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Biomedical subjects

A Mori

Publications and source records attributed to A Mori.

At least 37 records · Page 2Linked to original sources

Influence of Helicobacter pylori on platelets after bone marrow transplantation from unrelated donors.

This study was performed to clarify the influence of Helicobacter pylori on the platelet count in patients undergoing bone marrow transplantation (BMT) from unrelated donors. Of 23 consecutive patients undergoing BMT from unrelated donors, the H. pylori antibody test did not change from before conditioning until recovery of the platelet count in 15 patients. These patients were classified into H. pylori antibody-positive (n=8) and -negative (n=7) groups. In the H. pylori antibody-positive group, the platelet count exceeded 20 x 10(9)/l significantly faster after BMT, than in the H. pylori antibody-negative group. When myelosuppression was most severe, the interleukin-6 (IL-6) level was significantly higher in the positive group than in the negative group (67.0+/-10.6 vs 9.9+/-2.4 pg/ml, P<0.05). In addition, the thrombopoietin level was significantly lower in the positive group than in the negative (510.1+/-313.9 vs 3209.1+/-2006.7 pg/ml, P<0.01). These data suggest that H. pylori infection accelerates recovery of the platelet count after BMT from unrelated donors, possibly by stimulating IL-6 production.

Adult↗

Prognostic value of cyclic GMP in patients undergoing allogeneic bone marrow transplantation after conditioning with total body irradiation.

This study was performed to investigate whether measurement of cyclic GMP (cGMP), a marker for nitric oxide production, before and after allogeneic bone marrow transplantation (BMT) with total body irradiation (TBI) conditioning was of prognostic value. cGMP levels were monitored in 23 consecutive patients who received TBI as conditioning for BMT, and were compared with the outcome. cGMP became positive during the aplastic phase after BMT in 12 patients. In nine of these 12 patients, cGMP level decreased during the recovery phase. Eight of the nine patients survived, one dying after relapse. In three other patients, the cGMP level continued to increase even during the recovery phase and they died of severe complications. cGMP became positive on day 0 of BMT and during the leukocyte recovery phase after BMT in two and seven of the 23 patients, respectively. Subsequently, all patients died of severe complications. The two patients who were negative for cGMP both before and after BMT survived without complications. These results suggest that monitoring cGMP from early after BMT may be useful for predicting outcome and that it may be a useful prognostic marker.

Adolescent↗

Both estrogen and raloxifene cause G1 arrest of vascular smooth muscle cells.

The proliferation of vascular smooth muscle cells (VSMC) is a crucial pathophysiological process in the development of atherosclerosis. Although estrogen is known to inhibit the proliferation of VSMC, the mechanism responsible for this effect remains to be elucidated. In addition, the effect of raloxifene on VSMC remains unknown. We have shown here that 17beta-estradiol (E(2)) and raloxifene significantly inhibited the platelet-derived growth factor (PDGF)-stimulated proliferation of cultured human VSMC. Flow cytometry demonstrated that PDGF-stimulated S-phase progression of the cell cycle in VSMC was also suppressed by E(2) or raloxifene. We found that PDGF-induced phosphorylation of retinoblastoma protein (pRb), whose hyperphosphorylation is a hallmark of the G1-S transition in the cell cycle, was significantly inhibited by E(2) and raloxifene. These effects were associated with a decrease in cyclin D1 expression, without a change in cyclin-dependent kinase 4 or cyclin-dependent kinase inhibitor, p27(kip1) expression. ICI 182,780 abolished the inhibitory effects of E(2) and raloxifene on PDGF-induced pRb phosphorylation. Next, we examined which estrogen receptor (ER) is necessary for these effects of E(2) and raloxifene. Since VSMC express both ERalpha and ERbeta, A10, a rat aortic smooth muscle cell line that expresses ERbeta but not ERalpha, was used. The dose-dependent stimulation of A10 cell proliferation by PDGF was not inhibited by E(2) or raloxifene in contrast to the results obtained in VSMC. Moreover, E(2) and raloxifene significantly inhibited the PDGF-induced cyclin D1 promoter activity in A10 cells transfected with cDNA for ERalpha but not in the parental cells. These results suggested that E(2) and raloxifene exert an antiproliferative effect in VSMC treated with PDGF, at least in part through inhibition of pRb phosphorylation, and that the inhibitory effects of E(2) and raloxifene may be mainly mediated by ERalpha.

Animals↗

Upper respiratory tract infections and pediatric anesthesia.

