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Biomedical subjects

S Tashiro

Publications and source records attributed to S Tashiro.

At least 19 recordsLinked to original sources

The prognostic value of cytogenetic analyses in patients with acute nonlymphocytic leukemia treated with the same intensive chemotherapy.

BACKGROUND: Some specific chromosome abnormalities for the leukemias have been proven to be associated with the prognosis of acute nonlymphocytic leukemia (ANLL). However, most of these reports included patients treated with different protocols. Therefore, some bias has been involved in the evaluation of the prognostic factors in such reports. METHODS: The authors studied the morphologic, cytogenetic, and clinical features of 136 patients (86 males and 50 females) with de novo ANLL treated with the same protocol of intensive induction chemotherapy using multivariate analyses. RESULTS: Chromosome abnormalities were detected in 62.5% of the patients. The overall complete remission (CR) rate of disease was 85.5% in these patients. More than 90% of the patients with t(8;21) and pseudodiploid abnormalities achieved experienced CR. However, CR rates in the patients with abnormalities of chromosome 5 or 7 were 50%. With multivariate analyses by the type of karyotypic abnormality, CR duration and survival time of the patients with t(8;21) were longer than those of patients with normal karyotype and abnormalities of chromosome 5 or 7. Abnormalities of chromosome 5 or 7 and hyperdiploid were associated with poor prognosis. Older age and lower platelet counts also were factors contributing to shorter survival times. With the analysis with French-American-British (FAB) classification, only hypoplastic leukemia was a poor prognostic factor. CONCLUSIONS: These data suggest that cytogenetic analyses plays an important role in estimating the prognosis of patients treated with intensive induction chemotherapy.

Adolescent

Cytogenetic 2; 18 and 18; 22 translocation in chronic lymphocytic leukemia with juxtaposition of bcl-2 and immunoglobulin light chain genes.

The majority of follicular lymphoma cells carry the typical chromosome translocation 14;18, which juxtaposes the bcl-2 gene to the immunoglobulin heavy-chain (IgH) gene. Variant translocations of the bcl-2 gene to the Ig lambda or Ig kappa gene have been found by molecular biological techniques in a significant fraction (approximately 10%) of chronic lymphocytic leukemia (CLL). However, there have been no reports describing the presence of cytogenetic 18;22 and 2;18 translocations in CLL, in spite of extensive karyotypic studies. We present here two cases of CLL, one with cytogenetically detected t(2;18)(p11;q21) and the other with the t(18;22)(q21;q11). The molecular analysis revealed that these translocations juxtaposed the bcl-2 and immunoglobulin light-chain (IgL) genes. The t(18;22) broke the 5' flanking region of the bcl-2 gene and juxtaposed to the immunoglobulin lambda light-chain (Ig lambda) gene in a head-to-head configuration, as in the cases previously described. In the case of the t(2;18), the bcl-2 gene and immunoglobulin kappa light-chain (Ig kappa) gene were juxtaposed in a head-to-tail configuration, which is opposite to that expected from the orientation of the genes on chromosomes. The breakpoint was located within the 5' untranslated region of the bcl-2 gene. The results presented here indicate that the bcl-2/immunoglobulin light-chain (IgL) gene juxtaposition seen in a fraction of CLL is the result of cytogenetically detectable reciprocal chromosome translocations 2;18 and 18;22.

Base Sequence

Establishment of a human acute myeloid leukemia cell line (Kasumi-1) with 8;21 chromosome translocation.

A novel leukemic cell line with an 8;21 chromosome translocation, designated as Kasumi-1, was established from the peripheral blood of a 7-year-old boy suffering from acute myeloid leukemia (AML). The Kasumi-1 cells were positive for myeloperoxidase showing a morphology of myeloid maturation. The response in proliferation assay was observed in the culture with interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor (G-CSF), and granulocytemacrophage CSF (GM-CSF), but not with IL-1 or IL-5. Neither granulocytic nor eosinophilic maturation was observed in the liquid culture by the addition of dimethyl sulfoxide, G-CSF, or IL-5, respectively. In contrast, induction of macrophagelike cells was seen by the addition of phorbol ester. This is the first report of a human AML cell line with t(8;21) that has characteristics of myeloid and macrophage lineages. The cell line could be a useful tool for elucidating the pathophysiology of AML with t(8;21).

Antigens, CD

The significance of serum mitochondrial aspartate aminotransferase activity in the surgical field.

