Life-threatening hepatic toxicity caused by all-trans-retinoic acid in a patient with acute promyelocytic leukaemia.
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Adult↗
Biomedical subjects
Y Shimamoto
Publications and source records attributed to Y Shimamoto.
Two cases of acute lymphocytic leukaemia associated with bone marrow necrosis--a brief review of recent literature.
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Adult↗
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↗
A human T-cell lymphotropic virus type I carrier with temporal arteritis terminating in acute myelogenous leukemia.
A human T-cell lymphotropic virus type I (HTLV-I) carrier with temporal arteritis (TA) in whom acute myelogenous leukemia (AML) developed 1 year after successful treatment of the autoimmune disease is described. This case suggested that the induction of immunodeficiency by infection with HTLV-I may be related to the development of the autoimmune disease and malignancy.
Aged↗
[Effects of slow-release nifedipine on hemodynamics and pharmacokinetics in elderly hypertensives].
Ten elderly hypertensives (4 men, 6 women) were studied before and after 8-week administration of 20 mg/day slow-release nifedipine. Systemic and regional hemodynamic data were measured using a pulsed Doppler technique. Slow-release nifedipine reduced mean arterial pressure, while cardiac output remained unchanged, resulting in a decrease in total peripheral resistance. None of common carotid, vertebral, celiac, superior mesenteric, renal, or terminal aortic flow changed significantly before or after administration of slow-release nifedipine. Pharmacokinetic parameters were as follows: Cmax, 59.1 ng/ml; AUC, 288.2 ng hr/ml; Tmax, 3.4 hr; t1/2, 5.5 hr. There was a direct relationship between the concentration of slow-release nifedipine and its depressor effect. Slow-release nifedipine had no influence on humoral factors such as plasma renin activity, angiotensin II, aldosterone, atrial natriuretic peptide, noradrenaline or adrenaline. Slow-release nifedipine may provide desirable hemodynamic effects in elderly hypertensives.
Aged↗
Clinical significance of monocytosis and human monocytic colony-stimulating factor in patients with adult T-cell leukaemia/lymphoma.
We studied 79 patients with adult T-cell leukaemia/lymphoma (ATL) and 11 human T-lymphotropic virus-type I (HTLV-I-carriers to investigate the clinical significance of absolute monocyte counts in peripheral blood. Monocytosis was observed in 20% of ATL patients, but in none of the HTLV-I carriers. ATL patients with absolute monocyte counts above 1.5 x 10(9)/l had a poorer prognosis than those with counts less than 1.5 x 10(9)/l. We also investigated serum levels of human monocytic colony-stimulating factor (hM-CSF) in 7 ATL patients and 11 HTLV-I carriers at the time of diagnosis before chemotherapy, and also in 5 normal healthy individuals. The differences among the 3 groups were not statistically significant. However, markedly increased serum hM-CSF levels were found in 3 ATL patients who were considered to be in the accelerated phase of the disease and 2 of whom were previously diagnosed and had received chemotherapy. There was no correlation between serum hM-CSF level and absolute monocyte count in ATL patients or HTLV-I carriers. The results of hM-CSF assay of supernatants of cultured ATL cells revealed that the ATL cells did not produce hM-CSF themselves. In an ATL patient with pleural involvement, the pleural hM-CSF level was lower than the serum level. These facts indicate that absolute monocyte count is one of the prognostic factors in ATL and the source of the elevated hM-CSF level in some patients with ATL is not ATL cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Cerebral cysticercosis treated with praziquantel--a case report].
We report a patient with cerebral cysticercosis treated with praziquantel. The patient, a 30-year-old man, was admitted to our hospital with a 12-year-history of generalized convulsion. MRI of the brain showed multiple cysts and the largest one in the right frontal lobe measured 3 cm in diameter. The intensity of cyst contents was same as that of the CSF on T1- and T2-weighted images. X-Ray of extremities and blood examinations showed no abnormal findings. The immunological testing for cysticercosis was negative in the serum. An operation was performed for the largest cyst in the right frontal lobe. The cyst was pathologically confirmed as cysticercosis. He was treated with praziquantel 50 mg/kg body weight in 3 divided doses per day with steroid cover for 7 days. The same therapy was repeated at an interval of 14 days. The patient was suffering from headache and scintilating scotoma only for a few days during the therapy. MRI revealed reduction in the size of the cysts in the right occipital lobe but no change in the other cysts. He was given praziquantel 600 mg per day for two months. As a result, the cysts in the right occipital lobe disappeared and the other cysts diminished on MRI.
