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Biomedical subjects

M T Gallagher

Publications and source records attributed to M T Gallagher.

At least 19 recordsLinked to original sources
PubMed1985

Extravascular hemolysis following the administration of cefamandole.

Hemolytic anemia occurred in a 70-year-old female after a five-day course of intravenous cefamandole. The patient's serum contained an IgG antibody which was reactive with red blood cells which had been coated in vitro with cefamandole but not with uncoated cells. An in vitro assay of allogeneic mononuclear phagocytosis of cefamandole-coated red cells sensitized with the patient's anti-cefamandole indicated that the anti-cefamandole could induce significant phagocytosis. The anti-cefamandole was easily inhibited in vitro by cefamandole as well as by a variety of related cephalosporins indicating broad cross-reactivity, with the antigenic site primarily the 7-amino-cephalosporanic acid nucleus. Penicillins could inhibit the anti-cefamandole but only when using concentrations 3-10 X those of cephalosporins. Eleven examples of anti-penicillin tested failed to react with cefamandole-coated red cells. Screening of 344 random sera from hospitalized patients found only five (1.5%) reactive with cefamandole-coated red cells; three of these sera were also reactive with penicillin-coated red cells. The patient's hemolysis subsided following cessation of the drug. This is the first report of anti-cefamandole-induced hemolytic anemia.

Aged↗
PubMed1985

A 64,000 dalton matrix protein of human cytomegalovirus induces in vitro immune responses similar to those of whole viral antigen.

Human cytomegalovirus contains approximately 30 to 35 structural polypeptides. Although antibodies to several of these proteins are made during natural infection, their relationship to T cell recognition of this virus and subsequent control of infection is poorly understood. We have purified one of these proteins (HCMVgp64) that is found in abundance in infected cell lysates in order to delineate the relationship of single viral proteins to the immune response caused by the virus. HCMVgp64 induced T cell reactivity only in individuals with serologic evidence of past infection. In addition, HCMVgp64 elicited similar in vitro immune reactions as the whole virus including T cell proliferation, interleukin 2 production, and receptor expression as well as interferon production. These studies suggest that single proteins of HCMV such as HCMVgp64 are capable of inducing T cell responses and may be important in the development of immune reactivity to HCMV.

Antigens, Viral↗
PubMed1984

In vitro determination of red cell alloantibody significance using an assay of monocyte-macrophage interaction with sensitized erythrocytes.

One hundred and forty-eight red cell alloantibodies, of specificities generally considered to be of clinical significance, were studied in vitro for their ability to induce phagocytosis of sensitized red cells by allogeneic mononuclear phagocytes. Results indicate that only 53% of the alloantibodies studied mediated significant phagocytosis in vitro. The percentages for each blood group system were as follows: Kell, 73%; Jka, 32%; Jkb, 67%; D, 75%; E, 60%; Fya, 62%; Yta, 25%; Ge, 22%; and Vel, 25%. Significant phagocytosis was independent of the strength of the indirect antiglobulin test. The percentage of anti-Jka and anti-Fya mediating significant phagocytosis was increased when fresh complement was added during the sensitization procedure and/or red cells homozygous for the antigen in question were used. The in vivo clinical significance or lack of significance was documented for nine alloantibodies; five caused haemolysis and four did not. Those causing in vivo haemolysis mediated in vitro phagocytosis by monocyte-macrophages whereas the antibodies that did not result in haemolysis showed no increased in vitro phagocytosis. Autologous monocytes were more reliable than random allogeneic monocytes in that phagocytosis was increased over that obtained using allogeneic monocyte-macrophages with two of four alloantibodies having documented clinical significance. The use of target red cells homozygous for the antigen in question, the addition of fresh complement in the antibody sensitization procedure, and use of autologous and allogeneic monocyte-macrophages appear necessary for optimal results. Since 47% of those alloantibodies generally considered to be clinically significant failed to mediate phagocytosis in vitro, the monocyte-macrophage assay should not be considered a predictive assay of a given alloantibody's in vivo significance or lack of significance until more extensive correlation of these assays with in vivo red blood cell survival is obtained.

