Biomedical subjects

K Nishida

Publications and source records attributed to K Nishida.

At least 181 records · Page 10Linked to original sources

PubMed1998

Teprenone, an anti-ulcer agent, increases gastric mucosal mucus level via nitric oxide in rats.

We examined whether the increasing action of teprenone (TP) on mucus synthesis and content in rat gastric mucosa is related to nitric oxide (NO) formation via NO synthase (NOS) in the tissue. TP (200 mg/kg)-induced increases in levels of gastric mucosal hexosamine and adherent mucus were inhibited with decreased gastric mucosal NOS activity and nitrite/nitrate concentration by co-administration of NG-monomethyl L-arginine (100 mg/kg), a NOS inhibitor, but not its D-isomer. These results suggest that TP exerts an increasing action on gastric mucus synthesis and content possibly under the condition of maintained NO production via NOS in gastric mucosal tissues, although the precise mechanisms for the action of TP is still unclear.

Animals↗

PubMed1998

Evaluation of rheumatoid arthritis using a scoring system devised from magnetic resonance imaging of rheumatoid knees.

We studied the magnetic resonance imaging (MRI) of 120 knees in 86 rheumatoid arthritis (RA) patients and of 14 unaffected knees in 12 control cases. We also developed a scoring system as a quantitative analysis method. We divided the MRI into 10 items, and classified the severity of the symptoms into 4 grades (score 0 to 3). The average total score increased according to the radiographic grade. Soft tissue lesions were clearly detected, even in the early stages of RA. Items such as synovial proliferation showed a high score even in the early stages, suggesting that it was the initial symptom of RA. The score also showed a correlation with the inflammatory signs. These results suggest that this scoring system is very sensitive and yields a good reflection of RA activity. We demonstrated that this system is simple and convenient for routine diagnostic use. We further demonstrated that it is useful for following the advancement of RA and for evaluating the response to treatment.

Adult↗

PubMed1998

Fibrous structure and connection surrounding the metacarpophalangeal joint.

The fibrous components of the metacarpophalangeal (MP) joint including the palmar plate, the collateral ligament and the dorsal plate were studied with particular attention paid to the fibrous structure of the fibrous tendon sheath and the deep transverse metacarpal ligament. The tough fibrillar structure around the MP joint, especially the force nucleus, consisted of three types of mixed fibers: the fibrous tendon sheath of the A1 pulley, the deep transverse metacarpal ligament, and the palmar plate. The tendon sheath was located on the ulnar side in the index and middle fingers, on the central position in the ring finger, and on the radial side in the little finger. These fibrous connections among the fingers formed a transverse arch in the hand. The palmar plate of the MP joint was relatively rigid and appears to function as a cushion when flexed. A fold-like protrusion of the synovial layer of the palmar plate of the MP joint had a meniscoid function, which was larger than that of the proximal interphalangeal joint. The capsule of the MP joint was thicker at the dorsal area, forming a dorsal plate, which is a sliding floor of the extensor mechanism and has a meniscoid function for joint congruity. The main lateral stabilizer consisted of collateral ligaments and accessory collateral ligaments anchored to the palmar plate. These structures act together as a "phalangeal cuff", connecting the proximal phalanx to the metacarpal head and stabilizing the MP joint.

Aged↗

PubMed1998

Mast cells in osteoarthritic and rheumatoid arthritic synovial tissues of the human knee.

The distribution and density of mast cells in the normal and diseased synovial membranes were investigated. The mast cell count (MCC) in the osteoarthritic (OA) synovium (36.9 +/- 26.9 cells/mm2) was significantly higher than that in the rheumatoid arthritic (RA) synovium (18 +/- 12.3 cells/mm2). There was a marked positive correlation between the MCC and the volume of joint fluid in OA (r = 0.544). There was a marked negative correlation between the MCC and the volume of joint fluid in RA (r = -0.478). The synovial inflammatory score had a poor correlation with the MCC in OA (r = 0.377) and RA (r = 0.305). No correlation was noted between MCC and age, sex, roentgenographic grades, disease duration, C-reactive protein or leucocyte number in synovial fluid. Our data suggests, thus, that mast cells could be involved in the pathogenesis of inflammatory diseases of the synovium, especially in the mechanism of hydroarthrosis.

