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Biomedical subjects

J McCullough

Publications and source records attributed to J McCullough.

At least 127 records · Page 7Linked to original sources
PubMed1987

The failure of neonates to form red blood cell alloantibodies in response to multiple transfusions.

Red blood cell alloantibody production was studied in 90 neonates who received a mean of 14.1 transfusions (range 2-35) from an average of 8.9 donors during the first three months after birth. Standard antibody detection procedures were done with the use of a selected red blood cell panel. No unexpected alloantibodies were detected. These findings suggest, at a 99% confidence level, that neonates do not make red blood cell alloantibodies in response to transfusion, indicating that repeated compatibility testing is probably unnecessary. Thus, following initial antibody screening and compatibility tests, further compatibility testing can be eliminated.

Antibody Formation↗
PubMed1987

Natural history of primary autoimmune neutropenia in infancy.

Five patients with primary autoimmune neutropenia were evaluated during their first 2 years of life. Their illness resolved spontaneously after 6 to 41 months (median 13 months), and the patients were subsequently followed for 13 to 73 months (median 28 months). None required immunosuppressive therapy to induce remission, and routine antibiotic therapy adequately controlled all infectious episodes. An increased rate of infection, particularly otitis media and upper respiratory tract infection, occurred during the neutropenic period. No other noninfectious illnesses, particularly no other autoimmune diseases, were reported in any of these patients at any time. In each case, resolution of neutropenia paralleled the disappearance of neutrophil autoantibodies which were specific for the NA1 antigen. This report describes the clinical and laboratory findings and the long-term history of primary autoimmune neutropenia in these five patients.

Agranulocytosis↗
PubMed1987

Unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia.

Eight patients received allogeneic bone marrow transplantation (BMT) as therapy for chronic myelogenous leukemia (CML) using marrow from unrelated donors. In all cases donors and recipients were HLA DR identical and had low MLC reactivity. In three cases recipients received marrow that was identical at the HLA A,B loci. In five cases HLA identity differed for one HLA A locus antigen. The unrelated donor search interval ranged from 2 to 28 months (median, 3 months). All recipients were prepared with a combination of cyclophosphamide, 60 mg/kg/d administered intravenously (IV) (days -6,-5) and with total body irradiation administered in 165 cGy fractions twice daily for four days (days -4, -3, -2, -1). Engraftment occurred in all cases (range, 18 to 48 days; median, 35 days), and return to a complete Philadelphia chromosome (Ph') negative state was documented in six of eight cases. Moderate or severe acute graft v host disease (GVHD) occurred in seven of eight cases, and extensive chronic GVHD in four of six evaluable recipients. A B cell lymphoproliferative disorder developed in one patient. Four recipients have died within 2 to 4 months of transplant. Four of eight patients survive at 11+ to 24+ months following transplantation (median, 15+ months) with normal peripheral blood counts and without evidence of leukemia. Current Karnofsky activity assessments are 90% or 100% in all survivors. Curative therapy of CML has been available only to the minority of patients eligible for sibling donor BMT. Unrelated donor BMT can be effective in the treatment of CML and may be particularly useful in this disorder since the prolonged stable phase of disease offers an opportunity to locate suitable donors.

B-Lymphocytes↗
PubMed1986

Three sera defining a new granulocyte-monocyte-T-lymphocyte antigen.

Three sera containing antibodies recognizing a previously undescribed antigen on granulocytes were found during testing of sera from multiparous donors. All of the antibody producers were in good health. None had a history of transfusion. Using the granulocyte agglutination assay the sera recognize a single antigen which is not associated with the neutrophil antigens NA1, NA2, NB1, NC1, ND1, NE1, 5a, 5b, 9a, nor common red blood cell or HLA antigens. The three sera did not react with autologous cells or with the cells of the other antibody producers. Granulocytes from one antibody producer did not absorb antibody activity from any of the three sera. The antigen was found in large quantities on granulocytes and monocytes, in smaller quantities on T lymphocytes, and not on B lymphocytes, red cells, and platelets. The sera reacted with 340 of 343 random donors (99.1%) and were negative with the same donor cells. Family studies showed autosomal dominant inheritance of the antigen. Five of 12 sibs in three families lacked this antigen (not statistically different from the expected ratio). The calculated gene frequency for the gene controlling the production of this antigen is 0.906. There appeared to be no association to the HLA, NA or Rh loci or to the X or Y chromosomes. None of the infants of these three women showed clinical signs of alloimmune neonatal neutropenia.

