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Biomedical subjects

A Wake

Publications and source records attributed to A Wake.

At least 37 records · Page 2Linked to original sources

[Allogeneic peripheral blood stem cell transplantation for multiple myeloma].

We report here with a 46-year-old man with refractory multiple myeloma receiving allogeneic peripheral blood stem cell transplantation from his HLA-matched brother. The preparative regimen consisted of TBI (12Gy), VP16 (15 mg/kg) and cyclophosphamide (120 mg/kg). GVHD prophylaxis consisted of cyclosporin A and short course of methotrexate. The donor received G-CSF at 10 micrograms/kg/day for 5 consecutive days and underwent leukapheresis on days 5 and 6. The neutrophil recovery to 500/microliter and platelet recovery to 20,000/microliter were day 12 and day 15, respectively. The patient is currently well with no GVHD or graft failure and a complete donor's chimerism.

Hematopoietic Stem Cell Transplantation↗

Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin triggering and its mediated adhesion to endothelial cells.

Leukocyte migration from circulation into tissue depends on leukocyte integrin-mediated adhesion to endothelium, but integrins cannot function until activated. However, it remains to be understood how tumor cells adhere to endothelium and infiltrate into underlying tissue. We studied mechanisms of extravasation of leukemic cells using adult T cell leukemia (ATL) cells and report the following novel features of cell surface heparan sulfate proteoglycan on ATL cells in ATL cell adhesion to endothelium: ATL cells adhere to endothelial cells through already activated integrins without exogenous stimulation; different from any other hematopoietic cells, ATL cells express a characteristic heparan sulfate capable of immobilizing heparin-binding chemokine macrophage inflammatory protein (MIP)-1 beta, a potent T cell integrin trigger, produced by the cells themselves; competitive interruption of endogenous heparan sulfate proteoglycan synthesis reduces cell surface MIP-1 beta and prevents ATL cells from integrin-mediated adhesion to endothelial cells or intercellular adhesion molecule-1 triggered through G-protein. We propose that leukemic cells adhere to endothelial cells through the adhesion cascade, similar to normal leukocyte, and that the cell surface heparan sulfate, particularly on ATL cells, is pivotally involved in chemokine-dependent autocrine stimulation of integrin triggering by immobilizing the chemokine on them.

CD4-Positive T-Lymphocytes↗

[A clinical evaluation of fluconazole in deep seated fungal infections associated with hematological disorders].

The effectiveness of fluconazole on deep seated fungal infections associated with hematological disorders was evaluated in a multicenter clinical study. The underlying diseases included acute myeloblastic leukemia, acute lymphocytic leukemia, malignant lymphoma, adult T cell leukemia, multiple myeloma and others. Fluconazole (FLCZ) was administrated 100-400 mg/day intravenously or orally to 79 patients with systemic fungal infections complicated with hematological disorders and it was possible to evaluate clinical efficacies in 60 patients. 27 patients were diagnosed as having determinate systemic fungal infections and 33 patients suspected fungal infections. The clinical efficacies were 81.5% (22/27) in patients with diagnosed fungal infections and 57.6% (19/33) in patients with suspected fungal infections. The overall clinical efficacy was 68.3% (41/60). No side effects such as gastrointestinal symptoms, vascular pain and renal dysfunction were observed in this study. As for abnormal laboratory test, transient increases in GOT, GPT, Al-P, LDH, serum Na, Cl and decrease in serum K were observed in 9 patients (11.4%). These results indicated that FLCZ has a high therapeutic efficacy on deep seated fungal infections in patients with hematological disorders.

Aged↗

Calcium-dependent homotypic adhesion through leukocyte function-associated antigen-1/intracellular adhesion molecule-1 induces interleukin-1 and parathyroid hormone-related protein production on adult T-cell leukemia cells in vitro.

Adult T-cell leukemia (ATL) is a human T-cell leukemia virus type I (HTLV-I)-infected lymphoproliferative disorder that shows a characteristic nodular infiltration into various tissues, hypercalcemia, and subsequent rapid increase of peripheral ATL cell number. ATL cells and HTLV-I-infected T-cell lines also make cluster formation rapidly after the non-stimulative culture. However, the mechanism of the acute proliferation of ATL cells remains to be understood. We report the following novel features of homotypic adhesion via leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1 (ICAM-1) pathway that suggest a role for it in cytokine production and rapid proliferation of ATL cells: (1) ATL cells show clustering in a calcium dependent manner, even at the higher concentration; (2) ATL cells consistently and highly express ICAM-1 and an active form of LFA-1, whereas integrin expression, except for LFA-1, is rather lower compared with that of normal CD4+ T cells; (3) ATL cells make conjugate formation within 6 minutes and clustering within 48 hours, both of which are inhibited by the addition of monoclonal antibodies (MoAbs) against LFA-1 and ICAM-1; (4) spontaneous mRNA transcription and protein secretion of both interleukin-1 and parathyroid hormone-related protein are observed consistently in ATL cells, and these productions are inhibited by anti-LFA-1 and anti-ICAM-1 MoAbs but are markedly increased by cross-linking of LFA-1 and ICAM-1 by the immobilized specific MoAbs; and (5) proliferative responses of ATL cells are also inhibited by these MoAbs. We propose that ATL cells proliferate in sequential events: the homotypic and calcium-dependent adhesion through LFA-1/ICAM-1, the signal transduction through these adhesion molecules, the production of cytokines, and the proliferation.

