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Biomedical subjects

M Kishida

Publications and source records attributed to M Kishida.

At least 37 records · Page 2Linked to original sources

Serum total cholesterol of new students enrolled at Okayama University: trend during 1989-1998.

To clarify the trend of hypercholesterolemia in Japanese adolescents, we investigated the serial changes in body mass index (BMI) and serum total cholesterol (TC) concentrations among 5,700 new students enrolled at Okayama University in 1989, 1993, and 1998. After confirming the stability of the TC assay of serum samples stored at -80 degrees C, we measured serum TC levels in stored serum samples using an automated assay system. Although serum TC levels were higher in females than in males, these levels correlated weakly and positively with BMI (r = 0.21, P < 0. 001) in males but not in females. Serum TC concentrations progressively increased from 1989-1998 in both sexes, irrespective of changes in BMI. In subjects with normal BMI (> or = 19 and < 23 kg/m2), a significant increase in serum TC was noted from 1989-1998 in both males (157.2 +/- 1.0 to 163.6 +/- 0.9 mg/dl) and females (172.0 +/- 1.1 to 175.6 +/- 1.0 mg/dl). Our results indicate on increased incidence of hypercholesterolemia even in nonobese young Japanese adolescents. A concerted effort by health and education officials together with parents is necessary to prevent a further rise in the incidence of hypercholesterolemia among young Japanese.

Adolescent↗

[Effects of cilostazol in patients with bradycardiac atrial fibrillation].

OBJECTIVES: Cilostazol, an antithrombotic agent, directly and indirectly increases the heart rate. This study investigated whether cilostazol increases the heart rate, and whether it has chronotropic effects on cardiac failure in patients with bradycardiac atrial fibrillation. METHODS: Twelve patients (6 males and 6 females) with bradycardiac atrial fibrillation underwent Holter monitoring (24-hour total heartbeat counts and frequency of pause), echocardiography (left ventricular end-diastolic diameter, percentage fractional shortening), chest roentgenography (cardiothoracic ratio), and measurements of brain natriuretic peptide and atrial natriuretic peptide before and 6 months after daily oral administration of 100-200 mg cilostazol. RESULTS: Cilostazol administration increased the 24-hour total heartbeat counts from 69,685 +/- 1,690 (mean +/- SE; mean heart rate: 48 beats/min) to 87,352 +/- 3,123 (60), and decreased the frequency of pause from 362.3 +/- 72.9 to 112.3 +/- 41.0. Cardiothoracic ratio decreased from 55.8 +/- 1.1% to 52.5 +/- 1.1%, left ventricular end-diastolic diameter from 56.1 +/- 0.9 to 52.9 +/- 0.8 mm, but percentage fractional shortening was not significantly changed (from 33.0 +/- 2.2% to 33.7 +/- 2.1%). Brain natriuretic peptide decreased from 97.9 +/- 20.5 to 33.5 +/- 4.8 pg/ml, and atrial natriuretic peptide from 69.5 +/- 12.1 to 46.7 +/- 8.3 pg/ml. CONCLUSIONS: Cilostazol has beneficial effects in patients with bradycardiac atrial fibrillation. The increase of heart rate may be mediated by improvement of conductivity in the atrioventricular node and increase of coronary blood supply caused by dilation of vessels.

Aged↗

Complex formation of adenomatous polyposis coli gene product and axin facilitates glycogen synthase kinase-3 beta-dependent phosphorylation of beta-catenin and down-regulates beta-catenin.

