Flow cytometric characterization of phenotype,DNA indices and p53 gene expression in 55 cases of acute leukemia

OBJECTIVE: To characterize the phenotype of acute leukemia cases using flow cytometry, to detect mixed lineage cases and to use DNA index determination, including S-phase fraction (SPF) and p53 detection, to find if there was any correlation of SPF and p53 expression with outcome. STUDY DESIGN: Fifty-five cases of acute leukemia were enrolled in this study. A complete hemogram and routine bone marrow examination, including cytochemistry, was done. Mycloperoxidase-negative cases were evaluated on a flow cytometer using monoclonal antibodies. DNA indices were determined by flow cytometry in all cases, and p53 was detected immunohistochemically using the alkaline phosphatase/antialkaline phosphatase technique. RESULTS: Acute myeloblastic leukemia (AML) was diagnosed in 32 cases; acute lymphoblastic leukemia (ALL) was diagnosed in 18 (14 B lineage and 4 T line age). Four cases showed mixed lineage leukemia, and undifferentiated acute leukemia was diagnosed in one case. The mean/range of SPF for these groups were 3.76/0.33-6.91, 6.25/0.15-21.4, 2.89/0.35-10.64, 2.60/0.72-6.94 and 7.34, respectively. Aneuploidy was detected in two cases of B-lineage ALL and tetraploidy in a case of AML-M7, while all others were diploid p53. Was detected in 6 of 55 cases (10.90%). Follow-up was available for 24 patients. Five patients relapsed, and four had B-cell type ALL and were diploid and expressed no p53 gene. SPF% did not show any correlation with outcome. CONCLUSION: These data suggest that within acute leukemia subtypes, there is a wide variation in SPF. SPF does not seem to correlate with outcome. Immunophenotyping is essential to determine the lineage in myeloperoxidase-negative cases. It is perhaps the only way to diagnose mixed lineage leukemia and aberrant expression of markers presently. The p53 gene was detected less frequently. However, more studies are required from different centers with longer follow-up to evaluate prognostic significance.     

Common Variants of FTO Are Associated with Childhood Obesity in a Cross-Sectional Study of 3,126 Urban Indian Children

Background

FTO variants are robustly associated with obesity and related traits in many population and shown to have variable impact during life course. Although studies have shown association of FTO variants with adiposity in adult Indian, its association in Indian children is yet to be confirmed.

Methods

Here we examined association of FTO variants (rs9939609 and rs8050136) with obesity and related anthropometric and biochemical traits in 3,126 Indian children (aged 11–17 years) including 2,230 normal-weight and 896 over-weight/obese children. We also compared effects observed in the present study with that observed in previous studies on South Asian adults and children of other ethnic groups.

Results

The variant rs9939609 showed significant association with risk of obesity [OR = 1.21, P = 2.5×10⁻³] and its measures BMI, weight, waist circumference and hip circumference [β range = 0.11 to 0.14 Z-score units; P range = 1.3×10⁻⁴ to 1.6×10⁻⁷] in children. The observed effect sizes in Indian children were similar to those reported for European children. Variant rs9939609 explained 0.88% of BMI variance in Indian children. The effect sizes of rs9939609 on BMI and WC were ∼2 fold higher in children than adults. Interestingly rs9939609 was also associated with serum levels of thyroid stimulating hormone (TSH) [β = 0.10 Z-score, P = 5.8×10⁻³]. The other variant rs8050136 was in strong linkage disequilibrium with rs9939609 (r² = 0.97) and provided similar association results.

Conclusion

The study provides first report of association of FTO variants with obesity and related anthropometric traits in Indian children with higher impact in children compared to adults. We also demonstrated association of FTO variant with serum levels of TSH, indicating putative influence of FTO in hypothalamic-pituitary-thyroid axis.     

PASS-predicted design, synthesis and biological evaluation of cyclic nitrones as nootropics

Out of 400 virtually designed imidazoline N-oxides, five cyclic nitrones were selected on the basis of PASS prediction as potent nootropics and were evaluated for their biological activities in albino mice. The selected N-alkyl and aryl-substituted nitrones were found to be excellent nootropics. A series of lead compounds acting as cognition enhancers have been provided, which can be further exploited in search of such New Chemical Entities (NCEs).     

