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Biomedical subjects

T Tobe

Publications and source records attributed to T Tobe.

At least 271 records · Page 15Linked to original sources
PubMed1989

Radical pancreatectomy for ductal cell carcinoma of the head of the pancreas.

Seventy-four patients were treated with a radical or a nonradical pancreatectomy for ductal cell carcinoma of the head of the pancreas. Their survival rates and the selection of the operative procedure were evaluated. In 32 patients, a radical pancreatectomy was attempted where there was sufficient clearance of regional or juxta-regional lymph nodes beyond the group of suspected metastatic nodes, as well as a resection of a greater margin of soft tissue around the pancreas. These patients' cumulative 5-year survival rate was 33.4%. In 14 Stage I or Stage II patients, the cumulative 5-year survival rate was 46.4%. In 18 Stage III or Stage IV patients, the cumulative 5-year survival rate was 20.7%. For 42 patients treated with a nonradical pancreatectomy with the dissection of lymph nodes adjacent to the pancreas or of regional lymph nodes but with insufficient clearance of the soft tissue around the pancreas, the cumulative 2-year and 3-year survival rates were 5.4% and 0%, respectively. In seven patients with Stage II carcinoma, the survival rate was 16.7% after 2 years and 0% after three years. In 35 Stage III or Stage IV patients, the survival rate was 3.2% after 2 years and 0% after 3 years. Thus, the survival rates were significantly higher in patients treated with radical operation than in patients who had nonradical operation. These results indicate that a radical pancreatectomy with sufficient lymph node clearance with the surrounding connective tissue around the pancreas is indispensable to cure patients with ductal cell carcinoma of the pancreas.

Adult↗
PubMed1989

[Oral administration of OK-432 (picibanil). (8th report) clinical application: its immunomodulatory effects on the patients with gastrointestinal cancers].

A streptococcal preparation, OK-432 at a dose of 5 KE was orally administered to the patients with gastric or colorectal cancer for 7 approximately 14 days before operation, and its immunomodulatory effects on peripheral blood lymphocytes (PBL), regional lymph node lymphocytes (RLNL) and tumor infiltrating lymphocytes (TIL) were assessed. OK-432 treated group included 5 gastric and 6 colorectal cancers, and control group included 6 gastric and 8 colorectal cancers. After oral administration of OK-432 the proportion of Leu 7+ and Leu 11+ cells in PBL increased, and NK cell activity of PBL also was augmented. The proportion of OKT8+ cells increased in PBL and those of OKT3+ cells and OKT8+ cells decreased in RLNL after oral administration of OK-432. The responsiveness of TIL to autologous tumor extracts in the presence of interleukin-2 was enhanced in oral OK-432 group. These results indicate that oral OK-432 affects on NK and T cells and augments the antitumor immunity of the patients with gastrointestinal cancer.

Administration, Oral↗
PubMed1989

In vivo and in vitro synergistic antitumor effect of interleukin-2-cultured tumor-bearer spleen cells and immune fresh spleen cells.

The synergistic antitumor effect of interleukin-2(IL-2)-cultured tumor-bearer spleen cells (cultured lymphocytes) and immune fresh spleen cells was examined. Tumor-bearer cultured lymphocytes were obtained by culturing BALB/c spleen cells from syngeneic MOPC104E-tumor-bearing mice for 11 days with crude IL-2 and a soluble tumor extract. These cultured lymphocytes had weak antitumor activity when transferred i.p. into tumor-bearing mice that had been inoculated i.p. with 10(5) tumor cells 5 days previously. Immune fresh spleen cells, obtained from mice in complete remission after the treatment with cyclophosphamide, also had weak antitumor activity when transferred at the same schedule. The cultured cells and the fresh cells, mixed together before transfer, significantly augmented the therapeutic effect. At least 1 x 10(7) tumor-bearer cultured lymphocytes and 4 x 10(7) immune cells were needed for the synergistic effect. A tumor-specific combination was needed for both cultured and fresh cells. The effective subpopulation of tumor-bearer cultured lymphocytes was a cytotoxic one from an Lyt2+ precursor, and that of the immune fresh spleen cells was noncytotoxic, Lyt1+ and Lyt2+ T-cells. A similar synergistic effect was also observed during in vitro coculture of tumor-bearer and immune cells. Cytotoxicity, as assessed by the 51Cr-release test, of tumor-bearer IL-2-cultured lymphocytes was maintained most effectively after 3 or 4 days of culture without IL-2 when the lymphocytes were cocultured with immune fresh spleen cells and tumor cells.

