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Biomedical subjects

T Kudo

Publications and source records attributed to T Kudo.

At least 343 records · Page 19Linked to original sources
PubMed1995

[Endocrine effects of nicardipine on intraoperative hypertension under droperidol-fentanyl-ketamine (DFK) anesthesia].

Effects of nicardipine on endocrine functions were evaluated in 10 surgical patients who received surgeries under total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK). Plasma levels of norepinephrine (NE), epinephrine (E), plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (hANP) were measured following nicardipine injection during 30 minutes of intraoperative hypertension. When the systemic blood pressure exceeded 160 mmHg systolic and 95 mmHg diastolic for five minutes, 0.5 mg approximately 10 mg of nicardipine was administered for 30 minutes to maintain the systolic blood pressure below 160 mmHg. Following the injection of nicardipine a significant reduction by 20% in the mean systolic and diastolic pressure was observed. Mean heart rate increased by 5%, but the increase was not significant. Plasma NE increased significantly 1.7 time from the control level at 15 minute following the injection. Plasma levels of E, PRA, aldosterone and hANP showed no significant changes.

Adult↗
PubMed1995

[Recent progress in development of psychotropic drugs (1)--Anti-anxiety drugs].

Anti-anxiety drugs are widely used for patients with neurosis or psychosomatic diseases due to the stress of contemporary society. The high efficacy of benzodiazepine (BZD) or its analog, which contains diazepam, is well-known. While these compounds have strong anti-anxiety effects, it has recently been pointed out that they have some side effects when used as daytime tranquilizers and induce drug dependence. The cause of these side effects is thought to be that typical BZD is a full agonist of BZD receptors. For this reason, partial agonists, inverse agonists and antagonists of BZD receptors are being developed. Furthermore, some non-BZD anti-anxiety drugs are also being developed to avoid the side effects of BZD. One of these is a 5-HT1A agonist, which has a high affinity for 5-HT receptors, because it is reported that 5-HT is related to anxiety in the septum-hippocampus system. In addition, the anti-anxiety effect of 5-HT3 agonist is being investigated, while the anti-anxiety effect of cholecystokinin agonists is also attracting attention. Because these new anti-anxiety drugs are more potent and have fewer side effects than BZD, they may achieve widespread clinical use.

Animals↗
PubMed1995

[Retinoic acid-induced hyperostosis in the murine spine, particularly in the cervical spine].

In order to investigate the role of retinoic acid in inducing spinal hyperostosis, the murine spine was radiologically and histologically examined after a 24-week peroral administration of synthetic retinoic acid (etretinate). In the cervical spine, osteophytes on the ventral rims of the vertebral bodies were more developed after etretinate administration than in controls. Histologically, chondrocytes after etretinate administration proliferated in the anterior longitudinal ligaments at the junction of the ventro-caudal rim and the epiphyseal region of the C2 and C3 vertebral bodies. Endochondral ossification was a characteristic feature and immature chondrocytes and mesenchymal cells were found in the region. After etretinate administration, the incidence of proliferative changes was 67.6% at the C2 ventro-caudal rim, and 79.4% and 70.6%, respectively in the C2 and C3 ventral epiphyseal regions. These percentages were highly significant compared with controls, but they were not dosage-dependent. These findings suggested that retinoic acid was involved in the differentiation and proliferation of chondrocytes in ligaments.

Animals↗
PubMed1995

[Arterial plasma keton body levels during isoflurane anesthesia and surgery].

