Biomedical subjects
Publications and source records attributed to Y Mishima.
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The purpose of this study was to identify human melanoma-associated Ag (MAA) that are immunogenic in patients, because these molecules may be useful immunogens to implement active specific immunotherapy. To this end, an expression cDNA library constructed from the human melanoma cell line A375 was screened with sera from patients with melanoma. A 1029-bp cDNA (designated D-1) was isolated. Its nucleotide sequence showed no significant homology with viral and mammalian sequences stored in GE-NETYX. cDNA D-1 hybridized to a 2.0-kb mRNA species from human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cell lines but not from a renal carcinoma cell line, PBL, and cultured skin fibroblasts. The D-1 clone produced a fusion protein that displayed a significantly higher reactivity with sera from patients with melanoma than from healthy controls. Furthermore, D-1 fusion protein induced in mice antibodies that immunoprecipitated a 50-kDa component from cultured human melanoma cells. The structural properties of D-1 MAA are different from those of previously described MAA. These results suggest that the approach we have applied may be useful to identify novel MAA expressed by melanoma cells. Furthermore, the immunogenicity of recombinant D-1 protein suggests that it may be a valuable immunogen to implement active specific immunotherapy in patients with melanoma, if additional experiments show that it has the appropriate tissue distribution.
We have found a novel spermidine-dependent endoribonuclease activity in mouse FM3A cell extracts. This endoribonuclease cleaves RNA substrates containing a sequence CCCCCGGUUUGU in its middle. This activity is lost either by heat- or micrococcal nuclease-pretreatment. When heat-pretreated extracts and micrococcal nuclease-pretreated ones are mixed, the activity is restored, suggesting that this activity requires both RNA and protein components. Testing the restoration of the lost endoribonuclease activity in micrococcal nuclease-pretreated extracts by addition of fractionated cellular RNAs, we identified an approximately 65 nucleotide RNA required for this endoribonuclease activity.
Antitumor effect of N-1554 (alpha-dihydrodecaprenyl phosphate containing eight trans internal isoprene residues) against B16-F10 melanoma in syngeneic C57BL/6 mice was examined. B16-F10 cells were inoculated into the footpad of mice and N-1554 was intraperitoneally administered after the inoculation. The drug significantly inhibited the tumor growth in the footpad and dramatically reduced the pulmonary metastasis from the tumor. The antitumor effect of N-1554 was almost abolished when the immunosuppressant carrageenan or anti-asialo GM1 antibody was administered to mice. In addition, pretreatment of host mice with N-1554 reduced the growth of subcutaneously inoculated B16-F10 melanoma. These results suggest that enhancement of host immune system may be involved in the antitumor effect of N-1554.
Based upon the detailed dissections of the lymphatic system of four adult cadavers, the lymphatic drainage of the gallbladder was divided into three pathways. 1) The cholecysto-retropancreatic pathway, which can be regarded as the main pathway, had two routes, one running spirally and posteriorly from the anterior surface of the common bile duct to the right, and the other running almost straight down from the posterior surface of the common bile duct. At the retroportal segment, these routes converged at a large lymph node, which appeared critical as the main terminal lymph node of this pathway. We designated this node the principal retroportal node. 2) The cholecysto-celiac pathway was the route by which some of the lymphatics from the gallbladder ran to the left through the hepatoduodenal ligament to reach the celiac nodes. 3) The cholecysto-mesenteric pathway was the route by which some of the lymphatics ran to the left in front of the portal vein and connected with the nodes at the superior mesenteric root. These three pathways converged with the abdomino-aortic lymph nodes near the left renal vein; in particular, the nodes in the interaortico-caval space were considered important.
A 63 year old female with familial adenomatous polyposis (FAP) complicated by carcinoma of the thyroid and ampulla of Vater and a nonfunctioning adrenocortical adenoma is reported herein. We reviewed 23 cases of duodenal or periampullary carcinoma, 10 cases of thyroid carcinoma and 4 cases of adrenal neoplasm presented in the Japanese literature. From studying these cases, we identified that FAP patients had a high risk of developing periampullary carcinoma and consequently, it is very important to periodically examine the ampulla of Vater. Thyroid carcinomas in patients with FAP were well differentiated carcinomas and occurred earlier than in the general population. The use of medical imaging equipment with mean that insidious abdominal tumors in cases of FAP will be detected more frequently in the future and as patients with FAP have a high risk of developing malignancies, surgery should be indicated for incidentally found adrenal tumors.
