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S Hansen

Publications and source records attributed to S Hansen.

At least 109 records · Page 6Linked to original sources

Structural aspects of collectins and receptors for collectins.

The collectins are oligomeric molecules composed of C-type lectin domains attached to collagen regions via alpha-coiled neck regions. Five members of the collectins have been characterized. Mannan-binding lectin (MBL), conglutinin and collectin-43 (CL-43) are serum proteins produced by the liver. Lung surfactant protein A (SP-A) and lung surfactant protein D (SP-D) are mainly found in the lung, where they are synthesized by alveolar type II cells and secreted to the alveolar surface. The collectins are believed to play an important role in innate immunity. They bind oligosaccharides on the surface of a variety of microbial pathogens. After binding of the collectins to the microbial surface effector mechanisms such as agglutination, neutralizing or opsonization of the microorganisms for phagocytosis are initiated. SP-A and SP-D stimulate chemotaxis of phagocytes and once bound to the phagocytes, the production of oxygen radicals can be induced. In the case of MBL the opsonization can be further enhanced by complement activation via the MBLectin pathway while conglutinin interacts with the complement system by binding to the complement degradation product iC3b. A number of receptors and binding molecules interacting with the collectins are found on the membrane or in association with the membrane of various cells responsible for phagocytosis and clearance of microorganisms. This paper focus on the structural aspects of the collectins and the receptors for collectins.

Amino Acid Sequence↗

A woman's build and the risk of breast cancer.

A woman's build and the risk of breast cancer seem to be related. While relative overweight, as described by the body mass index, seems to be associated with increased breast cancer risk in postmenopausal women, overweight in premenopausal women seems slightly protective. Papers from a MEDLINE search are reviewed regarding the association between build and the development of breast cancer. Different aspects of build, such as height, weight, body mass index and body shape, are discussed. The more prominent associations found through this search are a positive association between height and breast cancer risk both in pre- and postmenopausal women. Regarding body mass index, the association is negative in premenopausal women and positive in postmenopausal women. Body shape described as masculine versus feminine seems to have no impact on breast cancer risk in premenopausal women, but seems to be positively associated with breast cancer in postmenopausal women. Possible biological mechanisms responsible for the associations with breast cancer risk are discussed, including endogenous oestrogens, androgens and glucose metabolic substances. Avoiding or reducing postmenopausal overweight may modify breast cancer risk indicators in a more favourable direction.

Body Mass Index↗

Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer.

The uPA-mediated pathway of plasminogen activation is central to cancer metastasis. Whether uPA and PAI-1 are related to local recurrence, metastatic spread or both is not clear. We present a retrospective study of 429 primary breast cancer patients with a median follow-up of 5.1 years, in which the levels of uPA and PAI-1 in tumour extracts were analysed by means of an enzyme-linked immunosorbent assay. The median values of uPA and PAI-1, which were used as cut-off points, were 4.5 and 11.1 ng mg(-1) protein respectively. The levels of uPA and PAI-1 were correlated with tumour size, degree of anaplasia, steroid receptor status and number of positive nodes. Patients with high content of either uPA or PAI-1 had increased risk of relapse and death. We demonstrated an independent ability of PAI-1 to predict distant metastasis (relative risk 1.7, confidence limits 1.22 and 2.46) and that neither uPA nor PAI-1 provided any information regarding local recurrence.

Adult↗

Anatomic bases of a new technique of juxta-acetabular osteotomy. Technical principles and performance.

Pelvic osteotomies were developed to increase or restructure the acetabular surface. Periacetabular osteotomies are considered the most difficult from the technical point of view and necessitate sufficient residual cartilaginous surface. Juxta-acetabular osteotomies avoid major disorganization of the pelvic framework and allow easier reorientation of the acetabulum. The authors present a technical variant that preserves the entire posterior column, as in the Ganz osteotomy. The effects on the vascularisation of the periacetabular region are strictly the same and there is no necrosis of the subchondral bone. This osteotomy is easier to perform, because of a single positioning associating two simultaneous approaches. The osteotomies are rectilinear and easy to check peroperatively by fluoroscopy thanks to this positioning. Another valuable aspect of this double approach consists of very easy correction of "automatic" unwanted retroversion due to the lowering of the acetabular roof. This unintended displacement is rarely reported in the literature, despite its anatomic evidence in 3-dimensional CT-scan reconstructions for pre- and peroperative evaluation.