A study was carried out on the clinical significance of changes in the serum level of mitochondrial aspartate aminotransferase before and after surgery on patients suffering from various hepato-biliary diseases. The patients included those whose livers were impaired with cirrhosis, jaundice, or direct surgical intervention such as hepatectomy. It was found that the postoperative liver function of patients whose preoperative values of serum mitochondrial aspartate aminotransferase had been less than 10 Karmen units recovered with a favorable course, whereas that of patients whose values had exceeded 20 units deteriorated with persistent jaundice, ascites or hepatic insufficiency. Both the sensitivity and specificity of respective liver function tests were examined by the preoperative values of routine liver function tests and the postoperative liver functions. The results revealed the serum value of mitochondrial aspartate aminotransferase to be more sensitive than the other tests, while specificity was not significantly different. A safety limit for a favorable postoperative course in terms of liver function was observed in patients showing a preoperative serum mitochondrial aspartate aminotransferase activity of below 10 units. Thus, serum mitochondrial aspartate aminotransferase activity could be applied as a useful marker for hepato-biliary surgery.

Adolescent

Endotoxin-induced lung hemorrhages in obstructive jaundiced rats.

Endotoxemia in patients with biliary obstruction contributes to the high morbidity and mortality rates following surgery. We developed an animal model of disseminated intravascular coagulation (DIC) in rats on which bile duct ligation was performed following an injection of endotoxin (200 micrograms/kg bw). Macroscopic hemorrhages and microthrombi in the lung were found in jaundiced rats 6 hours after the injection of endotoxin and yet these phenomena were not found in non-jaundiced rats following an injection of the same amount of endotoxin. Coagulation studies also revealed characteristic findings of DIC in the jaundiced rats following the injection of endotoxin. This study confirms that obstructive jaundice is one of the main predisposing factors in the course of endotoxin-induced DIC.

Animals

Enzyme-induced aggregation and disaggregation of tumor cells via the cell surface glycocalyx in association with deoxyribonucleic acid.

Serine proteases cause aggregation of the rat ascites tumor cell lines AH-130, AH-109A and YS in vitro, and the tumor cell aggregates are dissolved by treatment with DNase I. We previously demonstrated that these events played a critical role in the augmentation or reduction of experimental blood-borne metastasis of these cell lines. In the present study, the ultrastructural features of this protease-dependent aggregation were analysed. Transmission and scanning electron microscopy revealed that after the protease treatment each tumor cell was surrounded by a thin membranous (sleeve-like) structure. This sleeve-like structure was stained with ruthenium red to an intensity similar to the cell surface of the control. Adjacent cells became attached to each other with microvilli via this fine structure. Immuno-electron microscopy revealed DNA antigen as dense patches on the sleeve-like structure or as faint and diffuse deposits on the outer surface of the cells by indirect immunoperoxidase staining using an anti-DNA monoclonal antibody. Both the sleeve-like structure and immunopositive deposits disappeared after treatment with DNase I. Neither cell viability nor the normal ultrastructure of their organelles was influenced by the enzyme treatment. These results indicate that serine protease-induced tumor cell aggregation is due to cellular contact via the sleeve-like structure, which probably originates from the cell surface glycocalyx in association with DNA molecules of unknown origin.

Animals

Mechanism for enterohepatic injury caused by circulatory disturbance of hepatic vessels in the rat.

We reported previously that a transient occlusion followed by reperfusion of the portal vein and the hepatic artery of the rat significantly decreased the transhepatic transport of a cholephilic compound, and that this decrease was prevented by pretreating animals with poly(styrene co-maleic acid butyl ester)-conjugated superoxide dismutase (SM-SOD). To elucidate the mechanism for oxidative injury of the liver and the site for the generation of superoxide radicals, the effect of a portosystemic bypass on the liver function was examined in the rat whose hepatic vessels were temporarily occluded. A portosystemic bypass inhibited the reperfusion-induced decrease in hepatic transport of bromosulfophthalein as effectively as did SM-SOD. Kinetic analysis using 125I-labeled albumin revealed that the permeability of the small intestine markedly increased after a transient occlusion. The increase in intestinal permeability was also inhibited either by SM-SOD or by the portosystemic bypass. Xanthine oxidase activity in portal plasma markedly increased during occlusion and reperfusion, while it remained within normal ranges in the bypassed group. Thus, superoxide radical, and/or its metabolite(s), might play a critical role in increasing the intestinal permeability and in the pathogenesis of reperfusion-induced liver injury.

Animals

[The significance of cytogenetic analysis in the diagnosis of leukemia].

