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Biomedical subjects

N Suzuki

Publications and source records attributed to N Suzuki.

At least 469 records · Page 26Linked to original sources

Evaluation of the alleviative action of neurotropin for penile pain associated with intracavernous injection of prostaglandin E1 assessed using the visual analogue scale.

We examined whether penile pain associated with intracavernous injection of PGE1 could be alleviated with a intracavernous injection of neurotropin, a non-protein, bioactive agent extracted from skin tissue with inflammation elicited by the Vaccinia virus. Twenty-three patients with erectile dysfunction were enrolled in this study. They were divided into two groups. The first group was allocated 20 micrograms of PGE1 alone first, followed by PGE1 plus 1.5 ml of neurotropin after two weeks. The second group was allocated PGE1 plus 1.5 ml of neurotropin first, followed by PGE1 alone after two weeks. Pain was evaluated by the visual analogue scale (VAS). In the 17 patients reporting discomfort, pain scores for PGE1 injection with neurotropin were significantly lower than those without neurotropin. No patients showed local or systemic complications that might be related to neurotropin. From these data we conclude that neurotropin may be an effective and safe drug for penile pain associated with PGE1 intracavernous injection.

Adult↗

Modulation by proinflammatory cytokines of Fas/Fas ligand-mediated apoptotic cell death of synovial cells in patients with rheumatoid arthritis (RA).

Synovial cell hyperplasia is a characteristic of patients with RA. Excessive proliferation of RA synovial cells is, in part, responsible for the synovial cell hyperplasia. In addition, synovial cell death that would reduce synovial cell number may be defective, leading to the hyperplasia. Thus, the defective control of cell death as well as cell proliferation may be of central importance in the pathogenesis of RA. In this study we analysed effects of proinflammatory cytokines on Fas/Fas ligand (FasL)-induced synovial cell apoptosis, and evaluated apoptosis-associated protein expression in the synovial cells in patients with RA. RA synovial cells expressed Fas antigen and lymphocytes infiltrating into RA synovium expressed FasL. Apoptotic synovial cells were detected within the sublining layer of RA synovium. Anti-Fas MoAb induced apoptosis of RA synovial cells in vitro, and proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-1beta, but not IL-6 or IL-8, inhibited the anti-Fas-induced apoptosis accompanying up-regulation of Bcl-2 protein expression and reduced expression of CPP32 and ICH-1L. Immunohistochemical study revealed that CPP32 and ICH-1L were expressed weakly in the RA synovial lining cells compared with osteoarthritis (OA) synovial lining cells. Thus, we found that although RA synovial cells could die via apoptosis through Fas/FasL pathway, apoptosis of synovial cells was inhibited by proinflammatory cytokines present within the synovium. Inhibition of apoptosis by the proinflammatory cytokines may contribute outgrowth of synovial cells that leads to pannus formation and the destruction of joints in patients with RA.

Antibodies, Monoclonal↗

Primary structure of a 120 kDa protein associated with the fucose sulfate glycoconjugate constituting the acrosome reaction-inducing substance of the sea urchin, Hemicentrotus pulcherrimus.

A fucose sulfate glycoconjugate (FSG), a natural acrosome reaction-inducer, was purified from the egg jelly of the sea urchin Hemicentrotus pulcherrimus. The FSG is composed primarily of four constituents: a 120 kDa protein, a 237 kDa protein, a 258 kDa protein, and a polysaccharide-containing protein. Among them, the 120 kDa protein was thought to play a critical role in the association of other FSG constituent proteins, and therefore was characterized from a structural point of view. The protein was isolated from the carboxymethylated FSG by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions, and then digested with trypsin to obtain information regarding the primary structure. Based on the partial amino acid sequences of three internal peptides (FSG120KA: LHNNEYGYGDTAAGEPELAQEEID, FSG 120KG: AIDIPAETGHYGR, and FSG120KC: RPTFDLADAVDT) and the N-terminal peptide (LHNNEYGYGDTAAGEPELAQQEID) of the 120 kDa protein obtained from intact FSG, degenerate oligonucleotide primers were synthesized and used to amplify a 297 bp cDNA fragment. This fragment enabled us to obtain the full-length cDNA (3176 bp) by 5'- and 3'-rapid amplification of cDNA ends. The deduced amino acid sequence revealed that the 120 kDa protein is composed of 663 amino acid residues including 72 cysteine residues, and hence, about 40% is presumed to be carbohydrate by weight. The 120 kDa protein plays an important role in the association of FSG constituent proteins (258 and 237 kDa) through disulfide bonds.

