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Biomedical subjects

T Seki

Publications and source records attributed to T Seki.

At least 469 records · Page 26Linked to original sources

[An evaluation of automated hematology analyzers in detecting abnormal blood cells].

We report the usefulness and capability of two hematology analyzers with different principles in characterization of abnormal cells such as immature granulocytes and blasts. We studied a total 1635 specimens which included 69 cases with hematopoietic malignancies. THMS H-1 (Technicon Instruments) and NE-8000 (Toa Instruments) were used as analyzers. An effort was made to determine the sensitivity and specificity of positive abnormal cell flag in comparison with the presence of abnormal cells seen on a manual differential. True positive rate for immature granulocytes in H-1 and NE were 43% and 30%, respectively. False positive rate for immature granulocytes in H-1 and NE were 0.01% and 0.03%, respectively. With both analysers, cases with low percentage of immature granulocytes generated negative flag for abnormal cells. True positive rate for blasts in H-1 and NE were 74% and 65%, respectively. False positive rate for blasts in H-1 and NE were 1.8% and 0.2%, respectively. With both instruments, in all cases with blast count over 100/microliters, blasts were detected. Only H-1 detected the cases with blast counts less than 100/microliters. In H-1 all cases with ATL, one case with AMMoL and another with ALL generated negative blast flag. Upon morphologic examination, these blasts were found to be large and peroxidase negative with convoluted and irregularly shaped nuclei. On the other hand, NE detected blasts regardless of those morphology. In conclusion, Both instruments are useful in screening abnormal blood cells, while their unique capability must be considered.

Autoanalysis↗

[A case of bilateral internal thoracic artery bypass grafting in sudden death survivor with multivessel coronary spasms].

We report a 58-year-old male with a history of cardiac arrest due to coronary artery spasm, preoperative coronary arteriograms showed multivessel coronary spasm after the administration of ergonovine maleate associated with triple vessel fixed stenotic lesions. Under the use of cold diltiazem potassium-blood cardioplegic solution to prevent perioperative coronary spasm, coronary artery bypass grafting was performed. The right internal thoracic artery (ITA) was anastomosed to the left anterior descending artery and the left ITA to the circumflex artery. A saphenous vein graft was anastomosed to the right coronary artery. The postoperative course was uneventful. In postoperative coronary angiography with ergonovine stimulation, neither ITA grafts showed spastic changes, and the coronary artery distal to the anastomotic sites were well perfused through the ITA grafts. The patient has been free of angina without administration of calcium antagonist and been doing well for 2 years and 5 months since the operation.

Coronary Artery Bypass↗

[A quantitative angiographic study of characteristics of internal thoracic artery grafts in coronary artery bypass surgery].

In adult patients with atherosclerotic coronary artery disease and in pediatric patients with Kawasaki heart disease, characteristics of internal thoracic artery grafts (ITA grafts) used for coronary artery bypass grafting (CABG) were quantitatively assessed by postoperative angiography. In 142 adult patients with a ITA graft for the left anterior descending artery (LAD), the diameter ratio between ITA graft and recipient LAD at the point close to the anastomotic site (ITA/LAD diameter ratio) was determined by postoperative angiography. This ratio for the adult patients as a whole was 1.04 +/- 0.34. The multivariate analysis (Quantification I) was performed to assess the effects of the following 12 factors on the ITA/LAD diameter ratio: (1) age at the time of operation, (2) sex, (3) time-duration from the operation to angiography, (4) laterality of the ITA used, (5) presence of an undivided major side branch of the ITA graft, (6) presence of blood flow competition between the ITA graft and other grafts, (7) presence of distal stenosis of the recipient LAD, (8) severity of LAD stenosis after the operation, and (9-12) presence of hyperlipidemia, diabetes mellitus, hypertension, or smoking history. The standardized category scores of 25% LAD stenosis, 50% LAD stenosis, and blood flow competition between the ITA and other grafts were -0.815, -0.359, and -0.306, respectively. Insignificant stenosis of the recipient coronary artery was associated with reduction of the ITA/LAD diameter ratio, and this ratio strongly correlated with the severity of LAD stenosis (partial correlation coefficient: 0.627). However, no other factors significantly influenced on the ITA/LAD diameter ratio. In 15 pediatric patients, the length and diameter of 19 ITA grafts and 5 saphenous vein grafts (SVGs) which remained patent in the early (about one month) and late (14 +/- 4 months) postoperative period were determined. Only in the ITA graft, increases in graft length and diameter associated with patient growth were recognized. In the present study, the physiological characteristics of the ITA graft were demonstrated as a viable conduit with flow adaptability and growth potential.

Adult↗

[A penetrating cardiac wound by a flying metallic fragment].

