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Biomedical subjects

T Matsubara

Publications and source records attributed to T Matsubara.

At least 91 records · Page 5Linked to original sources

Sodium valproate inhibits production of TNF-alpha and IL-6 and activation of NF-kappaB.

Sodium valproate (VPA) is frequently used to treat epilepsy and convulsive disorders. Several reports have indicated that anti-epileptic drugs (AED) affect the immune system, but the mechanism has not been clear. We examined whether the commonly used AEDs, diazepam (DZP), carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and VPA, can inhibit activation of the nuclear transcription factor kappa B (NF-kappaB), in human monocytic leukemia cells (THP-1) and in human glioma cells (A-172). NF-kappaB is essential to the expression of the kappa light chain of immunoglobulin and proinflammatory cytokines. Electrophoretic mobility shift assays (EMSA) of nuclear extracts demonstrated that VPA inhibits NF-kappaB activation induced by lipopolysaccharide (LPS), but the other AEDs do not. Western blot analysis revealed that this inhibition is not linked to preservation of expression of IkappaBalpha protein. Chloramphenicol acetyltransferase (CAT) assay indicated that NF-kappaB-dependent reporter gene expression is suppressed in glioma cells pretreated with VPA. VPA significantly inhibited LPS-induced production of TNF-alpha and IL-6 by THP-1 cells, whereas other AEDs did not. The findings are consistent with the idea that VPA suppresses TNF-alpha and IL-6 production via inhibition of NF-kappaB activation. Our results suggest that VPA can modulate immune responses in vitro. These findings raise the possibility that such modulation might occur with clinical use of VPA.

Anticonvulsants↗

Determination of a sulfur-containing drug in human plasma by an improved method for sulfur chemiluminescence detection in combination with capillary gas chromatography.

An improved method for sulfur chemiluminescence detection in combination with capillary gas chromatography was established. The method was applied to the analysis of a sulfur-containing antiasthma drug, S-1452, and its nine metabolities in human plasma. The high selectivity and sensitivity of the method allowed accurate quantitation of trace levels of these compounds in human plasma with no interferences from the biological components present. To enable stable measurements and maintain reproducibility over a long period, the performance characteristics of a commercially available instrument were investigated. The gas seal in the injection port was found to easily corrode through interaction of the sulfur analyte with the metal gas seal. To prevent this, a disk made from an alloy of platinum and gold (60:40) was mounted on the gas seal. The reproducibility of the measurement was improved remarkably by using the disk. The use of compressed air of high purity significantly lowered the signal-to-noise ratio. The optical filter was kept clean by using a nickel catalyst to trap ozone in place of copper manganese oxide (CuMn2O4). These improvements raised the sensitivity and selectivity with the lower quantitation limits of 0.5-1.0 ng/mL in human plasma.

Air↗

The development of an elevated lesion associated with colitis cystica profunda in the transverse colonic mucosa during the course of ulcerative colitis: report of a case.

We report the case of a 53-year-old man with a long history of ulcerative colitis in whom an elevated lesion in the epithelium of the affected transverse colon was initially diagnosed as a benign inflammatory polyp by endoscopic biopsies. After 4 years of follow-up, because the tumor had enlarged and villous components were endoscopically observed on the surface, a colonic resection was performed. The tumor was found to consist of hyperplastic colonic epithelium associated with multiple mucinous cysts lined with dysplastic colonic epithelial cells. Moreover, the mucinous cysts were primarily located beneath the submucosal layer and appeared to intrude into the muscularis propria of the colonic wall. This lesion had a unique pathological feature, presumably indicating neither benign inflammatory epithelium nor a neoplastic lesion of the colonic epithelium. Mucinous cysts lined with colonic epithelial components in the muscularis propria suggest a loss of normal integrity of the colonic wall. Areas of the epithelial cell lining of the mucinous cysts showed apparent structural and nuclear atypia and positive expression for p53, suggesting that this portion of the specimen was dysplastic epithelium. These pathological findings may indicate one longitudinal aspect of tumor development which could provide evidence of premalignant change or initial pathological features during the long-standing course of ulcerative colitis.

Colitis↗

Hyperplastic polyp of the gallbladder in a child.

