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Biomedical subjects

Y Takeda

Publications and source records attributed to Y Takeda.

At least 703 records · Page 39Linked to original sources

[Evaluation of bone mineral turnover in children with nephrotic syndrome--the implications of original disease and the effects of corticosteroids on bone metabolism].

A long term corticosteroids (CS) treatment is often required for children with nephrotic syndrome (NS), which may affect their bone metabolism. In this study we evaluate the effects of CS, and also the implication of the character of NS itself on bones. We divided sixteen cases of idiopathic NS in children into two groups, such as CS responder group (R; male/female = 8/4, mean age 10.9 years old), and CS non-responder group (NR; male/female = 4/0, mean age 10.2 years old). We measured the bone mineral density of lumber vertebrae by quantitative computed tomography (QCT), some biochemical and endocrinological markers for about half a year. The bone mineral density was significantly decreased soon after the beginning of CS therapy. A significant decrease in the serum osteocalcin level and a slight tendency for an increase in urinary excretion of the free hydroxyproline in the both R and NR groups. In addition, NR group showed hypocalcemia, a decrease in the serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3, and a slight tendency for an increase in the C-parathyroid hormone and highly sensitive parathyroid hormone levels. In conclusion, the results suggested that the effects of CS on bone metabolism were mainly the suppression of bone formation. In addition, the effects of CS and the character of NS itself should be evaluated separately when we consider about bone metabolism in children with NS and in greater detail.

Administration, Oral↗

[Clinical assessment of meningeal carcinomatosis; from the viewpoint of the analysis of intracranial pressure].

Meningeal carcinomatoses (MC) have been mainly studied from the viewpoint of the analysis of intracranial pressure (ICP). From the CT findings, ten patients were divided into two groups: group I, six patients showed characteristics of MC; group II, four showed normal characteristics. Ventricular fluid pressure (VFP) was continuously measured by a controlled ventricular drainage tube using a Spectramed P-10EZ at 3.1 +/- 2.1 months after the onset of the neurological symptoms. At the same time as VFP monitoring, the CBF by 133Xe method was measured in 5 cases and RI cisternography was performed in 9 cases. "A" wave was observed in 5 cases of group I and in 3 cases of group II. "B" wave was observed in all cases of both groups. In all 10 cases, the occurrence rate of both A and B waves (ORA, ORB) were high, averaging 2.34 +/- 0.54 times/hour, 74.0 +/- 16.6% time, respectively. Mean resting pressure(R) and mean peak pressure(P) tended to be high, averaging 28.8 +/- 12.2mmHg, 58.9 +/- 13.7mmHg, respectively. Mean cerebral perfusion pressure corresponding with R and P (CPPR, CPPP) was markedly reduced, averaging 79.1 +/- 15.9mmHg, 50.9 +/- 12.7mmHg, respectively. Both ORA and ORB in group I were higher, and both CPPR and CPPP in group 1 were lower, than in group II. Statistically, this is significant. Both R and P in Group I tended to be higher than in group II. This has no statistical significance. CBF in all 5 cases averaged 34.8 +/- 8.4ml/100g/min. No significant difference in the impairment of CBF was found between both groups. RI cisternography showed delayed clearance in all 9 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A case of cortical deafness with bilateral putaminal hemorrhage].

