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Biomedical subjects

H Shimada

Publications and source records attributed to H Shimada.

At least 649 records · Page 36Linked to original sources

Mitochondrial breakage induced by the herbicide paraquat in cultured human lung cells.

Although the intracellular toxic sites of paraquat, a herbicide toxic to human bodies, have remained unclear for a long time, we recently demonstrated paraquat-induced mitochondrial injury in rat lung and liver in vivo. In the present study, cultured human lung cells (A549 adenocarcinoma cell line) which received 0.15 mM paraquat (equivalent to 40 mg/kg i.v.) showed selective mitochondrial breakage at 6-24 hr and died at 36-48 hr. These results suggest that mitochondria are the initial toxic site of paraquat in vitro as well as in vivo in contrast to the previously proposed microsome theory.

Adenocarcinoma↗

Hepatic encephalopathy secondary to a large-caliber porto-hepatic venous shunt. A case report.

A case of hepatic encephalopathy secondary to a large-caliber porto-hepatic venous shunt in a 61-year-old woman with gastric cancer is reported. Mild confusion, flapping tremor and hyperammonemia were noted preoperatively. Abdominal ultrasonography showed a large-caliber porto-hepatic venous shunt in the left lateral segment of the liver. Percutaneous transhepatic portography and superior mesenteric angiography were confirmatory. Intraoperative portal scintigraphy was performed before and after temporary shunt occlusion to measure the intrahepatic shunt rate, which decreased markedly after occlusion. Portal pressure was also measured, and increased only slightly after occlusion. Left lateral hepatic segmentectomy, and subtotal gastrectomy with splenectomy were performed. Hepatic encephalopathy resolved postoperatively. The shunt was thought to be acquired. The relevant reports on large-caliber porto-hepatic venous shunts in the literature are reviewed.

Female↗

[Clinical characteristics and prognosis of secondary amyloidosis in patients with rheumatoid arthritis--renal involvement and therapy].

Secondary amyloidosis is an important complication that may have a strong influence on the prognosis of patients with rheumatoid arthritis (RA). We studied 21 RA patients with secondary amyloidosis. The two major initial signs were gastrointestinal symptoms and renal involvement. When 15 of the 21 patients were diagnosed as having secondary amyloidosis, they displayed renal involvement including proteinuria, hematuria and hypercreatininemia. The 15 patients with amyloidosis were either subjected to dialysis or died within 35 months on the average. The causes of death in 13 patients were cardiac failure, gastrointestinal bleeding and infection, which were strongly implicated with renal failure. Dialysis was applied to seven patients. Three of them were maintained with chronic dialysis. We discussed the induction-time and the method of dialysis in patients with amyloidosis secondary to RA.

Adolescent↗

Anticoagulant action of rare earth metals.

Some of the lanthanides, the rare earth metals, lanthanum (La), cerium (Ce), neodymium (Nd), samarium (Sm), terbium (Tb), dysprosium (Dy), erbium (Er) and ytterbium (Yb) prolonged the clotting time of normal human plasma in a dose-dependent manner when clotting was induced either by thromboplastin or by kaolin in the presence of cephalin and Ca2+. They also prolonged the activated factor X induced clotting time of platelet-rich plasma. The amidolytic activities of activated factor X and thrombin progressively decreased with increasing amount of rare earth metals. These results suggested that the rare earth metals appear to show their anticoagulant effect with mechanisms in part the inhibition of the enzymatic activities of both activated factor X and thrombin.

Anticoagulants↗

[Clinical significance of serum CA130 level in women with spontaneous abortion, hydatidiform mole and early normal and tubal pregnancy].

We examined the serum CA130 level in women in early pregnancy with normal (n = 13), and abnormal (n = 28) course. The abnormal course consisted of intrauterine spontaneous abortion (n = 10), hydatidiform mole (n = 3) and tubal pregnancy (n = 15). The serum CA130 level was higher than for normal nonpregnant women (35u/ml) in 69% (9/13) of women with normal pregnancy, 90% (9/10) of those with intrauterine spontaneous abortion and 100% (3/3) of those with hydatidiform mole; the mean value and standard deviation for these three groups were 131 +/- 150u/ml (n = 13), 197 +/- 253u/ml (n = 10), and 47 +/- 15u/ml (n = 3), respectively. In contrast, the serum CA130 level of the 15 women with tubal pregnancy was 28 +/- 21u/ml. Among these patients, all of the 13 women without genital bleeding had a CA130 level within the normal range for nonpregnant women (mean +/- SD; 20 +/- 6u/ml). Since CA130 is abundant in the decidual tissue but is scant in tubal tissue, a high CA130 level in maternal sera during early pregnancy may indicate the presence of the destruction of decidual tissue, while a low or normal CA130 level throughout early pregnancy is regarded as characteristic of tubal pregnancy.

