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Biomedical subjects

K Hayashi

Publications and source records attributed to K Hayashi.

At least 145 records · Page 8Linked to original sources
PubMed2001

Involvement of 1,2-diacylglycerol in improvement of heart function by etomoxir in diabetic rats.

Abnormal lipid metabolism has been proposed to be involved in the pathogenesis of diabetic cardiomyopathy. In this study, we measured myocardial lipid levels, including 1,2-diacylglycerol (1,2-DAG) and ceramide (CM), and myocardial function in diabetic rats. We also evaluated the effects of etomoxir (ETM), a carnitine palmitoyl transferase I inhibitor, on diabetic rat hearts from the viewpoints of alterations in lipid second messengers and myocardial function. Rats were injected with streptozotocin (60 mg/kg) to induce diabetes and were treated 5 weeks later with ETM (18 mg/kg) for 8 days. In diabetic rats, heart rate, systolic blood pressure, and fractional shortening were significantly reduced compared with those in controls. Treatment of diabetic rats with ETM ameliorated myocardial dysfunction other than heart rate. Myocardial 1,2-DAG levels in diabetic rats were significantly elevated compared with those in controls, while myocardial CM levels were not. ETM treatment caused an additional increase in myocardial 1,2-DAG levels in diabetic rats, but the CM levels did not change. There was a marked difference in fatty acid pattern of 1,2-DAG between diabetic and ETM-treated diabetic rat hearts. The fatty acids 18:1 and 18:2 were significantly increased and the fatty acids 16:0, 18:0, 20:4, and 22:6 were significantly reduced in ETM-treated diabetic rat hearts. These data suggest 1,2-DAG is involved in ameliorating myocardial dysfunction in diabetic rats and that its source is different between diabetic and ETM-treated diabetic rats. CM is unlikely to be involved in the pathogenesis of diabetic cardiomyopathy or the improvement of cardiac contractility in diabetic rats by ETM.

Animals↗
PubMed2001

Effect of quinapril on intimal hyperplasia after coronary stenting as assessed by intravascular ultrasound.

We studied whether angiotensin-converting enzyme inhibition with quinapril treatment can prevent in-stent restenosis after successful implantation of Palmaz-Schatz stents. Intravascular ultrasound study, but not quantitative coronary angiography analysis, revealed that quinapril treatment significantly prevented the loss of both minimal lumen cross-sectional area and lumen volume in stents, in addition to reducing the increase in intimal hyperplasia volume.

Aged↗
PubMed2001

Additive and inhibitory effects of simultaneous treatment with growth factors on DNA synthesis through MAPK pathway and G1 cyclins in rat hepatocytes.

Several growth factors play an important role in liver regeneration. Once hepatic injury occurs, liver regeneration is stimulated by hepatocyte growth factor (HGF), transforming growth factor (TGF)-alpha, and heparin-binding epidermal growth factor-like growth factor (HB-EGF), whereas TGF-beta1 terminates liver regeneration. In this study, we analyzed the effect of a combination of HGF and epidermal growth factor (EGF) on mitogen-activated protein kinase (MAPK) activity and G1 cyclin expression in primary cultured rat hepatocytes. Treatment with a combination of HGF and EGF, in comparison with that of either HGF or EGF, induced tyrosine phosphorylation of both c-Met and EGF receptor (EGFR) independently and additively stimulated MAPK activity and cyclin D1 expression, resulting in additive stimulation of DNA synthesis. On the other hand, although TGF-beta1 treatment did not affect tyrosine phosphorylation of c-Met and EGFR, MAPK activity, and cyclin D1 expression, which were stimulated by HGF and EGF, DNA synthesis was completely inhibited through a marked decrease in cyclin E expression. These results indicate that potent mitogens, such as HGF, TGF-alpha, and HB-EGF, could induce the additive enhancement of liver regeneration cooperatively through an increase in Ras/MAPK activity followed by cyclin D1 expression, and that TGF-beta1 suppresses the growth factor-induced signals between cyclin D1 and cyclin E, resulting in the inhibition of DNA synthesis.

Animals↗
PubMed2001

Characterization of low dose streptozotocin-induced progressive diabetes in mice.

