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Biomedical subjects

M Miyamoto

Publications and source records attributed to M Miyamoto.

At least 91 records · Page 5Linked to original sources

Participation of leukocyte function-associated antigen-1 and NK cells in the homing of thymic CD8+NKT cells to the liver.

A distinct CD8+NKT cell population expressing TCRalpha/beta or TCRgamma/delta has been identified in liver and thymus. We wondered whether cell adhesion molecules play a role in the homing of CD8+NKT cells to the liver. The number of liver CD8+NKT cells was markedly reduced in leukocyte function-associated antigen (LFA)-1-/- mice compared with wild-type (WT) mice. The reduction was restricted to the liver only and no measurable alterations were found in other organs. In the liver of SCID mice reconstituted with thymocytes from LFA-1-/- or WT mice, the number of donor-derived CD8+NKT cells was comparable and the vast majority of these cells expressed TCRalpha/beta. In a reciprocal radiation thymocyte reconstitution system with LFA-1-/- and WT mice, LFA-1 expressed on liver cells other than CD8+NKT cells appeared to be required for the homing of thymic CD8+NKT cells to the liver. The accumulation of donor thymocyte-derived CD8+NKT cells in the liver of SCID mice was severely impaired by in vivo depletion of NK cells, but not of Kupffer cells. These results not only indicate that thymus provides a source for CD8+NKT cells expressing TCRalpha/beta in the liver, but also suggest that LFA-1 expressed on NK cells is involved in the homing of thymic CD8+NKT cells to the liver.

Animals↗

Clinicopathological evaluation in non-episode biopsies of renal transplant allograft.

Histopathological findings in renal allograft with stable function remain unclear. We therefore performed non-episode biopsy in the long-surviving renal allograft to investigate the histopathological changes. Our data show that, although arteriolopathy is characteristic of drug-induced nephropathy, it is unrelated to dosage and concentration of cyclosporine or tacrolimus in non-episode biopsy. We evaluated therefore the clinicopathological findings of arteriolopathy in this study. Non-episode biopsy was defined as follows: as serum creatinine level lower than, 2.0 mg/dl and a urinary protein level lower than 500 mg/day. A total of 65 biopsy specimens were enrolled in this study as non-episode biopsy. Twenty-nine specimens revealed arteriolopathy. There were no statistically significant differences between arteriolopathy and dosage or concentration of cyclosporine or tacrolimus. Arteriolopathy in non-episode biopsy was related to time of biopsy, kidney age, hypertension, and hyperlipidemia, suggesting that it is important for graft survival to strictly control blood pressure and blood lipid level.

Adult↗

Islet transplantation.

Recently, significant advances have been made in the number and purity of islets that can be retrieved from the human pancreas, thus enabling several centers to initiate or resume clinical trials of islet transplantation in type I diabetic patients. Although the success rate of islet transplantation is lower than that of pancreas transplantation in terms of achievement of insulin-independence, islet transplantation has significant potential advantages over vascularized pancreas transplantation: it is a simple and safe procedure; it has the potential to be performed on an outpatient basis; it offers access to cell banking after cryopreservation; it offers the potential advantages of pre-transplant reduction of immunogenicity; and it even offers the future feasibility of xenotransplantation. In this article, the current status of clinical trials and future perspectives of islet transplantation, including immunomodulation, immunotolerance, immunoisolation, and xenotransplantation, are reviewed.

Animals↗

Clinical efficacy of insulin-like growth factor-1 in a patient with autoantibodies to insulin receptors: a case report.

The type B insulin-resistance syndrome is characterized by the presence of anti-insulin receptor antibodies that cause severe insulin resistance. Treatments including steroids, cyclophosphamide, plasmapheresis, or insulin-like growth factor-1 (IGF-1) are chosen according to severity of insulin resistance. We describe a patient with type B insulin resistance syndrome who was treated successfully with human recombinant (hr) IGF-1, although this treatment provoked a severe allergic reaction. An elderly man with impaired glucose tolerance and unpredictable hypoglycemic episodes which were gradually worsening increased in hemoglobin (Hb)A1c concentration from 6.5 to 13.4%. His fasting and postprandial hyperglycemia were associated with severe hyperinsulinemia. The patient was diagnosed with type B insulin-resistance syndrome by the presence of anti-insulin receptor antibodies. Double-filtration plasmapheresis, plasma exchange, and immunosuppressive therapy with cyclophosphamide and cyclosporin all failed to suppress anti-insulin receptor antibodies more than transiently. When we attempted the treatment by daily administration of hrIGF-1, fasting and postprandial plasma glucose concentrations became normal and HbA1c levels decreased to 7.1% over 2 months, until on one occasion administration resulted in anaphylaxis. After the patient became stable, desensitization therapy was performed successfully, and hrIGF-1 could be administered again with the plasma glucose returning. We concluded that IGF-1 therapy was an effective treatment choice for type B insulin-resistance syndrome in cases whose plasma exchange and immunosuppressive therapy have failed.

