Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB

Usher syndrome is recognized as the most frequent cause of hereditary deaf-blindness. Usher syndrome type I (USH1), the most severe form of the disease, is characterized by profound congenital sensorineural deafness, constant vestibular dysfunction, and retinitis pigmentosa of prepubertal onset. This form is genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar. However, only the gene responsible for USH1 B (which accounts for approximately 75% of USH1 cases) has been characterized. It encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence. Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequence were designed, allowing direct sequence analysis of each of the 48 coding exons and flanking splice sites in seven patients affected by USH1. Four novel mutations were thereby identified. The possibility should now be considered of a sequence-based prenatal diagnosis in some of the families affected by this very severe form of Usher syndrome.      

Missing canines: a novel aetiology

Infant oral mutilation is the practice of removing developing tooth germs, commonly the mandibular canine, in infants up to the age of 1 year. Subsequent complications include missing, impacted or hypoplastic permanent anterior and canine teeth. We report on a case of bilaterally missing lower canines thought to be due to infant oral mutilation. It is important that general dental practitioners are aware of this practice and resulting complications when treating families from sub‐Saharan East Africa.     

Cardiovascular risk in hypertensive patients: results of the Pandora project

BACKGROUND: The aim of the Pandora project is to collect epidemiological information, check diagnostic and therapeutic pathways, and assess outcomes in a large hypertensive population. This report presents the results on patients enrolled in the study between 1997-1999. METHODS: Twenty-one general practitioners working in the Ravenna Local Health Service took part in the study. They were supplied with IBM compatible PCs and were trained to enter the patient's data (age, gender, familiarity for cardiovascular diseases, smoking, hospitalisations for cardiovascular disorders, diabetes, blood pressure, total cholesterolemia, creatininemia, antihypertensive therapy) on So.Ge.Pa. software. Cardiovascular risk factors were assessed according to the WHO - ISH joint committee recommendations. RESULTS: 2,608 treated hypertensive patients were enrolled, 65% of whom showed inadequate blood pressure control. The prevalence of inadequate BP control was higher in patients on multiple-drug antihypertensive therapy compared with those on monotherapy (71.9% vs. 47.9%), in older than in younger patients (70.7% vs. 56.1%) and in patients with three cardiovascular risk factors, or diabetes, or affected target organs, compared to those with two or less risk factors (72.4% vs. 63.3%), (p < 0.001 for all). 63.6% of patients were at risk for age, 36.6% for family history of cardiovascular diseases and 31.7% for severe hypercholesterolemia. CONCLUSIONS: BP control was inadequate in a large percentage of patients, but it was particularly unsatisfactory in the elderly and in patients with high cardiovascular risk. A cluster of cardiovascular risk factors was found in both adequately and inadequately controlled hypertensive patients.     

Chemoprevention of spontaneous tumorigenesis in nullizygous p53- deficient mice by dehydroepiandrosterone and its analog 16alpha-fluoro- 5-androsten-17-one

Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non- competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency.      

Characterization of urothelial carcinoma with respect to the content of carcinoembryonic antigen in exfoliated cells.

A sutstance immunologically similar to carcinoembryonic antigen (CEA) was demonstrated in urothelial bladder carcinoma cells. When indirect immunofluorescence with specific anti-CEA antisera was used, CEA-containing cells were seen in 18 out of 40 cases in 5% to 30% of the cells. Among patients with tumor cells of well differentiated morphology, 61% had CEA-containing cells, compared with only 24% of patients with a poorly differentiated tumor. Microfluorometry of single cells was performed in six cases to estimate the range of CEA content. The mean fluorescence intensity with anti-CEA antiserum was three to six times that of the same tumor cell population stained with non-immune rabbit sera. This fluorescence was decreased when the anti-CEA anti-sera were incubated with CEA but not with nonspecific cross-reactive antigen. The results show a wide range of CEA antigen content in exofoliated bladder tumor cells. In addition to proliferative status and differentiation, quantitative CEA measurements give further possibilities to study characteristics of tumor cell populations.