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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 37 records · Page 2Linked to original sources

[Liver abscess formation after treatment of liver cancer by arterial injection using adriamycin/mitomycin C oil suspension (ADMOS)].

Of 210 patients with hepatocellular carcinoma (n = 135), metastatic liver cancer (n = 71) and cholangiocarcinoma (n = 4) who underwent intra-arterial infusion of adriamycin and/or mitomycin C oil suspension (ADMOS) and cisplatin, and both regimens, pyogenic liver abscess occurred in seven (3.3%). The percentages of abscess formation in the respective types of liver cancer were 0.8, 7.0 and 25%. These differences among the three types of liver cancer were attributed to the volume of the tumor vascular beds to be embolized, which might determine the relative amount or regional Lipiodol retention in the tumor and normal liver tissue. Four of seven patients with hepatic abscess had received the intra-arterial infusion of ADMOS, and their angiographic findings showed sequential decreases in the vascular beds of the tumor in comparison with those of previous infusion procedures; all had hypovascular liver tumors angiographically. We have never experienced this complication in other treatments such as embolization of the hepatic arteries and intra-arterial infusion of water-soluble anticancer drugs alone. These results suggest that the most important factor leading to abscess formation is the ischemic destruction of the intrahepatic ducts secondary to occlusion of the peribiliary arterial plexus by Lipiodol and/or the direct effects of anticancer drugs on these vessels. To avoid this complication, the volume of Lipiodol used for intraarterial infusion therapy should be carefully determined, especially when the patient has hypovascular tumors of the liver and a history of multiple previous intraarterial infusion procedures of anticancer drug. The use of ADMOS should be avoided in patients with hypovascular tumors of the liver such as secondary deposits and cholangiocarcinoma.

Adenoma, Bile Duct

Tyrosine-7 is an essential residue for the catalytic activity of human class PI glutathione S-transferase: chemical modification and site-directed mutagenesis studies.

The glutathione (GSH)-conjugating activity of human class Pi glutathione S-transferase (GST pi) toward 1-chloro-2,4-dinitrobenzene (CDNB) was significantly lowered by reaction with N-acetylimidazole, an O-acetylating reagent for tyrosine residues. Further, the replacement of Tyr7 in GST pi, which is conserved in all cytosolic GSTs, with phenylalanine by site-directed mutagenesis also lowered the activities toward CDNB and ethacrynic acid. The Km values of the mutant for both GSH and CDNB were almost equivalent to those of the wild type, while the Vmax of the former was about 55-fold smaller than that of the latter. Therefore, Tyr7 is considered to be an essential residue for the catalytic activity of GST pi.

Base Sequence

Role of sympathovagal interaction in diurnal variation of QT interval.

To elucidate the role of sympathovagal interaction in diurnal variation of QT interval, 24-hour ambulatory electrocardiographic recordings from 56 subjects (23 control subjects, 18 patients with atherosclerotic coronary artery disease, and 15 patients with diabetes mellitus) were studied. The QT interval at a heart rate of 60 beats/min (QT60) was determined for each of the day and night periods by regression analysis. Sympathetic and parasympathetic activities were assessed by spectral analysis of heart rate variability and represented by the low- and high-frequency components, respectively. The proportion of high-frequency component to the sum of low- and high-frequency components was used as an index of sympathovagal balance. The relative increase in QT60 at night (delta QT60 [%]) was larger in control subjects (4.2 +/- 2.1%) than in patients with coronary artery disease (2.2 +/- 1.8%; p less than 0.01) and diabetes mellitus (-1.5 +/- 4.0%; p less than 0.001). When the data from the 3 subject groups were pooled and analyzed, delta QT60 was correlated with the change in the sympathovagal balance (r = 0.554; p less than 0.001). Low-frequency component in the day alone was also related with delta QT60 (r = 0.554; p less than 0.001), but the ratio or difference of the high-frequency component value between day and night was not. These results indicate that although change in sympathovagal balance was responsible for the diurnal variation in QT interval, the enhanced sympathetic activity in the day was a major determinant of this phenomenon.