Adult↗
PubMed1986

Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-v-host disease.

Among 181 patients undergoing allogeneic bone marrow transplantation over a five-year period (1978 through 1982), cytomegalovirus (CMV) infection was a frequent and often lethal complication. Recipient pretransplant serology was the most important predictor of posttransplant CMV infection. CMV infection occurred in 26/137 seronegative recipients and in 28/44 seropositive recipients (P less than .001). Among patients who developed CMV infection, the time to infection was identical in seronegative and seropositive patients (median, 71 days post transplant). Bone marrow donor CMV serology did not significantly influence CMV infection rate. CMV infection was strongly associated with acute graft-v-host disease (AGVHD), occurring in 34/81 patients with AGVHD and 20/100 without GVHD (P less than .001). AGVHD preceded CMV infection by 33.7 days (mean) in patients developing both complications. Patients who developed CMV infections had also received more cellular blood products post transplant. These data suggest that CMV infection may occur through reactivation of latent virus (in seropositive recipients) or through exogenous exposure, possibly through transfused blood products, but that duration of immunoincompetence may be more critical than route of exposure in timing of clinically evident CMV infection. Prophylaxis tailored to the likely infectious source and more effective GVHD prevention both may be critical in preventing CMV infection after bone marrow transplantation.

Acute Disease↗
PubMed1986

A novel approach for obtaining and identifying monoclonal antibodies that react with differentiation-specific antigens using human hybrid cells.

HeLa X keratinocyte hybrid cells have been used as immunogens to generate monoclonal antibodies against differentiation-specific antigens. A key feature of the experimental system is that the hybrid cells are undifferentiated in culture and yet terminally differentiate in the mouse. The properties of these cells allow one a facile approach to obtaining and characterizing monoclonal antibodies against differentiation-specific antigens. Use of hybrid cells derived from HeLa X differentiated cell fusions as immunogens should prove to be a general method for identifying differentiation-specific antigens from a variety of differentiated cell types.

Animals↗
PubMed1986

Epinephrine-induced leukocytosis in acute asthma.

We studied epinephrine-induced changes in leukocyte counts in twelve persons with acute asthma and nine healthy, nonasthmatic individuals. Twenty-five minutes after subcutaneous injection of 0.3 mg of epinephrine, a significant increase in the mean numbers of total leukocytes was observed in both the asthmatic and control subjects, 9,195 to 10,519 and 6,733 to 9,222, respectively. Compared with controls, asthmatic individuals had increased numbers of total leukocytes, segmented neutrophils, and eosinophils prior to epinephrine, and the elevations in segmented neutrophils and eosinophils persisted after epinephrine. The increase in total leukocytes was largely secondary to an increase in lymphocytes. Lymphocyte increases were greater in control than in asthmatic individuals (P less than .001). Of clinical importance is the finding that leukocyte counts drawn shortly after treatment with epinephrine do not suggest infection in patients whose pre-epinephrine counts were normal.

Acute Disease↗
PubMed1986

Effect of leukocyte antibodies and HLA matching on the intravascular recovery, survival, and tissue localization of 111-indium granulocytes.

