Posted by James
This report uses the microsatellite repeats (TCAT)n on chromosome 11 to investigate the tyrosine hydroxylase gene as IDDM2, the second major candidate gene for susceptibility to type-1 diabetes. No significant association was found either at the allele level or at the genotype level. This data is in contrast with findings in previous association studies that detected a significant association of hTH with type-1 diabetes in Caucasians. The data reported here for African Americans was consistent with findings reported by Field and coworker in a family study that failed to demonstrate significant evidence of linkage between type-1 diabetes and hTH, either by lod score or affected sibling pair linkage analysis. No association was found with hTH in another study that used restriction fragment polymorphism. The exact localization of the IDDM2 and the depiction of its effect on the expression of hTH, INS, and IGF2 may prove to be important in understanding the biological mechanisms that lead to the onset of type-1 diabetes and its complications. The study of microsatellite sequences has shown that they may have a function in recombination, in the generation of nucleosome positioning signals, and more subtle effects on expression. Previous studies have shown that hTH tetranucleotide repeat acts as a transcriptional enhancer in vitro. Moreover, these repeated sequences interact specifically and with high affinity with nuclear proteins.
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Posted by James
Five alleles were identified in this African-American population in the Washington, DC area labeled K5 (244 bp), K4 (248 bp), КЗ (252 bp), K2 (256 bp), and Kl (260 bp) (Table 2). The allele frequencies of the five alleles were estimated from 196 chromosomes of unrelated controls and 96 chromosomes of type-1 diabetes individuals. The heterozygosity of the TCAT marker was larger than 0.75. The most frequent allele of the hTH microsatellite repeats was K5 (248 bp), with a frequency 0.62 in controls and 0.66 in type-1 diabetes patients, which was not significantly different. The largest allele (260 bp) showed the greatest difference in allele frequency between patients and controls.
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Posted by James
All type-1 diabetes cases were African-American, randomly selected from a Washington, DC population-based type-1 diabetes registry. The patients included in this registry were collected between from 1990 to 1999 as part of the World Health Organization’s multinational Project for Childhood Diabetes (Diamond project). The age range of disease onset was 0.5-17 years and the male/female ratio was 0.733. The World Health Organization (WHO) definition of type-1 diabetes was employed for this study. The criteria include history of ketoacidosis and daily insulin injection before the 17th birthday. All patients were residents of the Washington, DC metropolitan area at the time of the first insulin administration.
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Posted by James
INTRODUCTION
Polymorphisms in the tyrosine hydroxylase-insulin-insulin like growth factor 2 gene-regions (TH-INS-IGF2) on chromosome 11 were shown to have an association with type-1 diabetes. It is not yet clear whether TH gene carries susceptibility for type-1 diabetes. In the human, hTH molecules are encoded by at least three distinct messenger RNAs. The expression of these mRNAs varies in different parts of the nervous system. The calculated relative molecular mass of the deduced protein sequence is 55,473. Tyrosine hydroxylase is the first enzyme in the pathway of catecholamine synthesis. It catalyzes the formation of 3,4-dihydrox-yphenylalanine (DOPA) from tyrosine. hTH plays a central role in the neuronal transmission and hormonal action of catecholamines. Expression of the hTH gene is regulated in a tissue-specific fashionand is modulated by a variety of factors, such as cyclic AMP, glucorticoids, and trans-synaptic stimuli. The pathogenesis of some disorders of cate-cholaminergic neurons, such as schizophrenia, may be related to changes in hTH. The role of hTH in the pathogenesis of type-1 diabetes is not known, but many investigators are examining target organs, such as islet cell nerve and retina, for possible functional roles of hTH polymorphism. The hTH gene is located on chromosome llpl5.5 is composed of 14 exons interrupted by 13 introns, and spans ~8.5 kb.
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Posted by James
The findings are encouraging in that physicians in Nigeria demonstrated an awareness of smoking among their patients, routinely assessed smoking status, and believed that counseling patients about smoking would help them quit. Physician estimates of smoking among adults in Nigeria (31% for males, 7% for females) were somewhat higher than published prevalence data (15% for adult males, 2% for adult females), indicating that they either have inflated perceptions of smoking or smokers are disproportionately represented in their patient population. Also encouraging is that the majority of physicians made an effort to identify patients who are smokers and believed it was important for these patients to quit. Additionally, physicians in Nigeria thought that counseling smokers would help them quit, suggesting their belief in the importance of physician-assisted smoking cessation interventions.
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Posted by James
Of the 619 physicians surveyed, 373 completed the survey (60% response rate). Of the final sample, 187 physicians were from Hospital A, and 186 were from Hospital B. Characteristics of the sample are presented in Table 1.
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Posted by James
Participants and Study Setting
Participants were physicians at two teaching hospitals, University of Ilorin, Ilorin, Kwara State and University College Hospital, Ibadan, Oyo State, both located in the southwestern region of Nigeria. Hospitals were comprised of a main campus made up of multiple hospital buildings. The physicians participating in this study worked in different buildings throughout the hospital campus. The workplace smoking policy was determined by the hospital; however, enforcement of the policy was the responsibility of the department(s) occupying each building (K.S. Okuyemi, personal communication, January 21,2004).
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