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Biomedical subjects

F Vogel

Publications and source records attributed to F Vogel.

At least 181 records · Page 10Linked to original sources

The delivery of genetic counseling services in Europe.

Organizational forms and the current status of genetic counseling within the health care system of 15 European countries were evaluated by questionnaire and at a symposium, with individuals present from Austria, Belgium, Czechoslovakia, Denmark, the Federal Republic of Germany, the German Democratic Republic, Finland, France, Hungary, Italy, the Netherlands, Norway, Switzerland, the United Kingdom, and the Soviet Union. In spite of wide differences between these countries, certain similarities with respect to the delivery of genetic counseling services could be observed: (i) most genetic counseling is done within university institutions or closely linked to it, (ii) governmental support of genetic counseling is developing slowly, and genetic counseling is usually not yet fully integrated into the health care system; (iii) there is lack of qualified personnel; (iv) no guide lines for formal education have been developed, but a postgraduate training period of no less than four years is considered a minimum; (v) without appropriate support, genetic counseling is a burden for research in human genetics; yet, a strict separation of genetic counseling and research activities is not recommended; (vi) on the average, a team providing genetic counseling for about 1-2 million people should consist of 3--4 physicians, 5-10 technicians, 2-3 secretaries, and other supportive personnel.

Delivery of Health Care↗

EEG differences in neurotic as compared with normal twin pairs.

The resting EEGs of 17 twin pairs originally traced through one neurotic co-twin (10 monozygotic and 7 dizygotic pairs aged between 18 and 63 years) have been described and compared with the neuroticism scores (Schepank, 1974) of these twins. EEG comparison according to the customary visual criteria failed to show any consistent EEG differences between monozygotic co-twins, whereas dizygotic pairs often showed EEG discordance. Computerized time-domain (interval-amplitude) analysis failed to show a higher degree of EEG discordance between neurotic MZ co-twins than between co-twins in 25 adult nonneurotic male MZ pairs (age range 18--33; mean age 22.9 years). There were no significant correlations between EEG differences and differences in the neuroticism score among ten MZ pairs traced through a neurotic co-twin. It is concluded that the individual and genetically determined EEG pattern is manifest even in the face of the long-lasting psychological alterations observed in neurotics.

Adolescent↗

Isolation of a SV40-like Papovavirus from a human glioblastoma.

A human glioblastoma multiforme (M27) tested in early cell cultures by indirect immunofluorescence staining showed SV40-related tumor (T)-antigen, 95% of the cells being positive. SV40-related viral capsid (V)-antigen was absent in all cells tested. Experiments to rescue this virus were performed by fusing M27 cells with CV-I monkey cells, which were permissive for SV40, using polyethylene glycol (PEG) as fusion factor. We succeeded in isolating virus particles SV40-GBM which electron microscopy showed to correspond in size and morphology to papovaviruses. Serological tests (hemagglutination, neutralization, fluorescent antibody) revealed that the virus is indistinguishable from SV40. Despite this apparent antigenic identity SV40-GBM differs slightly from SV40 wild type. This virus can propagate and produce CPE in both CV-I cells and primary fetal human kidney cells. Furthermore digestion of SV40-GBM DNA with the HindII/III restriction endonucleases revealed minor differences compared with the SV40 DNA. Therefore the virus SV40-GBM obtained from glioblastoma cells seems to be closely related to the SV40-PML viruses described earlier.

Antigens, Viral↗

Genetics of retinoblastoma.

The genetic basis of retinoblastoma is reviewed and the following conclusions are drawn: 1) The mode of inheritance of the hereditary variety of retinoblastoma (R) is autosomal dominant with about 90% penetrance. 2) About 68% of inherited cases are bilateral, and about 32%, unilateral. There is an intrafamilial correlation between penetrance as measured by segregation ratio and expressivity as measured by the fraction of bilaterally affected patients. 3) The vast majority of all R patients are sporadic cases, i.e., they are the only affected members of otherwise unaffected families. The porportion of bilateral cases is much lower among sporadic than among hereditary cases. 4) All bilaterally affected patients with sporadic R and patients with unilateral sporadic R with more than one primary tumor have to be regarded as germ cell mutants; they will transmit the gene to 50% of their offspring. Only 10%-12% of unilateral sporadic cases are germ cell mutants; 88%-90% are nonhereditary; in these cases the tumor is probably caused by a somatic mutation. 5) In a minority of cases, deletion of the chromosome segment 13q14(=intersitital deletion of the long arm of chromosome 13) has been observed. In addition to R, the patients show a variable degree of general or mental retardation; often there are few external indications of a chromosome aberration. Other chromosome studies suggest anomalies of chromosome 13 in tumor tissue even in cases not showing an anomaly of this chromosome in blood cultures, and possibly a slightly increased chromosome instability. 6) Patients with bilateral, and possibly in general with hereditary, R run an increased risk of becoming affected with other tumor diseases, such as osseous sarcomas, in later life. 7) Knudson's hypothesis of two mutational steps leading to both the hereditary and the nonhereditary variants of R is discussed critically, and the alternative possibility is suggested that in the nonhereditary variant a single mutational step--possibly a small chromosome aberration--could be enough to produce a tumor. 8) Evidence indicating a possible viral origin of R is cited, and animal experiments are mentioned in which R-like tumors have successfully been produced by local DNA virus inoculation. 9) As a consequence of improved survival and reproduction of R patients, an increased in the incidence of R and in the proportion of bilateral cases among all R patients must be anticipated. 10) Detailed rules for genetic counseling in families affected by R are given.

