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Biomedical subjects

S Matsuno

Publications and source records attributed to S Matsuno.

At least 145 records · Page 8Linked to original sources
PubMed1999

Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer.

Pancreatic cancer has one of the poorest prognoses among malignant diseases. To understand its molecular mechanisms, we studied allelic losses on the long arm of chromosome 6. Using 55 paired DNAs of tumors and their corresponding normal tissues and 30 microsatellite markers that spanned the entire 6q chromosome arm, we found three distinct regions of common allelic loss: region A, a less than 500-kb region bordered by D6S449 and D6S283 on 6q21 with a loss of heterozygosity (LOH) frequency of 69% (38/55); region B, a 7-cM region bordered by D6S292 and D6S308 on 6q23-q24 with a LOH frequency of 60% (33/55); and region C, a 13-cM region bordered by D6S305 and D6S264 with a LOH frequency of 51% (28/55). We further focused on region A and constructed a physical map using yeast artificial chromosome (YAC) clones, their derived cosmid clones, and bacterial artificial chromosome (BAC) clones. Region A was completely covered by three overlapping BAC clones. Our results in the present study should shed light on the cloning and characterization of tumor suppressor genes in pancreatic carcinogenesis.

Adult↗
PubMed1999

[Therapeutic strategy for the recurrence of pancreatic cancer following pancreatectomy].

It is well-known that the patients with pancreatic cancer are vulnerable for recurrence such as local relapse and liver metastasis after surgical resection. We revealed that a patient with local relapse without liver metastasis showed better prognosis as compared with a patient having liver metastasis. We usually adapt further therapeutic intervention for local recurrence using external radiation therapy accompanied with 5FU infusion as a radiosensitizer, if the patient is not revealed with liver metastasis. On the other hand, there is no effective intervention for liver metastasis accompanying pancreatic cancer, as small lesions of multiple liver metastases progress rapidly. We insert the tip of catheter in proper hepatic artery in order to infuse MMC once a week at outpatient clinic. However, we were not yet able to evaluate the effect of arterial infusion therapy.

Infusions, Intra-Arterial↗
PubMed1999

Long term follow-up of atrioventricular valve function after repair of atrioventricular septal defect.

To elucidate the factors which are associated with early and late operative results of atrioventricular septal defects, 102 consecutive patients who underwent reparative operation of atrioventricular septal defects (AVSD) in our institution since 1968 were studied. Our operative technique was basically the same through this period. That is the two patch method in its complete form (the so-called Shirotani's method) and preferential use of cleft closure supplemented with Kay-Reed-Wooler type annuloplasty. Early mortality (< 30 days) rate was 18.6%. More than 80% of the early deaths were not related to atrioventricular valve malfunction. Non-complete closure of the cleft, high preoperative pulmonary vascular resistance, deficient atrioventricular valve, and complete form showed independent correlations with early mortality in multiple logistic regression analysis. For operative survivors, event-free survival curves, for atrioventricular valve related reoperations were drawn for various factors. Two late deaths and 3 late atrioventricular-valve-related reoperations occurred. The event-free actuarial survival for operative survivors at 5, 10, and 20 years were 97.0%, 89.4%, and 89.4%, respectively. The survival analysis revealed that preoperative high pulmonary vascular resistance, preoperative severe atrioventricular regurgitation, and preoperative large cardiothoracic ratio in chest radiogram were related with late event occurrence. Higher early mortality in our series may be attributable to relatively advanced pulmonary vascular occlusive disease rather than post repair atrioventricular valve malfunction. On the other hand, our late results were rather good. We concluded that the Shirotani's method and preferential use of cleft closure supplemented with Kay-Reed-Wooler type annuloplasty was effective for most of atrioventricular valves in atrioventricular septal defects. Early surgical intervention before pulmonary vascular disease progression or atrioventricular valve regurgitation development is also important.

Cardiac Surgical Procedures↗
PubMed1999

[Microcirculatory derangement and ischemia of the pancreas].

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and introduce our experimental results on pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction, and intravascular thrombus formation. We achieved direct-visualization and quantification of changes in microvascular permeability and leukocyte behavior in the pancreas with acute pancreatitis using an in vivo microscope system and off-line computer analysis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increased vascular permeability in the early stage of cerulein pancreatitis. Gabexate mesilate (FOY) prevents the increase in vascular permeability, resulting in a decreased number of rolling leukocytes. Leukocyte adherence to the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during aggravation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. The diamino-pyridine derivative IS-741 inhibits the progression of pancreatic inflammation by down-regulating the expression of CD11b/18.

Acute Disease↗
PubMed1999

Total number and size distribution of hepatic metastases of carcinoma.

