Alloimmunization by blood group antigens from bone allografts.

The purpose of this report is to heighten awareness of the risk of blood group antigen sensitization following hone allografting. Two Rh-negative females of childbearing age developed multiple antibodies to Rh antigens following transplantation of bone from Rh-positive donors. A previous pregnancy and/or blood transfusions were ruled out as factors influencing the antibody production. It is postulated that red cells or red cell stroma in the allografts stimulated the antibody production. Therefore, young, Rh-negative bone allograft recipients at risk (especially women) should receive Rh-negative bone allografts. Alternatively, they should receive Rh immune globulin at the time of transplanting if the allograft is from an Rh-positive donor. Bone allografts processed to deplete the hemopoietic marrow and red cells should minimize the risk of blood group antibody sensitization.

Partially purified bacteriocin kills malignant cells by apoptosis: programmed cell death.

Bacterial proteins, partially purified bacteriocin (PPB), were investigated for their selective killing of malignant cells. It is shown here that upon PPB-cell interaction DNA fragmentation starts within one hour and peaks at 6 hrs. This process requires an on-going cellular metabolism. It is prevented by both actinomycin D, a DNA dependent RNA synthesis inhibitor, and cycloheximide, a protein synthesis inhibitor. We show here that the DNA fragmentation is triggered by PPB-cell membrane-receptor interaction which signals the activation of endogenous cellular endonucleases rather than actually penetrating the cell and interacting directly with the DNA, or serving as a nuclease itself. Thus, it is suggested that the cell death initiated by the lethal bacterial proteins, PPB, is a programmed, step-wise cell death involving apoptosis.

Fluorescence assay to monitor phagocytosis by blood-clot derived polymorphonuclear leucocytes. 1. Study of patients with diabetes and phagocytosis of different staphylococcal species.

A recently developed simple and rapid fluorescence assay of phagocytosis by polymorphonuclear leucocytes (PMNs) was used to compare the phagocytic activity of PMNs from diabetic patients and healthy people. Differences in phagocytosis have been described in these systems. Different bacterial strains were used to challenge the phagocytic capabilities of bacterial ingestion and killing for both patient and control groups. Staphylococcus epidermidis derived from clinical isolates was prone to faster ingestion and more rapid killing once the bacteria were intracellular, compared with S. epidermidis derived from normal skin. The pathogen, S. aureus, though ingested rapidly, was not so easily killed. PMNs from diabetics appeared to ingest S. aureus and kill ingested pathogenic bacteria not as effectively as PMNs from healthy volunteers. These difference were not found for non-pathogenic skin isolates of S. epidermidis.

Fluorescence assay to monitor phagocytosis by bloodclot derived polymorphonuclear leucocytes. 2. Study of patients with psoriasis and the effect of exposing leucocytes to psoriatic skin scales.

Comparisons of phagocytic parameters were carried out by a recently developed fluorescence test which is reproducible, simple and fast. Phagocytosis by polymorphonuclear leucocytes (PMNs) obtained from patients with psoriasis was compared with that of healthy individuals. Psoriatic skin scales, non-sterile and sterile, were tested for stimulatory effect on PMNs and compared with the effect of normal skin scrapings. Results confirm enhanced phagocytosis of bacteria by PMNs from patients with psoriasis over that of PMNs from healthy volunteers. Furthermore, the supernatant fluid from suspensions of psoriatic skin scales, non-sterile and sterile, stimulated PMNs activity.

Transfusion-induced specific anti-factor XI inhibitor in a patient with previously unrecognized factor XI deficiency.

This article reports the rare occurrence and investigation of a specific anti-factor XI inhibitor that arose after fresh-frozen plasma infusion into a patient with previously unrecognized Factor XI deficiency. The IgG fraction of the patient's plasma that contained anti-Factor XI antibody was isolated by chromatography on DEAE-Affigel and concentrated. It was shown to exert inhibitory effect on purified Factor XI and XIa both in the activated and nonactivated partial thromboplastin time assay.

Factor XI deficiency presenting as hemarthrosis during pregnancy.

This report describes events and findings in a pregnant patient with factor XI deficiency who suffered at least one episode of hemarthrosis. The incidence and rarity of this complication are discussed and views on management expressed.

Acute lymphoblastic leukemia of childhood monitored by bacteriocin and flowcytometry.

Bacteriocin and flowcytometric analysis of 106 blood samples from children with acute lymphoblastic leukemia were correlated with clinical stages of disease. Bacteriocins interacted selectively with malignant, and not with normal, lymphocytes causing cell cycle perturbation which was rapidly and objectively recorded by the flowcytometer. The patients were grouped as: (A) newly-diagnosed (15); (B) early induction (11); (C) remission with viral infection (7); (D) remission (64); (E) bone marrow relapsed (5); (F) extramedullary relapsed (3); (G) non-malignant pediatric controls (8). Bacteriocin reacted usually with groups A, B, C, E and not with groups D, F and G. Repeated testing correlated well with the clinical status. Blood from 7 patients in remission and from 3 normal individuals, each with transient viral infection, reacted with bacteriocin. A quantitative correlation between peripheral blood blasts or surface markers for ALL and bacteriocin reactivity was not established. Unexpected results were obtained only in 13% (false-positive 11% and false-negative 3%). This test can be recommended for preliminary diagnosis and possibly prognosis of lymphoblastic leukemia and provides means of monitoring progress during chemotherapy.

