Biomedical subjects

S Matsuda

Publications and source records attributed to S Matsuda.

At least 91 records · Page 5Linked to original sources

PubMed2000

Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase.

A full-length cDNA encoding a novel protein was isolated and sequenced from a human hepatocellular cDNA library. This cDNA consists of 7037 base pairs and has a predicted open reading frame encoding 1924 amino acids. It possesses an RNA-helicase motif containing a DEXH-box in its amino-terminus and an RNase motif in the carboxy-terminus. From a striking homology to Caenorhabditis elegans K12H4.8, it might be a human homolog of the K12H4.8. PCR-based mapping with both a monochromosomal hybrid panel and radiation hybrid cell panels placed the gene to human chromosome 14q31 near the marker D14S605.

Amino Acid Sequence↗

PubMed2000

Clustered cysteine residues in the kinase domain of v-Src: critical role for protein stability, cell transformation and sensitivity to herbimycin A.

We have previously reported the activation of Src by mercuric chloride based on the sulfhydryl modification. To evaluate the significance of cysteine residues in v-Src, we replaced each cysteine to alanine by oligonucleotide-directed mutagenesis and examined its effect on cell transformation. Of ten cysteine residues scattered over v-Src, four cysteines clustered in kinase domain, Cys483, Cys487, Cys496 and Cys498, were important for protein stability and cell transformation, whereas those in SH2 domain were dispensable. A single mutation in Cys498 yielded suppression of kinase activity and a temperature-sensitivity in anchorage independent growth. Double mutation either in Cys483/Cys487 or in Cys496/Cys498 yielded clear temperature-sensitivity in cell transformation and in stability of Src protein. Instability of Src protein was magnified by quadruple mutation in the cysteines, which decreased the half-life of Src to be less than one quarter of that of wild-type. In addition, both Cys483/Cyr487 and Cys496/Cys498 kinases became resistant to in vitro inactivation by herbimycin A, which directly inactivates v-Src in addition to its effect on HSP90. Taken together, our results strongly suggest that the cysteine clustered motif of v-Src are critical for protein stability, cell transformation and in vitro inactivation by herbimycin A.

Amino Acid Sequence↗

PubMed2000

Synergistic effects of IL-4 and IL-18 on IL-12-dependent IFN-gamma production by dendritic cells.

Mouse splenic dendritic cells (DCs) produce IFN-gamma in response to IL-12. In the present study, we analyzed effects of Th1 and Th2 cytokines on IFN-gamma production by DCs. IL-18 produced by DCs and macrophages acts in an autocrine manner and augments IL-12-induced IFN-gamma production by DCs as also observed in T and NK cells. Surprisingly, IL-4, a Th2 cytokine, also acts synergistically with IL-12 on IFN-gamma production by DCs. In addition, IL-4 markedly enhances IFN-gamma production when DCs are stimulated through CD40 or MHC class II. These results indicate that both Th1 and Th2 cytokines act on DCs during T cell-DC interaction upon Ag presentation. p38 mitogen-activated protein kinase is constitutively activated in mature DCs and is required for IFN-gamma production by DCs. IL-18 but not IL-4 or IL-12 further activates the p38 mitogen-activated protein kinase activity, suggesting that IL-4 and IL-18 enhance IFN-gamma production through distinct intracellular signal transduction pathways in DCs.

Adjuvants, Immunologic↗

PubMed2000

Molecular cloning and characterization of human MAWD, a novel protein containing WD-40 repeats frequently overexpressed in breast cancer.

A full-length cDNA clone encoding a novel protein containing WD-40 repeats, which were frequently involved in protein-protein interactions, was isolated and sequenced. This clone had a predicted open reading frame (ORF) encoding 350 amino acids possessing six repeats of WD-40 motif. It was most closely homologous to TRIP-1, a phosphorylation substrate of the transforming growth factor-beta type II receptor. In the process of characterizing the function of the new gene product, we found that overexpression of the gene seemed to activate mitogen-activated protein kinase and to promote anchorage-independent growth of the cells. Moreover, the gene product was frequently overexpressed in human tumor breast tissues compared with their normal breast tissues, suggesting that the gene might be involved in the tumor progression. Radiation hybrid mapping placed the gene into human chromosome 12q11-12 near the marker D12S1593.

Amino Acid Sequence↗

PubMed2000

Synthetic absorbable film for prevention of air leaks after stapled pulmonary resection.

