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Biomedical subjects

S Yamada

Publications and source records attributed to S Yamada.

At least 469 records · Page 26Linked to original sources

[Efficacy of intra-arterial chemotherapy on life prolongation in patients with hepatic metastasis from colorectal cancer].

The efficacy of intra-arterial chemotherapy for life prolongation was investigated in patients with hepatic metastasis from colorectal cancer who visited our hospital from Jan. 1989-Mar. 1999, but without any other remote metastasis when the presence of their hepatic metastasis was detected. The subjects were assigned to 4 groups; group A (n = 8) was only treated by hepatectomy, group B (n = 27) by intra-arterial chemotherapy combined with hepatectomy, group C (n = 42) with intra-arterial chemotherapy alone, and group D (n = 23) by systemic chemotherapy through intra-venous or oral administration. The survival rates of these groups were determined, and the recurrence risk after hepatectomy was compared between group A and B. Further, the survival rate of the patients treated by intra-arterial chemotherapy was compared between the cases of PD and not-PD (including CR, PR, and NC). The median survival in cases of H1 and H2 was 405 days for group A, 1,018 days for group B and 245 days for group C, showing that group B had a significantly more favorable prognosis than either group A or group C. There were also significant differences in the median survival of H3 cases between group C (422 days) and group D (113 days). One-year cumulative recurrence risks in the residual livers of group A and group B were 79% and 28%, respectively. Thus, significant differences in the recurrence risk were found in the two groups. Meanwhile, the median survival of PD and non-PD cases was 240 and 588 days, respectively. These results suggested that local control by intra-arterial chemotherapy is useful for life prolongation.

Antineoplastic Combined Chemotherapy Protocols↗

[Magnetic resonance imaging of breast cancer: correlation between contrast enhancement and tumor angiogenesis].

PURPOSE: To evaluate the association between enhancement characteristics of breast cancers obtained by three-dimensional dynamic MRI and histopathologic findings, especially tumor angiogenesis. MATERIALS AND METHODS: Forty-four women with invasive breast cancer under went preoperative MR imaging. Three-dimensional fast low angle shot (3D-FLASH) images of the whole breast (section thickness, 2 mm; gap, 0 mm; number of sections, 50; acquisition time, 87 sec) were obtained at 90-second intervals for three images (the first image before the injection of Gd-DTPA). Microvessel densities were evaluated in specimens immunohistochemically stained with anti-CD34 antibody. Pearson correlation tests were used to determine the strength of the relationships between enhancement parameters and microvessel densities. Univariate and multivariate analyses were performed to explore the associations with histopathologic factors, including histological grade. RESULTS: The enhancement parameters were correlated with microvessel densities (p < 0.0001). The peripheral microvessel densities were significantly higher than central microvessel densities (p < 0.0001). A significant association with histological grade was observed for the steepest slopes of the dynamic curve and microvessel densities (p < 0.05). CONCLUSION: A correlation between three-dimensional dynamic MRI parameters and microvessel densities, and associations with histological grade were seen. This may allow MRI to be used in the prediction of tumor angiogenesis and tumor grade.

Adult↗

Dopamine D(3) receptors modulate evoked dopamine release from slices of rat nucleus accumbens via muscarinic receptors, but not from the striatum.

It is not clear whether dopamine D(3) receptor contributes to the regional difference in dopamine antagonist-induced increase in the evoked dopamine release from the nucleus accumbens and striatum. We investigated the regional differences in augmentation of electrically evoked dopamine release induced by preferential dopamine D(2) or D(3) receptor antagonists from slices of the rat striatum and nucleus accumbens. Haloperidol, a preferential dopamine D(2) receptor antagonist, enhanced the evoked dopamine release from both the striatum and nucleus accumbens. Preferential dopamine D(3) antagonists, cis-(+)-(1S, 2R)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin HCl [(+)-UH232] and 5,6-dimethoxy-2-(di-n-propylamine)indan (U-99194A) resulted in a greater increase in the evoked dopamine released from the nucleus accumbens compared with that from the striatum. Moreover, U-99194A attenuated the quinpirole-induced reduction of evoked dopamine release from the nucleus accumbens but not from the striatum. When slices were superfused with pirenzepine, a muscarinic receptor antagonist, the increase in the evoked dopamine release by (+)-UH232 or U-99194A was reduced in the nucleus accumbens to the same level as that in the striatum. Our results indicate that the preferential D(3) receptor antagonists-induced increase in evoked dopamine release is probably mediated by the cholinergic system in the nucleus accumbens, which contains more postsynaptic dopamine D(3) receptors than the striatum.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia.

