[Case of primary amyloidosis complicated with intramuscular hemorrhage and Factor IX and X deficiencies].
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Biomedical subjects
Publications and source records attributed to M Kosaka.
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We have studied effects of sodium butyrate on embryonal carcinoma F9 cell differentiation. In the presence of sodium butyrate, F9 cells underwent rapid and drastic morphological changes and expressed marked increases in mRNA levels of various differentiation markers. When sodium butyrate was removed from the cultures, all the examined phenotypes of F9 cell differentiation rapidly reverted to the characteristics of undifferentiated stem cells. However, under the same conditions, when cycloheximide or actinomycin D was added to the cultures, such phenotypic reversion was not observed, but high mRNA levels of the differentiation markers as well as altered cell morphology were retained. These results indicated that the effects of sodium butyrate on induction of teratocarcinoma cell differentiation were reversible and that de novo syntheses of some mRNA(s) and protein(s) were necessary for the reversion of differentiated cells to stem cells.
1-beta-D-Arabinofuranosylcytosine-5'-stearylphosphate (fosteabine) was administered orally to patients with myelodysplastic syndromes (MDS); refractory anemia with excess of blasts (RAEB), RAEB in transformation, acute leukemia derived from RAEB and chronic myelomonocytic leukemia, in an early phase II study in a multi-institutional study. Among 62 evaluable patients, 2 patients achieved a complete remission, 6 a good response and 8 partial response by daily oral administration of 100-200 mg of fosteabine. The overall response rate was 25.8%. The response rates were almost the same among the four subtypes of MDS. Responses were reached 2-23 weeks (median, 8 weeks) after the start of therapy and continued for 3-50 weeks (median, 10 weeks). Major side effects were myelosuppression and gastrointestinal toxicities. In spite of the disadvantages, such as unpredictable absorption, this newly developed orally administrable cytarabine analogue will be a useful drug in the treatment of MDS.
Two cases of occupational vitiligo were observed in a resin factory where p-tert-butylphenol (PTBP) has been used as a starting material or an intermediate of synthetic resin. In this resin factory (A shop) and another resin factory (B shop), occupational exposure to PTBP was assessed in workers charging this chemical into the reaction vessel by means of a gas-chromatographic measurement of the environmental PTBP concentration and their urinary PTBP excretion. Assessment in A shop was made after the working condition was partly improved. Geometrical mean values of 8 h-time-weighted-average (8 h-TWA) of PTBP in air near the charger's breathing zone (personal air) were 0.215 mg/m3 in A shop and 2.12 mg/m3 in B shop. Continuous measurements of PTBP concentration in some stationary air of the shops showed that the maximum environmental PTBP values occurred during charging. Urinary PTBP concentration was increased to the maximum values 2 to 4 h after charging of this chemical and then rapidly decreased. Biological half-lives of urinary PTBP were estimated as 4.4 h in A shop and 4.8 h in B shop. The urinary PTBP concentration was correlated to 8 h-TWA of PTBP in the personal air. In particular, PTBP in urine collected at the end of the shift showed an excellent correlation to PTBP in the personal air (r = 0.84, n = 9, A shop; r = 0.88, n = 11, B shop). These results indicate that biological monitoring using urinary PTBP concentration is a suitable means of assessing exposure to this alkylphenol and the urine collected at the end of shift is the best sample for monitoring. In addition, the present environmental and urinary PTBP values were compared with those described in the literature and the relation of the occupational vitiligo with PTBP exposure is discussed.
The rotatostereoradiographic device uses an x-ray tube coupled with an image intensifier rotating through a 180 degree arc in 2.25 seconds. The rapidly rotating x-ray tube allows 180 degree-arc angiograms to be obtained with a single injection of contrast medium. Subtracted fluoroscopic angiograms can be viewed immediately after injection of the contrast medium with digital recording. These three-dimensional images are displayed on side-by-side monitors stereoscopically. The mortality and morbidity of subarachnoid hemorrhage can only be greatly reduced by surgical treatment of unruptured aneurysms and arteriovenous malformations detected by a wide survey of subarachnoid hemorrhage. Such a wide survey would be possible utilizing intra-arterial digital subtraction angiography via the ascending aorta and this new three-dimensional radiodiagnostic method. A fluoroscopic device must be used to allow easier manipulation of the catheter from the axillary or brachial artery.
