Abhijit Chakraborty

Weighted trade network in a model of preferential bipartite transactions.

Using a model of wealth distribution where traders are characterized by quenched random saving propensities and trade among themselves by bipartite transactions, we mimic the enhanced rates of trading of the rich by introducing the preferential selection rule using a pair of continuously tunable parameters. The bipartite trading defines a growing trade network of traders linked by their mutual trade relationships. With the preferential selection rule this network appears to be highly heterogeneous characterized by the scale-free nodal degree and the link weight distributions and presents signatures of nontrivial strength-degree correlations. With detailed numerical simulations and using finite-size scaling analysis we present evidence that the associated critical exponents are continuous functions of the tuning parameters. However the wealth distribution has been observed to follow the well-known Pareto law robustly for all positive values of the tuning parameters.

Stem cell transplant: An experience from eastern India.

Background: Hematopoietic stem cell transplant using human leukocyte antigen (HLA)-matched sibling or unrelated bone marrow, or related or unrelated cord blood has been performed successfully to treat patients with different types of hematological malignancies, genetic disorders and hereditary immune deficiencies. Since 1983, stem cell transplantation has been carried out in different institutes of India. But, till then, no transplantation was performed in eastern India. Materials and Methods: Our present study is reporting for the first time stem cell transplantation in eastern India. From August 2000 to June 2011 (with a 3-year gap for up-gradation), we have performed a total of 22 transplants. Thirteen patients (M:F:9:4) with indications of aplastic anemia, thalassaemia, acute myeloid leukemia and chronic myeloid leukemia underwent allogenic transplant, whereas autologous transplant was performed for nine patients (M:F:2:1) of multiple myeloma, Hodgkins and non-Hodgkins lymphoma and neuroblastoma. The median age of the patients was 19.6 years, with a range of 5 years 8 months to 52 years. Fourteen patients received myeloablative conditioning regime whereas eight patients received immunosuppressive and less myeloablative protocol. Sources of stem cells in case of allogenic transplant are bone marrow and related or unrelated umbilical cord blood and in case of autologous transplant, these are peripheral blood stem cells or self-bone marrow. Standard prophylactic medication was followed prior to transplants. Results: A disease-free survival of 68.18% and overall survival of 86.3% were seen at the median follow-up period of 4.6 years. Common post-transplant complications were mucositis, infection, venoocclusive disease, graft versus host disease, hemorrhagic cystitis, etc. Conclusion: The use of cord blood as a source of stem cells has been proved inferior as compared with the bone marrow stem cell source in cases of thalassaemia in our institute and thus is not recommended for thalassaemia. But, it has been proved to be a very useful and effective stem cell source (both related and unrelated cord blood) in cases of aplastic anemia and other immunological disorders.

Incidence of the Hb E [β26(B8)Glu→Lys, GAG>AAG] Variant In Totos, One of the Smallest Primitive Tribes in the World

Toto is one of the smallest tribes in the world. This primitive sub Himalayan, endogamous tribe lives in a small, isolated village called Totopara in the Jalpaiguri district of West Bengal in India. The tribal communities of West Bengal are vulnerable to various genetic disorders such as β-thalassemia (β-thal). We have studied 443 Totos to define their Hb E [β26(B8)Glu→Lys, GAG>AAG] status. Awareness and screening camps have been organized in various parts of Totopara during the last 2 years. We collected 3 mL peripheral blood from each individual aseptically on which to use the naked eye single tube red cell osmotic fragility test (NESTROFT); complete hemogram and high performance liquid chromatography (HPLC) were done to detect their carrier status. The Hb E variant had been found to be prevalent among the Totos. To confirm the codon 26 (GAG>AAG) mutation in the β-globin gene, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed. Restriction fragment length polymorphism (RFLP)-PCR was carried out with 44 Hb E alleles to construct the haplotype(s) of the Totos. Our extensive studies have revealed that 49.21% of Totos are Hb E heterozygotes and 19.19% Totos are Hb E homozygotes. The most prevalent haplotype linked with the codon 26 mutation in the Totos is [+ − − − − −] (HincII 5′ϵ, HindIII Gγ, HindIII Aγ, HincII 5′ψβ, HincII 3′ψβ and HinfI 3′β). Consanguineous marriages have resulted in a significant increase of the percentages of heterozygotes and homozygotes of Hb E in the Totos. Genetic counseling is essential and important to prevent the spread of this mutation and hence to save them from having any kind of clinically significant hemoglobinopathy in the future.

Acute toxicity test of a natural iron chelator and an antioxidant, extracted from Triticum aestivum Linn. (wheat grass)

Triticum aestivum (wheat grass) is widely used in traditional medicine to treat various diseases. Previously the purified compounds and crude extract of T. aestivum were established to have iron chelation potency and antioxidant activity. So it is necessary to evaluate the toxic properties of any compound isolated from plant extract to prevent any untoward side effects. The aim of this study was to determine the acute oral toxicity level of our purified compounds, i.e. mugineic acids and methylpheophorbide a., and crude extract of T. aestivum, on Swiss albino mice at dosage of 2000 mg/kg for a period of 14 days using the organisation for economic co-operation and development guidelines 423. There was no mortality. No change in behavioural pattern, clinical signs, body weight and blood biochemistry profile were observed. Kidney and liver showed normal histo-pathological architecture. Hence, the oral administration of compounds and extract of T. aestivum did not produce any significant toxic effect on mice. Thus we may conclude that the extract can be utilised for pharmaceutical formulations as iron chelator and antioxidant agent for various diseases.