Bone Resorption↗

Autopsy findings of Addison's disease caused by systemic cytomegalovirus infection in a patient with acquired immunodeficiency syndrome.

We previously reported a case of Addison's disease associated with acquired immunodeficiency syndrome (AIDS) (Endocr J, 41:13, 1994). A 46-year-old man with hemophilia B and AIDS was diagnosed as Addison's disease. The positive cytomegalovirus (CMV) antigen in urine suggested that CMV adrenalitis may have caused the adrenal insufficiency. Despite treatment with ganciclovir, the patient died one year later. Autopsy findings revealed that the typical inclusions of CMV were seen in the lung, adrenal glands (both cortex and medulla) and small intestine. Here, we describe the subsequent clinical course and postmortem findings of this case.

AIDS-Related Opportunistic Infections↗

Sjögren's syndrome terminating with multiple myeloma.

We describe a patient (49 years old, female) with a more than 7-year history of both Sjögren's syndrome (SjS) and benign monoclonal gammopathy (BMG) of IgG lambda who later developed multiple myeloma (MM). SjS is frequently complicated with malignant lymphoproliferative disorders, especially malignant lymphoma or Waldenström's macroglobulinemia. Association of SjS with MM seems to be extremely rare, although BMG has been observed frequently in SjS, and there are many reports concerning the association between rheumatoid arthritis and MM.

Antineoplastic Combined Chemotherapy Protocols↗

[Successful treatment of acute myelomonocytic leukemia developed from MDS with cytarabine ocfosfate (SPAC)].

A 65-year-old female with acute myelomonocytic leukemia (AMMoL) developed from myelodysplastic syndrome (MDS), successfully treated with cytarabine ocfosfate (SPAC) is reported. Ubenimex, calcitriol and corticosteroid had a minor effect on her MDS. Since she had severe anemia and congestive heart failure on developing leukemia, she was treated with oral administration of SPAC, a cytidine deaminase resistant derivative of Ara-C. After the second course of SPAC (200 mg/day, for 14-28 days), marked erythroid bursts were found and she entered complete remission. The samplings of SPAC and its metabolites of SPAC were investigated in 2 cases including this case, but there seemed to be no relation between their content and effects. In AML patients, especially in cases developed from MDS, SPAC might be useful because it can be given orally even in an outpatient.

Aged↗

Adrenal insufficiency in a patient with acquired immunodeficiency syndrome.

A 46-year-old man was admitted because of hypotension and consciousness disturbance. He was a patient with hemophilia B, and diagnosed as having an AIDS-related complex 2 years prior to admission. On admission he had severe hyponatremia. Hormonal studies revealed that he had Addison's disease. Serum cytomegalovirus (CMV) antibody titers were high, and a CMV antigen was detected in his urine, which suggested CMV adrenalitis caused by an active CMV infection. After the administration of hydrocortisone and ganciclovir, his general clinical condition and biochemical test results were back to normal. However, the adrenal dysfunction was irreversible, despite the treatment with ganciclovir. With an increase in the number of AIDS patients, we have to consider adrenal insufficiency due to a CMV infection in patients with AIDS.

AIDS-Related Complex↗

Enhancing effect of interleukin-2 on production of parathyroid hormone-related protein by adult T-cell leukemia cells.

Leukemic cells from patients with adult T-cell leukemia (ATL) can produce a calcium-regulating protein, parathyroid hormone-related protein (PTHrP). Moreover, it has been reported that ATL cells produce some cytokines besides PTHrP and that these cells respond to the T-cell growth factors, interleukin-2 (IL-2) and interleukin-4 (IL-4). To elucidate whether PTHrP produced by ATL cells is regulated by IL-2 or IL-4, we investigated the in vitro effects of IL-2 and IL-4 on the release of PTHrP. IL-2 increased the release of PTHrP into the conditioned medium from leukemic cells in some, but not all, ATL patients; however, IL-4 did not affect the PTHrP release. PTHrP messenger RNA (mRNA) levels were increased in ATL cells cultured in the presence of IL-2. These data suggest that IL-2 plays a role in the regulation of hypercalcemia by enhancing the production of PTHrP in ATL patients.

Aged↗

Angiotropic lymphoma of paranasal sinuses with initial symptoms of oculomotor nerve palsy.

A 78-year-old female was found to have angiotropic lymphoma, a rare fatal disease, with initial symptoms of oculomotor nerve palsy. A biopsy of the paranasal sinus mucosa showed that the small vessels were occupied by large mononuclear cells which upon immunohistochemical examination tested positive for pre B-cell markers. She felt a gradually increasing pain in her left thigh. Magnetic resonance imaging suggested the involvement of neoplastic cells in the left femoral bone marrow. Following chemotherapy treatment remission was achieved. Early diagnosis of angiotropic lymphoma appears very significant, as this disorder could be well controlled by systemic chemotherapy.

