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Biomedical subjects

M Miura

Publications and source records attributed to M Miura.

At least 19 recordsLinked to original sources
PubMed1995

Gamma-glutamylcysteine synthetase gene overexpression results in increased activity of the ATP-dependent glutathione S-conjugate export pump and cisplatin resistance.

The ATP-dependent glutathione S-conjugate export pump (GS-X pump) has been suggested to play a role in the mechanism of cisplatin resistance. The purpose of this study was to determine the relationship between intracellular glutathione (GSH) levels and GS-X pump activity and whether GS-X pump overexpression results in cisplatin resistance. We transfected the human gamma-glutamylcysteine synthetase (gamma-GCS) gene into a human small-cell lung cancer cell line, SBC-3, producing SBC-3/GCS. The intracellular GSH content of SBC-3/GCS was twice that of the parental line, its GS-X pump activity was significantly enhanced and cellular cisplatin accumulation decreased. SBC-3/GCS showed higher resistance (relative resistance value of 7.4) to cisplatin than the parental line SBC-3. These data indicate that gamma-GCS gene overexpression induces cellular cisplatin resistance associated with increases in both the GSH content and GS-X pump activity, resulting in reduced cisplatin accumulation. In conclusion, GS-X pump expression is related to cellular GSH metabolism and involved in cisplatin resistance.

Adenosine Triphosphate↗
PubMed1995

Different effects on mitogenesis and transformation of a mutation at tyrosine 1251 of the insulin-like growth factor I receptor.

The wild type insulin-like growth factor I (IGF-I) receptor has both mitogenic and transforming activities. We have examined the effect of point mutations at tyrosine residues 1250 and 1251 on these two properties of the receptor. For this purpose, we stably transfected plasmids expressing mutant and wild type receptors into R- cells, which are 3T3-like cells, derived from mouse embryos with a targeted disruption of the IGF-I receptor genes, and therefore devoid of endogenous IGF-I receptors. A tyrosine to phenylalanine mutation of either the 1250 or 1251 residue, or both, has no effect on the ability of the receptor to transmit a mitogenic signal. However, the tyrosine 1251 mutant receptor and the double mutant have lost the ability to transform R- cells (colony formation in soft agar), even when the receptors are expressed at very high levels, while the Y1250F mutant is fully transforming. These experiments show that the 1251 tyrosine residue is required for the transforming activity of the IGF-I receptor.

3T3 Cells↗
PubMed1995

Tumor necrosis factor-induced apoptosis is mediated by a CrmA-sensitive cell death pathway.

We report here that the activation of the interleukin 1 beta (IL-1 beta)-converting enzyme (ICE) family is likely to be one of the crucial events of tumor necrosis factor (TNF) cytotoxicity. The cowpox virus CrmA protein, a member of the serpin superfamily, inhibits the enzymatic activity of ICE and ICE-mediated apoptosis. HeLa cells overexpressing crmA are resistant to apoptosis induced by Ice but not by Ich-1, another member of the Ice/ced-3 family of genes. We found that the CrmA-expressing HeLa cells are resistant to TNF-alpha/cycloheximide (CHX)-induced apoptosis. Induction of apoptosis in HeLa cells by TNF-alpha/CHX is associated with secretion of mature IL-1 beta, suggesting that an IL-1 beta-processing enzyme, most likely ICE itself, is activated by TNF-alpha/CHX stimulation. These results suggest that one or more members of the ICE family sensitive to CrmA inhibition are activated and play a critical role in apoptosis induced by TNF.

Apoptosis↗
PubMed1995

Grafts of genetically modified fibroblasts expressing neural cell adhesion molecule L1 into transected spinal cord of adult rats.

L1, a neural cell adhesion molecule, is known to promote neurite elongation via a homophilic interaction in vitro. In the present study, fibroblast L cells that were genetically modified to express the L1 molecule were grafted to a lesion of rat spinal cord immediately after hemisection. Grafts drastically promoted regeneration of the axons in the injured spinal cord 2 weeks after grafting. A number of regenerating axons penetrated the glial scar along the host-graft interface, and elongated into the graft. These results suggest that grafts of genetically modified cells expressing L1 can provide an environment suitable for regeneration of the axons in the injured spinal cord.

Animals↗
PubMed1995

Neuronal expression of FOS protein in the nucleus tractus solitarii and the dorsal motor nucleus of the vagus nerve after i.p. injection of ulcerogenic aspirin.

