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M J Cline

Publications and source records attributed to M J Cline.

At least 145 records · Page 8Linked to original sources
PubMed1977

Thyroid hormones stimulate erythropoiesis in vitro.

Thyroid hormones have important effects on erythropoiesis in man and animals. We performed in vitro culture studies with murine and human bone marrow in order to define the interaction of these hormones with erythroid and granulocyte-monocyte progenitor cells. The methylcellulose clonogenic assay was used with the appropriate addition of erythropoietin or colony-stimulating activity. L-thyroxine, D-thyroxine and L-triiodothyronine potentiated erythropoientin-stimulated erythroid colony formation in concentrations of 50-100 ng/ml. These hormones had no effect on granulocyte-monocyte colony formation at concentrations up to 500 ng/ml. Testing of various thyroid analogues showed no clear correlation between potentiation of erythropoiesis and known calorigenic potency. Reverse triiodothyronine also had potentiating activity in this system. The active thyroid hormones stimulated erythroid colony formation at several concentrations of erythropoietin but could not substitute for erythropoietin. These data suggest that thyroid hormones have a direct effect on erythroid precursor proliferative capacity, a finding which may have relevance to the mechanism of erythropoietic dysfunction in human thyroid disease.

Animals↗
PubMed1977

The Philadelphia chromosome in human macrophages.

Three patients with chronic myelocytic leukemia in different phases of the natural history of the disease were studied. Their bone marrow cells were cultured under conditions favoring macrophage proliferation, and parallel cytogenetic and cytochemical studies were performed. All cell metaphases examined contained the Ph1 chromosome at a time when more than 80% of these metaphases were in identifiable macrophages. We conclude that the mononuclear phagocyte cell line contains the abnormal chromosome in Ph1-positive chronic myelocytic leukemia.

Cell Differentiation↗
PubMed1977

Monocyte function in man.

The monocyte-macrophage cell line is an important member of the host defense system. This report describes a series of assays that can be applied routinely in the evaluation of human monocyte function and gives information as to the activity of normal monocytes in these systems. Tests were chosen to assess various aspects of monocyte function that give some insight into the host defense status and the degree of "activation" of the monocyte. The assays outlined in this report are relatively simple to perform and include measurements of human monocyte chemotaxis, phagocytosis, fungal and bacterial killing, adhesion, and spreading.

Candida albicans↗
PubMed1977

Discrete clusters of hematopoietic cells in the marrow cavity of man after bone marrow transplantation.

Discrete aggregates of hematopoietic cells were observed in the bone marrows of patients with aplastic anemia or acute leukemia 14 days after marrow transplantation. The great majority of such colonies were of a single cell type, and less than 3% contained two or more cell types. Erythroid, myeloid, and undifferentiated hematopoietic colonies were approximately equal in frequency.

Anemia, Aplastic↗
PubMed1977

Polycythemia vera: hormonal modulation of erythropoiesis in vitro.

We performed in vitro culture studies examining the interaction of erythropoietin with red cell progenitors in polycythemia vera. Bone marrow was obtained from five patients with typical disease and from five healthy volunteers, and assayed for erythroid colony formation (CFU-E) by the methylcellulose technique. In cultures without added erythropoietin, a mean eightfold greater cloning efficiency was noted with the polycythemia vera marrows, as compared to normal. There was prominent stimulation of colony formation by erythropoietin, and the shape of the erythropoietin dose-response cruves appeared to be similar in both patients and controls. Anti-erythropoietin antibody reduced the number of CFU-E in cultures not containing added erythropoietin, but did not eliminate them. Dexamethasone (10(-9) M) caused a consistent increase in CFU-E in the patients' cultures. These studies provide evidence for functional erythropoietin and glucocorticosteroid receptor mechanisms on erythroid precursors in polycythemia vera. The observations are consistent with a concept of this disease as a disorder of hematopoietic stem cells in which peripheral erythrocytosis is caused by an expanded erythroid progenitor compartment which maintains responsiveness to hormonal modulation.

