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  • 1
    ISSN: 1129-2377
    Schlagwort(e): Key words Cluster headache ; Familial occurrence ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A Danish genetic study showed increased risk of cluster headache (CH) among relatives of CH patients. We studied the families of 191 CH patients (118 males, 73 females; mean age 45.9 years) attending the Milan Headache Center. Information on 3589 relatives was collected by direct interview of the probands (n = 118) or by mailed questionnaire (n = 73). The diagnostic criteria of the IHS were used. A positive family history was found in 19% (37 of 191) of the families. A total of 32 first-degree (32 of 1036, 3.1%) and 15 second-degree (15 of 2553, 0.6%) relatives were affected. The relative risk of CH was 26.89 (95% CI, 17.57–36.21) in the first-degree relatives and 4.35 (95% CI, 2.13–5.21) in second-degree relatives. This study shows increased familial risk of cluster headache in an Italian population and confirms that cluster headache is, in some families, and inherited disorder.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    The journal of headache and pain 1 (2000), S. S135 
    ISSN: 1129-2377
    Schlagwort(e): Key words Migraine ; Headache ; Genetics ; Serotonin ; Dopamine ; Mitochondria
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Migraine carries a significant hereditary determination. Familial hemiplegic migraine (FHM) has been recently linked to mutations in the CACNA1A gene on chromosome 19. CACNA1A codes for a subunit of a neural calcium channel. Other linkage loci on chromosome 1q21-23 and 1q31 have been reported. Several linkage and association studies have been performed to determine the role of the CACNA1A gene, and of other candidate genes implicated in the metabolism of serotonin and dopamine, in the more common types of migraine. Co-morbidity of migraine with vascular events has been analysed versus genetic prothrombotic factors and mitochondrial DNA, and genes involved in the inflammatory cascade have been explored. Though no definite conclusions have emerged from these studies as yet, molecular genetics of migraine can be expected to unravel the complex aetiologies of these fascinating diseases.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    The journal of headache and pain 1 (2000), S. S147 
    ISSN: 1129-2377
    Schlagwort(e): Key words Dopamine ; Migraine ; Genetics ; DRD2
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Molecular genetics offers a novel approach to the understanding and management of migraine since the disorder is known to have a strong genetic component. In recent studies, polymorphisms in the genes for dopamine receptors have been evaluated. Both positive and negative association studies have been reported. In particular, these data suggest that activation of the DRD2 receptor plays a modifying role in the pathophysiology of migraine. As a result, existing data provide a molecular rationale for the documented efficacy of dopamine D2 receptor antagonists in the treatment of migraine. Therefore, at the present time, molecular genetic data provide support for the hypothesis that susceptibility to migraine may be modified, in part, by variations in dopamine DRD2 receptor function.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    The journal of headache and pain 1 (2000), S. S157 
    ISSN: 1129-2377
    Schlagwort(e): Key words Migraine ; Chronic tension type headache ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Pathophysiological studies have dominated migraine research for several years. However, these studies are difficult to interpret because it is difficult to decide whether the observed phenomena are primary or secondary to the migraine attack. For that reason it is important that future migraine research focus on studies that concern migrain etiology. Migraine is a paroxysmal disorder. It is most likely and ion-channel disorder like familial hemiplegic migraine. The present paper focuses on genetic factors in migraine and chronic tension-type headache.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1437-2320
    Schlagwort(e): Key words Von Hippel-Lindau disease ; Hemangioblastoma ; Endolymphatic sac tumor ; Angiogenesis ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Von Hippel-Lindau disease (VHL) is a hereditary cancer syndrome caused by germline mutations of the VHL tumor suppressor gene. Major progress has been made in the last decade in both clinical and fundamental aspects of VHL. The VHL gene product, pVHL, has major and multiple functions: pVHL regulates not only first angiogenesis but also extracellular matrix formation and the cell cycle. A molecular diagnosis of VHL is now available, leading to a transformation in clinical management of patients and their families. Diagnosis of VHL has to be suspected in patients with a VHL-related tumor without familial history and especially in case of hemangioblastoma or endolymphatic sac tumors. Such patients should be systematically investigated for clinical and molecular evidence of VHL disease. Treatment of symptomatic hemangioblastomas remains mainly neurosurgical, often in emergency, but stereotactic radiosurgery is emerging as an alternative therapeutic procedure. In the future, antiangiogenic drugs could represent a potential medical treatment of CNS hemangioblastomas in view of their highly vascular structure. Lastly, visceral manifestations of VHL disease are also of critical importance and require early detection for effective treatment.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    The journal of headache and pain 1 (2000), S. S153 
    ISSN: 1129-2377
    Schlagwort(e): Key words Migraine ; Genetics ; Dopamine ; Hypersensitivity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Migraine is a common chronic disorder with an etiology still mostly unknown. Several neurotransmitters such as dopamine and serotonin are considered to be involved in the pathogenesis of the disease and the study of their systems is crucial in the understanding of migraine. Dopaminergic receptors are variously represented in human CNS and periphery. The hypothesis that a hypersensitivity of the dopaminergic system may have a role in migraine is based on clinical and genetic data. Genetic data are represented by association studies using dopaminergic genes as candidate genes which show that the D2 receptor gene appears to be involved in the pathogenesis of migraine.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    The journal of headache and pain 1 (2000), S. S141 
    ISSN: 1129-2377
    Schlagwort(e): Key words Migraine ; Genetics ; Human leukocyte antigens ; Heredity ; Susceptibility
