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Biomedical subjects

K Tanabe

Publications and source records attributed to K Tanabe.

At least 379 records · Page 21Linked to original sources
PubMed1992

[Optimal dose of cyclosporin in living related kidney transplantation].

We performed in total 528 kidney transplantations from Feb. 1983 to Dec. 1988 in Kidney Center of Tokyo Women's Medical College. Of the 528 kidney transplantations, 450 were living related kidney transplantations. The living related renal transplant recipients treated with CYA were divided into 3 groups: high dose CYA double drug therapy group (group 1), high dose CYA triple drug therapy group (group 2) and low dose CYA triple drug therapy group (group 3). Group 1 (n = 263) was treated with CYA (initial dose 12 mg/kg) and methylprednisolone (MP). Group 2 (n = 106) was treated with CYA (initial dose 10 mg/kg), MP and azathioprine (AZ) (1 mg/kg). Immunosuppression of group 3 (n = 81) consisted of CYA (initial dose 6 mg/kg), MP and AZ (2 mg/kg) (or mizoribine (MZ) (3-5 mg/kg). CYA serum trough level (polyclonal) was lowered according to the initial dose of CYA, and in particular trough level in group 3 was controlled at a low level (50-150 ng/ml in induction phase) to reduce CYA nephrotoxicity. However, even if strict control of serum trough level was accomplished, we could not get improvement of renal function in Group 3. Group 3 had more frequent and severe accelerated acute rejections (AAR) than the other groups. These data showed that inadequate immunosuppression in group 3 caused more frequent and severe rejection episodes. Also, renal biopsy revealed CYA nephrotoxicity even in group 3 and this nephrotoxicity may have been caused by ischemic damage by severe rejections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Pentacoordinate oxyphosphorane intermediate always exists in aqueous solution.

Gas-phase ab initio calculations indicate that dianionic pentacoordinate oxyphosphoranes do not have a kinetically meaningful intermediate. The simplest oxyphosphorane PO5H3(2-) has the least tendency to have a pentacoordinate intermediate. However, it does have a pentacoordinate intermediate when it is solvated with six water molecules. These results support the hypothesis that the phosphoryl transfer reactions take place via pentacoordinate intermediate not only in acidic but also in basic media.

Kinetics↗
PubMed1992

[The relation of physical and mental stress to magnesium deficiency in patients with variant angina].

In this study we assessed the role of psychological factor in the etiology of coronary vasospasm using the Cornell Medical Index (CMI), focusing attention on the relationship between stress and serum magnesium (Mg). The study subjects consisted of 25 patients with variant angina (VA), 32 with old myocardial infarction without vasospasm (OMI), and 34 healthy men (controls). On a neurosis-discriminative diagram of CMI, areas I and II were considered as normal and areas III and IV were considered to be a neurotic disorder. The stress test included exercise and a quiz. Exercise test was performed in 8 patients with VA, 6 with OMI, and 5 controls, and a quiz was given to 4 patients with VA. Plasma catecholamines [noradrenaline (NA), adrenaline (Ad), dopamine], aldosterone, adrenocorticotropic hormone (ACTH) and serum electrolytes (Mg, Ca, Na, K, Cl) were measured before and after exposures to stress. The following results were obtained: 1) Of the patients with VA, 40.0% were categorized as area III or IV, compared to 18.7% of the patients with OMI, and 2.9% of the control subjects. 2) Among patients with VA, 64.0% exhibited anxiety states compatible with a psychological disorder. 3) NA and Ad were increased after exercise stress. 4) Serum Mg and Ca were also increased after exposure to exercise stress in all groups, and the degrees of these changes were correlated to the exercise intensity. The %delta Mg/%delta NA ratio, a parameter of the effect of catecholamine on the serum Mg, was greater in patients with VA than in those with OMI and the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Development of computer software in ramp slope controller for treadmill ergometer].