The authors measured arterial plasma levels of acetoacetate, 3-hydroxybutyrate, free fatty acid and the blood levels of lactate and glucose to evaluate fat metabolism during isoflurane anesthesia and surgery in twenty patients who ranged in age from 17 to 67 years. They underwent non-abdominal surgery (orthopedic surgery) or abdominal surgery (gastrointestinal or gynecological surgery). The operation started at 9 AM following starvation after 9 PM of the day before surgery. Anesthesia was induced with intravenous thiopental followed by intravenous succinylcholine to facilitate tracheal intubation, and maintained with isoflurane in 50 % nitrous oxide and 50 % oxygen. Vecuronium was given intravenously during surgery. Lactated Ringer's solution at a speed of 5-15 ml.kg-1.h-1 was also administered intravenously throughout the procedures. Patients who had received glucose solution or blood transfusion were excluded. Plasma acetoacetate and 3-hydroxybutyrate levels increased significantly with surgical stimulation in both groups and they were slightly higher in the abdominal group than those in the non-abdominal group. However there was no statistical difference in plasma keton body levels between the groups. Mild increases in plasma free fatty acid and blood lactate levels were detected during surgery in both groups to the same extent. Blood glucose increased significantly during surgery in both groups and the increase was statistically higher in the abdominal group than that in the non-abdominal group. The findings suggest that there is no difference in fat metabolism between non-abdominal and abdominal groups during surgical intervention lasting as long as 3 hours when patients are starved and do not receive any glucose during surgery.

Adolescent↗
PubMed1995

[The experimental study on teleradiology system using HDTV and ISDN].

A teleradiology system is very useful to transmit radiological images rapidly in a wide area as Hokkaido. But the conventional teleradiology systems have been limited by slow transmission rates of public telephone circuit and also by the poor quality of their images. We have developed and tested an experimental teleradiology system using integrated services digital network (ISDN) for the purpose of high-speed image transfer, and high-definition television (HDTV) for the purpose of high image quality. The images of CT, MRI and chest XP were taken with HDTV camera and compressed by personal computer. The compressed images were transmitted by ISDN within one minute. The qualities of CT images and MRI images using HDTV were very good. The total quality of the experimental system using ISDN and HDTV is acceptable.

Computer Communication Networks↗
PubMed1995

mRNA levels and enzyme activities of protein phosphatases in drug-resistant rat ascites hepatomas.

mRNA levels and enzyme activities of the serine/threonine protein phosphatases (EC 3.1.3.16) type 1 (PP1) and 2A (PP2A) in drug-resistant rat ascites hepatoma cells were examined and compared with those in the parental drug-sensitive cell lines, under drug-free conditions. The mRNA levels of PP1 alpha were much higher in all the hepatomas, either sensitive or resistant, compared with normal liver. The mRNA level of PP2C alpha was decreased in the drug-resistant hepatomas compared with the parental drug-sensitive hepatomas, whereas mRNA levels of PP1 alpha, PP1 gamma 1 and PP2A alpha in resistant hepatomas showed diverse deviations, which are not drug-resistance-specific. However, both spontaneous and potential PP1 activities in particulate fractions of the resistant hepatomas were markedly increased compared with those of the sensitive hepatomas and normal rat liver. Western blot analysis showed that the resistant hepatomas contained larger amounts of PP1 alpha in both cytosolic and particulate fractions than the sensitive hepatomas and rat liver. In both groups of hepatomas, spontaneous and potential activities of PP2A were kept lower than those in normal rat liver, but there was no difference between drug-sensitive and -resistant hepatomas. These results suggest an involvement of PP1 in development of drug-resistant phenotype.

Animals↗
PubMed1994

Construction of a human B cell line, TKHMY, suitable for production of stable human hybridomas.

In order to produce stable hybridomas for generation of human monoclonal antibodies (HMAbs), an attempt was made to construct a suitable human parental B cell line with double selection markers, the strategy being to produce HMAbs by fusing a parental B cell line with EBV-transformed B cells producing specific antibodies. The resultant TKHMY cell line, constructed by transfecting the Blasticidin S resistant (bsr) gene into the HAT sensitive human B cell line LTR 228 could be used as a fusion partner for very efficient production of human hybridomas. Secretion of IgG monoclonal antibodies to antigens on lung cancer cells by one such hybridoma was very stable, indicating that this TKHMY cell line has practical advantage in the area of antibody production.

Aminohydrolases↗
PubMed1994

Ubiquitin in cerebrospinal fluid: a rapid competitive enzyme-linked immunoflow assay.

