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B Christensson

Publications and source records attributed to B Christensson.

At least 91 records · Page 5Linked to original sources
PubMed1995

The expression of glutathione transferase isoenzymes in human malignant lymphoma biopsies.

Glutathione transferase (GST) activity as well as the expression of different classes of GST isoenzymes were studied in 14 lymphoma biopsies. The GST activity measured with 1-chloro-2,4-dinitrobenzene as a substrate, varied almost 9-fold. The expression of GSTs classes Pi, Alpha and Mu was studied by immunoblotting using antibodies against human GSTs. All lymphoma samples displayed high levels of class Pi GST. Class Alpha and Mu GSTs expression varied from not detectable to high. The observations were confirmed by quantitation of the three classes of GST with an ELISA technique. Nine of the patients were treated with bifunctional alkylating agents. A correlation between a clinical complete response to chemotherapy and low expression of GST Alpha was noted (p < 0.02).

Alkylating Agents↗
PubMed1994

Effect of beta-lymphocyte- and NPC-derived EBV-LMP1 gene expression on in vitro growth and differentiation of human epithelial cells.

The effect of expression of the Epstein-Barr-virus (EBV) latent membrane protein (LMP1) derived from B-lymphocytes (B) and nasopharyngeal carcinoma (NPC) (C) on the in vitro growth and differentiation of a human keratinocyte line, Rhek-1, was analyzed in clonal growth and in in vitro differentiation assays. In contrast to the polygonal parental cells, the B-LMP1-expressing sublines were spindle-shaped while the C-LMP1-expressing cells were pleomorphic. Both B- and C-LMP1-expressing sublines showed increased proliferation as evidenced by: (1) higher colony-forming efficiency (CFE) and larger colony size at reduced serum levels; (2) an increased number of epithelial cell layers formed in the air-liquid-interface culture system and (3) increased expression of proliferative cell nuclear antigen (PCNA). At low serum concentration, the C-LMP1-expressing sublines formed larger colonies than those expressing B-LMP1. In the air-liquid-interface culture system, both B- and C-LMP1-expressing lines showed reduced epithelial differentiation resulting in reduced stratification and reduced involucrin expression similar to those of the cancer cell line, Siha. The results of the present study indicate that the expression of LMP1 in human keratinocytes is associated with morphological transformation and predisposes these cells to a more neoplastic phenotype. The structural difference between the 2 genes responsible for the functional differences and transforming ability will be pinpointed in further experiments.

Antigens, Viral↗
PubMed1994

Expression of Bruton's agammaglobulinemia tyrosine kinase gene, BTK, is selectively down-regulated in T lymphocytes and plasma cells.

The gene mutated in the human disease, X-linked agammaglobulinemia (XLA), is related to the Src gene family of cytoplasmic protein-tyrosine kinases and is designated Btk (Bruton's agammaglobulinemia tyrosine kinase; formerly Atk/Bpk; the human gene is denoted BTK, using capital letters according to the kinase nomenclature). We have recently reported that this gene is expressed in B lymphocytes and that the specific mRNA was undetectable in T cells using Northern blotting. Further analyses of different sources of B and T lymphocytes confirmed this pattern. However, BTK transcripts were undetectable in four plasmacytoma lines. Moreover, as virtually normal amounts of BTK transcripts were found in PBMC from two patients carrying a point mutation in BTK, despite low B cell numbers, we anticipated that the gene would also be expressed in cells of other lineages. The erythroleukemia cell line K-562, the promyelocytic line HL-60 and the histiocytic lymphoma line U-937 were found to have BTK mRNA levels comparable to B cells. BTK mRNA was also detected in monocytes from healthy donors as well as in the human immature basophilic cell line KU812, in the human mast cell leukemia cell line HMC-1 and in the CD34 expressing myeloblast KG-1. A similar expression pattern was obtained when BTK protein was analyzed by immunoprecipitation and Western blotting. Using a polymerase chain reaction-based analysis, a small amount (less than 1% of the level in B cells) of BTK mRNA was identified in T lymphocytes. Our findings are compatible with a general expression of the BTK gene in hematopoietic cells, except in T lymphocytes and plasma cells, in which the transcript level is selectively down-regulated.

Agammaglobulinemia↗
PubMed1994

Expression of Ki67 antigen, epidermal growth factor receptor and Epstein-Barr virus-encoded latent membrane protein (LMP1) in nasopharyngeal carcinoma.

