Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa

The RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%-15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis.     

The effect of shock deformation on the anodic polarization behavior of polycrystalline nickel in 1N sulphuric acid

The results of anodic potentiostatic polarization of shocked nickel polycrystals in 1N H₂SO₄ are reported. With increasing shock pressure, passivation and Flade potentials shift in the cathodic direction, the critical current density decreases, and the passive current density decreases. These effects are discussed in terms of substructural changes accompanying shock loading.     

Metabolic myopathy as a cause of the exercise limitation in lung transplant recipients

BACKGROUND: Cardiopulmonary exercise (CPEx) studies of lung transplant (LTx) recipients have found low maximum oxygen consumptions because of an as yet unexplained mechanism. Although it is likely that a significant problem resides within the mitochondria, this study determines whether a defect in oxygen uptake or utilization is present. METHODS: Six LTx recipients and six age- and sex-matched, healthy control subjects were studied to assess the possibility of a mitochondrial myopathy in LTx recipients. We used standard CPEx testing in conjunction with near-infrared spectroscopy (NIRS), a noninvasive optical technique to assess peripheral oxygen uptake in exercising muscle. NIRS analyzes the absorption spectra of hemoglobin and myoglobin at 760 and 850 nm to determine the relative oxygen saturation of these compounds during exercise with respect to baseline values. Relative changes in oxygen saturation are determined from the application of Beers law to changes in absorbance to compute changes in optical density (deltaOD). The LTx recipients and control subjects performed maximal noninvasive CPEx studies with NIRS analysis of the vastus lateralis muscle. RESULTS: All subjects had a circulatory limitation to exercise. The LTx group had a significantly lower percent predicted maximum oxygen consumption than the control group (45.3%+/-14% vs 100.8%+/-15.6%, [mean +/- SD] P < .001) and earlier onset of the anaerobic threshold (30.3%+/-7.6% vs 60.3%+/-8.0% of predicted VO2max, P < .0001) The LTx recipients demonstrated a significantly smaller deltaOD at maximum exercise as determined by NIRS analysis (0.024+/-0.005 deltaOD vs 0.054+/-0.03 deltaOD, P < .05). CONCLUSIONS: LTx recipients have an impaired maximal exercise capacity because of a disorder of peripheral oxygen utilization. This may be caused by a cyclosporine-induced mitochondrial myopathy.     

Gastrointestinal manifestations of vascular anomalies in childhood: varied etiologies require multiple therapeutic modalities

BACKGROUND/PURPOSE: Vascular anomalies, including hemangiomas and vascular malformations afford complex diagnostic and therapeutic challenges when gastrointestinal (GI) manifestations are present. METHODS: Twenty-one patients evaluated or treated in our Vascular Anomalies Program from 1993 through 1997 were reviewed retrospectively with regard to presentation, treatment modalities, and outcome. RESULTS: Four patients had hemangiomas, and 17 had various vascular malformations. GI symptoms began in infancy or early childhood in all patients. Manifestations included GI bleeding (n = 15), obstruction (n = 2), diarrhea (n = 2), ascites (n = 2), pain (n = 1), emesis (n = 1), ileo-ileal intussusception (n = 1), protein-losing enteropathy (n = 1), and hypersplenism (n = 1). Four patients had proven portal hypertension. Fourteen had associated musculoskeletal or cutaneous lesions. Congestive heart failure, partial anomalous pulmonary venous return, pulmonary edema, and pleural or pericardial effusion occurred in one patient each. Bleeding was the most common symptom of both hemangiomas and malformations. Of four patients with hemangiomas, three were treated with corticosteroids or interferon. Endoscopic banding and embolization of an associated arterioportal hepatic shunt were each used in one patient. One patient died. The malformations were treated with resection (n = 8), endoscopic banding or sclerosis (n = 7), percutaneous or intraoperative sclerosis (n = 5), embolization or device interruption (n = 3), and portosystemic shunt (n = 2). GI symptoms were ameliorated in 12 patients with malformation, improved in two, unchanged in two, and one died after prolonged palliation. CONCLUSIONS: Vascular anomalies with gastrointestinal manifestations are heterogeneous in their presentation and type. Although bleeding is the most common symptom of both hemangiomas and vascular malformations, treatment differs. Pharmacological angiogenesis inhibition is the mainstay of hemangioma therapy. Resection, endoscopic or radiologic vascular obliteration, and portal decompression are important in treating vascular malformations. An individualized and interdisciplinary approach is often required to successfully diagnose and treat these complex lesions.     

A program system interpreting recording of long-latency evoked potentials

An algorithm and a personal computer program for automatic distinguishing between EEC records containing evoked and no potentials, based on the detected invariants reflecting experts' experience in evoked potential analysis have been developed. The efficiency of the programme (its high accuracy and speed, low volume) has been demonstrated in the system for automatic determination of the hearing level by long-latent evoked potentials. It is easily modifiable to identify evoked potentials from other modalities (visual, somatosensory ones) in the systems using the traditional and/or up-to-date computerized EEC equipment.     

Adenosine and other low molecular weight factors released by muscle cells inhibit tumor cell growth

In this study, we investigated the basis of the resistance of muscles to tumor metastases. We found that a low molecular weight fraction (Mr <3000) of skeletal muscle cell-conditioned medium (MCM) markedly inhibits the proliferation of carcinoma, sarcoma, or melanoma cell lines in vitro. The MCM exerts a cytostatic effect on tumor cell growth and arrests the cells in G0/G1 of the cell cycle. However, normal cell proliferation of cells such as bone marrow cells or fibroblasts was found to be refractory to the influence of the MCM. A reduction in melanoma growth was observed in mice treated with the MCM. Adenosine was identified as one of the active components in the MCM by using high-performance liquid chromatography separations, mass spectra, and nuclear magnetic resonance analyses. At a concentration of 4 microM, equal to that found in the MCM, adenosine inhibits the proliferation of tumor cell lines (Nb2 lymphoma, K-562 leukemia, and LNCaP prostate carcinoma cells) while stimulating the proliferation of normal murine bone marrow cells. By similar methods, additional inhibitory components were detected in the MCM in a molecular mass range of 600-800 Da. The ability of adenosine and other low molecular weight components to specifically inhibit tumor cell growth in vitro and in vivo may account for the resistance of muscle to tumor metastases.     

On the feasibility of a CDMA overlay for personal communicationsnetworks

Because of the continually increasing demand for mobile communications, it has been suggested that personal communication networks (PCNs) be established in the 1850-1990 MHz range. However, that band of frequencies is currently occupied by various microwave signals transmitted by users ranging from utility companies to state and local agencies. In order to allow both sets of users to occupy these frequencies as well as improve the spectral efficiency of this band, a spread-spectrum overlay is proposed, whereby a code-division multiple-access (CDMA) PCN would share the spectral band with the existing narrowband microwave traffic. The results of several field tests which have been designed to demonstrate the feasibility of an overlay of this type are discussed