Genetic alterations in ulcerative colitis-associated neoplasia focusing on APC, K-ras gene and microsatellite instability.

The status of genetic alterations in ulcerative colitis (UC)-associated neoplasia (UCAN) was investigated focusing on microsatellite instability (MSI) which is seen in a certain fraction of colorectal carcinomas, and adenomatous polyposis coli (APC) gene and K-ras gene, in which mutations occur in the early stage of sporadic colorectal tumorigenesis. Thirty-one UCAN from 15 UC patients who had undergone colorectal resection at our institution were investigated. There were 8 lesions of invasive carcinoma, 15 high-grade dysplasia (HGD) and 8 low-grade dysplasia (LGD). DNA was extracted from each neoplastic lesion and corresponding non-neoplastic tissue by a microdissection method. MSI status at 9 microsatellite loci, loss of heterozygosity (LOH) at the APC locus, and K-ras codon 12 point mutation were examined. As for MSI, 4/31 (13%) UCAN (carcinoma: 1/8 (13%), HGD: 2/15 (13%), LGD: 1/8 (13%)) were MSI-high (3 or more unstable loci) and 12/31 (39%) UCAN (carcinoma: 3/8 (38%), HGD: 6/15 (40%), LGD: 3/8 (38%)) were MSI-low (1 or 2 unstable loci). LOH at the APC locus was not found in 9 UCAN from 6 informative (heterozygous) cases. The K-ras mutation rate of UCAN was 3/31 (9.7%) (carcinoma: 2/8 (25%), HGD: 1/15 (7%) and LGD: 0/8). MSI is relatively common in UCAN and is present at the early stage of tumorigenesis of UCAN, while the involvement of genetic alterations of the APC gene and K-ras gene is small. MSI may be one of the mechanisms of the increased neoplastic risk in UC, and UCAN may develop through a different carcinogenic pathway from sporadic carcinomas.     

Preparation and clinical evaluation of orally-disintegrating clonidine hydrochloride tablets for preanesthetic medication

Orally-disintegrating tablets of clonidine hydrochloride, an alpha 2-adrenergic agonist, were prepared by the method of drying an aqueous suspension. The suspension was prepared using powdered lactose, and the composition ratio was 2:1 (powdered lactose: 0.048% clonidine hydrochloride solution). The suspension was dried under 4 +/- 1 degrees C (72 +/- 15% R.H.). We obtained tablets containing clonidine hydrochloride (40 micrograms/tablet). Physical properties of the tablets were as follows: hardness was 4.0 kgf, and disintegration time was 41.7 s (in vitro). In the clinical use, 8 patients, aged 1-2 year and weighing 9-11 kg, received approximately 4 micrograms/kg body weight as clonidine hydrochloride. The tablet was administered 90 min before entering the operating room. All patients were willing to accept the tablet. The quality of separation from parents, sedation and a mask acceptance were excellent on all patients. These results suggest that the orally-disintegrating tablet of clonidine hydrochloride was useful in a clinical situation for the preanesthetic medication of pediatric patients aged 1-2 year.     

Observation of occlusal force in prosthetic crown cementings

The method of pressure force in crown cementing was examined. Continuous occlusal force was always supported by the patients' personal occlusal force in cementing crowns. We found that continuous occlusal force continuously decreased as the occlusal force increased, and the decreasing morphologies were classified into four types, 'Rapid decrease', 'Step-wise decrease', 'Intermediate decrease' and 'Gradual decrease'.     