Staple-line reinforcement buttresses made of bovine pericardium (BP), expanded polytetrafluoroethylene (ePTFE), and so on have been shown to be effective in preventing air leaks after stapled lung volume reduction operations, and some of them have been clinically utilized. However, each buttress suffers at least one disadvantage such as risk of viral infection and chronic inflammation. A new buttress was made using a poly(L-lactic acid-co-epsilon-caprolactone) film (L/C film) and its effectiveness as a staple-line reinforcement was examined by performing lung volume reduction operation on a canine model. Soft tissue responses to the buttress were compared with those to the BP strip and the absorbable behavior was studied. The L/C film buttress was flexible and thin enough to easily cut. Death of dogs, infection, acute and prolonged air leaks, and any complications related to its use were not observed. The tissue responses to the film were more mild and favorable than those to BP. The L/C film was absorbed after the staple line was covered by a connective tissue. The results described above suggest that the buttress made of an L/C film is a promising staple-line reinforcement material.

Absorption↗

PubMed2000

ZAP-70 is required for calcium mobilization but is dispensable for mitogen-activated protein kinase (MAPK) superfamily activation induced via CD2 in human T cells.

Stimulation with specific pairs of anti-CD2 antibodies can induce T cell activation and proliferation. In this study, we investigate the significance of ZAP-70 in CD2 signaling using ZAP-70-deficient T cells derived from a CD8-deficient patient and show that ZAP-70 is necessary for cellular proliferation and cytokine production in T cells stimulated via CD2. Biochemical analyses show that CD2 stimulation induces activation of mitogen-activated protein kinase (MAPK) superfamily in ZAP-70-deficient T cells, indicating that a ZAP-70-independent pathway(s) exists for MAPK superfamily activation via CD2. In contrast, intracellular Ca(2+) mobilization and activation of nuclear factor of activated T cells (NFAT) upon CD2 triggering were impaired in T cells lacking ZAP-70. Furthermore, we found that pharmacological Ca(2+) elevation combined with CD2 stimulation restored NFAT activation and subsequent cytokine production in ZAP-70-deficient T cells. These results indicate that in CD2 signaling, ZAP-70 plays an essential role in Ca(2+) mobilization and NFAT activation.

Animals↗

PubMed2000

Two YxxL segments of a single immunoreceptor tyrosine-based activation motif in the CD3zeta molecule differentially activate calcium mobilization and mitogen-activated protein kinase family pathways.

Immunoreceptor tyrosine-based activation motifs (ITAM), consisting of two YxxL segments, transmit signals leading to IL-2 gene activation in T cells. We investigated here the functional difference in signal transduction between these two YxxL segments in the CD3zeta membrane-proximal ITAM. N-terminal YxxL mutants failed to induce ZAP-70 phosphorylation, elevation of intracellular Ca2+ concentration ([Ca2+]i) or extracellular signal-regulated kinase (ERK) activation even in the presence of CD28 co-stimulation, whereas a mutant of the leucine residue at the C-terminal YxxL segment retained the ability to induce these events although this mutation abrogated the ability to induce IL-2 gene activation. In marked contrast to ERK activation, c-Jun N-terminal kinase (JNK) activation was observed in all mutants when co-stimulated with CD28. The mutant of the leucine residue at the C-terminal YxxL segment had a defect in the transcriptional activation at the NF-AT cis-element, which was restored to wild-type level by addition of a Ca2+ ionophore, suggesting that the intensity and/or duration of [Ca2+]i elevation defines the threshold of T cell activation in this mutant. Our data collectively indicate that the activation pathways of ERK, JNK and Ca2+ mobilization are differentially regulated through YxxL segments of an ITAM.

Amino Acid Sequence↗

PubMed2000

Antibody-regulated neurotoxic function of cell-surface beta-amyloid precursor protein.

APP is a transmembrane precursor of beta-amyloid, and its mutations cause early-onset familial Alzheimer's disease. We report a toxic function of normal wild-type APP (wtAPP). Treatment of neuronal F11 cells, immortalized embryonic day 13 neurons, overexpressing wtAPP with anti-APP antibodies caused death. Death was not induced by antibody in parental F11 cells. Death by antibody occurred through cell-surface APP, not through secreted APP, in a pertussis toxin-sensitive manner and was typical apoptosis, not observed in primary astrocytes or glioma cells overexpressing wtAPP, but observed in primary cortical neurons. Cell-surface APP thus performs a toxic function as an extracellularly controllable regulator of neuronal death. This study provides a novel insight into the normal and pathological functions of cell-surface wtAPP.

Alzheimer Disease↗

PubMed2000

Nerve sheath ganglion of the ulnar nerve.

We report a case of a nerve sheath ganglion of the ulnar nerve at the canal of Guyon. This case involved a ganglion which was confined to the epineurium of the ulnar nerve. and it was completely excised without any damage to the nerve fiber. A nerve-sheath ganglion is rare, but it should be considered in the differential diagnosis of any tumor which is causing neural disturbance.

