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Biomedical subjects

S Hagen

Publications and source records attributed to S Hagen.

At least 19 recordsLinked to original sources
PubMed2000

Helicobacter pylori gastritis in cats with long-term natural infection as a model of human disease.

A natural infection with Helicobacter pylori (H. pylori) in domestic cats (Felis cattus) less than 2 years of age has been well described in a closed colony of animals. Six cats from this colony that were serially evaluated by culture, polymerase chain reaction, and light and electron microscopy for a period of 3 years demonstrated persistent gastric colonization with a single cag(-) vac(+) strain of H. pylori. In these cats, as well as five other 5- to 6-year-old cats that were examined, a long-term infection resulted in chronic diffuse lymphofollicular atrophic gastritis with areas of mucosal dysplasia in the antrum and predominantly midsuperficial gastritis in the body and cardia. Topographically, the distribution of lesions was similar in both young and older cats and closely resembled that found in humans, with the most severe changes occurring in the gastric antrum. Few granulocytes and no significant elevation in mast cells were seen in older H. pylori-infected cats compared with uninfected controls; however, marked increases in interepithelial globule leukocytes and numerous active mucosal lymphoid follicles were present in infected animals. Indices of gastritis were significantly greater in older infected cats when compared with uninfected controls and younger cats (P < 0.05). The antral cell proliferation index of infected older cats was significantly (P = 0.021) greater than that of uninfected controls. Apoptotic indices of the gastric antrum and body of infected cats were significantly (P = 0.01) increased versus controls. Chronic infection with H. pylori in cats shares many features of long-term H. pylori infection in humans, including the development of preneoplastic processes. This similarity provides useful, comparative insights into host-pathogen interactions.

Animals↗
PubMed2000

Complementary DNA cloning and expression of a newly recognized high molecular mass allergen phl p 13 from timothy grass pollen (Phleum pratense).

BACKGROUND: Grass pollen extracts contain a range of different allergenic components that can be classified as having low, middle or high molecular mass. Almost 75% of patients allergic to grass pollen display immunoglobulin (Ig) E-reactivity to allergens in the high molecular mass range of 55-60 kDa. These proteins have not yet been fully characterized on the protein and DNA level. OBJECTIVE: The aim of this study was to identify and characterize an allergen of the high molecular mass fraction of Phleum pratense pollen by N-terminal protein sequencing and molecular cloning. METHODS: A previously uncharacterized allergen which migrates as a double band with a molecular mass of 55-60 kDa was biochemically purified and investigated by N-terminal sequencing. Subsequently, a DNA primer was designed to amplify the corresponding cDNA using PCR. The cloned cDNA and deduced amino acid sequence were compared with sequence data bases. Immunoblots carrying the recombinant expression product were developed with monoclonal antibodies and sera derived from allergic subjects. The IgE-binding capacity of natural and recombinant allergen was determined using EAST. RESULTS: The nucleic acid sequence as well as the deduced amino acid sequence consisting of 394 amino acids indicated homology with pollen specific polygalacturonases. Four potential sites for glycosylation and 16 cysteine residues were found. The recombinant expression product exhibited the same molecular size as the natural allergen and was clearly IgE-reactive. CONCLUSION: The newly characterized allergen Phl p 13, which shows homology with polygalacturonases, is clearly different from the allergen designated as Phl p 4 and therefore the high molecular mass fraction is composed of at least two different allergens. A possible reason why this important allergen has not been detected until now is that Phl p 13 and Phl p 4 are hardly separable by one dimensional SDS-PAGE.

Allergens↗
PubMed1999

Rapid and efficient purification of Phleum pratense major allergens Phl p 1 and group Phl p 2/3 using a two-step procedure.

The standardization of natural allergenic extracts and the characterization of recombinant allergens ensures a continuing requirement for highly purified natural allergens. The extraction and purification methods have to be reproducible and also preserve the biological and immunological activity of the allergen. A simple two-step purification system has been established in order to provide milligram amounts of purified natural Phl p 1 and Phl p 2/3. Both major allergens were separated from other proteins of timothy grass pollen extract in one step by hydrophobic interaction chromatography (HIC) under mild conditions. The allergens elute in the flow-through fraction while the rest of the proteins remain bound to the column. The very different molecular weights of Phl p 1 and Phl p 2/3 permitted separation of the allergens by a second step using gel filtration.

