Search PubMed⌕ Search

Biomedical subjects

P Aggarwal

Publications and source records attributed to P Aggarwal.

At least 19 recordsLinked to original sources

Expression of constitutively nuclear cyclin D1 in murine lymphocytes induces B-cell lymphoma.

Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by overexpression of cyclin D1 due to the t(11;14) chromosomal translocation. While expression of cyclin D1 correlates with MCL development, expression of wild-type (WT) cyclin D1 transgene in murine lymphocytes is unable to drive B-cell lymphoma. As cyclin D1 mutants that are refractory to nuclear export display heighten oncogenicity in vitro compared with WT D1, we generated mice expressing FLAG-D1/T286A, a constitutively nuclear mutant, under the control of the immunoglobulin enhancer, Emu. D1/T286A transgenic mice universally develop a mature B-cell lymphoma. Expression of D1/T286A in B lymphocytes results in S phase entry in resting lymphocytes and increased apoptosis in spleens of young premalignant mice. Lymphoma onset correlates with perturbations in p53/MDM2/p19Arf expression and with BcL-2 overexpression suggesting that alterations in one or both of these pathways may contribute to lymphoma development. Our results describe a cyclin D1-driven model of B-cell lymphomagenesis and provide evidence that nuclear-retention of cyclin D1 is oncogenic in vivo.

Animals↗

Tumor necrosis factor-alpha levels in patients with HIV with wasting in South Asia.

Tumor necrosis factor (TNF)-alpha is thought to play an important role in wasting; but TNF-alpha levels have not been consistently found to be high in AIDS wasting. We conducted this study to determine any correlation between TNF-alpha levels and wasting in HIV-positive patients in a developing country. TNF-alpha levels were measured in four groups of patients: Group 1, HIV/AIDS with wasting (n = 25); group 2, HIV/AIDS without wasting (n = 47); group 3, HIV-negative patients with tuberculosis with wasting (n = 25); and group 4, healthy controls (n = 25). Wasting was defined as a body bass index (BMI) </=16.0 kg/m(2). TNF-alpha was measured by a solid-phase sandwich enzyme linked immunosorbent assay (ELISA) kit. The mean BMI in HIV-positive patients with wasting (group 1) and without wasting (group 2) was 15.192 +/- 1.142 and 19.507 +/- 2.457, respectively, while group 3 and 4 had a BMI of 14.878 +/- 3.234 and 21.862 +/- 2.763 kg/m(2). The mean TNF-alpha level in group 1 was 50.864 +/- 99.13 pg/mL and 43.39 +/- 66.372 pg/mL in group 2. There was no significant difference between the two groups. TNF-alpha was significantly higher in the HIV/AIDS groups (group 1 and 2) compared to the tuberculosis group (10.74 +/- 7.854) and healthy controls (5.846 +/- 3.40) at p = 0.01. TNF-alpha was significantly (p = 0.002) higher in symptomatic patients compared to asymptomatic patients (16.03 +/- 7.61 versus 64.70 +/- 98.70). In conclusion, TNF-alpha levels were higher in HIV patients, regardless of the presence of wasting, compared to normal healthy controls of patients with tuberculosis with wasting.

Adolescent↗

Bleomycin-induced scleroderma.

Systemic sclerosis is a connective tissue disease, which can be triggered by environmental factors. We report one such case of bleomycin-induced scleroderma.

Antibiotics, Antineoplastic↗

Clinical expression and EEG features of patients with juvenile myoclonic epilepsy (JME) from North India.

