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Biomedical subjects

Y Mishima

Publications and source records attributed to Y Mishima.

At least 109 records · Page 6Linked to original sources

Molecular and biological control of melanogenesis through tyrosinase genes and intrinsic and extrinsic regulatory factors.

Non-premelanosomal melanogenic compartments and their melanogenesis-controlling functions have been further elucidated. In addition to enzymatic and nonenzymatic controlling factors, we have also been exploring the role of melanogenesis-related genes. Naturally occurring intrinsic melanogenic inhibitors, MW < 6,000(alpha), 6,000-30,000(beta), and > 30,000(gamma), having different modes of action, have been identified within melanoma cells. One of the alpha-type melanogenic inhibitors of isolated tyrosinase(Ty) nonsuppressive types, later identified as lactic acid, induces depigmentation of cultured B-16 cells by the reduction in Ty activity level due to the inhibition of its mRNA expression. The transfection of Ty cDNA, rather than nuclear DNA-binding master regulatory gene, can induce, within both Ty-deficient amelanotic melanoma cells and also within fibroblasts, melanin polymer formation. This multisequential step occurs not only by the induction of Ty synthesis but also by the induction of other regulatory proteins and factors such as dopachrome tautomerase, DHICA-oxidase, catalase, Ty-glycosylation in GERL, and Ty-transfer by coated vesicles to newly assigned melanogenic vacuoles in which not only eumelanin but also rather pronounced concomitant pheomelanin formation is seen. Investigation of melanin-producing vacuoles in transfected fibroblasts and reexamination of premelanosomes in pigment cells has revealed the following: 1) Melanosomes possess phagocytic ability; 2) melanosomes receive tyrosinase and hydrolases via coated vesicles from GERL; 3) melanosomes possess lysosome-associated membrane protein 1 (LAMP-1); 4) amelanotic melanoma contains lysosome-like vacuoles with myelin figures that acquire typical premelanosome structure after Ty-cDNA transfection. Thus it is proposed that melanosomes are specialized lysosomes in pigment cells. Coated vesicles synthesize melanin monomers such as DHICA and some DHI, and have a monomer-stabilizing system. Thus they can transport them in intact form with Ty to premelanosomes, which subsequently polymerize these monomers by the action of DHICA-oxidase and T3-Ty. Selective eradication and diagnosis of malignant melanoma using our 10B-dopa analogue has been successfully performed in human melanoma patients using combined thermal neutron irradiation for the former and positron emission CT for the latter.

Animals↗

Expression of vimentin in gastric cancer: a possible indicator for prognosis.

Expression of vimentin in gastric cancer was immunohistologically examined in 85 surgically resected specimens and evaluated in terms of various clinicopathological features. Vimentin expression was more pronounced in gastric cancers of more advanced type and in those exhibiting a higher degree of infiltrative growth, lymph node involvement and vascular invasion. These results indicate that vimentin expression by gastric cancer might be related to the invasion and metastatic process of cancer cells and could be useful as a prognostic indicator for patients with gastric cancer.

Aged↗

[A case of AFP (alpha-fetoprotein) producing gastric cancer successfully treated with EAP (etoposide, adriamycin, cisplatin) therapy].

A case of AFP producing gastric cancer successfully treated with EAP therapy is reported with a review of the literature. A 56-year-old male was admitted complaining of epigastralgia and back pain. He was diagnosed as having a gastric cancer with multiple liver metastases by endoscopy and computed tomography. Serum AFP level was 2,791,000 ng/ml and biopsy specimen showed AFP-positive tumor cells by PAP (peroxidase-antiperoxidase) method in hepatoid structure. Preoperative combination chemotherapy with etoposide, adriamycin and cisplatin resulted in a remarkable decrease in serum AFP level. Subtotal gastrectomy (R3) with hepatic artery cannulation was performed. The therapeutic effect by histological examination showed Grade 3 in the primary site and Grade 2 in both resional lymph nodes and liver metastasis.

Antineoplastic Combined Chemotherapy Protocols↗

Indications for local excision of ampullary lesions associated with familial adenomatous polyposis.

