Search PubMed⌕ Search

Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 361 records · Page 20Linked to original sources

[Acquired resistance and cross-resistance of gemcitabine to cisplatin or vindesine in human lung cancer xenografted in nude mice].

One of the problems in the treatment of cancer is the development of resistance to anti-tumor agents when used repeatedly. We described the induction of resistance, cross-resistance to cisplatin (CDDP) or vindesine (VDS) and the side effects of gemcitabine, a new Ara-C derivative, in human lung cancers, Mqnu-1 or H-74 xenografted in nude mice. We investigated the effects of 4-week observation period. Gemcitabine was effective and did not show the acquired resistance when given repeatedly. In contrast, CDDP but not VDS, when given repeatedly, showed a decrease of the anti-tumor effect in the second course. Gemcitabine was still effective to the large tumor grown after CDDP or VDS therapy. Thus, gemcitabine may not develop resistance nor show cross-resistance to CDDP or VDS. In addition, repeated treatment with gemcitabine was much safer than CDDP or VDS. These results suggest that gemcitabine is a candidate for the first choice drug in cancer treatment.

Adenocarcinoma, Papillary↗

[Combination chemotherapy of BOF-A2, a new 5-FU derivative, with various anticancer agents against human cancer xenografts in nude mice].

In order to select a suitable combination chemotherapy with BOF-A2 from the view of both anti-tumor effect (IR) and decrease of side effect, we studied a combination significance of BOF-A2 with CPT-11 that promised for a new anticancer drug, CDDP or mitomycin C (MMC) that used widely to many cancer patients and interferon-alpha (IFN-alpha) against colon, stomach and renal cancer, respectively, by using xenografted nude mice. The combination therapy of BOF-A2 with CDDP was effective against stomach cancer (H-111) from the cellular change and decreased side effect. The combination therapy of BOF-A2 with MMC showed additive effect against stomach cancer (H-111) from IR and cellular changes. The combination effect of BOF-A2 with IFN-alpha was additive and synergistic against renal cancer (H-12). The combination therapy with CPT-11 was effective (IR > or = to 58%) from antitumor effect, additive from IR and synergistic from cellular change against lung cancer (H-74) and colon cancer (H-110), to which conventional drugs were generally insensitive and spontaneously tolerant. BOF-A2 was expected to be a promising new anti-cancer agent in the future clinical trial.

Animals↗

[Extramedullary pleural myelo-megakaryoblastic crisis during hematological chronic phase in chronic myeloid leukemia].

A 77-year-old man, in whom chronic myeloid leukemia (CML) had been diagnosed in October 1990, was admitted to hospital with right chest pain in November 1992. Bone marrow examination revealed the chronic phase of CML. Chest X-ray showed right pleural effusion. The cells from pleural effusion were positive for CD7, CD13, CD33, CD41a, including CD33, CD41a-double positive cells in 57.5%. Southern blot analysis revealed 3'bcr rearrangement. Electron microscopic examination showed the presence of platelet peroxidase. An abnormal karyotype with various additional chromosomes was observed. This is a rare case of extramedullary pleural myelo-megakaryoblastic biphenotypic crisis during the chronic phase of CML.

Aged↗

Analysis of crystalline lens coloration using a black and white charge-coupled device camera.

To analyze lens coloration in vivo, we used a new type of Scheimpflug camera that is a black and white type of charge-coupled device (CCD) camera. A new methodology was proposed. Scheimpflug images of the lens were taken three times through red (R), green (G), and blue (B) filters, respectively. Three images corresponding with the R, G, and B channels were combined into one image on the cathode-ray tube (CRT) display. The spectral transmittance of the tricolor filters and the spectral sensitivity of the CCD camera were used to correct the scattering-light intensity of each image. Coloration of the lens was expressed on a CIE standard chromaticity diagram. The lens coloration of seven eyes analyzed by this method showed values almost the same as those obtained by the previous method using color film.

Cataract↗

[Autologous fibrin glue from concentrated platelet rich plasma: intraoperative plasma sequestration using autotransfusion device].

