MicroRNAs expression profiles as biomarkers and therapeutic tools in Turkish patients with chronic myeloid leukemia.

AIM: In 95 % of Chronic myeloid leukemia (CML) patients, chromosomal translocation resulting in the formation of the Philadelphia (Ph) chromosome (t:9;22) is observed, which in turn leads to the formation of the BCR-ABL fusion gene. MicroRNAs (miRNAs) are a group of small and non-coding RNAs modulating gene expression via binding to the target mRNAs. We aimed to characterize the expression profiles of various miRNAs in different stages of Ph(+) CML patients. METHODS: This case-controlled study was conducted in 75 CML patients and 25 healthy controls. The subjects were categorized into 4 groups; newly diagnosed patients, treatment-response patients, treatment-failure patients, and healthy controls. Expressions of miRNAs was analyzed by RT-PCR. RESULTS: miR-150 expression was downregulated in the treatment failure patients compared to the control group (p = 0.003212) while miRNA 148b expression up-regulated in the treatment failure patients than the control group (p = 0.038016). miR-10a expression was up-regulated in newly diagnosed and treatment response patients compared to control group (p = 0.003934, p = 0.000292, respectively). It was found that miR-10a expression increased 11.17- fold in newly diagnosed patients and 9.82-fold in treatment response patients than in the control group. CONCLUSION: Our data suggest that expression profiles of miR-10a, miR-150, and miRNA 148b were correlated as biomarker and therapeutic tool in Turkish patients with CML (Tab. 2, Fig. 1, Ref. 30).

Prevalence of non-communicable disease risk factors in three sites across Papua New Guinea: a cross-sectional study.

Papua New Guinea (PNG) is a culturally, environmentally and ethnically diverse country of 7.3 million people experiencing rapid economic development and social change. Such development is typically associated with an increase in non-communicable disease (NCD) risk factors. AIM: To establish the prevalence of NCD risk factors in three different regions across PNG in order to guide appropriate prevention and control measures. METHODS: A cross-sectional survey was undertaken with randomly selected adults (15-65 years), stratified by age and sex recruited from the general population of integrated Health and Demographic Surveillance Sites in West Hiri (periurban), Asaro (rural highland) and Karkar Island (rural island), PNG. A modified WHO STEPS risk factor survey was administered along with anthropometric and biochemical measures on study participants. RESULTS: The prevalence of NCD risk factors was markedly different across the three sites. For example, the prevalences of current alcohol consumption at 43% (95% CI 35 to 52), stress at 46% (95% CI 40 to 52), obesity at 22% (95% CI 18 to 28), hypertension at 22% (95% CI 17 to 28), elevated levels of cholesterol at 24% (95% CI 19 to 29) and haemoglobin A1c at 34% (95% CI 29 to 41) were highest in West Hiri relative to the rural areas. However, central obesity at 90% (95% CI 86 to 93) and prehypertension at 55% (95% CI 42 to 62) were most common in Asaro whereas prevalences of smoking, physical inactivity and low high-density lipoprotein-cholesterol levels at 52% (95% CI 45 to 59), 34% (95% CI 26 to 42) and 62% (95% CI 56 to 68), respectively, were highest in Karkar Island. CONCLUSION: Adult residents in the three different communities are at high risk of developing NCDs, especially the West Hiri periurban population. There is an urgent need for appropriate multisectoral preventive interventions and improved health services. Improved monitoring and control of NCD risk factors is also needed in all regions across PNG.

Genetics analysis with down syndrome and histopathological examination of buccal epithelial cells / Análisis genético y examen histopatológico de las células epiteliales bucales en pacientes con síndrome de down

Down syndrome is primarily caused by trisomy of chromosome 21. We reviewed cytogenetic studies performed on 1048 patients who were referred to the Cytogenetics Unit at Dicle University Hospital, Diyarbakir, Southeast Turkey, between 2000 and 2009. The cases were grouped according to the reason of referral for cytogenetic analysis. The highest frequencies of abnormal karyotypes were found among cases that were referred due to suspicion of Down syndrome (84.8 percent). For histologic examination to persons with Down syndrome and normal, buccal mucosa smear was prepared by rubbing. Down syndrome are disabled and control groups were compared statistically buccal epithelial cells and nuclei (p<0.05). Periphery of the nucleus in some patients with Down's syndrome, while the bud structures in the form of micronuclei was observed in the karyolytic cells.

El síndrome de Down es causado principalmente por la trisomía del cromosoma 21. Se revisaron los estudios citogenéticos realizados en 1.048 pacientes que fueron remitidos a la Unidad de Citogenética del Dicle University Hospital, Diyarbakir, sudeste de Turquía, entre los años 2000 y 2009. Los casos se agruparon de acuerdo a la razón de referencia para el análisis citogenético. Las frecuencias más altas de cariotipos anormales se encontraron ent los casos que fueron remitidos por sospecha de síndrome de Down (84,8 por ciento). Para el estudio histológico de las personas con y sin síndrome de Down, se realizó el frotis de mucosa oral por hisopado. Los grupos con síndrome de Down y de control (sin síndrome) se compararon estadísticamente en relación a las células epiteliales orales y los núcleos (p <0,05). Se observaron núcleos periféricos en algunos pacientes con síndrome de Down, mientras que estructuras de tipo brotes en la forma de micronúcleos se observaron en las células cariolíticas.

