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Biomedical subjects

Y Noguchi

Publications and source records attributed to Y Noguchi.

At least 37 records · Page 2Linked to original sources

Plasma concentration of tissue inhibitor of matrix metalloproteinase 1 in patients with colorectal carcinoma.

BACKGROUND: The expression of tissue inhibitor of matrix metalloproteinase (TIMP) 1 in tumour tissue from patients with colorectal carcinoma has been reported to be related to disease progression. However, the clinical significance of plasma TIMP-1 has not been fully elucidated. METHODS: The plasma level of TIMP-1 protein was determined by enzyme-linked immunosorbent assay in samples from 54 patients who underwent resection of the primary tumour. RESULTS: Plasma TIMP-1 levels were associated significantly with depth of invasion and metastasis to lymph nodes and liver. Circulating TIMP-1 levels were significantly higher in patients with serosal invasion, liver metastases and Dukes' stage C tumours. Using a cut-off value of 160 ng/ml, serosal invasion and Dukes' C stage could be predicted with an accuracy of 68.5 per cent. With a cut-off value of 170 ng/ml, metastasis to the lymph node and liver could be predicted with an accuracy of 66.7 and 70.4 per cent respectively. These values were greater than those for carcinoembryonic antigen and CA19-9. CONCLUSION: These data suggest that the plasma concentration of TIMP-1 correlates with both invasion and metastasis in patients with colorectal carcinoma.

Adult↗

Electronystagmographic findings in patients with cerebral degenerative disease.

Cerebral degenerative diseases produce a variety of abnormal neuro-otological findings on electronystamography (ENG). To assess their diagnostic value and determine which manifestations are helpful in making a diagnosis, ENG findings from 72 cases of confirmed cerebral degenerative disease were analyzed. We observed a high incidence of saccadic pursuit and upward ocular dysmetria, which is likely to be useful in diagnosing cerebral degenerative disease. In contrast, moderate incidences of horizontal ocular dysmetria, gaze-evoked and rebound nystagmus, vertical positioning nystagmus and impaired visual suppression appeared to reflect the degree of dysfunction, while optokinetic nystagmus appeared to reflect both the presence of disease and its severity. Cases of spinocerebellar ataxia 6 and spinocerebellar ataxia 3 tended to produce horizontal and vertical gaze-evoked nystagmus, whereas progressive supranuclear palsy produced a higher incidence of upward gaze-evoked nystagmus, and positioning nystagmus at the sagittal plane appeared frequently in cases of non-hereditary spinocerebellar degeneration.

Electronystagmography↗

Regulation of FRTL-5 thyroid cell growth by phosphatidylinositol (OH) 3 kinase-dependent Akt-mediated signaling.

Thyrotropin (TSH)-initiated cell cycle progression from G1 to S phase in FRTL-5 thyroid cells requires serum, insulin, or insulin-like growth factor 1 (IGF-1) and involves activation of 3-hydroxy-3-methylglutaryl-CoA reductase, geranylgeranylation of RhoA, p27Kip1 degradation, and activation of cyclin-dependent kinase (cdk) 2. In the present report, we show that the serine-threonine kinase Akt is an important mediator of insulin/IGF-1/serum effects on cell cycle progression in FRTL-5 thyroid cells. The phosphoinositol (OH) 3 kinase inhibitors, Wortmannin (WM) and Ly294002 (LY), block the ability of insulin/IGF-1 to reduce p27 expression, to induce expression of cyclins E, D1, and A as well as cdk 2 and 4, and to phosphorylate retinoblastoma protein. They also inhibit insulin/IGF-1-increased DNA synthesis and cell cycle entrance (S+G2/M). Insulin/IGF-1 rapidly induced activation of Aktl in a PI3 kinase-dependent manner, and increased Aktl RNA levels. Most importantly, FRTL-5 cells transfected with a constitutively active form of Aktl have higher basal rates of DNA synthesis and no longer require exogenous insulin/IGF-1 or serum for TSH-induced growth. In sum, Aktl appears to have an important role in insulin/IGF-1 regulation of FRTL-5 thyroid cell growth and cell cycle progression.

Animals↗

A high low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio as a potential risk factor for corticosteroid-induced osteonecrosis in rabbits.