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Human leukocyte Antigens (HLA) are encoded by genes located on chromosome 6p21. Genes important in migraine are being recognized in two basic ways: association studies and linkage analysis. One of the strongest associations is with the HLA region. Actually, genome scan studies suggest that multiple genes are involved in both migraine without aura (MWoA) and migraine with aura (MWA). However, both MWoA and MWA are disorders in which multiple factors, including environmental and genetic factors, confer disease susceptibility. Linkage analysis is identifying new candidate genes that will help to explain the etiology of migraine. In this review previous studies regarding genetic susceptibility to migraine are analyzed, particularly those related to the HLA region. I discuss evidence that HLA shared-hyplotypes in MWoA-affected pairs in different than that expected, that HLA-DR2 antigen provides additional basis for the proposed genetic heterogeneity between MWoA and MWA, and lastly that TNFB gene studies seem to play an important role in the susceptibility to MWoA. In the past years, major advances hae been made in understanding the genetic foundation of MWoA and MWA. Our reported genome-scan studies support the concept that MWoA/MWA are coinherited with a particular HLA region. However, the examination of candidate genes (Ca2+ channel, vascular, CNS, etc.) in a large migraine population seems to be the correct direction in which we have to move. More MWoA/MWa gene studies are needed to test this developing hypothesis and to further establish the complete genetic scenario of migraine.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1364-6753
    Schlagwort(e): Key words Parkinson's disease ; Familial Parkinson's disease ; Synuclein ; Parkin ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: ABSTRACT¶Parkinson's disease (PD) is a neurodegenerative disease with clinical features resulting from deficiency of dopamine in the nigrostriatal system. Most PD cases are sporadic and the primary cause of the disease is still unknown. Recently, familial PD and parkinsonism have received much attention because these forms of the disease might provide clues to the genetic risk factors involved in the pathogenesis of idiopathic PD. To date, two causative genes, α-synuclein and the parkin gene, have been identified. α-Synuclein is involved in the pathogenesis of an autosomal dominant form of PD and constitutes a major component of the Lewy body, which is a pathological hallmark of idiopathic PD. In addition, mutations in the parkin gene have been identified as the cause of autosomal recessive juvenile parkinsonism (AR-JP). AR-JP manifests itself as a highly selective degeneration of the substantia nigra and the locus coeruleus, but without Lewy body formation. In addition to these two genes, four chromosomal loci have been linked to other forms of familial PD. Furthermore, there are a number of other pedigrees of familial PD in which linkage to known genetic loci has been excluded. Molecular cloning of these disease genes and elucidation of the function of their gene products will greatly contribute to our understanding of the pathogenesis of idiopathic PD.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Environmental geology 39 (2000), S. 1372-1384 
    ISSN: 1432-0495
    Schlagwort(e): Key words Aries River ; Capillary electrophoresis ; Mining effluent ; Romania
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Geologie und Paläontologie
    Notizen: Abstract  This paper examines two issues, the extensive pollution occurring in the Aries River, NW Romania, as a result of unchecked discharge of mining effluents into the river system, and the suitability of capillary electrophoresis (CE) as an analytical method for investigations into water chemistry. The results confirm the first objective by providing details on the pollution of the Aries River and its geochemical system and demonstrate the usefulness of CE. In its upper reaches, the river system is characterized by high contents of SO4 2– as a direct result of acid mine effluents and the oxidation of sulphide minerals on mine dumps as well as inflows from settling ponds. Although continuous dilution by natural branch waters and natural water-rock interaction reduces the pollution to some extend, the total level of SO4 2– remains above European averages. The waters of the Aries River, by comparison, contain contents of Cu2+ and Zn2+ up to 100 times higher than those of unpolluted river water.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-1211
    Schlagwort(e): Key words Skin ; Genetics ; TNFA ; ¶Inflammation ; PCR-RFLP
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  Mechanisms underlying susceptibility to skin irritants are not clearly understood. Cytokines play a key role in inflammation, and functional polymorphisms in cytokine genes may affect responses to irritants. We investigated the relationship between polymorphism in the tumor necrosis factor (TNF) α-chain gene and responses to irritants. Volunteers (n=221) tested with sodium dodecyl sulfate (SDS) and benzalkonium chloride (BKC) were divided into responders and nonresponders and high and low irritant-threshold groups. DNA was assayed for the TNF-308 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism method. There was a significant increase in the A allele (P=0.030) and AA genotype (P=0.023) in both the SDS low irritant-threshold group and in SDS responders (A allele P=0.022, AA genotype P=0.048). In the BKC low irritant-threshold group, we found a significant increase in the A allele (P=0.002) and AA genotype (P=0.016). Individuals with a low threshold to both irritants demonstrated a significant increase (P=0.002) in the A allele. This is the first description of a nonatopic genetic marker for irritant susceptibility in normal individuals. Genotyping for theTNF-308 polymorphism may thus contribute to screening of individuals deemed at risk of developing irritant contact dermatitis.
    Materialart: Digitale Medien
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    Intensive care medicine 26 (2000), S. S057 
    ISSN: 1432-1238
    Schlagwort(e): Key words Critical illness ; Intensive care ; Severity of illness ; Scoring systems ; Genetics ; Susceptibility ; Education
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Risk of critical illness is determined both by genetic and environmental influences, particularly those relating to infectious and cardiovascular diseases. Physiologically-based scoring systems cannot measure prior risk because they do not quantify physiological reserve independently of the acute illness. Genetic profiling could be useful for risk assessment. Early detection of critical illness involves identifying physiological ’triggers' for referral; this requires the education of nursing and medical staff in their significance. Analysis of the relationship between risk factors and interventions may need complex modelling techniques. Therapeutic strategies depend on the nature of the underlying problem: the most useful are likely to be those which enhance tissue oxygen delivery and resistance to infection.
