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Biomedical subjects

D H Cowan

Publications and source records attributed to D H Cowan.

At least 37 records · Page 2Linked to original sources
PubMed1985

Low dose cytosine arabinoside in acute myeloid leukemia: remission is not due to differentiation induction.

A patient with acute nonlymphoblastic leukemia (FAB M4), showing a near tetraploid chromosome complement on his marrow cells, was treated with low dose cytosine arabinoside and achieved remission. During remission the near tetraploid marrow chromosome complement disappeared and reappeared upon relapse of leukemia. These findings are interpreted as evidence against differentiation induction in the leukemic cell line as a mechanism for remission of the disease in this patient.

Aged↗
PubMed1985

IgDK multiple myeloma presenting as unilateral proptosis.

A 72-year-old woman presented with painful proptosis of the right eye and a large destructive tumour of the middle cranial fossa. A diagnosis of IgDK multiple myeloma was made, based on histopathologic and immunologic studies of the biopsy. Biochemistry and bone marrow examination further confirmed the myeloma as IgDK type. The clinical, radiological, and pathological findings are presented. The patient was treated with radiotherapy with satisfactory results.

Aged↗
PubMed1983

Influence of platelet lysate on colony formation of human breast cancer cells.

The effect of platelet lysate on the growth of human breast cancer cells was studied in the two-layer soft agar culture system. Lysate was prepared from frozen-thawed outdated human platelets. Eighteen to 446 colonies (mean: 85) grew from 50 of 57 tumors plated at a density of 5 X 10(5) cells/plate, yielding control plating efficiencies from 0.004-0.089. The viability of the cells plated ranged from 10-80%. All tumors were also plated with 200 micrograms/ml platelet lysate. Significant enhancement of colony formation (CF) (p less than 0.025) appeared in 26 of the 57 tumors tested. The number of colonies grown from these 26 tumors ranged from 36-580 (mean: 152). The extent of enhancement varied from 1.25-3.19. Significant suppression of CF (p less than 0.025) appeared in 6 of the 57 tumors. The extent of the suppression varied from 0.35-0.67. Platelet lysate induced no change in CF in the 7 tumors that failed to form colonies in control plates. There was no relationship between tumor cell viability and either the number of colonies appearing in control plates or the response of CF to platelet lysate. By contrast, there was a significant correlation (p less than 0.005) between viability and the extent of enhancement of CF by lysate. Concentrations of lysate varying from 50-400 micrograms/ml did not yield a consistent dose-related increase in CF. The results indicate that platelet lysate significantly enhances colony formation from a substantial percentage of human breast tumors.

Agar↗
PubMed1983

Stimulation of human tumor colony formation by platelet lysate.

The effect of platelet lysate on the growth of colonies of human tumor cells was examined in vitro by using the human tumor stem cell assay. Lysates were prepared from freeze-thawed outdated platelets. Eighteen to 446 colonies (mean 85) grew from 211 of 299 tumors plated at a density of 5 X 10(5) cells/plate. The plating efficiency ranged from 0.001% to 0.35%. The viability of the cells plated ranged from 10% to 90%. Platelet lysate significantly enhanced (p less than 0.05) colony formation from cells from 99 (47%) of 211 patients. The number of colonies grown with lysate from these 99 tumors ranged from 36 to 580 (mean 152). The enhancement factor varied from 1.25 to 6.69. Platelet lysate significantly decreased colony formation (p less than 0.05) from cells from 27 (13%) of the 211 tumors and had no effect on 85 (40%). Maximum increases over control occurred after 6 days in 79 (94%) of 84 tumors and after 10 days in 5 (6%). The extent of enhancement by platelet lysate of tumor colony formation correlated with cell viability (r = 0.545, p less than 0.005). The growth-promoting activity for human tumors was nondialyzable, stable with heating at 56 degrees or 70 degrees C for 30 min and at 100 degrees C for 2.5 min, substantially inactivated by heating at 100 degrees C for 5 min, and totally inactivated by heating at 90 degrees C for 30 min. It was partially inactivated by trypsin and abolished by periodate oxidation. The results suggest that a proportion of tumors of epithelial and mesodermal origin are responsive in vitro to growth-promoting factor(s) derived from human platelets.

Blood Platelets↗
PubMed1981

Platelet adherence to collagen: role of plasma, ADP, and divalent cations.

