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Biomedical subjects

B Christensson

Publications and source records attributed to B Christensson.

At least 145 records · Page 8Linked to original sources

Treatment of patients with metastasizing colo-rectal carcinoma with mouse monoclonal antibodies (Moab 17-1A): a progress report.

Eight patients with metastasizing colo-rectal carcinoma have been treated with Moab 17-1A. Before infusion the antibodies were incubated in vitro with isolated autologous blood mononuclear cells (AMC) enriched for monocytes/macrophages. Treatment was given in repeated courses (2-4 times) up to a maximum amount of 1000 mg Moab 17-1A. Two patients had an objective tumor reduction. In further four patients a period of stable disease varying between 3-6 months on was observed. Therapy was well tolerated. Out of 24 treatment courses only on one occasion an anaphylactoid reaction occurred at the third infusion. All patients developed anti-mouse antibodies of IgG and IgM class with increasing levels during the course of therapy. Repeated tumor biopsies and immunohistochemical analyses showed no antigenic modulation, a weak staining for mouse IgG, no deposits of complement components but no obvious increases in the number of cells infiltrating the tumors 24 h after infusion of antibody-armed AMC.

Adult↗

Imbalanced serum IgG subclass pattern in toxic shock syndrome patients: deficiency of specific IgG1 and IgG4 subclass antibodies to toxic shock syndrome toxin 1.

An imbalanced serum IgG subclass pattern was identified in 10 patients with toxic shock syndrome (TSS) showing remarkably low subclass levels of various combinations. IgG2 levels were significantly reduced as compared to normal controls. The IgG subclass-specificity of antibodies to toxic shock syndrome toxin (TSST-1) was investigated by a solid-phase radioimmunoassay. TSS-patients lacked pre-immunity to TSST-1 in all four IgG subclasses. Normally acquired immunity to the toxin as well as the serological response developing in two patients with TSS was generally restricted to IgG1 and IgG4. A strong booster response of all four IgG subclasses was seen in three patients with S. aureus septicaemia due to TSST-1 producing strains. The lack of specific IgG1 and IgG4 antibodies to TSST-1 and the low serum IgG subclass levels found in the TSS-patients could be of pathogenetic significance and help to explain the susceptibility to TSS in certain individuals.

Acute Disease↗

A new serological assay for Staphylococcus aureus infections: detection of IgG antibodies to S. aureus lipase with an enzyme-linked immunosorbent assay.

Purified Staphylococcus aureus lipase was used as antigen in an enzyme-linked immunosorbent assay (ELISA) that detected IgG antibodies in 169 patients with infections due to S. aureus, in 122 patients with infections not due to S. aureus, and in 167 healthy controls. Eighty-eight percent (21 of 24) of the patients with endocarditis due to S. aureus showed a positive level of antibody to lipase or a significant change in antibody titer during the first month, as did 89% (17 of 19) and 28% (5 of 18) of the patients with complicated and uncomplicated septicemia due to S. aureus, respectively. The specificity for S. aureus infections was high; only one patient in the non-S. aureus endocarditis and septicemia groups showed a significant rise in antibody titer, and this rise did not reach a positive antibody level. Patients with recurrent furunculosis or chronic osteomyelitis due to S. aureus responded in only 15% and 23% of cases, respectively. We suggest that the antibody-to-lipase ELISA could be used as a valuable complement to other serological assays in diagnosing serious S. aureus infections because of its high sensitivity and specificity.

Adolescent↗

Immune phenotype heterogeneity in AML.

Blood cells from 46 patients with acute myeloid leukaemia were studied for expression of various surface markers, defined by a panel of 12 monoclonal antibodies and the expression of Fc gamma receptors. Corresponding studies were done on normal bone marrow cells. Antibodies which bound to leukaemic cells in high frequencies were those which most frequently also bound to normal bone marrow cells. Immunophenotypic analysis revealed a marked antigenic heterogeneity in AML, also evident within single FAB subclasses. However, leukaemic cells of FAB subclass M1 significantly more often expressed HLA class I antigen than those of FAB subclass M5a, whereas Fc gamma receptors which were expressed only on a few cells in M5a, were increasingly frequent on leukaemic cells of M1-M2, M4, and M5b leukaemias. The frequency of cells reacting with the monoclonal antibody T50/12,11,2 was related to the complete remission rate of the patients. Patients with high frequencies of cells reacting with this antibody had a better complete remission rate than patients with fewer cells binding to this antibody. The immunophenotypic heterogeneity an AML may reflect a great biological variability of this disease. This variability may be of importance for the classification and treatment of AML.

