Search PubMed⌕ Search

Biomedical subjects

Y Hoshi

Publications and source records attributed to Y Hoshi.

At least 127 records · Page 7Linked to original sources
PubMed1998

Evidence that CD31, CD49b, and CD62L are immunodominant minor histocompatibility antigens in HLA identical sibling bone marrow transplants.

Despite complete matching of siblings for the HLA loci, after bone marrow transplantation (BMT), approximately 20% develop graft-versus-host disease (GVHD). This is presumably due to incompatibility of minor histocompatibility antigens (mHa). We investigated the polymorphisms of 14 adhesion molecules (CD2, CD28, CD31, CD34, CD36, CD42, CD44, CD48, CD49b, CD54, CD62L, CD86, CD102, and CD106) in Japanese subjects and their association with the occurrence of GVHD after allogeneic HLA identical BMT. Six molecules (CD2, CD31, CD42, CD49b, CD54, and CD62L), which were found to be polymorphic, were then examined in 118 HLA identical sibling donors and recipients who had undergone BMT. Association of the incompatibility of the polymorphic molecules with the presence or absence of GVHD was examined. In these six, we observed a significant correlation between acute GVHD and the compatibility of CD31 (codons 563/670) (Pcorrected = .018), and CD31 (codons 563/670) + CD62L (Pcorrected = .018) in patients with the HLA-B44-like superfamily. In patients with the HLA-A3-like superfamily, the compatibility of CD62L (Pcorrected = .03) and CD62L + CD49b (P = . 004, Pcorrected = .078) was associated with acute GVHD. Therefore, CD31, CD49b, and CD62L might be candidates for immunodominant mHa.

Adolescent↗
PubMed1998

Relationship between fluctuations in the cerebral hemoglobin oxygenation state and neuronal activity under resting conditions in man.

Simultaneous measurements by near-infrared spectroscopy and electroencephalography were performed during 15-min resting periods in nine healthy adult brains. The peak frequencies of the frontal and occipital rhythms varied with the time course like the hemoglobin oxygenation state. Changes in the amount of oxygenated hemoglobin in the frontal region by more than 50% of the maximum resting variation range were accompanied by changes in peak frequency at the electrode position between two optodes. The results suggest that spontaneous neuronal activity is responsible for fluctuations in the hemoglobin oxygenation state in the resting state.

Adult↗
PubMed1998

Bronchiolitis obliterans after bone marrow transplantation: evaluation with lung scintigraphy.

Bronchiolitis obliterans (BO) has been described as a main pulmonary complication following allogeneic bone marrow transplantation (BMT). Diagnosis of BO is usually based on clinical findings, pulmonary function tests, and computed tomography scan. However, histological examination of an open-lung biopsy specimen may sometimes be necessary to confirm the diagnosis, despite its relative invasiveness. The ventilation lung scan is another useful but non-invasive diagnostic method. In this study, we present two post-transplant BO cases, each showing different clinical conditions, characterized by delayed wash-out on 133Xe gas and airway depositions on radioaerosol inhalation scans. These methods succeeded in revealing pulmonary obstruction in cases where the pulmonary function tests were within normal range and the high-resolution CT scans (HR-CT) of the chest were only minimally abnormal, suggesting their usefulness as an additional tool in the diagnosis of post-transplant BO, as well as in the follow-up to pulmonary obstruction.

Adult↗
PubMed1998

Changes of telomere length in children after hematopoietic stem cell transplantation.

Telomeres are responsible for keeping the stability not only of chromosomes but also of genes. To investigate the effect of hematopoietic stem cell transplantation (HSCT) on telomeres, we studied telomere length in the peripheral blood mononuclear cells of 31 children who received HSCT. In the auto-HSCT groups telomere length ranged from 8.6 to 12.0 kb and in the allo-HSCT groups from 8.4 to 12.0 kb. Comparison of the telomere length between before and after auto-HSCT showed shorting up to 1.0 kb. Moreover, comparison between donors and recipients in allo-HSCT revealed that telomeres of recipients were up to 1.0 kb shorter than those of the donors. Patients who received allo-HSCT from donors older than 18 years had significantly shorter telomeres than those transplanted from donors under 18 years old (P < 0.05), indicating that donor age is an important factor for recipient's telomere length. These findings suggest that the effects which might be induced by shortening of telomeres in recipients are within the biologically tolerable range. However, if hematopoietic stem cells from elderly donors are transplanted into younger patients, the telomere length may become too short for acceptable lifetime risks of genetic instability in the recipient.

