John Akabutu

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Dr. John J. Akabutu MD

Clinical Interests

I have been involved in the Northern Alberta Comprehensive Hemophilia Clinic since its creation in 1972. The clinic developed with the help and support of many people including the minister of health the right honorable Gordon Mneilly, Dr. Garner King, myself, Mr. Robert Verreau of the Alberta Branch of the Canadian Hemophilia Society and others.

Research Interests

The reproduction of blood cells is a complex, poorly understood process in which pluripotential stem cells are recruited to differentiate and replicate themselves at the same time. The replicated stem cells must remain dormant till recruited, while the differentiating cells must go through a complex process of division and differentiation to produce all of the mature blood cells. We are interested in dissecting mechanisms by which these processes happen and the signals which direct this.

We have recently developed the facilities to characterize, purify, freeze and store stem cells from the the umbilical cord of newborn infants in Edmonton. These stem cells will then serve as a bank of stem cells which can be used for bone marrow transplantation for people with malignancy, gene therapy for peope with a varitey of genetic and acquired diseases.

Selected Publications

  1. Tan JS, Strauss RG, Akabutu J, Kauffman CA, Mauer AM, Phair JP. Persistent neutrophil dysfunction in an adult. Combined defect in chemotaxis, phagocytosis and intracellular killing. Am J Med 1974 Aug;57(2):251-8
  2. Gelfand ET, Taylor RF, Hendin D, Akabutu J, Callaghan JC. Melanotic malignant schwannoma of the right atrium. J Thorac Cardiovasc Surg 1977 Nov;74(5):808-12
    AB - A melanotic malignant schwannoma of the right atrium occurring in a 14-year-old girl is described. No previous such tumors in this location have been reported.
  3. Maclean GD, Mosmann TR, Akabutu JJ, Longenecker BM. Preference of the early murine immune response for polymorphic determinants on human lymphoid-leukemia cells and the potential use of monoclonal antibodies to these determinants in leukemia-typing panel. Oncodev Biol Med 1982;3(2-3):223-32
    AB - 28 monoclonal antibodies (MCAs) which were produced following immunization of mice with human lymphoid leukemia or lymphoma cells were subjected to extensive specificity testing using immunofluorescence and complement-mediated cytotoxicity assays. All except one of the MCAs reacted with lymphocytes from at least one normal donor, but only 36% reacted with at least one subpopulation of lymphocytes from every normal donor tested. 60% of the MCAs detected polymorphic determinants, the frequency of polymorphism ranging from 27 to 91%, 50% of these MCAs reacting with B lymphocytes but not T lymphocytes. The marked heterogeneity observed when testing human lymphoid leukemias with these MCAs could be explained by both polymorphism and heterogeneity in lymphocyte differentiation marker expression. An awareness of the preferential murine immune response to polymorphic determinants on human lymphoid leukemia cells is essential when interpreting unexpected positive or negative results when testing with MCAs. An MCA believed to be detecting a monomorphic determinant may be detecting a high-frequency (supratypic) polymorphic determinant, and a putative leukemia-specific MCA may be detecting a low-frequency polymorphic determinant. Our panel, which includes MCAs which detect polymorphic determinants, appears useful in following the course of leukemia and may be useful for leukemia classification.
  4. Krikler SH, Ferguson DJ, Akabutu JJ, Lomas CG. Transient anti-D in an Rh-positive patient with congenital dyserythropoietic anemia type II. Transfusion 1984 Mar-Apr;24(2):169-70
    AB - A multiply transfused Rh-positive patient with congenital dyserythropoietic anemia type II or hereditary erythroblastic multinuclearity with a positive acidified serum test is described in whom a transient anti-D was accompanied by a positive direct antiglobulin test. A brief review of the literature and possible mechanisms for this observation are presented.
  5. Dewar GJ, Lim CN, Michalyshyn B, Akabutu J. Gastrointestinal complications in patients with acute and chronic leukemia. Can J Surg 1981 Jan;24(1):67-71
