Search PubMed⌕ Search

Biomedical subjects

M Miyata

Publications and source records attributed to M Miyata.

At least 343 records · Page 19Linked to original sources

Morphological study of the cataractous lens of the senescence accelerated mouse.

A murine model of accelerated aging, the senescence accelerated mouse (SAM), has been developed. There are three accelerated senescence-resistant (SAM-R) strains and eight senescence-prone (SAM-P) strains. The SAM-P strains have an earlier onset and more rapid advancement of senescence resulting from a significantly shorter lifespan compared with the SAM-R strains. Spontaneous cataracts have been found in some individuals of the SAM-P/9 strain. The SAM-P/1 strain, which was used in the present study, has such systemic senescent characteristics as senile amyloidosis and alopecia, but it was previously thought that cataract does not occur in this strain. However, we found cataractous changes in the lens of these animals at early stages of their life. The earliest change was the appearance of a ripple-mark body at about 3 months of age. The number of rippled rings increased with age. These changes later induced refractive distortion of retinal vessels. Whole-mount flat preparations of the epithelium showed that the number of cells was markedly decreased at the advanced stages of cataract. At the late stages of life the lens cortex became liquefied and developed into a mature cataract. Cataract formation in this strain may be related to reduced viability of the lens epithelium.

Aging↗

Calcium regulating activity of 24a-homo-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 and 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3.

Two fluoro analogs of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24a-homo-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24aF2-homo-1,25(OH)2D3], and 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24F2-1,25(OH)2(Me)2D3] were examined for calcium (Ca)-regulating activity. The objective of the present study was to determine whether or not fluoro substitution at 24-position would alter activities of the original compounds, that is, 26,27-dimethyl 1 alpha,25-dihydroxyvitamin. D3[1,25(OH)2(Me)2D3] and 24-homo-1 alpha,25-dihydroxyvitamin D3 [24homo-1,25(OH)2D3], respectively. The relative activities of 24aF2-homo-1,25(OH)2D3, 24F2-1,25(OH)2(Me)2D3, and 1,25(OH)2D3 in competing with 1,25(OH)2D3 for binding to chick intestinal cytosol receptor were 0.28:0.5:1.0. The relative potencies of the same series of compounds in competition for the vitamin D-deficient rat serum binding sites were 0.04:0.15:1. Bone-resorbing activities of two fluoro analogs in cultures of neonatal mouse parietal bones were more potent than that of 1,25(OH)2D3. Similar results were recognized in stimulating activities of osteoclast-like cell formation. Responses of two fluoro analogs to intestinal Ca absorption were similar to that of 1,25(OH)2D3. The potencies of 1,25(OH)2D3 and its fluoro analogs in bone Ca mobilization were the highest with 1,25(OH)2D3, followed by 24F2-1,25(OH)2(Me)2D3 and 24aF2-homo-1,25(OH)2D3, in that order. From these results and the data of Paulson et al., fluoro substitution in 24-position of 1,25(OH)2D3 apparently does not alter their activities,hence, the fluoro substitution at 24-position of 1,25(OH)2D3 and the elongation of side chain of 1,25(OH)2D3 may not intensify Ca-regulating activity.

Animals↗

Eradication of metastatic tumour cells from lymph nodes by local administration of anti-CD3 antibody.

The possibility of in vivo removal of metastatic tumour cells from lymph nodes by local intradermal administration of an anti-CD3 monoclonal antibody (mAb) was examined. Murine tumour cells in the lymph nodes were completely eradicated by intradermal injections of the mAb. This treatment was effective for removal of Lewis lung cancer cells from lymph nodes, but not for removal of subcutaneous tumours of this cell line. This treatment induced in vivo cytotoxicity in the regional lymph nodes against the syngeneic tumour cells. The following in vitro studies suggested that the cytotoxicity was probably mediated mainly by CD4+ T cells, with slight participation of CD8+ T cells. Normal lymph node and spleen cells showed cytotoxicity after in vitro incubation with the mAb for 2 days. Cell sorting with a fluorescein-activated cell sorter showed that CD4+ T cells developed during the incubation to lyse syngeneic tumor cells directly by themselves, macrophages not being involved in this tumour cell lysis. The lytic activity was detected in the cellular fractions, but not in the culture supernatants of these T cells. Furthermore, it was completely blocked by specific antiserum for tumour necrosis factor-alpha (TNF alpha). An immunoprecipitation study revealed that these T cells expressed TNF alpha molecules of 26 kDa, but not of 17 kDa, suggesting that tumour cell lysis was caused by membrane-integrated integrated TNF alpha molecules. These results strongly suggest that local administration of anti-CD3 antibody is a very effective and appropriate procedure for eradication of metastatic tumour cells from regional lymph nodes.