Aspirin, a common analgesic-antipyretic and anti-inflammatory drug, often induces gastric ulcer, but its pathogenesis remains unsettled. The purpose of this study was to identify the CNS neurons that express FOS protein after i.p. injection of aspirin (100-300 mg/kg). This was done in the unanesthetized Wistar rats with careful physiological controls. Dose-dependently, many FOS-immunoreactive (FOS-ir) neurons were found in the medial part of the nucleus tractus solitarii (NTSm) and the dorsal motor nucleus of the vagus nerve (DMX) of the lower medulla, but none in the paraventricular nucleus of the hypothalamus (PVH). Distribution of FOS-ir neurons in the DMX corresponds with that of the visceromotor neurons involved in gastric secretion. This study suggests that the aspirin-induced gastric ulcer may not originate in the PVH but in the NTSm-DMX system.

Animals↗
PubMed1995

Effect of a mutation at tyrosine 950 of the insulin-like growth factor I receptor on the growth and transformation of cells.

Recent evidence has shown that the insulin-like growth factor I (IGF-I) receptor plays a major role in the establishment and maintenance of transformation. To identify domains in the IGF-I receptor that are necessary for transformation, the tyrosine at residue 950 of the human IGF-I receptor cDNA was mutated to phenylalanine, and the plasmid expressing the mutant receptor was stably transfected into R- cells, which are mouse embryo fibroblasts with a targeted disruption of the type 1 receptor for the insulin-like growth factors. At variance with the wild-type receptor, the Y950 mutant receptor has lost its ability to transmit an IGF-I-mediated mitogenic signal or to transform R- cells. These experiments show, for the first time, that tyrosine 950 of the IGF-I receptor is necessary for its mitogenic and transforming activities.

3T3 Cells↗
PubMed1995

Voltage-gated Ca2+ channel blockers, omega-AgaIVA and Ni2+, suppress the induction of theta-burst induced long-term potentiation in guinea-pig hippocampal CA1 neurons.

It is widely believed that a rise in post-synaptic calcium concentration ([Ca2+]i) is a necessary step in the induction of long-term potentiation (LTP) (Bliss and Collingridge, Nature, 361 (1993) 31-39). In this experiment, we examine the involvement of voltage-gated Ca2+ channels (VGCC) in the induction of AP5-sensitive LTP induced by theta-burst stimulation in guinea-pig hippocampal CA1 neurons. The VGCC blockers, Ni2+ (25 microM, T-channel blocker) or omega-AgaIVA (60 nM, P-channel blocker), which have no effect on synaptic transmission, suppress 60% or 78% of the theta-burst induced LTP, respectively. This implies that Ca2+ entry through VGCC is an important step in this form of LTP.

2-Amino-5-phosphonovalerate↗
PubMed1995

Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer's disease.

Cerebrospinal fluid from 70 patients with Alzheimer's disease (AD) and 96 patients with non-AD neurological diseases as well as 19 normal control subjects was surveyed by sandwich enzyme-linked immunosorbent assay to quantitate levels of the microtubule-associated protein tau in cerebrospinal fluid. The tau level was significantly increased in AD patients as compared with that in patients with non-AD neurological diseases and control subjects. Increased tau levels were found irrespective of age at onset, apolipoprotein E genotype, and clinical stage. Western blots of AD cerebrospinal fluid proteins revealed two to three tau-immunoreactive bands with an apparent molecular mass between 50 and 65 kd consistent with phosphorylated cerebrospinal fluid tau. Taken together, our results suggest that cerebrospinal fluid tau might reflect the progressive accumulation of altered tau due to the progressive death of neurons in the AD brain, and that the enzyme-linked immunosorbent assay of cerebrospinal fluid tau may prove to be a reliable and early diagnostic test for AD.

Adult↗
PubMed1995

Prevalence of precore-defective mutant of hepatitis B virus in HBV carriers.

