Introduction: Accurate measurement of HbA1c is crucial in the diabetic control and diagnosis. Elevated levels of HbF are reported to falsely decrease the HbA1c result and effect is very much method dependent. Material & Methods: Commercial assay methods G8 HPLC analyzer and DCA 2000 were evaluated. G8 is an ion exchange, high performance liquid chromatography (HPLC) method that measures the HbA1c as a percentage of total amounts of hemoglobin present in the sample. Two whole blood EDTA patient pools were prepared with HbA1c concentrations in the normal (5% to 7%) and abnormal range (7% to 8%). All chromatograms from G8 were reviewed for any change in the peak resolution time due HbF concentrations. Results: The mean value for normal and abnormal pool was 5.8% and 7.5% resp. HbF showed no interference on Tosoh HbA1c results up to 30% in normal pool and up to 25% in abnormal pool. Observed difference between G8 and both Dimension EXL and DCA 2000 was clinically significant beyond 10% HbF. Conclusion: Accurate measurement of HbA1c is crucial for the decision making for diabetic control and diagnosis. The allowable error proposed by College of American Pathologist (CAP) is 6% therefore, appropriate knowledge about factors interfering with HbA1c results is absolutely important.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Objective: 1. To identify the common type of anaemia in our population and promote appropriate counselling for an effective plan of management & treatment. 2.To establish how thalassemia is diagnosed and assess type of counselling received among the thalassemic families and to provide appropriate Genetic Counselling. Method: Information was obtained from Anemic and Thalassemic patients to assess their awareness regarding their pathophysiology and assess what type of counselling they received, from different centres in Hyderabad, India. Result: It was found that after counselling, the patients and their attenders were more receptive to undergoing treatment for anaemia and genetic testing for thalassemia. Conclusion: Extended family screening, prenatal diagnosis and carrier testing should be explained and advised and the centres offering these tests should also be informed.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Chronic Myeloid Leukemia (CML) is associated with translocation between chromosome 9 & chromosome 22, t(9;22)(q34;q11.2) and with the formation of BCR-ABL fusion gene. In few newly diagnosed CML cases, complex cytogenetics variants of the Philadelphia (Ph) chromosome can be observed with the involvement of a third chromosome other than chromosome 9 & chromosome 22. Here in, we describe a 45 yrs old male, diagnosed as CML in Chronic phase with a complex translocation involving chromosomes 7, 9 & 22. Cytogenetics investigations for confirmation of CML revealed 46,XY, t(7;9;22)(q11.2;q34;q11.2) in 100% metaphases counted. Fluorescence in-situ hybridization (FISH) showed BCR-ABL fusion signals pattern in 100% nucleated cells analyzed. A review of the literature revealed that CML patients with this translocation tend to have an aggressive course and poor outcome. Additional 3-way chromosome translocations associated with CML are also reviewed.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Background: The purpose of this study was to investigate the genotype frequencies of CYP3A4*1B and CYP3A5*3 in lung cancer patients which may be useful in determining the patients' predisposition to platinum based therapies, and may be helpful for individualized drug dosing and improved therapeutics and disease management. Results: We evaluated these two common polymorphisms in south Indian population, based on case-control study of 126 lung cancer cases and 111 controls using a PCR-RFLP-based assay. The investigation of the CYP3A4*1B gene polymorphism revealed, no significant difference in distribution between the lung cancer patients and the controls (p=0.65) . The distribution of CYP3A5*3 homozygous genotypes and heterozygous plus homozygous genotypes were significantly associated (p=0.0004 & p=0.0001) with lung cancer patients, and the *3/*3 genotype had a 4.38 fold increased risk for lung cancer. In our study *1A/*1B heterozygous genotype patients were found to constitute a major percentage of patients receiving Gemcitabine plus carboplatin therapy. Conclusions: In conclusion, the results of our study indicated a relationship between CYP 3A4*1B and CYP3A5*3 polymorphisms and genetic predispositions to lung cancer. Thus detection of CYP3A4*1B/CYP3A4 and CYP3A5*3/CYP3A5 genotype frequencies in Indian population may be important in view of interindividualized drug dosing, improved therapeutics and disease management.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

