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K Hatakeyama

Publications and source records attributed to K Hatakeyama.

At least 361 records · Page 20Linked to original sources
PubMed1991

A correlation between GM-CSF gene expression and metastases in murine tumors.

Using 14 transplantable murine tumors, we investigated a possible correlation between their ability to produce the cytokine GM-CSF and the spontaneous metastatic potential when mice were subcutaneously inoculated. The following results were obtained: (1) seven tumors, which produced severe pulmonary metastases and metastatic swelling of lymph nodes, exhibited the ability to produce GM-CSF activity in culture. The cell population analysis revealed that the cells producing GM-CSF were tumor cells themselves, but that contaminating macrophages/granulocytes and T lymphocytes did not produce GM-CSF. The mRNA for GM-CSF was also found in all of these highly metastatic tumors tested. In mice inoculated with a highly metastatic tumor, the GM-CSF mRNA was also found in lungs; (2) in 3 other tumors, which produced histological but not macroscopical pulmonary metastases, no GM-CSF activity could be detected in the culture fluids. GM-CSF mRNA was, however, detected in the tumor cells in the presence of an mRNA-stabilizing agent, cycloheximide, suggesting the possibility that the tumor cells of this type were transcribing GM-CSF gene, and secreting it in undetectable levels; (3) in culture of the 4 remaining poorly or non-metastatic tumors, neither CSF activity nor GM-CSF mRNA could be detected even in the presence of cycloheximide. GM-CSF mRNA was also not found in lungs of tumor-bearing mice. Our results indicate that there may be a correlation between GM-CSF gene expression in tumor cells and spontaneous metastases.

Animals↗
PubMed1991

Cloning and sequencing of cDNA encoding rat GTP cyclohydrolase I. The first enzyme of the tetrahydrobiopterin biosynthetic pathway.

A full-length cDNA clone for GTP cyclohydrolase I, the first enzyme of the tetrahydrobiopterin biosynthetic pathway, was isolated and characterized. Synthetic oligonucleotides, constructed according to selected amino acid sequences of purified GTP cyclohydrolase I, were used to screen a rat liver cDNA library. Four clones were isolated, and the length of the longest cDNA insert was 1024 base pairs. The identity of the cDNA was confirmed by amino acid sequence data for eight fragments obtained by lysyl endopeptidase digestion of the purified protein. The coding region encoded a protein of 241 amino acid residues, but the NH2 terminus of the protein contained 11 additional amino acid residues not present in the purified protein. RNA blot analysis showed a single mRNA species of 1.2 kilobases in rat liver. A characteristic feature of the deduced amino acid sequence of GTP cyclohydrolase I was the presence of sequences similar to those proposed for the phosphorylation sites for casein kinase II and growth-associated histone H1 kinase. Furthermore, significant similarity was found to the highly conserved sequences of dihydrofolate reductases, which are known to be involved in the binding of the pterin group of dihydrofolate to the reductases. This region in GTP cyclohydrolase I may be assigned to the binding site of tetrahydrobiopterin, one of the inhibitors of this enzyme.

Amino Acid Sequence↗
PubMed1991

Supralevator pelvic exenteration with colonic J-pouch-anal anastomosis and Mainz pouch operation with anastomosis to the urethra. Report of a case.

This is the first documented case report in which construction of double pouches, a colonic J-pouch and a Mainz pouch with anastomosis to the urethra, was performed in a patient who underwent supralevator pelvic exenteration. We have shown that the operation is feasible; the patient was continent, except for nightly urinary leakage, and was able to defecate and urinate spontaneously without any catheterization. Based on the experience of this case, we believe that this combined operation results in a better quality of life for the patient because of the avoidance of both urinary and fecal stomas. If justified pathologically, this operation may represent an improvement for those patients with extensive cancer of the rectum, which invades the adjacent anterior viscera, or that of the bladder, which invades the posterior viscera.

Adult↗
PubMed1991

A new rat colon cancer cell line metastasizes spontaneously: biologic characteristics and chemotherapeutic response.

A new cell line (RCN-9) was established in culture from a transplantable rat colon adenocarcinoma, which was induced in the colon of a male Fischer F344 rat by subcutaneous administration of 1,2-dimethylhydrazine. When RCN-9 cells were injected subcutaneously or into the cecal subserosa of syngeneic rats, carcinomas with progressive growth were obtained and the development of lung (63.6%) and liver (40.0%) metastases, respectively, ensued. Antitumor effects of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC) against RCN-9 were examined in vivo and in vitro. 5-FU and ADM had antitumor effects both in vivo and in vitro; MMC had antitumor effects in vitro. These results show that the RCN-9 cell line can be used both as a model to study mechanisms of metastasis from colon carcinoma and as a model in chemotherapeutic studies of metastatic disease from colon carcinoma.

