Biomedical subjects

T Takeda

Publications and source records attributed to T Takeda.

At least 73 records · Page 4Linked to original sources

PubMed2001

Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma.

In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was expressed in 68% of the HCC examined and showed correlation with the proliferating activity, stage, intrahepatic metastasis and carcinoma differentiation. c-erbB-2 was expressed in only 21% of the cases and showed no relationships with the clinicopathological parameters. c-erbB-3 protein was observed in 84% of the HCC and 38.1% of the noncancerous lesions. Its expression in HCC was equal to or greater than noncancerous lesions in 90.5% of the cases, and was related to the stage, portal invasion, cell proliferating activity, tumour size, intrahepatic metastasis and carcinoma differentiation. c-erbB-4 protein was expressed in 61.0% of HCC and in as much as 86.1% of the noncancerous lesions. Unlike the expression of c-erbB-3, that of c-erbB-4 in HCC was less than that of the adjacent noncancerous lesions in 51.2% of the cases. No statistical significance could be established between this protein expression in HCC and clinicopathological features. EGF-R and c-erbB-3 affected disease-free survival, but were not recognized as independent prognostic factors by multivariate analysis. The present study suggests that, of the four receptors, EGF-R and c-erbB-3 play important roles in the progression of HCC.

Carcinoma, Hepatocellular↗

PubMed2001

Characterization of monoclonal antibodies against ascorbate peroxidase isoenzymes: purification and epitope-mapping using immunoaffinity column chromatography.

We have developed three monoclonal antibodies against spinach chloroplastic (chl-mAb3 and chl-mAb6) and cytosolic (cyt-mAb1) ascorbate peroxidase (APX) isoenzymes to analyze the cross-reactivity and the structure of the epitopes for each monoclonal antibody. All three antibodies reacted specifically with their respective isoenzymes, but none cross-reacted with the others. Immunoreactive fragments in proteolytic recombinant APX isoenzymes were detected by means of the absorption on the corresponding immunoaffinity column. The cyt-mAb1 reacted with a peptide fragment containing the distal His region obtained by the lysyl endopeptidase digestion. The chl-mAb6 was capable of binding to the fragment, D-I-K-E-K-R, which is consistent with an inherent region of chloroplastic isoenzymes. No fragments reacting to the chl-mAb3 could be found in this study, suggesting that the chl-mAb3 recognizes a conformationally constituted epitope of the chloroplastic APX molecule, which may be destroyed by the enzymatic cleavage. We concluded that the peptides identified as epitopes are characteristic evidence of monoclonal antibodies.

Amino Acid Sequence↗

PubMed2001

Preliminary experiment of fluorescent X-ray computed tomography to detect dual agents for biological study.

The simultaneous observation of various information, such as blood flow, tissue metabolism and distribution of receptors, is quite important in order to understand the functional state of biomedical objects. The simultaneous detectability of contrast agents by fluorescent X-ray computed tomography (FXCT) with synchrotron radiation is examined in this study. The system consisted of a silicon (111) double-crystal monochromator, an X-ray slit system, a scanning table, a PIN diode, a highly purified germanium detector and an X-ray charge-coupled device (CCD) camera. The monochromatic X-ray beam energy was adjusted to 37.0 keV and collimated into a pencil beam of 1 x 1 mm. The fluorescent spectra of the K alpha lines for iodine and xenon were detected simultaneously. FXCT could image the distribution of both iodine and xenon agents in a phantom clearly and the contrast ratio was significantly better than that of transmission X-ray computed tomography images.

Fluorescence↗

PubMed2001

NOTCH4 gene polymorphism and susceptibility to schizophrenia and schizoaffective disorder.