Detection of a novel mutation in exon 20 of the BRCA1 gene

Hereditary breast cancer constitutes 5–10% of all breast cancer cases. Inherited mutations in the BRCA1 and BRCA2 tumor-suppressor genes account for the majority of hereditary breast cancer cases. The BRCA1 C-terminal region (BRCT) has a functional duplicated globular domain, which helps with DNA damage repair and cell cycle checkpoint protein control. More than 100 distinct BRCA1 missense variants with structural and functional effects have been documented within the BRCT domain. Interpreting the results of mutation screening of tumor-suppressor genes that can have high-risk susceptibility mutations is increasingly important in clinical practice. This study includes a novel mutation, p.His1746 Pro (c.5237A>C), which was found in BRCA1 exon 20 of a breast cancer patient. In silico analysis suggests that this mutation could alter the stability and orientation of the BRCT domain and the differential binding of the BACH1 substrate.

Absence of 185delAG and 6174delT Mutations among Breast Cancer Patients of Eastern India

BACKGROUND The incidence of breast cancer in India is on the rise and is rapidly becoming the number one cancer in females, pushing the cervical cancer to the second position. Most of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in two tumor suppressor genes BRCA1 and BRCA2. Alterations in these genes have been reported in different populations, some of which are population- specific mutations showing founder effects. Two specific mutations in the BRCA1 (185delAG) and BRCA2 (6174delT) genes have been reported to be of high prevalence in different populations. The aim of this study was to estimate the carrier frequency of 185delAG and 6174delT mutations in eastern Indian breast cancer patients. MATERIALS AND METHODS We selected 231 histologically confirmed breast cancer patients from our tertiary cancer care center in eastern India. Family history was obtained by interview or a self-reported questionnaire. The presence of the mutation was investigated by allele specific duplex/multiplex-PCR on genomic DNA extracted from peripheral blood. RESULTS A total of 231 patients (age range: 26-77 years), 130 with a family history and 101 without were screened. The two founder mutations 185delAG in BRCA1 and 6174delT in BRCA2 were not found in any of the subjects. This was confirmed by molecular analysis. CONCLUSIONS Our findings suggest that these BRCA mutations may not have a strong recurrent effect on breast cancer among the eastern Indian population. The contribution of these founder mutations to breast cancer incidence is probably low and could be limited to specific subgroups. This may be particularly useful in establishing further pre-screening strategies.

Determinants of lymph node status in women with breast cancer: A hospital based study from eastern India

Background & objectives: Number of metastatic lymph nodes has a strong prognostic value in the course of breast cancer treatment, morbidity and mortality. This study was undertaken to determine the association between axillary lymph node metastasis and several variables such as age, tumour size, grade, lymphovascular invasion, oestrogen and progesterone receptor expression and HER2/neu status in patients with breast cancer. Methods: In this study 426 (with complete information on study variables) patients with breast cancer on treatment during March 2010 to December 2013, were analyzed. TNM (tumour node matastasis) staging was evaluated. The histological grading of tumours was done according to modified Bloom-Richardson Grading System. The immunophenotype of the tumour was determined as the expression of oestrogen (ER) and progesterone (PR) receptors and HER2/neu status. Univariate and multivariate analyses were carried out to determine the independent predictors of metastatic lymph node. Results: Among the studied patients, 44.36 per cent (189 of 426) of the patients had nodal metastases. Tumour histology, tumour grade, size and lympho-vascular invasion were related with node positivity. On univariate analysis, age, menopause, hormone receptor status did not relate with the node metastasis. Age, tumour grade, tumour size, lympho-vascular invasion and HER2/neu expression was likely to be associated with the number of lymph node metastasis. Interpretation & conclusions: The lymph node status was associated with clinical stage, tumour grade, tumour histology and HER2/neu status. These factors may be used for better management of such patients.

Erratum to: Detection of a novel mutation in exon 20 of the BRCA1 gene

[This corrects the article DOI: 10.2478/s11658-013-0110-3.].

384PSTUDY OF IMMUNOHISTOCHEMICAL AND CLINICOPATHOLOGIC FEATURES OF FEMALE BREAST CANCER PATIENTS WITH /WITHOUT BRCA1 MUTATION IN EASTERN INDIA

ABSTRACT Aim: Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing breast cancer. A hospital based study from Eastern India to find the associations among molecular, immunohistochemical, and clinicopathologic features of the breast cancer patients with and without BRCA1 mutations was aimed Methods: From March 2010 to November 2013, 214 patients undergoing surgical treatment in the Department of Surgery of our Institute were subjects of this study. Tumor size was evaluated & histological grading of tumors was done. All paraffin embedded surgical specimens were tested for immunohistochemical features (expression of ER, PR and HER2/Neu status). Detection of BRCA1 gene mutations for exons 2,8,10,11,14,15 and 20 were performed by ARMS-PCR followed by direct DNA sequencing. Co-relation of hormone receptors, BRCA1 gene mutations and outcome of therapy were assessed for prognostication. Results: Out of 214 patients, 126 and 88 were with and without family history respectively. Average age was 48.12 + 10.32 years. Invasive ductal carcinoma was the most common histology among them. Mean tumor size was 2.52 + 0.42 cm and 51.40% patients had Grade II tumor. Among these patients 41.12%, 53.27% and 18.22% patients were found having ER+, PR+ and triple negative cancer. Mutations of BRCA1 gene was found in 9 patients. Seven 5382insC, two missense mutations (c.5237A > C; p.His1746Pro and c.5210 G > A; p.Arg1737 Lys) in exon 20 were identified. Long term disease free survival (DFS) was seen in 9 patients who were BRCA1 & hormone receptor positive (ER+, PR+). Conclusions: These data showed a correlation between the BRCA1 mutations with clinical characteristics. BRCA1 mutation carriers who are older at first BC diagnosis are more likely to have ER+, PR+ tumors than younger BRCA1 mutation carriers. Disclosure: All authors have declared no conflicts of interest.