Search PubMed⌕ Search

Biomedical subjects

R Suzuki

Publications and source records attributed to R Suzuki.

At least 343 records · Page 19Linked to original sources

[A case of spontaneous middle cerebral artery occlusion associated with a cerebral aneurysm angiographically disappearing after STA-MCA anastomosis].

We report a case of a rapidly growing cerebral aneurysm in the basal abnormal vascular network associated with spontaneous middle cerebral artery (MCA) occlusion. The aneurysm disappeared spontaneously shortly after performing STA-MCA anastomosis. A 54-year-old female was admitted to our hospital because of repeated attacks of right hemisensory disturbance and dysarthria. CT scan and MRI images showed the infarcted focus in the left parieto-occipital lobe. Bilateral MCAs were undetectable on MRI images. Cerebral angiography revealed that the bilateral MCAs were occluded in their proximal origin with basal abnormal vascular networks. The distal MCA branches were perfused via the vascular networks. A small aneurysm was detected in the distal portion of the left Heubner's artery. There were no abnormalities in the bilateral internal carotid arteries, the anterior cerebral arteries, and the basilar artery. The follow-up angiography performed 29 days after admission revealed a growing aneurysm with a diameter of 3 mm in the distal enhanced lesion consistent with the aneurysm observed in the angiography. An STA-MCA anastomosis was performed for improvement of cerebral misery perfusion. Single photon emission tomography (SPECT) performed 9 days after the bypass operation revealed improvement of cerebral blood flow in the left parieto-occipital lobe, and her TIA attacks disappeared. The aneurysm was undetected in the cerebral angiography performed 24 days after the bypass operation. Spontaneous MCA occlusion is a rare condition of chronic cerebrovascular occlusive diseases. Diagnostic criteria of the disease includes the MCA occlusions or stenosis with basal abnormal vascular networks. Usually the phenomenon is seen unilaterally, which differs from moyamoya disease. Diagnosis must exclude diseases caused by the etiologies such as those of arteriosclerotic origin. There have been 24 reported cases of spontaneous MCA occlusion including our case. Among them, 9 cases presented cerebral aneurysm located in abnormal vascular networks, and all the reported cases presented cerebral hemorrhage at their onset. The abnormal basal vascular network may be developed as collateral vessels to supply blood to the ischemic regions in this disease. An increased hemodynamic stress in the abnormal basal vascular network may produce a true aneurysm in the distal portion of the perforating arteries. STA-MCA anastomosis reduced the TIA attacks, but also decreased the hemodynamic stress on the abnormal basal vascular network and resulted in reduction in size or thrombosis of the aneurysm. STA-MCA anastomosis can be considered effective to treat cerebral aneurysms located in vessels with increased hemodynamic stress.

Arterial Occlusive Diseases↗

Characterization of the I-E(d)--restricted peptide recognized by an anti-idiotypic CD4+ T cell line.

We have previously reported a CD3+ CD4+ CD8- T cell line, J-2R which specifically recognized J558 individual idiotope (IdI) of anti-alpha (1-->3) dextran antibodies in an I-E(d) restricted manner. The J-2R proliferated in response to J558 IdI-derived peptides; however, the ability of the peptides to evoke the proliferation of J-2R was different. In the present study, we investigated the interaction between J558 IdI-derived peptides and I-E(d) molecules in competition experiments using a M104E IdI-derived peptide, M88-105. The M88-105 inhibited the proliferation of J-2R induced by J558 IdI-derived peptides. Furthermore, the proliferation induced by the peptides J92-109 and J96-105 was inhibited by the M88-105 at much lower inhibitor/antigenic peptide ratios, compared to the proliferation induced by the J88-105. Thus, shift of the framework to C-terminus and deletion of N-terminus amino acid residues from the 18-mer peptide J88-105 made the peptides more susceptible to the inhibition by the M88-105. Sequencing of the J-2R T cell receptor (TcR) revealed that J-2R used TcR, V alpha 1, J alpha 44; V beta 15, D beta 1, J beta 1.5. These results suggest that the peptides, J88-105, J92-109 and J96-105, directly bind to I-E(d) molecules, and that the capacity of J558 IdI-derived peptides to activate J-2R depends on the affinity to the I-E(d) molecules.

