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Biomedical subjects

F Sasaki

Publications and source records attributed to F Sasaki.

At least 163 records · Page 9Linked to original sources

Morphological and cytogenetic characterization and N-myc oncogene analysis of a newly established neuroblastoma cell line.

A permanent cell line established from a xenograft of neuroblastoma which occurred in a 5-year-old girl was investigated for its morphological and biological characteristics. The cultured cells were tumorigenic in nude mice. Microscopically, each tumor consisted of small round to polygonal cells with irregular nuclei and prominent nucleoli, corresponding to the features of the primary and xenografted tumor cells. Electron microscopic examination revealed that both the transplanted tumor cells and the cultured cells contained scanty microtubules and dense-core neurosecretory granules. Chromosome analysis of this cell line showed monosomy for chromosomes 1, 10, 19 and X, and structural rearrangements involving chromosomes 8, 17 and 20, in addition to numerous double minutes. The N-myc oncogene was found to be amplified 40- to 80-fold in the transplanted and cultured tumor cells, as well as in the primary tumor cells. In situ hybridization with a digoxigenin-labeled uridine-triphosphate N-myc RNA probe detected abundant mRNA in the tumor cells. This neuroblastoma line may become a valuable in vitro experimental model system for studies aimed at better characterization of neuroblastoma.

Animals↗

Studies on hypotensive agents. Synthesis of 1-substituted 3-(2-chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-2,4(1H,3H)-quinazoline diones.

3-(2-Chlorophenyl)-6-ethoxycarbonyl-5,7-dimethyl-2,4(1H,3H)-quinazoline dione was newly prepared. 1-Hydrogen atoms of the compound were variously substituted in order to test for their hypotensive activities on relaxing effects of the blood vessels. The compounds with 2-(1-pyrrolidinyl) ethyl, 2-(1-piperidinyl)ethyl, 3-(dimethylamino)propyl, and 3-(N-benzyl-N-methylamino)propyl moieties showed significant activity. The 2-(1-piperidinyl)ethyl compound possessed activity approximately 23 times more potent than papaverine, however, it was less potent than cinnarizine.

Animals↗

Studies on antiatherosclerotic agents. Synthesis of 7-ethoxycarbonyl-4-formyl-6,8-dimethyl-1(2H)-phthalazinone derivatives and related compounds.

Derivatives of 7-ethoxycarbonyl-4-formyl-6,8-dimethyl-1(2H)-phthalazinone and closely related compounds were synthesized using Wittig and epoxidation reactions. Ring opening amination of the epoxides were carried out using dimethylaluminum amide reagents under mild reaction conditions. beta-Keto ester and beta-diketone moieties were introduced through diazo derivatives. These moieties were reacted with hydrazine hydrate to produce 4-pyrazolyl derivatives. The derivatives were tested for their inhibitory effect on platelet aggregation, and their relaxing effect on blood vessels.

Animals↗

[Therapeutic approach and associated problems of advanced liver tumors in children based on nuclear DNA ploidy pattern].

We evaluated the therapeutic approach and its associated problems in 14 hepatoblastomas (HB) and 3 hepatocellular carcinomas (HCC) based on the ploidy patterns determined from paraffin-embedded tissues by flow cytometry. Aneuploid pattern was seen more frequently in the patients with poorly differentiated and immature types of HB, and HCC. It was also observed in patients with tumors showing microscopic vessel invasion, and in patients showing resistance to the therapeutic approach. Among 4 patients with combined epithelial components of HB, 2 patients' tumors revealed both the aneuploid and diploid patterns and their prognoses were poor. The prognoses of patients with tumors showing the aneuploid pattern were significantly poorer. From our study we concluded that careful attention should be pain to the heterogeneity of these tumors and that more aggressive treatment for tumors showing aneuploid pattern should be developed.

Child↗

[Study on the clinical usefulness of NCC-ST-439 in breast cancer].

We investigated the usefulness of NCC-ST-439, a new tumor marker in breast cancer. The positive rate of NCC-ST-439 in cases of primary breast cancer was 46.9%. In cases of primary breast cancer, there were no significant differences in average and positive rate among each group of patient age, tumor size, number of metastatic node, clinical stage and status of hormone receptor (ER, PgR). The positive rate of NCC-ST-439 in early breast cancer was as high as that in advanced case. NCC-ST-439 had better sensitivity than CEA and CA15-3, and decreased in serum level after the curative operation. We concluded that NCC-ST-439 is useful as a screening marker for the detection of early breast cancer and as a post operative monitoring marker for the surveillance of the recurrence.