Chromosome Deletion↗

'Our load of mutation': reappraisal of an old problem.

H. J. Muller, in a paper in 1950 entitled 'Our load of mutation', predicted the genetic decay of the human species due to increasing mutation pressure combined with relaxation of natural selection. In the meantime, much information on spontaneous and induced mutations in humans has been accumulated, and a reappraisal of Muller's conclusions gives a much less gloomy overall picture. However, a certain increase of malformation and disease can be predicted as a result of ionizing radiation and chemical mutagens. On the other hand, genetic counselling and antenatal diagnosis of genetic anomalies may help to keep the genetic risks within tolerable limits. Research on the biological conditions for the untoward effects of mutagenic chemicals considered necessary for the wellbeing of humans may also help to reduce genetic risks. The extent and kind of the risks as well as possibilities for prevention are discussed with a few examples.

Animals↗

The electroencephalogram (EEG) as a research tool in human behavior genetics: psychological examinations in healthy males with various inherited EEG variants. I. Rationale of the study. Material. Methods. Heritability of test parameters.

In the first section of this paper, various research designs in human behavior genetics are compared. In this context, the commonly used concept of biometric genetics is critically evaluated from the point of view of science theory. It is contrasted with the Mendelian gene concept, which, in principle, leads to a much deeper theoretical understanding by offering clues for basic mechanisms. To explore this advantage fully, a research strategy is needed that first looks for genetic variability in a physiological parameter of possible importance for human behavior and then tries to explore the influence of this parameter on the function of the human brain and on behavior. If possible, this genetic parameter should be selected in a way that inferences as to the mechanism of its influence on behavior become feasible. Such genetic variability is provided by the hereditary variants of the normal EEG discovered by earlier work (cf. Vogel, 1970). In the following section, a research program on 298 adult healthy males, most of them soldiers, with various inherited EEG variants is described. Apart from controls with inconspicuous EEGs, this material comprises probands with the following EEG variants: low-voltage (N); low-voltage borderline (NG); monotonous alpha-waves (R); occipital fast alpha-variants (BO); fronto-precentral beta-groups (BG), and diffuse beta-waves (BD). In addition to an EEG examination, the probands were examined with various test methods measuring intelligence (IST; LPS; Raven); working speed and concentration (d-2; KLT); personal attitudes (MMPI; 16PF; RKS); and sensory and motor abilities (flicker fusion; tachistoscopy; reaction time to optic, acoustic and combined stimuli; two-hand dexterity; pursuit rotor; tapping). In a supplementary twin study on 52 male adult twin pairs (26 MZ, 26 DZ), heritabilities were determined for the test scores included in the main study. For most test scores, heritabilities are relatively low; the data are compared with those from the literature. We conclude that the test methods utilized in the main study (on EEG variants) are expected to demonstrate at the most a small to moderate correlation of the EEGs with psychological phenotypes as defined by test examinations, even if a major part of the genetic variability underlying these phenotypes would be due to differences in brain physiology that could be revealed by EEG variation.

Adult↗

The electroencephalogram (EEG) as a research tool in human behavior genetics: psychological examinations in healthy males with various inherited EEG variants. II. Results.