The NOTCH4 gene is located at 6p21.3, a site which several studies have shown to have significant linkage with schizophrenia. Recently, an exceptionally strong association was reported between NOTCH4 gene polymorphisms and schizophrenia in British patients. We re-examined their findings using a Japanese population. We genotyped three kinds of polymorphisms, SNP1 in the 5' flanking region, SNP2 in the promoter region and CTG repeats in exon 1 of the NOTCH4 gene of schizophrenics (N=188), patients with schizoaffective disorder (N=39) and controls (N=143). Genotypic distributions and allelic frequencies of SNP1, SNP2 and CTG repeats of the NOTCH4 gene did not show significant associations with schizophrenia or schizoaffective disorder. Neither they showed association with schizophrenia subcategories, hebephrenic and paranoid type schizophrenia, nor with subgroups of schizophrenia with and without positive family history of psychoses. The present study found that the NOTCH4 gene does not confer susceptibility to schizophrenia and schizoaffective disorders, at least in Japanese subjects, in contrast to the findings in British subjects.

Adult↗

PubMed2001

Dynamical fluctuation of the mesoscopic structure in ternary C12E5-water-n-octane amphiphilic system.

Dynamical fluctuations of the bicontinuous microemulsion and lamellar structures in ternary C12E5-water-n-octane amphiphilic system are studied by means of neutron spin echo (NSE) spectrometry. The decay rates of the time correlation of the concentration were analyzed in terms of three theories: (1) A. G. Zilman and R. Granek, Phys. Rev. Lett. 77, 4788 (1996), (2) M. Nonomura and T. Ohta, J. Chem. Phys. 110, 7516 (1999), and (3) R. Granek and M. E. Cates, Phys. Rev. A 46, 3319 (1992), in the first of which a Langevin equation for membrane plaquettes and in the latter two of which time-dependent Ginzburg-Landau equations for the order parameters are considered. The result shows that the intermediate correlation functions I(q,t) for the ranges of 0<t<15 ns and 0<q<0.2 A (-1) are well fitted to a stretched exponential function in time, I(q,t)=exp[-(Gammat)(2/3)], for the bicontinuous microemulsion and the lamellar phases of the same systems with the relaxation rate Gamma increasing as q(3) in agreement with theory (1) from which the bending modulus of the membrane kappa was estimated. For more restricted ranges of 0<t<5 ns and 0.05<q<0.15 A (-1) the NSE result can be expressed by an exponential function in time in agreement with theory (2) determined exclusively by hydrodynamic interactions and for extended range of 0<t<10 ns and 0.03<q<0.15 A (-1) by a nonexponential function in agreement with theory (3), from both of which the effective viscosities eta(0) and eta(eff) of the system were estimated. The effective viscosity from the nonexponential eta(eff) is five times greater than that from the simple exponential eta(0) that is almost the same as the literature value. The implication of this result is discussed in terms of the effective viscosity eta(eff) that takes into account the renormalization of the bending modulus of the membrane.

Journal Article↗

PubMed2001

Elevated expression of UDP-N-acetylglucosamine: alphamannoside beta1,6 N-acetylglucosaminyltransferase is an early event in hepatocarcinogenesis.

Previous reports have suggested that changes in oligosaccharide structures, especially beta1-6 branching in N-glycans, which are biosynthesized by UDP-N-acetylglucosamine:alpha mannoside beta1,6 N-acetylglucosaminyltransferase (GnT-V), are linked to tumor metastasis and invasion. In the present study, we investigated GnT-V expression in human hepatocellular carcinoma (HCC) tissues. High expression of GnT-V mRNA was observed in both HCC and the surrounding tissues but not in normal liver. Immunohistochemical study using a newly established monoclonal antibody against GnT-V revealed that positive staining of GnT-V was observed in 75% of HCC tissues and 60% of surrounding tissues and that liver cirrhosis showed much stronger staining of GnT-V than chronic hepatitis without liver cirrhosis (p = 0.0035). In contrast, all of 12 cases of atypical adenomatous hyperplasia diffusely expressed GnT-V. beta1-6 branching in N-glycans, products of GnT-V, was increased in HCC tissues with high expression of GnT-V, as judged by lectin blotting. Levels of GnT-V expression in HCC tissues were positively correlated with a low Ki-67 labeling index (p = 0.0009), small size (p < 0.0001), poor differentiation (p < 0.0001) and absence of portal invasion (p = 0.018). Furthermore, HCC cases with low or no expression of GnT-V were more likely to show recurrence than cases with high expression (p = 0.0373). These findings strongly suggest that GnT-V expression is concerned mainly with an early phase of hepatocarcinogenesis.

