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Biomedical subjects

J Clausen

Publications and source records attributed to J Clausen.

At least 19 recordsLinked to original sources

Genetic susceptibility to multiple sclerosis may be linked to polymorphism of the myelin basic protein gene.

The present paper compares the genetic polymorphism of a part of the myelin basic protein (MBP) gene in 64 Danish MS patients with that of 57 normal controls. PCR analysis, using primers flanking the 5' area from 479 to 1812 bp upstream the initiator methionine in the MBP gene, revealed that genetic susceptibility to MS is linked to polymorphism in the part of the MBP gene studied. Thus we found three different band patterns i.e. a homozygote with a 1445 bp long fragment, a homozygote with a fragment 1318 bp long and a heterozygote with both bands present. 59% of 64 patients with MS were homozygous for 1.445 kb allele, versus 40% of 57 control subjects, 18% of the control subjects were homozygous for the 1.318 kb, while only 0.7% of the MS patients possessed this allele. The differences between incidence of the three band pattern in the MS and the control group were significant at 1% level. Validation analysis furthermore support, the view that the 1445 bp PCR fragment is associated with MS.

Adult

The effect of sleep apnea on plasma and urinary catecholamines.

Numerous studies have suggested an alteration of sympathetic nervous system functioning in sleep apnea. However, most of these studies did not control for confounding factors such as diet, obesity, hypertension and anti-hypertensive medications. We examined plasma and urinary catecholamines in 43 patients, including hypertensive and normotensive individuals with and without sleep apnea. Hypertensive patients were studied at least 3 weeks following tapering of anti-hypertensive medication. All patients consumed similar diets and were of similar age and level of obesity. Twenty-four-hour urinary norepinephrine levels were significantly higher in apneics (58.2 ng vs. 40.2 ng in nonapneics, p < 0.002). Urinary norepinephrine in apneics was increased during both day and night. Plasma norepinephrine levels were not significantly elevated in apneic patients but were elevated in hypertensive patients both during sleep and in the morning (p < 0.05).

Adult

Uptake, distribution, and turnover rates of selenium in barley.

The present communication elucidates initially the topographic distribution of selenium in barley grains. Then by the fluorimetric method the uptake of selenium (selenite) in 8-16 d old germinating barley was estimated. Finally by means of 75Se the anabolic and catabolic rates (turnover) of 75Se (selenite) was compared. The distribution of selenium in barley was evaluated after micro-dissection of barley grains. In dried grains the highest concentration was found in husk and pericarp with about 0.6 ppm Se. Then followed Scutellum with 0.4 and 0.3 ppm in embryon. The aleurone layer, embryonic leaves, and initial root did only have 0.2 ppm Se. In order to know more about the uptake and distribution of selenium in 8-d-old barley, the plants were cultivated for a further 8 d in the culture medium with variation in selenite concentration. In roots and leaves, the uptake did not arrive at saturation during the period studied since the dose-response curve increased up to 0.34 mM selenite in the medium, whereas the selenium levels were about 200 ppm in roots and 30 ppm in leaves. However, the uptake was linear, with concentration during 8 d of cultivation up to 0.84 microM selenite for grain and stem. At higher concentrations the dose-response curve diminished its slope. At 0.34 mM selenite the concentration in grain increased to 6.87 ppm and in the stem to 8.13 ppm. The uptake, distribution, and catabolic rate of selenium components in germinating barley were further evaluated by exposing the plants to 0.0492 microCi 75Se (12.6 microM selenite) for up to 4 d. Then the plants were moved to a selenium deficient medium for further 4 d. Then finally the medium was supplemented with high doses of cold selenite (0.126 mM selenite) for further 4 d. The first third period made it possible to estimate the rate of uptake. It was highest in roots (313 fmol/h/mg dw), i.e., about 10 times those of grains, stems, and leaves. The intermediate period where the barley was transferred to a selenium deficient medium made it possible to estimate the kinetics and eventual sparing mechanisms. The selenium losses were highest for leaves (39%), then followed by roots and stems (22 and 25%, respectively). The losses were lowest in grain with 9% Se losses. The losses were three times more pronounced during the first day than in the following 3 d. These data may argue that the selenium is distributed into different pools and that sparing mechanisms may be in function.(ABSTRACT TRUNCATED AT 400 WORDS)

Hordeum

Epidemiology of invasive Haemophilus influenzae infections in Cape Town, South Africa.