Anesthesia for the child with an upper respiratory infection (URI) presents a challenge for the pediatric anesthesiologist. Differences in study design have made interpretation and comparison very difficult. The general lack of evidence-based research has led to disparities in the manner in which children which URI have been traditionally managed. Many studies have described associations between URIs and adverse events and we must decide whether to proceed or postpone the procedure and how long to postpone it. More recent research, however, suggests that children with uncomplicated infections can undergo elective procedures without significant increase in adverse anesthetic outcomes. This presentation summarizes the evolving literature about cancellation of surgery for the child with an upper respiratory infection, perioperative outcomes and anesthetic management.

Anesthesia↗

Autonomic cardiovascular function in high-altitude Andean natives with chronic mountain sickness.

We evaluated autonomic cardiovascular regulation in subjects with polycythemia and chronic mountain sickness (CMS) and tested the hypothesis that an increase in arterial oxygen saturation has a beneficial effect on arterial baroreflex sensitivity in these subjects. Ten Andean natives with a Hct >65% and 10 natives with a Hct <60%, all living permanently at an altitude of 4,300 m, were included in the study. Cardiovascular autonomic regulation was evaluated by spectral analysis of hemodynamic parameters, while subjects breathed spontaneously or frequency controlled at 0.1 and 0.25 Hz, respectively. The recordings were repeated after a 1-h administration of supplemental oxygen and after frequency-controlled breathing at 6 breaths/min for 1 h, respectively. Subjects with Hct >65% showed an increased incidence of CMS compared with subjects with Hct <60%. Spontaneous baroreflex sensitivity was significantly lower in subjects with high Hct compared with the control group. The effects of supplemental oxygen or modification of the breathing pattern on autonomic function were as follows: 1) heart rate decreased significantly after both maneuvers in both groups, and 2) spontaneous baroreflex sensitivity increased significantly in subjects with high Hct and did not differ from subjects with low Hct. Temporary slow-frequency breathing may provide a beneficial effect on the autonomic cardiovascular function in high-altitude natives with CMS.

Adult↗

Pneumococcal purulent genual arthritis after allogeneic bone marrow transplantation.

A 21-year-old male patient with non-Hodgkin's lymphoma (diffuse large T-cell type, clinical stage IV) received allogeneic bone marrow transplantation (BMT) from a partially HLA-mismatched unrelated donor in July 1998 and achieved complete remission. Thereafter, he suffered from chronic graft-versus-host disease (GVHD) and was continuously administered immunosuppressive drugs for a long time. Two years after the BMT, he complained of severe pain in the right knee, which was swollen, and was diagnosed as having pneumococcal purulent genual arthritis. He underwent arthroscopic synovectomy and was administered systemic and intra-articular antibiotics, leading to a gradual improvement. Streptococcal infections are often seen in patients in the late phase after allogeneic BMT because of immunodeficiency associated with chronic GVHD and hyposplenism. Most streptococcal infections are respiratory tract infections and septicemia, and there have been very few reports on cases of purulent genual arthritis. Administration of prophylactic antibiotics and control of chronic GVHD, which is a risk factor of pneumococcal infection, seem to be important to prevent purulent genual arthritis.

Adolescent↗

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome following allogeneic bone marrow transplantation.

We monitored the levels of various cytokines and chemokines, as well as an adhesion molecule and factors related to vascular endothelial damage, in three patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome after bone marrow transplantation. Measurements were done at the onset of this condition and during plasma exchange for treatment. At the onset of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, the levels of interleukin-8, thrombomodulin, and plasminogen activator inhibitor-1 were all markedly increased. A close relationship was observed between improvement in symptoms by plasma exchange and a decrease in interleukin-8 level, suggesting that this chemokine may be related to the development of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome after bone marrow transplantation.

Adult↗

Transient contribution of mast cells to pulmonary eosinophilia but not to hyper-responsiveness.