BACKGROUND: The relative risk of periampullary carcinoma is high in patients with familial adenomatous polyposis (FAP). We examined the possibility of local treatment of the ampullary lesion of these patients in an early stage. STUDY DESIGN: From August 1991 to April 1993, 37 patients with FAP underwent endoscopic examination and biopsy of the ampulla. Local excision of the ampulla was performed in seven patients. RESULTS: Two of the seven patients were diagnosed with carcinoma in situ; the ages of the patients were 35 and 46 years. A 38-year-old woman had ampullary carcinoma infiltrating into the muscle of the sphincter of Oddi. These three cases showed a protruding change or deformity of the ampulla endoscopically. The laboratory data, cholangiogram, and abdominal ultrasonography were within normal limits. The superficial change of the ampulla along with the young age of the patients were considered to be factors that warranted further observation. Postoperative complications in two cases were treated successfully. CONCLUSIONS: Indications for local excision of the ampulla of patients with FAP would be protruding change of the ampulla, biopsy showing adenoma with severe atypia or carcinoma, in situ, no jaundice with or without subclinical abnormality of laboratory data, no apparent dilatation in the bile duct, and age of more than 35 years.

Adenomatous Polyposis Coli↗

[Clinical study on the effect of intra-arterial injection of mitoxantrone-lipiodol emulsion for hepatocellular carcinoma].

To investigate the effect of intra-arterial injection of mitoxantrone emulsified with ethiodized oil, forty-eight patients with hepatocellular carcinoma were evaluated. After the treatment, ten of the patients underwent hepatectomy. In the thirty-eight unresected cases, there were 15 (39%) partial responses, which continued 1.2 to 11.8 months (mean, 5.8 months). The 1- and 2- year survival rates were 67% and 38%, respectively. The response rate was higher in cases with tumor under 5 cm in diameter. In the remaining 10 resected cases, the necrotic areas in main nodules ranged from 65% to 100% (mean, 85%). This treatment might be applied effectively to patients with small hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

[Therapeutic potential of sparfloxacin for preventing mycobacterial infections].

We studied the therapeutic potential of utilizing sparfloxacin (SPFX), a newly developed quinolone, to prevent various mycobacterial infections. The in vitro activity of SPFX as a preventive agent for various mycobacteria was determined using the actual count method on Ogawa egg medium. The minimal inhibitory concentrations (MICs) of SPFX were as follows: ofloxacin-sensitive M. tuberculosis, 0.16-0.32 microgram/ml; ofloxacin-resistant M. tuberculosis, 0.63-2.5 micrograms/ml; M. avium; 0.63-10 micrograms/ml (MICs were equal or less than 1.25 micrograms/ml in seven out of 11 strains); M. intracellulare, 2.5-10 micrograms/ml (MICs were equal or more than 10 micrograms/ml in 17 out of 23 strains); M. kansasii, < or = 0.08-0.16 microgram/ml; M. fortuitum, < or = 0.08 microgram/ml; M. chelonae subsp. abscessus, > 10 micrograms/ml; M. chelonae subsp. chelonae, 0.63 microgram/ml; M. scrofulaceum, < or = 0.08 microgram/ml; M. nonchromogenicum, 1.25 micrograms/ml; M. xenopi, < or = 0.08 microgram/ml; M. gordonae, < or = 0.08 microgram/ml. The average serum concentrations of SPFX during the period of multiple oral administration (200 mg once a day) were 0.35 +/- 0.16 microgram/ml before administration, 0.67 +/- 0.32 microgram/ml after one hour, 1.13 +/- 0.21 microgram/ml after two hours, 1.27 +/- 0.32 microgram/ml after four hours and 1.31 +/- 0.34 micrograms/ml after six hours. These results indicate that SPFX has a strong therapeutic potential to prevent infections due to M. tuberculosis, M. kansasii, M. fortuitum, M. chelonae subsp. chelonae, M. scrofulaceum, M. xenopi and M. gordonae. Moreover, it may be expected to be a promising agent against infections due to ofloxacin-resistant M. tuberculosis, M. avium and M. nonchromogenicum.

Anti-Infective Agents↗

[Henoch-Schönlein purpura associated with pulmonary tuberculosis].

A 34-year-old man was admitted to our hospital because of cough and fever. Chest radiograph showed multiple cavities mainly on the right lung. His sputum was positive for acid-fast bacilli on smear, and he was treated with daily isoniazide, rifampicin and streptomycin. Antituberculous treatment was successfully performed, so acid-fast bacilli of his sputa disappeared on smear and culture. Five months later, he developed a purpuric lesions over both legs accompanied by low grade fever and arthralgia, but proteinuria and abdominal pain could not be observed. Laboratory findings showed a normal platelet count and a normal bleeding time. High levels of serum IgG, IgA, C3 and C4 were evident. ASLO and ASK titer were elevated and they markedly increased within two weeks. A direct invasion of the vessel wall by tubercle bacilli is deniable because antituberculous treatment was successfully continued. Henoch-Schönlein purpura was diagnosed judging from these findings. High levels of ASLO and ASK suggest a preceding streptococcal infection for developing purpura but a possible infectious focus could not be identified. He was treated with 15 mg of prednisolone daily for two weeks and the lesion was subsided. The effect of prednisolone suggests that a subsequent antigen-antibody interaction caused by a streptococcal infection may participate in the formation of the purpura.

