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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 307 records · Page 17Linked to original sources

Crucial role of CD8-positive lymphocytes in glomerular expression of ICAM-1 and cytokines in crescentic glomerulonephritis of WKY rats.

CD8-positive lymphocytes (CD8+ lym) and ICAM-1/LFA-1 interaction have been implicated in the glomerular accumulation of monocytes/macrophages (Mo/Mphi) and crescent formation in antiglomerular basement membrane (anti-GBM) glomerulonephritis of WKY rats. In the present study, the role of CD8+ lym in the expression of ICAM-1 and inflammatory cytokines as well as in the accumulation of Mo/Mphi in the glomeruli was examined by RNase protection assay and immunofluorescence microscopy. ICAM-1 expression was apparent at 1 h and markedly enhanced at day 3 in glomeruli after an anti-GBM Ab injection in parallel with glomerular accumulation of Mo/Mphi. Expression of mRNA for IL-1beta, TNF-alpha, and IFN-gamma, known to enhance ICAM-1 expression, and MIP-1alpha, MIP-1beta, and MCP-1, known to activate leukocyte integrins or to act as chemokines, were also induced in the glomeruli at a mRNA level in a profile similar to that of ICAM-1 expression. By depleting the CD8+ lym in the circulation, the increased glomerular expression of ICAM-1 and the cytokines, except IL-1beta, and the Mo/Mphi accumulation were suppressed, indicating a crucial role of CD8+ lym in the accumulation of Mo/Mphi through stimulation of ICAM-1 and induction of cytokines.

Animals↗

Structural scoliosis model in dogs with experimentally induced syringomyelia.

STUDY DESIGN: Animal scoliosis model associated with syringomyelia. OBJECTIVE: To investigate the pathogenesis of scoliosis produced in dogs with kaolin-induced syringomyelia. SUMMARY OF BACKGROUND DATA: Kaolin injected into the cisterna magna produces basilar arachnoiditis, leading to hydrocephalus and syringomyelia. There have been no reports on scoliosis associated with kaolin-induced syringomyelia. METHODS: Kaolin was injected percutaneously into the cisterna magna of 11 beagles 6-8 weeks after birth. Roentgenograms, computed tomography, and magnetic resonance imaging were obtained. The spinal cord and the paraspinal muscles were examined histologically. Structural changes of the vertebral column were analyzed with calcein and tetracycline labeling. RESULTS: Hydrocephalus occurred in nine dogs. A communicating syringomyelia appeared in five dogs. Mild scoliosis developed in two dogs, and severe cervical scoliosis in one dog. In the syringomyelia cases, acute or subacute inflammatory changes were found in the spinal cord. Damage of the anterior and posterior horn cells was more marked in the scoliotic animals than in the nonscoliotic animals. In three of the syringomyelia cases, including two scoliosis cases, the paraspinal muscles revealed neurogenic changes. The deformed vertebrae appeared to diminish rather than to increase the deformity in severe scoliosis. CONCLUSION: The exact mechanism of the development of scoliosis could not be identified, although an etiologic relation with malfunction of the central nervous system was noted. This model may be useful to study scoliosis experimentally.

Animals↗

Juvenile amyotrophy of the distal upper extremity: pathologic findings of the dura mater and surgical management.

STUDY DESIGN: Five cases of juvenile amyotrophy of the distal upper extremity were reviewed retrospectively to elucidate the pathophysiology of spinal cord dysfunction and the results of surgical management. OBJECTIVES: To clarify the pathogenesis of juvenile amyotrophy of the distal upper extremity and to present the results of a new surgical treatment. SUMMARY OF BACKGROUND DATA: Hirayama first reported this disorder in 1959. It is characterized by juvenile onset, slow progression, and involvement of the unilateral distal upper extremity. Recently, compression of the cervical spinal cord during neck flexion was implicated as a possible etiology of the disorder, but the exact etiology is still unknown. The value of surgical treatment for patients with juvenile amyotrophy of the distal upper extremity has not been established. METHODS: The clinical and radiographic characteristics of five patients with juvenile amyotrophy of the distal upper extremity were examined. All five patients were treated surgically with duraplasty in combination with posterior spinal fusion. Dynamic and computed tomographic myelography were performed before and after surgery. Intraoperative ultrasonography and conductive spinal cord evoked potentials were recorded before and after duraplasty. The surgical results and the histology of the resected dura were studied. RESULTS: Myelograms taken with the neck in a neutral position showed that the spinal cord was flattened in all five patients. When the neck was flexed, the dura and the spinal cord were compressed further. Intraoperative ultrasonography during neck flexion revealed an anterior shift of the spinal cord and decreased spinal cord pulsation. Amplitude of the conductive spinal cord evoked potentials decreased with neck flexion but increased after dural incision. Histologically, the dura appeared abnormal in that it contained few elastic fibers without the normal wavy structure. CONCLUSIONS: Juvenile amyotrophy of the distal upper extremity was characterized by inelastic dura that constricts and compresses the cervical spinal cord when the neck is in either a neutral or a flexed position. Abnormal dura appeared to be the cause of juvenile amyotrophy of the distal upper extremity. Duraplasty with spinal fusion are proposed as treatments.

