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Biomedical subjects

S Matsuo

Publications and source records attributed to S Matsuo.

At least 19 recordsLinked to original sources
PubMed2003

High frequency of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive Clostridium difficile in a hospital in Japan and risk factors for infection.

Patients hospitalized in a hospital with a high incidence of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive (A-/B+) Clostridium difficile were retrospectively investigated to determine the clinical manifestations and risk factors for infection. Of 77 Clostridium difficile isolates obtained from 77 patients during the 1-year investigation period, 30 were A-/B+ and 47 were toxin A-positive, toxin B-positive (A+/B+). By pulsed-field gel electrophoresis analysis, 23 of the 30 A-/B+ strains were outbreak-related, suggesting nosocomial spread of a single type of bacterium, which mainly affected patients in the wards of respiratory medicine, hematology and neurology. Using regression analysis, three factors were found to be associated with infection by A-/B+ isolates: (i) exposure to antineoplastic agents ( P=0.01, odds ratio [OR]=5.1), (ii) the use of nasal feeding tubes ( P=0.008, OR=5.2), and (iii) assignment to a certain internal medicine ward ( P=0.05, OR=3.0). Between patients with Clostridium difficile-associated diarrhea caused by A-/B+ strains and those with A+/B+ strains, no statistically significant difference was found in body temperature, serum concentration of C-reactive protein, leukocyte count in whole blood, frequency of diarrhea, or type of underlying disease. These results indicate that A-/B+ strains of Clostridium difficile can cause intestinal infection in humans and they spread nosocomially in the same manner as A+/B+ strains.

Adolescent↗
PubMed2001

Antisense oligodeoxynucleotide targeted to Midkine, a heparin-binding growth factor, suppresses tumorigenicity of mouse rectal carcinoma cells.

Midkine (MK), a heparin-binding growth factor, is overexpressed in a wide range of human carcinomas and is believed to contribute to tumorigenesis and tumor progression. To develop an antitumor reagent, we designed a phosphorothioate antisense oligodeoxynucleotide molecule based on the secondary structure of MK mRNA. The antisense MK at the dosage of 5 microM suppressed MK production by CMT-93 mouse rectal carcinoma cells after cationic liposome-mediated transfection, to 13% of that in control cultures. The growth of CMT-93 cells and their colony formation in soft agar were inhibited by the addition of the antisense MK, whereas the control reagent, the sense MK, showed no effects. On s.c. injection into nude mice, CMT-93 cells transfected with the antisense MK formed tumors much smaller than those by control cells. Finally, untreated CMT-93 cells were inoculated to nude mice, and 7 days later the antisense MK (50 microM) with atelocollagen was directly injected into the preformed tumor region to evaluate the curative effect; the injection was repeated at the interval of 2 weeks. During the period of 10-41 days after initiation of therapy, the rate of increase of tumor volume treated with the antisense MK was found to be about 4.2-fold lower than that seen after treatment with the sense MK. On this occasion, proliferation of tumor cells as estimated by 5-bromodeoxyuridine incorporation was strongly inhibited, whereas angiogenesis was less affected. These findings strongly suggested the usefulness of MK antisense oligodeoxynucleotide as a new reagent for cancer therapy.

Amino Acid Sequence↗
PubMed2001

Humanization and epitope mapping of neutralizing anti-human Fas ligand monoclonal antibodies: structural insights into Fas/Fas ligand interaction.

Fas ligand (L)/CD95L, a proapoptotic member of the TNF family, is a potential target for clinical intervention in various diseases. In the present study, we generated a humanized anti-human FasL mAb and characterized the epitopes of neutralizing mAbs by extensive alanine-scanning mutagenesis of human FasL. The predicted molecular model of FasL trimer revealed that the mAbs recognize largely overlapped conformational epitopes that are composed of two clusters, one around the outer tip-forming D-E loop and another near the top of FasL. Both of these sites on FasL are critically involved in the direct interaction with the corresponding receptor, Fas. These results suggest that the mAbs efficiently neutralize FasL cytotoxicity by masking both of these FasL/Fas contact sites.

Amino Acid Sequence↗
PubMed2001

Midkine is involved in neutrophil infiltration into the tubulointerstitium in ischemic renal injury.

