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Biomedical subjects

S Matsumura

Publications and source records attributed to S Matsumura.

At least 19 recordsLinked to original sources

Increase in transforming growth factor-beta in the brain during infection is related to fever, not depression of spontaneous motor activity.

When viral infection occurs, this information is transmitted to the brain, and symptoms such as fever and tiredness are induced. One of the causes of these symptoms is the secretion of proinflammatory cytokines in blood and the brain. In this study, the i.p. administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA, to rats was used as an infection model. Poly I:C decreased spontaneous motor activity (SMA) 2 h after i.p. administration, and this decrease was maintained thereafter. The concentration of active transforming growth factor-beta (TGF-beta) in cerebrospinal fluid (CSF) increased 1 h after the administration. This increase occurred earlier than those in the concentrations of other proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), in serum. The intracisternal administration of an anti-TGF-beta antibody partially inhibited fever induced by poly I:C administration; however, this treatment did not affect the decrease in SMA. Furthermore, intracisternal administration of TGF-beta raised the body temperature. These results indicate that TGF-beta in the brain, which was increased by poly I:C administration, is associated with fever but not with a decrease in SMA.

Animals↗

Involvement of Rho-kinase in inflammatory and neuropathic pain through phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS).

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major in vivo substrate for protein kinase C in the brain and has been implicated in cellular processes associated with cytoskeletal restructuring such as synaptic trafficking and neurotransmitter release. A phosphorylation-site specific antibody against Ser159-phospho-MARCKS (pS159-Mar-Ab) revealed that MARCKS is phosphorylated at Ser159 by Rho-kinase and that its phosphorylation is inhibited by the Rho-kinase specific inhibitor H-1152. Since the function of MARCKS is regulated by phosphorylation at multiple sites, here we examined the involvement of Rho-kinase in relation to phosphorylation of MARCKS at Ser159 in inflammatory and neuropathic pain by H-1152. When intrathecally administered 10 min before s.c. injection of formalin, H-1152 at 10 and 100 ng attenuated the second-phase, but not the first-phase, pain-like behaviors in the formalin test. Neuropathic pain induced by selective L5 spinal nerve transection was also relieved by intrathecal injection of H-1152. Nitric oxide synthase activity visualized by NADPH diaphorase histochemistry increased in the superficial layer of the spinal cord 30 min after formalin injection and 7 days after nerve transection, which were blocked by H-1152. Phosphorylation of MARCKS at Ser159 was detected in the spinal cord by pS159-Mar-Ab and the level of phosphorylation increased in the superficial layer after nerve transection. In contrast, immunoreactivities of neuronal nitric oxide synthase and MARCKS did not change significantly in the spinal cord before and after nerve transection. Taken together, the present study demonstrates that Rho-kinase is involved in inflammatory pain and the maintenance of neuropathic pain through phosphorylation of MARCKS at Ser159.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[001] zone-axis bright-field diffraction contrast from coherent Ge(Si) islands on Si(001).

Coherent Ge(Si)/Si(001) quantum dot islands grown by solid source molecular beam epitaxy at a growth temperature of 700 degrees C were investigated using transmission electron microscopy working at 300kV. The [001] zone-axis bright-field diffraction contrast images of the islands show strong periodicity with the change of the TEM sample substrate thickness and the period is equal to the effective extinction distance of the transmitted beam. Simulated images based on finite element models of the displacement field and using multi-beam dynamical diffraction theory show a high degree of agreement. Studies for a range of electron energies show the power of the technique for investigating composition segregation in quantum dot islands.

Journal Article↗

High levels of genetic diversity in island populations of the island endemic Suzukia luchuensis (Labiatae).