The aims of this study were to develop a rapid immunoassay to determine the levels of ubiquitin in cerebrospinal fluid and to establish the ubiquitin levels in the spinal fluid of normal aged individuals. A competitive enzyme-linked immunoflow assay was developed. In this assay, ubiquitin is bound to nitrocellulose membrane, after which the primary antibody-test sample mixture and the enzyme-labeled secondary antibody under vacuum are applied sequentially. The final reaction product is collected in a microtiter plate by suction. This competitive assay requires only approximately 4 h and is potentially useful for determining in biological fluids the levels of any antigen or its antibodies that might be present. Employing this immunoassay, cerebrospinal fluid ubiquitin levels were found to be 147.5 +/- 5.2 ng ml-1 in non-neurological aged cases.

Aged↗
PubMed1994

Distribution of angiotensinogen in diseased human hearts.

Extrahepatic synthesis and localization of angiotensinogen (ATN) have been described in animals, thus establishing the tissue renin-angiotensin (RA) system. However, there had been no reports of tissue RA systems in human organs, including the heart. In earlier, we have reported the possibility of ATN synthesis in the human heart using ribonuclease protection assay system. ATN mRNA was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that ATN is synthesized in the human heart. In this report, we looked for the distribution of ATN in diseased human heart. Northern blot hybridization of cDNA with total RNA extracted from human liver, brain, kidney, atrial and ventricular tissues revealed that ATN mRNA exists in cardiac ventricule. Immunohistochemical studies using a specific antibody to ATN revealed a stronger reaction in the endocardial layer of the human left ventricle, than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. This distribution pattern was similar to that of human atrial natriuretic peptide (hANP), which functions a smooth muscle relaxant. Double immunostaining of ATN and hANP demonstrated that all myocytes in the right atrium had immunopositive reactions to ATN, hANP or both of ATN and hANP. Double immunoelectron staining enabled us to show more detailed localization of ATN and hANP; hANP only existed in the specific granules and ATN existed in the myofibril, but not in the granule. Furthermore, our experiments provide evidence of ATN in healthy human hearts and also reveal a widespread immunopositive reaction for ATN in the left ventricle of diseased hearts.

Angiotensinogen↗
PubMed1994

Activation of guinea pig platelets by a monoclonal antibody.

We herein describe the characterization of a monoclonal anti-guinea pig platelet antibody, termed GT2-12, which causes aggregation, ATP and [3H]serotonin release, and platelet protein phosphorylation. GT2-12 can bind to platelets and megakaryocytes in guinea pig bone marrow cells. A protein of 34,000 daltons was detected by immunoprecipitation of platelet lysates with GT2-12. Incubation of 32P-labeled guinea pig platelets with GT2-12 resulted in rapid phosphorylation of proteins of 40,000 and 20,000 daltons. GT2-12-induced aggregation and protein phosphorylation of platelets were inhibited by diltiazem, TMB-8 and dibutyryl cAMP and partially inhibited by indomethacin. The F(ab')2 fragment of GT2-12 IgG also induced platelet aggregation, indicating that activation is not mediated by Fc receptors. This type of antibody should be useful for studying platelet function in the guinea pig model.

Adenosine Triphosphate↗
PubMed1994

Alzheimer disease: correlation of cerebro-spinal fluid and brain ubiquitin levels.

Neurofibrillary degeneration is one of the histopathological hallmarks of Alzheimer disease (AD). Previous studies have shown an association of ubiquitin with the cytoskeletal protein pathology in AD. In the present study, we report (i) the measurement of ubiquitin levels in cerebrospinal fluid (CSF) from histopathologically confirmed AD and control cases, using a new rapid immunoassay, the competitive enzyme-linked immunoflow assay (CELIFA), (ii) the determination of ubiquitin levels in brain tissue taken from the same cases, using a competitive enzyme-linked immunosorbent assay (ELISA), and (iii) an evaluation of the correlation between levels of ubiquitin in CSF and in brain tissue. Ubiquitin levels in CSF of AD and neurological control groups are significantly higher than those of non-neurological aged controls. Ubiquitin levels in brain homogenates of the AD group are significantly higher than those of both non-neurological aged and neurological control groups. The source of this increase in brain ubiquitin in AD is the particulate fraction, because ubiquitin levels in the brain cytosol fraction are the same among the three groups. In AD and non-neurological aged controls, there is a significant positive correlation between ubiquitin levels in CSF and in homogenate of cerebral white matter. In contrast, the correlation in the non-AD neurological control group has a negative tendency. These studies suggest that in AD, elevated levels of ubiquitin in the CSF reflect the increased amount of the protein in the brain and, therefore, can serve as a biomarker of the neuropathology in this disease.