Chromosome heteromorphisms are more frequent in couples with recurrent abortions.

Chromosomal heteromorphism is considered a variant of a normal karyotype, but it is more frequent in couples with repeated miscarriages. We investigated chromosomal heteromorphism in couples with repeated miscarriages in comparison with a control group. A total of 455 couples who applied to our genetic diagnosis laboratory in Diyarbakir, Turkey, were evaluated for chromosome heteromorphisms; 221 of these couples (the study group) had recurrent abortions and 234 of them (the control group) had no history of abortions and had at least one living child. The patient group of couples with recurrent abortions were found to have a significantly higher rate of chromosome heteromorphism (8.4%) in comparison with the control group (4.9%). When the patients were evaluated according to gender, males had a significantly higher rate of chromosome heteromorphism (11.3%) than females (5.4%). We conclude that since couples with recurrent abortion and males have higher rate of chromosome heteromorphism, cases of heteromorphism should not be disregarded in the etiological investigation of recurrent abortions. Further research should be done to investigate the phenotypic effects of chromosome heteromorphism.

Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B

Polymorphisms of the p53 gene, which participates in DNA repair, can affect the functioning of the p53 protein. The Arg and Pro variants in p53 codon 72 were shown to have different regulation properties of p53-dependent DNA repair target genes that can affect various levels of cytogenetic aberrations in chronic hepatitis B patients. The present study aimed to examine the frequency of chromosomal aberrations and the mitotic index in patients with chronic hepatitis B and their possible association with p53 gene exon 4 codon 72 Arg72Pro (Ex4+119 G>C; rs1042522) polymorphism. Fifty-eight patients with chronic hepatitis B and 30 healthy individuals were genotyped in terms of the p53 gene codon 72 Arg72Pro polymorphism by PCR-RFLP. A 72-h cell culture was performed on the same individuals and evaluated in terms of chromosomal aberrations and mitotic index. A high frequency of chromosomal aberrations and low mitotic index were detected in the patient group compared to the control group. A higher frequency of chromosomal aberrations was detected in both the patient and the control groups with a homozygous proline genotype (13 patients, 3 control subjects) compared to patients and controls with other genotypes [Arg/Pro (38 patients, 20 control subjects) and Arg/Arg (7 patients, 7 control subjects)]. We observed an increased frequency of cytogenetic aberrations in patients with chronic hepatitis B. In addition, a higher frequency of cytogenetic aberrations was observed in p53 variants having the homozygous proline genotype compared to variants having other genotypes both in patients and healthy individuals.

Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B.

Polymorphisms of the p53 gene, which participates in DNA repair, can affect the functioning of the p53 protein. The Arg and Pro variants in p53 codon 72 were shown to have different regulation properties of p53-dependent DNA repair target genes that can affect various levels of cytogenetic aberrations in chronic hepatitis B patients. The present study aimed to examine the frequency of chromosomal aberrations and the mitotic index in patients with chronic hepatitis B and their possible association with p53 gene exon 4 codon 72 Arg72Pro (Ex4+119 G>C; rs1042522) polymorphism. Fifty-eight patients with chronic hepatitis B and 30 healthy individuals were genotyped in terms of the p53 gene codon 72 Arg72Pro polymorphism by PCR-RFLP. A 72-h cell culture was performed on the same individuals and evaluated in terms of chromosomal aberrations and mitotic index. A high frequency of chromosomal aberrations and low mitotic index were detected in the patient group compared to the control group. A higher frequency of chromosomal aberrations was detected in both the patient and the control groups with a homozygous proline genotype (13 patients, 3 control subjects) compared to patients and controls with other genotypes [Arg/Pro (38 patients, 20 control subjects) and Arg/Arg (7 patients, 7 control subjects)]. We observed an increased frequency of cytogenetic aberrations in patients with chronic hepatitis B. In addition, a higher frequency of cytogenetic aberrations was observed in p53 variants having the homozygous proline genotype compared to variants having other genotypes both in patients and healthy individuals.

New homozygous SPINK5 mutation, p.Gln333X, in a Turkish pedigree with Netherton syndrome.

Netherton syndrome (NS) is a rare autosomal recessive genodermatosis caused by loss-of-function mutations in the SPINK5 gene. The clinical features include congenital ichthyosis, trichorrhexis invaginata and atopy. In this study, we report a new homozygous SPINK5 mutation, p.Gln333X, responsible for NS in affected members of two closely related Turkish families, and provide an overview of the genotype-phenotype correlation in this condition.

