Mika Sakaguchi

Possible Effects of Hepatocyte Growth Factor for the Prevention of Peritoneal Fibrosis

Objective: Some patients who had carried out long-term continuous ambulatory peritoneal dialysis discontinued the treatment because of progressive peritoneal fibrosis. It has been previously reported that transforming growth factor-β1 (TGF-β1) is one of the factors that induces peritoneal fibrosis. Also, hepatocyte growth factor (HGF) plays a role in the prevention of fibrosis and in inhibiting TGF-β1 production. In this study, we examined the effects of HGF on peritoneal fibrosis by TGF-β1 induced by high concentrations of D-glucose. Design: We transfected a full-length human HGF cDNA in an expression vector into human peritoneal mesothelial cells (HPMCs) using the calcium phosphate method. Transfected HPMCs were cultured with high concentrations of D-glucose solution and co-cultured with fibroblasts using a transwell system. Cell proliferation was determined using the Tetra Color One method. TGF-β1 and HGF protein were measured by enzyme-linked immunosorbent assay. Results: In addition to recombinant HGF, the growth inhibition of HPMCs by high concentration D-glucose or TGF-β1 was significant. By transfecting HGF cDNA into HPMCs, growth inhibition by high concentration D-glucose was completely restored. Furthermore, the production of TGF-β1 was also significantly decreased. Conclusion: These results suggested that exogenous HGF could possibly prevent peritoneal fibrosis.

Anti-Glomerular Basement Membrane Nephritis after Extracorporeal Shock Wave Lithotripsy

Rapidly progressive glomerulonephritis was observed in a 37-year-old woman following the administration of extracorporeal shock wave lithotripsy (ESWL) for a single stone in her right kidney. The renal biopsy specimen showed diffuse cellular crescents in all glomeruli, with linear deposits of immunoglobulin G and complement component C3 along the glomerular basement membrane (GBM). Circulating anti-GBM antibodies were detected by enzyme-linked immunosorbent assay. Thus, the patient was diagnosed with anti-GBM nephritis. It is suggested that ESWL produced an alteration in the GBM leading to the production of anti-GBM antibodies.

Possible involvement of soluble erythropoietin receptor in resistance to erythropoietin in patients with renal anemia.

Accessible online at: www.karger.com/journals/ajn Dear Sir, Recombinant human erythropoietin (rHuEpo) is effective in treating anemia associated with chronic renal failure (CRF). However, patients with CRF have sometimes developed a resistance to rEpo. This resistance can be due to iron or folate deficiency, aluminum toxicity, hyperparathyroidism, or autoantibodies for rHuEpo [1]. In this study, we focused on soluble erythropoietin receptor (sEpoR) [2], which can bind to rEpo. To prove the possibility that the sweeping of rEpo by sEpoR results in resistance to rHuEpo, we performed a bioassay using Epo-dependent cell line UT-7/Epo [3]. The growth of UT-7/Epo is not known to be inhibited by any cytokine except sEpoR. Recombinant sEpoR can reduce the proliferation of UT-7/Epo induced by rHu/Epo in a dose-dependent manner. Furthermore, the binding of 125I-labeled rEpo on UT-7/Epo has been seen to be significantly inhibited by recombinant sEpoR. We considered that this cell line could be a useful tool in a bioassay to detect the inhibitory factor(s) against Epo. We selected sera from the two groups of patients with renal anemia associated with CRF receiving hemodialysis 3 times a week, one is patient group with resistance to rHuEpo and the other patient group sensitive to rEpo. The definition of the rHuEpo resistance was described as hemoglobin rise of 1 g/dl/month despite a rHuEpo dose of 1200 U/ kg/week. Furthermore, concerning the clinical characteristics of the rHuPo-sensitive and -resistant groups regarding factors (infection, hyperparathyroid bone disease, aluminum accumulation, vitamin B12 and/ or folate deficiency, hemolysis, bone marrow dysfunction malnutrition and inadequate hemodialysis) known to create Epo resistance, no significant differences were observed between the two groups. Serum was collected the day before regular hemodialysis. Interestingly, the proliferation of UT-7/ Epo determined with [3H]thymidine incorporation was reduced significantly by the addition of sera from Epo-resistant patients, but not by the addition of sera from the Eposensitive group. These results indicate that sEpoR in serum plays an important role in the signal transduction via EpoR on erythroid progenitor in CRF patients. References

Establishment of a Myeloid Cell Line, YM711, Characterized by Retinoid Resistance

A myeloid cell line (YM711) was established by transfecting exogenous PML/RARα cDNA into peripheral blood stem cells. The cells were positive for CD33, CD34, CD38, CD13, CD14, and CD11b, Cytochemical examination revealed YM711 cells to be positive for peroxidase, α-naphtyl butyrate esterase, and acid phosphatase as well. Karyotypic analysis showed them to be nearly tetraploid (92 XXYY). Reverse-transcription polymerase chain reaction showed that, although PML/RARα mRNA was detected in YM711, these cells could not be differentiated by all-trans retinoic acid (ATRA). We therefore designated the YM711 cell line as being ATRA resistant. Because YM711 expressed multi drug resistance 1 (MDR-1) mRNA and p-glycoprotein cell surface protein, we assessed whether verapamil and ATRA would induce the differentiation of YM711 cells; they did not. An increased expression of cellular retinoic acid-binding protein (CRABP)-II was also detected on YM711 cells compared with that of HL-60. These results suggest that high level of expression of CRABP-II may contribute to be the mechanism of ATRA resistance. This cell line may be useful in evaluating the mechanism of resistance to retinoid.