Acrosome Reaction↗

Relevance of periglomerular myofibroblasts in progression of human glomerulonephritis.

To clarify the pathological and clinical significance of periglomerular alpha-smooth muscle actin (alpha-SMA)-positive cells, we examined 51 needle-biopsy specimens from patients with human glomerulonephritis. Immunoelectron microscopy confirmed these cells were myofibroblasts showing characteristic features with abundant alpha-SMA-positive thin myofilaments. Nonsclerotic glomeruli with periglomerular myofibroblasts were larger in the Bowman's capsular planar area than nonsclerotic glomeruli without periglomerular myofibroblasts (24.7 +/- 6.0 x 10(3) microm2 v 19.9 +/- 8.5 x 10(3) microm2; P < 0.01). We studied the correlation between the clinical prognosis and the extent of periglomerular myofibroblasts in 24 patients with IgA nephropathy. Patients were divided into two groups; those with plasma creatinine levels within normal range at biopsy and significantly elevated at follow-up were designated group 1 (poor prognosis), and patients with plasma creatinine levels within normal range at biopsy and not significantly elevated at follow-up were designated group 2 (fair prognosis). In the kidneys of group 1 patients, periglomerular alpha-SMA was expressed more intensively than it was in the kidneys of group 2 patients (alpha-SMA expression score, 1.0 +/- 0.48 v 0.52 +/- 0.54; P < 0.05). These findings indicate that periglomerular myofibroblasts appeared surrounding the nonsclerotic hypertrophic glomeruli, which may lead finally to glomerulosclerosis. This report suggests that interaction between the glomerular cells and the periglomerular myofibroblasts may have a role in the progression of glomerular diseases.

Actin Cytoskeleton↗

Radiation-induced painless thyrotoxic thyroiditis followed by hypothyroidism: a case report and literature review.

A 68-year-old woman presented with a small painless goiter and thyrotoxic symptoms immediately after 50-Gy external radiation for mucoepidermoid carcinoma of the submandibular gland. Elevated serum thyroid hormone and thyroglobulin levels, and undetectable serum thyrotropin level, together with extremely low thyroidal radioiodine uptake established the diagnosis of painless thyrotoxic thyroiditis. Thyroidal autoantibodies were negative. At follow-up without medication, all the symptoms disappeared, and laboratory abnormalities normalized within 6 months. One year later, the patient developed compensated hypothyroidism as indicated by elevated serum thyrotropin level with low normal serum thyroid hormone levels.

Aged↗

Treatment of relapsed Hodgkin's disease using EBV-specific cytotoxic T cells.

Donor-derived Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) are successful in the prevention and treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD) in allogeneic bone marrow transplant (BMT) recipients [1, 2]. This finding prompted us to use a similar approach to the treatment of relapsed EBV-positive Hodgkin's disease [3]. Autologous EBV-specific CTL lines could be generated on the first or second attempt from 11 of 15 patients with Hodgkin's disease. Peripheral blood TCR zeta-chain levels were low, but increased in the activated CTL lines. Three patients have received gene-marked autologous CTL. The first two patients experienced alleviation of stage B symptoms and a drop in peripheral blood EBV load. However, this situation reversed between 6 and 12 weeks after infusion, when chemotherapy and radiation were reinstated. Both patients eventually progressed and died. The third patient had a pleural effusion, which increased after CTL infusion. Analysis of the pleural effusion revealed both tumor cells and levels of marker gene over 100 fold greater than in peripheral blood. The infused CTL line showed activity against LMP2. The patient initially improved and then remained stable for over eight months after CTL infusion, but now has progressive disease. We currently are evaluating methods for introducing the LMP2 gene into dendritic cells and using these to present LMP2 to autologous T cells. Using both retrovirus and herpesvirus vectors to express LMP2 in dendritic cells, LMP2-specific CTL were successfully generated from individuals who were EBV-seronegative or who were non-responsive to LMP2 when presented on autologous LCL. In future protocols, LMP2-specific CTL will be used for treatment.

