[Treatment of arthritis with cyclin-dependent kinase inhibitor p 16INK4a gene].
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Animals↗
Biomedical subjects
N Miyasaka
Publications and source records attributed to N Miyasaka.
Correlations between the apparent diffusion coefficient, water content, and ultrastructure after induction of vasogenic brain edema in cats.
OBJECT: The authors examined the correlation between changes in the apparent diffusion coefficient, regional water content, and tissue ultrastructure after vasogenic brain edema. METHODS: Vasogenic edema was induced in the white matter of six cats by cortical cold lesioning. The trace of diffusion tensor (Trace[D]) obtained from magnetic resonance imaging to measure the orientationally averaged water diffusibility was compared with the corresponding tissue water content determined by gravimetric studies and with ultrastructural water localization. Edema fluid had spread to the subcortical and deep white matter by 4.5 hours postlesioning. The increase in Trace(D) showed a significant linear correlation with the increase in tissue water content, both in the subcortical and deep white matter as follows: y = 45.5x - 2367 (r = 0.94) and y = 37.0x - 1769 (r = 0.93), respectively, where x is the water content (gram water/gram tissue) and y the Trace(D) (x 10(-6) mm2/second). On histological examination, nerve fibers were found to be dissociated in the white matter and the extracellular space was markedly enlarged with protein-rich fluid. No noticeable hydropic swelling of the cellular components was observed. CONCLUSIONS: A linear correlation was observed between increases in Trace(D) and increases in extracellular water volume in in vivo vasogenic brain edema. A similar correlation between the subcortical and deep white matter showing different arrangements of nerve fibers (parallel compared with intermingled, respectively) indicated that measurement of Trace(D) is a suitable parameter for the evaluation of vasogenic brain edema.
Animals↗
Heterogeneity of anterograde fast-pathway and retrograde slow-pathway conduction patterns in patients with the fast-slow form of atrioventricular nodal reentrant tachycardia: electrophysiologic and electrocardiographic considerations.
OBJECTIVES: This study sought to define the electrophysiologic and electrocardiographic characteristics of fast-slow atrioventricular nodal reentrant tachycardia (AVNRT). BACKGROUND: In fast-slow AVNRT the retrograde slow pathway (SP) is located in the posterior septum, whereas the anterograde fast pathway (FP) is located in the anterior septum; however, exceptions may occur. METHODS: Twelve patients with fast-slow AVNRT were studied. To determine the location of the retrograde SP, atrial activation during AVNRT was examined while recording the electrograms from the low septal right atrium (LSRA) on the His bundle electrogram and the orifice of the coronary sinus (CS). Further, to investigate the location of the anterograde FP, single extrastimuli were delivered during AVNRT both from the high right atrium and the CS. RESULTS: The CS activation during AVNRT preceded the LSRA in six patients (posterior type); LSRA activation preceded the CS in three patients (anterior type), and in the remaining three both sites were activated simultaneously (middle type). In the anterior type, CS stimulation preexcited the His and the ventricle without capturing the LSRA electrogram (atrial dissociation between the CS and the LSRA), suggesting that the anterograde FP was located posterior to the retrograde SP. In the posterior and middle types, high right atrial stimulation demonstrated atrial dissociation, suggesting that the anterograde FP was located anterior to the SP. In the posterior and middle types, retrograde P waves in the inferior leads were deeply negative, whereas they were shallow in the anterior type. CONCLUSIONS: Fast-slow AVNRT was able to be categorized into posterior, middle and anterior types according to the site of the retrograde SP. The anterior type AVNRT, where an anteriorly located SP is used in the retrograde direction and a posteriorly located FP in the anterograde direction, appears to represent an anatomical reversal of the posterior type which uses a posterior SP for retrograde and an anterior FP for anterograde conduction. Anterior type AVNRT should be considered in the differential diagnosis of long RP (RP > PR intervals) tachycardias with shallow negative P waves in the inferior leads.
Adult↗
[A case of isocyanate-induced hypersensitivity pneumonitis].
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Alveolitis, Extrinsic Allergic↗
Development of human peripheral TCRBJ gene repertoire.
