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Biomedical subjects

J Clausen

Publications and source records attributed to J Clausen.

At least 19 recordsLinked to original sources

Effects of dietary broccoli on human drug metabolising activity.

Eighteen volunteers received 500 g fresh broccoli every day for 12 days after a 6-day period of standard diet. The activity of CYP1A2, CYP2E1 and the estrone 2 and 16alpha-hydroxylation were determined prior to and after the broccoli diet. The average activity of CYP1A2 and the average 2/16alpha-hydroxyestrone ratio were increased 19% (P < 0.0005) and 29.5% (P < 0.05), respectively; however, no effects were observed on the CYP2E1 activity.

Anticarcinogenic Agents

Long-term follow-up of leukaemia patients after related cryopreserved allogeneic bone marrow transplantation.

We have previously shown that allogeneic bone marrow transplantation (BMT) with cryopreserved donor marrow cells can be used without prolonging the engraftment time or interfering with the reconstitution of haemopoiesis. In this report we extend our initial observations of the first 40 patients who underwent allogeneic bone marrow transplantation from related donors with cryopreserved donor bone marrow for haematological malignancies, including the long-term follow-up data of the previously reported patients. The outcome of these patients was compared with that of 40 related BMT recipients receiving fresh donor bone marrow (historic control group). Time until engraftment of all patients receiving cryopreserved bone marrow was not different from the control group (ANC > 0.5 x 10(9)/l 17d (range 11-24 d) versus 17.5 d (range 10-28 d): platelets > 20 x 10(9)/l 21 d (range 11-85 d) versus 22 d (range 13-69 d), respectively). There was the same incidence of acute and chronic GvHD in patients receiving either cryopreserved bone marrow or fresh bone marrow (acute GvHD > or = II 61% v 60% and chronic GvHD 56% v 52%, respectively). Chimaerism studies showed no difference between the patient groups. Furthermore, the two groups did not differ in day 100 survival (82% v 72%). With a median follow-up of 520 d (range 47-1365 d) and 1289 d (range 48-1849 d), 60% of the patients receiving cryopreserved and 53% of the patients receiving fresh allogeneic donor bone marrow, respectively, are alive. We conclude that cryopreservation of allogeneic related donor bone marrow does not adversely affect engraftment, does not decrease the incidence of severe acute GvHD, and does not seem to affect the day 100 survival or long-term haemopoiesis.

Adolescent

Possible involvement of endogenous retroviruses in the development of autoimmune disorders, especially multiple sclerosis.

Endogenous retroviruses are normal elements in vertebrate genomes. Many aspects concerning these genomic elements are still uncertain. In mice some endogenous retroviral sequences seem to be involved in the regulation of immune responses and there is even evidence that a retroviral element is responsible for the development of an autoimmune disease in a mouse strain. Whether endogenous retroviruses also contribute to the development of autoimmune diseases in humans is not known, but it is an interesting possibility. Below we briefly review endogenous retroviruses as potential etiological factors in autoimmunity and we discuss a possible association between MS and endogenous retroviruses on the basis of results from our laboratory.

Animals

Expression of endogenous retroviruses in blood mononuclear cells and brain tissue from multiple sclerosis patients.

OBJECTIVES: To compare the expression of endogenous retroviruses in MS patients and controls. MATERIAL AND METHODS: Peripheral blood mononuclear cells were obtained from 22 MS patients, a corresponding number of matched healthy donors and five patients with other central nervous system disease. Also brain specimens from MS patients and controls were obtained. Transcripts of various endogenous retroviruses in these samples were detected by RNA-PCR. RESULTS: Several endogenous retroviral sequences were transcribed in peripheral blood mononuclear cells and brain tissue from MS patients as well as controls. A composite transcript of an endogenous retrovirus and a zinc finger sequence was more frequently found in healthy donors than in MS patients. CONCLUSION: Some endogenous retroviruses are normally transcribed in white blood cells and brain tissue. The significance of those findings, which concerned the composite transcripts of the zinc finger sequence and its associated endogenous retrovirus is uncertain.

Adult

Sympathetic nervous system alterations in sleep apnea. The relative importance of respiratory disturbance, hypoxia, and sleep quality.

