Search PubMed⌕ Search

Biomedical subjects

N Tsuchiya

Publications and source records attributed to N Tsuchiya.

At least 127 records · Page 7Linked to original sources

Lambert-Eaton myasthenic syndrome associated with Sjögren's syndrome and discoid lupus erythematosus.

A 65-year-old woman with facial erythema and hypergammaglobulinemia developed excessive fatigability. A diagnosis of Lambert-Eaton myasthenic syndrome (LEMS) was made from electrophysiological studies. She had symptoms and laboratory data compatible with probable Sjögren's syndrome. Skin biopsy revealed the histological findings of discoid lupus erythematosus. Treatment with 3,4-diaminopyridine resulted in the improvement of fatigability. LEMS should be recognized as a treatable complication of systemic autoimmune diseases.

Aged↗

Antibodies to human cytomegalovirus 65-kilodalton Fc binding protein in rheumatoid arthritis: idiotypic mimicry hypothesis of rheumatoid factor production.

We previously reported that rheumatoid factors (RFs) might bear the internal image of Fc gamma-binding proteins (FcBPs) of herpes family viruses, suggesting the possibility that some RFs may be produced as antiidiotypic antibodies to anti-viral FcBP antibodies. Since human cytomegalovirus (HCMV) has been implicated in the pathogenesis of RA, we made an attempt to detect antibodies to 65 KD major HCMV FcBP in sera and synovial fluid from patients with RA. Western blotting was performed using HCMV-infected MRC-5 cell lysate as the antigen. Eleven of 23 patients with RA possessed strong serum antibodies to HCMV-65 KD protein, whereas such antibodies were found in only 2 of 23 normal controls. In the synovial fluid, 10 of 19 RA patients showed anti-HCMV 65 KD reactivity. Pepsin-digested IgG retained anti-65 KD reactivity, indicating that false-positive reaction due to the presence of IgG Fc portion and/or RF was unlikely. 65 KD protein was shown to be different from human heat shock proteins (hsps) using monoclonal antibodies against human hsps. Patients' IgG F(ab')2 also reacted with the 65 KD protein of purified HCMV virion itself. These results support the possibility that some RFs could be produced as antiidiotypic antibodies to anti-viral FcBP antibodies.

Adolescent↗

[Effects of endothelin-1 on the smooth muscle contractility of human urinary bladder, spermatic cord and prostatic adenoma].

Effects of endothelin-1 (ET-1) on the smooth muscle contractility of human detrusor, spermatic cord and hypertrophied prostatic adenoma were examined in muscle bath studies. ET-1 increased the contractile forces of all above smooth muscle strips in concentration dependent manner. The contractile force induced by 10(-6) M ET-1 was approximately 30% of that induced by 3 x 10(-5) M carbachol in detrusor muscle strips, approximately 40% of that induced by 10(-4) M norepinephrine in spermatic cord muscle strips and almost equal to that induced by 10(-5) M phenylephrine in prostatic adenoma muscle strips. The contractions induced by ET-1 in those muscle strips were not inhibited by any of tetrodoxine, atropine, phentolamine, propranolol and indomethacine. These results suggest that ET-1 may act as a constrictor on lower urinary tract and genital smooth muscles and especially on prostatic adenoma and that ET-1 may affect those smooth muscles directly not through autonomic receptors or prostaglandins.

Aged↗

[Interaction of midazolam and vecuronium in anesthetized patients].

The interaction between midazolam and vecuronium was investigated in 60 patients during isoflurane-nitrous oxide-oxygen anesthesia. Neuromuscular function was evaluated by recording the single twitch of the abductor pollicis muscle. Anesthesia was induced with thiamylal 4 mg.kg-1 or midazolam 0.2 mg.kg-1 followed by injection of vecuronium 0.1 mg.kg-1. Observed values after midazolam were compared with those observed in patients with thiamylal. the onset time and the duration of action until 25% recovery were similar with both groups. Midazolam caused no significant potentiation of neuromuscular blocking agents in comparison with the control. Therefore, there was no evidence of any interaction between midazolam and vecuronium during isoflurane-nitrous oxide-oxygen anesthesia.

Adult↗

Differential mapping of Fc gamma-binding and monoclonal antibody-reactive epitopes on gE, the Fc gamma-binding glycoprotein of herpes simplex virus type 1.