Previous studies of TCRBJ gene repertoires of human peripheral T lymphocytes showed that all TCRBV family transcripts had some common features in BJ gene usage, and nevertheless, transcripts of each BV family gene had a distinct pattern. To discern how the development of the peripheral BJ repertoire is controlled, the effects of preferential BJ gene rearrangement, thymic selection, and peripheral stimulation on the repertoire formation were investigated. A PCR-ELISA technique was used to examine the immature CD3- CD4+ CD8-, and mature CD3+ CD4+ CD8- and CD3+ CD4- CD8+ thymocytes, and peripheral CD4+ and CD8+ T lymphocytes for their BJ gene repertoires. Analogous to the peripheral repertoire, the BJ gene repertoires of the immature thymocytes displayed common features, and each BV transcript had a distinct pattern. All features were conserved well by those of mature thymocytes and peripheral T lymphocytes. In addition, the BJ gene repertoires of mature CD4 and CD8 thymocytes and peripheral lymphocytes with the same coreceptors were apparently different in a few BV-BJ combinations. The results showed that the overall BJ gene repertoire pattern was developed before antigenic selection. Thus, the preferential BJ gene expression, primarily based on preferential use of certain BJ gene rearrangements, dictates the peripheral BJ gene repertoire, which is then further modified by thymic selection and peripheral stimulation.
Adolescent↗
Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway.
Protein tyrosine phosphorylation plays a crucial role in signaling from the receptor for erythropoietin (Epo), although the Epo receptor (EpoR) lacks the tyrosine kinase domain. We have previously shown that the Jak2 tyrosine kinase couples with the EpoR to transduce a growth signal. In the present study, we demonstrate that Lyn, a Src family tyrosine kinase, physically associates with the EpoR in Epo-dependent hematopoietic cell lines, 32D/EpoR-Wt and F36E. Coexpression experiments in COS7 cells further showed that Lyn induces tyrosine phosphorylation of the EpoR and that both LynA and LynB, alternatively spliced forms of Lyn, bind with the membrane-proximal 91-amino acid region of the EpoR cytoplasmic domain. In vitro binding studies using GST-Lyn fusion proteins further showed that the Src homology (SH)-2 domain of Lyn specifically binds with the tyrosine-phosphorylated EpoR in lysate from Epo-stimulated cells, whereas the tyrosine kinase domain of Lyn binds with the unphosphorylated EpoR. Far-Western blotting and synthetic phosphopeptide competition assays further indicated that the Lyn SH2 domain directly binds to the tyrosine-phosphorylated EpoR, most likely through its interaction with phosphorylated Y-464 or Y-479 in the carboxy-terminal region of the EpoR. In vitro binding studies also demonstrated that the Lyn SH2 domain directly binds to tyrosine-phosphorylated Jak2. In vitro reconstitution experiments in COS7 cells further showed that Lyn induces tyrosine phosphorylation of Stat5, mainly on Y-694, and activates the DNA-binding and transcription-activating abilities of Stat5. In agreement with this, Lyn enhanced the Stat5-dependent transcriptional activation when overexpressed in 32D/EpoR-Wt cells. In addition, Lyn was demonstrated to phosphorylate the EpoR and Stat5 on tyrosines in vitro. These results suggest that Lyn may play a role in activation of the Jak2/Stat5 and other signaling pathways by the EpoR.
Animals↗
[Recent findings on etiological mechanism of autoimmune diseases].
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Apoptosis↗
Cloning and characterization of the rat MAdCAM-1 cDNA and gene.
A cDNA clone for rat MAdCAM-1 homologue was isolated from mesenteric lymph nodes by RT-PCR using primers prepared from the exon sequences of the gene isolated from a genomic library of the WKAH rat, using mouse cDNA as a probe. A 1279 bp cDNA fragment contained an open reading frame (ORF) for a protein of 394 amino acids. Homology of nucleotide sequences between the mouse and rat MAdCAM-1 ORF was 85.1% with an amino acid identity of 80.5%. The rat MAdCAM-1 had two immunoglobulin-like domains, a mucinlike domain and the third immunoglobulin-like domain with a homology to alpha 3 domain of the rat MHC class I molecule. Northern blot analysis demonstrated transcripts in Peyer's patches and mesenteric lymph nodes but not in spleen. Organization of the gene in the rat was similar to that in the mouse, consisting of 5 exons located at about a 4 kbp genomic region.