Adolescent↗

Postnatal ontogeny of striatal-enriched protein tyrosine phosphatase (STEP) in rat striatum.

The present study was undertaken to examine developmental change in expression of striatal-enriched protein tyrosine phosphatase (STEP) in the postnatal striatum of rats. For this purpose, immunohistochemical staining and transimmunoblotting analyses were carried out using a cDNA-generated polyclonal antibody to the STEP with a molecular weight of 46 kDa. Immunostaining showed that in neonatal striatum STEP-immunoreactivity was found in discrete patches composed of many immature cells, which corresponded to the tyrosine hydroxylase-immunopositive "dopamine islands." With development there was an increase in staining intensity and in the number of positively reacting cells. By 4 weeks postnatally, STEP-immunoreactivity was almost homogeneously distributed throughout the striatum, as was seen at the adult stage. Immunoblotting analysis showed that STEP protein expression abruptly increased from 2 to 4 weeks postnatally when it reached the adult level. These findings suggest that STEP is involved in development and maturation of the striatal neurons.

Animals↗

GABA receptor agonist promotes reformation of the striatonigral pathway by transplant derived from fetal striatal primordia in the lesioned striatum.

Striatal lesions are known to cause the anterograde transneuronal degeneration of the substantia nigra pars reticulata (SNr) neurons in consequence to loss of GABAergic inhibitory striatonigral efferents. The present study was undertaken to examine whether long-term intraventricular administration of the GABA agonist muscimol could promote reformation of the striatonigral pathway arising from transplants by rescuing host SNr neurons from transneuronal death in rats with striatal ischemic lesions. Compared to nongrafted rats with striatal lesions, (i) a prominent axonal projection from the transplants to the ipsilateral substantia nigra, (ii) a significant increase in number of survived neurons in the ipsilateral SNr, and (iii) a significant reduction in number of apomorphine-induced turning behaviors were found in grafted animals with muscimol infusion, but not in those without muscimol administration. These findings suggest that preservation of the host target neurons for grafted cells may increase an efficacy of cerebral implants in establishment of the host-graft fiber connections, possibly, leading to functional restoration.

Animals↗

Characterization of cytokine and iNOS mRNA expression in situ during the course of experimental autoimmune myocarditis in rats.

Ribonuclease protection assay was used to demonstrate mRNA expression of several cytokines as well as inducible NO synthase (iNOS), constitutive endothelial NO synthase (cNOS) and perforin in the myocardium during the course of experimental autoimmune myocarditis (EAM) in rats. Interleukin 2 (IL-2) appeared in the initial inflammatory phase (day 14), subsided in the maximum inflammatory phase (day 19) and disappeared by the recovery phase (day 25). mRNA of IL-3 beta, interferon gamma INF-gamma and tumor necrosis factor alpha (TNF-alpha) were detected only in the maximum inflammatory phase and iNOS also appeared for several days at this time. In contrast. IL-10 mRNA was detected after the maximum inflammatory stage and persisted into the recovery phase (days 25-36). Although transforming growth factor beta 1 (TGF-beta 1) could be detected in all phases, the expression was markedly enhanced in the maximum inflammatory phase and gradually diminished (around day 36) to basal levels. Perforin mRNA was not detected at any point in the disease. Besides macrophages and CD4 T cells, a number of neutrophils were found in the myocardium especially at peak inflammatory stage. We suggest that antigen (Ag) primed Ag presenting cells or macrophages interact with T cells (Th1) to produce IL-2 and subsequent IFN-gamma, which further activates macrophages in the myocardium. Consequently, TNF-alpha and iNOS may inflict tissue damage to myocardium. It is also suggested that TGF-beta) and one representative Th2 cytokine, IL-10, help inhibit inflammation. These findings suggest that Th1 and Th2 cytokines are produced at different stages of EAM and modulate the inflammation and the course of EAM.