Adenomatous polyposis coli gene product (APC) functions as a tumor suppressor and its mutations in familial adenomatous polyposis and colorectal cancers lead to the accumulation of cytoplasmic beta-catenin. The molecular mechanism by which APC regulates the stability of beta-catenin was investigated. The central region of APC, APC-(1211-2075), has the beta-catenin- and Axin-binding sites and down-regulates beta-catenin. Glycogen synthase kinase-3 beta (GSK-3 beta) phosphorylated beta-catenin slightly in the presence of either APC-(1211-2075) or Axin(delta)(beta)(-catenin), in which the beta-catenin-binding site is deleted, and greatly in the presence of both proteins. The enhancement of the GSK-3 beta-dependent phosphorylation of beta-catenin was eliminated by the APC-binding site of Axin. Axin down-regulated beta-catenin in SW480 cells, but not Axin(delta)(beta)(-catenin). In L cells where APC is intact, Axin(delta)(beta)(-catenin) inhibited Wnt-dependent accumulation of beta-catenin but not Axin-(298-832)(delta)(beta)(-catenin) in which the APC- and beta-catenin-binding sites are deleted. These results indicate that the complex formation of APC and Axin enhances the phosphorylation of beta-catenin by GSK-3 beta, leading to the down-regulation of beta-catenin.

Adenomatous Polyposis Coli Protein↗

A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation.

beta-Catenin is efficiently phosphorylated by glycogen synthase kinase-3beta in the Axin complex in the cytoplasm, resulting in the down-regulation. In response to Wnt, beta-catenin is stabilized and translocated into the nucleus where it stimulates gene expression through Tcf/Lef. Here we report a novel protein, designated Duplin (for axis duplication inhibitor), which negatively regulates the function of beta-catenin in the nucleus. Duplin was located in the nucleus. Duplin bound directly to the Armadillo repeats of beta-catenin, thereby inhibiting the binding of Tcf to beta-catenin. It did not affect the stability of beta-catenin but inhibited Wnt- or beta-catenin-dependent Tcf activation. Furthermore, expression of Duplin in Xenopus embryos inhibited the axis formation and beta-catenin-dependent axis duplication, and prevented the beta-catenin's ability to rescue ventralizing phenotypes induced by ultraviolet light irradiation. Thus, Duplin is a nuclear protein that inhibits beta-catenin signaling.

Amino Acid Sequence↗

Differential glomerular response to continuous infusion of vasopressin in spontaneously hypertensive rats and Wistar-Kyoto rats.

To determine the difference of glomerular response to exogenous vasopressin (VP) in vivo between normotensive and hypertensive rats, we examined the effects of 14-day continuous infusion of VP (1.0 ng/kg/min) on the physiological and histological aspects in 7-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. VP infusion did not result in significant changes in systolic blood pressure, heart rate, serum electrolytes, serum creatinine, urinary protein and N-acetyl-beta-glucosaminidase levels in both strains of rats. VP infusion significantly reduced daily urine volume associated with significant concentration of the urine in WKY rats but not SHR. Kidney and heart weights did not differ significantly after VP infusion between both strains. Glomerular mesangial expansion was significantly enhanced in VP infused SHR, but glomerular cellularity was not different between both strains following treatment. Competitive reverse transcription-polymerase chain reaction revealed that the level of glomerular transforming growth factor (TGF)-beta1 mRNA was significantly higher in SHR than WKY rats, and that this difference was significantly augmented after VP infusion in SHR. VP infusion, however, did not change the level of glomerular mRNAs of platelet-derived growth factor (PDGF) B-chain in both strains. Then, exogenous VP infusion contributes to the glomerular mesangial expansion in SHR, which involved overexpression of glomerular TGF-beta1 without any pressor effect. In contrast, the significant changes of glomerular expansion and TGF-beta1 level were not shown in WKY rats. These findings suggest that the glomerular response to the exogenous VP is preferentially enhanced in SHR.