Amino Acid Sequence↗
Formation of peripheral immunoreceptor repertoire for antigens: potential relationship to the pathogenesis of rheumatoid arthritis.
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Arthritis, Rheumatoid↗
A novel non-polyglutamable anti-folate, MX-68, inhibits the induction of experimental autoimmune uveitis in rats.
MX-68 is a novel antifolate which is chemically designed not to undergo intracellular polyglutamation thus preventing the development of adverse effects. The present study was carried out to examine both the in vitro and in vivo effects of MX-68 on experimental autoimmune uveitis (EAU) and to compare its effect on collagen-induced arthritis (CIA) in rats. EAU was induced by injecting Lewis rats with retinal S-antigen in complete Freund's adjuvant. Either MX-68 or methotrexate (MTX), which forms several polyglutamates intracellularly, was orally administered five days a week for three weeks beginning on the day of immunization. In vivo, both MX-68 and MTX significantly delayed the onset of EAU and inhibited the antibody response to S-antigen in a dose-dependent manner. High dose MX-68 (2.5 mg kg-1 day-1) completely abrogated the induction of EAU. No adverse effects were observed in either MX-68- or MTX-treated rats. However, the cessation of MX-68 administration after a period of three weeks resulted in the induction of EAU. In contrast, both MX-68 and MTX suppressed the severity of CIA without affecting the onset of the disease and inhibited anti-collagen antibody production in a dose-dependent fashion. Discontinuation of the drugs did not result in the recurrence of CIA. In vitro, both MX-68 and MTX significantly suppressed the proliferation of S-antigen- and Con A-stimulated lymph node cells obtained from immunized rats in a dose-dependent fashion. These data suggest that MX-68 may be useful for the treatment of autoimmune diseases including EAU and that the pathophysiology of EAU could be different from that of CIA.
2-Aminoadipic Acid↗
Coronary sinus pacing initiates counterclockwise atrial flutter while pacing from the low lateral right atrium initiates clockwise atrial flutter. Analysis of episodes of direct initiation of atrial flutter.
INTRODUCTION: Rapid atrial pacing in sinus rhythm may directly induce atrial flutter without provoking intervening atrial fibrillation, or initiate atrial flutter indirectly, by a conversion from an episode of transient atrial fibrillation provoked by rapid atrial pacing. The present study was performed to examine whether or not the direct induction of clockwise or counterclockwise atrial flutter was pacing-site (right or left atrium) dependent. METHODS AND RESULTS: We analyzed the mode of direct induction of atrial flutter by rapid atrial pacing. In 46 patients with a history of atrial flutter, rapid atrial pacing with 3 to 20 stimuli (cycle length = 500 - 170 ms) was performed in sinus rhythm to induce atrial flutter from 3 atrial sites, including the high right atrium, the low lateral right atrium, and the proximal coronary sinus, while recording multiple intracardiac electrograms of the atria. Direct induction of atrial flutter by rapid atrial pacing was a rare phenomenon and was documented only 22 times in 15 patients: 3, 11, and 8 times during stimulation, respectively, from the high right atrium, low lateral right atrium, and the proximal coronary sinus. Counterclockwise atrial flutter (12 times) was more frequently induced with stimulation from the proximal coronary sinus than from the low lateral right atrium (8 vs 1, P = .0001); clockwise atrial flutter (10 times) was induced exclusively from the low lateral right atrium (P = .0001 for low lateral right atrium vs proximal coronary sinus, P = .011 for low lateral right atrium vs high right atrium). CONCLUSIONS: Direct induction of either counterclockwise or clockwise atrial flutter was definitively pacing-site dependent; low lateral right atrial pacing induced clockwise, while proximal coronary sinus pacing induced counterclockwise atrial flutter. Anatomic correlation between the flutter circuit and the atrial pacing site may play an important role in the inducibility of counterclockwise or clockwise atrial flutter.
Adult↗
Upregulation of nucleobindin expression in human-activated lymphocytes and non-Hodgkin's lymphoma.