Two cases of ulcerative colitis with a positive Coombs test are reported herein. In a 30 year old woman, hemolytic anemia was well controlled by excision of a rectal stump left over from a former operation. A 53 year old woman had a positive Coombs test without clinical hemolytic anemia 10 years after undergoing a total procto-colectomy with ileo-anal anastomosis. Thus we concluded that total procto-colectomy may be preventive, as well as therapeutic, for Coombs positive hemolytic anemia associated with ulcerative colitis.
A case of Crohn's enterocolitis associated with diffuse tracheo-bronchitis is presented herein. Although respiratory tract involvement in Crohn's disease is extremely rare, our review of the world literature revealed several common clinical pathologic features. These features include a productive cough with chest X-ray films which are normal except for some peripheral involvement. Bronchoscopy, however, shows diffuse inflammation of the trachea and bronchi with widely scattered whitish lesions while biopsy reveals a granulomatous infiltration of inflammatory cells. This tracheobronchitis typically responds well to treatment with prednisone.
A case of omental torsion seen in a 16 year old male is reported herein. Abdominal pain in the right lower quadrant suddenly developed just after the patient twisted his waist and an emergency laparotomy revealed a hemorrhagic mass at the edge of the right omentum, which was excised. Histological examination of the resected specimen showed hemorrhage without any venous thrombosis or infarction, possibly suggestive of omental torsion with early spontaneous derotation. The patient was successfully treated as a case of omental torsion.
An 85-year-old male with a sudden onset of abdominal pain was operated on under the suspicion of intestinal ischemia and was later diagnosed as acute superior mesenteric venous thrombosis (SMVT). The patient was successfully treated by resecting the entire involved bowel and performing a double ileostomy. These procedures are considered to be the preferred method of choice for improving survival in poor risk patients.
The 18F-labeling of 4-borono-D-L-phenylalanine (BPA), a potential target compound for cancer treatment with boron neutron capture therapy, is described. By direct fluorination of BPA with [18F]AcOF or [18F]F2 followed by HPLC separation, 4-borono-2-[18F]fluoro-D,L-phenylalanine was prepared with radiochemical yields of 25-35% and with a radiochemical purity of over 99%. The tissue distribution study showed that the compound has potential as a tracer for pancreas imaging with positron emission tomography. Radiation dosimetry is also described.
We studied the tumor uptake and metabolism of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), an 18F-labeled target compound for boron neutron capture therapy. In mice bearing FM3A mammary carcinoma, the accumulation of [18F]FBPA in the FM3A for the first 2 h, and its decrease in all other tissues, resulted in high FM3A-to-tissue uptake ratios. In the FM3A, the tracer was stable for metabolic alteration, which was in contrast to the gradual increase of protein-bound radioactivity in plasma. Imaging of FM3A was demonstrated by whole body autoradiography. [18F]FBPA has potential for use as a PET tracer for tumor imaging with high contrast, even in the pancreas.
