Search PubMed⌕ Search

Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 343 records · Page 19Linked to original sources

Marked decrease of mitochondrial DNA with multiple deletions in a patient with familial mitochondrial myopathy.

Muscle mitochondrial DNA (mtDNA) from a patient with mitochondrial myopathy was examined by Southern blotting. Her family history suggests autosomal dominant inheritance of this disorder. In contrast to other cases of this myopathy that are associated with a compensatory increase of mitochondria, in this patient, the content of mtDNA was markedly decreased (15% of controls), whereas protein of the ATP synthase beta-subunit was not decreased appreciably as judged by Western blotting. In addition, the mitochondrial DNA had multiple deletions, which were located between the replication origins of the heavy strand and light strand.

Adult↗

Effect of laser irradiation on the dissolution kinetics of hydroxyapatite preparations.

This research investigated the effects of a laser irradiation treatment on the dissolution characteristics of hydroxyapatite (HAP), and the results provide an insight into the relationship between the effects of laser treatment and the two-site dissolution kinetics of HAP samples. The HAP samples prepared by aqueous precipitation and digestion at approximately 100 degrees C were irradiated with a CO2 laser (20-50 W) with a beam diameter of 14 mm for a total of 10-400 s. Dissolution rates of the laser-treated HAP samples were subsequently determined in acetate buffer (pH = 4.5, mu = 0.50) at various levels of partial saturation (0-24% with respect to the HAP thermodynamic solubility of pKsp = 116). The following were the important findings. The X-ray diffraction and the IR spectroscopy results suggested that the HAP crystalline structure was not changed by laser treatment. Laser treatment of HAP powder at 50 W for 400 s, however, caused an approximately 3.5-fold reduction in the specific surface area of HAP and reduced the initial dissolution rate of HAP in acetate buffer by a factor of approximately 22.9. Also, this laser treatment appeared to reduce the dissolution rate of HAP in 16 and 24% partially saturated acetate buffer from substantial levels to essentially zero. These results may be summarized as follows. Laser treatment of HAP results in a reduction in the dissolution rate and also a reduction in the specific surface area of this material. However, the dissolution rate reduction is significantly greater than the reduction in the specific surface area.(ABSTRACT TRUNCATED AT 250 WORDS)

Hydroxyapatites↗

Pain and neurotransmitters.

1. To study physiological roles of substance P (SP), gamma-aminobutyric acid (GABA), enkephalins and other endogenous substances, we developed several kinds of isolated spinal cord preparations of newborn rats. 2. In these preparations, various slow responses of spinal neurons evoked by stimulation of primary afferent C fibers were depressed by a tachykinin antagonist, spantide. These results together with many other lines of evidence suggest that SP and neurokinin A serve as pain transmitters in a subpopulation of primary afferent C fibers. 3. Some C-fiber responses in various isolated spinal cord preparations were depressed by GABA, muscimol, and opioid peptides. In contrast, bicuculline (GABA antagonist) and naloxone (opioid antagonist) potentiated the "tail pinch potential," i.e., a nociceptive response of the ventral root evoked by pinch stimulation of the tail in isolated spinal cord-tail preparation of the newborn rat. The latter results support the hypothesis that some primary afferents activate inhibitory spinal interneurons which release GABA and enkephalins as transmitters to modulate pain inputs.

Action Potentials↗

A population cytogenetic study of a common fragile site, fra(3)(p14), in a healthy population.

A population survey of a common folate-sensitive fragile site, fra(3)(p14), was carried out on PHA-stimulated peripheral lymphocytes of 1,078 healthy subjects. Fra(3)(p14) was expressed more frequently in the younger than in the older, and in males than in females. It also showed some seasonal variation. The age difference of the expression frequency was also observed by aphidicolin treatment. A positive correlation of the expression frequency was found, though not so strongly, between both culture conditions of folate deprivation and aphidicolin treatment, These findings suggest that the inter-individual variation in the expressivity of common fragile sites is not only ascribable to chance, but to some physiological conditions of blood donors such as response rate of lymphocyte to PHA stimulation and blood concentration of folic acid.

Adolescent↗

Comparison of I-123 IMP and Tc-99m HMPAO SPECT studies with PET in dementia.

We compared I-123 IMP and 99m-Tc HMPAO SPECT studies with 0-15 H2O and F-18 FDG PET studies, and evaluated the clinical significance of SPECT studies in dementia. Seventeen patients including 9 patients with Alzheimer's disease, 3 patients with Pick's disease and 5 patients with multi-infarct dementia were studied. IMP and HMPAO SPECT studies could not detect mildly affected areas when compared with FDG PET. However, they revealed decreased perfusion in the bilateral parietal regions in Alzheimer's disease and in the bilateral frontal regions in Pick's disease, while MRI and/or CT showed mild to moderate cerebral atrophy. IMP and HMPAO SPECT studies can be easily performed in clinical practice, and these findings were useful in the differential diagnosis of dementia. Our preliminary results suggested that SPECT studies with I-123 IMP and Tc-99m HMPAO, despite their limitations, are useful in the differential diagnosis of dementia.

