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Biomedical subjects

T Jørgensen

Publications and source records attributed to T Jørgensen.

At least 19 recordsLinked to original sources

The role of phospholipids and the factor VII Gla-domain in the interaction of factor VII with tissue factor.

Whether or not the factor VII Gla-domain is involved in the high-affinity interaction of factor VII and tissue factor via calcium-dependent interactions with surrounding phospholipids is unknown. To investigate this, we have purified the factor VII Gla-peptide (FVII-GP) from digested recombinant human factor VIIa and assessed its effect on factor VII:tissue factor interactions. FVII-GP inhibited the activation of factor X by factor VIIa in the presence of either soluble or cell surface tissue factor half-maximally at 0.5 microM and 2.7 microM, respectively. However, FVII-GP failed to inhibit the specific binding of factor VIIa to cell-surface tissue factor, and did not inhibit the ability of tissue factor to stimulate the amidolytic activity of factor VIIa. Unrelipidated tissue factor apoprotein stimulated the amidolytic activity of factor VIIa to the same extent as relipidated tissue factor apoprotein. These findings suggest that the factor VII Gla-domain does not directly interact with tissue factor, but rather is important for calcium binding and concomitant expression of other factor VII epitopes necessary for tissue factor recognition and binding. To test this hypothesis, we have prepared a monoclonal antibody against a putative factor VII epitope that participates in the interaction of factor VII with cell-surface tissue factor (peptide 195-206) and assessed its ability to bind to factor VII in the presence and absence of calcium. Binding of this monoclonal antibody (PW-4) to intact factor VIIa was calcium-dependent and could be inhibited in a dose-dependent manner by peptide 195-206.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal

Iron status markers, serum ferritin and hemoglobin in 1359 Danish women in relation to menstruation, hormonal contraception, parity, and postmenopausal hormone treatment.

Iron status was assessed by measuring serum (S-) ferritin and hemoglobin (Hb) in a population survey comprising 1359 nonpregnant Danish women, in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal. Median age for menarche was 14 years, for menopause (artificial and natural) 48 years. Premenopausal women had lower S-ferritin (median 37 micrograms/l) than postmenopausal women (median 71 micrograms/l; p less than 0.0001). Of the premenopausal women, 17.7% had S-ferritin less than 15 micrograms/l (i.e., depleted iron stores), and 23.1% S-ferritin of 15-30 micrograms/l (i.e., small iron stores). Corresponding figures in postmenopausal women were 3.3% and 10.3%. Hb values in premenopausal women were mean 137 +/- 10 (SD) g/l (8.5 +/- 0.6 mmol/l) vs. 140 +/- 10 g/l (8.7 +/- 0.6 mmol/l) in postmenopausal women (p less than 0.0001); 4.1% of pre- and 3.3% of postmenopausal women had values less than 121 g/l (7.5 mmol/l). Iron deficiency anemia (i.e., S-ferritin less than 15 micrograms/l and Hb less than 121 g/l) was found in 2.6% of pre- and 0.36% of postmenopausal women. Premenopausal multipara had lower S-ferritin than nulli- and unipara (p less than 0.04). The use of oral contraceptives had a marked influence on iron stores; premenopausal women taking the pill had higher S-ferritin and a lower frequency of depleted iron reserves than nonusers (p less than 0.01). Postmenopausal estrogen treatment had no influence on S-ferritin or Hb.

Adolescent

Gallstones and colorectal cancer--there is a relationship, but it is hardly due to cholecystectomy.

The prevalence of gallstone disease in 145 consecutive patients with colorectal cancer was compared with gallstone prevalence in 4,159 subjects randomly selected from a population. The group of patients had a significantly higher prevalence of gallstone disease than the population (odds ratio = 1.59; 95 percent confidence limits 1.04-2.45), whereas cholecystectomies occurred with equal frequency in the two groups. There was a nonsignificant trend toward more right-sided cancers in patients with gallstones than in patients without. These results, together with available literature, give substantial evidence for an association between gallstones and colorectal cancer, an association which is not due to cholecystectomy being a predisposing factor to colorectal cancer. Sporadic findings of an association between cholecystectomy and colorectal cancer can be explained by the above relationship.

Adult

Abdominal pain in a 70-year-old Danish population. An epidemiological study of the prevalence and importance of abdominal pain.