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The effect of DOPA and glutathione (GSH) on enzyme systems for 5-S-cysteinyl-DOPA (5SCD) genesis in murine melanoma cells cultured in tyrosine- and cystine-free medium were studied. DOPA at its optimum concentration (10(-5) M) when added alone did not alter tyrosinase, glutathione-S-transferase or gamma-glutamyl transpeptidase activities. In the presence of GSH at its optimum concentration (10(-5) M), DOPA loading did not cause any significant changes in tyrosinase or glutathione-S-transferase (GST) activities. This indicates that the higher 5SCD levels observed in the medium because of DOPA loading in the GSH dependent system results from increased substrate availability rather than the increased enzyme activity. An acute drop in 5SCD at DOPA concentrations above 10(-5) M observed in the GSH dependent system may be due to the inhibition of tyrosinase at high substrate concentrations (10(-4) M). Conversely, in the presence of DOPA, when GSH was increased, the resultant higher production of 5SCD could be explained by the increased activity of GST. When added alone, GSH (10(-5) M) caused a significant increase in GST (approximately 125%) and gamma-GTP (approximately 50%) activities. A drop in 5SCD in the medium when GSH was added beyond its optimum concentration (10(-5) M) in the DOPA-dependent system could be due to competitive inhibition of gamma-GTP by GSH. The data demonstrate that 5SCD genesis may be enhanced due to the accumulation of cytotoxic melanin precursors such as DOPA/DOPA quinone. The relative quantities of GSH at the sites of DOPA quinone formation and the levels of its metabolising enzymes can influence the type of product formed.(ABSTRACT TRUNCATED AT 250 WORDS)
Thymidylate synthetase (TS) is known to catalyse the methylation of deoxyuridine monophosphate (dUMP) for the de novo synthesis of deoxythymidine monophosphate (dTMP). Thymidine kinase (TK) catalyzes the formation of dTMP by the phosphorylation of thymidine via the pyrimidine salvage pathway. High TS and TK activities have been observed in rapidly proliferating tissues. Both TS and TK activities in human thyroid adenocarcinoma increased to approximately 2-fold that in normal thyroid tissue. The thyroid TK isozymes can be separated into two types by DEAE-cellulose column chromatography. One of them is associated with the cytosol cell fraction of rapidly proliferating cells, such as fetal or neoplastic cells. Its activity is not affected by low concentration of deoxycytidine triphosphate (dCTP), and its molecular weight and Km value for thymidine are 120 kD and 0.5 x 10(-6) M, respectively. The average activity of this cytosol-associated isozyme in thyroid adenocarcinoma was increased slightly to 2.3-fold that of normal thyroid tissue. These results obtained from the activities of TK and its isozyme may be indicative of the slow-growing property of thyroid adenocarcinoma compared to mammary or colonic adenocarcinoma, which has high activities of TK and its isozyme.
The N-linked sugar chains of melanoma cell membrane from five murine B16 melanoma clones (F1, F10, BL6, W1-4, and C4-1) with different degrees of metastatic abilities after intravenous and intrafootpad injections were released quantitatively as oligosaccharides by hydrazinolysis, and their structures were analyzed by serial lectin column chromatography, Bio-Gel P-4 column chromatography, and sequential glycosidase digestion. Sugar chain structures of each clone have shown to consist of the same elemental oligosaccharides, but to differ in their percent compositions. More than 84% of the neutral oligosaccharides were high mannose-type sugar chains. Most complex-type sugar chains were sialylated, of which the major structure was tetraantennary sugar chain. Highly lung-colonizing F10 cells had 1.4 and 1.7 times more non-repeated tetraantennary sugar chains than moderately colonizing F1 and C4-1 cells, respectively, and 2.5 times more than poorly colonizing W1-4 cells. BL6 cells, which are also highly lung-colonizing, had 1.5 and 1.9 times more non-repeated tetraantennary sugar chains than F1 and C4-1 cells, respectively, and 2.8 times more than W1-4 cells. These results suggest that increase of sialylated tetraantennary complex-type sugar chains without N-acetyllactosamine repeating units of B16 melanoma cells might correlate with the higher lung-colonizing ability after intravenous injection.
Normal human skin is shown to contain melanocyte growth factor (MeGF). We found MeGF activity in extracts of both the epidermal portion of skin and the dermal portion. This activity was completely adsorbed onto heparin beads and eluted by 2.5 M NaCl. In addition, the activity of both extracts was completely blocked by antibodies directed against basic fibroblast growth factor (bFGF). It is suggested that melanocytes in epidermis are supported by bFGF-like MeGF in normal human skin.
Effects of dexamethasone on melanogenesis and tyrosinase mRNA levels were determined in B16/F10 melanoma cells. Melanin content of B16 cells increased in a dose-dependent manner by the addition of dexamethasone to the culture medium. After 72 hr exposure, dexamethasone (10(-6) M) produced a 2.4-fold increase in melanin content. Northern blot analysis revealed that tyrosinase mRNA level also increased by the addition of dexamethasone to the culture medium. After 24 hr exposure, dexamethasone (10(-6) M) caused a 1.8-fold increase in tyrosinase mRNA levels. A tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) decreased tyrosinase mRNA level at 30 nM concentration. Dexamethasone antagonized this TPA-mediated decrease in tyrosinase mRNA. It is suggested that glucocorticoids are involved in the regulation of tyrosinase activity at the transcriptional level.