Search PubMed⌕ Search

Biomedical subjects

C W Jackson

Publications and source records attributed to C W Jackson.

At least 109 records · Page 6Linked to original sources
PubMed1983

Sequential changes in platelet function and coagulation in leukemic children treated with L-asparaginase, prednisone, and vincristine.

Coagulation and platelet function in 13 children with acute lymphoblastic leukemia were studied sequentially during a remission induction with L-asparaginase, prednisone, and vincristine. In the first weeks of therapy, which included four doses of L-asparaginase coagulation was characterized by significant decreases in plasma concentrations of plasminogen, antithrombin III alpha 2-macroglobulin, and fibrinogen. All measures gradually returned to normal after complication of L-asparaginase therapy. In the latter part of induction treatment, clotting times, especially partial Thromboplastin time, decreased significantly, while levels of factors V and VIII increased with recovery of platelet counts. At this time, 6 patients had an increased in vitro platelet aggregation response to adenosine diphosphate, and their partial thromboplastin times were significantly shorter than those of patients without increased aggregation. Concurrent abnormalities in coagulation and platelet function may account for the thrombotic complications that develop in some children receiving induction therapy with these agents.

Acute Disease↗
PubMed1983

Normal platelet function after therapy for acute lymphocytic leukemia.

The aggregation responses of platelets from 19 patients who had completed treatment of acute lymphocytic leukemia (ALL) and had remained in remission for two months to 4.8 years were studied both in vitro and in vivo. Responses to 0.5 micro M adenosine diphosphate (ADP), epinephrine, and collagen were all normal. One child had irreversible platelet aggregation to 0.1 micro M ADP, a concentration that only elicited a primary aggregation response from control platelets. The mean platelet-aggregate ratio was normal. We conclude that platelet defects, although a possible late effect of ALL or its chemotherapy, do not occur with any appreciable frequency in long-term survivors.

Adolescent↗
PubMed1983

Does cell density correlate with red cell age?

We have examined age-related changes in red cells by employing a serial hypertransfusion protocol to generate populations of in vivo-aged mouse red cells. Studies of these old cells have revealed alterations in membrane components; namely, a conversion of band 4.1b to 4.1a and an increase in the amount of membrane-associated, Triton-insoluble globin. Furthermore, we have found that the erythrocyte does change in density, but only during the earliest stages of its life-span. As the cell continues to age, there is no longer a correlation between age and density.

Animals↗
PubMed1983

Relationship of megakaryocyte size at diagnosis to chemotherapeutic response in children with acute nonlymphocytic leukemia.

Small megakaryocytes are frequently seen in patients with acute nonlymphocytic leukemia (ANLL). In this study, median megakaryocyte diameters were determined in marrow biopsy specimens of 32 children at diagnosis of ANLL and related to platelet count and chemotherapeutic response. The association between median megakaryocyte size and time-to-failure was striking. Seven of 9 patients with median megakaryocyte diameters greater than 20 microns remain in continuous complete remission for more than 3 yr, whereas 20 of 23 patients with smaller median megakaryocyte diameters failed therapy within 15 mo (p = 0.002). By Cox-regression analysis, megakaryocyte size had independent prognostic value (p less than 0.001), surpassing that of spleen size, the only other feature having significant association with time-to-failure. Megakaryocyte size at diagnosis may be useful for predicting the likelihood of prolonged complete remission in ANLL.

Acute Disease↗
PubMed1982

Acute megakaryoblastic leukaemia associated with intrinsic platelet dysfunction and constitution ring 21 chromosome in a young boy.

A 3-year-old boy with pancytopenia and a paucity of circulating blast cells was found to have acute megakaryoblastic leukaemia. Histopathologic investigation of the bone marrow biopsy disclosed replacement by megakaryoblasts and mild-to-moderate reticulin fibrosis, the megakaryocytic origin of these cells was confirmed by their staining properties and by cross-reactivity with rabbit anti-rat platelet serum. Treatment with adriamycin and cytosine arabinoside induced a complete remission of this otherwise rapidly fatal disease. Before chemotherapy, the patient's platelets showed decreased aggregation in response to thrombin and adenosine diphosphate, as well as a defective thrombin-induced serotonin release reaction. Neither functional defect resolved after remission induction, indicating that the platelets were intrinsically abnormal. Most striking was the finding of a constitution chromosomal defect, a ring No. 21 chromosome, in addition to an abnormal malignant stem line. This appears to be the first reported instance of a constitutional r(21) chromosome associated with acute leukaemia.

Bone Marrow↗
PubMed1980

Effect of VM-26 on the haematological responses of mice to L1210 leukaemia.

