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Biomedical subjects

I Petersen

Publications and source records attributed to I Petersen.

At least 19 recordsLinked to original sources

Evidence for a tumor suppressor gene on chromosome 19q associated with human astrocytomas, oligodendrogliomas, and mixed gliomas.

Previous studies have shown frequent allelic losses of chromosomes 9p, 10, 17p, and 22q in glial tumors. Other researchers have briefly reported that glial tumors may also show allelic losses of chromosome 19, suggesting a putative tumor suppressor gene locus on this chromosome (D. T. Ransom et al., Proc. Am. Assoc. Cancer Res., 32:302, 1991). To evaluate whether loss of chromosome 19 alleles is common in glial tumors of different types and grades, we performed Southern blot restriction fragment length polymorphism analysis for multiple chromosome 19 loci in 122 gliomas from 116 patients. Twenty-nine tumors had loss of constitutional heterozygosity of 19q, and four tumors had partial deletions of 19q. Allelic losses on 19q were restricted to grade III anaplastic astrocytomas (4/9) and grade IV glioblastomas (11/46), grade II oligodendrogliomas (2/5) and grade III anaplastic oligodendrogliomas (2/2), and grade II (5/8) and grade III (5/7) mixed oligoastrocytomas. These data demonstrate genetic similarities between astrocytomas, oligodendrogliomas, and mixed glial tumors and indicate the presence of a glial tumor suppressor gene on chromosome 19q.

Astrocytoma

p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma.

Loss of genetic material on the short arm of chromosome 17 is observed in approximately 40% of human astrocytomas (WHO grades II and III) and in approximately 30% of cases of glioblastoma multiforme (WHO grade IV). Previous studies of glioblastoma multiforme have shown that the p53 gene, located on the short arm of chromosome 17, is frequently mutated in these glioblastomas. To explore whether lower-grade astrocytomas are also associated with corresponding mutations of the p53 gene, we have investigated a series of 22 human astrocytomas of WHO grades II and III both for loss of heterozygosity on chromosome 17p and for p53 mutations. Mutations in the conserved regions of the p53 gene were identified by single strand conformation polymorphism analysis of exons 5, 6, 7, and 8 and were verified by direct DNA sequencing of the polymerase chain reaction products. p53 mutations were observed in 3 of 8 grade II astrocytomas and 4 of 14 grade II astrocytomas. In all 22 tumors, allelic loss of the short arm of chromosome 17 was investigated by restriction fragment length polymorphism analysis. One-half of the grade II astrocytomas (4 of 8) and grade III astrocytomas (7 of 14) exhibited allelic loss on chromosome 17p. Mutations in the p53 gene were exclusively observed in tumors with allelic loss on 17p. Our results show that p53 mutations are not restricted to glioblastoma multiforme and may be important in the tumorigenesis of lower-grade astrocytomas and that p53 mutations in lower-grade astrocytomas are associated with loss of chromosome 17p. These findings are consistent with a recessive mechanism of action of p53 in WHO grade II and III astrocytoma tumorigenesis.

Alleles

Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme.

Although the loss of tumor suppressor genes and the activation of oncogenes have been established as two of the fundamental mechanisms of tumorigenesis in human cancer, little is known about the possible interactions between these two mechanisms. Loss of genetic material on chromosome 10 and amplification of the epidermal growth factor receptor (EGFR) gene are the most frequently reported genetic abnormalities in glioblastoma multiforme. In order to examine a possible correlation between these two genetic aberrations, the authors studied 106 gliomas (58 glioblastomas, 14 anaplastic astrocytomas, five astrocytomas, nine pilocytic astrocytomas, seven mixed gliomas, six oligodendrogliomas, two ependymomas, one subependymoma, one subependymal giant-cell astrocytoma, and three gangliogliomas) with Southern blot analysis for loss of heterozygosity on both arms of chromosome 10 and for amplification of the EGFR gene. Both the loss of genetic material on chromosome 10 and EGFR gene amplification were restricted to the glioblastomas. Of the 58 glioblastoma patients, 72% showed loss of chromosome 10 and 38% showed EGFR gene amplification. The remaining 28% had neither loss of chromosome 10 nor EGFR gene amplification. Without exception, the glioblastomas that exhibited EGFR gene amplification had also lost genetic material on chromosome 10 (p less than 0.001). This invariable association suggests a relationship between the two genetic events. Moreover, the presence of 15 cases of glioblastoma with loss of chromosome 10 but without EGFR gene amplification may further imply that the loss of a tumor suppressor gene (or genes) on chromosome 10 precedes EGFR gene amplification in glioblastoma tumorigenesis.

Biomarkers, Tumor

[Occupational asthma caused by scented gravel in cat litter boxes].

Perfumes are now added to articles in everyday use to an increasing extent. One example of this is addition of perfume to gravel in cat toilets. It is recognized that perfumes may cause toxic and allergic skin reactions while perfume as the cause of asthma is not so well recognized. In the case described here, exposure to industrial perfume resulted in asthma on account of irritation.

