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Biomedical subjects

F H Gardner

Publications and source records attributed to F H Gardner.

At least 55 records · Page 3Linked to original sources
PubMed1981

Comparison of direct harvest and cultures for karyotyping EDTA anticoagulated marrow.

Studies were undertaken to determine whether EDTA was a satisfactory anticoagulant for tissue specimens for cytogenetic analysis and to investigate a modification of a currently used culture technique for obtaining metaphases. The latter involved to prolonged exposure to very low-dose colcemid and was successful in qualitative or quantitative enhancement, or both, of the temperature yield over that obtained from direct harvest in 53% of the patients studied. EDTA is a suitable anticoagulant for cytogenetic studies of specimens from either direct harvest or short-term culture if the specimen is either processed within 24 hr after collection or diluted 1:1 with Eagles minimal essential media, supplemented with fetal bovine serum and refrigerated until processed. Success has been obtained with specimens stored up to 144 hr.

Bone Marrow↗
PubMed1981

Adenylate cyclase and guanylate cyclase activity in normal and leukemic human lymphocytes.

Adenylate cyclase (AC) and guanylate cyclase (GC) activities were studied in normal B-enriched and T-enriched lymphocytes, in lymphocytes of children with acute lymphocytic leukemia (ALL), and in lymphocytes of adults with chronic lymphocytic leukemia (CLL). AC activity was greater in normal B than T lymphocytes (215 pmole/min/mg protein versus 80 pmole in the membrane-enriched fraction) and i both increased greatly after stimulation with isoproterenol and more so with prostaglandins E and F2 alpha. In leukemic lymphocytes, AC showed depressed activity (20 pmole in ALL cells and 55 pmole in CLL cells) and was less sensitive to hormonal stimulation: this loss of sensitivity occurred to a greater extent in ALL than in CLL lymphocytes. GC activity was greater in normal T than B cells (in membrane-enriched fraction: 10.2 pmole versus 5.3 pmole). It increased little with isoproterenol and prostaglandins stimulation, and much more with sodium azide and dehydroascorbic acid stimulation. GC activity was increased in both types of leukemic lymphocytes (23 pmole for ALL cells and 18 pmole for CLL cells) and was insensitive to stimulation. Possible derangement of cyclase and cyclic nucleotide regulation in leukemic cells is suggested.

Adenylyl Cyclases↗
PubMed1980

Aminocaproic acid. Use in control of hemorrhage in patients with amegakaryocytic thrombocytopenia.

The bleeding complications of some forms of thrombocytopenia are difficult to control. Many patients become refractory to platelet transfusions even when HLA-matched. We have successfully used aminocaproic acid to control bleeding in 13 patients with amegakaryocytic thrombocytopenia. Four patients receiving long-term therapy with this drug had striking reductions in the number of platelet transfusions required for capillary bleeding. No adverse effects have been noted save for orthostatic hypotension, which is ameliorated by a reduction in dosage. Quantitative platelet function changes have been impossible to demonstrate, but no changes were noted in four patients with normal platelet counts who were receiving high-dose aminocaproic acid for treatment of subarachnoid hemorrhage. Aminocaproic acid has proved to be a valuable agent in the management of patients with amegakaryocytic thrombocytopenia, especially in decreasing the need for platelet transfusions.

Adolescent↗
PubMed1980

The abrogation of in vivo resistance to parental bone marrow transplantation and of in vitro natural cell-mediated cytotoxicity to the YAC lymphoma by in vivo growth of a transformed thymus-derived cell culture.

A thymus-derived monolayer culture, referred to as E1, from (C57Bl/6 X A)F1 hybrid mice was continuously passaged in vitro for over three years and formed rapidly growing, non-metastasizing tumors when injected s.c. into syngeneic mice. The spleens of tumor-bearing mice were greatly enlarged, but no tumor cells were detected in these spleens. The natural cell-mediated cytotoxic activity of spleen cells of tumor-bearing mice decreased with increasing tumor size. In addition, the expression of genetic resistance to transplantation of C57Bl/6 parental bone marrow cells was decreased in the spleens of irradiated tumor-bearing mice. This correlation between the expressions of natural cell-mediated cytotoxicity and of genetic resistance to bone marrow transplantation is consistent with the hypothesis that both of these responses are mediated by the same population of effector cells.

Animals↗
PubMed1979

111In chloride bone marrow scintigraphy and ferrokinetic studies in a case of sickle cell anemia with transient erythroid aplasia.

A patient with sickle cell anemia was hospitalized because of an acute erythropoietic aplastic crisis. 111In chloride bone marrow scintigraphy performed during the aplastic crisis showed markedly impaired uptake of the radionuclide and simultaneous 59Fe clearance T 1/2 studies were prolonged (420.9 min). Following recovery from the aplastic crisis 111In scintigraphy revealed an expanded marrow and the radioiron clearance T 1/2 was accelerated (20.9 min). The clinical course, hemograms and bone marrow aspirations correlated with marrow scintigraphy. 111In appears to be a valuable marrow scanning agent for assessing the presence of intramedullary erythropoietic activity.

