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Biomedical subjects

S Matsuno

Publications and source records attributed to S Matsuno.

At least 19 recordsLinked to original sources

The mucus-hypersecreting tumor of the pancreas. Development and extension visualized by three-dimensional computerized mapping.

BACKGROUND: Mucus-hypersecreting tumor of the pancreas appears as dilated ducts and cystic spaces filled with mucus. To determine where such tumors arise and how they extend, computer-aided three-dimensional reconstruction was done of the ductal system. This also was used to visualize the spatial relationships among epithelial hyperplasia, dysplasia, and carcinoma in situ (CIS). METHODS: Surgically removed pancreases were studied from 12 patients with mucus-hypersecreting tumors. The specimens were fixed in buffered formaldehyde solution 10%, embedded in paraffin and semiserially sectioned at 3 microns at an interval of 60 microns. The ductal contours were differentiated among ducts lined by ordinary epithelia, hyperplastic epithelia, dysplastic cells, or CIS and were inputted into a computer system that integrated a three-dimensional image of ducts in the display. RESULTS AND CONCLUSIONS: (1) The tumors arose in the main pancreatic duct or its subbranches, and the cysts corresponded to segments expanded by the superficial growth of tumor cells; (2) areas of CIS arose in zones of preceding dysplasia, suggesting a dysplasia-carcinoma sequence; and (3) dysplastic or cancerous cells often extended intraductally over the dilated segments of ducts.

Aged

Effectiveness of planar image and single photon emission tomography of thallium-201 compared with gallium-67 in patients with primary lung cancer.

A comparative study of planar images and single photon emission tomography (SPET) of thallium-201 chloride and gallium-67 citrate was performed in 38 patients with proven primary lung cancer to detect the primary lung tumour and to establish the presence of metastasis in the lung hilum and mediastinum. The findings of planar images and SPET were compared with the pathological findings after thoracotomy. It was shown that 201Tl studies were superior to 67Ga studies for evaluation of the primary lesion and lymph node metastases.

Aged

An experimental study on the gastric acid and gut hormone secretion after pylorus preserving duodenectomy in dogs.

To clarify changes in gastric acid and gut hormone secretion after pylorus-preserving pancreaticoduodenectomy (PPPD), an experimental study was performed using a model of pylorus-preserving duodenectomy in dogs previously provided with Heidenhain pouch (HP). The duodenectomy involves resection of the duodenum and 10 cm of the proximal jejunum preserving 2 cm of juxtapyloric duodenum and round-shaped duodenal wall around pancreatic papilla. Reconstruction was done by anastomosing the rho-shaped jejunal loop to gallbladder, juxtapyloric duodenum and peripapillar round-shaped duodenal wall with ligation of the common bile duct. For these dogs, intravenous glucose tolerance test (IVGTT), oral glucose tolerance test (OGTT), meal ingestion test (TM) and histological studies of pancreatic specimen obtained at autopsy were performed investigating pancreatic, gastric acid and gut hormone secretion. Preservation of endocrine and exocrine pancreatic secretion after operation demonstrated our experimental model to be adequate for evaluation of the factor of duodenectomy in PPPD on gastric acid and gut hormone secretion avoiding the influences of changes in pancreatic secretion. Postprandial gastric acid secretion from HP did not change significantly after operation. Postprandial secretion of gastrin, glucagon, GIP and enteroglucagon did not alter significantly after operation. These results indicated that in the clinical PPPD procedure, preservation of more than 2 cm of duodenum from the pylorus produced neither postprandial gastric acid hypersecretion, which might be cause of postoperative stomal ulcer, nor any change of related gut hormone secretion.

Animals

De novo expression of aromatase in gastric carcinoma. Light and electron microscopic immunohistochemical and immunoblot study.