The entire 396 residue extracellular sequence of gE the HSV-1 Fc gamma-binding glycoprotein has been studied to determine epitopes binding to two mAb II-481 and 88S previously demonstrated to react with gE at or near the Fc gamma-binding regions. Overlapping 7-mers constructed from the established sequence were tested with mAb II-481 and 88S along with their Fab fragments. Control mAb of the same IgG 2b subclass as well as whole rabbit and human IgG and Fc were also tested for binding to overlapping linear sequences using the ELISA pin assay to map Fc gamma-binding regions. Six sequences PKTSWRRVS, GLYTLSV, QVASVVLVVQP, PAPPRSWP, CLYHPQLP, and ASTWTSRL were found that constituted major regions binding to the two different mAb of the same specificity. Glycine substitution for each residue within these sequences indicated that arginine 29, tryptophane 70, valine 144, valine 157, arginine 208, histidine 283, and arginine 305 constituted important portions of the II 481 mAb-reactive epitope. Many of the same regions along with one other, GPLHPSW, appeared to be involved in Fc gamma binding. Substitution of glycine for each residue indicated that histidine 67, tryptophane 70, valine 71, valine 157, valine 158, valine 160, valine 161, tryptophane 210, serine 279, cysteine 280, leucine 281, tyrosine 282, histidine 283, proline 284, glutamine 285, proline 287, tryptophane 302, and arginine 305 were important for Fc gamma-binding. Inhibition by gE peptides of rosetting of E sensitized with rabbit IgG antibody around HSV-1-infected cells, as well as inhibition of rosetting using F(ab)2 fragments of rabbit antibodies to these peptides was used to assay relative contributions of all seven regions to Fc gamma-binding activity. Our results provide a tentative map of mAb binding and Fc gamma-reactive sites on gE. mAb and Fc gamma binding of a limited number of individual antigenic amino acids widely distributed among the separate reactive regions suggest that many of the same separate residues contribute both to antigenicity as well as to Fc gamma-binding activity.

Amino Acid Sequence↗

Rheumatoid factors from patients with rheumatoid arthritis react with beta 2-microglobulin.

IgM rheumatoid factors (RF) from 18 sera of rheumatoid arthritis (RA) patients isolated from monomeric IgG affinity columns showed strongly positive ELISA reactions with human beta 2-microglobulin (beta 2m), as well as with recombinant beta 2m. When the same RA sera were adsorbed to beta 2m-Sepharose affinity columns, eluted material showed predominant IgM anti-Fc of IgG and anti-beta 2m reactivity. Inhibition reactions with "RF" obtained from IgG affinity columns showed slightly higher reactivity of RF for Fc over beta 2m; however, when RF from the same RA serum had been adsorbed to and eluted from beta 2m affinity columns, beta 2m showed greater inhibition than Fc for RF reacting with either beta 2m or Fc on ELISA plates. Thus two overlapping populations of RF were identified in RA sera showing reactivity with both beta 2m and Fc of IgG. When RF were isolated from IgG columns, affinity was slightly higher for Fc than beta 2m. Conversely, RF eluted from beta 2m Sepharose reacted slightly more with beta 2 m than Fc. Trypsin digests of a polyclonal RA IgM RF showed no beta 2m reactivity in Fc mu 5 fragments. Fab mu RF retained slight anti-Fc IgG but no residual anti-beta 2m activity. Monoclonal human IgM, IgG, or IgA RF either from mixed cryoglobulins or EBV-stimulated RA lymphoid cell lines showed negative or occasional weakly positive anti-beta 2m activity. Overlapping 7-mer peptide ELISA analysis of the entire 99-amino acid sequence of beta 2m showed a major RF-reactive linear hydrophilic sequence at positions 56-60 which included a 3-amino acid exact homology to positions 401, 403, and 404 of the C gamma 3 domain. A peptide encompassing this sequence produced 90% inhibition of RF binding to whole beta 2m. Substitution of neutral glycines for each amino acid throughout the reactive epitope at positions 56-66 indicated that lysine at position 58 aspartic acid at 59, and tryptophane at 60 represented major portions of the RF-reactive epitope. These findings indicate that human RF derived from patients with RA react with other epitopes besides those present on IgG Fc, including epitopes on human beta 2m. For many years serum RF3 found in patients with RA have been regarded as premier examples of autoantibodies to autologous IgG.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Amyotrophic lateral sclerosis with ophthalmoplegia and multisystem degeneration in patients on long-term use of respirators.