OBJECTIVE: To quantify the susceptibility of carcinoma to hepatic metastases by studying autopsy livers with carcinoma metastases, the primary sites of which were mostly the digestive organs. STUDY DESIGN: We developed a stereologic method of estimating the total number, N, and the size distribution of metastatic tumors in the liver based on a geometric model of spherical nodules with varying radii, r. This method proved to be sufficiently reliable by disector analysis simultaneously performed in some cases; it gave an approximate result. This method was applied to the 31 autopsy cases. Correlation and regression analyses were performed among N, the mean radius of nodules, rmean, and conventional pathologic features of the primary tumor. RESULTS: The estimates of N ranged from 10 to 3.2 x 10(5). A close negative correlation was confirmed between N and rmean. Neither significant correlation nor regression was observed among N and the other pathologic factors of the primary tumors. CONCLUSION: N turned out to serve as a useful index for evaluating the metastatic potential of a carcinoma. However, investigation has yet to be made to determine biologic factors in the primary tumor closely associated with N.

Carcinoma↗
PubMed1999

The herbal medicine Dai-Kenchu-Tou stimulates upper gut motility through cholinergic and 5-hydroxytryptamine 3 receptors in conscious dogs.

BACKGROUND: The herbal medicine Dai-Kenchu-To, composed of zanthoxylum fruit, ginseng root, and dried ginger rhizome, is clinically effective for uncomplicated postoperative adhesive intestinal obstruction. We investigated the effect of Dai-Kenchu-To and each ingredient on upper gastrointestinal motility and its mechanism of action. METHODS: Five mongrel dogs were equipped with 4-strain gauge-force transducers on the gastric body, antrum, duodenum, and jejunum to measure contractile activity of the circular muscle. Dai-Kenchu-To (1.5 g) or the separate ingredients zanthoxylum fruit, ginseng root, or dried ginger rhizome (1.0 g each) were administered by bolus into the gastric lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intragastric Dai-Kenchu-To-induced contractions was studied. RESULTS: Intragastric Dai-Kenchu-To induced phasic contractions in the antrum, duodenum, and jejunum. Zanthoxylum fruit elicited phasic contractions mainly in the duodenum and jejunum, whereas dried ginger rhizome induced phasic contractions in the antrum. Ginseng root had no effect. Phasic contractions induced by intragastric Dai-Kenchu-To were inhibited by atropine and hexamethonium at all sites, although ondansetron inhibited these contractions in the antrum and duodenum. CONCLUSIONS: Intragastric Dai-Kenchu-To stimulates upper gastrointestinal motility through cholinergic and 5-hydroxytryptamine 3 receptors.

Animals↗
PubMed1998

Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2.

Two complementary DNAs for the organic anion transporter subtypes oatp2 and oatp3, which transport thyroid hormones as well as taurocholate, were isolated from a rat retina cDNA library. The sequence of oatp2 is identical to that recently reported (Noé, B., Hagenbuch, B., Stieger, B., and Meier, P. J. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 10346-10350), whereas the sequence of oatp3 is novel. oatp3 consists of 670 amino acid residues and exhibits a structural architecture common to the organic anion transporter family, possessing the 12 putative membrane-spanning segments. Oocytes injected with oatp2 and oatp3 cRNAs showed taurocholate uptake in a saturable manner. The oatp2 and oatp3 cRNA-injected oocytes also showed significant uptake of both thyroxine and triiodothyronine. Northern blot and in situ analyses showed that the oatp2 mRNA was widely expressed in neuronal cells of the central nervous system, especially in the hippocampus, cerebellum, and choroid plexus as well as in the retina and liver. The oatp3 mRNA was highly expressed in the kidney and moderately abundant in the retina. This suggests that oatp2 and oatp3 are multifunctional transporters involved in the transport of thyroid hormones in the brain, retina, liver, and kidney.

Amino Acid Sequence↗
PubMed1998

Effective adoptive immunotherapy by T-LAK cells retargeted with bacterial superantigen-conjugated antibody to MUC1 in xenografted severe combined immunodeficient mice.

To reinforce cytotoxic activity and the targeting ability of lymphokine-activated killer cells with a T-cell phenotype (T-LAK) for adoptive immunotherapy against human bile duct carcinoma (BDC), staphylococcal enterotoxin A (SEA) was conjugated chemically with MUSE11 monoclonal antibody (MUSE11 mAb), directed to the MUC1 antigen, using N-succinimidyl 3-(2-pyridyldithio) propionate and 2-iminothiolane HCl. Both SEA-conjugated MUSE11 mAb (SEA-MUSE11) and the F(ab')2 of MUSE11 mAb (SEA-F(ab')2) showed significant enhancement of T-LAK cell tumor neutralization for MUC1 positive-target tumor cells, even with a concentration of 0.01 microg/ml at an E:T ratio of 5:1 in vitro. In this in vitro test, MUC1-positive BDC cells were observed to attach to surrounding T-LAK cells in the presence of SEA-MUSE11 or SEA-F(ab')2. Remarkable tumor growth inhibition was observed in BDC-grafted severe combined immunodeficient mice to which 2 x 10(7) T-LAK cells preincubated with 2 microg of SEA-MUSE11 or SEA-F(ab')2, together with recombinant interleukin 2 (500 IU), were administered i.v. for 4 consecutive days, when tumor size was 5 mm in diameter. These results point to a promising adoptive immunotherapy for patients with BDC.