The haematological responses of BDF1 mice were monitored after i.v. or i.p. inoculation of L1210 leukaemic cells. Although a marked decrease in haematocrit was observed in mice given L1210 by either route, the anaemia was most pronounced after the i.p. route. The leucocyte count was more markedly increased after i.v. inoculation than after i.p. inoculation. The number of platelets decreased following either route, but was more depressed by i.v. inoculation. When mice were treated with VM-26 on Day 4 and i.p. inoculation of 10(6) L1210 cells, the haematological responses were altered. VM-26 prevented the accumulation of haemorrhagic ascites fluid and the precipitous decline in haemotacrit. However, the number of leucocytes increased dramatically, most significantly during the 48 h before death. VM-26 caused a temporary restoration of platelet count to near baseline levels. By the time of death, however, a second decrease in platelets had occurred. The results suggest that the haematological response of mice to L1210 leukaemic cells varies according to the route of inoculation, and that these tumour-induced haematological responses of the host can be modified by treatment with VM-26.

Animals↗
PubMed1980

Effect of hypertransfusion on bone marrow regeneration in sublethally irradiated mice. I. enhanced granulopoietic recovery.

Hypertransfusion can enhance recovery from neutropenia in certain clinical and experimental situations. We have studied the pattern of myeloid recovery in mice hypertransfused after receiving 350 rads whole body irradiation. Both hypertransfused and control groups showed the degenerative phase, abortive rise, and regenerative phase that has been described following sublethal irradiation. The blood granulocyte counts in the hypertransfused group returned to normal more rapidly and were maintained at a significantly higher level during the regenerative phase. This difference is not the result of a shift in granulocytes from the marrow granulocyte reserve or marginal granulocyte pool to the circulating pool, but is associated with significantly enhanced bone marrow granulopoiesis. While the total bone marrow cellularity of the hypertransfused mice is less than that of the control mice, the hypertransfused group contains more CFU-GM and myeloid cells during the regenerative phase. The enhanced granulopoiesis is not due to increased colony-stimulating activity (CSA) levels in the hypertransfused mice, as the CSA levels were significantly lower in this group compared to the controls prior to and during the initial phase of granulopoietic recovery. This study suggests that hypertransfusion increases the rate of recovery of myelopoiesis by increasing the number of precursors available for myeloid differentiation from an earlier stem cell compartment.

Animals↗
PubMed1980

Effect of hypertransfusion on bone marrow regeneration in sublethally irradiated mice. II. Enhanced recovery of megakaryocytes and platelets.

Hypertransfusion can enhance myeloid recovery after bone marrow depletion, but its influence on thrombopoietic recovery has not been previously defined. We have studied the pattern of platelet and megakaryocyte recovery in mice hypertransfused after receiving 350 rad whole body irradiation. The platelet counts of the hypertransfused group showing an initial fall due to hemodilution in the expanded blood volume and then fell to a lower nadir than that of the control mice. The rate of platelet recovery was more rapid in the hypertransfused mice. Bone marrow megakaryocyte concentrations in both groups showed a degenerative phase, abortive rise, and regenerative phase. The decrease in megakaryocytes was the same in both groups. The hypertransfused mice showed a greater abortive rise in megakaryocyte concentration preceded by the appearance of a greater number of large megakaryocytes in the bone marrow. However, the most striking effect of hypertransfusion was on megakaryocyte recovery. Although the time of onset of recovery was not different, the rate of recovery was approximately twice as rapid in the hypertransfused group. Administration of daily erythropoietin to hypertransfused mice abolished this more rapid recovery. Thus, the presence of a simultaneous demand for erythroid precursors does affect the rate of megakaryocyte regeneration. Just as the more rapid recovery of granulopoiesis following hypertransfusion may be clinically beneficial, the more rapid reconstitution of thrombopoiesis may also offer clinical advantage in some circcumstances.

Animals↗
PubMed1980

Altered platelet kinetics in thrombocytopenic mice with L5178Y leukemia.

Thrombocytopenia is a consistent feature of murine leukemia L5178Y. To define the mechanism(s) associated with the decrease in platelets, serial thrombokinetic studies were performed on various days after intravenous inoculation of 10(6) L5178Y ascites cells. At the nadir of thrombocytopenia (day 5), the recovery and circulating half-time of transfused normal 51Cr-platelets was only one half of control values. The loss of circulating radioactivity (70%) at 1 hr was accounted for by splenic (40%) and hepatic (30%) accumulation of labeled platelets. However, the liver contained three times more radioactivity per milligram of tissue than the spleen. There was no increase in hepatic accumulation of 59Fe-labeled red cells under the same conditions. When 51Cr-labeled leukemic platelets (day 3) were infused into normal animals, the circulating half-time was 50% of control. Despite spleen and liver enlargement, the blood volume of the leukemic mice did not increase. The megakaryocyte concentration remained unchanged after inoculation of leukemic cells, but the diameter of megakaryocytes increased significantly from days 5 to 10. These studies show that thrombocytopenia in mice transplanted with L5178Y leukemia occurs as a result of shortened platelet survival and increased organ sequestration. The increase in hepatic platelet accumulation suggests that the mechanism of thrombocytopenia is platelet specific and is not due to passive organ pooling.

