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Biomedical subjects

S Larsen

Publications and source records attributed to S Larsen.

At least 127 records · Page 7Linked to original sources
PubMed1996

Overexpression of Bacillus subtilis phosphoribosylpyrophosphate synthetase and crystallization and preliminary X-ray characterization of the free enzyme and its substrate-effector complexes.

Bacillus subtilis phosphoribosylpyrophosphate (PRPP) synthetase has been expressed to high levels in an Escherichia coli host strain devoid of endogenous PRPP synthetase. A rapid and efficient purification protocol has been developed allowing production of enzyme preparations with purity conforming to the stringent criteria required for crystallization. Crystallization experiments, in combination with dynamic light scattering studies, have led to the production of three crystal forms of the enzyme. These forms include the free enzyme, the enzyme in a binary complex with the substrate adenosine triphosphate (ATP), and the enzyme in a quaternary complex with the substrate analog alpha, beta-methylene adenosine triphosphate (mATP), the substrate ribose-5-phosphate (Rib-5-P), and the allosteric inhibitor adenosine diphosphate (ADP). Diffraction data showed that all three crystal forms are suitable for structure determination. They crystallize in the same hexagonal space group, P6(3), with virtually identical unit cell dimensions of a = b = 115.6 angstroms, c = 107.8 angstrom, and with two molecules in the asymmetric unit. The self-rotation function showed the existence of a non-crystallographic twofold axis perpendicular to the c axis. The availability of the different complexes should allow questions regarding the molecular mechanisms of catalysis and allostery in PRPP synthetase to be addressed.

Adenosine Triphosphate↗
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

Reproducibility and stability of normalized EMG measurements on musculus trapezius.

The reliability of normalized EMGrms (root mean square value of the electromyographic signal) measurements from musculus trapezius were evaluated in a field study. The reproducibility and stability of the method as well as the reproducibility of the results for nine variables were examined. The variables were: static, median and peak values of the ADF (amplitude distribution function) and the total time and number of periods when the muscle's load was below 1, 2 and 5% of MVC (maximum voluntary contraction). Twelve data operators, performing entry work, were measured twice with an interval of a week. Coefficients of repeatability were calculated. The coefficient of repeatability for 5 of the variables showed that 95% of the differences between measurements 1 and 2 for each subject were less than two standard deviations from the group mean. The same was true for the other four variables if the result of one of the twelve measurements was removed. The agreement index, twice the standard deviation of the difference between the two measurements divided by the mean of the two measurements was low only for the static value of the ADF and the number of periods below 5% MVC. Six data operators performing entry work were examined six times at weekly intervals. The stability ratio SDmm/SDv was less than 1 for all variables except for time and number of periods when the muscle's load was below 5% MVC. SDmm is the standard deviation of the difference between minimum and maximum value for each of the subjects for the six measurements. SDv is the average of the standard deviations of the six measurements at each visit. Two groups, each consisting of 24 VDU operators doing similar work were compared using the results from one EMG measurement on the trapezius. No significant differences were found between the groups for any of the nine variables (0.07 < p < 0.87).

Adult↗
PubMed1996

Gastric emptying of pancreatin granules and dietary lipids in pancreatic insufficiency.

AIM: To investigate the emptying of enzyme granules and dietary lipids in patients with pancreatic insufficiency secondary to chronic pancreatitis. PATIENTS AND METHODS: Seven patients with chronic pancreatitis and exocrine pancreatic insufficiency ingested a test meal including colloidal 99m-technetium-radiolabelled liver paté, and swallowed two pancreatin capsules, in which half of the granules had been replaced with 111-indium-radiolabelled plastic particles of comparable physical dimensions. The passage of the two isotopes was followed simultaneously by gamma camera imaging for direct visual judgement and calculation of mean gastric emptying time. RESULTS: Pancreatin granules and dietary lipids were observed to empty simultaneously. In the duodenum the particles and the test meal were well mixed. Mean gastric emptying time of radiolabelled liver paté and radiolabelled plastic particles could be calculated in six patients. The median of these values were 47 and 43 min, respectively (P = 0.69). CONCLUSION: Pancreatin granules sized 1.0-1.5 mm seem to empty together with dietary lipids.

Aged↗
PubMed1996

Growth of colorectal polyps: redetection and evaluation of unresected polyps for a period of three years.

UNLABELLED: BACKGROUND, AIMS, AND PATIENTS: In a prospective follow up and intervention study of colorectal polyps, leaving all polyps less than 10 mm in situ for three years, analysis of redetection rate, growth, and new polyp formation was carried out in 116 patients undergoing annual colonoscopy. The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo. RESULTS: Redetection rate varied from 75-90% for each year, and was highest in the rectum and sigmoid colon. There was no net change in size of all polyps in the placebo group, however, polyps less than 5 mm showed a tendency to net growth, and polyps 5-9 mm a tendency to net regression in size, both for adenomas and hyperplastic polyps. This pattern was verified by computerised image analysis. Patients between 50 and 60 years showed evidence of adenoma size increase compared with the older patients, and the same was true for those with multiple adenomas (four to five) compared with those with a single adenoma. The new adenomas were significantly smaller and 71% were located in the right side of the colon. Patients with multiple adenomas had more new polyps at all the follow up examinations than patients with a single adenoma. One patient developed an invasive colorectal carcinoma, which may be evolved from a previously overlooked polyp. Two polyps, showing intramucosal carcinoma after follow up for three years, were completely removed, as judged by endoscopy and histological examination. CONCLUSIONS: The results show that follow up of unresected colorectal polyps up to 9 mm is safe. The consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations, but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice. The growth retardation of the medium sized polyps may partly explain the discrepancy between the prevalence of polyps and the incidence of colorectal cancer.

