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Biomedical subjects

V Andersen

Publications and source records attributed to V Andersen.

At least 109 records · Page 6Linked to original sources

Successful nonsibling bone marrow transplantation in severe combined immunodeficiency.

Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA-A antigen but was HLA-Dw2 homozygous like the patient; his lymphocytes showed a slight response to the patient's cells in mixed lymphocyte culture (MLC). At the age of 2 1/2 months and again at 5 months, she was given a bone marrow transplant from the father. During the entire course the patient had no infections, and apart from a transient eosinophilia she had no signs of graft-versus-host reaction. Immunological reconstitution was nearly complete at 9 months of age, when she was recontaminated. One year later plasma immunoglobulin concentrations are in the low normal range (IgG and IgM) or decreased (IgA); tests of cell-mediated immunity are normal. Apart from slight upper respiratory infections, the patient has been healthy. Physical and psychological development have been normal.

Bone Marrow Transplantation

Activation of primed rabbit blood lymphocytes by antigen: early phase of triggering and the specificity of the response.

The early phase of antigen-dependent triggering of rabbit blood lymphocytes (PBL) is described. Specific activation of PBL by streptococcal vaccines requires primed lymphocytes from high responder rabbits. B-cell memory is conferred by Ig receptors by both mu and gamma chains. Antigen-induced incorporation of leucine and thymidine reach peak values at day 5, with stimulation indices of 10 to greater than 100, closely followed by increases in the number of living cells. A second and less intensive phase of cell proliferation is seen on days 8--11. A large fraction of cells (between 3 and 33%) participates in proliferation. A rough calculation of the average doubling time of cells during the exponential growth phase gives values of 8--16 h.

Animals

Immunological studies in thymectomized and non-thymectomized patients with myasthenia gravis.

Eleven thymectomized and ten non-thymectomized patients with myasthenia gravis, matched with respect to sex, age, duration and severity of the disease were investigated with respect to routine clinical features, electrophysiological examination, HLA-typing, auto-antibodies, lymphocyte subpopulations in peripheral blood, Concanavalin A-induced release of leucocyte migration inhibitory factor (LIF), in vitro lymphocyte activation by mitogens and antigens and response to primary immunization with dinitrochlorobenzene measured in vivo and in vitro. The following conclusions could be drawn. The immune response to external antigens seems to be normal in myasthenia gravis and thymectomy is not followed by general defects in immune competence; at least as investigated by current techniques. The only reduction of responsiveness demonstrable in the thymectomized group was a decreased release of LIF by Concanavalin A-stimulated lymphocytes. Primary immune responses appear to be increased after adult thymectomy, which may be due to a decrease in suppressor T-lymphocyte activity. A hypothesis is formulated that Concanavalin A-induced release of LIF may reflect the competence of suppressor T-lymphocytes in man.

Adolescent

Production of leucocyte migration inhibitory factor (LIF) in infectious mononucleosis. Spontaneous release and lack of response to concanavalin A.

The spontaneous release of LIF from blood lymphocytes was studied in patients with infectious mononucleosis. Mononuclear cells were separated from the blood and cultured for 22 hr, and LIF activity in the supernatant was determined. Supernatants depleted of LIF activity by means of anti-LIF antibodies or by treatment at 80 degrees C for 30 min were employed as controls; these two methods gave essentially similar results. In nine out of eighteen patients, spontaneous LIF production was demonstrated during the acute stage of the illness; this was not seen in any of the normal persons studied. 6 weeks later, spontaneous LIF production had ceased in most patients. Concanavalin A stimulated all normal lymphocytes to LIF production, but in sixteen out of seventeen patients with infectious mononucleosis this response was absent or diminished. At the follow-up study 6 weeks later, the lymphocyte response to concanavalin A was still suppressed.

Adolescent

A method for autoradiographic studies of single clones of plaque forming cells.

By limiting dilution of B lymphocytes from spleens of immunized mice, microcultures were obtained that contained only one clone of plaque forming cells (PFC). The cultured cells were labelled with [14C]thymidine for varying periods of time. Plaques were obtained in monolayers of sheep erythrocytes in plastic dishes. After fixation with glutaraldehyde, the bottoms of the dishes were stripped off and autoradiograms prepared. By this method, it is possible to determine the proportion of labelled PFC within a given clone and to quantitate the incorporation of label. The method described can be applied to study the incorporation of other labelled molecules and for cytochemical investigations.

