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Biomedical subjects

G Paulsson

Publications and source records attributed to G Paulsson.

At least 19 recordsLinked to original sources
PubMed2001

Induction of inflammatory mediators during reperfusion of the human heart.

BACKGROUND: Cardioplegia and reperfusion may induce an inflammatory reaction, which may contribute to postoperative morbidity and mortality. METHODS: Gene expression of cytokines, adhesion molecules, and vasoactive substances was evaluated in left ventricular biopsies taken before cardioplegia (lasting approximately 70 minutes) and after reperfusion (approximately 40 minutes) from 19 patients (5 with valvular or combined disease, 7 with stable angina pectoris, 7 with unstable angina). mRNA was extracted and amplified with a semiquantitative reverse transcription polymerase chain reaction. RESULTS: Cardioplegia-reperfusion increased mRNA for E-selectin by a factor of 17 +/- 5 (p < 0.002) (mean +/- SEM), interleukin-1beta, with 9 +/- 3 (p < 0.007), tumor necrosis factor-alpha with 6 +/- 3 (p < 0.05), interleukin-2 receptor alpha chain CD25 with 2 +/- 0.6 (p < 0.04), and intercellular adhesion molecule-1 with 2 +/- 0.4 (p < 0.005). Before cardioplegia, mRNA for endothelial nitric oxide synthase was predominantly detected in unstable angina patients, and increased by a factor of 11 +/- 6 (p < 0.02) during reperfusion. mRNA for endothelin-1 decreased by a factor of 0.5 +/- 0.1 (p < 0.0005). The changes were more pronounced in unstable patients. The transcription factor nuclear factor kappa B (NFkappaB), which regulates expression of inflammatory mediators, was activated during reperfusion (n = 10, p < 0.0001). CONCLUSIONS: Open heart surgery induces an inflammatory response in the human heart, which is more pronounced in patients with unstable angina. It involves NFkappaB activation and expression of several NFkappaB-regulated genes.

Adult↗
PubMed2001

Recall of an oral health education programme by nursing personnel in special housing facilities for the elderly.

OBJECTIVES: To investigate the recall of oral health knowledge and confidence by nursing personnel in special housing facilities for the elderly, three years after an education programme. DESIGN: A cross sectional design using a questionnaire. SAMPLE: All nursing personnel, a total of 2,901 subjects, in five municipalities in south-western Sweden; of whom 950 had attended the programme. The response rate was 67% (1930 subjects). INTERVENTION: An oral health education programme consisting of four one-hour lessons. RESULTS: The oral health education programme still had an effect on the participants' attitudes towards oral health three years later. When comparing the trained group (OHEP+) which attended the programme with those who did not have training (OHEP-), the perceived ability, opportunity and the knowledge of oral health were significantly better in the former group, p < 0.01 Further, within the OHEP- group who did not attend the programme there was a significant difference in the perceived ability, opportunity and the knowledge of oral health between those with a higher level of health care education, p < 0.01. CONCLUSIONS: The effect of an oral health education programme on the participants' attitudes towards oral health persists at least for three years. The data indicate that trainees with a low level of health care education benefit most.

Attitude of Health Personnel↗
PubMed2000

Evidence for antigen-driven T-cell response in unstable angina.

BACKGROUND: Activation of T cells and macrophages has been associated with unstable angina (UA), but whether this reflects specific immune responses remains unclear. METHODS AND RESULTS: We analyzed the repertoire and the length of complementarity-determining region 3 of the T-cell receptor (TCR) beta-chain variable (BV) gene segments of activated lymphocytes in 23 patients with UA, 13 patients with chronic stable angina (CSA), and 6 normal control subjects. We also tested the proliferation of systemic T cells in response to autologous coronary plaque proteins, oxidized LDL, and Chlamydia pneumoniae as candidate antigens, in vitro. The activated T cell-TCRBV repertoire was perturbed in 13 (57%) of 23 UA patients versus 3 (23%) of 13 CSA patients (P=0.016) and was restricted to 6 (28%) of 21 expanded TCRBV families; all were significantly higher in UA than in CSA patients. At least one monotypic or oligotypic activated TCRBV population was found in 15 (65%) of 23 UA patients and in 3 (23%) of 13 CSA patients (P<0.001). Finally, T cells from UA patients, but not from CSA patients or normal control subjects, proliferated in response to autologous proteins from coronary culprit lesions and/or to oxidized LDL. CONCLUSIONS: Our findings suggest that the T-cell response observed in UA patients is antigen-driven and directed to antigens contained in the culprit coronary atherosclerotic plaques.