Aged↗

PubMed2001

Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma.

Unlike other types of cancer, hepatocellular carcinoma (HCC) is usually preceded by chronic inflammation caused by viral infection. The mutation of mitochondrial DNA (mtDNA) in hepatocarcinogenesis associated with viral infection was investigated. Compared with control liver tissue, the frequency of mtDNA mutations was markedly increased in both noncancerous and cancerous liver specimens from individuals with HCC. The accumulation of mtDNA mutations in HCC tissue reflected the degree of malignancy. The frequency of mtDNA mutations in HCC tissue was also greater than that described previously for other types of tumors. These observations suggest that the repeated destruction and regeneration of liver tissue associated with chronic viral hepatitis lead to the accumulation of mtDNA mutations. The genetic instability that results in the high rate of mtDNA mutation in cancerous liver tissue is also consistent with the multicentric hepatocarcinogenesis detected clinically.

Carcinoma, Hepatocellular↗

PubMed2001

Increased angiotensin-converting enzyme activity in coronary artery specimens from patients with acute coronary syndrome.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are effective in the secondary prevention of ischemic heart disease, but they do not reduce the rate of restenosis. Vascular ACE activity in the culprit coronary lesions of these patients, however, has never been quantified. METHODS AND RESULTS: We measured the ACE activity of vascular tissue obtained by directional coronary atherectomy in patients with acute coronary syndrome (n=17) and in patients with stable ischemic heart disease (n=36), with and without restenosis. The ACE activity of the culprit coronary lesions was significantly increased in patients with acute coronary syndrome (0.87+/-0.12 nmol. min(-1). mg protein(-1); P:<0.01) but not in patients with ischemic heart disease with restenosis (n=11, 0.19+/-0.05 nmol. min(-1). mg protein(-1)) when compared with those patients with ischemic heart disease without restenosis (n=25, 0.20+/-0.05 nmol. min(-1). mg protein(-1)). There was no difference between the ACE activity of the coronary tissue of the in-stent (n=5) and stent-unrelated (n=6) restenosis patients (0.24+/-0.10 versus 0.15+/-0.04 nmol. min(-1). mg protein(-1)). Serum ACE activity did not differ significantly among the patients. CONCLUSIONS: The present study demonstrates increased ACE activity in culprit lesions in acute coronary syndrome, indicating that enhanced ACE activity is related to the causative mechanism of active coronary lesions.

Acute Disease↗

PubMed2001

Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis.

In a prospective randomised controlled study, 90 patients with chronic active hepatitis C and compensated cirrhosis were assigned symptomatic treatment or interferon alfa (IFN-alpha). We report data on decompensation, detection of hepatocellular carcinoma, and mortality rates. IFN-alpha gave a sustained response in only a small proportion of patients, but worsening of compensated cirrhosis was prevented and development of hepatocellular carcinoma was inhibited, increasing the survival rate. The risk ratio of IFN-alpha versus symptomatic treatment decreased by 0.250 for progression to Child-Pugh grade B, 0.256 for detection of hepatocellular carcinoma, and 0.135 for a fatal outcome.

Antineoplastic Agents↗

PubMed2001

Activation of the caspase cascade during Stx1-induced apoptosis in Burkitt's lymphoma cells.

