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Biomedical subjects

T Yamauchi

Publications and source records attributed to T Yamauchi.

At least 73 records · Page 4Linked to original sources
PubMed2001

Acute fatty liver of pregnancy complicated with anterior pituitary insufficiency.

Acute fatty liver of pregnancy complicated with anterior pituitary insufficiency in a 24-year-old nullipara woman who presented fever and progressing liver damage after the delivery by Cesarean section is described. The liver biopsy revealed severe fatty changes with microvesicular fat drops in the hepatocytes. Serum growth hormone and adrenocorticotropic hormone levels were low, and did not respond to the stimulation. The daily urinary excretion of 17-hydroxycorticosteroid was also low. Acute fatty liver of pregnancy and antehypophyseal insufficiency were diagnosed. Secondary adrenal failure was also suspected. The co-existing hypercoagulable state could cause an ischemic attack on the pituitary gland.

Acute Disease↗
PubMed2001

Intraaneurysmal flow dynamics study featuring an acrylic aneurysm model manufactured using a computerized tomography angiogram as a mold.

OBJECT: To obtain precise flow profiles in patients' aneurysms, the authors developed a new in vitro study method featuring an aneurysm model manufactured using three-dimensional computerized tomography (3D CT) angiography. METHODS: A clear acrylic basilar artery (BA) tip aneurysm model manufactured from a patient's 3D CT angiogram was used to analyze flow modifications during one cardiac cycle. Stereolithography was utilized to create the aneurysm model. Three-dimensional flow profiles within the aneurysm model were obtained from velocity measurements by using laser Doppler velocimetry. The aneurysm inflow/outflow zones changed dynamically in their location, size of their cross-sectional area, and also in their shapes over one cardiac cycle. The flow velocity at the inflow zone was 16.8 to 81.9% of the highest axial velocity in the BA with a pulsatility index (PI) of 1.1. The flow velocity at the outflow zone was 16.8 to 34.3% of the highest axial velocity of the BA, with a PI of 0.68. The shear stress along the walls of the aneurysm was calculated from the fluid velocity measured at a distance of 0.5 mm from the wall. The highest value of shear stress was observed at the bleb of the aneurysm. CONCLUSIONS: This clear acrylic model of a BA tip aneurysm manufactured using a CT angiogram allowed qualitative and quantitative analysis of its flow during a cardiac cycle. Accumulated knowledge from this type of study may reveal pertinent information about aneurysmal flow dynamics that will help practitioners understand the relationship among anatomy, flow dynamics, and the natural history of aneurysms.

Acrylic Resins↗
PubMed2001

[Inflammatory pseudotumor of the kidney: report of a case].

We report a case of inflammatory pseudotumor of the kidney. A 73-year-old man presenting with general malaise and minimal grade fever visited a medical department in our hospital. Computerized tomography incidentally revealed a tumor, 3.5 cm in diameter, in the lower pole of the left kidney, and he was referred to our outpatient department. Selective left renal arteriography disclosed an avascular mass on the affected site. Left radical nephrectomy was performed under the diagnosis of avascular renal cell carcinoma. Histological examination demonstrated a tumor composed of spindle-shaped fibroblastic cells infiltrated by variable numbers of plasma cells, small lymphocytes and histiocytes. The pathologic diagnosis was renal inflammatory pseudotumor. Fourteen previously reported cases of this tumor have reviewed in the literature.

Aged↗
PubMed2001

[Predictive value of prostate specific antigen density in the detection of prostate cancer in patients with elevated prostate specific antigen levels and normal digital rectal findings or stage A prostate cancer].