Aged↗

Cutaneous nerve-evoked cholinergic inhibition of monosynaptic reflex in the neonatal rat spinal cord: involvement on M2 receptors and tachykininergic primary afferents.

The mechanisms of a cutaneous nerve-evoked inhibition of monosynaptic reflex were investigated in an isolated spinal cord-peripheral nerve preparation of the neonatal rat. Conditioning stimulation of the saphenous nerve, with five pulses at 50 Hz and a strength sufficient to activate C fibers, evoked an inhibition lasting about 20 s of the monosynaptic reflex that was elicited by stimulation of the nerve branch to quadriceps femoris muscle and recorded from the L3 ventral root. This inhibition of monosynaptic reflex was potentiated by an anticholinesterase, edrophonium, and mostly blocked by atropine. Application of acetylcholine, muscarine, bethanechol, carbachol, arecoline and oxotremorine induced an inhibition of monosynaptic reflex. From the effects of muscarinic antagonists, pirenzepine, AF-DX 116, and 4-diphenylacetoxy-N-methylpiperidine on the agonist-evoked and primary afferent-evoked inhibition of monosynaptic reflex it was concluded that the muscarinic receptors involved in the cutaneous nerve-evoked inhibition of monosynaptic reflex are of M2 type. When monosynaptic reflexes were evoked by two successive stimuli with intervals of 15 ms to 1 s, the second response was smaller than the first. This depression of monosynaptic reflex became less pronounced when the reflex was reduced by application of oxotremorine or arecoline or by conditioning stimulation of primary afferents, suggesting that the inhibition of monosynaptic reflex is presynaptic in nature. The late phase of the cutaneous nerve-evoked inhibition of monosynaptic reflex (5-20 s after conditioning stimulation) was markedly depressed by a tachykinin antagonist, spantide. Perfusion of the spinal cord with capsaicin (1 microM) for 1 h also abolished the late phase of the inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Differential diagnosis of bilateral parietal abnormalities in I-123 IMP SPECT imaging.

This report discusses the clinical significance of bilateral parietal abnormalities on I-123 IMP SPECT imaging in 158 patients with cerebral disorders. This pattern was seen in 15 out of 21 patients with Alzheimer's disease; it was also seen in 4 out of 5 patients with Parkinson's disease with dementia, in 3 out of 17 patients with vascular dementia, in 1 out of 36 patients with cerebral infarction without dementia, in 1 out of 2 patients with hypoglycemia, and in 1 out of 2 patients with CO intoxication. Detection of bilateral parietal abnormalities is a useful finding in the diagnosis of Alzheimer's disease, but one should keep in mind that other cerebral disorders may also show a similar pattern with I-123 IMP SPECT imaging.

Aged↗

Pharmacological profile of a tachykinin antagonist, spantide, as examined on rat spinal motoneurones.

1. The pharmacological profile of a tachykinin antagonist, [D-Arg1, D-Trp7,9, Leu11] substance P (spantide), was studied on motoneurones of the isolated spinal cord of the newborn rat. For this purpose, potentials were recorded from a lumbar ventral root extracellularly and drugs were bath-applied in the presence of tetrodotoxin (TTX). 2. Neurokinin A (NKA), a NK2-receptor selective agonist, induced concentration-dependent depolarizations, which were antagonized by spantide. Analyses of concentration-response curves suggested a competitive type antagonism with a pA2 of 6.5. 3. Depolarizations induced by acetyl-Arg6-septide, a NK1-receptor selective agonist, were also antagonized by spantide with a pA2 of 6.5. 4. Spantide (0.5-16 microM) had no depolarizing action on the ventral root in the presence of TTX. 5. Spantide antagonized the depolarizing action of substance P (SP) when SP was applied at low concentrations (0.1-0.3 microM) or by short duration pulses in artificial cerebrospinal fluid containing TTX, but much higher concentrations of spantide (4-10 microM) were needed to exert an antagonistic action against SP than against acetyl-Arg6-septide or NKA. 6. Thyrotrophin-releasing hormone, L-glutamate, GABA, and noradrenaline, also induced depolarizations of the ventral root in the presence of TTX but the responses to these agonists were not depressed by spantide (16 microM). 7. These results suggest that there is a subtype of tachykinin receptors on neonatal rat spinal motoneurones to which NKA, acetyl-Arg6-septide and spantide bind competitively with high affinity. The present results also suggest the existence on rat motoneurones of another class or other classes of tachykinin receptors that are less sensitive to the antagonistic action of spantide.

