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Biomedical subjects

C Madsen

Publications and source records attributed to C Madsen.

At least 19 recordsLinked to original sources

Immunotoxicity of the pyrethroid insecticides deltametrin and alpha-cypermetrin.

The synthetic pyrethroids deltametrin and alpha-cypermetrin were studied for effects on the immune system in 28-day studies in F344 male rats. Sixteen rats per group were dosed with either deltametrin 0, 1, 5, or 10 mg/kg body wt./day or alpha-cypermertin 0, 4, 8, or 12 mg/kg body wt./day in soy bean oil by gavage. Haematology, bone marrow cell counts, tests for natural killer (NK) cell activity and mitogen response (Con A and STM) as well as quantitation of lymphocyte subpopulations were performed. Spleen cells from immunized animals (six animals/group) were tested for antibody production (SRBC-PFC). Volumes of lymphoid compartments of mesenteric lymph nodes and thymus were estimated using stereological methods. In the deltametrin study an effect was found in the groups receiving 5 or 10 mg/kg body wt. The effects were: increased weight of mesenterial lymph nodes, decreased thymus weight in immunized animals and an increase in numbers of SRBC-PFC and splenic NK cell activity. An effect on relative adrenal weight was seen in the 10 mg/kg body wt. group. No severe effects on the immune system was found. The lowest effect level of alpha-cypermetrin was 12 mg/kg body wt./day based on increased relative adrenal weight.

Adrenal Glands

Stereological estimation of nuclear mean volume in invasive meningiomas.

A stereological estimation of nuclear mean volume in bone and brain invasive meningiomas was made. For comparison the nuclear mean volume of benign meningiomas was estimated. The aim was to investigate whether this method could discriminate between these groups. We found that the nuclear mean volume in the bone and brain invasive meningiomas was larger than in the benign tumors. The difference was significant and moreover it was seen that there was no overlap between the two groups. In the bone invasive meningiomas the nuclear mean volume appeared to be larger inside than outside the bone. No significant difference in nuclear mean volume was found between brain and bone invasive meningiomas. The results demonstrate that invasive meningiomas differ from benign meningiomas by an objective stereological estimation of nuclear mean volume (p<0.00005).

Adolescent

[Progressive multifocal leukoencephalopathy].

Progressive multifocal leucoencephalopathy (PML) is a rarely occurring demyelinating disease of the central nervous system caused by a neurotropic papovavirus named JC virus (JCV). The most frequently affected areas are the cerebral hemispheres, especially the parieto-occipital region, followed by the cerebellum and brain stem. The disease occurs predominantly in individuals with an immunocompromised state and impaired cellular mediated immunity (CMI) due to other underlying illness. More extensive use of irradiation and immunosuppressive therapy in relation to increased transplantational activities as well as treatment of autoimmune diseases and malignancies, in addition to the appearance of the acquired immunodeficiency syndrome (AIDS) as a consequence of infection with the human immunodeficiency virus (HIV), has caused a considerable increase in the occurrence of PML. The course of the disease is still most often rapidly progressive and fatal, but several cases with prolonged survival and even remission have been reported, and various antiviral treatments have been tried. The only drug that until now has shown favourable results is cytosine arabinoside. In HIV-infected PML-patients immunomodulation with AZT/zidovudine may alleviate the course and improve the prognosis in some patients. Suspicion of PML should lead to an extensive immunological investigation before considering of brain biopsy, which is still the only specific test. On the basis of the increased frequency of PML in relation to HIV-infection, it is likely that our knowledge of the pathogenetic aspects will increase, which, hopefully, may lead to an effective therapeutic strategy. A review of this disease, based upon studies of the literature, is presented.

Diagnosis, Differential

Induction of protein droplet (alpha 2 mu-globulin) nephropathy in male rats after short-term dosage with 1,8-cineole and l-limonene.

