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J Clausen

Publications and source records attributed to J Clausen.

At least 73 records · Page 4Linked to original sources
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

Comparison of DNA adduct formation by means of synchronous scanning and by isotope tracers: in-vitro study on formation of DNA adducts in human lymphocytes exposed to benzo(a)pyrene.

The P-450 complex transforms polyaromatic hydrocarbons (PA) into active intermediates that may cause mutations due to DNA adduct formation. The present communication compares the rate of DNA adduct formation in human lymphocytes incubated for varying times with different concentrations of benzo(a)pyrene (B(A)P). In the presence of B(A)P the cultures were standardized as to medium and lectin concentration. Then the cells were exposed to increasing levels of cold and 3H-labelled B(A)P for varying times. B(A)P adducted to DNA was estimated both by synchronous scanning (SS) and by counting radioactivity. SS revealed a synchronous signal at 382 nm, corresponding to data available from the literature, and the peak height declined linearly with dose of B(A)P. However, it appeared that the signal height decreased if the DNA was successively extracted with chloroform. Five times extraction gave rise to a stable content of B(A)P of about 25% of the B(A)P originally found in the DNA. This DNA could only be traced with the radioactive tracer, since the concentration of adducted B(A)P was below the lower level of detection by the SS method. Even at low B(A)P levels the carcinogen exists in two forms in DNA: as 'free' non-adducted (extractable with lipid solvents) and an adducted form. Time variation showed that the DNA was incorporated linearly with both forms of B(A)P for up to 2 hours, then the take-up was constant. Concentration variation showed linear incorporation up to 1 microM B(A)P. The present data may explain conflicting data on the extent to which lymphocytes adduct B(A)P to DNA. The lipid-soluble planar B(A)P of DNA may, like photosensitizers, intercalate between the two DNA strands. Like the intercalation of acridines into DNA, which is known to cause frameshift mutations, the intercalation of B(A)P may also have mutagenic consequences.

Benzo(a)pyrene↗
PubMed1993

Prediction of drug distribution in distribution dialysis and in vivo from binding to tissues and blood.

Relationships between the binding and the distribution of drugs have been studied in vitro and compared with in vivo data. By use of a standardized technique of distribution dialysis, 10 model drugs were allowed to be distributed among blood and homogenates of seven tissues. The drugs represented a variety of distinct molecules with different lipophilicities, ionization constants, and binding characteristics. The tissue/blood drug concentration ratios were below unity for salicylic acid and phenylbutazone, at about unity for antipyrine (phenazone) and morphine, and above unity for two barbiturates and four basic lipophilic drugs. The binding of the 10 drugs to blood and homogenates of seven tissues was determined by use of conventional equilibrium dialysis and experimental conditions identical to those used in distribution dialysis. From these binding values (free fractions), the theoretical concentration ratios were calculated. There was a good correlation between the calculated values and those determined by distribution dialysis. Thus, the distribution of drugs in the in vitro model of distribution dialysis clearly is the result of binding competition and is predictable from binding values. The correlation between distribution in vitro (or calculated from binding values) and distribution in vivo, on the basis of literature data, indicated a reasonable agreement for antipyrine and the acidic lipophilic drugs used, as well as for the basic lipophilic drugs, with respect to the brain, muscle, and adipose tissue. However, the distribution of the latter drugs in the lungs, liver, and kidneys was grossly underestimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1993

The effect of blood pressure cuff inflation on sleep. A polysomnographic examination.

Ambulatory blood pressure monitors are being used increasingly to define blood pressure in contexts other than the doctor's office. With increasing interest in both effects of treatment on quality of life and chronobiology of hemodynamic regulation, such monitors have also been used to define blood pressure during sleep. Unfortunately, few investigators have scrutinized the effect of such recordings on sleep, as defined precisely with polysomnography. We studied a diverse group of 12 unmedicated individuals, measuring BP by cuff inflation every 60 min. The polysomnogram was then analyzed for periods of wakefulness and arousals from sleep. Cuff inflation was associated with increased arousals (P < .0001) and wakefulness (P < .0001). In addition, subjects recalled 58% of the cuff inflations. Effects of cuff inflation on a second night of recording indicated some habituation. Nocturnal BPs measured by such techniques are still valuable, but one must have some reservations that these measures accurately reflect BP during sleep.

Blood Pressure Monitors↗
PubMed1993

Mercury and multiple sclerosis.

