Biomedical subjects

K Tsuchiya

Publications and source records attributed to K Tsuchiya.

At least 181 records · Page 10Linked to original sources

PubMed1999

Nitric oxide-forming reactions of the water-soluble nitric oxide spin-trapping agent, MGD.

The objective of this study was to elucidate the nitric oxide-forming reactions of the iron-N-methyl-D-glucamine dithiocarbamate (Fe-MGD) complex from the nitrogen-containing compound hydroxyurea. The Fe2+(MGD)2 complex is commonly used in electron paramagnetic resonance (EPR) spectroscopic detection of NO both in vivo and in vitro. The reaction of Fe2+(MGD)2 with NO yields the resultant NO-Fe2+(DETC)2 complex, which has a characteristic triplet EPR signal. It is widely believed that only NO reacts with Fe2+(MGD)2 to form the NO-Fe2+(MGD)2 complex. In this report, the mechanism leading to the formation of NO-Fe2+(MGD)2 was investigated using oxygen-uptake studies in conjunction with the EPR spin-trapping technique. We found that the air oxidation of Fe2+(MGD)2 complex results in the formation of the Fe3+(MGD)3 complex, presumably concomitantly with superoxide (O3*-). Dismutation of superoxide forms hydrogen peroxide, which can subsequently reduce Fe3+(MGD)3 back to Fe2+(MGD)2. The addition of NO to the Fe3+(MGD)3 complex resulted in the formation of the NO-Fe2+(MGD)2 complex. Hydroxyurea is not considered to be a spontaneous NO donor, but has to be oxidized in order to form NO. We present data showing that in the presence of oxygen, Fe2+(MGD)2 can oxidize hydroxyurea to yield the stable NO-Fe2+(MGD)2 complex. These results imply that hydroxyurea can be oxidized by reactive oxygen species that are formed from the air oxidation of the Fe2+(MGD)2 complex. Formation of the NO-Fe2+(MGD)2 complex in this case could erroneously be interpreted as spontaneous formation of NO from hydroxyurea. The chemistry of the Fe2+(MGD)2 complexes in aerobic conditions must be taken into account in order to avoid erroneous conclusions. In addition, the use of these complexes may contribute to the overall oxidative stress of the system under investigation.

Chelating Agents↗

PubMed1999

Polymorphisms in the 5'-flanking region of tumor necrosis factor-alpha gene in patients with rheumatoid arthritis.

Polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor (TNF)-a gene were examined to study the genetic background of rheumatoid arthritis (RA). Four variant alleles, -1,031C/ -863A, -1,031C/-238A, -857T and -308A, were identified and examined in 387 RA patients and 575 healthy Japanese controls. The frequency of the -857T allele in RA patients was significantly higher than that in the controls. However, the HLA-DRB1 analysis in the same subjects showed that the DRB1*0405 allele, which is in linkage disequilibrium with the -857T, was more strongly associated with the disease susceptibility than the -857T allele. These results suggest that the susceptible gene to RA is more closely linked to the HLA-DRB1 locus than to the TNF-alpha locus.

5' Untranslated Regions↗

PubMed1999

Triggering of neuronal cell death by accumulation of activated SEK1 on nuclear polyglutamine aggregations in PML bodies.