BACKGROUND: We have recently demonstrated that the transfer of interleukin (IL)-5-producing CD4+ T cell clones into unprimed mice is sufficient for the development ofeosinophilic inflammation in the bronchial mucosa upon antigen inhalation. OBJECTIVE: The aim of this study was to elucidate the possible contribution of mast cells in eosinophilic inflammation and bronchial hyper-responsiveness (BHR), and to discriminate between the roles of CD4+ T cells and mast cells. METHODS: Mast cell-deficient mice (WBB6F1-W/Wv) and their congenic normal littermates (WBB6F1-+/+) were immunized with ovalbumin and challenged by inhalation with the relevant antigen. RESULTS: Airway eosinophilia was induced with equivalent intensity in +/+ and W/Wv mice 6, 24, 96 and 216 h after antigen inhalation. In contrast, 48 h after antigen challenge, eosinophilic infiltration into the bronchial mucosa was significantly less pronounced in W/Wv mice than in +/+ mice. Anti-CD4 monoclonal antibody (mAb), anti-IL-5 mAb, and cyclosporin A were administered next, demonstrating that the airway eosinophilia of W/Wv mice induced 48 h after antigen challenge was almost completely inhibited by each of these three treatments, but that of +/+ mice was significantly less susceptible. Bronchial responsiveness to acetylcholine was increased 48 h after antigen challenge and was not significantly different between +/+ and W/Wv mice. Administration of anti-IL-5 mAb completely inhibited the development of BHR in both +/+ and W/Wv mice. CONCLUSION: These results indicate that, in mice, mast cells do have a supplemental role in the development of pulmonary eosinophilia but not BHR. CD4+ T cells totally regulate these responses by producing IL-5.

Administration, Inhalation↗

Transcriptional regulation of the IL-5 gene in peripheral T cells of asthmatic patients.

Mechanisms that underlie the regulation of IL-5 gene expression in human peripheral T cells remain incompletely defined because of the low efficiency of transfection of plasmid constructs into non-transformed T cells. To elucidate the cellular and molecular mechanisms of IL-5 production, concanavalin A (ConA)-stimulated blastocytes derived from peripheral blood lymphocytes of asthmatic patients were employed in this study. Transcriptional activity of the synthetic human IL-5 promoter in ConA-stimulated blastocytes correlated with the production of IL-5. Deletion analysis of the reporter gene showed that the cis-regulatory element located at - 119 to - 80 is critical for inducible IL-5 promoter activity. Electrophoretic mobility shift assay revealed that an oligonucleotide probe corresponding to the element (- 119 to - 90) gave two specific bands. The slower migrating band was absolutely dependent on stimulation and was composed of a co-operative complex of the transcription factors, nuclear factor of activated T cells (NFAT) and activating protein-1 (AP-1). The faster migrating band was also inducible and was identified as AP-1-less NFAT. Mutation of either the NFAT or AP-1 element abrogated the slower migrating band and at the same time abolished transcriptional activity of the human IL-5 promoter/enhancer gene. Cyclosporin A equivalently suppressed DNA-binding activity of the composite NFAT/AP-1 site, promoter activity and protein production of IL-5. In conclusion, these data suggests that the composite NFAT/AP-1 binding element (- 115 to - 100) plays a crucial role in IL-5 synthesis by peripheral T cells of asthmatic patients.

Adult↗

Superior vena cava syndrome after bone marrow transplantation caused by aspergillosis: a case report.

Aspergillosis is known for the variety of unusual presentations in immuno-suppressed patients. We report a patient in whom aspergillosis caused the superior vena cava (SVC) syndrome. A 37-year-old woman became febrile soon after bone marrow transplantation (BMT). Chest radiography demonstrated a 5-cm mass extending from the right lung apex to the right supraclavicular fossa beside her Hickman catheter. She then developed SVC syndrome, which progressed despite treatment. Despite recovery of the white blood cell count, the patient continued to deteriorate, became comatose, suffered a cardiac arrest and died 31 days after BMT. Autopsy revealed Aspergillus infection at the apex of the right lung associated with innominate artery thrombosis.

Adult↗

Similarity between eruptions induced by sulfhydryl drugs and acute cutaneous graft-versus-host disease after bone marrow transplantation.

Cutaneous GVHD is histologically similar to eruptions induced by drugs containing a sulfhydryl group. The levels of interleukin-2 and interleukin-2 receptor were determined in a group of patients undergoing bone marrow transplantation (BMT) without graft-versus-host disease or any other complications and in a group with cutaneous graft-versus-host disease (GVHD) alone. In patients who only developed cutaneous GVHD, both interleukin-2 and inter-leukin-2 receptor levels were elevated when the disease was evident. As the elevation of these parameters became more marked, the grade of cutaneous graft versus-host disease also increased. In some patients, only one of the two parameters was elevated and the grade of graft-versus-host disease was low or no skin manifestations were seen. These findings suggest that interleukin-2 and interleukin-2 receptor act together in the development of cutaneous GVHD. This study also showed that the mechanism of cutaneous GVHD resembles that involved in the induction of eruptions by sulfhydryl-containing drugs.

