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Biomedical subjects

B Christensson

Publications and source records attributed to B Christensson.

At least 109 records · Page 6Linked to original sources

Immunoglobulin production in severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells.

Immunodeficient C.B-17 scid/scid (SCID) mice were reconstituted with human peripheral blood mononuclear cells and analyzed for humoral immunity. The majority of adoptively transferred animals had serum levels of 1-4 mg/ml of human IgG 8-12 weeks after i.p. reconstitution with 20 x 10(6) PBMC, whereas the IgM and especially IgA concentrations were considerably lower. The half-lives of human IgG, IgM, and IgA in SCID mice were 12 days, 36, and 23 hours, respectively. Furthermore, IgA was rapidly secreted into bile indicating that the low IgA concentration was mainly caused by a high turnover rate. IgG subclass distribution in mouse serum was similar to that found in the donor serum. Irradiation with 3 Gy prior to adoptive transfer resulted in increased levels of human IgG early after reconstitution, whereas both IgM and IgA concentrations were impaired. A polyclonal serum Ig pattern was found 4 weeks after transfer of human cells later frequently followed by a predominance of oligoclonal bands. Unexpectedly, oligoclonal bands were also found using donors with a negative Epstein-Barr virus serology. Human cells were found to reside in the peritoneal cavity for several months. Within 2 weeks of reconstitution, human cells were also identified in lymphoid structures in the vicinity of the liver hilus with a later spread to other lymphoid organs. Homing of human cells to skin and gut was not seen.

Animals↗

Antibody response to Staphylococcus aureus whole cell, lipase and staphylolysin in patients with S. aureus infections.

Three assays to measure antibodies against Staphylococcus aureus whole cells, lipase and staphylolysin were used to try to discriminate between complicated and uncomplicated S. aureus septicaemia. Sera were examined from 8 patients with S. aureus endocarditis, 23 patients with complicated S. aureus septicaemia, 12 patients with uncomplicated S. aureus septicaemia and 93 febrile non-septicaemic controls. No single assay could distinguish between complicated and uncomplicated S. aureus septicaemia. If the criterion for a positive result is defined as positive antibody level in the anti-lipase ELISA as well as in at least 1 of the other 2 assays, 10/31 patients with S. aureus endocarditis or complicated septicaemia were positive compared to 0/93 non-septicaemic patients and 0/12 patients with uncomplicated S. aureus septicaemia. Therefore, the combined use of serological assays in the diagnosis of complicated S. aureus septicaemia, one of which is the anti-lipase ELISA, is recommended.

Antibodies, Bacterial↗

Nuclear protein content and Ki-67 immunoreactivity in nonneoplastic and neoplastic thyroid cells.

The nuclear DNA content in thyroid tumor cells has been shown to be closely related to the malignant potential of the neoplasm. Besides DNA, nuclear protein (NP) constitutes the major mass of the nucleus. The NP content may vary significantly in relation to the proliferative stage in growing as compared to growth-arrested cells. The increase in NP content associated with the transition from G0 to G1 occurs before the onset of DNA synthesis and may be used to assess growth activity. The nuclear DNA and NP contents were analyzed in 90 nonneoplastic lesions and 75 benign and 62 malignant thyroid tumors. All nonneoplastic specimens were euploid, and 1 of 90 was growth activated. In the group of benign tumors, 59 were euploid, and 16 were aneuploid. Among these there were 5 (9%) of 59 and 6 (38%) of 16 growth-activated specimens, respectively. In the group of malignant tumors 57 of 62 were classified as euploid, and in this group 12 (21%) showed growth activity according to the NP content. Five of 62 were aneuploid, and 3 (60%) of these 5 tumors were growth activated. Evaluation of the growth activity by means of monoclonal antibody Ki-67 was performed on a subgroup of 32 thyroid specimens, both nonneoplastic and neoplastic lesions. Ki-67 immunoreactivity was observed in 0-1.1% cells of 6 nonneoplastic lesions, in 0-3.1% cells of 14 benign cells and in 0.2-3.9% cells of 12 malignant thyroid tumors. Growth activity, as reflected by the NP/DNA ratio and Ki-67 immunoreactivity, appears to be low both in nonneoplastic thyroid lesions and thyroid tumors.

Adenoma↗

Arabinitol enantiomers in cerebrospinal fluid.

