The effects of chymase on matrix metalloproteinase-2 activation in neointimal hyperplasia after balloon injury in dogs.

Chymase is known to generate angiotensin II in the vascular wall. In this study we investigated a novel role for chymase other than angiotensin II production in vascular proliferation after balloon injury. Chymase promoted the migration of vascular smooth muscle cells in the matrix-coated invasion chambers and activated promatrix metalloproteinase-2 obtained from the culture medium of vascular smooth muscle cells. Two weeks after balloon injury, significant neointimal formation was found in dog carotid arteries. After injury, active matrix metalloproteinase-2 was increased in parallel with the augmentation of chymase activity that was seen in the proliferating region of the vascular wall. The oral administration of NK3201 (1 mg/kg per day), a chymase inhibitor, prevented neointimal formation and significantly suppressed both active matrix metalloproteinase-2 and chymase activities 2 weeks after injury. These results suggest that chymase inhibitors can prevent the development of intimal hyperplasia via the inhibition of matrix metalloproteinase-2 activation in balloon-injured arteries.     

Development of a simple image viewer designed for small X-ray field CT equipment 3DX

Objectives To develop a simple image viewer that utilizes image files in general-purpose formats that are written from the original 3DX volume data. Methods We used FLASH MX2004 for Macintosh to develop a simple image viewer. In developing the software for the simple image viewer, we decided that the viewer should provide the following features: (1) be available to both Windows OS and Mac OS, (2) allow interlocking of the 3D images, (3) display image enlargement, and (4) allow distance measurements. The accuracy of the distance measurements was evaluated. Results The procedure was as follows: (1) write 3D images in jpeg format to a folder on i-VIEW; (2) place the folder containing the 3D images into the directory of the simple image viewer software on a PC; (3) start the software and open the window to input the folder name containing the 3D images; and (4) display the 3D images. Our viewer had features such as image enlargement, interlocking 3D images, drawing, and distance measurements. No significant differences were shown between the measurements made by our simple viewer and the actual values of the images in any direction. Conclusions Our image-viewing software for 3DX is beneficial for clinical use.     

Comparative promoting activities of phosphate salts on rat two-stage bladder carcinogenesis under conditions of equivalent urinary Na+ or K+ levels.

Promoting effects of Na or K phosphate salts on rat two-stage bladder carcinogenesis were compared. Animals were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and thereafter received 1.4% Na3PO4, 2.0% NaH2PO4, 1.0% K3PO4, or 2.5% KH2PO4, these dietary concentrations being selected because they result in approximately equal levels of Na+ and K+ in the urine, equivalent to moderate natriuresis or kaluresis in comparison with our previous data. Treatment with Na3PO4 or K3PO4 induced significant increase in urinary pH compared with control values, whereas urinary pH in the NaH2PO4 and KH2PO4 groups was comparable to control values. With regard to preneoplastic lesion development, both incidences and multiplicity were significantly increased in the groups given Na3PO4 or K3PO4 compared with both controls and NaH2PO4 or KH2PO4 groups, respectively. Furthermore, treatment with Na3PO4 significantly increased multiplicity of papillomas, accompanied by a tendency to increased incidence. No statistically significant difference in promoting potential between Na3PO4 and K3PO4 groups was evident. The present results thus suggest that tumor promotion under conditions of moderate natriuresis or kaluresis depends primarily on high urinary pH.     

Intra-arterial ACNU chemotherapy employing 20% mannitol osmotic blood-brain barrier disruption for malignant brain tumors.

