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Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 1,027 records · Page 57Linked to original sources
PubMed1991

Reduced superoxide dismutase activity in UVB-induced hyperproliferative pig epidermis.

Decreased superoxide dismutase (SOD) activity has been reported in various hyperproliferative keratinocytes. In order to elucidate the relationship between epidermal SOD activity and keratinocyte proliferation, we employed in vivo UVB irradiation. Following UVB irradiation at twice the minimum erythema dose, pig epidermis revealed an initial decrease in thymidine incorporation and mitotic counts for at least 48 h, followed by a marked increase, the peak of which was observed at 96 h after irradiation, and a return to basal levels by 5-7 days. The SOD activity remained constant during the initial 48 h and then decreased to about 50% at 96 h, mainly due to a decreased Cu,Zn-SOD activity. Our results indicate that the increased keratinocyte proliferation induced by UVB irradiation is accompanied by a decrease in SOD activity, and that this decrease is mainly due to a decreased Cu,Zn-SOD activity. No alteration in SOD activity was noted during the initial hypoproliferative phase following irradiation.

Animals↗
PubMed1991

Dietary restriction reduces the incidence of 3-methylcholanthrene-induced tumors in mice: close correlation with its potentiating effect on host T cell functions.

All mice treated with 3-methylcholanthrene (MC) suffered with tumor 114 days after treatment. However, 40% dietary restriction caused a great inhibition of tumor incidence. In order to understand the mechanisms by which dietary restriction decreased the occurrence of tumor in mice, we investigated the correlation between tumor incidence and host T cell immune responses. At 114 days after MC administration, the mice were sacrificed and their T cell immune responses were assessed. Flow cytometry studies demonstrated that dietary restriction caused a marked increase of the proportion of Thy 1.2+, L3T4+ T cells in MC-treated diet-restricted mice. Consistent with this result, T cell responses against concanavalin A and interleukin-2 were also potentiated in spleen cells obtained from MC-treated diet-restricted mice, while spleen cells obtained from MC-treated unrestricted mice showed decreased T cell responses because of their tumor burden. Such potentiation of T cell functions by dietary restriction was also observed at earlier stages of MC-induced tumorigenesis. During the course of carcinogenesis, spleen cells obtained from diet-restricted mice showed decreased natural killer activity in vivo. However, in vitro induction of cytotoxic T cells was markedly augmented in MC-treated diet-restricted mice compared with unrestricted mice. These results strongly suggest that the increase of host T cell immune responses might be one of the major causes for the reduction of tumor occurrence by dietary restriction.

Animals↗
PubMed1991

Cardiogenic ballistograms of chicken eggs: comparison of measurements.

In the incubated avian egg, minute movements occur that are synchronised with embryonic cardiac contractions. We previously developed two systems to noninvasively record this cardiogenic ballistic movement of the egg (referred to as the ballistocardiogram, BCG); one was based on applying an audiocartridge and the other a laser speckle phenomenon. A third system, which detects the ballistic movement as the measurement of displacement (referred to as displacement BCG), is applied in the present study, together with the previous two systems, to the ballistocardiography of the egg. The BCG is measured with three systems simultaneously for comparison. The differentiation of the displacement BCG produces a pattern identical to the BCG recorded by the cartridge method, and the integrated pattern of the latter BCG is identical to the displacement BCG. This indicates that the cartridge system detects the cardiogenic movement as the measure of velocity and it may be referred to as velocity BCG. The BCG by the laser speckle method is not related to that recorded by the other two systems, which may be referred to as movement BCG.

Animals↗
PubMed1991

Designs for population pharmacodynamics: value of pharmacokinetic data and population analysis.

Analyses of simulated data from pharmacokinetic/pharmacodynamic (PK/PD) studies varying with respect to the amount and timing of observations were undertaken to assess the value of these design choices. The simulation models assume mono- or biexponential drug disposition, and Emax-type pharmacodynamics. Data analysis uses a combined PK/PD population analysis or a hybrid, individual-PK/population-PD analysis. Assuming that the goal of the PK/PD studies is to estimate population PD, performance of designs is judged by comparing the precision of estimates of population mean PD parameters and of their interindividual variability. The simulations reveal that (i) PK data, even in small number (2 points per person from as few as 25-50% of persons) are very valuable for estimating population PD; (ii) designs involving more individuals, even if many are sparsely sampled, dominate designs calling for more complete study of fewer persons; (iii) the population analysis is generally superior to the hybrid analysis, especially when the PK model is misspecified (biexponential assumed to be monoexponential for analysis); (iv) varying sampling times and doses among subjects protects against the ill effects of model misspecification. In general, the results are quite encouraging about the usefulness of sparse data designs to estimate population dose response.

