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Biomedical subjects

Y Miyauchi

Publications and source records attributed to Y Miyauchi.

At least 91 records · Page 5Linked to original sources

Carcinoembryonic antigen (CEA) and CEA-related substances in the bile of patients with biliary diseases.

The levels of carcinoembryonic antigen (CEA) in the bile of 10 patients with biliary cancer and 9 patients with cholelithiasis were examined immunochemically by the Western blot analysis. All samples of bile from the patients with biliary cancer showed three bands that corresponded to CEA, nonspecific crossreacting antigen, and biliary glycoprotein 1, respectively. The upper band (CEA) disappeared from the bile of patients who underwent curative operations, but it persisted in the bile of patients who underwent noncurative operations. All samples of bile from the patients with cholelithiasis did not show the upper band (CEA), even in those samples that had high levels of CEA by the conventional enzyme immunoassay. We suggest that, in order to diagnose the presence of tumor, to assess the therapeutic efficacy of surgery, and to detect any residual tumor, not only should the level of bile CEA be measured but also a Western blot analysis of the bile should be performed since it is more reliable.

Aged↗

Ultrastructural cytochemical demonstration of proteoglycans and calcium in the extracellular matrix of chondroblastomas.

To clarify the characteristics of the extracellular matrix of chondroblastomas, six cases were studied under the electron microscope, with special reference to proteoglycans and calcium in the cellular areas. In ruthenium hexammine trichloride (RHT)-stained sections the matrix was observed to be composed of rounded or polygonal fine granules and unbanded thin filaments that appeared to link neighboring granules together. Treatment with potassium-pyroantimonate showed intracellular accumulation of precipitates, mainly localized within the cisternae of the rough endoplasmic reticulum as well as in the extracellular matrix. The presence of calcium in the precipitates was confirmed using x-ray energy dispersive analysis. These findings, similar to characteristic features observed in calcifying systems, support the theory that chondroblastomas are of chondrogenic origin.

Calcium↗

Beraprost sodium protects occlusion/reperfusion injury in the dog by inhibition of neutrophil migration.

1. The effects of beraprost sodium (beraprost) on myocardial infarct size in an anesthetized open-chest canine model of regional myocardial ischemia and reperfusion were investigated. 2. Administration of beraprost (300 ng/kg/min, intravenously) to dogs 45 min after left circumflex coronary artery occlusion until 105 min after reperfusion resulted in a significant reduction in infarct size. 3. The values of control and beraprost treated infarct size expressed as a percentage of the total left ventricle were 15 +/- 3% and 4 +/- 2%, respectively. 4. Reperfusion arrhythmia, plasma creatine phosphokinase (CK) and lactate dehydrogenase (LDH) level were significantly suppressed by treatment with beraprost. 5. By histological examination, beraprost proved to reduce neutrophil migration in the ischemic myocardium after 5 h reperfusion. 6. Therefore, it is suggested that the cytoprotective effect of beraprost during myocardial ischemia and reperfusion may be the consequence of the inhibition of neutrophil migration.

Animals↗

Actin-severing and Ca(2+)-induced reversal of smooth muscle contraction that is independent of Ca2+.

1. Intracellular actin filament organization of gastric smooth muscle cells of the guinea pig in primary culture was examined with rhodamine-labelled phalloidin using a confocal laser fluorescence microscope. 2. The resting cells, both in the presence and absence of Ca2+, showed an even distribution of microfilamentous actin fibers. 3. The characteristic image of the stimulated cells with 10 microM acetylcholine in the presence of 1.8 mM Ca2+ was that the actin filaments were located only on the periphery of the cell. 4. The characteristic image of the cells stimulated as above, but in the absence of Ca2+, was that the actin filaments were unevenly distributed in the cell. 5. The characteristic image of the cells stimulated in the presence of 1 microM Ca2+, which inhibits the above contraction, was pultaceous with the actin filaments absent, indicating severing of actin filaments by a Ca(2+)-activated system, such as gelsolin.

Actins↗

Effects of tyrosine kinase inhibitor, genistein, and phosphotyrosine-phosphatase inhibitor, orthovanadate, on Ca(2+)-free contraction of uterine smooth muscle of the rat.