In order to assess the prevalence and importance of abdominal pain in the elderly, an epidemiological study of a 70-year-old Danish population was carried out. Seventy two percent of 1119 randomly selected persons answered a questionnaire concerning abdominal pain. One year prevalence of abdominal pain was 28% among women and 17% among men (p < 0.01). Among those with abdominal pain no significant sex difference was found as regards location, severity, frequency, or medicine consumption. Eleven percent of the men and 19% of the women had abdominal pain which they considered to be of importance to their well-being in terms of frequency, severity, or need of medicine (sex difference: chi 2 = 10.18, df = 2, p < 0.01). Participants who had no abdominal pain judged their general health to be better than those who had experienced abdominal pain (p < 0.01). It is concluded that abdominal pain is frequent in a 70 year old population and influences the well-being of the subjects. Further studies are needed to evaluate whether subjects with abdominal pain have a poorer prognosis than subjects without.

Abdominal Pain

Development of a gene transfer system for curing of plasmids in the marine fish pathogen Vibrio salmonicida.

All reported natural isolates of the marine fish pathogen Vibrio salmonicida contain plasmids, and in another marine fish pathogen, Vibrio anguillarum, it has been shown that a plasmid is important for expression of virulence by the organism. To study the function of the plasmids in V. salmonicida, we developed a gene transfer system based on the plasmid RSF1010 replicon. The gene transfer system was used to construct a plasmid-free strain, and this strain was found to behave similarly to the wild type in a fish pathogenicity test based on intraperitoneal injection of the bacteria. We were unable to detect any other phenotypic differences between the two strains. It could therefore be concluded that at least in the V. salmonicida strain tested, extrachromosomal DNA is not required for expression of virulence.

Animals

Increased activity of ionised calcium in gall bladder bile in gall stone disease.

The actual activity of ionised calcium (Ca2+) in gall bladder bile determined with an ion-selective electrode was significantly higher in patients with gall stone disease (n = 15) than in patients without gall stones (n = 10) (0.43 mmol/kg v 0.31 mmol/kg; p < 0.05). No change in the Ca2+ activity in any of the gall bladder bile samples was observed during equilibration with CO2. During titration with HCl/NaOH, however, the Ca2+ activity fell with increasing pH in a biphasic manner, with the breaking point occurring at a significantly lower median pH in patients with gall stones than in patients without (pH 7.1 v 8.2; p < 0.0001). The combination of a higher activity of calcium in bile and precipitation of bile salts taking place at a lower pH in patients with gall stone disease than in patients without gall stones suggests a major role for calcium and pH in the pathogenesis of gall stones. Strict anaerobic sampling is not necessary for the measurements of Ca2+ in gall bladder bile, because the Ca2+ was not significantly affected by the changes in pCO2. The metabolic studies suggest, however, that simultaneous measurements of the activity of Ca2+ and pH is important in order to interpret data for the calcium activity in gall bladder bile.

Adult

[Who has gallstones? Current epidemiologic studies].

Until a few years ago, our knowledge about the epidemiology of gall-stones was limited on account of the absence of diagnostic methods for investigation of extensive populations. Development of ultrasound scanning has had the result that, within the past six or seven years, a number of screening investigations for gall-stones in populations selected at random have been undertaken. These investigations reveal that the great majority of cases of gall-stones are undiagnosed. The prevalence increases with the age and is higher in women than in men. The latter observation is due to factors which are specific for women, mainly pregnancies but possibly also employment of hormones and the duration of the fertile period. Familial accumulation of gall-stone disease is also observed. Obesity, smoking and abstinence from alcohol appear also to be related to gall-stones while the significance of diet is still poorly elucidated. Gall-stones appear to be associated with both lipid and glucose metabolism. During the coming years, a series of incidence investigations may be anticipated and these will further increase our knowledge about risk factors for gall stones.

Adult

The Glostrup Population Studies, 1964-1992.

The Glostrup Population Studies, 1964-92, comprise descriptive and analytical, clinical epidemiological studies. Since 1964, different birth cohorts have been examined. More than 20,000 persons, randomly selected from the background population of 300,000 inhabitants (Copenhagen County), have been invited to participate. The project started in 1964 with a survey of the 1914 population on risk factors for coronary heart disease. As the 1914 population has been followed and new cohorts added, a time-sequential design, suited for studies of aging, has been constructed. The staff has been kept in the unit for up to 28 years. Doctoral candidates in medical science and Ph.D candidates have defended their analyses of Glostrup data in several fields and continue to belong to the group of representatives, supporting the board of leaders. The head of Medical Department C serves as chairman, thus maintaining a close connection with clinical medicine.