A 54-year-old man suddenly felt a strike on his chest while mowing with a machine. At first he had no symptoms except for wound pain, but several hours later, he suffered from high fever with chilliness. The chest roentgenogram showed a foreign body localized within the cardiac shadow. The echocardiogram revealed that the metallic fragment was embedded in the inferior wall of the left ventricle. It appeared that the fragment entered the left ventricular cavity through his anterior chest wall, the right ventricular outflow tract and the ventricular septum. At the operation, the location of the foreign body was again confirmed by the intraoperative echocardiography and the fragment was successfully removed through a left ventricular incision under cardiopulmonary bypass. The postoperative course was uneventful and the case was reported with a review of the literature.

Echocardiography↗

Microsurgical toenail transfer to the hand.

Free nonvascularized toenail grafts have been used to reconstruct congenital or traumatic nail defects of the thumb or finger. Unfortunately, these transfers often result in deformity or atrophy. To avoid these undesirable results, microsurgical free vascularized toenail transfer was performed in 10 patients, 3 for congenital nail absence and 7 for traumatic nail defects. Patient age averaged 17 years (range 2 to 32 years). In contrast with previous reports, the whole big or second toenail complex without pulp was used in reconstruction. All 10 nails were successfully transferred with complete survival. No digits required reexploration. There were no donor- or recipient-site problems. Follow-up averaged 3 years, with a range of 14 months to 5 years and 4 months. Appropriate nail growth occurred in the congenital patients. No atrophy of the nail complex was found as long as sufficient bony support was present (9 of 10 cases). Whole free vascularized toenail transfers for reconstruction of congenital and traumatic nailbed defects achieve excellent aesthetic results while maintaining normal hand function.

Adolescent↗

Isolation and expression of cDNA for different forms of hepatocyte growth factor from human leukocyte.

Human leukocyte cDNA library was screened to isolate cDNA clones coding for hepatocyte growth factor using cDNA from human liver as a probe. Nucleotide and deduced amino acid sequences were analyzed for two of four clones obtained. One of them contained an open reading frame coding for a polypeptide chain of 728 amino acid residues like that of cDNA clone derived from human liver. In another clone a spontaneous deletion of 15 base pairs was found within the coding sequence. When expressed transiently using COS-1 cells both clones produced protein with similar biological activity against rat hepatocyte in vitro.

Amino Acid Sequence↗

Determination of free catecholamines in human urine by direct injection of urine into a liquid chromatographic column-switching system with fluorimetric detection.

An ion-exchange chromatographic method combined with ion exclusion was developed for the determination of free catecholamines in human urine. Catecholamines were separated by ion exclusion from most acidic and neutral impurities by filtration through an anion-exchange column with a hydrophilic matrix (Asahipak ES-502N) and the excluded catecholamines were separated by ion-exchange chromatography on a column of weakly acidic ion exchanger with a hydrophilic matrix (Asahipak ES-502C), connected in series to the Asahipak ES-502N column with a four-way automatic valve. A sodium succinate-borate buffer of pH 6.7 (0.035 mol of succinic acid, 0.0075 mol of borate and 0.5 mmol of ethylenediaminetetraacetate were dissolved in 1 kg of water and the pH of the solution was adjusted to 6.7 with sodium hydroxide) was used as the mobile phase, and the temperature of both columns was kept at 30 degrees C. The catecholamines in the eluate were determined fluorimetrically by post-column derivatization with glycylglycine. A diluted urine sample was injected directly onto the first column. The first column was back-flushed with the mobile phase for 52.5 min after the elution of the catecholamines from the first to the second column. Then the columns were washed with the mobile phase for 10 min in the normal direction before the next sample was injected into the first column. Samples could be analysed every 70 min and 5 pmol/ml of epinephrine, 5 pmol/ml of norepinephrine and 25 pmol/ml of dopamine in human urine could be determined.

Catecholamines↗

Hormonal regulation of plasminogen activator production by rat hepatocytes in primary culture.

Hormonal regulation in the production of a plasminogen activator (PA) was studied in rat hepatocytes in primary culture. Insulin and epidermal growth factor had no effect on the hepatic PA activity. However, glucagon and epinephrine augmented the activity, whereas dexamethasone suppressed it by lowering the production of hepatic PA rather than by inducing plasmin inhibitors or a plasminogen activator inhibitor (PAI). Dibutyryl cAMP, an analogue of cAMP, also augmented hepatic PA activity. The augmented activity level was lowered by either H-8, cycloheximide, or actinomycin D, suggesting that A-kinase and protein biosynthesis are closely associated with the augmentation. Glucocorticoid and hormones that act to raise the intracellular cAMP level may participate in hepatic PA production by the liver.