We have performed immunohistochemical and immunochemical studies of steroidogenic enzymes involved in estrogen biosynthesis in 30 cases of gastric carcinoma in order to investigate possible in situ production of estradiol (E 2) in carcinoma cells. Positive incidence of immunoreactivity for E 2, testosterone (T), cholesterol side-chain cleavage enzyme (P-450 scc) and aromatase (P-450 arom) were 17/30 (56.7%), 11/30 (36.7%), 3/30 (10.0%) and 23/30 (76.7%), respectively on light microscopy. Estrogen receptor (ER) immunoreactivity was not observed in any of the 30 cases examined. Normal gastric mucosa was negative for P-450 arom and P-450 scc. Examination of serial sections revealed that immunoreactivity of E 2 and P-450 arom were located in the same cells of carcinomatous glands. Immunoelectron microscopy demonstrated that E 2 and P-450 arom were located along the membrane and cisternae of smooth endoplasmic reticulum (sER). Western blot analysis showed one major band of 55 kDa of P-450 arom in the gastric carcinoma tissues examined. Retrospective analysis of immunohistochemistry of E 2 in 108 cases of gastric carcinoma revealed that E 2 positive carcinoma cases were likely to demonstrate better survival rate than negative cases. These results above strongly suggest that E 2 is produced by de novo expressed aromatase in gastric carcinoma cells and is possibly involved in the biology of gastric carcinoma cells.

Aromatase

Phase I clinical studies of S-1108: safety and pharmacokinetics in a multiple-administration study with special emphasis on the influence on carnitine body stores.

S-1108, the prodrug of S-1006, was given to healthy volunteers three times a day (TID) for 8 days in a dose of 200 mg in a crossover placebo-controlled study. The safety of S-1108 and the pharmacokinetics of S-1006 and pivalic acid liberated from pivaloyloxymethyl ester of S-1108 were investigated. There were no abnormal symptoms or signs, as observed by physical and laboratory tests. The half-life and area under the concentration-time curve of S-1006 was reduced from 1.11 +/- 0.17 h at the first dose to 0.87 +/- 0.18 h at the last dose and from 7.30 +/- 1.10 to 5.20 +/- 0.85 micrograms.h/ml, respectively. However, there was no significant difference in the peak concentration between the two doses. Pivalic acid was found to be completely detoxified by conjugation with carnitine. The total urinary recovery of pivalic acid as pivaloylcarnitine was 98.7 +/- 3.6%, resulting in an increase of daily carnitine urinary excretion two- to threefold the predose value. During the multiple administration of S-1108, the plasma carnitine concentration was reduced to and maintained at 50 to 70% of the control value, suggesting that there might be enough carnitine store in the body to detoxify the pivalic acid in a dose of 200 mg TID. Moreover, the reduced plasma carnitine was rapidly returned to the control value within a few days after the cessation of the administration of 200 mg TID.

Adult

Portal venous pressure following splenectomy in patients with portal hypertension of differing etiology.

To clarify the effect of splenomegaly on portal hemodynamics in patients with portal hypertension and esophageal varices, manometric studies were carried out before and after splenectomy during an operation for esophageal varices. The 118 patients evaluated retrospectively had underlying liver cirrhosis (LC) (62), idiopathic portal hypertension (IPH) (42), and extrahepatic portal occlusion (EHO) (14). The weight of the spleen did not differ significantly among the three diagnostic groups: 640 +/- 473.5 g for LC, 780 +/- 414.6 g for IPH, and 683 +/- 457.2 g for EHO. Before splenectomy, portal pressure was significantly elevated in the patients with EHO (410 +/- 85.2 mm H2O) as compared to either the LC or IPH groups (348 +/- 64.1 and 348 +/- 73.5 mm H2O). Following splenectomy the reduction of portal pressure was significantly greater in the EHO group (29 +/- 15.5%) than in either the LC (18 +/- 17.4%) or IPH (19 +/- 17.0%) groups. Each group was subdivided according to severity of splenomegaly: marked (spleen weight > or = 500 g) or slight (spleen weight < 500 g). Patients with LC and marked splenomegaly showed a reduction in liver function parameters as shown by the prolongation of indocyanine retention rate at 15 min as compared to those with slight splenomegaly. Though it is not statistically significant, the average portal pressure tended to be higher among those with marked splenomegaly.(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal and Gastric Varices

Immunohistochemical identification of transforming growth factor-beta and its binding protein in human gastrointestinal carcinoma.