As part of a series of short-term studies on peppermint oil constituents for their possible induction of the encephalopathy found with peppermint oil, 1,8-cineole and l-limonene were studied. Groups of 10 male Wistar rats were given 0, 500, or 1000 mg 1,8-cineole/kg body wt./day or 0, 800, or 1600 mg l-limonene/kg body wt./day for 28 days. 1,8-Cineole and l-limonene both induced accumulation of protein droplets containing alpha 2 mu-globulin in proximal tubular epithelial cells in male rats. These results suggest that both 1,8-cineole and l-limonene possibly belong to the group of chemicals characterized by their induction of excessive alpha 2 mu-globulin accumulation. Neither of the 2 substances induced encephalopathy.

Alpha-Globulins

Point-mutations affecting the properties of tyrosineD in photosystem II. Characterization by isotopic labeling and spectral simulation.

The reaction center of photosystem II (PSII) contains two redox-active tyrosines, TyrD and TyrZ, which are Tyr160 and Tyr161 of the D2 and D1 proteins, respectively. We have introduced five site-directed mutations in the vicinity of TyrD to analyze the consequences of the mutations on spectral and functional properties of TyrD(ox). Characterization of three mutants, P161A and P161L (Pro161 changed to Ala and Leu, respectively) and Q164L (Gln164 mutated to Leu), is emphasized. Of these three mutants, only P161L is an obligate photoheterotroph; it is capable of oxygen evolution, but is photoinactivated rapidly. The D2 protein of this mutant migrates slower on a SDS-polyacrylamide gel. The EPR spectrum of TyrD(ox) is modified in the three mutants. The EPR spectra of TyrD(ox) in wild type and the mutants were characterized in detail by comparison of EPR spectra of thylakoids from cells grown in the presence and absence of tyrosine that was deuterated in specific positions. The experimentally obtained EPR spectra of wild type, P161A, and Q164L could be simulated satisfactorily using current theoretical models. The angle between one of the hydrogens on the beta-methylene carbon and the 2pz orbital at C1 of the tyrosine ring was found to change slightly but significantly as a function of the mutations (52 degrees in wild type, 50 degrees in P161A, and 48 degrees in Q164L). The overall electronic structure of TyrDox is quite unaffected; only minor redistribution of the unpaired electron spin is observed between the wild type and the mutated systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyanobacteria

Stereological analysis of nuclear volume in recurrent meningiomas.

A stereological estimation of nuclear volume in recurrent and non-recurrent meningiomas was made. The aim was to investigate whether this method could discriminate between these two groups. We found that the mean nuclear volumes in recurrent meningiomas were all larger at debut than in any of the control tumors. The mean nuclear volume of the individual recurrent tumors appeared to change with time, showing a tendency to diminish. A relationship between large nuclear volume at presentation and number of or time interval between recurrences was not found. We conclude that measurement of mean nuclear volume in meningiomas might help identify a group at risk of recurrence.

Adult

Prevalence of food additive intolerance.

1. The existing prevalence estimates of food additive intolerance are being reviewed. 2. In the EEC report the estimated frequency of food additive intolerance is 0.03% to 0.15% based on data from patient groups. 3. The British population study results in a prevalence estimate of 0.026%. The challenged population is 81 children and adults with a history of reproducible clinical symptoms after ingestion of food additives. 4. In the Danish population study a prevalence of 1-2% is found in children age 5-16. In this study a total of 606 children mainly with atopic disease have been challenged. 5. The prevalence estimates vary with a factor 100. As the results vary so do the study populations. 6. If the different study populations are accounted for, a common conclusion can be drawn: Food additive intolerance is found in adults with atopic symptoms from the respiratory tract and skin. The prevalence estimates are questionable but may be less than 0.15%. In adults and children with reproducible, and with more subjective symptoms, such as headache and behavioural/mood change the prevalence is even lower (0.026%). Food additive intolerance is primarily found in atopic children with cutaneous symptoms where the additive is aggravating an existing disease. The prevalence of food additive intolerance in children age 5-16 is 1-2%.

Adolescent

Modified EPR spectra of the tyrosineD radical in photosystem II in site-directed mutants of Synechocystis sp. PCC 6803: identification of side chains in the immediate vicinity of tyrosineD on the D2 protein.