Two hundred and seventy-three serum specimens from hepatitis B virus (HBV) carriers were examined for the presence of a characteristic one point mutation at nucleotide (nt) 1896 from the EcoRI site of the HBV genome in the precore region (the preC mutant) using restriction fragment length polymorphism (RFLP) analysis. This assay approach could detect preC mutants or wild-type sequences when either form constituted more than 10% of the total sample. Overall, 65.5% (76/116) of HBeAg-positive carriers had only the preC wild-type. All HBeAg-positive asymptomatic carriers (n = 14) had only the preC wild-type. In patients with chronic hepatitis B and in anti-HBe-positive asymptomatic carriers, increased prevalence of the preC mutant was associated with the development of anti-HBe antibodies and normalization of the serum alanine aminotransferase concentration. Furthermore, 27 (29.0%) of 93 HBeAg-negative carriers had unexpectedly preC wild-type sequences only. Direct sequencing of the HBV precore region of HBV specimens from 24 patients revealed no mutation at nt 1896, supporting the specificity of the RFLP analysis. These results suggest that RFLP analysis was accurate for the detection of the preC mutation and that the absence of serum HBeAg cannot be explained solely by the dominance of the preC mutant.

Base Sequence↗
PubMed1995

Elevated substance P content in induced sputum from patients with asthma and patients with chronic bronchitis.

In experimental studies, tachykinins, especially substance P (SP), cause many of the pathophysiological features of neurogenic inflammation. It is unclear whether these peptides are involved in human airway inflammation in diseases such as asthma and chronic bronchitis. To elucidate the relation between neurogenic inflammation and airway inflammatory diseases, we examined the SP concentration in sputum after hypertonic saline inhalation challenge in patients with asthma, patients with chronic bronchitis, and normal volunteers. SP concentration was measured by radioimmunoassay. The sputum SP concentration was significantly higher in patients with asthma (mean +/- SEM, 17.7 +/- 2.4 fmol/ml; p < 0.01) and patients with chronic bronchitis (25.6 +/- 5.5 fmol/ml; p < 0.01) than in normal volunteers (1.1 +/- 0.4 fmol/ml). In patients with asthma, the SP concentration was significantly related to the eosinophil cell count in induced sputum. In all subjects, the SP concentration in induced sputum correlated with FEV1/FVC. These data suggest that neurogenic inflammation may be involved in the airway inflammatory process and subsequent airway narrowing not only in asthma but also in chronic bronchitis.

Adult↗
PubMed1995

Urinary pyridinoline and deoxypyridinoline in healthy children and in children with growth hormone deficiency.

To assess the bone growth status in healthy children, urinary pyridinoline (PYR) and deoxypyridinoline (DPYR) levels, which are specific bone resorption markers, were studied in 192 healthy children, aged 3-14 yr. In healthy children ages 3-5 yr, the urinary PYR level was about 10 times higher than that in healthy adults (238.3 +/- 22.7 pmol/mumol Cr in boys and 261.8 +/- 14.2 pmol/mumol Cr in girls; mean +/- SE, and the level declined gradually with age. In boys, the urinary PYR level began to rise at about 10 yr of age and peaked 2 yr later, declining thereafter. In girls, urinary PYR level declined rapidly after 11 yr. The age-related changes in urinary DPYR levels closely resembled those in urinary PYR levels. We further studied PYR and DPYR levels in 17 GH-deficient children who were beginning treatment with GH. After 2-3 months of GH therapy, 1.3-fold significant increases in urinary PYR and DPYR levels were observed. These results indicate that the bone resorption in children is increased relative to that in adults, that urinary PYR and DPYR levels are increased during puberty when the growth rate is markedly elevated, and that bone resorption in children is accelerated by GH therapy.

Adolescent↗
PubMed1995

Training intensities for aerobic exercise determined on untrained healthy men.

The purpose of this study was to determine the aerobic training intensity from the maximal and submaximal running exercise in 21 untrained adult men. To accomplish this, we evaluated the relationship between physiological (oxygen intake and heart rate) and physical parameters (running speed) of training intensity, and determined the training intensity at the submaximal exercise. Oxygen intake and heart rate were measured by a treadmill test. The maximal oxygen intake (VO2 max), and the aerobic threshold (AerT) and anaerobic threshold (AT) were measured to determine respiratory gas exchange. Running capacity was measured by a 12-min running and treadmill test. For the maximal exercise, there was a significant correlation (r = 0.88, P < 0.01) between VO2 max and 12-min running distance (speed). In addition, the oxygen intake and heart rate at AerT and AT in the submaximal exercise were linearly correlated with running speed. Three levels of training intensity at the submaximal exercise were termed: light, moderate, and heavy. Since AerT was the lower limit intensity and AT was the upper limit, we took the middle of their values as the moderate intensity. The end point for the determination of the training intensity at the submaximal exercise was estimated to be 85% VO2 max and 180 beats.min-1.

