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Biomedical subjects

S Yorimitsu

Publications and source records attributed to S Yorimitsu.

At least 19 recordsLinked to original sources

[Apoptosis of peripheral leukocytes in patients with myelodysplastic syndromes].

Apoptosis of peripheral leukocytes in 9 patients with myelodysplastic syndromes (MDS) was examined in vitro, using peripheral blood that had been gently incubated at 37 degrees C for 5 hours. The MDS patients included 3 with refractory anemia, 2 with refractory anemia with ringed sideroblasts, and 4 with refractory anemia with excess blasts. Peripheral blood specimens were also obtained from a control group consisting of 10 patients with iron deficiency anemia (IDA), 10 with idiopathic thrombocytopenic purpura (ITP) and 10 healthy individuals. Apoptotic granulocytes (Apo-Gs) were identified by morphological changes, including nuclear fragmentation, and expressed as a percentage of every 300 granulocytes counted. Apo-Gs were counted 1, 2, 3, 4, and 5 hours after incubation. Although the percentage of apo-Gs climbed over time in the MDS patients, a small number of apo-Gs were also observed in the healthy individuals. In the MDS patients, the proportions of apo-Gs 5 hours after incubation (37 degrees C) were significantly higher than those in the IDA and ITP patients and healthy individuals (15.7 +/- 8.0% in MDS patients vs. 2.8 +/- 1.2% in IDA patients, 2.3 +/- 1.7% in ITP patients, and 0.7 +/- 0.6% in healthy individuals; p < 0.005). No significant differences were observed in the proportions of apo-lymphocytes. DNA fragments were observed in blood lymphocyte from an MDS patient examined. Negative correlations between the percentages of granulocytes and Apo-Gs tended to be observed in the MDS patients. These results suggest that a strong susceptibility to peripheral granulocyte apoptosis is one of possible causes of granulocytopenia in MDS patients.

Agranulocytosis

Establishment of a new myeloid cell line with i(17q) as the sole chromosomal anomaly from the bone marrow of a patient with myelodysplastic syndrome.

A new myeloid cell line, MTO-94, was established from the bone marrow of a patient with myelodysplastic syndrome (MDS). MTO-94 cells matured in culture medium without the addition of growth factors, and yielded neutrophils with pseudo-Pelger Huët anomaly or hypersegmentation until 6 months. Ten months after the start of cell cultivation, MTO-94 consisted of myeloblasts. Surface phenotypes were as follows: CD7 90.3%, CD13 99.6%, CD33 75.6%, HLA-DR 96.3% and CD34 0.9%. The karyotype was 46, XY i(17q). The proliferation of MTO-94 cells was enhanced by rhIL-3, G-CSF, rhGM-CSF and rhSCF but not by rhIL-6 and erythropoietin. MTO-94 cells with i(17q) might be useful in the study of biological aspects of not only MDS, but also hematological malignancies with i(17q) as the sole chromosomal anomaly.

Aged

Endoscopic injection sclerotherapy for esophageal variceal hemorrhage in a patient with idiopathic myelofibrosis.

A 74-year-old female with idiopathic myelofibrosis (IMF) was admitted to our hospital because of massive hematemesis and melena. Immediate upper gastrointestinal endoscopy revealed an intermittent spurting hemorrhage from extensive esophageal varices. Endoscopic injection sclerotherapy (EIS) was carried out and the bleeding ceased. After five courses of EIS, all the esophageal varices were eradicated. About 15 months later, the patient died, due to a cerebral hemorrhage, without further variceal bleeding. A postmortem examination was carried out and the portal hypertension was considered to be due not only to extramedullary hematopoiesis in the sinusoids, but also to increased splenic blood flow. We are confident that EIS is an effective therapeutic procedure for patients with IMF showing esophageal variceal hemorrhage. EIS should be the preferred choice of treatment for esophageal varices in patients with IMF, since it is less invasive than splenectomy.

Aged

[Unclassified chronic myeloproliferative disorder (Ph negative/bcr rearrangement negative CML) with late appearing Philadelphia like chromosome].

A 48-year-old male was diagnosed to be unclassified chronic myeloproliferative disorder (UCMPD)/Ph negative bcr rearrangement negative (Ph-/bcr-) CML by hematological, cytogenetical and DNA analyses (Jpn. J. Clin. Hematol. 33(4): 525-531, 1992). Three years and a half after the diagnosis of UCMPD/Ph-bcr- CML, Ph chromosome was observed in 17 of 20 examined cells. Hematological findings showed a transformation into blast crisis. The late appearing of Ph in a case of UCMPD/Ph1-bcr- CML described here is rare. Southern blot analysis using 3' and 5' bcr probe showed no bcr rearrangement. Analyses of BCR/ABL chimeric RNA by RT-PCR method were negative in both of Major- and Minor BCR/ABL chimeric RNA. In the present case it is speculated that Ph is developed as the result of multistep progression and also speculated that the breakpoint at BCR gene differs from Major- and Minor-bcr in usual Ph+CML and de nove Ph+ ALL. Therefore, it may be reasonable that the present case is understood to be a case with late appearing Ph-like chromosome.