Acrolein

The effect of prophylaxis with chloroquine and proguanil on delayed-type hypersensitivity and antibody production following vaccination with diphtheria, tetanus, polio, and pneumococcal vaccines.

In vitro studies have shown that anti-malarial drugs suppress immunity. In this study, the effects of chloroquine and proguanil (Paludrine) on the cellular and humoral immune system were measured by two in vivo methods: 1) cell-mediated immunity (delayed cutaneous hypersensitivity) i.e., skin tests with seven delayed-type common antigens (Multitest) and 2) humoral immunity by measurement of specific antibody response to vaccination. Sixty healthy young individuals were randomized into four groups and given 1) no treatment (controls), 2) chloroquine diphosphate (500 mg/week), 3) chloroquine diphosphate (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined on days 0, 28, and 42. The skin tests induced a significant increase in skin reactive areas from day 0 to day 28 in all groups. Furthermore, the skin test induced an increase in the level of specific IgG for diphtheria and tetanus, but had no effect on antibodies to antigens not included in the skin test. The results showed that there were no significant differences among the four groups regarding skin test areas and increases in antibody titers following vaccination. Therefore, it is concluded that in healthy persons, six weeks intake of chloroquine, even in double doses, or proguanil in chemoprophylactic dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens.

Adult

[Abscess of the omental bursa (lesser sac)].

Subphrenic omental bursa abscess is frequently overlooked and the overall mortality is 70%. Early diagnosis and drainage improve the prognosis considerably. In cases with abdominal symptoms followed by pyrexia, possibly with signs of sepsis, and pleural effusion but with no or only slight findings on objective clinical examination, subphrenic abscess should be suspected and a scanning of the abdomen should be performed.

Aged

EEG changes measured by spectrum analysis under hyperbaric conditions.

The EEG activity was followed during simulated diving to 20 m depth. Altogether 49 EEG records of 5 min length were taken in 5 divers breathing compressed air in a close system. No significant changes of the EEG could be found during either compression or decompression if only conventional indicators, such as the amplitude of theta activity, were tested. However, a complex "normality ratio," based on multivariate analysis of a normal material, was capable of showing significant impairment of the brain activity during the decompression. The indicator has been designed to reflect the abnormality level rather than the short-lasting EEG changes, the latter being mostly dependent on the alertness fluctuations. The EEG changes associated with alertness fluctuations were assessed separately by means of a specific "alertness indicator" and a prominent alertness increase was found during both compression and decompression phases of the diving experiment.

Adult

[Knowledge of, attitudes toward and participation in the new vaccinations against measles, mumps and rubella during the first 2 years].

The new vaccinations for measles, mumps and rubella (MMR) for children and the new vaccination for rubella for adult women were introduced in Denmark on 1.1.1987. An account is presented of 1) knowledge about and attitudes to the new vaccinations, investigated three months after commencement of the programme as assessed by means of a marketing investigation and 2) participation in vaccination during the first two years after introduction of the vaccination programme assessed by registration of services in the Danish National Health Service. The calculated participation in the MMR vaccination programme at the age of 15 months was found to be 72% and 31% at the age of 12 years. The calculated participation in the rubella vaccination programme at the age of 18 years was 13% in 1988 and even less for the remaining women. 95% of persons with children aged 0-12 years in the household who were questioned had heard about the new vaccinations for children and more than 50% had detailed knowledge about MMR vaccination. More than 10% were against MMR vaccination mainly because they considered that it was better for children to have these infections naturally. 90% of the women questioned knew why adult women were offered vaccination for rubella, although the percentage was less in the younger women. Compared with the goals established, participation in the MMR vaccination programme is insufficient. Participation in the rubella vaccination programme for adult women is entirely inadequate. The reasons for defective participation and proposed improvements are discussed. It is important that general practitioners and health nurses instruct parents about these possibilities.

Attitude to Health

[Dietary treatment of patients with lymphangiomyoma].

A case of lymphangiomyoma, manifested by chylous ascites, in a 32 year-old woman is presented. Treatment with dietary fat restriction supplemented with medium chain triglycerides was successful, and the patient has remained free from chylous effusions for nearly two years.

Adult

[Immunomodulation by cryosurgery in malignant melanoma].

Cryosurgery is a well-known, established method for the local destruction of tumor tissue by freezing. The assumption that, in addition to a physical and blood vascular phase, an immunological phase exists, has been discussed by many authors and tested using animal models. These results can only be transferred to humans in a limited sense. During the last year, we initiated a randomized study "Cryosurgery versus Conventional Surgery", whereby the peripheral blood and the normal skin from the areas surrounding the resection were compared. We were able to demonstrate in the peripheral blood of 8 cryosurgery patients a postoperative increase in the total and helper T-cells, HLA-DR-positive cells, and the ratio helper/suppressor T-cells in comparison to preoperative values. In the 8 patients treated with conventional surgery, these parameters decreased slightly or remained the same. The differences were highly significant (p = 0.001) to significant (p = 0.01). The results from the first 16 are patients studied presented and discussed here.