Genetic diversity and genetic differentiation within and among island populations was examined by allozyme electrophoresis in Suzukia luchuensis (Labiatae), which is endemic to four of the Ryukyu Islands, southern Japan, and one island near Taiwan. Intrapopulation allozyme diversity was very low in all the four Ryukyu Islands, probably due to the effects of random drift in small populations. In contrast, genetic diversity at the species level was high, possibly because of an ancient origin of populations and/or multiple colonization of the species on different islands. Genetic differentiation among the overall populations was high (G(ST)=0.863), while gene flow (Nm) as estimated from allozyme frequency data was 0.041, suggesting that its occurrence among populations is highly restricted. Hierarchical analysis of genetic differentiation indicated that a high proportion of the total allelic variance is attributed to variation among islands, corresponding to the fact that several alleles were fixed on only one island. However, intraisland genetic differentiation was small on all islands except Yonaguni Island, where S. luchuensis is relatively widely distributed. Most diversity was thus due to differences among islands.

Gene Frequency↗

Preoperative assessment of gastric cancer vascularity by flash echo imaging.

BACKGROUND: Tumor vascularity as indicated by immunohistochemical staining is a significant prognostic factor in gastric and other cancers. Non-invasive preoperative assessment of the vascularity of gastric cancers has not been possible. We aim to determine the reliability of harmonic flash echo imaging (FEI) for assessment of vascularity of gastric cancers by comparison with CD34 staining of resected specimens. METHODS: Twelve patients undergoing surgical resection of advanced gastric cancer were studied. An ultrasound system transmitting ultrasound pulses at 2.3 MHz and receiving them at 4.6 MHz (second harmonic image) was used for harmonic FEI. Approximately 30 s after intravenous injection of ultrasonic contrast medium (SHU 508A, Levovist), second harmonics (4.6 MHz) emitted from microbubbles were obtained to enhance the B-mode images. Using the tumor image showing strongest enhancement in each FEI series, regions of interest were determined to measure mean echo intensity in the tumor. Immunohistochemistry using antibodies against CD34 was carried out in resected specimens. Tumor vascularity was determined by counting stained microvessels. RESULTS: A significant positive correlation was noted between sonographic amplitude determined preoperatively by FEI analysis and number of CD34-stained microvessels in tumor specimens (r = 0.869, P = 0.004). CONCLUSION: Vascularity of gastric cancers now can be evaluated non-invasively by harmonic FEI.

Antigens, CD34↗

Ocular angiostrongyliasis without meningitis symptoms in Okinawa, Japan.

A 62-year-old female farmer presented with retinal detachment in her left eye, and an Angiostrongylus cantonensis worm was recovered by vitreous surgery. The case did not show typical clinical symptoms indicating meningitis, although the patient complained of a mild headache, a low-grade fever, and slight ataxia. The symptoms were treated as influenza before the onset of the retinal detachment. The present case is the first confirmed of ocular angiostrongyliasis in Japan.

Angiostrongylus cantonensis↗

Characterization of the glutamatergic system for induction and maintenance of allodynia.

Glutamate is the main excitatory neurotransmitter in the central nervous system and has been shown to be involved in spinal nociceptive processing. We previously demonstrated that intrathecal (i.t.) administration of prostaglandin (PG) E(2) and PGF(2 alpha) induced touch-evoked pain (allodynia) through the glutamatergic system by different mechanisms. In the present study, we characterized glutamate receptor subtypes and glutamate transporters involved in induction and maintenance of PGE(2)- and PGF(2 alpha)-evoked allodynia. In addition to PGE(2) and PGF(2 alpha), N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), but not kainate, induced allodynia. PGE(2)- and NMDA-induced allodynia were observed in NMDA receptor epsilon 4 (NR2D) subunit knockout (GluR epsilon 4(-/-)) mice, but not in epsilon 1 (NR2A) subunit knockout (GluR epsilon 1(-/-)) mice. Conversely, PGF(2 alpha)- and AMPA-induced allodynia were observed in GluR epsilon 1(-/-) mice, but not in GluR epsilon 4(-/-) mice. The induction of allodynia by PGE(2) and NMDA was abolished by the NMDA receptor epsilon 2 (NR2B) antagonist CP-101,606 and neonatal capsaicin treatment. PGF(2 alpha)- and AMPA-induced allodynia were not affected by CP-101,606 and by neonatal capsaicin treatment. On the other hand, the glutamate transporter blocker DL-threo-beta-benzyloxyaspartate (DL-TBOA) blocked all the allodynia induced by PGE(2), PGF(2 alpha), NMDA, and AMPA. These results demonstrate that there are two pathways for induction of allodynia mediated by the glutamatergic system and suggest that the glutamate transporter is essential for the induction and maintenance of allodynia.