Adult↗
[A juvenile onset case of moyamoya disease with intraventricular hemorrhage during pregnancy: case report].
We report a primipara with intracranial bleeding during pregnancy. The patient, a 23-year-old female, had history of cerebral ischemic attack during childhood and was diagnosed as having moyamoya disease at the age of ten. She did not undergo reconstructive vascular surgery but had not suffered from the cerebral ischemic attack in the last ten years. She suddenly lost consciousness in the eighth month of pregnancy and was admitted to our hospital. The brain CT scan revealed right paraventricular hemorrhage with ventricular perforation. After the newborn baby was delivered by cesarean section under spinal anesthesia, an emergency ventricle drainage was performed. The angiography demonstrated the occlusion of the internal carotid arteries at C1 portion with evidence of a moderate basal moyamoya network on both sides. Marked dilatation of the posterior lateral choroidal arteries was also seen on both sides, but no aneurysms were found. We supposed that the source of intracranial hemorrhage was a breakdown of the dilated perforating moyamoya vessels that formed the basal collateral network. We also supposed that the time of onset of intracranial hemorrhage might be related to the hemodynamic and hormonal changes occurring during pregnancy. Appropriate counterplans to pregnancy should be made by females with moyamoya disease, because pregnancy may be risky for them.
Adult↗
Amplification of 5-hydroxytryptamine-induced contractile responses via 5-hydroxytryptamine receptors and alpha-adrenoceptors in dog mesenteric artery and vein.
The interactions between 5-hydroxytryptamine (5-HT) and both serotonergic and alpha adrenoceptors were investigated by using isolated dog mesenteric vascular rings mounted in tissue baths for the measurement of isometric contraction. In the mesenteric artery, 5-HT elicited concentration-dependent contractions, producing 46.5% of the KCl maximal response. At low concentrations, the 5-HT-induced contraction was effectively inhibited by 10(-6) M methysergide and by 10(-6) M ketanserin, but was prazosin-resistant. At high 5-HT concentrations, the contractile response was effectively antagonized by 10(-7) M prazosin. The presence in the medium of 20 mM KCl, which increased resting tension less than 10% of the KCl maximal response, markedly enhanced the responses to 5-HT primarily at concentrations lower than 10(-5) M. These amplified responses were methysergide-sensitive, but prazosin- and ketanserin-resistant. In the mesenteric vein, exposure to 5-HT caused an extremely small contraction, producing 5.2 +/- 4.3% of the KCl maximal response. In the presence of 20 mM KCl, which had small contractile effects, 5-HT produced a biphasic concentration-response curve. Methysergide (10(-6) M) and 10(-6) M ketanserin effectively inhibited the responses to low concentrations of 5-HT, and only 10(-7) M rauwolscine effectively blocked the responses to high concentrations of 5-HT. In the dog mesenteric artery, our data suggest that addition of threshold concentrations of KCl enhanced the contractile response to 5-HT through amplification of 5-HT1-like receptor-mediated responses. In the dog mesenteric vein, KCl enhanced 5-HT responses via amplification of both 5-HT2 receptor- and alpha-2 adrenoceptor-mediated responses.
Animals↗
Inhibition by oxonic acid of gastrointestinal toxicity of 5-fluorouracil without loss of its antitumor activity in rats.
The possibility of decreasing the gastrointestinal (GI) toxic effects of 5-fluorouracil (5-FU) on the digestive tract such as its injury of cells and induction of diarrhea, without reducing its antitumor activity, was investigated in rats. Oxonic acid was found to inhibit the phosphorylation of 5-FU to 5-fluorouridine-5'-monophosphate catalyzed by pyrimidine phosphoribosyl-transferase in a different manner from allopurinol in cell-free extracts and intact cells in vitro. On p.o. administration of 5-FU (2 mg/kg) and a potent inhibitor of 5-FU degradation to Yoshida sarcoma-bearing rats, oxonic acid (10 mg/kg) was found to inhibit the formation of 5-fluorouridine-5'-monophosphate from 5-FU and its subsequent incorporation into the RNA fractions of small and large intestine but not of tumor and bone marrow tissues. This selective inhibition of 5-FU phosphorylation in the GI tract was due to the much higher concentrations of oxonic acid in GI tissues than in other tissues and the blood. On p.o. administration with the 5-FU derivative, UFT, which is a combined form of 1 M tegafur and 4 M uracil and usually administered p.o. to cancer patients in Japan, oxonic acid (10-50 mg/kg) markedly reduced injury of GI tissues and/or severe diarrhea without influencing the antitumor effect of UFT. These findings suggest that coadministration of oxonic acid suppresses the GI toxicity of 5-FU and its derivatives without affecting their antitumor activity and thus prolongs the life span of cancer-bearing rats.