Aged

Effect of extracellular phosphatidylinositol on c-myc gene-expressed human renal cancer cell line.

Effect of exogenously added soybean phosphatidylinositol on c-myc gene expressed and unexpressed human cancer cell lines was investigated. When phosphatidylinositol liposomes were introduced into culture media, viability of c-myc unexpressed cells was reduced, while that of c-myc expressed cells was not. Death of c-myc unexpressed cells by phosphatidylinositol liposomes was found to be caused by abnormally accumulated intracellular Ca2+, and it seemed to be related to reduction of protein kinase C activity.

Calcium

The role of 5'-methylthioadenosine on rat calvaria cell differentiation.

The role of 5'-methylthioadenosine (MTA), formed during the process of polyamine biosynthesis, on differentiation of osteoprogenitor cells was assessed by its effects on alkaline phosphatase (ALP) activity, bone nodule formation and osteopontin contents of cultured rat calvaria (RC) cells. These three markers were stimulated by exogenous MTA and were depressed by 5'-difluoromethylthioadenosine (DFMTA), a synthetic inhibitor of MTA phosphorylase, which cleaves MTA to adenine and 5-methylthioribose-1-phosphate. 5-Methylthioribose and 2-keto-4-methylthiobutyrate, metabolites of 5-methylthioribose-1-phosphate, had no effects on ALP activity and bone nodule formation in the presence or absence of DFMTA. On the other hand, adenine enhanced ALP activity, bone nodule formation and osteopontin contents in mineralized nodules and also partially reversed DFMTA-induced inhibition of these three markers. MTA, its metabolites and DFMTA did not affect the growth of RC cells under these culture conditions. These results suggest that adenine formed from MTA is important in the differentiation of RC cells.

Adenine

Recognition of bases in Escherichia coli tRNA(Gln) by glutaminyl-tRNA synthetase: a complete identity set.

The fidelity of protein biosynthesis rests largely on the correct aminoacylation of transfer RNAs by their cognate aminoacyl-tRNA synthetases. Previous studies have demonstrated that the interaction of Escherichia coli tRNA(Gln) with glutaminyl-tRNA synthetase (GlnRS) provides an excellent system for studying the basis of this highly specific recognition process. Correct aminoacylation depends on the set of nucleotides (identity elements) in tRNA(Gln) responsible for correct interaction with GlnRS. Specific contacts between tRNA(Gln) and GlnRS include the 2-amino group of guanosines. Therefore, we made a set of tRNA(Gln) variants in which specific guanosines were replaced by inosine using recombinant RNA technology. This resulted in a set of tRNAs that varied by single deletions of the amino group from guanine residues, thus allowing us to test the functional importance of these contacts. In addition, a number of mutants were made by transcription of mutated tRNA genes with base changes at position 10, 16 or 25. In vitro aminoacylation of these mutants showed decreases in the specificity constant (kcat/KM) of up to 300-fold, with kcat being the parameter most affected. These experiments reveal G10 as a new element of glutamine identity. In addition, the interaction of G2, G3 and G10 with GlnRS via the 2-amino group is significant for tRNA discrimination. Based on these results, and on earlier data, we propose a complete set of bases as identity elements for tRNA(Gln).

Amino Acid Sequence

Thyroid carcinoma in patients with secondary hyperparathyroidism.

There have been few reports of coexistence of secondary hyperparathyroidism (2 degrees HPT) and thyroid carcinoma. Eleven consecutive patients with 2 degrees HPT who underwent parathyroidectomy were analyzed. They consisted of six males and five females, whose age ranged from 34 to 55 years. None of the patients had a history of irradiation of the head or neck. Associated thyroid nodules were also present in seven patients (64%): four patients with benign nodules, and three patients with papillary carcinomas, and one with papillary carcinoma and two follicular adenomas. This incidence of thyroid carcinoma in the patient group with 2 degrees HPT (36%) was significantly higher than that of the autopsy group in the same geographical area (11%). The level of carboxyl-terminal parathyroid hormone in the patients with thyroid carcinoma was higher than that in the patients without thyroid carcinoma (P less than 0.05). The importance of searching for possible thyroid cancer in patients with 2 degrees HPT should be emphasized.