Acetabulum↗

Angiogenesis in breast cancer: a comparative study of the observer variability of methods for determining microvessel density.

The purpose of this study was to evaluate the reliability of different methods for estimating neovascularization in breast cancer and to compare them in terms of observer variability. The microvessel endothelium was stained immunohistochemically by antibodies against CD34. The investigated methods included Chalkley counting, estimation of intratumoral microvessel density (MVD) by one hot-spot, MVD by the mean value of three hot-spots, and the highest value of MVD in three hot-spots. In addition, we applied stereology in the quantification of angiogenesis in the whole tumor section by random and systematically distributed sampling fields. Each of forty tumors was measured with all methods, twice by the same observer and once by another observer. Observer variation was analyzed by orthogonal regression, estimating the slope and intercepts with 95% confidence intervals (CI), and by analysis of agreement using difference plots. Intraobservationally, the methods had variations of the same magnitude (coefficient of variation [CV] approximately 20%). Interobservationally, the stereologic estimate of vessel profiles, Q(A), from the whole tumor section and the Chalkley counting method had the lowest variation (CV approximately 21%), with a small contribution by observers alone (CV 8% to 9%). Interobservationally, the MVD methods had considerable variation with a large contribution by observers alone (CV approximately 30%), which was lowest using the mean of three hot-spots. Correlation slope and 95% CI of Chalkley were 1.18 (0.95, 1.48), CV 20%; slope of MVD (mean) was 1.14 (0.91, 1.43), CV 31%; and slope of MVD (max) was 1.15 (0.92, 1.45), CV 36%. The slope of MVD on one hot-spot was 1.33 (1.08, 1.63); CV 38%. Additional measurements performed using a conference microscope, eliminating subjectivity in hot-spot selection and field sampling, optimized the reproducibility: slope was 1.02 (0.99, 1.04); CV of differences, 3.5%. On the other hand, reproducibility was not necessarily optimized by choosing the same hot-spot area, because variation in selecting a microscopic field could yield different counting numbers. The stereologic estimation of QA based on the whole tumor section had a high reproducibility, with low variation due to observers. The Chalkley and MVD methods had moderate reproducibility, and the Chalkley method had low variation due to observers alone. For all methods, the biologic variation among patients was the major contributor to the total variation. The Chalkley and MVD methods have been published to provide significant prognostic estimates in breast cancer, but the Chalkley method has less observer variation and may be superior from a methodologic point of view.

Antigens, CD↗

Targeted inactivation of alphai2 or alphai3 disrupts activation of the cardiac muscarinic K+ channel, IK+Ach, in intact cells.

Cardiac muscarinic receptors activate an inwardly rectifying K+ channel, IK+Ach, via pertussis toxin (PT)-sensitive heterotrimeric G proteins (in heart Gi2, Gi3, or Go). We have used embryonic stem cell (ES cell)-derived cardiocytes with targeted inactivations of specific PT-sensitive alpha subunits to determine which G proteins are required for receptor-mediated regulation of IK+Ach in intact cells. The muscarinic agonist carbachol increased IK+Ach activity in ES cell-derived cardiocytes from wild-type cells, in cells lacking alphao, and in cells lacking the PT-insensitive G protein alphaq. In cells with targeted inactivation of alphai2 or alphai3, channel activation by both carbachol and adenosine was blocked. Carbachol-induced channel activation was restored in the alphai2- and alphai3-null cells by reexpressing the previously targeted gene and guanosine 5'-[gamma-thio] triphosphate was able to fully activate IK+Ach in excised membranes patches from these mutants. In contrast, negative chronotropic responses to both carbachol and adenosine were preserved in cells lacking alphai2 or alphai3. Our results show that expression of two specific PT-sensitive alpha subunits (alphai2 and alphai3 but not alphao) is required for normal agonist-dependent activation of IK+Ach and suggest that both alphai2- and alphai3-containing heterotrimeric G proteins may be involved in the signaling process. Also the generation of negative chronotropic responses to muscarinic or adenosine receptor agonists do not require activation of IK+Ach or the expression of alphai2 or alphai3.