Animals↗
PubMed1989

Clinicopathological features of malignancy in hepatocellular carcinoma.

The clinicopathological features showing the malignancy of hepatocellular carcinoma were investigated by retrospectively analyzing the postoperative prognosis after hepatic resection. The long-term prognosis was strongly affected by the existence of portal tumor invasion or intrahepatic metastasis as indicated by the following results. The 3-year cumulative survival rates were 61% and 38% for patients in portal vein tumor invasion groups (Vp0 and Vp1 (P less than 0.05). No patients with Vp2 or Vp3 could survive beyond 3 years after hepatic resection. Similarly, patients with intrahepatic metastasis IM0 showed a better prognosis, compared to those with IM2 or IM3 (P less than 0.05). In addition, the grade of tumor cell anaplasia to some extent affected the prognosis, but not the tumor growth pattern at the tumor/non-tumor boundary. The tumor growth rate, estimated by the alpha-fetoprotein doubling time, was not connected with venous invasion or intrahepatic metastasis, but it became shorter at the time of a recurrence. It is concluded that, from the standpoint of a long-term prognosis, the pathological features showing malignancy appear in venous invasion and intrahepatic metastasis.

Carcinoma, Hepatocellular↗
PubMed1989

Effect of natural peptide YY on pancreatic secretion and cholecystokinin release in conscious dogs.

The effects of natural peptide YY on pancreatic secretion under different stimulatory conditions and on fatty acid-induced cholecystokinin release were examined in five conscious dogs with pancreatic and gastric fistulas. Intravenous infusion of natural peptide YY at 1 and 0.2 microgram/kg/hr caused 60 and 40% inhibition of secretin- and cholecystokinin-stimulated secretion, respectively, and 40-50 and 20-40% inhibition of intraduodenal oleate stimulated secretion, respectively. A significant but transient decrease in the plasma cholecystokinin level was observed in response to peptide YY under oleate stimulation. The present study demonstrates that peptide YY has a potent inhibitory effect on both exogenously and endogenously stimulated pancreatic secretion and has a mild suppressive effect on fatty acid-induced cholecystokinin release suggesting that this peptide is an important colonic inhibitor of pancreatic secretion.

Animals↗
PubMed1989

Therapeutic efficacy of sequential therapy with OK-432, cyclophosphamide, IL2-cultured lymphocytes and in vivo IL2 against advanced murine plasmacytoma.

BALB/c mice inoculated IP with a syngeneic plasmacytoma MOPC104E were treated with a combination of a streptococcal preparation, OK-432 (1 KE, 0.1 mg/mouse), low-dose of cyclophosphamide (CPA, 1 mg/kg) and adoptive transfer of tumor-bearer-spleen cells (2 x 10(7) cells) cultured with IL2 and sonicated tumor extract (adoptive immunotherapy; AIT). The consecutive protocol of OK-432 (day 8, 9 post inoculation) - CPA (day 10) - AIT (day 11) was the most effective. Rate of complete remission was highest when recombinant (r-) IL2 was injected to the mice after AIT. Moreover, another bacterial preparation, Nocardia rubra cell wall skeleton and another low-dose chemotherapy, Mitomycin C could be used successfully instead of OK-432 or CPA. Transfer test of intraperitoneal cells (tumor cells plus host cells) of mice on day 11 post inoculation (on the day of AIT) revealed that OK-432 augmented the susceptibility of peritoneal cells to cultured lymphocytes in inhibition of transplantability, and that CPA after OK-432 augmented the anti-tumor effect of tumor-bearer-spleen cells which act synergistically with cultured lymphocytes. This therapy schedule seems to be the best model to augment the effect of AIT with minimal side effect.

Animals↗
PubMed1989

Successful esophagectomy for metastatic carcinoma of the esophagus from breast cancer--a case report.

A case of progressive dysphagia due to metastatic carcinoma of the esophagus from breast cancer is described herein. The patient was a 55-year-old Japanese woman who had undergone a right radical mastectomy for carcinoma of the right breast 9 years previously. We performed a subtotal esophagectomy and reconstruction, using the stomach. She is now well and working without any further symptoms, five years after surgery. Thus, palliative surgery for the complications caused by metastatic carcinoma of the esophagus may be worthwhile.