Dendritic Cells↗

Sulfation of alpha-hydroxytamoxifen catalyzed by human hydroxysteroid sulfotransferase results in tamoxifen-DNA adducts.

The formation of tamoxifen (TAM)-derived DNA adducts was investigated by incubation of DNA with (E)-alpha-hydroxytamoxifen [(E)-alpha-OHTAM], 3'-phosphoadenosine 5'-phosphosulfate (PAPS), and human recombinant sulfotransferase. Using 32P-post-labeling and HPLC analysis, two TAM-DNA adducts were detected in incubations that included the human hydroxysteroid sulfotransferase SULT2A1 (hHST). When compared with standards of stereoisomers of alpha-(N2-deoxyguanosinyl)tamoxifen 3'-monophosphate (dG3'P-N2-TAM), the major adduct was identified chromatographically as an epimer of the transform of dG-N2-TAM, and the minor adduct was identified as an epimer of the cis-form. The amount of TAM adducts formed by hHST was approximately three times less than that formed by an equivalent amount of rat hydroxysteroid (alcohol) sulfotransferase a. These results indicate that sulfation of alpha-OHTAM catalyzed by hHST results in the formation of dG-N2-TAMs, highly miscoding lesions, in human tissues.

Animals↗

Quantum-dye labeled proteins for glycobiology: a viable nonradioactive alternative tracer.

Quantum dye (QD), a macrocyclic europium-chelate, developed as a cytological marker, has never been used for quantitative applications. It would be ideal, however, if the same tracer can be used for both qualitative and quantitative purposes. We have labeled some lectins and neoglycoproteins with QD for the purpose of quantitative analyses in glycobiology, and tested its suitability in three different areas in glycobiology: (1) glycosyltransferase, (2) an animal lectin - mannose-binding protein, and (3) the Gal/GalNAc receptor of rat liver membrane. Usefulness of QD-labeled lectins was amply demonstrated by the quantification of galactosyltransferase activity using QD-soybean agglutinin and QD-RCA120 ( Ricinus communis agglutinin). We also showed that QD-labeled neoglycoproteins, QD-Man-BSA and QD-Gal-BSA, can replace radioiodinated counterparts in the binding assays of animal lectins (serum mannose binding protein and hepatic Gal/GalNAc receptor.) The advantage of QD and other europium labels is that it does not decay as radioiodides do. The long shelf-life results in more consistent results from repeated experiments.

Animals↗

Human dis3p, which binds to either GTP- or GDP-Ran, complements Saccharomyces cerevisiae dis3.

Saccharomyces cerevisiae Dis3p, which interacts with Ran/Gsp1p, complements Schizosaccharomyces pombe dis3-54. Consistent with the functional conservation of Dis3p in S. cerevisiae and S. pombe, the human ORF (accession number: R27667) was found to be highly homologous to yeast Dis3p. Based on its nucleotide sequence, we cloned a full-sized human DIS3 cDNA. The cloned human cDNA partly but significantly restored the temperature-sensitivity of S. cerevisiae dis3. Thus, Dis3p was found to be structurally and functionally conserved from yeast to mammals. Consistent with the report that S. cerevisiae Dis3p is identical to Rrp44p, which comprises the exosome involved in ribosomal RNA processing, S. cerevisiae Dis3p was found to be localized in the nucleolus. Similar to S. cerevisiae Dis3p, human Dis3p enhanced RCC1-stimulated nucleotide release from Ran, in a dose-dependent manner, and bound to GTP- or GDP-Ran.

Amino Acid Sequence↗

Morphological and functional aspects of reptilian ultimobranchial gland.

