Search PubMed⌕ Search

Biomedical subjects

Y Fujimori

Publications and source records attributed to Y Fujimori.

At least 37 records · Page 2Linked to original sources
PubMed2000

Evaluation of CMV/human herpes virus-6 positivity in bronchoalveolar lavage fluids as early detection of acute GVHD following BMT: evidence of a significant relationship.

We evaluated the relationship between CMV and human herpes virus-6 (HHV-6) reactivation and the incidence of grades 2 to 4 acute GVHD post BMT. Bronchoalveolar lavage fluid (BALF) samples extracted from 54 BMT recipients on post-BMT day 35 were analyzed by PCR for detection of CMV DNA, HHV-6 DNA and CMV plus HHV-6 DNA. CMV DNA was detected in 26 patients and 13 (50%) developed grades 2 to 4 acute GVHD. Of the 28 who were CMV negative, only six (21.4%) developed grades 2 to 4 acute GVHD. HHV-6 was detected in 18 patients, and 11 (61.1%) developed grades 2 to 4 acute GVHD. Of the 36 who were HHV-6 negative, only eight (22.2%) developed grades 2 to 4 acute GVHD. CMV and HHV-6 were detected in 13 patients, and eight (61.5%) developed grades 2 to 4 acute GVHD. Of the 23 who were negative for both CMV and HHV-6, only three (13%) developed grades 2 to 4 acute GVHD. In all experiments, the difference between the groups was significant (P<0.05, P<0.05 and P<0.01, respectively). We conclude that herpes virus infection, in particular CMV concurrent with HHV-6 reactivation, is predictive of moderate to severe acute GVHD.

Adolescent↗
PubMed2000

Complications after bone marrow transplantation are manifestations of systemic inflammatory response syndrome.

Bone marrow transplantation has been established as a useful treatment for various hematological disorders and is now performed widely, but the mortality rate is still high due to various complications. A clear therapeutic policy for such complications has not yet been established because of their complex nature. We investigated whether the major complications occurring after bone marrow transplantation could be classified as aspects of the systemic inflammatory response syndrome. Subjects were 10 patients who developed severe complications after bone marrow transplantation (graft-versus-host disease, thrombotic microangiopathy, respiratory disorders, and cytomegalovirus interstitial pneumonitis) and 16 patients without complications. Their symptoms, serum cytokines, and factors related to vascular endothelial damage were compared before and after transplantation. Whereas all 10 patients who developed complications had fever in the aplastic phase after transplantation, 15 of the 16 patients without complications remained afebrile (P < 0.001, t-test). When compared with the patients who did not develop complications, the patients with complications also showed significantly higher cytokine levels during the recovery phase after transplantation (P < 0.0001, t-test). Thus, the patients with complications developed fever in the aplastic phase and showed an increase of cytokines during the recovery phase, which triggered the occurrence of vascular endothelial damage shown by factors such as the thrombomodulin and plasminogen activator inhibitor type 1. This sequence of events corresponds with that occurring during systemic inflammatory response syndrome, so many of the complications of bone marrow transplantation can be considered as manifestations of this syndrome.

Adult↗
PubMed2000

Predicting the severity of intestinal graft-versus-host disease from leukotriene B4 levels after bone marrow transplantation.

Intestinal graft-versus-host disease (GVHD) produces clinical manifestations and histological changes resembling those of ulcerative colitis and has been treated with drugs which are used for ulcerative colitis. These two conditions also resemble each other with respect to changes of cytokines. Accordingly, we investigated whether the level of leukotriene B4, a risk factor for ulcerative colitis, was also a risk factor or prognostic indicator for intestinal GVHD. The pre-conditioning leukotriene B4 level was significantly related to the grade of intestinal GVHD in 42 patients (P < 0.01). Compared with patients who did not develop severe intestinal GVHD after bone marrow transplantation, those who did had significantly higher interleukin-2 and interferon-gamma levels during the aplastic phase (P <0.01), followed by higher tumor necrosis factor-alpha levels during the recovery phase (P < 0.0001), with significant elevation of tumor necrosis factor-alpha and interferon-gamma occurring in association with exacerbations of intestinal GVHD (P < 0.001). These findings suggest a similarity between the pathogenesis of ulcerative colitis and intestinal GVHD and raise the possibility that leukotriene B4 may be a useful prognostic indicator for intestinal GVHD.