Antibody Specificity↗
PubMed1983

Reticuloendothelial cell function in alpha-methyldopa-induced hemolytic anemia.

2 patients having alpha-methyldopa-induced hemolytic anemia were followed sequentially using an in vitro assay of autologous monocyte-macrophage activity to determine if their reticuloendothelial system (RES) function was abnormal and thus could be related to the mechanism of lysis. RES function was evaluated while the patients were actively hemolyzing and during remission, following discontinuance of the drug. The results indicated that RES activity is normal in patients having hemolytic anemia due to alpha-methyldopa administration. Also, following cessation of drug therapy, the patients' IgG-coated red cells interacted significantly for a prolonged period (4-5 months) with autologous or normal allogeneic monocyte-macrophages. This was associated with a concurrent reticulocytosis and indicates a persistent low-level hemolytic phase throughout this period, even though hemoglobin and hematocrit values remained within the normal ranges. Although levels of IgG sensitizing the patients' red cells were essentially constant during the hemolytic phase and when the patients were in complete remission, significant monocyte-macrophage activity was only evident during the hemolytic period. In an attempt to explain this phenomenon, it is postulated that hemolysis in patients receiving alpha-methyldopa is related to the interaction of drug with red cell membrane proteins which results in a variably expressed 'altered' antigen which is recognized by 'autoantibody'. The proper expression of the Fc portion of the immunoglobin molecule to result in specific recognition by receptors on monocyte-macrophages depends upon the extent of the antigen alteration by alpha-methyldopa. If the drug does not result in appropriate antigen alteration, then, although 'autoantibody' may still bind to the red blood cell, its Fc region is not readily recognized by monocyte-macrophages and little or no erythrophagocytosis occurs.

Aged↗
PubMed1983

Evaluation of reticuloendothelial function in autoimmune hemolytic anemia using an in vitro assay of monocyte-macrophage interaction with erythrocytes.

We have used an in vitro assay of monocyte-RBC interaction to study the correlation of in vitro monocyte activity with in vivo lysis in patients with autoimmune hemolytic anemia (AIHA). All of 16 patients with a positive direct antiglobulin test (DAT) (0.5 + to 4+) and clinical evidence of hemolysis showed elevated association (ARBC) and phagocytic (PRBC) indices. Of 6 patients studied with a positive DAT (0.5+ to 4+) without clinical evidence of hemolysis, none showed elevated PRBC while 2 showed slightly elevated ARBC. Thus, when using a PRBC index, our assay distinguished between hemolysing and non-hemolysing patients independent of the degree of red cell sensitization as determined by the DAT. In addition, we have studied 6 patients with a positive DAT following alpha-methyldopa therapy. Two of these patients were hemolysing, 4 were not. Again, our assay correlated with in vivo lysis. Finally, we have studied red cells from 11 patients with DAT-negative acquired hemolytic anemia. Seven of these patients showed elevated ARBC and PRBC indices, indicating a possible immune etiology involving extravascular lysis in some DAT-negative acquired hemolytic anemias.

Anemia, Hemolytic, Autoimmune↗
PubMed1981

Amelioration of graft-versus-host disease by pretreatment of allogeneic cells with Fab fragments.

We have previously reported the protective effect of pretreatment of semiallogeneic marrow and spleen cells with Fab fragments of horse anti-mouse thymocyte globulin against otherwise 100% fatal acute graft-versus-host disease (GVHD). We have now examined the effect of this pretreatment in three allogeneic strain combinations of mice, namely, A leads to C57, CBA leads to CAF1, and CBA leads to BALB/c. Acute GVHD mortality at 15 days postirradiation and transplantation of untreated marrow and spleen cells was 100% in all the strain combinations. However, pretreatment of cells with Fab reduced acute GVHD mortality to 6, 13, and 33% for the CBA leads to CAF1, CBA leads to BALB/c, and A leads to C57 strain combinations, respectively. The combined mortality from both acute and secondary GVHD and all other causes at 60 and 200 days postirradiation was 6 and 11%, 20 and 39%, 50 and 66% for each of these strain combinations, respectively. These results provide additional evidence for the effectiveness of Fab in ameliorating acute GVHD and establish its applicability to allogeneic strain combinations.