Nucleobindin (Nuc) was originally found to be an enhancement factor of anti-DNA antibody production secreted by a lymphoid cell line derived from a lymphoproliferative MRL/lpr mouse. It has been shown that Nuc has a unique structure containing a DNA- and two calcium-binding domains, and a leucine zipper motif, but its biological roles have not yet been fully elucidated. Expression of Nuc was first studied in human lymphocytes. Expression of Nuc mRNA in normal peripheral blood mononuclear cells was significantly increased upon mitogen stimulation. Anti-human Nuc monoclonal antibody H-1D8 immunoprecipitated Nuc protein in the nuclear extract of Molt-4 cells. Furthermore, in the immunohistochemical staining of tumor specimens from 108 patients with non-Hodgkin's lymphoma (NHL) with H-1D8, H-1D8-positive cells were observed in nearly all cases in varying frequency. According to the Working Formulation, the percentage of cases in which more than 90% of the tumor cells were stained with H-1D8 was 65% in the high grade of the histological malignancy, 54% in the intermediate grade, and 22% in the low grade; however, normal cells surrounding the tumor cells were virtually negative for H-1D8. These results showed that the level of Nuc expression in human lymphocytes reflects the status of activation or proliferation of the cells, thus providing a clue for the further investigation into biological roles of Nuc. In addition, it might be applicable to the clinicopathological estimation of NHL as a novel indicator.
Adolescent↗
Atypical form of the fourth criterion for transient entrainment.
The typical fourth criterion for transient entrainment is defined when both a sudden shortening in conduction interval to and a distinct change in electrogram morphology at a bipolar recording site are demonstrated while performing overdrive pacing of a reentrant tachycardia from a single pacing site at two different constant rates. The purpose of this article was to test the hypothesis that if an intracardiac recording site showing both orthodromic and antidromic capture with entrainment pacing is located suitably distant from the circuit, sudden shortening in conduction interval to that site may occur without any significant change in the bipolar electrogram morphology (i.e., atypical form of the fourth criterion). Atrial overdrive pacing of orthodromic tachycardia was performed in 20 patients with either left anterior (12 patients) or left posterior (8 patients) accessory pathways. We investigated the effects of overdrive pacing from the proximal or distal coronary sinus, specifically effects on the electrogram interval and the electrogram morphology at the right atrial appendage. Overdrive pacing of orthodromic tachycardia from the proximal coronary sinus was performed in 10 of the 12 patients with left anterior accessory pathways; those 10 patients demonstrated the first entrainment criterion at the right atrial appendage site. Overdrive pacing of orthodromic tachycardia at still shorter cycle lengths demonstrated a sudden shortening in conduction interval to the right atrial appendage site. Despite shortening in conduction interval the morphology of the right atrial appendage electrogram was completely or almost identical to that during orthodromic tachycardia, indicating an atypical form of the fourth criterion. This criterion was not demonstrated in patients with left posterior accessory pathways. Thus, atypical fourth entrainment criterion was demonstrated during overdrive pacing of orthodromic tachycardia from the proximal coronary sinus only in patients with left anterior accessory pathways. Demonstration of atypical fourth criterion seems largely dependent on the location of the accessory pathway, the pacing, and the recording sites.
Adolescent↗
Nonfluoroscopic guidance for catheter placement into the coronary sinus under direct vision using a balloon-tipped cardioscope.
The right atrial posterior septum, including the coronary sinus (CS) ostium, is an important landmark in radiofrequency catheter ablation therapy for supraventricular tachycardia or atrial flutter. The anatomical findings around the CS ostium would be useful to determine a target site or line during catheter ablation. The aim of the study was to test the ability of the imaging catheter to identify structures in the posterior septal area of the right atrium and to evaluate the feasibility of guidance for catheter placement in the CS using a cardioscope that we recently developed. In 12 anesthetized dogs, the cardioscope, consisting of a deflectable 7 Fr fiberoptic endoscope with an inflatable and transparent balloon, was introduced into the right atrium via the femoral vein. The cardioscope was manipulated to observe the right atrial posterior septum. A deflectable electrode catheter was inserted via the jugular vein and positioned in the CS under cardioscopic guidance. In 10 of 12 dogs, the right atrial posterior septum, including the CS ostium, and the tendon of Todaro could be anatomically identified by cardioscopy. It was possible to position an electrode catheter in the CS in all 10 dogs under direct vision without fluoroscopy. But the CS ostium could not be detected in the remaining two dogs, although the cardioscope was placed at as many sites as possible. No complication occurred. The balloon-tipped cardioscope appears to be useful in observing the right atrialposterior septum and in guiding an electrode catheter into the CS.
