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Biomedical subjects

J McCullough

Publications and source records attributed to J McCullough.

At least 145 records · Page 8Linked to original sources
PubMed1984

Role of the blood bank in bone marrow transplantation.

The wide variety of special blood components, special procedures, increased red blood cell serologic testing, the complexity of ABO and Rh type changes, difficulty in selecting the correct ABO and Rh type of component, and necessity to irradiate all blood and components for these patients present a challenge to the internal operation of the blood bank. Although the blood transfusion supportive care required by bone marrow transplant patients is complex, it also opens many new and exciting possibilities for blood bank activities, and presents many opportunities to better understand the basic nature and clinical relevance of blood groups.

ABO Blood-Group System↗
PubMed1983

Antibody-dependent lymphocyte-mediated granulocytotoxicity (ADLG) for the detection of granulocyte antibodies.

An antibody-dependent cell-mediated granulocytotoxic assay (ADLG) has been developed to detect antibodies to human granulocytes. This study examines some possible variables in this assay, the ADLG activity in serum from normal individuals, the contribution of ABO isohemagglutinins and the sensitivity and specificity of this technique. Significant differences in percentage cytotoxicity of ABO compatible and incompatible cell/serum combinations were detected in the normal population. Human serum with antibodies to the neutrophil specific antigens NA1 and NB1 gave positive results in the ADLG assay. However, differences in sensitivity and specificity were observed among various sera. ADLG activity was dependent on the source of effector cells. Effector and target cells stored in vitro were unsatisfactory in this assay. The ADLG assay may be a valuable addition to existing granulocyte serological methods and provide useful clinical information on mechanisms of immune neutropenias.

ABO Blood-Group System↗
PubMed1983

An improved technique for separating rosetted from non-rosetted lymphocytes.

An improved technique for separating rosetted from non-rosetted lymphocytes is described. The major advantage of this new technique is the elimination of the need to mechanically resuspend the cell pellet resulting from the rosette formation step before using a density gradient to separate the rosetted from the non-rosetted cells. Instead the rosette containing cell pellet is directly overlayed with Percoll at a density of 1.078 g/ml and during a subsequent centrifugation the non-rosetted cells float to the surface of the Percoll while the rosetted cells remain in the cell pellet. The utility of this technique is illustrated by separating human T lymphocytes forming rosettes with neuraminidase treated sheep erythrocytes (En) from other mononuclear cells obtained by Ficoll-Hypaque separation of whole blood. Using several markers the resulting T cells were contaminated with less than 0.3% monocytes and 2% B cells. The non-T cell population contained less than 3% T cells. This method offers a rapid and easily reproducible means for obtaining highly purified cell populations.

Antibodies, Monoclonal↗
PubMed1983

Granulocyte antigen systems and antibodies and their clinical significance.

Granulocyte alloantibodies and autoantibodies have a key role in the pathophysiology of several clinical problems. These include febrile transfusion reactions, severe pulmonary reactions to transfusion, isoimmune neonatal neutropenia, failure of effective granulocyte transfusion, autoimmune neutropenia, drug-induced neutropenia, and neutropenias secondary to many other diseases. Although many techniques are available for detecting granulocyte antibodies, the optimal in-vitro tests for predicting the antibodies' clinical effects are not established. Use of indium-111-labeled granulocytes may provide valuable information regarding the in-vivo effects of different granulocyte antibodies. Granulocyte transfusions continue to be used for a limited number of severely infected neutropenic patients who do not respond to antibiotic therapy.

Antibodies↗
PubMed1983

Steroid modulation of naturally occurring diurnal variation in circulating pluripotential haematopoietic cells (CFU-GEMM).

The number of committed granulocyte-monocyte precursors (CFU-GM) in circulation has been shown to increase following steroid administration in humans. To see if steroids could be used to improve the collection of peripheral blood stem cells for haematopoietic reconstitution, their effect on circulating CFU-GEMM was investigated. Six healthy young adults, three men and three women, were given 60 mg of prednisone orally at 8 a.m. on day 1. Blood CFU-GEMM and committed precursors (CFU-GM and BFU-E) were cultured in methylcellulose. Samples were taken at 4 p.m. the day before and at 8 a.m. on the day of steroid administration, and at 4, 8, 24 and, in a few cases, 48 h after steroid. Pre-treatment CFU-GEMM levels (per unit volume of blood) at 4 p.m. was 180 +/- 23% (mean +/- SEM) of that at 8 a.m., showing a significant (P less than 0.025) diurnal variation. 8 h after steroids there was a fall in CFU-GEMM to 28 +/- 4.5% of the 8 a.m. presteroid level. 24 h following steroid administration, CFU-GEMM rose significantly (P less than 0.05) to 188 +/- 33% of 8 a.m. baseline values; CFU-GM and BFU-E changes generally paralleled those noted for CFU-GEMM. These results suggest that blood levels of CFU-GEMM exhibit a significant diurnal variation. Oral prednisone given 24 h in advance of collection increases the 8 a.m. value to that found at 4 p.m. The steroid effect may be due to a resetting of the diurnal control mechanism. Use of this information may be important in collection of circulating haematopoietic stem cells for use in bone marrow reconstitution in man.