Animals↗

Regio- and diastereocontrol in carbonyl allylation by 1-halobut-2-enes with Tin(II) halides

Regio- and diastereoselective carbonyl allylations of 1-halobut-2-enes with tin(II) halides are described. Tin(II) bromide in a dichloromethane-water biphasic system is an effective reagent for unusual alpha-regioselective carbonyl allylation of 1-bromobut-2-ene to produce 1-substituted pent-3-en-1-ols. The addition of tetrabutylammonium bromide (TBABr) to the biphasic system produces 1-substituted 2-methylbut-3-en-1-ols via usual gamma-addition which is opposite to the alpha-addition without TBABr. The gamma-addition to aromatic aldehydes exhibits anti-diastereoselectivity, while that to aliphatic aldehydes is not diastereoselective. The allylation of benzaldehyde by 1-chlorobut-2-ene in 1,3-dimethylimidazolidin-2-one (DMI) does not occur with tin(II) chloride or bromide but does proceed with tin(II) iodide and exhibits gamma-syn selectivity which is unusual for a Barbier-type carbonyl allylation. In the carbonyl allylation by 1-chlorobut-2-ene with any tin(II) halide, the addition of tetrabutylammonium iodide (TBAI) accelerates the reaction and enhances gamma-syn selectivity. The use of tin(II) iodide and TBAI produces 2-methyl-1-phenylbut-3-en-1-ol with high yield and high syn-diastereoselectivity. The syn-diastereoselective carbonyl allylation of 1-chlorobut-2-ene using tin(II) iodide, a catalytic amount of TBAI, and NaI in DMI-H(2)O is applied to various aldehydes.

Journal Article↗

GSK-3beta-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by beta-catenin and protein phosphatase 2A complexed with Axin.

Axin forms a complex with adenomatous polyposis coli gene product (APC), glycogen synthase kinase-3beta (GSK-3beta), and beta-catenin through different binding sites and downregulates beta-catenin. GSK-3beta-dependent phosphorylation of APC-(1211-2075) which has the Axin-binding site was facilitated by Axin, but that of APC-(959-1338) which lacks the Axin-binding site was not. Axin-(298-506) or Axin-(298-832), which has the GSK-3beta- and beta-catenin- but not APC-binding sites, did not enhance GSK-3beta-dependent phosphorylation of either APC-(1211-2075) or APC-(959-1338). Furthermore, beta-catenin stimulated the phosphorylation of APC-(959-1338) and APC-(1211-2075) by GSK-3beta in the presence of Axin. Consistent with these in vitro observations, expression of beta-catenin or Axin in COS cells promoted an SDS gel band shift of APC. These results indicate that APC complexed with Axin is effectively phosphorylated by GSK-3beta and that beta-catenin may modulate this phosphorylation. In addition, the heterodimeric form of protein phosphatase 2A (PP2A) directly bound to Axin, and PP2A complexed with Axin dephosphorylated APC phosphorylated by GSK-3beta. Taken together, these results suggest that GSK-3beta-dependent phosphorylation of APC can be modulated by beta-catenin and PP2A complexed with Axin.

Adenomatous Polyposis Coli Protein↗

Paternal mouthbrooding in the black-chinned tilapia, Sarotherodon melanotheron (Pisces: cichlidae): changes in gonadal steroids and potential for vitellogenin transfer to larvae.

The black-chinned tilapia (Sarotherodon melanotheron) is a paternal mouthbrooder. Pairs of adult black-chinned tilapia were raised in freshwater and the males were sampled during the mouthbrooding cycle. Sampling also occurred 10 days after release of the free-swimming fry for comparison. During the first week of incubation of the eggs, total androgens and estradiol were low (<5 and <0.3 ng/ml, respectively). During the second week of brooding, when the eggs have hatched and they are called newly hatched embryos, plasma levels of gonadal steroids increased (13-38 ng androgen/ml and >0.6 ng estradiol/ml). The plasma concentrations of vitellogenin (VTG) in male parents changed during mouthbrooding, with decreases occurring between egg pickup and hatching of the embryo (Day 6 of mouthbrooding). The pattern of change in concentrations of VTG in surface mucus of male parents differed from the pattern in plasma, with peak concentrations occurring at the time of hatching. The amount of VTG in mucus was similar to that measured in the female Oreochromis mossambicus during mouthbrooding of embryos. The appearance of peak VTG levels in the mucus at the time of hatching when plasma levels have declined and the availability of comparable amounts of mucus VTG in both maternal and paternal mouthbrooding tilapia, despite unequivalent plasma levels, support the possibility that parental provisioning of the young occurs during mouthbrooding in tilapia.