Midkine (MK) is a multifunctional heparin-binding protein and promotes migration of neutrophils, macrophages, and neurons. In the normal mouse kidney, MK is expressed in the proximal tubules. After renal ischemic reperfusion injury, its expression in proximal tubules was increased. Immediate increase of MK expression was found when renal proximal tubular epithelial cells in culture were exposed to 5 mM H(2)O(2). Histologically defined tubulointerstitial damage was less severe in MK-deficient (Mdk(-/-)) than in wild-type (Mdk(+/+)) mice at 2 and 7 days after ischemic reperfusion injury. Within 2 days after ischemic injury, inflammatory leukocytes, of which neutrophils were the major population, were recruited to the tubulointerstitium. The numbers of infiltrating neutrophils and also macrophages were lower in Mdk(-/-) than in Mdk(+/+) mice. Induction of macrophage inflammatory protein-2 and macrophage chemotactic protein-1, chemokines for neutrophils and macrophages, respectively, were also suppressed in Mdk(-/-) mice. Furthermore, renal tubular epithelial cells in culture expressed macrophage inflammatory protein-2 in response to exogenous MK administration. These results suggested that MK enhances migration of inflammatory cells upon ischemic injury of the kidney directly and also through induction of chemokines, and contributes to the augmentation of ischemic tissue damage.

Animals↗
PubMed2001

Simultaneous measurement of anandamide and 2-arachidonoylglycerol by polymyxin B-selective adsorption and subsequent high-performance liquid chromatography analysis: increase in endogenous cannabinoids in the sera of patients with endotoxic shock.

Anandamide (ANA) and 2-arachidonoylglycerol (2-AG), two endogenous cannabinoids, can be generated by activated macrophages and platelets, respectively, in the context of endotoxic shock, and are proposed to play a crucial role in the induction of the shock-related hypotension. Taking advantage of our recently discovered function of polymyxin B (PMB) binding to ANA and 2-AG, we developed a new method for measuring ANA and 2-AG by applying PMB-immobilized beads to selectively adsorb them in biological fluids, instead of organic solvent extraction. The eluate from beads can be directly fractionated by reverse-phase high-performance liquid chromatography (HPLC), and the fractionations corresponding to authentic ANA and 2-AG are collected and derivatized with fluorogenic reagent and subsequently quantified by HPLC with fluorometric detection. The calibration graphs of ANA and 2-AG were linear over a range of 1 to 500 pmol/ml. The limits of detection for ANA and 2-AG were 20 and 50 fmol, respectively. Intraassay precision was 2.24-4.25 and 3.47-5.44%, and interassay was 4.05-6.14 and 4.92-7.28% for ANA and 2-AG, respectively. Using this method, we first determined a 4-fold and 3-fold higher level of ANA and 2-AG, respectively, in the sera of patients with endotoxic shock than in normal serum. This finding should help in elucidating the role of the endogenous cannabinoids in the hypotension of human endotoxic shock. This method is rapid, sensitive, and reliable for simultaneously quantifying ANA and 2-AG in biological fluids, and has potential for clinical usage.

Adsorption↗
PubMed2001

Isolation of novel heart-specific genes using the BodyMap database.

Two novel heart-specific genes, C3orf3 (chromosome 3 open reading frame 3) and MMGL (myomegalin-like), were isolated using BodyMap, a gene expression database based on site-directed 3' expressed sequence tags (3'-ESTs) which were collected from nonbiased cDNA libraries of various tissues. The cDNA of C3orf3 was 1667 bp and was composed of 12 exons within a 10-kb-long genomic sequence. MMGL consisted of 8 exons within a genomic sequence of over 70 kb, leading to four alternatively spliced transcripts. Both genes were strongly expressed in heart and also in skeletal muscle. C3orf3 and MMGL were mapped to 3p22 and 1q1, respectively. Subcellular localizations of their putative proteins were determined as being in the cytoplasm for C3orf3 and in the cytoplasm and nucleus for MMGL. This study showed that BodyMap is a useful database for the isolation of tissue-specific genes.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Developmental dependency of Merkel endings on trks in the palate.

