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Biomedical subjects

S Yoshida

Publications and source records attributed to S Yoshida.

At least 559 records · Page 31Linked to original sources

[Estimation of 99mTc-GSA receptor amount by non-linear 3-compartment model: ligand-receptor binding model without blood sampling].

99mTc-GSA (galactosyl serum albumin) receptor amount (Ro) was estimated by a non-linear 3-compartment model of the ligand-receptor binding without blood sampling. Forward/reverse rate constants and receptor amount were assumed to be variable. Relationship between this parameter and other conventional parameters including ICG R15 (15-minutes retention rate of indocyanine green) was evaluated for 43 surgical candidates with liver tumors. Linear relationships between Ro and HH15 and LHL15 were R2 = 0.73 and 0.72, respectively. Linear relationship between Ro and Rmax, the maximum removal rate, is also good (R2 = 0.84), and the regression line (y = 0.038x + 0.066) was slightly over 0 at y-interception. Linear relationship between Ro and ICG R15, was poor (R2 = 0.39) and relationship was rather a concave shape. Linear relationship of reduction rate between Ro and non-tumor tissue volume of the liver, which assessed at the same day of two weeks after the operation, was y = 1.09x - 0.01 (R2 = 0.82). GSA receptor amount, Ro, seems to change proportional to non-tumor liver tissue volume changing before and after hepatectomy. Complementary to ICG R15, it may be an useful and intuitive parameter for hepatectomy.

Asialoglycoprotein Receptor↗

Emergency off-pump coronary artery bypass grafting under a beating-heart.

BACKGROUND: Coronary artery bypass grafting (CABG) on a beating heart has been successfully performed for high risk patients, and is known to be less invasive than conventional CABG using cardiopulmonary bypass (CPB). We expanded the indication of beating-heart CABG in patients requiring emergency coronary revascularization. METHODS: A retrospective chart review was performed for patients who had undergone emergency CABG on a beating heart (EM-BH group), elective CABG on a beating heart (Elective-BH group) and emergency CABG under CPB (EM-CPB group), between January 1, 1997 and June 30, 1998. RESULTS: Four cases (1 male and 3 females with a mean age of 67.8 +/- 5.4) in the EM-BH group, 67 cases (48 males and 19 females with mean age of 67.3 +/- 7.8) in the Elective-BH group, and 41 cases (29 males and 12 females with mean age of 63.3 +/- 10.4) in the EM-CPB group were analyzed. The number of the grafts was 1.75 +/- 0.50 in EM-BH group, 1.37 +/- 0.55 in the Elective-BH group, and 2.95 +/- 1.07 in the EM-CPB group. The intubation period, ICU stay, and the postoperative hospital stay were significantly shorter in the EM-BH group (6.0 hours intubation, 1.5 days ICU stay, and 11.5 days postoperative hospital stay) and Elective-BH group (6.8 +/- 11.0 hours intubation, 1.6 +/- 1.5 days ICU stay, and 12.7 +/- 5.2 days postoperative hospital stay) than in the EM-CPB group (20.1 +/- 22.5 hours intubation, 3.6 +/- 2.4 days ICU stay, and 21.8 +/- 14.9 days postoperative hospital stay). CONCLUSION: The postoperative recovery period for EM-BH patients was almost the same as that for elective cases of beating-heart CABG, and was significantly shorter than that of conventional emergency CABG under CPB. Selected patients with coronary ischemia can be safely treated by beating-heart surgery.

Aged↗

Determination of thorium in organs from thorotrast patients by inductively coupled plasma mass spectroscopy and x-ray fluorescence.

Concentrations of thorium were determined by inductively coupled plasma mass spectroscopy in various organs collected from Japanese Thorotrast autopsy subjects to provide information on dosimetry for Thorotrast patients. Duplicate analyses were performed for 98 samples, and data for thorium in 27 different organs were obtained. The highest thorium level was found in spleen (mean: 16,000 microgram/g wet weight), followed by liver (2100 microgram/g wet weight) and bone marrow (600 microgram/g wet weight). The other concentrations decreased in the following order: lymph node, gallbladder, testis, lung, small intestine, adrenal gland, pancreas, dura, esophagus, muscle, thyroid, large intestine, stomach, fat, kidney, urinary bladder, main artery, prostate, diaphragm, trachea, heart, cerebellum, cerebrum and intervertebral disk. The last four organs showed markedly low concentrations of 2-7 microgram/g wet weight. Compared to the background thorium levels reported in the literature for human organs, the values for the organs from Thorotrast patients (even in the organs with the lowest concentrations) were at least several thousand times higher, suggesting the importance of also considering organs with minor deposition in dosimetry. Distributions of thorium in some selected organs were studied by microbeam X-ray fluorescence. The thorium conglomerates could be identified, and images of microdistributions of thorium in the organ slices were obtained.