Adult↗
PubMed1983

Severe delayed hemolytic transfusion reaction complicating an ABO-incompatible bone marrow transplantation.

A 26-year-old, blood group O bone marrow transplant recipient experienced a severe, delayed hemolytic transfusion reaction 6 days following transplantation of marrow from his HLA-mixed lymphocyte culture - identical, blood group AB sister. The patient's pretransplant serum contained both anti-A (IgG titer = 1:128; IgM = 1:32) and anti-B (IgG = 1:16; IgM = 1:64) which was reduced by a two-plasma volume plasma exchange followed by transfusion of four units of incompatible, donor type red cells. The patient experienced no immediate adverse reaction. On the 6th posttransplant day, he became acutely dyspneic. His hematocrit dropped to 18%; the direct antiglobulin test was positive for IgG and complement; anti-A and anti-B were eluted from his red cells. His peripheral blood smear demonstrated extensive agglutination resembling a mixed field reaction. This case demonstrates that significant morbidity may be associated with major ABO-incompatible bone marrow transplantation, that the transfusion of incompatible red cells should be undertaken with extreme caution, and that efforts should be continued to develop methods of pretransplant in vitro red cell removal from the infused bone marrow.

ABO Blood-Group System↗
PubMed1982

Collection of pluripotential hematopoietic stem cells by cytapheresis.

Successful complete hematopoietic reconstitution (CHR) using nonleukemic peripheral stem cells (PSC) after marrow ablation has been reported in animals but not man. Previous studies of cytapheresis products from humans, as a prelude to use for CHR, have documented the presence of committed myeloid (CFU-GM) and erythroid (BFU-E) precursors. We have examined mononuclear cell (MNC) products collected on the Fenwal CS3000 Blood Cell Separator for these plus the more primitive mixed (granulo-, erythro-, mono-, and megakaryocytic) cell colony-forming units (CFU-GEMM) and for various lymphocytic subpopulations (LSP). One to two-hour products contained 36 +/- 7 CFU-GEMM/10(6) MNC (mean +/- SE, n = 8) or 490 +/- 131/ml product. This compared favorably with blood (23 +/- .4/10(6) MNC or 46 +/- 8/ml, n = 14) and bone marrow (146 +/- 58/10(6) MNC, n = 12). Collection efficiency for E-rosette-positive cells approximated that for total lymphocytes and was variable for other LSP. Recovery of CFU-GEMM after freezing in 10% dimethylsulfoxide at a controlled rate and storage in liquid N2 was 54% +/- 8% (n = 8). Cytapheresis collection of large numbers of pluripotent hematopoietic precursors and demonstration of adequate recovery of these after cryopreservation, both previously unreported, are significant steps toward eventual CHR using nonleukemic PSC.

Blood Preservation↗
PubMed1981

A controlled trial of prophylactic granulocyte transfusions during initial induction chemotherapy for acute myelogenous leukemia.

To evaluate the role of prophylactic granulocyte transfusions during remission-induction chemotherapy for acute myelogenous leukemia (AML) we randomized 102 infected patients either to receive daily granulocyte transfusions when blood granulocytes fell below 0.5 x 10(9) per liter (54 patients) or not to receive them (48). Although the percentage of patients acquiring any infection was similar in the transfusion and control groups (46 and 42 per cent, respectively), granulocyte transfusions decreased the proportion of patients with bacterial septicemia (9 per cent of those with transfusions vs. 27 per cent of the controls; P = 0.01). Granulocyte transfusions did not reduce the incidence of other infections or improve bone-marrow recovery, remission rate and duration, or survival. Seventy-two per cent of the patients given transfusions had transfusion reactions. Pulmonary infiltrates were more common in the transfusion group than in the control group (57 per cent vs. 27 per cent; P = 0.002). Thirty-five per cent of the patients with pulmonary filtrates died, as compared with 5 per cent of those without filtrates. We conclude that prophylactic granulocyte transfusions should not be used during remission-induction chemotherapy in AML because the risks outweigh the benefits.

Bacterial Infections↗
PubMed1981

Application of marketing principles to improve participation in public health program.

The application of marketing principles to develop a program aimed at increasing participation in a cervical screening program appears to be more effective than the use of sales techniques. Standard methods of promotion such as posters, direct mail, and flyers were generally ineffective. Direct personal contact produced the majority of program participants, and mass media approaches also resulted in significant participant response. A consumer orientation led to development of effective program features designed to satisfy specific consumer needs. Use of female health practitioners, for example, reduced cultural barriers to participation and insured adequate screening in Mexican-American populations.