Animals↗

A case of anti-nuclear antibody negative systemic lupus erythematosus associated with penile ulcer.

We report here an old male patient with anti-nuclear antibody (ANA) negative systemic lupus erythematosus (SLE) with active renal disease and penile ulcer. He revealed nephrotic syndrome, malar rash and oral ulcer. SLE was discussed, however both ANA and anti-DNA antibody were persistently negative. A penile ulcer was also observed. He died of acute respiratory distress. Autopsy findings including onion skin lesion in the spleen and haematoxylin body in the kidney resulted in the final diagnosis of SLE. To our knowledge, association of penile ulcer with SLE has not yet been reported. Therefore, the present case is thought to be extremely unusual.

Antibodies, Antinuclear↗

An autopsy case of ulcerative colitis associated with Takayasu's disease with a review of 13 Japanese cases.

An autopsy was performed on a 42-year-old Japanese female who had been suffering from both ulcerative colitis (UC) and Takayasu's disease. Her UC started at age 27 with bloody stool, and Takayasu's disease was diagnosed at age 30 on the basis of absence of pulse in her left arm. After more than ten years she died of multiple cerebral infarction. An autopsy study revealed the scarring stage of UC in the entire colon and aortitis in the aortic arch and its major branches and pulmonary arteries. Her HLA type was positive for HLA-A2, 24, Bw52 and 61. Clinical features of a total of 13 Japanese cases that had both UC and Takayasu's disease have been reviewed in the Japanese and Western literature.

Adult↗

Detection of focal nodular hyperplasia of the liver with color Doppler ultrasonography.

A 3-cm lesion indicative of focal nodular hyperplasia (FNH) of the liver was coincidentally detected in a 21-year-old female. Ultrasonography (US), computed tomography (CT), magnetic resonance (MR) imaging and liver scintigraphy all proved nonspecific. However, color Doppler US demonstrated characteristic vascular patterns of FNH of the liver, including (a) hypervascularity of the mass, (b) an enlarged afferent blood vessel in the tumor with blood flow toward the center of the tumor, and (c) arterial pulse waves in all the vessels in the lesion, detected by means of the fast Fourier transformation (FFT). With selective hepatic angiography, a "spoke-wheel" pattern was revealed. The angiographic pattern corresponded well to that shown by color Doppler US. On the basis of the findings from these two modalities, the diagnosis of FNH was made. This report examines the effectiveness of color Doppler US in the differential diagnosis of FNH, compared with other imaging modalities.

Adult↗

Small bowel transplantation in rats: endoscopic and histological evaluation of graft rejection.

Heterotopic small bowel transplantation was performed using the cuff technique in DA(RT1a) to PVG(RT1c) rat fully allogeneic combination. In this model, the rejection course of the grafted intestine was evaluated endoscopically via double stomata and was classified into four stages. Early changes appeared on postoperative day 3. Stage I: The mucosa of the grafted intestine showed patchy paleness and loss of the capillary fine network patterns, accompanied by microerosions. Closer examination revealed irregularity of the epithelial height and arrangement. Stage II: The damage spread progressively over the entire mucosa on day 4-5. Stage III: On day 6-7, the necrotic epithelium became detached, showing multiple ulcers which provoked hemorrhagic enteritis. Stage IV: Graft rejection was completed with total necrosis and white scar tissue formation by day 10-14. These endoscopic findings of the mucosa of the grafted intestine corresponded closely to the time course of pathological examinations. We conclude that endoscopic examination of grafted intestine may be an effective diagnostic tool to detect the rejection phenomenon at an early stage, as well as a simple tool to use for postoperative follow-up in combination with pathological examination.

Animals↗

Detection of reperfusion 30 and 60 minutes after coronary recanalization by a rapid new assay of creatine kinase isoforms in acute myocardial infarction.

