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T Mori

Publications and source records attributed to T Mori.

At least 19 recordsLinked to original sources
PubMed1992

Schedule-dependent inhibition of thymidylate synthase by 5-fluorouracil in gastric cancer.

BACKGROUND: An optimal treatment schedule of 5-fluorouracil (5-FU) remains to be clarified. METHODS: A randomized study was conducted to investigate schedule-dependent thymidylate synthase (TS) inhibition by 5-FU in 16 patients with gastric cancer who underwent surgical resection. Surgical specimens of tumor, normal gastric mucosa, and regional lymph nodes were obtained 12 hours after administration of 5-FU either as a continuous infusion (1000 mg/m2 for 48 hours) or as a bolus injection (500 mg/m2 x 2 in 48 hours). RESULTS: The total TS activity (567.8 +/- 294 fmol/mg protein) and the rate of TS inhibition (74.7 +/- 23.1%) in cancer tissues were significantly higher in the continuous-infusion group than in the bolus-injection group (228.5 +/- 104.6 fmol/mg protein and 48.8 +/- 12%, respectively). Likewise, the total TS activity (807.4 +/- 440.3 fmol/mg protein) and the rates of TS inhibition in lymph nodes (72.3 +/- 17.1%) and in normal gastric mucosa (85.1 +/- 12.2%) were significantly higher in the continuous-infusion group than those in the bolus-injection group (232.4 +/- 142.3 fmol/mg protein and 53.6 +/- 17.0% in lymph nodes and 46.5 +/- 14.3% in normal gastric mucosa, respectively). There was a significant correlation between the total TS activity and TS inhibition. CONCLUSIONS: Continuous infusion of 5-FU provides a superior antimetabolic effect in the treatment of gastric cancer, which may lead to a superior antitumor effect.

Aged↗
PubMed1992

Effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on hemopoiesis and survival rate following allogeneic bone marrow transplantation in mice.

The effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the survival rate and hemopoiesis after allogeneic bone marrow transplantation (BMT) were examined. Specific pathogen-free (SPF) C3H mice and germ-free C3H mice, kept in an isolator for germ-free animals, received 10 Gy of total body irradiation (TBI) and all the mice died by day 9 after TBI. These survival rates were improved by BMT. In the case of SPF mice, survival rates at 14 and 100 days were 33% (12/36), 17% (6/36) and in the case of germ-free mice they were 79% (15/19), 74% (14/19) respectively. When SPF mice received rhG-CSF (30 micrograms/kg/day) subcutaneously for 14 consecutive days following BMT, their survival rates were improved to 79% (30/38), 79% (30/38) respectively. The survival rate of rhG-CSF treated SPF mice were equal to that of germ-free mice. When the effect of rhG-CSF treatment on hemopoiesis of SPF mice after allogeneic BMT was examined various hematopoietic progenitor cells in the bone marrow and spleen increased until day 10 after, BMT, while only neutrophils increased in the peripheral blood during the period. No adverse effects of rhG-CSF were observed throughout the study period. It was suggested that in SPF mice treated with rhG-CSF after BMT, the neutrophil recovered in counts quickly and increased neutrophil prevented endogenous infections and improved the survival rate without apparent complications.

Animals↗
PubMed1992

[Immune regulation of ovarian function].

Although it is well established that the pituitary gonadotropins and prolactin are the primary regulators of ovarian function, steroidal and nonsteroidal molecules produced locally in the ovary have been implicated in the modulation of gonadotropin action as autocrine or paracrine regulators. Recent studies suggest that the cells of the immune system play important roles in regulating ovarian function, and the immune regulation of ovarian function has become one of the topics in the field of ovarian physiology. Since it has become clear that the immune factors, cytokines, show a wide range of biological functions, not only on immune cells but also on nonimmune cells, the physiological significance of the resident immune cells, the widespread distribution of which in mammalian ovaries has been known for a long time, has reattracted attention as a third kind of regulator of ovarian function. In this article, current knowledge of the regulatory roles of immune cells as well as the cytokines in ovarian physiology is reviewed.