Abortion, Spontaneous↗

[Controversy in the treatment of superficial esophageal carcinoma--indications and problems of the procedures].

In our institution, 152 cases have been treated, which are 24.3% of total 626 cases with esophageal carcinomas. Analysis of these 152 cases revealed that neither intraepithelial cancer (ep), nor mm2 cancer, in which the lesion is limited within the upper two-thirds of the proper mucosal layer, had any vessels invasion and lymph node metastases. In addition, only 25% of the cases with mm3 cancer, limited within the deeper one-third of the proper mucosal layer, had vessels invasion without lymph node metastases. The 5-year survival of the cases less than sm1 was as good as 100%. However, those of sm2 and sm3 patients were 58.9% and 54.2%, respectively. Thus, we made the treatment strategy for superficial esophageal cancer as follows: 1. For ep to mm2 cases, endoscopic mucosal resection could be applied. 2. For the cases whose lesions widely spread in the esophagus, blunt resection would be indicated. 3. For the cases with mm3 to sm3 cancer, thoracotomy and laparotomy with wide lymph node dissection from neck to abdomen should be employed. Since a radical operation for esophageal cancer has high operative risk and poor postoperative quality of life, we should properly pick up and apply more cases with mucosal carcinoma for endoscopic mucosal resection.

Esophageal Neoplasms↗

Bucillamine inhibits T cell adhesion to human endothelial cells.

We investigated the ability of bucillamine [N-(2-mercapto-2-methyl-propionyl)-L-cysteine] to prevent T cell adhesion to endothelial cells (EC) isolated from human umbilical vein. When EC were pretreated with bucillamine, T cell binding to the EC was suppressed in a dose dependent fashion. The T cells could bind preferentially to recombinant interferon-gamma (rIFN-gamma) treated EC compared with untreated EC. Bucillamine could also suppress T cell binding to rIFN-gamma treated EC as well as untreated EC. Addition of copper sulfate to bucillamine decreased significantly the percent T cell adhesion to the EC compared with bucillamine alone. The magnitude of inhibition by bucillamine and copper sulfate was similar in EC treated with rIFN-gamma as well as in untreated EC. H2O2 also inhibited the T cell binding to both untreated and rIFN-gamma treated EC. The inhibitory effects of bucillamine with or without copper sulfate on T cell binding to EC were abolished completely by catalase but not by superoxide dismutase. Our results suggest that hydrogen peroxide generated by bucillamine, with or without copper sulfate, inhibits T cell binding to EC. We believe, therefore, that bucillamine may suppress inflammation, such as that in rheumatoid synovitis, by reducing the emigration of chronic inflammatory cells from capillaries into tissue.

Anti-Inflammatory Agents, Non-Steroidal↗

Successful aggressive treatment against multiple intra-abdominal metastases from renal cell carcinoma 18 years after nephrectomy.

The management of late metastases from renal cell carcinoma is often difficult because of multiple organ involvement. We report a case of multiple metastases from renal cell carcinoma in the duodenum, pancreas, intestine, falciform ligament and liver, 18 years after nephrectomy. The patient underwent a total pancreatectomy following a gastroduodenal arterial embolization to control duodenal bleeding, a resection of the ileum and falciform ligament at a second laparotomy and repeated hepatic arterial embolizations to control the growth of liver metastases. Aggressive treatment should be undertaken in cases of late recurrence of renal cell carcinoma after nephrectomy because of the possibly slow-growing biological character of the tumor.

Abdominal Neoplasms↗

Effect of repeated administration of chelating agents on distribution, excretion, and renal toxicity of gold sodium thiomalate in rats.

