Isolated Multiple Cutaneous Verruciform Xanthomas

Verruciform xanthoma (VX) is a rare benign skin condition, primarily of the oral mucosa that can also affect the skin and genital mucosa. The etiology is not yet completely understood; though its association with conditions of chronic inflammation or trauma, chronic lymphedema, chronic graft versus host disease and CHILD syndrome are mentioned in the literature. Here, we report the case of multiple verruciform xanthomas on the bilateral forearms and upper back of a 25-year-old man in the absence of chronic skin disease or systemic disease and surprisingly, he didn’t have mucosal VX too. Histopathology of the lesion showed nodular dense infiltrate of foamy macrophages in the papillary dermis which stained positive for CD68.

Topoisomerase IB of Deinococcus radiodurans resolves guanine quadruplex DNA structures in vitro.

The following correction is to be made in the printed version of the above article: On page 836, in the legend of figure 1, the concentration of a compound used in this study was wrongly mentioned as nanomolar. It should read as micromolar. The corrected figure and its legend are as below:

Topoisomerase IB of Deinococcus radiodurans resolves guanine quadruplex DNA structures in vitro.

Deinococcus radiodurans genome contains a large number of guanine repeats interrupted by a few non-guanine bases, termed G motifs. Some of these G motifs were shown forming guanine quadruplex (G4) DNA structure in vitro. How is the formation and relaxation of G4 DNA regulated in the genome of D. radiodurans is not known and is worth investigating. Here, we showed that the topoisomerase Ib of D. radiodurans (DraTopoIB) could change the electrophoretic mobility of fast migrating intramolecular recF-G4 DNA into the slow migrating species. DraTopoIB also reduced the positive ellipticity in circular diachroism (CD) spectra of intramolecular recF-G4 DNA structures stabilized by K+. On the contrary, when DraTopoIB is incubated with G-motifs annealed without K+, it showed neither any change in electrophoretic mobility nor was ellipticity of the CD spectra affected. DNA synthesis by Taq DNA polymerase through G4 DNA structure was attenuated in the presence of G4 DNA binding drugs, which was abrogated by DraTopoIB. This implies that DraTopoIB could destabilize the G4 DNA structure, which is required for G4 drugs binding and stabilization. Camptothecin treatment inhibited DraTopoIB activity on intramolecular G4 DNA structures. These results suggested that DraTopoIB can relax intramolecular G4 DNA structure in vitro and it may be one such protein that could resolve G4 DNA under normal growth conditions in D. radiodurans.

Role of computed tomography (CT) scan in staging of cervical carcinoma.

Background & objectives: Staging of cervical carcinoma is done clinically using International Federation of obstetrics and Gynecology (FIGO) guidelines. It is based on physical examination findings and also includes results of biopsy, endoscopy and conventional radiological tests like chest radiograph, intravenous urography and barium enema. These conventional radiological investigations have largely been replaced by computed tomography (CT) and magnetic resonance imaging (MRI) at present. FIGOo staging system does not consider CT and MRI mandatory; however, use of these modalities are encouraged. tThis prospective study was conducted to determine the role of CT in staging work up in women diagnosed with cervical carcinoma. Methods: Fifty three women diagnosed with cervical carcinoma were evaluated with contrast enhanced CT scan of abdomen and pelvis. CT scan images were especially evaluated to determine tumour size, invasion of parmetrium, pelvic walls, rectum, urinary bladder and ureters, pelvic or retroperitoneal lymphadenopathy and distant metastases. CT findings were associated with clinical findings and staging, including findings from cystoscopy and sigmoidoscopy. Results: There was a poor agreement between clinical and CT staging of cervical carcinoma. Primary tumour was demonstrated on CT in 36 (70%) of 53 patients. CT underestimated the parametrial, vaginal and pelvic wall invasion when compared with physical examination. CT overestimated the urinary bladder and rectal invasion when compared with cysto-sigmoidoscopy, however, CT had 100 per cent negative predictive value (NPV) to exclude bladder and rectal involvement. CT detection of lymph node enlargement and lung metastases influenced the management. Interpretation & conclusions: Our findings show that CT scan does not reliably correlate with clinical FIGOo staging of cervical cancer. However, it can detect urinary obstruction as well as nodal or distant metastases and thus improves the clinical FIGOo staging

Progressive multifocal leucoencephalopathy in HIV/AIDS: Observational study from a tertiary care centre in northern India.