The expression of Ki67 antigen, epidermal growth factor receptor (EGFR) and the Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP1) in nasopharyngeal carcinoma (NPC) was immunohistochemically determined. In cases with sufficient material western blot analysis was applied to analyse the LMP1 expression. Biopsies from 20 Chinese and 3 Swedish patients with NPC were included in the study. Our results demonstrated a nuclear Ki67 staining, a membrane EGFR staining, and a dot-like cytoplasmic and/or membrane LMP1 staining pattern in tumour cells of NPC. The proportion of Ki67-positive cells correlated with tumour stage. A strong expression of EGFR was frequently seen in patients with tumour stages III and IV and was paralleled by a higher proportion of Ki67-positive cells. The majority of the LMP1-positive cases strongly expressed EGFR and had a higher proportion of Ki67-positive cells, indicating a possible effect of EBV LMP1 on the proliferation of tumour cells in NPC. The increased expression of EGFR and Ki67 in NPC at late tumour stage indicates their possible use in malignancy grading of NPC.

Biomarkers, Tumor↗
PubMed1994

Epstein-Barr virus (EBV)-encoded membrane protein LMP1 from a nasopharyngeal carcinoma is non-immunogenic in a murine model system, in contrast to a B cell-derived homologue.

Epstein-Barr virus (EBV)-encoded LMP1 gene derived from a nude mouse passaged nasopharyngeal carcinoma (NPC) of Chinese origin (C-LMP1) and its B cell (B95-8 prototype)-derived counterpart (B-LMP1) were compared for their ability to induce tumour rejection in a mouse mammary adenocarcinoma system. Each of the two LMP1 genes was introduced individually by retroviral vectors into a non-immunogenic mammary carcinoma line, S6C, that originated in an ACA (H-2f) mouse. Syngeneic ACA mice were immunised for 3 consecutive weeks with irradiated B- or C-LMP1 expressors or control cells. The immunised and control mice were then challenged with graded numbers of viable cells from the corresponding cell line. Only the B-LMP1 expressing cells were highly immunogenic. Up to 10(5) cells were rejected in pre-immunised mice, whereas at least 10(2) cells grew in non-immunised controls. No rejection response was detected against the C-LMP1 expressing cells which grew equally well in control and immunised mice, with a minimum inoculum of 10(2) cells in the majority of the clones. In a previous study, we found numerous sequence differences between B- and C-LMP1. The question of whether any of these differences is related to the non-immunogenicity of C-LMP1 needs further investigation. Meanwhile, our findings raise the possibility that the NPC cells may escape host rejection by the development of a non-immunogenic LMP1 variant under the impact of immunoselection.

Animals↗
PubMed1994

Changing Swedish students' attitudes in relation to the AIDS epidemic.

In the present study we have evaluated the knowledge, attitudes and intention to act in relation to HIV/AIDS related issues among Swedish students aged 15-18 years. An intervention group (n = 368) and a comparison group (n = 180) were followed for 2 years between 1989 and 1991. The teachers of the intervention group were obliged to specifically give a continuous and in-depth education while the comparison group received ordinary traditional education. We present the results from questionnaires given to all students before and after the study. There was a significant increase in knowledge of facts in the intervention group, and also changes in attitudes towards, for example, gay people, drug users and HIV infected individuals, in a desirable direction. In sex related issues there was also a desirable change in intention to act, but this was not seen in students' relation to alcohol. No significant changes at all in knowledge, attitudes or intention to act were seen in the comparison group. Our results show that it is indeed possible to influence students' attitudes and intention to act in HIV/AIDS related issues provided teachers start by defining the students' central conceptions and their relation to each other, and promote individual thinking and reflection.

Acquired Immunodeficiency Syndrome↗
PubMed1994

In vivo expression of human immunoglobulin germ-line mRNA in normal and in immunodeficient individuals.

