat model of immediate pulmonary hypersensitivity was used to investigate the permeability changes in the tracheal epithelium produced by aerosol challenge with antigen. The rats were sensitised by the intraperitoneal injection of antigen (dinitrophenyl (DNP19) ovalbumin). Sensitised and control animals were then challenged for 60 minutes with an aerosol of the same antigen, which also contained the electron dense pore marker lanthanum. Histological examination and x ray probe microanalysis showed a greater intercellular concentration of lanthanum in the tracheal epithelium in sensitised than in control animals. The results show that in sensitised rats increased intercellular penetrance of antigen can occur after antigen challenge.     

Counter Intuitive Relations Between in vivo RF Lesion Size, Power, and Tip Temperature

Background: Radiofrequency (RF) lesion size in vitro is positively correlated with applied power and catheter tip temperature. However, the relation between RF lesion size, power, and tip temperature in vivo remains unclear. We hypothesized that due to flow, anatomy and tip contact effects in vivo, increased tip temperature would be inversely related to applied power and RF lesion size. Methods: RF lesions were created on the endocardium of 16 pigs using 5, 6, and 7 Fr catheters. The ablation generator was set to achieve a temperature of 70°C. RF lesions were created in different regions of the heart so as to encompass a wide range of blood flow and catheter movement conditions. RF lesions were measured acutely (DIMEN, mm) and correlated with average power applied (POWER, W), and average tip temperature (TEMP, °C). The POWER and TEMP relation was also examined. Results: For TEMPs below 55°C, the power output from the generator was typically maximized at 50 W. At TEMPs above 55°C, POWER decreased exponentially with increasing TEMP {POWER = 50 – exp(-((41-TEMP)/7)), r = 0.98, p < 0.05}. Further, DIMEN tended to be inversely related to TEMP (Slope: –0.07 ± 0.04, r = –0.15, p = 0.07); but, was positively related to POWER (Slope: 0.04 ± 0.02, r = 0.23, p < 0.05). These relations varied by tip size and estimated local blood flow characteristics. Conclusion: In vivo, variable tissue contact and flow yield DIMEN-POWER-TEMP relations opposite to those found in vitro. These counterintuitive results suggest that maximum in vivo RF lesion size is achieved when power is maximized at tip temperatures between 50 and 60°C.     

Clastogenic effect of fenfluramine in mice bone marrow cells in vivo

Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo.     

An immunodominant 30-kDa antigen of a candidate anti-leprosy vaccine,Mycobacterium w,shares T and B cell determinants withM. leprae andM. tuberculosis

Earlier we reported that vaccination of leprosy patients withMycobacterium w induces an immune response directed predominantly against low molecular weight antigens. One of these antigens, with a molecular mass of 30-kDa, was recognized by a majority of the vaccinated subjects as well as the tuberculoid leprosy patients and healthy contacts. In the present communication we report further characterization of this antigen. Immunofluorescence and Western blot studies with antibodies raised against this antigen demonstrate that it is associated with the cell surface and has homologues present inM. leprae andM. tuberculosis. Delayed-type hypersensitivity studies carried out in guinea pigs immunized with the 30-kDa antigen show that in addition to sharing B cell determinants, this immunodominant antigen ofM. w also shares T cell determinants withM. leprae andM. tuberculosis.     

Association of HLA antigens with differential responsiveness toMycobacterium w vaccine in multibacillary leprosy patients

Leprosy patients undergoing phase II trials in two hospitals of New Delhi, India, were HLA typed to see the association of HLA with differential responsiveness toMycobacterium w vaccine. The vaccine comprises an atypical, nonpathogenic mycobacterium,Mycobacterium w, which has cross-reactive antigens withM. leprae. Multibacillary patients who are lepromin negative are vaccinated at an interval of 3 months. Considerable improvement is evident in the patients in terms of a decline in bacterial indices and histopathological and immunological upgrading. But all the patients do not respond to the vaccine in the same manner; some are slow responders, while others are good responders. HLA-A28 and DQw3 (DQw8+9) were found to be associated with slow responsiveness, while DQw1 and DQw7 were found to be associated with a more rapid responsiveness to theM. w vaccine. However, these associations were not significant afterP correction for the number of antigens tested for each locus except for HLA-DQw3 (DQw8 and DQw9) and DQw7. DQw7, a new defined split of HLA-DQw3, seems to be associated with the responsiveness toM. w vaccine.