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Biomedical subjects

M Miyata

Publications and source records attributed to M Miyata.

At least 109 records · Page 6Linked to original sources

Suppressive effect of prostaglandin E1 on pulmonary hypertension induced by monocrotaline in rats.

The effect of administering prostaglandin E1 (PGE1) on the extent of monocrotaline (MCT)-induced pulmonary hypertension and cytokine production [interleukins (IL) 1 and 6 and tumor necrosis factor (TNF)] by macrophages during MCT induction of pulmonary hypertension was studied. Right ventricle/left ventricle plus septum weight ratios (RV/LV + S) were used as an index of the development of pulmonary hypertension. Administering PGE1 at a dose of 0.2 mg/kg/day for 4 weeks reduced significantly the RV/LV + S ratio from 0.428 +/- 0.070 to 0.243 +/- 0.059 (p < 0.01) and decreased the production of these cytokines: IL-1, from 4.675 +/- 3.558 to 1.800 +/- 0.722 units; IL-6, from 0.322 +/- 0.121 to 0.060 +/- 0.039 units; and TNF, from 0.578 +/- 0.369 to 0.004 +/- 0.004 units. In another series of experiments, a significant reduction of the RV/LV + S ratio was noted for only 1 week when we administered PGE1 immediately after the injection of MCT. We confirmed that histopathologic improvements of lungs were noted by administering 0. 2 mg/kg PGE1 for 4 weeks. In another experiment, PGE1 at a concentration of 2 microg/ml suppressed a rise in the cytosolic Ca2+ concentration of lipopolysaccharide-stimulated peritoneal macrophages of rats in vitro, suggesting that PGE1 suppressed cytokine production by macrophages through the suppression of the Ca2+ influx. These results suggest that administering PGE1 may be effective in the treatment of some forms of pulmonary hypertension in humans.

Alprostadil↗

Development of Purkinje cells in humans: an immunohistochemical study using a monoclonal antibody against the inositol 1,4,5-triphosphate type 1 receptor (IP3R1).

Immunohistochemical analyses were carried out on the Purkinje cells from 21 autopsied fetal and early postnatal normal cerebella using a monoclonal antibody against the inositol 1, 4, 5-triphosphate type 1 receptor (IP3R1) as a cytochemical marker of Purkinje cells. In normal adult cerebella used as positive controls, the cell bodies, axons, and dendrites, including spiny branchlets of the Purkinje cells, were specifically stained by the antibody. In the fetal cerebella examined, the IP3R1 immunoreactivity was first detected in the soma of multilayered cells just beneath the molecular layer at 16 weeks of gestation. The IP3R1 immunoreactivity gradually increased in area of positive staining from soma to dendrites and spiny branchlets, and the dendritic outgrowth rapidly progressed during 6 months after birth. The Purkinje cell maturation was more advanced in the vermis than in the hemisphere, more in the posterior lobe than in the anterior lobe, and more at the bottom of the folia than at the top. Partial absence of the Purkinje cells in the cerebellar cortex was observed in three cases. Heterotopias including Purkinje cells were often noted in the cerebellar white matter in five cases.

Antibodies, Monoclonal↗

Changes in fecal fat excretion from allo-intestine transplanted rats after discontinuance of immunosuppressive agents.

We have previously shown in a rat model of segmental small bowel transplantation, that an ileal graft was more favorable for lipid absorption than a jejunal graft. In the present study, we investigated changes in the lipid absorption of allo-ileal grafts after the withdrawal of an immunosuppressant (methyldeoxyspergualin; given for 1 or 2 weeks at 2.5mg/kg per day) and compared the findings with the results of histological examinations. Heterotopic segmental small bowel transplantation (SBT) was performed using cuff anastomoses in the inbred rat strain combination DA (RT1a) and LEW (RT1). Orthotopic SBT was performed as reconstruction SBT. Reconstruction after resection of the original intestinal tract of the recipient was performed on the seventh day after heterotopic segmental ileal grafting. For the histological evaluation of graft rejection, we performed biopsies in the heterotopic model and autopsies in the orthotopic model. Fecal fat excretion from the orthotopically reconstructed recipients was measured by Folch's method. One- and 2-week use of methyldeoxyspergualin allowed the heterotopic allografts to remain intact histologically for 16.8+/-5.6 and 25.3+/-3.3 (mean+/-SD) days, respectively, whereas the grafts were rejected at 7.3+/-1.1 days when the immunosuppressive drug was not used. All the recipients in the orthotopic group had died by 19 days after reconstruction. After discontinuance of the immunosuppressive agent, fat excretion in feces in the surviving orthotopic grafted rats had increased markedly prior to histologically assessed heterotopic graft rejection. Evaluation of fecal lipid excretion may be a useful parameter for detecting graft rejection in rats.