    Materialart: Digitale Medien
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  • 12
    ISSN: 1432-198X
    Schlagwort(e): Key words Glomerulocystic kidney disease ; Oligohydramnion ; Renal failure-neonate ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Two newborns with glomerulocystic kidney disease manifesting as late onset oligohydramnion and neonatal anuria, yet without severe respiratory distress, are presented. They had a similar perinatal course and associated clinical manifestations. No associated congenital or inherited malformation syndrome could be defined. Both infants’ parents were first degree cousins and belonged to the same small Bedouin tribe, and neither they nor the infants’ siblings had polycystic kidneys or renal insufficiency, pointing to either a possible genetic etiology or a common external toxic exposure.
    Materialart: Digitale Medien
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    European journal of pediatrics 159 (2000), S. S183 
    ISSN: 1432-1076
    Schlagwort(e): Key words Database ; Genetics ; Information services ; Internet ; Mutation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Thanks to the World Wide Web, most results of research in genetics are made available in public databases. At the present time there are resources on genetic diseases, genes and their location, mutations of already cloned genes and on laboratories performing the mutation analysis. The main resources on phenotypes are On-line Mendelian Inheritance in Man (OMIM), Pedbase, GeneClinics, London Dysmorphology Database (LDDB) and Orphanet. The main resources on human genes are, in addition to OMIM, the Genome Database, Genatlas and Genecard. There are also two major sequence databases. All of them can be queried using the OMIM number of the disease. Central databases of mutations, as well as locus specific databases have been created. Their list is maintained at the Human Genome Organisation mutation database initiative website. Several initiative have been taken to integrate all these data and help the clinician to find out quickly what he/she needs. The website of the National Center for Biotechnology Information is the best example of such an effort with sections on diseases, a genome guide, and locus links. Several databases of genetic testing resources have been established. GeneTests is an on-line genetics resource that contains a directory of North American laboratories providing testing for heritable disorders. Orphanet is a similar database on French services which is in the process of becoming a European database. Conclusion Even if clinicians do not have as many services at their disposal as the molecular geneticists, various useful databases already exist and should no longer be ignored in practice.
    Materialart: Digitale Medien
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    European journal of pediatrics 159 (2000), S. S208 
    ISSN: 1432-1076
    Schlagwort(e): Key words Cardiovascular disease ; Cystathionine β-synthase ; Genetics ; Methylenetetrahydrofolate reductase ; Mild hyperhomocysteinaemia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Over the last decade mild hyperhomocysteinaemia has widely been recognised as a new risk factor for arteriosclerosis and thrombosis. Main regulating enzymes of homocysteine (Hcy) metabolism are cystathionine β-synthase (CBS), methionine synthase and methylenetetrahydrofolate reductase (MTHFR). Early studies on patients with vascular disease described elevated Hcy concentrations after methionine loading and decreased CBS activity, resembling heterozygotes for CBS deficiency. Therefore, heterozygosity for CBS deficiency was proposed as the main cause of mild hyperhomocysteinaemia. However, more recent enzymatic and molecular genetic studies have demonstrated that heterozygosity for CBS deficiency is not or only a very minor cause of mild hyperhomocysteinaemia in vascular disease. We discovered two common genetic causes of mild hyperhomocysteinaemia, the 677C 〉 T and the 1298A 〉 C mutations in the coding region of MTHFR. The 677C 〉 T mutation causes reduced enzyme activity with thermolabile protein properties, elevated Hcy and low-normal or decreased plasma folate levels. The 1298A 〉 C mutation relates also to decreased enzyme activity, but not to thermolabile protein, and Hcy and folate levels are not influenced. However, compound heterozygosity for these two mutations, i.e. individuals with the 677CT/1298AC genotype, have elevated Hcy and decreased plasma folate levels. Gene-enviroment interactions between 677C 〉 T and folate is demonstrated in individuals with the 677TT genotype. Those with low-normal folate have elevated Hcy, whereas those with high-normal folate have normal Hcy concentrations. The elevated Hcy levels due to these mutations can be normalised by administration of folate, but whether folate reduces the risk of cardiovascular disease remains to be established. Conclusion Heterozygosity for cystathionine β-synthase deficiency is a minor cause of hyperhomocysteinaemia. The current data on mutations in the methylenetetrahydrofolate reductase gene do not tell us whether elevated plasma homocysteine plays a causal role in vascular disease. Low cellular vitamin status may be a possible cause and homocysteine may just be a marker for this situation.
    Materialart: Digitale Medien
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    European journal of pediatrics 159 (2000), S. S35 
    ISSN: 1432-1076
    Schlagwort(e): Key words Obesity ; Genetics ; Child ; Nutrient balance ; Energy balance ; Environment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The epidemic diffusion of obesity in industrialised countries has promoted research on the aetiopathogenesis of this disorder. The purpose of this review is to focus mainly on the contribution that European research has made to this field. Available evidence suggests that obesity results from multiple interactions between genes and environment. Parents obesity is the most important risk factor for childhood obesity. Twin, adoption, and family studies indicated that inheritance is able to account for 25% to 40% of inter-individual difference in adiposity. Single gene defects leading to obesity have been discovered in animals and, in some cases, confirmed in humans as congenital leptin deficiency or congenital leptin receptor deficiency. However, in most cases, genes involved in weight gain do not directly cause obesity but they increase the susceptibility to fat gain in subjects exposed to a specific environment. Both genetic and environmental factors promote a positive energy balance which cause obesity. The relative inefficiency of self-adapting energy intake to energy requirements is responsible for fat gain in predisposed individuals. The role of the environment in the development of obesity is suggested by the rapid increase of the prevalence of obesity accompanying the rapid changes in the lifestyle of the population in the second half of this century. Early experiences with food, feeding practices and family food choices affect children's nutritional habits. In particular, the parents are responsible for food availability and accessibility in the home and they affect food preferences of their children. Diet composition, in particular fat intake, influences the development of obesity. The high energy density and palatability of fatty foods as well as their less satiating properties promotes food consumption. TV viewing, an inactivity and food intake promoter, was identified as a relevant risk factor for obesity in children. Sedentarity, i.e. a low physical activity level, is accompanied by a low fat oxidation rate in muscle and a low fat oxidation rate is a risk factor of fat gain or fat re-gain after weight loss. Conclusion Further research is needed to identify new risk factors of childhood obesity, both in the genetic and environmental areas, which may help to develop more effective strategies for the prevention and treatment of obesity.
