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Biomedical subjects

Y Shimamoto

Publications and source records attributed to Y Shimamoto.

At least 19 recordsLinked to original sources

Adult T-cell leukemia/lymphoma with two distinct clones in the peripheral blood and lymph node.

A case of adult T-cell leukemia/lymphoma (ATL) with two different clones in the peripheral blood and lymph nodes is reported here. When cellular DNA from the lymph node was digested with EcoRI, one band larger than 9 Kb was detected. Digestion of the cellular DNA with PstI resulted in one clear band in addition to three internal fragments. In contrast, when cellular DNA from malignant peripheral blood lymphocytes (PBL) was digested with the same endonucleases, distinct bands at positions different from those observed in the lymph node were detected, indicating two separate malignant clones in the patient. Monoclonality of the tumor cells was shown by T-cell receptor-beta (TCR-beta) gene rearrangement in both PBL and lymph node. Furthermore, there was a difference in the surface phenotype between tumor cells taken from peripheral blood (CD4+, CD8-) and lymph node (CD4+, CD8+). These findings suggest the presence of two different ATL clones in PBL and lymph node in a single patient simultaneously, which is distinguishable by the integration pattern of human T-cell leukemia virus type I (HTLV-I) proviral DNA.

Aged

Intracellular multiplication of Legionella pneumophila in HL-60 cells functionally differentiated in response to 22-oxacalcitriol.

The agent 1,25-dihydroxyvitamin D3 (D3) induces the differentiation of HL-60 human leukemia cells into functional monocyte-like cells that can support the intracellular multiplication of Legionella pneumophila. 22-Oxacalcitriol (OCT), a synthetic analogue of D3, exhibits greater differentiation-inducing activity than D3 in WEHI-3 mouse leukemia cells and has been suggested to be clinically more useful because of its lower hypercalcemic activity. The abilities of OCT and D3 to induce the functional differentiation of human leukemia HL-60 cells have now been investigated. OCT induced the differentiation of HL-60 cells into monocyte-like cells to a similar extent as D3. Thus, both OCT and D3 increased (1) the surface expression of CD11b, CD11c, CD14, and CD35; (2) nonspecific esterase staining; and (3) phagocytic activity toward fluorescent beads. HL-60 cells differentiated in response to OCT also supported the intracellular multiplication of L. pneumophila. Activation of both OCT- and D3-treated HL-60 cells with human recombinant interferon-gamma (IFN-gamma) for 24 h before infection markedly inhibited L. pneumophila multiplication. IFN-gamma activation enhanced superoxide anion generation by D3-treated HL-60 cells but not by OCT-treated HL-60 cells, suggesting that the inhibition of L. pneumophila multiplication in IFN-gamma-activated cells is independent of superoxide generation. Finally, D3, but not OCT, markedly stimulated the formation of osteoclast-like multinucleated cells from mouse bone marrow cells, consistent with the lower hypercalcemic activity of OCT.

Animals

Mantle cell lymphoma with the features of mucosa-associated lymphoid tissue (MALT) lymphoma in an HTLV-I-seropositive patient.

A case of small lymphocytic B-cell lymphoma with seropositivity for human T-cell leukemia virus type I (HTLV-I), whose clinical features were closely related to those of mucosa-associated lymphoid tissue (MALT) lymphoma, is presented. The neoplastic cells of the lymph node were immunologically positive for CD5, in addition to several B-cell markers, but negative for CD10, and cytogenetically carried a t(11;14)(q13;q32). These findings were fully consistent with so-called mantle cell lymphoma (MCL). In addition to the lymph nodes and bone marrow, multiple extranodal sites including lacrimal and salivary glands, lung and stomach (where MALT is present) were occupied by lymphoma cells. These extranodal lesions were immunologically identical to the lymph nodes (CD5(+), CD10(-)), but histologically showed lymphoepithelial lesions (LEL) characteristic of MALT lymphoma. These findings suggest a possible relationship between MCL and MALT lymphoma, and the neoplastic cells are thought to originate from the CD5-positive B cells, which are present near the areas across the mantle and marginal zones. Furthermore, HTLV-I-infection, which appears to create an immunodeficient state or modulate the B-cell response, is thought to play a role in B-cell lymphomagenesis.

Antigens, CD

Risk factors for the development of acute disseminated intravascular coagulation in patients with systemic lupus erythematosus.

