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Mondal M.,CSIR - Central Electrochemical Research Institute | Sengupta M.,CSIR - Central Electrochemical Research Institute | Samanta S.,Calcutta National Medical College and Hospital | Sil A.,Netra Niramay Niketan | Ray K.,CSIR - Central Electrochemical Research Institute
Gene | Year: 2012

Albinism represents a group of genetic disorders with a broad spectrum of hypopigmentary phenotypes dependent on the genetic background of the patients. Oculocutaneous albinism (OCA) patients have little or no pigment in their eyes, skin and hair, whereas ocular albinism (OA) primarily presents the ocular symptoms, and the skin and hair color may vary from near normal to very fair. Mutations in genes directly or indirectly regulating melanin production are responsible for different forms of albinism with overlapping clinical features. In this study, 27 albinistic individuals from 24 families were screened for causal variants by a PCR-sequencing based approach. TYR, OCA2, TYRP1, SLC45A2, SLC24A5, TYRP2 and SILV were selected as candidate genes. We identified 5 TYR and 3 OCA2 mutations, majority in homozygous state, in 8 unrelated patients including a case of autosomal recessive ocular albinism (AROA). A homozygous 4-nucleotide novel insertion in SLC24A5 was detected in a person showing with extreme cutaneous hypopigmentation. A potential causal variant was identified in the TYRP2 gene in a single patient. Haplotype analyses in the patients carrying homozygous mutations in the classical OCA genes suggested founder effect. This is the first report of an Indian AROA patient harboring a mutation in OCA2. Our results also reveal for the first time that mutations in SLC24A5 could contribute to extreme hypopigmentation in humans. © 2012 Elsevier B.V. Source


Ghosh J.,Indian Institute of Chemical Technology | Das S.,Indian Institute of Chemical Technology | Guha R.,Indian Institute of Chemical Technology | Ghosh D.,Indian Institute of Chemical Technology | And 4 more authors.
Journal of Lipid Research | Year: 2012

Leishmania donovani (LD), the causative agent of visceral leishmaniasis (VL), extracts membrane cholesterol from macrophages and disrupts lipid rafts, leading to their inability to stimulate T cells. Restoration of membrane cholesterol by liposomal delivery corrects the above defects and offers protection in infected hamsters. To reinforce further the protective role of cholesterol in VL, mice were either provided a high-cholesterol (atherogenic) diet or underwent statin treatment. Subsequent LD infection showed that an atherogenic diet is associated with protection, whereas hypocholesterolemia due to statin treatment confers susceptibility to the infection. This observation was validated in apolipoprotein E knockout mice (AE) mice that displayed intrinsic hypercholesterolemia with hepatic granuloma, production of host-protective cytokines, and expansion of anti-leishmanial CD8 +IFN-γ+ and CD8+IFN- γ+TNF-α+ T cells in contrast to the wild-type C57BL/6 (BL/6) mice when infected with LD. Normal macrophages from AE mice (N-AE-Mφ) showed 3-fold higher membrane cholesterol coupled with increased fluorescence anisotropy (FA) compared with wild-type macrophage (N-BL/6-Mφ). Characterization of in vitro LD-infected AE macrophage (LD-AE-Mφ) revealed intact raft architecture and ability to stimulate T cells, which were compromised in LD-BL/6-Mφ. This study clearly indicates that hypercholesterolemia, induced intrinsically or extrinsically, can control the pathogenesis of VL by modulating immune repertoire in favor of the host. Copyright © 2012 by the American Society for Biochemistry and Molecular Biology, Inc. Source


Mukherjee S.,CSIR - Central Electrochemical Research Institute | Mukherjee B.,CSIR - Central Electrochemical Research Institute | Mukhopadhyay R.,CSIR - Central Electrochemical Research Institute | Naskar K.,CSIR - Central Electrochemical Research Institute | And 4 more authors.
PLoS Neglected Tropical Diseases | Year: 2012