    Materialart: Digitale Medien
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  • 16
    ISSN: 1432-1459
    Schlagwort(e): Key words Amyotrophic lateral sclerosis ; Genetics ; Presenilin-1 intron 8 polymorphism ; Apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n=72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P 〈 0.04) and allele (P 〈 0.03) distribution between patients and controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis.
    Materialart: Digitale Medien
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neurology 247 (2000), S. 81-87 
    ISSN: 1432-1459
    Schlagwort(e): Key words Dementia ; Vascular ¶dementia ; Alzheimer’s disease ; Risk factors, stroke ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This review describes differing profiles of vascular risk factors in different types of dementia. Although vascular risk factors are related to various types of strokes, their independent effect on the occurrence of poststroke dementia appears to be small. Various risk factors have been identified for microangiopathy-related cerebral abnormalities, such as white matter changes and lacunae, which are the core lesions for the development of a vascular dementia syndrome without stroke symptoms. Most consistently, arterial hypertension and diabetes mellitus have been found to be associated with such brain abnormalities. Diastolic blood pressure seems to be of particular importance as recent investigations demonstrate that this factor is related to the course of multiple lacunar strokes and the progression of white matter disease. Epidemiological studies report that various vascular risk factors including arterial hypertension, diabetes mellitus, and atrial fibrillation may also be associated with Alzheimer’s disease. There is also evidence of a direct relationship between Alzheimer’s disease and general atherosclerosis. Further investigations are needed to determine whether these associations are due to the weakness of diagnostic criteria, or whether vascular risk factors indeed modulate the clinical expression of primary degenerative dementia. Common susceptibility genes leading to shared risk factors may be one of the reasons for a higher coincidence of Alzheimer’s disease and vascular dementia than can be expected by chance. A modulatory effect of vascular risk factors in the development of primary degenerative dementia may extend treatment options.
    Materialart: Digitale Medien
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  • 18
    ISSN: 1432-1459
    Schlagwort(e): Key words Parkinson’s disease ; Monoamine oxidase B ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Monoamine oxidase B (MAOB) metabolises dopamine and activates neurotoxins known to induce parkinsonism in humans and primates. Therefore the MAOB gene (MAOB; Xp15.21–4) is a candidate gene for Parkinson’s disease (PD). Longer length dinucleotide repeat sequences in a highly polymorphic GT repeat region of intron 2 of this gene showed an association with PD in an Australian cohort. We repeated this allele-association study in a population of 176 Chinese PD patients ¶(90 men, 86 women) and 203 age-matched controls (99 men, 104 women). Genomic DNA was extracted from venous blood and the polymerase chain reaction was used to amplify the appropriate regions of the MAOB gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis. There was no significant difference in allele frequencies of the (GT) repeat allelic variation between patients and controls (χ2 = 2.48; df = 5, P 〈 0.75). Therefore the longer length GT repeat alleles are not associated with PD in this Chinese population. Possible reasons for the discrepancy between Chinese and Australian populations include a different interaction between this genetic factor and environmental factors in the two populations and the possibility that the long length GT repeat alleles may represent a marker mutation, genetically linked to another susceptibility allele in whites but not in Chinese. Methodological differences in the ascertainment of cases and controls in this cohort could also explain the observed differences. Further study is required to determine whether the longer length GT repeat alleles are true susceptibility alleles in PD.
    Materialart: Digitale Medien
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  • 19
    ISSN: 1432-1459
    Schlagwort(e): Key words Progressive ¶supranuclear palsy ; Genetics ; Clinical characteristics ; Parkinsonism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Genetic studies have detected an association between the presence of the τ gene A0 allele and patients with progressive supranuclear palsy (PSP). This study examined whether patients with this polymorphism exhibit distinct demographic or clinical characteristics. We studied 26 patients who fulfilled clinical criteria for the diagnosis of PSP, 20 who had the A0/A0 genotype and 6 who had other genotypes. A questionnaire on demographic data, past medical history, familial history, and initial symptoms was completed as part of the consultation. A complete neurological examination was performed and PSP symptoms were quantified following Golbe’s PSP disability scale. We found a significant difference in the age at onset of PSP symptoms, which was 65.9 ± 5.3 years in the A0/A0 group and 71.2 ± 5.6 in the non-A0/A0 group (P = 0.016). There were no significant differences in the years from disease onset between the two groups. Symptom severity did not differ significantly in patients with the different A0/A0 genotypes. The detection of significantly lower age at onset with the A0/A0 alleles is consistent with the known association of this genotype as a risk factor for PSP. No significant differences were detected in symptom severity between the two groups of patients.