To validate plasma cell enrichment technique for improving the detection of cytogenetic abnormalities in the Plasma cell myeloma (PCM)/multiple myeloma (MM). We compared the abnormality detection rate for overnight unstimulated bone marrow cultures to that for the plasma cell enriched fractions obtained with the use of CD138-coated immunomagnetic beads. Average enrichment factor (EF) was 11. One or more abnormalities were detected in 90% of enriched samples vs. 65% of non-enriched samples, thus resulting in a significantly higher detection rate of total cytogenetic abnormalities in enriched plasma cells (p=0.0038). Additional findings of RB1 deletion, TP53-, 1p-, 1q+ and [email protected] rearrangement seen in the 25% of enriched samples could contribute to the altered risk in the patient. One of the three cases with plasma cells as low as 1% by morphology was positive for a residual disease marker in the enriched sample and negative in the non-enriched sample. The plasma cell enrichment technique increased the detection rate of diagnostic and prognostic markers and is a very sensitive method for detecting minimal residual disease.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Background: Increasing incidence of Squamous Cell Carcinoma (SCC) has emphasized the challenges of managing this condition. Traditional microscopic information often fails, especially when based on H & E methods. Immunohistochemistry (IHC) and molecular studies in combination with traditional histopathology may fill this gulf. Aims: The study was conducted to introduce new a grading system based on both histopathological and biological correlation of SCC. Settings and Design: A descriptive study included 180 cases of SCC of the skin (all regions of skin and oral mucosa). Cellular proliferation index (Ki-67 and p53 expression) was studied in SCC by immunohistochemistry (IHC). This study was carried out in the Department of Pathology from January 2006 to December 2008. Methods and Material: The clinicopathological information regarding age, sex, primary tumor site, tumor size, local recurrence, distance metastasis and follow-up status was collected for each case. Patient outcome was verified and updated through the medical records. Five micron thick (5μm) sections were cut from archival formalin fixed, paraffin embedded specimens. The first section was stained with haematoxylin and eosin (H&E) for histopathological analysis. Other sections were stained immunohistochemically with p53 and Ki-67 and then independently scored for the expression of p53 proteins and Ki-67 index. Results: SCC was designated low, intermediate, and high tirade grades based on the sum of point values assigned to each 4 scores of histological differentiation, staging, expression of p53 protein and Ki-67 index. Expression of p53 was found to be related to the Ki-67 and the scores of histology and stages of SCC. A significant correlation was found among the newly assigned grades, stages (Spearman correlation = 0.721, P value = 0.000). The grades were also significantly correlated with other prognostic factors like local invasion, lymph node and distance metastasis (Kendall's Tau-b = 0.394;p-value = 0.00). Tumor recurrence was also significantly based on grades of SCC (Kendall's Tau–b = 0.966, P value = 0.025). Conclusion: It was concluded that a new grading system is an important prognostic indicator of squamous cell carcinoma. This practical approach has potential to improve clinical evaluation of SCC in understanding the pathological as well as clinical behavior of SCC.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Objective: We investigated the association of MTHFR C677T polymorphism with ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian Population from Andhra Pradesh. Methods: Six hundred and twenty ischemic stroke patients, 220 hemorrhagic stroke patients and 620 age and sex matched healthy controls, were included in the present study. The polymorphism was determined using PCR-RFLP technique. Results: The strength of association between genotypes and stroke types was measured by the odds ratio with 95% confidence interval and chi-squared analysis. We found significant association of the CT genotype with ischemic stroke as well as haemorrhagic stroke (p<0.05). Further, evaluating the association of this polymorphism with stroke subtypes, we found significant association with intracranial large artery (p<0.05), lacunar stroke (p<0.05) and undetermined etiology (p<0.05). However, there was no significant difference in genotypic or allelic frequencies between ischemic and hemorrhagic strokes. Conclusion: Our study suggests that MTHFR (C677T) is an important risk factor for ischemic stroke, its subtypes and hemorrhagic stroke in the South Indians from Andhra Pradesh but it cannot help in distinguishing between the two types of stroke.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

The successful arrest or cure of tuberculosis (TB) depends largely on early case detection and proper treatment. Currently, several promising diagnostic tools with improved sensitivity and speed are available. Old microscopic and culture based technologies have been revisited and new molecular technologies have been developed. In recent years, World Health Organization (WHO) evaluated and endorsed different TB diagnostic tools and published various policy statements. These policy statements address improvements in smear microscopy, use of commercial and non-commercial culture based techniques and rapid molecular assays. This is the first comprehensive review compiling pros and cons of WHO recommended TB diagnostic tools for effective implementation in TB endemic regions.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Infertility is an emerging major health issue affecting the physical, psychological and social status of the general population across the globe. There are innumerable causes of infertility, viz., ovarian and testicular disorders, advanced maternal age, obesity, chromosomal abnormalities etc. Most of these causes are linked to the genetic disorders. With recent advances in the field of reproductive biology, it has become imperative to have a concise knowledge of the genetic basis of infertility, for better outcome in Assisted Reproductive Techniques (ART).