Adolescent↗
PubMed2000

Increased expression of Fas (APO-1, CD95) on CD34+ haematopoietic progenitor cells after allogeneic bone marrow transplantation.

Up-regulation of Fas/APO-1 (CD95) on haematopoietic progenitors and Fas-mediated apoptosis have been suggested to occur in a possible pathological mechanism in some bone marrow failure syndromes. We examined the expression of Fas antigen and susceptibility to Fas-mediated suppression of donor-derived haematopoietic cells of allogeneic bone marrow transplantation (BMT) recipients. Cytofluorometric analysis revealed low expression of Fas on CD34+ bone marrow cells from marrow donors or healthy controls. However, significantly higher expression of Fas antigen was observed on CD34+ bone marrow cells of BMT recipients, in whom engraftment of donor bone marrow (BM) cells was confirmed. The addition of an agonistic anti-Fas antibody (Ab) (CH-11) to haematopoietic stem cell culture of BM cells more strongly suppressed colony formation from granulocyte-macrophage colony-forming units (GM-CFU) and erythroid burst-forming units (BFU-E) after BMT. Pretreatment by blocking anti-Fas Ab (ZB4) abrogated the Fas-mediated GM-CFU and BFU-E suppression. Purified marrow CD34+ cells from BMT recipients were also susceptible to the Fas-mediated colony suppression. Thus, donor-derived CD34+ haematopoietic cells increased their expression of Fas antigen and were susceptible to Fas-mediated haematopoietic suppression. These findings provide new insight for understanding the haematological condition after BMT.

Adult↗
PubMed2000

Elevated interleukin (IL)-18 levels during acute graft-versus-host disease after allogeneic bone marrow transplantation.

Acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation (BMT) is mediated by grafted T lymphocytes after their polarization into type 1 T cells. Interleukin (IL)-18, a novel immunoregulatory cytokine, strongly stimulates type 1 T cells, therefore we postulated that IL-18 may be involved in the pathogenesis of aGVHD. Using an enzyme-linked immunosorbent assay (ELISA), we serially measured serum levels of IL-18 in 37 patients with haematological malignancy before and after allogeneic BMT. Patients with aGVHD had high levels of IL-18 that strongly correlated with the severity of aGVHD. We also found that they showed reduced serum levels of IL-18 after appropriate treatment or at a state of resolution. IL-18 levels were not affected by the pretransplant regimen, engraftment or bacterial infection. Compared with circulating interferon (IFN)-gamma or IL-12 levels, serum levels of IL-18 showed a more sensitive and specific correlation with the disease status of aGVHD. These findings suggest that IL-18 may play important roles in the pathogenesis of aGVHD and that measurement of serum IL-18 levels can be useful indicator of aGVHD.

Acute Disease↗
PubMed2000

Long-term administration of oral low-dose topoisomerase II inhibitors, MST-16 and VP-16, for refractory or relapsed non-Hodgkin's lymphoma.

It is known that the topoisomerase II inhibitors, MST-16 (sobuzoxane) and VP-16 (etoposide), are effective for the treatment of lymphoma. Five patients with refractory or relapsed non-Hodgkin's lymphoma (NHL) were treated with a combination of oral MST-16 and VP-16 over a long period. Two patients had severely refractory NHL. The remaining 3 patients could not be treated with intensive chemotherapy because of severe organ dysfunction or a poor hematopoietic reserve. All 5 are alive and well after MST-16 and VP-16 treatment. MST-16 and VP-16 are effective for NHL when intensive chemotherapy is ineffective or contraindicated.

Administration, Oral↗
PubMed2000

New imaging findings in a patient with central nervous system dysfunction after bone marrow transplantation.