Carbachol↗

Protein interactions at the carboxyl terminus of p53 result in the induction of its in vitro transactivation potential.

The tumor suppressor protein p53 is a transcription factor frequently inactivated in human cancers. We have studied the DNA binding potential and the transcriptional activity of p53 variants and p53 protein complexes in in vitro transcription assays. p53 specific transcription was measured via introduction of radioactive UTP into G-free cassette transcripts regulated by promoter sequences containing p53 response elements. Latent and activated p53 fractions were prepared from insect cells infected with p53 encoding baculoviruses by chromatography on heparin columns. p53 fractions distinguishable by their specific DNA binding activities and their recognition by monoclonal antibody PAb421 were obtained. Specific DNA binding and binding to PAb421 are mutually exclusive. The C-terminus of p53 can be phosphorylated by casein kinase II, protein kinase C and cyclin dependent kinases. The antibody PAb421 binds within the PKC phosphorylation site of p53 and is able to activate DNA binding of latent p53 in vitro. Activation of p53 by PAb421 also results in enhanced transactivation in vitro. Dephosphorylation of latent p53 with phosphatase 2A does not change these properties. This suggests that a conformational change in the carboxyl terminal domain of p53 controls the transactivation potential of p53.

Animals↗

Trends in the incidence of ovarian cancer and borderline tumours in Norway, 1954-1993.

Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumours in Norway were examined, based on data from the population-based Cancer Registry of Norway. A total of 14,352 cases of ovarian cancer were diagnosed between 1954-1993, of which 94% of the histologically verified ovarian cancers were epithelial tumours. The age-adjusted incidence rate rose from 10 per 100,000 person-years in 1954-1958 to a peak of 14 per 100,000 person-years in 1984-1988. In women older than 50 years, there was an increasing trend in incidence rates during the entire study period. From the cohort perspective, the largest increase was observed among women born between 1870-1899. A total of 2,343 borderline tumours was diagnosed between 1970-1993. The age-adjusted incidence rate has increased since 1970, reaching 4.8 per 100,000 person-years in 1989-1993.

Age Factors↗

Esophageal and gastric carcinoma in Norway 1958-1992: incidence time trend variability according to morphological subtypes and organ subsites.

The occurrence of adenocarcinoma (AC) of the esophagus and gastric cardia has shown large increases in many but not all examined populations. This trend is in contrast with a decrease in distal gastric AC and a relative stability of esophageal squamous cell carcinoma. Our study aimed to describe esophageal and gastric carcinoma time trends in the Norwegian population between 1958 and 1992 based on data from the Cancer Registry of Norway. Estimated esophageal AC rates have accelerated over the study period, reaching average annual increases of 17% in men and 14% in women between 1983 and 1992. The occurrence of esophageal squamous cell carcinoma was relatively stable in both sexes. Proximal gastric cancer rates were stable in males and decreased somewhat in females. Distal gastric tumors showed decreases in both sexes, but were more pronounced in females. The strong increase in esophageal AC incidence parallels similar increases in the United States and some other countries. Although the observed increase may be explained to some extent by a shift in the classification of esophago-cardial adenocarcinomas, the figures are compatible with a real increase. AC of the esophagus, the proximal stomach and the distal stomach exhibit different epidemiological features, both in terms of sex ratios and time trends, suggesting risk factor differences between the subsites.

Adenocarcinoma↗

A second serine protease associated with mannan-binding lectin that activates complement.

The complement system comprises a complex array of enzymes and non-enzymatic proteins that is essential for the operation of the innate as well as the adaptive immune defence. The complement system can be activated in three ways: by the classical pathway which is initiated by antibody-antigen complexes, by the alternative pathway initiated by certain structures on microbial surfaces, and by an antibody-independent pathway that is initiated by the binding of mannan-binding lectin (MBL; first described as mannan-binding protein) to carbohydrates. MBL is structurally related to the complement C1 subcomponent, C1q, and seems to activate the complement system through an associated serine protease known as MASP (ref. 4) or p100 (ref. 5), which is similar to C1r and C1s of the classical pathway. MBL binds to specific carbohydrate structures found on the surface of a range of microorganisms, including bacteria, yeasts, parasitic protozoa and viruses, and exhibits antibacterial activity through killing mediated by the terminal, lytic complement components or by promoting phagocytosis. The level of MBL in plasma is genetically determined, and deficiency is associated with frequent infections in childhood, and possibly also in adults (for review, see ref. 6). We have now identified a new MBL-associated serine protease (MASP-2) which shows a striking homology with the previously reported MASP (MASP-1) and the two C1q-associated serine proteases C1r and C1s. Thus complement activation through MBL, like the classical pathway, involves two serine proteases and may antedate the development of the specific immune system of vertebrates.