Transient eosinophilia by HIV infection.

Abstract We describe a case of early human immunodeficiency virus infection characterized by transient eosinophilia without an elevated immunoglobulin E concentration, allergic symptoms, or atopic dermatitis. Possible mechanisms of the eosinophilia are discussed.

A case of hypoplastic chronic myelogenous leukemia initiating with pancytopenia

Chronic myelogenous leukemia (CML) is the clonal expansion of hematopoietic progenitor cells and is characterized clinically by myeloid hyperplasia, leukocytosis with basophilia, and giant splenomegaly. The initial chronic phase of expanded clonal myelopoiesis lasts several years, but commonly evolves slowly into the accelerated phase, finally progressing to blast crisis. Here we describe a CML case that initiated with pancytopenia and had an unusual clinical course. A previously healthy, 52-year-old woman was admitted to the hospital because of persistent fever in September 2000. Patient data are shown in Table 1. Severe pancytopenia was diagnosed and was managed mainly with red blood cell and platelet transfusion. Two weeks later, the patient was referred to our hospital. On admission, she was afebrile and had mild hepatosplenomegaly. She had no previous history of exposure to myelotoxic agents. Blood test results showed normal values for electrolytes and liver and renal function. Results of tests for hepatitis B virus, hepatitis C virus, parvovirus B19, and human immunodeficiency virus were negative. Multiple blood cultures were sterile. Results of tests for anti-DNA and anti-nuclear antibodies were negative. Although pancytopenia was improving, the bone marrow showed hypoplasia with no blasts or fibrosis, and cytogenetic analysis showed the Philadelphia chromosome (Ph1), t(9;22) (q34;q11), in 7 (35%) of 20 metaphases and major breakpoint cluster region (M-bcr) chimeric messenger RNA. Follow-up of the patient had not included any medication or transfusion. On the 22nd hospital day, the appearance of Ph1 had increased to 18 (90%) of 20 metaphases without blasts. A Case of Hypoplastic Chronic Myelogenous Leukemia Initiating With Pancytopenia

Exogenous PML/RARα Fusion Gene Responds to All-trans Retinoic Acid Results in Differentiation of the Human B Cell Line.

The interaction of an exogenous PML/RARα fusion gene, associated with acute promyelocytic leukemia, with all-trans retinoic acid (ATRA) was examined in B-lymphoid cell lines. RPMI8866 cells were transfected with PML/RARα cDNA in the expression vector pGD and two stable transformants (RPMI8866Y-4 and RPMI8866Y-17) were established by selection with G418. ATRA inhibited the growth of those stable transformants, as assessed by [3H]-thymidine incorporation, but had no effect on the growth of control cells stably transformed with neomycin resistant gene alone. ATRA also increased expression of CD38 and immunoglobulin production in RPMI8866Y-4 cells but not in control cells. When these results are taken together, it can be observed that the exogenous PML/RARα fusion gene responds to ATRA, which results in cell differentiation of the human B cell line.

A Case of Minimally Differentiated Acute Leukemia (AML—M0) Complicated by Ventricle Thrombosis During Remission-induction

Sudden chest pain, dyspnea, and tachypnea occurred in a 21-year-old female who was undergoing induction chemotherapy under a diagnosis of minimally differentiated acute leukemia (M0). The arterial blood gas (ABG) tensions were decreased (PO2 71.6 mm Hg, PCO2 23.7 mm Hg), and an electrocardiogram showed a right-bundle branch block. Coagulation abnormalities (PT 73.1%, APTT 39.4 s, FDP 235mg/dl) were observed 72 h before onset. Echocardiography revealed a large thrombus in a right ventricle. A diagnosis of pulmonary thromboembolism (PTE) was made, and a tissue-type plasminogen activator (monteplase) was administered under percutaneous cardiopulmonary support (PCPS). The complete lysis of thrombus was confirmed by an echocardiogram 8 h later. Symptoms and ABG data were also improved. PTE in adult AML cases is rare, but should be considered as one of the life-threatening complications in AML patients under chemotherapy who develop respiratory difficulties. We suggest a careful monitoring of coagulation abnormalities for the prediction of PTE during chemotherapy for AML, and the use of tissue-type plasminogen activator (t-PA), monteplase, for the treatment of PTE in these cases.