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Yuzo Hayashi

Publications and source records attributed to Yuzo Hayashi.

12 recordsLinked to original sources

The presence of BRAF point mutation in adult papillary thyroid carcinomas from atomic bomb survivors correlates with radiation dose.

In papillary thyroid carcinogenesis, the constitutively activated mitogen-activated protein (MAP) kinase signaling pathway caused by a genetic alteration such as RET/PTC rearrangement or mutation of RAS and BRAF genes, is thought to be a major early event. Among these, the recently identified BRAF(V600E) mutation has been found at high frequency in adult patients with papillary thyroid carcinoma (PTC). However, the association between this mutation and radiation exposure in adult PTC is still unknown. In this study, we examined the BRAF(V600E) mutation in 64 PTCs among adult atomic bomb survivors in Hiroshima, Japan, comprising 17 nonexposed (0 mGy) and 47 exposed patients who developed the carcinoma after the bombing, and assessed the association of BRAF(V600E) mutation with clinico-pathological and epidemiological variables. The median radiation dose in PTCs with the BRAF(V600E) mutation was significantly lower than that without the mutation (18.5 vs.156.9 mGy, Wilcoxon rank-sum test, P=0.022). A significant difference was found in the median latency period (years elapsed from atomic bombing to diagnosis) between exposed patients with and without BRAF(V600E) mutation (29 vs. 21 yr, Wilcoxon rank-sum test, P=0.014). These findings were further confirmed by logistic regression analysis with BRAF(V600E) mutation status as a dependent variable and taking into account possible interactions between the variables. We found that the log-transformed radiation dose and latency period were independently associated with the BRAF(V600E) mutation (P=0.039 and P=0.010, respectively). These results suggest that involvement of BRAF mutation in thyroid carcinogenesis in exposed people may differ from that in the nonexposed people.

Adult↗

A case of multiple hepatic peribiliary cysts which contributed to the obstructive jaundice and led to liver failure at the young man with von Recklinghausen's disease.

We treated a young man with obstructive jaundice, in whom multiple hepatic peribiliary cysts were detected at autopsy. He had been diagnosed with von Recklinghausen's disease in early childhood and had undergone surgery for a ventricular septal defect with massive blood transfusion at the age of 4 years. Examination at the age of 21 revealed prominent splenomegaly and a low platelet count. He underwent splenectomy and liver cirrhosis was confirmed by open biopsy of the liver. He was followed up at a local hospital and was admitted several times. When he was 41 years old, he was transferred to our hospital with severe jaundice and hepatic encephalopathy. Computed tomography showed marked dilation of the intrahepatic bile ducts and liver function tests showed that jaundice was mainly due to an increase of direct bilirubin. Despite endoscopic nasobiliary drainage, plasma exchange, and continuous hemodiafiltration, he died of hepatic failure after 5 days. At autopsy, multiple hepatic peribiliary cysts were found. Although peribiliary cysts have generally been considered to cause no symptoms, this report describes a patient with multiple hepatic peribiliary cysts which appear to have been responsible for the progression of obstructive jaundice.

Journal Article↗

Impact of plasma aldosterone levels for prediction of in-stent restenosis.

Aldosterone promotes vascular smooth muscle cell proliferation and endothelial dysfunction, suggesting the contribution to in-stent restenosis (ISR). This study evaluated any relation between plasma aldosterone levels and ISR 6 months after successful coronary stenting. We enrolled 156 consecutive patients with stable angina who underwent coronary bare metal stenting. Plasma aldosterone levels and other serum markers known to influence cardiovascular events were measured in all patients at baseline. Patients with restenosis were found to have significantly higher plasma aldosterone levels than their counterparts without restenosis (162 +/- 60 vs 122 +/- 60 pg/ml, p = 0.007). On logistic regression analysis, even after adjusting for clinical, angiographic, and other confounding variables, plasma aldosterone level per 10 pg/ml (odds ratio 1.34, 95% confidence interval 1.10 to 1.63, p = 0.006) proved to be the independent predictor of ISR. The area under the receiver-operating characteristic curve for plasma aldosterone level was 0.75, and the optimal cut-off value identified by receiver-operating characteristic analysis was 141.9 pg/ml, which had a predictive accuracy of 69%. In conclusion, the present findings indicate that plasma aldosterone levels at baseline are independent predictors of ISR and may constitute a potential therapeutic target.

Aged↗

Inverse correlation between soluble CD40 ligand and soluble CD40 is absent in patients with unstable angina.

