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Biomedical subjects

T Tobe

Publications and source records attributed to T Tobe.

At least 253 records · Page 14Linked to original sources

Changes in lipid peroxide and oxygen radical scavengers in cerulein-induced acute pancreatitis. Imbalance between the offense and defense systems.

The role of free radicals in the development of cerulein-induced pancreatitis was evaluated by measuring the activity of the endogenous scavengers, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHpx), as indicators of the defense system, and the level of lipid peroxide (LPO) in the pancreas, as an indicator of the offense system. Acute pancreatitis was induced by 5 hourly intraperitoneal administrations of cerulein (50 micrograms/kg body weight), in 0.9% NaCl, to mice. The presence of acute pancreatitis was confirmed by changes in serum amylase levels and in typical microscopical features. Regarding the changes in the levels of endogenous scavengers, the SOD level was decreased significantly from a basal level of 52.6 +/- 3.94 to 43.1 +/- 2.79 mU/micrograms DNA at 6 h (p less than 0.01) to 38.8 +/- 5.18 mU/micrograms DNA at 9 h (p less than 0.05) and to 31.7 +/- 3.10 mU/micrograms DNA at 12 h (p less than 0.01) after the first intraperitoneal cerulein injection. The CAT level also decreased significantly from a basal level of 7.80 +/- 0.27 to 5.86 +/- 0.46 mU/micrograms DNA at 9 h (p less than 0.01) and to 4.52 +/- 0.21 mU/microgram DNA at 12 h (p less than 0.01). GSHpx increased from a basal level of 6.80 +/- 0.43 to 7.58 +/- 0.50 mU/micrograms DNA at 9 h and to 10.2 +/- 0.52 mU/micrograms DNA at 12 h after the first intraperitoneal cerulein injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Immunohistochemical distribution of CA19-9 in normal and tumor tissues of the kidney.

The immunohistochemical distribution of CA19-9 in normal and tumor tissue of the kidney was investigated. CA19-9 was detected in the cytoplasm and apical surface of renal proximal tubules, distal tubules and uroepithelium of the renal pelvis. Eight of 28 renal cell carcinomas (29%) expressed CA19-9. CA19-9 was also detected in 2 cases of transitional cell carcinoma and 1 of 4 cases of Wilm's tumor, but not in angiomyolipoma. As the measurement of CA19-9 is widely used to detect gastrointestinal carcinoma, the expression of CA19-9 in normal and neoplastic kidney tissue might have some clinical significance.

Antigens, Tumor-Associated, Carbohydrate↗

Solution synthesis of human peptide YY (hPYY).

Human peptide YY (hPYY) was synthesized in a conventional manner by assembling six peptide fragments followed by deprotection with 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf)-thioanisole in trifluoroacetic acid (TFA). After purification by gel-filtration on Sephadex G-25, followed by reversed-phase high-performance liquid chromatography, a highly purified sample of synthetic hPYY was obtained. When administered in dogs, synthetic hPYY was as active as synthetic porcine PYY in terms of the effects on systemic arterial blood pressure, and splanchnic blood flow.

Amino Acid Sequence↗

Measurement of splanchnic circulation in dogs: changes induced by prostaglandin E1.

In seven anesthetized dogs the effects of intravenously administered prostaglandin E1 on mesenteric arterial and portal venous blood flows and pancreatic capillary blood flow were measured with a transit-time ultrasonic volume flowmeter and a laser Doppler flowmeter. Basal blood flow of the superior mesenteric artery and of the portal vein were 5.7 +/- 0.6 and 11.2 +/- 1.0 ml/min/kg, respectively. Prostaglandin E1 caused a dose-dependent increase in these blood flows. The maximal effect was observed at a dose of 1.0 microgram/kg, when the superior mesenteric arterial blood flow increased 117.9 +/- 3.2% and the portal venous blood flow increased 99.4 +/- 1.7%. Prostaglandin E1 produced an initial rapid increase, followed by a decrease in pancreatic capillary blood flow. The results indicate that the flowmeters used in the present study are widely available for the study of splanchnic circulation and may have a possibility for clinical application.

Alprostadil↗

Pancreatic lysosomal enzyme secretion is changed by hepatectomy in rats.