A case of leiomyosarcoma of the kidney

Leiomyosarcoma of the left kidney seen in a 58-year-old man is reported. On April 10, 1982, he complained of left flank pain. He visited our hospital and left solitary renal cyst was suspected. He had been treated as an outpatient, but left flank pain became exacervated. On May 18, he was admitted to our hospital. On June 7, radical nephrectomy was done under the diagnosis of left renal cell carcinoma. At operation, the tumor invased directory to the psoas muscle and abdominal wall, and could not be completely resected. Pathological diagnosis was renal cell carcinoma with sarcomatoid change. On July 1, he was discharged from the hospital. In December, left flank distention appeared and back pain became exacervated. On February 8, 1983, he was readmitted to our hospital. Low density area was found in left psoas muscle by CT scanning and recurrence of renal cell carcinoma was suspected. alpha-Interferon therapy had been done, but tumor increased remarkably and caused ileus. He died on June 14, 1983. The autopsy revealed a child head-sized cystic tumor in the upper retroperitoneal space, a 5 X 5 X 5 cm metastasis of the left lobe of the liver, a 3 X 3 X 4 cm tumor to the left upper lobe with cavity formation and direct invasion into the spleen, diaphragma and gastric serosa. These metastatic lesions were leiomyosarcoma. Retrospectively, the primary tumor of kidney revealed primary leiomyosarcoma of kidney.     

Salvage Gastrectomy Following a Combination of Biweekly Paclitaxel and S-1 for Stage IV Gastric Cancer

Background and aim  We investigated the clinical benefits of salvage gastrectomy for stage IV gastric cancer patients whose distant lesions showed complete response after chemotherapy. Methods  We enrolled 18 stage IV gastric cancer patients whose distant metastases had disappeared or were controlled by a combination of biweekly paclitaxel (PTX) and S-1. After chemotherapy, these patients received gastrectomy with lymph node dissection. The postoperative outcome was analyzed with respect to both the histological effects of chemotherapy and tumor behavior. Results  Of the 18 patients, 8 had distant lymph node metastases, 9 had peritoneal dissemination, and five had multiple liver metastases prior to chemotherapy. Fourteen patients received curative surgery (R0). No severe postoperative complications were encountered. Pathological evaluation revealed grade 3 and grade 2 tumor regression in the primary lesion in one and five patients, respectively, and grade 3 and grade 2 tumor regression in the lymph nodes in one and six patients, respectively. Univariate analysis of the patients’ prognosis identified R number, gross tumor type, histological grade of tumor regression, and gender as significant factors. Multivariate analysis showed that only the R number was an independent prognostic factor. Conclusion  R0 salvage gastrectomy following a combination of biweekly PTX and S-1 may have significant clinical efficacy for advanced gastric cancer patients.     

Acoustic analysis of experimental prosthetic apparatus on spatial distribution formants

This study concerns the effects of various prosthetic apparatus on speech perception. In this study we analyzed not only the first and second formant frequencies (as have often been studied previously) but also the third formant frequencies, and the three formant frequencies en masse. Our study demonstrated that of the six kinds of prosthetic apparatus we examined, the least effective apparatus was the L.S. type, while the most effective was the M.P. type.     

Senescence marker protein 30 is up‐regulated in kainate‐induced hippocampal damage through ERK‐mediated astrocytosis

Senescence maker protein 30 (SMP30) is decreased in an androgen‐independent manner in kidney and liver with age. However, regulation of SMP30 expression in the brain has not been examined in aging and neurodegenerative diseases. To investigate SMP30 expression in the brain, we utilized aging and kainate (KA)‐induced neurodegenerative disease models. Interestingly, expression of SMP30 was unlikely to decrease in the aged brain, but total levels of SMP30 protein were increased at 4 weeks after KA injury. Increased glial fibrillary acidic protein (GFAP) with elevated SMP30 expression was observed at the same time post‐KA, indicating that regulation of SMP30 expression in the brain may be associated with astrocytosis. We confirmed that KA induced GFAP expression with increased SMP30 in rat astrocyte cells. Moreover, we found that ERK1/2 activation was involved in the up‐regulation of SMP30 in astrocytes. Our results suggest that elevated SMP30 in activated astrocytes plays an important supportive role after brain damage. © 2009 Wiley‐Liss, Inc.