Angina, Unstable↗
PubMed2000

Gene expression of inflammatory mediators in different chambers of the human heart.

BACKGROUND: Inflammatory genes may be unevenly expressed in different heart chambers. METHODS: Biopsies were taken simultaneously from the right atrium (RA), left atrium (LA), and left ventricle (LV) of 19 patients before cardioplegic arrest during open heart surgery. The mRNA expression of tumor necrosis factor alpha (TNFalpha), interleukin 1beta (IL-1beta), inducible and endothelial nitric oxide synthase (iNOS and eNOS), endothelin-1 (ET-1), E-selectin (CD62E), intercellular adhesion molecule-1 (ICAM-1) and its ligand CD18, and CD25 was evaluated with semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Expression of TNFalpha mRNA was higher in RA than LA and LV (p<0.05), whereas IL-1beta was more expressed in LA than RA (p<0.05), which was higher than LV (p<0.0001). There were no significant regional differences in the expression of ICAM-1, CD62E, CD25, iNOS, and eNOS. CD18 was higher in RA than LA (p<0.05); ET-1 was more expressed in RA than LV (p<0.04). Patients with stable angina had no expression of eNOS. CONCLUSIONS: Gene expression of inflammatory mediators was detected in the hearts of patients with different cardiovascular disorders, and was unevenly distributed in different heart chambers. Cardiac biopsies should be taken from the same site.

CD18 Antigens↗
PubMed2000

The role of adaptive immunity in atherosclerosis.

Atherosclerosis is an inflammatory disease induced by a lipid metabolic disturbance at sites of hemodynamic strain in the vasculature. Studies in both man and experimental animal models show an involvement of innate and adaptive immune mechanisms in the disease process. Our recent studies in apoE-knockout mice show that the level of hypercholesterolemia affects the functional properties of the immune response. Modulating immune activity by injections of polyclonal immunoglobulins inhibits disease progression, suggesting that immunomodulation may be useful to treat atherosclerosis. Analysis of T cell receptor (TCR) mRNA in atherosclerotic lesions shows expansions of T cells expressing TCR-V beta 6, a receptor type that is also expressed by T cells recognizing oxidized low density lipoprotein (oxLDL). This suggests that oxLDL is an autoantigen that induces strong, local T cell responses in the plaque. Further characterization of this and other candidate antigens, such as heat shock proteins and macromolecular components of Chlamydia pneumoniae, may provide important information on which specific interference with the disease process could be based.

Animals↗
PubMed2000

Oligoclonal T cell expansions in atherosclerotic lesions of apolipoprotein E-deficient mice.