To explore the effect of hepatectomy on the secretion of lysosomal enzymes into the pancreatic juice when stimulated by gut hormones, we evaluated the cerulein-stimulated amylase output and cathepsin B output into pancreatic juice, the amylase and cathepsin B content in pancreatic tissue, and the distribution of cathepsin B in acinar cells in the regenerating (4 days) and recovering (8 days) stages after about 70% hepatectomy in rats. Amylase output was significantly higher after hepatectomy than in the control groups. Cathepsin B was secreted into the pancreatic juice after stimulation by cerulein in both the control and the hepatectomized groups, but, particularly 4 days after hepatectomy, cathepsin B output was significantly higher than in the controls, and in the acinar cells redistribution of cathepsin B was found. These changes in cathepsin B disappeared in the recovery stage (8 days) after hepatectomy. In addition, the amylase content in pancreatic tissue was significantly greater in the hepatectomized than in the control rats, but the cathepsin B content did not show any significant change. These results indicate that cerulein can stimulate the secretion of lysosomal enzyme into the pancreatic juice, as it does the secretion of digestive enzymes. Moreover, it appears that the synthesis and secretion of amylase in and from the acinar cells is increased after hepatectomy and that a redistribution of lysosomal enzyme occurs in the acinar cells.

Amylases↗

[Role of free radicals in the development of acute mild and severe pancreatitis in mice].

In order to clarify the role of free radicals in the pathogenesis of acute pancreatitis, we observed the effect of a new synthetic free radical scavenger (CV-3611) on the pathological state in the models of both caerulein and CDE-diet induced acute pancreatitis in mice. In both models of acute pancreatitis, the levels of serum amylase activity were reduced significantly by the treatment of CV-3611. Pancreatic edema formation was also reduced significantly at 3.5 and 9 h after the first caerulein i.p. injection. The 4 days survival rate in CDE-diet induced pancreatitis was significantly elevated from 41.2% to 81.3% by the treatment of CV-3611. These results indicate that this synthetic scavenger, which has a long circulation half life, high affinity to biomembrane and good cell penetration ability, is effective on the development of both severe and mild pancreatitis. The main pathogenesis of both models is suggested to be radical reactions on the biomembrane which is caused by the interreaction between endothelium and neurophile in caerulein induced pancreatitis, and by the lipid peroxidation on the biomembrane of the organella in the cell in CDE-diet induced pancreatitis.

Acute Disease↗

[Changes of lysosomal enzymes in pancreatic juice following hepatectomy in rats].

To explore the changes in the exocrine pancreas and the possible stimulation by gut hormones of secretion of lysosomal enzyme into the pancreatic juice, we measured the caerulein-stimulated amylase output, the cathepsin B output into the pancreatic juice and the pancreatic tissue amylase and cathepsin B contents, as well as the distribution of cathepsin B in acinar cells in both the regenerating (4 days) and recovery (8 days) stages after about 70% hepatectomy in rats. The amylase output increased significantly after hepatectomy. Cathepsin B was secreted into the pancreatic juice after stimulation by caerulein in both the control and hepatectomized groups. Four days after hepatectomy, the cathepsin B output was significantly greater than that of the control group, and redistribution of cathepsin B in acinar cells was noted. These changes in cathepsin B disappeared in the recovery stage (8 days) after hepatectomy. In addition, the pancreatic amylase content was significantly higher than in the control group, but the pancreatic cathepsin B content did not change significantly. These results suggest that caerulein stimulated the secretion of lysosomal enzyme into the pancreatic juice in the same way as digestive enzymes and that lysosomal enzymes in the pancreatic juice play an important physiological role. Furthermore, these results indicate the increased synthesis and secretion of amylase in and from acinar cells as well as the fragility of acinar cells.

Amylases↗

Increased number of suppressor T-cells and impaired IL-2 mediated T-cell function in peripheral blood of gastric cancer patients.

The present study was designed to investigate the mechanisms responsible for suppressed T-cell immunity in gastric cancer patients. The peripheral blood T-cell functions in gastric cancer patients were evaluated by measuring responses to PHA and IL-2, and T-cell subpopulations were assessed by flow cytometry. Both the PHA and IL-2 responses decreased in patients with gastric cancer, although the proportions of CD3+ and CD25+ cells were the same for gastric cancer patients and healthy volunteers. The PHA response, but not that of IL-2, was lower in patients with liver metastasis or peritoneal dissemination than in patients without these conditions. Single regression analysis showed that with lymph node involvement in the disease the IL-2 response was more strongly suppressed than PHA response. The serum level of IAP did not correlate with the response to either PHA or IL-2. The proportion of CD4+ cells was not affected by any factor related to gastric cancer, although CD4+/CD8+ and CD8+11b-/CD8+11b+ ratios did decrease in patients with distant lymph node involvement. These changes may be due to a comparative increase in suppressor cells. These results suggest that gastric cancer patients exhibit impaired IL-2 mediated T-cell function and that the number of suppressor cells may increase with progressive lymph node involvement. These two serial effects may be indeed responsible for the impaired blood T-cell function in patients with gastric cancer.