    Materialart: Digitale Medien
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  • 20
    ISSN: 1432-1459
    Schlagwort(e): Key words Multiple sclerosis ; Siblings ; Genetics ; Oligoclonal bands ; Measles
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We found that 19% (9/47) of healthy siblings of patients with clinically definite multiple sclerosis had an intrathecal immunological reaction with two or more 2 CSF-enriched oligoclonal bands (OCBs), in contrast to (4%) (2/50) unrelated healthy controls. Furthermore, in this group of nine healthy sibs the measles CSF IgG antibody titers were higher than that of the other sibs and that of controls. There were also differences in the serum titers for measles IgG antibody, which were higher in the group of all healthy sibs than in healthy volunteers, and (as with CSF titers) higher in the subgroup of healthy sibs with two or more 2 CSF-enriched OCBs than the other sibs. Thus a significant proportion of healthy siblings to MS patients have a partially hyperimmune condition similar to that occurring in MS, which in 19% manifested itself as an OCB reaction, in 9% as increased CSF measles IgG antibody titers, and in 21% as increased serum measles IgG antibody titers, these phenomena tending to occur in the same individuals. This condition is characterized by CSF-enriched OCBs with undefined specificity, although some increased antiviral reactivity is found both in the serum and CSF. While it needs further characterization, a genetic trait interacting with common infections is suggested. The recurrence risk of this condition is approximately five times higher than the 3–4% recurrence risk for manifest MS reported for sibs.
    Materialart: Digitale Medien
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  • 21
    ISSN: 1432-1327
    Schlagwort(e): Key words Cisplatin ; Nucleoside monophosphates ; Capillary electrophoresis ; Platinum complexes ; Matrix-assisted laser-desorption ionization mass spectrometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The binding behaviour as well as the time-dependent reaction of five platinum(II) complexes with 5′-GMP have been investigated by capillary electrophoresis under simulated physiological conditions referred to chloride concentration, pH and temperature. Different amine ligands influenced the binding properties towards 5′-GMP and resulted in different half-times of the overall reaction. Complexes with bidentate ligands reacted faster with the monophosphate compared to complexes with monodentate ligands. Complexes consisting of two monodentate hydroxyethylamine ligands reacted very slowly owing to a competitive intramolecular reaction of the hydroxyethyl residues, which was proven by NMR investigations. Reducing the number of hydroxyethyl residues increased the half-times of the reactions. Moreover, the major adducts formed with 5′-GMP were identified by MALDI-MS analysis.
    Materialart: Digitale Medien
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  • 22
    Digitale Medien
    Digitale Medien
    Springer
    Child's nervous system 16 (2000), S. 809-820 
    ISSN: 1433-0350
    Schlagwort(e): Keywords Pediatric neurosurgery ; Molecular biology ; Genetics ; Novel therapeutics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The new millennium beckons for novel advances in the diagnosis and treatment of pediatric neurosurgical conditions. Almost every aspect of pediatric neurosurgery has changed over the last decade. Undoubtedly with the application of knowledge in molecular biology to human disease many aspects of neurosurgery, especially neuro-oncology and the field of neuro-developmental anomalies, will change appreciably over the next decade. Overall, the trend in surgery in general and neurosurgery in particular is toward less invasive procedures and possibly non-surgical interventions. This review will briefly cover many of the important areas of pediatric neurosurgery. We will describe the state-of-the-art of our subspecialty and discuss possible future directions.
    Materialart: Digitale Medien
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    Theoretical and applied genetics 101 (2000), S. 234-240 
    ISSN: 1432-2242
    Schlagwort(e): Key words Cherry ; Genetics ; Compatibility ; Incompatibility ; Isoelectric focusing ; Prunus avium ; Ribonuclease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  The (in)compatibility genotypes of two self-compatible sweet cherry selections, JI 2420 and JI 2434, originating from the John Innes Institute were re-examined. The selections and seedlings derived from them were analysed for stylar ribonucleases, which are known to correlate with S alleles, and the outcome of test crosses was recorded. JI 2420, which had been reported previously as S 3 S 4 ", where " indicates loss of pollen activity, was deduced to have the genotype S 4 S 4 ’. For JI 2434, which had been reported previously as S 3 S 4 0 , S 3 S 3 0 or S 3 S 3 ", where 0 indicates loss of pollen and stylar activity, two different clones were identified. One, at East Malling, was deduced to be S 3 "S 4 ; the other, at Ahrensburg, appeared to be S 3 S 3 " or S 3 S 3 0 .
    Materialart: Digitale Medien
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  • 24
    ISSN: 1432-2242
    Schlagwort(e): Key words Avicennia marina ; Microsatellite ; Mangrove ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  An enriched microsatellite library of the mangrove species Avicennia marina was constructed, in which 85.8% of the clones contained microsatellite sequences. Of the microsatellite repeat sequences isolated, 55.0% were di-nucleotides, 34.2% were tri-nucleotides, 50.0% were perfect, 24.2% were imperfect, and 15.0% were compound. Four different di-nucleotide repeats were isolated with repeat lengths ranging from 5 to 33; ten different tri-nucleotide repeats were isolated with repeat lengths ranging from 3 to 25. The most common di-nucleotide was the AC/TG repeat; the most common tri-nucleotide was the CCG/GGC repeat. Sixteen microsatellite sequences were selected for primer design, and 6 primers were selected to investigate the polymorphism detected among 15 individuals of A. marina from three natural populations in Australia. A total of 40 alleles were detected at 6 microsatellite loci. The number of alleles per microsatellite locus ranged from 5 to 13. On average, 7 alleles were detected per locus. All microsatellite loci showed high levels of gene diversity (heterozygosity), with values ranging from 0.53 to 0.88; the mean value of gene diversity was 0.70. Microsatellite loci were also tested for conservation across Avicennia species. There was a decline in amplification success with increasing divergence between Avicennia species. The results indicate that microsatellites are abundant in the Avicennia genome and can be valuable genetic markers for assessing the effects of deforestation and forest fragmentation in mangrove communities, which is an important issue for mangrove conservation and afforestation schemes.