Since acute disseminated intravascular coagulation (DIC) often contributes to a fatal outcome in patients with systemic lupus erythematosus (SLE), prediction of its development is important to prevent the occurrence of such an event. To analyze the risk factor(s) contributing to the development of acute DIC in SLE, we carried out a retrospective study of a series of 129 SLE patients, eight of whom developed DIC during the course of this disease, to assess which of the easily assessable parameters, present at the time of first medical examination, were of predictive significance. The important individual variables, determined by univariate analysis, were male sex, leukopenia, and infection. These factors were placed in a multivariate logistic regression model, and only one factor, infection at first medical examination, was found to have predictive significance for the development of acute DIC in SLE patients. The prevention and control of infection in SLE patients might have implications for preventing the development of acute DIC.

Acute Disease

Morphology of defensin-treated Staphylococcus aureus.

Defensins are a family of broad-spectrum antimicrobial peptides found abundantly in the cytoplasmic granules of mammalian neutrophils and Paneth cells of the small intestine. Defensins are known to form ion channels on the membranes of target cells. These channel formations and the cytotoxicity of defensins are intimately linked. We showed the morphological effects of defensins on the cytoplasmic membranes of Staphylococcus aureus by transmission electron microscopy. S. aureus exposed to defensins developed characteristic mesosome-like structures but did not show remarkable changes in cell walls. Defensins induced such structural changes not only at high concentration but also at low concentrations that were not bactericidal. We also showed that increasing the concentration of NaCl in the reaction mixture completely inhibited the occurrence of membranous changes of target cells exposed to defensins. These findings are, to our knowledge, the first report of morphological changes in gram-positive bacteria treated with defensins. Our results indicate that the first effect of defensins in S. aureus is to damage cytoplasmic membranes directly; they also support previous reports that the cell membrane is the principal target of defensins.

Animals

Detection of minimal residual disease in a patient with acute myeloid leukemia and t(6;9) at the time of peripheral blood stem cell transplantation.

A 16-year-old Japanese woman with acute myelogenous leukemia (AML) and t(6;9) received peripheral blood stem cell transplantation (PBSCT). Although chromosomal studies just prior to and following PBSCT showed a normal karyotype, reverse transcription-polymerase chain reaction (RT-PCR) detected the mRNA derived from the dek-can fusion gene of t(6;9) following PBSCT and in the harvested stem cells. Following PBSCT, she relapsed. To our knowledge, this case is the first report from Japan in which minimal residual disease was detected with RT-PCR in AML with t(6;9). These methods should improve the use and outcome of PBSCT.

Adolescent

Ten-year survey of incidence of infection as a cause of death in hematologic malignancies: study of 90 autopsied cases.

We investigated 90 autopsied cases with hematologic malignancy, including malignant lymphoma (ML), acute leukemia (AL), and adult T-cell leukemia (ATL) peculiar to our district, during the 10-year period 1982-1991 to determine the change in incidence of infection as a cause of death. We divided the cases into two groups representing the first half decade (1982-1986) and the second half decade (1987-1991) and compared the findings made in the two groups. Although infection was the major cause of death in those autopsied cases, the incidence of fatal infections decreased during the latter period. The incidence of fatal bacterial infections decreased, while fungal infections showed a relative increase. Pneumocystis carinii pneumonia and cytomegalovirus (CMV) infection occurred more frequently in patients with ATL than in those with ML or AL. Combined infection by more than three pathogens was observed in 2 cases of ATL. Our study revealed the characteristics of ATL specific to our district, and indicated the need to apply new strategies to prevent and treat fungal and viral infections in patients with hematologic malignancies.

Acute Disease

Lisinopril improves aortic compliance and renal flow. Comparison with nifedipine.

We compared the systemic and regional hemodynamic effects of nifedipine and lisinopril in 26 elderly hypertensive patients with the use of the pulsed Doppler ultrasound technique. Nifedipine is a dihydropyridine calcium antagonist, and lisinopril is an angiotensin-converting enzyme inhibitor. The study had a single-blind crossover design: nifedipine and lisinopril were given for 8 weeks each after washout periods of 4 weeks. Both nifedipine and lisinopril significantly reduced mean arterial pressure to the same extent (P < .01); cardiac output remained unchanged in both nifedipine- and lisinopril-treated groups. Lisinopril increased renal flow significantly (P < .01), but nifedipine did not. Common carotid, vertebral, celiac, and superior mesenteric arterial and diaphragmatic and terminal aortic flows did not show a significant change with either nifedipine or lisinopril. The specific action of lisinopril on the thoracic aorta was a marked improvement of aortic compliance compared with nifedipine, which might be partly responsible for an increase in renal flow. Lisinopril may provide more desirable regional hemodynamic effects and additional benefits for elderly hypertensive patients.