Animals↗
PubMed1992

Lung cancers associated with thorotrast exposure: high incidence of small-cell carcinoma and implications for estimation of radon risk.

The widely accepted concept that the alpha-emitting radionuclide radon (222Rn, 220Rn) induces lung cancers in humans has been based on the excess of lung tumours observed in underground miners extracting uranium or other substances. However, this poses the important question of whether radon is the only carcinogenic factor because such miners are also heavily exposed to mine dusts including silicates, diesel exhaust, etc. in their working environment. Patients to whom Thorotrast was administered continuously exhale radon (220Rn) derived from 232Th deposits in the body and therefore provide a good model for lung carcinogenesis by radon without concomitant dust exposure. We therefore investigated lung-cancer incidence in our epidemiological follow-up series, analysing the histological types of 11 lung cancers which were found among 359 Thorotrast autopsy cases and measuring radioactivity in the breath of living Thorotrast patients. The study revealed that, while the proportion of small-cell lung cancers considered to be related to alpha-particles was significantly increased, the overall lung cancer incidence was not significantly higher than in controls, in spite of the high level of 220Rn in the patients' breath. This result suggests that radon in the lung does induce cancers (particularly small-cell carcinomas) but that the induction rate is not as high as expected from risk factors associated with mining. Thus, excess lung cancers among the miners might be related to the combined effects of exposure to radon and mine dusts, and not solely to radon.

Aged↗
PubMed1992

Stage-specific expression of cancer-associated type 1 and type 2 chain polylactosamine antigens in the developing pancreas of human embryos.

Expression of type 1 and type 2 chain carbohydrate antigens during the course of morphogenesis of human embryonic pancreas was investigated using specific monoclonal antibodies and compared with the carbohydrate antigen profiles of human pancreatic cancers. The type 2 chain antigens, such as stage-specific embryonic antigen 1 (Le(x)) and I-antigens, appeared much earlier than the type 1 chain antigens; the epithelial cells of primitive foregut were Le(x)+I-antigen- in the embryos at Carnegie stages 16-23, while the pancreatic primordial cells, which had differentiated from the Le(x)+ gut epithelial cells, were Le(x)-I-antigen+ at Carnegie stages 22-23. The type 1 chain antigens, such as Le(a), Le(b), Le(c), and their sialylated derivatives, were not expressed in any cells at these stages and appeared much later in the pancreas of the 10-12-week embryos, when the primitive pancreatic ductal cells in the primordia exhibited an extensive budding of the daughter cells. At this stage, Le(a) appeared and was expressed strongly in the epithelial cells of primitive pancreatic ducts as well as in the daughter cells that were destined to differentiate into future centroacinar cells; Le(b) was localized in the daughter cells which were to become future acinar cells; and Le(c) was specifically expressed in the daughter cells which were to form future Langerhans islets. With regard to the sialylated derivatives of Le(a), expression of the 2-3 sialyl Le(a) antigen was limited to the epithelial cells of the primitive pancreatic ducts, while the 2-6 sialyl Le(a) antigen was strongly expressed in the future centroacinar cells, which had differentiated from the corresponding daughter cells. Among these antigens, the Le(a) and 2-3 sialyl Le(a) antigens showed the highest incidence in human pancreatic cancer tissues. These results indicate that the expression of these carbohydrate antigens in embryonic pancreas is differentiation dependent and cell lineage specific and that most human pancreatic cancer cells mimic the carbohydrate antigen profile of the epithelial cells of the primitive pancreatic ducts in human embryos.

Adult↗
PubMed1992

Novel positive inotropic agents: synthesis and biological activities of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone derivatives.