Animals↗

Clinico-laboratory characteristics of patients with dermatomyositis accompanied by rapidly progressive interstitial lung disease.

The clinico-laboratory features of 16 patients with dermatomyositis (DM) were compared between patients with accompanying rapidly progressive interstitial lung disease (RP-ILD, n = 7) and those with chronic interstitial lung disease (C-ILD, n = 9), and also between deceased (seven RP-ILD and three C-ILD) and living patients (six C-ILD). The extent of muscle weakness of the extremities and frequency of autoantibody positivity were significantly lower in DM patients with RP-ILD than in DM patients with C-ILD. Furthermore, significantly lower serum creatine kinase/lactate dehydrogenase levels (0.26+/-0.27) were found in the 10 patients who died than in the six living patients (1.21+/-1.09). A higher CD4+/CD8+ T-lymphocyte ratio in the peripheral blood (3.51+/-2.65) was detected in the four DM patients with RP-ILD who died than in the six living DM patients with C-ILD (1.22+/-0.49).

Adult↗

Experimental small bowel transplantation using newborn intestine in rats: I. Lipid absorption restored after transplantation of nonvascularized graft.

BACKGROUND/PURPOSE: Utilizing the characters of neovascularized activity of newborn organs, the authors developed a rat model of small bowel transplantation with a free graft of newborn intestine into the recipient's omentum. METHODS: Segmental intestine from newborn rats were grafted into the omentum without vascular anastomosis in a syngeneic combination (n = 19). The transplanted intestine was examined morphologically and electrophysiologically 4 weeks after grafting. Then, recipients' small intestine was totally substituted by the transplanted newborn intestine, and recipients' survival was recorded after orthotopical reconstruction. During the experimental periods, feces of these rats were collected, and total lipid excretion was measured. The short-gut rats, whose small bowel was totally resected, served as a control (n = 12). RESULTS: Thirteen of 19 grafts (68.4%) were judged as a histologically mature intestine. They showed typical slow waves that were identical to those of native small intestine. After all of the mature grafts were interposed, six recipients (46.2%) survived longer than 15 weeks. Control short gut animals severely lost weight and died except for one. CONCLUSION: Newborn intestinal transplantation could restore severe weight loss in the short-gut rats and save them.

Animals↗

Immunotherapy for experimental rat autoimmune thyroiditis using a novel immunosuppressant, FTY720.

While autoimmune disease needs to be continuously treated via long term, administration of immunosuppressants conventional immunotherapy using drugs such as cyclosporin and tacrolimus may cause adverse effects. Recently, a novel agent, FTY720, which was structurally modified from a natural product, has been shown to have a moderate and different immunosuppressive effect from conventional drugs. In this study, we examined the effect of FTY720 on experimental autoimmune thyroiditis (EAT), which was induced in rats by neonatal thymectomy, followed by subsequent sublethal irradiation. Thyroid stimulating hormone (TSH) was measured before and at the end of drug therapy. Histological and hematological examinations were performed using the samples from sacrificed animals. High TSH levels in the animals returned to the normal range following treatment with FTY720. The severity of the thyroiditis was lower in the FTY720 group than in the control group. FTY720 markedly decreased the number of circulatory lymphocytes, and no infections episodes were observed under this treatment. Thus, FTY720 treatment might be preferred for continuous immunotherapy for autoimmune disease without adverse effects.

Animals↗

Corticotropin-releasing factor plays a permissive role in cerebellar long-term depression.

This study of rat cerebellar slices yielded two lines of evidence indicating that the corticotropin-releasing factor (CRF) found in climbing fibers (CFs) is critical for the induction of long-term depression (LTD) at the parallel fiber (PF) synapses of Purkinje cells (PCs) by their conjunctive activation with either stimulation of CFs or depolarization of PCs. First, LTD induction was effectively blocked by specific CRF receptor antagonists, alpha-helical CRF-(9-41) (alpha-h CRF) and astressin; and second, LTD was no longer observed in CF-deprived cerebella but was restored by CRF replenishment. The data obtained in this study suggest that these effects are mediated by protein kinase C (PKC) and not by Ca2+ signaling or cyclic GMP (cGMP) production.