Adenocarcinoma↗
PubMed1991

Gastric bleeding and increased gastric vascular permeability induced by platelet activating factor (PAF): effect of drugs that affect arachidonate metabolism.

The injurious effect of platelet activating factor (PAF) on gastric mucosa was studied by measuring bleeding in the acid perfused stomach of anesthetized rats. The effect of PAF on gastric mucosal vascular permeability (GMVP) was assessed by dye-leakage in the saline perfused stomach of anesthetized rats. Intravenous infusion of PAF (100 ng/kg/min for 20 min) apparently caused gastric bleeding under the gastric luminal perfusion with 150 mM HCl solution,, with the peak response at 50-70 min; biopsy indicated the presence of mucosal lesions. GMVP was markedly increased with the peak response at 20-40 min. Pretreatment with CV-3988 (1 or 10 mg/kg, i.v.), a PAF antagonist, dose-dependently blocked the PAF-induced gastric bleeding and increase in GMVP. Pretreatment with hydrocortisone acetate (20 or 40 mg/kg, s.c.) reduced PAF-induced gastric bleeding and increase in GMVP, in contrast to the aggravation by caffeic acid (1 or 5 mg/kg, s.c.). Indomethacin (1 or 5 mg/kg, s.c.) prevented PAF-induced gastric bleeding, and it depressed the increase in GMVP in the case of the lower dose. Prostaglandin E2 (50 or 500 micrograms/kg, s.c.) significantly reduced PAF-induced gastric bleeding, but had little effect on PAF-induced increase in GMVP. 1-Benzylimidazole (10 or 50 mg/kg, s.c.) also inhibited PAF-induced gastric bleeding and depressed the increase in GMVP at the higher dose. These results suggest that increased GMVP plays a significant role in producing the gastric damage by PAF. Changes in the mucosal level of cyclooxygenase products, especially thromboxanes, by drugs modifying the arachidonate metabolism would be closely associated with their prevention or aggravation of gastric damage induced by PAF.

Animals↗
PubMed1991

[Multiple sclerosis with higher cerebral dysfunction: a case report].

Higher cerebral dysfunctions such as aphasia, apraxia and agnosia have seldom been reported in multiple sclerosis (MS). 12 year-old right-handed boy felt unsteadiness of the body and headache for several days. Two months later, he had the same episode and complained of visual disturbance, and weakness and sensory disturbance on the face and the extremities. Additionally, he showed amnestic aphasia, acalculia, ideomotor apraxia, finger agnosia and right-left disorientation. Cerebrospinal fluid examinations revealed increases IgG, myelin basic protein and neuron specific enolase (11%, 25 ng/ml and 28.8 ng/ml, respectively). X-ray CT scan and MRI-CT examinations revealed sclerotic lesions on the left parietal white matter and the right mid-brain. The diagnosis was made as MS. He was treated with m-PSL (methyl-prednisolone) pulse therapy for three weeks and consecutively treated with PSL for four weeks. He recovered gradually, but visual disturbance and facial palsy remained. After seven months MRI-CT showed a high signal intensity on the left parietal white matter in spite of the disappearance of the lesion on X-ray CT scan. We suggest that these higher cerebral dysfunctions may result from the lesion of the left parietal white matter which produces a disconnection between each cortical area.

Agnosia↗
PubMed1991

[The usefulness of nucleolar organizer regions in diagnosis of colonic epithelial neoplasia].

The Ag-NORs technique, staining nucleolar organizer regions, was performed on 23 areas of colonic normal mucosa, 17 adenomas with low grade atypical and 8 adenocarcinoma invading submucosa, to examine its possibility of application to the pathological diagnosis of colonic epithelial neoplasia. In normal colonic gland, the average number of Ag-NORs per 1 nucleus in cells of lower two-thirds showed significantly higher value (p less than 0.01) than higher one-third, and the mean cross-section area per 1 Ag-NOR in lower two-thirds showed a tendency to be larger than higher one-third. This results suggested that there was a positive correlation between the proliferative activity of cells and the number and size of Ag-NORs. A comparison of normal gland, adenoma and adenocarcinoma showed that the mean cross-section area of Ag-NORs correlated positively to their histological grade of atypia, but the average number did not. However using these two parameters, these three lesions had a tendency to be discriminated respectively at the average Ag-NORs number of 2.8 dots and the area of 2 microns. These results suggested that the Ag-NORs technique was expected to be a useful method for histopathological diagnosis of colonic epithelial neoplasia.

Adenocarcinoma↗
PubMed1990

Cloning of a full-length cDNA encoding bovine thymus poly(ADP-ribose) synthetase: evolutionarily conserved segments and their potential functions.

