Prevalence and Association of Obesity with Self-Reported Comorbidity: A Cross-Sectional Study of 1321 Adult Participants in Lasbela, Balochistan.

Association of fatness with chronic metabolic diseases is a well-established fact, and a high prevalence of risk factors for these disorders has increasingly been reported in the third world. In order to incorporate any preventive strategies for such risk factors into clinical practice, decision-makers require objective evidence about the associated burden of disease. A cross-sectional study of 1321 adults from one of the districts of Balochistan, among the most economically challenged areas of Pakistan, was carried out for the measures of fatness and self-reported comorbidities. Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) were measured and demographic information and self-reported comorbidities were documented. The prevalence of obesity was 4.8% (95% CI: [3.8, 6.1]) and 21.7% (95% CI: [19.5, 24.0]), as defined by the World Health Organization (WHO) international and Asia/Asia-Pacific BMI cut-offs, respectively. The proportion exhibiting comorbidity increased with increasing levels of fatness in a dose-response relationship (p value < .001). An interaction of weight status with gender was observed to produce a significantly (p = .033) higher comorbidity among overweight women (odds ratio (OR) = 6.1 [1.2, 31.7]) compared with overweight men (OR = 1.1 [0.48, 2.75], p = .762).

t(8;21) myelodysplasia, an early presentation of M2 AML.

The reciprocal translocation of genetic material between chromosomes 8 and 21, t(8;21), is usually restricted to cases of acute myeloid leukaemia (AML). Cases of AML with t(8;21) exhibit characteristic dysplastic features in myeloid and erythroid lineages with reduction in megakaryocytes. We report details of three patients presenting with myelodysplastic features; two had a typical t(8;21), and the third had a variant t(8;21) translocation. We discuss the significance of t(8;21) in the aetiology of myelodysplastic syndrome (MDS) and implications for the management of such patients.

Retrovirally transduced antisense sequences stably suppress P210BCR-ABL expression and inhibit the proliferation of BCR/ABL-containing cell lines.

There is now strong evidence that the BCR-ABL gene product of the Philadelphia chromosome (P210) plays a crucial role in the pathogenesis of chronic myeloid leukemia (CML). We have previously shown that introduction of antisense oligonucleotides into K562 cells could transiently block the expression of P210 and specifically inhibit cellular growth in culture. In this report, we describe the use of a retroviral vector to introduce selected antisense and sense sequences, first into murine B10 cells, previously rendered interleukin-3 (IL-3) independent by transfection of BCR-ABL sequences, and second into K562 cells. The antisense transcripts generated under the control of MoMLV promoter specifically killed B10 cells in the absence of IL-3 and inhibited P210 expression almost completely. In K562 cells, the antisense sequences led to a dramatic reduction of P210 expression and increased their doubling time by more than twofold. This effect was not reversed by the addition of exogenous IL-3 to the culture medium. Control HeLa or HL60 cells infected with the same constructs did not show any change in proliferation rate, despite abrogation of the normal BCR gene products. Rather unexpectedly, P210 suppression was not lethal in K562 cells, showing that such a cell line does not rely entirely on the expression of P210 for surviving, but depends on it as far as growth properties are concerned. We conclude that this approach can successfully achieve stable suppression of the oncogenic protein P210 and may be used to study further the mechanisms by which P210 is transforming cells. The effect on fresh CML cells in bone marrow cultures remains to be assessed before we can tell whether this technique may be used for selective suppression of leukemic hematopoiesis in vitro.

Inhibition of P210BCR/ABL Expression in K562 Cells by Electroporation with an Antisense Oligonucleotide.

We designed experiments to study the effects on P210BCR/ABL expression of introducing antisense oligonucleotides into K562 cells. We used two antisense oligonucleotides: one (AS1) is complementary to the first coding codon of the BCR/ABL mRNA and the two 5' and three 3' codons, and the other (AS2) to BCR coding codons 5 to 11 inclusive. To facilitate entry of the oligonucleotides the K562 cells were subjected to electroporation on three occasions at 24 hr intervals (0, 24 and 48 hr). P210BCR/ABL expression was assayed by in vivo phosphorylation followed by immune precipitation with a BCR antibody. Introduction of AS1 inhibited P210BCR/ABL expression at 72 and 96 hrs, whereas AS2 and the control oligonucleotide had no effect. AS1 also killed K562 cells. We conclude that selected antisense oligonucleotides can modify leukaemia-specific protein expression in K562 cells. This approach could prove valuable for purging CML bone marrow cells in vitro.