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Biomedical subjects

H Miyajima

Publications and source records attributed to H Miyajima.

At least 37 records · Page 2Linked to original sources

Stress and coping behavior in patients with diabetes mellitus.

Diabetes mellitus is a disease which must be controlled over the lifetime of a patient. We investigated the issues of stress and coping for diabetes mellitus which may influence self-management. In addition, we examined the association of these factors with blood glucose control, in order to review self-management instructions for diabetes mellitus. The study included 153 patients with diabetes mellitus. The patients were divided into two subgroups: good-control group, comprising patients with glycohemoglobin (HbA1c) values less than 7.0%; and poor-control group, comprising those with HbA1c values of 7.0% or more. All patients responded to a questionnaire regarding stress tolerance, Jalowiec and Power's coping scale and awareness of diabetes mellitus. Stress tolerance was not significantly different between the good-control and poor-control groups. No significant gender differences in coping score were evident for the good-control group. However, in the poor-control group, the coping score in men was significant higher than that in women. The problem-oriented coping score for men in the poor-control group was significantly higher than that for the good-control group (p < 0.01). In a comparison of awareness of diabetes mellitus, the proportion of patients who replied that they were rigidly following diabetes treatment was higher in the poor-control group than the good-control group. Patients with diabetes mellitus may have a knowledge of the disease and a strong will to resolve problems. This is especially true for male patients in that their will appeared to be stronger, but they may not have the resolve to establish appropriate behavior patterns. In the future, methods for evaluating self-management should be included in diabetes education.

Adaptation, Psychological↗

Age-related changes in the magnitude of ventricular depolarization vector: analyses by magnetocardiogram.

The magnetocardiogram has the beneficial feature that permits the strength and location of the current dipole to be estimated. This study examines the issue of whether the magnitude of the heart current during depolarization phase was influenced by the age of healthy subjects. The magnetocardiograms were recorded by means of a second-derivative SQUID (superconducting quantum interference device) magnetometer (BT Corp, Model BMP, San Diego, CA) in 150 healthy subjects. The subjects were subgrouped into 5 age-based categories according to the age. The current dipole of the maximum QRS complex was determined from isofield contour maps during the ventricular depolarization phase, and no significant differences were observed in the magnitude in the current source for any age category. However, the amplitudes of the RV5 and SV1 + RV5 in the standard electrocardiogram were larger in 65 to 74-year-old women than other age groups, and the SV1 + RV5 was smaller for the 45 to 74-year-old men than for the men aged 25 to 44 years. These findings suggest that the age-associated changes in the QRS complex observed by the electrocardiogram are caused by increased electric resistance and not by the heart current itself. The results additionally suggest that no effects of aging were observed in the actual heart current of the heart during the depolarization phase.

Action Potentials↗

Is autonomic dysfunction a necessary condition for chronic peptic ulcer formation?

BACKGROUND: The relationship between 1/f fluctuation of the heart rate variability and Helicobacter pylori infection was evaluated, in order to clarify whether autonomic nervous dysfunction is a necessary condition for chronic peptic ulcer formation. METHODS: The subjects were 11 patients with recurrent chronic peptic ulcer and 20 age-matched normal subjects. Holter ECGs were recorded over 24 h, and the 1/f(-x) fluctuation of the heart rate was computed. The 1/f(-x) fluctuation of the heart rate is a novel index of autonomic function that has been shown to reflect a patient's pleasant mood. For 1/f(-x) fluctuation, the slope of the regression line (-x) was determined and cosine fitting of the absolute slope of the regression line over a 24-h period was performed. RESULTS: For the normal group, the absolute slope of the regression line during daytime and night-time were 0.53 +/- 0.16 and 1.05 +/- 0.18, respectively. For the peptic ulcer group, the corresponding values during daytime and night-time were 0.94 +/- 0.15 and 1.84 +/- 0.18, respectively. The mean value of the cosine curve was 0.76 +/- 0.23 in the normal group and 1.12 +/- 0.25 in the peptic ulcer group. Thus, these values were significantly higher for the latter group than for the former group (P<0.05). No statistically significant difference in H. pylori infection between the two groups was observed. CONCLUSIONS: Autonomic nervous dysfunction as well as H. pylori infection appears to be a necessary condition for chronic peptic ulcer formation.