Animals↗
PubMed1980

Shortened platelet survival as a cause of thrombocytopenia in mice with L1210 leukemia.

Thrombocytopenia is a frequent complication of acute leukemias of humans and animals. To define the possible causes of this decrease in platelets, we have studied platelet kinetics in mice after transplantation of 10(6) ascites cells from mice bearing L1210 leukemia. The circulating half-time of 51Cr-labeled platelets was reduced to approximately one-half that of controls when studied 1 or 3 days posttransplantation. Recovery of transfused 51Cr-labeled platelets was reduced to approximately one-half that in controls when studied 3 days after introduction of L1210 cells. Megakaryocyte concentration showed no change during the 5-day survival after i.v. infusion of leukemic cells but was increased on Day 5 and i.p. inoculation with an average host survival of 7 days. Megakaryocyte diameter distributions were significantly shifted toward larger sizes beginning on Day 2 after i.v. inoculation and on Day 3 after i.p. inoculation. Twenty-four-hr [3H]thymidine labeling indices of megakaryocytes were significantly increased beginning on Day 3 after i.v. inoculation but were significantly decreased on Days 5 and 6 after i.p. introduction of L1210 cells. We conclude that the decrease in platelets in mice transplanted with L1210 leukemia results primarily from shortened platelet survival and organ pooling. Megakaryocytes remain normal in concentration but increase in size, a usual response to decreases in platelet count.

Animals↗
PubMed1979

Relationship between packed cell volume, platelets, and platelet survival in red blood cell-hypertransfused mice.

In this study we have measured platelet and megakaryocyte concentration, blood volume, and platelet survival of mice after RBC hypertransfusion to PCVs of 62% to 90%. The platelet concentration of mice with PCVs up to 75% was decreased by up to one half. At higher PCVs a more severe thrombocytopenia developed, with platelet concentrations decreased to less than 10% of baseline in approximately one half of the mice. Blood volumes of the hypertransfused mice were increased up to twofold. Megakaryocyte concentrations were normal or increased. Platelet survival in mice with PCVs less than 75% was normal but was sharply decreased for mice with higher PCVs. The decrease in platelet concentration at moderately elevated PCVs may be explained by hemodilution in the larger blood volume. However, hemodilution alone cannot explain the severe thrombocytopenia at higher PCVs. The presence of decreased platelet survival with normal or increased megakaryocyte concentrations in this latter group suggests that the severe thrombocytopenia is the result of more rapid platelet destruction. In summary, elevation of the PCV by RBC hypertransfusion produces thrombocytopenia. The severity of the thrombocytopenia and the mechanisms involved in producing it change abruptly when the PCV exceeds 75%. These findings should be considered in interpretations of the influence of RBC hypertransfusion on hematopoiesis and in clinical and experimental studies of thrombopoiesis in polycythemic subjects.

Animals↗
PubMed1977

Biphasic thrombopoietic response to severe hypobaric hypoxia.

Thrombopoiesis has been studied during and after an 11 d exposure to discontinuous hypobaric hypoxia. Exposure of rats to 0.4 atmospheres for 16--17 h daily initially caused an increase in platelet count which reached a peak of 1.5 times baseline on days 4 and 5. This thrombocytosis was followed by a decrease in platelets to a nadir of 50--60% of baseline on days 12 and 13. That thrombocytosis results from increased platelet production is supported by increased [35S]sulphate incorporation into platelets and increased megakaryocyte size and turnover. The thrombocytopenia with continued hypoxia seems to result from decreased platelet production since 51Cr-platelet survival was normal while megakaryocyte concentration was decreased to one-half that of untreated controls. These observations suggest that differentiation of precursors into megakaryocytes was decreased during the thrombocytopenic period, although the fewer remaining megakaryocytes appeared stimulated because of their larger size and increased [3H]thymidine labelling. Thus, hypobaric hypoxia had a biphasic effect on thrombopoiesis with increased platelet production in the first few days of exposure followed by subnormal production.

Animals↗
PubMed1977

Evidence that stimulation of megakaryocytopoiesis by low dose vincristine results from an effect on platelets.