Adult↗

PubMed1998

Changes in nitric oxide production with lesion development in the gastric mucosa of rats with water immersion restraint stress.

In rats with gastric mucosal lesions induced by water immersion restraint (WIR) stress over a 6 h period, increases in the serum and gastric mucosal concentrations of nitrite/nitrate, the breakdown products of NO, occurred with a drastic increase in inducible NO synthase (iNOS) activity in the gastric mucosa. Pretreatment with aminoguanidine (100 mg/kg), a relatively selective iNOS inhibitor, attenuated not only gastric mucosal lesion development, but also increases in serum and gastric mucosal nitrite/nitrate concentrations with inhibition of increased gastric mucosal iNOS activity in rats with 6 h of WIR stress. A good positive correlation between either serum or gastric mucosal nitrite/nitrate concentration and gastric mucosal iNOS activity in all rats used (r = 0.741 or 0.842, respectively, p < 0.001) was found. These results suggest that in WIR-stressed rats, an increase in NO production via iNOS in the gastric mucosa could contribute to gastric mucosal lesion development.

Animals↗

PubMed1998

Isolation and characterization of human cathepsin V: a major proteinase in corneal epithelium.

PURPOSE: To isolate and characterize a novel cathepsin gene, as part of the systematic isolation of genes uniquely active in corneal epithelium. METHODS: For the isolation of a full-length cDNA clone, a probe was selected from a set of expressed sequence tag clones classified as unique to corneal epithelium. Inserted cDNA was introduced into insect cells using a baculovirus expression system, and the secretion of recombinant protein was identified using antisera against a synthetic peptide. Proteolytic activity was determined using bovine serum albumin (BSA) as substrate. The expressions of the novel cathepsin in human cornea and other tissues were examined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The full-length cDNA clone encoded a peptide of 334 amino acids with 82% identity with bovine cathepsin L and 77% identity with human cathepsin L when aligned. The recombinant protein produced in the baculovirus expression system cleaves BSA, and its activity was inhibited by the cysteine proteinase inhibitors E-64 and leupeptin, but not by pepstatin A, phenylmethylsulfonyl fluoride, and EDTA. By RT-PCR, a low level of expression was observed in some other epithelial tissues of ectodermal origin, but only in cornea was it higher than cathepsin L, which is known to be a general lysosomal cathepsin. Cathepsin V protein was detected in human corneal epithelium by western blot analysis, but not in tear fluid. CONCLUSIONS: The amino acid homology and proteolytic activity of the recombinant protein indicate that the novel gene is a new member of the cathepsins that have features of cysteine proteinase. Its uniquely high expression in corneal epithelium strongly implies an important role in corneal physiology.

Amino Acid Sequence↗

PubMed1998

Analysis of urinary albumin, transferrin, N-acetyl-beta-D-glucosaminidase and beta2-microglobulin in patients with impaired glucose tolerance.

We investigated the changes in urinary albumin and urinary transferrin as glomerular proteins, and in urinary N-acetyl-beta-D-glucosaminidase and urinary beta2-microglobulin as tubular proteins, in patients with impaired glucose tolerance. We attempted to compare the proteins of normal subjects to those of diabetics with pre-nephropathy. Transferrin and N-acetyl-beta-D-glucosaminidase levels were significantly increased in patients with impaired glucose tolerance, while albumin and beta2-microglobulin levels were only slightly increased. In addition, there was no significant difference in transferrin levels between patients with impaired glucose tolerance and type 2 diabetics with pre-nephropathy. In our observation, although albumin levels were only slightly increased in patients with impaired glucose tolerance, a sharp increase in transferrin levels was reflected in patients with glomerular disorders. In addition, since N-acetyl-beta-D-glucosaminidase levels varied markedly, tubular disorders were suspected. It should be stressed that increased parameters for both glomerular and tubular disorders in group C--patients who showed abnormal levels in three proteins--had already been observed in some patients with impaired glucose tolerance. Therefore, the evaluation of the mutual relationships between various urinary protein components in patients with impaired glucose tolerance will become a more important assessment tool than that of single urinary protein components.