Animals↗

Association of autoimmune hepatitis with HLA-Bw54 and DR4 in Japanese patients.

Human leukocyte antigen-D region-related alleles (human leukocyte antigen DR and DQ) and human leukocyte antigen class I alleles were typed serologically in 31 Japanese patients with autoimmune hepatitis. These patients had increased serum levels of AST and IgG, high titers of autoantibodies, no history of blood transfusion and were negative for HBsAg and antibodies to HBc. Three hundred eighty-six healthy subjects and 30 patients with cryptogenic chronic hepatitis served as control groups. The frequency of DR4 was significantly higher in autoimmune hepatitis patients (90.3%) than in healthy subjects (38.6%) and in cryptogenic chronic hepatitis patients (30%). The frequency of Bw54 was significantly higher in autoimmune hepatitis patients (45.2%) than in healthy subjects (10.9%). The risk to DR4-positive subjects for autoimmune hepatitis was 14.8 relative to healthy subjects. Two of 31 patients (6.5%) with autoimmune hepatitis were positive for antibody to hepatitis C virus; both clearly satisfied criteria for autoimmune hepatitis and both had Bw54 and DR4. This study revealed a highly significant association of autoimmune hepatitis with human leukocyte antigen Bw54 and DR4 in Japanese patients. Among the DR4-positive patients with autoimmune hepatitis, no significant differences were seen between those positive or negative for Bw54 with regard to clinical or laboratory data, relapse of disease or efficacy of prednisolone. Thus human leukocyte antigen class II alleles contribute to susceptibility and resistance to autoimmune hepatitis in Japanese patients, with distinct racial differences from those in white patients.

Adult↗

Ester prodrugs of zidovudine.

Ten novel ester prodrugs of zidovudine (azidothymidine; AZT) were synthesized with aliphatic acids (acetic-stearic), and the enzymatic regeneration of AZT from the prodrugs was investigated both in vitro and in vivo. The enzymatic hydrolysis rates of the AZT esters in the presence of mouse enzyme systems (plasma, liver, and intestine, and kidney) were highly dependent on the lengths of the acyl chains of the prodrugs. The caprate or caprylate of AZT showed the highest reactivity to three of the four enzyme systems; either the decrease or the increase in the acyl chain length resulted in the decrease of the reactivity to the enzymes. Zidovudine (AZT) and three of the prodrugs (acetate, caprate, and stearate) were administered to mice intraperitoneally, and the plasma concentrations of AZT and a corresponding prodrug were measured. The AZT concentrations in plasma following the acetate administration rapidly decreased with a half-life of 14.5 min. This tendency is similar to that shown in direct AZT administration. On the other hand, the concentrations following the caprate or stearate administration decreased slowly and were maintained for as long as 4 h after dosing. The prodrug concentrations in plasma after the prodrug administration were under the detection limit (0.01 micrograms/mL), except for acetate. The absence of the caprate and stearate in plasma may be attributed to the high hydrophobicity or favorable tissue distribution of the ester derivatives.

Animals↗

Controlled release of 3',5'-diester prodrugs of 5-fluoro-2'-deoxyuridine from poly-L-lactic acid microspheres.

Poly-L-lactic acid (MW 6000) microspheres (PLA-MS) containing 5-fluoro-2'-deoxyuridine (FUdR) or four ester prodrugs of FUdR were prepared and examined with regard to the in vitro release kinetics. The incorporation efficiency of the lipophilic prodrugs into the PLA-MS was higher than that of FUdR or the hydrophilic prodrugs. The release of the lipophilic FUdR prodrugs from PLA-MS was sustained as compared with that of FUdR from PLA-MS. The release kinetics of the FUdR prodrugs appears to fit the Higuchi, Baker, and Lonsdale model in the early stage of the release process. The slope of the Baker and Lonsdale plots of the release of divaleryl-FUdR from PLA-MS decreased as the initial drug loading was decreased. The order of the release rates of FUdR prodrugs from PLA-MS with the same prodrug content was similar to that of the water solubilities of the prodrugs. These results suggest that the ester prodrugs could be released from PLA-MS by diffusion through water-filled capillaries or a series of pores rather than by diffusion through the PLA matrix.

Chemical Phenomena↗

Depression of drug metabolizing activity in the human liver by interferon-alpha.