Numerous alterations in the sympathetic nervous system have been reported in patients with obstructive sleep apnea. It is unclear whether such alterations can be attributed to the respiratory disturbance itself, the resulting hypoxia, or disruption of sleep. We examined urinary norepinephrine levels in 45 individuals with varying amounts of respiratory disturbance and sleep disruption. All were of similar age (40 to 60 years) and body weight (100 to 160% ideal body weight), and all were free from antihypertensive medications that could influence norepinephrine levels. Twenty-four-hour urinary norepinephrine levels were correlated with respiratory disturbance index (r = 0.39, p < 0.01) and mean oxygen saturation (r = -0.36, p < 0.05). These variables, together with the time in slow-wave sleep, accounted for a statistically significant but modest percentage of the variance in urinary norepinephrine (R2 = 0.19, p < 0.05). However, the variables were so tightly intercorrelated that no single variable independently predicted norepinephrine levels in multiple regression analysis.

Adult

Allogeneic transplantation with CD34+-selected cells.

We report the outcome of eight patients with different hematological malignancies who were transplanted with allogeneic CD34-selected mononuclear cells following myeloablative therapy. Four patients received G-CSF mobilized CD34-enriched peripheral blood progenitor cells (PBPC) together with CD34-enriched bone marrow (BM), two patients were transplanted with allogeneic G-CSF mobilized CD34-enriched PBPC alone, and two patients received only allogeneic CD34-enriched BM cells. On average, patients received 2.66 x 10(6) CD34+-cells/kg BW (range: 0.53-8.40 x 10(6) CD34+-cells/kg body weight) and 0.57 x 10(6) CD3+-cells/kg BW (range: 0.20-1.10 x 10(6) CD3+-cells/kg BW), respectively. Seven of the eight patients engrafted (ANC > 0.5 x 10(9)/L median: day +19 (range: 16-23 days); platelets > 20 x 10(9)/L median: day +34 (range: 21-47 days); one patient died on day +16 after transplantation and was not evaluable for engraftment. Three of seven patients evaluable for acute graft-versus-host disease (GvHD) developed acute GvHD grade II which resolved upon steroid treatment. Five of the eight patients are still alive and in remission with a median follow-up of 215 days (range: 80-420 days). Causes of death included fungal infection, cerebral bleeding and sepsis. These preliminary data suggest that CD34-enriched cells can be successfully given during for allogenic transplantation following myeloablative therapy in hematological malignancies. The impact of T-cell depletion by enrichment for CD34+-cells in an attempt to reducing the incidence and/or severity of acute and/or chronic GvHD still remains to be determined.

Adult

Sleep apnoea and sympathetic nervous system activity: a review.

A review was made of the literature relating sleep apnoea to sympathetic nervous system (SNS) activity, as inferred from catecholamine levels or muscle sympathetic nerve activity (MSNA). Twenty-four studies were located. Most studies reported an elevation of norepinephrine and MSNA, both during sleep and wakefulness among individuals with sleep apnoea. However, studies rarely controlled for known confounders of sympathetic activity, making the validity of the findings questionable.

Arousal

Effects of dietary broccoli on human in vivo drug metabolizing enzymes: evaluation of caffeine, oestrone and chlorzoxazone metabolism.

Ingestion of cruciferous vegetables may prevent chemically induced carcinogenesis by their influence on specific cytochrome P450 enzymes (CYP) and phase II drug metabolizing enzymes in humans and rodents. Thus CYP enzymes are involved in transformation of procarcinogens, mutagens, steroid hormones and a large variety of other endogenous and exogenous components. In order to learn more about the influence of cruciferous vegetables on drug metabolizing enzymes in man two CYP enzymes previously suggested to be induced by vegetables were selected in an in vivo experiment in humans. Sixteen healthy non-smoking subjects, two females and 14 males, were exposed to three different types of diets and afterwards assayed for CYP1A2 catalysed caffeine metabolites and for CYP2E1 catalysed 6-hydroxylation of chlorzoxazone. Further, 2-hydroxyoestrone:16 alpha-hydroxylation ratios were determined in urine by means of a monoclonal antibody-based enzyme immunoassay. The three dietary periods were: (A) a customary home diet; (B) a 6 day standard diet avoiding well-known dietary inducers and inhibitors of CYP; (C) a 12 day dietary supplement to the standard diet of 500 g/day broccoli. The average 6-hydroxychlorzoxazone:chlorzoxazone ratio decreased by 21% (P < 0.05) after diet B compared with diet A in a 2 h plasma sample after ingestion of 500 mg chlorzoxazone. The ratio increased by 19% after diet C, however, this was not statistically significant. The caffeine metabolic ratio (CMR) was determined in urine 6 h after ingestion of 100 mg caffeine. The mean CMR increased by 5.5% when changing from diet A to diet B. When shifting to diet C the mean CMR increased a further 19% (P < 0.0005). The average 2-hydroxyoestrone:16 alpha-hydroxyoestrone ratio decreased by 1.3% when comparing diet A with diet B. Daily broccoli intake increased the ratio by 29.5% (P < 0.05). A low correlation of CMR with the 2-hydroxyoestrone:16 alpha-hydroxyoestrone ratio indicates that human CYP1A2 and other CYP enzymes involved in oestrone 2-hydroxylation are induced by dietary broccoli. On the other hand, the catalytic activity of CYP2E1 is not affected to the same degree by dietary broccoli.

