Somatic mutations are frequent and increase with age in human kidney epithelial cells

We have used a primary cloning assay to determine the frequency of 6- thioguanine (TG)-resistant tubular epithelial cells in kidney tissue from 72 human donors ranging in age from 2 to 94 years. The frequency of TG-resistant mutants ranged from approximately 5 x 10(-5) for donors in the first decade of life to approximately 2.5 x 10(-4) for donors in the eighth and later decades of life. Two different statistical analyses indicated that this increase in mutant frequency is exponential with age. We also observed a 2-fold higher TG-resistant mutant frequency in nephrectomy kidneys containing a coincident renal carcinoma. DNA sequence analyses revealed HPRT gene mutations in each of 14 TG-resistant mutants from seven unrelated donors. Thirteen of these 14 mutants resulted from independent mutational events. These results suggest that somatic mutations are common in renal--and perhaps in other human--epithelia, and thus could play an important role in the genesis of age-associated disease.      

Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are two human autosomal dominant skeletal dysplasias characterized by variable short stature, joint laxity and early-onset degenerative joint disease. Both disorders can result from mut-ations in the gene for cartilage oligomeric matrix protein (COMP), an extracellular matrix glycoprotein. About one-third of PSACH cases result from heterozygosity for deletion of one codon within a very short triplet repeat, (GAC)5, which encodes five consecutive aspartic acid residues within the calmodulin-like region of the COMP protein. We have identified two expansion mut-ations in this repeat: an MED patient carrying a (GAC)6allele and a PSACH patient carrying a (GAC)7allele. These are among the shortest disease-causing triplet repeat expansion mutations described thus far, and are the first identified in a GAC repeat. A unique feature of this sequence is that expansion as well as shortening of the repeat can cause the same disease. In cartilage, both patients have rough endoplasmic reticulum inclusions in chondrocytes. The inclusions are also present in tendon tissue and can be reproduced in cultured tendon cells, suggesting that the pathophysiology of disease is similar in both cartilage and tendon.      

De novo microduplications at 1q41, 2q37.3, and 8q24.3 in patients with VATER/VACTERL association

The acronym VATER/VACTERL association describes the combination of at least three of the following congenital anomalies: vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). We aimed to identify highly penetrant de novo copy number variations (CNVs) that contribute to VATER/VACTERL association. Array-based molecular karyotyping was performed in a cohort of 41 patients with VATER/VACTERL association and 6 patients with VATER/VACTERL-like phenotype including all of the patients'' parents. Three de novo CNVs were identified involving chromosomal regions 1q41, 2q37.3, and 8q24.3 comprising one (SPATA17), two (CAPN10, GPR35), and three (EPPK1, PLEC, PARP10) genes, respectively. Pre-existing data from the literature prompted us to choose GPR35 and EPPK1 for mouse expression studies. Based on these studies, we prioritized GPR35 for sequencing analysis in an extended cohort of 192 patients with VATER/VACTERL association and VATER/VACTERL-like phenotype. Although no disease-causing mutation was identified, our mouse expression studies suggest GPR35 to be involved in the development of the VATER/VACTERL phenotype. Follow-up of GPR35 and the other genes comprising the identified duplications is warranted.     

iGluR expression in the hippocampal formation,entorhinal cortex,and superior temporal gyrus inAlzheimer 's disease

Alzheimer's disease (AD) constitutes the largest proportion of dementia worldwide, with a significant associated medical burden. The major pathological hallmark...     

CSF rhinorrhea: detection and localization using overpressure cisternography with Tc-99m-DTPA

We performed 32 overpressure radionuclide cisternography (ORNC) studies to examine 26 patients who were clinically suspected of having cerebrospinal fluid (CSF) fistula with rhinorrhea. Fifteen (47%) of these cisternography studies were positive, and the site of the leak was identified. No leak could be demonstrated in the other 17. Of 23 examinations performed in patients who had clinically documented CSF rhinorrhea, 15 (65%) were scintigraphically positive. The rapid cephalad transit of the radionuclide bolus allowed completion of the study within 30 to 45 minutes. Seven examinations were also performed with overpressure metrizamide CT cisternography (OMCTC), and five demonstrated concordant results with the radionuclide study. Patient discomfort and side effects were minimal. We conclude that radionuclide infusion cisternography is a safe, rapid, and accurate method of investigating a suspected or proven CSF rhinorrhea and that it is complementary to metrizamide cisternography.     

Renal abscess: a complication of ethanol embolization

The authors describe a previously unreported complication of ethanol ablation of a renal tumor in one case. A renal abscess developed in a patient with preexisting silent urosepsis 5 weeks following ablation. Routine urinalysis, Gram stain, and urine culture are recommended as preprocedure tests to avoid such complications.     

An epidemiologic study of headache among children and adolescents of southern Brazil

To study the epidemiology of pediatric headache, we conducted a cross-sectional study of a randomized and proportional sample of 538 male and female students, 10 to 18 years old. They were in the 5th to 8th grade of the schools of Porto Alegre, RS Brazil. The headache disorders were classified on the basis of clinical interview as well as a physical and neurological examination using the operational diagnostic criteria of the International Headache Society (IHS The following headache prevalences were found: lifetime, 93.2%; last year, 82.9%; last week, 31.4%; last 24 h, 8.9%. Last week and last 24 h headache complaints were twice as prevalent in the female group. During the last year the prevalence of headache disorders was 72.8% for tension-type and 9.9% for migraine headache and was not associated with age distribution. Only the last year and last week prevalences of tension-type headache were significantly higher in the female group. The last year prevalence of headache disorder-proved to be positively associated with sex and age variables. The prevalence of headache disorders was found to be extremely high in this population group, requiring more attention on the part of investigators as a public health problem.