The oxidizing side of photosystem II contains two redox-active tyrosyl side chains, TyrZ and TyrD, and a cluster of Mn atoms involved in water oxidation. The structural environment of these components is unknown, and with computer-assisted modeling we have created a three-dimensional model for the structures around TyrZ and TyrD [Svensson et al. (1990) EMBO J. 9, 2051-2059]. Both tyrosines are proposed to form hydrogen bonds to nearby histidine residues (for Synechocystis 6803, these are His190 on the D1 and His189 on the D2 proteins). We have tested this proposal by electron paramagnetic resonance (EPR) spectroscopy of TyrDox in mutants of the cyanobacterium Synechocystis 6803 carrying site-directed mutations in the D2 protein. In two mutants, where His189 of the D2 protein is changed to either Tyr or Leu, the normal EPR spectrum from TyrDox is replaced by narrow, structureless radical signals with g-values similar to that of TyrDox (g approximately 2.0050). The new radicals copurify with photosystem II, are dark-stable, destabilized by elevated pH, and light-inducible, and originate from radicals formed by oxidation. These properties are similar to those of normal TyrDox, and we assign the new spectra to TyrDox in an altered environment induced by the point mutation in His189. In a third mutant, where Gln164 of the D2 protein was mutated to Leu, we also observed a modified EPR spectrum from TyrDox. This is also consistent with the model in which this residue is found in the immediate vicinity of TyrDox. Thus the results provide experimental evidence supporting essential aspects of the structural model.

Computer Simulation

[The value of serological examination in neuroborreliosis].

Over a period of 18 months, 155 patients with indications for lumbar puncture (LBP) on account of neurologic symptoms were examined for specific antibodies to Borrelia burgdorferi (BB) in the serum and for production of specific antibodies against BB in the cerebro-spinal fluid (CSF). Positive anti-BB-antibody-production in CSF was found in one patient and the clinical manifestations were consistent with the third stage of neuroborreliosis (NB). Three patients with NB as a tentative diagnosis were found negative for anti-BB-antibody-production in the CSF, and a clinical reevaluation excluded NB as a final diagnosis. The study showed a very high predictive value of the test for anti-BB-antibody-production in the CSF both with positive and negative results. The results suggest further that NB is of a low incidence in Denmark and not often misdiagnosed in favour of more well known diseases.

Aged

Carcinogenicity study of the emulsifier TOSOM and the release agent TOS in Wistar rats.

Groups of 60 Wistar rats of each sex were fed diets containing 3, 6 or 12% of the margarine emulsifier TOSOM (thermally oxidized soybean oil interacted with mono- and diglycerides of fatty acids) for 2.5 yr. In addition, three groups of 60 rats of each sex were fed two products of the release agent TOS (thermally oxidized soybean oil) in dietary levels of 1.2% TOS(G) (TOS from Grindsted Product A/S, Denmark) and 0.3 and 1.2% TOS(N) (TOS from Nexus Aps, Denmark), respectively for 2.5 yr. 120 rats of each sex fed a diet containing mono- and diglycerides served as controls. The diets given to all groups were isocaloric. Clinical appearance, food consumption, body weight and weight gain, survival, haematology, and clinical chemistry parameters were examined. Gross and histopathological examinations, including neoplastic and non-neoplastic lesions, were performed on all groups. Time to occurrence of tumours was recorded. No substance-related effect, including carcinogenicity, was found.

Animals

Effects of high-fat diet on incidence of spontaneous tumors in Wistar rats.

In a 2.5-year carcinogenicity study, two groups, both including male and female Wistar rats, were fed two different diets with 4% and 16% fat. In addition to 4% soybean oil, the high-fat diet contained 12% mono- and diglycerides, of which 85% was stearic acid and 13% palmitic acid. There was no difference in food consumption, body weight, weight gain, and longevity between the two groups. A statistically significant increase in the incidence of tumors in the high-fat group was seen in fibroadenoma of the mammae (female, p = 0.05). No statistically significant difference was seen when the incidence of benign mammary tumors (adenomas and fibroadenomas) was combined, just as the overall incidence of mammary tumors (adenomas, fibroadenomas, and adenocarcinomas) was not significantly different between the groups. A statistically significant decrease in the incidence of tumors in the high-fat group was seen in adenoma of the parathyroid gland (male, p = 0.04) and medullary carcinoma of the adrenal gland (male, p = 0.04). Combining the incidence of benign and malignant tumors of the adrenal medulla led to a further increase in the level of significance (p = 0.02). The present study showed that a high-fat diet influenced the tumor incidence in certain organs of rats. However, the overall differences in tumor incidence between rats fed the low- and the high-fat diet are considered marginal. Therefore we were not able to confirm or deny the hypothesis that a high-fat diet promotes the development of cancer. It should be noted that, in our study, fat accounted for about 30% of the total energy in the high-fat diet. This is much below the amount of fat normally found in the western diet but corresponds well to the level recommended for human intake. In addition, the rats fed the high-fat diet did not gain more weight, even though no difference was recorded in food consumption (g/kg body wt) between the groups.