Two hundred and forty-one mentally retarded persons, institutionalized in three private welfare facilities in Oita Prefecture, were assessed for dental status and tooth brushing ability. Information on their life style was also obtained by a questionnaire completed by their supervisors in the facilities. 1) Dental status of mentally retarded subjects was found to be inferior compared to the general Japanese population studied in the survey of dental disease in 1987 by the Ministry of Health and Welfare. Inferior dental status was characterized by a low score for filled teeth and a high score for missing teeth. 2) Both low tooth brushing ability and low intelligence quotient were associated with their poor dental status. 3) Discrepancy between supervisor assessment of tooth brushing ability and actual ability was observed. 4) Periodontitis was observed in young epileptics taking antiepileptic medication at a high rate. However there was no association between the taking of antiepileptic medication and missing teeth score. These results indicate a necessity for more active dental services including the teaching of tooth brushing and early treatment by dentists and supervisors.
The effects of erythroid differentiation factor (EDF) on normal human hematopoietic progenitor cells were examined by bone marrow colony assay. Addition of EDF to the erythroid colony assay system enhanced erythroid burst-forming unit (BFU-E)-derived colony formation, and this effect disappeared on removal of adherent cells. Conditioned medium of EDF-treated monocytes also enhanced BFU-E colony formation, whereas conditioned medium of EDF-treated T cells did not. In contrast, EDF inhibited erythroid colony-forming unit (CFU-E) colony formation dose-dependently, although it had no effect on colony formation by myeloid cells. These data show that EDF has a specific effect on human hematopoietic progenitors of the erythroid lineage. The results also indicate that EDF enhanced BFU-E colony formation by stimulating adherent cells to produce factors with burst-promoting activity (BPA), but suppressed CFU-E colony formation by promoting differentiation of these cells.
Between 1978-1988, seven cases of multiple myeloma were found in T Town (population 9,000), which is located at the mouth of a large river within the boundaries of Tokushima City, Japan. This is a significantly high incidence, 7.06 per 100,000 as compared with an incidence of 1.20 in Tokushima City itself and 1.53 in Japan as a whole. The clinical and laboratory features of these patients were typical of myeloma. Although the causes of this small but apparent cluster of multiple myeloma remain obscure, the fact that five of the seven patients had been working for long periods as fishermen was notable.
The effect of erythroid differentiation factor (EDF) on the colony formation of erythroid cells (CFU-E and BFU-E) inhibited by the sera from the patients with chronic renal failure (CRF) was evaluated by methylcellulose assay. EDF restored the inhibited formation of CFU-E colony irrespective of the absence or presence of the accessory cells. In addition, EDF was considered to recover BFU-E colony formation through the burst promoting activity (BPA) secreted by the adherent cells. A suicide experiment using 3H-thymidine revealed that EDF acted to induce BFU-E from resting phase to S phase of the cell cycle. Moreover, the number of circulating BFU-E and the secretion of BPA by the mononuclear cells, both of which were significantly low in CRF patients, were also moderately increased by the addition of EDF. These data suggest that EDF could be utilized as a therapeutic agent for pathogenetic factors except hypoproduction of erythropoietin on the anemia of the patients with CRF.
