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Biomedical subjects

T Uchida

Publications and source records attributed to T Uchida.

At least 343 records · Page 19Linked to original sources

[Reproducibility of spasm in patients with long-term remission of vasospastic angina by medical treatment].

The reproducibility of coronary vasospasm was assessed in nine patients with complete remission of vasospastic angina by medical treatment by reexamination at intervals of mean [+/-SD] 5.7 +/- 0.9 years. Twenty-one segments were defined as spastic, demonstrating more than 90% narrowing after acetylcholine injection at the initial angiography. The degree of spasticity, type of spasm (diffuse or focal) and coronary artery diameter in these segments at the initial and follow-up studies were compared. Of the 21 segments, 17 (81%) still had some spasticity (> 25%) at the follow-up study and 8 (38%) of these 17 showed spasticity with greater than 90% narrowing. On the other hand, spasm was not reprovoked in 4 (19%) segments. Luminal diameter of the spastic segments decreased significantly at the follow-up study (2.52 +/- 0.83 vs 2.26 +/- 0.62 mm, p = 0.01), but percentage stenosis was not different between the initial and follow-up studies (9.1 +/- 7.2 vs 10.3 +/- 8.0%, NS). The reproducibility of the type of spasm provoked was 83%. Coronary vasospasticity persists to some extent in spite of complete remission of angina by medical treatment, and the type of spasm provoked has high reproducibility. Therefore, the cessation of drug treatment should be done carefully.

Acetylcholine↗

Lymph node metastases detected in the mesorectum distal to carcinoma of the rectum by the clearing method: justification of total mesorectal excision.

BACKGROUND: Total mesorectal excision effectively reduces the local recurrence rate of carcinoma of the rectum. This study was undertaken to clarify the rationale for total mesorectal excision. STUDY DESIGN: We retrospectively reviewed the records of 198 patients who underwent resection of a carcinoma of the rectum. The presence of nodal metastases in the mesorectum distal to the primary tumor was examined by the clearing method. RESULTS: The metastatic rate in the distal mesorectum was 20.2 percent. The metastatic rates according to the extent and site of the tumor were as follows: pT1, 0 percent; pT2, 0 percent; pT3, 21.9 percent; pT4, 50 percent; rectosigmoid, 10 percent; upper rectum, 26.3 percent; and lower rectum, 19.2 percent. The longest distal spread from the primary tumor to the metastatic node was 2 cm in carcinoma of the rectosigmoid, 4 cm in carcinoma of the upper rectum, and 3 cm in carcinoma of the lower rectum. CONCLUSIONS: Total mesorectal excision is required for patients with T3 and T4 tumors in the lower rectum, and excision of all mesorectal tissue down to at least 5 cm below the tumor is required for patients with T3 and T4 tumors in the upper rectum.

Humans↗

Pharmacokinetics of incadronate, a new bisphosphonate, in healthy volunteers and patients with malignancy-associated hypercalcemia.

We investigated the pharmacokinetics of incadronate, a new bisphosphonate, after a 2-hour intravenous infusion to healthy volunteers and patients with malignancy-associated hypercalcemia. Following administration at 0.025-1.6 mg to healthy volunteers, peak plasma concentration of incadronate increased in a dose-proportional manner. Plasma concentration thereafter declined biexponentially with a half-life of 0.26-0.40 h (t1/2 alpha) and 1.58-1.98 h (t1/2 beta). AUC increased dose-proportionally, whereas distribution volume (Vdss), total body clearance (CLt), renal clearance (CLr) and nonrenal clearance (CLnr), corresponding to bone uptake clearance, changed little among doses, indicating the linear pharmacokinetics of the drug after intravenous administration. Within 24 h, 55.1-69.5% of the dose was excreted into urine as the unchanged drug, most in the first 6 h. CLr and CLnr accounted for about 60% and 40% of the CLt, respectively, suggesting that the pharmacokinetics of incadronate are affected by changes in these clearances. In patients, plasma concentration at 2 h increased dose-proportionally in the range of 2.5-10.0 mg. Urinary excretion of YM175 up to 24 h after dosing was as low as 10.5% of the dose, being 1/6 of those in volunteers. A positive correlation (r > 0.89) was observed between creatinine clearance and urinary incadronate excretion in all volunteers and patients, indicating that the reduction of urinary excretion in patients is due to the decrease in renal function accompanying hypercalcemia. Based on comparison of the dose-normalized plasma concentration, the plasma level at 2 h in patients was comparable with that in volunteers, whereas the level at 8 h was 3 times higher in patients, suggesting that elimination from plasma in patients is delayed due to decreased renal function. Nevertheless, the plasma concentration profile in patients was lower than that predicted from the decrease in CLr. This finding suggests that the increase in plasma concentration with decreasing renal excretion in hypercalcemic patients was compensated for by enhanced bone uptake of the drug.