Aged↗

Evaluation of autonomic nervous function in patients with essential hypertension complicated with peptic ulcer.

BACKGROUND AND AIMS: The relationship between peptic ulcer, autonomic activity and the incidence of Helicobacter pylori infection in untreated hypertensive patients complicated with peptic ulcer were evaluated. METHODS: Ten hypertensive patients with peptic ulcer (HT-PU group), 15 untreated essential hypertensive patients without peptic ulcer (HT group) and 10 normal subjects (N group) were enrolled, and a power spectral analysis was performed in each subject. A biopsy urease test was used to detect infection by H. pylori. RESULTS: No significant differences were observed in the values of mean low-frequency (LF) power between the three groups. However, the mean high-frequency (HF) power in the HT-PU group was significantly greater than those of the HT and N groups (P<0.01). The mean LF/HF ratios in the HT-PU and HT groups were significantly greater than that of the N group (P<0.01). With respect to H. pylori infection, no significant differences between the three groups were observed. Sympathetic activity (LF power) was increased in the HT and HT-PU groups. Furthermore, parasympathetic activity (HF power) was increased in the HT-PU group. CONCLUSIONS: These findings suggest the participation of increased parasympathetic activity in peptic ulcer patients. Therefore, it is suggested that new techniques, such as spectral analysis of heart rate variability, as used in this study, will clarify the relationship between peptic ulcer and autonomic nervous function.

Autonomic Nervous System↗

Expression of receptors for glial cell line-derived neurotrophic factor (GDNF) and neurturin in the inner blood-retinal barrier of rats.

The retina is protected from somatic circulation by the blood-retinal barrrier (BRB) composed of tight junctions between retinal vascular endothelial cells (the inner BRB) and those between retinal pigment epithelial cells (the outer BRB). Our recent studies showed that glial cell line-derived neurotrophic factor (GDNF) secreted from astrocytes regulates the permeability of the BBB. In the present study, we immunohistochemically examined the expression of GDNF, neurturin (NTN) and their receptors, GFRalpha1 for GDNF and GFRalpha2 for NTN, because the capillaries of the inner BRB show specialization very similar to the blood-brain barrier (BBB). GDNF and NTN were detected in glial fibrillary acidic protein (GFAP)-positive cells, including Müller cells. GFRalpha1 and GFRalpha2 were localized in von Willebrand factor-positive cells. GDNF and NTN enhanced the barrier function of endothelial cells derived from porcine brain cortex. These results strongly suggest that the barrier function of the BRB is regulated by GDNF and NTN secreted from glial cells, like the BBB.

Animals↗

Decreased GlcNAc 6-O-sulfotransferase activity in the cornea with macular corneal dystrophy.

PURPOSE: Macular corneal dystrophy (MCD) is an autosomal recessive inherited disorder that is accompanied by corneal opacity. Explants from MCD-affected corneas have been reported to synthesize low-sulfated KS, suggesting that sulfate groups attached to KS may play critical roles in maintaining corneal transparency. To clear the biosynthetic defect in the MCD cornea, sulfotransferase activities were determined that are presumably involved in the biosynthesis of KS: galactose-6-sulfotransferase (Gal6ST) activity and N-acetylglucosamine 6-O-sulfotransferase (GlcNAc6ST) activity. METHODS: Gal6ST and GlcNAc6ST activities, which were contained in the corneal extracts from corneas affected by MCD and keratoconus and from normal control corneas, were determined by measuring the transfer of (35)SO(4) from [(35)S]3'-phosphoadenosine 5'-phosphosulfate into the Gal residue of partially desulfated KS and the nonreducing terminal GlcNAc residue of GlcNAcbeta1-3Galbeta1-4GlcNAc (oligo A), respectively. RESULTS: The level of Gal6ST activity in corneal extracts from eyes with MCD, which was measured by using partially desulfated KS as an acceptor, was nearly equal to that in eyes with keratoconus and normal control eyes. In contrast, GlcNAc6ST activity in the extracts from MCD-affected corneas, which was measured by using oligo A as an acceptor, was much lower than in those in corneas with keratoconus and in normal control corneas. CONCLUSIONS: The decrease in GlcNAc6ST activity in the cornea with MCD may result in the occurrence of low- or nonsulfated KS and thereby cause corneal opacity.