BACKGROUND: A novel class of inherited human neurodegenerations is now known to be caused by expanded CAG repeats encoding polyglutamines. Polyglutamine-containing protein fragments have been shown to accumulate as aggregates in the nucleus and in the cytoplasm, and to induce cell death when expressed in cultured cells, leading to the proposal that polyglutamine aggregation is an important step in the pathogenesis. Supporting this, nuclear inclusions containing expanded polyglutamines have been identified in neurones from the brains of patients and in neurones from transgenic mouse models of this class of neural disorders. RESULTS: We analysed the consequences of polyglutamine expression in PC12 neuronal cells. Activated SEK1 accumulated with nuclear but not cytoplasmic polyglutamine aggregations, which consequently triggers cell death. Cell death induced by polyglutamine expression was inhibited by a dominant-negative SEK1 (DN-SEK1), but not by DN-SEK1 tagged with a nuclear export signal. Steady state SEK1 expression itself was enhanced two to three-fold. Nuclearly aggregated polyglutamines, which were identified in PML bodies, co-localized with not only activated SEK1 but also activated c-Jun. We also observed that nuclear inclusion-positive neurones from brains with Huntington's disease expressed SEK1. CONCLUSIONS: This study provides molecular links between the neurodegeneration observed in polyglutamine diseases, cell death signalling kinase cascades and nuclear subdomains related to cell death. We propose that the nuclear PML bodies containing polyglutamine aggregates activate the SEK1-JNK kinase cascade, resulting in the transduction of a death signal.

Animals↗

PubMed1999

Age-related endothelium-dependent vascular relaxation in rat thoracic aorta in response to colforsin.

BACKGROUND: Colforsin, a novel water-soluble forskolin derivative, increases intracellular cyclic AMP by direct stimulation of adenylate cyclase and has strong positive inotropic and vasodilative effects. However, it is not known whether colforsin causes nitric oxide (NO) release and enhances endothelium-dependent vascular relaxation. METHODS: We studied NO production and relaxation on exposure to colforsin in thoracic aorta from rats aged 4, 12 and 60 weeks. RESULTS: When a low concentration of colforsin was added to a solution bathing ring segments of aorta from 12-week-old rats, relaxation was greater in the ring segments with intact endothelium than in those from which the endothelium had been removed. A high concentration of colforsin induced the same degree of relaxation of ring segments with or without endothelium, probably by a direct effect on vascular smooth muscle cells. Production of NO in response to colforsin by cultured endothelial cells from 12-week-old rat aorta was demonstrated by the electron paramagnetic resonance spin trapping method. A low concentration of colforsin relaxed aortic segments with intact endothelium from 4-week-old rats more than those from 12-week-old or 60-week-old rats. Reversal of relaxation by NG-nitro L-arginine, an NO synthesis inhibitor, was most significant in arteries from 4-week-old rats. Production of NO after exposure to colforsin was greater in aortic segments from 4-week-old rats than older rats, as detected by an NO-selective electrode. CONCLUSIONS: Colforsin induces vasodilation in part by releasing NO from the endothelium in rat thoracic aorta. In addition to a direct vasodilative effect on the vascular smooth muscle cells, an endothelium-dependent vasodilative effect is also important in younger arteries.

Aging↗

PubMed1999

Clinical evaluation of the effect of percutaneous transluminal angioplasty and intra-arterial papaverine infusion for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage.

The clinical efficacy of percutaneous transluminal angioplasty and intra-arterial papaverine infusion for treatment of vasospasm following subarachnoid hemorrhage was investigated. Between 1990 and 1993, 84 patients were treated for cerebral vasospasm in National Defense Medical College Hospital. Angioplasty was performed for asymptomatic vasospasm in 18 patients and for symptomatic vasospasm in 12 patients. Intra-arterial papaverine infusion was performed for asymptomatic vasospasm in 10 patients and for symptomatic vasospasm in four patients. The other 40 patients were treated with standard conservative therapy including hypervolemic and hypertensive hemodilution. The outcomes of these patients were analyzed using the Glasgow Outcome Scale. The outcome tended to be better for patients treated with angioplasty, but not for those treated with papaverine infusion, than for those treated conservatively. Recurrence of vasospasm was more frequent after papaverine infusion than after angioplasty. Undesirable complications such as abrupt development of unconsciousness were experienced during papaverine infusion but not during angioplasty. We conclude that percutaneous transluminal angioplasty is superior to intra-arterial papaverine infusion for prevention and treatment of vasospasm following aneurysmal subarachnoid hemorrhage.