Allergens↗
PubMed1999

4-hydroxy-5,6-dihydro-2H-pyran-2-ones.3. Bicyclic and hetero-aromatic ring systems as 3-position scaffolds to bind to S1' and S2' of the HIV-1 protease enzyme.

5,6-Dihydro-2H-pyran-2-ones are potent inhibitors of HIV-1 protease, which bind to the S1, S2, S1', and S2' pockets and have a unique binding mode with the catalytic aspartyl groups and the flap region of the enzyme. Efforts to explore 3-position heterocyclic scaffolds that bind to the S1' and S2' pockets have provided a number of selected analogs that display high HIV-1 protease inhibitory activity. reserved.

Binding Sites↗
PubMed1999

Stroke patients' informal caregivers. Patient, caregiver, and service factors that affect caregiver strain.

BACKGROUND AND PURPOSE: Research has revealed that caring for a stroke patient can result in caregiver strain and a myriad of other difficulties for caregivers. This study aims to identify the level of strain experienced by caregivers in the early months after stroke and to assess the relationship between caregiver strain and caregiver characteristics, patient characteristics, and service inputs. METHODS: Stroke patients were identified through a random stratified sample of general practices. Patients were asked to identify their principal informal caregiver. Strain was measured with the Caregiver Strain Index, and all data were collected from caregivers at 1, 3, and 6 months after the patient's stroke. Multiple regression analysis was used to examine the factors associated with caregiver strain. RESULTS: Six months after stroke, 37% of caregivers were experiencing considerable strain. The amount of time a caregiver spent helping a stroke patient, the amount of time the caregiver spent with the patient, and the caregiver's health were all significantly associated with the level of strain experienced. Although none of the services or patient factors tested in this study were consistently associated with strain, an indicator of stroke severity was significant at each time point. CONCLUSIONS: Caregivers are experiencing strain, which has implications for research and service provision. Service providers need to identify caregivers at risk of greater strain and to help caregivers work through situations that services cannot alter. Research is needed to identify services that are effective in strain alleviation. Future research should also aim to identify the interface between patient characteristics and strain, burden, and depression and particularly to assess the caregiver's perception of these relationships.

Adult↗
PubMed1998

Risks of silicosis in coalworkers exposed to unusual concentrations of respirable quartz.

OBJECTIVES: To describe the radiographic changes in coalworkers exposed to unusual concentrations of respirable quartz during the 1970s, and to relate these to exposure measurements. METHODS: Men who had worked at one Scottish colliery during the 1970s were invited to a health survey. Chest radiographs were taken from 547 subjects. Classifications of these films under the International Labour Organisation (ILO) 1980 scheme were related, by logistic regression, to existing data on individual men's exposures to respirable dust and quartz. RESULTS: Taking the median of the three readers' results on profusion of small opacities, 203 men (38%) showed progression of at least one profusion category on the 12 point scale, from the various 1970s surveys to the follow up in 1990-1. A total of 158 men (29%) had a profusion of at least 1/0, and 47 (8.6%) of at least 2/1 at the follow up survey. Large opacities were recorded as present by at least two readers for 14 (2.6%) of the men. Profusion of small opacities was strongly related to exposures experienced in the 1970s, and more strongly for quartz than for the non-quartz fraction of the dust. Estimates of risk are presented over the range of quartz exposures experienced. CONCLUSIONS: The quartz exposures experienced by some men at this colliery have caused considerable progression of radiographic abnormalities since exposure ended. The data accumulated offer opportunities for further more detailed analyses to inform debate on occupational limits for quartz exposures, both in collieries and in other industries where there is exposure to quartz in mixed dust.

Adult↗
PubMed1998

Hormone receptor measurements and survival in 1335 consecutive patients with primary invasive breast carcinoma.