Adenocarcinoma↗
PubMed1989

The reappraisal of prognostic classifications for colorectal cancer.

The prognostic usefulness of four variables and four staging systems were evaluated by the Akaike Information Criterion (AIC) and conventional statistical tests for survival time analysis (log rank test, generalized Kruskal-Wallis test, and linear trend test), based on the data of 394 colorectal cancer patients who had been followed for more than 5 years after surgery. The four variables were the histopathologic findings of cancer penetration through the bowel wall (w), lymphnode metastasis (n), intraoperative observations of liver metastasis (H), and peritoneal dissemination (P). They were graded according to the general rules proposed by the Japanese Society for Cancer of the Colon and Rectum (JRSCCR). The staging systems were Turnbull's modification of Dukes' classification, UICC's TNM system, the Japanese classification proposed by JRSCCR, and the authors' modification of the latter. AIC calculated changing the cutoff points of survival time, as well as by reclassifying predictor variables into two categories by different levels. The results of the standard tests differed from those of AIC in the evaluation of the four variables. The former statistics showed that the intraoperative observations were of more prognostic importance than the histopathologic findings, whereas AIC revealed that the histopathologic variables have more prognostic information except for prediction of early outcome. Further analysis of the w-factor showed that survival is more drastically changed by serosal involvement or extensive extramuscular invasion than by penetration of the muscularis propria. Analysis of the n-factor indicated that a major change in survival time occurs twice, i.e., when lymphnode metastasis occurs and when it extends beyond the paracolic level. Compared with single variables, the staging system using multiple factors gives more information on both early and long-term outcomes. The authors conclude that AIC analysis provides prognostic information that cannot be obtained with conventional tests.

Colorectal Neoplasms↗
PubMed1989

Direct ESR measurement of free radicals in mouse pancreatic lesions.

In this experiment, free radicals in the pancreas of endotoxemia and ethionine induced acute pancreatitis in mice were attempted to be detected directly by ESR spectroscopy, using 77 K freeze-trapping and 25 degrees C DMPO spin trapping techniques. In the 77 K freeze-trapping method, Mn (II) ion and R-00. radical were detected in endotoxemia and ethionine induced pancreatic lesions. The heme-NO radical was observed at 6 and 24 h after isolation of the normal pancreas, and signal intensity was increased with time. This finding supports that ESR spectroscopy is a useful method for detecting the tissue degeneration process from ischemia to necrosis. Using the DMPO spin trapping technique (25 degrees C), 6-line was detected at 6 h after intraperitoneal administration of E. coli in the model of endotoxemia, and 3- and 6-lines and a signal suggestive of DMPO-OH adduct were noted at 12 and 24 h in ethionine pancreatitis. These findings suggest that impaired pancreatic tissues exist in a considerably oxidative environment and oxygen derived free radicals may be considered to play an important role in the development of pancreatic lesions.

Animals↗
PubMed1989

Changes in microvascular structure of the fibrotic pancreas and their influence on pancreatic endocrine function.

The objectives of this study were to clarify the microvascular structure in and around the Langerhans' islands of the normal pancreas, elucidate how the structure changes with advance of pancreatic fibrosis owing to stagnation of pancreatic juice, and how these changes influence the endocrine function of the pancreas. For these purposes, the changes in microvascular structure of the fibrotic pancreas, produced by ligation of the pancreatic duct in mongrel adult dogs, were investigated by microangiography and injection replica scanning electron microscopic methods. In addition, the endocrine function of the pancreas was studied by the intravenous (iv) glucose tolerance test. The results revealed that the basic blood vessel structure of the Langerhans' islands, and its insulin secretory function, were maintained relatively well in the long-term, duct-ligated pancreas though the capillary network spreading in the pancreatic exocrine part could hardly be observed.

Animals↗
PubMed1989

Effect of synthetic physalaemin on splanchnic circulation in dogs.

Physalaemin has been reported as one of the most potent vasodilator and hypotensive peptides (1-4). In spite of these studies, however, the effect of the peptide on splanchnic circulation is not known precisely. In the present study, the effect of synthetic physalaemin on superior mesenteric arterial blood flow, portal venous blood flow and pancreatic capillary blood flow was investigated in dogs. Dose dependent increases of superior mesenteric arterial blood flow and portal venous blood flow were induced in response to physalaemin (0.1-10.0 ng/kg). Superior mesenteric arterial blood flow and portal venous blood flow attained maximal increases of 77 +/- 8.9% and 70 +/- 8.6%, respectively, at a dose of 5 ng/kg. Physalaemin caused a dose-related decrease in systemic arterial blood pressure. Pancreatic capillary blood flow did not show significant change with the administration of physalaemin. These data suggest that physalaemin may play some physiological roles in the regulation of splanchnic circulation.