Animals↗

Mouthbrooding in the black-chinned tilapia, Sarotherodon melanotheron (Pisces: Cichlidae): the presence of eggs reduces androgen and estradiol levels during paternal and maternal parental behavior.

The black-chinned tilapia (Sarotherodon melanotheron) is considered a paternal mouthbrooder in which the male churns the eggs in his mouth for 14-18 days after they are fertilized. We previously showed that plasma androgen and estradiol concentrations increased significantly between the beginning and end of mouthbrooding. Here we provide evidence that androgen and estradiol are relatively high in prespawning male tilapia, decrease significantly with the initiation of mouthbrooding, and return to and slightly surpass prespawning levels by the end of mouthbrooding. We then test the hypothesis that the initiation of mouthbrooding causes a decrease in androgen and estradiol. We raised single pairs of tilapia in seawater aquaria and conducted two experiments. In the first, we removed eggs from males on the morning of Day 1 of mouthbrooding, followed changes in plasma androgen and estradiol in the afternoon of Day 1 and on Days 6, 11, and 16, and compared them to levels in control males who kept their eggs. Removing eggs from mouthbrooding males on the morning of Day 1 eliminated the decrease in plasma androgen and estradiol observed in the afternoon of Day 1 of mouthbrooding. This demonstrates that the eggs are necessary for the decrease. We observed that, infrequently, the female of the pair would pick up the eggs to brood them in her mouth. In a second experiment, in the afternoon of Day 1, we sampled both the male and female of pairs in which the female brooded eggs. In female-brooding pairs, the females had significantly lower androgen and estradiol levels than prespawning females. The black-chinned tilapia in captivity exhibits both paternal and maternal parental behavior. In both sexes the initiation of mouthbrooding triggers a decrease in androgen and estradiol concentrations. We conclude that the presence of eggs inhibits the pituitary-gonadal axis in both males and females and hypothesize that a chemical signal from the eggs is delaying the initiation of the next brood.

Androgens↗

Differential effect of chronic inhibition of calcium channel and angiotensin II type 1-receptor on aldosterone synthesis in spontaneously hypertensive rats.

We have investigated the in vivo effect of chronic blockade of Ca(2+)-channels and angiotensin II type 1 (AT(1))-receptors on aldosterone (Aldo)-synthesis in the adrenal glands of spontaneously hypertensive rats (SHR). Male SHR were administered Ca(2+)-antagonist, amlodipine (10 mg/kg per day) or AT(1)-receptor-antagonist, TCV-116 (1 mg/kg per day) from 7 until 11 weeks of age. Systolic blood pressure (SBP) and heart rate (HR) were significantly higher in SHR than Wistar-Kyoto (WKY) rats. Both treatments resulted in equivalent and significant reduction in SBP in SHR. Aldo-secretion in SHR, which was significantly higher than in WKY rats, was profoundly suppressed by TCV-116 compared with amlodipine. Both treatments resulted in thickening of the zona glomerulosa, which immunohistochemically contains Aldo, at the end of therapy. Competitive reverse transcription-polymerase chain reaction (RT-PCR) showed that CYP11A (P450scc) mRNA regulating the first step of Aldo-synthesis was significantly reduced from week 9 of age by amlodipine, and that CYP11B2 (P450aldo) mRNA regulating the last step of Aldo-synthesis was potently suppressed from 9 weeks of age by TCV-116. Our results indicate that chronic treatment with different antihypertensive agents directly modulates adrenocortical aldosterone synthesis in SHR in vivo via different mechanisms.

Adrenal Cortex↗

The Schizosaccharomyces pombe spo6+ gene encoding a nuclear protein with sequence similarity to budding yeast Dbf4 is required for meiotic second division and sporulation.

