Familial Monosomy 7 Syndrome Associated with Myelodysplasia

Indian Journal of Pediatrics -     

Risk conferred by tagged SNPs of AGT gene in causing susceptibility to essential hypertension

Introduction: AGT gene harbors several variants of which 21 are found to be in high linkage disequilibrium as per Hapmap database. Studies delineating the importance of these tagged SNPs are very limited and lacking from Indian population. In the present study, we evaluated the contribution of four tagged SNPs namely, g.6635G?>?A, g.6506G?>?A, g.12840G?>?A, and g.13828T?>?C at AGT locus along with the analyses of haplotype and epistatic interactions in causing susceptibility to essential hypertension (EHT).

Methods: About 215 hypertensives and 230 normotensives were genotyped for selected tagged SNPs using PCR-RFLP method.

Results: Significant association was obtained for g.6635G?>?A and g.6506G?>?A polymorphisms wherein GG homozygotes for both the markers were at risk for developing the condition. g.13828T?>?C polymorphism specially, female heterozygotes (TC) were found to be at increased risk for EHT. Haplotype GGGC was found to have a significant protective effect (p?=?0.0059). Markers g.6506G?>?A and g.12840G?>?A resulted in the creation of new enhancer sites thereby affecting splicing process.

Conclusion: The present report is the first one in the literature showing general- and gender-specific association of g.6506G?>?A and g.13828T?>?C polymorphisms, respectively, with EHT. However, further studies for replication of present observations are warranted from other populations and other parts of India.     

Subcutaneous histiocytoid Sweet's syndrome in a patient with myelodysplastic syndrome and acute myeloblastic leukemia

Subcutaneous histiocytoid Sweet's syndrome is a rare variant of histiocytoid Sweet's syndrome (SS). We present a 68‐year‐old woman with subcutaneous histiocytoid SS in association with refractory myelodysplastic syndrome transformed to acute myeloblastic leukemia (AML), status post induction chemotherapy and with persistent blasts (50%) in the bone marrow and blood, accompanied with neutropenia. The patient presented to the emergency room with fever and altered mental status. Clinical examination revealed approximately 20 scattered 0.5–2 cm, pink to pink‐purple non‐tender firm nodules on the legs and left arm. The differential diagnosis included Sweet's syndrome (deep), leukemia cutis, infection, polyarteritis nodosa and erythema nodosum. Histopathologic examination of a biopsy from the left arm revealed a nodular infiltrate of neutrophils and histiocytoid mononuclear cells solely in the lobular compartment of the subcutaneous fat with focal areas of necrosis. Most cells in the infiltrate labeled with myeloperoxidase (MPO) including the histiocytoid cells. The cells were negative for CD34 and CD117. All special stains for microorganisms were negative. A diagnosis of subcutaneous histiocytoid SS was made. A subcutaneous histiocytoid SS should be suspected when a neutrophilic/histiocytoid panniculitis, occurring in the setting of myeloid disorders, is encountered and after exclusion of an infectious process and leukemia cutis.     

Influence of cigarette smoking on blood and salivary super oxide dismutase levels among smokers and non‐smokers

Aim: To determine the influence of smoking on the blood and salivary superoxide dismutase levels among smokers, and to demonstrate the significance in alterations in the levels of superoxide dismutase in association with patient age, periodontal disease status, and duration and smoking frequency. Methods: Sixty healthy male patients (aged 20–60 years) constituted the target population. Blood and saliva samples were collected, and the periodontal index was measured using a Community Periodontal Index probe. Blood and salivary superoxide dismutase levels were calculated with the reagents prepared, and values were measured in a UV spectrophotometer. Results: There was a significant decrease in mean superoxide dismutase levels with an increase in age and smoking duration and frequency (0.23–0.05 U/mL). There was a range of 0.31–0.06 U/mL variation in the mean superoxide dismutase levels as the periodontal disease condition deteriorated. Conclusions: There was a significant reduction in the superoxide dismutase levels in the blood and saliva of smokers with increased duration and frequency of smoking, and as the periodontal disease condition worsened. Thus, this study emphasizes the importance of saliva as an easy, non‐invasive procedure in the diagnosis of patients who are more prone to precancerous lesions and conditions, and its importance in patient education and motivation programs for smoking cessation.     