T cells are present in atherosclerotic lesions at all stages of development. They exhibit activation markers and are particularly prominent at sites of plaque rupture. This suggests that T-cell-mediated immune responses are involved in the pathogenesis of atherosclerosis. Antigen-specific T cells reactive with oxidized lipoproteins and heat shock proteins have been isolated from plaques, indicating that local activation and clonal expansion might occur. To analyze different stages of atherosclerosis, we have used a murine model. Targeted deletion of the apolipoprotein E gene results in severe hypercholesterolemia and spontaneous atherosclerosis, with lesions containing large numbers of T cells and macrophages. We have analyzed mRNA for T-cell antigen receptors (TCRs) from aortic fatty streaks, early fibrofatty plaques, and advanced fibrofatty plaques of such mice. Polymerase chain reaction amplification of complementarity-determining region 3 (CDR3 region) of TCRs was followed by spectratyping of fragment lengths. This analysis detected all types of variable (V) segments with a gaussian distribution of CDR3 in lymph nodes. In contrast, a restricted heterogeneity was found in atherosclerotic lesions, with expansion of a limited set of Vbeta and Valpha segments and a monotypic or oligotypic CDR3 spectrum in each lesion. Vbeta6 was expressed in all lesions; Vbeta5.2, Vbeta16, Valpha34s, and Valpha9, in the majority of lesions; and Vbeta6, Vbeta5.2, and Valpha34S, in lesions at all 3 stages of development. The strongly skewed pattern of the CDR3 region in the TCR is indicative of oligoclonal expansions of T cells and suggests the occurrence of antigen-driven T-cell proliferation in atherosclerosis.

Animals↗
PubMed2000

Induction of neonatal tolerance to oxidized lipoprotein reduces atherosclerosis in ApoE knockout mice.

BACKGROUND: In the course of atherosclerosis, humans and apolipoprotein (apoE) Knockout (KO) mice exhibit an active cell-mediated and humoral immune process, both at the systemic level and within atheromata. Low density lipoproteins (LDL) infiltrate the vascular wall, where they are oxidatively modified. This oxidative modification may generate new epitopes for which tolerance is not achieved during ontogenesis. Such epitopes could constitute new targets for autoreactive immune responses that may have a physiopathological role in disease development. MATERIALS AND METHODS: Exposing mice to high dose of antigens during thymic T-cell education induces immunological tolerance to the administered antigens. We injected newborn apoE KO mice with oxidized LDL. They were fed a cholesterol-rich diet and aortic atherosclerosis, cell-mediated immune response, and T-cell repertoire were analyzed after 5 months. RESULTS: Injection of oxidized LDL at birth reduced not only the immune response to oxidized LDL, but also susceptibility to atherosclerosis in apoE mice. Injection of oxidized LDL induced T-cell tolerance due to clonal deletion, rather than anergy of the reactive T cells. The T-cell repertoire of apoE KO mice was affected by the development of the disease, whereas tolerization normalized it. CONCLUSIONS: This study demonstrates that the immune response against oxidized LDL has a deleterious role in atherogenesis and that a fine-tuning of this response could modify the course of the disease.

Animals↗
PubMed2000

Ability to estimate oral health status and treatment need in elderly receiving home nursing--a comparison between a dental hygienist and a dentist.

The aim of this study was to compare the estimation ability of a dental hygienist to that of a dentist when, independently, recording the oral health status and treatment need in a population of elderly, receiving home nursing. Seventy-three persons, enrolled in a home nursing long-time care programme, were recruited. For the oral examination a newly developed protocol with comparatively blunt measurement variables was used. The oral examination protocol was tested for construct validity and for internal consistency reliability. Statistical analyses were performed using Wilcoxon matched pairs signed rank sum test for testing differences, while inter-examiner agreement was estimated by calculating the kappa-values. Comparing the two examiners, good agreement was demonstrated for all mucosal recordings, colour, form, wounds, blisters, mucosal index, and for the palatal but not the lingual mucosa. For the latter, the dental hygienist recorded significantly more changes. The dental hygienist also recorded significantly higher plaque index values. Also regarding treatment intention and treatment need, the dental hygienist's estimation was somewhat higher. In conclusion, when comparing the dental hygienist's and the dentist's ability to estimate oral health status, treatment intention, and treatment need, some differences were observed, the dental hygienist tending to register "on the safe side", calling attention to the importance of inter-examiner calibration. However, for practical purpose the inter-examiner agreement was acceptable, constituting a promising basis for future out-reach activities.