Antigens, Tumor-Associated, Carbohydrate↗

[Clinical study of eel calcitonin for relief of pain from metastatic bone lesions].

Thirty patients with bone metastasis were treated with eel calcitonin (CT) to relieve severe pain from metastatic bone lesions. Patients were two males and twenty-eight females with a mean age of 52.8. CT was administered intramuscularly in twenty-seven patients and intravenously in three. CT was effective on 55.6% of patients to reduce severe bone pain but did not decrease the amount of analgesics in most patients. Serum Ca and P were not changed markedly. As side-effects, two patients complained of nausea and vomiting after administration of CT but they weren't severe. These results indicate that CT is quite useful drug for relief of severe bone pain from metastatic lesions in patients with breast or digestive tract carcinomas.

Adult↗

Fifteen years' experience of neuroblastoma: a prognostic evaluation according to the Evans and UICC staging systems.

Our policy of preoperative and postoperative adjuvant therapy of advanced neuroblastoma changed from mild to aggressive chemotherapy in 1978. In order to evaluate the clinical effects of this policy, 39 cases before 1977 and 37 cases after 1978 were retrospectively reviewed using the Evans and the International Union Against Cancer (UICC) staging systems. Both clinical stages (CS) and postsurgical histopathological stages (PS) of the UICC staging system showed an almost 100% cure rate in stages I (CSI, PSI) and II (CSII, PSII). The cure rates of CS III, PS IIIA, and PS IIIB cases were remarkably improved after 1978, but those of CS IV and PS IV cases remained extremely low. However, it was found that a disease-free survival rate of advanced neuroblastoma could be produced by complete resection of the tumor accompanied by adjuvant chemotherapy. In these conditions, we found that for predicting the prognosis of advanced neuroblastoma, the UICC staging system, especially the PS staging system, may be more rational than the Evans staging system.

Evaluation Studies as Topic↗

Determination of plasma total renin level by RIA with a monoclonal antibody: value as a marker for nephroblastoma.

Plasma total renin is a new, useful marker for nephroblastoma, but the conventional method for determining its level is sophisticated and requires large blood samples. To develop a simpler technique, a monoclonal antibody specific for both inactive and active renin (inactive + active = total) was raised, and a radioimmunoassay (RIA) system was established. This monoclonal antibody stains only the juxtaglomerular apparatus; values determined by this RIA did not change before and after activation. So far, the RIA system has been applied to 136 samples from 92 patients. Plasma total renin levels were also determined with the conventional method: samples were activated, then renin activity was assayed by measuring angiotensin I. The coefficient of the data obtained by these two different techniques was 0.921 (P less than .01). Plasma total renin levels in patients with nephroblastoma were significantly increased (546.5 +/- 297.8 pg/mL) over those in patients with neuroblastoma (218.6 +/- 46.5 pg/mL) and in controls (165.8 +/- 67.5 pg/mL, P less than .01). After removal of Wilms' tumors, the levels decreased to normal when sampled every 2 weeks. It was concluded that a newly developed RIA system is more useful in determining plasma total renin levels in patients with nephroblastoma.

Antibodies, Monoclonal↗

Pancreatic hormone changes in infantile obstructive jaundice.

Metabolic disturbances of pancreatic hormones in obstructive jaundice in infancy were evaluated experimentally and clinically. In our experimental study, using young rats, the level of plasma insulin (IRI) gradually increased after ligation of the common bile duct. These levels were a little lower than those in the non-treated controls. The level of plasma glucagon (IRG) increased remarkably 4 weeks after ligation of the common bile duct. Clinically, there were no significant differences in the levels of IRI and IRG among normal controls and cases of neonatal hepatitis and congenital biliary atresia (CBA). In CBA patients, these levels can be correlated with the progression of hepatic fibrosis; an increase in IRG and a decrease in the IRI/IRG mol ratio was noticed in patients with grade III of hepatic fibrosis. These results indicate that, in obstructive jaundice in infancy, the more severe the hepatic damage due to obstructive jaundice, the higher the level of plasma glucagon concentration will rise.