The purpose of this study was to investigate the biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia (ALL). We carried out in vitro tests with a 4-day culture and a methyl-thiazol-tetrazolium assay on bone marrow samples from 209 children newly diagnosed with ALL. After testing the resistance of leukemic cells to 14 drugs, we classified the patients into two groups according to their sensitivity to three drugs (prednisolone, L-asparaginase, and vincristine) used in remission induction therapy. The three-drug resistant group (RR: sensitive to no drugs or to one drug) correlated with both short-term and long-term treatment failure. Three-year event-free survival (95% confidence interval) for the sensitive group (SS: sensitive to two or three drugs) was 0.813 (0.773-0.853) and that of the RR group was 0.616 (0.569-0.669) (P = 0.0001). Univariate analysis showed that Philadelphia-chromosome (Ph1) positivity and immunophenotype of mixed lineage were also prognostic factors in the 209 patients. The prognosis of the SS/RR drug resistance profile within 14 Ph1 patients was marginally significant (P = 0.062). Multivariate Cox regression analysis showed that Ph1 was an overwhelmingly adverse factor in event-free survival, with a relative hazard of 5.37 (2.57-11.21, P < 0.0001), followed by RR, with a relative hazard of 2.98 (1.69-5.25, P = 0.0001). Furthermore, we clarified the characteristics of the RR group by examination of the pattern of drug resistance to other drugs in comparison with the SS group. The leukemic cells of RR patients were more resistant than those of SS patients (P < 0.0001) to all the drugs tested, with resistance ratios of 1.6 to 13.1 (mean 3.4). In conclusion, in vitro three-drug resistance at the initial stage is an important independent predictor of treatment failure for both induction response and long-term outcome in childhood ALL.

Adolescent↗

[Compartment analysis of 123I-iomazenil brain SPECT in patients with moyamoya disease].

We investigated 11 patients with moyamoya disease about 123I-Iomazenil kinetics in the brain using three-compartment, two-parameter model. The transition rate constant (K1) from the blood to the brain and the binding potential (BP) of the benzodiazepine to the receptors were calculated for every ROI (right and left side of cerebellum, frontal lobe, parietal lobe, occipital lobe and temporal lobe; 10 ROIs a case). The K1 value correlated with BP value significantly, but not so closely (r = 0.639). And there is no significant difference in BP value among low-K1 group (mean (of K1) -S.D. < or = K1 < or = mean) and high-K1 group (mean < K1 < or = mean + S.D.). This means that CBF and BP do not correlate closely in the average Moyamoya disease patients. And we showed a case with IMP/IMZ discrepancy. The nerve cell in the hypoperfused area which has almost normal BP value is ischemic but viable. IMZ-SPECT presents an important information about the viability of the hypoperfused area in Moyamoya disease patients' brain.

Adult↗

Changes of hepatic vitronectin levels in patients with chronic hepatitis C treated with interferon alpha.

Hepatic vitronectin expression was assessed in 27 patients with chronic hepatitis C before and after interferon alpha treatment and in 7 control patients. Before interferon therapy, vitronectin was localized in the hepatocytes and in the portal and central venous regions. A high correlation was found for the vitronectin expression level with the histological grading and staging scores in the hepatocytes as well as in the portal region. After interferon therapy, the hepatic vitronectin was significantly decreased in the sustained and transient responders, but it was not as markedly decreased in the nonresponders and the non-treated group. A good correlation was found for the vitronectin expression with the staging scores but not with the grading scores in the portal region. These findings suggest that hepatic vitronectin is influenced by interferon therapy and that it may play an important role as a hepatic adhesion molecule through the improvement of inflammation, necrosis and fibrogenesis.

Antiviral Agents↗

Blood grouping of mixed bloodstains using immunocytochemical methods.

