Borna disease virus-reactive antibodies and recent-onset psychiatric disorders.
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Biomedical subjects
Publications and source records attributed to T Sawada.
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In this study the detailed ultrastructure of the dental cuticle at the dentogingival border in monkeys (macaques) was observed. The deciduous molars and permanent premolars with associated gingiva were prepared for thin section electron microscopy. The dental cuticle, seen as a dense amorphous, usually unlaminated layer, was localized between the tooth enamel and the junctional epithelium of the gingiva in close association with the internal basement membrane of the junctional epithelium. High resolution electron microscopy showed that its basic structure was a fine network of irregular anastomosing strands identified as the cord network of the basement membrane which was continuous with that of the lamina densa of the internal basement membrane of the junctional epithelium. In the cuticle. openings of most of the network were filled with a dark amorphous material. These observations suggest that an additional layer of a cord network formed from the basement membrane components, which is probably secreted by the cells of the junctional epithelium during formation of the cuticle, is added to the cord network of the lamina densa of the basement membrane. In addition, a dark amorphous material is deposited within the newly added cord network at the enamel side of the basement membrane. The origin of this dark material still remains to be clarified, but the possibility is that it originates, as has previously been suggested, from either serum protein in gingival exudate or from hemoglobin produced by the degradation of red blood cells.
Certain anti-Fas antibodies, such as RMF2, induce apoptosis of Fas-expressing cells. We applied the Fas/anti-Fas system to induce killing of Fas-expressing immunocytes with resultant immunosuppression. W7TM-1 tumour cells, a rat T-cell line, were inoculated subcutaneously in BALB/c mice and tumour growth was monitored in untreated mice and in mice treated with RMF2. Prior to treatment with RMF2, we examined the expression of Fas in isolated splenocytes and in tumour-infiltrating lymphocytes by flow cytometry and immunohistochemistry, respectively. There was a remarkable increase in Fas-positive lymphocytes, including natural killer (NK) cells, among splenocytes at day 5 after tumour cell inoculation. The number of Fas-positive infiltrating lymphocytes also increased markedly, from day 5 to day 10. We then examined whether RMF2 could induce apoptosis of Fas-positive activated lymphocytes isolated from the spleen at day 5 in vitro. Terminal deoxy (d) -UTP nick end labelling (TUNEL) and Annexin V staining methods showed apoptosis of isolated cells when incubated with RMF2, and typical apoptotic features were confirmed by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) staining. Furthermore, suppression of cellular and humoral immunity was noted in RMF2-treated mice by mixed lymphocyte reaction and assay of serum levels of immunoglobulin G, respectively. Finally, treatment of animals with RMF2 daily from day 5 to day 9 could maintain the tumour size, while the tumour mass began to diminish in untreated mice immediately after reaching a maximum size. We confirmed the enhancing effects of long-term treatment with RMF2, through the induction of immunosuppression, on the growth of unvascularized xenogeneic tumour cell grafts.
The prevalence of antihepatitis virus C (HCV) antibodies in chronic hemodialysis (HD) patients is higher than in normal populations, and yet hepatocellular carcinoma (HCC) is infrequent in chronic HD patients who are HCV antibody positive. In this study, we investigated the characteristics of HCV-antibody-positive patients with HCC on chronic HD. A total of 6,366 cases of HCV-antibody-positive patients on chronic HD therapy was analyzed on the basis of answers to questionnaires on the incidence rate of HCC in 314 Japanese dialysis institutions. HCC was a complication in 114 of 6,222 (1.8%) HCV-antibody-positive patients, and cirrhosis was a complication in 536 of 6,242 (8.6%). The incidence rate of both complications was significantly higher in males than in females, and the incidence rate in the chronic HD patients was much lower than in normal populations. Specific immunological status in patients on chronic HD therapy may be an important key for preventing the progression of chronic HCV hepatitis. However, further research is needed because this study was preliminary and excluded the type of HCV virus, pathological findings, and laboratory data.