We describe two patients with sporadic amyotrophic lateral sclerosis (ALS), who had developed progressive external ophthalmoplegia of a predominantly supranuclear type while they survived on respirators, and displayed histopathological abnormalities both typical and atypical of ALS. Patient 1 was a 43-year-old man with ALS of 5-year duration, who had initially exhibited fulminant ALS, and remained on a respirator for 4 years. Patient 2 was a 51-year-old man with ALS of 13-year duration, who remained on a respirator for 8 years. Both patients died in a "totally locked-in state". Autopsy of both patients revealed not only histopathological abnormalities consistent with ALS, but also multisystem degeneration which involved the pontine tegmentum, substantia nigra, Clarke's dorsal nuclei and spinocerebellar tracts. In addition, Patient 2 displayed intracytoplasmic neuronal basophilic inclusion bodies which exhibited marked immunoreactivity to anti-ubiquitin antibodies. Our case reports indicate that the longer survival which is possible through the use of respirators may make one subgroup of ALS patients prone to develop atypical clinical and neuropathological features which are not observed during the natural course of ALS.

Adult↗

Prolonged survival of MRL-lpr/lpr mice treated with Tripterygium Wilfordii Hook-F.

MRL-lpr/lpr mice were treated with Tripterygium Wilfordii Hook-F (TWHF), a Chinese herbal medicine successfully used for human rheumatoid arthritis. Dramatic prolongation of survival and the reduction of urinary protein were observed in mice treated with a high dose of TWHF (20 mg/kg, three times a week) compared to the control animals receiving solvent alone. A slight but significant reduction was also seen in the degree of lymphadenopathy and arthritis with the high dose treatment. Surprisingly, no significant difference was present in IgM rheumatoid factor and IgG anti-double-stranded DNA antibody levels or in the histopathology of lupus nephritis. These results indicate the dissociation of histopathological renal disease and the degree of proteinuria or the life span. Although further pharmacological analysis is required, TWHF might be potentially useful for diseases such as systemic lupus erythematosus or nephrotic syndrome.

Animals↗

Changes of autonomic receptors following castration and estrogen administration in the male rabbit urethral smooth muscle.

Effects of castration and estrogen administration on the distribution of autonomic receptors in the male rabbit urethral smooth muscle were examined. Thirty-eight mature Japanese white rabbits were used. Eight rabbits were used as untreated control. The other 30 rabbits were castrated and 10 of them were administered intramuscularly with 5 mg/kg estrogen 3 times a week for 4 weeks from 12 weeks after castration. Autonomic receptor densities in the urethral smooth muscle were measured by radioligand binding techniques. alpha 1-Adrenergic and muscarinic cholinergic receptor densities decreased significantly after castration and were not affected by estrogen administration. alpha 2-Adrenergic receptor density increased slightly after castration and markedly after estrogen administration. beta-Adrenergic receptors were not affected either by castration or estrogen administration. No significant changes were observed in any receptor affinities. These results demonstrate the effects of castration and estrogen administration on the autonomic receptors in the male rabbit urethral smooth muscle.

Animals↗

Molecular mimicry--hypothesis or reality?

A number of observations support molecular mimicry as a possible pathogenetic mechanism in diseases such as acute rheumatic fever, reactive arthritis after enteric infection or associated with Reiter's syndrome, myasthenia gravis, or even in rheumatoid arthritis. Molecular mimicry can be defined as a sharing of epitopes in linear or 3-dimensional presentation on disparate proteins from entirely different sources--for instance, group A streptococcal membranes and human cardiac myosin. How exposure to or infection with organisms sharing molecular similarity with antigens of the human host can evade tolerance and actually induce a self-reacting humoral or cellular immune response is still not clear; however, a large body of evidence has now been accumulated that documents apparent molecular mimicry mechanisms in these disorders. In some diseases, the molecular mimicry appears to involve human target organs and specific components of the infectious organism, whereas in others the host HLA cell surface molecules appear to share antigens with presumed bacterial or viral initiators of disease.

Arthritis↗

Rheumatoid factors react with Fab fragments of monoclonal antibodies to herpes simplex virus types 1 and 2 Fc gamma-binding proteins.

Human polyclonal IgM rheumatoid factors (RF) were tested in an enzyme-linked immunosorbent assay with monoclonal antibodies (MAb) (II-481 and B10/A8) to glycoprotein E (gE), the Fc gamma-binding protein of herpes simplex virus type 1 (HSV-1), as well as with MAb 88-S to gE of HSV-2. Most of the RF reacted with II-481 and 88-S. Positive reactions were recorded for RF reacting with whole MAb II-481 and 88-S, as well as with their Fab, but not their Fc, fragments. Human monoclonal IgM RF isolated from mixed cryoglobulins showed a similar profile, with reactivity for both whole MAb II-481 and 88-S and for their Fab fragments. Reactivity with MAb to gE was observed regardless of the Gm specificity of the polyclonal RF and the cross-reactive idiotypes (6B6, 17.109, or G6) of the monoclonal RF. No positive reactions were noted between protein A and Fab fragments of any of the anti-gE MAb. These findings indicate that many RF may bear the internal image of the Fc gamma-binding regions of 2 different herpesviruses: HSV-1 and HSV-2.

