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Biomedical subjects

Y Hata

Publications and source records attributed to Y Hata.

At least 289 records · Page 16Linked to original sources

[Relationship between external auditory canal temperature and caloric nystagmus--the problem with the ordinary cold-warm caloric test].

The cold-warm caloric test is performed with water irrigation, using a hot temperature of 44 degrees C and a cold temperature of 30 degrees C, which are thermally equidistant from the body temperature 37 degrees C. However, the 30 degrees C irrigation nearly always produces a stronger nystagmic response than that of the 44 degrees C stimulation. The purpose of this study is to investigate the difference in nystagmic response between cold and hot stimulation. The achieved hot (44 degrees C) and cold (30 degrees C) water samples were prepared, and irrigation was with a disposable plastic syringe. Temperature changes in the external auditory canal were monitored by tympanic thermometry during the cold-warm caloric test. Maximal slow phase velocity and the duration of induced nystagmus were recorded on an electro-nystagmograph. The following conclusions were drawn; 1) The average normal external auditory canal temperature was 36.8 degrees C, and there was no side difference between the right and left ears. External canal temperature was higher than that of the axilla. 2) When 20 ml of 30 degrees C water was instilled the temperature change in the external canal was larger than that in response to the 44 degrees C water and the maximal slow phase velocity of nystagmus for cold stimulation was stronger than that for hot. However, the duration of nystagmus for the cold was not significantly longer than that of the hot stimulation.

Adult↗

[Cochlear nerve conduction block restoration of hearing after removal of cerebellopontine tumors].

Hearing restoration after removal of cerebellopontine tumors has only infrequently been observed. We present 5 cases with dramatic improvement of both pure tone threshold and speech threshold after excision of tumors. Two patients had acoustic neuroma, 2 meningioma and one cerebellar hemangioblastoma. Preoperatively, the patients suffered severe sensorineural hearing loss and had no measurable speech discrimination score. Recordings of the auditory brain stem response were absent or showed only wave I. However, results of the electrocochleogram were within normal limits. After removal of the tumors, their hearing returned to normal and remained stable thereafter. The data are consistent with the hypothesis that pressure from the tumor causes cochlear nerve conduction block and hearing impairment.

Adult↗

[Combination therapy with low dose adriamycin for advanced or recurrent breast cancer. Hokkaido Breast Cancer Treatment Study Group].

Comparative clinical trials among 3 regimens for patients with advanced or recurrent breast cancer were performed as a multi-institutional joint study. Arm-I of 3 regimens consisted of a 3-day consecutive administration of adriamycin (ADM) at 10 mg/body every 4 weeks, a daily oral administration of cyclophosphamide (CPA), 5-FU and tamoxifen (TAM) at 100 mg, 200 mg, and 20 mg, respectively, and a once-a-week intramuscular or subcutaneous injection of OK-432 (OK) gradually increased from the initial dose of 1 KE to the maintenance dose of 5 KE. Arm-II contained methotrexate (MTX) at 10 mg/body for 3 consecutive days every 4 weeks in place of ADM in Arm-I. Arm-III contained neither ADM nor MTX. Of 69 cases registered, 52 were eligible, leaving 6 non-eligible and 11 incomplete cases. The results of the overall evaluation of 48 complete cases other than 4, in which the tumor was not exactly measured, were as follows. Arm-I resulted in 2 CR and 3 PR out of 19 cases, the response rate being 23.6% (5/19). Arm-II resulted in 1 CR out of 15, the response rate being 6.7% (1/15). In Arm-III, no response cases were found. No significant difference was observed among three treatment groups (p = 0.055), but in Arm-I, the response rate was higher than in the other treatment groups, suggesting that there is a probability of useful combined use of ADM.

Adult↗

Tiazofurin decreases Ras-GTP complex in K562 cells.