Aged↗

Shear bond strengths of orthodontic plastic brackets.

The purpose of the present study was to evaluate the shear bond strengths of plastic brackets and the influences of the bracket filler contents on the bonding. The shear bond strengths of 4 plastic brackets (Spirit; Spirit MB; Clear Bracket; Aesthetic-Line) bonded to enamel with 4 orthodontic adhesives (Orthomite Superbond; System 1+; Transbond XT; and Kurasper-F) were compared with the strength of a conventional metal bracket. The findings of this study indicated the following: (1) shear bond strength of the 4 plastic brackets was significantly lower than that of the conventional metal brackets (P <.05), with most of the values ranging from 3 MPa to 6 MPa; (2) when comparing the bond strengths of plastic brackets, Aesthetic-Line had the largest value followed by Spirit MB, Spirit, and Clear Bracket, and when the plastic brackets were bonded with Orthomite Superbond, they showed relatively stronger bond strengths than when bonded with the other adhesives. Clear Bracket showed relatively lower values especially when bonded with System 1+; (3) the application of primer did not increase the durability of the bond strengths when bonding Spirit and Clear brackets; and (4) fillers contained in each plastic bracket ranging from 9.18% to 19. 52% were fairly well distributed and showed the same morphology of a fiber type 10 microm in diameter with different lengths. The filler concentration tended to correlate with the bond strength. The exposed fillers on the bracket base surface may play a more important role in plastic bracket adhesion than the macro-morphology of the base surface.

Dental Bonding↗

Molecular characterization of the hlyX-like gene of Actinobacillus actinomycetemcomitans Y4.

We isolated and characterized a possible regulatory gene, designated actX gene, from Actinobacillus actinomyctemcomitans Y4, which defined the Actinobacillus pleuropneumoniae hlyX-like regulatory gene. DNA sequence analysis for plasmid clone pKM317 containing a 1.6-kb DNA insert indicated an open reading frame encoding a polypeptide of 257 amino acid residues. Analysis of the deduced amino acid sequence showed the presence of five characteristic cysteine residues in the N-terminal region and a putative DNA binding residue in the C-terminal region, indicating that actX might belong to a regulatory gene family. Escherichia coli DH5alpha and a mutant strain JRG1728 transformed by plasmid carrying actX manifested apparent hemolytic activity on sheep blood agar and grew anaerobically, although the original strains did not.

Aggregatibacter actinomycetemcomitans↗

Effects of the mycelial extract of cultured Cordyceps sinensis on in vivo hepatic energy metabolism and blood flow in dietary hypoferric anaemic mice.

The beneficial effects of a traditional Chinese medicine, Cordyceps sinensis (Cs), on mice with hypoferric anaemia were evaluated by NMR spectroscopy. Experimental hypoferric anaemia was induced in mice by feeding with an Fe-free diet for 6 weeks. They were then given extract from cultured Cs (200 mg/kg body weight daily, orally) and were placed on an Fe-containing recovery diet (35 mg Fe/kg diet) for 4 weeks. In vivo 31P and 2H NMR spectra acquired noninvasively and quantitatively at weekly intervals were used to evaluate hepatic energy metabolism and blood flow in the mice. During the 4-week Cs-extract treatment, consistent increases were observed in liver beta-ATP: inorganic phosphate value by liver 31P NMR spectroscopy, representing the high energy state, and in blood-flow rate as determined by 2H NMR spectroscopy of deuterated water (D2O) uptake after intravenous injection of D2O. The haematological variables (the packed cell volume and the haemoglobin level) and the hepatic intracellular pH, which was determined from the NMR chemical shift difference between the inorganic phosphate peak and the alpha-phosphate peak of ATP, were not significantly different between Cs-extract-treated and control mice. As blood flow and energy metabolism are thought to be linked, the Cs-extract-increased hepatic energy metabolism in the dietary hypoferric anaemic mice was concluded to be due to increased hepatic blood flow.

Adenosine Triphosphate↗

Analysis of Helicobacter pylori vacA gene and serum antibodies to VacA in Japan.