Adult

A repetitive DNA sequence 5' to the human myelin basic protein gene may be linked to MS in Danes.

The myelin basic protein (MBP) gene is a candidate locus for disease susceptibility in multiple sclerosis (MS). In the present study a part of the tetranucleotide (TGGA)n repeat polymorphism 5' to the MBP gene was examined in 90 Danish MS patients and 106 controls. Lymphocyte DNA was isolated and used in PCR assay. The PCR fragments produced were separated by agarose and acrylamide electrophoresis. Hereby we found three different bandpatterns i.e. a homozygote with a 450 bp fragment, a homozygote with a fragment 375 bp and a heterozygote with both bands present. The 450 bp fragment occurred significantly more often among MS than in the control group and the 375 bp fragment was underrepresented among MS than in the control group. The differences between incidence of the three band pattern in the MS and the control group were significant different at 1% level. Our study thus indicate that there is an association between MS and a length polymorphism of the 5' end to the MBP gene in Danish MS patients.

Adult

Methylcholanthrene-induced sarcomas in nude mice have short induction times and relatively low levels of surface MHC class I expression.

In order to study the role of the T-cell-mediated immune defense in tumor development, a total of 93 sarcomas were induced using different doses (8 micrograms (0.1%), 40 micrograms (0.5%) and 400 micrograms (5%)) of 3-methylcholanthrene in athymic nude Balb/c mice and phenotypically normal immunocompetent Balb/c mice. A shorter tumor induction time and a higher tumor incidence after treatment with low doses of methylcholanthrene were seen in nude mice than in immunocompetent mice, indicating that they have a lower resistance to the carcinogen. Contrary to expectations we found that the MHC class I expression of tumors from nude mice was lower than that of tumors from normal mice. Higher surface expression of MHC class I was demonstrated on high dose tumors from normal mice than on low dose tumors from normal mice. The cellular composition of the individual tumors raised in nude mice was more heterogeneous with respect to MHC class I expression. Since the mice differ genetically only with respect to the nu gene, these results indicate that a lack of T-cell-mediated defense mechanisms may confer upon the bearer a lower resistance to 3-methylcholanthrene and a different MHC profile of the ensuing tumor.

Animals

Sequencing and detection of polymorphisms in the 5' end of the human endogenous retroviral element, HRES-1.

Fragments of the 5' long terminal repeat (LTR) of the human endogenous retroviral element, HRES-1, were amplified. Single strand conformation analysis of these fragments in combination with sequencing revealed two polymorphic nucleotides, namely a HindIII and an Eco571 polymorphic site. Moreover, a number of differences from the previously published HRES-1 LTR sequence were detected. The linkage pattern of the two polymorphisms suggested the existence of three allelic forms of HRES-1. The frequencies of the genotypes and alleles of HRES-1 were determined in 158 individuals. The detection of HRES-1 markers may be useful to study associations between this endogenous retrovirus and various diseases.

Base Sequence

Three allelic forms of the human endogenous retrovirus, ERV3, and their frequencies in multiple sclerosis patients and healthy individuals.

A possible association between the endogenous retrovirus, ERV3, and multiple sclerosis (MS) was examined. Samples of DNA from 74 MS patients and 159 healthy blood donors were subjected to enzymatic amplification followed by single strand conformational analysis to detect polymorphisms in the long terminal repeats of ERV3. Using this approach we detected six single base pair variations and a drop-out of a nucleotide. The linkage pattern of these base pair variations enabled us to define three allelic forms of ERV3. Polymorphisms exclusively present in the group of patients were not found and the distribution of the three allelic forms did not differ significantly between the group of controls and the MS group. Neither was there a significant difference in the distribution of the three alleles between MS patients with the progressive form and patients with relapsing/remitting MS. Our results are not in support of an association between ERV3 and MS.

Alleles

The roles of growth factors and neural activity in the development of the neocortex.

