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Biomedical subjects

K Atkinson

Publications and source records attributed to K Atkinson.

At least 199 records · Page 11Linked to original sources

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression.

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.

Antilymphocyte Serum

Yeast mutant defective in phosphatidylserine synthesis.

Phospholipid biosynthesis in a mutant of Saccharomyces cerevisiae (cho1) which lacks phosphatidylserine (Atkinson, K. D., Jensen, B., Storm, E., Kolat, A. I., Henry, S. A. & Fogel, S. (1980) J. Bacteriol. 141, 558-564) has been examined. The ability of cells of this strain to synthesize phosphatidylserine in vitro in a cell-free system is reduced at least 10-fold, whereas other phospholipid-synthesizing activities are present at normal or slightly elevated levels. While all phospholipid biosynthetic activities, except phosphatidylserine synthesis, can be demonstrated in vitro in the cho1 mutant, the entire pattern of phospholipid synthesis, accumulation, and turnover in vivo is distorted. Phosphatidylinositol synthesis is elevated, as is phosphatidylcholine synthesis. In addition, the turnover of phosphatidylcholine is more rapid in the cho1 mutant. The cho1 mutant appears to use almost exclusively the alternative pathway described by Kennedy and Weiss (1956) J. Biol. Chem. 222, 193-214) for the production of phosphatidylethanolamine and phosphatidylcholine, bypassing phosphatidylserine as an intermediate.

Ethanolamines

Varicella-zoster virus infection after marrow transplantation for aplastic anemia or leukemia.

Nearly one-half of marrow transplant recipients who survive at least 6 months develop varicella-zoster virus (VZV) infection. Of 92 cases studied, 82 occurred within the first 12 months after transplant. Only one patient had recurrent infection. Seventy-seven patients had herpes zoster, 22 with subsequent cutaneous dissemination, and 15 had varicella. The overall mortality rate was 8%, and all deaths occurred within 9 months of transplant. Twenty-six of 32 patients studied had significant rises in VZV antibody during recovery. Among patients with acute leukemia, those with syngeneic transplants had a significantly lower incidence of VZV infection than those with allogeneic transplants. Incidence was slightly, but not significantly, decreased among patients with aplastic anemia. In contrast to other infections, the incidence of VZV infection was not influenced by graft-versus-host disease or predicted by the results of dinitrochlorobenzene skin testing.

Adolescent

Recurrent reproductive failure due to severe placental villitis of unknown etiology.

A case is reported of recurrent reproductive failure due to a severe placental villitis of unknow etiology. Five successive pregnancies ended in four unexpected third-trimester deaths in utero and one live birth at 37 weeks' gestation. This infant of the fourth pregnancy showed severe intrauterine growth retardation but no other stigmata of chronic infection. The placentas of the last three pregnancies showed marked focal chronic parenchymal inflammation with widespread necrosis, villous vasculitis and a lymphocytic deciduitis of the maternal floor. Microbiologic, serologic and electron microscopic techniques variously employed on maternal, fetal and placental specimens failed to demonstrate a possible causative agent although the placental inflammatory pattern was strongly suggestive of recurrent infection.

Adult

Erythroid colony stimulating and inhibiting cells in peripheral blood of transfused dogs: separation of function by velocity sedimentation.

We have previously shown that the addition of normal dog peripheral blood lymphocytes (PBL) to cultures of allogeneic marrow increases the number of marrow-derived erythroid colonies (EC), but that PBL from transfused dogs usually inhibit EC growth from marrow of the transfusion donor. In this study, the cells in normal dog PBL responsible for stimulating EC growth were shown to sediment in a narrow peak at 4.30 mm/hr. A similar population of stimulating cells exists in transfused dogs and can be separated, on the basis of size, from cells that inhibit EC growth. EC-stimulating cells from transfused dog PBL sediment at 3.3--5.0 mm/hr, while cells responsible for inhibition are larger and sediment more rapidly at 5.4--8.1 mm/hr. These data demonstrate that cells capable of stimulating allogeneic EC are present in transfused dogs, but their stimulating ability is masked by the presence of EC-inhibiting cells. Thus, coculture experiments designed to test lymphocyte/marrow cell interactions may miss significant but opposing effects if unfractionated cells are used.

Animals

Deposition of IgM and complement at the dermoepidermal junction in acute and chronic cutaneous graft-vs-host disease in man.

The presence of cutaneous immunoglobulin and complement was investigated in 88 patients with and without graft-vs-host disease (GVHD) after transplantation of bone marrow from HLA identical siblings for the treatment of acute leukemia or aplastic anemia. For comparison, skin biopsies from the patients obtained before transplantation, from 58 healthy individuals (mostly marrow donors) and from four syngeneic marrow recipients were studied. A direct immunfluorescent staining technique was used. Dermo-epidermal IgM deposits were found in 11% of healthy individuals and patients before grafting but were present in 86% of patients with chronic and 39% of patients with acute GVHD. Patients with allogeneic grafts who never had GVHD or who had recovered from it and patients with syngeneic grafts showed findings not different from those in healthy individuals. Findings similar to those with IgM, although less striking, were made for C3, i.e., patients who had chronic or acute GVHD had a high incidence and intensity of C3 deposits at the dermo-epidermal junction. This observation raises the possibility that humoral immunity is involved in the development of GVHD.

Acute Disease

Alcohol pain in Hodgkin's disease.

Thirty-five patients with Hodgkin's disease experienced alcohol pain. Nodular sclerosis was the predominant histological grade (77%). Alcohol pain was associated with other factors generally considered to indicate an unfavorable prognosis--systemic symptoms, Stage II disease with multiple site involvement, Stage III or IV disease. Enlargment and a rise in temperature of lymph nodes were both present at or appeared at the site of pain in the majority (86%) of patients with this symptom.

Ethanol

Meningeal leukemia after blastic transformation of chronic myeloid leukemia.

In two patients with blastic transformation of chronic myeloid leukemia complete remission was induced, but meningeal leukemia subsequently developed. The recognition of blast cell crisis as the presenting feature of chronic myeloid leukemia is discussed, together with treatment of this condition and its rare complication, meningeal leukemia. The development of meningeal leukemia in this disease is almost certainly due to the increased survival that has been produced by advances in therapy for blastic transformation.

Adult

The results of radiotherapy for Hodgkins' disease.

The results of radiation therapy in 212 patients with stages I and II Hodgkin's disease treated between 1963 and 1973 show that approximately 60% remain disease-free following treatment. Multiple node involvement in stage II, particularly associated with infraclavicular node disease, is identified as a group where the relapse rate is high. This presentation is associated particularly with NS. In a group of 78 patients treated with radiotherapy following staging laparotomy and splenectomy approximately 80% remain in complete remission. The preliminary results of treatment in PS IIIa patients are substantially the same as those for PS I and II; the results of treatment for NS and MC disease are similar. The significance of involvement of the spleen is discussed. Although it is probable that Hodgkin's disease spreads to the spleen through the blood stream it is suggested that splenic involvement does not necessarily indicate that the involvement of other extralymphatic structures such as liver and marrow has occurred. However, when the nodes in the porta hepatis are involved splenic Hodgkin's disease may well be associated with an increased risk of occult hepatic infiltration.

Female