Adult↗

Serological response to toxic shock syndrome toxin in Staphylococcus aureus infected patients and healthy controls.

The prevalence of antibodies to Toxic Shock Syndrome Toxin (TSST-1) in a Swedish healthy control population was investigated using an enzyme-linked immunosorbent assay (ELISA). 88% of the control group above the age of 10 showed positive antibody levels as compared to 31% of those who were under 10 years old. These results indicate a very common normal exposure to TSST-1 during early life and also identify the small risk-group of potential TSS-patients. Patients with S. aureus endocarditis and septicemia showed slightly higher antibody levels as compared to the controls (p less than 0.05). The difference was in part due to 3/4 septicemia patients, infected with TSST-1 producing strains, who showed very high antibody levels. None of these 4 patients developed any signs of TSS. 5/5 menstrual associated TSS-patients were negative in the ELISA in serial serum samples as were 3/5 non-menstrual associated TSS-patients. The TSST-1 ELISA is proposed for identifying chiefly young women at risk of acquiring menstrual related Toxic Shock Syndrome.

Antibodies, Bacterial↗

Antibody response against whole Staphylococcus aureus in patients with staphylococcal septicaemia and endocarditis investigated by ELISA.

A whole cell Staphylococcus aureus enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies against S. aureus has been developed. To avoid non-specific binding of IgG to protein A, the protein A-poor strains of S. aureus, E 1369 and Wood 46, were used as antigens. One-hundred and eighty serum samples from 120 patients with S. aureus endocarditis, non S. aureus endocarditis, S. aureus septicaemia and non S. aureus septicaemia were tested together with sera from 155 healthy controls. The sensitivity was similar for the E 1369 ELISA and the Wood 46 ELISA and positive test values were detected in 84.2% of patients with S. aureus endocarditis and 41.2% of patients with complicated S. aureus septicaemia. No distinction could be found between complicated and uncomplicated S. aureus septicaemia. The E 1369 ELISA was more specific showing cross reactions with sera from patients infected with other bacteria than S. aureus in 3.6%. Furthermore, the reproducibility was better for the E 1369 ELISA with a coefficient of variation at 0.054. The absence of need for purified antigens makes the whole S. aureus ELISA easy, rapid and cheap. Therefore, we suggest the whole S. aureus ELISA as a good alternative to previously reported assays using purified cell wall antigens.

Adolescent↗

Leukemic myeloblasts expressing lymphoid markers.

Out of 60 patients with acute myeloid leukemia not preceded by chronic myelocytic leukemia or any preleukemic phase, 7 had both lymphoid and myeloid markers. All patients expressed common acute lymphatic leukemia antigen (CALLA) in 20% or more of their leukemic cells, which also showed positive peroxidase reaction. In addition, 4 patients had Auer rods. Two additional patients had morphologically clear acute monocytic leukemia (FAB M5b) and cells expressing CALLA. In 4 of the 7 patients the sum of the percentages of peroxidase or Leu M1 + and CALLA-positive blast cells exceeded 100%, suggesting that at least some of the cells had both myeloid and lymphoid markers. Moreover, out of 3 patients where double staining with the CALLA antibody J5 and the myeloid marker Leu M1 was performed, 2 had both markers on the same cells.

Adult↗

Serological assays against Staphylococcus aureus peptidoglycan, crude staphylococcal antigen and staphylolysin in the diagnosis of serious S. aureus infections.