D-Arabinitol is a metabolite of Candida species, and its presence in serum above endogenous concentration may indicate disseminated candidiasis. The o-trifluoroacetylated derivatives of arabinitol enantiomers in cerebrospinal fluid (CSF) were separated using perpentylated cyclodextrin capillary columns and measured by selected ion monitoring using negative chemical ionization mass spectrometry. The presence of D-arabinitol was confirmed using highly specific D-arabinitol dehydrogenase. The mean D/L-arabinitol ratio, 16.7 +/- 4.8 (range: 8.6-22.8), in CSF of the "controls" is approximately 10-fold higher than the ratio previously found in normal serum and urine. At the same time, the mean L-arabinitol concentration, 0.13 +/- 0.05 (range: 0.09-0.2), is virtually identical to that in serum. Therefore, the high D/L-arabinitol ratio in CSF is attributed to D-arabinitol. Persistently high D/L ratios were found in a variety of diseases (without Candida infection). The finding of D-arabinitol in CSF suggests that serum D-arabinitol may originate from the brain or the spinal cord, rather than from resident Candida species in the gut, and that the accumulation of D-arabinitol in CSF may be caused by non-consumption or, conversely, the high concentration may be maintained in order to have it readily available for metabolism in the brain.

Biomarkers↗

Diagnosing Staphylococcus aureus endocarditis by detecting antibodies against S. aureus capsular polysaccharide types 5 and 8.

Consecutive serum samples from patients with Staphylococcus aureus endocarditis or septicemia or non-S. aureus endocarditis and febrile nonsepticemic controls were tested for antibodies against S. aureus capsular polysaccharide (CP) types 5 and 8 by ELISA. The upper normal antibody levels were defined as the upper 99.5% confidence limits of the values from the febrile controls. All available patient isolates were tested for the presence of CP type 5 or 8 (85% of the isolates expressed either serotype), and all five patients with S. aureus endocarditis had positive antibody levels against the corresponding serotype within the first 10 days of infection. Three other endocarditis patients lacked isolates for CP testing but two of these were positive. Positive antibody levels were found in 0 of 28 septicemia patients, in 1 of 12 non-S. aureus endocarditis patients, and in 3 of 37 febrile controls. Thus, testing for anti-CP 5 or 8 antibodies, especially together with CP serotyping of the patient's isolate, seems to provide important information in the differential diagnosis of endocarditis in patients with S. aureus septicemia.

Antibodies, Bacterial↗

The topographic distribution of lymphocytic gastritis in gastrectomy specimens.

Forty-eight entire gastrectomy specimens received consecutively at this Department were cut into blocks for histologic examination. Focal or more extended areas of chronic gastritis (i.e. superficial or atrophic with or without intestinal metaplasia) were present in all 48 specimens. In addition, two of the 48 specimens had a large number of lymphocytes in the surface and foveolar epithelium of the mucosa. In the literature the latter is regarded as "lymphocytic gastritis". Lymphocytic gastritis was found in all 156 sections obtained from the two specimens. This lympho-epithelial phenomenon was present even in areas lacking chronic inflammation in the subjacent lamina propria mucosae. From our results it would appear that while chronic gastritis has a focal or a regional topographic distribution, lymphocytic gastritis includes the entire surface-foveolar epithelium of the gastric mucosa.

Adenocarcinoma↗

Syringe exchange for prevention of HIV infection in Sweden: practical experiences and community reactions.

An HIV prevention project, including syringe exchange, among intravenous drug users was started in Lund, Sweden, in November 1986. The program has been effective in reaching local addicts. Practical problems have been few. The educational and epidemiological effects on HIV infection are promising, and local drug treatment programs have benefited from the project in that previously untreated users have been attracted to treatment. The syringe exchange has been much debated. In general, the medical society, local authorities, and mass media have been supportive, while many politicians and social workers, especially in other parts of the country, have been strongly opposed. At present, the existence of the project is threatened.

HIV Infections↗

HIV prevention among injecting drug users: three years of experience from a syringe exchange program in Sweden.

Exchange of syringes and needles has for the last 3 years been offered to injecting drug users as part of an HIV prevention project in a small university town in south Sweden. The program at the local hospital has been visited by 979 drug users, of which 182 have participated on a more regular basis. The typical participant is a 30-year-old male who has injected amphetamine or heroin for at least 10 years. The seroprevalence for HIV among drug users in south Sweden has been maintained at approximately 1% in contrast to up to 60% in subpopulations from other Scandinavian regions with a comparable drug problem. No project participant has become HIV infected during the study period and a reduction in risk behavior has been noted among local drug injectors. The HIV prevention project has attracted many individuals with no previous contact with drug rehabilitation programs; for a number of drug users, the syringe exchange has served as an introduction to such treatment efforts.