BACKGROUND: Sporulation of the fission yeast Schizosaccharomyces pombe is a cell differentiation process which accompanies meiosis. The spo6+ gene was identified as a sporulation-specific gene, whose transcription was regulated by the forkhead family transcription factor Mei4. RESULTS: spo6+ encodes a protein with sequence similarity to Saccharomyces cerevisiae Dbf4p, which is required for the initiation of DNA replication. However, doubling time and cell morphology of spo6 deletion mutants and spo6-cDNA over-expressing cells were indistinguishable from wild-type cells. Spliced mature mRNAs of spo6+ appeared when diploid cells committed to meiosis. Spo6p fused to green fluorescent protein (GFP) preferentially localized in a nucleus. Although spo6Delta diploids normally underwent premeiotic DNA replication and meiosis-I, approximately 80% of cells were blocked at the binucleate stage during meiosis and virtually no asci were formed. Anti-tubulin staining revealed that only 25% of the binucleate cells assembled spindle microtubules for meiosis-II. In a small number of tetranucleate cells, sister nuclei insufficiently separated and spindles were frequently fragmented. The meiosis-II arrest phenotype was exaggerated at low temperature and in the presence of caffeine. CONCLUSIONS: These results indicate that Spo6p is a novel Dbf4-related nuclear protein, which is expressed during meiosis and is indispensable for normal progression of meiosis-II and sporulation.

Amino Acid Motifs↗

Pseudomalabsorption of levothyroxine: a case report.

A 51-year-old woman who had been treated with levothyroxine sodium because of hypothyroidism after total thyroidectomy for thyroidal cancer was admitted to our hospital for persistent hypothyroidism despite large dose administration of levothyroxine (600 microg/day). The patient complained of severe general fatigue and body weight gain. Free thyroxine, free triiodothyronine and thyrotropin levels were 0.97 ng/dl, 1.55 pg/ml and 24.51 microU/ml, respectively, under oral administration of levothyroxine. Levothyroxine loading test performed by liquid form, pulverized tablets via nasogastric tube and intravenous administration revealed no evidence of malabsorption or metabolic disorder of levothyroxine, although oral intake of tablets was ineffective due to her factitiousness. We report here a possible case of "pseudomalabsorption of levothyroxine" to emphasize the clinical recognition of this disorder in patients with resistant hypothyroidism.

Dose-Response Relationship, Drug↗

Hyperthyroidism in a patient with TSH-producing pituitary adenoma coexisting with thyroid papillary adenocarcinoma.

A 27-year-old woman who presented with a left thyroid nodule was found to have hyperthyroidism caused by a syndrome of inappropriate secretion of TSH. The levels of free T3, free T4 and TSH were 9.50 pg/mL, 4.05 ng/dL and 2.16 microU/mL, respectively. Magnetic resonance imaging of the head revealed a pituitary macroadenoma. The TSH response to TRH stimulation was normal and responses of other anterior pituitary hormones to stimulation tests were also normally preserved. Administration of octreotide with iodine successfully reversed hyperthyroidism prior to total resection of pituitary adenoma, which was followed by hemithyroidectomy of the left thyroid five months later. Histologically, the resected pituitary adenoma was a TSH-producing adenoma (TSH-oma) and the thyroid nodule was a papillary adenocarcinoma. Serum TSH diminished to undetectable levels immediately following pituitary adenomectomy but gradually normalized over nine months. Coexistence of a TSH-oma with thyroid cancer is very rare and only two similar cases have previously been documented. This combination raises the possibility that TSH may be involved in tumorigenesis in the thyroid gland.

Adenocarcinoma, Papillary↗

Axin directly interacts with plakoglobin and regulates its stability.

Plakoglobin is homologous to beta-catenin. Axin, a Wnt signal negative regulator, enhances glycogen synthase kinase (GSK)-3beta-dependent phosphorylation of beta-catenin and stimulates the degradation of beta-catenin. Therefore, we examined the effect of Axin on plakoglobin stability. Axin formed a complex with plakoglobin in COS cells and SW480 cells. Axin directly bound to plakoglobin, and this binding was inhibited by beta-catenin. Axin promoted GSK-3beta-dependent phosphorylation of plakoglobin. Furthermore, overexpression of Axin down-regulated the level of plakoglobin in SW480 cells. These results suggest that Axin regulates the stability of plakoglobin by enhancing its phosphorylation by GSK-3beta and that Axin may act on beta-catenin and plakoglobin in similar manners.