Humans↗

Characteristics of human T-lymphotropic virus type-1 (HTLV-1)-infected cell line MT-2, which is not killed by a natural killer cell line NK-92 but is killed by lymphokine-activated killer cells.

Natural killer (NK) cell-mediated cytolysis (NK-lysis) is triggered by costimulatory signals of adhesion molecules and is downregulated by negative signals of killer cell inhibitory receptors (KIRs). Recently, a NK cell line, NK-92, was established. This cell line can kill several tumor cells, which possess adhesion molecules CD54 and CD102. However, the NK-92 cannot kill a human T-lymphotropic virus type 1 (HTLV-1)-infected cell line, MT-2, although lymphokine-activated killer (LAK) cells can kill MT-2. In this report we investigated the reason for LAK sensitivity but NK-92 resistance of the MT-2. The MT-2 highly expressed CD54 and CD102, suggesting that the costimulatory signals may be intact. Then we tested the responsibility of the negative signals by determining HLA type of the MT-2 and KIRs of the effector cells. The MT-2 expressed HLA-A24, B40, B51, Cw3, and HLA-G. The NK-92 did not express KIR2DL1, KIR2DL2,3, nor KIR3DL1, but 24% of the cells weakly expressed CD94. The blocking tests against these HLA class I molecules and KIRs did not restore the NK-92 resistance, although blocking against HLA-G slightly increased its lysis. Finally, in order to eliminate the class I molecules from the cell surface, we treated the MT-2 using a buffered citric acid solution (pH 3.8). By using this treatment, the expression of class I molecules and HTLV-1 antigen decreased, and then the MT-2 was killed by the NK-92. These findings suggest that an aberrant class I molecule of the MT-2 transferred a negative signal to the NK-92 and induced the NK-92 resistance. It remains to be elucidated whether or not the HTLV-1 infection contributed to the alteration of the class I molecule.

Antigens, CD↗

Problems regarding the integration of medical images into the total hospital information system.

Since 1989, the integration of medical images into the total hospital information system (HIS) has been investigated and developed at Kochi Medical School. The basic concept of the integration is that, in the same way they can view text based data, doctors can retrieve and view images using the PC terminals of the total HIS. The possibility of utilizing the PC terminals of the total HIS as image viewing stations was investigated. A test run was performed in the period from October 1995 to July 1997. The test run revealed that fast image access is crucial in order for the system to be useful for doctors. After making various improvements, the final system became well used in the clinical practice. However, in order to progress to the film-less stage, the final system still has three problems that must be solved: quality of the image display, operation of multi-exams, and quality assurance of the digital image.

Computer Systems↗

Double lung cancer combined with idiopathic thrombocytopenic purpura. A case report.

A 68-year-old woman was admitted because of two abnormal lung shadows, which later proved to be differentiated double cancer. Preoperative hematology tests showed a low platelet count and the result of bone marrow aspiration was compatible with idiopathic thrombocytopenic purpura (ITP). A normal platelet count was once obtained by preoperative percutaneous partial splenic arterial embolization (PSE). However, as there was a tendency for the platelet count to decrease just before surgery, one shot high-dose immunoglobulin (Ig) was administered, which is thought to have a short term effect. The operation was performed successfully. After resection of lung cancer, her platelet count was maintained at around 15x10(4) mm3 without taking drugs for ITP. These findings suggest a relationship between lung cancer and ITP.

Adenocarcinoma↗

The effect of detergents on chemical occult blood test.

OBJECTIVES: Our previous investigation showed that toilet sanitizers and their main constituents, detergents, caused false negative reactions of the immunological occult blood test. Therefore, we investigated the effects of detergents on the chemical occult blood test. MATERIALS AND METHODS: Twenty-nine kinds of detergents were added to a Hb solution and measured Hb concentration by a quantitative chemical occult blood test (modified colorimetric o tolidine method) and the results were compared with those by the immunological test. The detergents' effects on Hb spectra were also analyzed. RESULTS: The chemical test was affected slightly by most of the detergents tested although the immunological test was markedly to moderately affected. The spectrum of hemoglobin was not affected by the detergents examined except for the high concentrations of SDS and DTAB. CONCLUSION: The chemical occult blood test is affected by some detergents, but less than the immunological tests.