Adult↗

Expression of Epstein-Barr virus-encoded proteins and B-cell markers in fatal infectious mononucleosis.

We assessed 33 lymphoid tissues from 15 patients, including 7 with X-linked lymphoproliferative disease (XLP) and 8 patients with sporadic fatal infectious mononucleosis (IM), to determine whether the cellular infiltrate had the immunophenotype and expressed Epstein-Barr virus (EBV)-encoded proteins characteristic of either EBV-immortalized lymphoblastoid cell lines (LCL) or EBV-carrying Burkitt lymphoma (BL) cells. The results of these studies revealed that in 13 cases the proliferating B cells were polyclonal, LCL-like, and in 2 cases they were monoclonal, malignant lymphoma-like.

Adult↗

Immunophenotypic characterization of follicle-center-cell-derived non-Hodgkin's lymphomas.

The distribution of the BLA, CALLA (CD 10), AC-2 (CD 39), MHM-6 (CD 23), LB-I, and 351C5 (CD 45R) antigens in 40 non-Hodgkin's lymphomas was demonstrated by immunohistochemical staining of frozen tissue sections. Nine out of 10 centroblastic and centrocytic follicular and diffuse type of lymphomas (CB/CC F/D) and all 10 cases of CB/CC follicular lymphomas were BLA+ and CALLA+. A few cases also showed weak expression of activation antigens (AC-2, MHM-6 and LB-I) and 351C5. In contrast, 3 CC and 3 lymphoblastic (non-Burkitt) lymphomas showed a heterogeneous pattern of distribution with dominating activation antigen expression. A single case of lymphoblastic lymphoma of Burkitt-like type expressed BLA and CALLA but not activation antigens. In reactive follicular center and FCC lymphomas different cell populations appeared to express BLA and activation antigens, respectively. Assessment of staining intensity and proportion of the stained cells indicated that almost all BLA+ cells are CALLA+. CALLA+ BLA- cells were regularly present, in addition. The co-expression of BLA and CALLA in the same cell was confirmed by double immuno-enzymatic staining. By the same technique, BLA+ and CALLA+ cells were shown to be activation-antigen negative.

Antigens, Differentiation, B-Lymphocyte↗

Mass spectrometric quantitation of muramic acid, a bacterial cell wall component, in septic synovial fluids.

This is the first report describing the use of gas chromatography-mass spectrometry for detection of muramic acid in infected synovial fluid (SF). Muramic acid is a ubiquitous component of bacterial cell walls, and it has been proposed that it could serve as a chemical marker for the presence of live bacteria or bacterial debris in rheumatoid joints. Our goal was to determine whether muramic acid was present at detectable levels in septic SF, since this would serve as a positive control for studies of reactive and rheumatoid arthritis. Muramic acid was found to be present at levels of less than 250-1,700 ng/ml in 12 septic SF samples (10 of which were culture positive for Staphylococcus aureus and 1 each for Escherichia coli and Streptococcus pneumoniae). Among these samples, those containing low bacterial colony counts did not contain detectable muramic acid. Muramic acid was also not detected in any SF samples from 20 control patients. We conclude that muramic acid can be used as a marker for the presence of bacterial peptidoglycan in SF. With further lowering of gas chromatography-mass spectrometry detection limits, determination of the quantities of bacterial debris present in joints of patients with rheumatoid or reactive arthritis will be attainable.

Cell Wall↗

The clinical use of monoclonal antibodies, MAb 17-1A, in the treatment of patients with metastatic colorectal carcinoma.

Increasing doses of MAb 17-1A (mouse IgG2A) have been given for therapy of patients with metastatic colorectal carcinoma (n = 28). Serum half-life (T beta 1/2) of MAb 17-1A after a single infusion was about 24 h. A constant serum level of MAb 17-1A could be maintained for a long time period by infusions every 2-3 days. Patients received 500 mg 3 days a week for 12 weeks (total dose 12 g). Side effects were mild and dose related but never required medical intervention except for three times (out of 243 infusions) when allergic reactions appeared. All patients developed IgM and IgG antibodies. Two patients experienced immune complex-related symptoms. Six out of 22 evaluable patients (27%) had objective evidence of tumor cell regression/lysis. One of these achieved a complete remission. Median survival for all patients was 12 months, for responding patients 19 months and for non-responding 11 months. 5/17 patients were studied for the development of anti-anti-idiotypic antibodies (Ab3). The presence of Ab3 in serum correlated favourably to the clinical outcome of the disease.