Analgesics↗

Effect of surface characteristics of theophylline anhydrate powder on hygroscopic stability.

The hygroscopicity of theophylline anhydrate has been investigated by gas adsorption and hydration kinetic methods. Type 1 theophylline anhydrate was obtained by recystallization from distilled water at 95 degrees C, and type II was obtained by dehydration of theophylline monohydrate. The X-ray diffraction pattern of types I and II agreed with the data of theophylline anhydrate. However, the diffraction peaks of the (200) and (400) planes of type I were much stronger than those of type II. The particles of type I were clear crystalline-like single crystals. However, the particles of type II had many cracks. The gas affinity balance (H/N) of type II, measured by gas adsorption, was about 7 times that of type I. After the hygroscopicity of types I and II had been tested at various levels of relative humidity (RH) at 35 degrees C, type I was stable at less than 82% RH, but transformed into the monohydrate at more than 88% RH. Type II was stable at less than 66% RH and transformed into the monohydrate at less than 75% RH. The hydration data of type I at 88% RH and type II at 75% RH were calculated for hydration kinetics using various solid-state kinetic models, but no particular model could be preferred from these data.

Adsorption↗

Cerebral hemodynamic change in the child and the adult with moyamoya disease.

To clarify the differences in cerebral hemodynamics and metabolism between children and adults with bilateral moyamoya disease, we measured regional cerebral blood flow, regional oxygen extraction fraction, regional metabolic rate for oxygen, regional cerebral blood volume, and regional transit time using positron emission tomography in nine patients (five children and four adults) and compared the values with those in controls (four children with unilateral moyamoya disease and six normal adults). The major differences between pediatric and adult patients were in regional cerebral blood volume and regional oxygen extraction fraction. Regional cerebral blood volume was more markedly increased relative to the control value in the children than in the adults. Also, regional oxygen extraction fraction was greater than control in areas with low blood flow in the children but was never increased in the adults. However, in the adults, only regional transit time was significantly prolonged relative to the control values. The increased regional oxygen extraction fraction relative to the control value observed in children with moyamoya disease may explain why transient ischemic attacks are a common symptom in this group.

Adolescent↗

A novel skeletal drug delivery system for anti-bacterial drugs using self-setting hydroxyapatite cement.

To solve the problem of delivering drugs to skeletal tissue at high enough local concentrations for desirable therapeutic effects, we report a novel approach using a self-setting hydroxyapatite cement, with cephalexin and norfloxacin as model drugs. After setting, the cement was transformed into hydroxyapatite with affinity for hard bone tissue. Continuous in-vitro drug release profiles from loaded cement pellets (0.9-4.8% by weight) in phosphate buffer at pH 7.4 and 37 degrees C followed the Higuchi equation.

Anti-Infective Agents↗

The effect of graded doses of ascorbic acid on the tissue carnitine and plasma lipid concentrations.

Ascorbic acid (AsA) is known to be required for the synthesis of carnitine. The present study was designed to clarify the effect of AsA on the carnitine synthesis and lipid metabolism in guinea pigs. The animals were divided into four groups, and fed AsA-free diets for three weeks. Each group was supplemented with AsA in the following doses; high-AsA group, 100 mg AsA/day/animal; control group, 5 mg AsA/day/animal; AsA-deficient group, 0.1 mg AsA/day/animal; pair-fed group, 5 mg AsA/day/animal. The pair-fed group was restricted to the amount of diet consumed by the AsA-deficient group. Tissue carnitine levels of the AsA-deficient group were significantly lower than not only the control group but the pair-fed group. Total cholesterol and phospholipid levels in plasma of the AsA-deficient group were found to be similar to those of the pair-fed group; however, plasma triglyceride levels were significantly higher than that of the pair-fed group. Furthermore, there was an inverse relationship between tissue AsA and plasma triglyceride levels. We concluded that carnitine synthesis and triglyceride metabolism in guinea pigs may be impaired by the decrease of tissue AsA level rather than by the insufficient food intake. It is suggested that tissue carnitine level altered by tissue AsA content affects plasma triglyceride level.

Alkaline Phosphatase↗

Cell proliferation and abnormal nuclei induced by radiation in renal tubule epithelium as an early manifestation of late damage.