The effects of halothane (H) or enflurane (E) concentration on the circulatory system were studied in dogs. Two hours of halothane or enflurane anesthesia resulted in a linear dose-dependent decrease in circulatory indices including mean arterial pressure (mAP), cardiac index (CI) and left ventricular peak dp/dt/IP (peak dp/dt/IP). Systemic vascular resistance (SVR) was unchanged during either anesthesia. The correlations between the percent change of circulatory indices and the logarithm of the blood anesthetic concentrations were expressed by correlation coefficients (r): mAP, r = -0.718 (H), and -0.650 (E): HR, r = -0. 329 (H), and -0.352 (E): CI, r = -0.597 (H), and - 0.596 (E): SI, r = -0.389 (H), and -0.449 (E): SVR, r = -0.161 (H), and -0.030 (E): peak dp/dt/IP, r = -0.708 (H), and -0.871 (E). Using several indices of anesthetic depth including MAC, MAC-EI and MAC-BAR, the percent changes of mAP, CI and peak dp/dt/IP were calculated at the same anesthetic depth using halothane or enflurane. These results indicate that enflurane depresses these circulatory indices more than halothane. The differences were: mAP, 14.51 +/- 1.46%: CI, 8.14 +/- 1.86%: peak dp/dt/IP, 7.38 +/- 3.95% (mean +/- SD).
We report a rare case who developed pure red cell aplasia (PRCA) and pseudothrombocytopenia associated with hepatitis. A 50-year-old woman was admitted to the hospital because of acute hepatitis A. On the 22nd hospital day, normocytic normochromic anemia without reticulocytosis was developed. A bone marrow aspirate revealed erythroid hypoplasia with a small percentage of proerythroblasts and basophilic erythroblasts, but almost complete absence of polychromatophilic and orthochromic erythroblasts. This case was diagnosed as PRCA characterized by the maturation arrest of erythropoiesis. Anemia was spontaneously recovered following marked reticulocytosis. Afterward, transient EDTA-dependent pseudothrombocytopenia developed for 3 months. The serum taken during the acute phase of clearly inhibited BFU-E colony formation. This data suggests that some humoral factor in the serum of this patient may be involved in the pathogenesis of PRCA.
Two patients with primary Epstein-Barr virus (EBV) infection followed by pancytopenia were studied. They showed increased numbers of DR-positive, activated T-cells and serological evidence of persistent EBV infection over a 12 and 18 week period. Bone marrow granulocyte-macrophage colony formation (CFU-GM) was investigated by limiting dilution assay (LDA) and methylcellulose assay. CFU-GM of bone marrow mononuclear cells (BMMNC) was markedly suppressed in both patients during the pancytopenic phase. Removal of bone marrow T-cells by E-rosetting resulted in a significant increase of CFU-GM to normal levels in BMMNC of both patients, while no significant increase was observed in the BMMNC of normal subjects. CFU-GM in BMMNC from Patient 1 in the recovery phase was normal when DR-positive T-cells were within normal levels, irrespective of the presence or absence of T-cells. These results suggest that pancytopenia due to infectious mononucleosis in these patients was due to bone marrow suppression by activated T-cells. In vitro studies with Con A activated T-cells and their culture medium showed that suppression of CFU-GM by T-cells was mediated by a lymphokine.
The effects of erythroid differentiation factor (EDF) on the levels of zeta-globin and several proto-oncogene mRNAs and transferrin receptors (Tf-R) of K-562 cells were examined. EDF decreased Tf-R expression and increased the level of zeta-globin mRNA. The mRNA level of c-fos began to rise within 3 hours and continued to increase up to 72 hours, but the levels of c-myb and c-abl decreased to 23 and 19%, respectively, of their initial levels after 48 hours. In contrast, the mRNA levels of c-myc and c-fms decreased transiently, but recovered within 48 hours. The modulation of several proto-oncogene mRNA levels was observed much earlier than the differentiation induction and the growth inhibition of K-562 cells by EDF.
Regeneration of rat sciatic nerve across a 5-mm excised gap was investigated after the proximal and distal stump were inserted into a silicone tubing including a native artery. Usual tubulation (silicone tube only) was used as the control. After 4, 8, and 15 weeks, the extent of nerve regeneration was evaluated electrophysiologically and histologically. The nerve regeneration and intraneural vascular reconstruction that occurred within silicone tubing with an arterial blood supply were more successful than those that occurred in the control. In the 4 weeks following implantation, the enhancement of maturation in the regenerating axons was especially noticeable. The advantages of the present procedure are (i) the provision of continuous guidance for neural outgrowth; (ii) an increased supply of nutrients for regenerating nerve fibers and Schwann cells; (iii) an increased supply of oxygen by arterial highly oxygenated blood; and (iv) the stimulation of an exchange effect within the tube due to the pumping action of artery.
