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Biomedical subjects

B Christensson

Publications and source records attributed to B Christensson.

At least 127 records · Page 7Linked to original sources

Clonal immunoglobulin gene rearrangements in primary mediastinal clear cell lymphomas.

Cells from two patients with primary mediastinal tumors of clear cell type were characterized by immunological and molecular biological techniques. In both cases a B cell immunophenotype was suggested by the positive staining for the B1 (CD20), B4 (CD19), Leu 14 (CD22), as well as staining with other B monoclonal antibodies by immunohistochemistry. However, no definitive evidence for the expression of Ig light or heavy chains at the protein level was found. Southern blot analysis of Ig heavy and light chain gene rearrangements revealed clonal B cell populations in both cases. There was no indication of a somatic joining of T cell receptor (TCR) genes using probes for TCR beta and or TCR gamma genes. Thus, our results suggest a clonal B cell origin of clear cell lymphomas in the mediastinum.

Antigens, Differentiation↗

Immunohistochemical monitoring of metastatic colorectal carcinoma in patients treated with monoclonal antibodies (MAb 17-1A).

A therapeutic trial using repeated doses of a mouse monoclonal antibody against the tumor-associated antigen (TAA) CO17-1A in metastatic colorectal carcinomas was carried out. Metastatic lesions sampled by repeated thick needle (1.2 mm) biopsies during therapy were examined immunohistochemically for the presence of various TAAs, mouse IgG, complement, and infiltrating leukocytes. The CO17-1A was consistently expressed in all cases along the basement membrane of tumor glands and could only be demonstrated on cryostat sections whereas the TAAs GICA19-9, GA73-3, and Br55-2 were also visualized in B5-fixed paraffin-embedded biopsies. The CO17-1A and GA73-3 were predominantly present at the basal region in contrast to the GICA 19-9 and Br55-2 which were predominant at the luminal and the apical region of the tumor glands. Antigenic modulation was not seen either after 24-72 h or during prolonged treatment. In all cases the infused mouse IgG was detected, from 24 h after infusion up to 6-8 weeks, mainly along the basal region of tumor glands. In 13/14 posttreatment biopsies, complement factor C3 was found at the same sites as mouse IgG. In 6 out of 9 posttreatment biopsies an increase in mononuclear cells (monocytes, natural killer (NK) cells and/or T cells) was observed. Monocytes were close to the tumor cells whereas NK cells and T cells were predominantly scattered in the stroma.

Adult↗

Prognostic significance of immunoglobulin isotype expression in B-cell non-Hodgkin's lymphoma.

Lymph node biopsies from 170 patients with untreated non-Hodgkin's lymphomas (NHL) of B-cell type were immunophenotyped and analyzed for the Ig heavy and light chain isotypes and their relation to prognosis. IgM alone was more frequently seen in high grade (53%) compared to low grade (20%) NHL. In contrast, IgM/IgD isotypes were more frequent in low grade (47%) than in high grade NHL (20%). IgG or IgA heavy chain, alone or in combination with other heavy chain isotypes, were expressed with the same frequencies in both low (32%) and high (27%) grade NHL. Clonally restricted kappa light chain expression was noted in 64% of low grade and 66% of high grade NHL patients. Only in chronic lymphocytic leukemia (CLL) and immunocytoma (IC) was a shorter survival time noted for patients with tumors expressing IgG and/or IgA heavy chains compared to those expressing IgM or IgM/IgD (P less than 0.001). This difference was not seen as being low grade follicle center cell-derived (FCC) or high grade NHL. The expression of kappa light chains on the tumor cells was associated with a significantly longer survival in CLL and IC patients only (P less than 0.01).

Adult↗

Clinical effects of monoclonal antibodies (MAb 17-1A) in patients with metastatic colorectal carcinomas.