We developed computer software to produce a treadmill ramp protocol through which oxygen uptake (VO2) is increased in a linear fashion, thus enabling subjects to walk until the end of exercise. The developed software simulates the increases in speed and grade of the treadmill displayed on a personal computer screen, and produces the ramp protocol by arbitrarily determining the variables of the following formula: 1) Increments of VO2 = a1t+a2 (ml/min/kg) [t = exercise time (min)] 2) Predicted VO2 by speed (S) and grade (G) = a3S2 + a4G2 + a5SG + a6S + a7G + a8 (ml/min/kg) [S = speed (km/hr); G = grade (%)] 3) Speed suitable for desired exercise time (S or S2) = a9t2 + a10t + a11 (km/hr) 4) Grade suitable for desired exercise time (G or G2) = a12t2 + a13t + a14 (%) In this study, the increment of VO2 was determined by considering the subject's exercise capacity (VO2 = 4t + 7 ml/min/kg), using the Ito's formula (VO2 = 0.067S2 + 0.289SG + 7.73 ml/min/kg). The formula of grade was determined following the formula arbitrarily (G2 = 25t + 5%). The formula of speed for exercise time was calculated automatically. The new ramp protocol, which was applied to 10 healthy subjects (mean age: 24.8 +/- 4.8 years old), disclosed a similar linear relationship between the predicted VO2 and the measured VO2.

Adult↗
PubMed1992

[Hemodynamic effects of alcohol ingestion on anaerobic threshold].

Hemodynamic influence of alcohol ingestion was evaluated using expiratory gas analysis in 10 healthy men whose mean age was 26.1 +/- 2.2 years. Protocol of the control study (C) was as follows: Oxygen uptake (VO2) at rest and during warm-up, anaerobic threshold (AT) and peak VO2 were measured with ramp protocol using a bicycle ergometer. AT was determined by the V-slope method. Protocol of the alcohol study (A) was as follows: On a different day, the same parameters as C were measured after the ingestion of 0.7 g ethanol per kg body weight. The following results were obtained: 1) The serum ethanol concentration was 79.1 +/- 13.5 mg/dl. 2) VO2 in the resting state was higher in A than in C (4.51 +/- 0.74 vs 3.61 +/- 0.62 ml/min/kg), (p < 0.05). 3) AT and peak VO2 in C and A were 17.15 +/- 2.76, 32.09 +/- 6.77 ml/min/kg and 15.43 +/- 2.86, 29.60 +/- 5.35 ml/min/kg, respectively. 4) Exercise time to the AT in C and A was 222.90 +/- 37.32 and 172.0 +/- 33.1 sec, respectively. 5) The heart rate was higher in A than in C. It was concluded that peak VO2 and AT decreased by alcohol ingestion.

Adult↗
PubMed1992

Analysis of glycated albumin in postmortem blood samples as the diagnostic parameters of diabetes mellitus.

Glycated hemoglobin (GHb), fructosamine and glycated albumin (GA) in hemolytic sera from cadavers were analyzed for the postmortem diagnosis of diabetes mellitus. The levels of GHb and fructosamine were determined by boronate affinity chromatography and colorimetry, respectively. Albumin fraction was isolated from the samples by Affi-Gel Blue affinity chromatography. The glycated and non-glycated molecules were separated by boronate affinity chromatography, and quantitated by bromcresol green method. Fructosamine could not be analyzed from highly hemolytic sera containing more than 10 g/l hemoglobin. In such samples, the levels of GHb and GA were deviated from the standard values, indicating their postmortem degradation. In less hemolytic samples, GA was as informative as GHb and fructosamine for the diagnosis of diabetes mellitus.

Blood Specimen Collection↗
PubMed1991

Cloning and sequencing of the gene encoding the large subunit of glutathione synthetase of Schizosaccharomyces pombe.

The gene for the large subunit of glutathione synthetase (EC 6.3.2.3) of Schizosaccharomyces pombe was cloned from a S. pombe genomic DNA library by complementation of cadmium hypersensitivity of a glutathione synthetase deficient mutant of S. pombe. A long open reading frame was found in the cloned DNA sequence. Amino acid sequence predicted from the long open reading frame coincided with amino acid sequences of peptides obtained by V8 protease digestion of the large subunit of the purified glutathione synthetase. The glutathione synthetase deficient mutant which harbored plasmids containing the glutathione synthetase large subunit gene exhibited glutathione synthetase activity higher than the activity in the wild type strain, though the plasmid did not contain the gene for the small subunit of the enzyme.

Amino Acid Sequence↗
PubMed1991

Development-dependent expression of isozymogens of monkey pepsinogens and structural differences between them.

