Search PubMed⌕ Search

Biomedical subjects

S Larsen

Publications and source records attributed to S Larsen.

At least 19 recordsLinked to original sources
PubMed1996

Purification and characterization of dihydroorotate dehydrogenase A from Lactococcus lactis, crystallization and preliminary X-ray diffraction studies of the enzyme.

Lactococcus lactis is the only organism known to contain two dihydroorotate dehydrogenases, i.e., the A- and B-forms. In this paper, we report the overproduction, purification, and crystallization of dihydroorotate dehydrogenase A. In solution, the enzyme is bright yellow. It is a dimer of subunits (34 kDa) that contain one molecule of flavin mononucleotide each. The enzyme shows optimal function in the pH range 7.5-9.0. It is specific for L-dihydroorotate as substrate and can use dichlorophenolindophenol, potassium hexacyanoferrate (III), and, to a lower extent, also molecular oxygen as acceptors of the reducing equivalents, whereas the pyridine nucleotide coenzymes (NAD+, NADP+) and the respiratory quinones (i.e., vitamins Q6, Q10 and K2) were inactive. The enzyme has been crystallized from solutions of 30% polyethylene glycol, 0.2 M sodium acetate, and 0.1 M Tris-HCl, pH 8.5. The resulting yellow crystals diffracted well and showed little sign of radiation damage during diffraction experiments. The crystals are monoclinic, space group P21 with unit cell dimensions a = 54.19 A, b = 109.23 A, c = 67.17 A, and beta = 104.5 degrees. A native data set has been collected with a completeness of 99.3% to 2.0 A and an Rsym value of 5.2%. Analysis of the solvent content and the self-rotation function indicates that the two subunits in the asymmetric unit are related by a noncrystallographic twofold axis perpendicular to the crystallographic b and c axes.

Bacterial Proteins↗
PubMed1996

Characterization of 'winners' to enoxaparin in the prevention of postoperative venous thromboembolism in digestive surgery.

BACKGROUND: A total of 826 patients were included in three 'play-the-winner' studies to investigate the safety of prophylaxis against venous thromboembolism in digestive surgery. To characterize patients benefiting from prophylaxis with low-molecular heparin, the 445 patients allocated to enoxaparin were investigated. METHODS: A training set consisting of 292 patients from 2 of the studies was analysed by using a linear discriminant model. The reliability of the results was verified on a test set consisting of 153 patients from the third study. RESULTS: A typical 'winner' was a young patient, preferably female, with serum bilirubin in the lower normal range, combined with body temperature, serum sodium, creatinine, and albumin in the upper normal ranges. By using the discriminant function on the test set, 81.7% of the 'winners' and 21.1% of the "losers' were correctly classified. CONCLUSION: The discriminant function for characterization of winners to enoxaparin was found adequate. No rule was acceptable for characterization of losers.

Anticoagulants↗
PubMed1995

Risk factors and cofactors for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica.

Human T-cell lymphotropic virus type I (HTLV-I) has been etiologically associated with a neurologic syndrome called HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as with adult T-cell leukemia/lymphoma. The authors sought to quantify the risk in Jamaica of HAM/TSP associated with HTLV-I infection and cofactors associated with this disease among infected individuals. Between 1988 and 1989, prevalent and incident HAM/TSP patients and controls with other neurologic diseases were enrolled in a retrospective study. A second control group was composed of HTLV-I-seropositive, asymptomatic carriers in Jamaica, ascertained in a separate study conducted in 1988. Although HTLV-I seropositivity was not a component of the case definition for HAM/TSP, all 43 HAM/TSP patients were HTLV-I seropositive compared with two (4.0%) of the controls with other neurologic diseases. Given HTLV-I seropositivity, one cofactor associated with the risk of HAM/TSP was young age at initial heterosexual confidence interval 1.29-12.46 for individuals aged < or = 15; odds ratio = 4.26, 95% confidence interval 1.41-12.90 for individuals aged 16-17 years at initial intercourse). Among individuals who reported this early age at initial sexual intercourse, an increased risk of HAM/TSP was associated with having reported more than five lifetime sexual partners (odds ratio = 2.88, 95% confidence interval 0.90-8.70). Neither an early age at initial sexual intercourse or the number of lifetime sexual partners was a risk factor for adult T-cell leukemia/lymphoma. These data support the hypothesis that HAM/TSP is associated with sexually acquired HTLV-I infection, whereas adult T-cell leukemia/lymphoma is not.