Angioplasty, Balloon↗

PubMed1999

MR myelography of sacral meningeal cysts.

PURPOSE: To describe the findings of sacral meningeal cysts (SMCs) on MR myelography and assess its value for the diagnosis of SMCs. MATERIAL AND METHODS: We evaluated the MR images and MR myelograms obtained from 10 patients with SMC. MR myelograms were obtained using a 2D or 3D single-shot fast spin-echo sequence. In 5 patients, X-ray myelograms and postmyelographic CT images were compared with the MR myelograms. RESULTS: A total of 33 SMCs were diagnosed within the spinal canal and/or sacral foramen. MR myelograms clearly revealed each cyst as a well-defined mass showing hyperintensity (10 cysts) or isointensity (23 cysts) compared to cerebrospinal fluid. MR myelograms demonstrated SMCs better than X-ray myelograms and postmyelographic CT images in 3 of the 5 patients. CONCLUSION: MR myelography can be an adjunct to conventional imaging techniques when surgical treatment is indicated, because it can precisely delineate the extent of SMCs.

Adolescent↗

PubMed1999

The clinical efficacy of low-dose step-up follicle stimulating hormone administration for treatment of unexplained infertility.

The present study was designed to compare the clinical efficacy of low-dose step-up follicle stimulating hormone (FSH) administration with conventional FSH protocol (FSH was injected daily starting with a dose of 150 IU), both combined with intrauterine insemination (IUI), for the treatment of unexplained infertility. A total of 97 unexplained infertility couples was randomly assigned to one or other of the two treatment groups, either conventional FSH with IUI (48 patients) or low-dose step-up FSH with IUI (49 patients), and only the first treatment cycle was evaluated in each protocol. The difference in pregnancy rates per cycle was not statistically significant between the low-dose FSH group and the conventional group [seven of 49 (14.3%) and seven of 48 (14.6%) respectively]. A significant reduction in the incidence of ovarian hyperstimulation syndrome (OHSS) was observed in the low-dose group (8.3% versus 27.1%, P < 0.05). The incidence of moderate OHSS requiring hospitalization was reduced significantly in the low-dose group (low-dose 0% versus conventional 16.7%, P < 0.01). However, the low-dose protocol did not completely prevent multiple pregnancies. Our results suggest that the low-dose step-up FSH treatment appeared to be useful for the treatment of unexplained infertility because of the high pregnancy rates and the significant decrease in the incidence of OHSS.

Adult↗

PubMed1999

Mechanism of endothelin-1-(1-31)-induced calcium signaling in human coronary artery smooth muscle cells.

We have found that human chymase produces a 31-amino acid endothelin [ET-1-(1-31)] from the 38-amino acid precursor (Big ET-1). We examined the mechanism of synthetic ET-1-(1-31)-induced intracellular Ca2+ signaling in cultured human coronary artery smooth muscle cells. ET-1-(1-31) increased the intracellular free Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner (10(-14)-10(-10) M). This ET-1-(1-31)-induced [Ca2+]i increase was not affected by phosphoramidon, Bowman-Birk inhibitor, and thiorphan. The ET-1-(1-31)-induced [Ca2+]i increase was not influenced by removal of extracellular Ca2+ but was inhibited by thapsigargin. ET-1-(1-31) at 10(-12) M did not cause Ca2+ influx, whereas 10(-7) M ET-1-(1-31) evoked marked Ca2+ influx, which was inhibited by nifedipine. ET-1-(1-31) also increased inositol trisphosphate formation. These results suggest that the ET-1-(1-31)-induced [Ca2+]i increase at relatively low concentrations is attributable to the release of Ca2+ from inositol trisphosphate-sensitive intracellular stores, whereas Ca2+ influx into the cells evoked by high concentration of ET-1-(1-31) probably occurs through voltage-dependent Ca2+ channels. We concluded that the physiological activity of ET-1-(1-31) may be attributable to Ca2+ mobilization from intracellular stores rather than influx of Ca2+ from extracellular space.