We compared the usefulness of PSA and PSA density (PSAD) in diagnosing prostate cancer in 102 men who had a PSA value higher than 4.0 ng/ml and normal digital rectal examination and who had undergone transrectal ultrasonography-guided systematic sextant biopsies of the prostate between August 1996 and October 1999. In addition, for a group of 53 patients who underwent retropubic simple prostatectomy, PSA, PSAD and PSA transition zone (PSA-TZ) examination results for those with stage A prostate cancer were compared with the results for those with benign prostatic hyperplasia (BPH). Of the former 102 men, 20 (19.6%) had prostate cancer. There was no significant difference in mean PSA level between patients with negative and those with positive biopsy results (mean 9.3 and 11.8, respectively, p = 0.295), but the mean PSAD of patients with positive biopsy results was significantly higher than that of those with negative results (mean 0.55 and 0.29, respectively, p = 0.0007). Of the 53 men who underwent retropubic simple prostatectomy, 10 (18.9%) were diagnosed with stage A prostate cancer. There was no significant difference in mean PSA, PSAD and PSA-TZ examination results between patients with BPH and those with stage A prostate cancer. For all 102 patients and for 71 patients with PSA levels of 4.1-10.0 ng/ml, a PSAD cutoff value of 0.1 reduced the number of biopsies 15.7% (16 of 102 cases), and 22.5% (16 of 71 cases), respectively. These results suggest that by measurement of PSAD some patients with benign disease could be spared a biopsy which would have been performed based on PSA results alone.

Aged↗
PubMed2001

[Seminal vesicle cyst with ipsilateral renal agenesis: a case report].

A 26-year-old man was referred to our hospital for further evaluation of a cystic lesion in the pelvis. He was completely asymptomatic, although he experienced gross hematuria 10 months before his visit. Drip infusion pyelography (DIP) and abdominal computerized tomography (CT) showed a cystic structure behind the bladder and absence of the left kidney. Transrectal ultrasonography (TRUS) suggested left ejaculatory duct obstruction and seminal vesicle deformity. On cystoscopy a large bulging mass under the left side of the bladder was seen. The left half of the trigone and left ureteral orifice were absent. Vasovesiculography demonstrated dilated and tortuous left seminal vesicle. Three days after this procedure, the patient suffered left epididymitis. It did not respond rapidly to antibiotic therapy, so percutaneous drainage of the cyst was performed. He has been completely free of symptoms and no seminal vesicle cysts have been detected on TRUS at five months follow-up.

Adult↗
PubMed2001

[Three-dimensional computed tomography angiography of coronary artery bypass graft with electron beam tomography].

OBJECTIVES: Assessment of coronary artery bypass graft patency by three-dimensional reconstructed computed tomography angiography (3D-CTA) derived from electrocardiography-gated contrast-enhanced electron beam tomography (EBT) was evaluated. METHODS: Thirty-nine patients with 99 grafts (45 arterial grafts and 54 venous grafts) underwent 3D-CTA and selective coronary angiography within a 3-week interval. 3D-CTA images of the coronary bypass grafts were compared with the coronary angiography images used as the control. RESULTS: 3D-CTA defined 42 of 44 arterial grafts as patent (sensitivity: 95%), all 47 venous grafts as patent (sensitivity: 100%) and all 7 venous grafts as occlusive (specificity: 100%). The overall sensitivity and specificity were 98% and 88%, respectively. CONCLUSIONS: 3D-CTA is an useful noninvasive technique with adequate sensitivity and specificity to assess coronary artery bypass graft patency.

Aged↗
PubMed2001

DNA repair initiated in chronic lymphocytic leukemia lymphocytes by 4-hydroperoxycyclophosphamide is inhibited by fludarabine and clofarabine.

PURPOSE: Chronic lymphocytic leukemia (CLL) lymphocytes respond to DNA alkylation by excision repair, with the extent of repair increasing as the cells acquire resistance to alkylating agents. Because incorporation of nucleotide analogues into the repair patches elicits death signals in quiescent cells, the increased capacity for excision repair in alkylator-resistant cells could facilitate incorporation of nucleotide analogues. We hypothesized that the mechanism-based interaction of nucleoside analogues with alkylating agents could elicit greater than additive killing of CLL cells. EXPERIMENTAL DESIGN: Lymphocytes from 50 patients with CLL that were not refractory to alkylators were treated in vitro with 4-hydroperoxycyclophosphamide (4-HC) with or without prior incubation with fludarabine nucleoside (F-ara-A) or with clofarabine (Cl-F-ara-A). DNA damage repair kinetics were determined by the single-cell gel electrophoresis (comet) assay. Cytotoxicity was assessed by staining with annexin V. RESULTS: CLL lymphocytes promptly initiated and completed excision repair in response to 4-HC. A 2-h preincubation with 10 microM F-ara-A or 10 microM Cl-F-ara-A inhibited the repair initiated by 4-HC, with inhibition peaking at the intracellular concentrations of 50 microM F-ara-ATP or 5 microM Cl-F-ara-ATP. Combining 4-HC with either F-ara-A or Cl-F-ara-A produced more than additive apoptotic cell death than the sum of each alone. The increase in cytotoxicity was proportional to the initial magnitude of the DNA incision and to the extent of repair inhibition by the nucleoside analogues, suggesting close correlation between the repair inhibition and induction of cell death. CONCLUSIONS: DNA repair, which is active in CLL lymphocytes, may be a biological target for facilitating the incorporation of nucleoside analogues and increasing their cytotoxicity. Thus, the increased repair capacity associated with resistant disease may be manipulated to therapeutic advantage.

