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Biomedical subjects

M Miyata

Publications and source records attributed to M Miyata.

At least 127 records · Page 7Linked to original sources

Rhabdomyolysis and aggravation of arthritis in a rheumatoid arthritis patient as a result of sepsis due to Staphylococcus aureus infection of a rheumatoid nodule; a catastrophic outcome.

A 63-year-old man with rheumatoid arthritis presented with rhabdomyolysis and intractable arthritis of acute onset. He was diagnosed to have sepsis due to Staphylococcus aureus infection through of an ulcerated rheumatoid nodule. Staphylococcus aureus isolated from pus in the ulcerated rheumatoid nodule and a blood sample obtained from the heart post-mortem produced the toxic shock syndrome toxin-1 (TSST-1). The TSST-1 and/or unmethylated CpG motifs in the oligonucleotides present in a bacterium, Staphylococcus aureus in this case, might be implicated in the induction of rhabdomyolysis and intractable arthritis.

Arthritis, Rheumatoid↗

CpG motif-containing DNA fragments from sera of patients with systemic lupus erythematosus proliferate mononuclear cells in vitro.

OBJECTIVE: To characterize DNA in sera of patients with systemic lupus erythematosus (SLE) in terms of size, guanine plus cytosine (G+C) content (by percentage), CpG dinucleotide (CpG) (percentage), and effects on mononuclear cells (MNC). METHODS: Nine DNA clones were sequenced. Oligodeoxynucleotides with the characteristic CpG motif (TTCGAA or PuPuCGPyPy) were examined for their proliferative effect on MNC by [3H]thymidine incorporation, expression of HLA-DR and intercellular adhesion molecule (ICAM)-1 on monocytes by flow cytometry, and mRNA levels encoding interleukin 12 (IL-12) and interferon-gamma (IFN-gamma) by semiquantitative reverse transcription polymerase chain reaction. RESULTS: The size of DNA clones ranged from 87 to 318 bp (mean +/- SD, 177+/-68) and enrichment in G+C and CpG ranged from 34.7 to 69.7% (48.1+/-10.7) and 0.63 to 12.8% (4.0+/-4.1), respectively. Three of 9 clones contained the characteristic CpG motif. Oligonucleotides proliferated MNC, and augmented HLA-DR and ICAM-1 expression in company with an increase of mRNA encoding IL-12 and IFN-gamma. CONCLUSION: Circulating CpG motif-containing DNA fragments in SLE increased mRNA encoding IL-12 and IFN-gamma, which in turn increased HLA-DR and ICAM-1 on monocytes, resulting in MNC proliferation. This mechanism could contribute to the pathogenesis of SLE.

Base Sequence↗

High incidence of esophageal cancer in esophageal achalasia by the oral administration of N-amyl-N-methylnitrosamine and its prevention by nicardipine hydrochloride in mice.

Esophageal achalasia (EA) is a rare disease in man and animals and there are many discussions on its higher risk of esophageal cancer. N-Amyl-N-methylnitrosamine (AMN) which specifically induces esophageal tumors in mice and rats was given to three mutant mouse strains, i.e. 101/N, STX/Le and BXH-8, which develop a high incidence of EA. The incidence of EA in 101/N, STX/Le, BXH-8 and normal C57BL/6J mice was 38.5% (110/286), 30.1% (43/143), 91.8% (190/207) and 0% (0/167), respectively. The average numbers of AMN-induced esophageal tumors in EA(+) were significantly higher than those of EA(-) in all of the 101/N, STX/Le and BXH-8 mice. Furthermore, significantly larger size tumors and invasive squamous cell carcinomas were found in EA(+) mice than in EA(-) mice. These results indicate the higher sensitivity of EA for both tumor induction and promotion, possibly due to the longer retention of AMN. In fact, relaxation of the lower esophagus by a smooth muscle relaxing calcium-channel blocker, nicardipine hydrochloride, significantly prevented the induction of esophageal tumors.

Administration, Oral↗

Agonist-induced desensitization of adenylyl cyclase activity mediated by 5-hydroxytryptamine7 receptors in rat frontocortical astrocytes.