Acute Disease↗

Treatment of non-inflamed obstructive meibomian gland dysfunction by an infrared warm compression device.

AIM: To test the short term efficacy and safety of an infrared warm compression device (IWCD, Eye Hot, Cept Co, Tokyo, Japan) as treatment for non-inflamed meibomian gland dysfunction (MGD). METHODS: 37 subjects with non-inflamed obstructive MGD, with and without aqueous tear deficiency (ATD) dry eye, participated in a prospective non-comparative interventional case series. Symptom scores, face scores, tear evaporation rates, fluorescein and rose bengal vital staining, tear break up time (BUT), Schirmer test, meibomian gland obstruction, and meibography were compared before and after 2 weeks of therapy. RESULTS: In a total of 37 cases, total subjective symptom scores and subjective face scores improved significantly, from 12.3 (SD 5.9) to 8.4 (6.1), and from 7.0 (1.7) to 5.3 (2.0) (both p <0.0001). The results for tear evaporation rates during forced blinking (p = 0.002), fluorescein staining (p = 0.03), rose bengal staining (p = 0.03), BUT (p <0.0001), and meibomian gland orifice obstruction score (p <0.0001) had also improved significantly at the end of the 2 week period of infrared thermotherapy. No complaints and/or complications of the IWCD were reported. CONCLUSION: The IWCD was effective and safe for the treatment of MGD. Improved tear stability associated with release of meibum is a possible mechanism of this treatment.

Adult↗

Analysis of mixed chimerism in patients after allogeneic stem cell transplantation using a capillary electrophoresis system.

We analyzed mixed chimerism (MC) after allogeneic stem cell transplantation (SCT) using a capillary electrophoresis system with four kinds of fluorescence-labeled primers for microsatellites (D3S1359, D6S89, ACTBP2, HGH). The sensitivities of all microsatellites were at least 3%. The present method is sufficiently rapid: only 3-4 h are needed to perform all the procedures. For analysis of MC in 30 patients who had undergone allogeneic SCT, heterozygosity of all microsatellites was over 88% and informativeness of ACTBP2 and HGH was over 73%. We analyzed MC using this technique to determine whether it was useful for prediction of the prognosis of 22 patients who had undergone allogeneic SCT. MC was more frequently observed in patients who were treated without total body irradiation (TBI) than in patients who were treated with TBI (p = 0.009). MC was also seen in a larger percentage of patients without acute graft-versus-host disease (p = 0.027). Six patients developed graft failure or relapse among 12 patients with MC. The graft failure or relapse was higher in patients with MC than in patients with complete chimerism (CC) (p = 0.009) especially if they were over 30 years of age (p = 0.0005). In contrast, graft failure or relapse was not higher in patients with MC compared with patients with CC under 30 years of age (p = 0.78). These results show that MC is an important predictive factor, especially in patients over 30 years of age.

Adolescent↗

Effect of serotonin (5-HT) on trigeminal rhythmic activities generated in in vitro brainstem block preparations.

We used rat isolated brainstem block preparations to analyze the functional roles of serotonin receptors in the generation of trigeminal rhythmic activities. We previously reported that trigeminal rhythmic activities could be induced by some pharmacological applications in an isolated brainstem preparation with a rostral boundary at the border between the inferior and superior colliculus, and a caudal border at the level of the rostral facial nucleus. However, the same stimulation did not induce trigeminal rhythmic activities in a whole brainstem block preparation with the same rostral boundary and a caudal border at the obex level. In the present study, both the 5-HT(1A) phthalimido-butyl-piperazine, and the 5-HT(2C) agonist, 1-2,5-dimethoxy-4-iodophenyl-2-aminopropane, combined with N-methyl-D,L-aspartate and bicuculline, elicited trigeminal rhythmic activities in a whole brainstem block preparation. Our results suggest that serotonin has both facilitation and inhibition effects on the generation of trigeminal rhythmic activities in an isolated brainstem block preparation in vitro.

Animals↗

Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass.