We attempted to clarify the tissue localization of TGF-beta and latent TGF-beta binding protein (LTBP) in human gastrointestinal carcinomas by immunohistochemistry. The immunoreactivity for TGF-beta was observed in both carcinoma cells and stromal cells, particularly in diffuse-type gastric carcinoma. The immunoreactivity for LTBP was observed only in stromal cells. These results suggest that both carcinoma cells and stromal cells may produce TGF-beta, and that only stromal cells may produce LTBP in gastrointestinal carcinoma.

Gastrointestinal Neoplasms

Long-term results of pylorus-preserving gastrectomy for gastric ulcer.

The postoperative results of pylorus-preserving gastrectomy (PPG) for gastric ulcer performed in 134 patients during the past 25 years (mean postoperative period, 16.6 years) were studied. The incidence of postoperative complications was low. Dumping syndrome occurred in only 4.4% and 0% of cases as assessed by questionnaire and interview, respectively. Four (5.4%) of 74 patients available for this study had ulcer recurrence. In one of these four patients concurrent gastroduodenal ulcer was suspected from preoperative gastric analysis. The site of recurrence was found in all cases to be the remnant antral gland area along the greater curvature between the proper gastric gland area and the duodenum. Basal and maximal acid outputs at the time of relapse were significantly higher in patients with recurrence than in patients without recurrence. The fasting and postprandial serum gastrin levels were high in one patient with recurrence, whose antrum was preserved as long as 3 cm proximal to the pyloric ring; this was longer than that described in our original method of PPG. In two other recurrent cases the serum gastrin levels were not different from those in nonrecurrent cases. Immunohistochemical examination of the residual antrum showed no increase in the G-cell density in patients either with or without recurrence. These results suggest that the long-term quality of life of patients treated with PPG remains favorable. Recurrence rate can be further reduced if PPG is strictly indicated for gastric ulcer only and carried out by meticulous surgical techniques. In the pathogenesis of the ulcer recurrence the role of gastrin release from the residual antral mucosa seems to be limited.

Adult

Immunolocalization of mineralocorticoid receptor in human kidney, pancreas, salivary, mammary and sweat glands: a light and electron microscopic immunohistochemical study.

Using a polyclonal antibody against a synthetic fusion protein corresponding to 167 amino acids of the N-terminal region of the human renal mineralocorticoid receptor (MR), an immunohistochemical study was performed to investigate the intraglandular and intracellular localization of the receptor in human kidney, salivary gland, pancreas, mammary gland and sweat gland both at the light and electron microscopic levels. In the kidney, immunoreactivity was observed in distal convoluted tubules, branches of Henle's loop, and collecting tubules in the renal cortex, and papillary and Henle's loops' ducts in the renal medulla. No significant differences in the distribution of immunoreactivity were observed using different fixatives (10% neutral formalin, 100% methanol, 4% paraformaldehyde, PLP (periodate-lysine-2% paraformaldehyde) solution and Zamboni solution) and processing methods (paraffin embedding and frozen sectioning). Immunoreactivity in the kidney was observed in both the cytoplasm and nucleus, with cytoplasmic staining predominant, regardless of the methods of tissue preparation. Immunoelectron microscopy, employing a pre-embedding method, demonstrated the presence of immunoreaction precipitates in nuclei, endoplasmic reticulum, perinuclear cisternae, free cytoplasm and cell membranes. In nuclei, immunoreactivity was observed in euchromatin but not in heterochromatin, which is consistent with an association of MR with specific DNA regulatory elements located in transcriptionally active euchromatin. In other organs, MR was expressed in cells of the excretory ductal system where mineralocorticoids are known to play a role in electrolyte homeostasis.

Animals

[Relationship between venous invasion and hematogenous metastasis in the colorectal cancer patients].