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Objective: Scientists are to develop novel antibacterial therapeutics in order to eliminate medically significant pathogens resistant to antibiotic. Lysostaphina zinc metalloprotease with the sub-atomic weight of 27kDa and particularly tic action against Staphylococcus aureus degrades the S. aureus by hydrolyzing the pentaglycine cross-links introduce in its cell wall. Because of such potential, lysostaphin will be a decent agent for treatment of antibiotic-resistant staphylococcal infections. Also, due to the broad needs of society to increase localization of sciences, the national production of this drug in research laboratories would be necessary. Materials and Methods: First, with the aid of articles we identified Lysostaphin sequences without signal peptide via Gene Bank data base. In order to achieve the correct protein sequence, we add the entrokinase cutting site to our sequence. To ensure the correct cloning process, the entire process of cloning and protein expression was evaluated in silico. The sequence obtained for the synthesis was sent to the Biomatik Company in Canada (BIOMATIK). After the primer design and synthesis of the DNA fragment of the gene, we amplified the gene using PCR. The mature lysostaphin gene was cloned in plasmidpET28a and expressed in E.coli with the carboxyl terminal hexa-histidine fusion tag under the transcriptional control of T7/lac promoter/operator. Result: The transformed E.coli BL2 (DE3) cells produced catalytically active recombinant lyso staphin after being induced by IPTG. Conclusion: This study shows that the E. coli expression system is suitable for expression of recombinantly so staphin and according to the conducted bioassay in this study, the expressed protein can be considered as an effective therapeutic agent against antibiotic resistant staphylococcus aureus.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Aim: This study was an attempt at investigating the variation in growth and morphology of primary avian chondrocyte and neural cell cultures established under standard laboratory conditions. Methods: For establishing chondrocyte cultures, the tibia were dissected from chick embryos that were 12 (E12), 14 (E14) and 15 (E15) days old. For the neural cell culture initiation, the two lobes of the forebrain were dissected from chick embryos that were 4 (E4), 8 (E8) and 12 (E12) days old. The final characterization of the cells was performed by H&E and CFV staining. Results: In the chondrocyte cultures, two forms of morphology were observed which is reversible in process.The primary variation evaluated in chondrocytes cultures was the effect of the media on the state of the cells. Based on whether the cells were cultured in DMEM or MEM, there was a difference in the transformation of the attached cells from the differentiated to de-differentiated forms. The primary variation examined in neuron cultures was the embryonic age of the tissue and the effect that it had on the proliferation and neurite formation of the cells. E8 embryo neural cells cultures result in well-developed cells with neurite formation along with axonal and dendritic outgrowths with highly complex interconnections between them. Conclusion: Ultimately, this study demonstrated the composition of culture media had an effect on the morphological appearance of the chondrocytes, as well as, confirmed that the culture of primary neurons is best performed using cells from an E8 embryo.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Introduction: Aggressive NK-cell leukemia (ANKL) is a highly aggressive disease with extremely poor prognosis. A few malignant NK cell lines reflecting ANKL biology have been generated; however, these NK cell lines require the inclusion of exogeneous IL2 in the culture medium continuously, which increases the cost of cell culture significantly. Methods: IL2 coding sequenced was cloned into MSCV-IRES-YFP (PMIY) vector by directional PCR-cloning. IL2 was ectopically expressed in KHYG1 cell line through retroviral transduction. The transduced cells were cultured in limiting IL2 concentrations during which they were quantified with flow cytometry in regular time intervals to track the transduced population. IL2 transduced KHYG1 cells were then sorted to generate IL2-KHYG1 cells. PRDM1 was ectopically expressed in IL2-KHYG1 cells through retroviral transduction. Trypan blue count was performed to test proliferation of IL2-KYHG1 cells in the absence of IL2. Results: IL2-KHYG1 cells were enriched (from ~7% to ~16% YFP⁺ cells) during cell culture in limiting (6.25IU) IL2 concentrations. Complete removal of IL2 further enriched the transduced portion to 27% YFP-positivity, which did not increase with additional culturing. IL2 expressing KHYG1 cells were further enriched by sorting transduced IL2-KHYG1 cells with high level IL2 expression. IL2-KHYG1 cells survived and continued to grow without IL2. IL2-KHYG1 cells were transduced successfully using a PRDM1 construct having GFP as a marker under cell culture conditions having no IL2. Conclusion: IL2-KHYG1 cell line may decrease the cost associated with culturing ANKL cell lines, and it may facilitate in vitro investigation of the molecular basis of this malignancy.