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Biomedical subjects

S Matsuno

Publications and source records attributed to S Matsuno.

At least 109 records · Page 6Linked to original sources

A case with myasthenia gravis (MG) emerging after splenectomy for idiopathic thrombocytopenic purpura (ITP): possible effects of thymectomy on autoantibodies.

The combination of idiopathic thrombocytopenic purpura (ITP) and myasthenia gravis (MG) has been reported infrequently. We report here the development of MG in a patient who underwent splenectomy for ITP ten years earlier, and describe the serum levels of anti-acetylcholine receptor antibodies (anti-AchR) and platelet-associated IgG (PAIgG) followed over 11 years. The concentrations of both autoantibodies have been decreased after thymectomy, suggesting that this procedure is potentially beneficial for treating both MG and ITP.

Adult↗

Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1.

We have isolated a novel liver-specific organic anion transporter, LST-1, that is expressed exclusively in the human, rat, and mouse liver. LST-1 is a new gene family located between the organic anion transporter family and prostaglandin transporter. LST-1 transports taurocholate (Km = 13.6 microM) in a sodium-independent manner. LST-1 also shows broad substrate specificity. It transports conjugated steroids (dehydroepiandrosterone sulfate, estradiol-17beta-glucuronide, and estrone-3-sulfate), eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, leukotriene E4), and thyroid hormones (thyroxine, Km = 3.0 microM and triiodothyronine, Km = 2.7 microM), reflecting hepatic multispecificity. LST-1 is probably the most important transporter in human liver for clearance of bile acids and organic anions because hepatic levels of another organic anion transporter, OATP, is very low. This is also the first report of the human molecule that transports thyroid hormones.

Amino Acid Sequence↗

Controlling tumor angiogenesis and metastasis of C26 murine colon adenocarcinoma by a new matrix metalloproteinase inhibitor, KB-R7785, in two tumor models.

Experimental evidence has directly implicated matrix metalloproteinases (MMPs) in the remodeling of the stromal tissue surrounding tumors. Thus, MMP inhibitors could limit the expansion of both neoplastic cell compartment and endothelial cell compartment of a tumor. Much of the work on the role of MMP inhibitors has concentrated on their inhibitory effects on tumor cell invasion. We have examined the effects of a new MMP inhibitor, KB-R7785 (acting on MMP-1, MMP-3, and MMP-9), on tumor angiogenesis and metastasis of murine colon adenocarcinoma (C-26) in two tumor models in BALB/c mice (transparent chamber model and lung colonization model). KB-R7785 has not shown inhibitory effects on in vitro growth of either C-26 or KOP2.16 murine endothelial cells. In vivo, KB-R7785 administrated twice daily for 15 days (100 mg/kg, i.p.), starting the day of tumor inoculation (5 x 10(5) C26 cells) in transparent chamber, has resulted in 88.2% suppression of tumor growth, compared with that in vehicle-administered mice (controls). Tumors grown in controls have doubled their area in 3.3 days, whereas those treated by KB-R7785 progressed almost four times slower (tumor area doubling time, 12 days). KB-R7785 rendered centrally avascular tumors with only a rim of peripheral neovasculature, which had significant lower functional vascular density and vascular area than the corresponding parameters in control tumors 10 days after inoculation [79.9+/-6.7 cm/cm2 versus 164.1+/-10.1 cm/cm2 (P < 0.01) and 19.8+/-1.5% versus 42.6+/-2.7% (P < 0.01), respectively]. In the lung colonization model (tail vein inoculation of 5 x 10(5) C-26 cells), administration of KB-R7785 (100 mg/kg, i.p.) twice daily for 20 days has reduced the number of surface metastasis by 85.8% and abolished the tumor burden, as compared with controls. The few metastatic colonies found in the lungs of KB-R7785 treated mice appeared to be dormant (i.e., staining with von Willebrand factor antibody revealed few, if any, positive cells within the metastatic foci from MMP inhibitor-treated lungs, whereas terminal deoxynucleotidyl transferase-mediated nick end labeling showed a 4-fold increase in the rate of tumor cell apoptosis compared with controls. The fact that KB-R7785 interferes with early steps of angiogenesis and cancer spread suggests that MMP inhibitors may control both primary and secondary tumor growths by limiting the expansion of endothelial cells, as well as cancer cells, composing the tumors.

Adenocarcinoma↗

SEA-scFv as a bifunctional antibody: construction of a bacterial expression system and its functional analysis.