Amino Acid Sequence↗
PubMed1989

Molecular cloning and characterization of MACIF, an inhibitor of membrane channel formation of complement.

Human erythrocytes contain a membrane protein, MACIF, which inhibits the formation of a membrane attack complex (MAC) of complement. We have cloned and sequenced the complementary DNA of MACIF messenger RNA. The amino acid sequence predicted from its nucleotide sequence consists of 128 amino acids. The amino-terminal 25 residues may correspond to a signal peptide. The carboxy-terminal sequence confirmed that MACIF is a glycosylphosphatidylinositol (GPI)-anchored protein. The amino acid sequence of MACIF was partially determined by established techniques for protein chemistry and the resultant sequence was consistent with that predicted from the nucleotide sequence. The results of sequence analyses also suggested that asparagine at the 18th position was N-glycosylated. When mRNA obtained from the MACIF cDNA clone with SP6 RNA polymerase was microinjected into Xenopus oocytes, the oocytes synthesized a product which exhibited MACIF activity and reacted with anti-MACIF antibody. Comparison of the predicted sequence revealed significant homology with mouse Ly-6 antigens.

Amino Acid Sequence↗
PubMed1989

Curative resection of multiple gastrinomas aided by selective arterial secretin injection test and intraoperative secretin test.

Recently a number of surgeons have recommended radical resection of gastrinomas in Zollinger-Ellison syndrome (ZES). We have developed a useful technique for preoperative localization of gastrinomas--the selective arterial secretin injection test (SASI)--and we recommend an intraoperative secretin test (IOS) for deciding the radicality of resection of gastrinomas. Here the results of SASI and IOS tests in 11 patients with ZES are examined and compared with the results of other techniques. The SASI test localized gastrinomas in all of the patients, while the sensitivity of ultrasonography, computed tomography, arteriography, or portal venous blood samplings was between 1/11 and 5/11. On the basis of the results of the SASI test, radical resection of gastrinoma was performed in four patients (three pancreatoduodenectomies and one extirpation). After pancreatoduodenectomy, immunohistologic study of the specimen revealed multiple microgastrinomas and lymph node metastases in two patients and the coexistence of a microgastrinoma and a gastinoma in one patient. The IOS test was useful in the estimation of the advisability of radicality, and in two patients total gastrectomy was not performed because of the results of the IOS test. These four patients are well and have returned to work, and their serum gastrin levels are below 35 pg/mL. Thus we believe SASI and IOS tests are helpful for planning curative resection of gastrinomas.

Adolescent↗
PubMed1989

A dual transcriptional activation system for the 230 kb plasmid genes coding for virulence-associated antigens of Shigella flexneri.

The expression of plasmid-encoded, invasion-related antigens lpa b, c and d of Shigella flexneri was found to be positively regulated at transcriptional level by a 33kD protein produced by the previously defined, virulence-associated Region 1 on the SalI fragment B of the 230 kb invasion plasmid. The gene (designated virB) was identified and its nucleotide sequence determined. No Ipa b or c was produced in the absence of an intact virB gene although lower levels of d were produced. The previously reported regulatory activity of the virF gene some 30 kb distance away was shown to act exclusively through virB. In contrast, the activation of the virG gene necessary for intercellular spread occurred directly by virF without the requirement for virB. This study thus ascribes a critical function to a previously recognized, but functionally undefined, virulence locus on the large invasion plasmid of S. flexneri. The virF gene appears to have a central role in activation of the 230 kb plasmid-encoded virulence genes.

Amino Acid Sequence↗
PubMed1989

Functional organization and nucleotide sequence of virulence Region-2 on the large virulence plasmid in Shigella flexneri 2a.