OBJECTIVE: This study was designed to determine the potential risk factors for corticosteroid-induced osteonecrosis (ON) based on lipid metabolism, using a rabbit ON model. METHODS: Blood samples were obtained from 38 rabbits, which then received a single intramuscular injection of 20 mg/kg methylprednisolone acetate. Four weeks after the injection, the femora and humeri were examined histopathologically for the presence of ON, and the sizes of the bone marrow fat cells were also measured. RESULTS: Rabbits with and without ON differed significantly in the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL/HDL cholesterol ratio), which is considered to be a serological marker of lipid transport (P=0.026). The marrow fat cells were significantly larger in the rabbits with ON than in those without ON (P<0.0001). CONCLUSION: A higher LDL/HDL cholesterol ratio was significantly associated with the development of ON, and such an elevated ratio may partly contribute to the increased size of marrow fat cells.

Adrenal Cortex Hormones↗

Triggering the induction of myofibroblast and fibrogenesis by airway epithelial shedding.

Myofibroblasts have been thought to participate in subepithelial fibrosis in asthma, but the mechanism of myofibroblast induction has not been fully understood. In this study we investigated injury-related myofibroblast induction in a coculture system of guinea-pig epithelial cells and fibroblasts cocultured in a human amnion chamber. After pseudostratified epithelial cells were mechanically scraped, migrated flat epithelial cells differentiated into cuboidal appearances on Day 4 and then returned to their original shapes on Day 8. During the course of the epithelial redifferentiation, it was found by Northern blot analysis, immunohistochemistry for alpha-smooth muscle actin, and electron microscopic observation that the myofibroblasts were transiently induced on Day 4. The myofibroblast induction was inhibited by the blocking of transforming growth factor (TGF)-beta1 and thrombospondin (TSP)-1, indicating that the activation of TGF-beta1 by TSP-1 would induce myofibroblasts. This finding was also supported by a transient upregulation of TSP immunoreactivity and TSP-1 messenger RNA (mRNA) in fibroblasts. Interestingly, epithelial injury reduced TGF-beta1 immunoreactivity in the amnion membrane but did not affect TGF-beta1 mRNA in epithelial cells and fibroblasts, indicating that TGF-beta1 supplied from the extracellular matrix can participate in myofibroblast induction. Concurrently with myofibroblast induction, procollagen type I and III mRNAs were upregulated in fibroblasts, and obvious collagen deposition was observed ultrastructurally around the myofibroblasts compared with the fibroblasts. These results indicate that induced myofibroblasts can be functionally more active in producing collagen than are resting fibroblasts. The present study suggests that epithelial injury stimulates TGF-beta1 release from the extracellular matrix and its activation via TSP-1 production, causing collagen synthesis through myofibroblast induction.

Actins↗

Pseudohyperkalaemia caused by recentrifugation of blood samples after storage in gel separator tubes.

Because hyperkalaemia above a certain level is life-threatening, erroneous interpretation of serum potassium concentration may misguide and complicate diagnostic procedures. We investigated a number of cases with pseudohyperkalaemia, which was assumed to have been caused by the recentrifugation of blood samples after storage in gel separator tubes. The time trend of serum potassium concentration was explored before (January-March 1997) and after (May-July 1997) ceasing the practice of recentrifuging blood samples after overnight storage. Next, we conducted an experiment on a volunteer's serum. The sample was divided into two groups and centrifuged once (control group) or twice (recentrifugation group). For both groups, serum potassium concentrations were measured immediately, and at 24, 48 and 72 h. For the recentrifugation group, the second centrifugation was done just before the measurement. The time series study showed that the mean serum potassium concentrations measured after overnight storage were 4.68 (95% CI: 4.60-4.76) mmol/L before and 4.14 (4.07-4.20) mmol/L after ceasing the practice of recentrifugation. The experiment showed that the mean serum potassium concentrations in the control group versus the recentrifugation group were 3.95 (95% CI: 3.89-4.01) mmol/L versus 4.05 (3.92-4.17) immediately (P=0.0979), 3.95 (3.89-4.01) versus 5.95 (5.61-6.29) at 24 h (P=0.0001), 4.13 (4.05-4.22) versus 6.90 (6.46-7.34) at 48 h (P=0.0001), and 4.22 (3.85-4.58) versus 7.61 (6.94-8.30) at 72 h (P<0.0001). Recentrifugation of blood samples after storage causes a spurious rise in serum potassium concentration to the degree of clinical significance. Clinicians and biochemists should take appropriate measures to stop this practice.

Artifacts↗

Solitary infantile myofibromatosis in the lateral orbit floor showing spontaneous regression.