    Materialart: Digitale Medien
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  • 25
    ISSN: 1433-8491
    Schlagwort(e): Key words Pharmacogenetics ; Genetics ; Risk factor ; Choreoathetotic movements
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the search for genetic factors contributing to tardive dyskinesia, dopamine receptor genes are considered major candidates. The dopamine D3 receptor is of primary interest as dopamine D3 receptor knock-out mice show locomotor hyperactivation resembling extrapyramidal side-effects of neuroleptic treatment. Furthermore, Steen and colleagues (1997) recently reported an association between tardive dyskinesia and a dopamine D3 receptor gene variant. In the present study we tried to replicate this finding. We investigated 157 patients with schizophrenia or schizoaffective disorder receiving long-term neuroleptic medication who never or persistently displayed tardive dyskinesia. As advanced age is a main risk factor for tardive dyskinesia, we also compared older patients with a long duration of schizophrenia not displaying tardive dyskinesia to younger patients with a shorter duration of the illness displaying tardive dyskinesia. However, we found no evidence that the dopamine D3 receptor gene is likely to confer susceptibility to the development of tardive dyskinesia.
    Materialart: Digitale Medien
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  • 26
    ISSN: 1433-8491
    Schlagwort(e): Key words Dopamine receptor D4 ; Genetics ; Personality inventory ; Polymorphism ; Excitement-Seeking
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract An association between long alleles of a variable number tandem repeat (VNTR) polymorphism in the dopamine receptor D4 gene and the extraversion related personality traits Excitement and Novelty Seeking has been reported in healthy subjects. In an attempt to replicate the previous findings, 256 healthy Caucasian volunteers were analysed for a potential relationship between the dopamine receptor D4 exon III VNTR polymorphism and Extraversion as assessed by the Revised Neo Personality Inventory (NEO PI-R). The present study did not yield evidence for an association between Extraversion and the dopamine receptor D4 polymorphism.
    Materialart: Digitale Medien
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  • 27
    ISSN: 1432-1459
    Schlagwort(e): Key words Multiple sclerosis ; Genetics ; ICAM-1 gene
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract An increased amount of the intercellular adhesion molecule (ICAM) 1 molecule has been found in the blood of actively relapsing multiple sclerosis (MS) patients, but is unclear whether this enhanced expression is partially causative of the MS process, or whether it is merely an epiphenomenon of the inflammatory-immunological reaction. Using the transmission disequilibrium test (TDT), we studied exon 4 and exon 6 polymorphism of the ICAM-1 gene from 157 families with both parents, one affected and one healthy sib coming from Sardinia, an Italian island having a high incidence and prevalence of MS. TDT did not show variation in the expected 50:50 frequency in transmission in either healthy or affected sibs, using phenotypic or genotypic analysis. Moreover, independence from the predisposing HLA-DRB1-DQA1-DQB1 haplotype was confirmed by TDT analysis performed on the patients stratified according to the presence or absence of the HLA-DRB1, DQA1, DQB1 Sardinian predisposing haplotypes. Our data suggest that the increased expression of the ICAM-1 molecule observed in both blood and periplaque microvessels may be considered a consequence of the inflammatory process rather than the result of a genetic variation.
    Materialart: Digitale Medien
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    Theoretical and applied genetics 100 (2000), S. 401-408 
    ISSN: 1432-2242
    Schlagwort(e): Key words Complementary genes ; Extreme virus resistance ; Genetics ; Necrotic tubers ; Restricted virus distribution ; Solanum tuberosum
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  The potato cultivar ’Shepody’ is susceptible to a number of potato viruses including potato virus Y (PVY, potyvirus) but was found to possess extreme resistance to another potyvirus, potato virus A (PVA). ’Shepody’ plants were resistant to PVA infection in manual and graft inoculations. PVA replication was not detected in any of the inoculated plants by ELISA, an infectivity assay and RT-PCR. However, ’Shepody’ plants grafted with shoots containing PVA developed a novel symptomology which resembled a virus infection in appearance and in rate of translocation to the entire plant. Efforts to transmit the symptom-inducing agent manually failed. Graft-inoculation to potato virus indicator plants and PVA-susceptible potato plants showed that the symptom inducer was PVA at an extremely low concentration, detected using RT-PCR followed by Southern blot assay. Tubers from grafted but resistant ’Shepody’ plants had necrotic surfaces and internal spots. PVA was detected from necrotic areas but not from the non-necrotic ones. However, plants resulting from necrotic tubers were free from aerial leaf symptoms observed in grafted plants and produced non-necrotic normal tubers. A trace-back of the parental lineage of ’Shepody’ indicated that the resistance had been introgressed from the cultivar ’Bake King’. Analysis of progeny of a cross of resistant ’Shepody’ to the susceptible ’Goldrus’ indicated that this resistance is controlled by two independent dominant complementary genes in contrast to monogenic resistance reported for other potato viruses.