We measured creatine kinase (CK) isoforms by a new immunoinhibition method to evaluate their usefulness in detecting early coronary reperfusion. Blood samples were collected at 15-minute intervals from 50 patients with acute myocardial infarction. CK isoforms were determined by a 10-minute immunoinhibition method with an autoanalyzer. Values for inhibited isoforms (MM3, MM2/2, and MB2/2) were divided by those of noninhibited isoforms (MM1, MM2/2, MB1, MB2/2, and BB) to calculate the isoform ratio. In the reperfused group the increase in the isoform ratio was 2.69 +/- 1.80 (SD) 30 minutes after reperfusion and 2.41 +/- 2.01 at 60 minutes, which was significantly higher than the corresponding values in the nonreperfused group (0.17 +/- 0.16 and 0.32 +/- 0.26, respectively). When an increase of 0.70 or more in the isoform ratio was used as the criterion for reperfusion, the sensitivity and specificity were 92% and 100% at 30 minutes and 100% and 100% at 60 minutes after recanalization, respectively. We conclude that the isoform ratio obtained by the new 10-minute assay of CK isoforms is useful for the noninvasive detection of reperfusion 30 and 60 minutes after recanalization in acute myocardial infarction.

Angioplasty, Balloon, Coronary↗

Early detection of coronary reperfusion by rapid assessment of plasma myoglobin.

We assayed plasma myoglobin and creatine kinase to elucidate the usefulness of rapid assessment of myoglobin for detecting coronary reperfusion in 31 patients with acute myocardial infarction. Reperfusion was achieved in 20 patients by thrombolytic therapy or angioplasty, and it was not in 11 patients. Blood sampling was performed before and 43 +/- 15 (+/- SD) min after the start of treatment. In the reperfused group, blood samples were obtained before and 26 +/- 10 min after reperfusion. Myoglobin was assayed by a new quantitative test based on latex agglutination turbidimetry which required an assay time of 10 min. After treatment, the rate of increase of plasma myoglobin was significantly higher than that of plasma creatine kinase in the reperfused group (9.7 +/- 9.5 and 2.8 +/- 1.6-fold), but not in the occluded group (1.8 +/- 0.6 and 1.5 +/- 0.3-fold). When a 3.0-fold or greater increase in myoglobin (1.9-fold or greater increase in creatine kinase) was taken as evidence of coronary reperfusion, the sensitivity and specificity were 95% and 100% (70% and 82% in creatine kinase), respectively. In conclusion, using the rate of increase of myoglobin, as measured by latex agglutination turbidimetry, coronary reperfusion can be diagnosed within 1 h after reperfusion.

Adult↗

Tissue factor production by cultured rat glomerular epithelial cells.

It is well known that fibrin deposition in Bowman's space in association with crescent formation may play an important role in progressive glomerular injury in crescentic glomerulonephritis. Recent reports describe the presence of a procoagulant activity (PCA) in the glomeruli and its increased expression in human and experimental nephritis. The cells that synthesize PCA have not yet been identified. We attempted to determine if glomerular epithelial cells (GEC), one of the prominent cell populations in the crescent, can produce PCA. The PCA of cultured rat GEC was measured by clotting and amidolytic assays. The cultured GEC yielded PCA with the characteristics of a tissue factor, and this PCA was stimulated by interleukin 1, tumour necrosis factor-alpha, and lipopolysaccharide. We concluded that GEC produce tissue-factor-like PCA and thereby may contribute to fibrin deposition, which, along with macrophage or monocyte infiltration, leads to crescent formation in crescentic glomerulonephritis.

Animals↗

Comparison of potentiality to induce graft-versus-host reaction with small bowel, pancreas/spleen, and liver transplantation in the rat.