Previous research on primarily the peripheral nervous system has shown that soluble growth factors help control key developmental events by contributing to dynamic autocrine and paracrine signalling systems. Much less is known about the roles of these substances in neocortical development. Using cell and tissue culture paradigms, we have demonstrated that soluble growth factors are produced by the neocortex and its subcortical targets, and that these tissues can respond to them. There are several possible functions for these factors in neocortical development in vivo: they may initiate axonal growth from neocortical neurons and/or their afferents; accelerate or guide that growth; and/or play a role in the later refinement of connections. Although none of these possibilities can be excluded, the existing evidence strengthens the hypothesis that soluble growth factors are important for the early postnatal growth and refinement of neocortical connections, when their levels of release may be regulated by neocortical activity. At present we do not know which growth factors are involved in these processes, but the results of preliminary experiments indicate that neurotrophins and fibroblast growth factor are prime candidates.

Animals

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

Maternal smoking during childhood and increased risk of smoking in young adulthood.

BACKGROUND: Effective prevention of smoking depends on the identification of factors that determine smoking onset. We examined the influence of family factors during childhood (household income, parents' education and smoking behaviour) on the subsequent risk of smoking in young adults. METHODS: In 1979, 1300 children aged 6-18 years, whose parents were randomly selected for participation in the Copenhagen City Heart Study were invited to a health examination. Information about health and smoking behaviour was obtained from 73% of the children. A random sample of 579 of the children were invited to a follow-up examination 13 years later. In all, 486 (84%) participated in the follow-up. RESULTS: The influence of household income, parents' smoking behaviour and education on the child's risk of becoming a smoker in young adulthood was estimated. Household income and parents' education did not significantly affect the risk of adult smoking. Maternal smoking during childhood increased the risk in comparison with the mother being a non-smoker (adjusted odds ratio = 1.95; 95% confidence interval: 1.07-3.58). CONCLUSION: Maternal smoking during childhood increases children's risk of becoming young adult smokers, independent of age and smoking behaviour in childhood, gender and social background. In Denmark 28% of smoking in young adults could be attributed to maternal smoking.

Adolescent

Dietary effect on mixed function P450 1A2 activity assayed by estimation of caffeine metabolism in man.

Two studies were performed in order to evaluate cytochrome P450 1A2 mediated caffeine metabolism during different nutritional conditions. 1. In the first study, 23 healthy male non-smokers, mean age 25, changed from a customary mixed diet to a standard diet in 6 days. The 6 day's standard diet was based on bread, potatoes, rice and boiled meat. Thus, broccoli, cabbage and other cruciferous vegetables, spinach, leeks, onion, parsley, grapefruit, toasted bread, fried and charcoal grilled food, smoked fish and meat, ham and sausages were avoided. 2. In the second study, 33 healthy non-smoking subjects, 24 men and nine women mean age 25 years, volunteered. The study was designed to compare a customary home dietary period with the 6 day period of low dietary P450 induction and with a 5 day supplementary dietary period, i.e. ingestion of known dietary inducers. None of the women were using oral contraceptives or were pregnant during the experimental period. In the period of diet supplementation, the volunteers received charcoal grilled hamburger as a supplement to the standard low induction diet for lunch for 5 days. The hamburgers were made with 150 g beef (18-20% fat) and were grilled on charcoal for 10 min on each side until they were 'well done'. In the present study P450 1A2 activity was estimated from the caffeine metabolic ratio, the so-called CYP 1A2 index:(AFMU + 1-MX + 1-MU/ 17 -DMU) of the caffeine metabolites formed after oral ingestion of 200 mg caffeine. Urine was collected 4-8 h after caffeine ingestion in study 1 and 5 h after caffeine ingestion in study 2. In study 1 the CYP 1A2 index decreased from 4.28 +/- 0.98 in the customary home dietary period to 3.87 +/- 0.69 in the standard dietary period corresponding to 10.6% (P < 0.06) decrease in the CYP 1A2 index. In study 2 the CYP 1A2 index decreased from 4.47 +/- 1.76 in the customary home dietary period to 3.90 +/- 1.12 in the standard dietary period corresponding to a 14.6% decrease (P < 0.2) in P450 1A2 activity. The female subjects had a mean index value of 3.89 +/- 1.14 which was 16.8% (P = 0.09) lower than the mean male index value of 4.68 +/- 1.76 during the home dietary period. After the 5 day period with charcoal grilled hamburgers as a dietary supplement, the CYP 1A2 index increased to almost the same level as in the customary home dietary period. The index increased to 4.45 +/- 1.57 in the whole group of volunteers, corresponding to a 14.1% (P < 0.05) increase. The mean increase in the CYP 1A2 index covered a large inter-individual variation in response to ingestion of charcoal grilled meat ranging from a 29% decrease to a 147% increase.

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