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T Mochizuki

Publications and source records attributed to T Mochizuki.

At least 145 records · Page 8Linked to original sources
PubMed1998

[Three-dimensional reconstruction of mitotic cells of Cryptococcus neoformans based on serial section electron microscopy].

Ultra-thin serial sections of mitotic cells of Cryptococcus neoformans were observed by transmission electron microscope and computer-aided reconstruction of three-dimensional models were performed to understand the kinetics of the nucleus and mitochondria during mitosis. The separation of chromosomes occured in the protrusion of the nucleus extending in the bud (=daughter cell), followed by one set of chromosomes being moved back into the mother cell. These findings were similar to those reported in the heterobasidiomycetous yeasts. No giant mitochondrion, composed of a coalescence of all the mitochondria, was found. Volumetric analysis revealed the fluctuations in the mitochondrial volume: total cytoplasmic volume ratio were minimum during mitosis. In addition, methods, usefulness and limitations of observation of ultra-thin serial sections for understanding the morphology of cells and intracellular organelles were reviewed.

Cryptococcus neoformans↗
PubMed1998

[Release of biogenic amines in the brain during sleep-wakefulness cycle].

Biogenic amines, including acetylcholine, act as neurotransmitters or neuromodulators in the brain of mammals. Accumulated evidences suggest the relevance of these amines to the regulatory system of sleep-wakefulness cycle. Recent development of an in vivo, microdialysis technique has revealed the existence of circadian variation in the release of these amines from various brain regions related to the regulation of sleep-wakefulness. This review focuses on the characteristics of the release of these amines determined by the microdialysis method in rats and cats during sleep-wakefulness cycle, and speculates their roles in the mechanism underlying the control of sleep and arousal state.

Animals↗
PubMed1998

Thallium-201 scintigraphy to predict therapeutic outcome of iodine-131 therapy of metastatic thyroid carcinoma.

UNLABELLED: We studied the relationship between 201Tl uptake and the efficacy of radioiodine therapy in thyroid carcinoma. METHODS: Forty-four patients with metastases of well-differentiated thyroid carcinoma received 201Tl scintigraphy within the 2 mo before their initial 131I therapy. Patients were classified into two groups according to the tumor-to-background (T/B) ratio on the late 201Tl scan: high 201Tl uptake (T/B > or = 2.1) and low 201Tl uptake (T/B < 2.1). The therapeutic outcome was judged by the percent reduction in the tumor diameter at 6 mo after the treatment. The treatment was defined as effective when the tumor showed more than 50% reduction in the tumor diameter. The patients in whom radioiodine was ineffective were followed up to determine if the tumor showed further growth. RESULTS: Of the 44 patients, 25 had high 201Tl uptake and 19 had low 201Tl uptake. The therapy was effective in 15 patients and was ineffective in 29. All the patients in whom radioiodine was effective had low 201Tl uptake. On the other hand, 25 of 29 patients in whom radioiodine was ineffective had high 201Tl uptake. Eight patients, in whom radioiodine was ineffective despite good 131I uptake, had high 201Tl uptake. There were no significant differences in the positive predictive value and the negative predictive value for effective treatment between 201Tl scintigraphy and therapeutic dose 131I scintigraphy. Among the 25 patients in whom radioiodine was ineffective and who had high 201Tl uptake, the tumor diameter increased in 7 (28%). However, none of the tumors with low 201Tl uptake increased in size during the follow-up period. CONCLUSION: Thallium-201 scintigraphy has a high predictive value for the efficacy of radioiodine therapy in metastatic thyroid carcinoma. Thus, it is helpful in determining the indication for radioiodine therapy and it seems to be an adjunct to tracer dose 131I scintigraphy.

Adenocarcinoma, Follicular↗
PubMed1998

[Comparison of single sample methods for determination of plasma clearance using 99mTc-MAG3].