Immunocytochemical methods to determine the ABO blood group of each blood of mixed bloodstains have been developed. Mixed bloodstains were made on surgical blades and a cedar board. The blades were dipped into blood and then dipped into blood of a different group at intervals of 30, 20, 15, 10 and 5 s. Two drops of blood were dropped on a cedar board and then two drops of blood of a different group were dropped there at the same intervals. The bloodstains were dried for a week. The blood samples were removed from the blades or the cedar board and processed according with a routine histological method. Three serial thin sections were obtained. After deparaffinization, the sections were treated in papain solution for 2 h at 36 degrees C, to unmask antigenic sites on red cell membranes. The labeled streptavidin-biotin (LSAB) and peroxidase-anti-peroxidase (PAP) methods were used to detect A and B antigens, and an indirect immunocytochemical method for H antigen. These immunocytochemical methods showed specific immunologic reactions and allowed determination of the blood group of each blood of mixed bloodstains. Further, these methods indicated a possibility to determine who was stabbed first, in cases where two or more victims were stabbed with a single knife.

ABO Blood-Group System↗

Structural determination of sulfated tetrasaccharides and hexasaccharides containing a rare disaccharide sequence, -3GalNAc(4,6-disulfate)beta1-4IdoAalpha1-, isolated from porcine intestinal dermatan sulfate.

In the course of structural studies on sulfated oligosaccharides isolated from porcine intestinal heparin after extensive digestion with Flavobacterium heparinase, we isolated several heparitinase-resistant unsaturated oligosaccharides. Amino sugar analysis of these oligosaccharides indicated that they contained galactosamine residues but no glucosamine residues. They were sensitive to chondroitinase ABC but resistant to chondroitinase AC-II, and therefore derived from dermatan sulfate, which was presumably contained as a minor component in the starting heparin preparation. The structures of these oligosaccharides were characterized by enzymatic digestions in conjunction with HPLC analysis of the digests and by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. Structures of two tetrasaccharides and two hexasaccharides were determined as deltaHexAalpha1-3GalNAc(4S)beta1-4IdoAalpha1-3GalNAc(4S), deltaHexAalpha1-3GalNAc(4S,6S)]beta1-4IdoAalpha1-3GalNAc(4S) , deltaHexAalpha1-3GalNAc(4S)beta1-4IdoAalpha1-3GalNAc(4S)beta 1-4IdoAalpha1-3GalNAc(4S), and deltaHexAalpha1-3GalNAc(4S)beta1-4IdoAalpha1-3GalNAc(4S,6S)b eta1-4IdoAalpha1-3GalNAc(4S), where deltaHexA, IdoA, GalNAc, 4S and 6S represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid, L-iduronic acid, N-acetyl-D-galactosamine, 4-O-sulfate and 6-O-sulfate, respectively. The latter three compounds have never been reported as discrete structures. Since the four isolated oligosaccharides contained an unsaturated uronic acid residue at the nonreducing terminus, they appear to have been generated by eliminative cleavage by the action of Flavobacterium chondroitinase that was probably present as a minor contaminant in the Flavobacterium heparinase preparation used. Two out of the four oligosaccharides shared the rare disulfated disaccharide sequence, -3GalNAc(4S,6S)beta1-4IdoAalpha1-. These oligosaccharides will be useful as authentic reference compounds for microanalyzing biologically active domains of dermatan sulfate.

Amino Sugars↗

A phosphatidylinositol 3-kinase inhibitor wortmannin induces radioresistant DNA synthesis and sensitizes cells to bleomycin and ionizing radiation.

ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) have been shown to have sequences homologous to the catalytic domains of mammalian phosphatidylinositol 3-kinase (PI3-kinase). In order to determine the contribution of ATM and DNA-PKcs to the increased sensitivity of cells to DNA-damaging agents observed in the presence of PI3-kinase inhibitors, we examined the effects of a PI3-kinase inhibitor, wortmannin, on cellular sensitivity to bleomycin (BLM), mitomycin C (MMC), X-irradiation and ultraviolet (UV)-irradiation using 2 human tumor cell lines (T98G and A172), a human fibroblast cell line (LM217), an ataxia telangiectasia (AT) cell line (AT3BISV), a scid murine cell line (SCF) and a control murine cell line (CBF). Wortmannin sensitized all of the cells, including AT3BISV and SCF, to BLM and X-irradiation, but not to MMC or UV-irradiation. Hypersensitivity to BLM and X-irradiation and normal sensitivity to MMC and UV-irradiation are characteristic phenotypes of both AT and scid mice. DNA-dependent protein kinase (DNA-PK) activity was suppressed by wortmannin to 45-65% of the control values in all of the cells except SCF, in which DNA-PK activity was not detected. Wortmannin also induced radioresistant DNA synthesis, which is a cellular phenotype of AT, in T98G and SCF cells, but did not change the DNA synthesis rates after X-irradiation in AT3BISV. Our data suggest that wortmannin decreases the activities of both the ATM protein and DNA-PK, indicating that it might be of use as a sensitizing agent for radiotherapy and chemotherapy.