Adult

EEG changes under hyperbaric conditions: spectral analysis during simulated diving.

Continuing investigations of the influences of the hyperbaric pressure upon EEG record in divers during simulated diving. The hyperbaric ecological system exerts influences on brain bioelectric activity manifesting itself by changes of alpha frequency and appearance of slow waves. The changes in the brain activity are mostly observable at the changes in chamber pressure values. The changes in EEG recordings are smallest at constant pressures. EEG examination can be used as a measure of the safety of newly developed decompression schedules.

Adult

Prevalence of IgG-antibodies to mumps and measles virus in non-vaccinated children.

The prevalence of mumps and measles IgG antibodies in a randomly selected population of children was determined by an enzyme-linked immunosorbent assay (ELISA) before routine measles-mumps-rubella (MMR) vaccination was introduced in Denmark. Testing of sera from about 2,520 Danish children between one and 17 years of age showed that mumps antibodies were acquired at an early age. The peak acquisition rate was between the ages of four and five; before the age of 15, 90% of children had antibodies to mumps. Immunity to measles occurred at an even earlier age; more than 50% of four-year-old and nearly all (98%) nine-year-old children had IgG antibodies to measles virus. The study showed that about 10% of the young adult Danish population was still susceptible to mumps infection whereas only about 1% of individuals at age 17 had not acquired immunity to measles virus.

Adolescent

Intratypic differentiation of poliovirus strains by enzyme-linked immunosorbent assay (ELISA): poliovirus type 2 and poliovirus type 3.

A double-antibody sandwich ELISA was developed for the detection of antigenic differences between wild and vaccine-derived strains of poliovirus type 2 and poliovirus type 3. Antibodies were prepared in rabbits by immunization with purified antigens of vaccine strains (type 2: Sabin P712, and type 3: Sabin Leon) and wild type strains (type 2: MEF, and type 3: Pool 30). Immunoblotting analysis of all antisera demonstrated that the IgG antibodies raised in rabbits have specificity towards the main structural proteins (Vp1, Vp2 and Vp3) of poliovirus. IgG fractions were purified from antisera by affinity chromatography, on a protein A-activated Sepharose 4B column. Purified IgG antibodies were used for coating of microtest plates (catching antibodies). The same reagents labelled with horseradish peroxidase were used as conjugates, after cross-adsorption with antigens of the same type heterologous virus strains (strain-specific conjugates). 29 poliovirus type 2 strains and 73 poliovirus type 3 strains isolated from clinical samples, were differentiated intratypically, as vaccine-derived or wild types, no intermediate strains were found and all samples tested fell in two distinct (vaccine/wild) categories. As little as 40 ng of poliovirus antigens was detected in stool samples from healthy children or from polio patients cultivated in monkey kidney tissue cultures. Preparation of strain specific conjugates did not require large amounts of poliovirus antigens. The developed ELISA, which is economic and capable of (1) detection of low amounts of poliovirus antigens in cultivated clinical samples, and (2) intratypic differentiation of poliovirus antigens as either vaccine-derived or wild type, is therefore well suited for large scale screening of poliovirus isolates.

Antibodies, Viral

EEG changes measured by spectrum analysis under hyperbaric conditions.

The subject of experimental, saturated dividing to 20 m depth was alertness level measured by means of spectral analysis of EEG records. Air was served as breathing mixture compressed to a given depth in closed circulating system. Altogether 49 EEG records made during compression, plateau and decompression, were analysed. Two methods of analysis were applied. "Normality ratio" combined the information from 20 different EEG values and "EEG alertness indicator" showed in three cases pathological slowing and fluctuations of the alertness. According to index of alertness, the most prominent changes were seen during the compression and decompression phase. During the plateau phase sleepiness was recorded. The applied method could provide information when slowing is due to metabolic impairment of brain activity from that of sleepiness.

Adult

Circadian and diurnal variation of circulating immune complexes, complement-mediated solubilization, and the complement split product C3d in rheumatoid arthritis.

Nine patients with active classical rheumatoid arthritis (ARA criteria) were studied with reference to circadian variation of immunological and clinical parameters. Complement-mediated solubilization (CMS) of immune complexes (IC) and the level of circulating IC were found to be inversely related with low CMS and increased IC levels in the morning, and vice versa in the afternoon. Bed rest and exercise did not influence these fluctuations. The C3d concentration in plasma was increased but showed no diurnal or circadian periodic fluctuations when the levels were corrected for fluctuations in plasma albumin concentration. Clinical assessment by means of pain score exhibited marked variations, with high scores in the morning, and lower in the daytime, whereas measurements of Ritchie's joint index showed no consistent pattern. The circadian variations in CMS, serum IC and clinical parameters indicate the need to collect blood specimens and perform clinical examinations of patients at a fixed time of day.

Adult