1. The effects of a protein-tyrosine kinase inhibitor, genistein, and a protein-tyrosine phosphatase inhibitor, orthovanadate, were tested on the Ca(2+)-free contraction of the estrogen-dominated rat, which has been proved to be induced mainly via protein kinase C entirely independently of Ca2+. 2. Genistein (30 microM) significantly inhibited the contraction indicating participation of tyrosine kinase activity in the contraction. 3. Orthovanadate caused contraction concentration-dependently and augmented the Ca(2+)-free contraction at concentrations of more than 1 microM. The contraction by orthovanadate was not inhibited so significantly by genistein (30 microM). 4. Possible participation of tyrosine kinase activity in Ca(2+)-free contraction is discussed in addition to the formerly reported participation of protein kinase C.

Animals↗

Changes in receptor-mediated endocytosis in liver sinusoidal cells after partial hepatectomy in the rat.

Liver sinusoidal cells play an important role in host defense by clearing particulate matter and macromolecules from the circulation. In this study, receptor-mediated endocytosis in sinusoidal cells was examined in two-thirds hepatectomized rats using 125I-labeled formaldehyde-treated bovine serum albumin (fBSA) as an endocytable macromolecule. The liver-weight to body-weight ratio in hepatectomized rats returned to the control value 10 days after hepatectomy. The endocytotic index for fBSA in sinusoidal cells decreased significantly to 0.0210 +/- 0.0017 (controls, 0.0598 +/- 0.0019) on the first day, then returned to the control level at 5 days (0.0554 +/- 0.0030). The changes in hepatic uptake for fBSA showed a similar time course of the endocytotic index. A transient increase in the uptake of fBSA per unit weight of liver of 22-39% above control occurred 2 to 3 days after hepatectomy. In contrast to fBSA, the endocytotic index in hepatocytes evaluated with 125I-labeled asialofetuin reached the minimum level on the second day, and then recovered to the control level 10 days after hepatectomy. These results suggest that endocytosis of fBSA by sinusoidal cells decreases after hepatectomy and rapidly recovers to normal before the completion of liver regeneration, whereas endocytosis of asialofetuin by hepatocytes decreases following hepatic resection and returns to normal when regeneration is substantially complete.

Animals↗

Treatment strategies for hepatic metastases from pancreatic cancer in patients previously treated with radical resection combined with intraoperative radiation therapy.

Since 1984, we have performed extended radical resection combined with extended intraoperative radiation therapy (IORT) for pancreatic cancer. This approach has provided a dramatic improvement in long-term survival and control of local recurrence. Hepatic metastases, however, remain an unsolved problem. Among patients with this combined therapy, we found hepatic metastases in 8 of 22 patients postoperatively. Four of these 8 were considered candidates for further therapy and underwent treatment for their hepatic metastases, the other 4 had too extensive disease. Two patients with multiple hepatic metastases underwent percutaneous ethanol injection therapy and chemotherapy, but they died within a year. Two patients with a solitary hepatic metastases underwent hepatic resection. One patient died two years and six months after the first operation because of multiple metastases in the liver and both lungs, while the other patient is still alive over six years after the first operation with an excellent performance status. When a patient has no local recurrence and a solitary metastasis in the liver, surgical resection of the liver metastasis should be performed.

Adenocarcinoma↗

HTLV-I-associated myelopathy in a patient with chronic renal failure.

A case of human T-cell lymphotrophic virus type I (HTLV-I)-associated myelopathy (HAM) occurring in a 62-year-old Japanese male with a history of hemodialysis and repeated blood transfusions due to chronic renal failure (CRF) is reported. The patient was a lifelong resident of Chiba Prefecture, a nonendemic area for HTLV-I infections. The clinical course was characterized by abrupt onset and rapid progression of neurological signs and symptoms, which appeared to have responded quite well to prednisolone. Although patients with a history of CRF, hemodialysis, and transfusion of blood units which were not screened for anti-HTLV-I antibodies appear to belong to the high risk group for HTLV-1 infections and subsequent development of HAM, reports on such cases have been scanty. Only 3 cases have been reported to date. It appears quite possible that many patients with CRF and HAM remain misdiagnosed.

Adult↗

[Treatment of the peripheral vascular diseases with prostaglandin].