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A 50-year-old woman who had undergone lung lobectomy because of lung adenocarcinoma presented with thyrotoxicosis, neck swelling, and cervical lymphadenopathy one month after the operation. The total serum triiodothyronine (T3) and thyroxine (T4) levels were markedly elevated to 514 ng/dL and 26.4 microg/dL, respectively, and serum thyrotropin (TSH) was suppressed to less than 0.005 microU/mL. Although the thyroid gland had been normal before surgery, chest computed tomography (CT) scan revealed a markedly enlarged thyroid gland only 1 month after surgery. 123I uptake for 24 hours was suppressed to 4% in the thyroid gland with no uptake elsewhere including the lung. Fine-needle aspiration cytology (FNAC) of the thyroid showed invasion of poorly differentiated adenocarcinoma cells, cytologically identical to the cells obtained from sputum and those infiltrating the resected sections of the lung adenocarcinoma. Immunohistochemical studies of resected lung tissues did not show positive staining for thyroglobulin, carcinoembryonic antigen (CEA), or surfactant protein A. Clinically, the thyrotoxicosis had spontaneously improved, followed by a hypothyroid state with shrinkage of the thyroid gland after chemotherapy. Despite repeated chemotherapy and the administration of thyroxine for hypothyroidism, the patient died of respiratory failure 9 months after the onset of thyrotoxicosis. From these findings and the clinical course, thyroid metastasis, developing subacutely from lung adenocarcinoma, was diagnosed. We speculate that aggressive invasion of tumor cells into the thyroid gland resulted in highly destructive thyrotoxicosis.
The aim of this study was to evaluate the efficacy of cross-linked hyaluronate hydrogel (HA gel) as an adjuvant for postoperative adhesion prevention, in a mouse uterine horn model. In experiment 1 uterine horns were abrased with iodine. HA gel was applied to the injured surface before closure in the treatment group. In experiment 2, after injuring the uterine horns, three stitches were placed at equal distances around the uterine horns to appose the injured medial surfaces of the two horns during healing. HA gel was inserted between the uterine horns in the treatment group. In experiment 3 prevention of adhesion reformation was assessed. After lysis of adhesions that were induced as in experiment 2, HA gel was introduced between the serosal surfaces of apposing uterine horns. Untreated animals served as controls in each experiment. Statistical analysis was carried out using Student's t-test. The adhesion score was significantly lower in the HA gel group on the 14th day compared with controls in all the experiments: in experiment 1, 0.3 +/- 0.4 versus 1.7 +/- 1.2; in experiment 2, 0.9 +/- 1.0 versus 2.6 +/- 0.5; and in experiment 3, 1.5 +/- 0.9 versus 2.2 +/- 0.6 respectively. Cross-linked HA gel significantly reduced de-novo adhesions (P< 0.03) and adhesion reformation (P < 0.03).
BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a life-threatening complication of continuous ambulatory peritoneal dialysis. To elucidate the mechanism and develop treatments for this condition, an experimental SEP model in mice was constructed. METHODS: C57BL/6 mice were administered 0.3 ml of 0.1% chlorhexidine gluconate and 15% ethanol dissolved in saline, intraperitoneally, on a daily basis for 56 days (group 1, n=15). A control group of C57BL/6 mice were administered 0.3 ml of phosphate-buffered saline only in the same manner (group 2, n=15). The mice were sacrificed on days 3, 7, 21, 56 and were prepared for histological analysis. RESULTS: In group 1, all mice had developed macroscopic evidence of SEP 56 days after the injection. Microscopically we observed peritoneal fibrosis and an increase in infiltrates of mononuclear cells over time. The peritoneal fibrosis reached the chronic inflammatory stage by 56 days after the injection. CONCLUSION: We have developed a convenient experimental model of SEP in mice, which may be useful in elucidating the pathogenesis of SEP and in establishing possible treatments.
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Serum samples collected from 854 cattle in nine prefectures of Japan, from Hokkaido to Okinawa, between 1988 and 1992 were examined for presence of antibodies against Erysipelothrix rhusiopathiae by growth agglutination test. Most of the sera showed positive reactions, and the antibody titers ranged from below 4 to above 128. Seventy-six percent of the sera showed titers of 32 or above, and 34% showed titers of 128 or above. The titers had a tendency to be higher in the south and lower in the north and were clearly low in sera from areas with no swine industry. These results indicated that Japanese cattle had been infected with E. rhusiopathiae and that clinical cases of the disease were possible.