ATP-Binding Cassette Transporters↗

The first total synthesis of concanamycin f (concanolide a).

A highly stereoselective total synthesis of the macrolide antibiotic concanamycin F (1), a specific and potent inhibitor of vacuolar H(+)-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 18-membered tetraenic lactone and beta-hydroxyl hemiacetal side chain subunits. The C1-C19 18-membered lactone aldehyde 4 was synthesized through the intermolecular Stille coupling of the C5-C13 vinyl iodide 24 and the C14-C19 vinyl stannane 25, followed by construction of the C1-C4 diene and macrolactonization. Synthesis of 4 via a second convergent route including the esterification of the C1-C13 vinyl iodide 45 and the C14-C19 vinyl stannane 47 followed by the intramolecular Stille coupling was also realized. The highly stereoselective aldol coupling of 4 and the C20-C28 ethyl ketone 5 followed by desilylation provided 1 which was identical with natural concanamycin F.

Anti-Bacterial Agents↗

Involvement of catalytic amino acid residues in enzyme-catalyzed polymerization for the synthesis of polyesters.

Recently, a variety of aliphatic polyesters have been synthesized using hydrolases such as lipases and PHB depolymerases, and the reaction mechanism for these enzyme-catalyzed polymerization has been discussed. In this paper, we have studied the involvement of the catalytic amino acid residues of the hydrolase in enzyme-catalyzed polymerization with an extracellular PHB depolymerase from Alcaligenes faecalis T1. A wild-type PHB depolymerase and three kinds of site-specific mutants (catalytic amino acids were substituted) were prepared and their polymerization activities for the ring-opening polymerization of (R)-beta-butyrolactone (BL) were compared. BL was polymerized at 80 degrees C in bulk by the wild-type enzyme to yield polymers consisting of cyclic and linear structures in a high monomer conversion. In contrast, none of the mutant enzymes showed obvious polymerization activity. These results have clearly demonstrated that the catalytic triad is indeed responsible for the enzyme-catalyzed polymerization of BL.

4-Butyrolactone↗

T cell repertoire in primary biliary cirrhosis: a common T cell clone and repertoire change after treatment.

T cell repertoire was analyzed in three early-stage primary biliary cirrhosis (PBC) patients, using reverse transcription-polymerase chain reaction and single-strand conformation polymorphism. Multiple expanded clones were demonstrated in livers and peripheral blood lymphocytes (PBL) of all three patients. Comparison of the repertoire of different parts of the liver demonstrated the presence of common clones in various Vbeta families. Comparison of the repertoire between the liver and PBL demonstrated that both CD4 and CD8 T cell clones were expanded. Sequence analysis of complementarity determining region 3 of the expanded clones revealed that relatively conserved amino acids were utilized in each patient and that an identical CD4 T cell clone having Vbeta16 was present in all three patients. The number of expanded T cell clones in PBL decreased markedly after the treatment with prednisolone. These results suggest that common T cell clones may play a pathogenic role in PBC.

Anti-Inflammatory Agents↗

Aberrant expression of cytokeratin 7 as a histological marker of progression in primary biliary cirrhosis.

