[Show abstract][Hide abstract] ABSTRACT: Intestinal transplant-associated microangiopathy (i-TAM) is an important complication after allogeneic hematopoietic SCT. From 1997 to 2006, 87 of 886 patients with diarrhea after transplantation received colonoscopic biopsy. i-TAM, GVHD and CMV colitis were diagnosed histopathologically. The median duration from transplantation to the onset of diarrhea was 32 days (range: 9-130 days) and that from the onset of diarrhea to biopsy was 12 days (range: 0-74 days). The median maximal amount of diarrhea was 2 l/day (range: 130-5600 ml/day). Histopathological diagnosis included i-TAM (n=80), GVHD (n=26), CMV colitis (n=17) and nonspecific findings (n=2) with overlapping. Among 80 patients with i-TAM, abdominal pain was a major symptom, and only 11 patients fulfilled the proposed criteria for systemic TAM. Non-relapse mortality (NRM) among patients without resolution of diarrhea was 72% and i-TAM comprised 57% of NRM. NRM was 25% among patients without intensified immunosuppression, but was 52, 79 and 100% among those with intensified immunosuppression before diarrhea, after diarrhea, and before and after diarrhea, respectively. In conclusion, i-TAM is a major complication presenting massive refractory diarrhea and abdominal pain, which causes NRM. Avoiding intensified immunosuppression that damages vascular endothelium until the resolution of i-TAM may improve transplant outcome.
Bone marrow transplantation 02/2009; 44(1):43-9. · 3.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thrombotic microangiopathy (TMA) is one of the severe complications after stem cell transplantation (SCT) and is associated with graft-versus-host disease (GVHD) prophylaxis including FK506. In this study, we experimented on rats using FK506 to demonstrate the occurrence of intestinal TMA. FK506 was administrated into Wistar/ST rats intraperitoneally for 7 days. Rats were examined histopathologically after FK506 injection using light and electron microscopy and immunohistochemistry. FK506 concentrations in whole blood were measured by enzyme immunoassay. In the acute phase, hemorrhagic lesions with multifocal erosions and crypt loss were found in the small intestines of all treated rats. Capillary vessels were dilated, and a few platelet thrombi were found. Electron microscopy demonstrated degenerative swelling of endothelial cells and platelet aggregates adhering to the vessel walls. In the later phase, epithelial regenerative failure, characterized by crypt ghosts, was found in the affected mucosa. Apoptotic epithelial cells were increased in number. The extent of intestinal injury was proportional to the whole blood levels of FK506. The intestinal lesions in rats were consistent with TMA and induced by the injection of FK506 alone. Apoptotic enteropathy was also observed and similar to intestinal GVHD. In this study, we established an intestinal TMA model induced by immunosuppressant (Tacrolimus) only without irradiation.
Bone Marrow Transplantation 04/2007; 39(6):367-72. · 3.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We used immunohistochemical analysis to investigate 146 bone marrow (BM) clot specimens from patients with fever of unknown origin (FUO) (n = 124) or hemophagocytic syndrome (HPS) (n = 22). Intravascular lymphoma (IVL) primarily involving BM was detected in 12 (8.2%) of the 146 patients. Diagnosis was based on the presence of CD20+ and CD79a+ tumor cells confined within the lumina of sinuses and surrounded by CD34+ endothelial cells. Of the 12 IVL cases, 6 were CD5+; of these 6 CD5+ cases, 5 were positive for vimentin. The finding of a considerably high prevalence of IVL tumor cells in BM from patients with FUO or HPS suggests that immunohistochemical examination of BM may be helpful in the diagnosis of IVL in these patients. Vimentin coexpression in CD5+ IVL might be evidence of origin from a subset of prefollicular B-cells.
International Journal of Hematology 03/2003; 77(2):159-63. · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship between the fetal hemoglobin-containing erythroblasts (F blasts) and apoptosis in myelodysplastic syndromes (MDS), we immunohistochemically assessed F blasts, F cells, and apoptosis in 137 patients with MDS. A marked increase in the number of F blasts in the bone marrow was identified in 116 of 137 patients (84.7%), and the number of F cells was elevated in 54 patients (39.4%). Among the erythroblasts stained by anti-glycophorin C antibody, the mean percentage of F blasts was 14.63 +/- 9.17% in MDS, which was significantly higher than that in non-MDS patients with stress erythropoiesis (4.82 +/- 3.35%, P < 0.01), although there were no significant differences in the number of F cells between these groups. In particular, 62 of the 137 MDS patients (45.3%) had an apparent increase in F blasts but no elevation of F cells. The apoptotic rate was significantly higher in the patients with a F blast/F cell (Fb/Fc) ratio >or=5.0 than in those with a Fb/Fc ratio <1.0 (P < 0.01). The results indicate that F cell precursors are incapable of maturing into functioning end-stage F cells, presumably owing to apoptotic cell death. The measurement of F blasts in the bone marrow is needed for the precise evaluation of fetal-type erythropoiesis in MDS.