A series of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinones has been synthesized and evaluated for positive inotropic activity on the canine heart. Some of these derivatives have a potent activity with none or negative chronotropic effect in isolated, blood-perfused dog heart preparations. They also display a high selectivity for positive inotropic effect over chronotropic and vasodilatory effects in anesthetized dogs. (+/-)-6-[2-Hydroxy-3-[(3-methoxybenzyl)amino]propoxy]-2(1H)-quinolinone (39) and (+/-)-6-[3-(3,4-dimethoxybenzyl)amino]-2-hydroxypropoxy]-2 (1H)-quinolinone (40) were further investigated in conscious dogs. After iv administration, they did not affect heart rate or mean blood pressure at the dose producing a 50% increase in the peak of the first derivative of the left ventricular pressure. The compounds (39, OPC-18750, and 40, OPC-18790) are the most promising agents with desirable biological activities, and now are currently undergoing clinical evaluation.

Animals↗
PubMed1992

Production and properties of novel human thyroid cancer specific monoclonal antibodies.

Monoclonal antibodies (TCM-7, -9 and -12) against human thyroid differentiated cancers were established by screening with human thyroid cancers, normal and benign thyroid tissue, and normal human serum protein. A monoclonal antibody (TCM-9) with strong specificity for human thyroid cancer but not for Graves' disease, adenoma or normal thyroid, was shown to recognize a 300 K protein but not to bind to native or mature human thyroglobulin. When TCM-9 was used in immunohistochemical staining tests on more than 30 types of non-thyroid lesions, no reactivity of TCM-9 was observed except with skin immature teratoma, lip squamous carcinoma and stomach adenocarcinoma, which revealed weak reactivities. TCM-9 also showed strong reactivity with two undifferentiated thyroid cancer cell lines and one tissue specimen. Thus TCM-9 is a novel monoclonal antibody against the thyroid cancer.

Adenocarcinoma↗
PubMed1992

[Metastatic carcinoma of the sigmoid colon to the thyroid gland].

A case of metastatic thyroid cancer from sigmoid colon cancer is presented. A 52-year-old woman had a sigmoidectomy due to adenocarcinoma of the sigmoid colon in April 1988. Serum carcinoembryonic antigen (CEA) levels gradually rose from July 1990 along with multiple metastatic lesions which appeared in the lung. They were resected in January 1991. Two months later the subject noticed a painless and firm lump on the left anterior neck. She was found to have a solitary mass in the left thyroid lobe. Thyroid function remained within normal range. Cytological findings obtained by fine-needle aspiration biopsy showed tall columnar carcinoma cells with an acinar pattern. Subtotal thyroidectomy was performed, and histological examination revealed metastatic adenocarcinoma from colon cancer. Immunohistochemical staining by anti-CEA was positive but anti-thyroglobulin was negative.

Adenocarcinoma↗
PubMed1992

Genetic changes of both p53 alleles associated with the conversion from colorectal adenoma to early carcinoma in familial adenomatous polyposis and non-familial adenomatous polyposis patients.

Mutation and loss of heterozygosity (LOH) in the p53 gene were analyzed in 274 colorectal tumors of 4 histopathological grades. Among 160 tumors from 40 familial adenomatous polyposis patients, none of 58 adenomas with moderate dysplasia had p53 mutations, whereas 8% (3 of 37) of severe adenomas, 15% (6 of 40) of intramucosal carcinomas, and 40% (10 of 25) of invasive carcinomas had p53 mutations. Only 3% (1 of 33) of severe adenomas showed both mutation and LOH, while 25% (6 of 24) of intramucosal carcinomas and 40% (10 of 25) of invasive carcinomas had both mutation and LOH. All intramucosal and invasive carcinomas that had mutations lost the other allele of the p53 gene. In 114 tumors from 86 non-familial adenomatous polyposis patients, similar results were obtained; no adenoma showed both mutation and LOH, but both alterations occurred in intramucosal and invasive carcinoma. As regards specificity in 56 mutations detected in the present study, the frequently affected codons were codons 175, 238, 245, 248, 273, and 282, 4 of these amino acids being arginine, and 72% (39 of 54) of all mutations were GC to AT transition. Although expression into p53 polyadenylated RNA was high in every invasive carcinoma irrespective of the presence of mutation or LOH, there was a correlation between mutation and protein level; immunostaining of p53 protein was negative in almost all adenomas, but it was positive in 86% of invasive carcinomas exhibiting p53 mutation. These data suggest that genetic changes on both alleles of the p53 gene through mutation and LOH, which result in abnormal protein accumulation, are involved in the conversion of adenoma to early carcinoma. Also, carcinoma cells with p53 mutations existing within adenoma tissues are detectable by immunostaining, even in formalin-fixed, paraffin-embedded specimens.