We aimed to characterize the clinical profile, EEG features and response to treatment of juvenile myoclonic epilepsy (JME) patients. We studied 103 JME probands with a standard protocol recording age of onset, type, frequency of seizures, EEG data, detailed family history and response to treatment in a superspeciality university hospital in New Delhi. The mean age of onset of disease was 14.01 +/- 3.14 years with a male to female ratio of 1.19 : 1. The myoclonic jerks were present in all the probands, generalized tonic-clonic seizures (GTCS) were present in 75.72% and 11.65% probands had absence seizures. The incidence of febrile convulsion (FC) was higher (9.7%) in our JME probands reflecting some ethnic variation or ascertainment bias. There was a considerable delay (of approximately 5.26 +/- 4.61 years) in the diagnosis of JME in our probands because most of the patients were referred from private physicians who were possibly not familiar with this epileptic syndrome in this part of the world or thought it was a milder variety of GTCS. The family history was positive in 25.24% JME probands among first- and second-degree relatives. An interictal EEG was found to be abnormal in 81 (78.64%) patients with the predominant abnormality being generalized polyspike and wave (PSW) discharges (39.80% probands). The majority of patients (80.58%) showed a good response to treatment with valproate alone. There was a subset of patients (11.65%) who required the addition of other antiepileptic drugs (AEDs) for control of GTCS: 7.76% of JME patients were diagnosed as cases of GTCS by private practitioners before they were registered in our study and their seizures were well controlled on other AEDs (without valproate) prescribed by the referring physicians (carbamazepine-4, phenytoin-2, clobazam-2). It is concluded that the clinical features and EEG data of JME probands were comparable to reports from other parts of the world except for the fact that the incidence of FC was higher in our JME patients. There was a delay in the diagnosis of JME due to unfamiliarity with the epileptic syndrome among private practitioners in this part of the world. There was a subset of JME patients who had complete seizure control on other AEDs besides valproate.

Adult↗

Panniculitides--a clinicopathologic study.

OBJECTIVES: To describe the clinical and pathologic features of panniculitides, an uncommon group of diseases, where the available Indian literature is sparse. MATERIAL AND METHODS: Prospective four years study of patients presenting with panniculitis to a large teaching hospital in North India. RESULTS: Erythema nodosum (EN) was the commonest panniculitis (79.3% cases) in our cohort. Other causes included erythema induratum, Weber Christian disease, cutaneous polyarteritis nodosa and panniculitis associated with Takayasu's arteritis and dermatomyositis-lupus overlap. Elevated ESR and leukocytosis were the common laboratory abnormalities encountered. Septal panniculitis without vasculitis was the most frequent histopathologic pattern observed. Patients of EN did well on nonsteroidal anti-inflammatory drugs while corticosteroids with or without azathioprine were used to treat other panniculitides. CONCLUSIONS: Physician awareness, clinical pattern recognition and histopathological confirmation, all play a key role in the identification and management of panniculitis.

Adipose Tissue↗

Identification of mtDNA mutation in a pedigree with gestational diabetes, deafness, Wolff-Parkinson-White syndrome and placenta accreta.

Mitochondrial DNA (mtDNA) defects are associated with a number of human disorders. Although many occur sporadically, maternal transmission is the hallmark of diseases due to mtDNA point mutations. The same mutation may manifest strikingly different phenotypes; for example, the A to G substitution at np 3243 was first reported in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (the MELAS syndrome), but is also found in patients with diabetes and deafness. Here we present a case of gestational diabetes, deafness, premature greying, placenta accreta and Wolff-Parkinson-White (WPW) syndrome associated with a mtDNA mutation. Although this is the first report of such an association, study of 27 other patients with WPW syndrome failed to confirm that this mtDNA mutation is a common cause of such pre-excitation disorders.

Adult↗

Classical polyarteritis nodosa and microscopic polyangiitis--a clinicopathologic study.

OBJECTIVE: To describe the clinical spectrum, laboratory features, histopathological findings and treatment outcome in patients with classical polyarteritis nodosa (PAN) and microscopic polyangiitis (MPA). MATERIAL AND METHODS: Patients with PAN and MPA seen at a large teaching hospital in north India over a period of five years (1994-99) were included in the present study. RESULTS: We encountered five patients with PAN and six patients with MPA during the study period. Of the five patients with PAN, two had systemic disease while three had limited PAN. The patients with limited PAN included two with cutaneous PAN and one with PAN confined to the nerves. Constitutional symptoms, musculoskeletal complaints, peripheral neuropathy and skin lesions dominated the clinical picture. Fifty percent of the MPA patients presented as pulmonary renal syndrome. All the patients with PAN were HBsAg and ANCA negative and had normal urinalysis findings. In contrast, all patients with MPA demonstrated an active urine sediment and 83.3% were pANCA positive. Some of the rare features encountered by us were the presence of antiphospholipid syndrome and extensive interstitial lung disease in MPA, and spontaneous recovery in one patient with systemic PAN. Treatment outcome was better in PAN as compared with MPA. CONCLUSIONS: The clinical spectrum of PAN and MPA is quite varied. A good outcome is possible with the use of corticosteroids and cyclophosphamide.