Adult

A trial of adjuvant chemoimmunotherapy with mitomycin C and OK-432 for stage III gastric carcinoma.

We previously found that the ability to generate cytotoxic cells induced by in vitro activation of peripheral blood mononuclear cells (PBM) with OK-432, a bacterial immunopotentiator, was markedly increased following intravenous administration of a single dose of mitomycin C (MMC) in cancer patients. On the basis of this clinical finding, we designed a treatment regimen that consisted of MMC 12 mg/m2 intravenously on day 1 and OK-432 5 Klinische Einheit (KE) intradermally on days 6, 8, and 11, when the generation of OK-432 activated killer cells had been shown to be significantly augmented. Then, it was followed by long-term tegafur. Fifteen patients with stage III gastric carcinoma who had undergone curative resection were treated with the above regimen. The survival of these patients was significantly better than that of 26 comparable stage III patients concurrently treated with MMC 12 mg/m2 alone, followed by long-term tegafur (P less than 0.01). The results indicate that OK-432 combined with MMC may be effective against stage III gastric carcinoma, when these agents are used probably in an appropriate combination.

Carcinoma

Estimated weight of the residual parathyroid gland after parathyroidectomy using plasma levels of the parathyroid hormone.

The possibility of estimating the total weight of the parathyroid glands based on the plasma concentration of the parathyroid hormone (PTH) would be of great help when searching for the parathyroid glands during surgery on patients with secondary hyperparathyroidism. Thus, we studied the relationship between the levels of carboxyl-terminal PTH (C-PTH), midportion PTH (M-PTH) and intact PTH, and the weight of the parathyroid glands resected for secondary hyperparathyroidism. The subjects studied were 11 patients with secondary hyperparathyroidism caused by chronic renal failure. The pre- and post-operative differences in the plasma C-PTH levels and plasma M-PTH levels were significantly correlated with the weight of the resected parathyroid glands (p less than 0.001 for both), but there was no correlation between the differences in the levels of intact PTH and the weight of the resected parathyroid glands. From these relationships we estimated the weight of the residual parathyroid gland after parathyroidectomy using the levels of each PTH. All patients in whom the residual parathyroid gland was estimated to be heavy based on the levels of M-PTH showed recurrence of hyperparathyroidism after the parathyroidectomy. We therefore found that estimation of the weight of the parathyroid glands from the levels of M-PTH is both possible and useful.

Adult

A single amino-acid substitution in the beta-tubulin gene of Neurospora confers both carbendazim resistance and diethofencarb sensitivity.

Two MBC-resistant mutants of Neurospora crassa, F914 and F939, were sensitive to diethofencarb at a concentration of 0.1 micrograms/ml, while the wild-type strain and other MBC-resistant mutants showed resistance to diethofencarb at a concentration of 100 micrograms/ml. Genetic analysis suggested that the mutations in these two strain were closely linked to the Bml locus which codes for beta-tubulin. When the wild-type strain was transformed by the cloned beta-tubulin gene of the F914 strain, the transformants showed both MBC resistance and diethofencarb sensitivity. On the other hand, the diethofencarb sensitivity of the F914 strain was cancelled by transformation with the wild-type beta-tubulin gene. DNA sequencing of F914 beta-tubulin revealed that glycine was substituted for glutamic acid at position 198 in the F914 strain. Therefore, a single base change in the beta-tubulin gene was proved to confer both MBC resistance and diethofencarb sensitivity.

Amino Acid Sequence

Comparison of the anticancer effect of ADMOS alone and ADMOS with CDDP in the treatment of hepatocellular carcinoma by intra-arterial injection.