The ras oncogene product (p21ras, Ras) is a GTP-binding protein and is thought to transduce signals regulating cellular proliferation and differentiation. The active form Ras-GTP is inactivated by hydrolyzing bound GTP to GDP. Tiazofurin, a specific inhibitor of IMP dehydrogenase, decreased cellular GTP pools and downregulated c-ras gene expression, leading to differentiation (Olah, E. et al., Proc. Natl. Acad. Sci. USA 85: 6533-6537, 1988; Weber et al., Cancer Commun. 3:61-66, 1991). To clarify the link between the action of tiazofurin on metabolic alterations and the induction of differentiation, we examined the effect of tiazofurin on the ratio of active Ras-GTP to total Ras in K562 cells in culture. Cells were labeled for 6 h with [32P]Pi in phosphate-free RPMI 1640. Tiazofurin (100 or 200 microM) was added to cells, and samples were taken at 0, 2, 4, 6 and 12 h of incubation. Cell lysates were immunoprecipitated with monoclonal anti-p21 antibody (Y13-259), then developed on thin layer chromatography. GTP and GDP bound to Ras were visualized by autoradiography. Tiazofurin treatment decreased Ras-GTP concentration in a time- and dose-dependent fashion. In the untreated K562 cells the Ras-GTP concentration was 26.3 +/- 1.4, and tiazofurin (200 microM) decreased it at 6 h to 16.6 +/- 2.9 and at 12 h to 10.6 +/- 2.1%. Inhibition of the GTP salvage pathway with hypoxanthine (100 or 200 microM) enhanced the tiazofurin-induced decrease of Ras-GTP, whereas addition of guanosine (100 microM) prevented the Ras-GTP decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimetabolites, Antineoplastic↗

[Molecular biology of apolipoproteins in genesis of hyperlipidemias and atherosclerosis].

The application of cell and molecular biology techniques has provided new information on the structure and function of the apolipoproteins, enzymes and receptors that mediate lipoprotein transport. The identification of human mutations at the gene level has established the molecular basis for several clinically important dialipoproteinemias and atherosclerosis.

Apolipoproteins↗

Surgical treatment of congenital biliary dilatation associated with pancreaticobiliary maljunction.

The excisional surgical treatment of 50 patients with congenital biliary dilatation (CBD) associated with pancreaticobiliary maljunction (PBMJ) was analyzed. There were two patients who had early complications of lesser bile juice leakage with a maximum duration of 21 days, but no pancreatic juice leakage was noticed. As a late complication, two strictures at the anastomotic portion of the hepaticojejunostomy and one intrahepatic gallstone formation were encountered, but no malignant lesion was evident. Both patients with strictures could be predicted using postoperative cholangiography performed two weeks postoperatively and underwent hepaticojejunostomy. Intrahepatic gallstones were treated with lateral segmentectomy of the liver and electrohydraulic lithotripsy through percutaneous transhepatic cholangioscopy. Accordingly, these results suggest that excisional surgical treatment is the most appropriate method for CBD with PBMJ; however, special care must be taken, such as creating a sufficiently wide anastomotic stoma to enable free drainage of bile into the intestine; also, there should be precautions against ischemia at the anastomotic portion. The importance of the postoperative cholangiography to predict the postoperative outcome should be emphasized. Furthermore, causes of intrahepatic gallstone formation should be studied in such instances.

Adolescent↗

[Host immunological status modification by various chemotherapeutic drugs].

There are many unsolved problems about the effects on a host's cellular immunologic status by various chemotherapeutics used routinely. Thus, we performed an experimental study mainly on these effects using mouse effector cells. We administered the usual therapeutic dosage of various chemotherapeutic agents to 8-week female C57BL/6 mice, and 3 days after these administrations all mice were sacrificed and splenectomised. The number of splenocytes in whole spleen, LAK precursor cell activity, NK cell activity, and IL-2 productivity were determined, and these results were compared with those for normal mice. Although CY, 5-FU, MMC and LIB exhibited immunologic depressive effects, BLM and PEP showed augmentative effects, and ADR and CDDP no effects. It seemed important that the appropriate drug selection be made on the basis of the above data in order to be the best therapeutic regimen for the individual patient's malignancy.

Animals↗

Site-directed mutagenesis at aspartate and glutamate residues of xylanase from Bacillus pumilus.

To elucidate the reaction mechanism of xylanase, the identification of amino acids essential for its catalysis is of importance. Studies have indicated the possibility that the reaction mechanism of xylanase is similar to that of hen's egg lysozyme, which involves acidic amino acid residues. On the basis of this assumption, together with the three-dimensional structure of Bacillus pumilus xylanase and its amino acid sequence similarity to other xylanases of different origins, three acidic amino acids, namely Asp-21, Glu-93 and Glu-182, were selected for site-directed mutagenesis. The Asp residue was altered to either Ser or Glu, and the Glu residues to Ser or Asp. The purified mutant xylanases D21E, D21S, E93D, E93S, E182D and E182S showed single protein bands of about 26 kDa on SDS/PAGE. C.d. spectra of these mutant enzymes show no effect on the secondary structure of xylanase, except that of D21E, which shows a little variation. Furthermore, mutations of Glu-93 and Glu-182 resulted in a drastic decrease in the specific activity of xylanase as compared with mutation of Asp-21. On the basis of these results we propose that Glu-93 and Glu-182 are the best candidates for the essential catalytic residues of xylanase.

