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Biomedical subjects

A Morell

Publications and source records attributed to A Morell.

At least 73 records · Page 4Linked to original sources

Proliferation of lymphoid precursor cells in the bone marrow of patients with various disorders of the immune system.

In the human bone marrow the nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is expressed by cells during early stages of lymphocyte differentiation. In order to investigate a possible regulation of lymphopoiesis at this level of differentiation, the relative frequency and the in vitro 3H-thymidine labeling index (3HdT-LI) of TdT-positive bone marrow cells were assessed in patients with different functional activities of the immune system. TdT-positive lymphoid precursor cells could be detected in the bone marrow of all children investigated, including six patients with various forms of immunodeficiency. Neither a transient hyperfunction of the immune system during the immunological rebound after cessation of long-term chemotherapy for acute lymphoblastic leukemia, nor a congenital or acquired hypofunction of the immune system had any detectable influence on the invariably high in vitro 3HdT-LI of TdT-positive bone marrow cells, a phenomenon possibly related to an autonomous and high turnover of this precursor cell compartment in the human bone marrow.

Adolescent↗

Humoral immune function in pediatric patients treated with autologous bone marrow transplantation for B cell non-Hodgkin's lymphoma. The influence of ex vivo marrow decontamination with anti-Y 29/55 monoclonal antibody and complement.

Elimination of neoplastic B cell populations from autologous bone marrow grafts also removes normal B lymphocytes. This is potentially hazardous for the reconstitution of the immune system in patients undergoing high-dose chemotherapy and total body irradiation followed by autologous marrow rescue. Five pediatric patients with B cell non-Hodgkin's lymphoma in first remission undergoing such a regimen were studied. They received bone marrow pretreated with anti-Y 29/55 monoclonal antibody and complement. B and T lymphocyte subpopulations reached normal levels within 6 months after autologous bone marrow transplantation (ABMT), and serum immunoglobulin levels became normal within 4 to 9 months. Vaccination with diphtheria and tetanus toxoid, trivalent poliomyelitis vaccine of the Salk type, and pneumococcal capsular antigens (38 to 54 months after transplantation) gave rise to specific antibody production. ABO isoagglutinins could be demonstrated in all patients. The response pattern was similar to that of patients who received unmanipulated autologous bone marrow. It is concluded that ex vivo anti-Y 29/55 depletion of the marrow graft does not induce relevant disturbances of humoral immune functions.

Adolescent↗

Survival of antigen-specific antibody following administration of intravenous immunoglobulin in patients with primary immunodeficiency diseases.

To measure the survival of IgG, IgG subclasses and antigen-specific antibody in immune-deficient patients, we infused 4 patients with X-linked agammaglobulinemia (XLA) and 6 patients with common variable immune deficiency (CVID) with modified immunoglobulin at a dose of 400 mg/kg per month until steady state was reached. Following the 8th monthly infusion, serial samples were obtained and analyzed for serum concentration of IgG, IgG subclasses and for specific antibody activities against a battery of antigens. Half-lives for IgG and IgG subclasses were between 30 and 40 days except for IgG3 which appeared to consist of two populations of molecules, one showing a rapid decay, the other disappearing at a rate suggesting a half life of 22-24 days. Antigen-specific antibodies, including antibodies to HBsAg, cytomegalovirus, pneumococcal polysaccharides and streptococcal group A carbohydrate were similar to that for total IgG. These studies demonstrate that protective antibody titers to infective agents can be maintained for several weeks following high-dose intravenous immunoglobulin infusion.

Adolescent↗

[Interleukin-2: molecular, physiological and pathophysiological bases and possible significance for clinical practice].

Interleukin-2, a lymphokine produced by T lymphocytes in response to antigenic or mitogenic stimulation, is necessary for the proliferation and differentiation of various cell populations including activated T lymphocytes, natural killer cells (NK), lymphokine-activated killer cells (LAK), B lymphocytes and macrophages. In addition, IL2 induces or increases the production of important cytokines and thus plays a central role in regulation of the immune response. A number of studies have demonstrated that in patients with primary and secondary immunodeficiency disease, including patients with human immunodeficiency virus infections, decreased immune response was associated with impaired production of, or abnormal reaction to, IL2. Furthermore, IL2 has been assessed, alone or in combination with IL2-activated killer cells ("adoptive immunotherapy"), for its anticancer potential in several animal models and in patients with various forms of advanced cancer. A brief synopsis of biochemical and biological properties of IL2 is presented. The potential pathophysiological role of IL2 in a variety of immunodeficiency states and its possible therapeutic use in cancer therapy are discussed.

Animals↗

The proliferative response of human peripheral blood lymphocytes to group A streptococcal vaccine.