Vacuolating cytotoxin, VacA, is one of the most important pathogenetic factors produced by Helicobacter pylori. However, it is not clear whether the diversity in disease outcome may be ascribed to variations in strain and/or to the host responses to virulence factors. In this study, we analyzed the vacA middle region sequence among 65 Japanese isolates to clarify the variation in strain and assayed antibody titer to VacA by ELISA using purified VacA to evaluate the host response to cytotoxin. The nucleotide sequence identities compared among Japanese isolates were 92.8 +/- 3.56%, and compared to 88.3 +/- 2.89% in tox+ strains reported in GenBank. Positive correlation was found between the antibody titers and the severity of atrophic change of the stomach. In Japan the nucleotide sequences of the vacA middle region were highly homologous and genetically closer to tox+ strains. Antibody titers and host response to cytotoxin may be associated with atrophy of the stomach.

Adult↗

Arteriolopathy in non-episode biopsies of renal transplant allograft.

PURPOSE: We have been performing protocol biopsies since 1995 to predict the outcome of renal allograft. However, histopathological findings in renal allograft with stable function remain unclear. For this reason, we performed non-episode biopsy on long-surviving renal allograft and investigated the histopathological changes. Among the several diseases seen in non-episode biopsies, arteriolopathy, such as drug-induced nephropathy, is one of the most frequent diseases. However, it is unrelated to the dosage and the concentration of cyclosporine or tacrolimus. Consequently, we evaluated the clinicopathological findings of arteriolopathy in this study in order to clarify whether cyclosporine (CsA) or tacrolimus (FK506) is responsible for these findings. MATERIALS AND METHODS: We defined non-episode biopsy as a case with a serum creatinine level less than 2.0 mg/dL and containing less than 500 mg/dL of urinary protein. Final results showed that 71 cases were identified as non-episode biopsy. We then evaluated the histopathological findings and the clinical characteristics of these cases. RESULTS: Thirty-two of the 71 non-episode biopsy specimens showed findings of arteriolopathy. The frequency and the severity of arteriolopathy are not concerned with dosage and concentration of CsA or FK506. The arteriolopathy seen in non-episode biopsy was related to the time of the biopsy and the kidney age. Arteriolopathy in nonepisode biopsy also had a relationship with hypertension, suggesting that it is important to strictly control blood pressure for graft survival.

Adult↗

The dominant negative H-ras mutant, N116Y, suppresses growth of metastatic human pancreatic cancer cells in the liver of nude mice.

In pancreatic cancer, the mutation of c-K-ras is a critical event of tumor growth and metastasis. We have previously demonstrated a dominant negative effect of N116Y on the growth of pancreatic cancer cells. To evaluate the potential of N116Y for suppressing the metastatic growth of pancreatic tumor cells, we made a replication-deficient recombinant N116Y adenovirus driven by the carcinoembryonic antigen (CEA) promoter (Ad CEA-N116Y). We demonstrated that the expression of N116Y, growth inhibition, and apoptotic death induction were all specific to pancreatic cancer cell lines (PCI-35 and PCI-43) that were promoter positive, whereas no growth retardation was observed in human embryonic pancreas-derived cell line 1C3D3 after Ad CEA-N116Y infection. We examined the effect of Ad CEA-N116Y on the metastatic growth of PCI-43 colonies in liver, which was generated by tumor injection into the spleen of nude mice. The results showed that Ad CEA-N116Y effectively reduced the number of metastatic colonies without any complication by injecting intrasplenically 5 days after tumor cell inoculation. Thus, N116Y can selectively suppress the metastatic growth of pancreatic tumor cell by using the CEA promoter-driven adenovirus vector indicating that N116Y gene therapy may be potentially useful for the treatment of pancreatic cancer patients with liver micrometastasis.

Adenoviridae↗

Brainstem function in rapid eye movement sleep behavior disorder: the evaluation of brainstem function by proton MR spectroscopy (1H-MRS).

Brainstem function was evaluated by proton magnetic resonance (MR) spectroscopy (1H-MRS) in a 69-year-old man with idiopathic rapid eye movement (REM) sleep behavior disorder. An analysis of spectral peak area ratios revealed an increase in the choline/creatine ratio. This change suggests that brainstem neurons have functional impairment at the cell membrane level. Further, our results suggest that 1H-MRS may provide for non-invasive, metabolic evaluation of brainstem neuronal function in REM sleep behavior disorder and find application in the differentiation of secondary REM sleep behavior disorders with neurodegenerative disorders from idiopathic disorders.

Aged↗