A SEA-antibody single chain Fv (SEA-scFv) fusion protein was produced by bacterial expression system in this study. SEA-scFv has both staphylococcal enterotoxin A (SEA) effects and antibody activity directed at the epithelial mucin core protein MUC1, a cancer associated antigen. It was expressed mostly in the cytoplasm as an insoluble form. The gene product was solubilized by guanidine hydrochloride, refolded by conventional dilution method, and purified using metal-chelating chromatography. The resulting SEA-scFv fusion protein preparation was found to react with MUC1 and MHC class II antigens and had the ability to enhance cytotoxicity of lymphokine activated killer cells with a T cell phenotype against a human bile duct carcinoma cell line, TFK-1, expressing MUC1. This genetically engineered SEA-scFv fusion protein promises to be an important reagent for cancer immunotherapy.

Antibodies, Bispecific↗

Immunohistochemical distribution and functional characterization of an organic anion transporting polypeptide 2 (oatp2).

The rabbit polyclonal antibody against rat organic anion transporting polypeptide 2 (oatp2) was raised and immunoaffinity-purified. Western blot analysis for oatp2 detected two bands ( 74 and 76 kDa) in rat brain and a single band (76 kDa) in the liver. By immunohistochemical analysis, the oatp2 immunoreactivity was specifically high at the basolateral membrane of rat hepatocytes. Functionally, the oatp2-expressing oocytes were found to transport dehydroepiandrosterone sulfate, delta1 opioid receptor agonist [D-Pen2,D-Pen5]enkephalin, Leuenkephalin, and biotin significantly, as well as the substrates previously reported. These data reveal the exact distribution of the rat oatp2 at the protein level in the liver, and that oatp2 appears to be involved in the multispecificity of the uptaking substrates in the liver and brain.

Animals↗

Differing expression of MMPs-1 and -9 and urokinase receptor between diffuse- and intestinal-type gastric carcinoma.

Gastric cancer is classified into intestinal and diffuse types, which exhibit different biological behavior. Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and matrix metalloproteinases (MMPs)-1 and -9 are considered to play important roles in cancer invasion and metastasis. We have already suggested a functional duality of these matrix-degrading enzymes/factors; they may also be involved in the matrix turnover (remodeling) or host immune/inflammatory reactions as far as they are expressed by host cells. We performed a retrospective study on the immuno-histochemical expression of these enzymes/factors in surgical specimens from patients with gastric cancer, including 26 with the diffuse and 78 with the intestinal type. We also evaluated macrophages since they are major sources of uPAR. The positivity rate for uPA in cancer cells was significantly lower in diffuse-type than in intestinal-type. Stromal expression was seen mainly along the invasive margin (tumor-host interface). The degree of stromal expression of uPAR and MMP-9 and the macrophage number were markedly decreased in diffuse-type compared with intestinal-type. Stromal expression of uPAR and macrophage number in intestinal-type were higher in patients without liver metastasis than in patients with liver metastasis, while uPA expression in cancer cells was more pronounced in patients with liver metastasis. Studies using frozen sections revealed that the expression of MMP-1, restricted to the stromal area, was more decreased in diffuse-type (18 patients) than in intestinal-type (21 patients). Our results show that the in situ expression of matrix-degrading enzymes/factors in gastric cancer is significantly more diminished in diffuse-type than in intestinal-type, suggesting a multifunctional aspect of the matrix-degradation process in cancer tissue.

Antigens, CD↗

Plasma glicentin in diabetic and gastrectomized patients.

Recent successful synthesis of human glicentin prompted us to establish an immunoassay method for determination of human glicentin in plasma. Human glicentin in plasma was measured using a newly developed sandwich ELISA. The mean fasting levels of human glicentin were 18.6+/-2.4 and 19.7+/-2.1 pM in normal subjects and diabetic patients, respectively. In diabetic patients with renal failure, plasma glicentin was elevated, exceeding 100 pM. In normal subjects, plasma glicentin increased to a peak level of about 130 pM at 60 min after an oral glucose load, and then decreased. In patients who underwent gastrectomy, plasma glicentin rapidly increased to a peak of about 300 pM at 30 min after oral glucose load. In a patient with short bowel syndrome plasma glicentin did not change following an oral glucose load. These results correspond with previous findings for gut glucagon-like immunoreactive materials (GLI) or enteroglucagon. We conclude that glicentin is secreted from the small intestine in response to intraluminal glucose stimulation in humans.

Blood Glucose↗

Intraductal papillary mucinous tumors of the pancreas comprise 2 clinical subtypes: differences in clinical characteristics and surgical management.