Adenofibroma

Prevalence of atopic disease among Danish school children.

As a result of a 1990 survey by questionnaire, the symptoms of atopy among all 4,952 school children aged 5 to 16 years in the municipal district of Viborg, Denmark, were registered. Random checks, made among children who were recorded as having symptoms, and others who were recorded as having none, accorded well with the information supplied by the parents about symptoms and the clinical diagnosis of a specialist; 10.5% of all school children had rhinitis, 7% had atopic eczema, 3.2% had urticaria and 4.5% had asthma; 1/4 of all those questioned had shown symptoms within the last year, and a further 13% of all the children were reported as having had atopic symptoms that had disappeared more than a year previously. Of the children showing symptoms within the last year before the survey, 2/3 had gone to a doctor. Of the children with present symptoms, largely asthma, 1/4 had been referred to a hospital allergy clinic. For 1/3 of the children with present symptoms, these had led to no contact with a doctor. Of the cases with present symptoms, 6.5% had had contact with natural healers or chiropractors. Rhinitis and asthma were most frequent among boys, while atopic eczema was most frequent among girls. For both sexes, the frequency of rhinitis increased during their years at school, while the frequency of skin symptoms fell.

Adolescent

Prevalence of intolerance to food additives among Danish school children.

The prevalence of intolerance to food additives was assessed in a group of unselected school children aged 5-16 years. A study group of 271 children was selected on the basis of the results of a questionnaire on atopic disease answered by 4,274 (86%) school children in the municipality of Viborg, Denmark. The children in the study group followed an elimination diet for two weeks before they were challenged with a mixture of food preservatives, colourings and flavours. The challenge was open and the additives were prepared as a fizzy lemonade. If the open challenge was positive, a double-blind placebo controlled challenge with gelatine capsules was performed. The study included 281 children, 10 were excluded, and the remaining 271 children were given the open challenge (98 healthy controls and 173 with atopic symptoms). The open challenge was negative in all 98 healthy control children who had not reported any atopic symptoms. Of the 173 children reporting present or previous atopic disease 17 had a positive open challenge. Of these 17 children 1 experienced gastrointestinal symptoms, 13 reacted with aggravation of atopic eczema, and 3 with urticaria. Twelve of these 17 children went through the double-blind challenge which was positive in 6 cases. Five of these 6 children had positive reactions to synthetic colourings and 1 to citric acid. No serious reactions were seen. Based upon calculations of the results from this study and an earlier multi-center study in children referred to hospital clinics, the prevalence of intolerance to food additives in school children is estimated to be 1-2%.

Adolescent

Stereological estimation of nuclear volume in benign and atypical meningiomas.

A stereological estimation of nuclear volume in benign and atypical meningiomas was made. The aim was to investigate whether this method could discriminate between these two meningeal neoplasms. The difference was significant and it was moreover seen that there was no overlap between the two groups. The results demonstrate that atypical meningiomas can be distinguished from benign meningiomas by an objective stereological estimation of nuclear volume.

Adolescent

Subchronic toxicity study of peppermint oil in rats.

Peppermint oil was given p.o. to four groups of 28 rats at dosage levels of 0, 10, 40, and 100 mg/kg body wt. per day for 90 days. At the highest dose histopathological changes consisting of cyst-like spaces scattered in the white matter of cerebellum were seen. No other signs of encephalopathy were observed. Nephropathy was seen in the male rats in the highest dose group. A no-observed-adverse-effect level of 40 mg/kg body wt. per day was determined.

Administration, Oral