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Polycythaemia Vera or erythrocytosisis a medical condition with high concentration of red blood cells. The thicker blood is less able to travel through blood vessels and organs. Most symptoms of polycythaemia are related tothis sluggish blood flow. Moderate symptoms of polycythaemia include headache, blurredvision, red skin, tiredness, elevated blood pressure, dizziness, abdominal discomfort, bleeding problems, gout and itchy skin although more severe medical events like vas-occlusion, thrombosis and strokes may occur. This case reports a 50 year old female with an unusual presentation of polycythemia vera in the form of abrupt onset &one-day-old' history of massive hematemesis with otherwise unremarkable physical exam except caput medusa around umblicus. A diagnosis of Polythythaemiavera complicated by portal vein thrombosis induced portal hypertension was finally made.Patients with polycythemia vera are at high risk of vaso-occlusive events. While the etiology of events in polycythemic patients is likely to be multifactorial, hemodilution is potentially beneficial. Attending clinicians should be well aware of the unlikely associations and squeal of thrombotic events in polycythemia vera like portal venous occlusion and hypertension.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Gene therapy is a novel approach to treat, cure, or ultimately prevent disease by changing the expression of a person's gene. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The scope of this new approach to the treatment of a condition is broad, with potential in the treatment of many genetic conditions. Though single gene disorders are best treated than multifactorial disorder; the challenge of developing successful gene therapy for any specific condition is considerable. The problem of ‘gene delivery’ into the desired tissues is very complex and challenging. Some of the ‘vectors’ for delivering the working copy of the gene to the target cells include using harmless viruses and non viral vectors. Till date, in gene therapy, only somatic cells and not the germ cells are targeted for treatment. The possible genetic manipulation of the germ cells remains the subject of intense ethical and philosophical discussion. Though some devastation was recorded in gene therapy trial; the potential benefits of new treatments must always be balanced against such risks. In particular, safety will appropriately remain an important consideration as the field of gene therapy evolves. The purpose of this review is to focus on merit and demerit of gene therapy and to provide information about its future prospective.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

General anxiety disorder is a chronic disorder. The prevalence of GAD is variable in different part of world, with some region having higher figure than others. It's uncertain to quote if the variation is due to genetic loading or environmental factors. It is twice more common in females than males. It has constituted substantial burden on global economy as well as over all quality of life of an individual suffering from GAD. The prognosis of GAD is mainly correlated with the environmental constraints. However, the efficacy of response to pharmacological intervention is better explained on biological model. Certain studies are done to widen the ground of genesis of GAD. Although, by and large it still remains debatable about distinctive gene causing GAD. Nonetheless, the alteration of gene coding of 5-HTTLPR of serotonin is relatively favorable finding in studies, both independently done on GAD and in parallel to other anxiety disorders and psychiatric morbidities.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Background: ACE a renin-angiotensin system that regulates blood pressure, balance of fluids and salts in body and PAI-1 is a serine protease inhibitor, which inhibits tissue plasminogen activator andurokinase.They are thought to play an important role in pathophysiology of kidney disease in diabetes. Aim: In our present study, we studied the association of altered ACE-gene and PAI-1 gene with diabetic retinopathy (DR) and NDR in 592 samples consisted of (cohort I; 196 DR patients, cohort II; 200 diabetic non-retinopathy (DNR) and cohort III, 196 respective controls. Methods: For genotyping of ACE-gene and PAI-1 gene, genomic DNA was isolated and purified which was then amplified by PCR, and thePCR products analyzedwere by Agarose gel electrophoresis. Results: In first part, the ACE genotype and allele frequency distribution was studied. For ACE gene polymorphism, the genotype and allele frequency distribution were analyzed in DR subjects and respective controls. The results indicated that there is no statistically significant difference between DR males and females compared to respective controls. The results were significantly high between genotype frequencies of DR and DNR in males. The recessive model was found to be significantly