Base Sequence

[A case of Jordans' anomaly].

A 71 year-old female with jordans' anomaly was described. Fat-containing vacuoles were observed in neutrophils, eosinophils, basophils, monocytes and lymphocytes of the peripheral blood, but not in erythrocytes and platelets. In the bone marrow they were also observed in myeloid cells including myeloblasts, erythroblasts and megakaryocytes. In the granulocyte series, numbers of vacuole-containing cells and numbers of vacuoles increased as leukocytes matured. Histochemically, vacuoles were thought to contain neutral fat based on staining with Sudan III. However serum lipids showed no abnormalities. Both the reduction rate of NBT and the phagocytic activities for Candida albicans were normal.

Aged

[Two cases of unclassified chronic myeloproliferative disorders].

Two cases of unclassified chronic myeloproliferative disorders (UCMPD), diagnosed by hematological, cytogenetic and DNA analyses, are described. Case 1: a 63 year old female was admitted because of leukocytosis (96,800/microliters) and splenomegaly. Hematological examinations revealed an increase of the granulocytes in the peripheral blood and bone marrow. The neutrophil alkaline phosphatase (NAP) score was 121. The patient developed blast crisis after 12 months of the chronic phase. Case 2: a 48 year old male was presented with fever and leukocytosis (20,000/microliters). Hematological examinations revealed an increase of granulocytes in the peripheral blood and bone marrow. The NAP score was 33. Maturation-arrest in granulocytic series and morphological abnormalities of marrow cells were not observed in the two cases. Cytogenetic analysis of bone marrow cells disclosed 46, XX, i (17 q) in case 1 and 47, XY, +8 in case 2. Southern blot analysis using 3' bcr probe and TransProbe-1 showed no bcr rearrangement. These cases are thought to be valuable in order to clarify the relationship between UCMPD and CMPD such as Ph1 negative chronic myelocytic leukemia and myelodysplastic syndromes.

Blast Crisis

Increased accumulation of cytosine arabinoside in human leukemic cells and enhancement of its cell-killing activity by uridine.

The effects of uridine(UR) on the cell-killing activity of cytosine arabinoside(ara-C) against human leukemic cells, MOLT-4, and on ara-C accumulation in cells were studied. The 50% lethal dose(LD50) of ara-C as determined by clonogenic assay was decreased to 5.0 x 10(-8) mol from 9.0 x 10(-7) mol after 3 days exposure to 10(-3) mol of UR. The accumulation of 3H-ara-C at 24 and 48 h was significantly increased in culture medium containing 10(-8) mol of 3H-ara-C and 10(-3) mol of UR (5,129 +/- 123.5 vs 2,554 +/- 115.5 cpm/10(5) cells at 24 h, p less than 0.01, and 5,772 +/- 123.2 vs 1,372 +/- 51.8 cpm/10(5) cells at 48 h, p less than 0.01). It is noteworthy that cell-killing activity of ara-C against human leukemic cells was enhanced by the combination with a nucleoside(UR), but not with antileukemic agents.

Cell Survival

[Chemotherapy of chronic myelogenous leukemia--VP(M) regimen initiated during its chronic phase, and evaluation of MCNU in the phase of blastic crisis].

Seventy-four patients in the chronic phase of Ph1-positive chronic myelogenous leukemia (CML) have been treated with busulfan or other alkylating agents in a conventional way. During its chronic phase, 24 of these 74 cases had received additional intermittent therapy every 4 to 6 months, consisting of vincristine 2 mg or vindesine 3 mg per week, prednisolone 20-30 mg per day and partly 6 mercaptopurine 50 to 100 mg, combined with allopurinol 200 to 300 mg per day for 2 to 3 weeks. The 50% survival of these patients using the Kaplan-Meier's method was 73.7 months and 5-year survival was 69.6%, against 40.5 months and 14.4%, respectively, in the remaining patients. Nine patients in the blastic or accelerated phase of Ph1-positive CML have been treated with new regimens including MCNU. All cases had been refractory for usual types of induction chemotherapy. The new regimen consisted of MCNU 50-100 mg, combined with vindesine or 6-MP plus allopurinol or prednisolone. Five out of 9 cases attained complete remission and 1 partial remission. The major adverse effect of this regimen was slight liver damage. MCNU could be regarded as an useful agent in the blastic phase as well as in the chronic phase of CML.