Central nervous system disorders are an important complication of bone marrow transplantation (BMT). We have recently performed cerebral angiography to examine central nervous system dysfunction in a 22-year-old woman with acute lymphoblastic leukaemia who had undergone BMT. Angiography demonstrated multiple stenoses and occlusions in the peripheral branches of the anterior and middle cerebral arteries, a pattern similar to that seen in vasculitis. She was thought to most likely have cytomegalovirus (CMV) vasculitis, but other forms of vasculitis, such as angiitis-like-syndrome-associated graft-versus-host disease could not be excluded. This case suggests that CMV vasculitis may cause central nervous system dysfunction after BMT and that imaging studies may provide useful information about central nervous system disorders in these patients.

Adult↗
PubMed2000

Acute promyelocytic leukemia with marrow fibrosis at initial presentation: possible involvement of transforming growth factor-beta(1).

Although the occurrence of marrow fibrosis in acute myeloid leukemia has been described, there have been no reports of acute promyelocytic leukemia (APL) associated with marrow fibrosis. Here we describe an APL patient with severe marrow fibrosis at initial presentation. He had the typical manifestations of APL, except for marrow fibrosis. Complete remission was achieved by treatment with all-trans retinoic acid plus chemotherapy, and his marrow fibrosis gradually improved concomitantly with the decrease in leukemic cells. To clarify the mechanism of marrow fibrosis in this patient, we investigated the expression of genes for several cytokines promoting fibrosis by the reverse transcriptase polymerase chain reaction methods. An overexpression of transforming growth factor-beta(1) was noted in his leukemic cells at initial presentation, whereas no increase in expression was observed at the time of relapse when he no longer had marrow fibrosis. These findings suggest that overexpression of transforming growth factor-beta(1) was involved in the development of marrow fibrosis in this APL patient.

Adult↗
PubMed2000

Increased expression of Fas (APO-1, CD95) on CD4+ and CD8+ T lymphocytes during total body irradiation.

Fas/APO-1 (CD95) is a cell surface molecule that can transduce apoptotic signals into cells. We examined the expression of Fas antigen on CD4+ and CD8+ T cells of patients who received total body irradiation (TBI) as a preparative regimen for allogeneic bone marrow transplantation. Numbers of peripheral blood lymphocytes were significantly reduced after TBI. Cytofluorometric analysis revealed a significantly higher expression of Fas on CD4+ and CD8+ T cells after TBI. Serum soluble Fas concentrations were significantly elevated after TBI. Changes in the Fas system were therefore accompanied by TBI-induced lymphocytopenia, suggesting that Fas plays a role in irradiation-induced apoptosis in vivo.

Adult↗
PubMed2000

Effects of combined oral treatments with cyclosporine A and nifedipine or diltiazem on drug-induced gingival overgrowth in rats.

BACKGROUND: Cyclosporine A (CsA) and calcium channel blockers induce gingival overgrowth in humans and animals. Recently, nifedipine and diltiazem have often been used to control CsA-related hypertension in organ transplant patients. The purpose of this study was to examine the effects of a combined oral treatment of CsA and nifedipine or diltiazem on the severity of gingival overgrowth in rats. METHODS: Fifteen-day-old Fischer rats were treated orally with single or combined applications of CsA, nifedipine, and/or diltiazem for 40 days; and induced gingival overgrowth, rat growth, and blood drug levels were compared among the different experimental groups. The experiment consisted of 6 groups: one control group (group A) and 5 test groups treated with CsA (group B), nifedipine (group C), and diltiazem (group D), as well as those concurrently treated with CsA and nifedipine (group E), and CsA and diltiazem (group F). Gingival overgrowth was determined by measuring the depth of the gingival sulcus. RESULTS: The mandibular buccal gingival sulcus depth of group A was 365 +/- 41.2 microm. Among the test groups, the most remarkable gingival overgrowth was seen in group E (1,020 +/- 63.3 microm), followed by group F (895 +/- 43.8 microm), group B (870 +/- 48.3 microm), group C (525 +/- 116 microm), and then group D (505 +/- 83.2 microm). Rat body weight gain was reduced significantly by oral CsA treatment. Neither nifedipine nor diltiazem suppressed rat growth when used independently; however, rat growth reduced by CsA was further suppressed by a combined use of diltiazem, but not nifedipine. CsA blood levels were reduced by concurrent oral treatment with nifedipine or diltiazem along with the blood levels of those calcium channel blockers when treatment was in combination with CsA. CONCLUSIONS: These results suggest that gingival overgrowth is induced in rats as a side effect of CsA, nifedipine, or diltiazem, and the combined use of these drugs influences rat growth, blood drug levels, and the severity of gingival overgrowth.