Adolescent↗
PubMed1995

Hostility, incidence of acute myocardial infarction, and mortality in a sample of older Danish men and women.

An abbreviated version of the Cook-Medley Hostility Scale (ACM) was a predictor of documented acute myocardial infarction and total mortality. The sample consisted of 409 men and 321 women, residents of Glostrup, Denmark, who were 50 years old at the initiation of the study in 1964. Follow-up continued through 1991. Although not significant (relative risk (RR) = 1.22) in a model that contained only age and sex as covariates, the hostility scale scores were associated with increased risk of myocardial infarction in models controlling for traditional risk factors. A two standard deviation difference was associated with a RR of 1.53 (95% confidence interval (CI) 1.04-2.25), an effect that remained after eliminating the data of those with signs of ischemia at baseline. Hostility was also predictive of total mortality with controls for age and sex (RR = 1.35, CI 1.07-1.71), with controls for traditional risk factors (RR = 1.44, CI 1.13-1.83), and with additional controls for baseline ischemia and pulmonary function (RR = 1.36, CI 1.06-1.75). There were no sex differences in effect sizes. In cross-sectional analyses, high hostility was associated with higher body mass index, more physical activity at work, and poorer pulmonary function. These results constitute a rigorous test of the relation between hostility and health and increase the known generality of the phenomenon across sexes, age groups, and cultures.

Age Distribution↗
PubMed1995

IL-12 directly enhances in vitro murine erythropoiesis in combination with IL-4 and stem cell factor.

It has been demonstrated recently that in vivo administration of murine IL-12 to mice enhances the activity of cytotoxic NK cells and lymphocyte-activated killer cells, and that it has antitumor and antimetastatic activity. However, one side effect observed in response to systemic IL-12 treatment is anemia. In the present study, we examined for the first time the ability of IL-12 to affect directly the growth of murine erythroid progenitor cells in vitro. Whereas IL-12 alone or in combination with Erythropoietin (Epo) showed no stimulatory effect on erythroid progenitors, IL-12 potently enhanced the number of erythroid burst-forming unit (BFU-E) colonies formed in response to Epo+IL-4 by 63% and Epo+stem cell factor by 80%. The stimulatory effect of IL-12 occurred in a concentration-dependent fashion, with maximum enhancing effect observed at 50 ng/ml. Furthermore, single cell experiments suggested that the stimulatory effect of IL-12 on erythroid colony formation was directly mediated. Thus, IL-12 can directly enhance murine erythropoiesis in vitro, suggesting that IL-12-induced anemia is mediated through an indirect mechanism.

Animals↗
PubMed1995

Altered Th1/Th2 balance associated with the immunosuppressive/protective effect of the H-2Ab allele on the response to allo-4-hydroxyphenylpyruvate dioxygenase.

The H-2Ab allele exerts a dominant down-regulatory effect on the anti-allo-HPPD (4-hydroxyphenylpyruvate dioxygenase) antibody response, through a hitherto unknown mechanism. In the present study, the allo-variable peptide bound to responder H-2Ak molecules with higher affinity than to H-2Ab ones, arguing against the operation of an affinity hierarchy. Quantitative polymerase chain reaction revealed differences in cytokine mRNA expression between suppressed and high-responder mice. Lymph node cells of responder but not suppressed mice contained high levels of interleukin (IL)-4 mRNA as early as 11 h post-immunization and continued to do so for at least 8 days; this early burst was paralleled by a small burst in transforming growth factor (TGF)-beta mRNA level. Differences in IL-12 mRNA were not detected, although an early IL-12 effect could not be excluded. Interferon (IFN)-gamma appeared to contribute to the suppression at later time points. Early treatment of responder mice with anti-IL-4 monoclonal antibody (11B11) down-regulated the antibody response. The proliferative T cell response from hyperimmunized mice was reduced but still detectable in the presence of an H-2Ab allele. Thus, in the presence of this allele, the Th1 response is enhanced and that of Th2 cells suppressed, apparently as a result of the bias of H-2Ab-restricted T cells in favor of the Th1 subset.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1995

A case-control study of psychological and psychosocial risk factors for shoulder and neck pain at the workplace.

