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Biomedical subjects

K Tsukada

Publications and source records attributed to K Tsukada.

At least 91 records · Page 5Linked to original sources
PubMed1999

A study of therapy for pediatric hepatoblastoma: prevention and treatment of pulmonary metastasis.

Our results of treatment for pediatric hepatoblastoma are presented with special emphasis on pulmonary metastasis. The pulmonary metastasis rate of hepatoblastoma was 44% (11/25). In 19 patients with resected hepatoblastomas, the 5-year survival rate without pulmonary metastasis was 90% (9/10); while with pulmonary metastasis it was 22% (2/9). Six patients with unresected hepatoblastomas all died within 4 months regardless of chemotherapy and/or metastasis. To improve survival in patients with hepatoblastoma, preoperative or postoperative chemotherapy was thought to be essential for tumors extending over 2 hepatic segments and having predictable factors for pulmonary metastasis (large size or histological evidence of capsular invasion). A long-term multidisciplinary approach including hepatic lobectomy, current multiagent chemotherapy (including CDDP, THP-ADR), and partial pulmonary resection for localized lung areas with metastases would ultimately be needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Adhesion preventive effect of hyaluronic acid after intraperitoneal surgery in mice.

Prevention of intraperitoneal adhesion after gynaecological surgery is essential for maintaining postoperative fertility. In this study, the adhesion prevention effect was examined of a hyaluronic acid (HA) solution obtained from the fermentation method and having a molecular weight of 1.9x10(6) with high viscosity. Laparotomy was conducted on female mice 7 weeks old, whose menstrual periods were synchronized by pregnant mare serum gonadotrophin (PMSG) to injure the uterine horn surface. Intraperitoneal adhesions were favourably formed in 91.7% of cases induced with iodine abrasion, compared with 50% induced by electrosurgery. Intraperitoneal administration of HA was evaluated for its effect on the prevention of adhesions made by iodine abrasion. Adhesion prevention effects of HA were observed at concentrations of 0.3, 0.5, 0.75 and 1.0%, among which the most pronounced effect was with the use of a 0.3% solution (92.3% of cases). Compared with the control group adhesion score of 2.0 +/- 0. 8, significant decreases in adhesion scores were observed at all concentrations. HA with a molecular weight of 1.9x10(6) was recognized to have a definitive prevention effect on postoperative adhesions in mice after laparotomy and is considered to be a prospective material for future clinical use.

Animals↗
PubMed1999

Neutrophil accumulation and damage to the gastric mucosa in resuscitated hemorrhagic shock is independent of inducible nitric oxide synthase.

Polymorphonuclear leukocytes (PMN) and inducible nitric oxide synthase (iNOS) appear to play important roles in the liver and in lung injury induced by hemorrhagic shock. Their precise roles in hemorrhagic shock-induced acute gastric mucosal lesions (AGML), however, are still poorly understood. In this study, we investigated the effect of neutropenia on hemorrhagic shock-induced AGML. We also examined the roles of iNOS in PMN infiltration into the mucosa and AGML during hemorrhagic shock by using L-N6-(1-iminoethyl)-lysine, a potent inhibitor of iNOS, and by reverse transcriptase polymerase chain reaction. Remarkable gastric mucosal damage occurs after hemorrhagic shock. PMN depletion caused by Vinblastine pretreatment significantly attenuates this AGML. Although low-dose L-N6-(1-iminoethyl)-lysine (50 microg/kg, iNOS inhibition) has no effect on AGML, high-dose L-N6-(1-iminoethyl)-lysine (250 microg/kg, iNOS + endothelial NOS inhibition) significantly exacerbates AGML without increasing PMN infiltration into the mucosa. The mRNA expression of iNOS in the stomach during hemorrhagic shock cannot be detected by reverse transcriptase polymerase chain reaction. We conclude that PMN play a pivotal role in hemorrhagic shock-induced AGML, iNOS does not regulate PMN infiltration into the mucosa, and endothelial NOS provides important protection against AGML during hemorrhagic shock.

Animals↗
PubMed1998

A new pseudo-peptide analogue of the Arg-Gly-Asp (RGD) sequence inhibits liver metastasis of colon 26-L5 carcinoma cells.

