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N Dhar

Publications and source records attributed to N Dhar.

14 recordsLinked to original sources
PubMed2005

Increased expression of Mycobacterium tuberculosis 19 kDa lipoprotein obliterates the protective efficacy of BCG by polarizing host immune responses to the Th2 subtype.

Mycobacterium tuberculosis can not only neutralize immune effector functions, but also has the ability to modulate host-signalling cascades involved in the development of these responses. The 19 kDa antigen (Rv3763), a lipoprotein of M. tuberculosis, elicits high levels of interleukin (IL)-12 from macrophages in addition to its powerful immunomodulatory properties, leading to suppression of antigen-presentation signalling cascades. The present study was aimed at analysing the effect of overexpression of this antigen on the immunostimulatory properties of M. bovis Bacille Calmette-Guerin (BCG). We have constructed a recombinant BCG strain (rBCG19N) producing higher levels of the 19 kDa antigen in both the cytoplasmic (approximately eightfold) and extracellular (approximately fivefold) fractions as compared to the wildtype BCG. Immunization of mice with rBCG19N elicited high levels of interferon-gamma (IFN-gamma) and relatively low levels of IL-10 against the purified 19 kDa antigen. However, in response to total BCG sonicate, mice immunized with rBCG19N produced significantly high levels of IL-10 with relatively very low levels of IFN-gamma. This polarization of the host immune responses towards T-helper 2 subtype resulted in complete abrogation of the protective efficacy of BCG, when rBCG19N was used as a live vaccine against M. tuberculosis challenge in guinea pigs.

Animals↗
PubMed2003

Modulation of host immune responses by overexpression of immunodominant antigens of Mycobacterium tuberculosis in bacille Calmette-Guérin.

Based on their immunodominant nature and ability to induce appropriate immune responses in the host, several antigens of Mycobacterium tuberculosis have shown promise of protection. However, most of the candidate vaccines developed by employing various strategies have afforded protection that is at best comparable with bacillus Calmette-Guérin (BCG) in animal models. Due to the inherent ability of BCG to prime cellular responses in the host, it has become an attractive vehicle for development of a vaccine against intracellular infections. In this study, we have cloned the genes of three immunodominant antigens of M. tuberculosis viz. the ESAT6 (Rv3875), the 19 kDa lipoprotein (Rv3763) and the 38 kDa antigen (Pst homolog) (Rv0934) in pSD5 under the transcriptional control of Trrn, a strong mycobacterial promoter, and expressed them in BCG. The19 kDa antigen and the 38 kDa antigen were expressed at levels that were approximately five and eightfolds higher in the cytosols of recombinant BCG strains rBCG19T and rBCG38T, respectively, as compared with their corresponding levels in M. bovis BCG. Both these antigens were also secreted into the extracellular medium at enhanced levels (19 kDa antigen fourfold and 38 kDa antigen twofold) by rBCG strains in comparison with the wild type BCG. ESAT6 antigen, which is absent in M. bovis BCG, was also expressed at a very high level in the cytosol of the rBCG strain (rBCGE6T). Evaluation of immune responses induced by these three rBCG strains in mice shows a markedly different pattern. The rBCG strain overexpressing the 38 kDa antigen exhibited a predominant T helper 1 (Th1) response with high levels of interferon-gamma (IFN-gamma) production, whereas overexpression of the 19 kDa antigen resulted in completely polarized Th2 responses against the BCG sonicate. The rBCG-expressing ESAT6 antigen induced a mixed Th1/Th2 response. Our observations suggest that the 38 kDa antigen may hold excellent promise in the rBCG approach for the development of a vaccine against tuberculosis.

Animals↗
PubMed2000

Recombinant BCG approach for development of vaccines: cloning and expression of immunodominant antigens of M. tuberculosis.

In spite of major advances in our understanding of the biology and immunology of tuberculosis, the incidence of the disease has not reduced in most parts of the world. In an attempt to improve the protective efficacy of Mycobacterium bovis bacille Calmette-Guérin (BCG), we have developed a generic vector system, pSD5, for expression of genes at varying levels in mycobacteria. In this study, we have cloned and overexpressed three immunodominant secretory antigens of M. tuberculosis, 85A, 85B and 85C, belonging to the antigen 85 complex. All the genes were cloned under the control of a battery of mycobacterial promoters of varying strength. The expression was analysed in the fast-growing strain M. smegmatis and the slow-growing vaccine strain M. bovis BCG. The recombinant BCG constructs were able to express the antigens at high levels and the majority of the expressed antigens was secreted into the medium. These results show that by using this strategy the recombinant BCG approach can be successfully used for the development of candidate vaccines against infections associated with mycobacteria as well as other pathogens.