Amino Acid Sequence↗

Infarct size measurement by triphenyltetrazolium chloride staining versus in vivo injection of propidium iodide.

Infarct size delineation by triphenyltetrazolium chloride (TTC) staining is dependent on sufficient reperfusion. We therefore evaluated the possibility of using propidium iodide (PI), a reagent conventionally used in flow cytometry to fluorescently stain dead cells, for infarct size analysis after short periods of reperfusion. Forty-five rabbits were subjected to either 15 min, 2 h or 4.5 h of coronary artery occlusion without reperfusion, or to 15 min, 30 min and 2 h of coronary artery occlusion followed by 30 min, 1 h and 3 h of reperfusion. Fifteen min before terminating the experiment, PI was injected into the left atrium. Patent blue violet was used to delineate the area at risk. Following incubation in TTC, the area at risk was excised and cross sections obtained for microscopical infarct size quantification by PI fluorescence. PI fluorescence was absent after permanent occlusion and in control areas. Infarct sizes measured by TTC staining were significantly smaller after 1 h of reperfusion as compared to 3 h of reperfusion (30 min occlusion: 1+/-1 v 34+/-9%; P<0.05; 2 h occlusion: 9+/-6 v 47+/-8%; P<0.01). In contrast, infarct sizes determined by PI fluorescence reached values comparable to those measured by TTC staining or conventional histology after longer times of reperfusion already after 30 min of reperfusion (30 min occlusion: 35+/-16.5%; 2 h of occlusion: 61+/-8%). Therefore, after short times of reperfusion infarct size measurement by PI fluorescence is more reliable than by TTC staining.

Animals↗

Isolated partial rupture of the anterior cruciate ligament. Long-term follow-up of 56 cases.

The majority of previous studies on partial ruptures of the anterior cruciate ligament (ACL) include a relatively large proportion of knees with associated intra-articular injury or collateral ligament tear that contributes to an increase in the symptoms of instability and further deterioration of knee function. In the present study only patients with isolated, partial ruptures of the ACL were evaluated. Fifty-six patients with one injured knee were examined after a median of 5.3 (range 2.0-12.7) years using the IKDC evaluation form, Lysholm knee function score and Tegner activity score. Of the 56 knees, 6 underwent autologous reconstruction due to early progression to complete rupture. Of 34 knees evaluated for laxity, 25 had a negative Lachman test and 7 a positive (+) Lachman. In 2 knees a Lachman ++ result and a positive pivot shift were found. With instrumented laxity testing 24 knees had 2 mm or less difference in laxity compared with the contralateral uninjured knee. The largest side-to-side difference in knee laxity was 4.5 mm. Lysholm score was median 86 (range 52-100) points, and 62% had good or excellent knee function. A significant decline in activity was seen. Only 10 patients (30%) resumed their preinjury activities. We find that the majority of patients with an isolated, partial rupture of the ACL have an acceptable knee function and a stable knee after a median 5 years follow-up. There is, however, a marked reduction in activity.

Adolescent↗

Hodgkin's disease in a national and hospital population: trends over 20 years.

The aim of the study was to investigate the incidence rate and time trends in a national registry population of Hodgkin's disease (HD) and the effects of selection in a hospital population. A national registry population of all HD patients from Norway and a hospital population of HD patients treated at the Norwegian Radium Hospital (NRH) were studied retrospectively from 1971 to 1993. The incidence of non-Hodgkin's lymphomas (NHL) in Norway increased steadily from 1961 in contrast to a stable incidence pattern for HD before 1980 and a decreasing incidence since 1980. Due to improved diagnostic tools after 1980, an increasing proportion of patients previously diagnosed as lymphocyte depleted and unclassified HD were classified as NHL. As these histologies are dominant in older patients, the incidence of older patients with HD and the total population of HD have decreased since 1980. As a result, the proportion of young adults with a favourable histology has increased. These changes may partly explain the increased patient survival observed both in the national and the hospital population. The hospital population comprised 92% of patients aged 15-39 years, 80% of patients aged 40-59 years and 53% of patients aged > 60 years in the national population. The selection of younger patients in the hospital material may explain a higher survival rate as compared with the national population.