The results of psychological examinations on 298 adult male probands with various inherited EEG variants are described. They may be summarized as follows: 1) The low-voltage (N) group scored high in intelligence tests, especially in spatial orientation. Personality scores revealed this group as 'normal', extravert, group-dependent, and not very energetic. 2) The borderline low-voltage (NG) group showed slight weakness in abstract thinking, short-time memory, and motor skills and a relatively strong tendency to have 'neurotic' complaints. Reaction time and motor skills were poor. 3) The occipital fast alpha-variants (BO) group performed very well in tests of abstract thinking and motor skills. 4) The monotonous alpha (R) group showed average performance in most intelligence scores but above-average in short-time memory and in precision under stress conditions. Personality scores indicated high spontaneous activity and toughmindedness. 5) The BG (fronto-precentral beta-group) category showed very low MMPI scores, indicating little neurotic tendency. Intelligence could be above average. 6) The diffuse beta (BD) group scored low in intelligence tests, especially in spatial orientation, and had a high error rate in tests measuring concentration and precision. Most differences were relatively small; the whole range of test scores could be found in all EEG groups.

Adult↗

The electroencephalogram (EEG) as a research tool in human behavior genetics: psychological examinations in healthy males with various inherited EEG variants. III. Interpretation of the results.

Interpretation of the results from psychological examinations of 298 probands with inherited EEG variants requires (1) critical evaluation of previous literature on psychological EEG correlates, (2) knowledge of the main concepts and experimental approaches for elucidating the basic mechanisms of EEG rhythms, (3) discussion of previous attempts to link psychological variation in human populations with corresponding variation in brain function, and (4) interpretation of results from considerations at these three levels with the data from our own study. At the first level (previous psychological studies), comparison with Schmettau's study proved to be especially revealing: Her conclusions about personality correlates with high alpha-index and with "flat" EEGs were very similar to ours with the monotonous alpha- (R) and low-voltage (N) EEGs, respectively. Her EEG type with high beta-index overlaps with our beta-diffuse (BD) type; a tendency to psychasthenia and low resistance to stress is less obvious in our group, but is expressed indirectly by reduced speed and accuracy in tests requiring attentiveness and persistence. The correlation between alpha-frequency and intelligence found in other studies was confirmed by the especially high intelligence scores of our group with occipital fast alpha-variants (BO). At the second and third levels of the discussion (EEG mechanisms; neurophysiological theories), the cooperation of cerebral cortex (EEG battery), thalamus (pacemaker), and ARAS (tonic arousal) is discussed, and the personality typologies of Eysenck and Claridge are mentioned. From this and other evidence, the following hypotheses are discussed: 1) The personality profiles of the R group are influenced by high activity and efficiency of the thalamic alpha-pacemaker(s), which leads to a high degree of modulation, selection, and amplification of afferent stimuli. 2) In the countertype of this EEG variant, the N EEG, a low modulation and amplification by the thalamic alpha-pacemaker is assumed. This leads to relatively low intensity of feeling and to low spontaneous activity, but to faster information processing. Combined with an increased level of tonic arousal in the ARAS, it may cause certain 'neurotic' complaints (our low-voltage borderline (NG) group). 3) The EEG with diffuse beta-waves (BD) is caused by a high level of tonic arousal in the ARAS, which tends to distrub the thalamocortical circuit. This leads to reduced stress resistance and to impairment of intellectual functions, especially space perception. Due to limited evidence, the next two hypotheses are advanced only tentatively: 4) alpha-rhythm with very high frequency 16--19 c/s) leads to improvement of information processing and, hence, to high intellectual performance and motor dexterity. 5) Probands with frontoprecentral beta-groups (BG) show no psychological signs of increased tonic arousal; therefore, these beta-groups are caused not by increased tonic arousal of the ARAS, but by a genetic variant of a thalamic subsystem.

Adult↗

[The sex differences in the normal resting EEG of young adults (author's transl)].

In order to investigate the sex differences in the normal resting EEG, 488 healthy students (290 males and 198 females) were examined using a computer program for time domain analysis. Women show on the average more beta-waves, less alpha-waves, higher beta-amplitudes, higher average frequencies, and other signs of a higher average level of arousal. However, the total variability of all examined EEG parameters is present in both sexes. There are some hints that laterality of EEG in precentral leads could be more pronounced in males than in females.

Adult↗

[The resting EEG in relation to neurovegetative status and spatial perception in normal young adults (author's transl)].