HYPOTHESIS: Intraductal papillary mucinous tumors (IPMTs) of the pancreas may be meaningfully construed as representing 2 clinically distinct subtypes: main duct tumors (MDT) and branch duct tumors (BDT). DESIGN: Retrospective study. SETTING: University hospital from January 1988 through December 1994. PATIENTS AND INTERVENTION: We reviewed diagnostic findings and late results of surgical treatment in 30 patients with IPMT. RESULTS: The tumor was located in the head of the pancreas more often in BDT than in MDT (65% [11/17] and 23% [3/13], respectively). Of the 13 patients with MDTs, 12 (92%) had intraductal papillary adenocarcinoma (noninvasive and minimally invasive types) and/or carcinoma in situ (carcinoma in situ: low papillary and/or flat tumor cells), and 3 (23%) had stromal invasion. Of the 17 patients with BDTs, 5 (29%) had intraductal papillary adenocarcinoma and/or carcinoma in situ. Two pancreatoduodenectomies and 8 pylorus-preserving pancreatoduodenectomies were performed in 10 of the 17 patients with BDTs, distal pancreatectomy in 7 patients with MDTs, and total pancreatectomy in 4 patients with MDTs. The 5-year survival rates were 47% for MDT and 90% for BDT. Four of 6 patients with MDTs who died had local recurrence. One patient died of liver metastasis and 1 of esophageal cancer. Only 1 patient with BDT of the 2 who died had recurrent disease. CONCLUSIONS: Intraductal papillary mucinous tumors may be composed of 2 clinically distinct subtypes: MDTs and BDTs. Initially, although distal pancreatectomy can be recommended for most MDTs, the need for cancer-free margins in this more aggressive type may necessitate total pancreatectomy. Pylorus-perserving pancreatoduodenectomies is recommended for most BDTs, but, because these tumors are more often adenomas, a good prognosis can be expected.

Aged↗

Monitoring and antibacterial treatment for postoperative bacterial overgrowth in Crohn's disease.

PURPOSE: Bacterial overgrowth sometimes complicates the clinical course of Crohn's disease and may lead to inappropriate treatment. To clarify the effect of antibiotic therapy, we monitored the hydrogen concentration in expiratory breath after fasting. METHODS: We evaluated 18 patients (15 males; median age, 32.7; range, 22.3-60 years) for postoperative bacterial overgrowth symptoms and for intestinal dilation by plain abdominal x-ray. Five patients had ileitis and 13 patients had ileocolitis. Various intestinal resections were performed in all, and strictureplasties were done at the same time in 13 patients. The median postoperative period was 10.2 (range, 1.2-102) months. Nine patients, who had symptoms such as bloating, nausea, vomiting, or pain, were classified as the symptomatic group, whereas nine other patients, who had no symptoms, were classified as the symptom-free group. Sixteen patients who had undergone intestinal resections for noninflammatory bowel disease served as the control group. After overnight fasting, hydrogen concentration in end-expiration, breath was measured with gas chromatography. At the same time clinical examinations of white blood cell count, hemoglobin, total protein, serum albumin, iron, sialic acid, and C-reactive protein in the peripheral blood were performed. To assess the effect of antibacterial treatment, changes in symptoms were assessed in eight patients who received antibacterial treatment. Hydrogen concentration was measured repeatedly before and after treatment in six patients. RESULTS: The symptomatic group had an expiratory hydrogen concentration level significantly higher (median, 40; range, 20-139 ppm) than the control group (median, 3; range, 1-6 ppm) and the symptom-free group (median, 4; range, 1-10 ppm). After the antibiotic treatment the symptoms were improved in all of the patients, and the hydrogen concentration level was significantly reduced (median, 4.5; range, 2-13 ppm). CONCLUSIONS: Antibacterial treatment was useful in the postoperative patients whose assessments were complicated by bacterial overgrowth. Using a hydrogen breath test, bacterial overgrowth was effectively monitored and managed, effecting a change in clinical symptoms.

Adult↗

Handlebar hernia with intra-abdominal extraluminal air presenting as a novel form of traumatic abdominal wall hernia: report of a case.

An 18-year-old male was admitted to our Emergency Department with a traumatic abdominal wall hernia (TAWH) of the left lower quadrant (LLQ) after suffering hypogastric blunt injury and urogenital lacerations in a motorcycle accident. Upright chest X-ray showed a small amount of right infradiaphragmatic free air, and a computed tomographic (CT) scan demonstrated an abdominal wall hernia. At surgery, no impairment was found in the digestive tract, and an abdominal herniorrhaphy was performed. It is suggested that the free air had passed through a connection between the scrotal laceration and the contralateral abdominal defect via the subcutaneous space and was palpated as emphysema. This is a new type of TAWH, which suggests that blunt abdominal trauma may result in negative pressure in the subcutaneous and peritoneal cavity, and this could reflect the pathophysiology of TAWH.