Animals↗
PubMed1998

Emergence of immunoreactivities for phosphorylated tau and amyloid-beta protein in chronic stage of fluid percussion injury in rat brain.

Head injury is one of the potential environmental factors in Alzheimer's disease (AD). To study the chronic stage of concussive brain injury, histological analyses were performed 2-6 months after right lateral fluid percussion (FP) brain injury (3.6-4.8 atm) in rats. Six months after injury, numerous normal-looking neurons in the telencephalon and brain stem were immunoreactive with either antibody to phosphorylated tau or with four antibodies to beta-amyloid protein. Neuronal counts in the cortices were gradually decreased after injury, up to 42% loss at 6 months after injury. These neuropathological changes suggest that this animal model could serve as a good animal model of neurodegenerative diseases such as AD.

Amyloid beta-Peptides↗
PubMed1998

Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer.

Using the method of microsatellite analysis, we studied 40 tissues with pancreatic ductal adenocarcinoma and identified two commonly deleted regions on the long arm of chromosome 12. One (region A) was found between D12S81 and D12S1719 at 12q21 at a frequency of 67.5%, and the other (region B) was located between D12S360 and D12S78 at 12q22-q23.1 at a frequency of 60%; the latter was reported previously (M. Kimura, et al. Genes Chromosomes Cancer, 17: 88-93, 1996). The results of microsatellite analyses were verified by fluorescence in situ hybridization. We further analyzed 19 pancreatic cancer cell lines by fluorescence in situ hybridization and found that 10 of them showed allelic loss at D12S81 and 6 showed allelic loss at D12S360. Yeast artificial chromosome contigs were constructed to cover the deleted regions. Region B was completely covered by a 650-kb yeast artificial chromosome clone. The frequently deleted regions in chromosome 12q in pancreatic cancer that were identified here may provide new avenues for isolating novel tumor suppressor genes.

Adult↗
PubMed1998

A novel class II phosphoinositide 3-kinase predominantly expressed in the liver and its enhanced expression during liver regeneration.

We report herein the cloning and characterization of a novel class II phosphoinositide 3-kinase, termed PI3K-IIgamma, from the cDNA library of regenerating rat liver. This cDNA encodes a protein of 1505 amino acids with a calculated molecular mass of 170,972 Da. The amino acid sequence of PI3K-IIgamma is highly similar to those of class II PI 3-kinases, including murine Cpk-m/p170 and human HsC2-PI3K. It contains a C2 domain at the C terminus but no recognizable protein motifs at its N terminus. PI3K-IIgamma displays a restricted substrate specificity for PtdIns and PtdIns 4-P, but not for PtdIns 4,5-P2. By epitope tag immunocytochemistry, the immunoreactivity for PI3K-IIgamma is localized in the juxtanuclear Golgi region at high levels and also in the plasma and nuclear membranes at low levels. By Northern blot analysis and in situ hybridization histochemistry, PI3K-IIgamma mRNA expression is confined to the liver throughout the development with much higher expression in adult liver than in fetal liver. In addition, its expression increases during liver regeneration after partial hepatectomy with maximal expression after the growth period, suggesting that PI3K-IIgamma may function mainly in highly differentiated hepatic cells.

Adult↗
PubMed1998

The inhibitory effect of an EGF receptor-specific tyrosine kinase inhibitor on pancreatic cancer cell lines was more potent than inhibitory antibodies against the receptors for EGF and IGF I.