Adenoma↗
PubMed1992

Bedside monitoring of warfarin therapy by a whole blood capillary coagulation monitor.

A recently developed portable capillary coagulation monitor device allows rapid determination of prothrombin time (PT) in sec. and in International Normalized Ratio (INR) from a drop of whole blood. Considering a possible application of this device for monitoring of warfarin therapy at bedside or at outpatient clinic, a comparative study was performed in patients receiving warfarin between the whole blood capillary PT(WBC-PT) and conventional laboratory tests such as plasma PT (LAB-PT) and Thrombotest (TTO). There was an excellent positive correlation (r = 0.95, n = 49) between LAB-PT(sec) and WBC-PT(sec). As the correlation coefficient between WBC-PT(sec) and the reciprocal of LAB-PT(%) was excellent (r = 0.95, n = 49), it is feasible to convert WBC-PT(sec) to LAB-PT(%) by the following formula; y = 313.48x +8.29 (x:reciprocal value of LAB-PT(%), y:WBC-PT). As the correlation between WBC-PT(sec) and TTO(sec) was also excellent (r = 0.85, n = 63), TTO(%) may be likewise estimated by the following formula; y = 66.49x + 11.36 (x:reciprocal value of TTO(%), y:WBC-PT). From these observations it is concluded that the determination of WBC-PT is simple and accurate and that the monitoring of warfarin therapy is easily performed by the present method.

Ambulatory Surgical Procedures↗
PubMed1992

22-oxacalcitriol suppresses 25-hydroxycholecalciferol-1 alpha-hydroxylase in rat kidney.

22-oxacalcitriol can decrease the serum level of 1,25-dihydroxycholecalciferol by increasing its metabolic clearance rate and decreasing its production rate. To determine whether 22-oxacalcitriol suppressed the renal 25-hydroxycholecalciferol-1 alpha- hydroxylase we treated rats with 200 ng of 22-oxacalcitriol daily for 1 week. Enzyme activity was measured in vitro by measurement of production of 1,25-dihydroxycholecalciferol by renal slices incubated with 25-hydroxycholecalciferol. 22-oxacalcitriol significantly decreased the 25-hydroxycholecalciferol-1 alpha-hydroxylase activity from 797 +/- 208 pg of 1,25-dihydroxycholecalciferol/g of kidney/h in the control group to 257 +/- 150 pg of 1,25-dihydroxycholecalciferol/g of kidney/h (p less than 0.05). This is the first demonstration of suppression of the renal 25-hydroxycholecalciferol-1 alpha-hydroxylase by the vitamin D3 analog, 22-oxacalcitriol.

Animals↗
PubMed1992

Blood compatibility of venous prosthesis made of textile or non-textile material.