We report a case of hyperplastic polyp of the gallbladder in a 6-year-old girl, successfully treated by laparoscopic cholecyctectomy after a 2-year follow-up from the original diagnosis. On her first admission, serum amylase level was very high, so that congenital pancreaticobiliary maljunction (PBM) was suspected. Although it became clear afterwards that the high serum amylase level was derived from a mumps infection, the diagnosis of PBM was not excluded until intraoperative cholangiography was conducted. The tumor in the gallbladder had doubled in size in 2 years. It was not possible to obtain biopsy specimens for histological diagnosis, so the risk of the tumor being malignant could not be completely excluded until surgical resection had been carried out. In spite of the rapid tumor growth, no neoplastic features were seen in the tumor by histopathological examination of the resected specimen; thus, a diagnosis of a hyperplastic polyp of the gallbladder was made.

Child↗

Hepatic parenchymal transection using ultrasonic coagulating shears: a preliminary report.

Ultrasonically activated coagulating shears (CS) can coagulate and divide blood vessels of up to medium size by a tissue-welding technique. We present an application of CS in hepatic parenchymal transection during liver surgery. Intrahepatic vessels are uncovered by the so-called forceps fracture method, and they are coagulated and divided by CS. Larger vessels are tied only on the preserving side before the application of CS. Although further refinement of the CS tip is needed, this method has the potential to significantly simplify and improve surgical procedures for hepatic parenchymal transection.

Adult↗

Submucosal dermoid cyst of the rectum: report of a case.

Despite the relatively common incidence of sacrococcygeal dermoids, rectal cysts are uncommon. We report the case of a submucosal dermoid cyst occurring in the rectum. A 30-year-old woman visited the Gynecology Department because of pregnancy. A pelvic tumor was accidentally found during the checkup after miscarriage. A barium enema showed an anterior shift of the rectum by the presence of the tumor. Computed tomography and magnetic resonance imaging revealed a tumor located posterior to the rectum occupying almost the entire pelvic cavity, and the tumor was resected. The tumor was located in the submucosal layer of the posterior rectal wall and was well circumscribed. The resected tumor was a cyst entirely covered with a fibrous and firm capsule, which was filled with an amorphous white creamy substance. The histological findings showed the cyst consisting of a keratinizing stratified squamous epithelium with sebaceous gland and hair follicles, which was compatible with benign cystic teratoma. Primary rectal teratoma is very rare and only 36 cases have been reported in the literature worldwide. Furthermore, while the majority of cases were polypoid-shaped dermoid cysts protruding into the rectal lumen, only 3 cases were submucosal dermoid cysts. Therefore, such cases are considered to be extremely rare.

Adult↗

Metastasis to the forearm skeletal muscle from an adenocarcinoma of the colon: report of a case.

While the liver and lung are primary targets for distant metastasis from colorectal carcinoma, metastasis in other distant sites is rarely found. We report herein an unusual case of metastasis to the skeletal muscle of the right forearm from an adenocarcinoma of the transverse colon. A 60-year-old man was originally admitted to our hospital for surgical treatment of an intestinal obstruction caused by a transverse colon carcinoma. Transverse colon resection along with lymph node dissection was performed and no evidence of distant metastatic foci was found. Angiography-enhanced computed tomography scanning done 14 months after the first operation revealed multiple hepatic metastases which were resected. A metastasis was subsequently detected in the right extensor carpi ulnaris muscle 2 years after the primary resection, and a major part of the right extensor carpi ulnaris and the extensor digiti minimi muscle were resected, warranting a sufficient margin of 5 cm of normal tissue from the tumor. Reattachment of the residual muscles into the ulna was performed. Metastases to bone and/or soft tissues from colorectal carcinomas are extremely rare and to our knowledge, only eight other cases have been reported in the world literature. This low incidence may be related to the anatomical characteristics and/or the biochemical environment of the skeletal muscle, but it is also possible that the true incidence is underestimated. Recent improvements in interventional radiological procedures may facilitate a diagnosis of skeletal muscle metastasis being made more frequently.

Adenocarcinoma↗

Negative NO3- difference in human coronary circulation with severe atherosclerotic stenosis.

To examine whether or not the levels of NOx (nitrite; NO2- and nitrate; NO3-) in coronary circulating blood reflect endothelial dysfunction due to coronary atherosclerosis, NOx levels in plasma obtained from ostium of left coronary artery and coronary sinus of patients who complained of chest pain were evaluated in relation to their coronary angiographic findings. Prior to the study, a HPLC-Griess system for NOx measurement was critically evaluated. This system has a detection limit of 0.1 microM of NO2- and NO3- by 10 microl of loading and was able to distinguish a difference of 0.1-0.2 microM of these substances. Heparin (1 U/10 microl) did not affect the detective and discriminative abilities. NO3- difference, calculated from sino-arterial difference of NO3-, was almost zero (-0.2 +/- 0.2 microM) in patients with either normal coronary arteries or mild organic coronary stenosis (< or = 20% narrowing), while a significant negative value (-5.9 +/- 1.7 microM) was obtained from patients with significant stenosis (> or = 70% narrowing) in the left coronary arteries. These results demonstrate reliable ability on the HPLC-Griess system in evaluating NO2- and NO3- in biological samples, and that the negative NO3- difference through coronary circulation may reflect endothelial dysfunction in the patients with coronary atherosclerosis with severe organic stenosis.