Whole blood and component use in resource poor settings

Data on blood collection, testing and component preparation has improved worldwide; however, there is limited information on blood utilization from the developing countries. Blood requirement in the Southeast Asia region is 15 million units against a collection of 9.3 million. There is huge diversity in the management of blood transfusion services, the voluntary blood collection (range 40–100%) and proportion of blood separated into components (10–95%). The major indications for transfusion are for emergency obstetric care, surgery, pediatric and trauma patients. The prevalence of thalassemia in this region is high and in India alone 2 million units of packed red cells are required for transfusion to these patients. The Blood Safety Program in India has developed as a component of the National Aids Control Program and has lead to infrastructure development, blood component separation facilities and formulation of a National Blood Policy. In order to facilitate emergency obstetric care nearer home, blood storage centers are being established at primary health care centers. Emerging infectious threats like dengue hemorrhagic fever necessitate platelet transfusion therapy. A few centers in India issue NAT screened blood. It is envisaged to establish a nationally co-ordinated transfusion service for cost-effective quality blood/components for appropriate clinical use.     

Cytomorphologic aspects of thyroiditis. A study of 51 cases with functional, immunologic and ultrasonographic data

Fine needle aspiration provided material for detailed cytomorphologic study in 51 cases of thyroiditis, 40 of which were diagnosed as Hashimoto's (autoimmune) thyroiditis. Of these 40 cases, 22 were found to be euthyroid on clinical examination and radioimmunoassay (RIA), 10 were hyperthyroid and 8 were hypothyroid. Of the 11 cases of subacute thyroiditis, 4 were thyrotoxic and 7 were euthyroid. Radioactive iodine uptake (RAIU) showed decreased to negligible uptake in ten and normal uptake in one case of subacute thyroiditis, whereas all of the thyrotoxic cases of Hashimoto's thyroiditis showed markedly increased RAIU. Echography showed a hypoechoic or anechoic pattern in most of the cases. Antimicrosomal and/or antithyroglobulin antibodies were positive in 25 cases of Hashimoto's thyroiditis and in 1 case of subacute thyroiditis. The cytologic features that characterized subacute thyroiditis were the presence of multinucleated giant cells and a polymorphonuclear and lymphocytic population associated occasionally with epithelioid-cell granulomas. Hashimoto's thyroiditis was characterized by Hürthle-cell changes and a significant lymphoid population consisting of mature and transformed lymphocytes, often impinging on follicular cells. There was an overlap in the cytomorphologic features between some cases of Hashimoto's and subacute thyroiditis. In such cases, the final diagnosis was arrived at by an integrated approach incorporating all of the diagnostic parameters available.     

Electrophysiological actions of neurotensin in rat cerebellum

The electrophysiological actions of neurotensin (NT) and its analog d-Arg⁹NT were studied in rat cerebellar Purkinje neurons. NT applied by pressure ejection was a potent depressant of Purkinje (P) neuron firing. In contrast, iontophoretically applied NT was a weak depressant. Pressure-ejected d-Arg⁹NT, which is largely inactive in peripheral systems, had little effect on P neurons. The depressant effects of pressure-ejected NT were blocked by intraperitoneally administered haloperidol, iontophoretically applied magnesium or 6-OHDA pretreatment. After such treatments, locally applied NT evoked only excitations.The results of this study suggest that NT, when applied by pressure ejection, produces two effects on the Purkinje neuron. The potent inhibitory effects of locally applied NT appear to result from release of the inhibitory transmitter, norepinephrine from locus coeruleus-derived afferents. We postulate that the excitations, which appear when postsynaptic effects of norepinephrine are antagonized or release is reduced, may be the direct result of NT action at the postsynaptic P neuron membrane.     

Dermatoglyphics in turner syndrome

Finger and Palmar dermatoglyphics in 25 karyotypically proven cases of Turner syndrome representing Northwestern region of India are presented and compared with those obtained on their 102 normal female counterparts. Predominance of ulnar loops over other patterns was recorded in turner patients. Mean total finger ridge count in Turner syndrome (147.4) remained higher than the normal females (121.1). c-d interdigital ridge count in turners remained significantly (p≤0.05) higher than their normal female counter-parts. In contrast to their western counterparts distal placement of axial triradius in both the palms of none of the Turner syndrome patients representing the current series was recorded. Occurrence of whorls and arches in hypothenar region of 12% and 4% was respectively noticed in right palm of patients. The use of distinctive dermatoglyphic features recorded amongst Turner syndrome patients representing this study may be made to corroborate diagnosis of this entity in settings where facilities to carry out karyotyping do not exist.