A 56 years old right-handed female, a housewife, had suffered from right putaminal hemorrhage which had been treated surgically in July, 1985. Since it was difficult to approach the trans-sylvian fissure, evacuation of the hematoma was performed transcortically through the superior temporal gyrus. She was neurologically free and lived normally until she suddenly became completely deaf in April, 1991. On admission, she was alert, well oriented and spontaneously stated that she was deaf. She showed no response to verbal commands or loud noises but followed complex written commands. No other neurological deficit was observed. In addition to an irregular low-density area in the right temporal lobe, CT scan revealed a left putaminal hemorrhage. Audiological testing disclosed pure tone thresholds to be below 90db on both sides. Auditory brain stem response (ABR) showed waves I to VI in normal latency ranges, but wave VII was not observed. She was treated conservatively. Although her hearing loss had been gradually improving for 1 month, she suffered from word deafness, an inability to comprehend speech, for the following 2 months. Clinical features, CT findings as well as results of ABR suggest that hearing loss observed in this case, cortical deafness, was presumably due to bilateral damage of acoustic radiation of the temporal lobe. It was also suggested that, although she was asymptomatic, cortical and subcortical damage to the right temporal lobe following evacuation of the putaminal hematoma may have been extensive. During surgical procedures for evacuation of the putaminal hematoma, it has to be always kept in mind not to damage the auditory cortex and its radiations.

Cerebral Hemorrhage↗

Detection of topoisomerase I gene point mutation in CPT-11 resistant lung cancer cell line.

CPT-11, a recently developed topoisomerase I (Topo I) inhibitor, attracts the attention not only of basic researchers but also of clinicians because of its high antitumor activity. The CPT-11 resistant human lung cancer cell line, PC-7/CPT, showed 10-fold resistance compared to parental cell line, PC-7. The total activity of Topo I in the resistant cell line was one fourth that of the parental sensitive cell line. The Topo I from the resistant cells was also 5-fold more resistant to the inhibitory effect of CPT-11 than that of the parental cells. We speculated that the alteration of the Topo I gene may be responsible for the change in topoisomerase activity of the CPT-11 resistant cell line. Therefore, we analyzed the mutation of Topo I gene using the method of single strand conformation polymorphism of polymerase chain reaction and the reverse transcriptase. We divided Topo I cDNA into ten fragments which overlapped each other and covered whole coding sequences of the Topo I cDNA. We observed mobility shift of two fragments in the PC-7/CPT, suggesting the presence of some mutations in these fragments. We performed the direct-sequencing of these portions by the dideoxy chain termination method and observed an altered sequence having a G to A base change in PC-7/CPT. This base substitution results in replacement of the conserved threonine at 729 position with alanine. These results suggest that the point mutation of Topo I gene is related to the decreases of Topo I activity and the sensitivity to Topo I inhibitor in PC-7/CPT cells.

Antineoplastic Agents, Phytogenic↗

A new endo-beta-galactosidase acting on the Gal beta 1-3Gal linkage of the proteoglycan linkage region.

A new type of endo-beta-galactosidase acting on the linkage region of peptidochondroitin sulfate was isolated from the mid-gut gland of the mollusk Patinopecten. The purification procedure included ammonium sulfate precipitation, Sephacryl S-200HR gel filtration, DEAE-Sephacel chromatography, and TSKgel Phenyl-5PW RP high performance liquid chromatography. The purified enzyme was free from exoglycosidases, sulfatases, and phosphatases. The specificity of the enzyme was as follows. 1) It acted on the internal galactoside linkage of sugar chains; 2) it specifically hydrolyzed the galactosylgalactose (Gal beta 1-3Gal) linkage, but not the galactosylxylose (Gal beta 1-4Xyl) linkage in the linkage region of peptidoglycans; 3) the enzyme activity was unaffected by the type of glycosaminoglycan, chondroitin sulfate, dermatan sulfate or heparan sulfate used as a substrate; 4) keratan sulfate and some oligosaccharides from glycolipid were not degraded by the enzyme. These properties of the endo-beta-galactosidase characterize it as a new endo-beta-galactosidase with unique specificity.

Animals↗

Thermodynamics of Cro protein-DNA interactions.