Adenine Nucleotides↗
PubMed2001

[The molecular mechanisms by which PPAR gamma/RXR inhibitors improve insulin resistance].

Potent activation of PPAR gamma by thiazolidinediones(TZD) increases TG content of WAT, thereby decreasing TG content of liver/muscle, leading to amelioration of insulin resistance at the expense of obesity. Moderate reduction of PPAR gamma activity by PPAR gamma/RXR inhibitors decreases TG content of WAT/muscle/liver due to increased leptin and increase in fatty-acid combustion and decrease in lipogenesis, thereby ameliorating HF diet-induced obesity and insulin resistance. Moreover, PPAR gamma/RXR inhibitors decrease lipogenesis in WAT, while TZD stimulate adipocyte differentiation and apoptosis, thereby both preventing adipocyte hypertrophy, which is associated with alleviation of insulin resistance presumably due to decreases in FFA, and TNF alpha, and upregulation of adiponectin. We conclude that although by different mechanisms, both PPAR gamma/RXR inhibitors and PPAR gamma agonist improve insulin resistance, which is associated with decreased TG content of muscle/liver and prevention of adipocyte hypertrophy.

Adipocytes↗
PubMed2000

Induction and alternative splicing of delta isoform of Ca(2+)/calmodulin-dependent protein kinase II during neural differentiation of P19 embryonal carcinoma cells and during brain development.

Since the expression of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) is regulated during brain development, the developmental change of the enzyme was investigated during the neural differentiation of murine P19 embryonal carcinoma cells. CaM kinase II activity was induced during the differentiation of P19 cells treated with retinoic acid. Expression of the enzyme was induced 2 days after the treatment and maximized at 5 days. The enzyme activity increased about approximately 8-fold. The enzyme protein was shown to differ between differentiated and undifferentiated cells. The delta isoform of CaM kinase II was found as the major isoform in P19 cells by immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). A total of four and three alternatively spliced variants of delta isoform were detected in P19 cells by RT-PCR analysis and by immunoblotting, respectively. Although multiple alternatively spliced forms have been reported, the major splice variants of delta isoform in differentiated cells were delta l and delta 9 isoforms, which were specifically detected in differentiated cells. In undifferentiated cells, the major splice variant corresponded to delta 2 isoform. These results indicated that the expression of delta isoform of CaM kinase II was induced, and the splicing pattern of the isoform changed, during neural differentiation. Cell type distinctive changes of splicing pattern of delta isoform were also observed not only during differentiation of cultured neuronal cells, but also during development of rat forebrain and cerebellum.

Alternative Splicing↗
PubMed2000

Analysis of cytogenetic and developmental effects on pre-implantation, mid-gestation and near-term mouse embryos after treatment with trichlorfon during zygote stage.

Trichlorfon has been widely used in agriculture as a broad spectrum insecticide. We examined cytogenetic and developmental effects on early mouse zygotes exposed to trichlorfon in vivo. Pregnant female mice were intraperitoneally administered a single dose of trichlorfon (100 or 200mg/kg) at 6h post presumed conception and either sacrificed on day of gestation (dg) 3, 9 or 17 to assess the developmental toxicity and mutagenic effects on embryos. Mean cell number (dg 3) and somite number (dg 9) of embryos in the two trichlorfon-treated groups were significantly fewer than in the control group and the mean micronucleus (MN) number (dg 3) and the frequency of mosaic aneuploidies including monosomic or trisomic cell lines (dg 9) was significantly increased in both trichlorfon-treated groups compared with the control group. However, there was no difference in fetal body weight (dg 17) between the control and trichlorfon-treated groups and no increased incidence of external malformations was observed in the trichlorfon-treated groups. These findings suggest that acute exposure of trichlorfon around fertilization induces a high frequency of MN, mosaic aneuploidies and developmental retardation in pre-implantation and mid-gestation embryos, and thereafter these embryos with MN or chromosome damage appear to develop past mid-gestation and catch up with normal embryos by near-term.