The CD40/CD40 ligand (CD40L) system mediates inflammatory processes important in atherogenesis and plaque instability. The expression of CD40L on activated T cells was suppressed by soluble CD40 (sCD40) in vitro. However, the relationship between soluble CD40L (sCD40L) and sCD40 in unstable angina (UA) is still unknown. Thirty-seven consecutive patients with recent chest pain or discomfort were recruited. Patients with both Braunwald's class IB-IIIB and with coronary stenosis (or stenoses) of >75% were assigned to the UA group (n = 19, aged 67.2 +/- 8.2 years), and the rest to the control group (n = 18, aged 63.4 +/- 8.7 years). The serum levels of sCD40L and sCD40, and the plasma levels of matrix metalloproteinase (MMP)-9, were measured by enzyme-linked immunosorbent assays. A significantly inverse correlation between sCD40L and sCD40 was shown in the controls (r = -0.72, P = 0.0007), but was absent in the UA group (r = -0.16, P not significant), although there was no statistical significance between these groups in terms of serum levels of sCD40L or sCD40. The difference of the regression slopes of these regression lines was statistically significant (P < 0.01). Additionally, there was a significant correlation between sCD40 and plasma levels of MMP-9 in the patients with and without UA (r = 0.58, P = 0.0096), but no significant correlation between sCD40L and MMP-9 levels (r = 0.00, P not significant). The balance between CD40 and CD40L may be lost in patients with UA. Soluble CD40 expression may also be related to MMP-9 expression in atherosclerotic tissues.

Aged↗

Designing in vitro assay systems for hazard characterization. basic strategies and related technical issues.

Adverse effects of chemicals on humans are typically assessed following four steps: hazard identification, hazard characterization, exposure assessment and risk characterization. Hazard characterization is defined as the qualitative and/or quantitative evaluation of the nature of the adverse effects associated with biological, chemical and physical agents of interest. For chemical agents, hazard characterization is based on a series of in vitro and/or in vivo data obtained from mechanistic, kinetic and dose-response studies on the agent of concern, which are analyzed and integrated for extrapolation to eventually match human conditions. Thus, an accurate experimental design and the development of test methods capable of generating data relevant to hazard characterization are essential for the useful risk assessment of chemicals, including inhaled materials. It should, however, be stressed that hazard characterization has widely been limited to single chemicals. The hazard characterization of airborne mixtures therefore poses a new problem in toxicology, which calls for a novel approach to its scientific assessment. During the last three decades, a number of epidemiological and experimental studies have been conducted focusing on two kinds of inhaled complex mixtures, namely cigarette smoke and diesel exhausts. A new approach to the assessment of airborne complex mixtures may be elaborated through the appropriate, combined use of the findings of such studies. In this context, the present review article is intended to illustrate some basic strategies for and technical issues related to the hazard characterization of inhaled complex mixtures, thereby taking up representative epidemiological and experimental data from published papers on tobacco smoke.

Air Pollutants↗

Metastatic leiomyosarcoma of the brain manifesting as multiple hemorrhages. Case report.

A 74-year-old man presented with a rare metastatic leiomyosarcoma of the brain manifesting as subacute development of multiple cerebral hemorrhages. Cerebral angiography demonstrated no tumor staining or vascular malformation. Whole body computed tomography revealed abnormal masses in the liver, left adrenal gland, and duodenum. Histological examination of an open biopsy specimen identified the lesion as metastatic leiomyosarcoma. Whole brain irradiation controlled the intracranial lesions, but the patient's general condition progressively deteriorated and he died of pneumonia. Metastatic leiomyosarcoma is a very uncommon tumor in the central nervous system with a poor response to existing treatment options. Consequently, new approaches to the treatment of this disease are needed.

Aged↗

The pathology of ligamentum flavum in degenerative lumbar disease.

STUDY DESIGN: A pathologic study of the ligamentum flavum in degenerative lumbar disease. OBJECTIVES: To elucidate the clinical significance of each pathologic finding of the ligamentum flavum. SUMMARY OF BACKGROUND DATA: In many reports, researchers observed the ligamentum flavum removed partially during surgery and did not evaluate the whole image of the ligamentum flavum. In addition, there are only a few reports that examined the possible association between various histologic findings and clinical findings. And, thus, there are many unclear points in the clinical significance indicated by each pathologic finding. METHODS: The study participants were 50 patients with degenerative lumbar diseases who underwent surgical decompression with removal of the ligamentum flavum of the affected spinal level. Tissue specimens of the removed ligamentum flavum in cross section were prepared, and changes in the elastic fibers and collagen fibers were evaluated in three grades to evaluate the whole image. In addition, we observed the presence or absence of any focal lesions and statistically analyzed the possible association between these histologic findings and clinical symptoms or image findings. RESULTS: In regard to the association between histologic findings and clinical symptoms or image findings, calcification was observed in significantly older patients, who tended to have low scores in preoperative JOA score, and was frequently observed in patients with cauda equina symptoms. Patients with ossification had a significantly greater % slip, and chondroid cells were frequently observed in patients with spondylolisthesis. CONCLUSION: Various pathologic findings provided important foundations for discussing the pathogenesis of lesions in ligamentum flavum. Calcification was frequently observed in elderly patients and those with cauda equina symptoms, and these patients tended to have severer preoperative symptoms. Chondroid cells were frequently observed in patients with spondylolisthesis, and patients with ossification had a greater % slip, suggesting involvement of mechanical load in ossification of ligaments. The pathologic findings were significantly related to the clinical features, and these findings will be profitable for understanding the pathogenesis of degenerative lumbar disease.