Making autologous fibrin glue from intraoperatively collected concentrated platelet rich plasma (C-PRP) was attempted in 5 patients who underwent elective coronary artery bypass. The autologous blood was withdrawn from the patient before cardiopulmonary bypass and sequestrated for C-PRP, concentrated red cells (CRC) and platelet poor plasma (PPP) using an Electromedics Elmd-500 autotransfusion device. CRC and PPP were returned intravenously to the patient as needed intraoperatively or postoperatively. Aprotinin was dissolved in C-PRP to yield a concentration of 1000U/ml to the aim of suppressing the plasmin activity. In another syringe, thrombin was dissolved in 2% calcium chloride solution to 1000U/ml. The C-PRP/aprotinin was mixed in ratios of 20:1, 10:1, 5:1, 3:1 to the thrombin/C a++ solution and observed the time for clotting. The 10:1 and 5:1 mixture usually clotted within 3-5 seconds, whereas it was necessary 5 or more seconds in other ratios. Therefore we used in the ratio of 5:1 for all patients. The fibrin glue from this technique is little different from the fibrin glue on the market in its viscosity, and has some major advantages 1. large amount of glue is available 2. simple and inexpensive 3. eliminate the risk of side effect such as virus transmission.

Blood Platelets↗

[Intravascular ultrasound imaging as adjunct to vascular interventions: preliminary experience in patients with atherosclerotic disease].

Catheter-based intravascular ultrasound (IVUS) imaging is new, evolving technique in which a high-frequency transducer is attached to the tip of a catheter. In this study, we evaluated the usefulness of catheter-based IVUS in 11 patients with atherosclerotic disease as an adjunct to PTA or atherectomy. A 30-MHz ultrasound catheter was inserted through a 6 F sheath to obtain real-time and cross-sectional images. The IVUS images demonstrated a three-layered appearance of muscular arteries, intimal thickening and calcification. IVUS was performed in 11 patients undergoing percutaneous transluminal angioplasty (7 patients) or atherectomy (4 patients). The presence of dissection between the media and atheroma was observed after balloon angioplasty, while IVUS imaging demonstrated a smooth wall after atherectomy. There was a good correlation between IVUS and angiography in the quantitative assessment of luminal %diameter stenosis before vascular intervention, but a poor correlation was observed after angioplasty, probably due to the dissections from balloon dilatation that resulted in irregular crescentic pathways with unclear borders to the lumen on angiography. The results of our study illustrate the potential utility of IVUS as an adjunct to transluminal vascular intervention.

Aged↗

Two independent macrophage receptors for acetylated high-density lipoprotein.

We previously demonstrated that acetylated human high-density lipoprotein (acetyl-HDL) was recognized by a scavenger receptor of rat sinusoidal liver cells (Murakami, M., Horiuchi, S., Takata, K. and Morino, Y. (1987) J. Biochem. (Tokyo) 101, 729-741). The present study describes the interaction of acetyl-HDL with rat peritoneal macrophages in vitro. Acetylation of HDL enhanced its cell-association by 2-fold and cellular degradation by > 25-fold. The cell-association of [125I]acetyl-HDL was effectively inhibited by unlabeled acetyl-HDL (> 85%), whereas the inhibition by HDL or acetylated human low-density lipoprotein (acetyl-LDL) was partial (60% and 50%, respectively). However, when both HDL and acetyl-LDL were present, the cell-association of [125I]acetyl-HDL was effectively inhibited by > 80%, a level identical or closely similar to that by acetyl-HDL. The cellular degradation of [125I]acetyl-HDL was effectively suppressed by acetyl-LDL whereas the effect of HDL was much weaker. These findings indicate that acetyl-HDL is endocytosed by both the HDL receptor and the scavenger receptor for acetyl-LDL in which the ligands bound to the latter might be subjected to lysosomal degradation.

Acetylation↗

[Quantitative assessment of lipiodol delivered intra-arterially into hepatoma: with evaluation of MR signal intensity].