The clinical effects and problems of intra-arterial water-soluble antitumor nitrosourea (ACNU) therapy following osmotic blood-brain barrier modification are discussed. Twenty-one patients with malignant brain tumors were divided into two groups. Group 1 consisted of 16 patients treated by operation, irradiation, and two or more courses of intracarotid infusion of ACNU 100 mg/body (1.7-2.2 mg/kg) following 20% mannitol 200 ml (1.3-1.6 ml/sec) (7 grade 4 astrocytomas, 5 grade 3 astrocytomas, and 4 others). Group 2 consisted of five patients treated by operation, irradiation, and repeated intracarotid infusion of ACNU 100 mg/body alone (grade 4 astrocytoma). The 2-year survival rate in Group 1 was 79% (11 of 14 cases followed up for longer than 2 years) and the 3-year survival rate was 67%. Five of seven grade 4 astrocytoma patients (71%) in Group 1 survived for more than 1 year 6 months, whereas four of five grade 4 astrocytoma in Group 2 died within 1 year 6 months. The measurement of the ACNU concentration in tumor tissues and blood in 11 brain tumors, after intracarotid infusion of ACNU with blood-brain barrier disruption, showed peak values in the tumor tissues of 3.02-32.53 micrograms/gm (mean, 9.67 micrograms/gm), about three to five times as high as that in blood in most cases. This method used in Group 1 appears to be relatively safe without permanent neurological deficits and offers a potential therapeutic effect when used in combination with appropriate premedication in suitable patients.     

Eosinophilic gastroenteritis in the esophagus, stomach, and small intestine in a patient with a choking feeling in the esophagus]

A 75-year-old man was admitted to our hospital with the chief complaint of a choking feeling around the esophagus. Laboratory examinations revealed eosinophilia, and high levels of serum immunoglobulin (Ig) E. A computed tomography scan (CT) showed wall thickening of the esophagus and terminal ileum, and ascites around the liver. An endoscopic examination revealed mild mucosal edema in the esophagus, stomach, and small intestine. Biopsy specimens showed diffuse eosinophilic infiltration in the mucosa. We therefore diagnosed eosinophilic gastroenteritis. Oral prednisolone relieved clinical conditions and the CT image improved. This case was considered valuable, because there have been few reports of eosinophilic esophagitis in Japan.     

Deoxycorticosterone-secreting adrenocortical carcinoma

A case of DOC-secreting adrenocortical carcinoma in a 66-year-old man is reported. He had hypertension, hypokalemia, suppressed PRA, and excessive serum levels of DOC. His serum aldosterone level was normal. The resected adrenal mass weighed 230 g. Histologically, the tumor was mainly composed of compact cells associated with necrosis and atypical mitoses. Invasion of venous structure, sinusoids, and capsule was also present. Immunohistochemically, P450 C21 (21 -hydroxylase) was positive in many tumor cells, and P450 C17(17 α-hydroxylase) was intensely positive in a relatively small number of tumor cells. The patient died 9 months after operation due to rupture of metastatic liver tumor.Endocr Pathol 4:165–168, 1993.     

Dose- and time-dependent responses for micronucleus induction by X-rays and fast neutrons in gill cells of medaka (Oryzias latipes)

Medaka fish (Oryzias latipes) were exposed to various doses of X-rays or fast neutrons, and the frequency of micronucleated cells (MNCs) was measured in gills sampled at 12- or 24-hr intervals from 12 to 96 hr after exposure. The resulting time course of MNC frequency was biphasic, with a clear peak 24 hr after exposure, irrespective of the kind of radiation applied and the dose used. The half-life of MNCs induced in the gill tissues by the two exposures fluctuated around 28 hr, with no significant dose-dependent trend for either X-ray- or neutron-exposed fish. As assayed 24 hr after exposure, the MNC frequency increased linearly over the control level with increasing doses of both X-rays and fast neutrons. The relative biological effectiveness (RBE) of fast neutrons to X-rays for MNC induction was estimated to be 4.3 +/- 0.6. This value is close to the RBE value of 5.1 +/- 0.3 reported for fast neutron induction of somatic crossing-over mutations in Drosophila melanogaster that arise from recombination repair of DNA double-strand breaks. These results and other data support our conclusion that the medaka gill cell micronucleus assay is a reliable short-term test for detecting potential inducers of DNA double-strand breaks.