The intention of this review is to compare studies on the morphology and histology (light and electron microscopic) of ultimobranchial glands of various groups of reptiles. Moreover, experiments (including our investigations) on suppression or stimulation of the ultimobranchial gland are included. Adult reptiles possess one (on the left side) or two ultimobranchial glands (UBG). The UBG lie just anterior to the heart. Light as well as electron microscopically, the gland has been shown to contain follicles and cell cords (cell aggregates). The follicular epithelium is lined by simple cuboidal or pseudostratified columnar cells. Ciliated and goblet cells may be present in the follicular epithelia in some groups. The lumen may contain a colloid-like substance with desquamated cells or debris. The UBG of reptiles seem to be an active secretory organ with influence on calcium regulation. Other functions of calcitonin have also been suggested in reptiles for example in neurotransmission, in volume regulation, phosphate balance and promotion of bone calcification (at least in juveniles).

Alligators and Crocodiles↗

Lactic acid-mediated suppression of Helicobacter pylori by the oral administration of Lactobacillus salivarius as a probiotic in a gnotobiotic murine model.

OBJECTIVES: We examined whether or not the lactobacilli administered to treat Helicobacter pylori (H. pylori) infection can suppress the colonization of H. pylori, and we also sought to elucidate the mechanism of such suppression. METHODS: We used an in vitro culture system and an H. pylori-infected gnotobiotic murine model. RESULTS: Among the lactobacillus species examined in vitro, Lactobacillus salivarius (L. salivarius) but not L. casei or L. acidophilus proved to be capable of producing a high amount of lactic acid and thus completely inhibiting the growth of H. pylori in a mixed culture. The validity of L. salivarius as a probiotic to suppress H. pylori and thus reduce the inflammatory response was again confirmed in vivo by using an H. pylori-infected gnotobiotic murine model. CONCLUSION: Based on our findings, L. salivarius was found to be a potentially effective probiotic against H. pylori.

Animals↗

An autopsy case of Ki-1 lymphoma associated with hepatic failure.

A 62-year-old man was admitted to our hospital because of severe jaundice and fever. Physical examination demonstrated hepatosplenomegaly. The laboratory data revealed elevated serum bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase, and the reduced hepaplastin test (Normotest). Computed tomography showed hepatosplenomegaly and swelling of the paraaortic lymph nodes. Although he was treated with antibiotics and steroids, he died of hepatic failure 22 days after admission. At autopsy, his liver weighed 1910 grams, and a histological examination of the liver revealed marked infiltration of CD30 (Ki-1) positive lymphoma cells. He was diagnosed as having non-Hodgkin lymphoma, large cell anaplastic type, Ki-1 lymphoma. We herein report our findings of this very rare case of Ki-1 lymphoma associated with hepatic failure.

Autopsy↗

Purification and characterization of virginiamycin M1 reductase from Streptomyces virginiae.

Virginiamycin M1 (VM1), produced by Streptomyces virginiae, is a polyunsaturated macrocyclic lactone antibiotic belonging to the virginiamycin A group. S. virginiae possesses an activity which stereospecifically reduces a 16-carbonyl group of VM1, resulting in antibiotically inactive 16R-dihydroVM1. The corresponding VM1 reductase was purified to homogeneity from crude extracts of S. virginiae in five steps, with 5,650-fold purification and 23% overall yield. The N-terminal amino acid sequence was determined to be MAIKLVIA. The purified enzyme showed an apparent Mr of 73,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an Mr of 280,000 by native molecular sieve high-performance liquid chromatography, indicating the tetrameric nature of the native enzyme. NADPH served as a coenzyme for the reduction, with a Km value of 0.13 mM, but NADH did not support the reaction, even at a concentration of 5 mM, indicating the NADPH-specific nature of the enzyme. The Km for VM1 was determined to be 1.5 mM in the presence of 2 mM NADPH. In the reverse reaction, only 16R-dihydroVM1, not the 16S-epimer, served as a substrate, with a less than 0.1% overall reaction rate compared to that of the forward reaction, confirming that the VM1 reductase participates solely in VM1 inactivation in vivo.