The developmental changes in the expression of monkey pepsinogens and structural differences between the polypeptides were investigated. Monkey pepsinogens included five different components, namely, pepsinogens A-(1-4) and progastricsin. Their respective relative levels and specific activities changed significantly during development. The sequential expression of genes for type-A pepsinogens was particularly noteworthy. Pepsinogen A-3 was the major zymogen at the newborn stage, accounting for nearly half of the total pepsinogens at this stage. Pepsinogen A-2 became predominant at the 4-month stage, and pepsinogen A-1 predominated at the juvenile and adult stages. Enzymatic properties of pepsinogens A-1, A-2 and A-3 were similar but not identical to those of pepsinogen A-4 and progastricsin, in particular with respect to the activation processes. Each pepsin digested various protein substrates but some differences in specificity were evident. cDNA clones for five pepsinogens were isolated, and the nucleotide sequences were determined. Each cDNA contained leader, pro, and pepsin regions that encoded 15, 47, and 326 amino acid residues, respectively, with the exception of the cDNA for progastricsin in which the pro and pepsin regions encoded 43 and 329 amino acid residues, respectively. Type-A pepsinogens exhibited a high degree of similarity, with over 96% of bases in the nucleotide sequences of the protein-coding regions being identical. Northern analysis revealed that the level of expression of genes for type-A pepsinogens and for progastricsin was significant at the fetal stage and increased with development.

Aging↗
PubMed1991

Inhibition of topoisomerase II by antitumor agents bis(2,6-dioxopiperazine) derivatives.

Several recently developed derivatives of bis(2,6-dioxopiperazine) have been shown to be new antitumor agents and are currently under clinical trials. We found that the mother compound of the bis(2,6-dioxopiperazine)s, ICRF-154, and its derivatives, ICRF-159, ICRF-193, and MST-16, are all inhibitors of mammalian type II DNA topoisomerase. By decatenation assay using kinetoplast DNA from Crithidia fasciculata, inhibition of purified calf thymus topoisomerase II by these compounds was investigated. Potency of inhibition was in the following order: ICRF-193 greater than ICRF-154 = ICRF-159 greater than MST-16. The doses giving 50% inhibition were 2, 13, 30 and 300 microM, respectively, for these compounds. ICRF-193, the most potent inhibitor, however, did not inhibit topoisomerase I at concentrations up to 300 microM. Addition of excess enzyme, but not of the substrate DNA, overcame the inhibition by ICRF-193. The drug did not stimulate the formation of cleavable complex between DNA and the enzyme. Furthermore, ICRF-193 even inhibited the formation of enzyme-mediated DNA cleavage induced by etoposide or 4'-[9-acridinylamino)methanesulfon-m-anisidide. These observations, together with the finding that ICRF-193 did not intercalate into DNA, suggest that ICRF-154 and related compounds are specific inhibitors of topoisomerase II with different modes of action: i.e., they interfere with some step(s) before the formation of the intermediate cleavable complex in the catalytic cycle. This is a property quite distinct from previously known cleavable complex-forming type topoisomerase II-targeting antitumor agents such as acridines, anthracyclines, and epipodophyllotoxins, but rather, mechanistically similar to the recently reported group of inhibitors that includes merbarone, aclarubicin, and fostriecin.

Antineoplastic Agents↗
PubMed1991

Inhibition of intracellular topoisomerase II by antitumor bis(2,6-dioxopiperazine) derivatives: mode of cell growth inhibition distinct from that of cleavable complex-forming type inhibitors.

In the accompanying paper (K. Tanabe, Y. Ikegami, R. Ishida, and T. Andoh, Cancer Res., 51: 4903-4908, 1991), we showed that ICRF-154 and -193, dioxopiperazine derivatives, inhibited the activity of purified topoisomerase II, without formation of a cleavable DNA-protein complex. In order to see whether ICRF-154 and ICRF-193 affect cellular topoisomerase II in situ or not, we examined the effect of these drugs on etoposide (VP-16)-induced, topoisomerase II-mediated DNA breaks in RPMI 8402 cells by alkaline sedimentation analysis. When RPMI 8402 cells were exposed to VP-16 in the presence of ICRF-154 or ICRF-193 for 1 h, VP-16-induced DNA strand breaks were greatly inhibited by both ICRF compounds. In parallel with this observation, VP-16-induced growth inhibition was also reversed by ICRF-193. Exposure of cells to ICRF-154 resulted in a progressive accumulation of cells with 4C DNA content. Although mitotic index did not significantly increase, mitotic abnormalities were seen in cells exposed to ICRF-193 or ICRF-154: all mitotic cells exhibited early mitotic figures with fewer condensed and entangled chromosomes. The most sensitive phase of the cell cycle to ICRF-154 was the G2-M. ICRF-154 did not affect the spindle formation. However, abnormally oriented spindles were observed in drug-treated cells in parallel with the appearance of multinucleated cells. The results suggest that ICRF-154 and -193 inhibit topoisomerase II activity in RPMI 8402 cells, and this effect resulted in the appearance of cells in G2 and early M phase with fewer condensed and entangled chromosomes and of cells with multilobed nuclei.