Adult↗

[Pancreatic anastomosis after pancreatoduodenectomy].

Leakage from a pancreatic anastomosis after a pancreatoduodenectomy is one of the serious problems that can bring on life-threatening complications and lead to operative mortality. To minimize these complications, various reconstruction methods have been proposed. A series of 183 patients underwent pancreatoduodenectomy between August 1981 and December 1996 at 1st Department of Surgery, Teikyo University School of Medicine. Our pancreatic anastomoses were classified into four groups based on "Classification of Pancreatic Carcinoma (Japan Pancreas Society, FirstEnglish Edition, Kanehara, Tokyo 1996)",: (a) mucosa-to-mucosa pancreatico jejunostomy in 58 cases, (b) tube assisted (telescoped typed) pancreaticojejunostomyin 104, (c) pancreaticojejunostomy through dunking method in 2, and (d) panc reaticogastrostomy in 19. The leakage occured in 5 out of 104 of tube-assisted pancreaticojejunostomy, in 1 out of 19 of pancreaticogastrostomy. Due to the smooth healing process of anastomosis, mucosa-to-mucosa pancreaticojejunostomy have been applied, leading to results were no leakage occurred in 58 consecutive cases.

Anastomosis, Surgical↗

IFN-gamma-mediated protection against intracerebral challenge with Bordetella pertussis in mice.

Mice inoculated with whole cell pertussis vaccine (WCV) acquired protection against intracerebral challenge with Bordetella pertussis without any appreciable antibody production against pertussis toxin or filamentous hemagglutinin. Spleen cells from mice immunized with WCV produced a significant amount of IFN-gamma upon stimulation in vitro with WCV. Furthermore, mice inoculated with recombinant IFN-gamma along with a suboptimal dose of WCV survived longer than those that received WCV alone. These results suggest that, in WCV-immune mice, IFN-gamma plays an important role in protection against intracerebral challenge with B. pertussis.

Animals↗

[Acute myeloblastic leukemia showing pronounced skin infiltration during administration of low-dose cytarabine and etoposide with granulocyte colony-stimulating factor].

A 26-year-old woman was admitted to our hospital for lumbago on November 29, 1995. The white blood cell count was 6,500/microliter with 26.5% myeloblasts and the bone marrow was hyperplastic due to myeloblasts. Myeloblasts were negative for myeloperoxidase and positive for alpha-naphthyl butylate esterase, CD11a (89%), CD11b (38%), CD11c (92%), CD33 (91%) and HLA-DR (58%). Chromosomal abnormalities were recognized: 46, XX, t(9;11) (p22;q23), 45, XX, -7, t(9;11) (p22;q23) and 47, XX, +19, t(9;11) (p22;q23). Acute myeloblastic leukemia (M5a) was diagnosed. Disseminated intravascular coagulation was also present. The patient received induction therapy and achieved remission on January 9, 1996, but myeloblasts increased to 3.6% in bone marrow despite consolidation therapy. Low doses of cytarabine (AraC) and etoposide were instituted on March 7, granulocyte colony-stimulating factor (G-CSF) was started on March 15, and pronounced skin infiltration developed on March 18. The patient received reinduction therapy from April 16 and administration of G-CSF was combined for 2 days, and a marked increment of myeloblasts in the peripheral blood was observed. After discontinuation of G-CSF, myeloblasts decreased and skin infiltration disappeared. However, the patient died of cerebral infiltration on June 30. The response of myeloblasts to G-CSF by in vitro liquid culture was noteworthy. The present case stresses the requirement for great caution to be exercised in the use of G-CSF in patients receiving low dose AraC.