Immunoglobulin G antibody levels against Staphylococcus aureus peptidoglycan (PG) and crude staphylococcal antigen (SA) using enzyme-linked immunosorbent assay (ELISA) and antistaphylolysin (ASTA) antibody levels by gel diffusion were determined in 53 patients with S. aureus and 54 patients with non-S. aureus endocarditis and septicemia as compared with 63 febrile control patients. The two ELISAs were the most sensitive assays indicating S. aureus endocarditis in 83% and 88% in the PG- and SA-assays, respectively. 39% of non-S. aureus endocarditis patients were positive in the PG-assay due to antibodies cross-reacting with streptococci. A 100% specificity for S. aureus infections was obtained with the ASTA test, but this assay was less sensitive. A significant rise in anti-PG or anti-SA antibody levels was not only seen among S. aureus infections but also in some streptococcal and S. epidermidis infections as well as in 3 febrile control patients. When at least 2 of the 3 assays showed positive peak antibody levels 1-4 weeks after onset of infection together with a significant rise of both anti-PG and anti-SA antibody levels the S. aureus endocarditis diagnosis was highly suggestive. Thus, we recommend the combined use of these 3 assays using paired serum samples in diagnosing serious S. aureus infections.

Adolescent↗

Rabbit antiserum to a citric acid extract of human skeletal muscle staining thymomas from myasthenia gravis patients.

Rabbit antiserum to a citric acid extract of human skeletal muscle (CA) stained both the cell membrane and the cross-striational bands of skeletal muscle cells. The rabbit antiserum also stained the cell membrane of epithelial thymoma cells from myasthenia gravis (MG) patients. Normal and hyperplastic thymus tissue were not stained, apart from scattered myoid thymic cells. Absorption of the antiserum with CA abolished staining of the thymoma, indicating that human skeletal muscle and epithelial thymoma cells possess common antigens.

Absorption↗

Prognostic significance of terminal transferase activity and glucocorticoid receptor levels in acute myeloid leukemia.

A retrospective study was undertaken to evaluate terminal transferase activity and glucocorticoid receptor content as predictors of prognosis in 52 adult patients with acute myeloid leukemia (AML). Eighteen patients who had detectable levels of TdT in their leukaemic cells (greater than or equal to 0.1 unit microgram-1 DNA), had a higher complete remission rate than patients with low TdT activity. Patients below 60 years with increased TdT activity also had longer survival as compared to those with low TdT levels. By combining cytochemical analysis of peroxidase and immunocytochemical staining for TdT it was possible to show that the enzyme was located in leukaemic cells of myeloid origin. Leukemias of monocytic origin had no detectable TdT activity in 10/11 cases. The cellular content of the cytoplasmic glucocorticoid receptor varied from 0 to 2.8 fmol micrograms-1 DNA. There was no difference in receptor content between the different FAB subgroups. High levels of the receptor (greater than or equal to 0.22 fmol microgram-1 DNA) were positively correlated with the remission rate. Patients with TdT levels of greater than or equal to 0.1 unit microgram-1 DNA and a glucocorticoid receptor concentration of greater than or equal to 0.22 fmol microgram-1 DNA had significantly higher remission (P = 0.001) and survival rates (P = 0.007) compared with those with undectectable levels of both TdT and low receptor content. It is thus concluded that combined measurements of TdT and the glucocorticoid receptor are useful predictors of prognosis in AML.

Adult↗

Acute leukaemia in a defined geographic area--incidence, clinical history and prognosis.

A consecutive series of patients (1978-1981) comprising all patients with acute leukaemia from a population of 475000 inhabitants was reviewed. Thus, 94 patients were diagnosed as having acute leukaemia. No patients were lost from follow-up. The incidence figures of ALL and AML differed significantly from those of Sweden as a whole. 9 patients were less than 15 years old. The median age of adult patients was 64 years, 60.8% being greater than or equal to 60 years old. Of adult patients with AML, 20% had a preleukaemic history (chronic myeloproliferative disorders, myelodysplastic syndromes and others). None of 6 patients with leukaemia as a metamorphosis of a chronic myeloproliferative disorder achieved a complete remission. The overall remission rate of the remaining adult patients was 25%. Treated patients, 15-39 years old, with AML without any preleukaemic history, had a complete remission rate of 80% compared to 12% for patients greater than or equal to 60 years old with the same diagnosis. Of 60 patients with 'primary' AML, 14 were not treated, mainly because of advanced age and complicating diseases. Most of these patients died within a week of admission.