The relationship between measurable EEG-parameters and an index of irritability of the autonomous system was examined. The data consisted of the resting EEGs of 488 adult students, 290 male and 198 female. Time-domain analysis was used for computerized evaluation. Females showed a significantly higher average autonomous irritability index than males. Moreover, positive correlations were found between this index and the number of occipital beta-waves; the correlation with number of alpha-waves was negative. Amplitudes tend to be correlated negatively with the index; most correlations are stronger in females than in males. In 73 proband, 35 male and 43 female,--carriers of various inherited EEG-variants and age- and sex-matched controls,--spatial perception was examined by the WU-subtest of the "Intelligenzstrukturtest" (Amthauer). Males showed significantly higher average test values than females, and in women, a significant relationship between occipital EEG and space perception was found. There appears to be a positive association between space perception and amplitude of occipital alpha- and beta-waves. On the other hand, however, carriers of the typical low-voltage EEG show very good space perception despite their low amplitudes of occipital alpha- and beta-waves.

Adult↗

Cyclical changes in the carbohydrate composition of dog endometrium.

In the first part of prooestrus glucuronic acid could not be detected, but small amounts of glucose, fructose, inositol and sorbitol were found. When progesterone was formed a small amount of glucuronic acid could be observed and sorbitol had disappeared. During the first weeks of metoestrus the amounts of fructose and glucose increased gradually, but those of glucuronic acid remained low. When more progesterone and pregnanedione were found in the endometrium the amounts of glucuronic acid began to increase and the highest values were reached in anoestrus. During the last days of anoestrus a sudden change in the carbohydrate composition of the endometrium occurred: glucuronic acid and fructose could no longer be detected, the amounts of glucose and inositol decreased and sorbitol was found. These findings show that next to the cyclical ovarian events, there is a cyclical change in te carbohydrate composition of dog endometrium.

Animals↗

The HLA system and leprosy in Thailand.

To investigate immunogenetics of leprosy, 205 leprosy patients (26 with tuberculoid, 57 with borderline-tuberculoid, 21 with borderline, 31 with borderline-lepromatous, and 70 with lepromatous leprosy) have been typed for HLA antigens, and compared with 183 healthy controls from the same region (Northern Thailand). There was no significant difference between the overall group of leprosy patients or the three borderline classes and the controls. The two polar forms, tuberculoid and lepromatous leprosy, however, showed significant associations: HLA-A2 is decreased and HLA-Bw17 is increased in tuberculoid leprosy; HLA-B7 is increased in lepromatous leprosy. When both polar forms are compared with each other, HLA-A2 is significantly higher, HLA-Bw40 lower in patients with lepromatous than in those with tuberculoid leprosy. The results are discussed with respect to the different immune responsiveness in the two polar forms of leprosy.

Female↗

A twin study on three enzymes (DBH, COMT, MAO) of catecholamine metabolism. Correlations with MMPI.

Ina a sample of 48 healthy adult male twin pairs (24 MZ, 24 DZ) the activities of DBH (serum), COMT (red blood cells), and MAO (platelets) were determined. The twins had undergone a detailed psychodiagnostic test procedure before. Interindividual variability of enzyme activities is almost exclusively genetically determined. No correlation between enzyme activities within one subject is found. Correlations between enzyme activities and MMPI test scores were calculated. As in a comparable investigation by Murphy et al. (1977), negative correlations between MAO activity and MMPI scores prevailed.

Adult↗

[Distribution of the HL-A antigens in patients with pigeon breeder's lung].

HLA B8 was found in 29% of patients suffering from pigeon fancier's lung, as compared with a normal frequency of HLA B8 of 17%. In patients suffering from the acute form of the disease HLA B8 was found in 42%. HLA B13 and HLA BW17 could not be demonstrated in any patient with pigeon fancier's lung.

Adolescent↗

HLA antigen, gene, and haplotype frequencies in Thailand.

Antigen, gene, and haplotype frequencies as well as phenotype distribution of the HLA system were studied in a series of 213 individuals in northern Thailand. The series consisted of 160 northern Thais, 23 Thai individuals from various other regions of Thailand, and 25 persons of Chinese origin. Most frequently found were the alleles HLA-A11 and HLA-Bw40 and the haplotype HLA-A2,B-. Phenotype distribution followed a Hardy-Weinberg expectation. Significant differences were found especially between our results for the alleles of locus B and the results of a series from Bangkok reported by Chiewsilp and Chanarat (1976).

Adolescent↗

Genetic aspects of induced mutation.

Genetic variability within the human species as well as within animal species used for mutagenicity testing may lead to misclassification of potentially mutagenic agents. Such genetic variability should be considered on three levels: uptake of the agent, its metabolism, and its action on the DNA. Testing of a possibly mutagenic agent in vitro on cells of the individuals to whom the agent is to be administered would help to avoid part of the hazard.

DNA Repair↗