The distribution of estrogen and progesterone receptors (ER, PR) was assessed in the primary tumour in 1335 of 2704 (49%) consecutive new breast carcinoma patients (HORMREC). In a subgroup of 757 radically treated patients without systemic adjuvant treatment (RADOP) the relation of the ER and PR content to relapse and survival was evaluated. Three levels were defined for ER: ER-: <10 fmol/mg protein, ER+: moderate ER content >/= 10-99 fmol/mg protein, and high ER content >/= 100 fmol/mg protein. In 1288 patients of the HORMREC group who were evaluable for ER, 1061 (82%) had ER+ tumours, 685 (65%) of moderate content and 376 (35%) of high content, respectively. Among 917 patients, evaluable for PR, 723 (79%) tumours were PR+ (>/= 20 fmol/mg protein), of them 352 (49%) with a moderate content (>/= 20-99 fmol/mg protein) and 371 (51%) with a high content ( >/= 100 fmol/mg protein). The median ER content was significantly increased among the post-menopausal women as compared to the premenopausal women, whereas the median PR content showed no such differences. For the RADOP patients, no correlation between ER status and the first site of relapse was seen, whereas PR+ tumours tended to relapse more often locally than PR- tumours. In the univariate analysis the five-and 10-year tumour-related survival rates for all patients were not correlated with ER or PR positivity. One subgroup of patients with favourable outcome was identified on the basis of hormone receptors: Premenopausal women with tumours of moderately elevated ER content. In the multivariate analysis tumour size and axillary node status were the only independent predictors of survival. Measurements of hormone receptor status give weak prognostic information in radically treated patients with breast cancer as long as no adjuvant systemic treatment is applied. As todays' adjuvant treatment is based on the knowledge of hormone receptor status of the primary tumour, this information should be obtained routinely.

Breast Neoplasms↗
PubMed1997

4-hydroxy-5,6-dihydropyrones. 2. Potent non-peptide inhibitors of HIV protease.

The 4-hydroxy-5,6-dihydropyrone template was utilized as a flexible scaffolding from which to build potent active site inhibitors of HIV protease. Dihydropyrone 1c (5,6-dihydro-4-hydroxy-6-phenyl-3-[(2-phenylethyl)thio]-2H-pyran-2-one) was modeled in the active site of HIV protease utilizing a similar binding mode found for the previously reported 4-hydroxybenzopyran-2-ones. Our model led us to pursue the synthesis of 6,6-disubstituted dihydropyrones with the aim of filling S1 and S2 and thereby increasing the potency of the parent dihydropyrone 1c which did not fill S2. Toward this end we attached various hydrophobic and hydrophilic side chains at the 6-position of the dihydropyrone to mimic the natural and unnatural amino acids known to be effective substrates at P2 and P2'. Parent dihydropyrone 1c (IC50 = 2100 nM) was elaborated into compounds with greater than a 100-fold increase in potency [18c, IC50 = 5 nM, 5-(3,6-dihydro-4-hydroxy-6-oxo-2-phenyl-5-[2-phenylethyl)thio] -2H-pyran-2-yl)pentanoic acid and 12c, IC50 = 51 nM, 5,6-dihydro-4-hydroxy-6-phenyl-6-(2-phenylethyl)-3- [(2-phenyl-ethyl)thio]-2H-pyran-2-one]. Optimization of the 3-position fragment to fill S1' and S2' afforded potent HIV protease inhibitor 49 [IC50 = 10 nM, 3-[(2-tert-butyl-5-methylphenyl)sulfanyl]-5,6-dihydro-4 -hydroxy-6-phenyl-6-(2-phenylethyl)-2H-pyran-2-one]. The resulting low molecular weight compounds (< 475) have one or no chiral centers and are readily synthesized.

Anti-HIV Agents↗
PubMed1997

Respiratory health effects of opencast coalmining: a cross sectional study of current workers.

OBJECTIVE: To identify whether there is evidence of pneumoconiosis and other respiratory health effects associated with exposure to respirable mixed dust and quartz in United Kingdom opencast coalmines. METHODS: A cross sectional study of current workers (1224 men, 25 women) was carried out at nine large and medium sized opencast sites in England, Scotland, and Wales. To characterise a range of occupational groups within the industry, full shift measurements of personal exposures to respirable dust and quartz were taken. Up to three surveys were carried out at each site, covering all four seasons. For the purposes of comparisons with health indices these groups were further condensed into five broad combined occupational groups. Full sized chest radiographs, respiratory symptoms, occupational history questionnaires, and simple spirometry were used to characterise the respiratory health of the workforce. Logistic or multiple regression techniques were used to examine relations between indices of exposure and respiratory health. RESULTS: None of the group geometric mean dust concentrations, based on 626 valid dust samples, exceeded 1 mg.m-3, and 99% of all quartz concentrations were below 0.4 mg.m-3, the current maximum exposure limit. The highest quartz concentrations were experienced by the rock drilling team and drivers of bulldozers (used to move earth and stone from layers of coal). There were clear differences in mean respirable dust and quartz concentrations between occupational groups. These were consistent across the different sites, but depended in part on the day of measurement. The variations between sites were not much greater than between days, suggesting that differences between sites were at least partly explained by differences in conditions at the time of the measurements. The prevalence of radiographic small opacities profusion category > or = 1/0, based on the median of three readings, was 4.4%. Five men had category 2 pneumoconiosis and two men (including one of these five) had progressive massive fibrosis category A. From regression analyses, the relative risk of attaining a profusion of category > or = 0/1 was estimated to be doubled for every 10 years worked in the dustiest, preproduction opencast jobs, after allowing for age, smoking, and site effects. Risk was not associated with time worked in any other occupation within the industry, nor with previous employment in underground mining or other dusty jobs. Symptoms of chronic bronchitis were present in 13% of the men. Frequency of chronic bronchitis was influenced by years worked in dusty jobs outside opencast mining, but not by time spent in occupations within the industry. Asthmatic symptoms were reported by 5% of the workforce, close to the mean frequency found in adult men. No positive associations were found between asthma and occupational exposures. Lung function on average was close to predicted value and showed no relation to time worked in opencast occupations. CONCLUSIONS: Frequency of (mostly mild) chest radiographic abnormalities is associated with working in the dustier, preproduction jobs in the industry. Although some of these mild abnormalities may be non-occupational (due to aging or smoking), the association with exposure indicates a small risk of pneumoconiosis in these men, and the need to monitor and control exposures, particularly in the high risk occupations.