Adult↗

Flow cytometric DNA analysis: a prognostic tool in non-Hodgkin's lymphoma.

Surgical biopsies from 234 untreated patients with non-Hodgkin's lymphoma (NHL), classified according to the Kiel nomenclature, were analysed with respect to proliferative activity (S-phase) and DNA content by flow cytofluorometric (FCF-DNA) analysis. The percentage of cells in S-phase was significantly higher in lymphomas of high compared to low grade NHL (p less than 0.001). Patients with lymphomas of high grade histology and low S-phase values (less than 5.6%) achieved complete remission (CR) more often (p less than 0.05) and survived significantly longer than those with high S-phase values (p less than 0.05). In the low grade NHL group the S-phase value did not correlate to response. S-phase correlated to survival for patients with the lymphocytic (CLL & IC) (p less than 0.05) and follicle center cell (FCC) derived (p less than 0.01) but not in blastic (LB, IB, Burkitt) NHL. DNA-aneuploidy was associated with poor response to therapy and shorter CR duration in low grade NHL (p less than 0.05 for both). However, the degree of DNA-ploidy (neardiploid or aneuploid) did not correlate to survival in any of the NHL groups analysed (high- or low grade, lymphocytic, FCC derived or blastic). The Cox regression analysis indicated that the S-phase value was a stronger predictor of survival than histopathology, stage or age, especially in low grade NHL. These results suggest that S-phase analysis should be included in the clinical evaluation of NHL patients as a prognostic indicator.

DNA↗

In vitro culture of human thymic epithelial cells in serum-free media.

Epithelial cells from human thymus were cultured in vitro at various serum concentrations and under defined serum-free conditions. A total of 238 cultures from 46 thymuses (MG and normal) were analyzed. Cells from fresh thymic tissue were explanted either as fragments or single cells after enzyme treatment. Serum-free as well as fetal calf serum (FCS) containing media based on Dulbecco's minimal essential medium and Ham's F-12 (DMEM/F-12) were found to be superior to MCDB 151 based serum-free media combinations, for the selective growth of thymic epithelial cells. In contrast, cultures based on RPMI 1640 medium supplemented with 1% FCS or more showed less epithelial cell selectivity and also supplement Ultroser G gave less fibroblast contamination. In serum-free media containing less than 0.1 mM ionic Ca, the cells had a smaller surface area and appeared more angular and also contained less keratin as compared to culture media with higher calcium contents. The development of serum-free conditions for in vitro growth of human thymic epithelial cells free of fibroblast contamination will facilitate studies of growth and maturation of the epithelial cells as well as investigations of their possible role in the development of myasthenia gravis.

Cell Communication↗

Induction of proliferation and blast transformation by interferon in human malignant and non-malignant lymph node B cells.

The influence of interferon (IFN) on cellular proliferation, blast transformation, and differentiation was studied in lymph node cells from 17 patients with B-cell lymphomas, one patient with T-cell lymphoma, and eight patients with enlarged, non-malignant lymph nodes. The effects of IFN on lymph node cells were compared with effects on mononuclear blood cells from chronic lymphocytic leukemia (CLL) patients and healthy donors. Natural IFN-alpha (nIFN-alpha) induced a proliferative response in cells from seven of 17 of the B-cell lymphomas, in two of eight of the non-malignant lymph nodes, and in lymphoid blood cells from two of 32 CLL patients. With few exceptions, the proliferating cells were B cells and the data suggest that IFN acts directly on the B cells. Proliferation was not induced with IFN in cells from the T-cell lymphoma or in mononuclear blood cells from 13 healthy donors. nIFN-alpha induced blast transformation in cells from ten of 14 of the B-cell lymphomas and in four of seven of the non-malignant lymph nodes. Also beta- and gamma-IFN were shown to induce proliferation and blast transformation in lymph node cells from some patients. No major effect on the expression of various differentiation markers could be observed following culture in the presence of nIFN-alpha. We conclude that IFNs can induce proliferation and blast transformation in malignant and non-malignant B cells from lymph nodes.

Adult↗