Adolescent↗

Seroepidemiology and active surveillance of dengue fever/dengue haemorrhagic fever in Delhi.

The aims of the present study were to carry out surveillance for dengue virus infection in adults with short-duration fever, and serological study of dengue virus infection in persons without fever. Patients were divided into two groups. Group 1 included patients above 12 years of age with fever of 2-12 days duration without any apparent cause. Of these, patients who presented with fever for 2-5 days were included for virus isolation (group 1a) while those who presented within 6-12 days of the onset of fever were included for the dengue-specific IgM serology (group 1b). Group 2 included a sample of population belonging to all age groups but without pyrexia and blood was collected for dengue-specific IgG serology. Twenty-six patients were enrolled in group 1a over a period of 4 months (September to December, 1997). Of these, DEN1 was isolated in 5 cases. Group 1b included 182 patients, out of which 34 (18.68%) were positive for dengue-specific IgM antibodies. Significantly, all the positive cases were detected during the months of September to November. Retro-orbital pain was present in a significantly more number of IgM-positive cases as compared to IgM-negative cases. Group 2 included 125 cases without fever. The overall positivity for dengue-specific IgG antibodies was 77.6%, with the highest positivity of 100% in the age group of 31-40 years. It was concluded that dengue virus infection is endemic in and around Delhi with peak incidence between September and Novemver. The prevalent serotype during September and December 1997 was DEN1. Since previous epidemic of DHF was due to DEN2 type, isolation of DEN1 serotype indicates changes of another epidemic of DHF due to DEN1 serotype. The stresses the urgent need for implementation of measures to control the transmission of dengue infection.

Adult↗

A clinico-bacteriological study of peripheral tuberculous lymphadenitis.

OBJECTIVE: Tuberculous lymphadenitis is the commonest form of extra-pulmonary tuberculosis. It is most often caused by M. tuberculosis though several reports from other countries have shown mycobacteria other than tuberculosis (MOTT) to be responsible for a significant proportion of tuberculous lymphadenitis cases. The present study was conducted to find the prevalence of M. tuberculosis and MOTT as aetiological agents in patients with peripheral tuberculous lymphadenitis. METHODS: A total of 138 patients with tuberculous lymphadenitis were included in the study. Diagnosis of tuberculosis was established on the basis of fine needle aspiration cytology, histopathology, presence of mycobacteria on Ziehl Neelson stain or auramine rhodamine stain, or aspiration of pus with negative Gram's stain and pyogenic cultute with radiologic evidence of pulmonary tuberculosis. Mycobacterial cultures were performed on aspirated material and species identified using standard methods. RESULTS: Of 138 patients, single lymph nodal enlargement was found in 48.6% patients while others had more than one lymph nodes. Lymph nodes were matted in 26.8% cases while fluctuation could be elicited in 12.3% patients. Chest X-ray showed evidence of active pulmonary lesions or mediastinal lymphadenopathy in 28.3% cases. The fine needle aspiration cytology was positive for tuberculous lymphadenitis in 41.3% cases while it revealed granulomas or necrosis in another 13% cases. The Ziehl-Neelson and the auramine-rhodamine staining were positive in 19.6% and 26.8% patients, respectively. On culture, the lymph node aspirate was positive for Mycobacterium species in 40.6% patients. In all but two cases, the culture revealed presence of Mycobacterium tuberculosis. The other two cultures revealed growth of Mycobacterium fortuitum chelonae complex. Of the two HIV-positive patients, M. tuberculosis could be isolated in one case. CONCLUSION: Findings of this study suggest that M. tuberculosis is still the most common cause of tuberculous lymphadenitis and MOTT are responsible for very few cases. However, such studies need to be carried out frequently at various centres so as to see any periodic and geographic variations within India.

Adolescent↗

A study of autoimmune markers in hepatitis C infection.