Acetylglucosaminidase↗

PubMed1998

[Augmented antitumor efficacy of combination chemotherapy of nedaplatin with 5-fluorouracil in in vivo murine and human tumor model].

Augmented antitumor activity was demonstrated in combination chemotherapy of Nedaplatin (NDP) or Cisplatin (CDDP) with 5-fluorouracil (5-FU) against murine lung carcinoma and human squamous carcinoma from head and neck. Either NDP or CDDP (1/4 to 1 maximum tolerated dose; MTD) was injected once and 5-FU (1/16 MTD) was injected daily for five days via tail vein to tumor-implanted mice. The sequential administration of either NDP or CDDP prior to 5-FU (NF or CF therapy) showed severe body weight loss followed by the toxic death of tumor-bearing mice at the MTD of NDP or CDDP. In contrast, the reverse sequence of the treatment, that is, 5-FU prior to NDP or CDDP (FN or FC therapy), resulted in the synergistically enhanced inhibition of tumor growth and the prolonged survival in comparison with NDP, CDDP or 5-FU monotherapy. The antitumor activities of the combinations of CDDP with 5-FU was less than those of the combination of NDP with 5-FU. Especially, at the MTD of NDP in FN therapy, long-term tumor-free survival was frequently observed. Thus, FN therapy was thought to be the most efficient regimen in combination of NDP with 5-FU as a clinical therapy.

Animals↗

PubMed1998

Dissecting aortic aneurysm involving an anomalous right subclavian artery and isolated left vertebral artery: case report and review of the literature.

A 54-year-old hypertensive woman was admitted with severe interscapular back pain. A chest radiograph showed marked widening of the mediastinum. Aortography demonstrated a DeBakey type III, a thoracic aortic dissection and an anomalous right subclavian artery which was associated with an isolated left vertebral artery. The patient underwent aortic arch replacement with 5 branches and made an uneventful recovery. As far as we can determine, this is the first reported occurrence of these anomalies together with acquired disease of the aorta.

Aortic Dissection↗

PubMed1997

Identification of regulatory elements of human alpha 6 integrin subunit gene.

The integrin alpha 6 subunit associates with either the beta 1 or beta 4 subunit to form receptors for laminin, a major component of the basement membrane. Here, we characterized basal promoter of the human integrin alpha 6 subunit gene. The transcription start site, mapped by primer extension analysis, was 208 bp upstream of the translation start site. The promoter region lacked canonical TATA and GC boxes, but did contain a TATA-like sequence (GATAAA) 23 bp upstream of the major transcription start site. Consensus binding sites for Sp1 and the NF-kappa B complex were also present in the promoter region. A putative glucocorticoid/progesterone receptor responsive element (GRE/PRE), together with the Ap1 and c-myc binding sites located around 350-360 bp upstream of the transcription start site, represented positive regulatory sequences. Our current study showed a molecular model by which progesterone promotes tumor cell invasion through the basement membrane by up-regulating the laminin receptor.

Antigens, CD↗

PubMed1997

Glycine facilitates gamma-glutamylcysteinylethyl ester-mediated increase in liver glutathione level.

gamma-Glutamylcysteinylethyl ester (gamma-GCE) increases reduced glutathione (GSH) levels in GSH-depleted rat hepatocytes. Because glycine, a constituent of GSH, exists at 0.3 to 0.4 mM in rat plasma, we examined the influence of glycine added to the medium on the action of gamma-GCE to increase GSH levels in the rat hepatocytes. Glycine (0.2-0.8 mM) dose-dependently enhanced gamma-GCE-mediated increase in intracellular GSH levels with an increase in intracellular gamma-GCE levels. These results indicate that exogenous glycine facilitates gamma-GCE-mediated increase in intracellular GSH levels in rat hepatocytes possibly by enhancing the uptake of gamma-GCE into the cells.

Animals↗

PubMed1997

Role of gastric mucosal constitutive and inducible nitric oxide synthases in the development of stress-induced gastric mucosal lesions in rats.