We compared relationship among three single blood sampling methods which have been proposed for determination of plasma clearance with 99mTc-MAG3. Russell's and Bubeck's algorithms were employed for 48 adults (average age: 53 years) and Bubeck's and Piepsz's algorithms were used in 9 children (average age: 5.8 years). Three methods showed very high correlation among them. However, Russell's and Piepsz's methods were about 1.4 times higher than Bubeck's method in calculating plasma clearance of 99mTc-MAG3. The present study indicates that three methods discussed here are useful for the determination of plasma clearance with 99mTc-MAG3. In addition, Bubeck's method may be preferable as a reference for single plasma sampling method because of common application to adults and children.

Adolescent↗
PubMed1997

A simple probe measures the pharmacokinetics of[125I]RTI-55 in mouse brain in vivo.

A simple external radiation detector system was used to assess brain dopamine and serotonin transporters in mice in vivo using [125I]RTI-55. The results were compared to ex vivo dissection data. Methyl 3beta-(4-iodophenyl) tropane-2beta-carboxic acid methyl ester (RTI-55 or beta-CIT), a high-affinity cocaine antagonist, binds to presynaptic dopamine and serotonin transporters in the brain. Radiotracer accumulation increased for the first 150 min after intravenous injection and then remained constant. When unlabeled RTI-55 was injected, either before or 60 min after radiotracer administration, a significant decrease in tracer accumulation was observed. [125I]RTI-55 binding was also displaced by blocking doses of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine dihydrochloride (GBR 12909) and paroxetine. The results were similar to the ex vivo dissection data. The results demonstrate the feasibility of using the probe detector system to study the presynaptic transporter system in vivo in the mouse brain. The technique is applicable to other cerebral neurotransmitter systems.

Absorptiometry, Photon↗
PubMed1997

Caspase-dependent apoptosis of COS-7 cells induced by Bax overexpression: differential effects of Bcl-2 and Bcl-xL on Bax-induced caspase activation and apoptosis.

Bcl-2 family proteins and ICE/CED-3 family proteases (caspases) are regarded as the basic regulators of apoptotic cell death. They are evolutionarily conserved and implicated in a variety of apoptosis. However, the precise mechanism by which these two families interact to regulate cell death is not yet known. In this study, we found that the overexpression of the Bcl-2 family member Bax induced apoptotic cell death in COS-7 cells through the activation of CPP32 (caspase-3)-like proteases that cleaved the DEVD tetrapeptide. This apoptotic cell death was suppressed by the viral proteins CrmA and p35, as well as by the chemically synthesized caspase inhibitors Z-Asp-CH2-DCB and zVAD-fmk. We also found that the Bax-induced apoptosis of COS-7 cells was suppressed by Bcl-xL and Bcl-2, though both Bcl-xL and Bcl-2 similarly prevented etoposide-induced apoptosis in COS-7 cells. In addition, Bcl-xL inhibited the activation of caspase-3-like proteases accompanying Bax-induced COS-7 cell death but Bcl-2 did not. These results indicate that the caspase activation is essential for Bax-induced apoptosis, and that the ability of Bcl-2 and Bcl-xL to prevent the Bax-induced caspase activation and apoptosis in COS-7 cells could be differentially regulated. Our results also suggest that Bcl-2 family proteins function upstream of caspase activation and control apoptosis through the regulation of caspase activity.

Animals↗
PubMed1997

Molecular cloning, cDNA sequence analysis, and chromosomal localization of mouse Pkd2.

The gene responsible for the second form of autosomal dominant polycystic kidney disease, PKD2, has recently been identified. We now describe the cloning, genomic localization, cDNA sequence, and expression analysis of its murine homologue, Pkd2. The cloned cDNA sequence is 5134 bp long and is predicted to encode a 966-amino-acid integral membrane protein with six membrane-spanning domains and intracellular NH2 and COOH termini. Pkd2 is highly conserved with 91% identity and 98% similarity to polycystin-2 at the amino acid level. Pkd2 mRNA is widely expressed in mouse tissues. Pkd2 maps to mouse Chromosome 5 and is excluded as a candidate gene for previously mapped mouse mutations resulting in a polycystic kidney phenotype.