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  • 29
    ISSN: 1432-136X
    Schlagwort(e): Key words Calcium ; Capillary electrophoresis ; Hemolymph volume ; Isopod ; Molting
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract We analyzed ion composition and volume of the hemolymph of Ligia pallasii in four different stages of the molt cycle using capillary electrophoresis and 3H-inulin. The main ions in the hemolymph were Na+, K+, Mg2+, Ca2+, and Cl−. The Ca2+concentration increased significantly during the molt by 47% from intermolt to intramolt and by 37% from intermolt to postmolt, probably due to resorption of Ca2+ from the cuticle and sternal CaCO3 deposits. The K+ concentration increased significantly by 20% during molt. The hemolymph volume normalized to the dry mass of the animals decreased by 36% from intermolt to late premolt. This was due to a reduction in the hemolymph volume and to an increase in dry mass of the animals during premolt. A sudden increase in the hemolymph volume occurring between late premolt and intramolt served to expand the cuticle. Since the Na+, K+, Mg2+, and Cl− concentrations did not change significantly from late premolt to intramolt, the increase in hemolymph volume suggests an uptake of seawater rather than freshwater.
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    Neurological sciences 21 (2000), S. S89 
    ISSN: 1590-3478
    Schlagwort(e): Key words Evoked potentials ; Ceroid lipofuscinoses ; Mutation ; Classification ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The importance of visual evoked potential (VEPs) and electroencephalography for diagnosing and distinghishing the infantile (INCL), late-infantile (LINCL) and juvenile (JNCL) forms of neuronal ceroid lipofuscinoses (NCL) is well established. Variant forms with protracted clinical courses and atypical symptoms have been described recently, whose neurophysiological characteristics sometimes overlap those of LINCL and JNCL. It is unclear whether these variant forms are due to phenotypic variability of known genetic defects, or represent new mutations. Twenty-eight NCL patients have been diagnosed at our institute; a proportion of them were investigated genetically. In 17 we performed neurophysiological investigations including VEPs, brainstem auditory (BAEP) and upper limb somatosensory (SEP) evoked potentials. We found typical and diagnostic electrophysiological involvement of the visual system in 8 patients with classic forms of NCL. Furthermore, the distinctive features of the multimodal evoked potentials in most of the six patients with variant NCL suggest that these are distinct genetic entities.
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  • 31
    ISSN: 1590-3478
    Schlagwort(e): Key words Nervous system ; Cavernous angiomas ; Genetics ; Onset symptoms
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We performed a clinical and genetic study of patients affected by cavernous angiomas (CA) of the nervous system. We examined initial signs and symptoms in sporadic and familial cases. We obtained clinical, neuroimaging and genetic data on 15 Italian patients with CA of the nervous system with positive, doubtful or apparently negative family history. Genetic markers surrounding three different gene regions (7q, 3q and 7p) were analysed. In one small family, genetic linkage was consistent with all chromosome loci. In another family with the unusual association of cerebral and spinal CA, linkage with chromosome 7q and, likely, 7p was excluded, while linkage with locus 3q was possible. Our results indicate that Italian families with CA may show genetic heterogeneity. Non-specific and subtle onset symptoms hide the presence of CA within families. Patients with multiple CA may have silent cerebral lesions confirming the low penetrance of clinical signs in spite of radiological ones.
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  • 32
    Digitale Medien
    Digitale Medien
    Springer
    Neurological sciences 21 (2000), S. 373-377 
    ISSN: 1590-3478
    Schlagwort(e): Key words Myoclonus-dystonia ; Essential myoclonus ; Dystonia ; Alcohol ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We present the clinical profile of a group of patients with myoclonus and dystonia sensitive to alcohol and address these cases in the context of essential myoclonus. Six patients from 4 families were selected: 4 men and 2 women with myoclonus affecting predominantly the arms. Active movements of these segments elicited the dystonic and myoclonic movements. A marked improvement with alcohol intake was seen. Laboratory findings including EEG, SSEP, and cranial CT and MRI were normal. Surface EMG recording showed bursts with duration of 30–112 ms in 3 patients. One patient showed a triphasic recording pattern (agonist-antagonist-agonist) of ballistic type. Our findings suggest that the myoclonus-dystonia disorder is present in Brazilian patients.
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  • 33
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 23 (2000), S. 413-429 
    ISSN: 0935-6304
    Schlagwort(e): Capillary electrophoresis ; enantiomer separation ; chiral drugs ; TM-γ-cyclodextrin ; Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: ---High-throughput screening is a promising new approach in analytical chemistry. Within the framework of an extended screening program (The German-Chinese Drug Screening Program), the enantioseparation of 86 drugs was investigated by capillary zone electrophoresis in the presence of the chiral solvating agent (CSA) octakis-(2,3,6-tri-O-methyl)-γ-cyclodextrin (TM-γ-CD). By this means, 15 drugs could be separated into enantiomeric pairs. Approximate measures for the degree of interaction (migration retardation factor, Rm) and for the degree of enantiomer recognition (migration separation factors, αm) revealed intriguing patterns that were compared with those found for native γ-cyclodextrin (γ-CD). Although there is a distinct influence of the analyte structure on the electrophoretic data, interpretation remains difficult. Most remarkably, permethylation of γ-CD leads neither to a higher affinity nor to better chiral recognition, in contrast to the findings with α-CD.
    Zusätzliches Material: 10 Ill.