Adult↗

[Simultaneous repair for funnel chest and intracardiac lesions in two pediatric patients].

Two successful cases underwent simultaneous repair for funnel chest using sternal turnover with rectus abdominal flap and intracardiac lesions were reported. A 7-year-old female (case 1) was diagnosed with funnel chest and annulo-aortic ectasia due to Marfan's syndrome. Second patient was a 12-year-old male (case 2) with funnel chest and ventricular septal defect (VSD). Both patients underwent sternal turnover and intracardiac repair (case 1: Bentall's operation, case 2: patch closure of VSD), simultaneously. Removing the cost-sterno complex before cardiac operation allowed an excellent surgical exposure. Bleeding was minimum, especially no homologous blood transfusion was needed in case 2. Simultaneous surgery consisted of intracardiac repair and sternal turnover is recommended even for pediatric patients.

Aortic Valve Insufficiency↗

Stimulation of phospholipid synthesis in HeLa cells by epidermal growth factor and insulin: activation of choline kinase and glycerophosphate acyltransferase.

The cultivation of HeLa cells in the absence of growth factors reduced proliferation with a considerable decrease in the phospholipid content. A single addition of EGF or insulin was not enough to stimulate proliferation, but still sufficient to efficiently restore the phospholipid content to the level of serum-grown cells. Both EGF and insulin stimulated the synthesis of major phospholipids in HeLa cells. Irrespective of whether cells were stimulated or not, the phospholipid composition and the phospholipid/protein ratio remained constant, suggesting the existence of a mechanism that keeps them constant under varying conditions. The degradation of phosphatidylcholine was not affected by EGF or insulin. Both EGF and insulin increased choline kinase activity equally and promoted the conversion of choline to cholinephosphate, accompanied by an expansion of the cholinephosphate pool in treated cells. The level of glycerophosphate acyltransferase was enhanced by EGF and insulin but EGF was more effective than insulin. The present results provide evidence that one of the roles of EGF and insulin during cell growth is to stimulate the synthesis of phospholipids.

Choline↗

Quantification of estrogen receptor messenger RNA by quantitative polymerase chain reaction using internal standard fragment.

A simple and reliable polymerase chain reaction-based method for quantifying human and rat estrogen receptor (ER)-mRNA is described. This method involves co-amplification of cDNA transcribed from sample RNA with an internal standard to reduce tube to tube amplification variations. Human and rat internal standards were synthesized by insertion of a DNA fragment near the midportion of human and rat target ER cDNA molecules. After co-amplification, both products of target ER cDNA and internal standard were separated on agarose gel by electrophoresis and transferred onto a membrane filter. The radioactivity hybridized with 32P-labeled ER cDNA was counted. The ER mRNA content was calculated by linear regression analysis after obtaining a logarithm of ratios between the sample and the internal standard radioactivity. The coefficient of variation of this assay was 18.8%. An absolute amount of ER mRNA in less than 10(4) cultured cells could be measured.

Animals↗

Mg/Ca Thermometry in Coral Skeletons

The magnesium-to-calcium (Mg/Ca) ratio of coral skeletons from Ishigaki Island, Ryukyu Islands, Japan, closely tracked sea surface temperature (SST) over an 8-year period. Measurements were made with the fast technique of inductively coupled plasma-atomic emission spectrometry. The variation of the coral Mg/Ca ratio with SST change is about four times that of the current, widely used coral strontium-to-calcium ratio. The temporal and geographic variation of the seawater Mg2+/Ca2+ ratio probably has little influence on coral Mg/Ca variation. Results indicate that the coral Mg/Ca ratio has the potential to provide fast, precise, high-resolution proxies for past tropical SSTs.