Risk factors associated with work-related shoulder and neck myalgia were investigated in a case-control study with pairs matched for age, gender, and physical exposure. Guided interviews with standardized and self-constructed questionnaires were performed among manual (n = 15 pairs) and office (n = 24 pairs) workers. Perceived general tension was the variable with the strongest association with shoulder and neck pain in both work groups. Otherwise, the results in the two groups were very different, indicating that different risk factors and mechanisms were associated with shoulder and neck pain in the two work groups. The study provides background information for future attempts to establish causal relationships between physical and psychosocial exposure and shoulder and neck pain, which can be more accurately investigated in a longitudinal rather than a cross-sectional experimental design.

Adult↗
PubMed1995

Sexual behavior, sexually transmitted diseases, and risk of cervical cancer.

To explore sexually transmitted diseases and sexual behavior as risk factors for cervical cancer, we analyzed data from a population-based case-control study of breast and cervical cancer in Costa Rica. Data from 415 cases of cervical carcinoma in situ, 149 cases of invasive cervical cancer, and 764 controls were included in the analysis. Multivariate analysis showed that lifetime number of sex partners, first intercourse before age 15 years, number of livebirths, herpes simplex virus type 2 seropositivity, and serologic evidence of previous chlamydial infection were predictors of carcinoma in situ. Serologic evidence of previous syphilis was not associated with carcinoma in situ. Predictors for invasive cervical cancer included lifetime number of sex partners, first intercourse before age 15 years, number of livebirths, serologic evidence of previous syphilis, herpes simplex type 2 infection, and chlamydial infection. Cigarette smoking, socioeconomic status, self-reported history of sexually transmitted diseases, and douching were not associated with either carcinoma in situ or invasive cervical cancer.

Adult↗
PubMed1995

Dietary factors and colorectal polyps: a case-control study.

In the case-control study we compared dietary habits among 108 patients with small (< or = 5 mm, n = 26), medium (5-9 mm, n = 48) or large (> or = 10 mm, n = 34) colorectal polyps with 35 healthy age- and gender-matched controls. A food record by weighing during 5 consecutive days was performed. The intake of fat was significantly higher among the patients, in contrast to a significantly lower intake of carbohydrate, dietary fibre and iron, compared with controls. The intake of vitamin C and calcium was shown to be lower among the patients, but this was significant only for women. There was a tendency among the patients to consume a lower-antioxidant, fibre and cereal fibre diet, and a calcium-rich and more cholesterol-rich diet with increasing size of polyps. The patients with the smallest polyps tended to consume less starch. Our results are too preliminary to draw conclusions with regard to the influence of nutritional factors on the size and growth of polyps. However, our risk factors for the presence of polyps are in agreement with previous studies. Further studies taking into account the size of the polyp are needed to corroborate our findings.

Aged↗
PubMed1995

Can a regular leg extension bench be used in testing deficits of the quadriceps muscle during rehabilitation?

Fifty-nine people, 31 healthy subjects with no previous knee injuries and 28 who had undergone an intra-articular anterior cruciate ligament reconstruction 6-12 months prior to testing took part in the study. The subjects were randomly tested bilaterally on a Cybex 6000 isokinetic testing device (ITD) and on an ordinary leg extension bench (LEB). Strength and endurance were tested with both methods. The linear relationships for paired strength and endurance differences between ITD and LEB were found to be acceptable for the operated group. The LEB alone explained 57% and 38% of the ITD outcome for strength and endurance, respectively. The agreement between observed and predicted ITD values based on the LEB measurements was found satisfactory with a positive standardized agreement index. This indicates that the LEB can be used as a helpful tool in evaluation of quadriceps muscle strength deficits.

Adolescent↗
PubMed1995

Respiratory tract infection and bronchial responsiveness in elite athletes and sedentary control subjects.

To assess the effect of physical exercise during an acute respiratory tract infection (RTI) on bronchial responsiveness, methacholine bronchial challenge tests were performed prospectively in 19 nonasthmatic male cross-country skiers and 22 healthy control subjects with minimal physical activity. Twelve skiers and 10 controls contracted RTI and were studied before and 1, 3 and 6 weeks after the onset of symptoms. The skiers were given no restrictions in their training routines during the period of illness. The geometric mean provocation concentration of methacholine causing a 10% fall in the forced expiratory volume in the first second (PC10), was lower 1 week after onset of infection than at the initial test in the skiers. From the level at 1 week, PC10 increased to levels at 3 and 6 weeks after infection. The PC10 values at 3 and 6 weeks were not significantly different from the initial test. No significant changes in PC10 occurred after infection in the control group. No significant changes in pulmonary function tests were found during the study period in either of the two groups. In conclusion, RTI was associated with a transient increase in bronchial responsiveness in athletes performing physical training during the symptomatic period of respiratory illness but not in nonactive control subjects.