Computer Simulation↗
PubMed1991

The effects of a thromboxane A2 receptor antagonist on neurologic recovery after 15 min complete global brain ischemia in dogs.

The effects of a thromboxane A(2) receptor antagonist (anti-TXA(2); ONO-3708) on the neurologic recovery after 15 min complete cerebral ischemia were investigated in dogs. Complete cerebral ischemia was achieved by occlusion of the trunk of the aorta, the superior and the inferior caval vein. Seventeen dogs were divided into 2 groups; 1) control group (no drug, n = 9), 2) Anti-TXA(2) group (anti-TXA(2) 200 mcg.kg(-1) in iv bolus soon after recirculation followed by continuous infusion at a rate of 10 mcg.kg(-1).min(-1) for 3 days, n = 8). EEG, auditory brainstem response (ABR), middle latency response (MLR), and somatosensory evoked potential (SEP) recordings were obtained before ischemia, 120 min after re-circulation and on the 7th day after ischemia. The neurologic recovery score (NRS) were determined on the 3rd and the 7th day. Impaired EEG score was significantly higher in the anti-TXA(2) group on 7th day after ischemia ( P < 0.05). Anti-TXA(2) increased the reappearance rates of the ABR-Vth ( P < 0.05) and the SEP-N(3) waves ( P < 0.01) at 120 min after ischemia. The survival rate tended to be higher in the anti-TXA(2) group. However, NRS did not significantly differ in the groups.

Journal Article↗
PubMed1991

The effects of calcium antagonists on EEG, evoked potentials and neurologic recovery after complete global brain ischemia for 15 minutes in dogs.

The effects of three calcium antagonists on the recovery from neurologic damages after complete global brain ischemia were examined by evaluating the change of a electroencephalogram (EEG), evoked potentials (EP) and a neurologic recovery score (NRS) in dogs. Fifteen minutes global brain ischemia was achieved by occluding the ascending aorta and the caval veins. Nicardipine (NC), flunarizine (FL) and diltiazem (DL) were administered with continuous infusions for three days after the ischemia. The EEG-EP scores (0 : no response - 6 : normal) 3 hr after the ischemia were 1.4 +/- 0.4 (mean +/- SE) in the control, 2.2 +/- 0.3 in the NC, 2.2 +/- 0.4 in the FL and 2.1 +/- 0.2 in the DL. There were no significant differences between the 4 groups. The survival rates on the 7th day after the ischemia were 67% (6/9) in the control, 78% (7/9) in the NC, 56% (5/9) in the FL and 89% (8/9) in the DL. No significant differences were presented between the 4 groups. The NRSs (0 : death - 100 : normal) on the 7th day were 40.3 +/- 7.3 in the control, 59.0 +/- 8.5 in the NC, 63.2 +/- 9.7 in the FL and 55.7 +/- 3.3 in the DL. Each treated group showed a tendency to have a higher NRS than that in the untreated control group. The NRS in all dogs treated by the Ca(++) antagonists on the 7th day was 58.7 +/- 4.1, which was significantly higher than that in the control group ( P < 0.05). We conclude that the continuous administration of calcium antagonists for three days after the global brain ischemia would be beneficial for the neurologic recovery.

Journal Article↗
PubMed1991

Pharmacokinetics of bronchial artery infusion of mitomycin in patients with non-small cell lung cancer.

The pharmacokinetics of bronchial artery infusion of 20 mg (11.4-14.0 mg/m2) mitomycin was studied in 14 patients with non-small cell lung cancer (NSCLC). The mean elimination half-life was 34.3 min (range 6-72), and the area under the plasma concentration-time curve (AUC) was 166 ng h/ml (39-312). The mean maximum plasma drug concentration (Cmax) was 178 ng/ml (12-540) and back-extrapolated plasma drug concentration was 308 ng/ml (17-1423). The mean volume of distribution in the one-compartment model was 0.183 l/kg (0.010-0.887) and the rate constant for unchanged drug appearing in the urine was 1.91/min (0.57-7.27). There was considerable variation among individuals with respect to the pharmacokinetics of mitomycin, and the mean Cmax and AUC were lower than those reported after intravenous administration.