The clinical usefulness of prostaglandin derivatives was reviewed for the treatment of peripheral vascular diseases such as arteriosclerosis obliterans, Buerger's disease, Raynaud's disease, and collagen disease etc. PGE1 was initially used for this purpose, however, it had to be infused intra-arterially or intravenously for hours. PGE1 incorporated in lipid microsphere (Lipo PGE1) was made for one-shot use and the targeting drug delivery because the lipid microsphere is easily taken up by some inflammatory cells. Lipo PGE1 was revealed to be effective to improvement of considerably large ischemic ulcer and pain. Beraprost sodium (PGI2 derivative) was produced for oral use, and has been widely used. The effectiveness was similar to Lipo PGE1, but the complications such as hypotension, headache, and numbness were more common in PGI2.

Alprostadil↗

Preoperative chemotherapy for esophageal cancer based on chemosensitivity testing.

To examine the role and significance of in vitro chemosensitivity testing on cells cultured from endoscopic biopsy specimens, we evaluated outcomes in 57 patients with squamous cell carcinoma of the thoracic esophagus. Over 3 1/2 years, 57 patients were treated with a single course of preoperative combination chemotherapy based on the results of chemosensitivity testing utilizing eight antineoplastic agents. A radiologically evident response (partial response) was seen in 23 patients (40.4%) and histologic effects on grade IIb tumors were seen in six patients (10.5%). The median survival time of all 57 patients was 16.3 months. The median survival time of nine patients who received palliative resection was 4.5 months. The median survival times after curative resection of the 19 patients with a partial response and 29 patients with no response were 27.7 months and 17.3 months, respectively (p < 0.009). The most frequent combination chemotherapy used was cis-dichlorodiammine platinum (II) vindesine/5-fluorouracil, and a high rate of response was noted after therapy with etoposide and 4'-D-tetrahydropyranyl-doxorubicin. Chemosensitivity testing appears to be useful in selecting preoperative chemotherapeutic agents for patients with esophageal cancer, decreasing tumor recurrence after surgery and resulting in more partial responses than conventional chemotherapy.

Adult↗

Increased expression of nucleoside diphosphate kinase/nm23 and c-Ha-ras mRNA is associated with spontaneous lung metastasis in rat-transplantable osteosarcomas.

The relationship between expression of nucleoside diphosphate kinase (NDP kinase)/nm23, c-Ha-ras, and c-myc genes and metastatic potential was assessed in rat-transplantable osteosarcoma lines, derived from spontaneous and chemical carcinogen (4-hydroxyamino quinoline 1-oxide)-induced osteosarcomas in Fischer 344/NS1c rats. These osteosarcomas possess metastatic potential and highly metastatic lines spontaneous osteosarcoma-selected lung metastatic lesions and 4-hydroxyamino-quinoline 1-oxide-induced osteosarcoma-selected lung metastatic lesions were respectively established by selectively transplanting lung metastatic lesions. Northern blot analysis revealed that the levels of NDP kinase/nm23 and c-Ha-ras gene expression were increased in line with metastatic ability; thus transcript levels were remarkably greater in both spontaneous osteosarcoma-selected lung metastatic lesions and 4-hydroxyamino-quinoline 1-oxide-induced osteosarcoma-selected lung metastatic lesions highly metastatic lines than in their respective low metastatic spontaneous and chemical carcinogen (4-hydroxyamino quinoline 1-oxide)-induced osteosarcoma counterparts. c-myc mRNA expression was observed in all tumor lines, without any correlation with metastatic ability. Southern blot analysis did not show evidence of gross rearrangement or amplification of NDP kinase/nm23, c-Ha-ras, or c-myc genes suggesting regulation of their gene expression at the transcriptional and/or posttranscriptional level. These results indicate that NDP kinase/nm23 and c-Ha-ras might be cooperatively involved in a positive manner in signal transduction processes, especially involving G-protein reactions, responsible for metastasis of rat-transplantable osteosarcomas.

Animals↗

Preoperative in vitro chemosensitivity test of esophageal cancer with endoscopic specimens.