Arteries↗

PubMed1999

Plasma levels of free and sulfoconjugated catecholamines in patients with atherosclerosis.

We have studied the relationship between free and sulfoconjugated catecholamines (CAs) in the plasma of patients with various cardiovascular diseases and have described the physiological significance of sulfoconjugated CAs in plasma. In the present study, we measured free and sulfoconjugated dopamine (DA) and noradrenaline (NA) in the plasma of patients with atherosclerosis (AS). Results showed that the plasma levels of free DA and NA in patients with atherosclerosis were higher than those in control subjects. Moreover, it was also observed that the plasma levels of conjugated DA and NA in patients had a tendency to be higher than the levels in control subjects. These results suggest the involvement of free CAs in atherosclerosis and that elevated free CAs may be converted to sulfoconjugated forms in patients with atherosclerosis.

Adult↗

PubMed1999

Development of a new analytical method for the electrocardiogram using short-time first Fourier transforms.

To detect the minute electric potential inside the QRS complex, a new frequency domain method was designed using short-time First Fourier Transforms (SFFT) and high-frequency sampling (oversampling). SFFT improved the frequency resolution by oversampling that was applied to this analysis. The electric potential data of 15,000 points received weighted, running average processing and was subtracted from the original waveform to reduce the low-frequency component. The data in a segment of 160 ms, including QRS, was processed by frequency analysis with the SFFT computation routine. The ECG of healthy individuals was analyzed by this method and its usefulness evaluated. The processing waves of the X-axis, Y-axis, and Z-axis of a representative normal subject were formed into 3 groups of peak electric potential. SFFT enabled the detection of the structure inside the QRS complex without signal averaging, and is considered capable of evaluating the process of excitement inside the QRS complex in the various heart diseases.

Adult↗

PubMed1999

Comparison of the effects of endothelin-1, -2 and -3 (1-31) on changes in [Ca2+]i in human coronary artery smooth muscle cells.

We have previously found that human chymase selectively cleaves big endothelins (ETs) at the Tyr31-Gly32 bond to produce 31-amino-acid endothelins, ETs (1-31). In the present study, we investigated the effects of ETs (1-31) on changes in intracellular free Ca2+ ([Ca2+]i) in cultured human coronary artery smooth muscle cells (HCASMCs) using confocal laser microscopy. ETs (1-31) increased [Ca2+]i in a concentration-dependent manner. Phosphoramidon did not inhibit the increases in [Ca2+]i caused by ETs (1-31). The [Ca2+]i increases induced by ETs (1-31) were compared to those of ETs (1-21) and big ETs. ET-1 (1-21) was about 10-times more potent than big ET-1 or ET-1 (1-31), whereas big ET-2 was 10-times less potent than ET-2 (1-21) or ET-2 (1-31). ETs (1-31) may induce [Ca2+]i increase through ET(A)-type or ET(A)-type-like receptors. The 10(-12) M ET (1-31)-induced increases in [Ca2+]i were not affected by removal of extracellular Ca2+, but were inhibited by thapsigargin. These results suggested that ET-1, -2 and -3 (1-31) showed similar potencies in increasing [Ca2+]i and mechanisms of ET (1-31)-induced increases in [Ca2+]i may be similar among the three ETs (1-31).

Arteries↗

PubMed1999

Fifteen-year follow-up of a heterozygous Fabry's disease patient associated with pre-excitation syndrome.

A 47-year-old woman with heterozygous Fabry's disease with pre-excitation syndrome has been followed up for 15 years. Diagnosis was confirmed by the typical electron microscopic feature of the endomyocardial specimen and a decreased plasma alpha-galactosidase activity. As the disease progressed, the interventricular septum thickened from 11 to 17 mm as measured by echocardiography, while the AH interval was prolonged from 80 to 140 msec. In Fabry's disease, the PR interval has been reported to be variable from short PR to AV block. Therefore, this case may be helpful to understand the time course in the AV conduction abnormalities with the progression of Fabry's disease.