Previous in vitro studies suggest that transcription of the unrearranged immunoglobulin switch region and its 5' flanking region precedes isotype switching. These transcripts, which are devoid of a variable region, contain unique exons and are called germ-line (GL) mRNA. A crucial point in this regard is whether such transcripts could be detected in vivo, and if their expression correlates with immunoglobulin class switching in health and disease. To understand the in vivo role of this transcriptional activity we have adapted the reverse transcription-polymerase chain reaction (PCR) to analyse the GL transcripts from unstimulated peripheral blood mononuclear cells (PBMC) in healthy individuals and in different immunological diseases. Furthermore, mononuclear cells from different human organs were also analysed. We report here that GL (I alpha, I gamma and I epsilon used to designate the GL mRNA for IgA, IgG and IgE, respectively) mRNA are expressed differentially during ontogeny of B cells. Unexpectedly, no difference of I alpha mRNA expression between the PBMC and the secondary lymphoid organs was detected. Rather, the levels of GL transcripts were correlated to the number of sIgM+ cells. GL mRNA of all three isotypes could be detected in PBMC from healthy donors, whereas there was a decrease of specific GL transcript synthesis in individuals with immunoglobulin deficiency. Furthermore, during the in vivo immune response in a parasitic infection, we could demonstrate an induction of GL I epsilon mRNA during in vivo immune response. Concomitantly, there was also increased synthesis of productive epsilon transcripts. These findings implicate a potential role of GL transcription during in vivo immunoglobulin class switching.

Base Sequence↗
PubMed1994

Gas chromatographic determination of D-arabinitol/L-arabinitol ratios in urine: a potential method for diagnosis of disseminated candidiasis.

A gas chromatographic procedure was developed to determine the relative amounts of D- and L-arabinitol in urine. Samples were filtered, diluted, purified through extractions, evaporated, and treated with trifluoroacetic anhydride; the arabinitol derivatives thus obtained were separated on a chiral stationary phase and registered by using an electron-capture detector. Urine samples from a patient with disseminated candidiasis had higher D-arabinitol/L-arabinitol ratios (referred to as D/L-arabinitol ratios)--up to 19.0--than samples from 96 study individuals with no signs of deep Candida infections (range, 1.1 to 4.5). D/L-Arabinitol ratios in urine samples from hospitalized patients without Candida infections were slightly higher than those in samples from healthy individuals; ratios in urine from children were slightly higher than those in adult urine samples. The D/L-arabinitol ratios in several urine samples culture positive for Candida albicans, but from patients without symptoms of disseminated candidiasis, did not differ from those in the urine of healthy individuals. The described gas chromatographic method is straightforward and can be implemented clinically to determine urine D/L-arabinitol ratios as a means of diagnosing disseminated candidiasis.

Adult↗
PubMed1994

Induction of nasal and nasopharyngeal tumours in Sprague-Dawley rats fed with Chinese salted fish.

Epidemiological studies have implied that Chinese salted fish is a human nasopharyngeal carcinogen. In the present study, 162 Sprague-Dawley rats were randomly assigned to one of four experimental groups. Rats in groups 1 (n = 41) and 3 (n = 40) were exposed to salted fish from birth through the breast feeding period by giving the maternal rats a diet containing 10% and 5% salted fish, respectively, later feeding the rats with pellets containing 10% and 5% of salted fish respectively. In group 2, the rats (n = 41) were given pellets containing 10% of salted fish from 6 weeks of age. Rats in group 4 (n = 40), serving as controls, were only given ordinary pellets. Three rats had nasopharyngeal tumours, 2 from group 1 had a poorly differentiated carcinoma and a squamous cell carcinoma. One rat from group 2 had a squamous cell carcinoma. Four rats had nasal tumours, one fibrosarcoma and one adenocarcinoma were found in rats from group 1. One rhabdomyosarcoma was found in group 2, and one soft tissue sarcoma was found in a rat in group 3. No nasal or nasopharyngeal tumours appeared in the control group. The difference in the occurrence of malignant nasal and nasopharyngeal tumours among the four experimental groups was statistically significant (one tailed p for trend = 0.041). The frequency of tumours appearing in other organs such as the breast, kidney, lung, liver and brain was not significantly different between the salted fish treated groups and the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Expression of EBV encoded latent membrane protein 1 (LMP-1) and bcl-2 protein in childhood and adult Hodgkin's disease: application of microwave irradiation for antigen retrieval.

