eMedicine创建于1996年，由近万名临床医师作为作者或编辑参与此临床医学知识库的建设，其中编辑均是来自美国哈佛、耶鲁、斯坦福、芝加哥、德克萨斯、加州大学等各分校医学院的教授或副教授。

eMedicine

Breast cancer (BC) is the most common cancer of women all over the world. BRCA1 and BRCA2 gene mutations comprise the most important genetic susceptibility of BC. Except for few common mutations, the spectrum of BRCA1 and BRCA2 mutations is heterogeneous in diverse populations. 185AGdel and 5382insC are the most important BRCA1 and BRCA2 alterations which have been encountered in most of the populations. After those Ashkenazi founder mutations, 300T>G also demonstrated sparse frequency in African American and European populations. This review affords quick access to the most frequent alterations among various populations which could be helpful in BRCA screening programs.

/pdf/a-comprehensive-focus-on-global-spectrum-of-brca1-and-brca2-1jxc60czt4.pdf

A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer.

Introduction: Spirooxindole, a unique and versatile scaffold, has been widely studied in some fields such as pharmaceutical chemistry and synthetic chemistry. Especially in the application of medicine, quite a few compounds featuring spirooxindole motif have displayed excellent and broad pharmacological activities. Many identified candidate molecules have been used in clinical trials, showing promising prospects.Areas covered: This article offers an overview of different applications and developments of spirooxindoles (including the related natural products and their derivatives) in the process of drug innovation, including such as in anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, antimalarial, and antiviral activities. Furthermore, the crucial structure-activity relationships, molecular mechanisms, pharmacokinetic properties, and main synthetic methods of spirooxindoles-based derivatives are also reviewed.Expert opinion: Recent progress in the biological activity profiles of spirooxindole derivatives have demonstrated their significant position in present-day drug discovery. Furthermore, we believe that the multidirectional development of novel drugs containing this core scaffold will continue to be the research hotspot in medicinal chemistry in the future.

An overview of spirooxindole as a promising scaffold for novel drug discovery.

Thalassaemia and sickle cell disease have been recognized by the World Health Organization as important inherited disorders principally impacting on the populations of low income countries. To create a national and regional profile of β-thalassaemia mutations in the population of India, a meta-analysis was conducted on 17 selected studies comprising 8,505 alleles and offering near-national coverage for the disease. At the national level 52 mutations accounted for 97.5% of all β-thalassaemia alleles, with IVSI-5(G>C) the most common disease allele (54.7%). Population stratification was apparent in the mutation profiles at regional level with, for example, the prevalence of IVSI-5(G>C) varying from 44.8% in the North to 71.4% in the East. A number of major mutations, such as Poly A(T>C), were apparently restricted to a particular region of the country, although these findings may in part reflect the variant test protocols adopted by different centres. Given the size and genetic complexity of the Indian population, and with specific mutations for β-thalassaemia known to be strongly associated with individual communities, comprehensive disease registries need to be compiled at state, district and community levels to ensure the efficacy of genetic education, screening and counselling programmes. At the same, time appropriately designed community-based studies are required as a health priority to correct earlier sampling inequities which resulted in the under-representation of many communities, in particular rural and socioeconomically under-privileged groups.

https://link.springer.com/content/pdf/10.1007%2Fs11568-010-9132-3.pdf

Profiling β-thalassaemia mutations in India at state and regional levels: implications for genetic education, screening and counselling programmes

Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function.

The most common genetic neuromuscular disease of childhood, Duchenne and Becker muscular dystrophy (DMD/BMD) is caused by deletion, duplication or point mutation of the dystrophin gene located at Xp 21.2. In the present study DNA from seventy unrelated patients clinically diagnosed as having DMD/BMD referred from different parts of West Bengal, a few other states and Bangladesh are analyzed using the multiplex polymerase chain reaction (m-PCR) to screen for exon deletions and its distribution within the dystrophin gene. Out of seventy patients forty six (63%) showed large intragenic deletion in the dystrophin gene. About 79% of these deletions are located in the hot spot region i.e., between exon 42 to 53. This is the first report of frequency and distribution of deletion in dystrophin gene in eastern Indian DMD/BMD population.