Adult↗

[Neutron capture therapy for cancer].

Boron neutron capture therapy (BNCT) is a selective radiotherapy using boron-10 which absorbs thermal neutrons and releases high LET alpha particles by 10B(n, alpha)7Li reaction. In this paper, the present status of BNCT for malignant melanoma was introduced. As a melanoma-targetting 10B-compound, 10B-paraboronophylalanine (BPA) was used. It was administered by multiple subcutaneous injection or intravenous drip infusion. We adopted the maximum tolerance dose to the skin as a therapeutic dose regardless of the tumor 10B concentration, because we cannot directly measure it. For this purpose, an approximation of skin concentration was made using blood data just after the administration. We treated 14 melanoma patients in this way and obtained good local control of the tumor with tolerable skin reaction. More experience with logical analysis and basic research is necessary for further development of this therapy.

Boron Compounds↗

Differential effect of host microenvironment and systemic humoral factors on the implantation and the growth rate of metastatic tumor in parabiotic mice constructed between young and old mice.

B16 melanoma cells were injected into the tail vein of young mice, old mice and parabiotic mice constructed between young and old mice, and the number and shape of pulmonary metastases were compared among three experimental groups. In unpaired mice, the number of metastatic colonies in the lungs was 10-fold larger in young than in old mice. In parabiotic mice, the number in young mice was almost comparable with that of unpaired young mice, but the number in old mice approached the level of young mice. Metastatic colonies on the pulmonary surface of young mice were mostly nodular in shape, while those of old mice were flat in shape. The shape of colonies reflecting the tumor growth rate did not change in parabiotic old mice in spite of an increase in number. In young parabiotic mice, the large and intermediate colonies decreased with a concomitant increase of small ones as compared with unpaired young mice. These results suggest that the implantation of metastatic colonies in the lung is mainly dependent on systemic humoral factors and their growth is mainly dependent on the host local factors in the microenvironment, and distinct age changes of both factors greatly influence the metastatic mode of tumors, respectively.

Aging↗

Intestinal ischemia resulting from Buerger's disease: report of a case.

A 42-year-old man who had undergone below-the-knee amputations for Buerger's disease 9 and 14 years earlier required emergency surgery for intestinal ischemia caused by arterial occlusive lesions in the mesentery. The cecum and proximal part of the ascending colon were resected, and marked hyperemic thickening of the wall and severe fibrous adhesions were found. Postoperative angiography revealed occlusions in the superior mesenteric and right external iliac arteries. The resected specimen showed mucosal necrosis of the cecum and circular ulcers at Bauhin's valve and at the ascending colon. Microscopically, small mesenteric vessels were occluded by organized and recanalized thrombi with preserved vascular architecture. The patient has remained free of any further intestinal symptoms for 1 year following his discharge from hospital.

Adult↗

Jejunal perforation caused by blunt abdominal trauma in a patient with Crohn's disease: report of a case.

We report herein the case of a 23-year-old man with Crohn's disease who was found to have a perforated small bowel following blunt abdominal trauma sustained in a traffic accident. The general findings of diffuse peritonitis were identified by physical examination, and a plain X-ray film showed free air in the abdominal cavity. An emergency laparotomy was performed which revealed three perforated ulcers in the affected intestine. An abrupt increase in intraluminal pressure due to the striking force of the steering wheel to the abdomen was assumed to have been the cause of these perforations.

Abdominal Injuries↗

Small aorta syndrome.

A 47-year-old female with a 10-year history of bilateral intermittent claudication was diagnosed as having small aorta syndrome (SAS) and was successfully treated by an aorto-bifemoral bypass with aortic thrombendarterectomy. The infra-renal aorta was narrow, being 10 mm in diameter, with thrombotic occlusion of the terminal aorta and common iliac arteries. These findings were compatible with the features of SAS, however, there were few atherosclerotic changes in the abdominal wall and no evidence of any prediposing risk factors such as smoking or hyperlipidemia. Computed tomography, in addition to arteriography, seemed imperative for making the preoperative diagnosis. SAS is not uncommon as an established entity in Western Countries, but in Japan there have been few reports to date. The etiology, diagnosis, and management of this entity are reviewed following the presentation of this case.