Alzheimer Disease↗
PubMed1994

High-dose chemotherapy and blood stem cell autografts for children with first relapsed acute lymphoblastic leukemia: a pilot study of the Children's Cancer and Leukemia Study Group of Japan (CCLSG).

This study was performed to determine the value of high-dose chemotherapy and peripheral blood stem cell autografts (PBSCT) in the treatment of children with first relapsed acute lymphoblastic leukemia (ALL). Eighteen children underwent PBSCT during the second complete remission (CR) and had a minimum 10 month follow-up. The median age of the patients was 11 yr (range, 2-17 yr). Fifteen patients received the "MCVAC" regimen, one received high-dose MCNU+busulfan therapy, one received high-dose melphalan+VP-16, and one received melphalan+carboplatin+cytosine arabinoside+MCNU. None of these regimens included total body irradiation. Eight patients developed recurrence of the disease at 1 to 19 mo (median, 3 mo) after PBSCT. Patients in whom the first relapse occurred sooner, that is, within 16 mo of initial therapy, tended to have a better survival rate than those who developed relapse after 30 mo (six of seven survived versus four of 11; not significant). Although the preliminary data provided little conclusive information, it did suggest that incorporation of PBSCT in the salvage protocol of relapsed childhood ALL can be justified.

Adolescent↗
PubMed1994

Microdynamics of the phospholipid bilayer in cardiomyopathic hamster heart cell membrane.

To investigate the microdynamics and the structural architecture of the membrane phospholipid bilayer during the course of cardiomyopathy, membrane fractions were prepared from hearts of cardiomyopathic Syrian hamsters (BIO 14.6) aged 4, 18 and 31 weeks and compared with age-matched control hamsters (F1b). Membrane cholesterol, phospholipids and phospholipid fatty acids were measured by thin-layer chromatography, gas-liquid chromatography and high performance liquid chromatography. Microdynamics of the phospholipid bilayer were determined by a nanosecond fluorometer using pulsed excitation of a fluorescent probe, diphenyl-hexatriene. At the age of 4 weeks, there was no difference in lipid compositions and microdynamics between the BIO 14.6 and F1b. At the age of 18 weeks, saturated fatty acids, 18:0 and 22:0 increased and 20:0, 20:2 and 32:4 decreased in the BIO 14.6. At the age of 31 weeks, adding to the above changes in phospholipid fatty acids, unsaturated fatty acids 20:4 and 22:6 decreased, moreover membrane phospholipids, especially phosphatidylinositol and phosphatidylethanolamine significantly decreased. The viscosity and the wobbling angle of phospholipid molecules were decreased significantly. We have previously demonstrated that intracellular Ca2+ accumulation might be responsible for the pathogenesis of cardiomyopathy. Thus, we conclude that cardiomyopathic membrane may alter its structure and function with age. These alterations in cell membranes might be involved in the cardiac hypertrophy and dysfunction through impaired Ca2+ handling in cardiomyopathic hamsters.

Animals↗
PubMed1994

A comparison of in vitro platinum-DNA adduct formation between carboplatin and cisplatin.