associated with the DR male subjects (OR=0.45 [95% CI=0.20-0.99], p<0.05), whereas in females these are non-significant as compared to respective controls individuals. In second part of study, the disease status analysis of ACE gene on basis of DR stages (NPDR and PDR) was observed. The χ² analysis indicated that results are significantly different between NPDR and respective controls (χ²=8.75, p=0.01) .And in third part of present study, disease status analysis for PAI-1 gene on the basis of DR stages (NPDR and PDR) was studied, which indicated statistically non-significance. The χ² analysis values for DNR and NPDR and for DNR and PDR was (χ²=0.48, p>0.05)(χ² =2.00, p>0.05) respectively, Conclusion: Our present study suggests that changes in genetic polymorphisms of ACE-gene and PAI-1 gene in DR, DNR and T2D Patients are risk factors, which may serve as useful prognostic markers.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Death is always dreadful and the diseases those causes sudden death are universal threats in health concern. Brugada syndrom is a recently identified entity of arrhythmia and sudden cardiac death. This genetic and male dominant disorder is prevalent in Southeast Asian region. At least seven genes have been identified to associate with its occurrence though the detail pathophysiological mechanism is till to be resolved. The correlation of ion channel genes to Brugada syndrom is still dubious as the same genes also related to other cardiac diseases. Here we review the genetic aspects of Brugada syndrom with a breif overview of epidemiology, diagnosis and management system.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Objective: Cervical carcinoma is one of the most common diseases in our setup studies show that it is preceded by precursor lesions. It has been suggested that persistent infections with human papillomavirus (HPV) is the major risk factor in the development of this invasive cervical neoplasia. The rationale of this study was, whether detection may contribute to the identification as a major risk factor in cervical neoplastic lesions. Study Design: Experimental study. Methods: 102 cases were selected after screening 1000 specimens through Papanicolaou stains of cervical cytology and histopathology for detection of HPV and its subtype PCR. Data for risk factors were collected by a questionnaire and association of HPV was seen with Positive PCR results. Patient demographics including their age, sexual partners, marital status, socioeconomic condition, contraceptive and screening history were evaluated to determine whether subsidiary risk factors are associated with HPV and the development of cervical lesions among Pakistani women. Major Outcome: 85% cases of cervical carcinoma were associated with high risk HPV infection. Results: 46/102 (45%) cases were low grade squamous cell intraepithelial lesions(L-SILs),twenty two (21.5%) cases were high grade squamous cell intraepithelial lesions (H-SILs), 14(13.7%) cases were squamous cell carcinomas(SCC), 6 (5.8%) cases showed features of adenocarcinoma, 10(9.8%) cases showed cytology of atypical squamous cells of undetermined significance(ASCUS) and 4(3.9%) cases were of atypical glandular cells of undetermined significance(AGUS). Out of 102 cases, 88/102(86.27%) were positive for HPV and among them 32/88 (36%) cases were of HPV-16 and 56/88(64%) cases of HPV-18. There was strong association of HPV positivity with young age, early marriages, poor socioeconomic condition, abortions, multiparity and smoking but there was no association with multiple marriages. Conclusion: Frequency of HPV-18 was greater than HPV-16 in cervical neoplastic lesions and was strongly associated with certain known risk factors for cervical carcinoma.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Introduction: The HUMACTBP2 (SE33) locus is one of the most polymorphic markers commonly used in forensic human identification. Variability of SE33 was studied in 2 Calabria and Malta populations using the AmpFlSTR NGM SElect™ PCR Amplification Kit (Applied Biosystems) and the PowerPlex ESI 17 (Promega). Material & Methods: A total of 41 different alleles were observed in the 2 examined populations with no allele being more frequent than 10,5%. In the Maltese population more intermediate alleles than in Calabria were found. Allelic frequencies and statistical parameters of forensic interest (Dp,PE, RMP) were calculated using PowerStats v.1.2 software. Hardy-Weinberg equilibrium and other population parameters were calculated using Arlequin v.3.1 and TFPGA v1.3 softwares. Results: No significant deviations from Hardy–Weinberg equilibrium were found. Calabria and Malta allelic frequencies were compared to previously published population data and no significant differences were found. When comparing with Sicily no overall significant genetic distances were found, while comparison to other populations showed significant ones. Moreover comparison with non-European population showed no big distances between Germany and Morocco and between Hungary and Turkey. Conclusion: confirmed the locus is effectively highly polymorphic and useful not only for forensic identification but also in paternity cases in addition to the set of STRs loci commonly used.