[Show abstract][Hide abstract] ABSTRACT: Making a morphologic distinction between hypocellular refractory anemia (hypo RA) and aplastic anemia (AA) is difficult. To investigate the significance of hemoglobin F-containing erythroblasts (F-blasts) and p53 expression in making the distinction between hypo RA and acquired AA, we immunohistochemically assessed F-blasts and p53 in bone marrow specimens from 16 patients with hypo RA, 31 patients with acquired AA, and 15 hematologically normal individuals. F-blast production was elevated in 87.5% (14/16) of patients with hypo RA, but in only 3.2% (1/31) of patients with AA (P < .01). p53 was overexpressed in 75.0% (12/16) of hypo RA patients and in 6.4% (2/31) of AA patients (P < .01). The mean contents of F-blasts and p53-positive cells in patients with hypo RA were 6.31% +/- 3.27% and 7.54% +/- 4.36%, respectively, of all bone marrow cells, which were significantly higher than for patients with AA (0.35% +/- 0.46% and 0.58% +/- 1.29%, P < .01). In conclusion, a high prevalence of elevated F-blast production is noted in hypo RA, suggesting that the assessment of F-blasts in bone marrow can be used as an additional tool for differentiating hypo RA from acquired AA.
International Journal of Hematology 05/2002; 75(3):257-60. · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated whether the anatomic distribution of hematopoietic cells determines the type of hemoglobin produced in patients with extramedullary hematopoiesis (EMH). Fetal hemoglobin (HbF) production is not restricted to fetal erythropoietic organs during EMH. A shift of erythropoiesis to fetal hematopoietic organs in EMH does not necessarily induce HbF synthesis in adulthood.
[Show abstract][Hide abstract] ABSTRACT: To date there are few antibodies available for the detection of fetal hemoglobin (HbF)-containing erythroblasts (F-blasts)
in paraffin-embedded hematopoietic tissues. Recently, we developed a new polyclonal antibody specific to F-blasts by immunization
of a rabbit with synthetic peptides of human HbF. Specificity and reactivity of the antibody were confirmed by enzyme-linked
immunosorbent assay (ELISA) and immunohistochemistry. ELISA confirmed that the antibody showed strong immunoreactivity to
fetal hemoglobin but no reaction to adult hemoglobin. The antibody could detect the presence of fetal blood hemolysates (10
μxg/mL) at a dilution of 10p-5. According to immunohistochemical analysis, there were strong positive reactions to fetal erythroblasts in the liver and
the spleen at 29 weeks of gestation and to erythroblasts from patients with myelodysplastic syndromes and erythroleukemia
but no reactions to normal adult erythroblasts in bone marrow. Fetal erythrocytes in fetal blood vessels of placental tissues
were strictly distinguished from maternal erythrocytes in the same sections by their positive reactions, indicating the presence
of HbF. This new antibody will be a useful tool for studying fetal hemoglobin synthesis and for detecting F-blasts in archival
specimens of various hematological diseases.
International Journal of Hematology 10/2001; 74(3):277-280. · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemolymph nodes (HLs) are unique lymph nodes, in that their lymphatic sinuses contain numerous erythrocytes. In this study, we compared the internal structure and immunologic function of HLs with those of ordinary lymph nodes (OLs) and the spleen. Electron microscopy revealed erythrocytes passing through the walls of blood vessels in the intermediate sinus area (IMSA) of a HL between expanded endothelial cell junctions. However, no direct communication was found between lymphatic sinuses and blood vessels. Numerous carbon particles appeared in the IMSA of HLs on 5 days after intravenous carbon particle injection, while OLs lacked particle deposition. Immunohistochemical studies showed that lipopolysaccharide (LPS) reached the IMSA of HLs and extravasated into medullary cords 4 hours after intravenous LPS injection, resulting in the appearance of more IgM-stained lymphocytes in the IMSA of HLs than in that of OLs on day 5. The ability of organs to produce antibodies was determined by counting the number of plaque forming colonies after intravenous injection of sheep red blood cells (SRBC). The HLs antibody-producing ability was between that of OLs and the spleen. These results suggest that HLs possess functionally open blood vessels in the IMSA and their immunologic capability is between that of OLs and the spleen. These findings suggests that HLs are lymphoid organs that have characteristics between those of the OLs and the spleen, both ultrastructurally and functionally.
Nagoya journal of medical science 12/1997; 60(3-4):129-37.
