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Biomedical subjects

M O'Leary

Publications and source records attributed to M O'Leary.

At least 73 records · Page 4Linked to original sources
PubMed1985

T-cell depletion of bone marrow does not inhibit in vitro hematopoiesis.

One approach to overcome the problem of histoincompatibility in bone marrow transplantation is to use T cell depleted marrow from a haploidentical donor in an attempt to ameliorate graft-versus-host disease. Since the T cell requirements for normal hematopoiesis are uncertain, experiments were performed to study the effects of E rosette-T cell depletion on in vitro growth of hematopoietic progenitor cells. Marrow mononuclear cells were cultured in a modified CFU-GEMM assay before and after T cell depletion. The number of 7 day granulocytic and erythrocytic colonies, and 14 day granulocytic, erythrocytic and mixed colonies were enumerated and expressed in terms of colonies per 10(5) non T cells plated. T cell depletion did not result in decreased proliferation of any of these progenitors save possibly for 14 day granulocytic colonies in one of four experiments. In two cases, T cell depletion resulted in increased growth of progenitor cells. Three of four patients transplanted with T cell depleted haploidentical marrow cells engrafted. It is concluded that E rosette depletion of T cells from marrow does not decrease the potential of these cells to establish hematopoiesis in vitro or in vivo.

Bone Marrow Cells↗
PubMed1983

Protein carboxyl-O-methyltransferase activity in cultured C-1300 neuroblastoma cells.

Protein carboxylmethyltransferase (PCM) has been identified in a variety of tissues derived from neural crest anlage, including in vivo C-1300 murine neuroblastoma (MNB). These observations have stimulated interest in further defining the role of PCM as a potential modulator of neoplastic cell behavior. The subcellular distribution and kinetic behavior of PCM have been characterized in a tissue culture line derived from the C-1300 murine neuroblastoma (clone NB41A3). The specific and total activities of PCM in the presence and absence of exogenous substrate were determined in subcellular fractions of MNB cells prepared by differential centrifugation. In the presence of exogenous substrate (+ gelatin), 40% of the total PCM activity was present in the 100,000 g supernatant fraction and 41% in the 800 g particulate fraction, whereas the higher specific activity of PCM was present in the 100,000 g supernatant fraction. Enzyme activity measured in the absence of gelatin, which reflects the concentration of endogenous methyl acceptor proteins in a cell fraction, was negligible. This activity represented less than 1.6 and 0.4% of the total PCM activity present in the 800 g particulate and 100,000 g soluble fractions respectively. Cytosolic PCM had an apparent Km of 13.9 x 10(-6) M for AdoMet and a Vmax of 33 pmoles per min per mg protein. Cytoplasmic PCM was inhibited competitively by S-adenosylhomocysteine (Ki equal 0.2 microM). These data demonstrate that the specific activity of PCM was greatest in the soluble component of subcellular fractions prepared from cultured MNB cells. This distribution pattern of PCM is similar to that observed in the C-1300 MNB tumor grown in situ and in non-malignant tissues. In contrast to the latter tissues, cultured MNB cells exhibited low PCM activity when assayed in the absence of exogenous substrate.

Adenosine↗
PubMed1983

Bone marrow transplantation for non-Hodgkin's lymphoma in children and young adults. A pilot study.

Allogeneic bone marrow transplantation was performed in 10 patients with disseminated Burkitt's lymphoma or poor-prognosis T-cell lymphoblastic lymphoma. All patients received a cytoreduction regimen consisting of cyclophosphamide, cytosine arabinoside, bis-chloro-nitroso-urea, and total-body irradiation. Eight patients received marrow from HLA-matched sibling donors. One patient received marrow from a parent donor and one patient died during initial cytoreduction and did not undergo total-body irradiation or marrow infusion. Six patients had Burkitt's lymphoma stages III and IV at diagnosis, and three of the six are alive at 18, 28, and 73 months. Four patients had T-cell lymphoblastic lymphoma, stages III and IV at diagnosis, and two of the four are alive at 29 and 49 months. Overall survival in the nine patients who underwent transplantation is 56 percent by life-table analysis. Follow up for the surviving patients ranges from 18 to 73 months (median 29 months). All five survivors are at home with unmaintained remissions.

Adolescent↗
PubMed1983

An improved method for T-cell depletion of allogeneic histoincompatible donor bone marrow.