Amino Acid Sequence↗
PubMed1997

Pim-1 kinase stimulates c-Myc-mediated death signaling upstream of caspase-3 (CPP32)-like protease activation.

Pim-1 oncoprotein is a serine/threonine kinase that can closely cooperate with c-Myc in lymphomagenesis, as does Bcl-2. Although the molecular mechanism of this cooperative transformation remains unknown, it is speculated that, similar to Bcl-2, Pim-1 contributes to transformation by inhibiting apoptosis. In this study, therefore, we examined the effect of Pim-1 expression on c-Myc-mediated apoptosis of Rat-1 fibroblasts triggered by serum deprivation. Our results showed that, rather than inhibiting apoptosis, Pim-1 expression stimulated c-Myc-mediated apoptosis in Rat-1 fibroblasts. Pim-1 stimulated c-Myc-mediated apoptosis through an enhancement of the c-Myc-mediated activation of caspase-3 (CPP32)-like proteases, since the suppression of this activity by a specific caspase inhibitor abolished the apoptosis stimulation by Pim-1. A kinase-defective Pim-1 mutant failed to stimulate c-Myc-mediated apoptosis, and Pim-1 expression alone in the absence of c-Myc overexpression did not induce apoptosis of serum-deprived Rat-1 cells, indicating that the kinase activity of Pim-1 and the activated c-Myc signaling pathway were required for apoptosis stimulation by Pim-1. Together, these results suggest that Pim-1 oncoprotein stimulates as a serine/threonine kinase the death signaling elicited by c-Myc at a step upstream of caspase-3-like protease activation in Rat-1 fibroblasts. Our results also suggest that Pim-1 kinase might function cooperatively with c-Myc through the phosphorylation of a factor(s) which regulates the common signaling pathway involved in c-Myc-mediated apoptosis and transformation.

Animals↗
PubMed1997

Characterization of the exon structure of the polycystic kidney disease 2 gene (PKD2).

PKD2, the gene defective in the second form of autosomal dominant polycystic kidney disease (ADPKD), has been identified by positional cloning and found to encode an integral membrane protein with similarity to the gene for the more common form of ADPKD and to calcium channels. We have determined the exon-intron structure of the PKD2 gene. PKD2 is encoded in at least 15 exons with the translation start site in exon 1. All the splice acceptor and donor sites conform to the AG/GT rule. We have designed a series of intronic oligonucleotide primers for amplifying the entire coding sequence from genomic DNA in segments well suited to mutation analysis using conventional screening strategies such as SSCA or heteroduplex analysis.

Cloning, Molecular↗
PubMed1997

Role of mast cell histamine in the formation of rat paw edema: a microdialysis study.

We determined the endogenous histamine concentration in the subplantar space of rat hind paws using an in vivo microdialysis technique. A microdialysis probe was implanted into the rat hind paw and the histamine content in dialysates was measured by high performance liquid chromatography-fluorometry. In wild type (+/+) rats, the histamine output (basal level 25.7 +/- 0.9 pmol/ml) increased 115-, 199- and 426-fold rapidly after subplantar injection of compound 48/80 at doses of 0.5, 5 and 50 microg/paw, respectively. In genetically mast cell-deficient (Ws/Ws) rats, the basal level of histamine was one third of that obtained from +/+ rats, and was not increased by compound 48/80 injection. With this treatment, marked, dose dependent, but relatively gradual development of the paw edema was found in +/+ rats. However, no edema formation was observed in Ws/Ws rats. Histological observations showed neither mast cells nor edema to be present in the paw skin of Ws/Ws rats. These findings indicate the critical role of histamine as a trigger for the development of edema in vivo. In addition, Ws/Ws rats will provide important information as to the roles of mast cells in the inflammatory response.