Ten patients with metastatic colorectal carcinoma were treated with MAb 17-1A (IgG2A). Before infusion, MAb was incubated in vitro with isolated autologous blood mononuclear cells. Treatment was given in repeated courses (2-4 times) to a maximum dose of 1000 mg of MAb 17-1A. One patient achieved a clinical complete remission, two patients had a minor response and one patient had stable disease for 5 months. The median survival for the four responders was 19 months compared to 7 months for the six non-responders. Therapy was well tolerated. In this series, 32 infusions of MAb 17-1A were given. The serum half-life of MAb 17-1A was approximately 22 hours. All patients developed anti-mouse antibodies of both IgG and IgM classes. No relation between adverse reactions and anti-mouse antibodies was seen. At 3 occasions allergic reactions were noted. Skin test with MAb 17-1A seems to reliably predict for allergic reactions.

Adult↗

B-cell compartment in the thymus of patients with myasthenia gravis and control subjects.

An increased number of CD19, 20, and 22 positive B cells, compared to the number of Ig-positive cells, is regularly found in the thymic medulla of normal thymus, suggesting that a B-cell population normally resides in thymic medulla that lacks Ig expression. However, some of the CD20-positive cells seem to co-express keratin and MR19, suggesting an epithelial origin. The medullary B cells found in normal thymus could be precursors of the tumor cells in "mediastinal clear cell lymphomas of B-cell type." In follicular hyperplasia in MG, the medullary epithelial network is deformed and partly destroyed, and the interlobular/perivascular spaces are expanded. Follicles with follicular dendritic cells are found in both interlobular/perivascular spaces and "punched out" lesions in the medullary epithelium. The B cells are greatly increased in MG thymuses compared with control thymuses. These cells are found mainly in the follicles, but they are also dispersed in the medulla and the interlobular/perivascular spaces. The immunophenotype and distribution of B and T cells as well as the follicular dendritic cells in the hyperplastic follicles are similar to those of reactive follicles in lymph nodes. Our findings are consistent with the contention that in MG there is an autoimmune activation of B cells that normally reside in the thymic medulla. This activation leads initially to follicular hyperplasia in the medullary epithelium with destruction of medullary epithelial cells. The prolonged immune reaction in the autoimmune process induces a fibronectin-rich stroma formation and increased vascularization. The result is a remodeling of the thymic architecture with expansion of the perivascular/interlobular spaces replacing the destroyed medulla.

Antigens, Differentiation↗

Cerebral cysticercosis successfully treated with praziquantel.

A 28-year-old woman presented with signs of relapsing meningeal inflammation 5 months after immigration from Chile. Cerebral cysticercosis was diagnosed with computed tomography (CT) scan, showing signs of intracranial hypertension and cystic lesions, and was confirmed by serological investigation. After treatment with praziquantel all clinical symptoms disappeared. A CT scan obtained 6 months after treatment showed almost complete resolution of the cystic changes in the brain.

Adult↗

Isolation of human immunodeficiency virus (HIV) from plasma during primary HIV infection.

Human immunodeficiency virus (HIV) has been isolated from plasma in 6 of 7 patients showing clinical symptoms of a primary HIV infection. Parallel cultures from peripheral blood mononuclear cells (PBMC) yielded virus in 5 patients. In one case, virus could only be isolated from the cerebrospinal fluid but not from peripheral blood. Detectable viremia was transient and preceded the appearance of HIV specific antibodies. After cessation of acute symptoms, the frequency of HIV isolations was similar to that of asymptomatic carriers (23 and 26%, respectively). The role of the immune response in terminating detectable viremia remains to be established.

Acquired Immunodeficiency Syndrome↗

Blood clonal B cell excess (CBE) at diagnosis in patients with non-Hodgkin lymphoma (NHL). Relation to clinical stage, histopathology and response to treatment.

Untreated non-leukemic (lymphocytes less than or equal to 4.0 X 10(9)/l) patients with non-Hodgkin lymphoma (NHL) of B cell type often show an excess of B cells in peripheral blood bearing the same light chain isotype as the lymph node tumor cells which may indicate a leukemic spread of the disease. The ratio between kappa- and lambda-bearing lymphocytes (normal range 1.0-3.3) was studied to evaluate the prognostic significance of clonal B cell excess (CBE) at diagnosis in 110 NHL patients. In total 43% had a CBE in peripheral blood. Fifty-two per cent of the patients in clinically advanced stages had CBE and 30% of the patients in stages I and II. CBE was detected in 49% of all patients with low-grade malignant lymphoma and in 32% with high-grade malignancy. Patients with a normal kappa:lambda ratio at diagnosis entered complete remission more often than those with CBE (P less than 0.01). In patients with high-grade but not with low-grade malignant lymphomas remission duration was longer for those with normal kappa:lambda distribution than for the patients with an abnormal ratio (P less than 0.01). Survival was not statistically significantly influenced.