Animals↗

The characterization of reconstituted passenger leukocytes on the induction of tolerance in rat liver transplantation.

The tolerance induced by orthotopic liver transplantation [DA (RT1a) rats to PVG (RT1c) rats] can be prevented by total body irradiation of the donor rat. Reconstitution of the irradiated donor with DA splenic leukocytes reintroduces this tolerance. To investigate the major histocompatibility complex (MHC) specificity of passenger leukocytes, irradiated DA donors were reconstituted by third-party BN (RT1n) splenic leukocytes. The reconstitution with BN splenocytes re-established DA-specific tolerance in PVG recipients, as confirmed by subsequent DA cardiac allografting, while BN hearts were rejected with second-set tempo. To determine which cell components play an important role in re-establishing liver graft tolerance, DA splenic leukocytes were further purified into three types: T, B, and adherent cells. Only "T-cell-enriched" preparations restored liver graft tolerance in three out of five PVG recipients. These results suggest that passenger leukocytes of differing MHC types can help to induce liver-specific tolerance and that T cells in the liver graft may be essential to regulate tolerance induction.

Animals↗

Bone morphogenetic protein-2 stimulates differentiation of cultured spinal ligament cells from patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by heterotopic bone formation occurring in spinal ligament, causing severe compression myelopathy. In order to investigate the mechanism of OPLL development, we isolated spinal ligament cells from OPLL patients as well as non-OPLL patients, and established 10 OPLL cell lines and 7 non-OPLL cell lines, respectively. We analyzed the effects of bone morphogenetic protein-2 (BMP-2) on these cells with respect to alkaline phosphatase (AP) activity, DNA synthesis, and collagen production. BMP-2 caused a significant increase of AP activity in 4 OPLL cell lines, whereas the activity did not change in any non-OPLL cells. Among OPLL cells, BMP-2 stimulated DNA synthesis in four cell lines and procollagen type I carboxyl-terminal peptide (PICP) synthesis in five cell lines. Some non-OPLL cells also responded to BMP-2, as there was an increase of DNA synthesis in three cell lines and PICP synthesis in one cell line. These data collectively indicate that BMP-2 preferentially induces osteogenic differentiation in OPLL cells rather than in non-OPLL cells. OPLL cells, therefore, exhibit a different response to BMP-2 than non-OPLL cells, suggesting that the expression of BMP receptor(s) and/or the signal transduction initiated by BMP-2 in the spinal ligament cells of OPLL patients somewhat deviate from those in normal spinal ligament cells. Such abnormal characteristics of OPLL cells as described here provide some clues to the clarification of the pathogenesis of OPLL.

Alkaline Phosphatase↗

Grapevine berry inner necrosis, a new trichovirus: comparative studies with several known trichoviruses.

Biological, morphological and serological properties of grapevine berry inner necrosis virus (GINV), the casual virus of grapevine berry inner necrosis disease occurring in Japan, were compared with those of several known trichoviruses. Host range and particle length of GINV were quite similar to those of apple chlorotic leaf spot trichovirus (ACLSV). In ultrathin sections of the infected tissues, GINV particles existed in aggregated masses in the cytoplasm of vascular parenchyma and mesophyll cells. No virus specific inclusion bodies, such as pinwheels, viroplasmas or vesicles were observed. Serological relationships were not found between GINV and ACLSV, grapevine virus A or grapevine virus B. The cDNAs of the 3'-terminal region of the GINV genome were synthesized from poly (A)+RNAs extracted from infected tissues by PCR-selected cDNA subtraction and 3'-RACE PCR. The sequence of the 3'-terminal 2469 nucleotides contained three open reading frames (ORF) encoding a protein with the conserved motifs of RNA polymerase (ORF1), a 39 kDa putative movement protein (ORF2) and a 22 kDa protein (ORF3). The 22 kDa protein expressed in Escherichia coli reacted with antiserum against GINV, indicating that it is the coat protein of GINV. Polymerase and coat protein amino acid sequence comparisons and phylogenetic analyses with nine species of the genera Trichovirus and Capillovirus indicated that GINV is a new trichovirus relatively close to ACLSV.