Adolescent↗
PubMed1997

Randomized controlled trial of postoperative radiotherapy and short-term time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer. Norwegian Adjuvant Rectal Cancer Project Group.

BACKGROUND: The purpose of the present study was to investigate whether a 1-month regimen of postoperative radiotherapy combined with 5-fluorouracil could reduce the local recurrence rate and improve survival in patients with Dukes B and C rectal cancer. METHODS: One hundred and forty-four patients were randomized to surgery alone or surgery combined with postoperative radiotherapy (46 Gy) and bolus 5-fluorouracil 30 min before six of the radiotherapy fractions. One hundred and thirty-six patients were eligible. RESULTS: The adjuvant treatment was well tolerated. After an observation time of 4-8 years, patients in the adjuvant treatment group had a cumulative local recurrence rate of 12 per cent compared with 30 per cent in the group that had surgery only (P = 0.01). The 5-year recurrence-free and overall survival rate was 64 per cent in the adjuvant group compared with 46 per cent (P = 0.01) and 50 per cent (P = 0.05) respectively in the surgery group. The adjusted relative risk of recurrence and death for the adjuvant group was 0.48 (95 per cent confidence interval 0.28-0.82) and 0.56 (0.33-0.94) respectively. CONCLUSION: The 1-month postoperative combination regimen improved treatment results in patients with Dukes B and C rectal cancer, in terms of local recurrence rate, recurrence-free survival and overall survival, without serious side-effects.

Adult↗
PubMed1996

[Prostatic cancer in Oslo--a real decline?].

Incidence of prostate cancer has increased steadily in Norway since the cancer registration started in the 1950s. In Oslo, however, the figures show decreasing incidence since the 1970s, a trend not observed in any other region. These changes have occurred in the groups older than 70 years of age. The most important change is a marked decrease in the number of cases first diagnosed at autopsy, from 12.7% in 1957-61 to 3.8% in 1987-91. However, even after these cases are excluded, a slight downward trend in incidence still exists. The same tendencies are not observed for other forms of cancer. It seems as if the diagnostic intensity has become lower in Oslo than in the rest of the country. This pattern may be explained by a change of priority in diagnostics, owing to scarce resources, but other reasons, such as stabilization of the incidence of prostatic cancer, are also possible.

Aged↗
PubMed1996

Treatment intention in hospitalized cancer patients in oncological wards in Norway: a national survey.

Clinicians often do not agree whether a treatment is given with a palliative or curative intent. A common clear definition does not exist. This study has assessed the usefulness of dividing the goal of treatment into three distinct categories: curative treatment; palliative, symptom preventive treatment; and palliative, symptom relieving treatment. In a cross-sectional study among all cancer centres in Norway, a total of 629 patients were included into the study. Of these patients, 60% received palliative treatment, with an equal distribution between symptom preventive and symptom relieving. The definitions were found easy to use by the physicians. It gave important information of differences between cancer diagnosis with respect to the number of patients receiving palliative treatment. In order to refine the classification system, the authors will, in future studies, include a fourth category, life prolonging treatment, which is located between curative and palliative treatment with respect to treatment intensity.

Cross-Sectional Studies↗