The effect of leukocyte antibodies detected under different conditions on the fate in vivo of granulocytes was studied using 111-indium-labeled granulocytes. Sera from patients were tested by granulocyte agglutination (GA), granulocytotoxicity (GC), granulocyte immunofluorescence (GIF), lymphocytotoxicity (LC), and antibody-dependent lymphocyte-mediated granulocytotoxicity. Granulocytes from donors to be studied were labeled with 111-indium and injected. Then the intravascular recovery and survival or tissue localization was determined in 93 studies. Antibodies detected by granulocyte agglutination were associated with a significant reduction in recovery (6.7% v 30.8% in controls; P less than .001) and t1/2 (0.3 hours v 5.6 hours in controls; P = .002). When all possible combinations of serum reactivity were considered, reactivity in the GA plus GIF assays had the best correlation with decreased recovery (R2 = .49; P less than .001) and t1/2 (R2 = .73; P less than .001). When the relationship between the strength of antibody reactivity and the recovery and t1/2 were analyzed, the best relationship was between the combination of LC and GIF with recovery (R2 = .62; P = .001). Because of the general availability of the HLA (LC) testing, the role of LC reactivity was investigated in other ways. There was a strong relationship between sera highly reactive by LC and those reactive by GIF. These highly reactive sera were also associated with reduced recovery and t1/2. The influence of specific HLA antigen mismatches was also studied. When donor and recipient were mismatched for the HLA-A2, B8, or BW44 antigens, there was a significant reduction in either recovery, t1/2, or both. Tissue localization was studied by body scans in patients with and without known sites of inflammation. Antibodies detected by a combination of GA and GIF caused abnormal pulmonary sequestration of granulocytes (three cases) and failure of granulocytes to localize at known sites of inflammation (three cases). HLA (LC) antibodies did not alter tissue localization despite the presence of the corresponding HLA antigens on granulocytes. It appears that GA, GIF, or a combination of these tests is the most effective predictor of altered in vivo fate of granulocytes. However, sera highly reactive by LC and GIF probably define a group of highly immunized patients in whom granulocyte recovery and t1/2 are also reduced. Mismatching for certain HLA antigens is also associated with reduced granulocyte recovery and survival. At present, GA, with or without the immunofluorescence assay, is the most effective predictor of altered in vivo granulocyte activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies↗
PubMed1985

Correlation of B-mode ultrasound imaging and arteriography with pathologic findings at carotid endarterectomy.

Presently most noninvasive methods for assessing extracranial carotid disease have relied on hemodynamic change associated with significant stenosis. Recent evidence has suggested that both ulceration and/or plaque hemorrhage may frequently play an important role in the pathophysiology of carotid disease. To assess the ability of B-mode ultrasound to provide this anatomic information, in a prospective blinded manner we compared B-mode ultrasound and selective four-vessel arteriography to pathologic specimens obtained at the time of 89 carotid endarterectomies. The presence of ulceration, plaque characteristics (particularly hemorrhage), and luminal diameter were described for each modality. While arteriography detected only 16 of 27 ulcerations (sensitivity, 59%), B-mode ultrasound had a greater sensitivity (24/27, 89%). Both modalities had comparable specificities (arteriography, 73%; B-mode ultrasound, 87%). Moreover, B-mode ultrasound was highly sensitive for demonstrating plaque hemorrhage (27/29, 93%), as well as being quite specific (84%). Assessment of luminal reduction by B-mode ultrasound improved with technologist/interpreter experience and was significantly improved by adding real-time spectral analysis. Because of B-mode ultrasound's sensitivity for imaging ulceration and plaque hemorrhage, it offers significant advantages for the noninvasive detection of extracranial carotid disease.

Arterial Occlusive Diseases↗
PubMed1985

Transplantation of major ABO-incompatible bone marrow depleted of red cells by hydroxyethyl starch.

23 bone marrow transplant recipients whose donors where major ABO-incompatible received marrow depleted of red cells prior to infusion utilizing gravity sedimentation in hydroxyethyl starch. The in vitro red cell-depletion procedure effectively removed 97.8% (mean) of the red cells from the harvested marrows and preserved 86.8% of the nucleated cells and 98.2% of the CFU-C activity in 25.4% of the original volume. All recipients had a significant quantity of isohemagglutinins of both IgM and IgG classes demonstrable in their serum at the time of the marrow infusion. Patients were premedicated and well-hydrated prior to the infusion and tolerated the infusion well. These patients demonstrated bone marrow engraftment at the same rate as did those patients whose marrow donors were either ABO-identical or minor ABO-incompatible. There was no difference in the incidence of or time to development of graft versus host disease, the incidence of graft rejection, or patient survival among the groups. Recipients of red cell-depleted major ABO-incompatible bone marrow transplants demonstrated production of donor-type red cells somewhat later and required slightly more red cell transfusion support that did the other groups of recipients. This red cell-depletion technique is safe and effective in the management of major ABO-incompatible bone marrow transplantation.