The effects of the repeated administration of D-penicillamine, 2,3-dimercaptosuccinic acid, 2,3-dimercaptopropane sulphonate, and N-(2-mercapto-2-methylpropanoyl)-L-cysteine 24 h after gold sodium thiomalate (AuTM) injection on the distribution, excretion, and renal toxicity of gold in rats were investigated. Three i.p. injections of these chelating agents (1.2 mmol/kg) at 1, 3, and 5 days after AuTM injection (0.026 mmol/kg) removed gold from kidney and liver through urinary and fecal excretion, and protected against the renal damage induced by AuTM. These findings indicate that these compounds are useful antidotes for gold toxicity.

Animals↗

Mutagenicity of the new quinolone antibacterial agent levofloxacin.

UNLABELLED: A new quinolone antibacterial agent (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6- carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), was studied for mutagenicity using the following short-term in vitro and in vivo tests. 1. IN VITRO STUDIES: reverse mutation test (Ames method) on S. typhimurium and E. coli; and HGPRT forward mutation test, cytogenetic test, and sister chromatid exchange (SCE) test, all on Chinese hamster cells. 2. In vivo studies: mouse micronucleus test, SCE test on mouse bone marrow cell, in vivo-in vitro unscheduled DNA synthesis (UDS) test on rat primary hepatocytes, and dominant lethal test in BDF1 mice. In the in vitro tests for SCE and for chromosomal aberration, DR-3355 gave dose-dependent positive responses, but no mutagenicity was observed in the same indicators of the in vivo studies, even at the maximum tolerated doses. This strongly suggested that DR-3355 would have no mutagenic effects when used in the treatment of infectious diseases. DR-3355 did not show any positive response in the reverse mutation test, the HGPRT mutation test, the in vivo-in vitro UDS test or the dominant lethal test. These results suggest that chemotherapy with DR-3355 should have no mutagenic effect in man.

Animals↗

Structural differences in 5'-flanking regions of rat cytochrome P-450aldo and P-450(11) beta genes.

Two rat genomic clones, one for cytochrome P-450aldo and the other for P-450(11) beta, were isolated and characterized. The two genes, encoding structurally homologous proteins, were closely similar in their intron-exon organizations. Their 5'-flanking regions, however, contained only a few homologous regions. A putative cyclic AMP responsive element, TGACGTGA, was found in the P-450aldo gene, but this sequence was altered at two positions in the P-450(11) beta gene. S1 nuclease protection assay revealed a single transcription initiation site for the P-450aldo gene, while multiple sites were found for the P-450(11) beta gene. These results suggest that transcriptional regulation of the rat P-450aldo and P-450(11) beta genes is due to differences in the sequences of their 5'-flanking regions.

Animals↗

Establishment of a rhabdoid tumor cell line with a specific chromosomal abnormality, 46,XY,t(11;22)(p15.5;q11.23).

The malignant rhabdoid tumor is a rare, poorly understood tumor which occurs primarily in children. The kidney is a frequent primary site of origin, but the tumor has arisen in other mesodermally derived tissues as well. Controversy exists regarding the embryonic origin of the rhabdoid tumor and recent histopathologic studies suggest that it may be of neuroepithelial origin. Our immunohistochemical and electron micrographic studies support this theory. No consistent chromosome abnormalities have been reported in this tumor and no cell lines are available for study. We have established and characterized the first rhabdoid tumor cell line. It possesses a specific chromosomal abnormality, 46,XY,t(11;22)(p15.5;q11.23). The translocation may provide an important clue to the pathogenesis of the tumor as well as an opportunity for further study of the involved chromosome regions.

Adult↗

Muscle-specific gene expression in rhabdomyosarcomas and stages of human fetal skeletal muscle development.