The involvement of Borna disease virus (BDV) in psychiatric diseases in humans remains controversial. T-cell memory response and seroprevalence of BDV in patients with psychiatric disorders and blood donors in Japan were evaluated collectively by Western blot (WB) analysis with inhibition test, electrochemiluminescence immunoassay, immunofluorescence assay, and T-cell proliferative response as well as detection of BDV p24 RNA in peripheral blood mononuclear cells (PBMCs). Positive proliferative responses to both BDV p40 and p24 proteins were detected in 9% of patients with mood disorders (4 of 45), 4% of schizophrenic patients (2 of 45), and 2% of blood donors (1 of 45). By WB analysis, the antibody to BDV p40 was detected only in 2% of patients with mood disorders (1 of 45). The BDV p24 antibody was detected in 2% of patients with mood disorders (1 of 45) and 9% of schizophrenic patients. (4 of 45) No plasma reacted with both BDV proteins. The finding of a lower seroprevalence than previously reported suggests the presence of false-positive cases in the previous report. BDV RNA was detected only in 2% of patients with mood disorders (1 of 45). In these three serological assays, T-cell responses, and PCR analysis, there was no significant difference in the prevalence among the three groups. However, we found three psychiatric patients who were positive for both BDV antibodies and T-cell proliferative responses and one patient who was positive for BDV RNA in PBMCs. These findings suggest the usefulness of the proliferative T-cell response and that certain individuals are infected with BDV or a BDV-related virus.
The effects of unilateral 6-hydroxydopamine (6-OHDA) treatment on striatal serotonin neurons in 12-day-old mice were studied using immunohistochemistry. The unilateral 6-OHDA lesions were evaluated with tyrosine hydroxylase (TH) immunohistochemistry. The majority of the TH-immunoreactive structures disappeared from the substantia nigra and neostriatum on the 6-OHDA lesioned side. However, the density of serotonin fibers was markedly increased throughout the 6-OHDA-depleted neostriatum 1 year later. These results suggest that serotonergic heterotypic sprouting may be permanent.
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have been reported to exert actions independent of their lipid-lowering effects. To critically assess the effects of statins on monocyte-endothelial cell interactions, we used an in vitro model that mimicked physiological flow conditions. Monocytic U937 cells were incubated in the presence of cerivastatin for 48 hours. Adhesive interactions of statin-treated U937 cells were then analyzed by use of activated (interleukin-1beta 10 U/mL, 4 hours) human umbilical vein endothelial cells in an in vitro flow apparatus. Flow cytometric analysis of adhesion molecules and measurement of F-actin content in U937 cells were performed before and after statin treatment. Preincubation with cerivastatin significantly decreased U937 firm adhesion to activated human umbilical vein endothelial cells, whereas U937 rolling was not decreased. Fluorescence-activated cell sorter analysis revealed downregulation of U937 surface expression of CD11a, CD18, and VLA4 after statin treatment. Cerivastatin significantly reduced F-actin content in U937 cells and inhibited RhoA translocation, whereas preincubation with C3 exoenzyme reduced U937 adhesion under flow. Cerivastatin reduces monocyte adhesion to vascular endothelium under physiological flow conditions via downregulation of integrin adhesion molecules and inhibition of actin polymerization via RhoA inactivation. Our findings have important implications for the lipid-independent effects of statins.