Although small bowel transplantation (SBT), or pancreas-spleen transplantation (PST) often lead to lethal graft-versus-host reaction (GVHR) in experimental animals, fatal GVHR is rare after clinical liver transplantation. This study describes a modified model of SBT and PST in the rat using cuff techniques applied to the renal artery and vein of the recipient. The ability of LEW (RT1(1)) or BN (RT1n) lymphocytes accompanying intestinal, splenic, or hepatic grafts to induce lethal GVHR in (LEW x BN) F1 hybrid recipients was compared. SBT and PST experiments showed that lethal GVHR always occurred in LEW-into-F1 combination, but was much less frequent in BN-into-F1 SBT. In mixed lymphocyte reaction (MLR), LEW mesenteric or splenic T cells showed significantly higher proliferative responses against BN stimulators than did BN mesenteric or splenic T cells against LEW. Adoptive cell transfer experiments using mesenteric or splenic cells also showed that LEW cells were higher responders than BN. In contrast with SBT and PST results, a lethal GVHR was not induced after liver or pancreas grafting alone in either parent-to-F1 combination. In MLR, hepatic T cells from either parent failed to elicit a proliferative response against allostimulators. These results indicate that the occurrence of lethal GVHR is dependent upon the reactivity of parental lymphocytes against allo-antigenicity of F1 hybrids and also upon the lymphoid tissue transplanted. The lack of alloreactivity of hepatic T cells accounts for the absence of lethal GVHR after liver grafting.

Animals↗

Localizing the replication origin region on the physical map of the Mycoplasma capricolum genome.

Four lines of evidence argue that the replication origin of the Mycoplasma capricolum genome lies within the 46-kb BamHI fragment bordered by two BamHI sites of the total of nine BamHI sites that have been located on the physical map (M. Miyata, L. Wang, and T. Fukumura, FEMS Microbiol. Lett. 79:329-334, 1991). First, this fragment lost its labeling in preference to other fragments when log-phase cultures were incubated in the presence of chloramphenicol for various times to inhibit the initiation of new rounds of replication and then further incubated with radioactive dTMP to allow DNA elongation to continue. Second, the relative frequencies of various restriction fragments of the genome DNA from exponentially growing cells decreased with increasing distance from the putative origin. Third, preferential labeling occurred when radioactive dTMP was added to cultures of a DNA elongation-defective, temperature-sensitive mutant with a simultaneous temperature downshift. Fourth, the M. capricolum homolog of the dnaA gene, which is located near the replication origin in many other bacteria, was found in the 46-kb fragment.

Chromosome Mapping↗

Anticardiolipin antibodies are associated with pulmonary hypertension in patients with mixed connective tissue disease or systemic lupus erythematosus.

Anticardiolipin antibodies (aCL) were studied in relation to pulmonary hypertension (PH) in 22 patients with mixed connective tissue disease (MCTD) or systemic lupus erythematosus (SLE). The mean pulmonary arterial pressure (mPAP) values were similar in the 12 MCTD and 10 SLE patients: 26 +/- 11 and 25 +/- 11 mm Hg, respectively. However, the frequency of PH was higher in SLE (60%) than in MCTD patients (33%). The titers of aCL were significantly higher in SLE (38 +/- 27 IU/ml) than in MCTD (17 +/- 7 IU/ml; p < 0.02). Two SLE patients with high titers of aCL had multiple cerebral infarction and transverse myelitis, and deep vein thrombosis, respectively. A significant correlation between the titers of aCL and mPAP was observed in patients with MCTD (p < 0.05), but not in patients with SLE.

Adult↗

Myocardial infarct size can be estimated from serial plasma myoglobin measurements within 4 hours of reperfusion.

BACKGROUND: An early estimation of infarct size is useful for the appropriate early treatment of patients with acute myocardial infarction. We evaluated how early and how accurately infarct size could be estimated from serial plasma myoglobin (Mb) measurements in patients with successful reperfusion. METHODS AND RESULTS: We measured plasma Mb and creatine kinase (CK) in 35 patients in whom reperfusion therapy was successfully performed. Blood samples were collected at 15-minute intervals for 2 hours after reperfusion, at 30-minute intervals for the subsequent 2 hours, and at 3-6-hour intervals until 52 hours after reperfusion. Plasma Mb was measured by a newly developed turbidimetric latex agglutination assay. Total Mb and CK release (sigma Mb, sigma CK) were calculated with a one-compartment model. The mean chord motion in the most hypokinetic 50% of the infarct-related artery territory was calculated from follow-up ventriculograms as an index of the severity of regional hypokinesis. There were significant correlations between sigma Mb and sigma CK (r = 0.89), between log sigma Mb and the severity of regional hypokinesis (r = -0.85), and between log sigma CK and the severity of regional hypokinesis (r = -0.74). The time required for the cumulative Mb release curves to reach a plateau was 64 +/- 28 minutes. An additional 53 +/- 14 minutes was required to calculate the disappearance rate constant of Mb, and 15 minutes was necessary for the assay. Therefore, the total time required for sigma Mb to be available was 132 +/- 40 minutes, significantly shorter than the time required for sigma CK, 24.3 +/- 9.1 hours (p < 0.001). The infarct size could be estimated from the sigma Mb in 34 of 35 patients within 4 hours of reperfusion. CONCLUSIONS: Infarct size can be estimated accurately 4 hours after reperfusion by calculating the sigma Mb in patients with successful reperfusion.