Role of tagged SNPs of the AGT gene in causing susceptibility to essential hypertension

Aim: Angiotensinogen (AGT) is one of the candidate genes that has been extensively investigated for association of its variants with essential hypertension. Studies focusing on the contribution of tagged single nucleotide polymorphisms (SNPs) in the AGT gene are limited and lacking from Indian population. Hence, the present study was carried out to examine the role of five tagged SNPs viz., g.6147G>A (rs7539020), g.5978A>G (rs2493134); g.6241T>C (rs1078499), g.7781G>T (rs11122577), and g.5855G>A (rs3789678) in the development of hypertension. Materials and Methods: 202 hypertensives and 222 normotensives were screened for five tagged SNPs using the method of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: The present study revealed significant association of g.5855G>A polymorphism with essential hypertension in different logistic regression models wherein protection was conferred by g.5855G>A against developing the condition. The polymorphism led to the creation of new exonic splicing enhancer and destruction of exonic splicing silencer site thereby enhancing the process of mRNA splicing. The haplotypes AGTG and GACG were found to have a significant protective effect. Other polymorphisms did not show any significant association with hypertension. Conclusion: The present study is the first one to report the protective role of g.5855G>A polymorphism in the development of essential hypertension. The results reflect possibility of ethnic variation in the contribution of g.5855G>A polymorphism of the AGT gene to essential hypertension.     

Pattern of missing probes in rifampicin resistant TB by Xpert MTB/RIF assay at a tertiary care centre in Mumbai

Setting

Department of Microbiology.

Thyroid hormone action on skin: diverging effects of topical versus intraperitoneal administration.

Previously, we demonstrated stimulation of epidermal proliferation and hair growth in triiodothyronine (T(3)) treated mice. To distinguish skin effects of directly applied T(3) from those of systemic hyperthyroidism, we treated CD-1 mice with either intraperitoneally (IP) or topically administered T(3). Relative to controls, mice receiving T(3) IP had 10% thinner epidermis (p < 0.01) and 48% fewer hairs (p < 0.001). By contrast, mice receiving T(3) topically had 78% thicker epidermis (p < 0.01) and 160% more hairs (p < 0.01). To gain insight into factors responsible for the diverging effects, we contrasted T(3) effect on proliferation of isolated keratinocyte cultures versus keratinocytes cocultured with dermal fibroblasts. For keratinocytes grown in the absence of fibroblasts, T(3) stimulated proliferation in a dose-dependent, biphasic pattern with the peak at 0.5 nM T(3) (84 +/- 30%, p < 0.05). Paradoxically, T(3) inhibited proliferation of keratinocytes cocultured with fibroblasts, the nadir at 0.1 nM T(3) (34% +/- 4%, p < 0.001). These studies are the first describing divergent effects of IP and topically administered thyroid hormone. The data suggest that while T(3) stimulated keratinocyte proliferation, T(3) also stimulated proliferation inhibitory factor(s) from skin fibroblasts. Insight into the interplay among the competing factors will be important in understanding thyroid hormone regulation of skin physiology.     

A novel site-II directed glycoprotein estimation ELISA to aid rabies vaccine manufacture for veterinary and human use

Although the World Health Organization recommends the use of in vitro techniques to qualify rabies vaccine lot release, very limited proposals have been made to arrive at a harmonized approach for wide scale usage. The present study proposed and evaluated the use of a novel avidin–biotin ELISA as an alternative to these in vivo tests in rabies vaccine manufacture. This assay utilized a neutralizing pan reactive monoclonal antibody (mAb) reactive with the conserved site-II of the natively folded rabies glycoprotein. Linear regression analysis of the in vitro glycoprotein estimates with the in vivo potency values, showed a good correlation (r² = 0.8) with veterinary vaccines, but a poor correlation (r² = 0.2) with human vaccines. However, we could qualitatively arrive at cut-off glycoprotein estimates from the ELISA, above which all the vaccines were declared to be protective by mouse challenge studies (>2.5 IU/dose).