It has occasionally been claimed that multiple sclerosis (MS) may be due to a chronic mercury intoxication, e.g. from mercury liberated from dental fillings. Therefore, the present communication compares the mercury content assayed by neutron activation in 8 macroscopically normal areas (frontal lobe) of MS autopsy brains with those of 8 control samples. No significant differences could be traced between the two groups concerning total mercury. However, the lipid-soluble mercury (preferably methyl mercury) expressed per cell unit (DNA) was found significantly decreased in MS. These data may be explained either by a wash-out of lipid soluble mercury due to break-down of the blood-brain barrier in MS or to abnormalities in methylation processes probably related to the vitamin B12 metabolism in MS.

Brain↗
PubMed1993

Do endogenous retroviruses have etiological implications in inflammatory and degenerative nervous system diseases?

Vertebrates carry large numbers of endogenous retroviruses (ERVs) and related sequences in their genomes. These retroviral elements are inherited as Mendelian traits. Generally, ERVs are defective without the ability of being expressed as viral particles. However, ERV sequences often have a potential for expression of at least some proteins. So far, the possible biological significance of ERVs is not clear. Nonetheless, there are observations suggesting a connection between ERVs and various diseases. This is the case with murine lupus and a spinal cord disease of certain mouse strains. In the present review, we discuss possible mechanisms by which ERVs could contribute to the development of human degenerative and inflammatory nervous system diseases, including direct effects on nervous system cells and immune cells. Interactions between ERVs and infectious viruses are also discussed. Finally, we review a possible retroviral etiology of multiple sclerosis.

Animals↗
PubMed1993

Lung function in insulation workers.

To evaluate the effects of working with modern insulation materials (rock and glass wool), the members of the Copenhagen Union of Insulation Workers were invited to participate in a study based on a health examination that included lung function tests. Three hundred and forty men (74%) agreed to participate, and 166 bus drivers served as the control group. Age distribution, height, and smoking habits were similar in the two groups. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were used as tests for lung function. There were no differences in FVC between the study and control groups, but the insulation workers had significantly lower values of FEV1 (mean 2.51) compared with the controls (mean 3.4 1), independent of smoking habits. Six years before the present study, 114 of the insulation workers participated in a similar study, and eight years after the initial study, the lung function of 59 of the bus drivers was tested. The decline in FVC in insulation workers who smoked was significantly higher (7.7 cl/year) than in bus drivers who smoked (3.1 cl/year); the decline in FEV1 was significantly higher in insulation workers independent of smoking habits (17.0 cl/year v 2.9 cl/year). Self assessed former exposure to asbestos was not associated with lung function in insulation workers. The study concludes that working with modern insulation materials is associated with increased risk of developing obstructive lung disease.

Adult↗
PubMed1993

[Amyotrophic lateral sclerosis--indications of increased antiretroviral seroreactivity without obvious epidemiology].

Of 25 male and 13 female patients diagnosed as sporadic cases of amyotrophic lateral sclerosis between 1989 and 1992, 17 had reproducible serum antibodies against human foamy virus (HFV = human spuma retrovirus, HSRV). HFV-positive ALS patients had higher IgG3 concentrations than HFV-negatives (P < 0.05) and competed better on maedi-visna retroviral antigen than HFV-negatives or controls (P < 0.05), but did not differ otherwise. Two HFV-positive patients were living in the same building; two other ALS patients lived within 300 m of one another, and three HFV gag reactive men (2 ALS, 1 control) were living in neighbouring villages. These were the closest geographic clusters found among current patients. We summarize recent findings compatible with a pathogenetic role for endogenous and/or exogenous retroviral sequences in adult motor neuron disease, and confirm a male preponderance as well as an inverse correlation between survival time and age at onset.

Adult↗
PubMed1993

Retroviral interference with neuronotrophic signaling in human motor neuron disease?

We tested 13/32 patients with non-familial amyotrophic lateral sclerosis (ALS) positive (41%) for human spuma retrovirus (HSRV) seroreactivity. Half the non-ALS HSRV-positive neurologic patients (12/25) reported multiple fasciculations within the last two years. Sera from four HSRV-env negative ALS patients measurably competed with visna antibodies on maedi-visna antigen. The serologies for bovine leukemia virus, Borna disease virus and GM1IgM-antibodies remained negative. Both visna and foamy virus sequences share epitopes with motor nervous system signal polypeptides, suggesting a retroviral interference with motor neurono-axonal function and neuronotrophic signals.

Adolescent↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