The results of a comprehensive study on 1,000 patients who had been cytogenetically diagnosed to have leukemia in our department since 1962 are reported, and the value of cytogenetic diagnosis for leukemia emphasized. In our series, we detected patients with FAB L1 and L2 showing an abnormality rate of 60 and 66%, respectively. They included 20% with Ph1 positive ALL. In FAB L3, we found t(8;14) in 5 of the 6 patients. The FAB M1 group showed the lowest abnormality rate (50%). Forty percent of the M2 patients exhibited t(8;21), 60% of which also showed loss of sex chromosome of either X or Y. Seventy-eight percent of the M3 patients presented t(15;17) (two patients with no detectable t(15;17) showed rearrangements of retinoic acid receptor alpha gene). Inversion of chromosome 16 was found in 10% of the patients with FAB M4. Patients with M6 exhibited relatively complex chromosomes aberrations. RAEB patients showed more frequent and complex type of chromosome aberrations than PARA patients. Cytogenetic and molecular-biological analyses provided valuable information on the pathophysiology of leukemia and suggested the possible localization of novel oncogene(s).

Chromosome Aberrations

Surgical indication and significance of portal vein resection in biliary and pancreatic cancer.

Tumor and vascular resection was carried out in 27 patients with biliary and pancreatic cancer. Vascular resection included resection and reconstruction of the both the portal vein and hepatic artery in two of the patients. Portal vein resection only was carried out in 23 patients, and resection of the side wall and plasty of the portal vein was carried out in the other two patients. The technical limit of portal vein resection without graft was 4 cm in the hepatic hilus and 7 cm after total pancreatectomy or pancreatoduodenectomy without grafts. On temporary occlusion of the portal vein between resection and reconstruction, simple occlusion was sufficient if it occurred within 30 minutes. In occlusion of more than 30 minutes, simultaneous occlusion of the superior mesenteric artery is better to prevent congestion of the intestine. If occlusion of more than 60 minutes is anticipated, a bypass between the superior mesenteric vein and the femoral vein with Anthron tube is recommended. The postoperative course was uneventful in 20 of the 27 patients. Two patients died within 1 month after surgery. The mortality rate for this aggressive surgery was 8.4%. Minor complications such as hydrothorax, small bile leakage, and localized abscess were observed but soon subsided in five patients. Fourteen of 27 patients survived or are alive after more than 1 year, and 9 of 14 patients survived or are alive after 2 years. Forty-seven percent of the patients who had no lymph node metastasis or peritumor lymph node metastasis without cancerous invasion of the portal vein intima survived more than 2 years. The longest length of survival of a patient with nonfunctioning islet cell carcinoma of the pancreatic head was 5 years 9 months. The longest surviving patient with ductal cell carcinoma of the pancreas is still living after 4 years. This approach is recommended in certain patients with vascular involvement but without lymph node metastasis or those patients with only peritumor lymph node involvement. Frozen section of mesenteric and paraaortic nodes should be standard practice before this aggressive resection.

Adult

Inhibition of ischemia and reflow-induced liver injury by an SOD derivative that circulates bound to albumin.

Ischemia followed by reflow often results in tissue injury. Although reactive oxygens seem to play an important role in the pathogenesis of postischemic reflow-induced tissue injury, the mechanism and an efficient way to inhibit oxidative injury are not known. We studied the mechanism by which hepatic transport function was inhibited by a transient occlusion followed by reflow of the portal vein and hepatic artery by using a superoxide dismutase (SOD) derivative (SM-SOD) which circulates bound to albumin with a half-life of 6 h. Occlusion of the hepatic vessels for 20 min followed by reflow for 60 min significantly inhibited transhepatic transport of cholephilic ligands, such as bromosulfophthalein (BSP) and taurocholic acid. Intravenous administration of SM-SOD markedly inhibited the reflow-induced decrease in transhepatic transport of these ligands. Thiobarbituric acid - reactive metabolites (TBAR) in the liver and plasma remained unchanged during occlusion and reflow, while TBAR in the bile increased significantly. Intravenous injection of SM-SOD inhibited the reflow-induced increase in biliary TBAR. Xanthine oxidase activity in plasma also increased during occlusion and reflow by an SM-SOD-inhibitable mechanism. Polymorphonuclear leukocyte-dependent chemiluminescence of the peripheral blood remained unchanged during occlusion, but increased markedly with time after reflow. SM-SOD also inhibited the increase in chemiluminescence almost completely. These and other results suggested that the superoxide radical and/or its metabolite(s) might play an important role in the pathogenesis of the reflow-induced liver injury and that SM-SOD might be useful for studying the mechanism for tissue injury caused by oxygen toxicity.

Animals

The significance of serum mitochondrial aspartate aminotransferase activity in obstructive jaundice: experimental and clinical studies.