Immunohistochemistry for protein gene product 9.5 was performed on Merkel cells in the palate of wildtype and knockout mice for trkA, trkB or trkC. In wildtype mice, numerous Merkel cells were observed at the top of anterior four rugae. In the posterior four rugae, Merkel cells were fewer and mostly located at the base of rugae. In knockout mice for trkA, trkB and trkC, Merkel cells at the top of rugae mostly disappeared although those at the base of rugae remained unchanged. Therefore, the number of Merkel cells in anterior four rugae decreased. In posterior four rugae, however, the number of Merkel cells in the mutant mice was similar to that for wildtype mice. Immunohistochemistry for S100 also demonstrated that the loss of genes for trkA, trkB and trkC caused the absence of the immunoreactive innervation of Merkel cells. The normal development of Merkel endings at the top of palatal rugae is probably dependent on trkA, trkB and trkC.

Animals↗
PubMed2001

Mechanism of specific nuclear transport of adriamycin: the mode of nuclear translocation of adriamycin-proteasome complex.

Adriamycin (ADM), an anthracycline anticancer agent, is selectively stored in the nuclei of a variety of proliferating cells, but the precise mechanism of specific nuclear transport of ADM is not well known. Recently, we demonstrated that ADM shows high binding affinity to the cytoplasmic proteasomes of L1210 mouse leukemia cells and that taken up ADM by the cells selectively binds to proteasomes. Nuclear targeting of proteasome in proliferating cells may be mediated by the nuclear localization signals that are found in several of the alpha-type subunits of the 20S proteasome. To confirm nuclear transport of the ADM-proteasome complex, we synthesized a photoactive ADM analogue, N-(p-azidohenzoyl)-ADM, and generated a photoaffinity-labeled proteasome complex. The 26S proteasome purified from the cytosol of L1210 cells had a high affinity to N-(p-azidobenzoyl)-ADM. SDS-PAGE analysis of the photoaffinity-labeled proteasome showed that low molecular weight bands (approximately 21-31 kDa) of 20S proteasome had the highest photoaffinity. The photoaffinity-labeled proteasome was distributed in the cytoplasm and nuclei of digitonin-permeabilized L1210 and B-16 mouse melanoma cells in the presence of the cytosolic fraction and ATP. The rate of nuclear translocation of the proteasome was low in the absence of ATP. These results suggest that the proteasome is a specific translocator of ADM from the cytoplasm to the nucleus and that 20S proteasome components are the dominant ADM-binding sites. The nuclear transport of ADM-proteasome complex is regulated by an ATP-dependent nuclear pore-mediated mechanism.

Active Transport, Cell Nucleus↗
PubMed2001

Membrane complement regulators protect against the development of type II collagen-induced arthritis in rats.

OBJECTIVE: To investigate changes in the distribution patterns of membrane complement regulators (MCRs) during the development of type II collagen-induced arthritis (CIA) and to examine the protective effects of these molecules against the augmentation of CIA in the knee joint. METHODS: Immunohistochemistry was used to examine the distribution of the MCRs Crry, DAF, and CD59 in the synovium of knee joints before and 2, 4, and 10 weeks after induction of CIA by immunization with type II collagen. In addition, at 2 or 10 weeks after induction of CIA, rats were injected intraarticularly with anti-Crry and/or anti-CD59 as the F(ab')2 fraction of monoclonal antibodies (mAb). Knee joint swelling and histologic changes in the synovium were examined 2 weeks after mAb injection. RESULTS: Synovial expression of Crry, DAF, and CD59 decreased in parallel with increased inflammation. When Crry and CD59 were functionally blocked at 2 weeks after the induction of CIA, swelling of the knee joints was markedly increased. Blocking of either regulator alone had no effect on swelling. Thickening of the synovial surface and proliferation of subsynovial tissue were all increased after blocking Crry and CD59, whereas blocking of either MCR alone had no effect. When both Crry and CD59 were blocked, deposits of membrane attack complex were found in the synovium. CONCLUSION: Our findings indicate that in rats with CIA and severely inflamed synovium, local expression of MCR is reduced. The MCRs Crry and CD59 appear to suppress the development of CIA.

Animals↗
PubMed2001

Detection of denervated but viable myocardium in cardiac sarcoidosis with I-123 MIBG and Tl-201 SPECT imaging.