Changes in gastric mucosal constitutive NO synthase (cNOS) and inducible NO synthase (iNOS) activities with the development of gastric mucosal lesions induced by water immersion restraint (WIR) stress were investigated in rats pretreated with and without NOS inhibitors. A decrease in cNOS activity and an increase in iNOS activity in the gastric mucosa occurred with gastric mucosal lesion development. Pretreatment with N(G)-monomethyl L-arginine, a non-selective NOS inhibitor, enhanced gastric mucosal lesion development with inhibition of gastric mucosal cNOS and iNOS activities, although the inhibited iNOS activity was still higher than the normal level. Pretreatment with aminoguanidine, a selective iNOS inhibitor, prevented gastric mucosal lesion development with inhibition of iNOS activity and maintenance of cNOS activity in the gastric mucosa. These results indicate that in WIR-stressed rats, an increase in iNOS activity and a decrease in cNOS activity in the gastric mucosa are closely related to the development of gastric mucosal lesions.

Animals↗

PubMed1997

The Ig heavy chain gene is frequently involved in chromosomal translocations in multiple myeloma and plasma cell leukemia as detected by in situ hybridization.

Chromosome rearrangement of 14q32.33 has recurrently occurred with variable partner sites, including 11q13.3, 8q24.1, 18q21.3, and 6p21.1 in multiple myeloma (MM). To assess the actual incidence of 14q32.33 translocation and to elucidate its implication in the pathogenesis of MM, we studied 42 patients with MM, plasma cell leukemia, or plasmacytoma and 5 with monoclonal gammopathy with undetermined significance (MGUS) by G-banding and molecular cytogenetic methods. Using double-color fluorescence in situ hybridization (DCFISH) with 2 Ig heavy chain (IgH) gene probes, a yeast artificial chromosome (YAC) clone containing variable region, and a phage clone containing gamma constant region, 14q32.33 translocation was detected as split signals of the IgH gene in 31 patients with plasma cell malignancies and 3 with MGUS. In contrast, of 40 patients who were assessed by G-banding, 3 (7.5%) showed the 14q+ chromosome. DCFISH detected a split of the IgH gene on interphase nuclei in 34 (73.9%) of 46 patients analyzed, whereas on metaphase spreads, it was in 22 (51.2%) of 43 patients analyzed. Interphase DCFISH was particularly useful to detect 14q32.33 translocation in 17 (65.4%) of 26 patients with normal karyotypes. Donor sites were identified in 11 of 22 patients demonstrated as carrying 14q32.33 translocation by metaphase FISH. Chromosome t(11;14)(q13.3; q32.33) was detected in 5 patients, t(8;14)(q24.1;q32.33) in 2, t(14;18)(q32.33;q21.3) in 2, and t(7;14)(q32.1;q32.33) in 1. A complex 14q32.33 translocation involving 3q and 16q24 was detected in 1 patient. Myeloma cells with t(7;14) showed myelomonocytoid surface antigen. Because rearrangements of 14q32.33 were closely associated with translocation of proto-oncogenes into the IgH gene, our findings indicate that 14q32.33 translocation with various partner chromosomes is a critical event in the pathogenesis of MM and MGUS.

Adult↗

PubMed1997

Detection of 14q32.33 translocation and t(11;14) in interphase nuclei of chronic B-cell leukemia/lymphomas by in situ hybridization.

Abnormalities of chromosome 14 involving band q32.33 are among the most commonly observed cytogenetic alterations in B-cell malignancies. To assess the incidence and pathogenetic implications of 14q32.33 translocation in chronic B-cell leukemia/lymphomas, we performed fluorescence in situ hybridization (FISH) analysis with variable region (V(H)) and gamma constant region (Cgamma) gene probes in 37 patients with these disorders. Chromosome 14q32.33 translocation was detected in 2 of 18 patients with chronic lymphocytic leukemia (CLL), 1 of 2 with CLL of mixed cell types (CLL/PL), 1 of 2 with pro-lymphocytic leukemia (PLL), 5 of 6 with leukemic mantle-cell lymphoma (MCL), 2 of 7 with splenic B-cell leukemia/lymphoma of possible marginal zone origin (SBLL) and 2 with leukemic follicular lymphoma (FL). To further characterize 14q32.33 translocations in these patients, we developed a new procedure using double-color FISH with PRAD1, BCL2, V(H) and Cgamma gene probes. Chromosome t(11;14) was detected in 1 patient with CLL/PL, 1 with PLL and 5 with MCL. Chromosome t(14;18) was detected in 2 patients with FL. In a PLL patient with t(11;14), the cosmid CPP29 containing the PRAD1 gene and its 5'-flanking region split and co-localized with both Cgamma and V(H) gene probes, thus spanning the breakpoint. In CLL and SBLL patients, donor chromosomes were other than chromosomes 2, 11, 18 and 19, suggesting the involvement of a novel oncogene(s) in the pathogenesis of these diseases. Interphase FISH rapidly detected 14q32.33 translocation, t(11;14) and t(14;18) in B-cell malignancies with low mitotic activity at the single-cell level, facilitating the correlation of the molecular features of these translocations with clinical characteristics.