We performed an experimental study using a CT phantom with various concentrations of Lipiodol emulsion. On the basis of these experimental data, we performed a quantitative analysis of Lipiodol delivered intra-arterially into hepatomas in order to evaluate the effect of Lipiodol accumulation on the MR signal intensities of hepatomas. The Lipiodol concentration and CT value showed an excellent linear correlation in the phantom study (r = 0.99). Lipiodol was estimated from 0.08 to 2.92 ml (8 to 77% of the injected dose) in hepatomas treated with Lipiodol-TAE. In the MR phantom study, signal intensities showed no remarkable change in cases of low concentrations of Lipiodol emulsion, while they decreased with increased Lipiodol concentrations both for T 1-and T 2-weighted SE and FLASH sequences in cases of high concentrations of Lipiodol emulsion. In the clinical materials, the signal intensities of tumors after Lipiodol-TAE tended not to show any apparent change in tumors with low estimated Lipiodol concentrations, but tended to decrease on all pulse sequences in tumors with high estimated Lipiodol concentrations. CT was useful for the quantitative analysis of Lipiodol accumulation in the tumor. Experimentally and clinically, a low concentration of Lipiodol had no apparent influence on MR signal intensities, while a high concentration tended to decrease signal intensities on all pulse sequences.

Adult↗

Tn antigen, a marker of potential for metastasis of uterine cervix cancer cells.

BACKGROUND: The expressions of Thomsen-Friedenreich antigen (T-Ag) and Tn antigen (Tn-Ag), precursors of MN blood group antigens, were examined in the tissues of squamous cell carcinoma of the uterine cervix from 111 patients to determine their clinicopathologic significance with regard to the biologic behaviors of cancer cells and the clinical course of the patients. METHODS: T-Ag and Tn-Ag were measured by the avidin-biotin-peroxidase (ABC) method with peanut (Arachis hypogaea) lectin (PNA) and Vicia villosa agglutinin (VVA), respectively. RESULTS: Unlike expression of T-Ag, that of Tn-Ag was correlated closely with vascular permeation of cancer cells, their parametrial spread and metastasis to the pelvic lymph nodes, and also with a low 5-year survival rate. No correlation was found between expression of Tn-Ag and other parameters, such as the clinical stage or histologic type. Furthermore, Tn-Ag expression was independent of the degree of cancer involvement in the fibromuscular stroma of the cervix, which seems to be a marker of the aggressiveness of cancer cell proliferation. CONCLUSIONS: These results indicate that Tn-Ag expression is a useful indicator of the potential for metastatic potential of cancer cells. Thus, a combination of estimations of the degree of cancer involvement in the cervical stroma and Tn-Ag expression seems the most useful for predicting the prognosis of patients with cervical cancer.

Antigens, Tumor-Associated, Carbohydrate↗

cDNA and protein sequence of polymorphic macaque albumins that differ in bilirubin binding.

The rhesus monkey, Macaca mulatta, exhibits a geographically restricted polymorphism of serum albumins Mac A and Mac B that is recognized by electrophoresis and is associated with a difference in bilirubin-binding parameters. To identify the basis of the polymorphism, the cDNA and protein sequences of serum albumin from M. mulatta were determined. Screening of a lambda gt11 rhesus liver cDNA library yielded a 1988-bp cDNA sequence that encodes the complete amino acid sequence of mature albumin, the entire propeptide, and part of the prepropeptide. Isoelectric focusing and amino-terminal protein sequencing of CNBr fragments of albumin from A/A and B/B homozygotes were performed, and the structural difference was localized to a CNBr fragment (MCB3) spanning residues 124-264. Sequence analysis of lysyl endopeptidase peptides of MCB3 established that Mac A albumin has a glutamine residue at position 188 while the Mac B albumin has a glutamic residue at the same position. PCR amplification, subcloning, and DNA sequence analysis of clones from A/A and B/B homozygotes confirmed the protein sequence data and the codon difference of CAA versus GAA, respectively. Comparison of macaque and human serum albumin shows a 93.5% identity at the amino acid level. In human serum albumin, Glu188 is located close to the IIA binding pocket for ligands, probably including bilirubin. Derivatives of coumarin compete more efficiently with bilirubin for binding sites on the Mac A albumin than on the Mac B albumin. In regions where coumarin-containing plants are important food resources, Mac B albumin may confer a selective advantage because bilirubin is less readily displaced from it.

Amino Acid Sequence↗

Immunoelectron microscopy on the localization of endothelin in the umbilical vein of perinatal rabbits.