Our previous study has demonstrated that astrocytes derived from the rat frontal cortex contain 5-hydroxytryptamine (5-HT)7 receptors positively coupled to adenylyl cyclase. In this study, we observed a desensitization of 5-HT7 receptors induced by a treatment with agonists (0.1, 1, and 10 muM, 0.5 to 3.5 h). Maximum responses, but not the EC50 values, in the concentration-response curve of 5-HT-induced cyclic AMP formation were decreased after pretreatment with 5-HT. Pretreatment with 5-carboxamidotryptamine (5-CT) elicited a potent desensitization of 5-HT-induced cyclic AMP formation. Neither 2-methyl-5-HT nor alpha-methyl-5-HT caused the desensitization. When the astrocytes were treated with isoproterenol, N-ethylcarboxamidoadenosine, and dibutyryl cyclic AMP (all of which increase intracellular cyclic AMP levels), 5-HT-induced cyclic AMP responses were not affected. Conversely, adenylyl cyclase activity mediated by either isoproterenol or N-ethylcarboxamidoadenosine was attenuated by pretreatment with each of these agonists, but not 5-HT. In addition, our study showed that the administration of 5-HT, 5-CT, and 8-hydroxy-2-(di-n-propylamino)tetralin to the astrocytes stimulated cyclic AMP formation both in the presence and absence of forskolin, whereas in neuron-rich cultures of the frontal cortex, these agonists did not change basal cyclic AMP levels and decreased forskolin-stimulated cyclic AMP formation. Neurons may predominantly contain 5-HT1A receptors that are negatively coupled to adenylyl cyclase. These results suggest that 5-HT7 receptors are highly expressed in astrocytes but not in neuronal cells, and that pretreatment with their agonists results in a homologous desensitization of the receptors.

Adenylyl Cyclases↗

A novel monoclonal antibody permitting recognition of NKT cells in various mouse strains.

By immunizing mouse lymphoma cell line tMK-2U derived from intermediate TCR cells of BALB/c nude mouse, U5A2-13 monoclonal antibody (mAb, a rat IgG2a) was established. U5A2-13 antigen (Ag) was expressed on around 65% of TCRint cells in the liver of the various mouse strains including both NK1.1- and NK1.1+ mouse strains, while NK1.1 Ag was expressed only in NK1.1+ C57BL/6 mouse strain. Among CD3+ cells, 26.3% cells co-expressed U5A2-13 Ag and NK1.1+ Ag, while small proportions of the CD3+ cells were U5A2-13+NK1.1- (9.2%) or U5A2-13-NK1.1+ (4.4%). Among NK1.1+ cells, 54.9% cells co-expressed CD3 and U5A2-13 Ag, while some proportions of the cells were U5A2-13+CD3- (19.4%) or U5A2-13-CD3+ (9.8%). It was found that approximately 85% of NK1.1+CD3+ cells coexpressed U5A2-13 Ag. U5A2-13 Ag with low fluorescence intensity was also expressed on 55% of NK1.1+CD3-NK cells. U5A2-13 Ag immunoprecipitated from tMK-2U cells consisted of three proteins, which were 65 kDa, 33 kDa and 32 kDa under both reducing and non-reducing conditions and these were apparently different from NK 1.1 Ag. These results indicated that U5A2-13 mAb was able to define a similar population to NK1.1+CD3+T cells and to 55% of NK1.1+CD3-NK cells in various strains, through recognizing a different molecule from NK1.1 Ag.

Animals↗

Auxiliary heterotopic liver transplantation in the rat: a simplified model using cuff technique and application for congenitally hyperbilirubimemic Gunn rat.

To study the immunological and metabolic effects of auxiliary liver transplantation (ALT), a simple ALT model in rats was developed using the cuff application. Effects of transient parking of normal liver were tested in congenitally hyperbilirubinemic Gunn rats. Serum bilirubin concentrations in Gunn rats, transplanted heterotopically with normal livers of Wistar rats, were dramatically reduced and maintained within normal levels. The graftectomy was performed safely 1 month after transplantation, but total bilirubin levels did not return to the preoperative value of the Gunn rats. It is possible that hepatic stem cells included in ALT liver migrated to the host liver and differentiated into cells capable of producing certain enzymes.