Antibodies, Monoclonal↗

[Anatomic analysis of canine ureteral smooth muscle structure].

We have investigated the structure of canine middle ureteral smooth muscle anatomically. In a transverse section inner fibers appeared to be longitudinal and outer fibers appeared to be circular. In the parallel sections with the wall of longitudinal ureteral muscle, inner and outer fibers appeared to be oblique in a mesh structure. In parallel sections with the wall of helical ureteral muscle, fibers appeared to be longitudinal. Anatomical analysis showed that canine ureteral smooth muscle is entirely composed of spinal fibers in a mesh structure and that the helical muscle strip have continuous fibers though the inner fibers have a tendency to run longitudinally and the outer fibers circularly.

Animals↗

Rheumatoid factors may bear the internal image of the Fc gamma-binding protein of herpes simplex virus type 1.

Affinity-purified rheumatoid factors (RF) from 20 patients with rheumatoid arthritis were tested for their reactivity with the mAb II-481 against glycoprotein E (gE), the Fc gamma-binding protein of HSV-1, as well as with a panel of mAb against human Fc gamma R. All RF bound to mAb II-481 in preference to mAb IV.3 (anti-human Fc gamma RII) or MOPC 141 (control mAb) which belong to the same IgG2b subclass. Five RF showed strong reactivity with II-481. No significant reactivity was observed between RF and mAb against human Fc gamma R. Non-RF human IgM did not react with any of the mAb. Clear-cut binding to II-481 was also seen with monoclonal IgM-RF derived from MRL/1 mice (mRF-2). The reaction between RF and II-481 was completely inhibited by human IgG. It was also inhibited by BHK cell extract infected with HSV-1, and with purified gE. II-481 inhibited the binding of human IgG Fc to the infected cell extract, confirming that II-481 recognizes the Fc-binding site on gE. II-481 did not react directly with human IgG or Fc of IgG. mAb to human IgG2 showed stronger binding to II-481 than to MOPC 141, suggesting II-481 has conformational similarity to human IgG H chain. These results suggest that at least some RF bear the "internal image" of HSV-1 Fc gamma-binding protein and support the hypothesis that some RF may be generated as anti-idiotype antibodies against antiviral antibodies.

Animals↗

Diagnostic significance of fluorocytophotometric DNA ploidy analysis of gastric cancer with special reference to its comparison with clinical and histopathological diagnosis.

Mithramycin binds stoichiometrically with G-C pairs of nucleotides, thus it is useful for nuclear DNA fluorocytophotometry. In the present study, relationships between clinical features and nuclear DNA ploidy values were explored in 80 gastric cancer cases. For the first time, nuclear DNA ploidy values of tumor tissues even in the same gastric cancer were found to be not always identical, when those were determined at two different sites in the same layer or at two different depths of cancer invasion. The highest DNA ploidy values greater than 9C of the original tumors were significantly more frequently observed in advanced cancer than in early cancer. The highest DNA ploidy values greater than 12 degrees C of the original tumors were significantly more frequently observed in gastric cancer cases with lymph node metastases than in those without lymph node metastases. The highest DNA ploidy values of metastatic tumors in lymph nodes were significantly greater than those of the original tumors. The cell lines with very high nuclear DNA ploidy values, however, usually do not establish new stem lines in metastatic lymph nodes. Borrmann 2 gastric cancer which was clinically diagnosed as the localized type often showed much greater nuclear DNA ploidy values and higher incidence of metastases than Borrmann 3. Therefore, it is not true that Borrmann 2 gastric cancer is less malignant than Borrmann 3. When cancer cells invaded onto the peritoneal surface, through the serosal layer, the highest nuclear DNA ploidy values are significantly reduced for unknown reasons. Therefore, it should be kept in mind that the reduction of highest nuclear DNA ploidy values in these invasive types of gastric cancer patients does not necessarily mean a good clinical sign. Nuclear DNA ploidy analysis is the effective means of cell biological diagnosis for gastric cancer.

Adult↗