Aspartic Acid↗

Methotrexate decreases thymidine kinase activity.

MTX cytotoxicity is not fully explained by its well-known inhibition of dihydrofolate reductase activity which leads to a decrease in the dTMP synthase reaction, since TdR kinase which converts TdR to dTMP could readily circumvent MTX action through this salvage activity. TdR kinase is of particular significance, since in various types of carcinoma cells its activity is orders of magnitude higher than that of dTMP synthase. To throw light on this problem, we tested the hypothesis that the impact of MTX treatment might in fact involve an inhibition or decrease in TdR kinase activity. Injection in rat of MTX (i.p.) decreased TdR kinase activity in a time- and dose-dependent fashion in liver (t1/2 = 46 h; IC50 = 95 mg/kg), bone marrow (t1/2 = 10 h; IC50 = 5 mg/kg) and rapidly growing transplantable hepatoma 3924A (t1/2 = 56 h; IC50 = 5 mg/kg). Injection in rat of cycloheximide (15 mg/kg, i.p.), an inhibitor of protein biosynthesis, rapidly decreased TdR kinase activity in the hepatoma (t1/2 = 3.6 h); activities of other purine and pyrimidine synthetic enzymes, dTMP synthase, IMP dehydrogenase, GMP reductase and GMP synthase, declined at a markedly slower rate (t1/2 = 11, 11.6, 12 and 22 h, respectively). MTX, by curtailing purine and pyrimidine biosynthesis, limits product of TdR kinase which is more sensitive to unopposed protein degradation than other enzymes of nucleic acid biosynthesis. TdR kinase is a newly discovered target of MTX treatment.

Animals↗

Structure of acidic phospholipase A2 for the venom of Agkistrodon halys blomhoffii at 2.8 A resolution.

The crystal structure of acidic phospholipase A2 from the venom of Agkistrodon halys blomhoffii has been determined by molecular replacement methods based on the known structure of Crotalus atrox PLA2, a same group II enzyme. The overall structures, except the calcium-binding regions, are very similar to each other. A calcium ion is pentagonally ligated to two carboxylate oxygen atoms of Asp-49 and each carbonyl oxygen atoms of Tyr-28, Gly-30 and Ala-31. A reason why the former enzyme functions as monomeric form, while the latter one does as dimer, could be presumed by the structural comparison of these calcium-binding regions. Although Gly-32 is usually participated as a ligand in the coordination with calcium ion in group I PLA2, it is characteristically replaced to Ala-31 in the present structure, and thus the coordination geometry of calcium ion is rather different from the usually observed one.

Amino Acid Sequence↗

Functional elements of the promoter region of the Aspergillus oryzae glaA gene encoding glucoamylase.

Analysis was made of the promoter region of the Aspergillus oryzae glaA gene encoding glucoamylase. Northern blots using a glucoamylase cDNA as a probe indicated that the amount of mRNA corresponding to the glaA gene increased when expression was induced by starch or maltose. The promoter region of the glaA gene was fused to the Escherichia coli uidA gene, encoding beta-glucuronidase (GUS), and the resultant plasmid was introduced into A. oryzae. Expression of GUS protein in the A. oryzae transformants was induced by maltose, indicating that the glaA-GUS gene was regulated at the level of transcription in the presence of maltose. The nucleotide sequence 1.1 kb upstream of the glaA coding region was determined. A comparison of the nucleotide sequence of the A. oryzae glaA promoter with those of A. oryzae amyB, encoding alpha-amylase, and A. niger glaA showed two regions with similar sequences. Deletion and site-specific mutation analysis of these homologous regions indicated that both are essential for direct high-level expression when grown on maltose.

Aspergillus niger↗

Liver regeneration following portacaval shunt in rats: 3',5'-cyclic AMP changes in plasma and liver tissue.