Amino Acid Sequence↗

Log-normality of distribution of occupational exposure concentrations to cobalt.

In evaluating occupational exposures, the daily exposure levels of a worker are generally assumed to be distributed log-normally between days. When there are many workers in a job group, the individual worker's arithmetic means are assumed to be distributed log-normally. Using the cobalt exposure data in a hard metal factory, these assumptions were examined with the Shapiro-Wilk W test. The hypothesis of log-normality was accepted in all cases, while the hypothesis of normality was rejected in some cases.

Cobalt↗

Expression of mRNAs of pancreatic and L type RNase inhibitors as a function of age in different tissues of SAMP8 and BDF1 mice.

Turnover of mRNAs could be influenced not only by the synthesis of different mRNA species but also by the altered levels of mRNA-degrading enzymes such as RNases and their endogenous inhibitors. In the present work we evaluated possible age-related changes in the mRNA levels of pancreatic as well as L type RNase inhibitors in five different tissues of the BDF1, SAMR1 and SAMP8 using Northern blots. The mRNA levels varied depending on the tissues and mouse strains studied. In certain instances such as the RNase L inhibitor mRNA levels in the lung of SAMP8, there was a statistically significant (P < 0.05) increase of 40% if we compared the young (3 months old) and old (18 months old) animals. These changes could possibly contribute to a certain extent to the already lower levels of mRNAs due to decreased transcriptional activities in aged animals.

Aging↗

Antibody efficacy as a keen index to evaluate influenza vaccine effectiveness.

The efficacy of the influenza vaccine is often understimated, due to the dilution of the outcome by noninfluenzal illnesses. We thus explored the methodology to evaluate the effect of the inactivated influenza vaccine under the following strict conditions: an assessment of the effectiveness on clinical illness among healthy adults in a small-scale mixed epidemic during the 1991-1992 season. The vaccine antigens included were A/Yamagata/32/89 (H1N1), A/Beijing/352/89 (H3N2), and B/Bangkok/163/90. Two indices were analyzed: "vaccine efficacy", a comparison between the vaccinees and the nonvaccinees; and "antibody efficacy", a comparison between those with and those without a protective level of pre-epidemic hemagglutination-inhibition (HAI) antibody. The odds ratio (OR) and its 95% confidence interval (95% CI) was calculated by the logistic regression model. A decrease in the age-adjusted OR of vaccination was not statistically significant: 0.54 (95% CI: 0.19-1.53) corresponding to vaccine efficacy (1-OR) of 46% (-53% to 81%). Among the vaccinees, a significantly decreased OR in those with a higher titer to A/Beijing was observed: 0.14 (0.02-0.92) adjusted for the mutual effects of pre-epidemic antibodies to different vaccine antigens. The adjusted ORs thus calculated for A/Yamagata and B/Bangkok were not found to be statistically significant. The antibody efficacy (1-OR) was estimated to be 86% (8% to 98%) against illnesses related to A/Beijing-like viruses. The product of antibody efficacy (86%) and the proportion of those who achieved a protective level of antibody after vaccination (73% for A/Beijing strain) was 63%, which is theoretically equivalent to the vaccine efficacy. Thus, the antibody efficacy is considered to be an important index, while the vaccine efficacy against clinical illnesses is easily disturbed by extraneous factors in the field trials.

Adult↗

Oxygen-induced embryopathy and the significance of glutathione-dependent antioxidant system in the rat embryo during early organogenesis.

