Although a considerable proportion of patients with myelodysplastic syndrome (MDS) achieve haematological recovery after receiving immunosuppressive therapy, the long-term prognosis for these responders has not been well clarified (Biesma et al, 1997; Molldrem et al, 1997; Jonasova et al, 1998). In such responders, the increased blood cells were still MDS clones and there have been no reports regarding the recovery of normal clone cells after immunosuppressive therapy. Here we report the first patient with refractory anaemia (RA) to demonstrate the recovery of normal clones after long-term administration of cyclosporin A (CyA). A 53-year-old-man was referred to our hospital for further evaluation of pancytopenia in August 1998. Laboratory data at admission showed a mild anaemia (red blood cell count 2·58 × 1012/l) with a decreased white blood cell (WBC) count (1·2 × 109/l, myelocytes 1%, bands 6%, segmented 49%, lymphocytes 22%, monocytes 13%, eosinophils 1%, basophils 1%) and platelet count (58 × 109/l), and elevated serum lactate dehydrogenase (691 IU/l). A nucleated cell count of the bone marrow aspirate was 405 × 109/l, with 24·2% erythroblasts, 1·0% myeloblasts, 1·7% promyelocytes, 10·2% myelocytes, 4·3% metamyelocytes, 22·5% stabs, 7·5% segmented, 2·8% eosinophils, 0·2% basophils, 2·0% monocytes, 25·2% lymphocytes, 0·5% plasma cells and 0·2% megakaryocytes. The bone marrow also showed multiple dysplastic changes, including defective granulation of granulocyte precursors, multinucleation of erythroblasts and micromegakaryocytes. The karyotype was shown to be 45XY, −7 in all cells examined (20/20). Upper and lower gastrointestinal endoscopies were normal. Abdominal computerized tomography showed no splenomegaly. The above findings indicated that this patient had MDS(RA). The search for a human leucocyte antigen (HLA)-identical donor among his relatives was unsuccessful. CyA administration (6 mg/kg) resulted in increased WBC and platelet counts and, 2 months after initiation of therapy, the Hb concentration also increased. In May 2001, the platelet numbers had increased further and, in September, the WBC count also increased. Concomitantly, the proportion of monosomy 7-positive cells in the bone marrow gradually decreased. In August 2002, the proportion of MDS clone cells had decreased to 50% and normal clone cells, which were not detected at the initial diagnosis, appeared to comprise 50% of the total (Table I). Several patients with MDS have been known to respond to immunosuppressive therapy, such as CyA or antithymocyte globulin, and show haematological improvement (Biesma et al, 1997; Molldrem et al, 1997; Jonasova et al, 1998). In these cases, the patients' lymphocytes were suspected of suppressing MDS cell differentiation by way of cell-mediated or antibody-mediated immunity (Tichelli et al, 1988; Sugawara et al, 1992; Molldrem et al, 1998). In the present patient, an increase in cell number was also seen within 2 months after the administration of CyA. A possible explanation is that CyA mediated the suppression of the MDS clones by the patient's lymphocytes. An increased number of normal cell clones after long-term CyA administration was found in this patient, and no similar patients have been reported in the literature. The MDS clone may suppress primitive, differentiated normal stem cells. The relief of this suppression by CyA may induce a gradual recovery of normal clones. The follow-up period in our patient was 48 months, and there are no other reported patients with such a long follow-up period. The fact that there are no other reports of recovery of normal clones may be explained by the lack of such long-term follow-up data. From our experience with this patient, we propose that the recovery of normal clones may be achievable for MDS patients through long-term immunosuppressive therapy.
Background Endotoxin plays an important role in the progression of alcoholic liver injury. However, the role of endotoxin in acute activation of NF‐κB by ethanol remains unclear. Methods In primary rat hepatocyte cultures treated with ethanol and/or endotoxin, the DNA‐binding activity of NF‐κB in the nuclear extract was estimated by electrophoretic mobility shift assay. After pretreatment of a CYP2E1 inhibitor, 4‐methyl pyrazole or diallyl sulfide, NF‐κB activity was also measured in the same manner. Results Ethanol or endotoxin caused activation of NF‐κB in primary rat hepatocytes. Taking 50 mM of ethanol and endotoxin together raised the rapid increase in NF‐κB activation, but both 100 mM of ethanol and endotoxin treatment reduced the increase. Addition of diallyl sulfide decreased the activity at rapid phase but increased it after 60 min, whereas addition of 4‐methyl pyrazole caused no change of the activity at rapid phase but raised it after 60 min. Pretreatment with both endotoxin and a CYP2E1 inhibitor raised the activation of NF‐κB constantly after ethanol addition. These findings suggest that endotoxin plays a critical role in the metabolism‐independent activation of NF‐κB by ethanol. Conclusions Endotoxin raised metabolism‐independent activation of NF‐κB by high ethanol in rat hepatocytes.
Three growth factors (acidic, neutral and basic) were partially purified from platelet lysate by DE 52 cellulose chromatography. The basic factor was proved to be identical to PDGF hitherto reported. The growth promoting activity of these three factors for variouse cell lines was studied in vitro.Basic factor (PDGF) promoted growth of fibroblast (Swiss 3T3, SV 3T3) as has been described previouly, but had relatively less activity of growth promotion to malignant tumor cell lines (K562, HeLa and RPMI 4788).On contrast, acidic factor strongly stimulated the proliferation of tumor cells and, to less extent, of fibroblasts.Malignant cells (K562) were synchronized to pre S phase by addition of excess of thymidine and hydroxyurea, and thus synchronized cells were also proved to be more sensitive to acidic factor than to PDGF, indicating that the sensitivity is not related to cell cycle.
An intraductal oncocytic papillary neoplasm is a rare pancreatic tumor which was first described by Adsay et al. in 1996. It has been defined as a new subgroup of IPMN.We report the case of a 76-year-old woman who presented with nausea. Imaging studies revealed a cystic mass in the body of the pancreas. She underwent a successful distal pancreatectomy and splenectomy, and has subsequently remained well. Microscopically, the cyst was lined by columnar epithelium similar to pancreatic duct epithelium, and the nodular projection consisted of arborizing papillary structures, lined by plump cells with abundant eosinophilic cytoplasm. These eosinophilic cells were immunohistochemically positively stained with anti-mitochondrial antibody. The cellular atypism was mild and the proliferating index was low, compatible with adenoma of an intraductal oncocytic papillary neoplasm. Although no ovarian type stroma was identified, in our case, no communication to main pancreatic duct (located in the pancreatic body) and rapid growth by intracystic hemorrhage were clinical characteristics of a mucinous cystic neoplasm, but not IPMN.With only 17 cases reported to date, the clinical and pathological details of an intraductal oncocytic papillary neoplasm are still unclear. We herein add one case with different characteristics from those of the past reports. To our knowledge, this is the first case report of an intraductal oncocytic papillary neoplasm with the clinical characteristics of a mucinous cystic neoplasm.