Aged↗
PubMed1996

Potentially avoidable perinatal deaths in Denmark and Sweden 1991.

BACKGROUND: Since 1950 the perinatal mortality has been significantly higher in Denmark than in Sweden. In 1991 the rate in Denmark was 8.0/1000 deliveries compared to 6.5/1000 in Sweden. An international audit was designed to investigate whether the perinatal death rates in the two countries to some extent could reflect differences in the quality of care, indicated by the numbers of perinatal deaths in categories of potentially avoidable deaths. MATERIAL AND METHODS: Medical records of 97% of all perinatal deaths in 1991 in the two countries were analyzed. A new classification focusing on potential avoidability from a health services perspective was elaborated at a Nordic-Baltic workshop, using the variables: time of death in relation to admission and delivery, fetal malformation, gestational age, growth-retardation and Apgar score at 5 min. RESULTS: Rates of perinatal deaths of malformed infants (0.00195 and 0.00145) and intrapartum deaths of non-malformed infants (0.00042 and 0.00019) was significantly higher in Denmark than in Sweden. CONCLUSION: Application of the Nordic-Baltic Perinatal Death Classification on perinatal deaths in Denmark and Sweden in 1991 raises the questions as to why the rate of perinatal death of malformed infants is higher in Denmark than in Sweden and whether intrapartum care in Denmark could be improved.

Cause of Death↗
PubMed1996

Polypectomy of adenomas in the prevention of colorectal cancer: 10 years' follow-up of the Telemark Polyp Study I. A prospective, controlled population study.

BACKGROUND: The efficacy of polypectomy in preventing colorectal cancer (CRC) has never been demonstrated in a controlled, prospective study. This must be done by randomization within a population with a high prevalence of colorectal polyps, and the feasibility and safety of endoscopic screening examination is a prerequisite for this type of study. METHODS: The present study is a randomized, controlled study of the feasibility and safety of flexible sigmoidoscopic screening of a normal population sample of 799 men and women aged 50-59 years, findings at 2 and 6 years' colonoscopic follow-up, and the appearance of clinical colorectal cancer (CRC) after 10 years. RESULTS: The attendance rate was high, and there were no complications. After 10 years 1 of 400 in the screening group had developed CRC (in the group of 76 (19%) not attending for screening examination). Four of 399 controls developed CRC. CONCLUSIONS: Poor yield of polyps at follow-up, slow growth of in situ polyps, and no clinical CRC among screenees after 10 years provides support to infrequent or no colonoscopic follow-up after initial polypectomy in individuals with otherwise average risk of CRC.

Adenomatous Polyposis Coli↗
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↗
PubMed1996

Occupational injuries among fishermen.

A sample of 187 medically treated injuries among fishermen was the basis for this study. Nearly half the injuries occurred while shooting or hauling fishing gear. The most common injuries were in the upper extremities (48.7%). Twenty-two percent of the injuries occurred while working with winches ropes and wires and about 30% were caused by falls or slips. Seventy-five percent of accidents occurred on trawlers, where the trawl doors (other boards) are a special hazard. Medical treatment ashore was delayed for more than 24 hours in 35% of the injuries, showing the need for providing optimal treatment facilities on board. Prevention measures should include technical improvements, safety training courses and efforts to enhance the motivation for safe work. The fishermen's proposals for prevention seem to be most useful and should be used to the full extent.

Absenteeism↗
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

Crystallization and preliminary crystallographic investigations of cytochrome c4 from Pseudomonas stutzeri.

Cytochrome c(4) from the bacterium Pseudomonas stutzeri has been crystallized and X-ray diffraction data have been collected to 2.2 A resolution. The crystals belong to the monoclinic system, space group P2(1) with cell parameters a = 49.49, b = 58.58, c = 63.51 A and beta = 96.96 degrees. The crystals contain two molecules it, the asymmetric unit. Cytochrome c(4) is known to contain two covalently bound haem groups per molecule and positions of the four haem Fe atoms in the asymmetric unit were determined from native anomalous-dispersion differences. The shortest Fe-Fe distances found in the crystal were 15.8, 16.9 and 19.0 A.

Journal Article↗
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

Is there a reduction in postural load when wearing progressive lenses during VDT work over a three-month period?

In an initial study, 18 VDT operators were found to have a higher muscle load in the neck/ shoulder region when using progressive lenses compared with single-vision lenses, while working on a VDT unit. For single-vision lenses, a higher flexion angle in the neck was also discovered. The present study investigates whether this higher muscle load is reduced when a progressive correction is worn for a three-month period. Adaptation in terms of reduced muscle load measured by electromyography (EMG) was not discovered. Head flexion angle was smaller when using progressive correction as compared with single-vision lenses. Some practical implications for occupational optometry are discussed.

Journal Article↗