Cell Cycle↗
PubMed1991

Rate limiting P-O(5') bond cleavage of RNA fragment: ab initio molecular orbital calculations on the base-catalyzed hydrolysis of phosphate.

In order to examine the energetics in base-catalyzed hydrolysis of RNA, a tentative pentacoordinated intermediate (3) has been characterized by molecular orbital calculations. Ab initio studies at the level of 3-21G* indicate that, under the Cs symmetry restricted conditions, the P-O(2) bond possessing antiperiplanar (app) lone pair electrons (Ip) on the equatorial oxygen (O(3)) can be cleaved with almost no barrier (TS1 transition state; 0.08 kcal mol-1), from the pentacoordinated intermediate (3) of base-catalyzed hydrolysis of phosphate, compared to the P-O(5) bond (TS2 transition state; 28.9 kcal mol-1) which lacks app lp assistance from O(3). The dianionic intermediate, however, loses the TS1 transition state thus its property as an intermediate when the Cs restriction is removed. The analysis of the entire potential energy surface enables us to conclude that, in a related system examined by Lim and Karplus [1990) J. Am. Chem. Soc., 112, 5872-5873) for attack by OH- on ethylene phosphate monoanion, the TS1 transition state had also been lost and thus no intermediate had been found. These results further support our earlier conclusions (Taira et al. (1990) Protein Engineering, 3, 691-701) of rate limiting transition state possessing extended P-O(5') bond breaking character (the TS2 transition state) in the base-catalyzed hydrolysis of RNA. Finally, although the lack of 2',3' -migration of phosphate moieties in basic condition appears to be in accord with the short-lived intermediate, it really does not prove the absence of the intermediate. The detail will be discussed in the text.

Hydrolysis↗
PubMed1991

A study on the inactivation of wheat carboxypeptidase. Implication of the transient active monomer and the half-site reactivity.

The mechanism of inactivation of carboxypeptidase from wheat at high pH was studied kinetically and spectrophotometrically. Inactivation of wheat carboxypeptidase is characterized by initial, transient high activity, soon followed by loss of activity, accompanied by an increase in both fluorescence intensity and anisotropy and a decrease in circular dichroism. A scheme was proposed in which the enzyme undergoes dissociation into monomers, the total activity of which becomes twice that of the normal dimer on a mass basis, and soon further denatures and aggregates. Treatment of the enzyme with a bifunctional reagent partly prevented denaturation of the monomer and hence increased the peptide synthetic activity.

Carboxypeptidases↗
PubMed1991

Evidence that Ser-82 is a unique phosphorylation site on vimentin for Ca2(+)-calmodulin-dependent protein kinase II.

We identified the sites on vimentin that are phosphorylated by Ca2(+)-calmodulin-dependent protein kinase II (CaM-kinase II). Sequential analysis of the purified phosphopeptides demonstrated that the sites are -Thr-Arg-Thr-Tyr-Ser(PO4)38-Leu-Gly-Ser-Ala- and -Val-Arg-Leu-Leu-Gln-Asp-Ser(PO4)82-Val-Asp-, which are located within the amino-terminal head domain of vimentin. For Ser-82 but not Ser-38, the proposed CaM-kinase II recognition amino acid sequence (Arg-X-X-Ser/Thr) was not found. Studies with a series of synthetic peptide analogs corresponding to Ser-82 and its surrounding amino acid sequence indicate that Asp-84 acts as an essential substrate specificity determinant for the Ser-82 phosphorylation by CaM-kinase II. The CaM-kinase II recognition site may be more extensive than heretofore determined.

Amino Acid Sequence↗
PubMed1991

Magnesium content of erythrocytes in patients with vasospastic angina.

The possibility that a magnesium deficiency might be the underlying cause of vasospastic angina (VA) and the efficacy of Mg administration in its treatment were studied. Subjects included 15 patients with VA and 18 healthy subjects as the control group. The erythrocyte Mg content was measured by atomic absorption, and serum Mg was measured by conventional chemical assay. The efficacy of Mg administration was studied in seven patients with VA. The results were as follows: a) The mean erythrocyte Mg content was less in the group with frequent episodes of angina (1.59 +/- 0.11 mg/dl) than in the group without angina (2.11 +/- 0.38 mg/dl, p less than 0.01) and in the control group (2.22 +/- 0.29 mg/dl, p less than 0.01). There was no significant difference between the control group and patients of each group with respect to serum Mg. b) Coronary arterial spasm was induced by ergonovine maleate in seven patients and was completely inhibited by the administration of Mg sulfate (40-80 mEq, hourly) in six of these patients; in the remaining patient neither obvious ST change nor chest pain occurred. Thus, it was concluded that the measurement of erythrocyte Mg content is useful to determine how easily vasospasm might occur in VA and that the administration of Mg might be developed as a new therapy for spasm associated with a low erythrocyte Mg content.