/pdf/analysis-of-dystrophin-gene-deletions-by-multiplex-pcr-in-3jdfhomjjs.pdf

Analysis of dystrophin gene deletions by multiplex PCR in eastern India.

7012 Background: A pilot study with wheat grass juice in major thalassaemia patients was done by a group of clinicians in IPGMR, Chandigarh, India. We performed a study of 200 patients of intermedi...

The role of iron chelation activity of wheat grass juice in patients with myelodysplastic syndrome

Objective
To control the birth of thalassemic children in India.

Methods
Mutations present in the population of eastern India and in carrier parents seeking prenatal diagnosis were detected by the PCR-based technique of ARMS (amplification refractory mutation system) or gap-PCR. To screen for maternal tissue contamination in CVS, haplotypes associated with the β-globin gene clusters were constructed using six polymorphic restriction sites. Prenatal diagnosis was accomplished by checking presence of parental mutation in the DNA from chorionic villus sampling (CVS) collected at 8 to 10 weeks' gestation by appropriate technique.

Results
Six hundred and fifty (650) unrelated β-thalassemia chromosomes were screened for 11 common mutations to characterize the mutation distribution in this population. Starting from early 2000, 63 families from different parts of West Bengal and from surrounding areas have been offered prenatal counseling for β-thalassemia.

Conclusion
The population of this region is conscious and willing to accept prenatal diagnosis as a means of control of thalassemia. Copyright © 2004 John Wiley & Sons, Ltd.

Profile of β-thalassemia in eastern India and its prenatal diagnosis

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.

http://koreascience.or.kr:80/article/JAKO201501255363361.pdf

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

1,4-Dihydropyridines (1,4-DHPs) are important as a class of heterocyclic compounds that exhibit wide range of biological actions. Many of its derivatives are already characterized as medicinally important drugs and used worldwide. In this study, we have screened some novel Hantzsch 1,4-DHP compounds using both in silico (QSAR and Pharmacophore) and in vitro (cytotoxic screening). 1,4-DHP showed selective cytotoxicity against five human cancerous cell lines; A375, A549, HeLa, HepG2 and SH-SY5Y but limited effect towards normal skin keratinocyte (HaCaT), lung fibroblast (WL-38) and healthy peripheral blood mononuclear cells. In A375 and HepG2 cells, one of the 1,4-DHP derivative (DHP-8) was found to inhibit cell proliferation, and simultaneously increased the apoptotic population as well as mitochondrial membrane depolarization. Furthermore, the mitochondrial signal was triggered with the activation of cleaved Caspase9, Caspase3 and PARP. The treatment with DHP-8 also increased the expression level of SIRT1, subsequently decreasing the level of pAKTser473 and survivin. Reduced pAKTser473 expression led to decrease the phosphorylated inactive form of GSK3βser9 and as a result, proteasomal degradation of Mcl-1 occurred in both the cell lines. Here, we suggest that the apoptotic effect of DHP-8 in A375 and HepG2 cells was mediated by AKT and survivin pathways through SIRT1 activation. The involvement of DHP-8 in SIRT1 activation was further verified by co-treatment of nicotinamide with DHP-8 in both A375 and HepG2 cells. Overall, this study emphasizes the possible potential and therapeutic role of DHP-8 in skin and liver cancer.

Jayasri Basak

Papers

Analysis of dystrophin gene deletions by multiplex PCR in eastern India.

The role of iron chelation activity of wheat grass juice in patients with myelodysplastic syndrome

Profile of β-thalassemia in eastern India and its prenatal diagnosis

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

Novel 1,4-dihydropyridine induces apoptosis in human cancer cells through overexpression of Sirtuin1.