The primary structure of bovine thymus poly(ADP-ribose) synthetase, as deduced from the nucleotide sequence of a cloned cDNA, indicated that this enzyme is composed of 1016 amino acids (aa) with an Mr of 113,481. An abundance of Lys and Arg residues was in accord with the known basic nature of this protein. A comparison with reported sequences of human counterparts revealed: (1) three functional domains separated by partial proteolysis, i.e., DNA-binding (N-terminal), automodification (central), and NAD-binding (C-terminal) domains, have, in this order, increasing degrees of homology; (2) the DNA-binding domain is composed of two distinct regions: one, less conserved, containing zinc-binding fingers and the other, more conserved, containing helix-turn-helix motifs; (3) all Glu and Asp residues in the automodification domain are conserved; and (4) a 78-aa stretch encompassing the nucleotide-binding fold in the NAD-binding domain is completely conserved. These results are compatible with specific features of each domain, i.e., complex DNA-enzyme interactions, multiple automodification at acidic aa residues, and a stringent specificity for the substrate, NAD.

Amino Acid Sequence↗
PubMed1990

Leukocyte surface markers in Rana catesbeiana, identified using mouse monoclonal antibodies.

Monoclonal antibodies (mAbs), each reactive with thymocytes, neutrophils, and thrombocytes of the bullfrog, Rana catesbeiana, were raised and used for studies of hematopoiesis of metamorphic larvae. The mAbRc-T1, which immunoreacted exclusively with thymocytes in adults, was also strongly reactive to larval thymocytes. Thus the determinant Rc-T1 may provide an appropriate marker for thymocytes, although antigenic sharing is also seen in larval ovarian tissue. Neutrophils detectable by both mAbRc-N1 and Rc-N2 originated primarily in the mesonephros and showed up increasingly in peripheral blood of larvae. Thrombocytes detectable by mAbRc-P may originate in the larval spleen and/or liver but not in the mesonephros.

Animals↗
PubMed1990

[Changes in thyroid function during ACTH therapy in patients with infantile spasms].

Serum triiodothyronine (T3), free T3, thyroxine (T4) and free T4 levels were measured before and immediately after daily ACTH-Z therapy (0.01 mg/kg/day, 1-2 weeks) for patients with 9 cases of infantile spasms and one case of myoclonus epilepsy. In some of them, serum reverse T3 (rT3) and thyroxine binding globulin (TBG) levels were also measured. All patients became seizure free after ACTH-Z therapy. Before ACTH-Z therapy, all of the hormone levels were within normal limits. Serum T3 and free T3 levels were markedly decreased after daily ACTH-Z therapy, and serum T4, free T4 and TBG levels were moderately decreased after the therapy. 1-6 weeks after the daily treatment, all of these hormone levels returned to pretreatment levels. Serum rT3 levels did not change after ACTH-Z therapy. These results suggest that the effect of long-term daily ACTH-Z therapy is very critical to the immature brain, and conventional ACTH-Z therapy has to be reconsidered.

Adrenocorticotropic Hormone↗
PubMed1990

[A case of retroperitoneal mucinous cystadenocarcinoma].

We reported is the histogenesis of a case of a primary retroperitoneal cystadenocarcinoma that was resected surgically in a 42-year-old woman who was admitted to hospital for SLE. On echographic examination, she was found to have a right abdominal tumor and underwent an operation for the complete removal of an abdominal tumor located in the right retroperitoneal cavity. A histological examination of the tumor revealed it to be compatible with a mucinous cystadenocarcinoma of the ovary. Only four cases of a primary retroperitoneal mucinous cystadenocarcinoma have been reported in the literature. This rare lesion was studied histopathologically and its histogenesis is discussed.

Adult↗
PubMed1989

Purification and characterization of rat liver GTP cyclohydrolase I. Cooperative binding of GTP to the enzyme.

GTP cyclohydrolase I, an enzyme that catalyzes the first step in the biosynthetic pathway of tetrahydrobiopterin, has been purified about 38,000-fold to apparent homogeneity from rat liver extract with a yield of 5%. The molecular weight of the enzyme was estimated to be 300,000 by gel filtration on Ultrogel AcA 34. The purified enzyme gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis at a position corresponding to a molecular weight of 30,000. N-terminal amino acid sequence analysis gave a single amino acid at every step of the Edman degradation up to residue 10. These results suggest that the enzyme is probably a homopolymer. The enzyme showed positive cooperativity with a Hill coefficient of 2.4 at a substrate (GTP) concentration of 10-50 microM. The Vmax value of the enzyme was 45 nmol/min.mg protein. The GTP concentration producing half-maximal velocity was 30 microM at a KCl concentration of 0.1 M. This value increased as the KCl concentration rose, without any change in Vmax or Hill number. Biosynthesis of tetrahydrobiopterin may be controlled by the intracellular level of GTP.