Bronchial Arteries↗
PubMed1991

Expression and induction of cytochrome P450 isozymes in hyperplastic nodules of rat liver.

The change of cytochrome P450 (P450) isozymes in a early stage of hepatocarcinogenesis in male F344 rats has been studied. Liver microsomes were prepared from normal rats (group 1), rats treated with diethylnitrosamine (DEN) alone, which developed no hyperplastic nodules (group 2), and rats treated with DEN plus 2-acetylaminofluorene, which developed many hyperplastic nodules (group 3). The amount and activity of P450IA1 and P450IA2 expressed in the liver were analyzed by several immunological methods using monoclonal antibodies against the P450 isozymes and a mutagenicity test. In the group 2 and 3 rats, the total amount of P450 and the amount of P450IA2 were much smaller than those in the group 1 rats, and P450IA1 was detected only from the group 3 rats. As observed by immunohistochemistry, P450IA1 was prominent in hyperplastic nodules developed in the group 3 rats, and the distribution of P450IA1+ cells in individual nodules was heterogeneous. When the rats were treated with a P450 inducer, 3-methoxy-4-aminoazobenzene or 3-methylcholanthrene, both P450IA1 and P450IA2 were induced in all groups of rats; however, the induction rates of the P450 isozymes, especially that of P450IA2, in the group 3 rats were smaller than those in the group 1 and 2 rats. The present work demonstrated that P450IA1, which is responsible mainly for detoxication of aromatic amine carcinogens, increased in level along with the development of hyperplastic nodules, whereas P450IA2, which is responsible for mutagenic or carcinogenic activation of these carcinogens, decreased in its amount and inducibility.

2-Acetylaminofluorene↗
PubMed1991

Two pathways for GM2(NeuGc) expression in mice: genetic analysis.

We have reported that WHT/Ht mice express neither GM2(NeuGc) nor GM1(NeuGc) in the liver or erythrocytes due to a defect on the Ggm-2 gene, which was demonstrated to control the activity of UDP-GalNAc:GM3(NeuGc) N-acetylgalactosaminyltransferase in mouse liver, and, in addition, WHT/Ht mice do not express a detectable amount of GM2(NeuGc) but do express GM1(NeuGc) in tissues other than the liver and erythrocytes, such as the spleen, thymus, heart, lung, kidney, and testis [Nakamura et al. (1988) J. Biochem. 103, 201-208]. In order to determine whether the phenotype of WHT/Ht mice exhibiting an undetectable amount of GM2(NeuGc) in these tissues is genetically controlled or not, we analyzed the expression of gangliosides in the progeny obtained on backcross mating between (BALB/c X WHT/Ht)F1 and WHT/Ht mice, and in a GM2(NeuGc) congenic mouse, WHT.C. Concerning the expression of GM2(NeuGc) in the liver, lung, and kidney, 102 backcross mice could be segregated into two types. One type expressed a detectable amount of GM2(NeuGc) in the liver, lung, and kidney, and the other type did not. The ratio of the numbers of mice exhibiting these two types was 42: 60, indicating that the two phenotypes were genetically determined by the involvement of a single autosomal gene. Recombination as to GM2(NeuGc) expression in the liver, lung, and kidney was not detected among the 102 backcross mice. Analysis of the GM2(NeuGc) congenic mouse indicated that a detectable amount of GM2(NeuGc) was expressed in the liver, erythrocytes, lung, kidney, heart, spleen, and small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Location and nucleotide sequence of the gene encoding the viral enhancing factor of the Trichoplusia ni granulosis virus.

The gene encoding the viral enhancing factor (VEF) of Trichoplusia ni granulosis virus has been cloned from a lambda gt11 expression library, and the complete nucleotide sequence determined. The VEF gene encodes a protein with a predicted Mr of 104K which does not share homology with any previously reported proteins. A possible promoter is located four nucleotides upstream of the initiation codon and represents a consensus baculovirus late promoter (ATAAG). This has been confirmed by the identification of VEF mRNA in Northern blots of infected larvae 6 days but not 3 days post-infection. Using an anti-VEF-TrpE polyclonal antiserum in Western blots of dissolved viral occlusion bodies, related proteins have been identified in both Pseudaletia unipuncta granulosis virus Hawaiian strain (PuGV-H) and Heliothis armigera GV (HaGV), but not in Erinnyis ello GV (EeGV), T. ni singly enveloped nuclear polyhedrosis virus (TnSNPV) or Autographa californica multiply enveloped NPV (AcMNPV). Similar results were obtained with Southern blots of genomic digests. DNA fragments homologous to an internal portion of the VEF gene were found in PuGV-H and HaGV but not in EeGV, TnSNPV or AcMNPV.