The proliferative response of human peripheral blood mononuclear cells to group A streptococcal vaccine (strain J17A4) was assessed by measurement of [3H]thymidine incorporation. This was maximal after 7 days in cultures containing 1 X 10(5) lymphocytes. Cells from 33 out of 38 adult donors (87%) yielded stimulation indices between 2.0 and 81. Responding cells were predominantly of the OKT4+, Ia+, Tac+ phenotype expressed by activated helper T lymphocytes. In contrast, no response was observed in 10 out of 12 samples of cord blood lymphocytes. Addition of conventional rabbit or monoclonal murine anti-Ia (HLA-DR) antibodies to the culture medium abrogated the vaccine-induced proliferative response. Frequencies of responding cells estimated by limiting dilution analysis were between 1 in 2370 and 1 in 4580 lymphocytes. The results suggest that lymphocyte stimulations induced with streptococcal group A vaccine represented an in vitro anamnestic cellular immune response.

Antibody-Producing Cells↗

Influence of exogenous interleukin-2 on the proliferation of lymphocytes from normal donors and from patients after autologous bone marrow transplantation.

The influence of two interleukin-2 (IL-2) preparations on the proliferative response of normal lymphocytes to phytohemagglutinin (PHA) was examined. A recombinant IL-2 (rIL-2) and an IL-2 containing conditioned medium (LyIL-2) markedly enhanced 3H-thymidine incorporations at low PHA concentrations, whereas at optimal mitogen concentrations, this effect was marginal. In lymphocyte cultures of 3 patients after autologous bone marrow transplantation (ABMT), exogenous IL-2 augmented PHA-induced stimulations. Moreover, a dose-dependent increase of the 3H-thymidine uptake was observed in unstimulated cultures of all normal donors and patients. Combined autoradiography and surface marker analysis allowed to identify cells spontaneously proliferating in the presence of exogenous IL-2. Comparison of phenotypes of these cells revealed pronounced differences between a normal donor and a patient after ABMT.

Bone Marrow Transplantation↗

Determination of ectoenzyme activities in leukemic cells and in established hematopoietic cell lines.

Ectoenzyme activities were determined in peripheral blood cells from patients with acute leukemias, from normal controls, and in cells of hematopoietic cell lines. In common acute lymphoblastic leukemia, cell membrane-associated 5'-nucleotidase (5'-N) activity was significantly higher than in acute T and unclassified lymphoblastic leukemias. In acute myeloblastic and myelomonocytic leukemias, cells contained significantly higher gamma-glutamyl transpeptidase (gamma-GT) activity than in lymphoblastic leukemias. Normal B lymphocytes differed from T cells and monocytes mainly in their 5'-N activity, whereas in monocytes, gamma-GT activity was more pronounced than in other normal blood cells. Hematopoietic cell lines showed some distinct patterns of ectoenzyme activity. Most B cell lines had high 5'-N and (Na-K-Mg) adenosine triphosphatase activities. In lines of myeloid origin, elevated gamma-GT values were found. In lymphoid stem cells and in T lymphoblast lines, most ectoenzyme activities were lower than in the other cell lines. In some cell lines, characteristic high-activity marker enzymes were detected.

5'-Nucleotidase↗

Susceptibility to infections in children with selective IgA- and IgA-IgG subclass deficiency.

This study included 36 children with IgA-deficiency, increased susceptibility to infections and/or other disorders. Recurrent, usually bacterial infections were noticed in 23 out of 26 patients (88%) with complete and in 7 out of 10 patients (70%) with partial IgA-deficiency. All patients with severe infections had complete IgA-deficiency. Complete IgA-deficiency was also present in the six children who had autoimmune disorders associated with recurrent infections. In 22 out of the 36 patients studied the serum could be analysed for concomitant IgG subclass deficiencies: one patient had marked decrease of IgG2. In a second patient IgG4 was not detectable. Two patients had combined IgG2-IgG4-deficiency. In a girl with severe acute and chronic infections and relapsing idiopathic thrombocytopenic purpura, IgA-IgG2-IgG4-deficiency was found to be the prodromal stage of common variable immunodeficiency with panhypogammaglobulinaemia.

Adolescent↗

Correlation of in vitro antibody synthesis with the outcome of intravenous gamma-globulin treatment of chronic idiopathic thrombocytopenic purpura.

Intravenous gamma-globulin (IVGG) effectively elevates the platelet count of most patients with chronic idiopathic thrombocytopenic purpura (ITP). This study examined whether this effect was related to changes in in vitro immunoglobulin secretion and suppression in coculture. Before treatment, patient in vitro immunoglobulin secretion was less than 50% of the concurrent control in all eight cases and the patients suppressed antibody synthesis in coculture an average of 39%. After treatment, increases in in vitro immunoglobulin secretion and decreases in suppression were closely related to a good response to IVGG therapy as measured both by acute increases in the platelet count (P less than 0.05) and by the long-term outcome from therapy (P less than 0.05). Decreases in platelet-associated IgG correlated with increases in in vitro immunoglobulin secretion (P less than 0.05). Data consistent with the lack of inhibition of in vitro immunoglobulin secretion following IVGG included long-term increases in both serum IgM and IgG (independent of transfused IgG) and maintenance of the percentage of total IgG that was IgG3. T-cell numbers and subsets and lymphocyte proliferation were unaffected by IVGG. IVGG tends to normalize in vitro immunoglobulin secretion and its suppression in those ITP patients with good clinical responses in conjunction with decreased levels of autoantibody. This evidence suggests that good responders to IVGG may have inhibition of antiplatelet antibody production. IVGG does not appear to interfere with normal antibody production.