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Introduction: Congenital heart diseases (CHD) are one of the neglected and challenging areas in undeveloped countries. In Pakistan approximately 40-50,000 children are affected annually. A majority of these patients belongs to rural areas where properly medical facilities are out of reach. In the etiology of these diseases genetic profile, consanguinity and other factors should be examined carefully. The current study aims to check the genetic manipulations in patients for the NKX 2.5 gene specifically the untranslated gene of this gene. NKX 2.5, a transcription factor and first progenitor in cardiac formation, it encodes 324 amino acid and contains a homeodomain (142-200aa) which is highly conserved among vertebrates. To date, no data is available about the mutations in this gene responsible for CHD in Pakistani population. Material and Methods: A cohort of 225, CHD patients who were registered at National Institute of Cardiovascular Diseases (NICVD) from 2006-2009 were included in the study; these are non-syndromic and sporadic cases. Healthy 200 controls were also included with informed consents and detail family history was obtained. DNA was extracted and NKX 2.5 gene was amplified and sequenced to check mutations. Results: The mean age for patients TOF (2.97±1.21), PDA (2.95±2.55), D-TGA (1.84±2.26) and for controls (3.14±1.82) .In present study, two UTR alterations have been reported for NKX 2.5 one at 5' and other at 3'.In our study we look social and genetic aspects for these diseases. Conclusion: CHD is a major cause of child death in the first year of life. Our study concludes a few aspects and will broaden it to other genes as it is a need to find etiology of these diseases and to combat it with the modern genetic therapeutics.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Introduction: Warfarin/Acitrom administration dosage varies based on patient genotype with respect to the gene: Vitamin K epoxide reductase complex 1 (VKORC1). Ethnic diversity contributes to genotype variation. The frequency of polymorphism at VKORC1 in population of Hyderabad has not been reported in literature; hence the present study was conducted. Material & Methods: Genomic DNA from peripheral blood leukocytes of patients on warfarin/acitrom as well as normal control population without any thrombotic disease was extracted and Restriction Fragment Length Polymorphism (RFLP) pattern was established for 1173C>T transition by standard protocols. Result: The incidence of homozygote dominants (CC) genotypes were 74.63% and that of heterozygotes (CT) were 25.37 %. No recessives were found in the study group. Conclusion: Presently genotype based dosage is not implemented. This study through its collaboration with practising cardiologist while establishing the test at our diagnostic centre has also enabled awareness and consequently if followed will improve patient safety.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Introduction: The exact etiology of pterygium is unknown. Most of population based studies implicating that pterygium has a benign behavior rather than destructive condition. Changed expression of cell cycle-related genes may lead to the abnormal cell proliferation and finally to malignancy phenotype. The aim of this study was evaluation the expression profiles of APC in pterygium. Materials and Methods: The RNA extracted from the 23 pterygium tissues and 18 healthy tissues. After converting RNA to cDNA. The expression levels of these genes were assessed by real-time PCR. Results: The relative expression of APC gene in pterygium tissues was significantly different in comparison to conjunctiva tissues of healthy controls (mean ± SD was 1.82 ± 0.15 for cases versus 1.70  0.12 for controls, P value = 0.048). Conclusion: Detection of expression changes, leading to find molecular mechanism underlying the disease. As well as exploring pterygium markers paving the road for better therapy. We would like to propose further studies to identify exact molecular function of this gene in pterygium by using advanced molecular techniques such as RNAseq in various and larger genetic populations.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Tuberous sclerosis or tuberous sclerosis complex (TSC) is a rare multi-system genetic disease that causes non-malignant tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. Non specific psychiatric symptoms occur in substantial number of patients with Tuberous Sclerosis. Tuberous Sclerosis is a rare disorder and most of patients present with behavioural changes, which may be mistaken for variety of psychiatric disorders, though Mania has been rarely reported. Here we report a case of Tuberous Sclerosis with classic radiological findings and manic features. Skin showed typical facial angiofibromas and Ash leaf macules and MRI displayed classic Tubers. There have been very few case reports of Bipolar disorder manic phase and all studies have till now proposed the anatomical relation of tubers in the brain as the underlying mechanism of this psychopathology. The neuroanatomical abnormalities found in this patient could be a possible explanation of his manic symptoms.