Benzidines↗

The Arabidopsis dwf7/ste1 mutant is defective in the delta7 sterol C-5 desaturation step leading to brassinosteroid biosynthesis.

Lesions in brassinosteroid (BR) biosynthetic genes result in characteristic dwarf phenotypes in plants. Understanding the regulation of BR biosynthesis demands continued isolation and characterization of mutants corresponding to the genes involved in BR biosynthesis. Here, we present analysis of a novel BR biosynthetic locus, dwarf7 (dwf7). Feeding studies with BR biosynthetic intermediates and analysis of endogenous levels of BR and sterol biosynthetic intermediates indicate that the defective step in dwf7-1 resides before the production of 24-methylenecholesterol in the sterol biosynthetic pathway. Furthermore, results from feeding studies with 13C-labeled mevalonic acid and compactin show that the defective step is specifically the Delta7 sterol C-5 desaturation, suggesting that dwf7 is an allele of the previously cloned STEROL1 (STE1) gene. Sequencing of the STE1 locus in two dwf7 mutants revealed premature stop codons in the first (dwf7-2) and the third (dwf7-1) exons. Thus, the reduction of BRs in dwf7 is due to a shortage of substrate sterols and is the direct cause of the dwarf phenotype in dwf7.

Alleles↗

TX-1877: design, synthesis, and biological activities as a BRM-functional hypoxic cell radiosensitizer.

PURPOSE: 2-Nitroimidazole acetamide TX-1877 and its derivatives (TX-1877 analogs) were designed, synthesized, and evaluated by their in vitro and in vivo radiosensitization, tumor growth control, suppression of lung metastasis, and immunopotentiation, as biological response modifier (BRM)-functional hypoxic cell radiosensitizers. MATERIALS AND METHODS: TX-1877 analogs were designed and synthesized in our laboratory. In vitro radiosensitizing ability was estimated using EMT6/KU cells under hypoxic conditions. In vivo radiosensitization, antimetastasis, and immunopotentiation were evaluated using female C3H/He mice bearing the SCCVII tumor. Days (15 or 10) after the inoculation of 10(5) SCCVII tumor cells into the hinder thigh, a drug (0.4 mg/g) was administered i.p. and local irradiation of 30 Gy was given at 30 min after its administration. Tumor growth was observed for 20 days and mice were euthanized to count the number of metastatic nodules on the surface of the lungs. Tumor tissues were extirpated and stained by the ABC method at 1, 2, and 3 weeks after treatment for immunological evaluation. RESULTS: Novel types of bifunctional radiosensitizers, TX-1877 and its analogs possessing BRM-functions (i.e., antimetastatic and immunopotentiation effects) were developed. In vitro radiosensitizing abilities of TX-1877 and its analogs, with their partition coefficient values of more than 0.050, were comparable to misonidazole (MISO) at their doses of 1 mM. Tumor regrowth was suppressed evidently 20 days after the treatment in the irradiated group with TX-1877 (TX-1877 plus R) and with KIN-806 (KIN-806 plus R). The former group reduced markedly the mean number of metastatic lung nodules regardless of radiation therapy. TX-1877 and KIN-806 plus R induced helper T lymphocytes. The TX-1877, TX-1877 plus R, KIN-806, and KIN-806 plus R enhanced macrophage infiltration for 3 weeks after treatment. CONCLUSION: TX-1877 is an excellent BRM-functional hypoxic cell radiosensitizer, expected to be useful for clinical use.

Animals↗

Molecular cloning and distinct developmental expression pattern of spliced forms of a novel zinc finger gene wiz in the mouse cerebellum.