Androstadienes↗

Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle.

Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( < 0.02). This atrophy was significantly attenuated 41 to 55% (p < 0.02) in animals that received C2-BAM implants, but not in animals receiving daily injections of purified rhGH (1 mg/kg/day). These data support the concept that delivery of rhGH from BAMs may be efficacious in treating muscle-wasting disorders.

Animals↗

Novel therapeutic strategy for atherosclerosis: ribozyme oligonucleotides against apolipoprotein(a) selectively inhibit apolipoprotein(a) but not plasminogen gene expression.

BACKGROUND: Because mechanisms of atherosclerosis by lipoprotein(a) [Lp(a)] have been postulated in the decrease in active transforming growth factor-beta conversion by decreased plasmin, selective decrease in apolipoprotein(a) [apo(a)] independent of plasminogen may have therapeutic values. Although antisense can decrease apo(a), its application may be difficult because of very high homology of apo(a) gene to plasminogen. Thus we used ribozyme strategy that actively cleaves targeted genes to selectively inhibit apo(a) expression. METHODS AND RESULTS: We constructed ribozyme oligonucleotides containing phosphorothioate DNA- and RNA-targeted kringle 4 of the apo(a) gene that showed 80% homology to plasminogen. Transfection of human apo(a) gene produced Lp(a) in medium of HepG2 cells, whereas Lp(a) could not be detected in control cells. Cotransfection of ribozyme and apo(a) gene resulted in the decrease in mRNA of apo(a) but not plasminogen. Moreover, marked decrease in Lp(a) was also observed in the medium transfected with ribozyme and apo(a) gene compared with apo(a) gene alone (P<0.01), whereas there was no significant change in plasminogen level between ribozyme-transfected and control cells. Incubation of human vascular smooth muscle cells (VSMC) with conditioned medium from apo(a)-transfected HepG2 cells resulted in a significant increase in VSMC number, whereas addition of conditioned medium from cells cotransfected with ribozyme oligonucleotides and apo(a) gene resulted in no VSMC growth (P<0.01). DNA-based control oligonucleotides and mismatched ribozyme oligonucleotides did not have an inhibitory effect on Lp(a) production. CONCLUSIONS: Overall, our data revealed that transfection of ribozyme against the apo(a) gene resulted in the selective inhibition of the apo(a) but not the plasminogen gene, providing novel therapeutic strategy for treatment of high Lp(a), a risk factor for atherosclerosis.

Aorta↗

Tumor necrosis factor-beta is associated with thymic apoptosis during acute rejection.

BACKGROUND: Intrathymic events undergoing allograft rejection remain undefined. The present study investigated the role of tumor necrosis factor-beta on acute thymic involution in rat hepatic allograft recipients during rejection. METHODS: Apoptosis and cellular phenotypic changes in the thymus were studied after hepatic transplantation. RESULTS: Thymocytes in both the medulla and cortex were sparse during acute rejection. Phenotypically, CD4+CD8+ T cells decreased significantly, whereas there were relative increases in CD4-CD8-, CD4+CD8-, and CD4-CD8+ T cells in untreated allograft recipients. Additionally, thymic apoptosis was found by in situ DNA end labeling and electron microscopy. Apoptotic cells were predominantly distributed in the cortex. Biologic lymphotoxin (tumor necrosis factor-beta)/tumor necrosis factor-alpha cytotoxic activity in the serum was significantly increased in untreated hepatic allograft recipients. Tumor necrosis factor-beta mRNA was detected in untreated allograft livers, and intraperitoneal administration of recombinant human tumor necrosis factor-beta induced extensive apoptosis of thymocytes in vivo. In contrast, no significant thymic involution was observed in donor-specific blood transfusion-treated allograft and isograft recipients. Intraperitoneal administration of rabbit anti-human tumor necrosis factor-beta polyclonal antibody or recombinant human interleukin-10 inhibited thymic apoptosis in untreated hepatic allograft recipients. CONCLUSIONS: Allograft rejection, but not donor-specific transfusion-induced immunologic unresponsiveness, is associated with thymic involution, a process that may be mediated by tumor necrosis factor-beta.