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Introduction: Leishmania and Mycobacterium Tuberculosis share many similarities in their pathogenesis and both pathogens are macrophage parasites. The present study was carried out to determine the diversity of TLR4 gene in VL and pulmonary TB as innate immunity marker. Materials and Method: Confirmed VL patients, pulmonary TB patients and healthy individuals DNAs were analyzedfor TLR 4 exon1 mutationsafter stimulation with live Leishmania promastigotes and BCG. PCR based sequencing was done to determine the diversity of for toll-liked receptor 4 exon-1. Results: Three polymorphisms were detected for the first time in TLR4 exon1, TLR4-35C/T and TLR4-5C/T located in the transcription factor binding site, and TLR4+18C/T located in the coding region which resulted in the change from the amino-acid Threonine (polar) to Alanine (non-polar). Conclusion: The diversity in TLR4 suggests possible variation in the innate immune responses of the two patients groups.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Introduction: Suicide attempt (SA) is in the middle of continuum of complex suicidal behavior phenotype. Psychiatric disorders and acute stressful life events (SLEs) are triggers for suicidal behavior. Serotonin system genes are often implicated in suicidal behavior. Tryptophan hydroxylase 2 (TPH2), exclusively expressed in the brain, is the rate-limiting enzyme for serotonin biosynthesis. TPH2 may be enrolled in stress-response mechanisms via hypothalamic–pituitary–adrenal axis, while TPH2 variant rs7305115 has been reported to affect gene expression in postmortem human pons. To date, only poor examination of this variant in etiology of suicidal behavior has reported conflicting results. The aim of the present study was to assess rs7305115 main effect and its interaction with acute SLEs in SA pathology among Serbian psychiatric patients. Methods: 165 suicide attempters and 188 suicide non-attempters, suffering from major psychiatric disorders, participated in the study. Acute SLEs score was assessed using the List of Threatening Experiences Questionnaire. Variant rs7305115 was genotyped using TaqMan-based allelic discrimination assay. Statistical analyses were done in SNPstats by applying logistic regression adjusted by psychiatric diagnoses. Results: Variant rs7305115 was not associated with SA in Serbian psychiatric patients, neither alone, nor in combination with acute SLEs, for all five models of inheritance tested (P>0.05). Discussion: Our finding does not support the main and moderating implication of TPH2 variant rs7305115 in SA liability among Serbian psychiatric patients. Further examination in larger samples of this variant in SA patology is necessary due to its functional relevance.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Cancer is nowadays one of the main causes of death worldwide. The numbers have shown that one in three people will develop cancer at some point in their lives. Cancer is a major issue for the whole humanity, and therefore a lot of research has been running for the past years in order to understand the mechanisms that underlie tumorigenesis and eventually cancer formation, with the perspective to discover new approaches for effective treatment. Gene therapy strategies that intended to tackle cancer systemically are often impaired by inefficient delivery of the vector to the tumor site. Several studies have shown the possibility of using mesenchymal stem cells (MSCs) as a future therapeutic mechanism against cancer, since they possess important features such as the ability to home to and target cancer cells. The engineering of MSCs to produce and deliver an apoptotic factor, calledtumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been studied excessively. TRAIL is a transmembrane protein that causes selective apoptosis of tumor cells but does not have any harmful effects on the normal neighboring cells. Experiments have shown that this approach has significant results in mouse models and has now proceeded for clinical trials.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Aim: we investigatedthe frequency of expression of HOXA9 gene in adult Egyptian acute myeloid leukemia (AML) patients and its relation to different cytogenetic abnormalities. Methods: 30 newly diagnosed AML patients (group 1) were the subject of our study. Ten healthy persons of matched age and sex were considered group ll (controls). Estimation of HOXA9 expression in AML blasts by RT-PCR was done to both groups. Results: Normal cytogenetic analysis was present in 20 cases (66.6%), t(15,17) in 3 cases, t(8,21) in 3 cases, 45 xy -7 in 1 case, t(16,16) in 1 case, 45 xy-20 in 1 case and 46 XX 1P+ in 1 case. NUP 98 -HOXA 9 gene was not detected in any of the studied case or in the control group. Conclusion: absence of HOXA9 gene in our randomly selected patientsmay be related to its rarity in Egyptian population. However, further studies including larger population is still needed to confirm this finding with special stress on poor cytogenetic group