In the course of a study conducted to identify the mouse homologue of Drosophila eyes absent (eya), we isolated a novel mouse cDNA fragment which show little homology to eya but encodes a protein with Krüppel (C2H2)-type zinc finger motifs. By further screening using this cDNA fragment as a probe, we obtained the short and long forms of full-length cDNAs, which were apparently alternatively spliced products from one gene. Since both mRNAs encode proteins with widely-interspaced zinc finger motifs, we termed this gene wiz and refer to the short and long wiz transcripts as wizS and wizL, respectively. In situ hybridization studies using the probe against the region common to wizS and wizL showed that these mRNAs were expressed abundantly in the granule cell layers of the mouse cerebellum, the olfactory bulb, and the dentate gyrus, whereas the same technique using the probe against only wizL could not detect positive signals in the developing cerebellum, indicating that there is no expression of wizL mRNA there. Northern blot and in situ hybridization analyses demonstrated that the extracerebellar regions expressed both wizS and wizL mRNAs from the midgestational period to adulthood. The finding that two types of wiz transcripts (wizS and wizL) are expressed with different developmental patterns might indicate separate transcription functions in the cerebellar granule cells and the extracerebellar regions.

Alternative Splicing↗

Regulation of the trunk-tail patterning in the ascidian embryo: a possible interaction of cascades between lithium/beta-catenin and localized maternal factor pem.

Embryonic cell specification and pattern formation in the ascidian embryo are controlled by prelocalized egg cytoplasmic determinants. In previous studies, we showed that overexpression of a maternal gene, posterior end mark (pem), whose transcript localizes to posterior-vegetal cytoplasm of the fertilized egg, causes a loss of the anterior and dorsal structures of the larva (Yoshida et al., Development 122, 2005-2012, 1996). In the present study, first we observed that lithium treatment resulted in reduction of the larval tail. Lineage tracing analyses revealed that descendants of the A4.1 blastomere of the 8-cell-stage embryo (which forms the greater part of notochord and nerve cord) were missing from the tail region, that they were translocated anteriorly into the trunk region, and that the fate of the A4.1-line notochord cells had changed to endoderm. These results suggest that lithium treatment affects the trunk-tail patterning during embryogenesis by changing the cell fate of specific cell lineages. Second, we showed that lithium treatment could rescue the anterior and dorsal structures in pem-overexpressed larvae. This result suggests that pem plays a role in the patterning of the ascidian embryo via a signaling cascade that is affected by lithium. Third, we isolated an ascidian beta-catenin gene and found that overexpression of beta-catenin in the A4.1 blastomere had effects very similar to lithium treatment, such as reduction of the tail and anterior translocation of A4.1 descendants. These results suggest that the target of lithium is, at least in part, the Wnt-signaling cascade and that pem may also function via this cascade.

Amino Acid Sequence↗

Production of human compatible high mannose-type (Man5GlcNAc2) sugar chains in Saccharomyces cerevisiae.

A yeast mutant capable of producing Man5GlcNAc2 human compatible sugar chains on glycoproteins was constructed. An expression vector for alpha-1,2-mannosidase with the "HDEL" endoplasmic reticulum retention/retrieval tag was designed and expressed in Saccharomyces cerevisiae. An in vitro alpha-1,2-mannosidase assay and Western blot analysis showed that it was successfully localized in the endoplasmic reticulum. A triple mutant yeast lacking three glycosyltransferase activities was then transformed with an alpha-1, 2-mannosidase expression vector. The oligosaccharide structures of carboxypeptidase Y as well as cell surface glycoproteins were analyzed, and the recombinant yeast was shown to produce a series of high mannose-type sugar chains including Man5GlcNAc2. This is the first report of a recombinant S. cerevisiae able to produce Man5GlcNAc2-oligosaccharides, the intermediate for hybrid-type and complex-type sugar chains.

Amino Acid Sequence↗

4-Hydroxy-17-methylincisterol, an inhibitor of DNA polymerase-alpha activity and the growth of human cancer cells in vitro.

An ergosterol derivative, 4-hydroxy-17-methylincisterol (HMI), was found to be an inhibitor of mammalian DNA polymerases in vitro. HMI inhibited the activity of calf thymus DNA polymerase alpha (pol. alpha). Among the polymerases tested, pol. alpha was the most sensitive to inhibition by HMI, and the inhibition was concentration dependent. The inhibitory effect of HMI on pol. alpha was almost the same as that shown by aphidicolin, a well-known potent pol. alpha inhibitor. HMI had relatively less effect on rat DNA pol. beta, human immunodeficiency virus type 1 reverse transcriptase (HIV-RT), and calf thymus terminal deoxynucleotidyl transferase (TdT) in vitro, and did not influence the activities of prokaryotic DNA polymerases such as Klenow Fragment of DNA polymerase I, or the DNA-metabolic enzyme DNase I. HMI was found to be able to prevent the growth of human cancer cell lines originating from patients with leukemia or various solid tumors; its IC50 values ranged from 7.5 to 12 microM. We also synthesized other ergosterol derivatives and tested them, and found that two compounds, 17-methylincisterol and 4-acetyl-17-methylincisterol, have similar inhibitory effects.

