Citations

We present an efficient feature selection algorithm for computer aided detection (CAD) computed tomographic (CT) colonography. The algorithm (1) determines an appropriate piecewise linear network (PLN) model by cross validation, (2) applies the orthonormal least square (OLS) procedure to the PLN model utilizing a Modified Schmidt procedure, and (3) uses a floating search algorithm to select features that minimize the output variance. The undesirable "nesting effect" is prevented by the floating search approach, and the piecewise linear OLS procedure makes this algorithm very computationally efficient because the Modified Schmidt procedure only requires one data pass during the whole searching process. The selected features are compared to those obtained by other methods, through cross validation with support vector machines (SVMs).

The genetic study of titin has been notoriously difficult because of its size and complicated alternative splicing routes. Here, we have used zebrafish as an animal model to investigate the functions of individual titin isoforms. We identified 2 titin orthologs in zebrafish, ttna and ttnb , and annotated the full-length genomic sequences for both genes. We found that ttna , but not ttnb , is required for sarcomere assembly in the heart as well as the subsequent establishment of cardiac contractility. In fact, ttna is the earliest sarcomeric mRNA that is expressed in the heart, which makes it an early molecular marker for cardiomyocyte differentiation. Surprisingly, ttna is required for later steps of sarcomere assembly, including the assembly of Z-discs and A-bands, but not for early steps such as the assembly of Z-bodies and nonstriated myosin filaments. Reduction of individual titin isoforms in vivo using morpholino-modified antisense oligonucleotides indicated that (1) both N2B exon–containing and N2A exon–containing isoforms of ttna are required for sarcomere assembly in the heart; (2) N2A exon–containing isoforms of both ttna and ttnb are required for sarcomere assembly in the somites; and (3) the N2B exon–containing isoforms of ttnb are expressed later than other titin isoforms and are probably involved in modulating their expression; however, these isoforms of ttnb are not required for sarcomere assembly. Collectively, our results reveal distinct functions of different titin isoforms and suggest that various phenotypes in “titinopathies” may be attributable to the disruption of different titin isoforms.

Purpose Our purpose was to evaluate the results of transphyseal anterior cruciate ligament (ACL) reconstruction with medial hamstring autograft in skeletally immature patients. Methods We reviewed the records of all skeletally immature patients who underwent transphyseal ACL reconstruction with medial hamstring autograft between 1988 and 2002 at our institution. Inclusion criteria were age less than 15 years for male patients, age less than 14 years for female patients, and radiographic evidence of wide open physes. We identified 16 patients (11 male and 5 female). All underwent preoperative and postoperative clinical evaluation (physical examination and modified Lysholm and International Knee Documentation Committee scores), and knee radiographs. Each patient was followed up until skeletal maturity was confirmed, with a mean clinical follow‐up of 41.1 months (range, 24 to 112 months). Results The mean time from ACL injury to reconstruction was 5.6 months (range, 0.7 to 26.9 months). During the preoperative time period, 4 patients (25%) developed meniscal tears that were not visualized on the index magnetic resonance imaging scans. At last follow‐up, the mean leg length discrepancy measured 0.62 cm (range, 0.2 to 1.5 cm), and clinical or radiographic evidence of malalignment was not present in any of the patients. In 1 patient a symptomatic 1.5‐cm limb overgrowth developed, which was treated with an internal shoe lift. At follow up, the mean modified Lysholm score was 98.8 (range, 94 to 100), and the mean International Knee Documentation Committee score was 89.9 (range, 73.6 to 94.3). Of the patients, 7 (43.8%) underwent a reoperation, and 2 suffered traumatic graft disruption. Conclusions ACL reconstruction with a medial hamstring autograft via a transphyseal technique yields satisfactory clinical results in skeletally immature patients. No new meniscal tears were identified after ACL reconstruction, and most patients (87.5%) returned to their previous level of activity. The rate of reoperation was high (43.8%). Physeal growth arrest did not occur. Level of Evidence Level IV, therapeutic case series.

Abstract Congenital erythropoietic porphyria (CEP), an autosomal recessive disorder, is due to mutations of uroporphyrinogen III synthase (UROS). Deficiency of UROS results in excess uroporphyrin I, which causes photosensitization. We evaluated a 3-year-old boy with CEP. A hypochromic, microcytic anemia was present from birth, and platelet counts averaged 70 × 109/L (70 000/μL). Erythrocyte UROS activity was 21% of controls. Red cell morphology and globin chain labeling studies were compatible with β-thalassemia. Hb electrophoresis revealed 36.3% A, 2.4% A2, 59.5% F, and 1.8% of an unidentified peak. No UROS or α- and β-globin mutations were found in the child or the parents. The molecular basis of the phenotype proved to be a mutation of GATA1, an X-linked transcription factor common to globin genes and heme biosynthetic enzymes in erythrocytes. A mutation at codon 216 in the child and on one allele of his mother changed arginine to tryptophan (R216W). This is the first report of a human porphyria due to a mutation in a trans-acting factor and the first association of CEP with thalassemia and thrombocytopenia. The Hb F level of 59.5% suggests a role for GATA-1 in globin switching. A bone marrow allograft corrected both the porphyria and the thalassemia.

AbstractPrevious studies with macrophages that had been prelabeled with [14C]arachidonic acid (20∶4) have shown that condensed tannin is a potent agonist for the release of arachidonic acid. However, it has not been demonstrated that the percentage release of [14C]20∶4 accurately reflects the metabolic activity of the endogenous 20∶4 pool. In order to measure the 20∶4 mass release relative to the total cellular 20∶4 pool, the free fatty acids of freshly isolated alveolar macrophages were derivatized with a fluorescent reagent, and then separated and quantified by high‐performance liquid chromatography. The amounts of esterified fatty acids were measured by gas chromatography of the methyl esters. Free fatty acid levels were compared to those of the total esterified plus unesterified fatty acids to determine the actual percentage released of each fatty acid. Tannin‐stimulated release of 20∶4 mass reflected that previously reported for the release of [14C]20∶4 label but at a slower rate and at a much lower percentage indicating that [14C]20∶4 had been incorporated into part of a more reactive pool. The specificity of the fatty acid release induced by tannin and β‐1,3‐glucan, a known agonist for 20∶4 release, was also examined. Both agonists promoted an increase in the levels of free 20∶4 and of other fatty acids. A comparison of the absolute increases of each of the fatty acids indicated that tannin caused a preferential increase in the mass of free 20∶4, whereas β‐1,3‐glucan evoked a selective increase in the mass of 16∶0.