Adult↗
PubMed1979

Bromochlorophenol blue. A new stain for erythroblasts.

In erythroblasts of varying maturational stages, cytoplasm stained bright yellow with bromochlorophenol blue. Since this staining reaction appeared to be distinctive among various cytological types of marrow cells, it may constitute a rapid method for visualization of cells of erythroid origin.

Bone Marrow↗
PubMed1978

Template bleeding time and clinical hemorrhage in myeloproliferative disease.

In 32 patients with myeloproliferative disorders (MPD), correlations were made among clinical observations of hemorrhagic tendency, template Ivy bleeding time, and platelet aggregation studies. Bleeding time was commonly prolonged, particularly in myelofibrosis. In two cases, this prolongation appeared to reflect a defect in platelet function, which resulted in clinical bleeding. Prolongation of bleeding time did not correlate with degree of thrombocytosis. Two patients with thrombocytosis had serious clinical bleeding at a time when bleeding time was normal. Of the patients, 35% had abnormal findings from aggregation studies, but there was no correlation between aggregation studies and prolongation of bleeding time or clinical hemorrhage. We conclude that bleeding in MPD arises either from a defect in platelet function, which is reflected in a prolonged bleeding time, or from thrombocytosis.

Blood Cell Count↗
PubMed1978

Androgen therapy of aplastic anaemia.

The current published reports have indicated that the young patient with aplastic anaemia who has a compatible marrow donor can obtain a successful marrow graft, especially if sex matched and with a past record of little or no transfusion therapy. Despite these encouraging results, only a small number of patients will have such donors available. Immunosuppressive therapy has been considered as an alternative, but this treatment has high risk in older patients. Past studies with androgen therapy have reported a response rate at one year similar to the current recovery rates with bone marrow transplantation. However, contemporary reports have indicated a marked decrease in the recovery rate following androgens, and some of these comparisons may be related to differences in supportive transfusion therapy. In part, the decreased rates may be related to an inadequate evaluation of residual marrow function in the aplastic patient. Patients to be treated with androgens always should have a physiological evaluation of residual erythropoietic committed bone marrow cells. In the absence of such an erythropoietic nidus, one may anticipate a poor response to any steroid therapy. Supportive blood component transfusions should be provided, especially in the initial three months of androgen treatment. In past studies the majority of patients have received only oral androgens, predominantly oxymetholone. Other androgens may be more effective in a particular patient, and there is an urgent need to develop procedures that define stem cell receptors for specific testosterone preparations. Current investigations have indicated that the 5 beta steroid metabolites of testosterone are haematopoietic without the complication of virilization. It is anticipated that a variety of these metabolites can be prepared for evaluation in the patient with aplasia. While there is continuing evaluation of the immune responses and suppressive therapies the clinician should continue to treat the aplastic patient with vigorous supportive transfusion therapy and different androgens for comparative evaluation.

Acute Disease↗
PubMed1978

Microscopic platelet size and morphology in various hematologic disorders.

Microscopic evaluation of apparent platelet size and morphology was examined in a variety of hematologic disorders. The time of preparation of the blood smear was important. An artifactual increase in platelet size was noted on blood films from 20 normal individuals that were prepared either immediately or 180 min after venipuncture. The clearest differentiation of patient categories was obtained with smears prepared 60 min after venipuncture using blood anticoagulated with K3EDTA. Under these conditions, normal size and morphology values were found in thrombocytopenic patients with aplasia or with increased splenic pooling. In contrast, large size values were a reliable finding in idiopathic thrombocytopenic purpura patients, whose platelet counts were less than 50,000/microleter. Large size values were also noted in patients with infiltrated bone marrows or myeloproliferative syndromes regardless of the platelet count. The last two groups usually showed abnormal platelet morphology with greater than 10% hypogranular platelets. Normal platelet size and morphology were observed in patients with iron-deficiency and megaloblastic anemias and in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosus who had normal platelet counts.

Anemia, Hypochromic↗
PubMed1977

Aetiocholanolone and prednisolone therapy in patients with severe bone-marrow failure.

Ten patients with bone-marrow failure from myelofibrosis, aplastic anaemia, paroxysmal nocturnal haemoglobinuria, and "hairy cell" leukaemia, who had failed to respond to androgens and/or glucocorticosteroids, were treated with a combination of aetiocholanolone and prednisolone. All patients except one with aplastic anaemia responded with an increase in reticulocytes, haematocrit, red blood cell mass, and blood neutrophils and platelets. These data suggest that aetiocholanolone, and similar 5beta-hydroxy steroids, may be valuable in treating certain patients with chronic marrow failure.

Adult↗
PubMed1977

The onset of a refractory response to androgens in the anemia of bone marrow failure.

Patients with bone marrow failure may have a hematopoietic response to an androgen preparation after they have no response from the use of a previous testosterone preparation. The failure to try a variety of hormone preparations may lead to improper conclusions as to a potential marrow proliferation for a clinical response. In some instances the use of a 5beta steroid metabolite may initiate stem cell proliferation in patients previously refractory to testosterone or nontestosterone esters. These obsevations suggest that some patients refractory to testosterone may be unable to form adequate 5beta metabolities by alterations in 5alpha reductase or enhanced metabolic transformation of the androgen. All patients should be evaluated with several androgen esters before concluding that their marrow cannot achieve a hematopoietic response.