Animals↗

cDNA cloning and expression of a novel serine protease, TLSP.

A cDNA for a putative novel serine protease, TLSP, was cloned from human hippocampus cDNA with polymerase chain reaction based strategies. The putative amino acid sequence of TLSP is similar to the trypsin-type serine proteases. TLSP mRNA is expressed in keratinocytes. Overexpressed TLSP protein in neuro2a cells was detected in culture medium.

Amino Acid Sequence↗

A mushroom fruiting body-inducing substance inhibits activities of replicative DNA polymerases.

We found and isolated two natural products in the extract from a basidiomycete, Ganoderma lucidum, as eukaryotic DNA polymerase inhibitors. The compounds were identified as cerebrosides, (4E,8E)-N-D-2'-hydroxypalmitoyl- 1-O-beta-D-glucopyranosyl-9-methyl-4,8-sphingadienine and (4E,8E)-N-D-2'-hydroxystearoyl-1-O-beta-D-glucopyranos yl-9-methyl- 4,8-sphingadienine and were found to be identical to the mushroom fruiting body-inducing substances (FIS) reported. These cerebrosides selectively inhibited the activities of replicative DNA polymerases, especially the alpha-type, from phylogenetically broad eukaryotic species, whereas they hardly influenced the activities of DNA polymerase beta, prokaryotic DNA polymerases, terminal deoxynucleotidyl transferase, HIV reverse transcriptase, RNA polymerase, deoxyribonuclease I, and ATPase. The inhibition of another replicative polymerase, the delta-type, was moderate. The inhibitions of the replicative polymerases were dose-dependent, and the IC50 for animal or mushroom DNA polymerase alpha was achieved at approximately 12 micrograms/ml (16.2 microM) and for animal DNA polymerase delta at 57 micrograms/ml (77.2 microM). FIS is possibly a DNA polymerase inhibitor specific to the replicative enzyme group, and the fruiting body formation may be required for the suppression of the DNA replication or the vegetative growth of the mycelium.

Animals↗

Benzoxazole derivatives as novel 5-HT3 receptor partial agonists in the gut.

A series of benzoxazoles with a nitrogen-containing heterocyclic substituent at the 2-position was prepared and evaluated for 5-HT3 partial agonist activity on isolated guinea pig ileum. The nature of the substituent at the 5-position of the benzoxazole ring affected the potency for the 5-HT3 receptor, and the 5-chloro derivatives showed increased potency and lowered intrinsic activity. 5-Chloro-7-methyl-2-(4-methyl-1-homopiperazinyl)benzoxazole (6v) exhibited a high binding affinity in the same range as that of the 5-HT3 antagonist granisetron, and its intrinsic activity was 12% of that of 5-HT. Compound 6v inhibited 5-HT-evoked diarrhea but did not prolong the transition time of glass beads in the normal distal colon even at a dose of 100 times the ED50 for diarrhea inhibition in mice. Compounds of this type are expected to be effective for the treatment of irritable bowel syndrome without the side effect of constipation.

Animals↗

Change in telomerase activity of rat organs during growth and aging.

Telomerase activity is usually undetectable in adult human tissues, but is positive in embryonic tissues and in cancers. In rodents, however, several organs of normal adult animals express substantial amounts of telomerase activity. In this study, we observed the changes in the telomerase activity in rat organs during growth and aging and found that telomerase activity showed chronological patterns which were characteristic to organs. In lung and brain, the high telomerase activity of embryonic stage decreased rapidly after birth. In lymphoid tissues, telomerase activity increased after birth and reached to its maximum at 4 to 7 week. In liver, it stayed at nearly constant level throughout life. The telomerase activity in regenerating rat liver decreased temporally immediately after partial hepatectomy, then increased to a level that is higher than normal control. In contrast, it rapidly diminished in the occluded lobes after ligation of portal vein branch.

Aging↗