Administration, Oral↗
Spontaneous regression in adult T-cell leukemia/lymphoma.
BACKGROUND: Spontaneous regression of adult T-cell leukemia/lymphoma (ATL) is considered to be extremely unusual. Of the 82 patients with ATL who the authors saw between 1981 and 1991, spontaneous regression occurred in 3 (3.7%), 2 of whom were previously untreated and one who had been previously treated. Surgical excisional biopsy triggered the spontaneous regression in these patients. METHODS: In two of these patients with spontaneous regression, gene analysis studies of human T-cell leukemia virus type I (HTLV-I) proviral DNA, and T-cell receptor (TCR) were carried out by Southern blot analysis in lymph node cells or peripheral lymphocytes before regression and after recurrence. RESULTS: One patient exhibited monoclonal integration of HTLV-I proviral DNA and the rearranged band of the TCR-beta gene at the same positions both before regression and after recurrence. The other patient showed them at the different positions before regression and after recurrence. CONCLUSIONS: The authors' studies indicated heterogeneity in ATL patients with spontaneous regression. Temporary spontaneous regression could occur in typical ATL and might be associated with a longer survival time than that for prototypic ATL.
Blotting, Southern↗
Primary T-cell lymphoma of the gastrointestinal tract associated with human T-cell lymphotropic virus type I. An analysis using in situ hybridization and polymerase chain reaction.
BACKGROUND: During a population-based local cancer registry, a peculiar type of T-cell lymphoma restricted to the gastrointestinal tract was found in patients living in southwestern Japan. METHODS: Five cases of gastrointestinal (GI) tract T-cell lymphoma were analyzed with immunohistologic examination, ultrastructural analysis, in situ hybridization (ISH), and polymerase chain reaction (PCR). RESULTS: All cases satisfied the criteria of primary GI tract lymphoma at presentation or operation. Four showed a close relationship to human T-cell lymphotropic virus type I (HTLV-I). Those four had positive results for anti-HTLV-I antibody and positive surface markers for CD4, positive hybridization signals by ISH, and HTLV-I gene products by PCR, but they had no lymphoma cells in peripheral blood or bone marrow. The fifth case showed negative signals by ISH and PCR. CONCLUSIONS: These findings suggest that some of the putative adult T-cell leukemia/lymphoma (ATLL) types can be further classified as GI-tract-type lymphoma. The prognosis for the GI tract type is as poor as it is for conventional ATLL.
Aged↗
Improved or fatal acute disseminated intravascular coagulation in systemic lupus erythematosus.
To analyze the outcome of systemic lupus erythematosus (SLE) associated with acute disseminated intravascular coagulation (DIC) and also to clarify the clinical factor(s) contributing to the outcome, we retrospectively investigated 120 SLE patients treated between 1981 and 1991. Eight of these patients (6.7%) developed acute DIC; four recovered and the other four died within 2 weeks of onset. Infection preceded acute DIC in all these patients. Acute DIC associated with atypical pneumonia was always fatal, while the patients with pharyngitis or urinary tract infection survived when they were treated adequately. Comparison of the dead and surviving groups revealed that the activity of SLE before the onset of DIC, the severity of DIC, and the treatment given for DIC and the coexistent infection were not significantly related to a fatal outcome. However, severe infection such as atypical pneumonia in patients with secondary immunodeficiency was likely to be fatal irrespective of the presence of DIC.
Acute Disease↗
Combined hereditary factor XI (plasma thromboplastin antecedent) deficiency, von Willebrand's disease, and xeroderma pigmentosum in a Japanese family.
We report a 28-year-old-Japanese male who had a skin tumor derived from variant type xeroderma pigmentosum (XP), combined with factor XI (FXI) deficiency and type IIB von Willebrand's disease (vWd). The patient had abnormal bleeding history on tooth extraction. FXI clotting activity (FXI:C) and antigen (FXI:Ag) were remarkably decreased (< 0.01 U/ml, < 0.02 U/ml, respectively). Factor VIII (FVIII) clotting activity, von Willebrand factor antigen (vWf:Ag), and ristocetin cofactor (RCoF) were 0.43 U/ml, 45%, and 57%, respectively. Ristocetin-induced platelet agglutination (RIPA) revealed hyper-aggregation compared with a normal control. Multimeric composition of vWf in plasma showed a reduction in high molecular weight forms. The family study revealed two other subjects with homozygous hereditary FXI deficiency and vWd, and five subjects with heterozygous FXI deficiency. The relationship between FXI deficiency and vWd is discussed and previously reported cases are reviewed.