Analysis of Variance↗

Changes in immune-endocrine response after surgery.

The authors evaluated the relationship between hormonal and cytokine responses after surgery. Patients who underwent thoracic oesophagectomy (O group; n = 7), pulmonary lobectomy (P group; n = 5), modified mastectomy (M group; n = 5) and laparoscopic cholecystectomy (LC group; n = 7), were randomly selected. Circulating neutrophil and lymphocyte numbers were assayed. Changes in the concentration of the hormones [adrenocorticotrophic hormone (ACTH), cortisol, and antidiuretic hormone (ADH)] and cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, and IL-10] were analysed. In O and P groups, neutrophils were still seen on post-operative day (POD) 3, while the leukocyte counts of M and LC groups returned to normal. The number of lymphocytes significantly decreased on POD1 and POD3 only after oesophagectomy. The pattern of hormonal levels was consistent in all groups. While TNF-alpha and IL-1 beta were undetectable in the peripheral blood, the concentration of IL-6 and IL-10 increased in O and P groups, but not in M and LC groups. The degree of lymphocytepenia and neutrophilia correlated well with the extent of surgical trauma.

Adrenocorticotropic Hormone↗

The effect of interleukin-6 on enhancing the invasiveness of head and neck cancer cells in vitro.

Patients with head and neck cancers that produce a high concentration of granulocyte colony-stimulating factor (G-CSF) or patients with esophageal squamous cell carcinomas who have elevated serum interleukin-6 (IL-6) concentrations have been found previously to be at significant risk for tumor invasion to adjacent organs as well as frequent metastases. This suggests that G-CSF and Il-6 enhance the invasiveness and metastatic potential of cancer cells. We studied the in vitro invasiveness of head and neck cancer cell lines with and without recombinant human G-CSF (rhG-CSF) and human IL-6 (hIL-6) in an extracellular matrix membrane system. The degree of invasiveness was affected by incubating cells with hIL-6, but not by pre-incubating the cell-matrix with hIL-6. The maximum concentration of hIL-6 for enhanced invasiveness was approximately 5,000 u/ml. In addition, rhG-CSF enhanced the invasiveness of tumor cells that produced large amounts of G-CSF. The present study also suggests that tumor cells tend to invade and metastasize in an environment rich in hIL-6.

Carcinoma, Squamous Cell↗

Endoscopic findings in transplanted allo-intestine of rats after discontinuance of immunosuppressive agent.

In clinical practice, graft rejection in small-bowel transplantation should be diagnosed before irreversible condition of the graft. We have already reported the usefulness of endoscopic examination for the early detection of acute rejection in a rat model. Here we evaluated rejection after discontinuance of methyl-deoxyspergualin by endoscopy. Heterotopic small-bowel transplantation was performed by the cuff method from a DA to a LEW rat. Endoscopic and histological examinations were performed through the stomas. Two-week administration of methyl-deoxyspergualin significantly prolonged graft survival. Graft rejection after discontinuance of the agent occurred much more slowly than rejection without the immunosuppressive drug. Erosive mucosal changes were endoscopically observed in the early phase of rejection in rats that did not receive the immunosuppressant. However, endoscopic findings after discontinuance of methyl-deoxyspergualin indicated edematous changes and thickening of the wall without erosion, and, histologically, the grafted intestine showed slowly-progressing rejection with flattened villi. If we pay attention to edematous changes and hardening of intestinal wall, and take selective biopsies, endoscopic examination may improve the early diagnosis of slowly progressive rejection in the clinical setting.

Animals↗

Analysis of peripheral blood mononuclear cell stimulated with pyruvate dehydrogenase complex, T-cell receptors from patients with primary biliary cirrhosis.