Adult↗

[Neuronal cell damage in aceruloplasminemia].

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism that causes neurodegeneration of the retina and basal ganglia, as well as diabetes mellitus. The neurological symptoms in affected patients include involuntary movements, ataxia, and dementia reflecting the sites of iron deposition detected by MRI, and the regions of neurodegeneration observed at autopsy. Excess iron functions as a potent catalyst of biologic oxidation. CSF from affected patients revealed a threefold increased iron concentration associated with increased superoxide dismutase activity and lipid peroxidation products. We found that the amount of iron accumulated in various regions of the brain and visceral organs is correlated with the levels of the oxysterols, including 7-hydroxycholesterol, and 7-ketocholesterol, which are directly produced from cholesterol by active oxygen species. Positron emission tomography done on brains of aceruloplasminemia patients showed cortical glucose hypometabolism. Enzyme activities in the mitochondrial respiratory chain of the cerebral cortices of the patients were reduced to approximate 62% and 71%, respectively, for complexes I and IV. These findings suggest that iron-mediated free radicals contribute to lipid peroxidation and the impairment of mitochondrial energy metabolism in aceruloplasminemia.

Brain↗

[Aceruloplasminemia].

Ceruloplasmin is an abundant alpha 2-serum glycoprotein that contains greater than 95% of the copper present in human plasma. It is synthesized mainly in the liver. Aceruloplasminemia is an autosomal recessive disorder affecting iron metabolism, originally called familial apoceruloplasmin deficiency, which manifests late-onset blepharospasm and retinal degeneration. Subsequent investigations have found patients with late adult onset of ataxia and diabetes mellitus. Our patients have also shown diabetes. Clinically, aceruloplasminemia is a triad consisting of neurologic disease, retinal degeneration, and diabetes. This disease is characterized by mutations in the ceruloplasmin gene and iron accumulation in the retina and basal ganglia as well as in parenchymal tissues caused by a complete deficiency of ceruloplasmin ferroxidase activity. The neurological symptoms in affected patients include involuntary movements, ataxia, and dementia reflecting the sites of iron deposition detected by MRI as well as the regions of neurodegeneration observed at autopsy. Consistent with this observation, ceruloplasmin gene expression is detected in the retina and basal ganglia revealing that this protein is essential for iron homeostasis neuron survival in the central nervous system. The unique involvement of the central nervous system distinguishes aceruloplasminemia from other inherited and acquired iron storage disorders.

Adult↗

A novel mutation (Cys6Gly) in the Cu/Zn superoxide dismutase gene associated with rapidly progressive familial amyotrophic lateral sclerosis.

Autosomal-dominant familial amyotrophic lateral sclerosis (FALS) is associated with mutation in the gene that encodes Cu/Zn superoxide dismutase (SOD1). We identified a novel missense mutation of SOD-1 (Cys6Gly) in exon 1 in a Japanese woman and her family. The illness showed rapid progression similarly to the FALS with a mutation of Cys6Phe that was reported by Morita et al. (1996) (Morita, M., Aoki, M., Abe, K., Hasegawa, T., Sakuma, R., Onodera, Y., Ichikawa, N., Nishizawa, M. and Itoyama, Y., A novel two-base mutation in the Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis in Japan. Neurosci. Lett., 205 (1996) 79-82). Mutation of the cystein at amino acid 6 might be associated with the rapid progression of ALS.