The effect of varying methods of platelet preparation and the role of ADP and divalent cations in supporting platelet adherence to collagen and the release of 14C-serotonin were assessed by affinity chromatography on collagen/Sepharose to define physiological conditions for this interaction. Platelets were separated by centrifugation or gel filtration from blood anticoagulated with EDTA or citrate and suspended in native plasma or buffer. After labelling with 51Cr or 14C-serotonin, they were passed though columns of collagen covalently linked to cyanogen bromide-activated Sepharose. Adherence to collagen was less in plasma as compared to buffer, was increased by centrifuging the platelets before testing, and was unaltered by addition of ADP. Removal of ADP with CP/CPK decreased the adherence of gel-filtered citrated and EDTA platelets and washed EDTA platelets (P less than 0.001) but not EDTA platelets in plasma. Adherence and release of citrated platelets in plasma or buffer containing CP/CPK were greater than that of EDTA platelets (P less than 0.01); no difference existed with gel-filtered platelets. The addition of 1 mM Mg++ to citrate or EDTA-anticoagulated washed platelets increased adherence and release (P less than 0.01). The results indicate that the choice of experimental conditions affect the assessment of factors which influence or promote platelet interaction with collagen. Platelet-collagen adherence is enhanced by laboratory manipulations and partially inhibited by normal plasma. Maximal adherence and release occur when divalent cations, particularly Mg++, and ADP are available. Their absence reduces but does not inhibit these reactions.

Adenosine Diphosphate↗
PubMed1981

Platelet adherence to collagen: role of prostaglandin-thromboxane synthesis.

The effect of aspirin and indomethacin on adherence of human platelets to collagen was assessed by affinity chromatography on collagen/Sepharose. Studies were done using platelets from normal subjects and subjects ingesting aspirin. Blood was anticoagulated with EDTA, EGTA or citrate, and platelets were suspended in plasma or buffer after separation by centrifugation or gel filtration. The adherence to collagen of platelets from subjects ingesting 1200 mg aspirin per day decreased significantly (P less than 0.05 or below). A significant reduction in adherence also occurred after exposure to aspirin and indomethacin in vitro. The reduction in adherence was associated with inhibition of malondialdehyde (MDA) production and was unaffected by the presence of CP/CPK. Exposure of platelets to aspirin at 24 degrees C caused no impairment of adherence. The addition of 1.0 mM Ca++, 0.5 or 1.0 mM Mg++, or 1 mM arachidonic acid significantly diminished the inhibition of adherence by aspirin. Imidiazole had an effect on adherence opposite to that of aspirin. Changes in release of 14C-serotonin in general paralleled changes in adherence. The data suggest that aspirin and indomethacin impair but do not fully inhibit platelet adherence to collagen. Factors affecting this inhibitory activity in our system are the presence of plasma and availability of divalent cation. Platelet-collagen adhesion appears partly dependent upon prostaglandin-thromboxane synthesis and may be promoted by a different pathway that is stimulated by divalent cations and unaffected by inhibition of prostaglandin synthesis.

Adenosine Diphosphate↗
PubMed1980

Effect of alcoholism on hemostasis.

Ample data exist indicating that alcoholism profoundly affects the hemostatic mechanism. In alcoholic patients without cirrhosis, the primary effect is on the blood platelet. Both quantitative and qualitative abnormalities appear during ethanol ingestion. Alcohol-related thrombocytopenia appears to be due to a combination of events: an increased rate of platelet destruction leading to decreased platelet survival and ineffective thrombopoiesis resulting in decreased effective platelet production. The qualitative abnormalities are also multiple and include decreased platelet aggregation, release, and procoagulant activity and decreased storage pool nucleotides, cyclic AMP, and MAO activity. The functional and metabolic abnormalities are associated with striking disturbances in ultrastructural morphology. These defects cause prolongation of the bleeding time and place affected patients at risk for hemorrhagic complications. The relationship between the quantitative abnormalities and the occurrence of thrombocytopenia is obscure, although their severity appears to increase in parallel. The various defects are readily corrected after cessation of drinking. Hence, their long-term significance, absent development of cirrhosis, is questionable. In alcoholic patients with cirrhosis, both platelet abnormalities and coagulation defects may be present. Which predominates in severity varies with each individual. Due to the chronicity of the underlying clinical state, the duration of the defects is more likely to be prolonged if not permanent. In addition, owing to the mechanism of their development, treatment or correction of the defects is difficult and of transitory benefit.

Alcoholism↗
PubMed1979

Platelet interaction with synthetic copolypeptide films.

Kinetic and equilibrium studies of blood platelet binding to copolypeptide films show that attachment and serotonin release are not dependent upon the composition of the copolypeptide. Data may be explained by postulating that platelets frequently collide elastically with the surface but leave behind material that modifies subsequent behavior. Similarly, material released from platelets adsorbs at the interface and the extent of attachment and serotonin release are modified and controlled by these adsorbed species. Basically, if the platelet is exposed to a clean surface, its collision with the surface leads to activation and release. In the presence of inert protein, the collision is cushioned by the protein and platelets do not attach or release to any extent. Finally, if protein (or other entities) released from the platelet provide attachment sites, then attachment occurs without release. It is postulated that the behavior of platelets at surfaces is controlled by these interrelated processes.