A 58-year-old man, who had biopsy-proven cardiac sarcoidosis, underwent TI-201 and I-123 MIBG cardiac scintigraphy. Although no perfusion defect was identified by Tl-201, mild heterogeneity of I-123 MIBG uptake was present in the myocardium. The denervated but viable myocardium was demonstrated in the heart with sarcoidosis. Cardiac sympathetic nerve function was impaired in cardiac sarcoidosis, slightly improved with steroid therapy. I-123 MIBG scintigraphy may be useful to assess extent of myocardial involvement and response to therapy.

3-Iodobenzylguanidine↗
PubMed2001

Differences in intracellular sites of action of Adriamycin in neoplastic and normal differentiated cells.

PURPOSE: This study was performed to clarify the intracellular specificity of the differential cytotoxic effects of Adriamycin (ADM) on neoplastic and normal cells. METHODS: The mouse lymphocytic leukemia cell line L1210 and pig kidney proximal tubular epithelial cell line LLC-PK1 were used as neoplastic and normal cells, respectively. These cells were treated with various concentrations of ADM for 24 h and toxicological parameters were determined. RESULTS: ADM (0.1-10 microM) significantly down-regulated cell growth rate and [3H]thymidine incorporation into DNA in the log phase, and at concentrations of more than 1 microM reduced the viability of both cell lines. Lipid peroxidation was increased at 1 microM ADM in L1210 cells and at 10 microM ADM in LLC-PK1 cells. The microsomal and nuclear fractions of both cell lines showed approximately the same level of ADM-induced superoxide anion (O2-) production, while the mitochondrial fraction of differentiated LLC-PK1 cells produced the highest levels of O2-. Differentiated LLC-PK1 cells showed the highest mitochondrial NADH-cytochrome c reductase activity. L1210 cells showed lower mitochondrial activities of enzymes involved in scavenging of reactive oxygen species, such as superoxide dismutase, glutathione peroxidase and catalase, than the other cells. CONCLUSIONS: These results suggest that ADM exerts cytostatic effects on neoplastic and normal undifferentiated cells through the inhibition of DNA synthesis by DNA intercalation, and cytotoxic effects on neoplastic cells through the accumulation of reactive oxygen species resulting from low scavenger enzyme activities. The cytotoxic effects on normal differentiated cells may be related to the high levels of production of reactive oxygen species due to high mitochondrial NADH-cytochrome c reductase activity.

Animals↗
PubMed2001

Attenuated familial adenomatous polyposis associated with advanced rectal cancer in a 16-year-old boy: report of a case.

We herein present a case of attenuated familial adenomatous polyposis (AFAP) with advanced rectal cancer in a 16-year-old boy. His mother and younger brother both had subcutaneous soft tissue tumors in the back and sparse-type colorectal polyposis. His mother also had dental anomalies and gastric fundic gland polyposis. The patient was admitted to our hospital for investigation of bloody stools. Barium enema and colonofiberscopy revealed advanced rectal cancer and sparse (<50) colorectal polyps. He also had dental anomalies, a subcutaneous soft tissue tumor in the back, and gastric fundic gland polyposis as extracolonic manifestations. A total proctocolectomy and ileoanal anastomosis were performed, and histological examination of the resected specimens confirmed moderately differentiated adenocarcinomas of the rectum with metastases to the regional lymph nodes. The other colorectal polyps were tubular adenomas with no evidence of malignancy. Germline mutations in the APC gene were observed in codons 486, 545, 1493, and 1556. This case serves to demonstrate that a total proctocolectomy with ileoanal anastomosis should be the procedure of choice for young patients found to have advanced rectal cancer associated with FAP.

Adenocarcinoma↗
PubMed2001

Ruptured aneurysm of the visceral artery: report of two cases.

We present herein two cases of a ruptured aneurysm of the visceral artery. The first case involved a 74-year-old man with abdominal pain who was admitted to our hospital with a tentative diagnosis of intra-abdominal bleeding of unknown origin. Computed tomography revealed a hematoma in the greater curvature of the stomach. At surgery, a hematoma along the right gastroepiploic artery was found and totally removed. Histological examination showed a pseudo-aneurysm of unknown etiology. The second case involved a 68-year-old man with progressive anemia who presented with spontaneous intra-abdominal bleeding. A ruptured aneurysm of the accessory middle colic artery was diagnosed by superior mesenteric angiography. The ruptured aneurysm was ligated and totally resected without a colectomy. Histological examination showed a pseudoaneurysm of unknown etiology. The postoperative courses were uneventful, and both patients were doing well at the time of writing.