Aged↗

[Special proposal].

Various kinds organs and tissues obtained from operations and autopsies are preserved for a certain period of time after obtaining samples for histopathological examination and are later disposed of. Some of these organs and tissues are occasionally used for research or educational purposes. Although consent is usually obtained from the patient or from the family of the deceased patient before performing an operation or autopsy, the use and disposal of residual organs and tissues have been performed by clinicians or pathologists without obtaining consent from the patient or from the family of the deceased patient. Now, however, consent must be obtained after sufficient explanation to the patient or to the family of the deceased patient for the storage, use and disposal of residual organs and tissues. It must be kept in mind that residual organs and tissues are parts of a human body and that these parts belong to the patient from which they were obtained or to the family of the deceased patient. These points are important and provide an ethical basis for use and disposal of residual organs and tissues.

Ethics, Medical↗

Application of the concepts of risk assessment to the study of amino acid supplements.

Risk assessment is defined as the use of available scientific information to characterize potentially adverse effects associated with exposure of humans to an agent under known or expected conditions. Practically, risk assessment is intended to provide the scientifically sound basis for regulatory or nonregulatory action to manage the risks in humans from the agent. Therefore, the final goal of risk assessment for supplementary use of amino acids is to provide scientific evidence and scientific logic for the establishment of tolerable upper intake levels (UL) for amino acids. At present, however, execution of risk assessment for amino acids is hampered by deficiencies in necessary scientific information, particularly, experimental or clinical/epidemiological data related to the estimation of no-observed-adverse-effect-levels (NOAEL), and scientific principles for the allocation of uncertainty factors (UF) in extrapolation from experimental/clinical data to the general human population. This paper attempts to identify the scientific data and scientific thoughts/methodologies required for deriving UL or assessing the margin of safety for the supplementary use of amino acids.

Aging↗

Inhibition of COX-2 prevents hypertension and proteinuria associated with a decrease of 8-iso-PGF2alpha formation in L-NAME-treated rats.

BACKGROUND: The inhibition of nitric oxide (NO) exerts injurious effects on the cardiovascular system by several mechanisms, such as the activation of the renin-angiotensin system, oxidative stress, and inflammatory cytokines. We examined whether COX-2, an inducible isoform of cyclooxygenase, is associated with the pathogenesis observed in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. METHODS: Three groups of 8-week-old male Sprague-Dawley rats were studied (n = 6 in each group): group 1, untreated controls; group 2, treated with L-NAME (1 g/l for 3 weeks, p.o.); and group 3, L-NAME co-treated with COX-2 inhibitor NS-398 (5 mg/kg per day, i.p.). The L-NAME-induced expression of COX-2 mRNA and protein was semi-quantified in the kidneys and the thoracic aorta. Urinary excretion of the prostaglandin 6-keto PGF(1alpha), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) was measured in the three groups. Moreover, urinary excretion of 8-iso-PGF(2alpha), a potent vasoconstricting arachidonic acid metabolite acting through thromboxane A (TXA) receptor activation, proposed recently as a marker of oxidative stress, was also measured. RESULTS: L-NAME induced significant increases in systolic blood pressure (P< 0.01), urinary protein (P< 0.05), and renal excretion of 8-iso-PGF(2alpha)(P< 0.01), compared with the control. In L-NAME-treated rats, the levels of COX-2 mRNA and protein were more than 50% higher in the kidneys (P< 0.05), and six-fold higher in the thoracic aorta (P< 0.01) than in control rats. NS-398 significantly ameliorated an increase in systolic blood pressure (P< 0.01) and urinary protein (P< 0.05) induced by L-NAME. CONCLUSIONS: These data indicate that an increase in COX-2 expression might have a hypertensive effect, partly associated with 8-iso-PGF(2alpha) formation in l-NAME-treated rats.

Animals↗

Dissecting basilar artery aneurysm growing during long-term follow up--case report.

A 58-year-old male presented with a dissecting aneurysm of the basilar artery manifesting as dysarthria, left hemiparesis, and numbness of the left side. Angiography revealed a double lumen at the midportion of the basilar artery which was consistent with a diagnosis of dissecting basilar artery aneurysm. The patient was treated conservatively, and remained neurologically stable for a 5-year period following initial presentation, but serial magnetic resonance imaging revealed growth of the aneurysm compressing the brain stem. His condition then worsened. Computed tomography revealed obstructive hydrocephalus. Ventriculoperitoneal shunting was performed and the patient's symptoms improved. However, he died of subarachnoid hemorrhage. Autopsy showed the patient had had a type 3 "dolichoectatic dissecting aneurysm." Surgical treatment should be seriously considered for treating the patients with dissecting basilar artery aneurysm causing brain stem ischemia, especially if the aneurysm is growing. High-flow bypass and proximal occlusion may be the choice in patients with poor collateral circulations.

Aortic Dissection↗