Background: In an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. The only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. Thus there is a genuine need for an orally active antileishmanial drug. Previously it was shown that imipramine, a tricyclic antidepressant alters the protonmotive force in promastigotes, but its in vivo efficacy was not reported. Methodology/Principal Findings: Here we show that the drug is highly active against antimony sensitive and resistant Leishmania donovani in both promastigotes and intracellular amastigotes and in LD infected hamster model. The drug was found to decrease the mitochondrial transmembrane potential of Leishmania donovani (LD) promastigotes and purified amastigotes after 8 h of treatment, whereas miltefosine effected only a marginal change even after 24 h. The drug restores defective antigen presenting ability of the parasitized macrophages. The status of the host protective factors TNF α, IFN γ and iNOS activity increased with the concomitant decrease in IL 10 and TGF β level in imipramine treated infected hamsters and evolution of matured sterile hepatic granuloma. The 10-day therapeutic window as a monotherapy, showing about 90% clearance of organ parasites in infected hamsters regardless of their SSG sensitivity. Conclusions: This study showed that imipramine possibly qualifies for a new use of an old drug and can be used as an effective orally active drug for the treatment of Kala-azar. © 2012 Mukherjee et al. Source


Chakraborti C.,Calcutta National Medical College and Hospital
Nepalese journal of ophthalmology : a biannual peer-reviewed academic journal of the Nepal Ophthalmic Society : NEPJOPH | Year: 2011

Orbital tuberculosis is rare even in endemic areas. The disease may involve soft tissue, lacrimal gland, or the periosteum or bones of the orbital wall. We present an Indian girl, who presented with a slowly growing left-sided superotemporal orbital mass, with no significant previous medical history. The swelling turned to an abscess and burst spontaneously giving rise to a discharging sinus. The discharge was negative for any organism on Gram and Giemsa staining. A tuberculin skin test was strongly positive. Incisional biopsy showed caseating granuloma and Langhan 's giant cells suggestive of tubercular aetiology. The patient responded well to tuberculous chemotherapy. Although tuberculous dacryoadenitis is a very rare manifestation of tuberculosis,still the possibility should be entertained in a slowly growing mass of the lacrimal gland, especially in developing countries where the prevalence of tuberculosis is high. Source


Sarkar M.,Chettinad Hospital and Research Institute | Konar H.,Calcutta National Medical College and Hospital | Raut D.,VM Medical College and Safdarjung Hospital
Asian Pacific Journal of Cancer Prevention | Year: 2013

Background: This cross-sectional observational study was undertaken to establish clinico-pathological characteristics of patients with gynecological malignancies, focusing mainly on symptoms, histological type and stage of the disease at presentation, in a tertiary care setting in Eastern India. Materials and Methods: In the gynecology out-patient clinic of a tertiary care hospital in Kolkata, India, the patients with suggestive symptoms of gynecological malignancies were screened. Their diagnoses were confirmed by histopathology. One hundred thirteen patients with histopathologically confirmed gynecological malignancies were interviewed. Results: The most frequently reported symptoms by the patients with histopathologically confirmed gynecological malignancies were excessive, offensive with or without blood stained vaginal discharge (69.0%), irregular, heavy or prolonged vaginal bleeding (36.3%) and postmenopausal bleeding (31.9%). The majority of the patients (61.0%) had squamous cell carcinoma on histopathological examination, followed by adenocarcinoma (30.1%). Nearly half of the patients (48.7%) were suffering from the Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage III, followed by stage II (40.7%) malignancy. Conclusions: This study highlights that most of the patients with gynecological malignancies present late at an appropriate health care facility. Ovarian cancer may often have non-specific or misleading symptomatic presentation, whereas cervical cancer often presents with some specific symptoms. These observations point to the need for increasing awareness about gynecological malignancies in the community and providing easily accessible adequate facilities for early detection and treatment of the disease by optimal use of available resources, i.e. strengthening the primary health care system. Source

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