Emergence and scattering of multiple neurofibromatosis (NF1)-related sequences during hominoid evolution suggest a process of pericentromeric interchromosomal transposition

Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase activating protein family and is considered to be a tumor suppressor gene. Its very high rate of de novo mutation in humans led us to study a specific feature of this gene: the presence of numerous NF1-related sequences. According to our results, the human genome contains at least 11 NF1-related sequences, nine of which are scattered near centromeric sequences of seven different chromosomes. These NF1-related sequences, whose extent is quite varied according to loci, are unprocessed copies of the NF1 gene, and bear numerous mutations. A phylogenetic analysis of the six largest sequences indicates that they are all derived from a common ancestor, which would have appeared 22-33 million years ago, and was subsequently duplicated several times during hominoid evolution. The most recent duplication and interchromosomal transposition occurred in the last million years suggesting that the process could still be ongoing. Intriguing similarities between the evolution of alpha- satellite DNA and NF1-related sequences suggest the involvement of a common genetic mechanism for the generation and pericentric spreading of these NF1 partial copies.      

Ghrelin expression in hyperplastic and neoplastic proliferations of the enterochromaffin-like (ECL) cells

Ghrelin, a recently discovered peptide isolated from the gastric corpus mucosa, is believed to be important in the regulation of growth hormone secretion and has been shown to increase appetite and food intake as well. It may also have other gastrointestinal and cardiac functions. Because a cell of origin for ghrelin has not been convincingly identified in the gastric mucosa thus far, we studied the immunohistochemical expression of ghrelin in proliferative lesions of the enterochromaffin-like (ECL) cells—a cell that is not only exclusively confined to the gastric corpus mucosa but is its dominant endocrine cell type as well. Formalin-fixed, paraffin embedded tissues from three cases of gastric ECL cell hyperplasia and five ECL carcinoids (three with coexisting foci of diffuse, linear, and micronodular hyperplasia) were immunohistochemically stained for ghrelin, using a commercially available antibody. The Sevier-Munger stain for ECL cells and immunohistochemical stains for chromogranin, gastrin, serotonin, somatostatin, and vesicular monoamine transporter-2 (VMAT-2) were performed on parallel sections for correlation with the ghrelin staining results. All ECL cell carcinoids and hyperplastic lesions were positive for both the Sevier-Munger and the immunohistochemical stains for chromogranin and VMAT-2. Immunoreactivity for ghrelin was seen in 4/5 ECL carcinoids, all cases of ECL cell hyperplasia, as well as in all areas with linear and micronodular hyperplasia adjacent to the ECL cell carcinoids. In each instance, such staining was confined to the Sevier-Munger, and VMAT-2 positive cells only. Our findings indicate that the ECL cells are either the ghrelin-producing cells of the gastric mucosa or acquire the capability to synthesize ghrelin during proliferative states encompassing the entire hyperplasia to neoplasia spectrum. In view of the orexigenic and other known actions of ghrelin, the functional and/or biologic significance of ghrelin production in such ECL cell proliferations needs to be investigated further.     

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

ANTIBIOTIC RESISTANCE PATTERN OF ISOLATES FROM WOUND AND SOFT TISSUE INFECTIONS

Two-hundred and eighty bacterial isolates from wound and soft tissue infections were studied for species identification and antibiotic resistance pattern. Amongst them 122 isolates were from community acquired infection and 158 were from nosocomial infections. The common community acquired pathogens were Staphylococcus aureus (67.8%) and Streptococcus pyogenes (10.7%), whereas Staphylococcus aureus (60.1%) and E. Coli (8.9%) were common in nosocomial infection. Only two anaerobes (Cl perfringens) were isolated. Penicillin resistance was found to be 87% and 92% for Staphylococccus aureus in community acquired and noscomial infections respectively. 85% of Proteus isolates were resistant to ampicillin. There was relatively lower level of resistance by all isolates to cefotaxime. Gentamicin showed higher rate of resistance than netilmicin and amikacin. Resistance of E. coli isolates to fluoroquinolones being 79% for norfloxacin, 81% for ciprofloxacin and 60% for ofloxacin. The study showed a higher resistance of methicillin resistant Staphylococcus aureus (MRSA) to other antibiotics. Amikacin and ofloxacin were the best recommended drugs for empirical therapy for all organisms, the susceptibility rate being 80.7% and 80.4%.KEY WORDS: Antibiotic resistance, Soft tissue infections, Wound infections     

再发性低血糖对幼鼠脑内GLUT1及GLUT3表达的影响

目的观察再发性低血糖后脑内葡萄糖转运蛋白1(glucose transporter 1,GLUT1)及葡萄糖转运蛋白3(GLUT3)表达的变化,从而探讨无症状低血糖的发生机制。方法将80只15日龄野生型小鼠随机分为正常对照组及低血糖组,每组40只。低血糖组给予正规胰岛素腹腔注射3次,每次剂量为5U/kg,对照组注射等体积生理盐水。两组分别在最后1次注射后12、24、48及72 h处死小鼠取脑组织(每组每时间点10只),应用免疫组化方法观察小鼠脑内GLUT1及GLUT3表达的变化。结果低血糖后脑内微血管上GLUT1表达有增加趋势,皮质增加高于海马,72 h皮质GLUT1表达显著高于对照组;低血糖后48、72 h皮质及海马GLUT3表达均显著高于相应对照组。结论再发性低血糖后脑内GLUT1及GLUT3适应性增高,这种适应既能节省神经元的能量代谢,但也能削减神经元对低血糖的反应。     

Management practices of tuberculosis in children among pediatric practitioners in Mangalore,South India

Introduction

In spite of having BCG vaccination and tuberculosis control program for the last 50 years, prevalence of tuberculosis continues to be high in India. Inadequate diagnostic methods, suboptimal treatment and monitoring, and the lack of vigilant reporting system are some of the contributing factors for the failure of TB control.

Prevalence of peripheral neuropathy among type 2 diabetes mellitus patients in a rural health centre in South India

International Journal of Diabetes in Developing Countries - There is a huge burden of diabetes-related complications, both microvascular and macrovascular, in India. With the rising prevalence of...     

How the Term ‘Self-Management’ is Used in HIV Research in Low- and Middle-Income Countries: A Scoping Review

AIDS and Behavior - This scoping review assessed how the term ‘self-management’ (SM) is used in peer-reviewed literature describing HIV populations in low- and middle-income countries...