Using a highly sensitive pulsed-flow microcalorimeter, we have measured the changes in enthalpy and determined the thermodynamic parameters delta H, delta S degree, delta G degree, and delta C(p) for Cro protein-DNA association reactions. The reactions studied include sequence-nonspecific DNA association and sequence-specific DNA associations involving single- and multiple-base alterations and/or single-amino acid alteration mutants. (i) The association of Cro protein with nonspecific DNA at 15 degrees C is characterized by delta H = +4.4 kcal.mol-1 (1 cal = 4.18J), delta S degrees = 49 cal.mol-1.K-1, delta G degrees = -9.7 kcal.mol-1, and delta Cp congruent to 0; the association with specific high-affinity operator OR3 DNA is characterized by delta H = +0.8 kcal.mol-1, delta S degree = 59 cal.mol-1.K-1, delta G degree = -16.1 kcal.mol-1, and delta Cp = -360 cal.mol-1.K-1, respectively. Both nonspecific and specific Cro-DNA associations are entropy-driven. (ii) Plots of delta H vs. delta Cp and delta S degree vs. delta Cp for the 20 association reactions studied fall into two correlation groups with linear slopes of +9.4 K and -20.5 K and of -0.03 and -0.14, respectively. These regression lines have common intercepts, at the delta H and delta S degree values of nonspecific association (where delta Cp congruent to 0). The results suggest that there are, at least, two distinct conformational subclasses in specific Cro-DNA complexes, stabilized by different combinations of enthalpic and entropic contributions. The delta G degree and delta Cp values form an approximately single linear correlation group as a consequence of compensatory contributions from delta H and delta S degree to delta G degree and to delta Cp. Cro protein-DNA associations share some similar thermodynamic properties with protein folding, but their overall energetics are quite different. Although the nonspecific complex is stabilized predominantly by electrostatic forces, it appears that H bonds, van der Waals contacts, hydrophobic effects, and charge interactions all contribute to the stability (delta G degree and delta Cp) of the specific complex. (iii) The variations in the values of the thermodynamic parameters are in general accord with our knowledge of the structure of the Cro-DNA complex.

Base Sequence↗

A new type of mitogenic factor produced by Streptococcus pyogenes.

A new type of mitogenic factor (protein) was purified from the culture supernatant of a strain of Streptococcus pyogenes by SP-Sephadex C-25 column chromatography, preparative isoelectric focusing and reversed-phase high-performance liquid chromatography. The purified factor, showing marked mitogenic activity in rabbit peripheral blood lymphocytes, gave a single-band staining for protein on SDS-PAGE. The molecular weight of the purified mitogenic factor was determined to be 25,370, which was different from those calculated from reported amino acid sequences deduced from 4 different nucleotide sequences of 3 kinds of streptococcal pyrogenic exotoxins (two SPEAs, SPEB and SPEC). The amino acid sequence of the N-terminal region of the purified mitogenic factor was determined to be Gln-Thr-Gln-Val-Ser-Asn-Asp-Val-Val-Leu-Asn-Asp-Gly-Ala-Ser-Lys-Tyr-Leu- Asn-Glu - Ala-, which was also different from the reported N-terminal sequences deduced from the 4 different nucleotide sequences. These data indicate that this mitogenic factor is distinct from the already described streptococcal pyrogenic exotoxins.

Amino Acid Sequence↗

[11 beta-hydroxysteroid dehydrogenase and steroid receptors].

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD), as its name implies, is the enzyme responsible for the conversion of cortisol to cortisone, and of corticosterone to 11-dehydrocorticosterone. Ulick et al. reported the detailed investigation of a patient with the syndrome of apparent mineralocorticoid excess (AME), who had the stigmata of florid hyperaldosteronism but low normal or suppressed levels of renin and aldosterone. Such patients show marked abnormalities of cortisol metabolism. From a series of studies, the consensus grew that AME reflects the absence, or very low activity, of 11 beta-HSD in the kidney of affected patients. In addition to providing a framework for understanding the pathogenesis of AME, these studies prompted a re-evaluation of other areas of steroid in the kidney. Glycyrrhetinic acid, the active principle of liquorice and carbenoxolone, exerted its mineralocorticoid action not by a direct effect on mineralocorticoid receptors but by inhibiting renal 11 beta-HSD, thus producing a mild, drug-induced form of AME. Recently Monder et al. reported the cloning and expression of rat and human cDNA encoding corticosteroid 11 beta-dehydrogenase. The physiological role of 11 beta-HSD in conferring aldosterone-selectivity on otherwise non-selective type I receptors has been focused using the genetic method in addition to the biological ones.