The full spectrum of invasive Haemophilus influenzae disease has not been documented previously in Africa. This 1-year prospective study was designed to determine the epidemiology of invasive Haemophilus influenzae disease in Cape Town children. During this period, 142 children with invasive disease were hospitalized; 85 (59.9%) presented with meningitis, 35 (24.6%) with pneumonia and 22 (15.5%) with other diseases. No cases of epiglottitis were seen. Sixty per cent of cases were male and 40% female. The median age of the children was 9 months, with a range of 1-144 months, and 65.5% were aged < 12 months. Neurological dysfunction was noted in 40% and 18% of children with meningitis on admission and discharge, respectively. The overall case fatality rate (95% confidence intervals) was 9.2% (4.9-15.7), and for meningitis, pneumonia and septicaemia it was 4.7% (1.2-16.4), 14.3% (4.6-31.8) and 40% (8-78.1), respectively. Serotype b accounted for 86.5% of all cases, 97.3% of cases of meningitis, 71.4% of cases of pneumonia, 50% of cases of septicaemia, all cases of arthritis and cellulitis and none of mastoiditis. The incidence rates (95% confidence intervals) for all invasive type b infections were 169 (122-198) and 47 (39-57) per 100,000 population for children < 1 and < 5 years, respectively. For meningitis the rates were 112 (84-148) and 34 (25-40) per 100,000, respectively. Rates for mixed race and white children were similar, but those for black children were more than double those rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Distribution

A technique for improved blood sampling during sleep studies.

Research protocols often require that blood samples be drawn during sleep. This study compares the efficacy of obtaining nocturnal blood samples using a standard heparinized intravenous setup versus the same intravenous setup used in conjunction with a small chemical heating pad. The chemical heating pad significantly improved the number of blood samples obtained and the maintenance of intravenous patency. The use of a chemical heating pad is an economical way to resolve the frustration of lost blood samples while maintaining a reasonable environment to monitor sleep.

Adult

Adipose tissue storage of drugs as a function of binding competition. In-vitro studies with distribution dialysis.

Distribution dialysis was used to study binding competition between homogenates of adipose tissue and of lean tissues. The concentration ratios adipose/X (X = blood, muscle, lung, liver) of eight lipophilic drugs were determined in the absence and in the presence of a competing binding system X. With drugs which do not undergo storage in adipose tissue in-vivo, yet have a high volume of distribution, such as imipramine or desipramine, there was strong binding competition, and the balance of distribution was shifted from adipose to lean tissues. In the case of indomethacin with a low volume of distribution this shift was from adipose tissue to blood. With diazepam there was a marked binding competition which was not, however, sufficient to shift the balance of distribution away from adipose tissue. Binding competition was negligible with thiopentone. In contrast, with the equally lipophilic hexethal a moderate binding competition was observed. This is consistent with a decreased adipose tissue storage of the latter barbiturate. It is concluded that binding competition exists not only between blood and tissues but also among individual tissues. It is suggested that occurrence and extent of adipose tissue storage of drugs are determined by binding competition between lean and adipose tissues and, more generally, that distribution of lipophilic drugs is largely a function of binding competition.

Adipose Tissue

Method for estimation of benzo[a]pyrene DNA adducts.

Polycyclic aromatic hydrocarbons, e.g., benzo[a]pyrene (B(a)P) are known carcinogens/mutagens. These compounds may be metabolized by the P450 mixed function monooxygenase to more nucleophilic compounds which may form adducts to the cellular macromolecules, e.g., DNA, RNA, and proteins. We have used synchronous fluorescence scanning for the assay of DNA adduct formation. In our earlier work with in vitro exposed human lymphocytes we estimated the adduct formation (femtomoles B(a)P per microgram DNA) to be higher than that estimated by other workers. We suggested that this difference may be related to the DNA isolation method used. In order to elucidate these differences we compared DNA adduct formation in human lymphocytes where DNA was isolated by the two different methods, i.e., using phenol extraction or the Gene Clean method. The data demonstrate that the phenol extraction procedure gives a yield of adducts per microgram DNA lower than that obtained by the Gene Clean method. The principle of the Gene Clean method for DNA isolation is protein denaturation by means of NaI followed by catching of DNA by absorption on silica particles. In contrast, the phenol extraction method is based upon phenol-mediated denaturation of proteins in the cell lysate leaving the hydrophilic nucleotides in the aqueous phase. However, during adduct formation more lipophilic adducts derived from DNA may redistribute between the aqueous phase and the phenol phase. In support of this theory we found higher adduct concentration per microgram DNA by the Gene Clean method 40 to 60 times than that found by the phenol method.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Search for a retrovirus in multiple sclerosis by enzymatic amplification of DNA from brain capillaries, brain tissue and mononuclear cells from peripheral blood.