CONCLUSION: Epidermal growth factor (EGF) increased the cell number of the two pancreatic cancer cell lines, MiaPaCa-2 and LN-36, in vitro. A blockade of the EGF-R tyrosine kinase with tyrphostin was more efficient in reducing the cell number than inhibiting receptor antibodies. IGF-1 increased the cell number, and blockade of the IGF-1-R initially decreased the cell number that later was followed by an increase in LN-36. BACKGROUND/AIM: The receptors and ligands of EGF and insulin-like growth factor-1 (IGF-1) are overexpressed in pancreatic cancer tissue. The aim of the present experiments was to study the effects of EGF and IGF-1 on the cell number in two pancreatic cancer cell lines. MATERIAL AND METHODS: MiaPaCa-2 cells were grown in 0.2% fetal calf serum (FCS) and the newly established LN-36 cells in serum-free medium (SFM). The cell number was measured with the XTT method. The effects of EGF and IGF-1 were studied in combination with inhibiting receptor antibodies and an EGF-R-specific tyrosine kinase inhibitor, tyrphostin B56. RESULTS: MiaPaCa-2 responded with increased cell number to stimulation with EGF, and at 10(-8) M or higher concentrations a dose-response pattern was seen. Administration of B56 to MiaPaCa-2 decreased the cell number by 87%. The inhibiting EGF-R-Ab only inhibited EGF-induced increase in cell number. IGF-1 doubled the cell number of MiaPaCa-2 and increased the cell growth induced by EGF. The inhibiting IGF-1-R-Ab reduced the cell number by 10%. The LN-36 cell line responded to EGF with an increased cell number with a maximum at 5 x 10(-9) M after 96 h. B56 reduced the cell number by 90% at 10(-5) M, with less effect during stimulation with EGF. In contrast to B56, the inhibiting EGF-R-Ab in the same experiment did not reduce the cell number. LN-36 responded to IGF-1 with an increased cell number, but EGF-stimulated growth was not influenced. The inhibiting IGF-1-R-Ab reduced the cell number and suppressed the IGF-1 stimulated increase after 24 h and later it induced an increased cell number.

Antibodies↗
PubMed1998

Pancreatic microcirculation in acute pancreatitis.

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and report our experimental results of the investigation of pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction and intravascular thrombus formation. Using an in-vivo microscope system and off-line computer analysis, we achieved direct visualization and quantification of changes in microvascular permeability and leukocyte behavior in pancreas with acute pancreatitis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increase of vascular permeability in the early stage of caerulein pancreatitis. Leukocyte adherence to the vessels in the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during exacerbation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18.

Acute Disease↗
PubMed1998

Staging systems for pancreatic cancer: differences between the Japanese and UICC systems.

Differences between the clinical staging system of the Japan Pancreas Society (JPS) and the Union Internationale Contre le Cancer (UICC) stage classification may account for reported differences in the prognosis of pancreatic carcinoma between Japan and the West. In the review, we compared the characteristics of the JPS and UICC staging in 1689 patients, registered with the JPS from 1981 to 1990, who underwent resection for carcinoma of the pancreatic head. The survival rates correlated well with the JPS stage classification. The UICC staging did not reflect differences in prognoses among the stages. The current JPS staging system, introduced in 1993, still differs from that of the UICC. To compare the results of treatment for patients with pancreatic cancer it is important to establish a more practical and universal staging system for carcinoma of the pancreas.

Humans↗
PubMed1998

Intraoperative radiotherapy for pancreatic adenocarcinoma.

Intraoperative radiotherapy (IORT) is an innovative treatment approach for cancer of the pancreas. The common causes of treatment failure in pancreatic cancer are regional recurrence and distant metastasis. While at present the benefit of IORT in unresectable pancreatic cancer is still controversial and awaits further prospective trials for its clarification, the experience gathered over a period of 30 years with IORT for pancreatic cancer does suggest that IORT should be part of the adjuvant therapy of surgical resection. A combination with pre- or postoperative external beam radiotherapy and chemotherapy may be beneficial for both resectable and unresectable patients. IORT was shown to be a relatively safe intervention and it notably improved the quality of life of patients with locally advanced pancreatic carcinomas by alleviating their pain. Here, we summarize and discuss the experience reported to date and present our historical analysis of IORT for pancreatic cancer.

Adenocarcinoma↗
PubMed1998

Simplified hepatic resection utilizing absorbable polyglycolic acid-based tape and other ligature apparatus.

Hepatic resection has been increasing in frequency in the management of metastatic or primary neoplasms of the liver. Although mortality for this procedure has steadily decreased, the associated morbidity remains high. Morbidity is mainly associated with operative time and blood loss, especially in jaundiced and cirrhotic patients. During hepatic resection, control of bleeding from various sources is the most important problem faced by surgeons. During conventional lobectomy, despite prior control of hepatic artery and portal vein to that lobe, bleeding still occurs from the opposite lobe or back flow from hepatic veins. We usually apply Pringle's maneuver for hemostasis, but consequently there is postoperative hepatic dysfunction. We have previously investigated methods for vascular occlusion at the site of liver resection. We developed a new absorbable polyglycolic acid-based tape (breadth, 3 mm; length, 70 cm) for use in hepatic mass ligation, as well as two types of ligature apparatus. Hemostasis was achieved with these devices, and all lobar, segmental, and non-anatomic resections were performed without prior control of the portal venous system, hepatic arterial inflow, and hepatic venous outflow before parenchymal resection. This significantly shortened the operative time, as well as decreasing the blood loss during hepatic resection, with consequent reduction of postoperative morbidity. The use of this absorbable tape may reduce the incidence of local infection, abscess formation, and septicemia.

Absorbable Implants↗