Adult↗

PubMed2000

Gastric amyloidosis with massive bleeding requiring emergency surgery.

We report a 66-year-old woman who had massive bleeding from a gastric ulcer complicating primary systemic amyloidosis, in whom emergency surgery proved lifesaving. Physical examination revealed anemia and macroglossia. Gastroscopy was performed, and an extensive, irregular, hemorrhagic ulcer was found in the gastric body. Biopsy resulted in a diagnosis of amyloidosis. On the 11th hospital day the patient went into shock as a result of a massive hemorrhage. Emergency surgery was performed, but the extent of the submucosal lesion in the stomach could not be identified, and total gastrectomy was unavoidable. Histological examination of the surgical specimen and biopsy tissue collected from other organs revealed amyloid deposition extending from the submucosa to the muscularis propria of the stomach. There was also deposition of large amounts of amyloid around the small blood vessels in the liver and under the mucosa of the small intestine. The amyloid was AA-antibody-negative and resistant to treatment with K2MO4, and a diagnosis of AL-type systemic amyloidosis was made. The patient's general condition recovered after the operation, but on the 103rd hospital day, she experienced sudden onset of arrhythmia and died. Patients with amyloidosis in whom gastrointestinal surgery is performed are rare; only 41 cases, including our own, have been reported in the Japanese literature since 1972.

Aged↗

PubMed2000

Video-assisted blebectomy using a flexible scope and a bleb implement.

We describe herein our new technique of performing video-assisted thoracic surgery (VATS) using a flexible scope and a bleb implement which allows for a reduction in the risk of overlooking small and flat blebs in patients with a spontaneous pneumothorax (SP). This technique was performed in 26 consecutive patients with a SP. A skin incision about 18 mm long was made in the area over which the patients had specified preoperatively, and meticulous observation of the apex and superior segment was performed using a bleb implement. Partial pneumonectomy with endoscopic staplers and laser ablation were carried out for pleural lesions. We found that VATS combined with a flexible scope and a bleb implement resulted in better visibility for detection and removal of any small and flat blebs.

Equipment Design↗

PubMed2000

Anatomic variations should be considered in total knee arthroplasty.

The effect of anatomic variations on the operative techniques used in total knee arthroplasty (TKA) was assessed. In 133 Japanese patients with medial osteoarthritis (OA), six parameters were measured on anteroposterior radiographs of the lower extremities taken with the patients in the supine position. The results showed that the characteristics of the knees were bowing of the femoral shaft and proximal tibia vara, with lateral offset of the tibial shaft with respect to the center of the tibial plateau. The angle between a perpendicular to the mechanical axis and the tangent to the distal femoral condyles can be used in determining the external rotation of the femoral component. This angle was more than 3 degrees in 20% of the patients. The femoral component should therefore be externally rotated more than 3 degrees relative to the posterior condylar line in such patients. Because the center of the tibial plateau is located medial to the central line of the tibial shaft in knees with medial OA, the central point of the tibial articular surface should not be used for alignment of the tibial component. The medial offset stem of the tibial component may impinge against the medial wall. Anatomic variations should be evaluated before TKA is attempted.

Aged↗

PubMed2000

Molecular cloning of a novel human gene (SIRP-B2) which encodes a new member of the SIRP/SHPS-1 protein family.

A full-length cDNA encoding a novel protein was isolated and sequenced from a human placental cDNA library. This cDNA consists of 1,735 base pairs and has a predicted open reading frame (ORF) encoding 354 amino acids. It possesses a putative signal sequence, a long extracellular domain, a transmembrane region, a short intracellular domain, and no catalytic domain, which is highly homologous to signal-regulatory protein (SIRP)-beta suggesting that it seems to be a new member of the SIRP family. Polymerase chain reaction (PCR)-based mapping with both a monochromosomal hybrid panel and radiation hybrid cell panels placed the gene to human chromosome 20p13 near the marker D20S906.

Amino Acid Sequence↗

PubMed2000

Non-adhesive cyanoacrylate as an embolic material for endovascular neurosurgery.

