Locally linear embedding for dimensionality reduction in QSAR.

Current practice in Quantitative Structure Activity Relationship (QSAR) methods usually involves generating a great number of chemical descriptors and then cutting them back with variable selection techniques. Variable selection is an effective method to reduce the dimensionality but may discard some valuable information. This paper introduces Locally Linear Embedding (LLE), a local non-linear dimensionality reduction technique, that can statistically discover a low-dimensional representation of the chemical data. LLE is shown to create more stable representations than other non-linear dimensionality reduction algorithms, and to be capable of capturing non-linearity in chemical data.

The zinc-binding site of Escherichia coli glutamyl-tRNA synthetase is located in the acceptor-binding domain. Studies by extended x-ray absorption fine structure, molecular modeling, and site-directed mutagenesis.

The zinc contents of fragments of Escherichia coli glutamyl-tRNA synthetase, as well as the conservation of the CYC sequence only in zinc-containing glutamyl-tRNA synthetases, suggested that the 98CYCX24-CRHSHEHHADDEPC138 includes some or all residues involved in binding its zinc atom (Liu, J., Lin, S.-X., Blochet, J.-E., Pézolet, M., and Lapointe, J. (1993) Biochemistry 32, 11390-11396). Extended x-ray absorption fine structure (EXAFS) shows that this zinc atom has a four-coordinate non-planar coordination environment with 3 sulfur and 1 nitrogen atoms with bond lengths, respectively, 2.37 +/- 0.02 A and 2.01 +/- 0.02 A, presumably belonging to 3 cysteine residues and 1 histidine residue. Conservative replacement of each histidine and cysteine residue of the 98C-138C segment, respectively, with glutamine (Q) and serine (S), yields variants H129Q, H131Q, H132Q, and C138S (which sustain the growth at 42 degrees C of E. coli JP1449, whose glutamyl-tRNA synthetase is thermosensitive) and C98S, C100S, C125S, and H127Q (which do not). The amount of this enzyme in these mutants is at least 1 order of magnitude larger than that in a wild type strain; however, no glutamyl-tRNA synthetase activity is detectable in extracts of the variants C100S and C125S, whereas its specific activity in those of C98S and H127Q is about 10-fold lower than in cells overproducing the wild type enzyme or the variants H129Q, H131Q, H132Q, and C138S. These results indicate that the zinc atom present in E. coli glutamyl-tRNA synthetase is bound by the 2 evolutionarily conserved cysteines at positions 98 and 100, and by Cys125 and His127. Molecular modeling of the N-terminal half of this enzyme, using the known structure of E. coli glutaminyl-tRNA synthetase, supports this conclusion and suggests that the 98C-127H segment does not have the characteristics of the classical zinc fingers.

An unusual cause of massive non-surgical pneumoperitoneum: case report.

A case of pneumoperitoneum due to cocaine abuse is presented. Although most commonly associated with surgical disease, pneumoperitoneum may actually be a manifestation of non-surgical intrathoracic pathology. In this patient percutaneous diagnostic peritoneal lavage resulted in return of a large quantity of air and was negative for bleeding or contamination.

Neuroblastoma presenting as central nervous system disease.

Neuroblastoma may be extremely difficult to recognize, particularly when the tumor presents as a primary central nervous system disease. Central nervous system involvement may be considered as primary intracerebral neuroblastoma, metastases to the cranium from an occult primary, primary intraorbital neuroblastoma originating in the ciliary ganglion, metastatic intraorbital neuroblastoma from an occult primary, primary intraspinal neuroblastoma originating in dorsal root ganglia, intraspinal metastatic disease, and distant effects such as myoclonic encephalopathy. Primary neuroblastoma within the ciliary ganglion and primary intraspinal neuroblastoma are extremely rare entities. Illustrative cases the demonstrate the broad spectrum of neurologic presentations are offered. The second known report of neuroblastoma in association with primary pulmonary hypoventilation (Ondine curse) is included.

Esophageal replacement with jejunum in children: an 18 to 33 year follow-up.

Since 1947 a total of 32 staged jejunal interpositions have been performed in children for total esophageal replacement. There have been no failures of the jejunum to reach the neck, no loss of graft, and no deaths. The first 16 of these 32 children have now reached adulthood and form the basis for this report on the late functional results of staged jejunal interposition. Among these 16 patients there occurred four cervical fistulas which healed without sequelae (25%), one cervical stricture which necessitated dilatation but not revision (6%), one early cervical revision for necrosis of the distal tip of the graft (6%), and no complications related to the distal anastomosis. Long-term follow-up (range 18 to 33 years; mean 27 years) was obtained in 100% (16/16) of patients. A barium swallow was obtained in 81% (13/16) at a mean of 25 years following initial reconstruction (range 14 to 33 years). The fact that all patients could eat a regular diet at normal speeds indicates satisfactory long-term function. Two patients (13%) reported mild cervical dysphagia. A barium swallow in one of these patients revealed no abnormalities. The other was found to have an apparent esophageal diverticulum which resulted because the jejunum was end-to-side to the esophagus. This was recently corrected 27 years after the initial reconstruction and represented the only late complication of the procedure. There were no late strictures or peptic ulcerations. Motility of the jejunal limb was normal in 12 of the 13 patients studied. These results demonstrate that staged jejunal interposition can be accomplished reliably and safely in children with excellent long-term functional results and a minimum of late complications. The jejunum should be considered as an alternative to colon and gastric tubes for total esophageal replacement in children.