Aged

IgD myeloma: clinical characteristics and a new staging system based on analysis of Japanese patients.

The aim of this review was to compare the clinical characteristics and prognostic factors of Japanese and Western IgD myeloma patients, and also to introduce our new staging system, based on the analysis of Japanese patients. We reviewed 165 Japanese with IgD myeloma reported since the first Japanese case report in 1967 and compared these patients with Western IgD myeloma patients reported in the literature. Parameters evaluated were recorded at diagnosis. The staging systems of Durie and Salmon and the British Medical Research Council (BMRC) were also applied to our series. Survival curves were calculated according to the method of Kaplan & Meier and generalized Wilcoxon test and log-rank test were used to assess differences in survival. Multivariate analysis was performed by the Cox proportional hazard model. We were able to confirm the similarity of clinical features in Japanese patients and those reported in Western countries. We did, however, find small differences in the incidence of lymphadenopathy, thrombocytopenia, and high serum levels of creatinine, and in the 5-year survival rates. Assessment of prognostic factors influencing survival was compared in Japanese and Western patients. A multiple regression model in our series showed that light chain subtype and leukocyte count had a strong predictive relationship for duration of survival. A new risk grouping using these two major factors was introduced since neither the common staging system of Durie & Salmon nor those of the BMRC predicted survival in these patients; to date, there are still no reports from Western countries in this regard.

Humans

Nilvadipine increases cerebral blood flow in elderly hypertensives: comparison with nifedipine.

We compared haemodynamic and humoral responses to nifedipine and nilvadipine in 25 elderly hypertensives. The study had a single-blind crossover design. Doppler flowmetry and laboratory examinations were performed before and after nifedipine and nilvadipine. Both nifedipine and nilvadipine significantly reduced mean arterial pressure to the same extent. Nilvadipine increased cardiac output, carotid flow and vertebral flow whereas nifedipine had no significant effect on either cardiac output or regional blood flows. Nilvadipine increased plasma atrial natriuretic peptide and decreased plasma noradrenaline. In the nilvadipine group, the relations between changes in these humoral parameters and those in cardiac output suggest that an elevation of pre-load may play a role in increasing cardiac output. The effects of nilvadipine on cerebral perfusion might provide additional benefits for the elderly hypertensives.

Aged

[Peripheral T-cell lymphoma with abundant ATL-like cells in the blood].

A 69-year-old woman was admitted to our hospital because of leucocytosis and systemic lymphadenopathy. On admission, white blood cell count was 163,000/microliters, most of which consisted of flower-like cells with convoluted nuclei in the peripheral blood. In the abnormal lymphocyte cells surface-marker test by flow cytometry showed that they expressed CD2, CD3, CD4, CD29, CD45RA, and CD38, but not CD8, CD16, and CD25. Serum anti-Human T-lymphotropic virus type-I (HTLV-I) antibody was negative in particle agglutination, enzyme-linked immunosorbent assay (ELISA) and western-blotting assay. HTLV-I proviral DNA in the abnormal lymphocyte cells was not detected by southern blotting hybridization technique. Moreover, HTLV-I provirus was not detected using a polymerase-chain-reaction (PCR). A monoclonal rearrangement of the TCR-beta chain gene was evident by using DNA probe in southern blot hybridization. Because of the rapid progress of the disease, chemotherapy was started immediately after admission. Though, this patient became refractory, and she died about 1 year after admission.

Aged

Clinical importance of extraordinary integration patterns of human T-cell lymphotropic virus type I proviral DNA in adult T-cell leukemia/lymphoma.