We have investigated the effect of the pseudo-peptide analogue (FC-336) of the Arg-Gly-Asp (RGD) sequence in a liver metastasis model by the inoculation of a highly liver-metastatic cell line of colon 26 carcinoma (colon 26-L5) into the portal vein of BALB/c mice. The intraportal injection of colon 26-L5 cells with FC-336 resulted in a marked suppression of liver metastatic colonies in a dose-dependent manner and it reduced the liver weights to a normal level. However, the co-injection of tumor cells with a high dose of RGDS tetrapeptide led to a slight inhibition of liver metastasis. The multiple i.v. administration of FC-336 after tumor inoculation as well as the injection of FC-336 with tumor cells caused significant inhibition of experimental metastasis in the liver. The multiple i.v. administration of the RGDS peptide did not show any inhibitory activity. FC-336 significantly enhanced the survival rate of mice compared with untreated controls when injected intraportally with tumor cells or when intravenously administered after tumor inoculation. Zymography analysis showed that FC-336 inhibited the degradation of gelatin substrate by matrix metalloproteinases (MMPs) produced by colon 26-L5 cells, while RGDS peptide did not affect the enzymatic degradation. These findings clearly indicate that the pseudo-peptides of the RGD sequence (FC-336) have a potent inhibitory activity on liver metastasis of colon 26-L5 carcinoma cells.

Animals↗
PubMed1998

Quantitation of telomerase activity in hepatocellular carcinoma: a possible aid for a prediction of recurrent diseases in the remnant liver.

Because telomerase activity is necessary for cell immortality and probably associated with tumor progression, we have evaluated a possible aid for quantitation of the activity to predict intrahepatic recurrences after surgery in patients with hepatocellular carcinoma (HCC). HCC tissues obtained by surgical resection from 20 patients were studied. Telomerase activity was expressed as peaks with a periodicity through a fluorescence-based telomeric repeat amplification protocol using an autosequencer, and the quantity of activity was calculated from peak areas. A ratio of fluorescence intensity depending on telomerase to that of an internal standard was used as a value of relative telomerase activity (RTA). RTA in serially diluted S100 extracts from HepG2 cells was well correlated with the amount of the extracts. The mean RTA value of 36.4 +/- 27.8 (mean +/- SD, 3.21 to 105) in 9 patients suffering from early recurrences after surgery was significantly higher than that (9.84 +/- 7.65; mean +/- SD, 3.00 to 29.0) in 11 patients without intrahepatic recurrences during the early period (P = .004). These results indicate that RTA value can be a useful predictor for intrahepatic recurrences during the early period after surgical resection of HCC.

Adult↗
PubMed1998

A case of resection under the IVC-atrial venovenous bypass of a hepatoblastoma after intraarterial chemotherapy.

An 11-month-old infant with a huge hepatoblastoma occupying almost the entire liver was admitted to the hospital. Serum alpha fetoprotein (AFP) level was elevated to 685,120 ng/mL. Combination chemotherapy with continuous arterial infusion of tetrahydropyranyl Adriamycin (THP-Adriamycin) and cisplatin based on the 91B1 protocol of the Japanese Study Group For Pediatric Liver Tumor (JPLT) was administered as the adjuvant chemotherapy. The tumor responded to three courses of chemotherapy and shrank in size, although venocavography showed that the inferior vena cava (IVC) was completely occluded below the entry of the hepatic veins. Right hepatic trisegmentectomy was performed with an IVC-atrial venovenous bypass that prevented massive bleeding. In this case, it was recognized that the IVC-atrial venovenous bypass was advantageous in an infant. The procedure is very simple and the blood flow obtained by the bypass was sufficient. Two weeks postoperatively, three courses of chemotherapy were initiated after the protocol. The patient remains well without signs of recurrence 39 months postoperatively, and the AFP value has remained within 10 ng/mL.

Antibiotics, Antineoplastic↗
PubMed1998

A role of neutrophils in the down-regulation of IL-6 and CD14 following hemorrhagic shock.

Hemorrhagic shock (HS) followed by resuscitation has been shown to initiate a series of events, including local cytokine production and PMN accumulation. To determine whether PMN are involved in the regulation of IL-6 expression in the liver or lungs, IL-6 mRNA levels were measured in rats made neutropenic by vinblastine pretreatment prior to HS. IL-6 mRNA levels were determined at 4 or 24 h following resuscitation from shock. Vinblastine alone in normal rats or sham-treated rats had no effect at 4 or 24 h. Vinblastine pretreatment had no effect on the HS-induced increase in IL-6 mRNA at 4 h but dramatically increased levels in both liver and lung at 24 h. Peripheral PMN counts were reduced by 95% in all vinblastine-treated animals. Similar changes seen in CD14 mRNA expression indicate that these effects are not limited to IL-6. These data show that normal PMN levels are not needed for induction of IL-6 and CD14 in HS, and suggest that PMN accumulation down-regulates the expression of these genes.