Peptic ulcer disease in early infancy: clinical presentation and roentgenographic features.

Sixteen infants under 11 weeks of age developed documented peptic ulcer disease involving the stomach, duodenum or pylorus during an eight-year period in a Newborn Intensive Care Unit. The precipitous onset of gastrointestinal bleeding and/or perforation commonly associated with ulcer disease in early infancy was present in only seven (44%) of the 16 patients. The remaining nine infants (56%) presented with recurrent emesis, a presentation of peptic ulcer disease rarely described in the first weeks of life. Contrast radiography was used to demonstrate a definite ulcer crate in 13 of these patients. Two had their ulcers diagnosed at surgery and one by endoscopy. Radiographic demonstration of pylorospasm and/or gastric retention was often associated with ulcer craters located in the pyloric channel or gastric antrum. Only two patients required surgery for massive bleeding and perforation. The remainder were successfully managed medically using orogastric suction antacids and gradual resumption of milk feedings. There were no deaths within our population attributable to peptic ulcer disease.

Unilateral pulmonary vein atresia.

Three cases of unilateral pulmonary vein atresia in children are described. The findings in all three cases were similar and consisted of hemoptysis, recurrent pulmonary infections, and a normal size or small lung with reticular markings. In combination, these findings should allow one to strongly suspect the diagnosis which then can be confirmed with radionuclide perfusion studies and pulmonary angiography. Both procedures demonstrate decreased blood flow to the involved lung, but the pulmonary arteriogram is the definitive study in that it shows a small pulmonary artery, pruned peripheral branches, stasis of contrast material, and nonvisualization of draining pulmonary veins. The condition generally is believed to be congenital and related to the somewhat more common, but still rare, focal congenital pulmonary vein stenosis. Treatment consists of surgical removal of the involved lung or lobe.

Malignant facial tumors in children: radiologic evaluation. Stressing value of conventional and computerized tomography.

Twenty-five cases of malignant tumors of the face in children under 16 years of age were reviewed. In each case the presenting complaint was related to a mass of the face, without a known primary malignancy. Rhabdomyosarcoma was the most common malignancy, followed by equal numbers of histiocystic malignancies and malignant lymphomas. Chloroma and neuroblastoma were less common. Plain films were obtained on every patient and were always felt to be an appropriate part of the work-up. The plain films suggested or made the diagnosis of malignancy in 16 of the patients. The most helpful additional study was tomography. CT was the modality of choice for tumors originating in or extending into the orbit, and for intracranial extension. Xeroradiography best demonstrated a superficial soft tissue tumor. In evaluating facial malignancies, the number and sequence of examinations must be individualized according to the presentation.

Pulmonary alveolar proteinosis: an uncommon cause of chronic neonatal respiratory distress.

A full-term newborn infant had the onset of respiratory distress immediately after birth. She required supplemental oxygen from birth, and had pulmonary alveolar proteinosis (PAP) documented by open lung biopsies at 6 and at 12 weeks of age. Light and electron microscopy showed dense, PAS-positive granular, homogeneous material within the alveolar spaces, diagnostic of PAP. No Pneumocystic carinii organisms were demonstrated on silver staining, and bacterial and viral cultures were negative. The infant died of progressive respiratory insufficiency at 1 yr or age. Pulmonary alveolar proteinosis should considered a rare cause of chronic respiratory distress in the newborn infant.

False-positive 111In-labeled leukocyte scan in cystic fibrosis.

A false-positive 111In-labeled leukocyte scan was obtained in a girl with cystic fibrosis and infection. There was focal accumulation of 111In activity in the abdomen and marked pulmonary uptake. Surgical exploration and postmortem examination revealed no abdominal abnormality. The abnormal activity was apparently due to swallowed sputum which contained labeled leukocytes. Broader clinical implications are discussed.

Cystic nephroma (so-called polycystic Wilms' tumor) of childhood: a CT-pathologic study.

The unique CT features, heretofore unreported, of a case of cystic nephroma of childhood are presented. The concept that cystic nephroma is part of thc diagnosis of cystic nephroma can be made utilizing excretory urography and computerized tomography.