Biocompatible Materials↗
PubMed1979

Migration of human vascular endothelial and smooth muscle cells.

Migration of endothelial and smooth muscle cells was studied in vitro by measuring the increase in surface area at specific time intervals of confluent cell colonies advancing under agarose gels that contained both Morgan's medium 199 and variuos types of sera. First passage cultures of endothelial cells or 3 to 6 passage smooth muscle cells were plated into wells punched in agarose gels, at a seeding density of 50,000 cells per well. At zero time the size of the cell colonies was 35.4 sq. mm. +/- standard error 0.1. Irradiation (1500 rads) did not affect the expansion of the cell colonies although 3H-thymidine uptake was inhibited. Endothelial cells migrated under the agarose gels concentrically as contiguous sheets. When exposed to either 20 per cent platelet-poor plasma serum, platelet-rich plasma serum, or whole blood serum, the average increase in surface area was approximately 9 sq. mm. per day. In contrast, arterial smooth muscle cell colonies expanded with an increment of approximately 9 sq. mm. per day when exposed to 10 per cent platelet-poor plasma serum but 12 sq. mm. per day when exposed to 10 per cent platelet-rich plasma serum (p less than 0.001). Platelet factors also had stimulatory effects on the migration of venous smooth muscle cells. Cytochalasin B, dibutyryl cyclic AMP, and theophylline inhibited the migration of both endothelial and smooth muscle cells, but the latter responded more to the inhibitory effects of all three agents. It is concluded that in contrast to vascular smooth muscle, endothelial cells do not require platelet factors for migration and are less responsive to specific inhibitors affecting cell movement.

Blood Platelets↗
PubMed1978

Abnormal platelet aggregation in severe combined immunodeficiency disease with adenosine deaminase deficiency.

The platelets from a boy with adenosine deaminase deficiency-severe combined immunodeficiency disease (ADA-SCID) showed markedly subnormal aggregation in response to collagen and ADP. In contrast with normal platelets, ATP, AMP and adenosine had little effect in inhibiting ADP-induced aggregation of ADA-SCID platelets. These observations suggest that altered adenosine metabolism exists in ADA-SCID platelets.

Adenosine Deaminase↗
PubMed1976

Platelet aggregation as a sign of septicemia in thermal injury. A prospective study.

Serial measurements of coagulation activity, platelet counts, and platelet aggregation were done in patients with full-thickness burns involving 25% or more of body surface area to detect specific changes that might correlate with the onset of septicemia. Mean and maximal values for prothrombin time, partial thromboplastin time, thrombin time, activities of factor V and factor VIII, and concentrations of fibrinogen and fibrinogen-related antigens observed in the presence of bacterial septicemia did not differ significantly from those observed in the absence of septicemia. Mean platelet counts were significantly less with sepsis, but values in individual subjects were not indicative of the presence of septicemia. By contrast, platelet aggregation in response to adenosine diphosphate, epinephrine, and collagen always became severely abnormal with the onset of septicemia but not in the absence of sepsis.

Anti-Bacterial Agents↗
PubMed1976

The use of oral BCG in the treatment or metastatic malignant melanoma.

This study assess the effects of oral BCG, as a single agent, on tumor progression and on cell-mediated immune function in patients with metastatic malignant melanoma. Thirty patients were studied including 22 with measurable metastatic lesions and 8 with no detectable disease, following treatment of metastases by surgery, radiotherapy, or 5-(3, 3-dimethyl-1 -triazeno)-imidazole-4-carboxamide (DTIC; DIC). Oral BCG was given in doses of 120--240 mg, 1--3 times per week for periods ranging from 9 to 80 weeks and to total doses of from 1.2 to 20.1 gm. Patients were assessed by direct measurements of tumor mass, PPD skin test and in vitro blastogenic responses to PPD PHA. Of the 22 patient with measureable disease, 19 showed tumor progression and none showed regression of any lesion. Of the 8 without apparent disease, 5 remained stable and 3 had tumor recurrence. Of the total group of 30 patients, 8 showed some increased sensitivity to skin testing with PPD. Of 19 tested, 3 showed an increased PPD response in vitro, while 3 showed a decreased response. Six of 20 tested showed an increased PHA response in vitro. Oral BCG alone was not effective as an antitumor agent in patients with metastatic malignant melanoma.

Adult↗