Adolescent↗

Methodological aspects of Staphylococcus aureus peptidoglycan serology: comparisons between solid-phase radioimmunoassay and enzyme-linked immunosorbent assay.

In the present studies we compared the ability of two commonly used assays, solid-phase radioimmunoassay and enzyme-linked immunosorbent assay (ELISA), to detect human antibodies to Staphylococcus aureus peptidoglycan. ELISA was superior, with a reproducibility of 12.0%, as compared with 18.1% in solid-phase radioimmunoassay. Much lower serum dilutions could be used in ELISA. We also studied the effects of solubilizing the antigen by lysostaphin, lysozyme, or ultrasonication. Lysostaphin-treated peptidoglycan cannot be recommended since solid-phase radioimmunoassay could not distinguish positive from negative serum samples with this preparation. On the other hand, the sensitivity in both assays was high when peptidoglycan treated with lysozyme for 240 min or with ultrasonication for 30 min was used as antigen. The interassay correlation between solid-phase radioimmunoassay and ELISA was slightly better with sonicated peptidoglycan (correlation coefficient = 0.94, P less than 0.01), as compared with lysozyme-treated peptidoglycan (correlation coefficient = 0.76, P less than 0.01). We recommend the ELISA with sonicated peptidoglycan as antigen for use in routine serology.

Adult↗

Failing transcervical thymectomy in myasthenia gravis. An evaluation of transsternal re-exploration.

Twenty cases of failing transcervical thymectomy are reported. They were selected for transsternal re-exploration from a series of 95 patients who had previously undergone transcervical thymectomy because of myasthenia gravis (MG). A specific method for pre-operative detection of remnants of the non-tumorous thymic gland is lacking, but the applied clinical selection criteria were so far reliable: generalized, disabling, fluctuating MG despite cholinesterase inhibitor and/or immunosuppressive treatment, and no or inconsistent improvement after transcervical thymectomy. At transsternal re-exploration the commonest findings were intact lower thymic lobes with persistent venous drainage into the brachiocephalic vein. Presence of thymic tissue was histologically confirmed in all the excised specimens (weight range 10-60, mean 23 g), and the examination showed thymic hyperplasia in 18 cases, fatty involution of the gland in two, and a lympho-epithelial thymoma in one case. The re-operation was followed by objectively registrable improvement in all but one of the 20 patients during observation periods of 8-75 (mean 21) months. There was statistically significant reduction in disability scores (means 8.2-4.9) and in need for anticholinesterase medication (to 67% of pretreatment dose). Immunosuppression became unnecessary in 6 of 11 patients and could be reduced in 4 patients. The incidence of failure in transcervical thymectomy was alarmingly high (27%), and more re-operations are anticipated. Since the transcervical approach involves a high risk of incomplete thymectomy, its use should be abandoned. However, in most of the patients with re-operation, subsequent progress has been sufficiently promising for advocacy of sternotomy whenever the clinical criteria of failure are fulfilled.

Adolescent↗

Characterization of malignant and non-neoplastic cell phenotypes in highly malignant non-Hodgkin lymphomas.