The energy supply for eukaryotic ciliary and flagellar movement is thought to be maintained by ATP-regenerating enzymes such as adenylate kinase, creatine kinase and arginine kinase. In this study, the energy-supplying system for the ciliary movement of Paramecium caudatum was examined. Arginine kinase and adenylate kinase activities were detected in the cilia. To demonstrate that phosphoarginine satisfactorily supplies high-energy phosphate compounds into the narrow ciliary space, we prepared an intact ciliated cortical sheet from live Paramecium caudatum. These cortical sheets, with an intact ciliary membrane, produced a half-closed system in which each cilium was covered with a ciliary membrane with an opening to the cell body. Ciliary beating on the intact cortical sheets was induced by perfusing not only ATP but also ADP. Addition of phosphoarginine (0.2 mmol l(-1)) increased the beat frequency. A further increase in beat frequency was observed in 0.4 mmol l(-1) phosphoarginine, and this was enhanced when the cilia were reactivated with relatively low concentrations of ATP. We have demonstrated that phosphoarginine supplies energy as a 'phosphagen' for ciliary beating in Paramecium caudatum, suggesting that phosphoarginine functions not only as a reservoir of energy but also as a transporter of energy in these continuously energy-consuming circumstances. http://www.biologists.com/JEB/movies/jeb3123.html
Preexcitation in Wolff-Parkinson-White syndrome (WPW) has been reported to induce long-lasting changes in ventricular recovery properties. However, there has not been a report concerning changes in the activation-recovery interval (ARI) in 12-lead ECGs before and after catheter ablation (CA) in patients with WPW syndrome. The present study compared changes in ARIs from 12-lead ECGs with those from body surface unipolar leads before and after CA to examine whether ARIs from limb leads of 12-lead ECGs provide useful information on changes in recovery properties in addition to the ARIs from precordial leads. The study population consisted of 27 manifest WPW patients with a left- (n=18, group A) or right-sided accessory pathway (n=9, group B). ARIs in leads I, II, and III were strongly correlated with those in unipolar leads over the left lateral, left lower, and right lower chest, respectively. ARIs in leads aVR, aVL, and aVF showed a significant correlation with those in unipolar leads over the right upper, left upper, and lower anterior chest, respectively. These correlations were maintained before and after CA. Furthermore, in group A, ARIs in lead V1 tended to increase on day 7 post CA compared with before CA and on day 1. In group B, ARIs in lead III significantly decreased on day 7 compared with before CA and on day 1. These findings suggest that ARIs from the limb leads of 12-lead ECGs may represent those from unipolar leads of a particular area over the body surface, and that ARIs from 12-lead ECGs may provide useful quantitative information on changes in recovery properties before and after CA in patients with manifest WPW syndrome.
Borna disease virus (BDV) is a neurotropic pathogen that infects a wide variety of vertebrates. We have developed a new electrochemiluminescence immunoassay (ECLIA) for the detection of antibodies to BDV, using three synthetic peptides corresponding to the amino acid residues 3-20 and 338-358 of p40 and 59-79 of p24 peptide of BDV. Using the ECLIA, we examined serum samples for the presence of anti-BDV antibodies in 20 rats (experimentally BDV-infected and uninfected) and 38 horses (13 US horses, experimentally infected and uninfected, and 25 Japanese horses, feral and domestic). The ECLIA, performed in a double-blind manner, detected anti-BDV antibodies in rats with a history of BDV infection, giving results that were in agreement with indirect immunofluorescence assay and/or Western blot (WB) analysis. The ECLIA also correctly identified all three experimentally infected horses and four domestic American horses that were seropositive for BDV antibodies by WB. Among the Japanese horses, at least two out of 10 feral and six out of 15 domestic horses were seropositive for BDV. In most of these cases, the specificity of immunoreactivity was verified by blocking with soluble p40 and p24 peptides.
In May 1994, about fifty Japanese quails out of ninety being bred for experimental purposes at Miyazaki University died of acute septicemia within a few days. At autopsy, there were no gross pathological lesions, however, severe bacteremia was observed in all cases. Bacterial examination revealed the presence of Pasteurella multocida in blood and several organs in pure culture and they were of Carter's capsular type A, Heddleston's type 3-4 and Namioka's type O-8-9. The LD50 of bacteria in quails and mice were 4.3 x 10(4) cfu and 3.9 x 10(2) cfu, respectively. All of the three chickens experimentally infected with 4 x 10(4) of the isolate died within 20 hr after the infection and several bacteria were recovered from their blood and organs. This, to our knowledge, is the first report on an outbreak of fowl cholera in Japanese quails in Japan.
Anti-Borna disease virus (BDV) antibodies were detected from cats in Japan, Philippines and Indonesia by using electrochemiluminescence immunoassay. Positive rates were 3.1%, 3.8% and 2.0% in Japan, Philippines and Indonesia, respectively. There was no differences in the positive rate of anti-BDV antibodies between male and female cats and among habitats. While, a significantly (P<0.05) higher prevalence (6.5%) was found in the oldest age group (more than 6 years) cats.