Chromatography, High Pressure Liquid↗

Multiple molecular forms of glucagon and insulin in the kaluga sturgeon, Huso dauricus.

Five molecular forms of glucagon and two molecular forms of insulin were characterized from the kaluga sturgeon. Substitutions occurred at two to thirteen internal amino acid residues among the five molecular forms of glucagons, indicating that these glucagons were encoded by five distinct genes. The amino acid sequences of two insulins from the kaluga sturgeon were identical to those of paddlefish insulin-II and Russian sturgeon insulin except that kaluga sturgeon insulin-I had an extension of five residues at the B-chain N-terminus. This is the first demonstration that more than two molecular forms of glucagon have been characterized from a single animal species.

Amino Acid Sequence↗

Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease.

OBJECTIVES: This study focused on 1) the determination of the optimal preconditioning (PC) duration, and 2) the protective effect of nicorandil (NC), a hybrid nitrate with a KATP channel opening effect, during a percutaneous transluminal coronary angioplasty (PTCA) model in humans. BACKGROUND: The ischemic PC effect is induced in 180 s ischemia, but not in 120 s ischemia in rabbit hearts. However, the duration of ischemia that induces PC effect and the role of the KATP channel in the PC effect in humans are still unclear. METHODS: Forty-six patients with stable angina were randomly allocated to four groups: the duration of the first inflation as PC ischemia was 60 s in the PC60 group (n = 12), and 180 s in the PC180 group (n = 12). In the other groups, NC (80 microg/kg) was intravenously given for 1 min in the NC group (n = 12), and isosorbide dinitrate (ISDN) (40 microg/kg) was given in the ISDN group (n = 10). Five minutes after first inflation or drug administration, a second inflation was conducted for 120 s in each group. In the ECG, the lead with the largest shift in ST segment (deltaST max), and the sum of elevated ST levels in all leads (sigmaST) were determined. RESULTS: In the PC60 group, no significant difference was observed in either deltaST max or sigmaST between the first and second inflation. However, the second inflation in the PC180 group showed significantly lower levels of deltaST max and sigmaST compared with those of the first inflation. In the NC group, both deltaST max and sigmaST measured at 30 s and 60 s after balloon inflation were significantly lower than those of the first inflation in the PC60 and PC180 control groups. In the ISDN group, no significant difference was observed in deltaST max or sigmaST. CONCLUSION: In human PTCA models, a PC effect is observed in 180 s ischemia, but not in 60 s ischemia. A pharmacological PC effect is induced by NC, a KATP channel opener with a nitrate-like effect but not ISDN. This suggests that the opening of KATP channels plays an important role in the protecting effect of NC.

Angina Pectoris↗

Insulin modulation of intracellular free magnesium in heart: involvement of protein kinase C.

In the present study of rat heart using (31)P-nuclear magnetic resonance, we examined the interaction between beta-adrenergic and insulin receptors in terms of the intracellular free Mg(2+) concentration ([Mg(2+)](i)) regulation. [Mg(2+)](i) was estimated from the separation of the chemical shifts of the alpha- and beta-adenosine triphosphate (ATP) peaks, using the dissociation constant of MgATP 87 microM (established recently). In normal (phosphate-free Krebs-Henseleit) solution, [Mg(2+)](i) was approximately 1.02 mM. Insulin at physiological and pathological concentrations increased [Mg(2+)](i) and contractility in a dose-dependent manner. Insulin (more than 100 micro(u) ml(-1)) suppressed the decrease in [Mg(2+)](i) caused by isoprenaline (100 nM), and these effects of insulin on [Mg(2+)](i) and contractility were blocked by LY333531 (macrocyclic bis (indolyl) maleimide, 100 nM), a protein kinase C (PKC) inhibitor. The isoprenaline-induced decrease in the concentrations of ATP ([ATP]) with insulin application was significantly smaller than that without insulin. Insulin modulates [Mg(2+)](i) and haemodynamics, presumably via activation of PKC, thereby antagonizing the reduction of [Mg(2+)](i) induced by beta-adrenoceptor stimulation.