The proviral DNA of human T-cell lymphotrophic virus type I (HTLV-I) is known to be integrated monoclonally in the malignant cells of adult T-cell leukemia/lymphoma (ATL), which is a peripheral T-cell malignancy caused by this virus. We studied the relationship between the integration patterns of HTLV-I and clinical characteristics in 89 patients with ATL. The proviral DNA of HTLV-I was examined by the standard Southern blot analysis using the endonucleases EcoRI and Pst I. One clear band of greater than 9 kb was detected in most of the patients (83 case) when cellular DNA was digested with EcoRI. On the other hand, extraordinary integration patterns of HTLV-I proviral DNA were detected in 6 patients; 3 of them showed two bands, while the other 3 showed one band smaller than 9 kb. When cellular DNA was digested with PstI, the band patterns of these patients were quite different from those of typical patients. The patients with the extraordinary integration patterns had clinical characteristics dissimilar to those of the other 83 patients with the ordinary integration pattern. The patients with two bands by EcoRI digestion always had severe hypoxemia with extremely high levels of serum lactate dehydrogenase at first presentation and showed peculiar organ infiltrations, such as retina and muscle, which were less frequent in the other ordinary 83 patients. They all died within 8 months after the onset. In contrast, the patients with one smaller band by EcoRI digestion always had small and mature T lymphocytes with bilobulated nuclei without lymphadenopathy and showed a favorable clinical course, which was uncommon in the ordinary cases. They were alive 20 to 38 months after diagnosis. Rearranged bands of the T-cell receptor gene were detected in all patients with unusual integration. These findings indicate that the integration patterns of HTLV-I proviral DNA have a clinical implication and may be one of the explanations for heterogeneity in the behavior of this disease.

DNA, Viral

New cell line from hairy-cell leukaemia producing interleukin-6 after Epstein-Barr virus immortalization.

A hairy-cell leukaemia (HCL) cell line, HCL-O, was established from the peripheral blood of a 62-year-old Japanese patient with a unique variant of HCL strongly expressing CD21, the receptor for the Epstein-Barr virus (EBV). The HCL-O cells expressed antigens similar and dissimilar to those expressed with the original hairy cells. The HCL-O cells were more mature than the original cells in their degree of B-cell differentiation, as indicated by a decrease of CD19 and surface immunoglobulin (sIg) expression together with the appearance of CD38 and cytoplasmic Ig (cIg). In addition, the cells expressed CD11c recognized by Leu-M5, a monoclonal antibody usually positive for HCL. Their karyotype and Ig gene rearrangement pattern were identical to those of the original cells. The EBV genome was detected in the HCL-O cells but not in the original cells. The HCL-O cells spontaneously produced a large quantity of interleukin-6 (IL-6) in the conditioned medium, whereas IL-6 serum level was not so high. These findings indicate that the HCL-O cell line is derived from the leukaemic hairy cells and possibly, in vitro EBV infection took place easily in the original hairy cells through their CD21, resulting in subsequent immortalization. IL-6 production by HCL-O cells may be induced or enhanced by EBV, and the secreted IL-6 might play a role in their own growth or differentiation.

Cell Transformation, Viral

Prophylaxis of symptoms of hyperhistaminemia after the treatment of acute promyelocytic leukemia with all-trans retinoic acid.

A 61-year-old man with acute promyelocytic leukemia (APL) is described in whom some leukemic promyelocytes contained granules similar to those of basophils, and hyperhistaminemia developed after treatment with all-trans retinoic acid. The symptoms of hyperhistaminemia, mediated via H2 receptors, were prevented by the administration of an H2-blocker, famotidine, but wheezing due to bronchospasms, mediated via H1 receptors, developed and was improved by administration of chlorpheniramine. In APL, it is generally thought that the maturation of neutrophilic leukocytes is arrested at the level of abnormal promyelocytes. However, heterogeneity of leukemic promyelocytes has been described and in a few patients some leukemic promyelocytes have been known to show basophilic features. Marked basophilia and severe symptoms due to hyperhistaminemia have recently been reported after the treatment of APL with all-trans retinoic acid. Our case presented similar basophilic features, but indicated that the symptoms of hyperhistaminemia after administration of retinoic acid can be prevented with antihistaminic drugs and suggested that both H1- and H2-blockers should be administered to such APL patients with basophilia.

Basophils

Essential thrombocythemia terminating in acute leukemia with minimal myeloid differentiation--a brief review of recent literature.

Essential thrombocythemia (ET), one of the chronic myeloproliferative disorders, is a clonal disorder of multipotent stem cells. Although most patients with ET have a prolonged benign course, a minority of patients may develop a blastic crisis similar to chronic myelogenous leukemia (CML). A case of ET terminating in blastic crisis 8 years after the initial diagnosis is presented. The blast cells were cytochemically and immunophenotypically consistent with the acute myelogenous leukemia with minimal myeloid differentiation subtype of the FAB classification. From the review of the literature on blastic transformation of ET, acute leukemia with an M4 or M7 phenotype occurred more frequently. In addition, three valuable factors to predict the leukemic transformation of ET appear to be karyotypic abnormalities, such as involvement of chromosome 21, previous therapies with a mutagenic potential, and the capability of bone marrow cells to form in vitro spontaneous colonies as in CML.

Acute Disease