Hepatic regeneration following portacaval shunt was evaluated in the light of the changes of 3',5'-cyclic AMP (cAMP) levels in plasma and liver tissue, and also plasma cAMP levels after glucagon administration, using a 70% hepatectomy and portacaval shunt model in rats. Ratios of liver to body weight recovered to 60% of pre-operative ratios 2 weeks after the operation. Plasma cAMP level decreased slightly, but insignificantly, 1 day and 3 days after the operation, then recovered to the pre-operative level. Hepatic cAMP concentration increased for 2 weeks after the operation. Plasma cAMP levels induced after glucagon administration did not increase until 3 days after the operation and were only 50% of pre-operative levels 4 weeks after the operation. From these results, liver regeneration following the portacaval shunt was remarkably delayed, but continued until at least 2 weeks after the operation.

Animals↗

Inflammatory pseudotumor of the liver in children: report of cases and review of the literature.

Two pediatric cases of inflammatory pseudotumor of liver were reported and compared with seven previously reported cases. Clinical presentation was variable but often consisted of fever and vague abdominal symptoms. These two cases were considered to be clinically malignant because angiographically one showed hypervascularity and the other showed the portal vein draining into the lesion to be occluded. There are four previous reports of similar cases complicated with occlusive phlebitis within and around the lesion. All but two of the reported cases underwent major hepatectomy or liver transplantation. However, because of the benign nature of the lesion, the treatment might be more conservative after adequate diagnostic procedures, including needle biopsy, are applied.

Child↗

Solidifying liquid with novel initiation system for detachable balloon catheters.

In endovascular surgery, to permanently hinder blood inflow into an aneurysm for example, a catheter is percutaneously introduced into an artery and the balloon is positioned and inflated by a solidifying liquid and then released into the diseased part. A novel solidifying liquid for the inflated balloon curable under the continuous feeding of oxygen through the wall of the balloon is described here. Glucose oxidase which oxidizes glucose producing hydrogen peroxide was used for polymerization of the solidifying liquid. This solidifying liquid cured even in the presence of oxygen and water. It was radiopaque when mixed with the iodinated X-ray contrast chemical iopamidol. In addition, the solidified liquid had appropriate mechanical properties. The endovascular surgery could be carried out safely using it.

Catheterization↗

Laminin and procollagen-III-peptide as a serum marker for hepatic fibrosis in congenital biliary atresia.

The extracellular matrix (ECM) is a complex of macromolecules that includes collagens, proteoglycans, and complex glycoproteins. In fibrotic liver tissue there is an increase in all of these matrix components, and they increase in serum in the patients with alcoholic hepatitis or liver cirrhosis. These ECM components have been used as a serum marker of hepatic fibrosis. Prolonged obstruction of bile flow results in morphologic and biochemical changes and the development of secondary biliary cirrhosis. In congenital biliary atresia (CBA) there is a close correlation between the degree of the hepatic fibrosis and bile flow after the operation. We estimated that, in CBA, ECM increased in serum, and it would reflect the degree of the hepatic fibrosis. To clarify this we examined the serum procollagen-III-peptide (P-III-P) and laminin in CBA patients. P-III-P was elevated in all preoperative patients but in two of the three postoperative patients whose jaundice disappeared P-III-P was in the normal range. In the all 3 patients whose jaundice continued, P-III-P was in normal range. Serum laminin was elevated in 12 preoperative patients with CBA, but there is no correlation between day of diagnosis and level of laminin. Mean concentration in CBA without jaundice after operation was 3.18 U/mL, 3.226 U/mL in CBA with jaundice and 3.3 U/mL in infantile hepatitis. There were no significant differences among three groups. With the elevation of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin, serum laminin level was also increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary Atresia↗

Immunotargeting chemotherapy for AFP-producing pediatric liver cancer using the conjugates of anti-AFP antibody and anti-tumor agents.

The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated experimentally and clinically. The conjugate was made from mouse monoclonal antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared with the same ratio. Each drug was injected intraperitoneally, three times at the total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP. Tumor growth was inhibited significantly in the conjugate group compared with the other mixture group, the ADM or CDDP group, and the control group. Clinically, the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs) and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from the viewpoint of volume suppression rate showed partial response in 2 cases and no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal antibodies may be a promising method for treatment of malignant epithelial liver cancer in children.

Adolescent↗