Amino Acid Sequence↗
PubMed1991

High-level expression of human c-jun gene causes cellular transformation of chicken embryo fibroblasts.

To analyze the transforming activity of c-jun, a Rous sarcoma virus (RSV) variant that carries human c-jun instead of v-src (JH1) was constructed. After infection onto chicken embryo fibroblasts (CEF), JH1 formed foci with a titer comparable to that of wild-type RSV, and the infected cells grew in soft agar, indicating that the human c-jun gene has transforming potential, like the v-jun gene. The expression of Fra-2, one of the recently isolated Fos-related antigens, but not Fos was detected in both JH1-infected CEF and CEF infected with the control retrovirus vector (DS3). Gel shift analysis using nuclear extracts from DS3-infected CEF revealed that the Fra-2/Jun complex contributes to the basal level of AP-1 DNA binding activity. A similar activity was detected in JH1-infected CEF, but these cells have an additional AP-1 binding activity derived from Jun homodimers that seems to play important roles in the cellular transformation.

Animals↗
PubMed1991

Adhesion molecules on murine lymphokine-activated killer cells responsible for target cell killing: a role of CD2.

Lymphokine-activated killer (LAK) cells were induced from C57BL/6 mouse spleen cells and the effects of culture time on the expression of cell surface phenotypes and cytotoxic activity of LAK cells were determined. The expression of CD2 remarkably decreased after culture of LAK cells for 30 days, while LFA-1, a principal adhesion molecule in LAK cells, and CD3 were not changed by the culture. LAK cells cultured for 90 days completely lost CD2. In accordance with the decrease of CD2, the cytotoxic activity of LAK cells declined but a certain leven was retained even after the complete loss of CD2. The established LAK cell clones were also strongly positive for the expression of LFA-1 but negative for CD2. When the LAK cell clones were transfected with the CD2 cDNA, they started to express CD2 on their cell surface and to show greater binding ability and stronger cytotoxicity to target tumor cells. These results indicated that CD2 plays a role as an adhesion molecule responsible for target cell killing in murine LAK cells.

Animals↗
PubMed1991

Release of esterase from murine lymphokine-activated killer cells in antibody-dependent cellular cytotoxic reaction.

Release of granule enzyme(s) (BLT esterase) in the antibody dependent lymphokine-activated killer (LAK) cell-mediated cytotoxic reaction (LAK ADCC) was studied using LAK cells induced from murine splenocytes and thymocytes, various human tumor cells and relevant monoclonal antibodies (mAbs) to the tumor cells. BLT esterase was not significantly released from LAK cells in direct LAK cell-mediated cytotoxic reactions (LAK CMC). However, cultures of LAK cells and IgG-coated target tumor cells resulted in release of the enzyme concomitantly with target cell lysis, although esterase release proceeded faster than target cell lysis. Anti-LFA-1 mAb showed an inhibitory effect on LAK CMC but not on either LAK ADCC or BLT esterase release in the ADCC. These results indicate that exocytosis of granule enzyme from LAK cells is triggered by stimulation of Fc receptor on LAK cells and that LAK CMC and LAK ADCC differ in their lytic mechanism in terms of the release of BLT esterase.

Animals↗
PubMed1991

T cell receptor-independent cell-mediated cytotoxicity by nude mouse lymphokine-activated killer cells.

Lymphokine-activated killer (LAK) cells, which can lyse a variety of tumor cells, can be induced from both normal and athymic nude mouse spleen cells by culture with high doses of recombinant interleukin 2 (rIL-2). LAK cells generated from nude mouse spleen cells (Nude-LAK cells) express just Thy 1.2 antigen, but not CD4 and CD8 antigens. Nude-LAK cells express neither T3 molecule, T cell receptor (TCR) alpha beta nor TCR gamma delta on their cell surface. The lack of TCR expression on Nude-LAK cells was confirmed by the results of northern blot analysis. LAK cells generated from normal mouse spleen cells (Nor-LAK) express TCR alpha, beta transcripts, while Nude-LAK cells express only sterile TCR beta transcript, but not TCR alpha transcript. TCR gamma delta transcripts were scarcely detected in both Nor-LAK cells and Nude-LAK cells. Thus, it is strongly suggested that Nude-LAK cells can recognize and lyse tumor cells by TCR-independent mechanisms. Monoclonal antibody against lymphocyte function-associated antigen (LFA-1) molecule can block the cytotoxicity of Nude-LAK cells, indicating an important role of such accessory molecules in Nude-LAK cell-mediated cytotoxicity.