The number of circulating hematopoietic progenitor cells was determined during 47 courses of chemotherapy in 23 patients with hematopoietic malignancies. rhG-CSF was given subcutaneously to 14 patients to rescue chemotherapy-induced neutropenia following 22 courses of chemotherapy. The mean numbers of CFU-GM in patients with malignant lymphoma (ML), acute leukemia (AL) and myeloma (MM) were 56.0 +/- 58.8 (mean +/- SD), 46.7 +/- 66.0 and 11.0 +/- 11.1 CFU-GM/ml, respectively. The number of CFU-GM in MM was significantly less than in normal subjects (51.2 +/- 30.6 CFU-GM/ml). The number of CFU-GM in PB in all patients began to rise between 2 days before and 8 days after nadir of WBC count, and then reached the peak at the subsequent 5 days. The peak values of CFU-GM in ML, AL and MM were 711.3 +/- 974.7, 660.0 +/- 374.7 and 403.6 +/- 232.5 CFU-GM/ml, respectively, but there was no statistical difference among them. When ML patients were treated with rhG-CSF, the CFU-GM peak values increased as much as 5.5-folds compared with those following chemotherapy only. However, neither the period from nadir to start of increase in the CFU-GM count nor the time of the CFU-GM peak showed any significant change. These results indicate that the administration of rhG-CSF makes it possible to increase the number of circulating progenitor cells. It appears possible in most of the patients with hematopoietic malignancies to harvest the sufficient number of progenitor cells which are necessary for autologous blood stem cell transplantation.
A 67-year-old man was admitted to our hospital because of bleeding tendency and high fever. The patient had a past history of gastrectomy and transverse colectomy for cancer of transverse colon at age 57, and rectum resection for rectum cancer at age 59. After these operations, Tegafur 645 g, MMC 56 mg, and Ara-C 560 mg were administered for about 6 years. Hematological examinations revealed hemoglobin of 7.7 g/dl, white cell count of 9,500/microliters with 8% myeloblasts, and platelet count of 7,000/microliters. A diagnosis of myelodysplastic syndrome (RAEB-T) was made from the finding of bone marrow smear, which showed 28% myeloblasts, and neutrophils and megakaryocytes with morphologically abnormal nuclei and cytoplasms. Chromosomal banding study of the bone marrow cells revealed -5, -8, 7q- in all analyzed cells. These findings suggest that the preceding adjuvant chemotherapy is probably related to the occurrence of myelodysplastic syndrome.
Hybridomas producing monoclonal antibodies (Mabs) against the variable (V) region of human immunoglobulin light (L) chains have been difficult to establish in most cases. After fusion of myeloma cells with spleen cells obtained from mice immunized with VL fragments or L chains by conventional protocol using Freund's complete adjuvant (CFA), no hybridomas secreting Mabs specific for the VL subgroup have been obtained. In order to produce such Mabs, we have developed a novel immunization protocol consisting of the use of monophosphoryl lipid A and trehalose dimycolate for primary and secondary immunization courses and an intrasplenic injection for a final booster. A number of specific Mabs were successfully obtained and examples of clinical application for such Mabs was demonstrated by flowcytometry.
A spontaneous complete remission was observed in a 47-year-old female with acute monocytic leukemia. Resolution of all abnormalities, including systemic papule, thrombocytopenia, increased numbers of immature monocytoid cells in the peripheral blood and bone marrow, elevation of serum lysozyme and LDH, and trisomy 8 on chromosome analysis, occurred without any treatment. Moreover, the remission was not associated with any infection or blood transfusion, and is persistent for 12-month duration.