Progressive destruction of the intrahepatic bile ducts in patients with primary biliary cirrhosis (PBC) is thought to be mediated by cytotoxic T cells which recognize certain epitopes, such as the pyruvate dehydrogenase complex (PDC). To clarify the T-cell repertoire in PBC, we analyzed T-cell receptor (TCR) Vbeta-chain messages expressed in peripheral blood mononuclear cells (PBMCs) stimulated with PDC and in liver biopsy specimens. PBMCs from 12 PBC patients and 6 healthy controls were examined. The TCR Vbeta repertoires of unstimulated PBMCs and PBMCs stimulated with PDC purified from bovine heart were analyzed, using the reverse transcriptase-polymerase chain reaction (RT-PCR) and single-strand conformation polymorphism (SSCP). Liver biopsy specimens from 5 PBC patients were also analyzed. In the PBC patients, several different T-cell clones, some of which showed the same mobility, were evident in both the PDC-stimulated and unstimulated PBMCs, as demonstrated by SSCP analysis. In addition, TCR clonality of infiltrating lymphocytes in the liver was also observed in PBC patients, showing common clonal T-cell accumulation with that seen in PBMCs stimulated with PDC. These data indicate that common clonal T-cell accumulation specific for PDC may be present in both peripheral PBMCs and the liver of patients with PBC.

Case-Control Studies↗

The relationship between apolipoprotein E and serum oxidation-related variables is apolipoprotein E phenotype dependent.

To examine the relationship between apolipoprotein E and serum oxidation status, we assayed apolipoprotein E level, apolipoprotein E phenotype, and levels of lipid peroxides and transition metal ions and their binding proteins in sera from apparently healthy individuals. The study group included 129 women aged 22-63 years and 53 men aged 22-56 years. Among subjects with apolipoprotein E 4/3 phenotype, lipid peroxide levels were higher compared with E 3/2 phenotype (786 +/- 182 nmol/l vs. 659 +/- 174 nmol/l, P = 0.015), and ceruloplasmin levels were slightly higher compared with apolipoprotein E 3/3 phenotype (0.28 +/- 0.08 mg/l vs. 0.26 +/- 0.06 mg/l, P = 0.035). In the study group as a whole, there were significant associations between serum apolipoprotein E level, and serum levels of ceruloplasmin (r = 0.266, P < 0.001) and ferritin (r = 0.2, P < 0.007). Among subjects with apolipoprotein E 4/3 phenotype, there was a significant association between serum apolipoprotein E and lipid peroxide levels (r = 0.470, P < 0.01), which was not apparent among subjects with E 3/3 or E 3/2 phenotypes. In multivariate analysis, apolipoprotein E phenotype was a small but significant independent contributor to variation in serum lipid peroxide levels. These data suggest that there may be heterogeneity among apolipoprotein E phenotypes in their relationships with serum lipid oxidation status.

Adult↗

Elevated serum level of thioredoxin in patients with hepatocellular carcinoma.

Thioredoxin (TRX) is known to contain an active site with a redox-active disulfide and has various biological activities. The objective of the present study was to investigate whether circulating TRX levels are elevated in patients with chronic hepatitis (CH) or liver cirrhosis (LC) and hepatocellular carcinoma (HCC). An anti-TRX monoclonal antibody and polyclonal antibodies that specifically recognize TRX, were generated and used for the development of an ELISA system to measure TRX levels in human serum. The geometric mean and its 95% confidence interval of serum level of TRX in healthy volunteers was 81.75 ng/ml (74.60-89.59 ng/ml). The serum level of TRX in LC/CH patients without HCC was 80.87 ng/ml (69.66-93.88 ng/ml). The value was not statistically different from that in serum from normal volunteers (p=0.69). In contrast, the serum level of TRX in patients with HCC was 147.35 ng/ml (125.53-172.96 ng/ml), which was significantly higher when compared with the level in serum of normal volunteers (p<0.001) and in serum of LC/CH patients without HCC (p<0.001). In four patients with HCC, the initially high level of serum TRX (>150 ng/ml) decreased below 150 ng/ml after surgical removal of the tumor. The data reported herein revealed that patients with HCC had a significantly elevated serum level of TRX, suggesting that measurement of serum of TRX might be a useful clinical parameter when HCC is suspected.