Animals↗
PubMed1981

Development of natural killer cell activity and genetic resistance to bone marrow transplantation with age: effect of neonatal thymectomy.

The effect of neonatal thymectomy on the development of splenic and bone marrow natural cell-mediated cytotoxicity and on genetic resistance to bone marrow transplantation was examined in mice. Natural cytotoxicity was measured by a 51Cr release assay; the ability to engraft foreign bone marrow was assayed by the spleen colony method. The natural cytolytic response of spleen cells increased progressively from youth to early adulthood, whereas that of the bone marrow declined during the same age period. Neonatal thymectomy significantly elevated the natural killer cell response of young mice only (4 weeks, spleen; 6 weeks, bone marrow). In other experiments, neonatally thymectomized and sham-operated mice were lethally irradiated at 4 or 6 weeks of age and injected with 2.5, 5.0 or 10 million rat marrow cells. Six days later spleen colonies were markedly reduced in both 4- and 6-week-old neonatally thymectomized mice with all rat marrow cell doses tested. Neonatal thymectomy did not alter the percentage of erythroid verus other colonies at either 4 or 6 weeks. In both thymectomized and sham-operated mice the number of colonies increased with increases in marrow cell dose. The data are suggestive of a production and dissemination to the spleen of cels involved in the natural cytotoxic response from the bone marrow.

Aging↗
PubMed1981

lack of suppressor cell activity for natural killer cells in infant, aged and a low responder strain of mice.

We have examined the reported role of suppressor cells in the regulation of NK activity in mice with naturally low NK activity (infant and aged (C57 X A)F1 hybrids (CAF1) and low responder strain AKR mice). Possible suppressor activity was assayed by mixing, at a 1 : 1 ratio, spleen cells from low activity mice with spleen effector cells from normally active 8 to 10 wk old CAF1 mice. The lytic activity of the mixture was compared with the activity of effector cells diluted with medium alone or diluted 1 : 1 with "non-suppressor" population which served as a control for nonspecific decreases in lysis. The control or "filler" cells employed were suspensions of adult CAF1 thymus, thymus from adult mice exposed to 2,000 R, and adult CAF1 spleen cells cultured for 24 hours, a procedure that depleted NK activity. In no case was the activity observed in the presumed suppressor-effector mixture significantly lower than that observed in the filler-effector cell mixtures. Thus, in infant (1 to 2 wk) and aged (12 to 18 mo) CAF1 mice and in 8 to 10 wk old AKR mice, we found no evidence for specific cell-mediated suppression of natural cytotoxicity.

Aging↗
PubMed1981

Augmentation of natural killer cell activity in spleens of infant, aged, and low responder strain mice by Corynebacterium parvum.

Murine natural killer (NK) cell activity is both age- and strain-dependent. NK activity does not appear in murine spleen cells until three weeks after birth. Activity peaks at approximately 10 weeks, decreasing thereafter with mice over one year old showing significantly reduced levels. Mice showing low or no NK activity because of age (aged and infant mice, respectively) can be stimulated to show significant levels of NK lysis by i.p. injection of formalin killed Corynebacterium parvum (CP). In addition, CP treatment is also capable of increasing NK activity in mice from the normally low responding AKR strain. The NK activity induced or stimulated by CP appears to be like normal NK reactivity in that it is not decreased by removal of T-cells or adherent cells. Thus, in addition to increasing NK activity in normally responsive mice, CP is capable of augmenting NK activity in mice which normally show low or no levels of NK lysis.

Aging↗