Abnormalities, Drug-Induced↗
PubMed2000

Ca(2+)-independent activity of Ca(2+)/calmodulin-dependent protein kinase II involved in stimulation of neurite outgrowth in neuroblastoma cells.

We investigated the involvement of Ca(2+)-independent activity of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) in stimulation of neurite outgrowth. When neuroblastoma Neruo2a (Nb2a) cells expressing the alpha isoform of CaM kinase II (Nb2a/alpha cells) were stimulated by plating, they changed shape from round to flattened, and began to form neurites within 15 min. Numbers of cells bearing neurites increased from 15 min to about 2 h. Neurite length increased markedly from 30 min to 2 h after stimulation. Ca(2+)-independent activity of CaM kinase II increased immediately after stimulation, peaked at about 30 min, and then gradually decreased. Autophosphorylation of Thr-286 followed the same time course as the increase in Ca(2+)-independent activity. The autophosphorylation and appearance of Ca(2+)-independent activity preceded the formation of neurites. The effect of mutation of the autophosphorylation site in the kinase whose Thr-286 was replaced with Ala (alphaT286A kinase) or Asp (alphaT286D kinase) was examined. alphaT286A kinase was not converted to a Ca(2+)-independent form, and alphaT286D kinase had Ca(2+)-independent activity significantly as an autophosphorylated kinase. Cells expressing alphaT286A kinase did not form neurites, and were indistinguishable from control Nb2a cells. Cells expressing alphaT286D kinase had much longer neurites than Nb2a/alpha cells expressing the wild type kinase, although the initiation of neurite outgrowth was very late. These results indicated that Ca(2+)-independent activity of the kinase autophosphorylated at Thr-286 involves for neurite outgrowth.

Animals↗
PubMed2000

Involvement of Ca2+/calmodulin-dependent protein kinase II in neurite outgrowth induced by cAMP treatment and serum deprivation in a central nervous system cell line, CAD derived from rat brain.

A central nervous system (CNS) cell line, CAD, is known to differentiate in the absence of serum. This cell line was found to differentiate by the treatment of cAMP. Expression of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) was induced to about 2-fold or more on day 1, and was continued at a high level for 5 days after the exposure to differentiating conditions. Neurite extension was stimulated from day 1 and continued for 5 days, suggesting that CaM kinase II activity is correlated with neurite outgrowth. Of the four distinct isoforms (alpha, beta, gamma, and delta) of the kinase, the delta isoform was the major isoform in CAD cells. The splicing pattern of this isoform in the differentiated cells differed from that in undifferentiated cells, suggesting that expression of CaM kinase II is regulated during neural differentiation.

Alternative Splicing↗
PubMed2000

Constitutive tyrosine phosphorylation of ErbB-2 via Jak2 by autocrine secretion of prolactin in human breast cancer.

Overexpression of the oncogene for ErbB-2 is an unfavorable prognostic marker in human breast cancer. Its oncogenic potential appears to depend on the state of tyrosine phosphorylation. However, the mechanisms by which ErbB-2 is constitutively tyrosine-phosphorylated in human breast cancer are poorly understood. We now show that human breast carcinoma samples with ErbB-2 overexpression have higher proliferative and metastatic activity in the presence of autocrine secretion of prolactin (PRL). By using a neutralizing antibody or dominant negative (DN) strategies or specific inhibitors, we also show that activation of Janus kinase Jak2 by autocrine secretion of PRL is one of the significant components of constitutive tyrosine phosphorylation of ErbB-2, its association with Grb2 and activation of mitogen-activated protein (MAP) kinase in human breast cancer cell lines that overexpress ErbB-2. Furthermore, the neutralizing anti-PRL antibody or erbB-2 antisense oligonucleotide or DN Jak2 or Jak2 inhibitor or DNRas or MAP kinase kinase inhibitor inhibits the proliferation of both untreated and PRL-treated cells. Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing unrestricted cellular proliferation. The identification of this novel cross-talk between ErbB-2 and the autocrine growth stimulatory loop for PRL may provide new targets for therapeutic and preventive intervention of human breast cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Distinct but overlapping roles of histone acetylase PCAF and of the closely related PCAF-B/GCN5 in mouse embryogenesis.