Background & objectives: Progressive multifocal leucoencephalopathy (PML) is seen mostly in advanced human immunodeficiency virus (HIV) infection. Little is known about the epidemiology and disease course of these patients from India. This study was aimed to determine the frequency of PML in patients with HIV/AIDS, and the clinical features and survival of these patients. Methods: The charts of HIV/AIDS patients with PML seen over a period of five years (2006-2011) at the Antiretroviral treatment (ART) centre at a tertiary care centre in New Delhi, India, were retrospectively reviewed. Results: Of 1465 patients with HIV/AIDS, 18 (1.2%) were diagnosed with PML; four were laboratory confirmed and 14 had consistent clinical and radiological features. PML was the initial presentation of HIV infection in 10 (56%) patients, and 16 (89%) patients had CD4 count less than 200/μl. Insidious onset focal limb weakness (78%) and visual disturbance (28%) were common symptoms. Magnetic resonance imaging (MRI) of the brain revealed characteristic white matter lesions in all the patients. The estimated median survival was 7.6 months (95% CI, 0-20 months). Interpretation & conclusions: Our results show that the patients present late to access treatment with advanced immunosuppression at presentation. PML is associated with high morbidity and mortality despite institution of highly active antiretroviral therapy (HAART). There is a need to address the lacuna in diagnostic and management services for these patients in India.

Transforming growth factor-1 induces angiogenesis in vitro via VEGF production in human airway smooth muscle cells.

Increase in size and number of bronchial blood vessels as well as hyperaemia are factors that contribute to airway wall remodelling in patients with chronic airway diseases, such as asthma and chronic obstructive pulmonary diseases (COPD). Expression of transforming growth factor 1 (TGF-1), a multifunctional cytokine as well as vascular endothelial growth factor (VEGF), a key angiogenic molecule, has been shown in the inflammed airways in patients with chronic airway diseases. TGF-1 has been implicated in the regulation of extracellular matrix, leading to airway remodelling in patients with chronic airway diseases. However, the role of TGF-1 in regulating VEGF expression in patients with chronic airway diseases, as well as the underlying mechanisms are not yet well established. We investigated whether TGF-1 stimulates VEGF expression in vitro and hence could influence vascular remodelling. Cultured human airway smooth muscle cells (HASMC) were serum deprived for 60 h before incubation with 5ng/ml of TGF-1 for different time points. Control cells received serum-free culture medium. TGF‑1, treatment resulted in time dependent HASMC cell proliferation with maximal values for DNA biosynthesis at 24 h and cell number at 48 h. Northern blot analysis of VEGF mRNA expression showed increased levels in cells treated with TGF-1 for 4 to 8 h. TGF-1 also induced a time-dependent release of VEGF proteins in the conditioned medium after 48 h of treatment. Furthermore, the ability of HASMC-released VEGF proteins to induce human umbilical vein endothelial cells proliferation was inhibited by VEGF receptor antagonist, confirming that TGF-1 induced VEGF was biologically active. We conclude that TGF-1 in addition to an extracellular matrix regulator also could play a key role in bronchial angiogenesis and vascular remodelling via VEGF pathway in asthma.

Recent Advances in i-Gene Tools and Analysis: Microarrays, Next Generation Sequencing and Mass Spectrometry.

Recent advances in technology and associated methodology have made the current period one of the most exciting in molecular biology and medicine. Underlying these is an appreciation that modern research is driven by increasing large amounts of data being interpreted by interdisciplinary collaborative teams which are often geographically dispersed. The availability of cheap computing power, high speed informatics networks and high quality analysis software has been essential to this as has the application of modern quality assurance methodologies. In this review, we discuss the application of modern ‘High-Throughput’ molecular biological technologies such as ‘Microarrays’ and ‘Next Generation Sequencing’ to scientific and biomedical research as we have observed. Furthermore in this review, we also offer some guidance that enables the reader as to understand certain features of these as well as new strategies and help them to apply these i-Gene tools in their endeavours successfully. Collectively, we term this ‘i-Gene Analysis’. We also offer predictions as to the developments that are anticipated in the near and more distant future.

Pulmonary vascular remodeling in congenital heart disease: Enhanced expression of heat shock proteins.