11-beta-Hydroxysteroid Dehydrogenases↗

[Quantitative evaluation of liver function using 99mTc-GSA in rats with liver injury induced by ischemia-reperfusion].

We evaluated quantitatively the liver injury of rats induced by ischemia-reperfusion, using 99mTc-DTPA-Galactosyl-Human-Serum-Albumin (99mTc-GSA). The vessels of the left lobe were clamped for 5, 10, or 45 minutes followed by 15 minutes reperfusion. Then, 99mTc-GSA was intravenously administered (170 micrograms/kg body weight) to rats. Two compartment analysis was made on measurement curves in the heart and liver to obtain clearance parameters. Significant difference was observed between the ischemic group (clamped for 10 and for 45 minutes) and the control. These results suggest that 99mTc-GSA is useful in the estimation of liver injury produced by ischemia-reperfusion.

Animals↗

Endothelin-1 release from the mesenteric arteries of cyclosporine-treated rats.

The release of endothelin-1 from mesenteric arteries from cyclosporine-treated rats was measured by a specific enzyme immunoassay after purification of the perfusate on an immunoaffinity column. Mesenteric arteries from cyclosporine-treated rats (25 mg/kg per day for 6 weeks) released a significantly larger amount of endothelin-1 than arteries from vehicle-treated control rats (P less than 0.05). Serum creatinine levels were not significantly different in the two groups. These findings indicate that cyclosporine is a potential inducer of endothelin release from the mesenteric artery.

Animals↗

Molecular genetic analysis of HLA-DR and HLA-DQ genes among anti-U1-70-kd autoantibody positive connective tissue disease patients.

OBJECTIVE: We have recently found that the presence of autoantibodies against the 70-kd polypeptide of U1 RNP (U1-70-kd) is associated with HLA-DR4 and DR2. To further characterize this association, we performed a molecular genetic analysis of HLA-DR and DQ genes among patients with autoantibodies against U1-70-kd. METHODS: The polymerase chain reaction (PCR), sequence-specific oligonucleotide hybridization, and solid-phase direct DNA sequencing of PCR-amplified DNA were utilized to analyze HLA-DRB1, DRB5, DQA1, and DQB1 genes. RESULTS: A comprehensive analysis of HLA-DRB1, DRB5, DQA1, and DQB1 from 27 patients and controls identified shared amino acids FDYFYQA (Phe, Asp, Tyr, Phe, Tyr, Gln, Ala) at positions 26, 28, 30-32, 70, and 73 of HLA-DRB1 on disease-associated haplotypes. CONCLUSION: A common cluster of shared amino acids, or a shared epitope, identified within HLA-DRB1 among anti-U1-70-kd autoantibody positive connective tissue disease patients may be important in regulating an autoimmune response to the U1-70-kd antigen.

Amino Acid Sequence↗

The replication origin of proplastid DNA in cultured cells of tobacco.

When tobacco suspension culture line BY2 cells in stationary phase are transferred into fresh medium, replication of proplastid DNA proceeds for 24 h in the absence of nuclear DNA replication. Replicative intermediates of the proplastid DNA concentrated by benzoylated, naphthoylated DEAE cellulose chromatography, were radioactively labelled and hybridized to several sets of restriction endonuclease fragments of tobacco chloroplast DNA. The intermediates hybridized preferentially to restriction fragments in the two large inverted repeats. Mapping of D-loops and of restriction fragment lengths by electron microscopy permitted the localization of the replication origin, which was close to the 23S rRNA gene in the inverted repeats. The replication origins in both segments of the inverted repeat in tobacco proplastid DNA were active in vivo.

Autoradiography↗