Adolescent↗
PubMed1998

Simultaneous quantitative analysis of prostaglandins and thromboxane after low-dose X irradiation.

The appearance of prostaglandins and thromboxane in mouse serum after X irradiation was observed by simultaneous quantitative analysis using gas chromatography/mass spectrometry/selected ion monitoring with stable isotope dilution methods. Mice of two strains (C57BL/CN Jcl and BALB/c) showed similar responses to X irradiation. In C57BL/6N Jcl mice, 0.2 Gy irradiation elicited a significant increase in generation of prostanoids: Immediately after irradiation, the 6-keto PGF1 alpha:TXB2 ratio and the level of PGE2 increased, after 20 min 6-keto PGF1 alpha and PGE2 increased, and after 4 h PGE1 and PGE2 increased. In BALB/c mice, generation of prostanoids was increased significantly immediately after irradiation (6-keto PGF1 alpha, 6-keto PGF1 alpha:TXB2 ratio, PGE2), and the increase was maintained from 20 min to 4 h (PGE1, PGE2) after 0.2 Gy irradiation. In C57BL/6N Jcl mice, a significant increase in production of 9alpha,11beta-PGF2 was observed at 20 min after irradiation. In BALB/c mice, a significant increase in 9alpha,11beta-PGF2 was seen immediately after irradiation and was maintained for 20 min. In C57BL/6N Jcl mice, the level of 8-epi PGF2 alpha was clearly increased 4 h after 4 Gy irradiation. A slight and slow increase was also seen after 0.2 Gy irradiation. In BALB/c mice, 8-epi PGF2 alpha was increased significantly at 20 min and 4 h after 4 Gy irradiation. These results show that 0.2 Gy irradiation stimulates production of prostanoids related to the inflammatory response in mice.

Animals↗
PubMed1997

p16INK4A promotes differentiation and inhibits apoptosis of JKB acute lymphoblastic leukemia cells.

Homozygous p16(INK4A) (p16) gene deletion is frequent in primary tumor cells from acute lymphoblastic leukemia (ALL), suggesting that loss of p16 may be an important precursor to transformation in ALL. We have previously described JKB, a human ALL cell line, that contains homozygous deletion of the p16 gene. Because ectopic expression of p16 suppresses cell growth, we created a temperature sensitive p16 mutant to develop a system for inducible p16 function in human ALL. JKB cells were transfected either with a p16 gene mutated at position 119 (E119G) to confer temperature sensitivity (JKB p16MT) or with control vector. The percentage of cells in G1 phase was similar in JKB control cells or in JKB p16MT cells cultured at restrictive conditions (40 degrees C). However, with lowering of temperature from 40 degrees C to permissive conditions (31 degrees C), the percentage of JKB p16MT cells in G1 phase and binding of p16 to CDK4 and CDK6 increased, with associated decreases in CDK4 and CDK6 kinase activities, and dephosphorylation of retinoblastoma protein (pRB). Culture of JKB p16MT cells at 31 degrees C for >/=3 days irreversibly inhibited growth. Moreover, JKB p16MT cells cultured under these permissive conditions showed a less transformed morphology and more differentiated phenotype than did these cells cultured under restrictive temperatures. Finally, dexamethasone (Dex) induced apoptosis of JKB p16MT cells cultured at 40 degrees C, but did not trigger death of these cells cultured at 31 degrees C. These results suggest that deletion of p16 gene in JKB human ALL cells is associated with dysregulated growth of less differentiated tumor cells, which nonetheless remain susceptible to apoptosis triggered by Dex.

Amino Acid Sequence↗
PubMed1997

Induction of thioredoxin in human lymphocytes with low-dose ionizing radiation.

Induction of the expression of the thioredoxin (TRX) gene, producing a key protein in regulating cellular functions through redox reaction as well as being a radioprotector, was followed after ionizing irradiation of lymphocytes from human donors. The TRX mRNA level increased to a peak, 5.7-fold higher than the control at maximum, 6 h after irradiation, and then decreased. The optimum radiation dose for enhancement of induction of the TRX mRNA was 0.25 Gy. The TRX protein also increased to a peak, a 3-fold increase at maximum, with the same timing as that for TRX mRNA.