Journal Article↗

Mechanism of spontaneous termination of functional reentry in isolated canine right atrium. Evidence for the presence of an excitable but nonexcited core.

BACKGROUND: According to the spiral wave hypothesis of reentry, the core of functional reentry remains excitable but not excited. We sought to determine whether the core remains excitable and whether excitation of the core by an outside wave front leads to termination of the reentry in the atrium. METHODS AND RESULTS: In nine isolated canine right endocardial atrial tissues (3.8 by 3.2 cm wide), reentry was induced by a premature point stimulus (S2). The isochronal activation maps and dynamics of the activation patterns were visualized with the use of 509 bipolar electrodes (1.6-mm resolution). The S2 applied after 8 regular beats induced reentry with a mean cycle length of 162 +/- 20 ms (15 episodes). Reentry had a large excitable gap (93 +/- 26 ms) as determined by early capture with twice the level of threshold stimuli. The central area (core) around which the wave fronts rotated had a mean surface area of 12 +/- 3 mm2. The electrograms located in the core of the reentry registered no or very low amplitude potentials. In 13 of 15 episodes, reentry terminated when an outside new wave front merged with the original wave front and excited the core. Core excitation caused disruption of the original wave front, and the newly formed wave front(s) vanished at the tissue border within 77 +/- 18 ms. In 2 episodes, reentry terminated abruptly when an outside new wave front propagating in a direction opposite to the reentrant wave front collided with the leading edge of the reentrant wave front. CONCLUSIONS: Functional reentry in the atrium is compatible with a spiral wave of excitation with an excitable but nonexcited core and a large excitable gap. Reentry may be terminated either by direct excitation of the core that displaces the wave front to the tissue border or by collision with an outside new wave front.

Animals↗

Inhibition of hepatitis-B-virus core promoter by p53: implications for carcinogenesis in hepatocytes.

The incidence of hepatocellular carcinoma (HCC) is particularly high in regions of Asia and sub-Saharan Africa where rates of infection with human hepatitis-B virus (HBV) and aflatoxin-B1 contamination of food are high. In HCC tumors occurring in inhabitants of these regions, a G-to-T mutation frequently occurs at position 249 of the tumor-suppressor gene p53. This suggests that HBV and p53 mutation may collaborate in the carcinogenic process in liver. We have examined the effect of the HBV protein HBX in HCC lines with exogenous wild-type p53 or mutated p53 on transactivation of 2 different reporter genes. Transfection of HCC lines with wild-type p53 and a reporter with the promoter from the p53-responsive gene WAF1/p21 resulted in a high level of expression, as expected. When cells were co-transfected with a reporter gene driven by the HBV core promoter and with the HBX gene, expression was enhanced in the Hep 3B, HLE, PLC/PRF/5 and HuH 7 lines, but not in the HuH 1 line. Co-transfection of the reporter with a plasmid containing wild-type p53 resulted in significant inhibition of the HBV core promoter in all of the lines, whereas the mutated p53 gene had no effect. Our results indicate that wild-type p53 can inhibit transcription from the HBV core promoter. In similar experiments, both HBX and p53 were co-transfected into HCC lines with the WAF1/p2l reporter gene. HBX inhibited p53-induced expression in 4 of the 6 lines (Hep 3B, HuH 1, HuH 7 and HLE), there was no effect in one line (HLF), and enhancement was evident in PLC/PRF/5. Our results indicate that inhibition of p53 transcriptional activity by HBX does occur in HCC, but is highly cell-context-dependent. Inhibition of transcription from the HBV core promoter by wild-type p53 appears to be more universal, and may represent a mechanism by which wild-type p53 can protect against the carcinogenic process in liver.

Carcinoma, Hepatocellular↗

Site-specific phosphorylation of synapsin I by mitogen-activated protein kinase and Cdk5 and its effects on physiological functions.