Adolescent

[Bone marrow scintigraphy with 111In-chloride--a clinical value for the hematological diseases].

Bone marrow scintigraphy with indium chloride (111In) was performed in fifty-one patients with the hematological diseases. The results of the investigation were that 1. in all patients, as well as in patients with aplastic anemia, no correlation was there between the degree of the indium chloride accumulation and peripheral blood counts, 2. in patients with aplastic anemia and pure red cell aplasia (PRCA) a tendency to reduction in uptake of indium chloride in bone marrow, 3. in patients with these two good correlation between the degree of indium chloride accumulation and histology of the erythroid bone marrow, but in patients with chronic myelocytic leukemia (CML) and atypical leukemia no correlation between the two, so it seemed unlikely that indium chloride should reflect the effective production of erythrocytes, 4. four patients with leukemia were studied with indium chloride bone marrow imaging two times to evaluate their responses to chemotherapy, and peripheral expansion was no change or reduced in two patients with acute myelocytic leukemia (AML) and one patient with acute lymphocytic leukemia (ALL) who obtained complete remission, but on the other hand, it enlarged in one patient with acute myelocytic leukemia who obtained partial remission, and 5. in two patients with chronic myelocytic leukemia it enlarged up to the ankle joints, which was considerably specific.

Acute Disease

[Clinical effects of K-18 (IgG-melphalan) in hypoplastic leukemia: a case report].

Five cases of hypoplastic acute myelocytic leukemia were treated with an IgG-melphalan conjugate, K-18. Eight tablets of K-18, containing 30 mg per tablet, were given daily. One patient, a 68-year-old female, obtained complete remission with a duration of 1.5 + months. Among the four remaining patients without remission, one showed a decrease in leukemic cells in the peripheral blood. No side effects of K-18 were observed except in one patient, showing a slight increase in serum GOT and GPT levels. Further studies with a large group will be necessary to clarify the effect of this drug on hypoplastic leukemia.

Administration, Oral

[Therapeutic effects of a combination of intermediate-dose cytosine arabinoside, adriamycin and vincristine in relapsed acute leukemia].

Eleven cases of acute leukemia, 8 relapsed and 3 refractory to a conventional induction chemotherapy, were treated with a combination of intermediate-dose cytosine arabinoside (ara-C), adriamycin (ADM) and vincristine (VCR). They consisted of 9 ANLL and 2 ALL. The therapeutic regimen consisted of 1-hour infusion of ara-C of a dose of 500 mg/m2 every 12 hours for 6 days from days 3 to 8, ADM, 40 mg/m2, on day 1 and VCR, 1.4 mg/m2, on day 2. Among 11 cases in which an evaluation was possible, 7 obtained complete remission (CR). The CR rate was 77.8% in the 9 cases of ANLL. The toxicity of this regimen included the following: conjunctivitis in 4 of 11 cases (36%), nausea and vomiting in 9 of 11 cases (91%) and hair loss in all cases, although no toxicities of the central nervous system of liver were observed. The mean level of serum concentration of ara-C was above 10 microM at 15, 30 and 60 minutes after the initiation of infusion. The therapeutic effect of this regimen consisting of intermediate-dose ara-C is expected to be useful not only in induction of refractory and relapsed acute leukemia, but also in the postremission therapy of CR cases.

Acute Disease

Aclarubicin in the treatment of elderly patients with acute nonlymphocytic leukemia.

Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.

Aclarubicin

Monocyte chemiluminescence and macrophage precursors in the aged.

Age-related alterations in the host defense system have been vigorously investigated because of increased susceptibility to infection and neoplasms in the aged. Although monocyte-macrophages form a major part of the cellular defense against microorganisms, the majority of investigations has been limited to neutrophils and lymphocytes. The present study, designed to determine the influence of age on mononuclear phagocytes, revealed no significant decrease in the absolute number of blood monocytes, but did reveal a tendency for the chemiluminescence of blood monocytes to decrease (p less than 0.10) and a significant decrease in the numbers of macrophage precursors (p less than 0.05) in the aged (over 70 year old), in comparison with controls (under 40 years old). On the basis of these findings, functional alterations of monocyte-macrophages seem to participate in the increased susceptibility to infection in the aged.

Adult

Interaction between human lymphoblastoid interferon and chemotherapeutic agents in vitro.

The combined effect of human lymphoblastoid interferon (HLBI) and anticancer agents on the growth of MOLT-4 was studied in vitro. The interferon showed a strikingly synergistic interaction in combination with aclarubicin, cytosine arabinoside or prednisolone. It was moderately synergistic in combination with adriamycin or 5-fluorouracil and tended to show additive effects with daunorubicin or vincristine. In vitro studies of combination chemotherapy with interferon and anticancer agents should yield valuable information as to the best combination for man.

Antineoplastic Agents