Immunoelectron microscopic localization of endothelin (ET) using the mouse monoclonal anti-ET sera was performed on the pre- and postnatal rabbit umbilical vein during stages when Weibel-Palade (WP) bodies increase in number in the endothelial cells. The immunoreactions are localized in the rough endoplasmic reticulum, Golgi cisterns, and WP bodies that are actively segregated from the Golgi apparatus. After degranulation and extracellular release of WP bodies was induced by compound 48/80, heavy immunoreactions were seen in both vascular lumen and cytoplasm near the degranulated WP bodies. These results indicate that ET is stored in WP bodies after segregation from the Golgi apparatus and released from the endothelial cells concomitantly with other components of these granules by exocytosis. Because the immunoreactions are also seen in pinocytotic vesicles that are occasionally in contact with WP bodies, it seems likely that WP bodies are also involved in the uptake and storage of ET from blood plasma.

Animals↗

Hypercoagulable state induced by thrombocytapheresis.

The influence of the continuous-flow automated blood cell separator. Fenwal CS-3000, on blood coagulation and the fibrinolytic system in blood donors was studied. Blood samples were taken from the collection line of donors undergoing extracorporeal circulation, before and after platelet pheresis. Of the molecular markers, prothrombin fragment-F1 + 2 (PF1 + 2) markedly increased from 0.8 +/- 0.3 to 2.9 +/- 2.0 nM/ml (P < .004), thrombin antithrombin III complex (TAT) also markedly increased from 2.6 +/- 1.3 to 56.0 +/- 24.0 micrograms/L (P < .001), fibrinopeptide A (FPA) increased slightly from 0.8 +/- 0.9 to 3.8 +/- 4.2 micrograms/L (P < .05), and alpha 2-plasmin inhibitor (alpha 2-PI) decreased slightly from 95 +/- 8 to 91 +/- 9% (P < .05). In one donor with the highest level of PF1 + 2, TAT, FPA, and plasmin inhibitor complex after platelet pheresis, protein C, protein S, C4b-binding protein, ATIII, plasminogen, alpha 2-PI, and coagulation factors were decreased. In blood donors undergoing platelet pheresis using the continuous-flow automated blood cell separator, Fenwal CS-3000, a hypercoagulable state was observed. Changing the materials of the plastic disposables to a more thromboresistant material may prevent the hypercoagulable state in donors induced by platelet pheresis using the blood cell separator.

Adult↗

Regulation of liver glycogen synthesis from [14C]glucose and [14C]lactate by portal-arterial glucose difference in the perfused rat liver.

To study effects of the portal-arterial glucose difference on the hepatic glycogenesis, the liver was isolated from fasted rats and was bivascularly perfused. Thirty-five milliliters of Krebs-Ringer buffer (pH 7.4) with 2 mM glucose, 3 mM lactate, 20 ng/ml insulin, and [1-14C]glucose or [U-14C]lactate was recirculated at flow rates of 14 ml/min via the portal vein and 7 ml/min via the hepatic artery. Glucose was continuously infused at a rate of 27.75 mumol/min into the portal (P experiment) and the arterial cannula (A experiment), and the portal-arterial glucose gradients were +1.98 and -3.96 mM. Perfusate glucose concentration was not different between the P and A experiments within 20 min. Perfusate lactate level was higher in the P experiment than in the A experiment at 20 min. Incorporation of radioactivity from [14C]glucose into glycogen was higher in the P experiment than in the A experiment (0.245 +/- 0.014%/20 min vs 0.175 +/- 0.022%/20 min, P < 0.01), and not influenced by the addition of insulin. Incorporation of 14C from [14C]lactate into glycogen was not different between the P and A experiments, and was significantly increased with the addition of insulin. This activity, in the presence of insulin, was higher in the P experiment than in the A experiment (0.490 +/- 0.028%/20 min vs 0.406 +/- 0.025%/20 min, P < 0.05). These results suggest that the portal-arterial glucose difference has an important role in the regulation of hepatic glycogenesis from exogenous glucose and gluconeogenesis.

Animals↗

Three cases of juvenile onset HTLV-I-associated myelopathy with pseudohypoparathyroidism.