The time of appearance and the dose response of radiation effects in the mouse kidney were assessed from the determination of increases in labeling index, the appearance of proximal tubule cells with abnormally large nuclei, and kidney weight loss. Increased labeling indices and abnormally large nuclei were observed in the irradiated proximal tubule cells before any other histological changes were seen. The labeling index increased with dose (from 3 to 15 Gy) but not with time (from 1 to 12 months after irradiation). Increased labeling was evident as soon as 1 month after irradiation. Cell depletion as measured by a decrease in kidney weights compared to those of age-matched controls was not significant until 6 or more months after 11-, 13-, or 15-Gy irradiation. The frequency of cells with large nuclei increased steadily during the first 9 months after 15 Gy and tended to decline between 9 and 12 months, coincident with accelerating renal weight loss. These findings are consistent with the hypothesis that the production of these cells is a result of an abortive mitotic division and their loss is an eventual result of such an aberration. The increased proliferation induced by irradiation increases the chance for an abortive mitosis and death, presumably at a subsequent mitosis, of radiation-damaged proximal tubule cells, which is a major factor in the appearance of late radiation damage in the kidney.

Animals↗

Direct evidence for ATP consumption due to iodide uptake by isolated, uncultured, pig thyroid epithelial cells.

The concept that iodide uptake by thyroid requires a supply of ATP is currently accepted. However, there is little direct evidence that the extents of iodide uptake and ATP consumption are correlated. To demonstrate this correlation, we used isolated, uncultured pig thyroid epithelial cells in basal media containing only glucose and the cations necessary for Na+,K(+)-ATPase, which prevented other possible cellular activities requiring ATP. The isolated cells were sensitive to various metabolic inhibitors of ATP-generating systems, confirming that they were intact. The extents of increase in iodide uptake and decrease in ATP content of the cells were entirely dependent on the presence of the cations, and were closely correlated with each other. Furthermore, the ATP content was not reduced in the absence of NaI, even when all necessary cations for the ATPase were present. These findings provide direct evidence for a correlation between the extents of iodide uptake and ATP consumption. Cells in medium with Mg alone did not show iodide incorporation or ATP consumption, confirming that Mg2(+)-dependent ATPase does not contribute to iodide uptake by the thyroid.

Adenosine Triphosphate↗

[Control of interstitial pneumonia with the application of immune transfer].

Allogeneic bone marrow transplantation (BMT) has been used successfully to treat patients with hematological malignancies. However, interstitial pneumonia has remained a major complication following BMT. We investigated the possibility of immune transfer in recipients treated with BMT from immunized donors. Bone marrow donors were vaccinated with tetanus toxoid (TT) before marrow harvest. After BMT, serum IgG anti-TT antibody titer and in vitro IgG anti-TT antibody production in recipients were assayed sequentially. IgG anti-TT antibody titer in serum increased from about day 20 after BMT. In addition, spontaneous IgG anti-TT antibody producing B cells and TT antigen-specific memory B cells derived from donors were also detected in peripheral blood and bone marrow of recipients from about day 60. We therefore considered that antigen-specific immunity of bone marrow donors is transferable to recipients with BMT, and the immunity continued for a long time in the recipients after BMT. The effectiveness of cytomegalovirus (CMV) vaccine on antibody production was next investigated in healthy adults. Live vaccine induced the production of humoral antibody but envelope vaccine did not. These results indicate that more effective procedure should be needed for the use of envelope vaccine.

Adult↗

[Antigen-specific antibody response in allogeneic bone marrow transplantation patients: in vivo and in vitro antibody production after the primary immunization with tetanus toxoid. Kanazawa University Bone Marrow Transplantation Team].

The ability of in vivo and in vitro tetanus toxoid (TT) antigen-specific antibody production after the primary immunization with TT vaccine was examined in 5 healthy adults and 3 long term survivors after HLA-identical allogeneic marrow grafting. Serum IgG anti-TT antibody titers became positive in 5 healthy adults but in only one of 3 patients. In vitro spontaneous IgG anti-TT antibody production was detected in 5 healthy adults but only one of 3 patients. In vitro TT antigen-dependent antibody production was detected in 5 healthy adults but only one of 3 patients and the pattern of the patient was different from one of healthy adults. These data indicate that long term survivors after marrow grafting are still disturbed in the ability of in vivo and in vitro TT antigen-specific antibody production after the primary immunization with TT vaccine. It is suggested that impaired spontaneous TT antigen-specific antibody producing B cells and TT antigen-specific memory B cells participate in the impediment.

Adolescent↗

An enzyme-linked immunosorbent assay for immune complex of HTLV-I.

A sandwich enzyme-linked immunosorbent assay (ELISA) for immune complexes of human T cell leukemia virus type I (HTLV-I) was developed using monoclonal antibody (MoAb) 3G1 which recognizes a different epitope on HTLV-I to that with which natural human anti-HTLV-I antibody binds. The assay was capable of titrating artificial immune complexes not only at antigen-antibody equivalence but also at antibody excess. Although the antigen-antibody ratios could not be determined in the individual sera from patients with overt ATL, the level of immune complexes in three out of four sera was estimated to be 250 +/- 36 ng/ml. Immune complexes of HTLV-I could not be identified in sera obtained from one patient with overt ATL, three healthy HTLV-I carriers and three normal human controls.

Adult↗