Malignant and non-neoplastic cells in 38 cases of highly malignant non-Hodgkin lymphomas: 3 centrocytic anaplastic, 18 centroblastic, 13 immunoblastic and 4 lymphoblastic (according to the Kiel classification) were immunophenotyped in cryosections and cell suspensions by means of monoclonal antibodies. Additionally, cell cycle analysis on cell suspensions was performed by DNA flow cytofluorometry. In 33 (87%) lymphomas the malignant cells expressed monoclonal surface immunoglobulin (Ig), which indicated B-cell origin of tumors. In 7 of the 19 B-cell lymphomas tested by the peroxidase-antiperoxidase method, cytoplasmic Ig was found. Four lymphomas were of T-cell and one of non-B/non-T-cell origin. In II B-cell and 2 lymphoblastic non-B-cell tumors, common acute lymphoblastic leukemia antigen (CALLA) was found. In 25 of 30 studied NHL the malignant cells expressed receptor for transferrin and in 19 of 28 cases a high percentage of cells in S-phase (greater than 10.85%) was found. Number and distribution as well as type of non-B-cells infiltrating B-cell-derived lymphomas varied considerably from case to case. Among these cells Leu 3+ (T helper/inducer) cells predominated. Leu 2+ (T suppressor/cytotoxic) and Leu 7+ (natural killer and killer) cells constituted less numerous groups. Correlation of cytodiagnostic analyses with clinical observations indicates that high content of infiltrating T cells may be a favorable prognostic feature in highly malignant B-cell lymphomas.

Adolescent↗

Blood and lymph node T-lymphocyte subsets in non-Hodgkin lymphomas.

Blood and lymph node T-lymphocyte subpopulations have been studied in untreated non-Hodgkin lymphoma (NHL) patients and healthy controls. T-lymphocytes were determined by the E-rosette technique and by OKT3/LEU4 monoclonal antibodies; OKT4/LEU3 and OKT8/LEU2 monoclonal antibodies were used to identify T-cell subsets with helper/inducer and suppressor/cytotoxic activity, respectively. OKT4+ T-cells were low in patients, while OKT8+ T-cell numbers were normal. The OKT4+/OKT8+ blood lymphocyte ratio was below the normal range in about 50% of the patients. The ratio was higher in lymph nodes than in blood of patients and controls. The results may suggest that untreated NHL patients have a reduced pool of T-cells with phenotypic markers of OKT4/LEU3. Monoclonal blood B-lymphocytes were found in 45% of the cases. The presence of such cells in blood was frequently associated with a low OKT4+/OKT8+ ratio.

Aged↗

Antibody response to alpha- and betahemolysin from Staphylococcus aureus in patients with staphylococcal infections and in normals.

One hundred and nineteen patients with S. aureus infections and 22 patients with non-S. aureus septicemia were investigated for anti-alpha hemolysin antibodies using a radioimmunoassay (RIA). As compared to 16- healthy controls, patients with S. aureus endocarditis, septicemia, chronic osteomyelitis and recurrent furunculosis showed significantly higher antibody levels, while the non-S. aureus septicemia group showed normal levels. Corresponding results were obtained using the conventional anti-staphylolysin (ASTA) test. Only patients with recurrent furunculosis had significantly elevated anti-beta hemolysin antibody levels assessed by RIA, in comparison with healthy controls. The highest antibody levels were found in furunculosis patients infected with S. aureus strains which were high producers of beta hemolysin. The results indicate that furunculosis patients do not have a defective serological response against S. aureus beta hemolysin.

Antigen-Antibody Reactions↗

Solid-phase radioimmunoassay of immunoglobulin G antibodies to Staphylococcus aureus peptidoglycan in patients with staphylococcal infections.

A solid-phase radioimmunoassay (SPRIA) for determination of antibodies against S. aureus peptidoglycan was used for serological diagnosis of staphylococcal infections. Elevated IgG antibody levels were found in 21/21 patients with S. aureus endocarditis and in 10/24 patients with S. aureus septicemia. Two patients with streptococcal and one patient with pneumococcal septicemia showed elevated antibody levels as well, probably due to cross reactions between peptidoglycans of different bacterial species. In cases of chronic osteomyelitis caused by S. aureus, 12/33 patients showed elevated antibody levels while all patients with recurrent furunculosis had normal antibody levels. Anti-peptidoglycan antibodies were also found in all healthy controls (n = 160) but at lower levels. This might explain the rapid booster response of IgG antibodies found in 73 per cent of patients with S. aureus endocarditis already within 10 days after the first symptoms. The best clinical value of the assay seems to be in separating S. aureus endocarditis from uncomplicated septicemia.

Adolescent↗