Abdomen, Acute↗
PubMed2001

trkA modulation of developing somatosensory neurons in oro-facial tissues: tooth pulp fibers are absent in trkA knockout mice.

To investigate the nerve growth factor requirement of developing oro-facial somatosensory afferents, we have studied the survival of sensory fibers subserving nociception, mechanoreception or proprioception in receptor tyrosine kinase (trkA) knockout mice using immunohistochemistry. trkA receptor null mutant mice lack nerve fibers in tooth pulp, including sympathetic fibers, and showed only sparse innervation of the periodontal ligament. Ruffini endings were formed definitively in the periodontal ligament of the trkA knockout mice, although calcitonin gene-related peptide- and substance P-immunoreactive fibers were reduced in number or had disappeared completely. trkA gene deletion had also no obvious effect on the formation of Meissner corpuscles in the palate. In the vibrissal follicle, however, some mechanoreceptive afferents were sensitive for trkA gene deletion, confirming a previous report [Fundin et al. (1997) Dev. Biol. 190, 94-116]. Moreover, calretinin-positive fibers innervating longitudinal lanceolate endings were completely lost in trkA knockout mice, as were the calretinin-containing parent cells in the trigeminal ganglion.These results indicate that trkA is indispensable for developing nociceptive neurons innervating oral tissues, but not for developing mechanoreceptive neurons innervating oral tissues (Ruffini endings and Meissner corpuscles), and that calretinin-containing, trkA dependent neurons in the trigeminal ganglion normally participate in mechanoreception through longitudinal lanceolate endings of the vibrissal follicle.

Animals↗
PubMed2001

Prognostic factors in hepatic metastases of colorectal carcinoma: immunohistochemical analysis of tumor biological factors.

The present study was designed to provide a systemic analysis of prognosis in 62 patients who underwent hepatic resection for colorectal liver metastasis. The analyzed factors included microvessel counts stained by CD34 and expression of two adhesion molecules, E-cadherin and CD44 variant exon 6-(v6) in these tumors. No significant factors related to recurrence were identified and only negative expression of CD44v6 tended to correlate with recurrence (P = 0.075). A short disease-free period to recurrence was noted in patients with high CEA levels (>10 ng/ml) and H2/3 classification. A short surgical margin, H2/3 classification, high microvessel counts (>60/field, x200), and negative expression of CD44v6 and E-cadherin tended to be associated with poor prognosis. A high microvessel count was the most significant prognostic factor by multivariate Cox proportional hazards regression model. Hepatic resection without tumor exposure and a careful follow-up in cases identified with poor prognostic factors are necessary.

Adult↗
PubMed2001

Syndecan-4 deficiency increases susceptibility to kappa-carrageenan-induced renal damage.

SUMMARY: The expression and roles of syndecan-4 in the kidney were investigated. Syndecan-4 expression was detected in the ureteric bud invaginating into the metanephric mesenchyme at 11.5 gestational days, and remained in the collecting ducts, distal renal tubules, glomeruli, and some capillaries between renal tubules until the mature kidney stage. However, organogenesis of the kidney was normal in syndecan-4-deficient (Synd4[-/-]) mice. Although most renal functions of Synd4(-/-) mice were not impaired, a significant increase in susceptibility to kappa-carrageenan-induced renal damage was observed in these mice. kappa-Carrageenan was heavily deposited in the collecting ducts of Synd4(-/-) mice and caused obstructive nephropathy, leading to death of 7 of 24 Synd4(-/-) mice within 7 days after administration, whereas none of 24 Synd4(+/+) mice died. After administration of kappa-carrageenan, blood urea nitrogen of Synd4(-/-) mice was significantly higher than that of Synd4(+/+) mice. Thus, syndecan-4 may function to prevent kappa-carrageenan deposition in the collecting ducts.

Animals↗