Animals↗
PubMed1998

Oral administration of a Kampo (Japanese herbal) medicine Juzen-taiho-to inhibits liver metastasis of colon 26-L5 carcinoma cells.

We have investigated the inhibitory effect of oral administration of Juzen-taiho-to, a Kampo Japanese herbal medicine, on liver metastasis by the inoculation of a liver-metastatic variant (L5) of murine colon 26 carcinoma cells into the portal vein. Oral administration of Juzen-taiho-to for 7 days before tumor inoculation resulted in dose-dependent inhibition of liver tumor colonies and significant enhancement of survival rate as compared with the untreated control, without side effects. We also found that liver metastasis of L5 cells was enhanced in BALB/c mice pretreated with anti-asialo GM1 serum or 2-chloroadenosine, and in BALB/c nu/nu mice, compared to normal mice. This indicates that NK cells, macrophages, and T-cells play important roles in the prevention of metastasis of tumor cells. Juzen-taiho-to significantly inhibited the experimental liver metastasis of colon 26-L5 cells in mice pretreated with anti-asialo GM1 serum and untreated normal mice, whereas it did not inhibit metastasis in 2-chloroadenosine-pretreated mice or T-cell-deficient nude mice. Oral administration of Juzen-taiho-to activated peritoneal exudate macrophages (PEM) to become cytostatic against the tumor cells. These results show that oral administration of Juzen-taiho-to inhibited liver metastasis of colon 26-L5 cells, possibly through a mechanism mediated by the activation of macrophages and/or T-cells in the host immune system. Thus, Juzen-taiho-to may be efficacious for the prevention of cancer metastasis.

2-Chloroadenosine↗
PubMed1998

Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury.

Hemorrhagic shock (HS) initiates an inflammatory cascade that includes the production of cytokines and recruitment of neutrophils (PMN) and may progress to organ failure, inducing acute respiratory distress syndrome (ARDS). To examine the hypothesis that interleukin-6 (IL-6) contributes to PMN infiltration and lung damage in HS, we examined the lungs of rats subjected to unresuscitated and resuscitated HS for the production of IL-6 and activation of Stat3. Using semiquantitative RT-PCR, we found a striking increase in IL-6 mRNA levels only in resuscitated HS, with peak levels observed 1 h after initiation of resuscitation. Increased IL-6 protein expression was localized to bronchial and alveolar cells. Electrophoretic mobility shift assay of protein extracts from shock lungs exhibited an increase in Stat3 activation with kinetics similar to IL-6 mRNA. In situ DNA binding assay determined Stat3 activation predominantly within alveoli. Intratracheal instillation of IL-6 alone into normal rats resulted in PMN infiltration into lung interstitium and alveoli, marked elevation of bronchoalveolar lavage cellularity, and increased wet-to-dry ratio. These findings indicate that IL-6 production and Stat3 activation occur early in HS and may contribute to PMN-mediated lung injury, including ARDS after HS.

Animals↗
PubMed1998

Expression of the anti-metastatic effect induced by Juzen-taiho-to is based on the content of Shimotsu-to constituents.

We investigated the inhibitory effect of oral administration of Juzen-taiho-to, a Kampo Japanese herbal medicine, and its related formulations on the experimental liver and lung metastasis of tumor cells in vivo. Oral administration of Juzen-taiho-to for 7 d before tumor inoculation significantly reduced the number of liver metastatic colonies of colon 26-L5 carcinoma cells and attenuated the increase of liver weight in a dose-dependent manner ranging from 4 to 40 mg/d. Its oral administration for this same period before tumor inoculation also significantly inhibited lung metastasis of B16-BL6 melanoma cells. Juzen-taiho-to originally consisted of 8 crude drugs derived from Shimotsu-to and Shikunshi-to prescriptions together with two crude drugs (Cinnamomi Cortex and Astragali Radix). Oral administration of Shimotsu-to as well as Juzen-taiho-to for 7 d before tumor inoculation resulted in a significant reduction in the number of metastatic colonies and the liver weight as compared with the control, whereas Shikunshi-to did not exhibit such an inhibitory effect. Unsei-in containing four Shimotsu-to constituents was also active in inhibiting liver metastasis. Toki-shakuyaku-san and Ninjin-yoei-to, which include all Shimotsu-to constituents except Rehmanniae Radix and Cnidii Rhizoma, respectively, did not show a significant anti-metastatic effect. Rikkunshi-to and Ninjin-yoei-to, which contain Shikunshi-to constituents, did not affect the inhibition of liver metastasis. Hochu-ekki-to treatment before tumor inoculation also led to a significant inhibition of liver metastasis, probably through an inhibitory mechanism different from Juzen-taiho-to. These results suggest that the anti-metastatic effect of Juzen-taiho-to is partly associated with its Shimotsu-to-derived constituents.