Acute Disease↗

Comparison of effects of ascorbic acid on endothelium-dependent vasodilation in patients with chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy versus patients with effort angina pectoris secondary to coronary artery disease.

Impaired endothelium-dependent vasodilation has been reported to play an important role in the pathogenesis of cardiovascular diseases such as coronary artery disease (CAD) and congestive heart failure (CHF). However, the precise mechanism of endothelial dysfunction has not been elucidated in these conditions. To evaluate the role of oxidative stress in endothelial dysfunction, the effect of antioxidant ascorbic acid on brachial flow-mediated, endothelium-dependent vasodilation during reactive hyperemia and nitroglycerin-induced endothelium-independent vasodilation was examined with high resolution ultrasound in 12 patients with CHF caused by idiopathic dilated cardiomyopathy without established coronary atherosclerosis and in 10 patients with CAD. Flow-mediated vasodilation in CHF (4.4+/-0.5%) and CAD (4.0 - 0.8%) was significantly (p <0.05) attenuated compared with that in 10 control subjects (9.6+/-0.9%). However, nitroglycerin-induced vasodilation was similar in 3 groups (13.7+/-1.3% in control, 13.9+/-1.1% in CHF, 12.7+/-1.4% in CAD). Ascorbic acid could significantly improve flow-mediated vasodilation only in patients with CAD (9.1+/-0.9%) but not with CHF (5.6+/-0.6%), and had no influence on nitroglycerin-induced vasodilation (13.6+/-1.1% in CHF, 14.0+/-1.3% in CAD). These results suggest that, in brachial circulation, augmented oxidative stress mainly leads to endothelial dysfunction in CAD but not in CHF caused by idiopathic dilated cardiomyopathy.

Adult↗

Metabolic changes in hibernating myocardium after percutaneous transluminal coronary angioplasty and the relation between recovery in left ventricular function and free fatty acid metabolism.

To elucidate the changes in oxidative metabolism in hibernating myocardium after coronary revascularization, we performed myocardial single-photon emission computed tomography with a free fatty acid analog, I-123 beta-methyliodophenylpentadecanoic acid (BMIPP), and thallium-201 before and 1 month after percutaneous transluminal coronary angioplasty (PTCA) in 11 patients with angina pectoris caused by single artery stenosis. All patients had improvement in wall motion after PTCA at the region with coronary stenosis; the wall motion abnormality score evaluated by left ventriculography decreased from 5.5+/-0.8 (mean +/- SE) to 2.1+/-0.9, p <0.01) after PTCA. The defect score of I-123 BMIPP images was significantly larger than that of thallium-201 images either before (14+/-1.3 vs 8.9+/-1.1, p <0.01) or 1 month after (7.4+/-1.5 vs 3.7+/-0.8, p <0.01) PTCA. The decrease in the defect score of both images was significant (p <0.01). Changes in the wall motion abnormality score showed a significant correlation with both the change in the defect score of thallium-201 images (r = 0.58, p < 0.01) and that of I-123 BMIPP images (r = 0.75, p <0.01). These results indicate that the metabolism of free fatty acid is impaired in hibernating myocardium, and that improvement in left ventricular function after successful PTCA is strongly associated with the recovery of oxidative metabolism.

Adult↗

Stimulatory effect of lipoprotein (a) on proliferation of human mesangial cells: role of lipoprotein (a) in renal disease.

As lipoprotein (a) [Lp(a)] abnormalities would accelerate glomerular injury, we studied the effect of Lp (a) on proliferation of cultured human mesangial cells (MC). Transfection of human apo (a) gene into human hepatoma cells, HepG2 cells, producing human apo B, resulted in the formation of Lp (a), while no Lp (a) was detected in control cells. In contrast, free apo (a) was detected in the medium of apo (a)-transfected MC. Incubation of cultured medium of HepG2 cells transfected with apo (a) gene with MC resulted in a significant increase in cell number compared to control (P<0.01). In contrast, little effect of transfection of apo (a) gene directly into MC on growth of MC was observed. Of importance, addition of LDL into the medium of MC transfected with apo (a) vector resulted in a significant increase in number of MC compared to control, whereas LDL did not show any effects on MC growth. As active TGF-beta was not detected in the medium of MC, and addition of neutralizing anti-TGF-beta antibody did not alter growth of MC, Lp (a) stimulated growth of MC via the independent mechanisms from the inhibition of TGF-beta activation.

Apolipoproteins A↗