Animals↗

Cytochemical studies of responses of corticotropes and thyrotropes to cold and novel environment stress.

Cold stress stimulates the release of both ACTH and TSH from the pituitary. More striking changes in ACTH content have been seen in the intermediate lobe after cold stress. Therefore, this study was designed to test responses of individual anterior lobe corticotropes to cold exposure. Male rats were exposed to either 30 min of cold (+3-5 C), 30 min of a novel, temperate environment (+24 C) or were unstressed (+24 C). Pituitaries were fixed and embedded in preparation for immunolabeling for ACTH or TSH-beta at the light (semithin sections) and electron microscopic levels. The semithin sections were used to measure areas of corticotropes and thyrotropes with Bioquant image analysis equipment. Separate groups of pituitaries were dissociated and the cells were cultured for 2 or 15 h. Then the cells were stimulated for 5-10 min with biotinylated analogs of corticotropin-releasing hormone (bio-CRH) or arginine vasopressin (bio-AVP) to detect the target cells cytochemically. A third group of dissociated cells were fixed for immunolabeling for ACTH, 16K fragment of pro-opiomelanocortin, beta-endorphin, or TSH-beta. Cold exposure resulted in a 1-4-fold increase in the levels of serum ACTH over that of unstressed rats. This was correlated with a 40% increase in the percentage of cells that contained 16K fragment and a 30-40% increase in percentages of cells storing ACTH or beta-endorphin. Cold stress also increased the percentage of cells that bound bio-CRH or bio-AVP by 45%. Analyses of semithin sections showed that areas of corticotropes increased by 21% following cold stress. The number of rows of immunolabeled (ACTH) secretion granules also increased in corticotropes from cold-stressed rats. Exposure to a novel environment for 30 min resulted in no significant increase in serum ACTH over that of unstressed rats. There was, however, a 20% increase in percentages of cells that stored 16K fragment, beta-endorphin, or target cells that bound bio-CRH. However, the corticotropes were not significantly larger. Many of the cells exhibited reduced numbers of immunolabeled secretory granules. Other corticotropes resembled those from cold-stressed rats. When TSH cells were studied, their percentages increased from 8 +/- 3% to 15.8 +/- 4% and their areas increased by 22% following exposure to cold. After exposure to a novel environment, percentages of cells that stored TSH-beta increased to 11 +/- 2%, however, no changes in areas of TSH cells were measured. These studies demonstrated that the anterior lobe corticotrope is clearly activated by exposure to both cold and novel environment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗

Bronchial hyperresponsiveness in patients with chronic congestive heart failure.

To investigate the relationship between pulmonary congestion and bronchial responsiveness, we measured bronchial responsiveness to acetylcholine in 51 patients with left heart disorders. The measurement of bronchial responsiveness was performed by inhaling doses of acetylcholine chloride (0.08 to 20 mg/ml) and calculating the PC20-FEV1. The median value for PC20-FEV1 was above 20 mg/ml in the subjects without history of congestive heart failure (n = 18), was 5.29 mg/ml in the subjects with clinical evidence of congestive heart failure in the past days (n = 18; p less than 0.01), and was 5.74 mg/ml in the subjects with clinical evidence of congestive heart failure at the time of study (n = 15; p less than 0.01). The hemodynamic variables by cardiac catheterization and the clinical symptoms were not correlated with the grade of bronchial responsiveness. These results suggest that the bronchial responsiveness was increased in most of the patients with chronic congestive heart failure. We concluded that continuous pulmonary congestion may contribute to the pathogenesis of bronchial hyperresponsiveness.

Acetylcholine↗

[Quantitative evaluation of right ventricular overload in cor pulmonale using 201T1 myocardial SPECT].