AIM: We evaluated the aberrant expression of cytokeratin 7 (CK-7) in hepatocytes as a marker of cholestasis and progression in primary biliary cirrhosis (PBC). PATIENTS AND METHODS: The expression of CK-7 was studied by immunohistochemistry in 83 cases of PBC. This expression was compared with biochemical data, the deposition of copper-associated protein, and previous histological classifications. RESULTS: In normal liver, CK-7 was expressed exclusively in bile duct epithelial cells (BDE). In PBC, the expression was also observed in hepatocytes. The expression pattern was classified as follows: Grade 0, BDE as in normal; Grade 1, proliferated bile ductules; Grade 2, periportal hepatocytes in addition to proliferated bile ductules; Grade 3, intralobular hepatocytes; Grade 4, the majority of hepatocytes. The grades correlated with serum bilirubin levels but not with serum levels of biliary enzymes. A discrepancy between the CK-7 grading and Ludwig's classification was noted in cases with Stage 1 of the CK-7 grading who were considered Stage 2 or 3 in Ludwig's classification, suggesting that cholestasis and inflammatory activity might be independent events. CONCLUSIONS: These results suggest that the aberrant expression of CK-7 in hepatocytes may be a marker of chronic cholestasis and progression in PBC.

Alkaline Phosphatase↗

High frequency of circulating HBcAg-specific CD8 T cells in hepatitis B infection: a flow cytometric analysis.

Viral antigen-specific T cells are important for virus elimination. We studied the hepatitis B virus (HBV)-specific T cell response using flow cytometry. Three phases of HBV infection were studied: Group A, HBeAg (+) chronic hepatitis; Group B, HBeAb (+) HBV carrier after seroconversion; and Group C, HBsAb (+) phase. Peripheral T cells were incubated with recombinant HB core antigen (HBcAg), and intracytoplasmic cytokines were analysed by flow cytometry. HBcAg-specific CD4 and CD8 T cells were identified in all three groups and the number of IFN-gamma-positive T cells was greater than TNF-alpha-positive T cells. The frequency of IFN-gamma-positive CD4 and CD8 T cells was highest in Group C, compared with Groups A and B. No significant difference in the HBcAg-specific T cell response was observed between Group A and Group B. The HBcAg-specific CD8 T cell response was diminished by CD4 depletion, addition of antibody against human leucocyte antigen (HLA) class I, class II or CD40L. Cytokine-positive CD8 T cells without HBcAg stimulation were present at a high frequency (7 of 13 cases) in Group B, but were rare in other groups. HBcAg-specific T cells can be detected at high frequency by a sensitive flow cytometric analysis, and these cells are important for controlling HBV replication.

Adult↗

Influence of thoracic radiotherapy on exhaled nitric oxide levels in patients with lung cancer.

BACKGROUND: To determine the physiological role of exhaled nitric oxide (NO) in patients with lung cancer. METHODS: We investigated changes in exhaled NO levels in 29 patients undergoing thoracic radiation therapy with or without chemotherapy. The exhaled NO level was assessed using a chemiluminescence analyzer. RESULTS: The level of exhaled NO was higher in patients with lung cancer before treatment than in controls. With radiotherapy, the exhaled NO level decreased for patients undergoing 40 Gy irradiation and post-radiotherapy. However, five patients showed elevated levels of exhaled NO three times or more than that before radiotherapy. Three of these patients showed signs of radiation pneumonitis. However, none of the other patients showed signs of radiation pneumonitis (p = 0.002). CONCLUSION: Radiation therapy can lower exhaled levels of NO and the levels of exhaled NO may be a useful index for the early prediction of radiation pneumonitis.

Aged↗

Membrane lipid components associated with increased filterability of erythrocytes from long-distance runners.

Deformability of red blood cells and the lipid composition of their plasma membranes were studied in ten long-distance runners, in comparison with ten sedentary matched controls. Mean corpuscular volume and corpuscular hemoglobin concentration did not differ between these groups, while the hemoglobin concentration and hematocrit were lower in the former. Deformability was measured in terms of the erythrocyte suspension filterability through 5 microm microchannels, using an array flow analyzer, and was significantly elevated in athletes. Analysis of the membrane phospholipid composition of red blood cells revealed an increased ratio of phosphatidylcholine to phosphatidylethanolamine and a decreased ratio of cholesterol to total phospholipids in athletes. The length and saturation levels of fatty acid acyl chains were unchanged. Multiple regression analysis showed clearly that these alterations of membrane lipids correlate with increased deformability and thus favor circulation in the microvasculature in long-distance runners.