Adult↗

[Organ specific ESR features in mouse main organs and ESR application to the model of pancreatic disorders].

Nine main organs in the mouse were studied by ESR spectroscopy at 77K. Manganese ions were readily detected in the pancreas, small intestine, stomach and kidney. In particular, the pancreas gave strong ESR signals for the transition metal, suggesting that Mn(II) plays an important role in pancreatic function. All organs reveal different ESR spectra indicating organ specificity. C-centered radical, R-OO radical and C0Q10 or ascorbate radical are stable in the tissue. In the brain, heart and pancreas, N-centered radical heme-NO adduct was detected at 6 and 24 h after excision since common process is involved in tissue degeneration and ESR is sensitive to proteolysis and necrosis of tissues. In endotoxemia and/or CDE-diet-induced pancreatic lesions, R-OO radical and Mn(II) ion were detected in the signal at 77K. By the spin-trapping method (DMPO) at 25 degrees C, DMPO-OH adduct and 3-Line and 6-Line were detected in CDE diet-induced acute pancreatitis. These results suggest that damaged pancreatic tissues are in a highly oxidative environment that probably contains oxygen radicals, and that free radicals are considered to play an important role in the development of pancreatic lesions.

Animals↗

[Large bowel cancer: prognostic factors, surgical treatments and their results].

Although the classification proposed by Dukes has been repeatedly modified, causing unnecessary confusion, his original concept remains unrefuted; cancer penetration through the bowel wall and lymph node metastasis are two major prognostic factors, of which nodal metastasis represents a more advanced stage. However, the results of our exhaustive computer analyses did not support this concept, and better classifications may be developed using our computer algorithm, enabling us to refine the indication for extensive surgery or limited resection. There are two trends of surgical treatment in Japan. One is an attempt to extend the area of resection including the paraaortic and parailiac nodes, and also iliac vessels. Patients treated by this method show a higher survival rate if compared with historical controls in Japan. However, extensive surgery of the rectum is associated with poor quality of life with bladder and anal dysfunctions as well as sexual impotence. The other trend is to limit the extent of resection and minimize the functional defect. The organs thus saved include the sphincter and autonomic nerves. The results are almost comparable with those of more radical surgery. With aggressive re-resection of recurrent tumors in the liver, lungs, lymph nodes and local areas, the number of long-term survivors is now increasing who would otherwise have died.

Colorectal Neoplasms↗

[The effect of partial hepatectomy on glucose-stimulated insulin release from the isolated perfused pancreas in rats].

To investigate the functional changes of endocrine pancreas in the early stage after partial hepatectomy, we evaluated the changes in the secretion of insulin to glucose load in perfused rat pancreas at 4 and 7 days after about 70% hepatectomy. Insulin responses to glucose load were significantly augmented at 4 days compared with both the normal and sham-operation rats and at 7 days also significantly augmented compared with the normal rats. These results are in accordance with the morphological changes of islet and indicate that in the early stage after hepatectomy, the response of islet B-cells to glucose load are increased in order to support the glucose metabolism in this stage. Thus, insulin seems to play an important role in the regenerating liver after hepatectomy and these changes seem to be one of the adaptation of endocrine pancreas after hepatectomy to support the regenerating liver.

Animals↗

Comparative studies of DU-PAN-2, carcinoembryonic antigen, and CA19-9 in the serum and bile of patients with pancreatic and biliary tract diseases: evaluation of the influence of obstructive jaundice.