Shiga toxin 1 (Stx1) produced by Escherichia coli has been reported to induce apoptosis in many different cell types, including Burkitt's lymphoma (BL) cells. Since it has been established that the caspases play essential roles as the effector molecules in the apoptotic process in most cases, we examined the kinetics of caspase activation during the process of Stx1-mediated apoptosis of BL cells. Using Ramos BL cells that are highly sensitive to Stx1-mediated cytotoxicity, we observed that multiple caspases, including caspase-3, -7, and -8 were promptly activated following Stx1 treatment, as indicated by both the procaspase cleavages and enhancement of cleavage of the tetrapeptide substrates of the caspases. In addition, the inhibition assay revealed that caspase-8 is located upstream of both caspase-3 and -7, suggesting that Stx1-mediated apoptosis utilizes a similar caspase cascade to that involved in Fas-mediated apoptosis. Neither anti-Fas mAb nor TNF-alpha, however, affected the Stx1-mediated apoptosis of Ramos cells. Although the precise mechanism of Stx1-mediated activation of caspase-8 is still unclear, we have demonstrated that crosslinkage of CD77, a functional receptor for Stx1, with specific antibody is sufficient to induce activation of caspase-8. Our findings should provide new insight into the understanding of the molecular basis of Stx1-mediated cell injury.

Antibodies, Monoclonal↗

PubMed2001

Single-step method for purification of Shiga toxin-1 B subunit using receptor-mediated affinity chromatography by globotriaosylceramide-conjugated octyl sepharose CL-4B.

A new single-step purification method for Shiga toxin (Stx) was developed using receptor-mediated affinity chromatography, in which Gb3Cer (globotriaosylceramide) was conjugated to octyl Sepharose CL-4B as a carrier. This method achieves high yield and high purity in a small column on which Gb3Cer has been immobilized at high density. Using this affinity column, the Stx1 B subunit was purified with homogeneity by a one-step procedure from a crude extract of recombinant Stx1 B subunit-producing Escherichia coli. The purified Stx1 B subunit conserved a natural pentamer structure confirmed by gel filtration and sedimentation equilibrium analysis. Furthermore, the purified Stx1 B subunit was able to bind specifically to Gb3Cer expressed on Burkitt's lymphoma cells. This versatile purification method can be used to isolate various types of natural as well as recombinant Stx, facilitating fundamental studies of human diseases caused by this toxin.

Blotting, Western↗

PubMed2001

Accessory spleen in the pelvis diagnosed by Tc-99m phytate scintigraphy.

We report a 58-year-old woman with an accessory spleen in the left side of the pelvis. She visited our outpatient clinic complaining of lower abdominal discomfort. Abdominal ultrasonography revealed a tumor 4 cm in diameter in the left side of the pelvis. Color Doppler ultrasonography demonstrated plentiful pulsating blood flow. Magnetic resonance angiography revealed that the blood supply for the tumor was from a branch of the splenic artery. Scintigraphy with Tc-99m phytate revealed accumulation of radioactivity concordant with a mass in the left side of the pelvis, and the spleen was normally visualized. These findings suggested that this tumor was an accessory spleen, and the patient underwent no further invasive procedures.

Female↗

PubMed2001

Cerebrovascular damage in young rabbits after intravenous administration of Shiga toxin 2.

Acute encephalopathy associated with Shiga toxin-producing Escherichia coli (STEC) primarily affects children. To elucidate the age-dependent vulnerability of the central nervous system (CNS), we injected Shiga toxin 2 (Stx2) intravenously to young rabbits and examined the clinical and pathological effects on the CNS. Although neurological disorders caused by Stx2 were similar between young and adult rabbits, the dose required to produce them in the young was one third of that required for the adults. Vascular lesions appeared as early as 24 h after injection in the young, but not at all in the adult. Arteriolar changes, such as hydropic swelling of the endothelial cells and karyorrhexis of the medial cells, were specific to the CNS of young animals. Evidence for apoptosis of vascular cells was scarce because DNA strand breaks and activation of caspases-3 and -9 were absent in the vast majority. Given our results, we conclude that the cerebral blood vessels of immature brains are more vulnerable to Stx2 than those of adults in the rabbit.