Antigens, Bacterial↗
PubMed1985

Long-term results after excision of fixed subaortic stenosis.

Forty-nine patients underwent surgical excision of fixed subaortic stenosis (discrete fibrous ring and tunnel) between 1968 and 1984 and were followed up for 1 to 16 years (5.8 +/- 4). Twenty-six patients (Group I) had isolated subaortic stenosis and 23 (Group II) had subaortic stenosis and associated cardiac defects. Discrete fibrous ring was present in 46 and tunnel type of obstruction in three patients. For the discrete ring, excision alone was done in 32 patients (four recurrences) and excision with myotomy in 17 (three recurrences). In Group I, there were no operative deaths and one late death from a noncardiac cause. In Group II, one early and two late deaths occurred. The actuarial survival rate for 10 years is 88%. Reoperations were performed in 10 patients, seven for recurrence and three for aortic valve replacement for preexisting aortic regurgitation that had progressed since the primary operation. Cardioplegia was used in 28 patients (one recurrence) and was not used in 21 patients (six recurrences). An operative residual gradient of less than 15 mm Hg was achieved in 25 of 28 patients in whom cardioplegia was used compared to 12 of 21 patients in whom cardioplegia was not used (p = 0.017). These results indicate that complete excision of the ring with the aid of cardioplegia has significantly reduced the recurrence rate of subaortic stenosis (p = 0.033), elimination of the residual gradient at the initial operation has been a significant factor in reducing the recurrence rate (p = 0.017), and addition of myotomy in this series has not altered the outcome.

Adolescent↗
PubMed1984

Congenital diverticulum of the heart of biventricular origin.

An extremely rare diverticulum arising from both ventricles at the caudal end of the intraventricular septum was diagnosed in a 2.9 kg infant. The diverticulum was removed successfully while a coexisting ventricular septal defect was left open for further management. The types and complications of such diverticula are described and the need for early surgical intervention is stressed.

Diverticulum↗
PubMed1980

Penetration injury to the heart. Nine consecutive cases at a community hospital.

During the past 25 years, great progress has been made in saving patients with serious cardiac injuries. This study is based on nine consecutive cases of penetrating wounds to the heart treated successfully by surgical intervention at a community hospital with no facilities for cardiopulmonary bypass. Early surgery is advocated for patients suspected of having penetrating injury of the heart.

Adult↗
PubMed1977

Spontaneous closure of ureterocolic fistula secondary to diverticulitis.

An 88-year-old woman with spontaneous closure of a ureterocolic fistula secondary to sigmoid diverticulitis is described. Initially, the patient was subjected to proximal transverse colostomy to divert the fecal stream. She was rehospitalized for a sigmoid colectomy, and left ureteral catheterization as well as a retrograde pyelogram showed spontaneous closure of the ureterocolic fistula. A review of the literature reveals that specific involvement of the ureter secondary to inflammatory bowel disease is rare. Most of the cases reported previously have alluded to active and radical measures. We do not recommend a radical resection in the acute stage, especially when the tissue planes may be obliterated owing to inflammation and difficulty in structure identification may lead to inadvertent injury.

Aged↗
PubMedDate not supplied

Hypopigmented lesions in early leprosy--a clinical and histological study.

26 Patients of leprosy presenting with hypopigmented lesions were divided on morphological grounds into 3 Sub groups, Group I (9 patients) with well-defined single patch with moderate to complete sensory loss; Group II (8 patients) with single ill-defined lesion having partial sensory loss; and Group III (9 patients) having multiple hypo-pigmented patches with mild to moderate sensory loss. Epidermal atrophy was a conspicuous histological finding in all groups. Only patients in Group I showed epitheloid cells in dermal infiltrate with erosion of epidermis in one case. This group may be labelled as maculoanesthetic leprosy. Patients in Group II and III showed mononuclear cell infiltrate in dermis, around neurovascular bundles and appendages. They were histologically consistent with indeterminate leprosy. Follow-up biopsy after six to eight months of treatment showed healing of the lesion of reduction in the infiltrate in most cases.

Adolescent↗