Adult↗

A therapeutic approach to roentgenographically occult squamous cell carcinoma of the lung.

BACKGROUND: The significance of limited resections, including wedge resection and segmentectomy, remains controversial because of their curability rates. In the current study, the objective was to determine a strategy for the treatment of patients with roentgenographically occult bronchogenic squamous cell carcinoma (ROSCC) based on the pathologic findings from 184 patients with ROSCC who underwent resection. METHODS: In Miyagi Prefecture, 1422 patients with lung carcinoma were diagnosed during a mass screening program between 1982 and 1995. Among them, 236 patients had ROSCC, and 184 patients with ROSCC underwent pulmonary resection followed by systemic lymph node dissection. RESULTS: Pathologically, only 0.9% of the ROSCCs that were within the range of endoscopic visibility were revealed to have lymph node involvement, whereas 13% of patients with extracartilage invasion had lymph node involvement. Early ROSCC, which means ROSCC that is limited within the cartilaginous layer and is without lymph node involvement, comprised 90% of ROSCCs that measured <10 mm in longitudinal extension, comprised 77% of ROSCCs that measured 10-29 mm in longitudinal extension, and comprised 33% of ROSCCs that measured >30 mm in longitudinal extension. Eighty-nine percent of the tumors with lymph node involvement had extracartilaginous invasion. The 3-year survival rate of patients after undergoing photodynamic therapy was 100% when their tumor was regarded as early ROSCC (i.e., within 10 mm in longitudinal extension and within the range of endoscopic visibility). To date, 18 patients with ROSCC underwent segmentectomy, and all of these patients are alive without tumor recurrence. The incidence rate of multiple lung carcinomas, including synchronous and metachronous tumors, in patients with ROSCC was 22%. CONCLUSIONS: The authors concluded the following: 1) Patients with lesions that are within the range of endoscopic visibility and that measure <10 mm in longitudinal extension are candidates for photodynamic therapy. 2) Patients with lesions that are beyond the range of endoscopic visibility or that measure >10 mm in longitudinal extension are candidates for segmentectomy as long as intraoperative examination shows a tumor free bronchial stump and negative lymph nodes 11-13. 3) Patients with lesions that show bronchial obstruction or extrabronchial invasion should undergo standard resection.

Carcinoma, Squamous Cell↗

An autopsy case of Klinefelter's syndrome suspected and its DNA analysis.

UNLABELLED: We experienced an autopsy case, small testes and tall stature, which suggested Klinefelter's syndrome. DNA analysis was performed to confirm the genetic abnormality. CASE HISTORY: A 28-year-old man who was single and lived with his parents. He suddenly lost his consciousness in a sitting room and died. Autopsy findings: He was 176 cm in height and 57 kg in weight. The post-mortem hypostasis was red-purple on his back, and rigor mortis was strong in each joint of the whole body. The heart weighted 340 g, in which dark red fluidal blood (300 ml) without coagulation was contained. The testes were smaller than normal adult male (left and right testes with epididymides weighted 8.1 g and 6.0 g, respectively). As a results of pathological examination, clumped Leydig cells, sclerotic and hyalined tubules were observed. Some germ cells with spermatozoid were also present. DNA Analysis: Generally, Klinefelter's syndrome is determined by karyotype analysis and/or the detection of sex chromatin. However, in this case, karyotype analysis and the detection of sex chromatin could not be demonstrated, because the blood which was collected in the autopsy became too old. Therefore, we tried sex determination and STR analysis (HPRT, HUMARA and DXS 1470) using DNA extracted from stored blood materials. Consequently, in the sex determination, no different situation was found in the X- and Y-specific bands from normal male's and as results of STR analyses, we could not corroborate the Klinefelter's syndrome.

Adult↗