    AB - Between July 1, 1972 and June 30, 1977, 541 leukemic patients were admitted to the University Hospital in Edmonton. Eight of 11 patients who underwent emergency operation for complications of leukemia or antileukemic therapy died within 30 days of operation. Six cases are reviewed to illustrate the four basic types of gastrointestinal lesions and complications of leukemia: hemorrhagic and agranulocytic necrosis, leukemic infiltrates and fungal lesions. A fifth type which is a mixture of the four basic types was also noted. As a result of their experience and a review of the literature the authors believe that an aggressive approach, consisting of close monitoring and early laparotomy combined with vigorous supportive therapy, should be used when dealing with suspected gastrointestinal complications in leukemic patients.
  6. Gualtieri RJ, Emanuel PD, Zuckerman KS, Martin G, Clark SC, Shadduck RK, Dracker RA, Akabutu J, Nitschke R, Hetherington ML, et al. Granulocyte-macrophage colony-stimulating factor is an endogenous regulator of cell proliferation in juvenile chronic myelogenous leukemia. Blood 1989 Nov 15;74(7):2360-7
    AB - Juvenile chronic myelogenous leukemia (JCML) is a rare myeloproliferative disorder of early childhood that is clinically and cytogenically distinct from the well-recognized adult type of chronic myeloid leukemia. Unlike the adult disease, growth of hematopoietic progenitors from peripheral blood (PB) occurs in the absence of exogenous stimulus even at low cell densities. This so-called spontaneous growth can be abrogated by adherent cell depletion and appears to depend on production of endogenous growth factors. We studied seven children with JCML to determine the nature of endogenous stimulators. With isolated PB mononuclear cells (PBMNCs) and a 3H-thymidine (3H-TdR) incorporation assay, JCML cells were shown to incorporate high levels of 3H-TdR when cultured in the absence of stimulus even at low cell densities. When neutralizing antisera prepared against each of the four known colony-stimulating factors (CSFs), GM-CSF, G-CSF, M-CSF, and interleukin-3 (IL-3), as well as antisera against interleukin-1 (alpha and beta) and tumor necrosis factor (TNF) were added to these cultures, only the antisera against recombinant human GM-CSF (rhGM-CSF) consistently resulted in significant inhibition of cell proliferation, achieving up to 72% inhibition of 3H-TdR incorporation in one case. Monoclonal antibodies (MoAbs) against rhGM-CSF resulted in a similar and highly significant degree of inhibition. A marked inhibitory effect of rhGM-CSF antiserum on spontaneous growth of PB CFU-GM derived colonies in semisolid medium was also demonstrated in four of five patients studied (87% to 90% inhibition). Production of growth factors by highly enriched JCML monocytes was variable. When initially studied in five of the seven patients, the monocytes from three of the patients revealed increased release of IL-1-like activities; two patients had levels similar to those of controls. One patient with normal levels when initially studied was later shown to have markedly increased amounts of IL-1-like activities in a second preparation of monocyte-conditioned medium (MCM). High levels of GM-CSF were detected in the initial MCM from one patient, but this may have indirectly reflected elevated IL-1-like activities present in the MCM. IL-3 and M-CSF levels were either low or undetectable in the patients studied as compared with MCM prepared with normal adult monocytes. These results clearly implicate GM-CSF as the primary endogenous regulator of JCML cell proliferation in culture and suggest that this malignant myeloproliferative disease may in part result from paracrine stimulation of marrow progenitor cells by growth factors/cytokines secreted by the malignant monocytes.
  7. Mant MJ, Akabutu JJ, Herbert FA. Lithium carbonate therapy in severe Felty's syndrome. Benefits, toxicity, and granulocyte function.
    AB - Lithium carbonate was administered to six patients with severe Felty's syndrome, five of whom had problems with infection. Two patients had granulocyte increments that persisted after therapy was discontinued; in one of them problems with infections resolved. In another patient a transient granulocyte rise accompanied treatment. There was no response in three patients. Granulocyte function was measured in three patients during treatment. It was normal except for subnormal hexose monophosphate shunt activity in two patients. Although serum lithium levels were less than 1.5 mmole/L, serious toxic effect occurred in one patient and significant side effects in the other five. These results support a short trial of lithium carbonate therapy in patients with severe symptomatic Felty's syndrome. Potentially beneficial granulocyte increases occur in a minority of patients only, however, and side effects and toxic effects are common. Arch Intern Med 1986 Feb;146(2):277-80