In patients with right ventricular overload, the free wall of the right ventricle is often visualized by 201T1 myocardial scintigraphy. To determine quantitatively the discriminant and characteristics of cor pulmonale, 201T1 myocardial perfusion single photon emission computed tomography (SPECT) was performed in 16 patients with chronic obstructive pulmonary disease (COPD) and seven with restrictive pulmonary disease (RPD). We selected one section of the short-axis image of SPECT in which the right ventricle was most clearly visualized, and defined the T1-score as the ratio of the sum of counts in the region of interest (ROI) at the anterior, mid and posterior regions of the right ventricular free wall to the sum of counts in the ROI at the posterior, lateral, anterior walls of the left ventricle, and the anterior and posterior regions of the interventricular septum. Correlation of the T1-score with mean pulmonary arterial pressure (mPAP), systolic pulmonary arterial pressure (sPAP), and total pulmonary vascular resistance (TPR), as obtained by right cardiac catheterization, arterial oxygen tension (PaO2), and arterial carbon dioxide tension (PaCO2) were evaluated. The results were as follows: 1. In the patients with COPD, the T1-score correlated positively with mPAP (r = 0.71, p less than 0.005), TPR ( r = 0.69, p less than 0.005), and PaCO2 (r = 0.63, p less than 0.01), and it correlated inversely with PaO2 (r = -0.58, p less than 0.05). However, there was no significant correlation between the T1-score and mPAP, TPR, PaCO2, and PaO2 in the patients with RPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Progress of imaging diagnosis for the cancer therapy--breast cancer].

As two main modalities for the breast cancer, ultrasonography (US) and mammography (MMG) were discussed about the efficacy and limitation of qualitative diagnosis. The accuracy rate of US and MMG for the breast cancer were 90.0% and 92.7% at the Aichi Cancer Center Hospital during these 2 years (1986-1988). The number of patients with the breast cancer is increasing recently in Japan. This cancer, however, is one of the curable cancer at the early stage. Therefore, it is very important thing to detect a small malignant mass less than 1cm in a diameter by using these modalities. In addition, the establishment of the mass screening system for breast cancer is desired. In order to make a precise diagnosis, it is necessary to add some devices on the ordinary modalities. For examples, mechanical improvement of the Moribuden tube with 0.1mm focus, operation of ductgraphy and cystography by double contrast method in MMG and application of 10MHz transducer in US. Furthermore, needle biopsy under US or X-ray is expected positively to make a fast diagnosis. On the other hand, DMR (Digital Mammo-Radiography) system has a bright prospect for the mass screening of the breast cancer in the respect of efficacy, cost and radiation hazard. DMR system has many advantages as follows, 1. The system is capable of bringing out clearly very minor differences of contrast. 2. Tumor shadows can be easily displayed. 3. The lateral projection only is sufficient (allowing examination of the chest wall also). 4. The X-ray dose is small: 0.03-0.05mSv. 5. The equipment is inexpensive to use. 6. Patient positioning is simple, and examinations take little time. 7. Long operator training programs are unnecessary. 8. The system uses digital signals, and so automatic diagnosis is possible. 9. Theoretically, at least, tumors as small as 0.2 mm in diameter can be detected.

Breast Neoplasms↗

Roentgenologic appearance of a thorotrast-induced small cholangiocarcinoma in a case of thorotrastosis. An autopsy case of massive gastrointestinal bleeding of esophageal varices.

A small cholangiocarcinoma was detected at autopsy in a patient with thorotrastosis who died from the rupture of esophageal varices at the esophagogastric junction. Prior to the advent of recent diagnostic imaging technique, a correct antemortem diagnosis could only be obtained from tumor markers. However, the tendency for the opacity of the liver to decrease slowly with time and develop uneven trabeculation suggests that small tumors may be difficult to detect against such a non-homogeneous background.

Adenoma, Bile Duct↗

Two types of mammosomatotropes in mouse adenohypophysis.

Two types of mammosomatotropes (MS), the small-granule and vesicle-granule MS, were detected in mouse adenohypophysis by electron microscopy and immunohistochemistry. Both cell-types were immunoreactive to prolactin (PRL) and growth hormone (GH) antisera. The small-granule MS contained small, round, solid secretory granules about 100 nm in diameter, and were smaller than the classical GH and PRL cell-types. The vesicle-granule MS contained secretory granules like cored vesicles, and were larger than classical GH and PRL cells. Small-granule MS were immunoreactive to both PRL and GH antisera in the same region of the cell cytoplasm; the vesicle-granule MS, however, were immunoreactive to only PRL antiserum in most cytoplasmic areas, and a positive response to both PRL and GH antisera was confined to only certain small areas.

Animals↗