Administration, Oral↗
PubMed2000

Changes in microbial flora in neutropenic patients with hematological disorders after the Hanshin-Awaji earthquake.

The earthquake that struck the Hanshin-Awaji district on January 17, 1995, was one of the most destructive to occur in Japan. We analyzed the changes in microorganisms isolated from patients with hematological disorders in relation to this earthquake. We reviewed a total of 4137 microbial cultures obtained over 1-year periods before and after the earthquake. There were 123 neutropenic patients admitted during the study period (54 before the earthquake and 69 afterwards). No significant differences in clinical characteristics and underlying diseases were found between the 2 groups. Polynomial analysis revealed a significant increase in the isolation of Candida albicans, Candida glabrata, and Pseudomonas aeruginosa from sputum and stool cultures after the earthquake. These microorganisms increased markedly in patients from severe earthquake-damaged areas. In neutropenic patients with hematological disorders, microbial isolates changed significantly after the Hanshin-Awaji earthquake. These changes may have been related to physical and emotional stress, as well as to the deterioration of environmental factors such as food, air, and water.

Adolescent↗
PubMed1999

Adult respiratory distress syndrome-like disorders after allogeneic bone marrow transplantation.

BACKGROUND: Adult respiratory distress syndrome-like respiratory disorders are a serious, but uncommon, complication of bone marrow transplantation. METHODS: We measured various cytokines in 2 patients with respiratory disorders and 11 patients without respiratory problems after allogeneic bone marrow transplantation. RESULTS: The patients with respiratory disorders had elevated levels of interferon-gamma and interleukin-2 in the aplastic phase, and elevation of tumor necrosis factor-alpha, intercellular adhesion molecule-1, and interleukin-8 at the time of leukocyte recovery. Both patients with respiratory disorders developed fever during the aplastic phase, whereas none of the patients without fever had respiratory disorders. Among patients who had fever during the aplastic phase but no respiratory disorders, there was no elevation of cytokines from the aplastic phase to the recovery phase. CONCLUSIONS: Respiratory disorders may occur after bone marrow transplantation when an inflammatory response during the aplastic phase stimulates cytokines that cause vascular endothelial damage and increases the levels of chemokines and adhesive molecules along with elevation of the leukocyte count.

Adult↗
PubMed1999

Thrombotic microangiopathy following allogeneic bone marrow transplantation.

Thrombotic microangiopathy is one of the complications of bone marrow transplantation and is related to other complications such as graft-versus-host disease, veno-occlusive disease, diffuse alveolar hemorrhage, and cytomegalovirus infection. Thrombotic microangiopathy occurred in three out of 12 patients who underwent allogeneic bone marrow transplantation over the past 1 year at our department. We compared the changes in cytokines and other molecules between patients with and without microangiopathy from before conditioning to the early post-transplantation period. All three patients with microangiopathy showed a significant increase of interleukin-12 at the time of leukocyte recovery after transplantation (two-way layout analysis of variance; P < 0.05), while none of the patients without microangiopathy showed an increase of interleukin-12. No significant differences were found between the two groups with respect to the other cytokines and molecules that were tested. These findings suggested that thrombotic microangiopathy might be predicted at an early stage after bone marrow transplantation by detecting an increase of interleukin-12 at the time of leukocyte recovery. The possibility that thrombotic microangiopathy is related to inflammation or autoimmunity was also suggested.

Adolescent↗