Animals↗
PubMed1997

Structure of the rat methionine adenosyltransferase 2A gene and its promoter.

In this study, to understand the regulation of methionine adenosyltransferase (MAT) gene expression, we isolated the rat MAT2A gene encoding MAT alpha2, the catalytic subunit of non-hepatic-type enzyme MAT II and characterized its structural organization and 5'-flanking region. The gene spans approximately 7 kbp and consists of nine exons interrupted by eight introns. The transcription initiation site, as demonstrated by primer extension analysis, is located 123 bp upstream of the translation start codon. Comparison of the structural organization of the rat MAT2A gene to that of the mouse MAT1A gene encoding MAT alpha1, the subunit of liver-type enzymes MAT I and III, shows that the exon structure of two genes is very similar and the insertion sites of all corresponding introns are identical. A canonical TATA box and a GC box, the potential Sp1-binding site, are found 32 bp and 70 bp upstream of the transcription initiation site, respectively. The 5'-flanking region also contains potential recognition sites for various transcription factors including AP-1, AP-2 and NF-IL6 (C/EBPbeta), and a large G+C-rich domain with the characteristics of a CpG island. The 5'-flanking sequence of the rat MAT2A gene has no significant similarity with those of the MAT1A genes. Transient transfection experiments using a luciferase reporter gene showed that the first 820-bp sequence of the 5'-flanking region directed high levels of luciferase activity in cultured rat kidney fibroblast (NRK-49F) and hepatocellular carcinoma (FAA-HTC1) cells, but not in primary rat hepatocytes. Deletion analysis suggested that the first 343 bp of the 5'-flanking region contained cell-type-specific promoter elements of this gene.

Animals↗
PubMed1997

Combined pancreaticoduodenectomy and hepatectomy for patients with locally advanced gallbladder carcinoma: long term results.

BACKGROUND: The objective of this study was to evaluate the efficacy of combined pancreaticoduodenectomy and hepatectomy for the treatment of patients with locally advanced gallbladder carcinoma. METHODS: Long term results over 5 years of follow-up were analyzed retrospectively in 17 consecutive patients with gallbladder carcinoma who underwent combined pancreaticoduodenectomy and hepatectomy with radical lymphadenectomy. The indications for pancreaticoduodenectomy were direct invasion of the adjacent organs (stomach, duodenum, or pancreas) and/or the presence of peripancreatic (head only) lymph node metastases. The hepatectomy performed was a nonanatomic resection of the gallbladder bed in 15 patients and an extended right hepatectomy in 2 patients. There was 1 in-hospital death (6%). RESULTS: Overall, 5 patients (29%) survived 5 years after surgery. Of these patients, four had Stage IVB disease with positive peripancreatic lymph nodes. Eight of the 10 patients who underwent a potentially curative resection survived longer than 3 years, whereas none of the 7 patients with residual tumor survived beyond 15 months. The 5-year survival of 50% (median survival: 58.5 months) in those undergoing a potentially curative resection was significantly better than the 5-year survival of 0% (median survival: 8 months) observed in those patients with residual tumor (P = 0.00086). CONCLUSIONS: Combined pancreaticoduodenectomy and hepatectomy is an efficacious treatment for patients with locally advanced gallbladder carcinoma, but only if a potentially curative resection is feasible. The presence of peripancreatic (head only) lymph node disease is not a contraindication for this procedure.

Adenocarcinoma↗
PubMed1997

Lymph node spread from carcinoma of the gallbladder.