Amino Acid Sequence↗

Establishment and characterization of an anti-idiotypic CD4+ CD8- T cell line to murine anti-alpha(1 --> 3) dextran antibody.

It is known that anti-alpha(1 --> 3) dextran antibodies of BALB/c mice are ordinarily of distinctive idiotypes (Id), one of which is the individual idiotype (IdI) that is represented by J558 or M104E to myeloma protein. In the present study, we established T cell line of Th1 type which recognized the Id of anti-alpha(1 --> 3) dextran antibody, and investigated its specificity and functions. The T cell line, named J-2R, had a phenotype of CD3+ CD4+ CD8- and expressed alphabeta-T cell receptors (TcR). J-2R proliferated in response to J558 in an I-Ed-restricted manner but did not respond to M104E which had substitution at amino acids 100 and 101. We confirmed that J-2R recognized J558 IdI, using synthetic peptides corresponding to two serial amino acid residues, Arg100 and Tyr101, spanning the J558 IdI in the third hypervariable region (hv3) of the heavy chain. alpha(1 --> 3) dextran-binding B cells which were isolated from dextran-immunized mice activated J-2R, but B cells from nonimmune mice did not. J-2R produced IL-2, IFN-gamma and IL-6, but did not produce IL-4, IL-5, or IL-10. Furthermore, J-2R inhibited the growth of J558 myeloma cells inoculated to the syngeneic mice in vivo. These findings suggest that Id-specific CD4+ T cells, J-2R, are involved in Id network and may play a role in vivo. J-2R is useful for analysis of the role of the Id-specific helper T cells in immune network because J558 IdI is frequently present on anti-alpha(1 --> 3) dextran antibodies.

Amino Acid Sequence↗

Specific clonal T cell accumulation in intestinal lesions of Crohn's disease.

The initial cellular events that take place at the outset of autoimmune diseases and that may be the most important in terms of understanding their pathogenesis are poorly understood, especially in humans. This is mainly due to the difficulties in the identification of primary lesions and the accessibility to such material. In this respect, it is noteworthy that the appearance of small reddish erosions, known as aphthoid lesions, is known to be an early event in Crohn's disease. In the present study, accumulation of lesion-specific clonal TCR bands in the intestinal lesions of Crohn's disease patients was demonstrated by means of a highly sensitive method based on single strand conformational polymorphism. Such clonal accumulation was demonstrated in both aphthoid and discrete ulcer lesions. There were several TCR BV bands that were present in both aphthoid lesions and discrete ulcer lesions, but some were specific to the aphthoid lesions. In addition, the same aphthoid lesion-specific/dominant T cell clones were found to be expanded in separate aphthoid lesions of a single patient, and were absent from intervening, non-inflamed mucosa. Some of these bands may represent T cell clones activated primarily at the onset of disease.

Adolescent↗

Defect of thymocyte emigration in a T cell deficiency strain (CTS) of the mouse.

As bone marrow progenitors migrate to the thymus, differentiate into immunologically competent T cells, then leave the thymus and home to the peripheral lymphoid organs, each migration or homing is an essentially critical process for T cell differentiation. Homing of thymocytes into peripheral lymphoid organs has been extensively analyzed. On the contrary, little is known about the mechanism whereby mature thymocytes emigrate from the thymus to peripheral lymphoid organs. In this work, we show that the mutant T cell deficiency strain (CTS) of mouse, previously described as a peripheral T cell deficiency strain, has a novel defect of mature thymocyte emigration process. Flow-cytometric analysis demonstrated a marked decrease in T lymphocytes in peripheral lymphoid organs and an accumulation of mature thymocytes in the thymus. Histologic study revealed the high concentration of thymocytes within the giant perivascular space at thymic corticomedullary junction. These accumulating cells closely resemble normal peripheral T lymphocytes in terms of cell surface phenotype and responsiveness to mitogens or allogeneic cells. They were found to express the Mel-14 Ag, the homing receptor to lymph nodes, and had a high capability of homing to peripheral lymphoid organs when explanted thymocytes were injected i.v. The intrathymic labeling methods detected hardly any emigrating CTS thymocytes from the thymus. These results indicate that emigration defect lies in the thymus of CTS mice, and suggest that this mutation is due to abnormal releasing mechanisms occurring between the thymus and the bloodstream. Complete delineation of the precise mechanisms of this defect, however, requires further studies.