Animals↗
PubMed1997

Role of N-terminal active sites of galanin in neurally evoked circular muscle contractions in the guinea-pig ileum.

Synthetic galanin-related peptides and several galanin-(1-15)ol analogs were used to examine structure-function relationships of the N-terminal active site of galanin in more detail, using the guinea-pig ileum. The synthetic peptides examined showed their inhibitory activity on the neurally evoked circular muscle contractions with the following order of potency: rat, human and tuna galanin, galanin-(1-15)ol and [D-Trp8]galanin-(1-15)ol > N alpha-acetylated galanin-(2-15)ol, [Ala6,D-Trp8]galanin-(1-15)ol, galanin-(1-15) > tuna galanin-(1-15), [D-Ala8]galanin-(1-15)ol, N alpha-acetylated galanin-(1-15)ol. In contrast, [D-Thr6]galanin-(1-15)ol, [D-Tyr9]galanin-(1-15)ol and [D-Trp9]galanin-(1-15)ol were ineffective and showed no antagonistic activities to galanin. These results suggest that the L-configuration at positions 6 and 9 seems to be important for the inhibitory action of galanin on the neurally evoked guinea-pig circular muscle contractions.

Amino Acid Sequence↗
PubMed1997

An integrated genetic and physical map of the autosomal recessive polycystic kidney disease region.

Autosomal recessive polycystic kidney disease is one of the most common hereditary renal cystic diseases in children. Genetic studies have recently assigned the only known locus for this disorder, PKHD1, to chromosome 6p21-p12. We have generated a YAC contig that spans approximately 5 cM of this region, defined by the markers D6S1253-D6S295, and have mapped 43 sequence-tagged sites (STS) within this interval. This set includes 20 novel STSs, which define 12 unique positions in the region, and three ESTs. A minimal set of two YACs spans the segment D6S465-D6S466, which contains PKHD1, and estimates of their sizes based on information in public databases suggest that the size of the critical region is < 3.1 Mb. Twenty-eight STSs map to this interval, giving an average STS density of < 1/150 kb. These resources will be useful for establishing a complete transcription map of the PKHD1 region.

Base Sequence↗
PubMed1997

Sequential change of BMIPP uptake with age in spontaneously hypertensive rat model.

UNLABELLED: Changes in myocardial perfusion and metabolism are often associated with myocardial hypertrophy, but there are few reports describing the serial assessment of fatty acid metabolism in hypertrophic myocardium. The aim of this study is to assess fatty acid metabolism serially in hypertrophic myocardium in spontaneously hypertensive rats (SHR) with 125I-BMIPP, a branched fatty acid analog. METHODS: SHR and Wistar-Kyoto rats (WKY) as the control were divided into 4 groups (12, 15, 18 and 51 weeks after birth). The heart was extracted 10 minutes after intravenous injection of 125I-BMIPP and 201Tl at the same time. The accumulation of each radiotracer in the myocardium was counted with a well gamma counter. In addition, 125I-BMIPP uptake was corrected by 201Tl uptake (B/T). RESULTS: The heart weight/body weight ratio was significantly higher in SHR than that in WKY (p < 0.001). In SHR, this ratio increased up to 18 weeks (12 weeks; 0.266 +/- 0.005, 18 weeks; 0.281 +/- 0.006: mean +/- SE, p < 0.05). The 125I-BMIPP uptake tended to be significantly reduced in SHR (12 weeks; 2.373 +/- 0.212, 18 weeks; 1.380 +/- 0.047; mean +/- SE, p < 0.05). Such a difference in BMIPP uptake was more evident when BMIPP uptake was corrected by Tl uptake (B/T), but no regional difference or heterogeneity of BMIPP distribution was observed in the hypertrophic myocardium in SHR. CONCLUSION: A change in fatty acid metabolism with age was observed in association with myocardial hypetrophy in this hypertensive rat model, which was well demonstrated with 125I-BMIPP and 201Tl.