Acute Disease↗
PubMed1995

The influence of training intensity, airway infections and environmental conditions on seasonal variations in bronchial responsiveness in cross-country skiers.

The influence of physical training, airway infections and environmental conditions on changes in bronchial responsiveness to methacholine during a training and competitive season was studied in 19 high-performance male cross-country skiers 19-21 years old. The longitudinal changes in the methacholine concentration required for a 10% fall in FEV1 (PC10) were negatively correlated with the changes in the volume of physical activity at an intensity level above 90% of maximal heart rate. The variation in physical activity at this intensity level accounted for 54.8% of the change in PC10. No association was found, however, with regard to physical activity at lower intensity levels. Seasonal variation in PC10 was not associated with the changes in occurrence or duration of airway infections provided that the PC10 measurement was postponed for 3-6 weeks after the onset of a recent infection. Seasonal variation in PC10 seemed not to be associated with variations in ambient levels of air pollutants or aeroallergens. PC10 was lowest at the end of the coldest part of the year. In conclusion, seasonal variation in bronchial responsiveness in high-performance cross-country skiers could to a great extent be explained by changes in the volume of physical activity at a very high intensity level.

Adult↗
PubMed1995

Comparison of polysulphated glycosaminoglycan and sodium hyaluronate with placebo in treatment of traumatic arthritis in horses.

A randomised double blind and placebo controlled clinical study was carried out. Standardbred trotters (n=77), age 3-4 years) with moderate to severe lameness were grouped according to number of affected joints and, within each group, were randomised for treatment with polysulphated glycosaminoglycan (PSGAG), sodium hyaluronate (SH) or placebo for 3 weeks. The horses were inspected weekly with a final examination 2-4 weeks after the end of treatment. Mean initial lameness score was significantly reduced during treatment and at the last examination in all 3 groups (P<0.01). Additionally, the prevalence of sound horses increased significantly from 1 to 3 weeks of treatment and to the last examination in all 3 groups (P < or = 0.03). Comparison of the 2 treatment groups with regard to development of the lameness curve and time until soundness indicated a small, non significant difference in favour of SH. No significant difference was detected between the 2 treatment groups in the prevalences or cumulative incidence of soundness. The study detected a superior effect of the 2 drugs compared with placebo for reduction in lameness score during the treatment period (P=0.03) and the total study period (P<0.01), time until soundness (P=0.04) and the prevalence of sound horses at the last examination (P<0.01). All 3 treatments affected traumatic arthritis in horses, but the SH and PSGAG gave better results than the placebo.

Animals↗
PubMed1995

Serum immunoglobulin G subclasses in patients with ulcerative colitis and Crohn's disease of different disease activities.

BACKGROUND: Different concentrations of immunoglobulin G (IgG) subclass-producing cells in the mucosa of patients with ulcerative colitis and Crohn's disease have previously been described. METHODS: To evaluate serum concentration of IgG subclasses as a tool for diagnosis and disease activity in chronic inflammatory bowel disease, we compared serum concentrations of IgG, IgA, IgM, and immunoglobulin subclasses IgG1, IgG2, IgG3, and IgG4 by means of the radial immunodiffusion technique in 66 patients with ulcerative colitis and in 68 patients with Crohn's disease of different clinical stages. Erythrocyte sedimentation rate, haemoglobin, and serum concentrations of albumin and orosomucoid were also determined. RESULTS: The serum IgG1 concentration in patients with ulcerative colitis was 8.0 g/l significantly higher than in patients with Crohn's disease (6.8 g/l) (p < 0.005), whereas the serum IgG2 concentration in patients with Crohn's disease was 3.8 g/l, significantly increased compared with patients with ulcerative colitis (3.1 g/l) (p < 0.004). In patients with active ulcerative colitis the serum IgA level (2.03 g/l) was significantly lower than that in the patients with less active disease (2.74 g/l) (p < 0.03). No significant differences in serum concentrations of total IgG, IgG3, IgG4, and IgM were found between groups of patients with ulcerative colitis and Crohn's disease. The differences observed in IgG1, IgG2, and IgA concentrations, however, are small. CONCLUSIONS: The serum concentrations of IgG, IgA, IgM, and IgG subclasses are of little value in the diagnostic procedures in individual patients and are not superior to conventional laboratory tests such as sedimentation rate and serum concentrations of orosomucoid and albumin.

Adult↗