Blotting, Northern↗
PubMed1997

The development of a model for the homing of multiple myeloma cells to human bone marrow.

Prior in vitro studies have suggested a role of adhesion molecules, bone marrow stromal cells (BMSCs), and cytokines in the regulation of human multiple myeloma (MM) cell growth and survival. Although in vivo models have been developed in severe combined immunodeficient (SCID) mice that support the growth of human MM within the murine BM microenvironment, these xenograft models do not permit a study of the role of adhesion proteins in human MM cell-human BMSC interactions. We therefore established an in vivo model of human MM using SCID mice implanted with bilateral human fetal bone grafts (SCID-hu mice). For the initial tumor innoculum, human MM derived cell lines (1 x 10(4) or 5 x 10(4) ARH-77, OCI-My5, U-266, or RPMI-8226 cells) were injected directly into the BM cavity of the left bone implants in irradiated SCID-hu mice. MM cells engrafted and proliferated in the left human fetal bone implants within SCID-hu mice as early as 4 weeks after injection of as few as 1 x 10(4) MM cells. To determine whether homing of tumor cells occurred, animals were observed for up to 12 weeks after injection and killed to examine for tumor in the right bone implants. Of great interest, metastases to the right bone implants were observed at 12 weeks after the injection of 5 x 10(4) MM cells, without spread of human MM cells to murine BM. Human MM cells were identified on the basis of characteristic histology and monoclonal human Ig. Importantly, monoclonal human Ig and human interleukin-6 (IL-6), but not human IL-1beta or tumor necrosis factor-alpha, were detectable in sera of SCID-hu mice injected with MM cells. In addition, specific monoclonal Ig light chain deposition was evident within renal tubules. This in vivo model of human MM provides for the first time a means for identifying adhesion molecules that are responsible for specific homing of human MM cells to the human, as opposed to murine, BM microenvironment. Moreover, induction of human IL-6 suggests the possibility that regulation of MM cell growth by this cytokine might also be investigated using this in vivo model.

Animals↗
PubMed1997

Interleukin-6 overcomes p21WAF1 upregulation and G1 growth arrest induced by dexamethasone and interferon-gamma in multiple myeloma cells.

Interleukin-6 (IL-6) is a growth factor for multiple myeloma (MM) cells and can inhibit MM cell apoptosis. Our recent studies show that IL-6 facilitates MM cell growth via phosphorylation of retinoblastoma protein (pRB); however, the effects of IL-6 on those cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CDIs) that are known to regulate phosphorylation of pRB have not been defined in MM cells. In the present report, we cultured MM cell lines and patient cells with IL-6 and/or dexamethasone (Dex) and characterized changes in cell cycle; expression and association of cyclins, CDKs, and CDIs; and phosphorylation of pRB. Dex induced G1 growth arrest in MM cells, whereas IL-6 facilitated G1 to S phase transition; moreover, the effect of Dex was blocked by IL-6. p21WAF1 (p21) protein was constitutively expressed in the majority of MM cells independent of the status of p53. Its expression was upregulated by Dex and downregulated by IL-6; again, IL-6 inhibited the increase in p21 triggered by Dex. These alterations in p21 expression in MM cells were associated with changes in p21 binding to CDK2, CDK4, and CDK6; CDK2, CDK4, and CDK6 kinase activities; and phosphorylation of pRB. In contrast, expression of G1 cell cycle regulatory proteins, including p27KIP1, cyclin D2, and cyclin E, was not altered in MM cells cultured with Dex and/or IL-6. Finally, interferon-gamma (IFN-gamma) also induced G1 growth arrest and upregulated p21 protein expression; as with Dex, affects of IFN-gamma were inhibited by IL-6. Our results therefore show that changes in cell cycle distribution in MM cells triggered by Dex, IL-6, and IFN-gamma correlate with changes in p21 protein expression and implicate p21 in the coupling of Dex-, IL-6-, and IFN-gamma-related signals to G1 cell cycle regulation in MM cells.