Among 201 patients diagnosed with HAM/TSP at Kagoshima University, 21 juvenile onset patients had manifested clinical signs and symptoms at less than 15 years of age. They appeared to have common characteristics such as short stature and slight mental retardation. These signs prompted us to investigate five of them endocrinologically; and three patients with pseudohypoparathyroidism (PHP) were confirmed. Serum calcium levels were low, and human parathyroid hormone (PTH) infusion (Ellsworth-Howard test) caused low response in urinary cyclic AMP and phosphorus excretion. The first case had IgA nephropathy, which is generally associated with infectious diseases, while the second case had muscular lymphocytic infiltration. The mothers of cases 1 and 2, who were both seropositive for HTLV-I, were suspected to have abnormal calcium metabolism based on Ellsworth-Howard test. A brother of case 1 and two sisters of case 3 had also HAM/TSP and short stature. The early clinical onset of HAM/TSP may be due to PTH receptor anomaly and a low level of 1,25-dihydroxyvitamin D, which is deficient in PHP and is involved in the regulation of the immune response. The association with IgA nephropathy or myositis may result from progressive HTLV-I infection.

Adult↗

Genotoxic potency in Drosophila melanogaster of selected aromatic amines and polycyclic aromatic hydrocarbons as assayed in the DNA repair test.

Drosophila melanogaster stock consisting of meiotic recombination deficient (Rec-) double mutant mei-9a mei-41D5 males and Rec+ females was exposed at the larval stage to an aromatic amine or a polycyclic aromatic hydrocarbon. After emergence as adult flies, the males and the females were scored separately. When the treatment caused a dose-dependent reduction in the male to female ratio from the control level; the experiment was repeated with a larval stock consisting of Rec+ males and Rec+ females under comparable conditions. A preferential killing effect upon Rec- larvae was taken as evidence of DNA damaging effect of the test compound. Among 16 compounds tested, 1-AP, B(a)P, 2-AF, DAF, 4-AAF, 2-AAF, 1-AA, 2-AA, DMA, B(a)A and DMBA were registered as positive; Py and 3-MC were weakly positive; and B(e)P, Fluo and Ant were negative. The selective killing effects of the compounds in each of the pyrene, fluorene and anthracene series varied drastically as a function of structure in a way similar to that reported for the genotoxicity in Drosophila and the carcinogenicity in rodents. The Drosophila DNA repair assay will serve as a simple adjunct to the already available means for studying the genotoxic potency of aromatic amines and polycyclic aromatic hydrocarbons.

2-Acetylaminofluorene↗

The evidence of platelet activation in bronchial asthma.

The possible involvement of platelets in bronchial asthma was investigated under three different conditions: (1) chronic asthma, (2) bronchial provocation inhaling house dust mite (HDM), and (3) status asthmaticus. Plasma levels of beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), and in part, platelet-activating factor (PAF) were measured. Approximately one third of the subjects with symptomatic or asymptomatic chronic asthma showed an increased level of beta-TG or PF4. Statistically significant differences occurred in beta-TG and PF4 levels only between healthy controls and symptomatic subjects. Five out of six subjects showed no elevation of beta-TG and PF4 during immediate asthmatic response. In two out of nine subjects with status asthmaticus, beta-TG or PF4 was elevated, and statistically significant correlations occurred between the initial level of PAF and that of beta-TG or PF4. Those results suggest that the platelet activation in the circulation is sometimes provoked in asthma, but plasma level of alpha-granule-derived proteins does not reflect the intensity or severity of asthma, and that PAF is likely to be a mediator responsible for the platelet activation.

Adolescent↗

An ultrastructural study of the mitotic preosteoblasts in the primary spongiosa of the rat mandibular condyle.

In this study, we observed mitotic preosteoblasts that have the structural features of osteoblasts in the primary spongiosa of the rat mandibular condyle. The rough endoplasmic reticulum and the Golgi apparatus showed remarkable disorganization during mitosis. The Golgi saccules were replaced by groups of large vacuoles and small vesicles. The cisternae of the rough endoplasmic reticulum also were vacuolized. Since this disorganization occurred in conjunction with the formation of the mitotic spindle, it is probably related to the changes of the microtubular cytoskeleton. Further, secretory granules were arrayed along the mitotic spindle microtubules at the metaphase, and concentrated around the midbody at the telophase. These findings indicate a close relationship exists between secretory granules and microtubules.

Animals↗