BACKGROUND & OBJECTIVES: Hepatitis C virus (HCV) infection is associated with several autoimmune markers. Despite HCV being common in India, no information on this aspect is available. This study was undertaken to ascertain the frequency and clinical significance of autoimmune markers like rheumatoid factor (RF), antinuclear antibodies (ANA), antibodies to double stranded deoxyribonucleic acid (dsDNA), anti neutrophil cytoplasmic antibody (ANCA), anti smooth muscle antibodies (ASMA), anti liver kidney microsomal 1 antibodies (anti LKM1), anti gastric parietal cell antibodies (anti GPCA), anti mitochondrial antibodies (AMA), anti cardiolipin antibodies (ACL) and cryoglobulins in HCV infection and to determine the effect of treatment on these markers. METHODS: Twenty five patients with chronic hepatitis C and 25 healthy controls were studied. Cryoglobulins were detected by cryoprecipitation, RF by latex agglutination, anti dsDNA and ACL by ELISA while indirect immunofluorescence was used to detect all other autoantibodies. RESULTS: Eighteen patients (72%) demonstrated autoimmune markers. RF, cryoglobulins and anti LKM1 antibodies were the most frequently detected markers (in 32% patients each). ASMA, perinuclear ANCA (pANCA), ANA and anti GPCA were seen in 24, 20, 12 and 4 per cent patients respectively. None of the patients exhibited ACL, AMA or antibodies to dsDNA. No antibodies were detected in healthy controls. Sixty per cent of the patients had rheumatological symptoms. Of the seven patients followed up after treatment with alpha interferon, only two exhibited persistence of RF, while symptoms and other markers disappeared. INTERPRETATION & CONCLUSION: Rheumatological symptoms and autoimmune markers are common in HCV infection and are usually overlooked. Patients with unexplained joint pains and/or palpable purpura should be screened for HCV. Further studies are needed to delineate fully the link between infection and autoimmunity.

Adult↗

Status of physical exercise and its association with obesity and hypertension in two urban assembly constituencies of East Delhi.

In a community based study using systematic random sampling in two urban Assembly constituencies in East Delhi, 420 subjects above the age of 30 years were interviewed to find out their status regarding physical exercise. People doing regular exercise were found to be only 44.8%. The commonest reason associated for not doing/irregular physical exercise was nonavailability of time (63.3%), followed by no need felt by the respondents to exercise (23.3%). The prevalence of obesity in the group doing regular exercise was much lower than the group that was not doing regular exercise and the results were statistically significant. Though a similar association was found with hypertension also, the results were not statistically significant.

Adult↗

Estrogen replacement does not prevent the loss of choline acetyltransferase-positive cells in the basal forebrain following either neurochemical or mechanical lesions.

Recent studies have shown that estrogen replacement can enhance the functional status of basal forebrain cholinergic neurons. Studies have also shown that estrogen has neuroprotective effects both in vitro and in vivo on a variety of cells and against a variety of insults. The present study examined the ability of estrogen replacement to protect basal forebrain cholinergic neurons from the effects of neurochemical and mechanical injury. Ovariectomized Sprague-Dawley rats received either estrogen replacement or sham surgery, and then received either a unilateral injection of ibotenic acid into the nucleus basalis magnocellularis, or unilateral transection of the fimbria fornix. Cholinergic neurons in the medial septum and nucleus basalis were detected and quantified using immunohistochemical techniques. The data show that neither 3 weeks nor 13 weeks of continuous estrogen replacement prevented the loss of choline acetyltransferase (ChAT)-containing cells in the nucleus basalis following a unilateral injection of ibotenic acid. Likewise, estrogen replacement did not prevent a decrease in ChAT-positive cells detected in the medial septum following unilateral transection of the fimbria fornix. Notably, increased numbers of ChAT-positive cells were detected in the contralateral nucleus basalis, and in the ipsilateral and contralateral medial septum, at 2 weeks following a unilateral injection of ibotenic acid into the nucleus basalis; however, these effects were not related to hormone treatment. These data suggest that estrogen replacement does not protect cholinergic neurons in the medial septum and nucleus basalis from the effects of excitotoxic or mechanical injury.

Animals↗