Adolescent↗

Estimates of the sources of variation (variance components) of bioelectric impedance and anthropometric measurements in an epidemiological case-control study of breast cancer.

OBJECTIVE: This study investigated the variability of anthropometric measurements and body fat estimated by bioelectric impedance analysis. Subsequently the methods were applied in a case-control study to investigate the association with breast cancer. DESIGN, SUBJECTS: The study group included 50 consecutive cases and 75 age-matched controls from the same area. The variation was investigated in 50 healthy women from the control group, who were repeatably measured using standardised measurement procedures, and the variation between-subjects, within-subjects, between-observers, and within-observers were estimated. RESULTS, CONCLUSIONS: The study showed that the variance components between-subjects were 64-99% of the total variance. The variables of skinfold thicknesses were characterised by having the highest relative observer variation and having many unavailable values that were out of the range of the Harpenden callipers. The mean body fat by bioelectric impedance analysis was 31.2%, and the total coefficient of variation 23%, while the variance components related to subject time, observer and measurement were 98.4%, 1.1%, 0.2%, and 0.4%, respectively. The body fat was significantly correlated with the variables of skinfold thicknesses. We decided to exclude the variables of skinfold thicknesses from the case-control study, and for the other variables to measure each subject only at one time by one observer. The case-control part of the study indicated a non-significant increase in body weight in the postmenopausal breast cancer patients (mean difference 3.6 kg; confidence interval from -0.9 kg to 8.0 kg). Similarly the body fat tended to be higher in the breast cancer patients (mean difference 1.2%; confidence interval from -1.6% to 4.0%).

Adult↗

The non-invasive acetylene rebreathing method for estimation of cardiac output: influence of breath-by-breath variation.

The inert gas rebreathing method enables non-invasive estimation of pulmonary capillary blood flow, lung tissue volume, transfer factor and functional residual capacity. In the present study, we have examined the influence of breathing pattern during the rebreathing manoeuvre on the precision of the rebreathing method, both theoretically and experimentally. We examined whether the precision of the method could be improved by the guidance and training of the subjects doing the rebreathing manoeuvre. The results of the theoretical study showed that the precision and accuracy of the rebreathing method are practically insensitive to random variation in the breathing pattern. Simulated breath-by-breath variations up to +/-50% of the average 3.01 VT resulted in coefficients of variation of about 3% for QC and about 5% for VTC. Simulated breath-by-breath variations indicate that with mean tidal volume or rebreathing bag volume lower than 1.01 the precision will worsen, and with tidal volume lower than 1.5 1 the accuracy will worsen. The experimental results showed no significant improvement in the precision of the rebreathing method by visual guiding and training of the subjects to optimize the breathing pattern during the rebreathing manoeuvre.

Acetylene↗

Risk for gastric lymphoma in persons with CagA+ and CagA- Helicobacter pylori infection.

Infection with Helicobacter pylori increases the risk for gastric non-Hodgkin's lymphoma (GNHL). Strains that express CagA protein are thought to be particularly virulent. It was determined whether CagA+ H. pylori infection increased the risk for GNHL more than CagA infection. Thirty-two cases and 130 controls previously tested for H. pylori antibodies were tested for CagA antibodies by ELISA. The risk for GNHL was compared among CagA+, CagA-, and uninfected persons by use of conditional logistic regression. CagA+ subjects had 8.2 times the risk for GNHL than uninfected persons (95% confidence interval [CI], 2.5-26.7). CagA- subjects had 4.4 times the risk for GNHL than uninfected persons (95% CI, 1.2-16.5). Among infected subjects only, CagA+ infection was not associated with significantly increased risk for GNHL when compared with CagA- infection (odds ratio, 2.1; 95% CI, 0.8-5.4). This study does not support a major role for CagA in lymphomagenesis.

Antibodies, Bacterial↗