Infantile myofibromatosis is a rare benign tumour usually occurring early in infancy. We describe the case of a 10-year-old boy with solitary infantile myofibromatosis in the left lateral orbit floor which regressed spontaneously. Although our patient was older than previously reported cases and showed bony destruction confirmed by computed tomography (CT), this tumour was diagnosed as infantile myofibromatosis based on immunohistochemical findings. The tumour disappeared spontaneously six months after incisional biopsy, that also indicated this tumour was an infantile myofibromatosis.

Child↗

Sequential computed tomography images demonstrating characteristic changes in fibrous dysplasia.

Images of fibrous dysplasia (FD) on computed tomography (CT) or magnetic resonance imaging (MRI) vary depending on the relative proportions of the fibrous and osseous components. Based on analysis of the literature, Camilleri suggested that structural changes revealed by conventional radiography may be indicative of the progression of FD. Here we describe the case of a boy who presented at 12 years of age with monostotic FD located in the right maxilla. The lesion first appeared as a lamellar, "onion peel"-like structure on CT; then over the course of the next five years, the structure became what has been termed an "egg-shell lesion", before eventually assuming the form of a "ground-glass lesion".

Adult↗

Audiological findings in patients with myoclonic epilepsy associated with ragged-red fibres.

Sensorineural hearing loss is a common symptom in patients with myoclonic epilepsy associated with ragged-red fibres (MERRF), one of the mitochondrial encephalomyopathies, although the lesion causing hearing loss in such cases remains unknown. Here we describe the audiological features in three MERRF patients, all of whom exhibited a point mutation in their mitochondrial DNA at nucleotide 8344. Pure-tone threshold audiometry revealed bilateral, sloping-type, sensorineural hearing loss in all three patients. Distortion product otoacoustic emissions, electrocochleography, and auditory brainstem responses were variable, even differing between the right and left ears of the same patient. Taken together, our findings suggest that the primary lesion underlying hearing loss in MERRF patients is in the cochlea, although a retrocochlear lesion may be involved in some patients.

Adolescent↗

Purification and molecular characterization of a quinoprotein alcohol dehydrogenase from Pseudogluconobacter saccharoketogenes IFO 14464.

We have cloned and verified a gene for a novel quinoprotein alcohol dehydrogenase (ADH) from Pseudogluconobacter saccharoketogenes IFO 14464 that has the ability to oxidize L-sorbose to 2-keto-L-gulonic acid (2-KLGA). The enzyme was purified from the soluble fraction of the bacterium and was estimated to be a monomeric protein with a molecular weight of 65 kDa from the analyses of SDS-PAGE and gel-filtration chromatography. An open reading frame of 1824 bp for 608 amino acid residues was estimated as the gene for ADH because of the consistency of the calculated molecular mass and the elucidated partial amino acid sequences of the native enzyme. Homology search revealed that the enzyme showed close similarity to quinoprotein alcohol dehydrogenases isolated from Methylobacterium extorquens and Acetobacter aceti, particularly in the tryptophan docking motifs in the alpha-subunits of those dehydrogenases. The ability to convert L-sorbose to 2-KLGA was found when the lysate of recombinant Escherichia coli DH10B transformed with the gene for ADH was mixed with CaCl2and pyrroloquinoline quinone (PQQ). These data indicate that the cloned DNA is the desired gene for the ADH in which CaCl2 and PQQ are essential for enzymatic activity.

Journal Article↗

The defibrillation system of basic emergency medical technicians in Japan: a comparison with other systems from a 14-year review of out-of-hospital cardiac arrest reports.

Although seven years have passed after basic emergency medical technician (EMT) defibrillation system was introduced in Japan, the overall survival for out-of-hospital cardiac arrest (OHCA) remains poor. We investigated factors leading to such an unanticipated result in Japan by comparing the data of OHCA in Japan with those in other countries. We obtained population-based OHCA data from three communities in Japan. We also performed a comprehensive literature and manual search to identify reports that included rates for incidence and survival or provided sufficient data for the calculation of these rates of OHCA. Statistical analysis was performed to compare survival and incidence rates between the communities. We identified 36 articles from 16 countries by a comprehensive literature search. There was no significant difference in incidence and survival rates among communities in Japan. Although the incidence rate of collapse-witnessed OHCA with ventricular fibrillation (VF) was much lower in Japan than western countries, the proportions of survival from it were comparable to those. Basic-EMT defibrillation system in Japan has yielded excellent result in terms of the survival of VF cases. However, much lower proportion of VF to all cases is responsible for lower overall rates of survival from OHCA in Japan.