To study blood compatibility of venous prosthesis made of textile or non-textile material, the inferior vena cava of 37 rabbits was partly replaced by 3 mm internal diameter synthetic tube graft made of textile material (T: woven tetron) or non-textile material (P: polytetrafluoroethylene). At designated time intervals after the replacement (5 hours to 4 weeks), graft patency was examined and the dry weight of intraluminal deposits was measured. The harvested grafts were then subjected to light and scanning electron microscopy. All the T-grafts were occluded as early as 5 hours after grafting but when ticlopidine was administered prior to the grafting, all the grafts were patent. All the P-grafts were patent up to 4 weeks after grafting, though the amount of intraluminal deposits was increased in a time related manner, narrowing the lumen of the grafts. The luminal surface of the P-grafts harvested at 5 hours after grafting was covered by piles of fibrin networks entrapping erythrocytes without an association of platelet aggregates, which resembles the finding in the T-grafts harvested from the ticlopidine treated rabbits. In the P-grafts, both the proximal and distal luminal surfaces near the anastomosis were fully covered with endothelial cells by 2 weeks and the entire luminal surface was covered with these cells by 4 weeks. From these results, the following conclusions were obtained; (1) P-graft was superior to T-graft for venous prosthesis, which is mainly due to the inertness of P against platelet activation. (2) Though the luminal surface of the P-grafts was completely covered with endothelial cells by 4 weeks after grafting, the lumen was markedly narrowed by intimal hyperplasia.

Animals↗
PubMed1992

Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients.

We searched for germ-line mutations of the APC gene in 79 unrelated patients with familial adenomatous polyposis using a ribonuclease protection analysis coupled with polymerase chain reaction amplifications of genomic DNA. Mutations were found in 53 patients (67%); 28 of the mutations were small deletions and 2 were 1- to 2-base-pair insertions; 19 were point mutations resulting in stop codons and only 4 were missense point mutations. Thus, 92% of the mutations were predicted to result in truncations of the APC protein. More than two-thirds (68%) of the mutations were clustered in the 5' half of the last exon, and nearly two-fifths of the total mutations occurred at one of five positions. This information has significant implications for understanding the role of APC mutation in inherited forms of colorectal neoplasia and for designing effective methods for genetic counseling and presymptomatic diagnosis.

Adenoma↗
PubMed1992

Receptors for IgG complexes activate synthesis of monocyte chemoattractant peptide 1 and colony-stimulating factor 1.

The chemotactic factors responsible for complement-independent macrophage accumulation in immune-complex diseases such as glomerulonephritis remain unknown. Fc receptors for IgG complexes are found on mesangial cells of the kidney, which produce the macrophage growth factor colony-stimulating factor 1 (CSF-1). We therefore investigated the possible stimulation of mesangial-cell expression of CSF-1 and the recently identified monocyte-specific chemoattractant protein 1 (MCP-1) by IgG complexes. IgG complexes, but not monomeric IgG or F(ab')2 fragments of IgG, rapidly (2-8 h) increased mRNA for both CSF-1 (10-fold) and MCP-1 (20-fold) in cultured mouse mesangial cells. The increase of mRNA for CSF-1 and MCP-1 was not reduced by either cytochalasin B or D, indicating that Fc receptor occupancy is sufficient for signaling and that phagocytosis is not required to elicit this response. IgG complexes also caused a 10-fold increase in the secretion of CSF-1 and a 3- to 5-fold increase in secretion of MCP-1 into the cell culture medium. The synthesis and release of CSF-1 and MCP-1 by mesangial cells as a consequence of Fc receptor occupancy may be responsible for macrophage recruitment and activation at sites of immune-complex deposition.

Animals↗
PubMed1992

A human gene responsible for Zellweger syndrome that affects peroxisome assembly.

The primary defect arising from Zellweger syndrome appears to be linked to impaired assembly of peroxisomes. A human complementary DNA has been cloned that complements the disease's symptoms (including defective peroxisome assembly) in fibroblasts from a patient with Zellweger syndrome. The cause of the syndrome in this patient was a point mutation that resulted in the premature termination of peroxisome assembly factor-1. The homozygous patient apparently inherited the mutation from her parents, each of whom was heterozygous for that mutation.

Amino Acid Sequence↗