Adult↗
PubMed1995

Central disorders in vestibular neuronitis.

Between 1972 and 1993 equilibrium and audiological examinations were made on 73 patients who had been diagnosed to suffer from vestibular neuronitis. In 23 of these patients, central nervous disorders (CND) were suspected from the result of tests of positional and positioning nystagmus, smooth pursuit, optokinetic nystagmus or auditory brainstem response. In this group of patients the frequency of associated disorders and vertiginous symptoms (dizziness) was statistically higher than in the remainder 50 patients who did not have CND. In the CND group the time interval between the onset and improvement or disappearance of all vertiginous symptoms, nystagmus and canal paresis was longer than in the non-CND group.

Adolescent↗
PubMed1995

Teleology of motion sickness.

We investigated motion sickness evoked by walking while wearing horizontally reversing goggles. The subjects were 36 healthy adults and 90 children aged 4 to 15 years. Most adults soon displayed not only severe sickness, but also dizziness and instability. Instability was certified by Graybiel's ataxia tests in 10 adults. Young children aged 4 to 5 years rarely became sick; however, they showed marked ataxia manifested as drunken gait, falling, or failure to stand up. In older children, autonomic nervous symptoms became manifest and more severe, but ataxia became less severe since locomotion was stopped by uncomfortable symptoms. The present study strongly suggests that motion sickness makes animals learn loss of spatial orientation, which inevitably produces loss of balance.

Adolescent↗
PubMed1995

[Syphilitic thoracic aortic aneurysm with destruction of vertebral body, producing numbness of lower extremities and paraplegia].

Numbness and paraplegia are uncommon complaints in patient with thoracic aortic aneurysm (TAA). The patient was a 64-year-old man. He suffered numbness and gait disturbance (paraplegia). The blood examination showed no positive findings except a Wassermann was positive. Roentgen examination of the chest showed two abnormal shadows like tumors. The CT and MRI revealed destruction of the vertebral bodies and TAAs adjacent to the spinal cord. After the graft replacement was performed, numbness and paraplegia disappeared. This suggests that in our patient the TAAs destruct the vertebral body and produce pressure on the spinal cord, causing numbness and paraplegia. We experienced a rare case of the syphilitic TAA producing bone destruction, numbness and paraplegia.

Aortic Aneurysm, Thoracic↗
PubMed1995

Metabolism of 3-acetylcoumarin in rat 9000xg supernatant fraction (S-9)and baker's yeast.

In the incubation of 3-acetylcoumarin in rat liver supernatant fraction (S-9), four metabolites were isolated, and two of which were inseparable diastereomeric mixture as a major product. However, when 3-acetylcoumarin was fermented with baker's yeast (Saccharomyces cerevisiae), only two compounds were obtained as the same as the above mixture. The structures of those metabolites were confirmed by NMR and Mass spectra. However, the above metabolites in rat 9000xg supernatant fraction were not induced by phenobarbital, nor inhibited with SKF-525A at all.

Animals↗
PubMed1995

Chronic allergen exposure enhances cholinergic neurotransmission in sensitized guinea-pigs.

Airway hyperresponsiveness in asthmatic patients may be related to cholinergic hyperresponsiveness. In this study, we examined whether chronic allergen exposure induces cholinergic hyperresponsiveness in ovalbumin (OA) sensitized guinea-pig airways. Three weeks after active sensitization, ovalbumin (0.03%, for 3 min, challenged group) or saline inhalation (control group) was repeated every day for 4 weeks. Cholinergic responses were assessed by isometric tracheal contraction after electrical field stimulation (EFS) or exogenously applied acetylcholine (ACh). The contractions were expressed as a percentage of the maximum response to ACh (10(-3) M) (AChmax). We calculated the effective frequencies producing 25% of AChmax (EF25) from frequency-response curves. EFS-induced contractile responses were significantly enhanced in the challenged group (logEF25 = 0.66 +/- 0.08 (mean +/- SEM)) compared with the control group (logEF25 = 1.12 +/- 0.16). In contrast, exogenous ACh-mediated contractile tracheal responses were almost the same in both groups. We conclude that repeated allergen inhalation causes cholinergic airway hyperresponsiveness, presumably due to the facilitation of cholinergic neurotransmission. This mechanism may be involved in the airway hyperresponsiveness in asthmatic airways.

Acetylcholine↗