The levels of DU-PAN-2 antigen, carcinoembryonic antigen, and CA19-9 in serum and bile of patients with pancreatic and biliary tract diseases were measured. The sensitivities (true positive) of DU-PAN-2 in serum to pancreatic carcinoma (64%) and to biliary tract carcinoma (62%) were similar to those of CA19-9 in serum (69% and 72%, respectively). Nine of 18 (50%) patients with CA19-9-negative pancreatic carcinoma tested positive for DU-PAN-2. The sensitivities of CEA to pancreatic carcinoma (56%) and to biliary tract carcinoma (52%) were lowest. The measurement of these antigens in bile seemed to be of little diagnostic value in differentiating between malignant and benign diseases. False positives of these three assays occurred frequently in patients with benign pancreatic or biliary tract disease coupled with obstructive jaundice. After percutaneous transhepatic biliary drainage, serum DU-PAN-2 and CA19-9 levels returned to normal ranges in patients with benign diseases, but not in patients with carcinoma of the pancreas or of the biliary tract. Serum CA19-9 and DU-PAN-2 antigens are useful tumor markers for pancreatic and biliary tract carcinomas. Longitudinal assays of these antigens may be useful for the differential diagnosis of patients with obstructive jaundice.

Antigens, Neoplasm↗

[Influence of alcohol ingestion on plasma gastrin and CCK levels in human beings].

We investigated the time courses of the plasma ethanol, acetaldehyde, gastrin and cholecystokinin (CCK) levels after the ingestion of ethanol (1g/kg, 21.5%, whisky) in healthy male adult volunteers. The ethanol level reached a peak at 15 to 45 minutes after the ingestion and then decreased almost linearly. The acetaldehyde level of the group who became flushed after drinking (the F group) peaked earlier than that of the other group whose faces became only slightly flushed (the N group). The gastrin level increased significantly and remained elevated for about 3 hours. In three of the nine subjects, the CCK level increased 75 minutes after drinking. As a result, the absorption of the ingested ethanol is more rapid than 15 minutes, followed by a quick catabolism of the absorbed ethanol to acetaldehyde, but the catabolic action of acetaldehyde in the F group is later than that in the N group. The plasma gastrin level is certified to increase after the ingestion of ethanol and this is not mediated by acetaldehyde because the intra-venous infusion of acetaldehyde was not increased the plasma gastrin level in dogs. CCK which stimulate the pancreatic enzymes may be considered to have a possibility relating to the development of alcoholic acute pancreatitis but the ingestion of ethanol showed no increase of the plasma CCK level. But we cannot deny the possibility of the individual differences in the hormonal reaction in these experiments.

Acute Disease↗

[Experimental study on the optimal treatment schedule for combination of BRM (immunostimulators, cultured killer cells or interleukin-2) and chemotherapy].

In the present study we tried to reevaluate the optimal combination timing in the experimental treatment with BRM and chemotherapeutic agents. BALB/c mice with advanced malignant ascites tumor (MOPC 104 E) were treated with cyclophosphamide (CPA, 2 mg/kg) and BRM such as immunostimulator (OK-432, Lentinan or Bestatin), interleukin-2 (IL 2) or cultured killer cells. The survival of mice was prolonged when immunostimulators were given before CPA. However, no combined effect was seen when immunostimulators were administered after CPA. Treatment with cultured killer cells and in vivo IL 2 after immunochemotherapy (immunostimulator followed by CPA) was the most effective protocol in which immunostimulator, chemotherapy, killer cells and IL 2 respectively seemed to induce, regulate, supplement and amplify anti-tumor effector cells.

Adjuvants, Immunologic↗

Semisynthetic promoters activated by cyclic AMP receptor protein of Escherichia coli.

Semisynthetic promoters activated by Escherichia coli cyclic AMP receptor protein (CRP) were created by combining a synthetic CRP-binding site (crb) and nucleotide sequences derived from cryptic promoter regions. A 22-bp oligodeoxyribonucleotide corresponding to an idealized crb was randomly placed into DNA regions that precede a promoterless lacZ gene on a plasmid. Several plasmid clones were obtained which allowed the expression of lacZ in crp+ cya+ cells carrying a chromosomal deletion of lac genes. The beta-galactosidase and the quantitative S1-nuclease assays of crp+ and delta crp cells harboring these plasmids indicated that the transcription from newly created promoters is dependent on CRP. Sequence analysis revealed that these promoters are divided into two types based on the location of the crb relative to the transcription start point (tsp). The distance from the center of the crb to the tsp is 70 bp in the first type and 38 bp in the second type. The sequences of all these promoters exhibit poor homology with the consensus promoter sequence.

Base Sequence↗