Adult↗

Antibody response to whole cells and teichoic acid of Staphylococcus aureus strain E 1369 in human sera.

A whole cell Staphylococcus aureus enzyme-linked immunosorbent assay (ELISA) using the protein A-deficient strain E 1369 as antigen was compared to an ELISA with cell-wall teichoic acid, extracted from the same strain, as antigen for the detection of IgG antibodies against S. aureus in human sera. A total of 178 serum samples from 119 patients with S. aureus endocarditis, complicated and uncomplicated septicaemia, non-S. aureus endocarditis and septicaemia were investigated together with sera from 155 healthy controls. The sensitivity in diagnosing S. aureus endocarditis was better for the whole cell-ELISA (83%) as compared to the teichoic acid-ELISA (61%), and the same was true for complicated septicaemia (41% vs 29%). The whole cell ELISA was also more specific for S. aureus infections with only 3.6% false positive test values compared to 7.1% for the teichoic acid-ELISA. The differences were however, not statistically significant. None of the assays were able to distinguish between complicated and uncomplicated S. aureus septicaemia.

Antigens, Bacterial↗

[3H]noradrenaline efflux from platelets and synaptosomes of ethanol-treated rats.

Platelets have the ability to take up, store and release biogenic amines and have therefore been used as models for neurons in studies of neuropsychiatric disorders and hypertension. We have studied the spontaneous efflux of [3H]noradrenaline from platelets and synaptosomes of rats chronically treated with ethanol. Male control rats had a more rapid [3H]noradrenaline efflux both from synaptosomes and platelets than female control rats. Ethanol treatment increased efflux in female rats, again both in platelets and synaptosomes. These results suggest that a parallelism exists in noradrenaline release between synaptosomes and platelets, both basal and in situations which stimulate the release.

Animals↗

Fulminant course of infectious mononucleosis with virus-associated hemophagocytic syndrome.

A fatal case of infectious mononucleosis due to serologically verified Epstein-Barr virus infection in a previously healthy 30-year-old man is presented. The clinical course was characterized by severe prostration, persistently high spiking fever, and continuous development of enlarged lymph nodes. Hematologic examination revealed peripheral leukopenia and thrombocytopenia, and in the bone marrow an increased number of benign histiocytes showed marked hemophagocytosis. At autopsy abnormal lymphoid infiltrates were present in several tissues. The pathogenesis of this infection-associated hemophagocytic syndrome is discussed in terms of the possibility of an impaired immune response to infectious agents.

Adult↗

Failure of doxycycline treatment in aquarium-associated Mycobacterium marinum infections.

Two cases of aquarium-associated Mycobacterium marinum infections are described. Neither was cured by the initial therapy consisting of surgical excision followed by doxycycline treatment. Both strains of M. marinum were shown to be resistant to doxycycline. In one patient the lesions were subsequently healed with cotrimoxazole. The other patient, a 12-year-old girl with sporotrichoid spread of the lesions on the lower arm, failed to respond satisfactorily to a combination of rifampicin and ethambutol despite favourable effect in vitro of both drugs. Nine months after the initial treatment, the infection was finally cured with renewed surgery followed by additional chemotherapy with rifampicin and ethambutol. No signs of immunological disorder could be detected in the patient. Increased awareness of the possibility of tetracycline resistance of M. marinum is advocated. A combination of adequate chemotherapy and surgical intervention may be required at least in complicated cases.

Adult↗

Myasthenic and nonmyasthenic thymoma. An expansion of a minor cortical epithelial cell subset?