A total of 135 patients with hepatocellular carcinoma (HCC) were treated by intra-arterial injection of an Adriamycin/mitomycin C oil (lipiodol) suspension (ADMOS) alone or of ADMOS plus cis-diammine-dichloroplatinum (CDDP). In all, 59 patients were treated with ADMOS alone and 76 were treated with ADMOS plus CDDP. A reduction of more than 25% in the tumor size was obtained in 13 of 38 (34%) evaluable patients in the former group and in 39 of 76 (51%) evaluable patients in the latter group. Serum alpha-fetoprotein (AFP) levels decreased by more than 50% in 10 of 17 (59%) and 23 of 33 (70%) patients in the respective groups whose pretreatment AFP level was estimated to be over 200 ng/ml. Overall, the 1-year survival value was 68% and the 2-year value was 41% as determined by the Kaplan-Meier method. No statistically significant difference in survival was observed between the two groups. The initial tumor response correlated with the survival value. No severe complication was encountered except for one case of liver abscess formation. No serious change in the laboratory data was observed following treatment with these regimens. Although the tumor response was significantly better in patients treated with ADMOS combined with CDDP injection than in those treated with ADMOS alone (P < 0.05), no significant difference in survival was found between the two groups.

Antineoplastic Combined Chemotherapy Protocols

Sialosylated Lewis chi expression in CD30-positive anaplastic large-cell lymphomas.

The expression of sialosylated Lewis chi (SLEX), a ligand for endothelial leukocyte adhesion molecule 1 in malignant lymphomas, was immunohistochemically examined, using the monoclonal antibody, CSLEX1, which specifically reacts with SLEX. It was expressed in 6 out of 64 non-Hodgkin's lymphomas, which consisted of 1 nasal large-cell lymphoma and 5 of 8 (62%) Ki-1-positive anaplastic large-cell lymphomas (ALCL). One nasal lymphoma positive for SLEX co-expressed a T cell marker, cluster of differentiation (CD) 5, and natural killer (NK) cell markers such as CD56 and CD16, indicating that SLEX+ nasal lymphoma cells are possibly malignant counterparts of SLEX+ NK cells. SLEX did not react with 30 B cell lymphomas or most Hodgkin's disease lymphomas, though it did with one lymphocyte predominance type. Although SLEX+ ALCL exhibit T cell markers in some cases, some ALCL expressing SLEX may represent histiocytic differentiation of the neoplastic cells. The lymphoma cells of ALCL were preferentially positive for SLEX, in contrast to Hodgkin's disease cells, and thus CSLEX1 in conjunction with CD30 and CD15 should be of use for analyzing and making differential diagnoses of routine paraffin-embedded sections of ALCL.

Antigens, CD

Immunohistochemical analysis of lymphocyte subsets infiltrating gastric carcinoma after mitomycin C administration.

The intensity of lymphoid cell infiltration and distribution of lymphocyte subsets in tumors were investigated immunohistochemically on tumor tissues obtained from 11 patients with gastric carcinoma, who had been treated with mitomycin C (MMC), 12 mg/m2, i.v. 5 days before operation. The results were compared with those obtained from 24 untreated patients as controls. In the tumor tissues from pretreated patients, the intensity of lymphoid infiltration was not significantly different from that of untreated patients. However, high-grade infiltration of CD4+ cells was observed in 55% of pretreated patients, whereas only 8% of control patients exhibited the high-grade infiltration (P < 0.02). Since the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells was more frequently estimated to be more than 1 in patients pretreated with MMC, as compared to untreated controls (P < 0.02). Further, CD25+ cells in pretreated tumor tissues were more predominant than those in control tumor tissues (P < 0.05). These results suggest that MMC administration induces these alterations in lymphocyte subsets in tumor tissue in patients with gastric carcinoma.

Aged

Correlation of eosinophilia with clinical response in patients with advanced carcinoma treated with low-dose recombinant interleukin-2 and mitomycin C.

On the basis of our clinical findings that the ability of cancer patients to generate lymphokine-activated killer cells became markedly augmented after mitomycin C administration, we designed a treatment regimen comprising mitomycin C 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 700 U/m2 (8000 IU/kg), i.v. every 12 h from day 4 through day 8. The treatment course was repeated at almost 7-day intervals. Altogether 33 patients with advanced carcinoma, including mainly gastrointestinal carcinoma, were treated with this regimen. Of these, 10 had a partial response (PR) and 4 had a minor response (MR). Since eosinophil counts peaked 1 day after either the first or second course of the therapy, the posttreatment values were compared to each pretreatment level, with regard to the clinical antitumor response to this treatment. When patients who showed PR were defined as responders, absolute eosinophil counts and the percentage of eosinophils in responders after both the first and second courses of the therapy were significantly greater than each pretreatment value or the posttreatment level in nonresponders. Further, these findings were almost identical, when both PR and MR were considered to be a true remission and therefore patients who exhibited PR or MR were defined as responders, although the difference between posttreatment levels of eosinophils in responders and nonresponders was not significant at the second course. These results indicate that eosinophilia induced by this treatment correlates with the clinical response to this therapy.