Posttranslational modifications of synapsin I, a major phosphoprotein in synaptic terminals, were studied by mass spectrometry. In addition to a well known phosphorylation site by calmodulin-dependent protein kinase II (CaM kinase II), a hitherto unrecognized site (Ser553) was found phosphorylated in vivo. The phosphorylation site is immediately followed by a proline, suggesting that the protein is an in vivo substrate of so-called proline-directed protein kinase(s). To identify the kinase involved, three proline-directed protein kinases expressed highly in the brain, i.e. mitogen-activated protein (MAP) kinase, Cdk5-p23, and glycogen synthase kinase 3beta, were tested for the in vitro phosphorylation of synapsin I. Only MAP kinase and Cdk5-p23 phosphorylated synapsin I stoichiometrically. The phosphorylation sites were determined to be Ser551 and Ser553 with Cdk5-p23, and Ser62, Ser67, and Ser551 with MAP kinase. Upon phosphorylation with MAP kinase, synapsin I showed reduced F-actin bundling activity, while no significant effect on the interaction was observed with the protein phosphorylated with Cdk5-p23. These results raise the possibility that the so-called proline-directed protein kinases together with CaM kinase II and cAMP-dependent protein kinase play an important role in the regulation of synapsin I function.

Actins↗

Extra Y chromosome in T-cell acute lymphoblastic leukemia.

We describe a 66-year-old man who developed T-cell acute lymphoblastic leukemia (ALL) with a sole clonal chromosomal abnormality of 47,XY,+Y. Leukemic cells were positive for CD2, CD7, terminal deoxynucleotidyl transferase and cytoplasmic CD3. T-cell receptor beta, gamma, and delta genes remained germline configurations. The bone marrow aspirate was 47,XY,+Y in all metaphase cells observed. The patient achieved complete remission by chemotherapy, and the bone marrow cells and the phytohemagglutinin stimulated peripheral blood lymphocytes showed a normal karyotype of 46,XY at that time. This fact suggests that an extra Y chromosome may be a kind of new chromosomal abnormality of T-cell ALL.

Aged↗

Expression of cytidine deaminase in human solid tumors and its regulation by 1 alpha,25-dihydroxyvitamin D3.

We found that vitamin D3 up-regulates the expression of cytidine deaminase (CDD) gene in some human solid tumor cell lines as well as the monocytic leukemia cell lines. Two kinds of full length CDD cDNA were identified from human placenta: one has glutamine and the other one has lysine at codon 27. The expression was tested in various normal tissues and the cancer cell lines. Northern blot analysis demonstrated high levels of CDD mRNA in leukocytes and moderate levels in liver, kidney, placenta, spleen and lung. Expression of CDD in 20 human cancer cell lines was highly variable and not related to its expression in normal tissues. Treatment of the cell lines with 1 alpha,25-dihydroxyvitamin D3 resulted in up-regulation of CDD expression in some lines but not others. Three of five gastric carcinoma cell lines and five of eight colorectal cancer lines had increased levels of CDD mRNA following 24 h treatment with vitamin D3. Increased mRNA was detected in gastric cancer MKN 45 cells after 3 h of treatment with vitamin D3 and increased enzyme activity was measured after 24 to 48 h. But no combined effect of calcitriol with 9-cis retinoic acid was found. Our results demonstrate that CDD can be up-regulated by vitamin D3 in some solid tumor cell lines.

Base Sequence↗

Amorphization of Serpentine at High Pressure and High Temperature

Pressure-induced amorphization of serpentine was observed at temperatures of 200° to 300°C and pressures of 14 to 27 gigapascals with a combination of a multianvil apparatus and synchrotron radiation. High-pressure phases then crystallized rapidly when the temperature was increased to 400°C. These results suggest that amorphization of serpentine is an unlikely mechanism for generating deep-focus earthquakes, as the temperatures of subducting slabs are significantly higher than those of the rapid crystallization regime.

Journal Article↗