Rhabdomyosarcomas (RMS) bear a morphological resemblance to developing striated muscle. It has been reported that two histologically distinct subtypes of RMS, embryonal and alveolar, behave differently in many clinical aspects, such as age distribution, primary site, and prognosis. We have investigated the expression of various genes, which are preferentially expressed in normal muscle tissue or cell culture (actins, myosins, and creatine kinases, and myogenic regulatory genes MyoD, myogenin, MRF4, and Myf5), in embryonal and alveolar subtypes and compared the results to the stages of developing human fetal limb muscle. The data showed that each of the RMS tumors tested, regardless of histological features, expressed MyoD1 and MRF4 transcripts. Expression of the myogenin gene was detectable in all alveolar RMS (n = 8), whereas only 5 of 8 embryonal RMS expressed myogenin transcripts. Trace levels of Myf5 transcripts were visible in all alveolar RMS and 7 of 8 embryonal RMS. The alpha-skeletal, alpha-cardiac, and beta- and gamma-cytoplasmic actin transcripts were detectable in all alveolar RMS. While the beta- and gamma-cytoplasmic actin transcripts were evident in all embryonal RMS, only 3 of 8 and 6 of 8 embryonal RMS expressed detectable levels of alpha-skeletal and alpha-cardiac actin transcripts, respectively. The embryonic form of myosin heavy chain was detectable in 1 of 8 of each type of tumor. Myosin light chain-1/3 transcripts were detectable in 4 of 8 alveolar RMS and 5 of 8 embryonal RMS. Brain creatine kinase transcripts were detectable in all alveolar RMS and 4 of 8 embryonal RMS, whereas none of the RMS samples contained detectable levels of the muscle form of creatine kinase. A comparison of the expression profiles with those of normal developing human fetal limb muscle (from 7.5 to 24 weeks' gestation) suggested that RMS resembled a relatively restricted segment of fetal muscle development. Furthermore, the data also showed a great deal of overlap in the differentiation state achieved by the embryonal and alveolar subtypes of RMS, suggesting that the clinicopathological difference between these two may not be due to malignant transformation of the cells from different positions in the normal pathway of myogenesis.

Actins↗

Antithrombotic effect of MCI-9042, a new antiplatelet agent on experimental thrombosis models.

The antithrombotic effect of MCI-9042, (+-)-2-(dimethyl-amino)-1-((o-(m- methoxyphenethyl)phenoxyl]methyl]ethyl hydrogen succinate hydrochloride was investigated in three different experimental thrombosis models in animals. Simultaneous injection of serotonin and collagen into the tail vein in mice induced acute pulmonary thromboembolic death. MCI-9042 reduced the mortality in a dose dependent manner and its ED50 value was 1.9 mg/kg po. Ticlopidine (TCP) which is a positive reference compound as an antithrombotic drug reduced the mortality at doses of 10 mg/kg po and above. Cyproheptadine (CPH) and ketanserin (KTS) which are S2-serotonergic antagonists were also effective on the reduction of mortality. In mesenteric arterial thrombosis induced by electric stimulation in mice, MCI-9042 prolonged the occlusion time resulted from platelet thrombus formation (PD50: 23 mg/kg po). CPH and KTS prolonged the occlusion time as potent as MCI-9042, but TCP prolonged the occlusion time only at the high doses of 100 mg/kg po and above. In experimental arterial thrombosis which generated in implanted polyethylene tubing, MCI-9042 reduced the incidence of thrombus formation in the tubing and its ED50 value was 18 mg/kg po. TCP was also effective in this model with an ED50 of 170 mg/kg po. The present results lead to the consideration that serotonin plays a more important role in thrombus formation than that conjectured formerly, and suggest that MCI-9042 becomes a new kind of antithrombotic drug with S2-serotonergic receptor antagonism.

Animals↗

A significant association of Ha-ras p21 in neuroblastoma cells with patient prognosis. A retrospective study of 103 cases.

To evaluate biologic characteristics of neuroblastoma, the authors examined the expression of Ha-ras gene (Ha-ras p21) in 103 primary tumors obtained at the time of diagnosis. Higher expression of the Ha-ras p21 in tumor cells showed a significant association with lower clinical stage of the tumor at diagnosis (chi-square = 35.418, degrees of freedom [df] = 9, P less than 0.001) and survival of the patients (chi-square = 37.111, df = 3, P less than 0.001). Thirty-six (84%) of 43 patients with decreased Ha-ras p21 expression died of aggressive disease. The Ha-ras DNA was examined in the 32 tumors by Southern blot analysis. Neither augmentation nor deletion of the Ha-ras DNA was observed. Amplification of the N-myc DNA was also examined in 43 cases in comparison with Ha-ras p21 expression. N-myc amplification was detected in 12 (55%) of 22 patients who died, and 19 (86%) of the 22 patients showed a low expression of the Ha-ras p21 in tumor cells. Eighteen (86%) of 21 survivors showed a high expression of the Ha-ras p21. The expression of Ha-ras p21 was thought to be a clinically important marker for prognosis in children with neuroblastoma.

Blotting, Southern↗