Chi-Square Distribution↗

[Mechanisms of cancer-induced anorexia].

Possible mediators of anorexia-cachesia syndrome are hormones, cytokines, and leptin at the peripheral tissues, and neuropeptides, cytokines, and hormones in the hypothalamus. Insulin resistance and relative hyper-glucagonemia might stimulate anorexia. Interleukin(IL)-6, and tumor necrosis factor(TNF)-alpha as well as IL-1 and leukemia inhibitory factor(LIF) are some of those cytokines. Although leptin in the adipose tissue is an attractive addition, changes in the tumor-bearing state does not support its active role in the induction of anorexia. Newer neuropeptides related with anorexia and oxygenia have been found in the hypothalamus. Hypothalamic neuropeptide Y(NPY) and ciliary neurotropic factor(CNTF) are some of those promising mediators. Although current trend has been progestational drugs, newer drugs such as anticytokines, anabolic agents, and neuropeptide agonists/antagonists are now under investigations.

Anorexia↗

Postoperative vestibular-evoked myogenic potentials in cases with vestibular schwannomas.

Although still the subject of discussion, vestibular-evoked myogenic potentials (VEMPs) have been considered to reflect the function of the saccular and, more recently, the cochlear tracts. To accurately determine the precise afferent pathway carrying VEMPs, we studied the outcomes of VEMPs and other examinations in patients with unilateral vestibular schwannomas. Eleven patients with unilateral vestibular schwannomas resected using a middle cranial fossa approach were included in the study. Patients underwent pure-tone threshold audiometry, caloric tests and analysis of auditory brainstem responses (ABRs) and VEMPs pre- and postoperatively. The results were compared with those obtained in patients with intact superior or inferior vestibular and cochlear nerves. Among the 11 patients studied, 4 retained their VEMPs postoperatively. Three of the 10 patients with inferior vestibular schwannomas exhibited normal VEMPs, preserved hearing levels (20 dB HL) and anatomically intact superior vestibular nerves. In all of these cases, ABRs more closely correlated with VEMPs than with caloric responses. In one of the cases with inferior vestibular schwannomas, VEMPs were preserved postoperatively and VEMP latencies were shortened, which indicates the preoperative presence of a conduction block in either the cochlear or superior vestibular nerve. VEMPs may be conducted in both the superior vestibular and cochlear nerves, as well as in the inferior vestibular nerve. Thus, evaluation of saccular nerve function should be performed carefully, especially in cases where hearing is preserved. It appears that cochlear conduction may proceed along two pathways, one direct and the other via the brainstem, but this remains to be verified.

Adult↗

Is gastric carcinoma different between Japan and the United States?

BACKGROUND: Analyses of surgical results for gastric carcinoma often lead to the conclusion that gastric carcinoma occurring in Japan is different from that diagnosed in the U.S. METHODS: To elucidate factors that might explain the differences in surgical results between the two countries, the authors compared data from a cancer center and a university hospital in Japan and a specialist cancer hospital in the U.S (Memorial Sloan-Kettering Cancer Center [MSKCC]). RESULTS: The mean age and body mass index were significantly greater in patients in the U.S. The N category appeared to be determined less accurately at MSKCC compared with the Japanese centers. The occurrence of early gastric carcinoma was not confined to Japanese patients because 20% of U.S. patients who underwent surgery were determined to have early stage disease. However, mucosal (in situ) carcinoma was detected rarely, and the proportion of advanced stage disease was greater in the U.S. Lesions in the upper gastric body, including the gastroesophageal junction, occurred in > 50% of cases at MSKCC but in only 20% of cases at the Japanese centers (P < 0.001). D2 lymph node dissection was possible with low morbidity and minimum mortality (31% and 3%, respectively, at MSKCC). The 5-year survival rates, stratified by tumor location and T category, revealed more similar results between Japan and the U.S. than had been reported previously. The marked difference between Japanese and American institutions only was observed for T1 and T2 tumors occurring in the lower gastric body and for T3 tumors occurring in the middle and upper third of the stomach. CONCLUSIONS: Based on the findings of the current study, it would appear that the more favorable outcome noted for gastric carcinoma patients in Japan primarily is explained by the differences in tumor location, a greater frequency of early stage disease, and more accurate staging compared with gastric carcinoma patients in the U.S. Results of gastric carcinoma treatment comparable to those obtained in Japan can be obtained in Western centers.