Animals↗

Arthroscopic surgery of the temporomandibular joint: comparison of two successful techniques.

We have compared two techniques of arthroscopic surgery for advanced internal derangement of the temporomandibular joint (TMJ). Patients with stage III or above TMJ internal derangement, who had not responded to three months of non-surgical treatment, were prospectively and randomly assigned to one of two types of treatment. One group had arthroscopic lysis and lavage (ALL) and the other had ALL plus arthroscopic anterolateral capsular release (AALCR). All patients were assessed preoperatively, and at 1, 3, 6, and 12 months postoperatively. Thirty-five patients (41 joints) had ALL and 66 patients (73 joints) had AALCR. The only significant difference was at 1 month, when the ALL group could not open their mouths as far as the AALCR group (P < 0.01). Both groups had significantly less pain in the joint and better jaw opening one year postoperatively. The stage of disease did not affect the outcome. Both ALL and AALCR gave good results in the management of advanced internal derangement of the TMJ. Unless early wide mouth-opening is required, the less invasive procedure of lysis and lavage should be chosen.

Analysis of Variance↗

Chemokine receptor-usage of clinical HIV-1 isolates obtained from patients with HIV-1 infection in late clinical stages using PHA-blast.

In the present sudy, chemokine receptor-usage of primary HIV-1 isolates was examined using U87-CD4 cells expressing chemokine receptors CCR3, CCR5 and CXCR4. HIV-1 was isolated from the peripheral blood mononuclear cells (PBMC) and/or plasma of eight HIV-1-infected individuals in late CDC-II and CDC-IV clinical stages using PHA-blast prepared from the PBMC of healthy blood donors. The primary HIV-1 isolates from patients in late CDC-II stage rarely infected monocyte-derived macrophages in the present study, whereas most isolates from patients in the CDC-IV stage infected the macrophages. In the experiments using U87-CD4 cells expressing chemokine receptors, the isolates from patients in the late CDC-II stage infected U87-CD4 cells expressing CXCR4, but not U87-CD4 cells expressing CCR5. In contrast, most isolates from patients in the CDC-IV stage infected both U87-CD4 cells expressing CXCR4 or CCR5. The isolates which infected both U87-CD4 cells were supposed to contain dual tropic HIV-1 or a mixture of CXCR4-tropic and CCR5-tropic HIV-1s. Analysis of the deduced amino acid sequence of the V3 region in proviral env gene showed that the V3 region in U87-CD4 cells infected with CXCR4-tropic HIV-1 isolates was largely different from that in the cells infected with CCR5-tropic isolates, but were highly similar to that in cells infected with dual tropic isolates. These results suggest that PHA-blasts may preferentially support the replication of the CXCR4-tropic and dual tropic HIV-1s, and that CXCR4-tropic and dual tropic HIV-1s are also present in peripheral blood from patients in the late stage of the asymptomatic phase.

Amino Acid Sequence↗

Partitioning, movement, and positioning of nucleoids in Mycoplasma capricolum.

The nucleoids in Mycoplasma capricolum cells were visualized by phase-combined fluorescence microscopy of DAPI (4', 6-diamidino-2-phenylindole)-stained cells. Most growing cells in a rich medium had one or two nucleoids in a cell, and no anucleate cells were found. The nucleoids were positioned in the center in mononucleoid cells and at one-quarter and three-quarters of the cell length in binucleoid cells. These formations may have the purpose of ensuring delivery of replicated DNA to daughter cells. Internucleoid distances in binucleoid cells correlated with the cell lengths, and the relationship of DNA content to cell length showed that cell length depended on DNA content in binucleoid cells but not in mononucleoid cells. These observations suggest that cell elongation takes place in combination with nucleoid movement. Lipid synthesis was inhibited by transfer of cells to a medium lacking supplementation for lipid synthesis. The transferred cells immediately stopped dividing and elongated while regular spaces were maintained between the nucleoids for 1 h. After 1 h, the cells changed their shapes from rod-like to round, but the proportion of multinucleoid cells increased. Inhibition of protein synthesis by chloramphenicol induced nucleoid condensation and abnormal positioning, although partitioning was not inhibited. These results suggest that nucleoid partitioning does not require lipid or protein synthesis, while regular positioning requires both. When DNA replication was inhibited, the cells formed branches, and the nucleoids were positioned at the branching points. A model for the reproduction process of M. capricolum, including nucleoid migration and cell division, is discussed.

