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T Murate

Publications and source records attributed to T Murate.

At least 109 records · Page 6Linked to original sources

Gene expression during terminal differentiation: dexamethasone suppression of inducer-mediated alpha 1- and beta maj-globin gene expression.

Previous studies demonstrated that hexamethylenebisacetamide (HMBA)-mediated murine erythroleukemia cell (MELC) commitment to terminal division could be suppressed by dexamethasone. A rapid (less than 2 hr) increase (step-up) in commitment to terminal cell division was observed if, after 60-70 hr in culture with inducer and steroid, MELC were transferred to medium with HMBA alone. This step-up commitment was not inhibited by actinomycin or cordycepin but was blocked by cycloheximide. In this study, we show that dexamethasone blocks HMBA-mediated activation of alpha 1- and beta maj-globin gene transcription but not the induced chromatin change characterized by appearance of DNase I-hypersensitive regions upstream from the 5' cap sites of the alpha 1- and beta maj-globin genes. A rapid (less than 2 hr) activation (step-up) of alpha 1-globin gene transcription was observed if, after 48-60 hr in culture with HMBA and dexamethasone, MELC were transferred to medium with HMBA alone. Activation of transcription of the beta maj-globin gene requires 12-24 hr of further culture. Cycloheximide inhibits step-up transcription of both globin genes. Thus, dexamethasone blocks HMBA-mediated modulation of transcription of several nonlinked genes whose expression is altered in a coordinated manner during induced MELC terminal differentiation. Further, the steroid blocks at a late step, a step after that which is rate-limiting to HMBA-mediated MELC differentiation.

Acetamides↗

Inducer-mediated commitment of murine erythroleukemia cells to terminal cell division: the expression of commitment.

Murine erythroleukemia cells (MELC) are transformed cells that can be induced to differentiate by a variety of agents, such as hexamethylenebisacetamide (HMBA) and dimethyl sulfoxide. Dexamethasone suppresses HMBA-mediated MELC differentiation, but MELC retain a memory for their exposure to HMBA since, on transfer from culture with HMBA and dexamethasone to medium without additions, a portion of the cells express characteristics of terminal differentiation. This study characterizes the steroid suppressed steps in the multi-step process of inducer-mediated MELC terminal differentiation. MELC in culture with HMBA and dexamethasone show low levels of commitment to terminal cell division; upon transfer to culture with inducer alone there is a rapid increase in the proportion of committed cells. The magnitude of this rapid or "step-up" expression of commitment increased with the length of prior culture with inducer and steroid. This step-up expression is not inhibited by actinomycin D or cordycepin but is blocked by cycloheximide. HMBA is required for step-up expression of commitment. In the absence of inducer, there is a rapid decay in the capacity for step-up expression. Thus, HMBA initiates a series of changes leading to the accumulation of factors--which may be mRNAs--whose expression is blocked by dexamethasone. Hemin, which induces MELC accumulation of globin mRNA but not commitment to terminal cell division, cannot, as does HMBA or dimethyl sulfoxide, cause step-up expression of commitment.

Acetamides↗

Modulation of gene expression during terminal cell differentiation: murine erythroleukemia.

MELC are virus-transformed cells capable of indefinite proliferation that are blocked in differentiation at an early erythroid precursor stage, probably corresponding to CFU-e. A variety of agents, among them HMBA and Me2SO, induce MELC to terminal differentiation and expression of characteristics similar to that associated with normal erythropoiesis. During inducer-mediated terminal differentiation, modulation of expression of a number of genes occurs. Studies to date have characterized inducer-mediated alterations in chromatin structure associated with activation of alpha and beta maj globin genes. Inducer-mediated MELC terminal cell division is also associated with a decrease in the synthesis of the nuclear protein p53, a protein that has been implicated as a requirement for the progression from G1 to S in the cell cycle. HMBA-mediated commitment to terminal cell division is suppressed by steroid. HMBA induces accumulation of mRNAs that may be required for commitment to terminal cell division and whose translation is suppressed by dexamethasone. At least two inducer-activated genes have been identified that may play a role in the transition of terminal cell division.

Animals↗

Maturation sequence hierarchy of murine macrophage progenitor cells.

The heterogeneity of murine macrophage progenitors was analyzed with special interest in their maturation sequence. The gross appearance of macrophage colonies formed by C57BL/6 marrow cells was classified into three types: compact, intermediate, and dispersed. Progenitors of each type could be segregated by sedimentation velocity. Findings of cell-cycle studies showed that different types of colonies were not derived from a single progenitor cell at different times in the cell cycle. Therefore, it is considered that the difference in colony types can be attributed to the heterogeneity of progenitors. Suspension cultures of fractionated marrow cells rich in compact, intermediate, and dispersed colonies yielded mainly intermediate colonies, dispersed colonies, and clusters, respectively. As suspension cultures containing colony stimulating factor were considered to induce cell division as well as maturation, it is supposed that progenitors of compact, intermediate, and dispersed colonies constitute a maturation sequence hierarchy in this order.