Acute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation is the most significant limiting factor preventing the widespread application of transplant therapy in acute leukemia and aplastic anemia. GVHD is mediated by T cells that contaminate harvested marrow in proportions ranging from 5-50% of the mononuclear cell population. T cell depletion (TCD) of large volumes of human marrow by E-rosetting for 24 h at 4 degrees C with modified sheep erythrocytes achieves removal of greater than or equal to 97% of all T cells, as judged by cytofluorographic analysis of the T-depleted bone marrow population with a broad panel of anti-T cell monoclonal antibodies, and abrogates functional T cell activity. Although T-depleted bone marrow cell recoveries were 2 logs below total harvested buffy coat cell numbers, the TCD mononuclear population was more than 99% viable and was enriched twofold for Ia+ cells as judged by cytofluorographic analysis. This method is at least the equivalent of those employing lectin column or monoclonal antibody/complement lysis techniques and is simpler to perform. Successful engraftment of adult patients can safely be obtained with as few as 4 X 10(8) total mononuclear cells following the 24-h procedure suggesting that prolonged or repeated T-depletion procedures do not interfere with stem cell engraftment. Preliminary results suggest that this method of TCD may ameliorate GVHD in histoincompatible transplants.

Bone Marrow↗
PubMed1982

Allogeneic bone marrow transplantation in acute nonlymphocytic leukemia: a pilot study.

The objective of the current study, initiated in 1976, was to improve upon the high relapse rate and subsequent mortality in children and young adults with acute nonlymphocytic leukemia (ANLL). Seventeen patients, ages 6--28, with ANLL in first bone marrow remission, received cyclophosphamide and total body irradiation using a radiation scheme of 750 rad (7.5 Gy) total dose, delivered at a dose rate of 26 rad (26 cGy) per minute. Allogeneic marrow from HLA-matched sibling donors was followed by prophylactic therapy or graft-versus-host disease (GVHD). Median follow-up of the entire group is 20+ mo; survivors have been followed for a minimum of 14+ mo. Interstitial pneumonitis was observed in 6% of patients, and GVHD was observed in 29%. Seventy percent of patients are alive and in complete continuous remission. Two patients have relapsed (at 7 and 24 mo). Actuarial relapse-free survival is 76% at 1 yr and 64% at 5 yr. Quality of life in this disease-free survivors is excellent; all patients are free of active GVHD, receive no maintenance chemotherapy, and have high Karnofsky performances scores. High dose rate total body irradiation plus cyclophosphamide followed by allogeneic BMT may provide an opportunity for long-term complication-free survival in a substantial proportion of children and young adults with ANLL.

Acute Disease↗
PubMed1981

The immune system and the histiocytosis syndromes.

The histiocytosis syndromes consist of a heterogeneous group of disorders referred to as histiocytosis X or differentiated histiocytosis. Although a large proportion of cases of histiocytosis remains to be of an idiopathic nature, there are cases in which the etiologic mechanism appears to be a defect in the immune system. Provided is a brief review of the literature regarding the immune system in histiocytic disease and a review of the experience at the University of Minnesota with immunologic evaluation of children with histiocytic reactions. Two general hypotheses on the relationship between the immune system and histiocytosis syndromes are discussed.

Child, Preschool↗
PubMed1980

Isolation of Chlamydia trachomatis from the lower respiratory tract of adults.

Chlamydia trachomatis was isolated from the lower respiratory tract of six patients who had pulmonary infection, the severity varying from acute bronchitis to severe diffuse interstitial pneumonia. The latter appeared in four immunosuppressed patients, from three of whom cytomegalovirus was also isolated. Therapy directed against C. trachomatis resulted in prompt clinical improvement in three patients. Two patients died. C. trachomatis causes disease in the adult respiratory tract, the prevalence of which has yet to be determined, and it may be an important cause of morbidity and mortality in the immunosuppressed patient.

Acute Disease↗
PubMed1977

Using the MMPI 168 with alcoholics.

The potential utility of the MMPI 168 with male alcoholics was explored. Correlations and some clinically relevant comparisons suggested that the MMPI 168 predicted the standard MMPI with a high degree of accuracy. However, high point codes and conclusions drawn from Goldberg's equations were not so promising, which suggests the need to establish the relative validity of the MMPI 168 by the use of external criteria.

Adult↗
PubMed1977

Brain damage and five MMPI items with alcoholic patients.

The validity of Hovey's brain damage MMPI index for male alcoholic inpatients was investigated. With educational level controlled, the scale did not show significant relationships with established tests of cognitive and organic impairment. Significant correlations were found with measures of psychopathology. This suggests that only in populations in which neurological deficit is the main factor in variations in emotional and physical well-being will this type of index be useful to screen patients for brain damage. The results stress the importance of local cross-validation prior to the clinical use of measures such as Hovey's scale.

Adult↗
PubMed1977

Rupture of a tuberculous pseudoaneurysm of the innominate artery into the trachea and esophagus: report of a case and review of the literature.

Spontaneous rupture of a tuberculous pseudoaneurysm of the innominate artery, undiagnosed until necropsy, occurred simultaneously into the trachea and the esophagus in a patient receiving anti-tuberculosis chemotherapy. This is the first reported instance of a tuberculous innominate artery aneurysm, the third tuberculous aneurysm with rupture into the trachea, the sixth into the esophagus, and the first with rupture into both structures. A review of the literature relating to tuberculous aneurysms of the major arteries is provided.

Aged↗