Aging↗
PubMed1997

Multiple haemorrhagic brain metastases from papillary thyroid cancer.

We report a 40-year-old woman, who initially developed cerebellar symptoms, with multiple hemorrhagic brain metastases from a papillary thyroid cancer. Intracranial masses gave heterogeneous high signal on T1-weighted and T2-weighted images, hemosiderin rims on the latter. Some of the tumors showed contrast enhancement. Metastatic thyroid cancer is a consideration in a patient with multiple hemorrhagic masses.

Brain↗
PubMed1997

Effect of glicentin, oxyntomodulin and related peptides on isolated gastric smooth muscle cells.

Glicentin (proglucagon 1-69 GLIC) and oxyntomodulin (proglucagon 33-69 or OXM) are two peptide hormones that are co-released from ileum and large intestine during digestion. They modulate in vivo gastric acid secretion and the gastro-pyloro-duodenal activity. The specificity of their effects is linked to the presence of their C-terminal octapepide. As yet, no isolated target cell that responds specifically to this family of peptides has been described. The present report describes the in vitro effect of human synthetic GLIC, OXM and octapeptide-bearing fragments on smooth muscle cells isolated from the rabbit antrum. GLIC or OXM decreased the mean length of the cells by: 13.9 +/- 0.8% and 15.5 +/- 0.9%, respectively - GLIC being 16 times more potent than OXM (respective EC50 values: 5 and 83 pM). The C-terminal fragments OXM(19-37) and OXM(30-37) were as efficient as GLIC or OXM. Their potencies were OXM = OXM(19-37)>>OXM(30-37). Glucagon, which corresponds to OXM without the C-terminal octapeptide, or glucagon-like peptide-1 (7-36 amide) did not have any effect. The response to OXM was not influenced by antagonists to muscarinic, cholecystokinin or substance P receptors. In conclusion, our studies demonstrate for the first time an isolated target cell that responds specifically to GLIC, OXM and other octapeptide-bearing peptides.

Animals↗
PubMed1997

Novel stop and frameshifting mutations in the autosomal dominant polycystic kidney disease 2 (PKD2) gene.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequent inherited disorders. The majority of cases are due to mutation of the PKD1 gene, on 16p13.3, while in most of the remainder the disease maps to the PKD2 locus, at chromosome 4q21-q23. Recently, the PKD2 gene has been positionally cloned and three nonsense mutations within the coding sequence of the gene identified. Here we report a systematic mutation screening of all 15 exons of the PKD2 gene in chromosome 4-linked ADPKD families, using heteroduplex and SSCP analyses. We have identified and characterized seven novel mutations, with a detection rate of approximately 90% in the population studied. All of the mutations result in the premature stop of translation: four nonsense changes and three deletions. The deletions are all frameshifting, of four T nucleotides in one case and one G nucleotide in the other two. All mutations are unique and are distributed throughout the gene without evidence of clustering. Comparison of specific mutations with the clinical profile in ADPKD2 families shows no clear correlation.

Chromosomes, Human, Pair 4↗
PubMed1997

A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2).

Recently the second gene for autosomal dominant polycystic kidney disease (ADPKD), located on chromosome 4q21-q22, has been cloned and characterized. The gene encodes an integral membrane protein, polycystin-2, that shows amino acid similarity to the PKD1 gene product and to the family of voltage-activated calcium (and sodium) channels. We have systematically screened the gene for mutations by single-strand conformation-polymorphism analysis in 35 families with the second type of ADPKD and have identified 20 mutations. So far, most mutations found seem to be unique and occur throughout the gene, without any evidence of clustering. In addition to small deletions, insertions, and substitutions leading to premature translation stops, one amino acid substitution and five possible splice-site mutations have been found. These findings suggest that the first step toward cyst formation in PKD2 patients is the loss of one functional copy of polycystin-2.

Adult↗