Antibodies↗
PubMed1977

Abnormal in vitro granulopoiesis in phenotypically normal parents of some children with congenital neutropenia.

Bone marrow from hematologically normal parents of congenitally neutropenic children showed defective myeloid differentiation in vitro. In one family only the mother's marrow differentiated abnormally; in the second family both parents demonstrated abnormal myeloid differentiation. In vitro culture of bone marrow may be useful in establishing the mode of inheritance of some forms of familial neutropenia.

Adult↗
PubMed1977

Evaluation of congenital neutropenic disorders by in vitro bone marrow culture.

The congenital neutropenias are a heterogenous group of diseases whose etiology and pathogenesis are largely unknown. We studied nine neutropenic patients from seven families. Evaluation included peripheral blood cell and differential cell counts, epinephrine and typhoid vaccine stimulation studies. Rebuck skin windows, and bone marrow aspirations for morphological assessment and for in vitro culture in liquid suspension and in agar plates. Parallel cultures were set up with and without colony-stimulating activity (CSA), and peripheral leukocytes were assayed for cellular production of CSA. Patients were initially classified on the basis of their clinical course: benign, mild, moderately severe, or severe disease. One patient in the moderately severe group had an immunoglobulin disorder. Morphologically normal mature granulocytes were seen in bone marrow aspirates of two patients, and maturational defects of varying degree were seen in the remaining seven. Colony formation in agar was markedly reduced below normal in three of seven, moderately reduced in two of seven, and greater than normal in two patients. Colonies in six of seven patients consisted exclusively of macrophages. Marrow from all but one of the nine patients demonstrated poor neutrophil development in suspension culture, and addition of CSA did not result in augmented granulocytic proliferation or maturation. A scheme of normal neutrophil maturation is proposed, and the nine patients were categorized according to this scheme. Four patterns of congenital neutropenia emerged: type 1 was the most benign form of disease with essentially normal clinical and in vitro parameters, and a defect considered to be due to a small committed stem cell pool, abnormal release, or excessive utilization peripherally; type 2 had mild disease with presumed defective committed stem cell differentiation along the granulocyte line; type 3 included benign to severe clinical expression with an apparent defect at the level of the committed granulocyte precursor more severe than in type 2; type 4 disease had varied clinical expression but evidence for a defect at the level of the pluripotent stem cell.

Adult↗
PubMed1977

Mobilization of hematopoietic stem cells (CFU-C) into the peripheral blood of man by endotoxin.

Pseudomonas endotoxin was administered to three normal subjects in order to assess possible effects on stem cell circulation. Increased numbers of granulopoietic stem cells (CFU-C) transiently appeared in the peripheral blood, reaching a maximum after the time of maximal leukopenia. There was a mean 4-fold increase in CFU-C per ml of blood following endotoxin. A high proportion of these CFU-C did not require an added source of colony-stimulating activity for growth in agar.

Adult↗
PubMed1976

Autoimmune panleukopenia.

A patient with episodic panleukopenia involving neutrophilic granulocytes, monocytes and lymphocytes had recurrent bacterial infections and a circulating cytotoxin that injured primitive myeloid cells as well as differentiated granulocytes and mononuclear cells. The cytotoxin was an immunoglobulin with activity against mouse, as well as human, myeloid stem cells. Clinical remission during cyclophosphamide therapy was associated with disappearance of the circulating leukocytotoxin. Serum from a period of active disease was cytotoxic for the patient's own lymphocytes obtained during clinical remission. Absorption of cytotoxic serum with granulocytes removed activity against both granulocytes and lymphocytes. These studies suggest an autoimmune disease in man characterized by episodic granulocytopenia, monocytopenia and lymphocytopenia due to humoral antibody against non-HLA antigens shared by several hematopoietic cell lines.

Adult↗
PubMed1976

Leukocyte function in familial Mediterranean fever.