Animals↗
Ceramide, a mediator of interleukin 1, tumour necrosis factor alpha, as well as Fas receptor signalling, induces apoptosis of rheumatoid arthritis synovial cells.
OBJECTIVES: To examine the effects of ceramide, which is a lipid second messenger of cell surface receptors, including tumour necrosis factor alpha (TNF alpha), interleukin 1 (IL1), and Fas receptors, on rheumatoid arthritis (RA) synovial cells. METHODS: Synovial cells from RA patients and normal skin fibroblasts were cultured with cell permeable ceramide (C2-ceramide). Apoptosis was assessed by microscopic observation of morphological changes, nuclear staining, and DNA electrophoresis. DNA synthesis was examined by thymidine incorporation. RESULTS: C2-ceramide induced reversible morphological changes of synovial cells such as cell rounding within four hours. Subsequently, irreversible nuclear changes characteristic to apoptosis were observed at 48 hours. DNA synthesis was not promoted. The addition of ceramide exerted similar effects on cultured dermal fibroblasts. CONCLUSION: Ceramide induced apoptosis in RA synovial cells. Ceramide could be a second messenger specific for apoptosis of RA synovial cells.
Apoptosis↗
Different apparent diffusion coefficient: water content correlations of gray and white matter during early ischemia.
BACKGROUND AND PURPOSE: Early and accurate diagnosis of brain edema in stroke patients is essential for the selection of appropriate treatment. We examined the correlations between the changes in the apparent diffusion coefficient (ADC), regional water content, and tissue ultrastructure during early focal cerebral ischemia. METHODS: The left middle cerebral arteries of cats were occluded with an intramagnet occlusion/recirculation device. T2-weighted, diffusion-weighted, and perfusion imaging were performed repeatedly during the initial 3 hours after occlusion. The ADCs obtained from ADC maps were compared with the corresponding tissue water content values determined by gravimetry and electron microscopic water localization. RESULTS: ADC reduction was detected in areas of low perfusion 15 minutes after occlusion and thereafter. The water content increase correlated linearly with the ADC decreases in both the gray and white matter. However, both the water content corresponding to an ADC value and the rate of ADC change of the gray and white matter differed significantly (P<.05) as follows: y = -10105x + 8533 (r=.86) and y = -6174x + 4611 (r=.67), respectively, where x is the water content (grams water per gram tissue) and y is the ADC (x 10(-6) mm2/s). Hydropic astrocytic swelling was seen in both structures, and in the white matter, oligodendroglial and myelinated axonal swelling and periaxonal space enlargement were observed. CONCLUSIONS: When early ischemic edema in experimental focal cerebral ischemia is evaluated with ADC mapping, the different slopes and intercepts of the water content and ADC correlation lines for the gray and white matter, which probably reflect different ultrastructural localization of water, should be taken into account.
Analysis of Variance↗
Enhancement of hydroxyl radical DNA cleavage by serum anti-dsDNA antibodies in SLE.
Autoantibodies reactive with double-stranded (ds) DNA are a hallmark of systemic lupus erythematosus (SLE), but it is not fully elucidated how these antibodies contribute to the various pathological changes observed in lupus patients. In a previous study, we have found a significant enhancement effect of two murine monoclonal anti-dsDNA antibodies on DNA cleavage by the hydroxyl radical. We have extended this study and have found that purified polyclonal anti-dsDNA antibodies from sera of lupus patients and an MRL/lpr mouse, but not anti-ssDNA antibodies, also enhanced radical cleavage of DNA. The cleavage was inhibited by EDTA, DMSO and thiourea. The antibody preparations per se did not cleave DNA. These results suggest that such an enhancement effect on DNA cleavage is a feature of a significant part of anti-dsDNA antibody population and a possible clue in understanding the roles of anti-dsDNA antibodies in the pathophysiology of SLE under certain circumstances.
Administration, Topical↗
Pulmonary hypertension complicating mixed connective tissue disease.
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Cardiac Catheterization↗