The authors report an immunohistologic study of primary thymomas from 23 cases with myasthenia gravis (MG) and 7 without. Typical T6+ cortical thymocytes were usually abundant. Most epithelial cells initially appeared to be of cortical type, too, though many bore subcapsular markers in most samples. However, two-color immunofluorescence revealed unexpected heterogeneity, numerous epithelial cells simultaneously expressing some or all of the markers of both these subsets (even in two pleural metastases). It is inferred that there is a common tumor stem cell whose normal counterpart may be related to the rare patches of similar phenotype in the cortex in control samples. The authors could detect no major differences in 5 of 7 samples from nonmyasthenics; thus, most thymoma cases may risk the development of MG. Finally, thymomas from 6 of 7 further MG cases pretreated with corticosteroids showed very few cortical thymocytes, and the (phenotypically similar) epithelium was more obvious.

Adult↗

Cell proliferation and DNA content in non-Hodgkin's lymphoma. Flow cytometry in relation to lymphoma classification.

Flow cytofluorometric (FCF) DNA analysis was performed on specimens from 154 patients with non-Hodgkin's lymphoma (NHL) and correlated to histopathology according to the Rappaport classification and the Working Formulation of NHL for clinical usage (WF). NHL associated with unfavorable prognosis (UP) had significantly higher proportions of cells in S-phase as compared to the favorable prognosis (FP) group. The proportion of S-phase cells also differed significantly between the low-, intermediate-, and high-grade malignancy groups of the WF. Aneuploidy was significantly more frequent in the UP (41%) than in the FP (15%) group. By stepwise discriminant analysis, the S-phase frequency was a stronger discriminator between prognostic groups than DNA content. Classification by discriminant analysis showed that over 90% of the low grade/FP lymphomas were allocated to the good prognosis group by their S-phase and DNA values. Due to the variation in the proportion of S-phase cells in the intermediate grade and high grade, as well as the UP lymphomas, only approximately 50% of the UP and 60% of the high-grade lymphomas were identified as such by this discriminant model, while almost one half of the intermediate-grade lymphomas were allocated to the low-grade group. The results suggest that S-phase analysis can be of value in distinguishing intermediate- and high-grade lymphomas with high and low proportions of proliferating cells, which may be prognostic importance.

Adult↗

Distribution of the methyl acceptor proteins within platelet granules.

Fractionation of platelet alpha-granules and dense bodies demonstrated that methyl acceptor proteins (MAP) were present in the alpha-granule fractions, but seemed to be low or absent in the dense body fraction. MAP activity in four intragranular proteins (albumin, fibrinogen, beta-thromboglobulin and platelet derived growth factor) was low or absent and could not explain the difference in methyl acceptor proteins distribution between alpha-granules and dense bodies.

Adenosine Triphosphate↗

The relation between protein carboxyl methylating and demethylating enzyme activities and noradrenaline efflux in platelets.

To test the hypothesis that the raised noradrenaline efflux rate constant in platelets observed in hypertensive individuals and some normotensive relatives to hypertensives could be ascribed to disturbances in the protein carboxyl methylation, protein carboxyl methylase activity and noradrenaline efflux rate constant were measured in platelets from 33 young healthy males. Sixteen had inheritance of hypertension. Protein methyl esterase activity and the noradrenaline efflux rate constant were measured in 43 men, 22 of whom had inheritance of hypertension. No correlation was found between unstimulated noradrenaline efflux from platelets and enzyme activity.

Adult↗

Biochemical and biological properties of Staphylococcus aureus septicemia strains in relation to clinical characteristics.

166 Staphylococcus aureus septicemia strains were phage grouped and tested for lipolytic activity, protein A content, alpha, beta and delta hemolysin activity and toxic shock syndrome toxin (TSST-1) production. These strain characteristics were correlated to the clinical features of the infections. Patients infected with phage group II strains showed the lowest mortality but were more prone to develop internal abscesses. Lipolytic activity and protein A positivity was found in most strains and no correlation to phage group or clinical signs could be shown. Alpha hemolysin was the most common of the investigated hemolysins though it was only produced by 58% of 88 investigated strains. Beta and delta hemolysin production was found in 25% and 24% of the strains, respectively. The lowest frequency of alpha hemolysin production (25%) was found among phage group I strains, especially those producing TSST-1, where only 1 of 12 strains was positive. The overall frequency of TSST-1 production was 18% in 88 tested strains and most positive strains were non-hemolytic. These results indicate that hemolysin production does not seem to be required for a strain to be invasive.

Bacterial Toxins↗