Antineoplastic Agents↗
PubMed1997

Localized near-infrared spectroscopy and functional optical imaging of brain activity.

Changes in cerebral blood flow (CBF) and cerebral metabolic rates (CMRO2) have been used as indices for changes in neuronal activity. Near-infrared spectroscopy (NIRS) can also measure cerebral haemodynamics and metabolic changes, enabling the possible use of multichannel recording of NIRS for functional optical imaging of human brain activity. Spatio-temporal variations of brain regions were demonstrated during various mental tasks. Non-synchronous behaviour of cerebral haemodynamics during the neuronal activation was observed. Gender- and handedness-dependent lateralization of the function between right and left hemispheres was demonstrated by simultaneous measurement using two NIR instruments during the mirror-drawing task. A lack of interhemispheric integration was observed with schizophrenic patients. These observations suggest an application for NIRS in psychiatric disease management, as an addition to clinical monitoring at the bedside. A time resolved 64-channel optical imaging system was constructed. This consisted of three picosecond laser diodes and 64 channels of TAC and CFD systems. Image reconstruction for phantom model systems was performed. Time-resolved quantitative optical imaging will become real in the very near future.

Adult↗
PubMed1997

Near-infrared optical detection of sequential brain activation in the prefrontal cortex during mental tasks.

To examine the spatiotemporal differences of brain activation during mental tasks, changes in the oxygenation and hemodynamics in two regions of the prefrontal cortex were measured simultaneously by near-infrared spectroscopy (NIRS). Subjects were eight healthy adults who attempted to solve three different mathematical problems. The behavior of concentration changes in oxy-, deoxy-, and total hemoglobin in one brain region varied with the time course (more than 10 min). This suggested that regional brain activity varied during the performance of the mental task. In each single subject, the pattern of these changes varied with each problem, and this variation differed from subject to subject. When NIRS traces in two regions were compared, it was seen that activated regions moved alternatively: when in one region total hemoglobin that had first increased returned to the resting level, in the other it started to increase. These region-dependent temporal variations of brain activity might reflect mental processes. It is thus concluded that NIRS has the potential for imaging the sequence of brain activation.

Adult↗
PubMed1997

Fluctuations in the cerebral oxygenation state during the resting period in functional mapping studies of the human brain.

Functional mapping studies using near-infrared spectroscopy have detected for the first time the existence of significant fluctuations in the concentration of cerebral oxygenated [oxy-Hb], and deoxygenated haemoglobin, [deoxy-Hb], during the resting period. The fluctuations are not related to alterations in the systemic circulatory system. The temporal pattern varies with each brain region. In some instances, the degrees of change in [oxy-Hb] and [deoxy-Hb] caused by highly integrated tasks are within this resting variation range. Thus, taking account of these fluctuations is essential to the interpretation of distribution patterns of cerebral activity.

Adolescent↗
PubMed1997

Role of CDK4 and p16INK4A in interleukin-6-mediated growth of multiple myeloma.

Interleukin-6 (IL-6) promotes growth of human multiple myeloma (MM) cells via phosphorylation of retinoblastoma protein (pRB). We therefore examined the kinetics of cyclin-dependent kinase 4 (CDK4), p16INK4A, and pRB activation during IL-6-mediated patient MM cell growth compared with growth of IL-6 unresponsive patient plasma cell leukemia (PCL) cells. CDK4 protein was more strongly expressed in PCL cells than in MM cells. On the other hand, p16 protein was present in MM cells but undetectable in PCL cells. Interestingly, IL-6 induced peak proliferation of MM cells at days 1-3, with a return to baseline levels of DNA synthesis by days 6-9 in spite of replenishing IL-6. In these cells, IL-6 triggered a sustained increase in CDK4 by day 1 and a gradual increase in p16 to day 9. The progressive increase in p16 without further increments in CDK4 resulted in a shift from cyclin D2-CDK4/CDK6 binding at days 1-3 to p16-CDK4/CDK6 complex formation at days 6-9. Both phosphorylated pRB and dephosphorylated pRB were present initially in patient MM cells; IL-6 triggered a shift to phosphorylated pRB and G1 to S transition at days 1-3, with return to baseline levels of dephosphorylated pRB and related G1 growth arrest by day 9. No similar changes in CDK4, p16, or cell cycle profile were observed in IL-6 nonresponsive PCL cells. Our data therefore suggest a feedback mechanism in IL-6-mediated MM cell growth which is absent in IL-6 nonresponsive PCL cells.