BACKGROUND: We performed this prospective randomized study to determine the effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. METHODS: Twenty-two children were included in this study. They were randomly allocated to 1 of the following groups; a control group (n=11) or a Ulinastatin group (n=11) in which patients received 5000 U/kg of Ulinastatin. Arterial blood samples were obtained before cardiopulmonary bypass (CPB), immediately after CPB, and 30 min after protamine administration, as well as 3 hours after and 18 hours after CPB, and Interleukin-8 and neutrophil elastase concentration were evaluated. RESULTS: CPB time and aortic clamp time did not differ between the groups. Interleukin 8 and neutrophil elastase concentrations before CPB increased significantly immediately after CPB, these concentrations did not differ between the groups. However, neutrophil elastase concentrations of a Ulinastatin group were significantly lower than that of a control group at 30 min after protamine administration (a Ulinastatin group: 1011.3+/-539.1 mg/ml, a control group: 1619.7+/-595.7 mg/ml, p<0.05) and A-aDO2 of a Ulinastatin group was significantly lower than that of a control group at 2 hours after CPB (a Ulinastatin group: 67.1+/-70.6 mmHg, a control group: 169.2+/-116.3 g, p<0.05). CONCLUSIONS: These results suggest that Ulinastatin suppresses the increase in neutrophil elastase and protects the respiratory function in pediatric patients undergoing cardiopulmonary bypass.

Cardiopulmonary Bypass↗

Oral eicosapentaenoic acid for acute colonic graft-versus-host disease after bone marrow transplantation.

We investigated whether pretreatment with eicosapentaenoic acid, an inhibitor of leukotriene (LT) B4, could ameliorate acute colonic graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). Seventeen patients undergoing unrelated BMT were divided into two groups, with eight patients receiving eicosapentaenoic acid and nine not receiving it. The grade of GVHD after transplantation was compared with that estimated from the pretransplantation LTB4 level. The levels of LTB4 and several cytokines were also monitored. The actual grade of GVHD was lower than that estimated from LTB4 levels in three of the eight patients from the treated group, and there was a significant difference between the treated and untreated groups (p < 0.05, chi 2 test). The levels of LTB4, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were all significantly lower in the treated group (p < 0.05, Student's t-test). These findings suggest that eicosapentaenoic acid may ameliorate acute colonic GVHD when administered from before BMT.

Acute Disease↗

Circadian profile of Per gene mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, and pineal body of aged rats.

Aging alters circadian components such as the free-running period, the day-to-night activity ratio and photic entrainment in behavioral rhythms, and 2-deoxyglucose uptakes and neuronal firing in the suprachiasmatic nucleus (SCN). A core clock mechanism in the mouse SCN appears to involve a transcriptional feedback loop in which Period (Per) and Cryptochrome (Cry) genes play a role in negative feedback. The circadian rhythm systems include photic entrainment, clock oscillation, and outputs of clock information such as melatonin production. In this experiment, we examined clock gene expression to determine whether circadian input, oscillation, and output are disrupted with aging. Circadian expression profiles of rPer1, rPer2, or rCry1 mRNA were very similar in the SCN, the paraventricular nucleus of the hypothalamus (PVN), and the pineal body of young and aged (22-26 months) rats. On the other hand, the photic stimulation-induced rapid expression of Per1 and Per2 in the SCN was reduced with aging. The present results suggest that the molecular mechanism of clock oscillation in the SCN, PVN, and pineal body is preserved against aging, whereas the impairment of Per1 induction in the SCN after light stimulation may result in impaired behavioral photic entrainment in aged rats.

Aging↗

sFlt-1 gene-transfected fibroblasts: a wound-specific gene therapy inhibits local cancer recurrence.

Local recurrence occurs frequently at the site of injury after surgical resection. On the other hand, fibroblasts have been shown to accumulate in the injured area to heal and remodel the damaged tissues. Therefore, fibroblasts are likely to be useful as wound-specific vectors for delivery of genes to sites of surgically injury. The present study was performed to investigate wound-specific migration of exogenously administered fibroblasts and efficacy of gene therapy using genetically engineered fibroblasts in an i.p. wound recurrence model in rats. We demonstrated that fibroblasts transfected with the GFP gene accumulated specifically around the site of injury immediately after i.p. injection. Then, fibroblasts transfected with an adenovirus designated as AdFex that encoded the soluble form of Flt-1 (sFlt-1), a vascular endothelial growth factor receptor, were administered i.p. to the rats to examine inhibition of tumor growth. At day 16 after implantation, a significantly smaller tumor volume and less microvessel density in wound sites were observed in the AdFex/fibroblast-treated rats than in controls. Furthermore, this treatment also resulted in an improved survival rate. In conclusion, autologous fibroblasts show promise as a wound-specific vector for gene therapy, and administration of sFlt-1 gene-engineered fibroblasts contributed to local control of the tumor around the injured tissue.

Animals↗