Aorta, Abdominal↗

An experimental study on intestinal vascular lesions: a comparison between the effects of arterial and venous occlusion in the acute phase.

In order to clarify what early ischemic changes are produced by venous interruption in the intestine, intestinal vascular lesions caused by peripheral venous ligation were compared with those caused by arterial ligation in rabbits. With less than 30 min ligation, there were only 4 specimens from a total 13 without injury following venous ligation, whereas there were 7 from a total 11 without injury following arterial ligation. After 30 min venous ligation, both the mucosal and submucosal layers of all 10 specimens were affected, while following arterial ligation, 3 of the 11 specimens showed no histological changes. Moreover, in 3 of the remaining 8 specimens from the latter group, the injury was confined to within the mucosal layer. Thus, in cases of venous interruption, intestinal injury might be evoked earlier with more severe damage than in cases of arterial interruption.

Acute Disease↗

A case of renal cell carcinoma with metastasis to the thyroid gland and concomitant early gastric cancer.

Metastatic lesions from renal cell carcinoma are commonly recognized in the lung and bone, however, thyroid metastasis has rarely been reported in the literature. We present herein a case of a man with lung and thyroid metastatic tumors from renal cell carcinoma. Although making a preoperative diagnosis of thyroid metastasis is difficult because there is no established diagnostic criteria, we were able to identify this thyroid lesion as a metastatic tumor from renal cell carcinoma by the pathological findings. Interestingly, hypercalcemia was recognized in this patient whose serum parathyroid hormone (PTH) level was not increased. Moreover, this patient also had early gastric cancer simultaneously, being a so-called 'double cancer'. After surgical resection of the right kidney and stomach, interferon was administered without any efficacy against the metastatic lesions of the lung and thyroid gland.

Carcinoma, Renal Cell↗

Transcription of mouse ribosomal RNA gene with inactive extracts is activated by NAD+ in vitro.

S100 extract prepared from rapidly growing mouse FM3A cells (approx. 5 x 10(5) cells/ml) transcribed ribosomal RNA gene (rDNA) much more actively in vitro than that from stationary phase cells (1-2 x 10(6) cells/ml). When the inactive S100 extract was preincubated with NAD+, rDNA transcriptional activity was restored almost to the level of the active extract. The extract activated with NAD+ exhibited a gel-shift band in the gel mobility shift assay and enhancement of protection of the sequence between -44 and -8 nt from the initiation site from exonuclease III digestion. Such an extract labeled with [32P]NAD+ was analyzed by immunoprecipitation with anti-RNA polymerase I (pol I) antibody; a protein with M(r) 130 kDa was detected. In contrast, the polypeptide was hardly labeled in the active extract. 3-Aminobenzamide, a specific inhibitor of poly ADP-ribosylation, did not inhibit the activation by NAD+. These results suggest that the activation by NAD+ is due to enhancement of the formation of initiation complex by mono ADP-ribosylation of the second-largest subunit (130 kDa) of pol I.

Animals↗

The impact of familial adenomatous polyposis on the tumorigenesis and mortality at the several organs. Its rational treatment.

The authors reviewed the case records of 1050 familial adenomatous polyposis (FAP) patients who were registered at their institution. The organ-specific morbidity and mortality rates of malignant tumor in FAP patients were compared with those of the general population of Japan, and the prognosis after rectum-preserving operation also was calculated. The cumulative prevalence of colorectal carcinoma at the age of 44 years was 0.52 for men and 0.61 for women. The observed/expected morbidity ratio was 20.9 (95% confidence interval, 10.8-36.6) for thyroid carcinoma, 3.08 (2.03-7.75) for gastric carcinoma, and 295 (263-330) for colorectal carcinoma. The observed/expected mortality ratios was 250 (112-447) for periampullary and small intestinal carcinoma, 3.43 (1.77-6.0) for gastric carcinoma, and 210 (183-241) for colorectal carcinoma. The risk of rectal carcinoma after ileorectal anastomosis was 13% (8.5-17.5%) at 10 years and 37% at 20 years. The results clarified the impact of FAP on the carcinogenesis in several organs as a whole including preserved rectum, and suggested a direction of the rational treatment of FAP.

Adenomatous Polyposis Coli↗