Animals

In vitro stimulation of human lymphocytes by Bordetella Pertussis.

Bordetella pertussis (B.p.) induces blast transformation of human lymphocytes; whole killed B.p. are more efficient than extracts obtained by sonication. Similar responses were obtained with each of the four strains used in the Danish pertussis vaccine. B.p. with low amounts of Protective Antigen and Histamine-Sensitizing Factor also induced lymphocyte transformation, but were less toxic to the lymphocytes at high concentrations. The supernatants of B.p. cultures were purified with respect to Lymphocytosis Promoting Factor; evidence is presented that these purified fractions possess T-lymphocyte mitogenic activity. Lymphocytes from all normal humans were stimulated by B.p., including cells from cord blood. Cells from childbearing women, obtained immediately after delivery, showed a general depression of lymphocyte transformation including the response to B.p. Children with whooping cough had a lower lymphocyte response to B.p. than healthy children. A highly significant correlation was observed between the responses to B.p. and to E. coli in the adults and newborn examined. It is concluded that the major part of the lymphocyte transformation induced by B.p. is non-specific.

Adult

Lymphocyte transformation studies in Mycoplasma pneumoniae infections.

The in vitro transformation of lymphocytes stimulated by a Mycoplasma pneumoniae preparation was measured by the uptake of 14C-thymidine. The lymphocytes from five patients with M.pneumoniae pneumonia showed a high degree of responsiveness when they were compared to the lymphocytes taken from eleven healthy control subjects who lacked M.pneumoniae antibodies. Another four patients with an acute affection of the central nervous system and serological evidence of an actual or recent M.pneumoniae infection had a lymphocyte response within the same range as that of the controls. The transformation of lymphocytes was studied at intervals for seven months after the onset of the illness in one of the patients with pneumonia. These studies showed an increasing response to a small dose of mycoplasma antigen. Lymphocyte transformation induced by other microbial antigens was studied in three pneumonia patients during and after convalescence. The first responses were low and increased more steeply than the response to M.pneumoniae. The later responses to the mycoplasmal and to the other microbial antigens increased in parallel. The usefulness of incorporating other microbial antigens in the evaluation of the patient's immune response to a relevant antigen in this type of experiment is discussed.

Adult

Sequential studies of lymphocytes, neutrophils and serum proteins during prednisone treatment.

Seven patients (6 with connective tissue diseases, 1 with bronchial asthma) have been studied before, during, and after prednisone therapy. Maximum dose was 15 mg daily, which was tapered off to zero within three months. All patients showed striking subjective improvement during therapy. The ESR reflected this improvement but the acute phase proteins did not. The serum concentration of prealbumin rose significantly during the period of most intensive steroid treatment. IgE decreased in the patient with bronchial asthma, but otherwise the immunoglobulins did not change, and positive serological tests remained unchanged. Contact sensitization to haptens was induced without impairment during therapy. Prednisone induced rises in blood lymphocyte and neutrophil concentrations. Lymphocyte transformation, both mitogen- and antigen-induced, was not influenced by therapy, but PPD-induced inhibition of leucocyte migration decreased. Neutrophil phagocytosis was unimparied, but bactericidal capacity, stimulated nitroblue tetrazolium reduction, and neutrophil and plasma lysozyme concentrations were all depressed during treatment with prednisone.

Adult

Immunological studies in children before and after splenectomy.

Fourteen children underwent splenectomy for congenital spherocytosis, splenomegaly, or thrombocytopenia. The patients were studied twice before the operation, three times during the first postoperative month, and one year later. A transitory rise in neutrophils and serum IgA was seen postoperatively; there was a modest but long-lasting increase in lymphocytes and a marked elevation of eosinophils. An immediate decline in serum IgM concentration was observed only in patients with an uncomplicated postoperative course, but one year after splenectomy the average IgM concentration had decreased by 23%. The in vitro lymphocyte transformation response to a panel of mitogens and antigens fell in the immediate postoperative period but was largely normalized 10 days postoperatively, except in the youngest of the patients who had repeated infections following the splenectomy. One year postoperatively the transformation response and the number of T- and B-lymphocytes in the blood were normal.

Child

Crossed immunoelectrophoretic analysis of Bordetella pertussis antigens and of corresponding antibodies in human sera.