Aged↗
PubMed1999

Conceptions of oral health among nurse managers. A qualitative analysis.

AIM: The aim of this study was to describe how nurse managers perceive oral health in general and the oral health of the care-receiver in particular. BACKGROUND: Oral health and general health are independent and influence each other through biological, psychological, emotional and developmental factors. To most adults, oral health is a natural daily routine of hygiene, whereas to people who are dependent on other people's assistance, it is a procedure carried out by nursing personnel. METHODS: Data were collected through interviews and analysed according to the phenomenographical method. FINDINGS: Five categories emerged describing how nurse managers perceive oral health: maintaining patients' well-being, having knowledge about oral health, behaviour towards the patient, feeling of being insufficient and creating the necessary conditions. CONCLUSION: The nurses considered oral health an important and obvious, but neglected, part of nursing. They expressed the wish to be updated in the knowledge area concerned, both for themselves and for their personnel. A majority called for standards for oral care, including documentation, which was considered necessary for the successful implementation. IMPLICATIONS: A suggestion for further research is to study whether the creation of national standards may increase its status and quality.

Adult↗
PubMed1999

Hydrogen peroxide induces mRNA for tumour necrosis factor alpha in human endothelial cells.

Reactive oxygen intermediates are important mediators of inflammation. We investigated if hydrogen peroxide (H2O2) induces tumour necrosis factor alpha (TNFalpha) expression in cultured human cells from umbilical vein endothelium (HUVEC), aortic smooth muscle cells (SMC), peripheral blood mononuclear cells (PBMC), or the cell line Mono Mac 6. Cultures were stimulated with 200 micromol/L H2O2 for 15 min. After 4 h cells were harvested, mRNA extracted, and amplified by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) with histone (H3) as reference gene. In HUVECs, mRNA for TNFalpha increased with a factor of 4 after stimulation (p < 0.001), in PBMC with a factor of 2 (p < 0.05), while mRNA from SMC and Mono Mac 6 did not increase significantly. Cellular TNFalpha protein in HUVECs was measured with flow cytometry (FACS) before and 6, 12, and 24 h after stimulation. TNFalpha protein was detectable in small, but reproducible amounts 12 h after stimulation, and increased further after 24 h. However, no secretion of TNFalpha was detected by ELISA. FACS analysis of the passaged HUVEC cultures did not reveal any contamination with non-endothelial cells. In conclusion, H2O2 induces TNFalpha mRNA in HUVECs and PBMC. In HUVECs an increase of intracellular TNFalpha protein was also detected, indicating that endothelial cells can produce small amounts of TNFalpha.

Cells, Cultured↗
PubMed1998

Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice.

Atherosclerosis is an inflammatory-fibrotic response to accumulation of cholesterol in the artery wall. In hypercholesterolemia, low density lipoproteins (LDL) accumulate and are oxidized to proinflammatory compounds in the arterial intima, leading to activation of endothelial cells, macrophages, and T lymphocytes. We have studied immune cell activation and the autoimmune response to oxidized LDL in atherosclerotic apo E-knockout mice. Autoantibodies to oxidized LDL exhibited subclass specificities indicative of T cell help, and the increase in antibody titers in peripheral blood was associated with increased numbers of cytokine-expressing T cells in the spleen. In addition to T cell-dependent antibodies, IgM antibodies to oxidized LDL were also increased in apo E-knockout mice. This suggests that both T cell-dependent and T cell-independent epitopes may be present on oxidized LDL. In moderate hypercholesterolemia, IgG antibodies were largely of the IgG2a isotype, suggesting that T cell help was provided by proinflammatory T helper (Th) 1 cells, which are prominent components of atherosclerotic lesions. In severe hypercholesterolemia induced by cholesterol feeding of apo E-knockout mice, a switch to Th2-dependent help was evident. It was associated with a loss of IFN-gamma-producing Th1 cells in the spleen, whereas IL-4-producing Th2 cells were more resistant to hypercholesterolemia. IFN-gamma but not IL-4 mRNA was detected in atherosclerotic lesions of moderately hypercholesterolemic apo E-knockout mice, but IL-4 mRNA appeared in the lesions when mice were made severely hypercholesterolemic by cholesterol feeding. These data show that IFN-gamma-producing Th1 cells infiltrate atherosclerotic lesions and provide T cell help for autoimmune responses to oxidized LDL in apo E-knockout mice. However, severe hypercholesterolemia is associated with a switch from Th1 to Th2, which results not only in the formation of IgG1 autoantibodies to oxidized LDL, but also in the appearance of Th2-type cytokines in the atherosclerotic lesions. Since the two subsets of T cells counteract each other, this switch may have important consequences for the inflammatory/immune process in atherosclerosis.