DNA damage induced by carboplatin [cis-diammine-(1, 1-cyclobutanedicarboxylato)platinum(II)] was studied in vitro in comparison with cisplatin [cis-diammine-dichloroplatinum(II)]. The drug-induced DNA damage monitored by conformational change of pUC18 plasmid DNA showed that carboplatin required 10 times higher drug concentration and 7.5 times longer incubation time than those of cisplatin to induce the same degree of conformational change on plasmid DNA. The carboplatin-induced DNA damage was promoted by the increase of pH of the reaction mixture for platinum-DNA adduct formation. Sequence gel analysis of carboplatin-damaged DNA indicated that carboplatin attacked preferentially the sequence of GG >> AG > GA > GNG in the order, similarly to the case of cisplatin. DNA adducts formed by carboplatin were analyzed by HPLC after a sequential digestion of carboplatin-treated DNA with deoxyribonuclease I and S1 nuclease. A single peak having the same retention time as that of bifunctional adduct of (dGMP)2Pt(NH3)2 appeared by treating DNA with carboplatin. The adduct was assigned to be d(pGpG) > Pt(NH3)2. These results suggested that carboplatin induces the same platinum-DNA adducts as those induced by cisplatin, and that the difference in efficiency or kinetics of DNA damage between carboplatin and cisplatin is due to difference of aquation rate between them.

Base Composition↗
PubMed1994

Colony-stimulating factor-producing tumours: production of granulocyte colony-stimulating factor and interleukin-6 is secondary to interleukin-1 production.

We have reported that tumours producing colony-stimulating factor (CSF) also secrete interleukin-1 (IL-1) and IL-6. In the present study, we characterised the role played by IL-1 in CSF production. IL-1 receptor antagonist inhibited the production of granulocyte (G)-CSF and IL-6 by approximately 90% in CSF-producing human lung carcinoma cell lines. Similar results were obtained with hydrocortisone, which suppresses IL-1 gene expression. In contrast, 15 non-CSF-producing human lung carcinoma cell lines did not show detectable IL-1 production, although seven of them were induced to produce G-CSF and IL-6 by exogenous IL-1 alpha. Cell lines that responded to IL-1 alpha, including the CSF-producing lines, expressed receptors for IL-1 alpha. These results indicate that CSF-producing tumours can be characterised by their constitutive IL-1 production, IL-1 receptor expression and IL-1-dependent excess production of G-CSF and IL-6. Furthermore, transcription factor(s) may be involved in the abnormal IL-1 alpha production.

Blotting, Northern↗
PubMed1994

Characterization of a gene responsible for the Na+/H+ antiporter system of alkalophilic Bacillus species strain C-125.

An alkali-sensitive mutant, 38154, of the alkalophilic Bacillus sp. strain C-125 could not grow at an alkaline pH. The nucleotide sequence of a 3.7 kb parental DNA fragment that recovers the growth of 38154 at alkaline pH has four open reading frames (ORF1-4). By subcloning the fragment, we demonstrated that a 0.25 kb DNA region is responsible for the recovery. Direct sequencing of the mutant's corresponding region revealed a G to A substitution. The mutation resulted in an amino acid substitution from Gly-393 to Arg of the putative ORF1 product, which was deduced to be an 804-amino-acid polypeptide with a molecular weight of 89,070. The N-terminal part of the putative ORF1 product showed amino acid similarity to those of the chain-5 products of eukaryotic NADH quinone oxidoreductases. Membrane vesicles prepared from 38154 did not show membrane potential (delta psi)-driven Na+/H+ antiporter activity. Antiporter activity was resumed by introducing a parental DNA fragment which recovered the mutant's alkalophily. These results indicate that the mutation in 38154 affects, either directly or indirectly, the electrogenic Na+/H+ antiporter activity. This is the first report which shows that a gene responsible for the Na+/H+ antiporter system is important in the alkalophily of alkalophilic microorganisms.

Amino Acid Sequence↗
PubMed1994

Characterization of a Protease from a Psychrotroph, Pseudomonas fluorescens 114.

A psychrotrophic bacterium isolated from river sediment was identified as Pseudomonas fluorescens 114. It grew at 0 degrees C and optimally at 20 degrees C. The bacterium produced a protease with a molecular weight of 47,000, which was stable in the pH range of 5 to 9 and worked optimally between pH 6.5 and 10. Activity was optimal at 35 degrees C and was lost immediately at 50 degrees C and after 5 min at 45 degrees C. At 0, 10, and 20 degrees C, 24, 38, and 57% of optimal activity were observed, respectively.

Journal Article↗