Amyotrophic Lateral Sclerosis↗

Procarbazine genotoxicity in the MutaMouse; strong clastogenicity and organ-specific induction of lacZ mutations.

Procarbazine, a drug used for cancer chemotherapy, is carcinogenic in rodent bioassays. We analyzed the mutagenicity of procarbazine in various organs and the clastogenicity of the drug in hematopoietic cells of the lacZ transgenic MutaMouse. This was part of the second collaborative study of the Mammalian Mutagenesis Study Group of the Japanese Environmental Mutagen Society on the transgenic mouse mutation assay. At 50 mg kg(-1), procarbazine induced micronuclei in hematopoietic cells, but it did not increase the lacZ mutant frequency (MF) in bone marrow. It was also negative in liver, testis, spleen, kidney, and lung. Five daily administrations of 150 mg kg(-1) yielded highly positive responses in the drug's target organs for carcinogenesis (lung, bone marrow, and spleen). Lower positive responses were detected in kidney, which is a minor target organ. Liver showed only a slight increase in lacZ MF and brain showed no increase. The testis MF more than doubled which suggest that procarbazine is mutagenic to germ cells. Thus, we demonstrated that procarbazine has a strong clastogenic effect in hematopoietic cells and is mutagenic in a variety organs after high dose treatment. The induced MF was especially high in procarbazine's target organs for carcinogenesis, which supports the relevance of the transgenic mouse mutation assay for the assessment of potential genotoxins in vivo.

Animals↗

Estimation of the gene frequency of aceruloplasminemia in Japan.

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism that causes neurodegeneration of the retina and basal ganglia as well as diabetes mellitus. We screened the serum ceruloplasmin concentrations of 4,990 healthy adult individuals. Subsequent sequence determination of the mutant alleles showed three mutations (5-bp insertion in exon 7, one heterozygote, one-bp deletion in exon 14, two heterozygotes, nonsense mutation in exon 15, one homozygote and two heterozygotes). The gene frequency was 70/100,000. In Japan, the incidence of aceruloplasminemia was estimated to be approximately 1 per 2,000,000 in the case of nonconsanguineous marriages.

Adult↗

Propagation of a magnetic domain wall in a submicrometer magnetic wire

The motion of a magnetic domain wall in a submicrometer magnetic wire was detected by use of the giant magnetoresistance effect. Magnetization reversal in a submicrometer magnetic wire takes place by the propagation of a magnetic domain wall, which can be treated as a "particle." The propagation velocity of the magnetic domain wall was determined as a function of the applied magnetic field.

Journal Article↗

A metalloproteinase inhibitor prevents acute graft-versus-host disease in mice after bone marrow transplantation.

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), which is a major complication after allogeneic bone marrow transplantation. We have examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in a murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 to irradiated (BALB/c x C57BL/6) F1 mice that received C57BL/6 bone marrow cells and spleen cells reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The KB-R7785 treatment did not affect hematopoietic reconstitution by donor cells. Therefore, KB-R7785 could be a potent therapeutic agent for GVHD after bone marrow transplantation.

Animals↗

Measurement of activities of human serum sulfotransferases which transfer sulfate to the galactose residues of keratan sulfate and to the nonreducing end N-acetylglucosamine residues of N-acetyllactosamine trisaccharide: comparison between normal controls and patients with macular corneal dystrophy.