BACKGROUND: Lymph node spread is the most common pattern of progression in gallbladder carcinoma (GBC) and is a prognostic factor. The purpose of this study was to determine the prevalence of lymph node metastases in patients with resected advanced GBC, and to evaluate the curative effects of radical surgery for patients with lymph node metastasis. METHODS: One hundred and eleven consecutive patients who had undergone radical surgery for GBC were included in this study. The pattern of lymph node metastases was examined histopathologically, using the TNM staging of the American Joint Committee on Cancer. RESULTS: There was no neurovascular invasion or lymph node involvement in 15 patients with pT1 tumors. Sixty of 96 patients with pT2-4 tumors had lymph node metastases. The pericholedochal lymph node was the most common metastatic lymph node, followed by the cystic lymph node. The frequency of metastases in retroportal, posterosuperior pancreaticoduodenal, and interaorticocaval lymph nodes was >15% in all cases. pT3-4 tumors had significantly more lymph node involvement (79%) and significantly higher N2:N1 ratios (2.5) than pT2 tumors (46% and 0.6, respectively). There was no difference in 5-year survival between N0 and N1 groups in pT2-4 tumors (66% in N0 and 53% in N1). Patients with N2 disease had a significantly worse prognosis, but 4 patients survived >5 years. CONCLUSIONS: The cystic and pericholedochal lymph nodes are the initial site of spread from GBC. The frequency of lymph node involvement is strongly influenced by the depth of invasion of the primary tumor. GBC limited to such lymph node metastases can be cured by surgery in >50% of such cases.

Adenocarcinoma↗
PubMed1997

Phosphorylation of human general transcription factors TATA-binding protein and transcription factor IIB by DNA-dependent protein kinase--synergistic stimulation of RNA polymerase II basal transcription in vitro.

DNA-dependent protein kinase (DNA-PK) has been known to catalyze phosphorylation of a number of regulatory factors involved in DNA replication and transcription such as simian virus 40 T antigen, p53, c-Myc, Sp1, and RNA polymerase II (Pol II). We examined the possibility that DNA-PK phosphorylates the general transcription factors TATA-binding protein (TBP) and transcription factor (TF) IIB, which play key roles in the formation of transcription initiation complex with Pol II. By using a highly purified preparation of DNA-PK from Raji cells, both TBP and TFIIB were shown to be phosphorylated in vitro by DNA-PK. We then investigated the effect of the phosphorylation of these factors on Pol II basal transcription. Stepwise analysis of preinitiation complex formation by electrophoretic mobility shift assay revealed that the phosphorylation of TBP and TFIIB by DNA-PK did not affect the formation of promoter (P)-TBP and P-TBP-TFIIB complexes but synergistically stimulated the formation of P-TBP-TFIIB-TFIIF-Pol II complex. Similarly, combination of the phosphorylated TBP and TFIIB synergistically stimulated Pol II basal transcription from adenovirus major late promoter. These observations suggest that DNA-PK could positively regulate the Pol II basal transcription by phosphorylating TBP and TFIIB.

DNA-Activated Protein Kinase↗
PubMed1997

Synchronous primary tumors of the extrahepatic bile duct and gallbladder.

BACKGROUND AND OBJECTIVES: This study aims to clarify clinicopathologic characteristics of synchronous primaries of the extrahepatic bile duct and gallbladder. Understanding multiplicity and its histologic confirmation is an important step for successful surgical management. METHODS: Of the 190 cases of resection of biliary tract neoplasms in this study, 10 had two separate tumors in the extrahepatic bile duct and gallbladder, which were investigated by the microscopic mapping technique for tumor extent using serial stepwise sectioning of specimens. RESULTS: Clinical diagnosis was made successfully in only two cases. Detailed histologic examination revealed seven cases with synchronous primaries and three cases with metastatic tumors. Several microscopic parameters had additional diagnostic value. The presence of synchronous primaries is not necessarily associated with a poor prognosis, since we had four long-term survivors. CONCLUSIONS: Diagnosis of synchronous extrahepatic biliary neoplasms is rarely made preoperatively. However, aggressive resection and careful microscopic examination are essential for the successful management and diagnosis of these special cases.

Aged↗
PubMed1997

Validity and reliability of Structured Interview for Competency Incompetency Assessment Testing and Ranking Inventory.

The Structured Interview for Competency and Incompetency Assessment Testing and Ranking Inventory (SICIATRI) is a structured interview guide to assess the competency for giving informed consent to treatment among psychiatric and medical patients. The competency levels of 48 psychiatric and medical inpatients were assessed by SICIATRI. A relatively high- inter-rater reliability of the SICIATRI items (over half of the items had kappa > or = .60) and concurrent validity (sensitivity = .83, specificity = .67 as measured against the global judgement of competency rating by the attending physician) were obtained. In addition to its brevity (it takes about 20 minutes to complete), these findings may warrant application of this instrument in a clinical setting.

Adult↗