Animals↗

Origins of hemopoietic and stromal cells in subcutaneous femur implants.

The origin of spleen colony-forming units (CFUs) and fibroblastoid colony-forming cells (CFUF) repopulating the marrow of femurs subcutaneously implanted in syngeneic and semi-syngeneic mice was studied by making use of a chromosome marker for CFUs and a cytotoxicity test for CFUF. The CFUs present in implants during first 4 weeks were of a mixture of those from the donor and the host, and thereafter, were exclusively of host origin. On the other hand, the colony growth of CFUF from the marrow of C57BL/6 femurs grafted in B6CBAF1 mice remained almost totally unaffected by treatment with C57BL/6 anti-B6CBAF1 serum as late as 40 weeks after implantation. Quite similar results were obtained from the marrow-depleted femur implants. It is concluded from the present studies that chimeric marrow consisting of hemopoietic cells of host origin and stromal cells of donor origin can repopulate the femurs within a matter of several weeks after subcutaneous implantation.

Animals↗

[Clinical experience of cefoxitin in the treatment of infections complicated by intractable blood disorders].

A total of 19 patients who had local or systemic infections with a variety of difficult-to-treat blood disorders were treated with cefoxitin (CFX). The following findings were obtained. 1. Fifteen out of 19 patients' responses were judged "excellent" or "good" with an overall cure rate of 78.9%. 2. As to the side effects of CFX, transient elevations in S-GOT, S-GPT were observed in 3 patients, urine protein in 2 patients, and hematuria in 1 patient. However, these abnormalities cannot be solely attributed to CFX because these patients were treated with either antitumor agents or aminoglycosides, and some had undergone blood transfusions. 3. CFX should be considered for the treatment of severe infections because it is well tolerated, has a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative pathogens and is highly resistant to beta-lactamases.

Adolescent↗

[Clinical evaluation of amikacin in severe infections with hematological malignant diseases (author's transl)].

Investigation was made on absorption, excretion and clinical responses following intravenous drip infusion of amikacin (AMK) and the following results were obtained. 1) Serum concentrations of AMK were determined after completion of a 1 hour-course of its intravenous drip infusion at a dose of 200 mg, involving 2 patients with normal renal function and 1 patient with impaired renal function. In the patients with normal renal function, a mean peak serum concentration of 15.9 micrograms/ml was reached at the termination of the intravenous drip infusion and, then, gradually declined to 0.97 microgram/ml at 6 hours after completion of the intravenous drip infusion. The half-lives were 1.64 and 1.41 hours, respectively. In the patients with impaired renal function, the elimination of AMK from blood flow was markedly delayed and the serum concentration was 5.52 micrograms/ml even at 6 hours after completion of the intravenous drip infusion. The half-life was prolonged, its value being 5.98 hours. 2) The mean urinary excretion rate for the patients with normal renal function was 67.7% within 7 hours, while the patient with impaired renal function had a lower rate of 14.0%. 3) Ten infectious patients with hematological malignant diseases were treated with AMK intravenous drip infusion. Clinical responses were excellent in 6, good in 2, fair in 1 and poor in 1. Thus, 80% of the patients responded to AMK. 4) In order to check the side effects of AMK, investigation was made on the results of various clinical laboratory tests and the subjective and objective findings. But, no side effects attributed to AMK were observed. Therefore, it is thought that the intravenous drip infusion of AMK will be very useful when attention is paid to infusion time, dose and interval.

Adolescent↗

Age-related changes in the function of hemopoietic stroma in mice.

Hemopoietic function of the marrow and splenic stroma in C57BL/6 mice aging from 2 to 24 months were evaluated with the use of subcutaneous implantation method. Although there was no significant difference in the concentration as well as the total number of CFU(S) in femoral marrows between aged and young mice, the rates of CFU(S) repopulation in the femoral marrows from aged donors were significantly lower than in those from young donors when grafted subcutaneously in the 2 month-old syngeneic hosts. On the other hand, the femoral marrow grafts from 2 month-old donors were constantly repopulated irrespective of the age of the hosts. An essentially similar finding was obtained in the study of spleen grafts. It is suggested that the defective hemopoiesis, if any, in aged mice is primarily caused by the changes in hemopoietic stroma rather than those in hemopoietic stem cells.

Aging↗

Circulating immunoglobulin-secreting cells in patients with plasma cell dyscrasia.

Immunoglobulin-secreting cells (ISC) in peripheral blood mononuclear cells (PBM) isolated from patients with plasma cell dyscrasia of various stages were studied using reverse hemolytic plaque assay. Normal healthy individuals contained 35 +/- 16 ISC/10(5) PBM. Aleukemic or subleukemic patients with overt myeloma contained 825 +/- 713 ISC, whereas leukemic patients contained 12,675 +/- 2520 ISC. Patients of premyelomatous stage, however, contained ISC/10(5) PBM of normal range. The relationship between ISC and clinical stage or laboratory data is discussed.

Aged↗