Animals↗

Regional differences in the response of the isolated sino-atrial node of the rabbit to vagal stimulation.

1. The effects of brief postganglionic vagal nerve stimulation on electrical activity in different regions of the rabbit sino-atrial node and surrounding atrial muscle were recorded. 2. At the centre of the node (the leading pacemaker site), the brief stimulation resulted in a large hyperpolarization followed by a depolarization and a shortening of the action potential. All effects were short lasting (time to 90% recovery of membrane potential, 0.8 s). 3. At other sites within the node and in the surrounding atrial muscle, although there was still a substantial action potential shortening, the hyperpolarization was smaller and the depolarization was small or absent. All effects were longer lasting (time to 90% recovery in atrial muscle, 11.4s). 4. The depolarization in the centre of the node was abolished by block of the hyperpolarization-activated current (i(f)) by Cs+ or zatebradine (UL-FS 49). It could, therefore, result from the activation of i(f) during the preceding hyperpolarization. 5. Block of acetylcholinesterase by eserine greatly slowed recovery from vagal stimulation at all sites, demonstrating that recovery is dependent on acetylcholinesterase. The longer lasting effects of vagal stimulation in atrial muscle, therefore, result from lower acetylcholinesterase activity. 6. Vagal stimulation resulted in a short lasting initial slowing of spontaneous action potentials followed by a long-lasting secondary slowing. Whereas the initial slowing coincided with the effects of vagal stimulation on the centre of the node, the secondary slowing coincided with the slower effects of vagal stimulation on the surrounding atrial muscle. The secondary slowing was reduced by 68 +/- 11% (n = 5) by cutting the atrial muscle away from the node. 7. It is concluded that the short-lasting initial slowing of spontaneous action potentials is the direct effect of vagal stimulation on the centre of the sino atrial node, whereas the secondary slowing is the result of the longer lasting effects of vagal stimulation on the surrounding atrial muscle and the electrotonic suppression of the node by the muscle.

Action Potentials↗

Chemistry of the lyxose-containing mycobacteriophage receptors of Mycobacterium phlei/Mycobacterium smegmatis.

Mycobacterium phlei (strain Timothy) (Mycobacterium smegmatis ATCC 19249) is characterized by the presence of a family of alkali-labile glycolipids, reminiscent of the trehalose-containing lipooligosaccharide class of antigens but lacking the nonreducing trehalose core. Through a combination of methylation analyses, 1H and 13C NMR, two-dimensional 1H/1H and 1H/13C NMR, fast atom bombardment-mass spectrometry, gas chromatography-mass spectrometry, and other analytical techniques, these new structures were shown to possess three distinct features. Firstly, they contained the pentose D-lyxose (Lyx), rarely found in biology, but an epimer of D-arabinose, a key component of the mycobacterial cell wall arabinogalactan and lipoarabinomannnan. Thus, it was apparent that these glycolipids are the same as those described by Bisso et al. and attributed with phage receptor properties [Bisso, G., Castelnuovo, G., Nardelli, M.-G., Orefici, G., Arancia, G., Lanéelle, G., Asselineau, C., & Asselineau, J. (1976) Biochemie 58, 87-97]. Secondly, the complex oligosaccharides within the glycolipids contain the repeating units Lyxn(6-O-CH3-Glc)m and Lyxn(6-O-CH3-Glc)mMan1, where n+m equal to approximately 16 glycosyl residues. Thirdly, the M. phlei glycolipids were found to be heavily O-acylated, such that every D-Lyx residue invariably possesses an acyl function at position -2 and, in some instances, at both positions -2 and -4. The chemical characterization of these glycolipids, not feasible 20 years ago, clearly demonstrates that they are distinct from the type- and species-specific glycopeptidolipids, lipooligosaccharides, phenolic glycolipids, and the genus-specific phosphatidylinositol-based lipoglycans of mycobacteria. This present and previous studies begin to define the precise structural requirements responsible for the attachment of mycobacteriophage to the host cell wall.