Adolescent↗

Transplacental passage of intravenous immunoglobulin in the last trimester of pregnancy.

Immunoglobulin G was given intravenously (IVIgG) to pregnant women (27 to 36 weeks gestation) with signs of chorioamnionitis who were at risk for preterm delivery. Twenty-four patients received antibiotics alone (control group). Twenty-seven patients received the same antibiotics in combination with IVIgG, either 12 gm in 12 hours (low IVIgG dosage) or 24 gm on each of 5 consecutive days (high IVIgG dosage). Transplacental passage of IVIgG was shown to be a function of gestational age and of dose. Up to the thirty-second week of gestation, IgG infusions had no effect on IgG concentrations in cord sera. After that time, cord serum IgG levels were significantly higher in the high-dose group compared with the low-dose and control groups. All four subclasses of IgG, and two different antibodies present in the IVIgG preparation passed from the mother to the fetus. Thus the infused IgG mimicked the transplacental passage of endogenous IgG.

Chorioamnionitis↗

Various immunoglobulin preparations for intravenous use.

In recent years, a number of intravenous immunoglobulin (IVIG) preparations have become available, primarily in Europe. Since these preparations differ in their physical, chemical and biologic properties, the physician is frequently presented with difficulties in selecting an appropriate product. Until now, in vitro studies have been the only reliable source of evaluating these preparations. This paper describes the commercially available IVIG preparations and assesses the properties of each.

Antibody Specificity↗

IgG subclasses and antibodies to group B streptococci, pneumococci, and tetanus toxoid in preterm neonates after intravenous infusion of immunoglobulin to the mothers.

High doses of intravenous immunoglobulin were given to seven pregnant women between the 27th and 36th wk of gestation who were at risk for preterm delivery. Determinations of IgG subclasses and of antibodies against group B streptococcal serotypes, pneumococcal polysaccharides, and tetanus toxoid were done in maternal serum before and after intravenous IgG infusion and after delivery in cord serum. Substantial transplacental passage of the infused material could be observed in five cases where delivery occurred at the 34th wk or later. After the 36th wk of gestation, IgG subclass and antibody concentrations in cord serum were increased up to the levels in the maternal serum.

Antibodies↗

[Immune defect following thymoma. Case description and review].

The clinical and immunologic findings in a 57-year-old woman with hypogammaglobulinemia are described. The immunodeficiency occurred 11 years after surgical removal of an invasive lymphocytic thymoma. The typical findings of hypogammaglobulinemia as a thymoma-associated clinical syndrome are absence of peripheral blood B-lymphocytes and deficiency of plasma cells in bone marrow. However, in our patient peripheral blood B-lymphocytes and plasma cells in bone marrow were within normal limits, while the total number of peripheral blood mononuclear cells was subnormal. This subnormality was found to be a diminution of peripheral blood T-helper cells. Our patient was anergic to a battery of skin test antigens and her lymphocytes showed a decreased in vitro response to mitogen stimulation. In particular, the response to phytohemagglutinin (PHA) was low, but could be improved by the addition of interleukin-2 to the culture medium. Cocultures between patient B-cells and normal T-cells revealed normal function of patient B-cells. However, cocultures between patient T-cells and normal B-cells showed a significant depression of mitogen-induced immunoglobulin synthesis. These results are suggestive of T-helper cell dysfunction. Consequently, in our case the hypogammaglobulinemia was assumed to be secondary to deficient T-helper cell function.

Agammaglobulinemia↗

[Bronchoalveolar immunoglobulins in sarcoidosis].

In 9 patients with active and 10 patients with inactive sarcoidosis, and in 6 normal controls, the concentration of IgM, IgA and IgG broncho-alveolar lavage (BAL) fluid was measured. Patients with active sarcoidosis showed significantly higher values of these immunoglobulins than patients with inactive sarcoidosis or normals. In addition, a significant correlation between the immunoglobulin levels and the number of helper-T lymphocytes in the BAL fluid was demonstrated.

Bronchi↗

Surface markers, 5'-nucleotidase activity, and in vitro functions of lymphocytes from patients with primary humoral immunodeficiency.

Immunologic surface markers, 5'-nucleotidase activity, and in vitro cell functions were determined on peripheral blood mononuclear cells from 20 patients with primary humoral immunodeficiencies. Imbalances of T-cell subsets were a frequent finding and often associated with a deficiency of helper T lymphocytes, predominantly in common variable immunodeficiency. The magnitude of the blastogenic response to mitogens was subnormal in the majority of the samples and showed no correlations to the proportions of helper, suppressor T cells or monocytes in the cultures. Moderate to marked suppression of the pokeweed mitogen-driven allogenic B-cell maturation was mostly mediated by T lymphocytes but modified by monocytes in some patients. In identical twins, T lymphocytes selectively suppressed IgA production. Both in sex-linked agammaglobulinemia and common variable immunodeficiency the activity of 5'-nucleotidase was significantly lower than in controls. This deficiency was mediated by T lymphocytes and showed no correlations to imbalances of T-cell subpopulations or to alterations of lymphocyte functions.

5'-Nucleotidase↗