Anti-Bacterial Agents↗

Monoclonal antibody against Babesia equi: characterization and potential application of antigen for serodiagnosis.

Monoclonal antibody (MAb) BEG3 was produced against Babesia equi parasites to define a species-specific antigen for diagnostic use. The MAb reacted with single, paired, and Maltese cross forms of B. equi, and no reaction was observed with this MAb on acetone-fixed Babesia caballi, Babesia ovata, or Babesia microti parasites in the indirect immunofluorescent antibody test. Confocal laser and immunoelectron microscopic studies showed that the antigen which was recognized by this MAb was located on the surface of B. equi parasites. This MAb recognized a 19-kDa protein of B. equi antigen and did not react with B. caballi antigen or normal horse erythrocytes in immunoblot analysis. This MAb also significantly inhibited the in vitro growth of the B. equi parasite. Preliminary studies using partially purified antigen, which was separated by high-pressure liquid chromatography and recognized by the MAb, suggested that it is a suitable antigen for enzyme-linked immunosorbent assay detection of anti-B. equi antibodies in naturally infected horse sera.

Animals↗

Involvement of simultaneous multiple transcription factor expression, including cAMP responsive element binding protein and OCT-1, for synovial cell outgrowth in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate possible roles of several transcription factors in the pathogenesis of rheumatoid arthritis (RA), the transcription factor expression in RA synovial tissue and their contribution to RA synovial cell functions were studied. METHODS: Single cell suspension of dissociated synovial tissue was cultured to induce in vitro tissue outgrowth of RA synovial cells. Transcription factors were immunohistochemically identified in RA synovial tissue obtained by joint surgery and in the in vitro tissue outgrowth, and confirmed by western blotting and gel shift assays. RESULTS: Immunohistochemical examination of RA synovial tissue revealed simultaneous expression of various transcription factors (NF-kappa B, c-Jun (a component of AP-1), cAMP responsive element binding protein (CREB), and OCT-1). The same set of transcription factors was expressed in the in vitro tissue outgrowth of RA patients. The early passage RA synovial cells were treated with interleukin 1 beta (IL1 beta) and confirmed translocation of transcription factors into the nucleus by western blotting, and their DNA binding activity by gel shift assays. CONCLUSION: This study emphasises the importance of the simultaneous expression of several transcription factors for the hyperactivity of RA synovial cells that leads to tissue outgrowth.

Adult↗

End-stage renal failure due to crescentic glomerulonephritis in a patient with Behçet's syndrome. Review of the literature.

We report a rare case of a patient with Behçet's syndrome who developed end-stage renal failure due to crescentic glomerulonephritis (GN). A 20-year-old male patient had suffered from uveitis, aphthous mouth ulcers and genital ulceration for the past 7 years. His renal function rapidly deteriorated and renal biopsy specimens obtained when his serum creatinine level was 3 mg/dl showed diffuse proliferative GN with fibrous crescent formation in 75% of glomeruli excluding totally sclerotic glomeruli. Immune complexes were identified by demonstration of complement and immunoglobulins in the glomeruli. He developed end-stage renal failure during a 1-year course and received maintenance hemodialysis. We reviewed the literature on severe forms of GN in patients with Behçet's syndrome.

Adult↗

Dental caries susceptibility in mice is closely linked to the H-2 region on chromosome 17.

The generation of dental caries in humans is thought to be regulated by many intrinsic and social factors. In this study, we examined the effect of MHC on susceptibility to dental caries in mice. The mean carious score of BALB.K/Ola, a H-2 congenic strain in which the H-2 region derived from C3H/HeJ (H-2(k/k)) is introduced into BALB/cJ (H-2(d/d)), was markedly reduced as compared with that of its recipient strain (BALB/cJ). Mating experiments confirmed a strong genetic linkage between H-2 haplotype and caries susceptibility. These results demonstrate that one of the genetic factors of the susceptibility in the mouse is mapped within the H-2 region. This finding of a host genetic factor influencing the generation of dental caries will help in developing clinical preventive strategies.

Animals↗