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Biomedical subjects

T K Bowers

Publications and source records attributed to T K Bowers.

12 recordsLinked to original sources
PubMed1983

Hyperacute pulmonary vasculitis in rabbits receiving prolonged infusions of activated complement. A possible model for triggering events in adult respiratory distress syndrome.

We have postulated a role for activated plasma complement and for stimulated granulocytes in the triggering events of the adult respiratory distress syndrome (ARDS). Because brief periods of complement activation have proved to be pale mimics of the clinical syndrome, we extended our earlier models by infusing potently activated plasma complement into rabbits over a prolonged period of time (3 h). The expected leukostasis occurred, but pulmonary dysfunction remained modest. Nonetheless, piecemeal microvascular necrosis did develop, rendering this current model more credible than former models as a mimic of triggering events in ARDS; longer-term follow-up of such animals will be necessary to determine if this is indeed the case. Perhaps of even greater interest, the neutrophilic leukostasis was observed to progress over the 3 h to a predominantly lymphocytic leukostasis, a dramatically more rapid progression than is typical of such immune complex diseases as serum sickness and the Arthus reaction; further studies are in progress to elucidate the mechanism of this lymphostasis.

Acute Disease↗
PubMed1981

Complement activation and neutropenia occurring during cardiopulmonary bypass.

Complement activation and pulmonary leukostasis with neutropenia occur in hemodialysis and filtration leukapheresis, with attendant pulmonary dysfunction. Wondering whether similar phenomena might attend cardiopulmonary bypass (CPB), we studied 34 patients undergoing coronary artery bypass operations. As in the other extracorporeal circulation systems, neutropenia (mean 44.7% +/- 4.3% SEM of prebypass PMN count) occurred during the first half hour of bypass and then a rebound neutrophilia followed. CH50 and C3H50 fell 22% to 25% (p for CH50 less than 0.01) during bypass, but C3 conversion and C5a were not demonstrable in patient plasmas. Nonetheless, polymorphonuclear neutrophils (PMNs) harvested late in bypass showed low adherence to nylon and selective chemotactic and aggregative insensitivity to C5a--functional aberrations which are seen after exposure to activated complement. Furthermore, smaller infusions of activated complement into animals produced neutropenia than were required to achieve a detectable [C5a] in the plasma. We conclude that neutropenia during CPB probably results from complement activation below the threshold of detection; complement-stimulated PMNs deserve study as possible mediators of tissue injury occurring during CPB.

Agranulocytosis↗
PubMed1980

Granulocyte aggregometry: a sensitive technique for the detection of C5a and complement activation.

We have previously shown that complement (C) activated plasma causes granulocyte (PMN) aggregation in vitro and that C5a is responsible. The C-induced aggregation of PMNs treated with cytochalasin-B (CB) is markedly enhanced and irreversible, and the magnitude of the response is proportional to the log (concentration of activated plasma), allowing use of this technique to detect C5a and hence C-activation. To compare the sensitivity of granulocyte aggregometry to that of more standard methods of detecting C-activation, we produced graded C-activation in vitro by treating fresh serum with varying amounts of zymosan. Aggregometry was the most sensitive index of C-activation, detecting C-activation, produced by 0.02 mg zymosan/ml of serum--1/10 that required to produce C-activation detectable by C3 immunoelectrophoresis (the next most sensitive technique). Granulocyte aggregometry may also be used to detect in vivo C-activation. We have found aggregating activity in plasmas from patients with systemic lupus erythematosus, immune vasculitis, transfusion reactions, and other conditions associated with in vivo C-activation, but not in the plasmas of normal subjects.

Cell Aggregation↗
PubMed1979

Therapy-related leukemia: a panmyelosis.

Fifteen patients developed acute nonlymphocytic leukemia (ANLL) 31 to 182 months following chemotherapy and/or radiotherapy for various malignancies and one non-neoplastic disorder. The ANLL was commonly heralded by a brief preleukemic phase consisting of cytopenias and a variety of morphologic abnormalities. At diagnosis of ANLL, all of the patients had a panmyelosis with variation in the predominant abnormal cell line. Neutrophilic and erythroid abnormalities were most striking in 12 of the patients, megakaryocytic abnormalities predominated in 2 and monocytic abnormalities in 1. Pancytopenia, marked anisopoikilocytosis, normoblastemia, large hypogranular platelets, hypogranular neutrophils, pseudo-Pelger-Huet nuclei, low myeloblast counts and basophilia were the most common abnormalities in the blood. Bone marrows were hypercellular with increased myeloblasts and basophils, abnormal neutrophil precursors, occasional monocytoid blasts, dyserythropoiesis with PAS positive erythroblasts, ring sideroblasts and micromegakaryocytes. All of the 7 patients who had bone marrow chromosome studies exhibited major chromosomal abnormalities. Response to anti-leukemic therapy was poor. The morphologic and clinical findings of these 15 patients appear to define a clinical-pathologic entity.

Adult↗
PubMed1978

Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage.