Abdominal Muscles↗

Management of urinary complications in Crohn's disease.

Among the 127 patients who underwent surgical treatment for Crohn's disease at Tohoku University Hospital, urinary complications were noted in 13 patients (10.2%), including urolithiasis in 6 patients (4.7%), a ureteral obstruction in 4 (3.1%), and urinary fistula in 3 (2.4%). In patients with urolithiasis, conservative therapy was effective. An ureteral obstruction was detected on the right side in all 4 of these cases because of the inflamed terminal ileum. In 2 of the 4 cases, the symptoms improved by either preoperative total parenteral nutrition or elemental diet therapy. A resection of the inflamed intestine was necessary in all cases. In patients with urinary fistulas, a resection of the inflamed intestine combined with a reconstruction of the urinary tract was carried out after total parenteral nutrition. In conclusion, conservative therapy with preoperative total parenteral nutrition or elemental diet therapy proved to be effective for a ureteral obstruction since it improved the intestinal inflammation. As a definitive treatment, surgery is still necessary for the management of urinary fistulas and ureteral obstruction. Based on our findings, patients with urolithiasis in Crohn's disease should thus be treated conservatively in the same way as patients without Crohn's disease.

Adolescent↗

Turcot syndrome with colonic obstruction and small intestinal invagination: report of a case.

We report herein the case of a 16-year-old boy diagnosed as having Turcot syndrome, otherwise known as glioma-polyposis syndrome. The patient was transferred from the Department of Neurosurgery where he was undergoing investigation of a brain tumor, to the Department of Medicine for investigation of gastrointestinal symptoms. The patient was diagnosed as having Turcot syndrome, and was then transferred to the Department of Surgery for treatment of an obstruction in the sigmoid colon and small intestinal invagination. A subtotal colectomy with side-to-end ileoproctostomy and release of the invaginations was carried out. Multiple polyps were found in the colon, two of which, including a large polyp that obstructed the colonic lumen, were confirmed histologically to be adenocarcinoma. The remaining polyps were adenomas. A biopsy of the brain tumor confirmed a diagnosis of astrocytoma (WHO grade II). This case report describes the characteristic features of Turcot syndrome presented by this patient.

Adenocarcinoma↗

The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection.

To investigate the prognostic factors of pancreatic cancer, a retrospective analysis of 193 patients who underwent curative resection was conducted. Of the 193 patients, 38 (20%) survived for more than 5 years, the 5-year survival rates for stages I, II, II, and IV disease being 41%, 17%, 11%, and 6%, respectively. According to a multivariate analysis, lymph node metastasis, intrapancreatic perineural invasion, and portal vein invasion were significant prognostic factors. Subsequently, a subgroup analysis concerning nodal metastasis and intrapancreatic perineural invasion was performed in 126 patients with records of these histological findings. In the group of patients without nodal metastasis, the 5-year survival rate for those without perineural invasion was 75%, whereas that for those with perineural invasion was 29%, the difference in survival of these subgroups being significant (P < 0.02). In the group of patients with nodal metastasis, the 5-year survival rate for those without perineural invasion was 17%, while that for those with perineural invasion was 10%. The most favorable 5-year survival of 89% was observed in the subgroup of patients with stage I disease without perineural invasion. Thus, pancreatic adenocarcinoma categorized by the combination of these independent types of biological behavior showed 5-year survival rates ranging from very high to low, indicating that these two factors play an important role in the prognosis of this disease.

Adenocarcinoma↗

Hand-assisted laparoscopic digestive surgery provides safety and tactile sensation for malignancy or obesity.

BACKGROUND: Some of the persistent problems associated with laparoscopic surgery stem from the inability of the surgeon to palpate the abdominal contents during the operation. This lack of tactile sensation can lead to poor abdominal exploration, difficulty in extracting the organs, and a relatively long operation time compared to conventional procedures. The Dexterity Pneumo Sleeve is a new device that allows the surgeon to insert his or her hand into the abdominal cavity through a small incision while preserving the pneumoperitoneum. METHODS: Recently, 13 of our patients underwent hand-assisted advanced laparoscopic surgery using this device. In this series, we had two cases of gastrectomy, two cases of gastric bypass for morbid obesity, two Whipple cases for periampullary tumor, and seven cases of bowel resection. On the basis of this series, we were able to assess the utility of this device. RESULTS: Satisfactory pneumoperitoneum was maintained in 12 of 13 cases. The length of the skin incision was 7.8 cm on average, which was almost the same size as surgeon's glove. The device proved to be very useful for tissue retraction and abdominal exploration in all cases and for intracorporeal knot tying in some cases. CONCLUSIONS: We found that the device permitted an easier dissection, resection, and anastomosis. It also helped to decrease the operation time.