Attempts were made to trace a possible retrovirus in multiple sclerosis (MS) by means of polymerase chain reaction. The primers derived from conserved sequences in the genome of human T cell leukemia/lymphoma virus type I (HTLV-I) and the amplifications were carried out at varying stringency conditions (i.a. annealing at low stringency to enhance the cross-reactivity of the primers). Included in the study were samples of DNA from brain capillaries (five MS patients), brain tissue (three MS patients) and peripheral blood mononuclear cells (three MS patients). Using an HTLV-I derived probe at relaxed conditions of stringency, hybridization signals were not recorded with amplified material from any of these samples. Aspects of infections with neurotropic retroviruses that could be relevant to the search for a retrovirus in MS are reviewed.

Adult

Seroreactivity to human T cell leukemia/lymphoma virus type 1 and related retroviruses in multiple sclerosis patients from Denmark and the Faroes.

A total of 40 multiple sclerosis (MS) patients from Denmark and 10 from the Faroes were examined for antibodies with affinity to human T cell leukemia/lymphoma virus type 1 (HTLV-I) and human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2). Using ELISA, MS patients and a group of healthy controls did not differ significantly in their reactivities to HTLV-I. However, elevated reactivities were recorded with 5 MS sera, whereas only 2 of the sera from the controls produced highly values. Ten patients with other neurological diseases all seemed to exhibit low reactivity in HTLV-I ELISA. The reactivities of 2 MS sera decreased considerably by absorption with an HTLV-I lysate. In immunofluorescence assay, two other MS sera reacted with HTLV-I transformed cell lines as well as with non-infected cells. Examined by Western blotting (WB), a single MS serum produced a distinct HTLV-I p19 band. With ELISA for detection of HIV-1 and HIV-2 antibodies, 2 MS sera exhibited borderline reactions. Further examination of these two sera by WB revealed weak reactivities against p24 and p53 of HIV-1. One the whole, the present observations do not suggest that a putative MS retrovirus would be closely related with HTLV-I, HIV-1 or HIV-2.

Adult

Blood pressure and mortality: an epidemiological survey with 10 years follow-up.

The Copenhagen City Heart Study is a prospective ischaemic heart disease population study designed to evaluate incidence of, and risk factors for, ischaemic heart disease. A random population sample of approximately 20,000 men and women was invited to participate in a health survey, which was carried out in 1976-78. The participation rate was 74%. Systolic (SBP) and diastolic blood pressure (DBP) was measured with the London School of Hygiene sphygmomanometer after 5 minutes in the sitting position. Risk factors were assessed by a questionnaire and non-fasting plasma cholesterol was measured. Information about subsequent death and causes of death was obtained from the Danish Death Register. Follow-up was virtually complete over an observation time of 10 years. Analysis of the independent effect of SBP and DBP measured at entry on the 10 year total and cause-specific mortality was performed using the Cox regression model. Antihypertensive medication and/or diuretic therapy, physical activity during leisure time, economic and educational status, tobacco and alcohol consumption, diabetes mellitus, body mass index, plasma cholesterol levels, age and sex were entered as confounders. Total mortality was increased only in the higher quintiles of SBP. Concerning ischaemic heart disease mortality and cerebrovascular mortality, the risk increased in a graded manner with increasing quintile of SBP and DBP. With regard to cancer mortality, a U-shaped association was observed between quintile of SBP (and DBP) and death rate. With advancing age, the predictive power of SBP on total and cause-specific mortality changed, especially in males, as a pronounced U-shape of the association between BP and mortality appeared. The reasons for this are discussed. The relative risk in subjects receiving antihypertensive medication was 1.7 (CL 1.5-2.0) regarding total mortality, 2.0 (CL 1.5-2.7) regarding ischaemic heart disease mortality, 0.8 (CL 0.5-1.4) regarding cerebrovascular mortality, and 1.3 (CL 1.0-1.7) regarding cancer mortality. This finding is in agreement with clinical trials experiences, and may have an impact on management of high blood pressure.