BACKGROUND: From January 1990 to June 1991, the authors tested in vitro chemosensitivity before surgery with endoscopic biopsy specimens from 23 patients with intrathoracic esophageal cancer. METHODS: The authors tested eight anticancer agents using the dye exclusion method, and all 23 patients received chemotherapy with the most sensitive three drugs according to the results of the chemosensitivity test. RESULTS: Ten patients (43.5%) had a tumor reduction of more than 50% on radiologic studies, and 4 patients (17.4%) had a good histologic effect. CONCLUSIONS: The chemosensitivity test is useful in selecting preoperative chemotherapeutic agents for patients with esophageal cancer.

Adult↗

The spleen can influence the metastasis of AH130 hepatoma cells in rats.

The effect of pathophysiological conditions due to disturbance of the spleen is still unclear. We studied the effects of splenectomy in normal and methylcellulose-induced hypersplenic rats on the development of pulmonary metastases created by intravenous injection of ascites containing AH130 hepatoma cells from male Hos-Donryu rats. Growth of metastatic lesions in the lung was not affected by splenectomy in normal rats, but was increased by splenectomy in hypersplenic rats. Overall, there were fewer pulmonary metastases in rats with hypersplenism, but after splenectomy rats with hypersplenism had a significantly greater number of metastases than did normal rats. The metastases rate correlated somewhat with changes in the blood coagulation and T lymphocyte profile. There is a relationship between the spleen and formation of metastases in cancer. Formation of metastases in the lung was affected most by splenectomy in hypersplenism. To elucidate the mechanism by which metastases are formed in the lung under these pathologic conditions, further studies on the exact role of the spleen are required.

Animals↗

Correlation between lack of bone Gla protein mRNA expression in rat transplantable osteosarcomas and expression of both c-fos and c-jun proto-oncogenes.

Alkaline phosphatase (AP) activity and expression of bone Gla protein (BGP), c-fos, and c-jun were compared in two transplantable osteosarcomas with high potentials for metastasis to the lung. The original spontaneous osteosarcoma (SOS) gradually became histologically undifferentiated, losing its osteogenic activity during serial transfer, whereas the chemical (4-hydroxyaminoquinoline 1-oxide)-induced osteosarcoma (COS) retained osteogenesis. The two osteosarcomas showed similar doubling times and levels of lung metastasis, and strong AP activity was detected on the cell membranes of both. Northern blot analysis revealed that lack of BGP mRNA expression was associated with expression of both c-fos and c-jun proto-oncogenes in SOS. In contrast, neither c-fos nor c-jun mRNAs were detected but BGP mRNA was expressed in the case of COS. These results suggest that the c-fos and c-jun genes may suppress the expression of BGP mRNA relevant to differentiation and osteoid formation in rat osteosarcomas. However, this does not appear to be directly related to proliferative or metastatic biological behavior.

Alkaline Phosphatase↗

A method for safe pancreaticojejunostomy.

We devised a new technique to increase the safety of pancreaticojejunostomy in patients with an extended operation for pancreatic cancer. This new pancreaticojejunostomy was created by end-to-side anastomosis with four layers about 7 cm distal to the jejunal stump. The cut surface of the pancreas was placed on the seromuscular coat of the ventral aspect of the jejunum to cover the posterior surface of the anastomosis, and the anastomosis between the pancreas and the jejunum was created using fibrin glue. The pancreatic duct was intubated with a silicone tube, and its stenting tube was brought out through a opening in the jejunum. The anterior surface of the pancreaticojejunostomy was covered by the proximal jejunum as a serosal patch. We used this technique in seven patients. No patient developed an anastomotic leak or any other complication. The anastomosis is covered by the jejunum and is not open to the peritoneum. This new technique of pancreaticojejunostomy may reduce the risk of pancreatic leak, especially when an extended operation is performed.

Humans↗

Deoxyribonuclease treatment prevents blood-borne liver metastasis of cutaneously transplanted tumour cells in mice.