Adult↗

Expression of facilitative glucose transporter 1 mRNA in colon cancer was not regulated by k-ras.

The expression of facilitative glucose transporter isoforms in colon adenocarcinoma and the possible role of k-ras in inducing GLUT (glucose transporter) mRNA were studied. RT-PCR demonstrated GLUT2 and GLUT3 expression in 100% of the ten normal colon mucosa samples but detected no GLUT1 mRNA. By contrast, GLUT1 mRNA was detected in all 20 (100%) colon cancer samples examined. GLUT4 mRNA was not detected in either normal mucosa or colon cancer tissues. Semiquantitative PCR demonstrated equal amounts of GLUT2 and GLUT3 mRNA in both normal mucosa and colon cancer samples. A point mutation in codon 12 of k-ras was detected in only six of the 20 (30%) colon cancer samples. Thus, a major difference between normal colon epithelia and colon cancer was the acquisition of GLUT1 expression, which was unlikely to have been induced by a point mutation in codon 12 of k-ras.

Adenocarcinoma↗

Suppression of facilitative glucose transporter 1 mRNA can suppress tumor growth.

We attempted to suppress glucose transporter 1 (GLUT1) expression by transfecting MKN45 cells with cDNA for antisense GLUT1. Glucose transport was significantly decreased in cells with antisense GLUT1 compared with wild-type cells or cells with vector alone. Suppression of GLUT1 mRNA resulted in a decreased number of cells in the S phase. This was accompanied by overexpression of p21 protein. Tumorigenicity in the nude mice injected with antisense GLUT1 expressing cells was significantly slower than in those with wild-type MKN45 cells. These results suggest that antisense GLUT1 mRNA inhibits tumor growth through a G(1) arrest and that expression of antisense GLUT1 mRNA via gene therapy can be used as a tool in the treatment of cancer.

Adenocarcinoma↗

Plasma concentrations of VEGF and bFGF in patients with gastric carcinoma.

We examined plasma levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 54 patients with gastric carcinoma. Postoperative survival was significantly poorer in patients with plasma VEGF levels more than 10.0 pg/ml at the time of surgery. By an univariate analysis of the factors affecting survival, serosal invasion, lymph node metastasis, peritoneal dissemination, lymphatic vessel invasion, curability, and VEGF proteins were significant. By a multivariate analysis only VEGF levels and curability remained significant. Patients with recurrent disease, including liver metastasis, had significantly higher plasma VEGF concentrations than those with resectable primary tumors. VEGF, not bFGF, may serve as an independent prognosticator and a sensitive indicator for liver recurrence in patients with gastric carcinoma.

Biomarkers, Tumor↗

Geranylgeranyl-pyrophosphate, an isoprenoid of mevalonate cascade, is a critical compound for rat primary cultured cortical neurons to protect the cell death induced by 3-hydroxy-3-methylglutaryl-CoA reductase inhibition.

We investigated the role of the intrinsic mevalonate cascade in the neuronal cell death (NCD) induced by the inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase in rat primary cortical neurons cultured from the brains of 17-d-old fetal SD rats. HMG-CoA reductase inhibitors induced NCD [HMG-CoA reductase inhibitor-induced NCD (H-NCD)] in time- and dose-dependent manners. The apoptotic characteristics were revealed by the formation of the DNA ladder and by the electron microscopical observation. During the progression of H-NCD, p53 was induced followed by the expression of Bax. Although the mevalonate completely inhibited H-NCD, the cholesterol did not. Thus, we examined two major metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP) and farnesyl-pyrophosphate (FPP), using a novel liposome system for uptake into the cells. GGPP, not FPP, prohibited H-NCD with inhibition of the induction of p53 and Bax. The inhibition of HMG-CoA reductase decreased the amount of membrane-associated Rho small GTPase families, but not Ras small GTPase, and GGPP restored the blockage by HMG-CoA reductase inhibitor in the translocation or redistribution of Rho small GTPase families to membrane. These data indicated that (1) the inhibition of the intrinsic mevalonate cascade induces the apoptotic NCD with the induction of p53 followed by that of Bax, (2) the inhibition of HMG-CoA reductase concomitantly causes blockage of the translocation or redistribution of Rho small GTPase families, not Ras small GTPase, to membrane, and (3) GGPP, not FPP, is one of the essential metabolites in the mevalonate cascade for protecting neurons from H-NCD.

Animals↗