During hemodialysis, alternative pathway complement activation leads to pulmonary sequestration of granulocytes, with loss of pulmonary vascular endothelial integrity and, at times, protein-rich pulmonary edema. An in vitro model of this phenomenon was constructed utilizing 51Cr-labeled human umbilical vein endothelial cell cultures. In this system, granulocytes, when exposed to activated complement (C), induce endothelial damage; this injury is mediated primarily by oxygen radicals produced by the granulocytes. C5a appears to be the C component responsible for granulocyte-induced cytotoxicity; studies with cytochalasin B-treated granulocytes suggest that close approximation of the granulocytes and endothelial cells is necessary for maximal cell injury.

Blood Vessels↗
PubMed1978

Monoclonal gammopathy in hereditary spherocytosis: a possible pathogenetic relation.

Two cases of monoclonal gammopathy in patients with hereditary spherocytosis led us to consider the possible pathogenetic relation between these two disorders. Twelve adult patients with hereditary spherocytosis had significant hypergammaglobulinemia in comparison to normal subjects. Retrospective analysis of previous illness in 140 patients with multiple myeloma showed a significant association between IgA myeloma and previous gallbladder disease. We propose that the chronic reticuloendothelial stimulation due to extravascular hemolysis, possibly potentiated by the inflammation associated with cholelithiasis and cholecystitis, may foster neoplastic transformation of immunocytes in patients with hereditary spherocytosis, ultimately leading to the development of monoclonal gammopathy.

Aged↗
PubMed1978

Leukopenia in anorexia nervosa. Lack of increased risk of infection.

To determine whether patients with anorexia nervosa (AN) and leukopenia have an increased risk of infection, we reviewed the incidence of leukopenia and infection in 68 cases of AN and studied the mechanism of profound neutropenia in one. Compared with controls, patients with AN had substantially lower total leukocyte counts and absolute neutrophil, lymphocyte, and monocyte counts. Despite frequent and often severe panleukopenia, the patients with AN had no more infections than did the control subjects. The patient with severe neutropenia ahd a hypocellular bone marrow biopsy specimen showing relative myeloid hyperplasia, normal distribution of neutrophils between the marginal and circulating pools, and normal bone marrow neutrophil reserves as estimated by response to hydrocortisone sodium succinate. We conclude that patients uith AN and associated leukopenia do not have increased infection propensity.

Adolescent↗
PubMed1977

Familial Hodgkin's disease and the major histocompatibility complex.

Two sisters who developed nodular sclerosis Hodgkin's disease (H.D., N.S.) within 3 months of their 25th birthdays were HLA and MLC identical. All family members possessed the HLA-B7 antigen. The propositi, a third HLA/MLC identical sister, and the mother, shared the maternal B7 and lacked Dw2. The father and a fourth sibling with the paternal B7 were heterozygous for Dw2. In six unrelated patients with H.D., N.S., the presence of B7 and Dw2 correlated precisely. In 69 consecutive patients with H.D., N.S., the frequencies of 23 HLA antigens did not differ significantly from the frequencies in 245 control subjects.

Adult↗
PubMed1977

Acquired granulocyte abnormality during drug allergic reactions: possible role of complement activation.

A profound defect in granulocyte chemotaxis was documented in an otherwise healthy 21-yr-old man who failed to localize granulocytes to an area of cellulitis during an allergic reaction to cephalothin. During the period of drug allergy, characterized by urticaria, eosinophilia, and profound hypocomplementemia, in vitro migration of the patient's granulocytes in the Boyden chamber was markedly impaired. Although devoid of hemolytic complement activity, the patient's serum possessed supranormal chemotactic activity, even following heat inactivation, suggesting the presence of chemotactically active complement split products. Chemotactic function improved concomitantly with steroid therapy and normalization of serum complement levels, and was entirely normal following clinical recovery and cessation of steroid therapy. The chemotactic abnormality noted in the patient's cells was reproduced in normal granulocytes by preincubation either with patient serum or with cobra venom-activated fresh (but not heated) normal serum, suggesting that in vivo exposure of granulocytes to activated complement was responsible for the patient's abnormal chemotactic response. This mechanism may contribute to the increased infection propensity noted in other conditions characterized by in vivo complement activation, such as rheumatoid arthritis and systemic lupus erythematosis.

Adult↗
PubMed1977

Postsurgical granulocyte dysfunction: studies in healthy kidney donors.

In order to determine whether surgical trauma affects granulocyte function, we performed sequential studies of granulocyte phagocytic and bactericidal function, chemotaxis, and adherence on 25 otherwise healthy subjects undergoing donor nephrectomy for kidney transplantation. All values were normal prior to surgery, and bacterial killing and phagocytosis were unaffected by surgery. Granulocyte chemotaxis and adherence were significantly impaired immediately following surgery, returning to normal in 24 hr. Anesthesia alone did not affect chemotaxis. Generation of chemoattractants from postoperative plasma was normal, and inhibitors of chemotaxis could not be demonstrated, suggesting an intrinsic cellular defect. We suggest that these postoperative abnormalities of granulocyte chemotaxis and adherence may contribute to the high incidence of infectious complications following surgery.

Cell Adhesion↗