Cell Count↗
PubMed1997

Redox behavior of cytochrome oxidase in the rat brain measured by near-infrared spectroscopy.

Using near-infrared spectroscopy, we developed a new approach for measuring the redox state of cytochrome oxidase in the brain under normal blood-circulation conditions. Our algorithm does not require the absorption coefficient of cytochrome oxidase, which differs from study to study. We employed this method for evaluation of effects of changes in oxygen delivery on cerebral oxygenation in rats. When fractional inspired oxygen was decreased in a stepwise manner from 100 to <10%, at which point the concentration of oxygenated hemoglobin ([HbO2]) decreased by approximately 60%, cytochrome oxidase started to be reduced. Increases in arterial PO2 under hyperoxic conditions caused an increase in [HbO2], whereas further oxidation of cytochrome oxidase was not observed. The dissociation of the responses of hemogloblin and cytochrome oxidase was also clearly observed after the injection of epinephrine under severely hypoxic conditions; that is, cytochrome oxidase was reoxidized with increasing blood pressure, whereas hemoglobin oxygenation was not changed. These data indicated that oxygen-dependent redox changes in cytochrome oxidase occur only when oxygen delivery is extremely impaired. This is consistent with the in vitro data of our previous study.

Animals↗
PubMed1997

[Rapid onset of hemolytic anemia after allogeneic bone marrow transplantation from an unrelated ABO major mismatched donor].

A 46-year-old woman with chronic myelogenous leukemia received allogeneic bone marrow transplantation from an unrelated human leukocyte antigen (HLA) matched (but mixed lymphocyte culture (MLC) positive to graft-versus host disease (GvHD) donor. The blood type of the recipient was A type Rh (+) while the donor blood type was B type Rh (+). The patient received busulfan 8 mg/kg, cyclophosphamide 120 mg/kg, and total-body irradiation 10 Gy before bone marrow transplantation. Short-term administration of methotrexate and cyclosporin was given for prophylaxis of GvHD. The mononuclear cells harvested from the donor were concentrated by COBE Spectra before bone marrow transplantation. Although engraftment of transplanted bone marrow in the recipient was confirmed on day 11, the patient suffered from severe anemia on day 10. Since the direct Coombs' test to A type red blood cells was positive, and anti-A antibody titer increased 16-fold, we diagnosed her anemia as hemolytic anemia caused by ABO mismatched transplantation. In addition to hemolytic anemia, she had skin symptoms of acute GvHD grade II, microangiopathic hemolytic anemia, and died of multiple organ failure on day 44. This experience indicated that some allogeneic transplant recipients are at risk of severe hemolytic anemia in the early stage after unrelated ABO mismatched donor and that it is necessary to establish proper treatment and prophylaxis.

ABO Blood-Group System↗
PubMed1997

The effects of unsaturated fatty acids, oxidizing agents and Michael reaction acceptors on the induction of N-ethylmaleimide reductase in Escherichia coli: possible application for drug design of chemoprotectors.

Menadione and dimethyl maleate, Michael reaction acceptors, induced N-ethylmaleimide (NEM) reductase activity in Escherichia coli strain DH5a. Linoleic acid also induced NEM reductase activity, but oleic acid, which is less susceptible to lipid peroxidation than linoleic acid, did not induce NEM reductase activity. In addition, NEM reductase activity was induced by menadione and linoleic acid also in strain DH5, Y1088 and Y1090. Linoleic acid is not a Michael reaction acceptor, but is known to produce Michael reaction acceptors such as alkenals and 4-hydroxyalkenals as a result of free-radical-initiated lipid peroxidation. Thus, our findings suggested that lipid peroxidation was involved in the induction of NEM reductase by linoleic acid. The electrophilic property of Michael reaction acceptors provides the signal for induction of phase II enzymes such as glutathione S-transferase and quinone reductase in mammals. The inducer potency of phase II enzymes has been used to design chemoprotective drugs. Therefore, the inducible nature of this enzyme will serve not only for the elucidation of its physiological function, but also for the evaluation of chemoprotective drugs.

Enzyme Induction↗