Animals↗

Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors.

The involvement of Ral and its downstream molecules in receptor-mediated endocytosis was examined. Expression of either RalG23V or RalS28N, which are known to be constitutively active and dominantnegative forms, respectively, in A431 cells blocked internalization of epidermal growth factor (EGF). Stable expression of RalG23V or RalS28N in CHO-IR cells also inhibited internalization of insulin. Internalization of EGF and insulin was not affected by full-length RalBP1 which is an effector protein of Ral, but was inhibited by its C-terminal region which binds directly to Ral and POB1. POB1 is a binding protein of RalBP1 and has the Eps15 homology (EH) domain. Deletion mutants of POB1 inhibited internalization of EGF and insulin. However, internalization of transferrin was unaffected by Ral, RalBP1, POB1 and their mutants. Epsin and Eps15 have been reported to be involved in the regulation of endocytosis of the receptors for EGF and transferrin. The EH domain of POB1 bound directly to Epsin and Eps15. Taken together with the observation that EGF and insulin activate Ral, these results suggest that Ral, RalBP1 and POB1 transmit the signal from the receptors to Epsin and Eps15, thereby regulating ligand-dependent receptor-mediated endocytosis.

Adaptor Proteins, Signal Transducing↗

Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability.

Axin forms a complex with glycogen synthase kinase-3beta (GSK-3beta) and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin, thereby stimulating the degradation of beta-catenin. Because GSK-3beta also phosphorylates Axin in the complex, the physiological significance of the phosphorylation of Axin was examined. Treatment of COS cells with LiCl, a GSK-3beta inhibitor, and okadaic acid, a protein phosphatase inhibitor, decreased and increased, respectively, the cellular protein level of Axin. Pulse-chase analyses showed that the phosphorylated form of Axin was more stable than the unphosphorylated form and that an Axin mutant, in which the possible phosphorylation sites for GSK-3beta were mutated, exhibited a shorter half-life than wild type Axin. Dvl-1, which was genetically shown to function upstream of GSK-3beta, inhibited the phosphorylation of Axin by GSK-3beta in vitro. Furthermore, Wnt-3a-containing conditioned medium down-regulated Axin and accumulated beta-catenin in L cells and expression of Dvl-1(DeltaPDZ), in which the PDZ domain was deleted, suppressed this action of Wnt-3a. These results suggest that the phosphorylation of Axin is important for the regulation of its stability and that Wnt down-regulates Axin through Dvl.

Adaptor Proteins, Signal Transducing↗

Axin prevents Wnt-3a-induced accumulation of beta-catenin.

When Axin, a negative regulator of the Wnt signaling pathway, was expressed in COS cells, it coeluted with glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, and adenomatous polyposis coli protein (APC) in a high molecular weight fraction on gel filtration column chromatography. In this fraction, GSK-3beta, beta-catenin, and APC were co-precipitated with Axin. Although beta-catenin was detected in the high molecular weight fraction in L cells on gel filtration column chromatography, addition of conditioned medium expressing Wnt-3a to the cells increased beta-catenin in the low molecular weight fraction. However, Wnt-3a-dependent accumulation of beta-catenin was greatly inhibited in L cells stably expressing Axin. Axin also suppressed Wnt-3a-dependent activation of Tcf-4 which binds to beta-catenin and acts as a transcription factor. These results suggest that Axin forms a complex with GSK-3beta, beta-catenin, and APC, resulting in the stimulation of the degradation of beta-catenin and that Wnt-3a induces the dissociation of beta-catenin from the Axin complex and accumulates beta-catenin.

Adenomatous Polyposis Coli Protein↗