The factor of factor XI deficiency in thyroid neoplasia.

Forty-three patients with factor XI deficiency detected by prolonged partial thromboplastin times were reviewed over an 11-year period. They were predominantly Ashkenazim--18 men and 25 women--ranging in age from 20 to 92 years. Thirteen patients had a history of bleeding, and eight had a family history of factor XI deficiency. Six patients with thyroid disease with four significant tumors were found for a 9% incidence of associated neoplasia. These consisted of two adenomas and two papillary-mixed cancers in two men distinguished by an aggressive course by virtue of extensive nodal disease, local recurrence, and systemic metastases in whom factor XI was profoundly decreased. It would appear that there is an undue association of factor XI deficiency and thyroid neoplasia suggestive of a shared genetic disturbance. These cases illustrate the benefit of routine preoperative coagulopathy screening by use of prothrombin time, partial thromboplastin time, and platelet counts. Factor XI deficiency is an infrequent cause of excessive bleeding, and the operative morbidity of surgical management of affected individuals can be avoided by the use of fresh-frozen plasma before and after surgery.

DNA histogram of parathyroid tissue in determining extent of parathyroidectomy.

In an attempt to better define hyperplasia from adenoma and for more accurate discernment of grossly normal but histologically abnormal presumed hyperfunctioning gland, parathyroid tissue obtained at operation was subjected to flow cytometric analysis producing DNA histogram. Seventeen abnormal specimens and seven normal specimens obtained from parathyroidectomy cases were placed in RPMI 1640 culture medium, treated to produce a monodispersed cell suspension, and stained with propidium iodide fluorescent dye to provide a measure of DNA content that could be graphically demonstrated. All cell cycles for affected cell populations could be demonstrated on DNA histogram in the G0G1, S, and G2M phases. Proliferative index was arbitrarily derived by combining percentages of G2M plus S phases. It was apparent that the value so derived showed a tendency for higher value for the abnormal parathyroid tissue but the overlap was sufficient so that no specific discriminating value could be placed on DNA histogram. While flow cytometry may not be of significant use in intraoperative identification of abnormal parathyroid tissue, the values obtained may indicate that a spectrum of activity occurs in hyperparathyroidism that cannot be fully appreciated at the present time and that may in the light of incomplete knowledge manifest itself in the clinical state of hyperparathyroidism and hypercalcemia. The findings of our flow cytometry study may indeed lend credence to the view that all hyperparathyroidism represents a four-gland hyperfunction although this does not support as a consequence routine subtotal parathyroidectomy but should stimulate further inquiry into the pathogenesis of primary hyperparathyroidism.

Multiple antibody formation in a primigravida: anti-D, anti-C, anti-Kpb.

A case of primigravida in whom anti-C, anti-D, and anti-Kpb developed during the third trimester is described. Her first-born infant, delivered at 40 weeks' gestation, was mildly affected with hemolytic disease of the newborn and responded well to phototherapy. Her second-born infant, delivered at 36 weeks' gestation, had a positive direct antiglobulin test, but required no treatment. Clinical and laboratory aspects of both pregnancies are discussed.

Pulmonary leukostasis and its relationship to pulmonary dysfunction in sheep and rabbits.

Pulmonary leukostasis, as a result of complement activation, has been invoked as a cause of pulmonary dysfunction. To investigate this phenomenon, we studied the pulmonary response to infusion of autologous complement-activated plasma in sheep and rabbits. Complement activation was produced by plasma incubation with zymosan. Leukopenia, with selective loss of polymorphonuclear leukocytes into the lungs, occurred in all animals immediately after the onset of plasma infusion. Complement-activated plasma infusion in sheep produced a significant fall in the arterial PO2 and a marked rise in pulmonary vascular resistance, whereas no such effects were observed in rabbits. Pretreatment of the sheep with sulfinpyrazone eliminated the pulmonary response to complement-activated plasma without altering the leukopenic response. Pulmonary histology in rabbits and sheep confirmed the presence of intracapillary leukostasis after the plasma infusions, whether or not sulfinpyrazone had been administered previously. The pulmonary response to complement activation is associated with pulmonary capillary leukostasis, but leukostasis alone is not an adequate explanation of the phenomenon.

Platelet satellitism--an ultrastructural study.

Ultrastructural studies by scanning and transmission electron microscopy were carried out on one of four cases of platelet satellitism. Adherence to the neutrophils was mainly by focal contact between small surface projections of the platelets and neutrophils. Phagocytosis was not seen with the neutrophils but was evident in the monocytes. The degree of satellitism noted increased with the time the blood anticoagulated with EDTA was left at room temperature. Mixing experiments with a patient's plasma and control cells and the patient's cells and control plasma were inconclusive but suggested that the abnormality may reside in the plasma.