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

A case of a derivative chromosome 7 formed by a ring chromosome 7 and t(7;9) was found who presented with dimorphic anaemia with no other anomaly. Ring chromosome 7 was characterized by conventional and molecular cytogenetic techniques.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

Most diseases involve many genes in complex interactions, in addition to environmental influences. The genetic susceptibility to a particular disease due to the presence of one or more gene mutations, and/or a combination of alleles need not necessarily be abnormal. Understanding genetic predisposition to disease and knowledge of lifestyle modifications that either exacerbates the condition or that lessen the potential for diseases is necessary for the societies to make informed choices. The aim of this narrative review is to identify an optimal candidate gene and its single nucleotide polymorphism in metabolic syndrome. The prevalence of non-communicable disorders such as metabolic syndrome (MetS) is high in developing countries such as Iran. The Tehran Lipid and Glucose Study (TLGS) was one of the first studies reporting this high incidence. The present review aims to discover the genetic variant reported in association with MetS. The database for genotypes and phenotypes (dbGaP) and the database for genetic associations and human genome (HuGE navigator) were utilized in order to search for genes and their corresponding polymorphisms related to MetS. Additionally, an electronic literature search for other Iranian studies and the genetic aspect of TLGS was completed using PubMed. The results distinguished six of the most important genetic regions found to have strong association with MetS.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

B cell ALL is a subtype of Acute lymphoblastic leukemia (ALL). Till date, 3 dicentric's: dic (7;9), dic(9;12) and dic(9;20) with t(9;22) were reported in B- ALL . The hematological profile revealed a white blood cell count of 324.3 ×10³/mm3 with 74% blasts, a hemoglobin level of 6.2 g/dl and a platelet count of 50X109 /mm. Trephine biopsy revealed proliferations of blasts which are medium sized to large and had vesicular nuclei with indented nucleoli. The biochemical parameters were normal except elevated liver AST (67U/L);ALT(121U/L);GGTP(159U/L), alkaline phosphatase (251U/L) profiles and renal urea (46mg/dl),Creatinine (1.446mg/dl) and sodium (135mEq/L). The patient was positive for the Immunophenotypic markers CD10/CD19/CD34/ CD33 by Flowcytometry. Diagnosis of B- ALL was made. To our knowledge this dic(1;15)(p11:p11) with t(9;22) (q34;q11) is the first kind of report in B-ALL. Further molecular studies are required to elucidate the pathogenesis and prognostic significance of dic(1;15) in leukemia.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Psychiatric diseases and their diagnosis are basically dependent upon phenomenology, other than a few conditions where the focus is on purely the medical condition. The changing and evolving picture of psychiatric nosology inculcates genetic findings as well. It has helped clinicians in understanding the disease pathology, its course, prognosis and the intervention options. This comprehensive, pedagogically-oriented review is aimed to include different advancements in genetic association studies along with various terms and findings in psychiatry, which have facilitated deeper understanding of illness at the molecular level. Findings on Alzheimer's disease, Autism spectrum disorder, schizophrenia and eating disorders are discussed. Existing interventions can be further modified by addition of modulators, inhibitors of A-beta aggregation, immunotherapy and inhibitors which can be generated on the basis of genetic association studies and its findings.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Relative contribution of genetic and environmental risk factors in complex disorders is widely explored through discordant identical twins. Multiple sclerosis is a demyelinating disease of the central nervous system in which the interplay of genetic and environmental risk factors define the disease pathogenicity. Robust epidemiological studies in different populations suggested that active levels of serum vitamin D and viral load implicate in MS pathogenicity and severity. In order to refine non-shared components of susceptibility factors in MS, we investigated the role of serum 25-hydroxyvitamin D and viral infection in a pair of identical twins remained discordant for MS during the course of 5 years follow up. Here we report serological finding regarding the viral load and serum 25-hydroxyvitamin D level in a pair of discordant monozygotic twins. Based on our observation, lower levels of serum 25-hydroxyvitamin D and higher anti-viral IgG titre was consistent with the disease statues in the affected sib.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]