Neutrophilic leukocytes of patients with familial Mediterranean fever and of normal control subjects were studied in vitro. FMF neutrophils were found to be morphologically normal by light and electron microscopy and to have normal quantities of the lysosomal enzyme lysozyme. FMF cells demonstrated a slight decrease in their ability to migrate randomly in capillary tubes, this was primarily seen in Armenian patients and in those experiencing an acute attack. The leukocytes of these patients functioned normally in regard to their chemotactic and Candida-killing activity.

Adolescent↗
PubMed1976

Pathogenesis of polycythemia vera--new concepts.

Data presently available suggest that polycythemia vera is an acquired clonal disorder of the pluripotent stem cell resulting in expansion of committed stem cell pools, most prominently in the erythroid line. In vitro and in vivo studies suggest that erythropoiesis in polycythemia vera is at least partially modulated by erythropoietin.

Erythropoiesis↗
PubMed1976

Inhibition of murine granulopoiesis in vitro by dexamethasone.

The effect of dexamethasone on mouse bone marrow granulocyte-monocyte precursor cells (CFU-C) was studied in vitro. Dexamethasone inhibited colony formation in the presence of maximally stimulating concentrations of colony-stimulating activity. A mean colony reduction of 55% occurred at 10(-9) M dexamethasone and inhibition was observed at concentrations as low as 10(-12)M. The dexamethasone suppression could be abrogated by progesterone. These studies provide evidence that the committed granulocyte-monocyte stem cell has a glucocorticoid receptor mechanism that when activated results in inhibition of cellular proliferation in vitro.

Agar↗
PubMed1976

Preservation of granulopoietic precursors in nonfrozen, stored human bone marrow.

We have examined procedures for maintaining human bone marrow in a viable state for a period of 1 to 3 days. Various fractionation methods and environmental conditions were compared, and these results indicate that unfractionated, washed bone marrow cells stored at 25 C in a CO2-charged incubator gave the highest total recovery of granulopoietic stem cells capable of colony formation in vitro. After 24- and 48-hr incubation, a mean of 93 and 89% were preserved. Room temperature storage of bone marrow may have clinical applicability in autologous marrow infusion after high-dose chemoradiotherapy.

Bone Marrow↗
PubMed1976

Potentiation of erythropoiesis in vitro by dexamethasone.

The effect of dexamethasone on erythropoiesis was examined in vitro. Hematopoietic cells from 13-day mouse fetal livers were cultured for 48 h in the presence or absence of erythropoietin and erythroid colonies enumerated. Colony formation occurring in cultures containing no added erythropoietin was inhibited by the incorporation of antierythropoietin antibody, suggesting that these colonies formed in response to endogenous hepatic erythropoietin. Maximal colony formation was observed with 0.5 U/ml of sheep erythropoietin. Dexamethasone increased erythroid colony formation with peak stimulation at 10(-9) M. Dexamethasone potentiation was most marked in cultures containing less than maximally stimulating concentrations of erythropoietin. The cells required only a brief exposure to glucocorticosteroid to exhibit the augmented cloning capacity, and dexamethasone stimulation was inhibited by progesterone (10(-6) M). A comparable response to dexamethasone was observed in cultures of adult murine and human bone marrow erythroid progenitors, implying that the phenomenon is not peculiar to fetal cells and is not dependent on the presence of fetal hepatocytes. These data suggest that erythroid progenitor cells possess a glucocorticoid receptor mechanism that can modulate the response to erythropoietin in vitro.

Animals↗
PubMed1976

Cytochemical reactions of human hematopoietic cells in liquid culture.

Growth of human bone marrow in liquid suspension cultures has been used to study normal hematopoietic cell differentiation and abnormalities in blood diseases. A variety of cytochemical stains were applied to human marrow cells cultured in vitro for up to 14 days. AS-D- CHLOROACETATE ESTERASE AND ALPHA-NAPHYHYL BUTYrate esterase were most useful in distinguishing different cell lines in culture. Peroxidase activity disappeared with mononuclear phagocyte morphogenesis and diminished with culture in intermediate and mature granulocytes. Acid phosphatase activity and methyl greed pyronin staining intensity increased with macrophage maturation.

Adult↗