Our previous study indicated that a single i.p. injection of 100 mg/kg streptozotocin (STZ) is able to induce slowly progressive diabetes mellitus in adult ICR mice. In the present study, the non-fasting serum insulin levels of the mice administered 100 mg/kg STZ were normal throughout the 24-week-observation after STZ injection. In the STZ-administered mice, the area of islets and the number of insulin-immunoreactive cells (beta-cells) were normal at 1 week and then continued to decrease gradually as the time went on. In contrast, there was a relative increase in the number of glucagon-immunoreactive cells (alpha-cells) in these mice. In addition, in the STZ-administered mice, the degree of glucose tolerance continued to reduce from 2 weeks till 12 weeks when the experiment terminated. The rise in serum insulin levels stimulated by glucose in the STZ-administered mice began to subside from about 2 weeks and had completely ceased by 12 weeks. These results indicate that 100 mg/kg STZ-induced diabetic mouse model is non-insulin-dependent diabetes, which is characterized by impaired insulin response to glucose stimulation.

Journal Article↗
PubMed2001

HUNT: launch of a full-length cDNA database from the Helix Research Institute.

The Helix Research Institute (HRI) in Japan is releasing 4356 HUman Novel Transcripts and related information in the newly established HUNT database. The institute is a joint research project principally funded by the Japanese Ministry of International Trade and Industry, and the clones were sequenced in the governmental New Energy and Industrial Technology Development Organization (NEDO) Human cDNA Sequencing Project. The HUNT database contains an extensive amount of annotation from advanced analysis and represents an essential bioinformatics contribution towards understanding of the gene function. The HRI human cDNA clones were obtained from full-length enriched cDNA libraries constructed with the oligo-capping method and have resulted in novel full-length cDNA sequences. A large fraction has little similarity to any proteins of known function and to obtain clues about possible function we have developed original analysis procedures. Any putative function deduced here can be validated or refuted by complementary analysis results. The user can also extract information from specific categories like PROSITE patterns, PFAM domains, PSORT localization, transmembrane helices and clones with GENIUS structure assignments. The HUNT database can be accessed at http://www.hri.co.jp/HUNT.

Computational Biology↗
PubMed2001

Outside-to-inside signal through the membrane TNF-alpha induces E-selectin (CD62E) expression on activated human CD4+ T cells.

The membrane TNF-alpha is known to serve as a precursor of the soluble form of TNF-alpha. Although it has been reported the biological functions of the membrane TNF-alpha as a ligand, the outside-to-inside (reverse) signal transmitted through membrane TNF-alpha is poorly understood. Here we report a novel function mediated by outside-to-inside signal via membrane TNF-alpha into the cells expressing membrane TNF-alpha. Activation by anti-TNF-alpha Ab against membrane TNF-alpha on human T cell leukemia virus (HTLV) I-infected T cell line, MT-2, or PHA-activated normal human CD4(+) T cells resulted in the induction of an adhesion molecule, E-selectin (CD62E), on the cells with the peak of 12-24 h, which completely disappeared by 48 h. When wild-type or mutant membrane TNF-alpha (R78T/S79T) resistant to proteolytic cleavage was introduced into Jurkat or HeLa cells, E-selectin was induced by the treatment with anti-TNF-alpha Ab with the similar kinetics. Membrane TNF-alpha-expressing Jurkat cells also up-regulated E-selectin when brought into cell-to-cell contact with TNF receptor-expressing HeLa cells. Northern blot analysis and RT-PCR analysis showed that the membrane TNF-alpha-mediated E-selectin expression was up-regulated at the level of transcription. These results not only confirmed our previous findings of reverse signaling through membrane TNF-alpha, but also presented evidence that E-selectin was inducible in cell types different from endothelial cells. It is strongly suggested that membrane TNF-alpha is a novel proinflammatory cell surface molecule that transmits bipolar signals in local inflammation.

CD4-Positive T-Lymphocytes↗
PubMed2001

Expression of hepatocyte growth factor and matrix metalloproteinase-2 in human glioma.

