Mutational analysis of the BMP-1 gene in patients with gastroschisis

BACKGROUND: Gastroschisis is a rare abdominal wall defect. Although the pathogenesis of gastroschisis is unknown, there is some evidence of the genetic etiology of gastroschisis. Recently, a functionally null deletion of the mouse bone morphogenic protein-1 (BMP-1) gene resulted in a phenotype that resembled a human neonate with gastroschisis. BMP-1 thus became the first potential candidate gene for gastroschisis. METHODS: To explore this possibility the authors collected blood samples from 11 patients who had gastroschisis. Mutational analysis of exons 2 to 15 of the human BMP-1 gene was performed using genomic polymerase chain reaction, single-strand conformation polymorphism analysis and direct sequencing methods. RESULTS: No mutation of the human BMP-1 gene was observed in any of these patients. CONCLUSION: Although heterogeneous etiologies might be proposed for gastroschisis, our results provide further evidence of a nongenetic etiology for gastroschisis. J Pediatr Surg 36:885-887.     

Identification of urinary metabolites of 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in rat, rabbit and dog.

The metabolism of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) in rat, rabbit and dog was studied. The urine of animals dosed with 14C-KC-764 was extracted with ethyl acetate after treatment with beta-glucuronidase and arylsulfatase. The metabolites were purified by TLC and HPLC from the extract. Unchanged KC-764 and 16 metabolites were isolated and their structures were identified or proposed by NMR and MS spectrometry. The metabolism of KC-764 took place by the oxidation of the tetrahydropyridine ring, 6,7-position and 2-methyl group of the pyrazolopyridine ring, and their combinations. The oxidation of the tetrahydropyridine ring was predominant in dog, whereas the oxidation of the pyrazolopyridine ring was more important in rabbit. Rat produced the various metabolites by their combination. 6-Oxo and 6-ureido derivatives of the tetrahydropyridine ring were common major metabolites in all animal species studied.     

A living case of pulmonary ossification associated with osteoclast formation from alveolar macrophage in the presence of T-cell cytokines

A 61-year-old woman had been coughing up blood-tinged sputum since May 1998. Chest radiography and computed tomography (CT) scans revealed a solitary mass (3 cm in greatest dimension) in the right lower field, accompanied by a surrounding area of ground glass and reticular appearance. Surgical lung biopsy was performed to the surrounding area. The pathological diagnosis was pulmonary ossification of the dendriform type. Alveolar macrophages obtained from her lung differentiated into tartrate-resistant acid phosphatase (TRAP)-positive multinucleated giant cells (MGCs) in the presence of autologous T cells or of macrophage colony stimulating factor (M-CSF) and interleukin-4 (IL-4). This results suggest the possibility that monocytes/macrophages may have the ability to form osteoclasts in the presence of cytokines that may be involved in the development of pulmonary ossification.     

A case of advanced ovarian clear cell adenocarcinoma responding to cisplatin-cyclophosphamide and paclitaxel-carboplatin]

We report a case of stage IV ovarian clear cell adenocarcinoma successfully controlled by a combination of cisplatin-cyclophosphamide (CP) and paclitaxel-carboplatin (TJ). A 64-year-old female with advanced ovarian cancer and pleural effusion underwent 4 courses of combination chemotherapy with CP. The giant ovarian tumor showed a relative reduction in size and the pleural effusion disappeared. Serum CA-125 levels and CA 19-9 levels markedly decreased. Thus, the patient underwent a total hysterectomy and bilateral salphingoophorectomy. During the operation, a giant ovarian clear cell adenocarcinoma was found, but there was no peritoneal dissemination and no cancer cells in her peritoneal fluid. Thereafter, she underwent 3 courses of combination chemotherapy with TJ. She has had 13 months of stable, tumor-free survival since the operation and normal serum CA-125 and CA 19-9 levels. Ovarian clear cell adenocarcinoma generally responds poorly to cisplatin and carboplatin, but in combination chemotherapy with paclitaxel-carboplatin these may be effective.