The 7 kb virulence Region-2 of the large (virulence) plasmid in Shigella flexneri 2a encodes several proteins required for invasion of intestinal epithelial cells. Insertion and deletion mutagenesis, DNA subcloning and SDS-polyacrylamide gel electrophoresis of proteins synthesized in minicells demonstrated five genes in this region. They encode 24, 18, 62 (IpaB), 41 (IpaC) and 37 (IpaD)-kiloDalton (kD) proteins. Complementation of Tn5-induced mutations in Region-2 with the above plasmid constructs indicated that Region-2 consists of two operons and that the three Ipa proteins are essential for the virulence phenotype. The transcriptional organization determined by Northern blotting, S1 nuclease protection and the effect of Tn5 insertions on expression of the Ipa proteins revealed that Region-2 has three promoters that transcribe RNAs of 4.0, 4.5 and 7.5 kb. The 4.0 kb RNA was the transcript for the operon encoding the 24, 18 kD, IpaB and C proteins and the 4.5 kb RNA for the ipaD gene. In addition, the full-length RNA of 7.5 kb which covers Region-2 supplemented full expression of the Ipa proteins. The 7663 nucleotides of Region-2 were determined to confirm the five open reading frames encoding 23,655, 17,755, 62,168, 41,077 and 36,660 Dalton proteins, respectively, and their regulatory sequences.

Amino Acid Sequence↗
PubMed1989

Changes of xanthine oxidase, lipid peroxide and superoxide dismutase in mouse acute pancreatitis.

The role of free radicals in the development of pancreatitis was evaluated by measuring the level of activities of xanthine oxidase (XOD), lipid peroxide (LPO) and superoxide dismutase (SOD). Acute pancreatitis was induced in female mice fed a choline-deficient meal containing 0.5% DL-ethionine (CDE meal). Acute pancreatitis was confirmed by the changes in serum amylase level and other typical features observed microscopically 24 h after the meal was taken. Activity of XOD was elevated significantly (p less than 0.05) from the baseline of 1.13 +/- 0.19 U/g tissue to 2.34 +/- 0.46, 2.59 +/- 0.33 and 3.46 +/- 0.70 U/g tissue, 8, 12 and 24 h, respectively, after the CDE meal. The LPO level was also increased from an undetectable amount to 1.10 +/- 0.47 nmol/ml (p less than 0.05), 1.03 +/- 0.18 (p less than 0.01) at 6 and 8 h, respectively, and then returned to an undetectable amount at 12 h. The peak level of LPO was shown at 24 h, 1.76 +/- 0.40 nmol/ml (p less than 0.01) and gradually decreased until 48 h, 1.17 +/- 0.37 nmol/ml (p less than 0.01) after the CDE meal. Changes of LPO took a biphasic pattern. SOD was decreased significantly from 47.1 +/- 3.4 mU/g tissue to 30.7 +/- 2.5, 24.8 +/- 1.7 and 20.6 +/- 1.1 mU/g tissue at 8 (p less than 0.01), 12 (p less than 0.01), and 24 (p less than 0.01) h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1989

Effect of endotoxin on digestive enzyme and superoxide dismutase in mouse pancreas.

In order to clarify the effect of endotoxin on pancreatic lesions, changes in the level of activity of pancreatic proteolytic enzymes and superoxide dismutase (SOD) were measured following the intraperitoneal administration of Escherichia coli endotoxin in mice. Microscopic examination revealed that congestion of zymogen granules in acinar cells appeared in the early stages. The accumulation increased gradually and was widespread at 24 h after E. coli endotoxin administration. The serum amylase level increased significantly from its basal level of 1,630 +/- 128 SU to 2,395 +/- 42 SU at 4 h (p less than 0.05), 3,172 +/- 513 SU at 8 h (p less than 0.05), and 2,572 +/- 229 SU at 12 h (p less than 0.05) after E. coli endotoxin administration. The serum lipase level also increased significantly from its basal level of 37.6 +/- 1.6 IU/l to 65.8 +/- 8.9 IU/l at 12 h (p less than 0.05). The level of trypsinogen in the pancreas increased markedly from its basal level of 161.8 +/- 15.7 U/g tissue to 270.0 +/- 9.6 U/g tissue at 2 h (p less than 0.001) after E. coli endotoxin administration and showed continued increases at 8 h (313.3 +/- 10 U/g tissue, p less than 0.001) and 24 h (352.9 +/- 19.3 U/g tissue, p less than 0.001); however, the level of net stimulated secretion of trypsinogen in the medium decreased significantly at 4 h (p less than 0.05) and 8 h (p less than 0.01) after E. coli endotoxin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