Fourty-four antigens were demonstrated in sonicated preparations of Bordetella pertussis (B.p.), using crossed immunoelectrophoresis against antiserum obtained from rabbits. No qualititative differences between the four strains of the Danish pertussis vaccine were found. In preparations of B.p. culture medium, purified with respect to Lymphocytosis Promoting Factor (LPF) activity, one antigen was possibly related to LPF. In human sera, antibodies against five of the B.p. antigens were demonstrated by means of crossed immunoelectrophoresis with intermediate gel. Antibody production was demonstrable in children during the pertussis vaccination period and was most marked after the second vaccination.

Antibodies, Bacterial

Cross-reactions between Bordetella pertussis and twenty-eight other bacterial species.

Cross-reactions between B. pertussis and 28 other bacterial species were studied by various quantitative immunoelectrophoretic methods. A sonicated B. pertussis antigen preparation and a corresponding pooled rabbit antiserum were used as reference system. Two of the B. pertussis antigens were cross-reactive with antigens from 17, respectively 19, other bacterial species mainly gram-negative species. As judged by absorption of antibodies, the degree of cross-reactivity of these B. pertussis antigens with antigens from other species was found to be in the range 25-30%. Antigens from B. parapertussis and B. bronchiseptica were found to cross-react very extensively with B. pertussis, and only 4, respectively 2, of the 44 antigens of the B. pertussis reference system could not be absorbed with antigens from these two Bordetella species.

Antibodies, Bacterial

Neutrophilic granulocytes in acute bacterial infection. Sequential studies on lysozyme, myeloperoxidase and lactoferrin.

The changes in intraneutrophilic and plasma concentrations of the three antibacterial proteins lysozyme, lactoferrin, and myeloperoxidase were studied sequentially during acute bacterial infection in nine patients. Intraneutrophilic concentrations of the three proteins were decreased by more than 50% during the 1st week of infection, followed by a slow increase over the following 2 weeks. Nadir values coincided with maximal toxic granulation of the neutrophils. The data suggest that neutrophilic granulocytes are deficient during early bacterial infection, possibly because of deficient synthesis of antibacterial proteins in the bone marrow, and that neutrophil toxic granulation is the visual counterpart of this defect. The plasma concentrations of the three proteins showed considerable differences: whereas plasma lysozyme did not show any sequential changes, plasma myeloperoxidase was high at the start of infection and quickly decreased towards normal values, and plasma lactoferrin, high in the first samples, showed a secondary peak 1 week after onset of disease, before normalization was seen. These differences may result from differences in the signals are specific for the individual antibacterial protein and not for the different types of neutrophil granules.

Adult

Sequential studies of lymphocyte responsiveness and antibody formation in acute bacterial meningitis.

Lymphocyte transformation responses in vitro were studied in eight patients with acute bacterial meningitis (in five due to Neisseria meningitidis). Sequential studies were done from 24--48 hr after the first symptoms of infection to complete recovery. In all cases lymphocyte transformation was depressed during the acute phases of illness. The responses to microbial antigens were more affected than the responses to mitogens. The course of the lymphocyte responses to the causative micro-organism showed no difference from the responses to other microbial species. A moderate shift towards increased sensitivity of the lymphocytes to lower doses of the causative micro-organism was observed during the course of illness in three cases. In N. meningitidis infection, a rapid rise was seen in the serum titres of complement-fixing antibodies and in the number of precipitating antibodies, whereas the rise in immunoglobulin concentrations was more prolonged. Characteristic patterns of elevation and return towards normal were found in the serum concentrations of the acute-phase reactants alpha1-antitrypsin, haptoglobin, and orosomucoid. It is concluded that the lymphocyte transformation responses in vitro during severe bacterial infection are largely governed by non-specific factors, and that studies of lymphocyte responses to micro-organisms should always include other microbial species as controls.

Antibody Formation

Hapten-specific lymphocyte transformation in humans sensitized with NDMA or DNCB.

The primary immune response to a contact sensitizing dose of para-N-dimethylnitrosaniline (NDMA) and dinitrochlorobenzene (DNCB) was obtained in humans and measured in vitro by increased thymidine incorporation into sensitized lymphocytes. No cross-reaction was found between these two haptens, and it is thus possible on two separate occasions to quantify and follow the primary cellular immune response in man.

Aniline Compounds