Endovascular neurosurgery is now becoming available as one of strategies for the treatment of cerebro-spinal arterio-venous malformations and aneurysms. For this treatment, a microcatheter is advanced into or close to a lesion and then an embolic material is administered through it to obliterate the lesion. N-butyl-2-cyanoacrylate (NBCA) has preferentially been used as an embolic material in Europe and America. However, its exceptionally strong adhesive force sometimes causes adhesion between the tip of the microcatheter and the artery. In this study, a new non-adhesive cyanoacrylate, isostearyl-2-cyanoacrylate (ISCA), was developed. It carries a long hydrophobic side isostearyl group with lower reactivity and adhesion than other cyanoacrylates. Its polymerization rate is, however, too low to obliterate a vascular lesion with a rapid blood flow. To increase the polymerization rate. ISCA was mixed with NBCA. As a result, the adhesive force of the mixture became extremely low, compared with that of NBCA. The viscosity of the mixture was low enough to allow its' use as an embolic material. Tissue reactions against the mixture was milder than those against NBCA. Radio-angiography became possible by mixing further with Lipiodol. The evaluation of this new embolic material with a rabbit renal artery showed that the obliteration effect of the mixture of ISCA and NBCA was excellent to use as an embolic material for clinical applications.

Animals↗

PubMed2000

Surface modification of polyethylene balloon catheters for local drug delivery.

Local drug delivery is an attractive approach to the associated problems of percutaneous transluminal coronary angioplasty (PTCA), including arterial injury. The objective of the present research was to deliver a high concentration of a potent anti-thrombin agent, argatroban (ARG), to the vessel wall in order to reduce arterial injury. Local delivery was accomplished by the ionic attachment of drug particles to a modified balloon surface. Surface graft polymerization of ionic monomers to a high-density poly(ethylene) (PE) substrate was performed utilizing ultra-violet (UV) methods. Acrylic acid (AAc) and 2(dimethylamino) ethyl methacrylate (DMAEMA) were successfully grafted onto PE surfaces. Surface grafting was verified by contact angle, X-ray photoelectron spectroscopy, and zeta potential measurements. The amount of ARG adsorbed onto the modified PE surface was highly dependent on the pH of the drug media for both anionic and cationic grafted monomers. The efficacy of local drug delivery to the arterial wall was analyzed using drug-immobilized PE balloon catheters in the rabbit common carotid artery model. High concentrations of ARG (280 nmol/g tissue) were found within the ballooned arterial segment immediately after angioplasty, followed by a decrease after blood flow was restored.

Acrylates↗

PubMed2000

Mechanisms of action of cyclosporine.

Cyclosporine (cyclosporin A, CsA) has potent immunosuppressive properties, reflecting its ability to block the transcription of cytokine genes in activated T cells. It is well established that CsA through formation of a complex with cyclophilin inhibits the phosphatase activity of calcineurin, which regulates nuclear translocation and subsequent activation of NFAT transcription factors. In addition to the calcineurin/NFAT pathway, recent studies indicate that CsA also blocks the activation of JNK and p38 signaling pathways triggered by antigen recognition, making CsA a highly specific inhibitor of T cell activation. Here we discuss the action of CsA on JNK and p38 activation pathways. We also argue the potential of CsA and its natural counterparts as pharmacological probes.

Animals↗

PubMed2000

Antioxidants inhibit TNFalpha-induced motility and invasion of human osteosarcoma cells: possible involvement of NFkappaB activation.

Osteosarcoma is the most frequent malignant bone tumor in children. It is highly invasive, however, the mechanisms behind osteosarcoma cell invasion are as yet still unknown. In the present study, treatment with TNFalpha enhanced the invasiveness of two human osteosarcoma cell lines, OST and MNNG. TNFalpha treatment also induced tumor cell motility, adhesion to laminin, the expression of matrix metalloproteinase 9 (MMP9), and the nuclear translocation of nuclear factor kappaB (NFkappaB) in the osteosarcoma cells. Moreover, antioxidants inhibited TNFalpha-induced osteosarcoma cell invasion, motility and NFkappaB nuclear translocation, but not adhesion to laminin or MMP9 expression. NFkappaB decoy, another NFkappaB inhibitor, also inhibited TNFalpha-induced osteosarcoma cell invasion and motility. Therefore, motility and NFkappaB activation were possibly related to TNFalpha-induced osteosarcoma cell invasion. However, adhesion to laminin or MMP did not demonstrate any correlation with TNFalpha-induced osteosarcoma cell invasion. Although NFkappaB is known to regulate TNFalpha-induced phenotypes, it may influence only motility and invasion, but not the MMP or laminin-mediated adhesion of these osteosarcoma cells.

Antioxidants↗

PubMed2000

Disassembly of a Howmedica modular resection system.

We report the postoperative disassociation of a Morse taper junction of a Howmedica Modular Resection system implanted after the resection of a malignant distal femoral bone tumor. The disassembly occurred without apparent trauma. This complication was managed by closed reduction under epidural anesthesia. This disassembly probably occurred because of decreased tension of the soft tissue around the prosthesis or an impaired locking mechanism.

Adult↗