The depressant effect of interferon-alpha on drug metabolizing activity in the liver has been investigated in 12 patients with chronic active hepatitis B. 7-methoxy-coumarin (7-MC) O-demethylase and 7-ethoxycoumarin (7-EC) O-deethylase, in specimens obtained by liver biopsy, were measured before and after interferon treatment. 7-MC and 7-EC O-dealkylase activity were significantly reduced after interferon treatment, from 13.4 to 9.24 nmol.g-1 liver.min-1, and from 3.22 to 2.16 nmol.g-1 liver.min-1, respectively. The magnitude of the fall varied widely between individual patients. The study provides the first direct evidence that interferon-alpha can impair the activity of drug metabolizing enzymes in the human liver.

7-Alkoxycoumarin O-Dealkylase↗

Thyrotropin-releasing hormone-immunoreactive system in the brain and pituitary gland of the sea bass (Dicentrarchus labrax, Teleostei).

The immunohistochemical distribution of thyrotropin-releasing hormone-like immunoreactivity (TRH-ir) in the brain and pituitary of the sea bass (Dicentrarchus labrax) was examined on cryostat sections of tissues perfuse fixed in a formaldehyde-glutaraldehyde mixture. TRH-ir fibres were found in many areas of the brain: dorsal and ventral telencephalon, preoptic and tuberal hypothalamus, thalamus, midbrain tegmentum, optic tectum, and medulla oblongata. In the hypothalamus the densest area of innervation was the nucleus anterioris tuberis and medial nucleus recessus lateralis, where small TRH-ir cell bodies were also found. In the pituitary gland, TRH-ir fibres were numerous in the posterior neurohypophysis, and these appeared to form varicosities between groups of melanocorticotropic cells of the pars intermedia. No clear relationship was seen between TRH-ir fibres and the thyrotropic cells, or any other cell type of the pars distalis. In the brain stem a notable feature was the prominent innervation of groups of motoneurons by beaded TRH-ir fibres. These observations suggest that in teleost fishes the role of TRH may be related to pars intermedia function, rather than the thyrotropin- or prolactin-releasing function established in tetrapods. In addition the tripeptide may act as a central neurotransmitter involved in sensory and autonomic motor integration.

Animals↗

Changes of egg retinoids during the development of Xenopus laevis.

The changes of egg retinoids during the development of Xenopus laevis were investigated by high-performance liquid chromatography (HPLC). All-trans retinal and 3-dehydroretinal are endogenous in the egg and are distributed to both the eyes and the ventral portion of the larval body. These retinals are converted to all-trans retinyl palmitate and 3-dehydroretinyl palmitate during the development up to stage 46. 11-cis retinal and 3-dehydroretinal can be detected after stage 40 in the eyes but not in the larval ventral portion. It is suggested that retinoids are transported from the larval ventral portion to the eyes after stage 41/42.

Animals↗

Enhanced delivery of zidovudine through rat and human skin via ester prodrugs.

In an attempt to improve the skin delivery characteristics of Zidovudine (AZT, azidothymidine), five aliphatic esters (acetate, butyrate, hexanoate, octanoate, and decanoate) of AZT were synthesized and assessed as prodrugs of AZT. While the water solubility of the esters is lower than that of AZT, the solubilities in isopropylmyristate (IPM) and the partition coefficients (n-octanol:buffer) are higher. Susceptibility to enzymatic hydrolysis in the rat skin homogenate increases as the acyl chain of the ester is lengthened. Among the esters, acetate (C2-AZT) and hexanoate (C6-AZT) showed 2.4- and 4.8-fold enhanced permeation in human skin from an apolar vehicle (IPM) relative to application of AZT itself, respectively.

Administration, Cutaneous↗

Calcium wave evoked by activation of endogenous or exogenously expressed receptors in Xenopus oocytes.

The mRNA encoding the cloned substance K receptor was microinjected into Xenopus laevis oocytes. After expression of the mRNA, Ca2+ was imaged in the oocytes with a digital imaging fluorescence microscopy system using the Ca2(+)-sensitive dyes fura-2 and fluo-3. Application of substance K caused a dose-related wave of Ca2+ mobilization to spread from a focus and to elevate the Ca2+ concentration in the oocyte. Activation of endogenous muscarinic or angiotensin II receptors in noninjected oocytes evoked a similar response. The Ca2+ rise in oocytes induced by substance K was due to internal Ca2+ mobilization and was independent of external Ca2+, since it occurred in Ca2(+)-free medium fortified with 2 mM EGTA. The Ca2+ imaging was well correlated with ion current measurements of voltage-clamped oocytes. Imaging, in addition to detecting the spatial spread of Ca2+ across the cell, was at least as sensitive as voltage clamping and much faster when screening oocytes for the expression of receptor mRNAs that stimulate Ca2+ mobilization. While it is known that fertilization of Xenopus eggs causes a spreading wave of Ca2+ mobilization, we found that activation of either native or newly expressed receptors in oocytes causes a similar change in Ca2+ distribution.

Animals↗