We investigated the correlation between venous invasion and hematogenous metastasis. In thirteen patients with colorectal carcinoma, depth of invasion (ss.s or a1.a2) was the same. Four cases had hepatic metastasis at operation (group A), 3 cases were identified with hematogenous recurrence after operation (group B), and 6 cases were disease free over 10 years after operation (group C). Specimens were all step-sectioned and serial sections were stained both with HE and EM. Results were as follows. 1. Venous invasion was found in all cases and average rates of venous invasion (ARVI) of groups A and B were higher than that of group C (A; 7.8%, B; 6.3%, C; 2.1%, p less than 0.05). 2. In ss.s layer, ARVI of group A and B were higher than that of group C (A; 6.1%, B; 6.2%, C; 1.5%, p less than 0.05). 3. Rates of venous invasion to larger veins (diameter greater than 200 microns) were higher in group A than in others (A; 53.5%, B; 25.6%, C; 7.9%, p less than 0.05), and those to the middle-sized veins (diameter; 50-200 microns) were higher in group B than in others. These facts suggest that cancer invasion to the veins located in ss.s (a1.a2) layer or ranged in diameter over 200 microns relates to hematogenous metastasis.

Colorectal Neoplasms

[Effect of prostaglandin E1 treatment on peripheral circulation during extracorporeal circulation--with special reference to its influence on body temperature recovery].

In patients undergoing open heart surgery, we assessed the effect of prostaglandin E1 (PGE1) treatment, 0.1 micrograms/min/kg dosage, during extracorporeal circulation. This treatment resulted in a marked perfusion pressure reduction. As a result, PGE1-treated group showed less urine volume than untreated control group. However, the degree of urine volume reduction relative to the decrease in blood pressure was less in PGE1-treated group than in untreated control group, suggesting a diuretic action of PGE1. We infer from these results that renal blood flow was maintained even after PGE1-induced intense perfusion pressure reduction, allowing for avoidance of renal impairment during extracorporeal circulation. In PGE1-treated adults, recovery of rectal temperature after hypothermic extracorporeal circulation was poorer but that of muscle temperature was better than in untreated adults. This phenomenon can be interpreted as representing improvement of blood-mediated heat transfer from deep regions of trunk to muscles and superficial skin due to PGE1-induced improvement of peripheral circulation. The ameliorative effect of PGE1 on peripheral circulation during extracorporeal circulation was further confirmed by the fact that the amount of NaHCO3 required for correction of metabolic acidosis was significantly lower in PGE1-treated group than in untreated control group. These results indicate that PGE1 treatment during extracorporeal circulation makes body temperature control easier, favorably affects postoperative body temperature recovery and improves peripheral tissue metabolism.

Alprostadil

Energy metabolism changes and oxidative attack after hepatic arterial embolization and chemoembolization in thioacetamide-induced cirrhotic livers.

Hepatic energy metabolism and oxidative attack were studied after transcatheter arterial embolization (TAE) and chemoembolization (TAC) of the left and median lobes of the liver using thioacetamide (TAA)-induced cirrhotic rats. TAE was carried out using gelatin sponge (1.5 mg/cm3) dissolved in saline solution (SS). TAC was performed by adding mitomycin C (MMC) (1.6 mg/kg body weight) to the previous embolic solution. The energy charge (EC) of embolized lobes decreased from 0.86 to 0.78 and 0.74 1 h after TAE and TAC, respectively, but was restored 3 h later. Adenosine 5'-triphosphate (ATP) and total adenine nucleotide content (TAN) of embolized and non-embolized lobes was also temporarily decreased. Total hepatic blood flow (THBF) of embolized and chemoembolized lobes was reduced in almost 50%, and it took 1 week to become normalized. After TAC (3 and 6 h, respectively), total glutathione (TGSH) content was reduced from 7.02 mumol/g of liver to around 4.5 mumol/g, and malondialdehyde (MDA) content increased from 196.94 nmol/g of liver to values above 300 nmol/g. TAE in cirrhotic livers did not induce any changes in these parameters. In conclusion, after TAE and TAC the hepatic energy metabolism is temporarily altered by ischemia. TAC-induced oxidative attack, in addition to ischemia and MMC, could be one of the mechanisms explaining the effectiveness of this therapy.