  8. Baydala LT, Yanofsky R, Akabutu J, Wenman WM. Aspergillosis of the nose and paranasal sinuses in immunocompromised children. Can Med Assoc J 1988 May 15;138(10):927-8
  9. Mant MJ, Gordon PA, Akabutu JJ. Bone marrow granulocyte reserve in chronic benign idiopathic neutropenia. Clin Lab Haematol 1987;9(3):281-8
    AB - Fifteen patients with chronic benign idiopathic neutropenia (CBIN) with neutrophil counts less than 1.0 X 10(9)/1 have been studied. The mean age was 33 years (range 23-50) comprising 11 females and 4 males. Bone marrow cellularity was normal except in two patients who showed slight reduction and one who had a slight increase. Bone marrow differential counts were normal apart from a small increase in the percentage of promyelocytes and reduction in the myeloid/erythroid ratio in some patients. Peripheral blood counts showed no 'compensatory' monocytosis. Epinephrine stimulation tests showed no evidence of excess neutrophil margination. After endotoxin administration there was a one- to two-fold increase in neutrophil counts in three patients, a three-fold increase in three patients and a greater than four-fold increase in the remaining nine patients. The findings suggest that the benign course of CBIN is not due to excess neutrophil margination nor to compensatory monocytosis, but that at least one mechanism includes a functionally adequate release of neutrophils to the peripheral blood under conditions of stress with subnormal delivery of neutrophils under basal conditions. The variability in responses to endotoxin suggests that CBIN is not entirely homogeneous with respect to mechanism. The findings of relatively normal bone marrow cellularity and differential counts and a normal or substantial neutrophil response to endotoxin appear characteristic. They may help predict a benign clinical course in neutropenic patients and assist diagnosis of the CBIN variant of idiopathic neutropenia.
  10. Akabutu JJ, Chan JR. Expansion of human umbilical cord blood CD34+ hematopoietic progenitor cells with recombinant growth factors. Prog Clin Biol Res 1994;389:399-404
  11. Choi MF, Mant MJ, Turner AR, Akabutu JJ, Aaron SL. Successful reversal of neutropenia in Felty's syndrome with recombinant granulocyte colony stimulating factor. Br J Haematol 1994 Mar;86(3):663-4
    AB - We report two patients with Felty's syndrome and chronic skin ulcers treated successfully with recombinant granulocyte colony stimulating factor (GCSF). In both cases granulocytes returned to the normal range within days of starting treatment, and their cutaneous ulcers improved. In one patient granulocytes were maintained at normal levels with a regimen of GCSF 3 micrograms/kg twice weekly for 14 months.
  12. Walker I, Pai M, Akabutu J, Ritchie B, Growe G, Poon MC, Card R, Ali K, Israels S, Teitel J, et al. The Canadian Hemophilia Registry as the basis for a national system for monitoring the use of factor concentrates. Transfusion 1995 Jul;35(7):548-51
    AB - BACKGROUND: Canada's publicly funded blood system has recently introduced high-purity concentrates as the standard treatment for individuals with hemophilia. The added cost and the need to document patient outcomes have prompted the consideration of a national blood product monitoring system. STUDY DESIGN AND METHODS: This study investigates the suitability of the Canadian Hemophilia Registry (CHR) as the basis of such a monitoring system by assessing the degree to which it represents users of factor concentrates. RESULTS: Currently, there are 1978 individuals registered with the CHR, of whom 1594 (81%) have hemophilia A and 384 (19%) have hemophilia B. The total prevalence is 7.2 per 10(5) population, with the prevalence of severe cases being 2.3 per 10(5). This overall prevalence is similar to that seen in other countries with national registries. The CHR national prevalence also compares favorably with that in the province of Quebec, where registration of users of blood products is compulsory. The CHR figures indicate that the number of persons currently infected with human immunodeficiency virus, both alive and dead, is 652, which is similar to the number of applicants (658) to the federal government's assistance program. The registry is stable, and the number of persons with severe cases, other than young children, newly registered or lost to follow-up during the last 2 years is very small. CONCLUSION: The CHR includes the vast majority of factor concentrate users and is therefore ideal as the basis for a national monitoring system.
  13. Findlay JM, Akabutu J, Johnson ES, McDonald S. Radiation-induced meningioma. J Neurosurg 1994 Mar;80(3):594-5