Hepatocyte growth factor (HGF) has a stimulatory effect on the synthesis of matrix metalloproteinase-2 (MMP-2), which is involved in glioma invasion. In this study, to clarify the correlation between the expression of HGF and MMP-2 in glioma tissues, immunohistochemical analysis of HGF and MMP-2 was performed in 11 cases of astrocytoma, 10 cases of anaplastic astrocytoma, and 9 cases of glioblastoma. As a result, expression of HGF and MMP-2 was correlated with the grade of malignancy (P = 0.0181 and 0.0001, respectively), and a significant correlation between the immunoreactivity of HGF and that of MMP-2 was observed (P < 0.05). Immunofluorescence study revealed the concomitant expression of HGF and MMP-2 in glioma tissue. In cultured glioma cell lines (SNB-19, U87MG, and U373MG), exogenous recombinant HGF effectively acted on the production of the active and latent forms of MMP-2 protein in a dose-dependent manner. Active MMP-2 increased more effectively than the latent form. Taken together, these results suggest that HGF may promote glioma invasion in vivo by production of MMP-2.

Astrocytoma↗
PubMed2001

Coexistence of lung cancer and hamartoma.

We present a rare case of a synchronous primary lung cancer adjacent to a hamartoma. A 71-year-old woman was admitted with congestive heart failure due to acute myocardial infarction. A chest radiogram on admission showed pulmonary edema with a tumor shadow in the right upper lung field. Because histological diagnosis was not obtained preoperatively, a wedge resection of the lung was conducted using video-assisted thoracoscopic surgery. The histopathological examination confirmed the coexistence of an adenocarcinoma with a chondromatous hamartoma. Right upper lobectomy was performed followed by excision of the mediastinal lymph nodes. Although hamartoma is generally considered to be a benign neoplasm, there have been several reports of increased risk to lung cancer in patients with a chondromatous hamartoma. Therefore, we recommend that patients with a hamartoma should be submitted to a complete evaluation and to regular follow-up, considering the risk to associated synchronous malignancy.

Adenocarcinoma↗
PubMed2001

Comparison of MET-PET and FDG-PET for differentiation between benign lesions and malignant tumors of the lung.

OBJECTIVE: We retrospectively assessed and compared the usefulness of 11C-methionine (MET)-PET with that of 18F-FDG-PET for the differentiation between benign lesions and malignant tumors of the lung. METHODS: We examined 101 patients with a suspected lung tumor including 79 patients with primary lung cancer and 22 patients with benign lesions. One hundred and forty PET studies (46 studies with MET-PET and 94 studies with FDG-PET) were performed. Both MET-PET and FDG-PET were performed on 39 patients. The MET-PET was performed 15 minutes after the administration of 67-740 MBq of MET, and FDG-PET 45 minutes after the administration of 30-437 MBq of FDG. The results were then evaluated by the standardized uptake value (SUV). RESULTS: The MET uptake in lung cancer was 3.69+/-1.22 (n = 37) which was significantly higher than that in benign lesions 1.81+/-1.04 (n = 9) (p < 0.001). The sensitivity, specificity and accuracy of MET-PET were 83.8%, 88.9% and 84.8%, respectively, when 2.66 of SUV was used as the cutoff value. The FDG uptake in lung cancer was 5.94+/-2.89 (n = 75) and was also significantly larger than that in benign lesions 2.46+/-1.01 (n = 19) (p < 0.001). The sensitivity, specificity and accuracy of FDG-PET were 81.3%, 78.9% and 80.9%, respectively (cutoff = 3.20). The MET uptake in the lesions correlated significantly with FDG uptake (r = 0.71, p < 0.001). According to an ROC analysis, the area under the curve for MET-PET (area = 0. 833) was higher than that for FDG-PET (area = 0.828), but the difference was not statistically significant. Furthermore, the combined use of MET-PET and FDG-PET did not improve the diagnostic ability. CONCLUSIONS: In conclusion, both MET-PET and FDG-PET were considered to be equally useful for the differential diagnosis of lung tumors. Furthermore, MET uptake in lung lesions was found to correlate significantly with FDG uptake.

Adult↗
PubMed2001

Effects of lifetime volleyball exercise on bone mineral densities in lumbar spine, calcaneus and tibia for pre-, peri- and postmenopausal women.