Adult

[Who has gallstones? Recent epidemiological studies].

Until a few years ago, our knowledge about the epidemiology of gall-stones was limited on account of the absence of diagnostic methods for investigation of extensive populations. Development of ultrasound scanning has had the result that, within the past six or seven years, a number of screening investigations for gall-stones in populations selected at random have been undertaken. These investigations reveal that the great majority of cases of gall-stones are undiagnosed. The prevalence increases with age and is higher in women than in men. The latter observation is due to factors which are specific for women, mainly pregnancies but possibly also employment of hormones and the duration of the fertile period. Familial accumulation of gall-stone disease is also observed. Obesity, smoking and abstinence from alcohol appear also to be related to gall-stones while the significance of diet is still poorly elucidated. Gall-stones appear to be associated with both lipid and glucose metabolism. During the coming years, a series of incidence investigations may be anticipated and these will further increase our knowledge about risk factors for gall-stones.

Cholelithiasis

Incidence of gallstones in a Danish population.

Five-year incidence of gallstone disease was assessed by ultrasonography in an age- and sex-stratified random population of Danish origin aged 30, 40, 50, and 60 years. The response rate was 82.8% (2987/3608). Nonrespondents did not differ from respondents regarding variables concerning gallstone disease. The 5-year incidence of gallstone disease in men aged 30, 40, 50, and 60 years was 0.3%, 2.9%, 2.5%, and 3.3%. Corresponding figures in women were 1.4%, 3.6%, 3.1%, and 3.7%. The incidence of gallstones was significantly higher in subjects aged 45 years or more compared with those aged 35 years. The sex difference in gallstone incidence decreased with increasing age. A significantly higher incidence of gallstone disease was found among subjects with former polyps in the gallbladder. Spontaneous disappearance of gallstones was seen in 4.5%.

Adult

Postphlebitic syndrome and general surgery: an epidemiologic investigation.

Of a random sample comprising 4581 subjects from The Copenhagen County, 3608 (79%) attended an interview and a general health examination. The subjects were defined as suffering from subjective postphlebitic syndrome if they claimed of lower extremity pain or cramps at rest and from objective postphlebitic syndrome if varicose veins, edema, lower extremity ulcers, or skin changes were present. By means of logistic regression analysis, subjective postphlebitic syndrome was found independently associated with previous thromboembolism, obesity, increasing age, female sex, hormonal therapy, varicose veins, and previous major abdominal surgery. Objective postphlebitic syndrome was associated with previous thromboembolism, obesity, former birthgiving, and high social status. The findings support the view that subclinical deep venous thrombosis in connection with previous surgery may give rise to symptoms in the lower extremities.

Adult

Persisting pain after cholecystectomy. A prospective investigation.

A prospective survey of the short-term outcome after cholecystectomy was carried out under circumstances in which the study itself did not influence preoperative decision making or surgical procedures. Of 122 consecutive patients, 115 were evaluable. In all cases gallstones were verified preoperatively either by oral cholecystography or by ultrasonography. Follow-up study was 6-12 months postoperatively. Ninety-one patients (79.1%) reported satisfactory outcome in terms of complete relief of preoperative symptoms. Age, sex, preoperative pain characteristics, history of disease, type of surgery, histology, and complications did not predict the surgical outcome. A test for psychic vulnerability was included among preoperative data items. Psychic vulnerability was significantly associated with persisting pain irrespective of the above-mentioned factors. This suggests that psychologic factors influence the outcome after cholecystectomy with regard to pain relief.

Acute Disease

Phylogeny of immune recognition: antigen processing/presentation in channel catfish immune responses to hemocyanins.

Studies were conducted to address the role(s) of antigen (Ag) processing/presentation in channel catfish immune responses. Vigorous and specific secondary in vitro proliferative and antibody (Ab) responses were obtained to keyhole limpet and Limulus polyphemus hemocyanins with peripheral blood leukocytes (PBL) from catfish previously primed in vivo with Ag. In addition, such antigen-specific in vitro proliferative and Ab responses were efficiently elicited by antigen-pulsed and subsequently paraformaldehyde-fixed autologous PBL used as putative antigen-presenting cells (APC) but not by APC fixed prior to Ag pulsing. Treatment of these putative APC with lysosomotropic agents, protease inhibitors, or the ionophore monensin prior to or during pulsing with Ag significantly inhibited both in vitro responses. Furthermore, the use of radiolabeled protein indicated that both untreated and inhibitor-treated PBL but not erythrocytes take up Ag; however, only untreated PBL were able to degrade Ag. Immune restriction was indicated by the use of allogeneic PBL as APC in that only strong MLRs were generated with no detectable antibodies produced in vitro. Finally, the employment of isolated leukocyte subpopulations demonstrated that both catfish B (sIg+) lymphocytes and monocytes were efficient Ag presentors.