Adult↗
PubMed1981

Successful engraftment of NA1 positive bone marrow in a patient with a neutrophil antibody, anti-NA1.

An 11-yr, 9-mo-old girl with a 5-hr history of severe aplastic anemia unresponsive to androgen or steroid therapy was treated a bone marrow transplant from her 7-yr-old, HLA-MLC identical, APO incompatible, male sibling. Donor neutrophils were positive for the NA1 antigen. The patient's pretransplant serum contained a neutrophil specific antibody, anti-NA1, reactive against donor neutrophils, which was demonstrable by both granulocyte agglutination and granulocyte cytotoxicity assays. The transplant preparative regimen consisted of cyclophosphamide, 50 mg/kg/day for 4 days, and total lymphoid irradiation (750 rads, 26 rads/min by 4 meV linear accelerator). A two plasma volume exchange (4,800 ml) by continuous flow centrifugation with an Aminco cell separator was performed one day prior to transplant because of ABO incompatibility. Following plasma exchange, anti-NA1 cytotoxic titer, 1:8 preexchange, was no longer detectable; anti-NA1 agglutinating titer had only decreased from 1:64 to 1:32. She experienced no adverse reaction to transplantation of 4:8 X 10(8) nucleated cells/kg. Marrow engraftment was demonstrable by Day 14 by steadily increasing leukocyte and platelet counts, red cells of donor ABO group, and bone marrow chromosomes showing a normal male, 46 XY karyotype. This case of successful bone marrow engraftment without delayed neutrophil recovery in the presence of a neutrophil specific antibody NA1 suggest that neutrophil specific antigens are not functionally present on the pluripotent stem cell. Histoincompatibility for neutrophil specific determinants need not eliminate the possibility of bone marrow transplantation for aplastic anemia between siblings identical for the major histocompatibility loci.

Agglutination Tests↗
PubMed1981

In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients.

Indium-111-labeled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labeling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111-leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients.

Adolescent↗
PubMed1981

Effects of temperature and duration of storage on granulocyte adhesion, spreading, and ultrastructure.

The effects of storage duration and temperature on granulocyte adhesion, spreading, and ultrastructure were examined. Normal adherence and spreading of granulocytes detected by either phase contrast or scanning electron microscopy was maintained for up to 48 hours when granulocytes were stored at 20 to 24 degrees C. By contrast, storage of granulocytes for 24 hours at 1 to 6 degrees C. led to a substantial decrease in granulocyte adherence and spreading. When granulocytes were stored for 24 hours at 1 to 6 degrees C. and then shifted to 20 to 24 degrees C. for a second 24 hours, granulocytes failed to regain the normal adherence and spreading. The cytoskeleton has been implicated in cell morphology, movement, chemotaxis, and spreading of cells. Transmission electron microscopy of thin sections of whole cells or cytoskeleton preparations revealed a well-organized system of microtubules and microfilaments in granulocytes stored for up to 48 hours at 20 to 24 degrees C. In granulocytes stored at 0 to 6 degrees C. that have the decreased adhesion and spreading, there is a paucity of microtubules, and the microfilaments have a disorganized criss-crossed appearance when compared with normal cells. It appears that storage of granulocytes at reduced temperatures is associated with decreased adhesion and spreading, and a concomitant alteration in the cytoskeleton may be responsible for this.

Blood Preservation↗
PubMed1981

Effect of leukocyte antibodies on the fate in vivo of indium-111-labeled granulocytes.

The effect of different leukocyte antibodies on the fate in vivo of granulocytes is not known. Thus, the optimum in vitro serologic tests to determine a safe and effective granulocyte transfusion or to diagnose immune destruction of granulocytes in other clinical situations have not been identified. We have studied the effect of granulocyte agglutinating (GA), granulocytotoxic (GC), and lymphocytotoxic (LC) antibodies on the intravascular recovery and half-life (t 1/2) and the extravascular localization of Indium-111-granulocytes in 50 patients. GA antibodies caused reduced granulocyte recovery and t 1/2 in three of three non-neutropenic patients (one with anti-NB1), increased sequestration of cells in the liver, and failure of granulocytes to localize at sites of infection in two of two patients (one with anti-NA1). In contrast, GC antibodies in five patients and LC antibodies in one patient did not cause reduced intravascular recovery or t 1/2 of granulocytes. In nine patients with GC and six patients with LC antibodies, incompatible granulocytes localized at known sites of infection. It appears that GA, but not GC nor LC, antibodies alter the fate in vivo of granulocytes.

Agglutination Tests↗
PubMed1980

Hematology.

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Blood Preservation↗