Adolescent↗

PubMed1997

Pentoxifylline decreases brain levels of platelet activating factor in murine AIDS.

Tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) have been implicated in the pathogenesis of human immunodeficiency virus (HIV)-associated encephalopathy. The effects of pentoxifylline on brain PAF levels were examined in mice infected with the LP-BM5 murine leukemia virus (MuLV). Seven weeks after viral inoculation, significant increases in serum TNF-alpha and brain PAF levels were observed. One week of treatment with pentoxifylline initiated 6 weeks postinfection significantly reduced both serum TNF-alpha and brain PAF levels. A significant positive correlation was observed between the levels of these substances (r = 0.62; P < 0.01). This study demonstrates that pentoxifylline treatment was effective in decreasing the levels of TNF-alpha in the serum and PAF levels in the brain of mice infected with the LP-BM5 MuLV.

Animals↗

PubMed1997

In vitro effects of a recombinant toxin, mSCF-PE40, targeting c-kit receptors ectopically expressed in small cell lung cancers.

Most small cell lung cancers (SCLCs) ectopically express high levels of the c-kit receptor. We have examined if the receptor can serve as a target for a chimeric toxin, mSCF-PE40 composed of murine stem cell factor (SCF) genetically fused to the N terminus of a modified form of Pseudomonas exotoxin (PE) lacking its cell recognition domain. Selective cytotoxicity was found for human c-kit receptor-negative cells. This agent thus warrants further evaluation for therapy of human CSLCs.

ADP Ribose Transferases↗

PubMed1997

Urinary nitrite/nitrate excretion in infancy: comparison between term and preterm infants.

We measured urinary nitrite/nitrate (NOx-) excretion, an index of endogenous nitric oxide formation, in term and preterm infants aged 1 week and 1, 4, 7 months. In normal term infants, urinary NOx excretion increased from 1 week to 1 month and then decreased until 4 months where it stabilized thereafter. Urinary NOx- excretion in preterm infants was significantly higher compared with term infants at 1 week of age. This finding suggests that the nitric oxide pathway in preterm infants may be activated compared with term infants in early life. With the reference values obtained in this study, this urinary marker can now be used for identifying infants with abnormal nitric oxide production.

Aging↗

PubMed1997

Hyperpolarisation of cultured human chondrocytes following cyclical pressure-induced strain: evidence of a role for alpha 5 beta 1 integrin as a chondrocyte mechanoreceptor.

Mechanical stimuli influence chondrocyte metabolism, inducing changes in intracellular cyclic adenosine monophosphate and proteoglycan production. We have previously demonstrated that primary monolayer cultures of human chondrocytes have an electrophysiological response after intermittent pressure-induced strain characterised by a membrane hyperpolarisation of approximately 40%. The mechanisms responsible for these changes are not fully understood but potentially involve signalling molecules such as integrins that link extracellular matrix with cytoplasmic components. The results reported in this paper demonstrate that the transduction pathways involved in the hyperpolarisation response of human articular chondrocytes in vitro after cyclical pressure-induced strain involve alpha 5 beta 1 integrin. We have demonstrated, using pharmacological inhibitors of a variety of intracellular signalling pathways, that the actin cytoskeleton, the phospholipase C calmodulin pathway, and both tyrosine protein kinase and protein kinase C activities are important in the transduction of the electrophysiological response. These results suggest that alpha 5 beta 1 is an important chondrocyte mechanoreceptor and a potential regulator of chondrocyte function.

Actins↗