Animals↗
PubMed1998

Promoter regions of four Balbiani ring genes in Chironomus tentans exhibit a common salivary gland-specific chromatin organisation, which is independent of the rate of transcriptional initiation.

The Balbiani ring (BR) gene family consists of four closely related genes which show some differences in transcriptional regulation. Here we analyse the chromatin structure of the promoter regions of the four BR genes. In cells in which the genes are inactive, digestion of chromatin with micrococcal nuclease suggests for the BR1 gene that precisely positioned nucleosomes are present from position +200 to -600. In salivary gland cells, a distinctly different organisation of the promoter chromatin leads to the appearance of two sites that are hypersensitive to both DNase I and micrococcal nuclease, located at the approximate positions -50 and -240. Nuclease digestion experiments suggest the presence of a nucleosome in the region between the two hypersensitive sites, and nucleosome disruption at the transcription initiation site. The positions of these hypersensitive sites in all BR genes is unaffected by extensive modulation of the rate of transcriptional initiation, although some alterations in the intensity of the hypersensitive sites were observed. We also show that total nucleosome displacement from the transcribing template is seen only when the RNA polymerase density exceeds one polymerase molecule per 100 bp.

Animals↗
PubMed1995

Laparoscopic prostaglandin injection in ectopic pregnancy: success rates according to endocrine activity.

OBJECTIVE: To investigate the clinical performance of local prostaglandin treatment of ectopic pregnancies (EPs) in relation to their biologic activity as determined by preoperative serum hCG levels. DESIGN: Prospective study over a 2-year period of 108 patients with 127 tubal pregnancies. SETTING: A department of obstetrics and gynecology in a central county hospital. PATIENTS: One hundred eight patients who presented with a clinical diagnosis of EP. INTERVENTIONS: Patients with EP were treated with laparoscopy-guided injection of prostaglandin F2 alpha in the surrounding tubal wall and the corpus luteum-bearing ovary. All members of the staff participated. MAIN OUTCOME MEASURES: Success rate, hospitalization cost, and convalescence period. RESULTS: Seven laparotomies (7.5%) were performed postoperatively due to increasing hCG levels or ruptures with circulatory reactions. All except one had an initial (preoperative) hCG value > 1,000 mIU/mL (conversion factor to SI unit, 1.00). The mean hospitalization period was 2.7 days and 90% of the medically treated patients returned home on the first postoperative day. The mean convalescence period was 18 days. CONCLUSION: The procedure is simple and carries an acceptable success rate in cases with hCG levels < 1,000 mIU/mL. The approach demands minimal technical resources and it may reduce health care costs substantially.

Abortion, Induced↗
PubMed1992

Balbiani ring 1 gene in Chironomus tentans. Sequence organization and dynamics of a coding minisatellite.