In congenital heart disease (CHD), mechanical wall stress by increased pulmonary artery pressure and pulmonary blood flow is believed to play a pivotal role in the pathogenesis of pulmonary plexogenic arteriopathy (PPA). The pathogenesis of this disease that involves significant pulmonary arterial remodelling, is, however, largely unknown. In the systemic circulation, upregulation of HSP-70 and HSP-27 in the arterial wall occurs in response to acute hypertension, whereas HSP-60 and increased titres of anti-HSP-60 antibodies are associated with atherosclerotic vessel disease. We looked for the involvement of HSPs in the stress response of pulmonary endothelial and vascular smooth muscle cells in different abnormal hemodynamic conditions in patients with CHDs. We analyzed the expression pattern of HSP-27, HSP-70 and HSP-60 in lung biopsies of 38 patients with CHD, using immunohistochemistry. These included 4 individuals with an essentially normal pulmonary circulation, who served as controls. Immunoreactivity against HSP-27 and also against HSP-70 was present in the pulmonary endothelium and vascular smooth muscle cells of patients and controls in a similar pattern. In contrast, expression of HSP-60 was absent in pulmonary arteries of both patients and controls. In patients with advanced PPA, cells within plexiform lesions showed strong staining for HSP-27 and HSP-70, but were again negative for HSP-60. The intensity of immunoreactivity against HSP-70 correlated inversely with medial thickness of pre-acinar arteries (r = -0.32; p = 0.04). Expression of HSP-27 and HSP-70 did not correlate with hemodynamic parameters, although immunoreactivity against HSP27 tended to be increased in cases with high pulmonary artery pressure (r = 0.37; p = 0.16) and was highest in patients with flow-associated pulmonary hypertension (p<0.01). HSP-27 and HSP-70, but not HSP-60 are engaged in the stress response of cells of small pulmonary arteries in pulmonary plexogenic arteriopathy. HSP-27 and HSP-70 are increasingly expressed in the advanced proliferative lesions of this disease.

Unusual lung mass: benign or malignant?

Primary adenoid cystic carcinoma of lung is a rare tumour. It is a slowly growing, indolent tumour. Average time that elapses before diagnosis is reported to be two years. We report the case of a patient who remained well inspite of harbouring primary adenoid cystic carcinoma of lung for 15 years.

Isolated tuberculosis of the pancreas diagnosed with needle aspiration: a case report and review of the literature.

Pancreatic tuberculosis is very rare, especially in immunocompetent patients, and represents a diagnostic challenge. The clinical features in patients with pancreatic tuberculosis are usually non-specific. The radiological features mimic pancreatic malignancy or pancreatitis. We describe a case of pancreatic tuberculosis mimicking carcinoma on Computed tomography scan. Ultrasound guided fine needle aspiration cytology (FNAC) showed caseating granulomatous inflammation. The diagnosis of pancreatic tuberculosis was made and the patient was put on anti-tubercular therapy. Five months later, a repeat CT scan of the abdomen revealed resolution of the pancreatic lesion. We emphasize that tuberculosis should now be included in the differential diagnosis of a pancreatic mass. Diagnostic indicators include the association of a pancreatic mass with fever, the presence of abdominal pain and a cystic pancreatic mass in a younger patient coming from a region where tuberculosis is endemic.

Cloning and characterization of an insecticidal crystal protein gene from Bacillus thuringiensis subspecies kenyae.

A sporulating culture of Bacillus thuringiensis subsp. kenyae strain HD549 is toxic to larvae of lepidopteran insect species such as Spodoptera litura, Helicoverpa armigera and Phthorimaea operculella, and a dipteran insect, Culex fatigans. A 1.9-kb DNA fragment, PCR-amplified from HD549 using cryII-gene-specific primers, was cloned and expressed in E. coli. The recombinant protein produced 92% mortality in first-instar larvae of Spodoptera litura and 86% inhibition of adult emergence in Phthorimaea operculella, but showed very low toxicity against Helicoverpa armigera, and lower mortality against third-instar larvae of dipteran insects Culex fatigans, Anopheles stephensi and Aedes aegypti. The sequence of the cloned crystal protein gene showed almost complete homology with a mosquitocidal toxin gene from Bacillus thuringiensis var. kurstaki, with only five mutations scattered in different regions. Amino acid alignment with different insecticidal crystal proteins using the MUTALIN program suggested presence of the conserved block 3 region in the sequence of this protein. A mutation in codon 409 of this gene that changes a highly conserved phenylalanine residue to serine lies in this block.

Immunology of chronic generalized periodontitis. 1. Estimation of cellular and humoral immune status.

Cell-mediated and humoral immune responses were assessed in forty patients with chronic generalized periodontitis (CGP), and in an equal number of control subjects. The cell mediated immunity assessed by enumeration of total rosette forming cells [TRFC] and high affinity rosette forming cells [HARFC], were found to be slightly depressed in CGP patients compared controls. The humoral immune response was assessed by estimation of serum immunoglobulins G,A,M,D and E by single radial immunodiffusion technique (RID). Except IgD all the other immunoglobulins were found to be elevated significantly. These immunological derangements found in CGP patients may be the cause or effect of the disease process.