Biopsy↗

PubMed1999

Diffusion-weighted MR imaging of encephalitis.

OBJECTIVE: Our purpose was to evaluate how well diffusion-weighted MR imaging shows viral or bacterial encephalitis in comparison with conventional MR imaging that includes T1- and T2-weighted spin-echo and fluid-attenuated inversion-recovery sequences. CONCLUSION: In nine of the 13 patients examined, diffusion-weighted imaging was superior to other diagnostic imaging sequences (fluid-attenuated inversion-recovery sequences in eight patients and a T2-weighted spin-echo sequence in one patient). Diffusion-weighted imaging can serve as a method of detecting early encephalitic changes.

Bacterial Infections↗

PubMed1999

[Curative report of two cases with MRSA mediastinitis after cardiovascular surgery, treated by new irrigation technique (intermittent mass-irrigation technique)].

We experienced a 42-year-old patient who underwent aortic valve replacement and a 63-year-old patient who underwent coronary artery bypass grafting with mediastinitis caused by methicillin-resistant Staphylococcus aureus (MRSA). They were successfully treated with the intermittent mass-irrigation technique. The irrigation device consistent of a irrigation tube which placed in upper half of mediastinum and three suction tubes which placed in lower half. We dripped the wash composed of 0.03-0.05% of Povidone-Iodine with 1,000 ml of physiological saline, for 3 to 5 times a day by condition. After each wash, we cross clamped the drainage tubes and filled mediastinum with 0.5 grams of vancomycin hydrochloride dissolved in 100 ml of physiological saline, dripped from irrigation tube, for 30 minutes. After 9-day irrigation in the former case and 16-day irrigation in the latter case, the culture of drainage turned negative. We presumed that this new method is effective for mediastinitis after cardiovascular surgery.

Adult↗

PubMed1999

A new technique of surface anatomy MR scanning of the brain: its application to scalp incision planning.

BACKGROUND AND PURPOSE: Surface anatomy scanning (SAS) is an established technique for demonstrating the brain's surface. We describe our experience in applying SAS with superposition of MR venograms to preoperative scalp incision planning. METHODS: In 16 patients, scalp incision planning was done by placing a water-filled plastic tube at the intended incision site when we performed SAS using half-Fourier single-shot fast spin-echo sequences. Two-dimensional phase-contrast MR angiograms were obtained to demonstrate the cortical veins and then superimposed upon the SAS images. The added images were compared with surgical findings using a four-point grading scale (0 to 3, poor to excellent). RESULTS: In each case, neurosurgeons could easily reach the lesion. Surgical findings correlated well with MR angiogram-added SAS images, with an average score of 2.56. CONCLUSION: Our simple technique is a useful means of preoperatively determining brain surface anatomy and can be used to plan a scalp incision site.

Adult↗

PubMed1999

[An autopsy case of multiple system atrophy presenting with rapid progression of autonomic disturbance].