Human serum sulfotransferase activities were measured in normal controls and patients with macular corneal dystrophy (MCD), an inherited disorder characterized by the decreased sulfation of keratan sulfate in the corneal stroma and serum, using two kinds of acceptor: partially desulfated keratan sulfate and a trisaccharide with a GlcNAc residue at the nonreducing terminal, GlcNAcbeta1-3Galbeta1-4GlcNAc. When partially desulfated keratan sulfate was used as the acceptor, only sulfotransferase activity which transfers sulfate to position 6 of the Gal residues was detected. In contrast, when GlcNAcbeta1-3Galbeta1-4GlcNAc was used as the acceptor, sulfotransferase activity which transfers sulfate to position 6 of the nonreducing terminal GlcNAc residue could be detected. Although keratan sulfate levels in the sera of MCD patients determined by ELISA were much lower than those in normal controls, there were no detectable differences in either the sulfotransferase activity responsible for the sulfation of position 6 of Gal residues or that responsible for the sulfation of position 6 of nonreducing end GlcNAc residues between normal controls and MCD patients. These results suggest that the sulfotransferase involved in the sulfation of keratan sulfate, which is assumed to be deficient in MCD patients, may not be secreted into the serum, and that direct measurement of the sulfotransferase activity present in affected tissues such as the cornea instead of serum may be necessary to confirm the postulated deficiency in the biosynthesis of keratan sulfate in MCD.

Acetylglucosamine↗

Evaluation of cardiac function in myocardial infarction patients by ECG 99mTc-MIBI gated SPECT using a three-dimensional perfusion/motion map procedure.

Three-dimensional (3D) radionuclear myocardial imaging has improved the evaluation of left ventricular wall motion. However, there have been no studies evaluating left ventricular function using 3D-perfusion/motion map techniques. We hypothesized that the 3D-perfusion/motion map could accurately evaluate left ventricular wall motion even in patients with a history of myocardial infarction. Electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT) using 99mTc-methoxy isobutyl isonitrile (MIBI) was performed in 20 patients with a history of myocardial infarction who underwent left ventriculography. Myocardial imaging data were collected during ECG-gated SPECT using a 3-headed gamma camera. Reconstructed 3D SPECT images were oriented to correspond to standard left ventriculography views (right anterior oblique and left anterior oblique projections), and the shortening fraction (SF) was calculated using the center line method. The SF and left ventricular ejection fraction from 3D SPECT images were compared with those determined by left ventriculography. There was a significant correlation between left ventriculography and the 3D-perfusion/motion map procedure in determining SF for all regions of the left ventricle except the anterobasal and posterior segments by using the Bland and Altman method. The 3D-perfusion/motion map procedure offers the advantage that the influences of contraction-related myocardial torsion and three-dimensional compression are minimized. In addition, this method facilitates evaluation of images from nonstandard projections. We conclude that this method may be useful for evaluating left ventricular function.

Aged↗

A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving the graft-versus-leukaemia effect of allogeneic bone marrow transplantation.

We examined the effect of a hydroxamic acid-based matrix metalloproteinase inhibitor (KB-R7785), which we previously demonstrated to have a potent ameliorating effect on acute graft-versus-host disease (GVHD), and on the graft-versus-leukaemia (GVL) effect of allogeneic bone marrow transplantation (BMT). KB-R7785 was administered to (C57BL/6 x BALB/c) F1 (CBF1) mice that had been inoculated with IgE-producing B53 hybridoma cells of BALB/c origin as a model tumour, along with or without transplantation of C57BL/6 (B6) bone marrow cells and spleen cells (BMS). Administration of KB-R7785 without BMS significantly prolonged the survival of B53-inoculated CBF1 mice by inhibiting the infiltration of B53 cells into the liver and spleen. Transplantation of B6 BMS without KB-R7785 resulted in the death of most recipients due to acute GVHD while efficiently eliminating B53 cells. Administration of KB-R7785 along with B6 BMS resulted in a 50% survival of B53-inoculated CBF1 mice over 50 d without histological manifestations of acute GVHD or residual B53 cells. These results indicate the beneficial effects of KB-R7785 that inhibit tumour infiltration and prevent acute GVHD while preserving the GVL effect of allogeneic BMT.

Animals↗