The serum level of mitochondrial aspartate aminotransferase was determined in experimental and clinical obstructive jaundice, using an immunoabsorbance method which allowed the differential determination of cytosolic and mitochondrial isozymes in the serum. In experimental obstructive jaundice using dogs, the serum mitochondrial aspartate aminotransferase value rapidly decreased to normal after biliary decompression following a period of biliary obstruction of within 3 weeks. On the other hand, when the period of jaundice was prolonged for 5 weeks, the activity of the enzyme after biliary drainage still continued to show high values, being 14.2 +/- 1.8 Karmen units at 4 weeks following biliary decompression. Determination of aspartate aminotransferase activity in tissue from such organs as the liver, heart, kidney, skeletal muscle and brain, as well as serum samples withdrawn from local veins, confirmed that high serum values of the enzyme in experimental obstructive jaundice were mostly attributable to hepatic impairment induced by biliary obstruction not by secondarily damaged tissues of other organs. Mitochondrial aspartate aminotransferase proved to be a more useful marker than other routine tests in icteric dogs. In 13 clinical patients with obstructive jaundice, decreasing rates of serum mitochondrial aspartate aminotransferase on the 7th and 14th postoperative days could be applied to evaluate the viability of the icteric liver. The decreasing rates were more advantageous than the preoperative activity itself in predicting the postoperative function of the liver. Thus, mitochondrial aspartate aminotransferase appears to serve as a useful marker for assessing the liver function in obstructive jaundice.

Adolescent

A case of type Ia glycogen storage disease complicated by hepatic adenoma.

A 31-year-old male patient with type Ia glycogen storage disease was admitted to our department complaining of general fatigue and right hypochondriac pain. He exhibited massive hepatomegaly with systemic hypoglycemia, lactic acidosis, hyperuricemia, hyperpyruvatemia and hyperlipemia. The failure of blood glucose levels to increase after a glucagon loading test, and a reduced lactate level on glucose tolerance test were also observed. Various imaging techniques suggested hepatic adenoma with hemorrhage in the tumor, which was confirmed histologically. There was a complete absence of glucose 6-phosphatase activity, as determined by an enzyme assay on resected liver specimens, which proved the case to be type Ia glycogen storage disease. We also reviewed all previously reported cases of hepatic tumor and glycogen storage diseases. We conclude that, since hepatic adenoma is not rare in this disease, and is complicated by hemorrhage, rupture and malignancy, careful follow-ups are necessary.

Adult

[CT image of the liver cancer after administration of SMANCS/lipiodol].

A new type of anticancer agent with an amphiphilic nature, poly (styrene-co-maleic acid)-conjugated neocarzinostatin [SMANCS], was dissolved in the lipid contrast medium Lipiodol [SMANCS/LPD]. This medium was injected intra-arterially and was found to be an invaluable tool for highly sensitive CT image analysis of tumors. Following administration, CT images revealed high-density areas which corresponded to the location and size of liver cancer, the smallest being 4 mm in diameter. The deposition pattern of SMANCS/LPD in liver cancers by CT was classified into 3 types. In type A, Lipiodol was distributed relatively evenly in the tumor lesion, while in type B it was accumulated predominantly around the tumor periphery, the central portion remaining low in density. A for cases exhibited a type C pattern which was a mixture of types A and B. Type A was found essentially in primary liver cancer, and types B and C in secondary liver cancer. Thus, the CT pattern was found to be useful for differential diagnosis. For a sufficient therapeutic effect, 0.08 ml of SMANCS/LPD per cm2 of the maximal CT cross-section of the tumor area was found to be necessary. As a routine protocol after SMANCS/LPD administration, CT scanning was recommended for primary liver cancer initially at one week and then once every month. Secondary liver cancer required more frequent CT follow-ups after administration, on the 3rd day, after one and two weeks, and every month, due to the relatively rapid disappearance of the stain than in primary liver cancer.

Antibiotics, Antineoplastic

Anticancer effects of local administration of mitomycin C via the hepatic artery or portal vein on implantation and growth of VX2 cancer injected into rabbit liver.

Rabbits were inoculated with a suspension of VX2 carcinoma cells in the liver, and mitomycin C was given via the hepatic artery or the portal vein for a study of the anticancer effects. Twenty-eight rabbits were killed for preliminary study at 1 h or 1, 3, 7, 9, 12, or 14 days after the inoculation. Another 36 rabbits were divided into three groups. Groups A and B were given the agent (0.5 mg/kg), 1 h after the inoculation and on Days 2, 4, 6, and 8, into the common hepatic artery or the splenic vein, respectively. Group C was not treated after inoculation. The mean numbers of cancer nodules per rabbit in Groups A, B, and C were 11.9, 36.4, and 83.4, respectively, at 12 days after inoculation. The number of cancer nodules of Group A was smallest (P less than 0.025, F test). The means of the total cross-sectional area of tumor nodules in Groups A, B, and C were 32.7, 79.7, and 217.3 mm2, respectively. The total cross-sectional area of the cancer nodules of Group A was smallest (P less than 0.05, F test). These results suggest that the anticancer agents given via the hepatic artery had better effects on early (small) metastatic liver tumor than those via the portal vein.

Animals