To clarify the effects of habitual volleyball exercise on bone in women during the menopausal periods, we measured bone mineral densities (BMDs) of the lumbar spine, calcaneus and tibia every 12 months for 2 years and estimated factors related to the baseline values and annual loss rates. Forty Japanese female volleyball players 42-62 years of age, who had belonged to the district non-professional club for more than 10 years on average, were recruited. Twenty women had regular menstruation at the start, but 7 underwent menopause during the study. Fifty-nine healthy women who did not participate in habitual exercise, but were otherwise comparable with the players, were recruited as the controls. The lumbar and calcaneus BMDs were measured by dual-energy X-ray absorptiometry (DXA), and both the volumetric BMDs and cross-sectional geometry at the diaphysis of the tibia were measured by peripheral quantitative computed tomography. The baseline BMDs of all measured sites and the values of the cortical area and moment of inertia of the tibia in the players were significantly higher than the values in the control women. In the peri- and postmenopausal players, the baseline values of the lumbar and calcaneus BMDs related to total years of participating in regular exercises during adulthood including volleyball (TYE), body mass index (BMI) and years since menopause (YSM). Tibia cortical area and moment of inertia values related to TYE. Annual bone loss rates in the tibia and calcaneus of players were significantly smaller than those values in the controls. However, the bone loss rates in the lumbar spine did not differ significantly between the groups. The bone loss rate in the calcaneus was significantly related to the current number of training hours per week and YSM. The rate of bone loss in the tibia was related to BMI. These data indicated that the total number of years participating in exercise activity during adulthood have positive effects on lumbar and calcaneus BMDs and the cortical structure of the tibia. Habitual volleyball exercise apparently did not alleviate the menopause-related bone loss in the lumbar spine.

Absorptiometry, Photon↗
PubMed2001

Risk factors for early death in patients undergoing treatment for multiple myeloma.

The survival time of myeloma patients improved from a few months to many years after treatment with melphalan. Perhaps chemotherapy more intensive than melphalan-prednisolone should be administered to patients at risk of early death. Therefore, early death must be accurately predicted. We analyzed 93 patients with recently diagnosed myeloma and found that 13 (14%) died within 6 months (early death). The most common cause of death was bacterial and fungal pneumonia when myeloma became uncontrollable. The response to conventional chemotherapy was poorer in patients at high risk of early death than the control group. Multivariate analysis showed that the serum level of beta-2 microglobulin was the only value that predicted early death.

Aged↗
PubMed2001

Differentiation between high-grade glioma and metastatic brain tumor using single-voxel proton MR spectroscopy.

The purpose of this study was to clarify the efficacy of single-voxel proton magnetic resonance spectroscopy (MRS) in differentiating high-grade glioma from metastasis. Thirty-one high-grade gliomas (11 anaplastic gliomas and 20 glioblastomas) and 25 metastases were studied. Proton MRS was performed using point-resolved spectroscopy with echo times (TEs) of both 136 and 30 ms. The peaks for lipid were evaluated at short TE, and those for N-acetyl-aspartate (NAA), creatine (Cr), and choline-containing compounds (Cho) were assessed at long TE. All the tumors exhibited a strong Cho peak at long TE. Twenty-one of 25 metastases showed no definite Cr peak. The remaining 4 metastases showed NAA and Cr peaks; however, the presence of NAA and relatively high NAA/Cr ratio (1.58+/-0.56) indicated normal brain contamination. All the gliomas, except for a single glioblastoma, showed a Cr peak with (n=16) or without (n=14) NAA. At short TE all metastases and glioblastomas showed definite lipid or lipid/lactate mixture, but anaplastic gliomas showed no definite lipid signal. Intratumoral Cr suggests glioma. Absence of Cr indicates metastasis. Definite lipid signal indicates cellular necrosis in glioblastoma and metastasis, and no lipid signal may exclude metastases.

Adolescent↗
PubMed2001

Antioxidant changes in the hypertrophied heart due to energy metabolic disorder.

Oxidative stress has been implicated in the pathogenesis of both heart hypertrophy and heart failure. Hypertrophied heart, in response to pressure overload, is associated with an increase in antioxidant capacity and a decrease in oxidative stress. However, in the hypertrophied heart due to energy metabolic disorder, antioxidant capacity has not been investigated. Antioxidant changes in juvenile visceral steatosis (JVS) mice, a model of heart hypertrophy due to disorder of fatty-acid oxidation, were examined at 4 weeks (developing hypertrophy stage) and 8 weeks of age (established hypertrophy stage). Superoxide dismutase activity in the JVS mice was higher than that in control mice at 4 weeks of age and was not different from that in the control mice at 8 weeks of age. Glutathione peroxidase activity in the JVS mice at 8 weeks of age was lower than that in the control mice. Catalase activity showed no significant differences between the control and the JVS mice. Lipid peroxidation in the JVS mice was significantly reduced at 4 weeks of age and increased toward control levels at 8 weeks of age. The levels of vitamin E in the heart were increased in the JVS mice at 8 weeks of age. To determine whether antioxidants affect the pathogenesis of hypertrophy in this model, long-term treatments of vitamin E and 2-mercaptopropionyl glycine were performed. Vitamin E treatment partially reduced the heart hypertrophy in these mice. The present study shows that heart hypertrophy in the JVS mice is accompanied with increased antioxidant capacity as indicated in other animal models of heart hypertrophy. The precise mechanism of heart hypertrophy in JVS mice is still unknown, but oxidative stress may play a role in the pathogenesis of heart hypertrophy.