Adenosine Triphosphate↗

CD14+CD16+ monocyte subpopulation in Kawasaki disease.

Kawasaki disease (KD) is an acute febrile illness caused by vasculitis, occurring in early childhood. We have demonstrated that the activation of monocytes/macrophages plays a central role during acute KD. Recently, it has been reported that the CD14+CD16+ monocyte subpopulation plays a more important role in inflammation. In this study, we investigated the peripheral blood CD14+CD16+ monocyte subpopulation by flow cytometry, and serum levels of IL-10 and IL-12 using a sandwich ELISA in 28 KD patients. We also investigated this subpopulation in patients with bacterial infections, mononucleosis and anaphylactoid purpura, since the cause of KD remains unknown. We observed an increase in the number of CD14+CD16+ monocytes with acute KD, which was a positive correlation with C-reactive protein levels, and we observed only the patients with severe bacterial infections had increased this subpopulation during the acute stage among control diseases. In addition, we found that the serum levels of IL-10, but not IL-12, were higher during acute KD. These data suggest that increased peripheral blood CD14+CD16+ monocytes are part of the regulatory system of monocyte function during acute KD.

Acute Disease↗

Angiomyomatous hamartoma and associated stromal lesions in the right inguinal lymph node: a case report.

Angiomyomatous hamartoma is a rare disease with a predisposition for the inguinal lymph nodes. A 51-year-old male patient visited a local hospital because of a right inguinal mass, measuring 3 x 4 cm in size, which was resected. The resected specimen showed irregularly distributed thick-walled vessels in the hilum, extending into the medulla and focally into the cortex of the node, eventually becoming more dispersed and associated with smooth muscle cells splaying into sclerotic stroma. These findings are compatible with an angiomyomatous hamartoma. Another tumor-like mass appeared shortly after the resection at the same location, but was not an angiomyomatous hamartoma, rather it was composed of edematous stromal tissue with proliferating smooth muscle cells. The stromal component included thick-walled blood vessels and lymphatics. Although it could not be determined whether these associated changes in the surrounding stroma are a cause or an effect of angiomyomatous hamartoma, they indicate the clinical difficulty in determining an appropriate area of resection and may provide clues to the pathogenesis of angiomyomatous hamartoma.

Actins↗

Mononuclear cells and cytokines in the cerebrospinal fluid of echovirus 30 meningitis patients.

The local immune response to echovirus 30 meningitis in children was investigated in 2 ways: using flow cytometry to examine the mononuclear cell and lymphocyte subsets and enzyme-linked immunosorbent assays to examine the cerebrospinal fluid (CSF) levels of cytokines, including monocyte chemoattractant protein-1 (MCP-1), interferon gamma (IFN-gamma) and interleukin-12 (IL-12). The numbers of macrophages in the CSF were increased, in particular during the early part of the acute stage. The levels of MCP-1, which is responsible for the accumulation of macrophages, as well as those of IFN-gamma and IL-12, which play important roles in the activation of macrophages and T helper (Th) 1 cells, respectively, were increased in the CSF of patients compared with the levels found in the controls. Likewise, numbers of activated CD4 + and CD8 + T lymphocytes were increased in the CSF. Since the ratio of CD4/CD8 correlated with the age of the patients, CD8 + T lymphocytes in the CSF might play a more important role in younger children.

Cerebrospinal Fluid↗

Different expression of ICAM-1 and LFA-1 alpha by peripheral leukocytes during respiratory syncytial virus and influenza virus infection in young children.

We compared the expression of intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 alpha (alpha) on the surfaces of peripheral immunocompetent cells of young children infected with respiratory syncytial virus (RSV) and influenza virus. Flow cytometric analysis revealed a significantly higher percentage of CD14 + monocytes/macrophages that were strongly ICAM-1-positive in the influenza group than in age-matched controls, whereas the ICAM-1 expression levels of the RSV and control groups did not differ significantly. Analysis of LFA-1alpha expression by CD3 + T lymphocytes showed a significantly higher percentage of strongly positive cells in the influenza group than in the age-matched controls. By contrast, the percentage of cells that were strongly LFA-1alpha-positive was significantly lower in the RSV group than in the age-matched controls. These results suggest that no increase of adhesion molecule expression occurs in vivo in patients with RSV infection, and also that there is little activation of peripheral blood monocytes/macrophages and T lymphocytes in young children with RSV infection.

CD3 Complex↗