Aged↗
PubMed1991

2-Chlorodeoxyadenosine inhibits the repair of DNA double-strand breaks and does not inhibit the repair of DNA single-strand breaks in X-irradiated Chinese hamster V79 cells.

The exposure of log-phase Chinese hamster V79 cells to 2-chlorodeoxyadenosine (CdA) for 3 h after X irradiation enhanced the lethal effects of X-rays in a concentration-dependent manner. The enhancement of the killing efficiency of X-rays by CdA was mainly observed in the reduction of quasi-threshold doses (Dq) of the dose-response curves. When the ability of CdA to inhibit the repair of X-ray-induced double- and single-strand breaks (dsb and ssb) of DNA was investigated by neutral- and alkaline-filter elution techniques, respectively, it was observed that 90% of dsb were rejoined in the absence of CdA within 30 min after X irradiation and 15-40% of dsb rejoining was suppressed by co-incubation of the cells with 5-10 microM of CdA for 3 h after X irradiation, whereas almost 100% of ssb were rejoined within 15 min regardless of the presence or absence of CdA. From these results it was concluded that CdA interfered exclusively with the repair of DNA dsb in X-irradiated Chinese hamster V79 cells and thereby increased the lethality of X-rays.

2-Chloroadenosine↗
PubMed1991

Efficient production of biologically active human prolactin in Escherichia coli.

To obtain an adequate amount of human prolactin (hPRL) for elucidation of the structure-function relationship, we have expressed the hPRL cDNA in Escherichia coli (E. coli) by using a high-expression vector. The vector contained a chimeric gene encoding a fusion of protein A, a peptide sensitive to collagenase digestion and hPRL, which was inserted downstream of the right direction promotor of lambda phage. The resulting protein fusion was purified through three column chromatographies of immunoglobulin G-linked Sepharose 4B, DEAE-5PW, and phenyl-5PW. In a typical experiment, a final sample with a purity of more than 80% was obtained with a recovery of more than 40% judged by enzyme-linked immunosorbent assay (ELISA). The fusion thus obtained was digested with collagenase, and protein reactive to anti-hPRL antibody was purified through phenyl-5PW column chromatography. The hPRL sample was found to be identical to authentic hPRL with respect to the amino acid composition and an N-terminal sequence of 20 residues, except that it contained an additional four amino acids at the N-terminal end. This peptide was presumed to be derived from the collagenase-target sequence. The hPRL thus obtained was found to be as active as the authentic hormone either immunologically judged by ELISA or biologically judged by the growth stimulatory effect on rat Nb2 lymphoma cells.

Amino Acid Sequence↗
PubMed1991

Ultrastructural changes associated with reversal of chloroquine resistance by verapamil in Plasmodium chabaudi.

Reversal of chloroquine (CQ) resistance by verapamil, a Ca2+ antagonist, has been shown in CQ-resistant human and rodent malaria parasites. Here, we report ultrastructural changes associated with this phenomenon in CQ-resistant Plasmodium chabaudi (AS strain) after infected mice were administered CQ and verapamil. At parasitaemias of 5-7%, CQ at 6 mg/kg caused little morphological effect on CQ-resistant parasites. In contrast, co-administration of CQ and verapamil at 50 mg/kg induced swelling of food vacuoles with clumped pigment at 2.5 h. Morphological changes other than food vacuole enlargement occurred at 21 and 45 h: disappearance of endoplasmic reticulum, formation of myelin structures, focal cytoplasmic vacuolization and coarse clumping of electron-dense material in nuclei. These structural changes appeared to be very similar to those observed in CQ-sensitive P. chabaudi in mice injected with CQ alone or CQ plus verapamil. On the other hand, verapamil at 50 mg/kg alone did not induce any effect on both CQ-sensitive and CQ-resistant P. chabaudi. These results suggest that swelling of the food vacuoles is an initial event associated with reversal of CQ-resistance by verapamil.

Animals↗