Adult↗
Intracellular multiplication of Legionella pneumophila in HL-60 cells differentiated by 1,25-dihydroxyvitamin D3 and the effect of interferon gamma.
We examined leukemic cells, HL-60, an acute promyelocytic leukemia cell line, after differentiation induced by 1,25-dihydroxyvitamin D3 (D3) and retinoic acid (A) for infection of Legionella pneumophila, the etiologic agent of Legionnaires' disease. We investigated the effect of interferon gamma (IFN-gamma) on the differentiated cells and on the intracellular growth of the bacteria. An examination of morphological and antigenic changes in the cells was also included in the study. After 4-day incubation with 10(-6)M D3 or A, the HL-60 cells differentiated into monocyte-like (D3-HL-60) or mature granulocyte-like (A-HL-60) cells, respectively. They were then infected with L. pneumophila. Intracellular multiplication of the bacteria was evident in D3-HL-60 cells but not in HL-60 or A-HL-60 cells. D3-HL-60 cells required a 24-h infection time for the intracellular growth of L. pneumophila. D3-HL-60 cells activated with human recombinant IFN-gamma for 1-24 h (gamma-IFN-D3-HL-60 cells) before infection markedly inhibited L. pneumophila multiplication, the effect of IFN-gamma being dose dependent. Surface marker analysis was carried out in HL-60, D3-HL-60, and gamma-IFN-D3-HL-60 cells. On D3-HL-60 cells, CD11b, CD11c, CD14, and CD35 antigen increased, whereas CD71 and HLA-DR antigen decreased. This finding suggested that HL-60 cells differentiated into monocyte-like cells; the acquisition of the complement receptors, CD11b(CR3) and CD35(CR1), seemed to be important for phagocytosis and for the subsequent intracellular multiplication of L. pneumophila. The gamma-IFN-D3-HL-60 cells showed an increase of CD16, CD36, CD71, and HLA-DR antigen, suggesting that they were in an activated state. Our study indicated, first, that D3 can induce human leukemic cells to differentiate into functional monocyte-macrophage-like cells that can support the intracellular multiplication of L. pneumophila and, second, that these differentiated leukemic cells can be activated by IFN-gamma to markedly inhibit bacterial growth.
Animals↗
Metabolic basis of the synergistic antitumor activities of 5-fluorouracil and cisplatin in rodent tumor models in vivo.
The biochemical mechanism of the synergy of 5-fluorouracil (FUra) and cisplatin (CDDP) was studied using transplantable tumors in rodents in vivo. The reduced folate 5,10-methylenetetrahydrofolate (CH2FH4) and its precursor tetrahydrofolate (FH4) are essential cofactors for the formation of a tight ternary complex of thymidylate synthase (TS) and 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) derived from FUra. Intraperitoneal administration of CDDP (5 mg/kg) inhibited the incorporation of exogenous L-methionine into ascitic tumor cells and increased the levels of CH2FH4 and FH4 in ascitic Yoshida sarcoma and P-388 cells transplanted into rats and mice to levels about 2-3 times those measured in cells from animals that were not treated with CDDP. Preincubation with 10(-6) M FUra in Hanks' medium inhibited [6-3H]-2'-deoxyuridine incorporation into DNA of tumor cells from CDDP-treated rats 3 times more than that into cells from untreated rats, indicating that the inhibition of TS by FdUMP derived from FUra was enhanced in the presence of CH2FH4. Intraperitoneal administration of CDDP on day 1 and continuous infusion of FUra from day 1 to day 6 had synergistic effects in inhibiting tumor growth in Yoshida sarcoma-bearing rats. Oral administration of UFT, a combined form of 1 M tegafur and 4 M uracil, for 7 consecutive days beginning at 24 h after tumor implantation and a single i.p. injection of CDDP on day 1 had a significantly greater effect than did either agent alone. These results suggest that CDDP significantly enhances FUra cytotoxicity by inhibiting intracellular L-methionine metabolism and consequently increasing the reduced folate pool in mammalian tumor models in vivo.
Animals↗