Ammonium Chloride

The production of tumour necrosis factor, tissue thromboplastin, lactoferrin and cathepsin C during lipopolysaccharide stimulation in whole blood.

The release of tumour necrosis factor (TNF), lactoferrin (LF) and cathepsin C (CC) into plasma and production of thromboplastin (TPL) in monocytes were studied in lipopolysaccharide (LPS) stimulated heparinized whole blood from 10 healthy donors. The influence of dextran 70, haemaccel and methylprednisolone on levels of these parameters were examined. TNF concentration in plasma 5 min after the addition of LPS (0 h) was 250 pg/ml (median), 520 pg/ml after 1 h and 1300 pg/ml after 3 h. The addition of dextran 70 to the blood in addition to LPS at the same intervals gave significantly higher values of 740 pg/ml and 1800 pg/ml after 1 h and 3 h respectively. Unstimulated cells had no TPL but after 1 h with LPS, the TPL activity in incubated cells was 2.3 mU/10(6) monocytes and after 3 h, 2.7 mU/10(6) monocytes. LPS induced the secretion of LF from granulocytes (PMN) and the levels 5 min after the addition of LPS (0 h) were 2.1 mg/l (control 0.2 mg/l) and after 1 h, 5.3 mg/l (control 1.3 mg/l) in plasma after LPS stimulation. Haemaccel enhanced the LPS-induced generation of TPL in monocytes and production of CC. The LPS-induced secretion of LF was, to a small extent, influenced by the three reagents tested. Methylprednisolone (1 mmol/l) reduced the production and appearance of TNF in plasma and the generation of TPL activity in monocytes. This model for stimulating heparinized whole blood is suitable for examination of the production and appearance of cellular factors and the influence of drugs on this production.

Adult

The epidemiology of gallstones in a 70-year-old Danish population.

A random sample of 540 men and women aged 70 years who lived in the western part of Copenhagen County was drawn from the National Central Person Register. The response rate was 74.8% among men and 63.7% among women. Each subject had the gallbladder examined by ultrasonography. The prevalence of gallstone disease was 30.2% and 18.8% among women and men, respectively, being significantly higher among women. Prevalence was assessed in relation to different social and clinical variables. In the univariate analyses gallstone disease was significantly associated with familial occurrence of gallstone disease and high body mass index, whereas it was not significantly associated with social status, childbirths, age at menopause, usage of menopausal hormone therapy, abstinence from alcohol, history of smoking, slimming treatments, and physical activity. By means of a multivariate analysis the history of smoking was found to be significantly associated with gallstone disease when body mass index was taken into account. The significant sex difference disappeared when childbirths and age at menopause were included, which means that clinical variables specific for women in the fertile period could explain the sex difference in gallstone prevalence.

Adult

Parapoxvirus papillomatosis in the muskoxen (Ovibos moschatus): genetical differences between the virus causing new outbreak in a vaccinated herd, the vaccine virus and a local orf virus.

Since 1981 a domesticated muskoxen herd had been successfully vaccinated against papillomatosis with homogenated, glutaraldehyde inactivated papilloma tissue. In the fall of 1985 a new clinical outbreak of disease occurred, affecting previously infected as well as vaccinated animals. The purification of parapox virions directly from papilloma tissue and orf scabs collected in a local sheep farm was followed by restriction endonuclease analysis of viral DNA. The morphological identity of purified virus was controlled by electron microscopy. Comparison of restriction endonuclease digests (10 different enzymes) by gel electrophoresis demonstrated that the muskoxen parapoxvirus from the new outbreak 1985 differed considerably from the 2 other isolates (muskoxen 1981 and local orf). The latter viruses demonstrated a high degree of homology, but differences were evident after digestion with the enzyme EcoRI. During metrizamide gradient purification minor bands containing morphologically intact virions were isolated in addition to the major fractions. The restriction enzyme digests indicated that the virions of the minor bands differed from those in the major bands.

Animals