Balbiani ring (BR) genes in diptera encode large secretory proteins and are classical model systems for studies of gene expression. In Chironomus tentans, four closely related BR genes, BR 1, BR 2.1, BR 2.2 and BR 6 form a gene family. The BR genes have been partially characterized and are known to contain long arrays of tandemly arranged repeat units with an hierarchical repeat organization. Here, we report the sequence organization of the complete transcribed part of the BR 1 gene in C. tentans. The gene contains five exons and four introns. Three of the introns are located at the 5' end and the fourth at the 3' end of the gene. Exon 4 is approximately 35,000 bases long and is built completely from tandemly organized repeats. We show that this long repeat block contains two types of related repeat units, beta and gamma. Each type forms a large uninterrupted array, a 5' beta array and a 3' gamma array with a sharp border between them. In the hierarchical repeat structure in each repeat array, all repeats are virtually identical at one level of repetition, but shown differences at the next level. The whole repeat block in the BR 1 gene fluctuates in size between different alleles, but not by more than 10%. In contrast, within the block, the beta and gamma arrays vary in length between 8000 and 29,000 bases in an inverse fashion, together keeping the overall length requirement. We propose that the length of exon 4 is conserved by selection of cross-over products of a given length, and that the internal hierarchical sequence organization in the BR 1 gene is a consequence of the combined action of several different sequence turnover mechanisms, all dependent on the unequal pairing of homologous sequences at different, competing levels of repetition.

Amino Acid Sequence↗
PubMed1992

Sequence organization of the Balbiani ring 2.1 gene in Chironomus tentans.

Balbiani rings are giant chromosomal puffs, containing related genes that provide unique possibilities for in vivo analysis of gene expression at the chromatin and ribonucleoprotein levels. Here, the 5' end of the Balbiani ring 2.1 gene in the dipteran Chironomus tentans has been isolated and the sequence organization of the entire Balbiani ring gene is presented. The gene contains five exons, one being extremely small, only 6 base pairs, and one being extremely large, approximately 30 kilobase pairs. Three introns are located at the 5' end and a fourth one is located at the 3' end. The central 30-kilobase-pair exon is entirely built from tandemly organized repeats. All repeats are virtually identical except for a few variant repeats at both ends of the repeat array. The number of repeats may vary between alleles and the length of the gene therefore changes between 30 and 35 kilobase pairs.

Amino Acid Sequence↗
PubMed1992

Conserved and variable repeat structures in the Balbiani ring gene family in Chironomus tentans.

The four Balbiani ring (BR) genes, BR1, BR2.1, BR2.2, and BR6 in the midge Chironomus tentans constitute a gene family encoding secretory proteins with molecular weights of approximately 10(6) daltons. The major part of each gene is known to consist of tandemly organized composite repeat units resulting in a hierarchic repeat arrangement. Here, we present the sequence organization of the 5' part of the BR2.2 and BR6 genes and describe the entire transcribed part of the two genes. As the BR1 and BR2.1 genes were also fully characterized recently, this allows the comparison of all genes in the BR gene family. All four genes share the same exon-intron structure and have evolved by gene duplications starting from a common ancestor, having the same overall organization as the BR genes of today. The genes encode proteins that have an approximately 10,000-amino acid residue extended central domain, flanked by a highly charged, approximately 200-residue amino-terminal domain and a globular 110-residue carboxy-terminal domain. Exons 1-3 and the beginning of exon 4 encode the amino-terminal domain, which throughout contains many regions built from short repeats. These repeats are often degenerate as to repeat unit and sequence and are present in different numbers between the genes. In several instances these repeat structures, however, are conserved at the protein level where they form positively or negatively charged regions. Each BR gene has a 26-38-kb-long exon 4, which consists of an array of 125-150 repeat units and encodes the central domain. The number of repeat units appears to be largely preserved by selection and all repeat units in the array are very efficiently homogenized. Occasionally variant repeats have been introduced, presumably from another BR gene by gene conversion, and spread within the array. Introns 1-3 at the 5' end of the genes have diverged extensively in sequence and length between the genes. In contrast, intron 4 at the 3' end is virtually identical between three of the four genes, suggesting that gene conversion homogenizes the 3' ends of the genes, but not the 5' ends.

Amino Acid Sequence↗