Adult↗

Colonization of microflora in mice: mucosal defense against luminal bacteria.

To investigate the pathogenesis of inflammatory bowel disease, it is critical to develop a system that uses simple and reproducible models for analyzing the "normal" mucosal defense mechanism. In the present study, germ-free mice were conventionalized by the oral administration of microorganisms prepared from the feces of genetically identical mice. Histological assessment and mucin characterization of small intestine and colon were then carried out. Histological findings in the gut were site-dependent and clearly time-dependent. Acute inflammation was most evident in the cecum. The cecal mucosa exhibited hyperplastic changes in epithelial cells, infiltration of polymorphonuclear cells, crypt abscesses, and epithelial projections on the epithelial surface 7 days after conventionalization. Some of the changes were similar to those seen in human ulcerative colitis. The histological findings in the conventionalized mice were comparable to those in specific pathogen-free mice after 28 days. Mucin histochemistry revealed that bacterial colonization altered the number of rectal goblet cells and the mucin composition in a time-dependent fashion. Although this model shares only some characteristics of human inflammatory bowel disease, it is unique in demonstrating the acquisition of mucosal defense. Understanding of this process is critical for the elucidation of inflammatory bowel disease pathogenesis.

Animals↗

Hepatic phosphatidylcholine hydroperoxide content in noncirrhotic, cirrhotic, and antioxidant-treated rats with endotoxemia.

Hepatic phosphatidylcholine hydroperoxide (PCOOH) was studied intensively to delineate its role in the altered pathophysiology of liver failure associated with endotoxemic shock. Endotoxemia was induced by cecal ligation and puncture (CLP) in three models using rats. Model 1 consisted of normal healthy rats; model 2, cirrhotic rats; and model 3, rats treated with catalase and superoxide dismutase (SOD). Samples were taken before CLP, then 12 h and 24 h following CLP. A progressive and significant increase in serum endotoxin was seen in all models; however, a significantly low energy charge (EC) and high PCOOH were seen in models 1 and 2, whereas no change was observed in model 3. The regional blood flow remained unchanged throughout the experiment in models 1 and 3, but not in model 2. An initial increase in alpha-tocopherol was seen in model 1. The survival rate was markedly better in model 3 than in models 1 or 2. The fall in EC corresponded to the increase in serum endotoxin as well as to the increase in tissue PCOOH in models 1 and 2. It was more likely that the elevated lipid peroxidation in model 1 resulted from endotoxemia rather than from tissue hypoperfusion. The early increase in alpha-tocopherol that occurred in models 1 and 2, but not in model 3, indicated the antiradical defense response to oxidative injury. Thus, antioxidant therapy significantly improved the survival rate and tissue adenine nucleotide level in spite of the increased serum endotoxin level.

Adenosine Triphosphate↗

Molecular characterization and functional regulation of a novel rat liver-specific organic anion transporter rlst-1.

BACKGROUND & AIMS: Recently, we isolated a new complementary DNA (cDNA) encoding human liver-specific organic anion transporter (LST-1), representing the multispecificity of human liver. The aim of this study was to isolate a rat counterpart of human LST-1 and examine the expression regulation of its messenger RNA (mRNA) to clarify the molecular basis of cholestasis. METHODS: A rat liver cDNA library was screened with human LST-1 cDNA as a probe. Xenopus oocyte expression system was used for functional analysis. Northern blot analyses were performed using the isolated cDNA (termed rlst-1). The bile duct ligation model and the cecum ligation and puncture model were used for expression analyses. RESULTS: rlst-1 encodes 652 amino acids, predicting at least 11 transmembrane regions. The overall homology with human LST-1 was 60.2%, which is the highest among all known organic anion transporters. rlst-1 also belongs to the same new gene family as human LST-1, located between the organic anion transporter family and the prostaglandin transporter. rlst-1 preferably transports taurocholate (K(m), 9.45 micromol/L) in an Na(+)-independent manner. The rlst-1 mRNA is exclusively expressed in the liver. In both the bile duct ligation model and the cecum ligation and puncture model, mRNA expression levels of rlst-1 were down-regulated. CONCLUSIONS: rlst-1 is a counterpart of human LST-1 and is one of the important transporters in rat liver for the clearance of bile acid. The expression of rlst-1 may be under feedback regulation of cholestasis by biliary obstruction and/or sepsis.

Amino Acid Sequence↗