Carbohydrate Conformation↗

Definition of the mitogenic factor (MF) as a novel streptococcal superantigen that is different from streptococcal pyrogenic exotoxins A, B, and C.

Human T cell activation by recombinant mitogenic factor (rMF) was investigated in comparison with that by recombinant streptococcal pyrogenic exotoxins (rSPE) A, B, and C. Recombinant MF, rSPEA, and rSPEC were mitogenic for peripheral blood mononuclear cells (PBMC), whereas rSPEB was not. Recombinant MF required only HLA-DR for the stimulation of PBMC, as determined using monoclonal antibodies (mAb) to HLA class II molecules and the mouse L cells transfected with HLA class II molecules. Recombinant SPEA and rSPEC required HLA-DR or HLA-DQ molecule. Recombinant MF selectively stimulated V beta 2, V beta 7, V beta 8, V beta 18 and V beta 21-bearing T cells, whereas rSPEA and rSPEC activated V beta 2 and V beta 6-bearing T cells as evaluated by the quantitative T cell receptor (TCR) analytical method. No clonality was observed in the nucleotide sequences of complementarity determining region 3 of TCR V beta in T cells responding to rMF. The profiles of cytokine production by PBMC in response to rMF, rSPEA, and rSPEC were quite similar. In summary, these results demonstrate that both HLA class II molecules and the TCR V beta required for rMF-mediated T cell activation are distinct from those required for rSPEA or rSPEC-mediated activation. Therefore, the MF is a novel streptococcal super-antigen which is different from SPEA, SPEB, and SPEC.

Bacterial Proteins↗

Acetazolamide produced blood flow velocity changes measured by laser Doppler in gerbils with reduced CBF.

The effect of acetazolamide on the cerebral blood flow was studied in gerbils with unilateral carotid ligation. According to the effect of ligation the animals were divided into three groups: first group-the reduction more than 70%, second-CBF reduction 30-70% and the third group-CBF reduction less than 30%. The effect of acetazolamide administration was closely related to the effect of carotid ligation. More reduction of CBF was produced by carotid ligation, less increase of CBF after acetazolamide injection was noticed. The acetazolamide vascular reserve test was found a sensitive and useful method for detecting even modest reduction of vascular reserve in animals with slight - less than 30% CBF decrease following carotid ligation.

Acetazolamide↗

Relationship between perinatal appearance of cellular retinol-binding protein, type II and retinal reductase activity in chick liver.

To explore a role of the transiently appearing cellular retinol-binding protein, type II (CRBP(II)) in perinatal chick liver, we have examined whether the relationships exist among the perinatal changes in hepatic CRBP(II) protein and mRNA levels, retinal reductase activity and beta-carotene levels in liver and serum. Northern blot analysis for hepatic CRBP(II) revealed a transient expression of CRBP(II) mRNA around hatching. The protein of CRBP(II) was also expressed transiently and the highest levels of CRBP(II) were found in the livers 1-3 days after birth. The retinal reductase activity was very low at embryonic age, but its activity rapidly rose at hatching, peaking at 1 day after birth, followed by a gradual decrease to a lower level in 7-day-old chicks. This perinatal pattern of the retinal reductase activities was similar to the pattern of transient appearance of the hepatic CRBP(II), and was also paralleled to the developmental changes in serum and liver beta-carotene concentrations. These findings suggest that hepatic CRBP(II) transiently appearing during the perinatal period may involve in metabolizing hepatic beta-carotene, directing the retinal to the retinal reductase and leading further to the subsequent esterification of the converted retinol.

Alcohol Oxidoreductases↗

Electropharmacology of Ro 22-9194, a new antiarrhythmic agent.