Animals↗
PubMed2001

Delineation of the critical interval for the familial exudative vitreoretinopathy gene by linkage and haplotype analysis.

Familial exudative vitreoretinopathy (FEVR) is an ocular disorder characterized by deficient vascularization of the peripheral retina and causes visual loss attributable to various types of retinal detachment. The locus of the gene responsible for the autosomal dominant form of FEVR (EVR1) has been assigned to 11q13-23. However, a detailed evaluation of the critical region has not been made. We present the results of linkage analysis of the EVR1 locus on 11q13-23 in 43 individuals belonging to seven unrelated families of Japanese origin. Multipoint analysis has shown that six families out of the seven are linked with 11q13-23 markers. Haplotype analysis reveals that the putative region is probably flanked by polymorphic markers D11S1362 and CHLC.GATA30G01, which are approximately 200 kb apart, although the recombination events in small families such as presented in this study should be interpreted cautiously.

Chromosomes, Human, Pair 11↗
PubMed2001

Different recurrence patterns after phototherapeutic keratectomy in the corneal dystrophy resulting from homozygous and heterozygous R124H BIG-H3 mutation.

PURPOSE: To report the recurrence pattern of corneal deposits after phototherapeutic keratectomy in patients with corneal dystrophies resulting from homozygous and heterozygous Arg124His (R124H) mutation of the BIG-H3 gene. METHODS: Slit-lamp examination was performed on patients with corneal dystrophy resulting from a genetically confirmed BIG-H3 R124H mutation. RESULTS: The recurrence of corneal deposits after phototherapeutic keratectomy in patient with heterozygous R124H mutation was mild; the granular opacities occurred as spot lesions in the central cornea. The patient with a homozygous mutation had a more severe pattern, and the recurrent lesions were diffuse and occurred in the periphery between the corneal epithelium and laser-ablated stroma. The recurrence-free interval in homozygous patients was shorter. CONCLUSION: The mutation genotype of BIG-H3 gene determines the recurrence pattern after phototherapeutic keratectomy.

Aged↗
PubMed2001

Influence of cataract surgery on automated perimetry in patients with glaucoma.

PURPOSE: To investigate the influence of cataract surgery on automated perimetry in patients with glaucoma. DESIGN: Interventional case series. METHODS: A total of 105 eyes of 105 consecutive patients with glaucoma who were scheduled for cataract surgery underwent Humphrey static threshold testing (30-2 program) before and at 1 month after surgery. These eyes were divided into two groups based on the presence of absolute or near absolute (dense) scotomata before surgery (minimum threshold value 5 decibels or less). Changes in numbers of the dense scotomata, mean deviation, pattern standard deviation, and corrected pattern standard deviation were analyzed. RESULTS: No significant changes were found in the numbers of dense scotomata and central dense scotomata within five-degree visual fields between before and after surgery. In the group with dense scotomata, the mean pattern standard deviation and corrected pattern standard deviation worsened significantly after surgery, whereas the mean deviation improved significantly. However, in the group without dense scotomata, the pattern standard deviation and corrected pattern standard deviation showed a slight improvement, whereas the mean deviation improved significantly. When the central scotoma was present in two or fewer meridians before surgery, the mean visual acuity after surgery reached 20/25 and was better than that in patients with three or four central scotomata (P =.0014). CONCLUSIONS: Cataract does not produce a dense scotoma on automated perimetry. However, because it does produce relative scotomata, actual glaucomatous visual field defects may be hidden to some extent. When a central dense scotoma is present before surgery in two or fewer meridians, the patient may well achieve substantial improvement in postoperative visual acuity.

Adult↗