ABO Blood-Group System↗
PubMed1985

Therapeutic cytapheresis using the Fenwal CS-3000 blood cell separator.

20 patients, 16 with acute or chronic leukemia and 4 with thrombocytosis, underwent 47 therapeutic cytapheresis procedures using the Fenwal CS-3000 cell separator. 16 of the 20 patients had acute clinical signs or symptoms secondary to high circulating cell counts; 14 showed symptomatic improvement following cytapheresis. An average of 2.0 whole blood volumes was processed per procedure. A mean white cell reduction of 64% and a mean platelet reduction of 53% were obtained per procedure on patients with leukemia and thrombocytosis, respectively. Hemoglobin levels decreased an average of 1.3 g/dl. Therapeutic cytapheresis procedures in which more than 1.5 blood volumes were processed did not result in significant additional cytoreduction.

Adult↗
PubMed1985

A microtiter modification of granulocyte immunofluorescence.

The granulocyte immunofluorescence test (GIFT) is valuable for detecting allogeneic and autologous granulocyte antibodies. However, the original tube technique (macro GIFT) requires 50-100 microliters of serum and 10(6) granulocytes with time-consuming washing steps which cause cell loss. We report a modification (micro GIFT) using microtiter trays which requires only 20 microliters of serum and 2 X 10(5) granulocytes. The modified method conserves reagents, reduces the time required for washing by 67%, decreases cell loss in washing by 74%, reduces the volume of conjugate required by 67%, and compares favorably with the macro GIFT in accuracy, specificity, and sensitivity.

Autoantibodies↗
PubMed1984

Severe pulmonary hypersensitivity associated with passive transfusion of a neutrophil-specific antibody.

A life-threatening pulmonary hypersensitivity reaction accompanied by profound leucopenia and transient hypocomplementaemia developed in a 73-year-old man after repair of an abdominal aortic aneurysm. A neutrophil-specific antibody, anti-NA2) was demonstrated by granulocyte immunofluorescence and microagglutination in one of the transfused donor units. In addition, activated complement component C5a was generated in vitro by incubation of the patient's serum with the aortic graft material. This severe clinical reaction may have resulted from the interaction of the transfused anti-NA2 antibody with complement activation induced by the aortic graft material.

Aged↗
PubMed1984

Response of psoriasis to red laser light (630 nm) following systemic injection of hematoporphyrin derivative.

Systemically injected hematoporphyrin derivative (HPD) in combination with red laser light (630 nm) was used to treat a patient with intraepithelial neoplasia of the vulva. Since the patient had psoriasis in the mons pubis area this region also was exposed to the red light. The psoriasis treatment area was divided into two regions receiving 40 and 20 J/cm2. Both psoriatic zones responded vigorously to the HPD + light treatment, forming eschars by 1 week postirradiation. All three treatment zones (the neoplastic area and the two psoriatic areas) underwent normal reepithelialization by 17 days.

Adult↗
PubMed1984

A modified microchamber method for chemotaxis and chemokinesis.

A 48 well chemotaxis microchamber, originally designed for use with polycarbonate filters, was used with nitrocellulose filters to quantitate chemotaxis and chemokinesis of granulocytes. Various features of the microchamber were compared to Boyden chambers. The accuracy and reproducibility of the method were found to be comparable to Boyden chambers in the variability between individual readings and superior in the variability between replicate values. Concentrations of optimal doses of chemoattractant for chemotaxis and chemokinesis were similar using both types of chamber. The data indicates that this method may be useful in studying components of the chemotactic response which require the use of cellulose filters. Advantages of this method over standard Boyden chambers include the use of a single filter rather than individual, non-identical filters and a reduction in the number of cells required, particularly for pediatric testing or in neutropenic patients.

Chemotaxis, Leukocyte↗