Bacterial Proteins↗

Primary biliary cirrhosis associated with painless thyroiditis.

A case of anti-mitochondrial antibody (AMA)-negative primary biliary cirrhosis (PBC) associated with painless thyroiditis is reported in a 47-year-old woman who diagnosed as PBC based on her elevated serum gamma-glutamyl transpeptidase and immunoglobulin M levels, as well as histological findings of destroyed bile ducts surrounded by mononuclear infiltrates in the biopsied liver. She was negative for AMA and had a depressed level of thyroid-stimulating hormone accompanied by increased free thyrosine, thyroxine and triiodothyronine levels and low titers of anti-microsomal and anti-thyroid peroxidase antibodies. Her thyroid disorder corresponded with painless thyroiditis. An association between PBC and hyperthyroidism is rare. Furthermore, an association between AMA-negative PBC and hyperthyroidism due to painless thyroiditis has not previously been reported.

Autoantibodies↗

Cytophagic histiocytic panniculitis improved by combined CHOP and cyclosporin A treatment.

In a 31-year-old Japanese man with cytophagic histiocytic panniculitis (CHP) remission was achieved by a combination of combined chemotherapy CHOP and cyclosporin A treatment. He was admitted to our hospital in January 1994 with recurrent high fever of 40.2 degrees C and tender and violaceous subcutaneous nodules on his trunk, arms and legs. He developed pancytopenia, hemorrhagic diathesis, liver dysfunction. Histological examination of the biopsied subcutaneous nodule revealed a lobular panniculitis with fat necrosis and a massive infiltration of histiocytes phagocytosing nuclear debris. He was treated initially with 40 mg/day prednisolone. However, following a reduction in prednisolone dosage, his symptoms reappeared. CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy was then initiated. Three courses of CHOP treatment alleviated his symptoms and cyclosporin A was used to maintain his condition for 15 months. His medication was then discontinued and he has been in complete remission for 10 months. Combined treatment of cyclosporin A and CHOP combined chemotherapy was shown to be effective for this patient with severe CHP.

Adult↗

[A clinical study of inoperable head and neck cancers].

Thirty two patients with inoperable head and neck cancer seen at Jichi Medical School Hospital during the period 1978 to 1995 were analyzed. Distribution of the affected site was as follows: 15 cases of oropharynx, 12 of hypopharynx, and 3 of larynx. In order to study a better performance status, prognosis and side effects were compared between radiotherapy alone (17 patients) and combined radiochemotherapy (15 patients). Patients who received the combined therapy survived longer than those patients who received radiotherapy alone. Moreover, high QOL was obtained longer in the combined therapy. Therefore, we conclude that radiotherapy should be combined with chemotherapy for cases with inoperable head and neck cancer.

Aged↗

IgG 1 subclass specificity for IgG rheumatoid factors in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the significance of IgG rheumatoid factors (IgG RF) in the pathogenesis of rheumatoid arthritis (RA), and to determine the specificity of IgG subclasses binding with IgG RF in RA (RA IgG RF) compared to IgG RF in normal subjects (NS IgG RF). METHODS: The reactivities of RA IgG RF and NS IgG RF for various IgG subclasses were studied by ELISA and inhibition assay, using purified IgG heavy chains of different IgG subclasses. RESULTS: In ELISA, the optical density (OD) value of the reaction of RA IgG RF with IgG 1 was significantly higher than with IgG 2, 3, or 4 (p < 0.01). Similarly, the OD value of the reaction of NS IgG RF with IgG 1 was significantly higher than with IgG 2 or 4 (p < 0.05). In the inhibition assay, the OD value of the reaction of RA IgG RF was decreased by IgG 1, 2, and 3 (p < 0.01), but not by IgG 4. The extent of inhibition by IgG 1 was significantly greater than that by IgG 2, 3, or 4 (p < 0.05). In contrast, the OD value of the reaction of NS IgG RF was not significantly inhibited by any of the IgG subclasses. CONCLUSION: RA IgG RF and NS IgG RF reacted most strongly with IgG 1. From the differences in reactivities between RA IgG RF and NS IgG RF in the inhibition assay, it can be inferred that RA IgG RF exhibits higher affinity for IgG than NS IgG RF.