PCAF plays a role in transcriptional activation, cell-cycle arrest, and cell differentiation in cultured cells. PCAF contributes to transcriptional activation by acetylating chromatin and transcription factors through its intrinsic histone acetylase activity. In this report, we present evidence for the in vivo function of PCAF and the closely related PCAF-B/GCN5. Mice lacking PCAF are developmentally normal without a distinct phenotype. In PCAF null-zygous mice, protein levels of PCAF-B/GCN5 are drastically elevated in lung and liver, where PCAF is abundantly expressed in wild-type mice, suggesting that PCAF-B/GCN5 functionally compensates for PCAF. In contrast, animals lacking PCAF-B/GCN5 die between days 9.5 and 11.5 of gestation. Normally, PCAF-B/GCN5 mRNA is expressed at high levels already by day 8, whereas PCAF mRNA is first detected on day 12.5, which may explain, in part, the distinct knockout phenotypes. These results provide evidence that PCAF and PCAF-B/GCN5 play distinct but functionally overlapping roles in embryogenesis.

Acetyltransferases↗
PubMed2000

Investigation of protein substrates of Ca(2+)/calmodulin-dependent protein kinase II translocated to the postsynaptic density.

To elucidate the physiological significance of the translocation of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II), we investigated substrates of CaM kinase II in the postsynaptic density (PSD). PSD proteins were phosphorylated by CaM kinase II of its PSD complex, and separated by two-dimensional gel electrophoresis. More than 28 proteins were phosphorylated under experimental conditions. Proteins corresponding to CaM kinase II substrates were excised from the gels, eluted electrophoretically, and then sequenced. Several substrates were identified, including PSD95, SAP90, alpha-internexin, neurofilament L chain, cAMP phosphodiesterase, and alpha- and beta-tubulin. Some substrates were also identified by immunoblotting, including N-methyl-D-aspartic acid (NMDA) receptor 2B subunit, 1-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor 1 (GluR1), neurofilament H chain and dynamin. PSD95, SAP90, dynamin, and alpha-internexin were demonstrated for the first time to be substrates of CaM kinase II. NMDA receptor 2B subunit and GluR1 existed as major substrates in the PSD. Moreover, translocation of CaM kinase II was inhibited by phosphorylation of PSD proteins. These results suggest that CaM kinase II plays important roles in the regulation of synaptic functions through phosphorylation of PSD proteins.

Amino Acid Sequence↗
PubMed2000

Effects of a fucoidan on the activation of plasminogen by u-PA and t-PA.

The effect of an anticoagulant fucoidan (C-I-H) from the brown seaweed Ecklonia kurome on the fibrinolytic system was studied in vitro using S-2251 as a substrate of plasmin. C-I-H enhanced the activation of Glu- and Lys-plasminogen by high molecular weight urokinase-type plasminogen activator (HMW u-PA) very effectively, but the activation by low molecular weight u-PA was hardly enhanced with C-I-H. C-I-H also potentiated moderately the activation by single- and two-chain tissue-type plasminogen activators (sct- and tct-PA). These effects of C-I-H were higher than those of heparin used. But C-I-H had no effect on the amidolytic activity of plasmin to S-2251. These results indicate that C-I-H promotes the generation of plasmin in the plasminogen activation by HMW u-PA and t-PA, but not the activity of generated plasmin. Kinetic analyses suggest that C-I-H enhances the HMW u-PA-mediated plasminogen activation by increasing the affinity of the activator for Glu- and Lys-plasminogen and by increasing the molecular activity of the activator. On the other hand, C-I-H had no effect on the affinity of tct-PA for both plasminogens. The catalytic efficiencies of HMW u-PA and tct-PA for the activation of both plasminogens were increased with C-I-H about 8- and 2-fold, respectively. The present results suggest that C-I-H has the fibrinolytic activity by stimulating the plasminogen activation by HMW u-PA and t-PA. The mechanism of the enhancement effect of C-I-H on the activation is presumed to be that C-I-H binds to plasminogen, thereby inducing a structural change of plasminogen susceptible to the action of plasminogen activators.

Anticoagulants↗