Adenine Nucleotides

Glucose overload and hepatic energy metabolism after resection of the cirrhotic liver in rats.

The effect of glucose hyperalimentation on energy metabolism in the cirrhotic rat liver after 70% hepatectomy was studied. After resection, rats received either 30 kcal/kg per day (group I) or 200 kcal/kg per day (group II) of glucose for 48 h. In both groups, hepatic mitochondrial ATP synthesis was accelerated when palmitic acid was used as substrate and suppressed when pyruvate was used. This suggests that the energy substrate of the remnant liver was principally fatty acids rather than glucose. Hepatic energy charge was within normal limits in group I, but decreased significantly in group II after hepatectomy. An abundance of glucose in the early postoperative period, therefore, caused a hepatic energy derangement by suppressing fatty acids utilization; this suppression was corroborated by the findings of lower immunoreactive glucagon and non-esterified fatty-acid concentrations in group II. To determine optimal glucose administration, the predicted value of glucose disposal rate (GDR) was calculated after an intravenous glucose tolerance test. GDR decreased significantly after hepatectomy and did not increase appreciably even with a large dose of insulin administration. These results suggest that glucose administration should be tailored to the GDR values after resection of the cirrhotic liver.

Adenosine Triphosphate

Immunohistochemical characterization, distribution and ultrastructure of lymphocytes bearing the gamma/delta T-cell receptor in the human gut.

The phenotypic characterization and distribution of lymphocytes bearing the gamma/delta T-cell receptor (TCR) in the human gut were investigated by an immunohistochemical technique. A mirror section technique and double staining method were used for the phenotypic analysis. Intraepithelial delta-positive cells were almost all CD8-positive and rarely negative for both CD4 and CD8. On the other hand, lymphocytes bearing TCR gamma/delta in the lamina propria were largely negative for both CD4 and CD8. The ratio of delta-positive to CD3-positive cells amongst intraepithelial lymphocytes was larger in the lower intestine. Delta-positive cells were also observed in paracortical areas of lymphoid follicles. Immunoelectron microscopic observation revealed granular structures in these delta-positive cells, which are also present in large granular lymphocytes. The role of lymphocytes bearing TCR gamma/delta in mucosal immune responses in the human gut are discussed.

Adult

Colonic motility in innervated and extrinsically denervated loops in dogs.

The control mechanism of canine colonic motor activity measured by means of chronically implanted force transducers was studied by comparing diurnal changes and migrating patterns in control dogs and dogs with innervated and extrinsically denervated colonic loops. Five force transducers (C1-C5) were placed on the colon, and the middle colon was transected to construct a loop including C2 and C3 transducers. Colonic continuity was established by an end-to-end anastomosis. In the fasted state, colonic motor complexes of 8-13 minutes' duration were observed to occur at intervals of 22-32 minutes in all three groups, but response to feeding was clearly different; significant enhancement of the colonic motor indexes lasting for 8-16 hours after feeding, which was observed at all recording sites in control dogs, was identified only in the proximal and distal colon in dogs with innervated and extrinsically denervated loops. In the innervated loop, significant enhancement of the motor indexes was observed only in the first 2 hours after feeding. In the extrinsically denervated loop, feeding did not induce any response. In both groups with loops, greater than 40% of the motor complexes that occurred in the proximal colon migrated to the distal colon directly across the anastomosis and less than 20% propagated to the loop. In addition, the migration time between the proximal and the distal colon was greatly reduced in both groups with loops compared with that in the control group. Another change observed within the loop was an increase in numbers of retrograde migrating colonic motor complexes. It is concluded that colonic motor activity is under the predominant control of intraluminal contents in the digestive state but that extrinsic nerves may play an important role in the response observed in the innervated loop in the first 2 hours after feeding, which should be defined as the gastrocolonic response in dogs. In the interdigestive state, the intrinsic nervous system and/or humoral factors may control the occurrence of colonic motor complexes.

Animals