Surgical biopsies obtained from 32 children, and 34 adults with Hodgkin's disease (HD) were investigated for the expression of the EBV encoded Latent Membrane Protein 1 (LMP-1), bcl-2 protein, markers for HD; LeuM1 (CD15), BerH2 (CD30) and the new BLA.36, as well as for B (L26) and T lymphocytes (UCHL1). Before immunostaining, sections were subjected to an Antigen Retrieval (AR) procedure based on microwave irradiation in citrate buffer. In 13 cases staining with and without the AR procedure was compared. Immunoreactivity for LMP-1 was found in 44% of the biopsies from adults and 53% from children. We also found reactivity for the bcl-2 protein in Hodgkin's and Reed Sternberg (HRS) cells in 48% of the biopsies from adults and 45% from children. Immunoreactivity with BLA.36 was found in 94% of the biopsies from adults and 100% from children, with LeuM1 in 83% from adults and 93% from children and with BerH2 in 24% from adults and 84% from children. Nuclear PCNA staining was seen in HRS in all cases both adult and childhood. The T cell marker (UCHL1) displayed no reactivity with HRS cells. In 21% of the adult and 9% cases from the childhood cases we observed reactivity with the B cell marker (L26) in HRS cells. We can conclude that antigen retrieval improves immunostaining results of paraffin sections which were previously negative for bcl-2, LeuM1 and BerH2 antibodies. The high percentage of LMP-1 positive cases, both in adults and in children, indicates that the potential pathogenetic effect of EBV may be of similar importance both in childhood and in adult HD. The new MAb BLA.36 gave consistent immunostaining with HRS cells but also with other cell types. In a panel of markers for HRS cells BLA.36 together with LeuM1 (CD15) and BerH2 (CD30) are useful.

Adult↗
PubMed1993

Gamma-globulin modulates growth of EBV-derived B-cell tumors in SCID mice reconstituted with human lymphocytes.

The effect of weekly gamma-globulin injection on the development of human B-cell tumors was studied in 120 mice with severe combined immunodeficiency (SCID). The mice were injected intraperitoneally (i.p.) with human peripheral mononuclear cells (PBMC) from 6 different Epstein-Barr virus (EBV)-seropositive donors. Animals repopulated with cells from 5 donors received gamma-globulin or saline for 20 weeks and were followed up to 24 weeks after reconstitution. A delay in the appearance of fata EBV-derived human B-cell tumors was noticed in the gamma-globulin-treated groups as compared to the controls. In a separate experiment, the effect of gamma-globulin treatment during the initial 4 weeks after reconstitution was compared to treatment from week 5 to week 8 as well as to a continuous 20-week treatment. The results from this experiment showed that B-cell tumor growth could be prevented just as efficiently when the animals were treated only during the first 4 weeks. In contrast, no preventive effect was seen when the first gamma-globulin dose was given at the beginning of week 5 after reconstitution. Our results indicate that gamma-globulin reduces the frequency of EBV-derived B-cell tumor development and suggest that SCID mice repopulated with human cells represent a useful in vivo model for evaluation of the prophylactic and/or therapeutic effects of immunomodulatory treatments in lympho-proliferative disorders associated with immunosuppression.

Animals↗
PubMed1993

Evaluation of new enzyme-linked immunosorbent assay based on a supernatant containing Staphylococcus aureus alpha-toxin produced by Bacillus subtilis.

The gene encoding alpha-toxin from Staphylococcus aureus was cloned into a Bacillus subtilis expression vector (pEF 231/alpha-Tox). The protease-deficient B. subtilis strain DB 104 transformed with pEF 231/alpha-Tox expressed and secreted 5 mg of alpha-toxin per liter into the growth medium. The alpha-toxin-containing supernatant was diluted 200-fold and used as coating antigen in an enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of septicemia and endocarditis caused by S. aureus. Paired sera from patients in acute and convalescent stages of S. aureus and non-S. aureus infections were used to evaluate this ELISA. To evaluate the effectiveness of the crude preparation, the results were compared with those of an ELISA based on a commercially available alpha-toxin. Similar rises in serum titers were obtained with either type of alpha-toxin preparation. This is the first time a crude supernatant without any further purification has been used as an ELISA coating antigen. We therefore conclude that B. subtilis is a suitable host organism for cheap and simple production of prokaryotic recombinant antigens to be used in serodiagnosis.

Antibodies, Bacterial↗
PubMed1993

Studies on etiological factors of nasopharyngeal carcinoma.

A case-control study of nasopharyngeal carcinoma (NPC) was performed in Guangzhou, southern China in 1987 to 1989. We investigated 205 cases and an equal number of matched controls. Epstein-Barr virus (EBV) infection with positive IgA against viral capsid antigen (VCA-IgA) was shown to be the most important predictor in NPC. Consumption of salted fish was also strongly associated with NPC but not to the same extent as EBV. In order to investigate the possible carcinogenic effect of salted fish, Sprague-Dawley rats were given a diet containing salted fish for 2 years. Three rats with nasal and 3 with nasopharyngeal tumors were found in the experimental groups of 122 rats but none in the control group. Nitrosodimethylamine (NDMA) was found in kidney and liver but not in urine in the rats fed with salted fish. In a non-tumorigenic human keratinocyte line, RHEK-1, transfection of EBV latent membrane protein (EBV-LMP, originated from NPC cell line) induced alterations of morphology and immunophenotype. The LMP expressing sublines showed higher proliferative capacity and lower differentiation in vitro and some of the sublines produced tumors in SCID mice. When cultured in media containing salted fish extract in vitro parental RHEK-1 cells died after 12 weeks. In contrast, LMP expressing sublines survived indicating that exposure to some chemical compounds in salted fish and expression of EBV-gene may be of importance for the transformation of epithelial cells and thus for the pathogenesis of NPC.