Clinical Enzyme Tests↗

Dexamethasone inhibits nitric oxide synthase mRNA induction by interleukin-1 alpha and tumor necrosis factor-alpha in vascular smooth muscle cells.

The effects of interleukin-1 alpha, tumor necrosis factor-alpha and dexamethasone on the induction of nitric oxide synthase mRNA in rat aortic smooth muscle cells were studied. Neither interleukin-1 alpha (up to 100 U/ml) nor tumor necrosis factor-alpha (up to 5000 U/ml) was capable of inducing nitrite/nitrate production and nitric oxide synthase mRNA in smooth muscle cells. In contrast, treatment for 12 hr or longer with a combination of the two synergistically induced nitrite/nitrate and cyclic GMP production in cell culture media and nitric oxide synthase mRNA, both of which were prevented by dexamethasone. Contamination with bacterial lipopolysaccharide, which may affect the induction of nitric oxide synthase, was below 30 pg/ml in all experiments. Our findings show that dexamethasone and these cytokines regulate the induction of nitric oxide synthase at the mRNA level in vascular smooth muscle cells.

Amino Acid Oxidoreductases↗

A patient with primary hyperparathyroidism associated with osteomalacia: markedly increased serum levels of intact PTH and 1,25-dihydroxyvitamin D with normo- and hypercalcemia.

A 65-year-old female patient was admitted with complaining chiefly of lower back pains and arthralgia in the bilateral knee joints of 10-years duration. The serum calcium concentration was normal or only slightly increased, whereas the serum intact PTH and 1,25-dihydroxyvitamin D concentrations were substantially increased. Serum phosphate and 25-hydroxyvitamin D concentrations were decreased. Renal function was normal. Serum alkaline phosphatase activity, the osteocalcin concentration and urinary hydroxyproline excretion were markedly increased. Bone X-ray examination showed severe osteopenia and bone biopsy revealed hyperosteoidosis without tetracycline deposition, consistent with osteomalacia. A parathyroid adenoma was demonstrated by echography and CT-scan. Surgical exploration of the neck revealed a chief cell adenoma behind the right upper pole of the thyroid gland. After parathyroidectomy, all the abnormal biochemical data gradually normalized and the patient has been doing well without any symptoms for the last 13 months. These clinical data suggest that osteomalacia of the patient was probably induced by hypophosphatemia of prolonged duration. When hypercalcemia is not evident in a patient with primary hyperparathyroidism, in whom serum alkaline phosphatase and intact PTH levels are inappropriately increased, osteomalacia should be taken into consideration.

Adenoma↗

Chronic intoxication of organophosphorus pesticide and its treatment.

Clinical manifestations of chronic intoxication due to organophosphorus pesticide (OP) and treatment by prifinium bromide, an anticholinergic drug (Padrin), have been introduced. All patients showed oculopathy, mainly neuro-ophthalmological impairments such as: 1. optic neuropathy, 2. degeneration of the retina, 3. defective vertical smooth pursuit, 4. myopia; spasm or paresis of accommodation with or without corneal astigmatism "with the rule" and mild general neurological impairments. These manifestations were more severe among children than in adults, who were environmentally exposed mainly to 3% Malathion sprayed by helicopters several times a year for over 3-5 years. Presumed intake of Malathion for a given child is a far lower dosage than considered previously. Padrin (prifinium bromide) with vitamin B12, C, and E were effective in regressing oculopathy exposed environmentally to OP pesticides.

Child↗