Aminohydrolases↗
PubMed1989

Evaluation of ileal W pouch-anal anastomosis for restorative proctocolectomy.

Clinical defaecatory function, neorectoanal manometry and pouchography were assessed in 16 patients treated by restorative proctocolectomy with ileal W-reservoir. The duration after ileostomy closure was 6 to 28 months (mean 17 months). There were no operative deaths and no failures where the reservoir had to be removed. Partial anastomotic dehiscence occurred in one patient, and intestinal obstruction requiring laparotomy in two. Anastomotic stricture, which could be corrected easily by dilatation, occurred in three patients. Daily stool frequency was 4.3 +/- 1.2 at 6 months after ileostomy closure, 3.8 +/- 1.2 at 12 months, and 3.3 +/- 1.0 at 24 months. The clinical score for neorectal function gradually and steadily improved with time as well as daily stool frequency. In the manometric and pouchographic studies, mean anal canal length (3.4 +2- 0.6 cm), mean maximal anal sphincter resting pressure (57.1 +/- 9.7 cm water) and mean maximal reservoir resting pressure (4.3 +/- 2.0 cm water) tended to be less than normal controls but not significantly so. Neorectoanal inhibitory reflex disappeared completely or was greatly decreased in all patients. However, all were capable of spontaneously controlled defaecation. There was an inverse linear relationship between daily stool frequency and maximal tolerated reservoir volume (p less than 0.01). There were inverse linear relationships also between daily stool frequency and horizontal diameter of the reservoir measured on pouchography (p less than 0.05), and daily stool frequency and dilatation ratio of the reservoir (p less than 0.01). From these results, we conclude that a large and wide reservoir allows better defaecatory function.

Adenomatous Polyposis Coli↗
PubMed1989

Platelet activating factor induced gastric damage in rats: participation of increased gastric vascular permeability.

Pharmacological factors involved in the injurious effect of platelet activating factor (PAF) on the gastric mucosa were studied in the acid (0.15 N HCI)-perfused stomachs of anesthetized rats. PAF infusion (100 ng/kg/min for 20 min, i.v.) induced distinct bleeding in the acid perfusate in proportion to mucosal lesions. Preceding the bleeding, a remarkable increase in mucosal vascular permeability was observed on dye-leakage assessment. Inhibition of the gastric bleeding and the dye leakage was achieved by pretreatment of the animals with CV-3988, a PAF antagonist, and hydrocortisone acetate, in contrast to the aggravation by caffeic acid. These results suggested the importance of mucosal vascular permeability in PAF-induced gastric mucosal lesions.

Animals↗
PubMed1989

[Clinical features and treatment of lower intestinal hemorrhage].

We have experienced 471 patients with anal bleeding during the past seven years. The Results are as follows: 1. As for the types of disease, incidence of hemorrhoid, colorectal cancer and ulcerative colitis (UC) was high, while that of small intestinal problems was low. 2. In the cases of remarkable bleeding from the lower intestinal tract, massive or acute progressive bleeding was less frequent than expected. 3. Inflammatory diseases were the main causes of massive bleeding. Bleeding by UC was the major indication for urgent operation. In the cases with acute massive hemorrhage, basic complications were often found and the possibility of the diseases of small intestine and blood vessel disorders also should be considered. 4. At the examination of bleeding patients, it is efficient to explore the lower colon and rectum first by colonoscopy or sigmoidoscopy, for most of the bleeding lesions are found in these portions. 5. As for surgical treatment, most of colorectal cancer patients with hemorrhage are able to be operated with wait- and -see management. For UC patients, complete cure operation is possible even if they have high-dose steroid medication.

Adult↗
PubMed1989

[A correlation between the abilities of tumor cells to produce GM-CSF and form metastasis].

Nearly a half of murine transplantable tumor cells upon in vitro culture were found to produce granulocyte/macrophage-colony stimulating factor-(GM-CSF) in the cultured fluids and express its mRNA in the cell. Tumor cells producing GM-CSF and expressing its mRNA in culture, when inoculated intramuscularly in the syngenic mice, developed severe metastasis with large tumor nodules in the lung and lymph nodes, whereas those producing no GM-CSF developed no visible metastatic nodules. With a possible mechanism involved in this intimate correlation between the production of GM-CSF and tumor metastasis, a role of GM-CSF as an autocrine growth factor in tumor growth and an immunopathological effect of GM-CSF on microenvironment of tumor cells in the metastatic tissues were discussed.

Animals↗