Appropriate low dosages of vincristine stimulate megakaryocytopoiesis and produce thrombocytosis. In this study of the thrombocytotic action of vincristine, administration of a single dose of 0.1 mg/kg to rats produced an increase in megakaryocyte concentration, diameter and 24 h [3H]thymidine labelling index. Transfusion of one body equivalent of platelets from normal donors prevented stimulation of megakaryocytopoiesis by vincristine whereas platelets from vincristine-treated donors did not. These results suggest that vincristine stimulates megakaryocytopoiesis by altering the functional role of circulating platelets in the regulation of thrombopoiesis.

Animals↗
PubMed1977

In vitro inhibition of platelet function and coagulation by pentamidine isethionate.

Pentamidine isethionate is a trypanocidal drug used for the treatment of Pneumocystis carinii pneumonitis. Hematological complications have occasionally been reported and include anemia, leukopenia, and thrombocytopenia. We report here several qualitative abnormalities of in vitro platelet function and coagulation that have not been described previously. Platelets were exposed in vitro to concentrations of pentamidine isethionate ranging from 0.5 to 100 mug/ml of platelet-rich plasma. Clot retraction, platelet adhesiveness to glass beads, and platelet aggregation (adenosine 5'-diphosphate [ADP], thrombin, epinephrine, collagen, and ristocetin) were inhibited in a dose-dependent fashion. The addition of pentamidine isethionate after aggregation had been initiated with ADP reversed both primary and, to a lesser degree, secondary aggregation. Platelet factor 3 availability and serotonin uptake and release (using collagen as the releasing agent) were not inhibited. Serotonin release with 10(-4) M ADP was slightly inhibited. Pentamidine isethionate prolonged the thrombin time of plasma at concentrations of 5 mug/ml and greater. The prothrombin time was prolonged at concentrations greater than 10 mug/ml of plasma. The inhibition of aggregation was reversed by washing and resuspension in plasma or by the addition of calcium or magnesium ions.

Amidines↗
PubMed1976

Platelet production capacity at intervals after acute thrombocytopenia.

Platelet producing capacity was examined at intervals after acute platelet depletion by reinduction of acute thrombocytopenia and assessment of the subsequent platelet recovery rates of 35S-sulfate incorporation into platelets. Platelet producing capacity was increased on days 1 and 2, somewhat decreased on days 3 and 4 and had returned to baseline by day 5. These studies suggest that there is an initial increase followed by a decrease on days 3 and 4 in cells which can respond to thrombopoietic stimulating factor after induction of acute thrombocytopenia.

Acute Disease↗
PubMed1976

Pregnancy and progeny in rats treated with prostaglandin A.

The effects of long-acting prostaglandin A1 upon pregnancy and fetal development were investigated in Long-Evans rats. The animals were treated by the intrauterine route either on gestational day 14 with 25 mug PGA1 or with 50 mug on day 17 of gestation. The incidence of fetal resorptions was significantly increased compared to the controls following treatment on gestational day 17. A significantly high incidence of nonspecific malformations was also induced in the offspring as a result of the treatment. There were no significant differences between experimental and control fetal and placental weights. The total protein content of fetal liver following treatment with PGA1 was not significantly reduced. Microscopic examination of placentas showed a consistent decrease in the thickness of the decidua basalis following treatment with 25 mug PGA1 on day 14 of gestation. The ovaries and umbilical cords showed no changes. In addition, treatment of rats daily with 200 mug PGA1, administered subcutaneously, on gestational days 9-12 or 12-15 did not affect the development of the conceptuses.

Abnormalities, Drug-Induced↗
PubMed1976

Stimulation of megakaryocytopoiesis by acute thrombocytopenia in rats.

Rats were made acutely thrombocytopenic by injection of antiplatelet serum. Marrow sections and squash preparations were made at intervals during 120 hr. Determinations were made of mitotic index, stage of maturation, ploidy level, and cell size of megakaryocytes; number and size of platelets were measured. Increased endomitosis among megakaryocytes was followed by an increase in the proportion of immature megakaryocytes, a greater average ploidy level of recognized megakaryocytes, and larger megakaryocytes. Maximum changes in these several parameters occurred between 32 and 72 hr after induction of thrombocytopenia. By 120 hr all megakarocyte parameters were near normal. For about 3 days, beginning at about 36 hr, platelet numbers increased rapidly. Average platelet size rose and returned to normal within about 60 hr. Changes in ploidy and size of megakaryocytes were measured in the immature and mature maturation stages. The results suggest that the initial stimulus in response to acute thrombocytopenia acts primarily on diploid precursors, programming them to mature into a population of megakaryocytes with an average ploidy approximately one level greater than in normal rats and a proportionate increase in cell size. The larger megakaryocytes presumably produce more platelets, accounting for a major part of the increased rate of platelet production. Since the changes in megakaryocytes begin to reverse before circulating platelet numbers have reached the normal level, reversal of the stimulus appears to be initiated by some change other than platelet mass.

Acute Disease↗