Murine L5178Y-ML cells, when transplanted subcutaneously into the flank of (BALB/c x DBA/2)F1 mice, grew locally and always formed spontaneous metastases in the liver. Even after surgical removal of the primary tumour mass 5 or 7 days after tumour cell inoculation, all mice died due to liver metastases within 18 days. Using this model of tumour metastasis, we examined whether serine protease or deoxyribonuclease I (DNase I) would affect metastasis. Spontaneous liver metastasis of L5178Y-ML cells was enhanced by systemic administration of alpha-chymotrypsin at 3, 4 and 5 days or at 5, 6 and 7 days after tumour cell inoculation. This result was consistent with a previous report on blood-borne lung metastasis. In contrast, systemic administration of DNase I at 3, 4 and 5 days or at 5, 6 and 7 days after tumour cell inoculation inhibited liver metastasis. Neither treatment affected primary tumour growth. An influence of DNase I on tumour cell arrest in the microvasculature of the liver was suggested by scanning electron microscopy. DNase I treatment resulted in a statistically significant prolongation of the survival period, however, the effect was not satisfactory. A more striking anti-metastatic treatment resulting in a greater prolongation of the survival period was achieved by combining surgical removal of the primary tumour mass with DNase I treatment. These results suggest that DNase I could be a potential therapeutic agent used in conjunction with surgery to prevent clinical blood-borne metastasis.

Animals↗

Prolongation of survival for carcinoma at the hepatic duct confluence.

BACKGROUND: Because of poor long-term results in resection for carcinoma at the hepatic duct confluence, we have adopted a more aggressive approach. METHODS: The records of 46 patients with carcinoma of the hepatic duct confluence were reviewed. Twenty-four patients underwent hepatic resection and 10 underwent local resection. The remaining 12 patients had unresectable lesions and received palliative treatment. Out of 24 patients who underwent hepatic resection, 17 underwent combined resection of the caudate lobe. Five patients who underwent hepatic resection and three patients who underwent local resection received intraoperative radiotherapy in a dose of 30 Gy of electron beam. Postoperative radiotherapy with a total dose of 50 Gy of external electron beam was performed for five patients who underwent nonradical hepatic resection and one patient who underwent nonradical local resection. RESULTS: None of the 10 patients who underwent local resection and only 1 (4.2%) of 24 patients who underwent hepatic resection died in the hospital. Among patients who underwent hepatic resection, the 1-, 3-, and 5-year survival rates were 62%, 37%, and 25%, respectively, whereas the respective survival rates in the group that underwent local resection were 50%, 20%, and 20%. The 1-, 3-, and 5-year survival rates for patients who underwent combined caudate lobectomy were 69.7%, 53.4%, and 23%, respectively, compared with 57.1%, 26%, and 14.3% for those who did not. The median survival time for patients who received radiotherapy after nonradical resection was 17 months, compared with 5 months for those who did not. CONCLUSIONS: These results suggest that major hepatic resection combined with caudate lobectomy should be performed for carcinoma of the heptic duct confluence. Postoperative radiotherapy after nonradical resection may be effective in prolonging survival.

Adult↗

Ca(++)-independent relaxation mediated by beta adrenoceptor in Ca(++)-independent contraction of uterine smooth muscle.

Isoproterenol (ISO)-induced relaxation of oxytocin-induced Ca(++)-independent contraction of the rat uterus was examined. Oxytocin induced Ca(++)-dependent phasic contraction in a solution containing Ca++ (normal contraction) and Ca(++)-independent sustained contraction in Ca(++)-free solution (Ca(++)-free contraction). Both contractions were completely suppressed by cyclic AMP-elevating relaxants such as ISO, dibutyryl cyclic AMP and forskolin. Moreover, the ISO concentration needed to inhibit the Ca(++)-free contraction was lower than that needed for normal contraction, although the relaxing effect of dibutyryl cyclic AMP and forskolin during Ca(++)-free contraction was not significantly different from that during Ca(++)-dependent contraction. The ISO-induced relaxation of the uterus in Ca(++)-free solution may involve three mechanisms. The first is cyclic AMP-dependent relaxation shown by high concentrations (more than 1 nM) of ISO. The second is stabilization via K+ channels by intermediate concentrations (10 pM to 1 nM) of ISO. These two actions appear to be mediated through beta-1 adrenoceptors. The third is, however, via an unknown subtype of adrenoceptor stimulated by extremely low concentrations (1 pM to 10 pM) of ISO. All of these relaxing mechanisms are independent of Ca++.

Adrenergic beta-Antagonists↗