We investigated the effect of glutathione (GSH)-dependent antioxidant system against hydrogen peroxide (H2O2) formation in oxygen-induced embryopathy. Exposure of rat embryos to a high concentration of oxygen (20%) during early neurulation (day 9 to 10) significantly increased the incidence of neural tube defects compared with control embryos (10% vs 0%, p < 0.01) exposed to a low O2 concentration (5%). The concentration of GSH in 20% O2-exposed embryos was significantly reduced compared with that in control embryos (10.68 +/- 0.72 vs 12.34 +/- 0.65 nmol/mg protein, p < 0.001). The activity of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting GSH synthesizing enzyme increased in 20% O2-exposed embryos (24.83 +/- 0.71 vs 21.00 +/- 0.94 microunits/mg protein). Increased activity of gamma-GCS was associated with increased expression of gamma-GCS mRNA. Substantial increases were also observed in the activities of glutathione peroxidase (GPX) and glutathione S-transferase (GST) in 20% O2-exposed embryos. The formation of intracellular H2O2, measured by flow cytometer using 2',7'-dichlorofluorescein diacetate (DCFH-DA), increased in isolated embryonic cells of 20% O2-exposed embryos. The addition of buthionine sulfoxamine (BSO), a specific inhibitor of gamma-GCS, to culture media exposed to 20% O2 produced a marked decrease in the concentration of GSH in association with a further increase in the incidence of embryonic malformations (24.4% vs. 10%, P < 0.01). The addition of 2.0 mM GSH ester to culture media exposed to 20% O2 prevented the development of embryonic malformations through the restoration of normal GSH contents and reduction of H2O2. Our results demonstrated that oxygen-induced embryonic malformations were induced by increased production of H2O2 in the presence of an immature free radical scavenger system. We suggest that impaired responsiveness of the GSH dependent antioxidant system against oxidative stress plays a crucial role in oxygen-induced embryopathy.

Animals↗

High altitude training increases reactive carbonyl derivatives but not lipid peroxidation in skeletal muscle of rats.

The oxidative stress related consequences of physical training at high altitude are not known. The hypothesis was tested that physical training and exposure to high altitude have adverse effects on free radical generation and activities of antioxidant enzymes. The present results showed that 4 weeks of exercise at an altitude of 4000 m increased the activity of Mn-SOD in both white and red types of skeletal muscle. The activities of Cu,Zn-SOD, catalase, and glutathione peroxidase, as well as the level of lipid peroxidation measured by TBARS and lipid hydroperoxides, did not change significantly. In contrast, the level of reactive carbonyl derivatives measured by anti-2,4-dinitrophenylhydrazone antibodies and spectrophotometry showed an increase in both types of muscle of altitude trained rats compared with sea level trained and control groups. It was suggested that the oxidative modification of certain amino acids is due to the increasing gap between activity of SOD and peroxide scavenging enzymes, which results in increases in the number of hydrogen peroxide molecules. Thus, since the mechanism of generation and/or the mode of action of radicals resulting in lipid peroxidation and protein oxidation appears to be different in vivo, both processes should be studied during oxidative stress.

Altitude↗

The prevention of graft-versus-host disease by the serum of liver retransplanted rats.

The effect of serum from orthotopic liver retransplanted rats (re-OLT serum) on graft-versus-host disease (GVHD) was studied in rats. In the re-transplantation model of rat liver, orthotopic liver transplantation (OLT) was carried out in the DA (RT1a) into PVG (RT1c) combination; two days later the DA liver was removed and a new PVG liver implanted into the same recipient (re-OLT). In the in vivo GVHD model, male PVG rats were sublethally irradiated and injected intravenously with 3 x 10(8) DA or BN (RT1n) spleen through the penial vein. Within 1 h of the inoculation, rats of the experimental group were injected with 1 ml of re-OLT serum taken at postoperative day (POD) 7. Rats in the control group received 1 ml of normal PVG serum or syngeneic re-OLT serum (PVG-PVG, PVG-PVG). All PVG rats in the control groups died of GVHD within 21 days after the inoculation of DA or BN spleen lymphocytes. However, when the animals were treated with re-OLT serum, 100% (6/6) of the rats survived more than 60 days, following inoculation with DA lymphocytes but not with BN lymphocytes. The POD 7 re-OLT serum showed a strong inhibition against DA anti-PVG mixed lymphocyte reaction (MLR), although re-OLT serum did not contain soluble DA class I antigens, anti-DA class I or II antibody. The potential GVHD inhibitory factors in re-OLT serum may be two unique immunosuppressive proteins, which have been detected by SDS PAGE and reported previously. We conclude that re-OLT serum has immunosuppressive factors, which, at least in part, prevented the induction of GVHD in rats.

Animals↗