Aged

High level expression of a frog alpha-amidating enzyme, AE-II, in cultured cells and silkworm larvae using a Bombyx mori nuclear polyhedrosis virus expression vector.

A Xenopus laevis peptidyl C-terminal alpha-amidating enzyme (AE-II) gene, modified by deletion of a region encoding the putative membrane-spanning domain and the putative C-terminal cytosolic tail, was expressed in BoMo-15 AIIc insect cells and silkworm larvae using a Bombyx mori baculovirus expression vector system. The expressed enzyme was identified predominantly in the culture medium and the hemolymph of silkworm larvae, indicating successful secretion of the expressed AE-II. The level of recombinant enzyme in the larval hemolymph at 4 days post-infection (40 micrograms/ml) was more than 100-fold the peak levels found in the culture medium (250 ng/ml). The enzyme activity in the larval hemolymph at 4 days post-infection was 3700 units/ml.

Animals

Role of anatomic architecture in sustained atrial reentry and double potentials.

To determine the role of anatomic architecture in atrial flutter, electrophysiologic findings were correlated with anatomic features in a modified model of atrial flutter with ligation of the crista terminalis. Crista ligation in the middle right atrium prolonged intraatrial conduction time in a rate-dependent manner in 12 dogs, particularly in the low right atrium. With burst atrial pacing, unidirectional block occurred either in the low right atrium or in the interatrial septal region near the superior vena cava, leading to initiation of atrial flutter. Atrial activation mapping revealed a slow conduction area in the low right atrium where conduction had been delayed by crista ligation. On the intact tissues between the venae cavae, double potentials were recorded, a finding indicative of functional block in the center of the reentrant circuit. The interdeflection time of double potentials changed with the activation sequence of atrial flutter. This change could be explained by assuming that the functional center of the reentrant circuit leaned on the right atrial free wall side. Anatomic study demonstrated that areas of slow conduction, unidirectional block, and functional block in the center of the reentrant circuit were closely related to the location of the intact crista terminalis. In conclusion, the intact portion of the crista terminalis played an important role in the genesis of atrial flutter after blockage of longitudinal conduction through the crista.

Animals

Effects of tolbutamide on fructose-2,6-bisphosphate formation and ketogenesis in hepatocytes from diabetic rats.

To assess the extrapancreatic action of sulfonylurea directly in the diabetic, effects of tolbutamide on hepatocyte fructose-2,6-bisphosphate (F-2,6-P2) formation and ketone production were investigated using isolated hepatocytes from streptozotocin (STZ)-induced diabetic rats. The basal level of hepatocyte F-2,6-P2 was significantly higher in diabetic rats within 2 weeks after STZ (40 mg/kg body weight) injection compared with that in the nondiabetic control group. Ultimately, a marked decrease in the F-2,6-P2 level was observed at 4 weeks after STZ administration (10% of the control). Although the addition of tolbutamide further increased the hepatocyte F-2,6-P2 level during the first week after STZ injection, no significant effect was observed after the second week and on from the initial STZ. Treatment of diabetes with insulin restored the stimulatory effect of tolbutamide on the hepatocyte F-2,6-P2 formation. Tolbutamide, independently of insulin treatment, lowered the ketone production of hepatocytes from diabetic rats. The present results indicate that insulin is necessary, in advance, for sulfonylurea to stimulate the liver F-2,6-P2 formation, while tolbutamide inhibition of hepatocyte ketone production is independent of insulin. These results provide further support for the role of sulfonylurea in regulating hepatic energy metabolism in the diabetic.

3-Hydroxybutyric Acid