1. Ro 22-9194 (> or = 10 microM) caused a concentration-dependent decrease in the maximum upstroke velocity (Vmax) and shortening of action potential duration in guinea-pig ventricular cells. 2. The Vmax inhibition by Ro 22-9194 was enhanced in a use-dependent manner. A time constant for Vmax recovery from the use-dependent block was 9.3 sec. Conditioning depolarizing clamp experiments in ventricular cells indicated that Ro 22-9194 may block sodium channels, mainly during the activated state. 3. Ro 22-9194 > or = 30 microM inhibited calcium inward current (Ica) of the ventricular cells. 4. In dogs in vivo Ro 22-9194 (0.1-3 mg/kg, IV) caused a dose-dependent prolongation of atrioventricular conduction time with greater prolongation of His-ventricular (HV) than atrio-His (AH) intervals. Ro 22-9194 had a potent inhibitory action against various types of model arrhythmias. 5. Ro 22-9194 may exert its antiarrhythmic activity primarily by a use-dependent sodium channel block. From the onset and offset kinetics of the use-dependent block, it belongs to the intermediate kinetic Class I drugs. From the state-dependence of the channel block, it belongs to activated channel blockers.

Action Potentials↗

Centroblastic and centroblastic-centrocytic lymphomas associated with prominent epithelioid granulomatous response without plasma cell differentiation: a clinicopathologic study of 12 cases.

To clarify the clinicopathologic features of B-cell lymphoma associated with prominent epithelioid granulomatous responses other than immunocytomas, 12 patients were studied. There were six men and six women. The lymphoma generally affected elderly patients (median age, 58.5 years) and was mostly nodal in origin. Seven of the 12 patients had a localized lesion (stage I or II), and five had an advanced lesion (stage III or IV). Histologically, four patients showed a follicular growth pattern and eight a diffuse growth pattern. Based on the updated Kiel classification, nine patients showed centroblastic lymphomas, and three showed centroblastic-centrocytic lymphomas. The epithelioid cells were accumulated in large, poorly demarcated masses. Trabecular fibrosis compartmentalized in the lymph nodes, producing a vague nodular pattern in low-power fields. Immunohistochemical studies of the tumor cells revealed positive membrane staining with L26 in all 12 patients and with LN-1 antibody in 9 of 10 patients. Expression of the bcl-2 protein was present in all seven patients tested. Genotypic investigation exhibited germline configuration of the immunoglobulin heavy chain gene, the T-cell receptor beta-chain gene and the bcl-2 gene in all three patients investigated. By in situ hybridization, Epstein-Barr virus genomes were detected in only a few tumor cells in three of the patients tested. This study indicated that most, if not all, of the B-cell lymphomas with prominent epithelioid granulomatous responses other than immunocytoma were of follicular center cell origin.

Adult↗

Root canal irrigation with citric acid solution.

The purpose of this study was to investigate various properties of citric acid and EDTA solution as decalcifying and cleansing agents in root canal irrigation, and antibacterial effects of citric acid and EDTA solution. Powdered dentin-resin mixtures were used for evaluating the decalcifying effect of citric acid and EDTA solution. Twelve bacterial strains isolated from infected root canals, were used to evaluate the antibacterial effects of citric acid and EDTA solution. Powdered dentin-resin mixture was found to be more soluble in a 0.5, 1, and 2 M citric acid solutions than in a 0.5 M EDTA solution. Citric acid solution showed antibacterial effects on all the bacteria used.

Anti-Infective Agents, Local↗

Ezrin, radixin and moesin are possible auto-immune antigens in rheumatoid arthritis.

In order to deduce which cellular molecules react with the sera from patients with rheumatoid arthritis (RA), human and mouse cellular extracts were fractionated stepwise, by ethanol precipitation and their reactivity analysed by Western blotting. It was found that three cytoplasmic molecules with molecular weights of 80,000, 81,000 and 77,000 were immunoreactive and they were identified as ezrin (E), radixin (R), and moesin (M), respectively, by partial amino acid sequencing. Using cDNA clones of these human molecules, recombinant proteins were produced in Escherichia coli and used to enable the antigens to detect the antibodies in the sera of patients with RA. Of 71 sera tested, 24 sera (33.8%) reacted with at least one of three recombinant antigens, although there was no significant correlation between the presence of the antibodies and clinical manifestations, such as disease duration or stage. There was also no discernible relationship to other auto-antibodies such as antinuclear antibodies (ANA) and rheumatoid factor. The results suggest that ERM proteins are possible novel auto-immune target antigens for RA.