Adult

The influence of selenium and vitamin E on the enhanced respiratory burst reaction in smokers.

The respiratory burst reaction (RBR) of neutrophilic granulocytes of the peripheral blood was estimated by means of the luminol reaction in 10 smokers and in 10 nonsmokers. Compared to the nonsmokers, the RBR of smokers' granulocytes showed a significantly higher rate of RBR. RBR consists of two enzymatic systems, i.e., NADPH-oxidase generating superoxide anions and myeloperoxidase, generating hypochlorous acid. Furthermore the superoxide anion may undergo dismutation to oxygen and peroxide. Thus, since the RBR may cause an oxidative stress, the smokers were supplemented for 10 d with antioxidants, i.e., 200 micrograms L-Se-methionine and 1000 mg vitamin E/d. After 10 d of supplementation with the antioxidants, the RBR of the smokers was significantly decreased by 20-75 percent. Since the oxidative stress associated with RBR may cause autodigestive reactions in the lungs of smokers, it may be beneficial for smokers to use relatively high doses of such antioxidants in order to hamper the pathological processes associated with smoking.

Adult

Uptake and distribution in rat brain of organic and inorganic selenium.

Polyunsaturated fatty acids (PUFAs) occur in relatively high amounts in phospholipids of the synapses. PUFAs may thus determine the fluidity of the synaptosomal membrane and, hereby, they may regulate the neuronal transmission. It was therefore tempting to suggest a system in the brain, that inhibits autooxidation of PUFAs. In order to trace such a protection system, Wistar rats were equally loaded with 4500 kBq of 75-Se either as selenite or as L-Se-methionine. By means of gradient ultracentrifugation, particulate fractions of the brains were isolated, and the radioactivity as well as the glutathione-transferase and -peroxidase activities were estimated. The distribution of the two selenium components among the particulate fractions was different. Thus, selenite gave higher radioactivity in myelin, then followed by the light synaptosomal and the vesicular fraction. L-Se-methionine was more equally incorporated in all particulate fractions, although highest activity was found in the mitochondrial fraction. Myelin and synaptic vesicles were devoid of transferase activity. On the other hand, the synaptosomal fraction showed highest specific transferase activity. The glutathione peroxidase activity was highest in the myelin fraction, followed by the vesicular and the synaptosomal fractions. The data obtained thus support the idea that the PUFAs of the synaptic compartment are protected against peroxidation, at least in part, by the selenium containing glutathione peroxidase.

Animals

Brainstem auditory-evoked responses with and without sedation in autism and Down's syndrome.

Brainstem auditory-evoked responses (BAER) were obtained from 46 control, 16 Down's syndrome, and 48 autistic male subjects. Six Down's syndrome and 37 autistic subjects were tested with sedation. Sedated and unsedated Down's syndrome subjects displayed shorter absolute and interpeak latencies for early components of the BAER whereas the sedated autistic group showed longer latencies for the middle and late components. The prolongation of latencies in the sedated autistic group was unrelated to age or intellectual level. Although individuals requiring sedation may have a higher probability of neurological impairment, an effect of sedation on the BAER cannot be ruled out.

Adolescent

Are blood pressure levels increasing in Denmark?

The Copenhagen City Heart Study is a prospective cardiovascular population study designed to evaluate the incidence of and risk factors for cardiovascular disease. A random population sample comprising approximately 20,000 individuals was invited to participate. Blood pressure was measured, and information regarding the use of antihypertensive medication was collected in an initial survey during the period 1976-1978 (attendance rate 74%) and from a second survey during the period 1981-1983 (attendance rate 70%). A significant increase in systolic and diastolic blood pressure between survey 1 and survey 2 was found among both men and women greater than 40 years of age and not using antihypertensive medication. The increase in blood pressure in the follow-up survey could not be explained by changes in methods, changes in the prescription of antihypertensive medication, or selection bias. Factors associated with changes in systolic and diastolic blood pressure were examined by multiple linear regression analysis. Both increase in body mass index and increase in alcohol consumption were positively correlated with changes in systolic and diastolic blood pressure, while use of antihypertensive medication, a high value of body mass index at survey 1 and a high level of education were negatively correlated with changes in systolic and diastolic blood pressure. Female sex and advanced age were also negatively correlated with changes in diastolic blood pressure. Consumption of tobacco and alcohol, income and changes in consumption of tobacco were not significantly correlated with changes in systolic and diastolic blood pressure.

Adult