Adult↗

Neuropathic bladder dysfunction in patients with ossification of the posterior longitudinal ligament.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) may cause neuropathic bladder dysfunction due to spinal cord involvement. OPLL, unlike a traumatic spinal cord lesion, progresses insidiously and sometimes affects longer cord segments. As the manifestation of bladder dysfunction may depend on the development of OPLL, we studied the relationship between bladder function and roentgenographic changes in the spinal canals of OPLL patients. PATIENTS AND METHODS: Eighteen surgical candidates (11 males and 7 females, 34 to 85 years old) were studied urodynamically. Sixteen underwent CO2-filling cystometry, uroflowmetry and measurement of their residual urine volume. Cystometry was omitted in the remaining 2 patients. The vertical extent of OPLL and the degree of stenosis in the spinal canal was estimated by x-ray films and CT. RESULTS: The cystometric study revealed detrusor hyperreflexia in 2 patients and areflexic or underactive detrusors in 5 patients. Intermittent flows or considerable amounts of residual urine were also observed in the arefilexia/underactive group. Uroflowmetry showed a normal flow with little residual urine in both patients in whom cystometry was omitted. Bladder sensation was maintained in all patients. The occurrence of abnormal detrusor activity had no relationship to the degree of canal stenosis, while the occurrence of an areflexic or underactive detrusor correlated with the vertical extent of OPLL. CONCLUSION: Although detrusor hyperreflexia is common in an upper spinal cord lesion, attention should also be paid to the development of detrusor underactivity in patients with a wide vertical extent of OPLL.

Adult↗

Solitary rectal ulcer syndrome accompanied by submucosal invasive carcinoma.

We report a case of carcinoma in solitary rectal ulcer syndrome. The diagnosis was made by colonoscopic appearance and biopsy. A tumor measuring 0.9 x 0.6 cm was found in a resected solitary rectal ulcer. The lesion exhibited typical histological features of solitary rectal ulcer syndrome, with a well differentiated adenocarcinoma invading submucosal layers and some dysplastic glands. We believe that the adenocarcinoma represents a malignant transformation from solitary rectal ulcer syndrome, because similar to longstanding chronic idiopathic colitis, colorectal dysplasia and carcinoma may develop.

Adenocarcinoma↗

Arthroscopic management of temporomandibular closed lock.

Sixty-three consecutive patients with painful closed lock involving 83 temporomandibular joints were treated by surgery and followed up for at least 24 months. Prior to surgical treatment all had imaging to demonstrate that the cause of their painful jaw locking was an anterior displaced disc without reduction. All patients had received at least three months non-surgical treatment without response. The arthroscopic surgery consisted of release of adhesions, manipulation and placement of 25 mg hyaluronic acid into the joint space. No significant surgical complications occurred. Postoperative treatment involved physical therapy and stabilization splints. At 24 months after surgery 57 patients (90.5 per cent) had no pain and month opening had improved from preoperative 27.2 +/- 5.4 mm to 44.4 +/- 4.1 mm (p < 0.001). This study shows that arthroscopic surgery with continuing non-surgical therapy is a highly effective treatment for painful closed lock.

Adolescent↗

Cell reproduction and morphological changes in Mycoplasma capricolum.

The cell reproduction of Mycoplasma capricolum was studied. The velocity of DNA replication fork progression was about 6 kb/min, which is 10 times slower than that of Escherichia coli. The time required for one round of DNA replication accorded with the doubling time. The origin/terminus ratio was 2.0. M. capricolum cell morphology was classified into two types, rod and branched. In the ordinary-growth phase, the rod cells accounted for about 90% of the total population, with branched cells comprising the remaining 10%. The proportion of branched cells increased to 90% following inhibition of DNA replication by nucleoside starvation. An increase in the proportion of branched cells was induced by transfer of a temperature-sensitive mutant deficient in DNA replication to the restrictive temperature. The rod cells had a regular structure, a fixed cell length, and constrictions in the center. The DNA contents of individual rod cells were distributed with a standard deviation of 0.40 of average. The branched cells had irregular structures and a wide distribution of DNA contents. Counting of viable cells revealed that the cells ceased division upon cell type conversion; however, branched cells maintained a reproductive capacity. A model for the reproduction process is proposed.

Bacterial Proteins↗