Adult↗

Ion channel blockers in the treatment of chronic heart failure.

Strategies for pharmacological treatment of chronic congestive heart failure (CHF) are discussed from the viewpoint of cardiac ion channel modulations. It remains controversial as to whether Na channel blockers, which are the most effective drugs to suppress ventricular arrhythmias, can improve the prognosis of chronic CHF. As far as recent knowledge of interactions between the Na channel and its blocker is concerned, lidocaine-like agents such as mexiletine, which inhibit the Na channel current by binding to the channel in the inactivated state, are recommended because they can suppress premature ventricular contractions without prolongation of QRS complexes of sinus beats. To develop a new agent for the treatment of chronic CHF, we extracted the common features of electropharmacologic actions shared by amiodarone and vesnarinone, both of which have been reported to reduce the mortality of patients with chronic CHF. It is concluded that increases in the action potential duration (APD) of ventricular muscle mediated through an inhibition of the delayed rectifier K channel (IK channel) and a reduction of sinus node firing through an inhibition of L type Ca channel in addition to IK channel inhibition, are essential for the treatment of chronic CHF.

Amiodarone↗

Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein.

Genetic and embryological studies in the mouse demonstrated functional differences between parental chromosomes during development. This is due to imprinted genes whose expression is dependent on their parental origin. In a recent systematic screen for imprinted genes, we detected Peg3 (paternally expressed gene 3). Peg3 is not expressed in parthenogenones. In interspecific hybrids, only the paternal copy of the gene is expressed in the embryos, individual tissues examined in d9.5-13.5 embryos, neonates and adults. Peg3 mRNA is a 9 kb transcript encoding an unusual zinc finger protein with eleven widely spaced C2H2 type motifs and two groups of amino acid repeats. Peg3 is expressed in early somites, branchial arches and other mesodermal tissues, as well as in the hypothalamus. Peg3 maps to the proximal region of chromosome 7. Consistent with our findings, maternal duplication of the proximal chromosome 7 causes neonatal lethality. This region is syntenic with human chromosome 19q13.1-13.3 (refs 10,11), where the genes for myotonic dystrophy and a putative tumour suppressor gene are located.

Amino Acid Sequence↗

In vitro differentiation and commitment of CD4+ CD8+ thymocytes to the CD4 lineage, without TCR engagement.

Thymocyte positive selection is based on protection of immature CD4/CD8 double-positive (DP) thymocytes from apoptosis and their differentiation into CD4 or CD8 single-positive (SP) cells. Intracellular signals essential for positive selection appear to be induced through the TCR and some of the accessory molecules including LFA-1, CD4 and CD8 upon interaction with thymic stromal cells. The signals, however, still remain to be identified. Since physiological levels of glucocorticoids potentially induce or enhance thymocyte apoptosis even in vivo, the signals are likely to inhibit the apoptotic effect of glucocorticoids. We have previously shown that proper cross-linking of TCR-CD3 with LFA-1, CD4 or CD8 inhibited glucocorticoid-induced thymocyte apoptosis in vitro, and that a proper combination of the calcium ionophore, ionomycin and the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), mimicked the inhibitory effect. Here we determined whether this combination of ionomycin and PMA induces differentiation of isolated DP thymocytes from normal and TCR transgenic mice. We found that pretreatment of DP thymocytes with ionomycin and PMA followed by 1 day culture of the cells without the reagents resulted in the differentiation of the cells into CD4 SP and CD4+ CD8lo T cells that have mostly committed to the CD4 lineage. The changes in expression of other differentiation markers were also in good accordance with those associated with positive selection, except the final maturation. The results indicate that moderate and transient increases in intracellular Ca2+ level and PKC activity induce differentiation and commitment of DP thymocytes to the CD4 lineage, and suggested that the biochemical pathway leading to positive selection is based on a similar mechanism.

Animals↗