[Show abstract][Hide abstract] ABSTRACT: There is a large body of evidence indicating that stress influences immune competence. For example, psoriasis and atopic dermatitis may be exacerbated by psychic stress and related to abnormalities in the cellular constituents of the immune system in the skin. However, the underlying mechanisms remain unclear. We therefore investigated the potential of acute immobilization stress to affect the DTH response in BALB/c mice. DTH was significantly reduced in an immobilization time-dependent manner when stress exposure was just before sensitization. Although the number of Langerhans cells (LC) did not change under these conditions, marked alteration of LC morphology was observed with a significant decrease in area. Recovery of LC was observed within 24 h when the DTH response was also restored. Expression of the calcitonin gene-related peptide (CGRP), which inhibits LC antigen presentation, was significantly increased up to 1.6-fold in nerve fibres of immobilized mice. We conclude that stress-induced suppression of DTH could be due to reduction of LC antigen presentation with morphological change in association with CGRP elevation.
[Show abstract][Hide abstract] ABSTRACT: A panel of rat monoclonal antibodies directed against mouse splenic stromal cells were isolated. These monoclonal antibodies were immunohistochemically divided into four groups which reacted with non-lymphoid cells of the murine spleen; (I) in the white pulp, (II) at the marginal zone, (III) in the red pulp, and (IV) on the endothelium of splenic blood vessels. These monoclonal antibodies were studied immunohistochemically in lymphoid organs by means of light and electron microscopy. Monoclonal antibodies SS-4 (group I) reacted with fibroblastic reticulum cells that were distributed only in the white pulp of the spleen and in the follicular areas of lymph nodes. The SS-4 staining cell, in clustered splenic stromal cells, formed colonies which included a small number of Thy-1 positive lymphocytes. Therefore, we concluded that SS-4 staining stromal cells comprise the lymphoid compartment. In contrast, monoclonal antibodies SS-1, SS-3 and SS-5 (group II) reacted with dendritic shaped cells in the marginal zone of the spleen. Examination of splenic extramedullary hematopoiesis in mice rescued by bone marrow transplantation after lethal irradiation revealed that SS-3 and SS-5 reacted with dendritic shaped stromal cells in clonal nodules of engrafted marrow in the red pulp. SS-3 and SS-5 staining cells could not be observed in physiologic hematopoiesis of non-transplanted mice. It was suggested that SS-3 and SS-5 staining stromal cells are involved in primitive hematopoiesis. Monoclonal antibodies SS-2, SS-6 and SS-7 (group III) mainly reacted with dendritic cells and macrophages in the red pulp. Monoclonal antibodies SS-B and SS-9 (group IV) reacted with endothelial cells of blood vessels and sinuses. These findings of heterogeneity in mouse splenic stromal cells are further evidence that specific micro-environments are composed by specialized stromal cells.
Pathology International 06/1997; 47(5):275-81. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Immunohistochemistry was used to study the kinetics of B lymphocytes (B-lys) in the early stages of the localized inflammatory response induced in SMA mice by the subcutaneous injection of lipopolysaccharide (LPS). At the injection sites, medium-sized B-lys formed early inflammatory lesions with neutrophils and activated macrophages on days 1 and 2. The B-lys were morphologically similar to monocytes, but were not stained with Mac1 antibody. Remarkably the B-lys showed the phenotypes of B220+, IgM+, IgD (slight to negative), Ly-1- and CD23- by double immunohistochemical staining. The B-lys were also positive for alkaline phosphatase. Consequently the B-lys could be identified as monocytoid B-lys or marginal zone B-lys. Plasmacytic B-lys and plasma cells were first observed on days 3 and 4, but no lymphoid follicles were found at the injection sites. In the inguinal lymph nodes, the same B-lys responses were mainly induced in the paracortical lesions (T cell areas) preceding the formation of activated germinal centers (GC). These findings suggested that the B-lys, induced by injections of LPS, matured into plasma cells in the localized inflammatory lesions independent of GC, and that they were different from follicular B-lys.
Pathology International 07/1996; 46(6):399-407. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To reveal the reconstitution process of the white pulp after bone marrow transplantation (BMT), spleens of 24 marrow recipients whose survival times ranged from 34 to 303 days after BMT, were analyzed at the histopathological and immunohistochemical level. Up to 3 months after BMT, the white pulp was atrophic and consisted mainly of T cells forming periarteriolar lymphatic sheaths (PALS). Approximately 100 days after BMT, B cells aggregated in some of the white pulp, forming primary follicles, whereas marginal zones could not be detected. Beyond 4 months after BMT, the PALS, the lymphoid follicle, and the marginal zone of the white pulp could be seen in most of the recipients' spleens. However, the recovery of the marginal zone was poor up to 10 months after BMT. Thus, the white pulp was reconstituted sequentially, beginning in the PALS, followed by reconstitution in lymphoid follicles, and finally in the marginal zone. The development of the PALS corresponded well with the appearance of interdigitating dendritic cell, as did the development of lymphoid follicles with the appearance of follicular dendritic cell. The sequential reconstitution of the white pulp demonstrated in this study provides the morphological basis for the functional immune recovery of marrow recipients. In particular, the delay of the marginal zone reconstitution seems to be responsible for the functional asplenia of long-term survivors.
American Journal Of Pathology 11/1993; 143(4):1111-20. · 4.60 Impact Factor