Vitamin A status of pre-school-age children aged 6 to 59 months in the National Capital District, Papua New Guinea.

Assessing the vitamin A status among pre-school-age children is essential for evaluating the magnitude and public health status of vitamin A deficiency in a population. This cross-sectional study assessed the vitamin A status of children aged 6 to 59 months resident in the National Capital District (NCD), Papua New Guinea. Children attending the Children's Outpatient Clinic at Port Moresby General Hospital participated in this study. Informed consent was obtained from parents before using blood samples from their children. Assay of plasma retinol was carried out using the 'Clin-Rep' complete kit for assay of vitamins A and E in plasma by high performance liquid chromatography (HPLC). A commercial enzyme immunoassay kit was used to assay C-reactive protein (CRP) in plasma. Of the 132 children in the study 108 (82%) had received vitamin A capsules. The median plasma retinol concentration of the 132 children was 0.98 micromol/l and the interquartile range 0.65-1.38 micromol/l. Of the 132 children, 35 (27%) had a plasma retinol concentration below 0.70 micromol/l. 75 children (57%) had normal plasma CRP levels and in 57 (43%) the CRP levels were elevated. The median plasma retinol concentration of the children with normal plasma CRP was 1.19 micromol/l and the interquartile range 0.93-1.50 micromol/l. The prevalence of vitamin A deficiency (VAD) in the children with normal plasma CRP was 11%, indicating a moderate public health problem. 74 (56%) males and 58 (44%) females were included in the study. The prevalence of VAD in the male and female children with normal plasma CRP was 14% and 8%, respectively, indicating a moderate public health problem among the male children and a mild public health problem among the female children. The prevalence of subclinical (mild to moderate) and marginal VAD among the children with and without elevated CRP strongly suggests the need for continuous monitoring of the vitamin A status of the vulnerable groups in NCD.

A small supernumerary marker chromosome, derived from chromosome 22, possibly associated with repeated spontaneous abortions.

We report a phenotypically normal couple with repeated spontaneous abortions and without other clinical features. Clinical, hematological, biochemical, and endocrinological aspects of the couple did not reveal any abnormalities. The karyotype of the wife was normal (46,XX), while the husband was found to have an abnormal karyotype, 47,XY,+der(22)mat. The marker chromosome was familial and non-satellite. Although the potential risk of small supernumerary marker chromosomes for spontaneous abortions cannot be defined precisely, marker chromosomes, together with methods used for ascertainment, are also factors to be considered when investigating infertility consequences. Furthermore, identification of the origin of a marker chromosome may provide additional information for patient karyotype-phenotype correlations. Further studies, such as molecular analyses to identify the breakpoint, are necessary for investigating phenotype-genotype correlations and assessment of genetic risks for small secondary chromosomes. The cause of repeated spontaneous abortions in this couple might be the presence of this marker chromosome in the husband. Consequently, we recommended genetic counseling before further pregnancies.

Cytogenetic analysis of 4216 patients referred for suspected chromosomal abnormalities in Southeast Turkey.

We reviewed cytogenetic studies performed on 4216 patients who were referred to the Cytogenetics Unit at Dicle University Hospital, Diyarbair, Southeast Turkey, between 2000 and 2009. The cases were grouped according to the reason of referral for cytogenetic analysis. The frequencies of the different types of numerical and structural abnormalities were determined, and the relative frequency of cases with abnormal karyotypes was calculated in each group. The most common reason for requesting cytogenetic testing was referral for Down syndrome and for repeated abortions. The highest frequencies of abnormal karyotypes were found among cases that were referred due to suspicion of Down syndrome (84.8%). Among the chromosomal abnormalities, sexual chromosomal abnormalities were found in 239 cases (17.6%), and Klinefelter syndrome was the most frequent sex chromosomal abnormality. Autosomal abnormalities were found in 1119 cases (82.4%), and Down syndrome was the most frequent autosomal chromosomal abnormality. In conclusion, the high rate of chromosomal abnormalities (32.2%) found in this population demonstrates the importance of cytogenetic evaluation in patients who show clinical abnormalities. This is the first report on cytogenetic testing in the southeast region of Turkey. This type of study provides a basis for determining the risks of recurrence and for deciding on clinical treatment and genetic counseling.

Surgical management of spinal tuberculosis in Papua New Guinea.

Two cases of spinal tuberculosis (TB) presented with deteriorating myelopathy despite chemotherapy. Surgery of anterior decompression and fusion was successfully carried out resulting in both the patients ambulating and being continent on discharge. This highlights the importance of early surgery and a multidisciplinary approach to the management of this condition.

Surgical management of spinal tuberculosis in Papua New Guinea

Two cases of spinal tuberculosis (TB) presented with deteriorating myelopathy despite chemotherapy. Surgery of anterior decompression and fusion was successfully carried out resulting in both the patients ambulating and being continent on discharge. This highlights the importance of early surgery and a multidisciplinary approach to the management of this condition.