Acute Disease↗

PubMed2001

Does ascorbic acid prevent retinopathy during interferon therapy in patients with chronic hepatitis C?

PURPOSE: Ascorbic acid was administered to patients with chronic hepatitis C to elucidate the mechanism of onset of retinopathy during interferon (IFN) therapy, and its prevention. METHODS: The subjects were 62 patients with chronic hepatitis C who had been admitted to our hospital. For the IFN therapy, 6 MIU of natural IFN-alpha, or 10 MIU of recombinant human IFN-alpha 2b was administered every day for the first 2 weeks, followed by administration three times a week for 22 weeks. The patients were randomly assigned to a group receiving 600 mg/day of ascorbic acid or a group not receiving ascorbic acid (control group). The optic fundi were examined by ophthalmologists before the IFN therapy began and subsequently at weeks 2 and 4 and then every 4 weeks during the IFN therapy. RESULTS: Retinopathy was found in 9 of the 31 patients (29%) in the ascorbic acid-treated group and in 11 of the 31 patients (35%) in the control group. The cumulative incidence of hemorrhage in the ascorbic acid-treated group was lower than that in the control group during the IFN therapy, but the difference between the two groups was not significant (P = 0.186). The cumulative incidence of cotton-wool spots in the ascorbic acid-treated group was almost same as that in the control group during the IFN therapy. The median platelet counts before the therapy was begun were 11.8 x 10(4)/mm2 in the group with hemorrhage and 16.6 x 10(4)/mm2 in the group without, and the lowest platelet counts during IFN therapy were 7.3 x 10(4)/mm3 in the group with hemorrhage and 9.5 x 10(4)/mm3 in the group without, indicating significantly lower values in the group with hemorrhage (P = 0.018 and P = 0.020, respectively). The lowest platelet counts during IFN therapy were 7.4 x 10(4)/mm3 in the group with cotton-wool spots and 9.7 x 10(4)/mm3 in the group without, indicating a significantly lower value in the group with cotton-wool spots (P = 0.036). CONCLUSIONS: Ascorbic acid was not considered to be useful for the prevention of the retinopathy associated with IFN therapy in patients with chronic hepatitis C.

Adult↗

PubMed2001

Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate.

The purpose of the present study was to compare the effects of etidronate and menatetrenone on bone mineral density (BMD) and the incidence of vertebral fractures in postmenopausal women with osteoporosis. Seventy-two osteoporotic women, more than 5 years after menopause, 53-78 years of age, were randomly divided into three administration groups: E group; intermittent cyclical etidronate (200 mg/day, 14 days per 3 months; n = 25); M group; menatetrenone (45 mg/day, daily; n = 23); and C group (control); calcium lactate (2 g/day, daily; n = 24). Forearm BMD was measured by dual-energy X-ray absorptiometry at 0, 6, 12, 18, and 24 months after the treatment started. There were no significant differences in age, body mass index, years since menopause, and initial BMD among the three groups. One-way analysis of variance (ANOVA) with repeated measurements showed a significant decrease in BMD in the C group (P < 0.0001). Two-way ANOVA with repeated measurements showed a significant increase in BMD in the M group compared with that in the C group (P < 0.0001), and a significant increase in BMD in the E group compared with that in the C and M groups (P < 0.0001 and P < 0.01, respectively). The indices of new vertebral fractures/1000 patient-years in the E and M groups were significantly higher than that in the C group (chi(2) = 47.7; P < 0.0001 and chi(2) = 42.4; P < 0.0001, respectively), and did not differ significantly between the E and M groups. The present preliminary study provides evidence to suggest that, despite the lower increase in BMD produced by menatetrenone, this agent, as well as etidronate, may have the potential to reduce osteoporotic vertebral fractures in postmenopausal women with osteoporosis.