Adolescent↗
PubMed1976

Effect of hyperoxia and androgen on red cell 2,3-diphosphoglycerate and oxygen affinity.

Increased plasma erythropoietin (ESF) activity, a rise in RBC 2,3-DPG, and a 'right shift' of the oxygen hemoglobin equilibrium curve following androgen administration to mice in ambient or hyperoxic conditions, was demonstrated. If androgens had a direct effect on the RBC metabolism, increased 2,3-DPG would result in a facilitated release of oxygen to the tissue. This would have been accompanied by a decrease rather than an increase in the level of ESF. Hyperoxia has abolished detectable rising levels of plasma ESF and RBC 2,3-DPG following androgen administration. These levels were close to those seen in the ambient nontreated mice.

Animals↗
PubMed1975

Biogenesis of erythrocyte membrane proteins. In vivo studies in anemic rabbits.

To study the process of red cell membrane protein synthesis we have followed the time course of [3-H]leucine appearance in total protein and individual peptides of the erythrocyte membrane following injection of the amino acid into phenylhydrazine-anemic rabbits. Multiple peripheral blood samples were taken from single animals over a 5-week period. Erythrocyte membrane proteins were separated by polyacrylamide gel electrophoresis in sodium dodecylsulfate and dithiothreitol; incorporation of radioactivity was determined by gel slicing and liquid scintillation spectrometry. Appearance of [3-H]leucine in circulating erythrocytes reached a peak at 1-3 days, with a steady decline thereafter. The radioactive amino acid appeared first in the lowest molecular weight peptides and last in the largest peptides; at the earliest time point (8 h), little radioactivity was observed in any of the four largest peptides present in the membranes (bands A, 1, 2 and 3). Certain smaller peptides (bands 4, 5 and 9) were the predominant species labeled at this time. By 24 h all peptides showed significant incorporation. With maturation of the red cells, label largely disappeared from bands A, 9 and several smaller peptides; this was confirmed by finding that the peptides are virtually absent from mature circulating erythrocytes. These data are interpreted as showing that red cell membrane proteins are synthesized asynchronously during the life cycle of the erythrocyte; the largest peptides are made predominantly in the earlier marrow stages of development, while certain of the smaller peptides are still being synthesized in the reticulocyte stage. Several membrane proteins appear to be specific to the reticulocyte and are lost during the process of cell maturation in the circulation.

Anemia↗
PubMed1975

Biogenesis of erythrocyte membrane proteins. In vitro studies with rabbit reticulocytes.

The capability of rabbit reticulocytes to synthesize red cell membrane proteins has been tested in vitro. Reticulocyte-rich blood from phenylhydrazine-treated rabbits was incubated in vitro in a complete amino acid medium containing ferrous salts, glucose, rabbit plasma and [3-H]leucine. Red cell ghost membranes were prepared by hypotonic lysis and leucine incorporation into hemoglobin and total membrane proteins determined. The pattern of incorporation into individual peptides was determined by polyacrylamide gel electrophoresis of labeled membranes on large (19 mm) gels which were then sliced into 1 mm sections; radioactivity was compared with densitometric tracings of Coomassie blue stained analytical (6 mm) gels. Incorporation of [3-H]leucine into both hemoglobin and membrane protein was linear over 1 h. Gel analysis of labeled membranes revealed that the amino acid was primarily incorporated into peptides with molecular weights of 90 000 or less; three peptides of molecular weights 90 000, 60 000 and 33 000 showed the highest specific activity. Synthesis of the four largest peptide species was negligible. Removable of ferrous salts inhibited synthesis of both globin and membrane protein equally (approx. 50%). However, puromycin and cycloheximide preferentially inhibited the synthesis of globin as compared to membrane proteins. Reticulocytes remain capable of synthesizing a number of membrane proteins; these results are consistent with studies of red cell membrane synthesis in anemic rabbits in vivo.

Anemia↗
PubMed1975

Post-transfusion purpura: a heterogeneous syndrome.

Three new patients with post-transfusion purpura (PTP) are described. As the manifestations in two differ significantly from those of previously reported cases, they serve to expand the definition of this syndrome. Although all 14 previously reported cases have occurred in Pl-A1-negative females, one of our patients was a Pl-A-negative male. Moreover, a female whose postrecovery platelets possessed the Pl-A1 antigen is described. Antiplatelet antibody activity was detected in all three patients by the 51Cr release test; in contrast, only one reacted in the complement (C) fixation assay. Serum obtained during the acute episode from the PlA1-positive patient reacted against platelets from four of 11 normals by C fixation and against platelets from 48 of 53 normals by 51Cr release, including five of nine Pl-A1-negative platelet samples. This case represents the first instance of PTP in which the platelet isoantibody was not specifically directed against the Pl-A1 antigen. These observations suggest that PTP may be a more heterogeneous disorder than previously realized.

Adult↗