Aged↗

[Successful treatment by ranimustine (MCNU) of a patient with B-cell prolymphocytic leukemia (B-PLL)].

A 66-year-old female was admitted to our hospital because of leukocytosis, anemia and splenomegaly in August 1989. The white cell count was 3.49 x 10(10)/l with 88.5% of the leukemic cells which were morphologically similar to prolymphocytes. On flowcytometric analysis, the leukemic cells were found to be positive for B-cell markers such as CD19, CD20, FMC7, Sm-IgM and Sm-IgD and negative for CD5 and CD25. The chromosome analysis demonstrated hyperdiploidy of 48, XX, (+3, +18). She was diagnosed as having B-cell prolymphocytic leukemia, and treated with alpha-interferon and VP therapy with progression. Complete remission was achieved after three courses of ranimustine (MCNU) administration. She relapsed after about one year without therapy, but when MCNU was administered again, a secondary remission followed. The prolymphocytes during the relapse stage also had the phenotypes of CD11b, CD13 and CD25. This case is considered to be rare with respect to both complete remission by MCNU and the immunophenotypic change of leukemic cells during the relapse period.

Aged↗

[Detection of granulocyte-macrophage colony-stimulating factor activity in the supernatant of the cultured leukemic cells of adult T-cell leukemia with eosinophilia].

An adult T-cell leukemia (ATL) accompanied with eosinophilia is described. A 75-year-old female was admitted to our hospital because of lymphadenopathy. Her leukocyte count was 73,300/microliters, with 35.5% abnormal lymphocytes and 19% eosinophils. A majority of lymphocytes expressed CD4+CD8-. Acute ATL was diagnosed, since anti-HTLV-1 antibody in her serum and monoclonal integration of HTLV-1 proviral DNA in her peripheral mononuclear cells were detected. She was treated with THP-adriamycin, cyclophosphamide (CPA), and vincristine (VCR). Abnormal lymphocyte and eosinophil counts decreased and there was improvement in the lymphadenopathy. However she then complained of lymphadenopathy again. Her leukocyte count rose to 76,300/microliters, with 89% abnormal lymphocytes. Combination therapy with CPA, VCR, and doxorubicin was started and there was a temporal regression in lymphadenopathy, but her lymphadenopathy recurred and she died. The activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) was detected in the supernatant of the cultured ATL cells, although interleukin-3, interleukin-5, and GM-CSF activities were not detected in her serum. It seems likely that the secretion of GM-CSF by ATL cells are responsible for the eosinophilia.

Aged↗

[Adult T cell leukemia with cytomegalovirus retinitis].

A 49-year old female in the course of chemotherapy for adult T-cell leukemia (ATL) noticed blurred vision and visual field defect in her right eye on February 26, 1991. Ophthalmoscopic findings showed exudative necrotizing retinitis with white exudative patches and scattered retinal hemorrhages in both eyes. CMV was isolated from the urine by the shell vial cell culture assay. Anti-viral therapy was commenced using ganciclovir and gamma-globulin, which are rich in anti-CMV antibodies. The exudative lesions were absorbed gradually. The ocular signs and symptoms agreed with the patient's systemic immunosuppressed T cell function state. CMV retinitis should be considered in the differential diagnosis of retinitis in immunocompromised patients. CMV retinitis will certainly be found more frequently in accordance with the increasing number of immunocompromised hosts who have received immunosuppressive therapy or transplantation.

Cytomegalovirus↗

[Urinary excretion of parathyroid hormone-related protein in patients with adult T-cell leukemia and other hematologic disorders].

Urinary excretion of parathyroid hormone-related protein (PTH-rP) was measured by radioimmunoassay in 25 patients with adult T-cell leukemia (ATL), in 68 patients with other hematologic disorders and in 13 asymptomatic individuals seropositive for human T-cell leukemia virus type I (HTLV-I). The mean levels of urinary PTH-rP in ATL patients with hypercalcemia (11.01 micrograms/g.Cr) were higher than in ATL patients with normocalcemia (5.16 micrograms/g.Cr). The mean levels in patients with acute type (8.84 micrograms/g.Cr), lymphoma type (4.18 micrograms/g.Cr) and crisis ATL (18.20 micrograms/g.Cr) were significantly higher than in urine of healthy controls. However, all asymptomatic carriers of HTLV-I and patients with chronic and smoldering ATL had normal urinary PTH-rP levels. In 7 patients with acute myelogenous leukemia, 1 patient with blastic crisis of chronic myelogenous leukemia and 3 patients with malignant lymphoma, the urinary levels of PTH-rP were above the normal range. Urinary levels of PTH-rP of the ATL patients with hypercalcemia correlated with the serum calcium levels. Urinary levels of PTH-rP of the all ATL correlated with serum lactic dehydrogenase level. These findings suggest that the measurement of urinary levels of PTH-rP is useful for evaluation of ATL and that some tumor cells of other hematologic diseases may produce PTH-rP.

Hematologic Diseases↗