Animals↗
PubMed1993

Candida albicans arthritis in a nonimmunocompromised patient. Complication of placebo intraarticular injections.

A nonimmunocompromised 32-year-old man with arthrosis of the knee participated as a placebo control in a clinical trial of intraarticular injections of hyaluronan. After the fourth weekly injection of saline, he developed a warm and swollen knee, and synovial fluid cultures revealed growth of Candida albicans. Oral fluconazole treatment was instituted 2 weeks after onset of symptoms, but failed to eradicate the infection. The patient recovered after treatment with local and systemic amphotericin B, systemic 5-fluorocytosine and surgical synovectomy. Quantitation of joint cartilage proteoglycan fragments in synovial fluid indicated extensive breakdown of cartilage during the acute phase of arthritis but, parallel to clinical recovery, these levels returned to normal.

Adult↗
PubMed1993

Human immunoglobulin germline alpha(IgA) transcripts are expressed in vivo and their level correlates to class switching.

Immunoglobulin isotype switching is preceded by transcription of exons located 5' of the immunoglobulin switch regions. These exons are referred to as 'I-exons' and transcription of these regions is believed to be an essential step in switch recombination. Such mRNA species lack a variable portion and are denoted 'germline' transcripts. We have previously identified I-regions in man and we have now investigated the in vivo expression of human germline transcripts. Germline alpha transcripts (containing an I alpha exon) were expressed in various lymphoid organs, including peripheral blood mononuclear cells. Decreased levels of germline transcripts were found in immunoglobulin deficiency diseases. These findings are compatible with an in vivo role of germline transcription in isotype switching and may contribute to the understanding of mechanisms underlying deficiency diseases.

Agammaglobulinemia↗
PubMed1993

Clonability and tumorigenicity of human epithelial cells expressing the EBV encoded membrane protein LMP1.

Two isolates of the EBV-LMP1 gene were compared for their ability to induce phenotypic changes in a non-tumorigenic human keratinocyte line, Rhek-1, immortalized with an adenovirus 12-SV40 hybrid virus. One isolate, designated B-LMP1, was derived from B95-8, a B-cell line of marmoset origin, that carries a viral strain from a mononucleosis patient. The other, designated C-LMP1, originated from a nude mouse passaged Chinese NPC tumor, CAO. Both types of transfectants were less serum dependent than the non-transfected and the vector-transfected controls. The ability to grow on low serum increased with increasing LMP1 expression. All transfectants were more highly clonable than the non-transfected or vector-transfected controls. Clonability in soft agarose increased with increasing LMP1 expression. Nine of 24 C-LMP1 transfectants produced tumors in SCID mice. Seven of them grew invasively into the surrounding tissue. Only one of 12 B-LMP1 transfected Rhek-1 clones was tumorigenic. It did not grow invasively. All tumorigenic transfectants expressed LMP1 at high or moderate levels. All tumors were found to express LMP1. Transfectants with low LMP1 expression did not produce tumors. The untransfected Rhek-1 cells and six vector control clones failed to produce tumors.

Adenoviridae↗
PubMed1992

Analysis of human IgA subclasses by in situ hybridization and combined in situ hybridization/immunohistochemistry.

In this report we describe a method for the analysis of the cellular expression of the two human IgA subclasses by in situ hybridization (ISH). The technique permits the detection of specific mRNA in individual cells using 35S-labeled oligonucleotide probes without any detectable cross-hybridization between the subclasses. This method was applicable both on cytospin preparation of peripheral blood mononuclear cells as well as in formalin-fixed, paraffin-embedded tissue sections. Furthermore, we describe a combined ISH/immunohistochemistry technique for the simultaneous detection of IgA subclass mRNA and protein at the single cell level. Examination of tissue sections from tonsils revealed a striking localization of labeled cells within the germinal center of some of the lymphoid follicles. The implications of this novel finding and the development of the method are discussed.

B-Lymphocytes↗