Somatic NF2 gene mutations in familial and non-familial vestibular schwannoma

Vestibular schwannoma occurs both as a sporadic tumour and in the dominantly inherited familial cancer syndrome neurofibromatosis type 2 (NF2). The gene for NF2 has recently been isolated on chromosome 22, and the demonstration of inactivating germline mutations in NF2 patients and NF2 associated tumours suggests that it act as a tumour suppressor. We have investigated 85 sporadic and 2 NF2 associated vestibular schwannomas, and one vagal schwannoma for chromosome 22 allele loss and NF2 gene mutations. A further 7 vestibular schwannomas were investigated for NF2 mutations only. Chromosome 22 allele loss was detected in 34 of 87 vestibular schwannomas and in the vagal nerve schwannoma. Six exons of the NF2 gene were investigated by SSCP analysis in all 95 tumours. Somatic NF2 gene mutations were detected in 13 non-familial vestibular schwannomas and in one of the NF2 vestibular schwannomas. Seven non-familial tumours with an NF2 gene mutation also displayed a chromosome 22 allele loss. Thirteen of the mutations were predicted to produce truncation of the NF2 protein. These results suggest that somatic mutations of the NF2 tumour suppressor gene are a critical step in the pathogenesis of both familial and non-familial vestibular schwannoma and that the mechanism of tumourigenesis complies with a 'two-hit' mutation model.     

The scale bandwidth of visual search

Observers were asked to locate a target in a brief, two-scale display. Accuracy of locating the target was measured as a function of the ratio between the two scales. At each scale ratio, the probability of locating the target as a function of the number of elements is well fit by the idea that the observer accurately monitors only a "critical" number of elements. The dependence of critical number on scale ratio is well accounted for by a model that assumes that the observer's decision is based on an evenly spaced array of samples. The sample spacing is under attentional control, but is always uniform.     

Rapid eye movements in myasthenia gravis. II. Electro-oculographic analysis

Voluntary saccades were studied by electro-oculography in ten patients with myasthenia gravis (MG) and in eight patients with other types of ophthalmoplegia. Despite limited range of eye movements, maximum velocities of 20 degree and 40 degree saccades in patients with MG were not significantly different from those in normal individuals, whereas maximum velocities in patients with other types of ophthalmoplegia were significantly decreased. In some myasthenic patients, small amplitude saccades were hypermetric and had high velocities, appearing clinically as "quiver" movements characteristic of MG. In MG the preservation of saccades with high initial velocities, even in the presence of severe ophthalmoplegia, suggests that muscle fibers generating rapid movements during saccades (twitch fibers) can be relatively spared when muscle fibers responsible for maintenance of excentric gaze (tonic fibers) are severely affected.     

Comparison of rest/exercise ECG, thallium-201 scans and radionuclide angiography in patients with suspected coronary artery disease

The results of rest and exercise ECG, 201Tl myocardial perfusion imaging and equilibrium radionuclide angiography were analyzed in 71 consecutive patients referred for diagnosis or evaluation of coronary artery disease (CAD). In 45 patients the diagnosis was established either by catheterization or typical history. In this group the overall sensitivity for rest/exercise ECG was 66%, for 201Tl scans 74%, for both combined 79% and for the ejection fraction response to exercise determined by radionuclide angiography 97%. If only the exercise response was considered, the corresponding sensitivity values were 58% (ECG), 50% (201Tl scans), 71% (ECG + 201Tl) and 97% (radionuclide angiography). The specificity for coronary artery disease was determined to be 71% for ECG, 86% for 201Tl scans and 42% for radionuclide angiography. All patients with false-positive results by radionuclide angiography had cardiomyopathies, thus this test has a high specificity for left ventricular dysfunction rather than for CAD alone. Criteria developed from the analysis of the test results in the 45 patients with definite diagnoses were then applied to the evaluation of 26 additional patients with atypical chest pain. A diagnosis could be made in all but 5 of them and radionuclide angiography was again the single most reliable test. Based on this study a new approach for the noninvasive evaluation of patients with suspected coronary artery disease is proposed.     

Biosynthesis of bikaverin in Fusarium oxysporum. Use of 13C nuclear magnetic resonance with homonuclear 13C decoupling to locate adjacent 13C labels

Bikaverin obtained by supplementing cultures of Fusarium oxysporum with singly and doubly 13C labeled acetate was enriched by approximately 0.5 atom percent with the 13C isotope. At this low enrichment 13C NMR spectra of samples labeled from (1-13C)- and (2-13C) acetate did not show, unequivocally, the pattern of isotopic incorporation. Small sample size, poor solubility and difficulties in the assignment of resonances also restricted the amount of information thacetate. The difficulty was overcome by using 13C homonuclear single-frequency decoupling in conjunction with 1H heteronuclear decoupling to locate bonded 13C-13C pairs. The carbon skeleton of bikaverin was shown to be biosynthesized entirely by condensation of acetate units and the pattern of assembly was established.     

The risk of exposure to potentially contaminated body fluids in urological surgery

To determine the risk of exposure to body fluids potentially contaminated with infectious organisms we instituted a prospective study of all urological procedures performed at our institution. Urological procedures were divided into 3 categories: open, cystoscopic and endoscopic surgical (transurethral resection of the prostate or bladder tumor, ureteroscopy and percutaneous procedures). We have complete data analysis on 594 consecutive patients who underwent an operation at our institution: 77 (13%) underwent an open procedure, 75 (13%) underwent an endoscopic surgical procedure and the remaining 442 (74%) underwent cystoscopic procedures. All procedures were performed by supervised house staff using universal precautions. The operating surgeon was exposed to potentially contaminated body fluids in 173 of 594 cases overall (29%). There was exposure in 17% of all open procedures, 41% of all endoscopic surgical procedures and 29% of all cystoscopic procedures. Urologists must consider themselves at high risk for exposure to potentially contaminated body fluids and take appropriate precautions.     

Experimental allergic encephalomyelitis raises betaine levels in the spinal cord of strain 13 guinea-pigs

Chronic relapsing experimental allergic encephalomyelitis, an animal model of multiple sclerosis, was induced in Strain 13 guinea-pigs by subcutaneous injection of spinal cord homogenate and Freund's incomplete adjuvant supplemented with Mycobacterium tuberculosis. High resolution 1H NMR spectra of CNS tissue extracts indicated that the levels of choline metabolites, particularly betaine, were elevated in the spinal cord tissue, the principal site of lesion formation in this guinea-pig strain. The spectra also show that N-acetylated compounds are slightly depleted in the disease. The results are discussed in relation to the biochemical interpretation of NMR spectra obtained in vivo from patients with multiple sclerosis.