We report an autopsy case of multiple system atrophy (MSA) presenting with rapid progression of autonomic disturbance. He was admitted to our hospital because of gait disturbance and dysarthria. The patient was a Japanese man, who first noticed gait disturbance and dysarthria at age 58, followed by syncope 3 months later. He developed urinary incontinence and frequency of urination 8 months after the disease onset. His gait disturbance, dysarthria, syncope, and urinary symptoms progressed, and he was admitted to the department of neurology 1 year after the onset of the disease. He was clinically diagnosed as having MSA and was followed in the outpatient office. He deteriorated rapidly and was readmitted to the department of neurology 19 months after the onset of the disease. Physical examination showed orthostatic hypotension. Neurological examination revealed nystagmus, dysarthria of cerebellar type, increased deep tendon reflexes, bilateral positive Babinski signs, ataxic and spastic gait, mild right hypesthesia and hypalgesia, impotence, constipation, and urinary incontinence. Routine blood examination showed slight anemia, elevated BUN, GOT, and blood sugar. Electrocardiography revealed sinus tachycardia and chest rentogenogram showed cardiac enlargement. Brain MRI showed atrophy of cerebellum and pons, and lacunae in basal ganglia. Autonomic function tests revealed abnormal in head-up tilt test, and CVR-R in May and November 1995. However 123I-MIBG myocardial scintigraphy showed normal uptake of MIBG in May 1995 and decreased uptake in November 1995. He deteriorated rapidly and died in May 1996. Autopsy findings revealed not only prominent olivopontocerebellar and slight striatonigral lesions, but also autonomic lesions with massive appearance of glial cytoplasmic inclusions. He was pathologically verified as having MSA. In the present patient, autonomic nervous system, especially cardiac sympathetic nerve, deteriorated rapidly, which might result in short duration of the illness.

3-Iodobenzylguanidine↗

PubMed1999

[Effects of methamphetamine on responsiveness to conditioned fear stress].

The present study examined the effect of repeated methamphetamine (MA) pretreatment on conditioned fear stress in male Wistar-King rats. Rats received MA or the vehicle according to the repeated escalating dose schedule (1.25, 2.5, 3.75, 5 mg/kg s.c x2/every other day for a week). After a 5 day drug abstinent period, the rats were exposed to conditioned fear stress (CFS; exposure to an environment paired previously with footshock). Repeated but not single MA pretreatment significantly increased conditioned freezing behavior, suggesting that rats previously exposed to chronic MA are hypersensitive to subsequent stress than control rats. Repeated MA treatment did not decrease basal dopamine concentrations in the brain. Furthermore, repeated co-administration of MK-801 (non-competitive NMDA antagonist), amfonelic acid (dopamine reuptake inhibitor) or fluoxetine (serotonin reuptake inhibitor) with MA did not alter the enhanced freezing behavior. Taken together, it seems that MA-induced hypersensitivity to stress is not due to the neurotoxic effect of MA. While co-administration of SCH23390 (D1/5 antagonist) or raclopride (D2/3 antagonist) had no effect on the MA-induced increase in freezing, co-administration of nemonapride (D2/3/4 antagonist) prevented this increase. These results suggest that MA-induced enhancement of anxiety might be mediated by D4 receptors. The homovanilic acid (HVA) levels in the striatum were elevated by footshock in MA-treated rats but not in saline-treated rats. Furthermore, MA-treated rats showed increased metabolism of dopamine (DA) in the medial prefrontal cortex (mPFC), even when placed in the shock chamber without shocks. The HVA levels in the striatum in MA-treated rats were more elevated by CFS than these in saline-treated rats. These results suggest that the striatum DA system, as well as the mPFC DA system suggested previously, may be associated with emotional hypersensitivity to stress following repeated MA treatment.

Animals↗

PubMed1999

Autosomal dominant spinocerebellar degenerations. Clinical, pathological, and genetic correlations.

Historical review on hereditary spinocerebellar degenerations (SCD) revealed that some CAG repeat diseases were formerly diagnosed under several different names because of their clinical and pathological heterogeneity. A genetic abnormality in these hereditary SCDs (often with expanded CAG repeat) corresponds to a definite prototypic combination of the principal lesions in the cerebellar, extrapyramidal, and oculomotor systems, which allows neuropathological differentiation between these entities. Variability of both clinical and pathological features is mainly related to the patient's age at onset, which is often correlated with the number of CAG repeat size. Several characteristics are suggestive of these SCD: preferential degeneration of specific systems, size reduction at cellular or tissue level not accompanied by glial reaction (simple atrophy or hypoplastic change) and presence of recently identified ubiquitin positive inclusions in neurons are characteristics of these SCDs. These features provide further insight into the phenotypic development of a genetic abnormality.

Atrophy↗