Absorptiometry, Photon↗

PubMed2001

Relationships between physical activity and metacarpal cortical bone mass and bone resorption in hemiplegic patients.

The aim of the present study was to investigate the relationships between physical activity and metacarpal cortical bone mineral density (BMD) and bone resorption in hemiplegic patients. Seventy-two male hemiplegic patients with cerebrovascular disease (mean age, 67.0 years; range 48-83 years) were recruited. Metacarpal cortical BMD in bilateral hands was measured by computed X-ray densitometry, and the levels of urinary cross-linked N-telopeptides of type I collagen (NTx), as a bone resorption marker, were measured by an enzyme-linked immunosorbent assay (ELISA). BMD (mean +/- SD) in the paralyzed hand was significantly lower than that in the nonparalyzed hand (2.52 +/- 0.46 and 2.64 +/- 0.45 mmAl; P < 0.05). On multiple regression analysis, BMD was significantly positively correlated with Brunnstrom stage (assessment of degree of paralysis) in the hand (P < 0.05), whereas urinary NTx levels were significantly negatively correlated with Brunnstrom stage in the hand, arm, and leg, and with walking ability (P < 0.05, P < 0.05, P < 0.01, and P < 0.01, respectively). These findings suggest that, in male hemiplegic patients, although metacarpal cortical BMD may be affected by only local physical activity, urinary NTx appears to be responsive to local and general physical activity.

Aged↗

PubMed2001

Effect of administration of lipoprostaglandin E(1) on physical activity and bone resorption in patients with neurogenic intermittent claudication.

The effect of the systemic administration of prostaglandin (PG) E(1) on physical activity and bone resorption was examined in patients with intermittent claudication (gait disturbance). Twenty male patients (age, 67.2 +/- 7.8 years; mean +/- SD) with neurogenic intermittent claudication caused by lumbar spinal canal stenosis were included in the study. Lipo-PG E(1) was administered intravenously, at a daily dose of 10 microg, on 3 days a week, for 6 months in all patients. Clinical symptoms, levels of urinary cross-linked N-telopeptides of type I collagen (NTx), and metacarpal cortical bone mineral density (BMD) were assessed before and just after the 6 months of treatment. Subjective symptoms, including leg pain and/or tingling and gait disturbance, and restrictions of the activities of daily living were significantly improved. However, no significant changes were observed in either urinary NTx levels or metacarpal cortical BMD. These findings suggest that the systemic administration of PG E(1) appears to improve subjective symptoms and activities of daily living in elderly male patients with neurogenic intermittent claudication, but does not affect either bone resorption or metacarpal cortical BMD. Short-term systemic administration of PG E(1) and increased physical activity in elderly male patients with gait disturbance caused by lumbar spinal canal stenosis may not affect bone resorption.

Aged↗

PubMed2001

Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis.

We examined the effect of exercise training and detraining on bone mineral density (BMD) in postmenopausal women with osteoporosis. Thirty-five postmenopausal women with osteoporosis, aged 53-77 years, were randomly assigned to three groups: a control group (n = 20), a 2-year exercise training group (n = 8), and an 1-year exercise training plus 1-year detraining group (n = 7). Exercise training consisted of daily brisk walking and gymnastic training. Calcium lactate, 2.0 g, and 1alpha-hydroxyvitamin D3, 1 microg were supplied daily to all subjects. No significant differences in initial lumbar BMD, measured by dual-energy X-ray absorptiometry (DXA) were found among the three groups. The mean percent change in BMD compared with the baseline was significantly higher at 1 and 2 years in the exercise training group and at 1 year in the detraining group than in the control group, and did not differ significantly at 2 years between the detraining and control groups. These findings indicate that our exercise training program led to a significant increase in lumbar BMD in postmenopausal women with osteoporosis compared with the control, but that the BMD reverted toward a level that was not significantly different from the control with detraining. Continued exercise training is needed to maintain the bone mass gained through exercise training.

Aged↗