Animals↗
PubMed1991

Establishment of mouse lymphokine-activated killer cell clones and their properties.

To assess the properties of lymphokine-activated killer (LAK) cells, we established mouse LAK cell clones from LAK cell lines induced from C57BL/6 mouse spleen cells. Although these clones expressed similar phenotypes to the parent LAK cells, Lyt-2 was expressed in a restricted portion of the clones. All clones were found to express T3 CD2 and T cell receptor (TcR) alpha beta on their cell surface. Rearrangement patterns of TcR beta were the same among the clones derived from the same parent cell line but differed in those from different cell lines as determined by using C beta 1 and J beta 2 probes. The molecules responsible for LAK-target cell binding were examined by using a monoclonal antibody (mAb) against lymphocyte function associated antigen 1 (LFA-1). This mAb (termed KBA) showed inhibitory effects on both LAK-target cell binding and cytolytic activity of LAK cell clones, indicating a principal role of LFA-1 in LAK cell clones. The magnitude of perforin mRNA expression in LAK cell clones was unrelated to their cytolytic activities.

Animals↗
PubMed1991

Augmentation by tumor necrosis factor alpha of the systemic therapeutic effect of lymphokine-activated killer cells in adoptive immunotherapy of murine tumor.

The therapeutic effect of a combined modality of lymphokine-activated killer (LAK) cells and tumor necrosis factor alpha (TNF alpha) on MBL-2 tumor in C57BL/6 mice was studied. Murine LAK cells induced from splenocytes by interleukin 2 (IL2) could lyse MBL-2 target cells in vitro. but no enhancement of the LAK activity was found by the treatment of LAK cells with TNF alpha in vitro. However, the treatment of MBL-2 with TNF alpha enhanced the sensitivity to LAK cells. Moreover, administration of TNF alpha to mice bearing solid MBL-2 tumor led to increased tumor vascular permeability within 1 h, and resulted in the enhanced accumulation of systemically transferred LAK cells in tumor tissue. Based on these results, we treated MBL-2-bearing mice with TNF alpha and then with LAK cells 1 h later. No therapeutic effect was observed when tumor-bearing mice were treated with TNF alpha alone or LAK cells plus IL2. However, adoptive immunotherapy using LAK cells and TNF alpha had therapeutic effects, i.e., growth inhibition of tumor nodules and prolongation of survival. These results indicated that appropriately timed pretreatment of tumor-bearing mice with TNF alpha augmented the anti-tumor efficacy of LAK cells.

Animals↗
PubMed1991

Cytosolic-nuclear tumor promoter-specific binding protein: association with the 90 kDa heat shock protein and translocation into nuclei by treatment with 12-O-tetradecanoylphorbol 13-acetate.

Suspension-cultured HeLa cells possess a cytosolic-nuclear tumor promoter-specific binding protein (CN-TPBP) which lacks protein kinase C activity. This CN-TPBP existed in cytosol of HeLa cells, but translocated into nuclear fraction of the cells after treatment of the cells with 12-O-tetradecanoylphorbol 13-acetate (TPA). The translocation of CN-TPBP induced by TPA became apparent within 10 min after the treatment with TPA, and was completed within 3 h. CN-TPBP bound TPA with the association constant of 1.4 x 10(10) M-1, and also bound teleocidin B, debromoaplysiatoxin, and thapsigargin in a mutually competitive manner. The binding affinity order of synthetic analogs of teleocidin B correlated with the adhesion-inducing potency order of the compounds toward human leukemia cell line HL-60. The apparent molecular weight of CN-TPBP under non-denaturing conditions was estimated to be 66-68 kDa. CN-TPBP forms a complex with the 90 kDa heat shock protein, and the complex was stabilized by the presence of molybdate. These characteristics of CN-TPBP are similar to those of the nuclear receptors of glucocorticoid and dioxin. These findings suggested that CN-TPBP acts as a nuclear receptor for tumor promoters, and that tumor promoters may exert their biological effects by binding to CN-TPBP.

Carcinogens↗