Antibody Specificity↗

[Emergency coronary artery bypass grafting with integrated myocardial protection].

In the following retrospective study we reviewed the early postoperative results of emergency CABG; the myocardial management was achieved by utilization of integrated myocardial protection including warm cardioplegic induction, performed at our hospital. From April 1st 1994 to October 30th 1998; 63 patients underwent emergency CABG with integrated myocardial protection. All surgical procedures were performed within 6 hours from the onset of disease or admission transferred from another hospitals. Age ranged 48 to 86 years (mean 69.9 +/- 8.5; 41 male, 22 female). AMI was present in 52, UAP in 11. Preoperative PTCA was done in 20 and IABP was inserted in 53. Cardiogenic shock in 26, mechanical complications in 6, three vessel disease in 48 and LMT disease in 17 was present. Eight patients (12.7%) died in the early postoperative period. Among evaluated risk factors for early postoperative death; the occurrence of cardiogenic shock, mechanical complications of AMI, preoperatively done PTCA and prolonged CPB time were significantly increasing the mortality rate in early postoperative death.

Aged↗

Significance of endogenous heat shock protein in adjuvant arthritis.

OBJECTIVE: To investigate the role of endogenous heat shock protein (HSP) (rat 60 kDa HSP, rHSP 60) in adjuvant arthritis (AA), the expression of rHSP 60 in AA-susceptible Lewis rats and AA-resistant Fisher rats was studied. METHODS: The extent of arthritis was assessed by measuring footpad thickness. The proliferative response of mononuclear cells (MNC) to mycobacterial 65 kDa HSP (mHSP 65) was measured by [3H] thymidine incorporation. The messenger RNA for rHSP 60 was quantified by dot blot hybridization in peripheral blood mononuclear cells (PBMNC), splenic MNC (SMNC), and ankle joint synovial membrane (SM). RESULTS: In Lewis rats: AA developed on Day 14 after immunization with Freund's complete adjuvant. Proliferative responses of PBMNC and SMNC to mHSP 65 were observed on Day 14 and thereafter according to the development of AA. Messenger RNA levels of rHSP 60 in PBMNC, SMNC, and SM did not increase until Day 21. In Fisher rats: AA and proliferative response of MNC to mHSP 65 were not observed throughout the observation period. Messenger RNA levels of rHSP 60 were significantly higher in preimmune Fisher rats than those in preimmune Lewis rats. Messenger RNA levels of rHSP 60 in PBMNC and SMNC increased significantly on Day 7 and decreased to preimmune levels until Day 21. CONCLUSION: We propose that elevated levels and rapid elevation of endogenous HSP 60 levels relate to resistance to AA in Fisher rats; however, lower levels and delayed increase of endogenous HSP 60 levels relate to susceptibility to AA in Lewis rats.

Animals↗

[Combined chemotherapy with low-dose cisplatin, tegafur and uracil for head and neck squamous cell carcinomas].

The mechanism for the effect of cisplatin (CDDP) as a modulator for 5-fluorouracil (5-FU) has already been described. The effective AUC of serum 5-FU concentration with oral administration of tegafur and uracil (UFT) has been revealed. We administered a dose of 200-600 mg/body of UFT orally every day, and 3.5-10 mg/m2 of CDDP by drip infusion 5 days a week. Hospitalized patients were administered these agents for 2-5 weeks. Eleven patients were enrolled, including 4 with untreated pharyngeal squamous cell carcinoma (SCC), 5 with locoregional recurrent SCC, and 2 with pulmonary multiple metastases. The mean age of the patients was 71 years, and all patients had a PS 3. Of the 4 patients with untreated pharyngeal SCC, PR was noted in 3 and NC in one, for a response rate of 75%. Of the 11 patients with locoregional recurrent and pulmonary metastatic SCC, PR was noted in only one patient for a response rate of 14%. Although on average these patients died of the primary disease 150 days after chemotherapy, 4 patients later showed an improved PS stage, and could were able to leave the hospital. These 4 patients could stay home with a PS 0 or PS 1 for an average of 133 days, and survived with the disease for an average of 240 days after chemotherapy. No side effects were observed in any patients. In side of the low response rate for locoregional recurrent and pulmonary metastatic SCC, the present therapy was thought to be useful from the viewpoint of the quality of life.

Administration, Oral↗