    Materialart: Digitale Medien
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  • 34
    ISSN: 0935-6304
    Schlagwort(e): Capillary electrophoresis ; UV detection ; organic acids ; background electrolyte optimization ; wine ; Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: ---A simple technique is described for the routine capillary electrophoretic determination of organic acids in wine samples. Several aromatic and non-aromatic compounds, including phthalic acid, benzoic acid, sorbic acid, boric acid, and phosphate, were evaluated as background electrolytes in order to obtain the highest resolution and detection sensivity. Factors that affect capillary electrophoretic separation such as the concentration and pH of the background electrolyte (BGE), the concentration of the electroosmotic flow modifier (EOF), and methanol addition to the electrolyte were investigated systematically. Tartaric, malic, succinic, acetic, and lactic acids were determined simultaneously in approximately six minutes using an electrolyte containing 3 mM phosphate and 0.5 mM myristyltrimethylammonium bromide (MTAB) as electroosmotic flow modifier at pH 6.5. This method is quantitative, with recoveries in the 90-102% range and linear up to 50 mg L-1. The precision is better than 1% and the procedure shows the appropriate sensibility, with detection limits between 0.015 and 0.054 mg L-1. The proposed method was successfully employed for the determination of organic acids in wine samples by direct sample injection after appropriate dilution and filtration.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    European food research and technology 209 (1999), S. 355-359 
    ISSN: 1438-2385
    Schlagwort(e): Key words Meat ; Thiamine ; Capillary electrophoresis ; High performance liquid chromatography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Abstract  A new capillary electrophoresis (CE) method for the analysis of thiamine in meat is proposed. Samples were submitted to acidic and enzymatic hydrolysis and the extracts were purified using ethanol and an ion exchange column. The thiamine content was determined by CE using 100 mM sodium tetraborate, 50 mM sodium phosphate (pH 7.6), 50 mM sodium dodecyl sulphate and 10% isopropyl alcohol as a separation buffer solution. The analysis was carried out at 15 kV and 50  °C in a 70 cm effective length× 75 μm i.d. fused-silica capillary using on-column UV detection at 254 nm and 7 s injection time (27 nl injection volume). The results obtained by CE for thiamine contents in meat were compared to those obtained by HPLC using an ion-pair reverse phase column with post-column derivatization and fluorescence detection.
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  • 36
    ISSN: 1364-6753
    Schlagwort(e): Key words Multiple sclerosis ; Genetics ; Myelin basic protein ; Myelin oligodendrocyte glycoprotein ; Proteolipid protein
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: ABSTRACT Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. A complex genetic etiology is thought to underlie susceptibility to this disease. The present study was designed to analyze whether differences in genes that encode myelin proteins influence susceptibility to MS. We performed linkage analysis of MS to markers in chromosomal regions that include the genes encoding myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMGP), and myelin oligodendrocyte glycoprotein (MOG) in a well-characterized population of 65 multiplex MS families consisting of 399 total individuals, 169 affected with MS and 102 affected sibpairs. Physical mapping data permitted placement of MAG and PLP genes on the Genethon genetic map; all other genes were mapped on the Genethon genetic map by linkage analysis. For each gene, at least one marker within the gene and/or two tightly linked flanking markers were analyzed. Marker data analysis employed a combination of genetic trait model-dependent (parametric) and model-independent linkage methods. Results indicate that MAG, MBP, OMGP, and PLP genes do not have a significant genetic effect on susceptibility to MS in this population. As MOG resides within the MHC, a potential role of the MOG gene could not be excluded.
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  • 37
    Digitale Medien
    Digitale Medien
    Springer
    Italian journal of neurological sciences 20 (1999), S. 89-108 
    ISSN: 1126-5442
    Schlagwort(e): Key words Neurofibromatosis ; Nf1 ; Nf2 ; Mosaic/segmental neurofibromatosis ; Variants ; Classification ; Neurological manifestations ; Genetics ; Childhood ; Adulthood
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The last two decades have seen clinical and molecular delineation of the different forms of neurofibromatosis. Differentiation of these forms is not just an academic exercise: their natural history, management and genetic counselling are quite different. Of the numerical classifications of neurofibromatosis proposed in the past, only neurofibromatosis type 1 (Nf1) and neurofibromatosis type 2 (Nf2) are now well delineated clinically and have been shown to be distinct at the molecular level. For both forms of neurofibromatosis, patients with clinical generalised disease have been demonstrated to be mosaic at the molecular level, and features of segmental or mosaic Nf1 and Nf2 have been delineated. Other reported forms of neurofibromatosis are rarer; they include Watson syndrome, hereditary spinal neurofibromatosis, familial intestinal neurofibromatosis, autosomal dominant café-au-lait spots alone, autosomal dominant neurofibromas alone, and schwannomatosis, the latter believed to be a variant of Nf2. Further delineation is neeeded for individuals having overlapping features of Noonan's syndrome and neurofibromatosis (the so-called Noonan/neurofibromatosis syndrome) and the syndrome of “multiple naevi, multiple schwannomas and multiple vaginal leiomyomas”. In this article we review the forms of neurofibromatosis which we believe are true clinical entities. Particular attention is given to the neurological manifestations of neurofibromatosis.
    Materialart: Digitale Medien
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    International journal of legal medicine 113 (1999), S. 26-32 
    ISSN: 1437-1596
    Schlagwort(e): Key words STRs ; Capillary electrophoresis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Rechtswissenschaft
    Notizen: Abstract Capillary electrophoresis with laser-induced fluorescence was applied to the analysis of six STRs and the amelogenin sex test with the purpose of verifying accuracy and precision of the sizing method with the GS500 internal standard. Sequenced dye-labeled, PCR-amplified alleles from amelogenin, HumVWA31, HumTH01, HumF13A01, HumFIBRA, D21S11 and HumCSF1PO loci were run several times on the same capillary and on multiple capillaries and the offset of computer-measured fragment sizes from the expected molecular weights was calculated and analysed. All loci except D21S11 showed a poor degree of accuracy. Precision results from run-to-run and day-to-day injections displayed a maximum standard deviation (SD) 〉 0.15 nt for HumVWA31, HumF13A01, D21S11 and HumFIBRA, although the maximum range of calculated sizes in multiple runs was lower than 1 basepair. No variation in precision was observed according to the quality of the DNA template. Allele typing by comparison with allelic ladders for each locus is recommended.
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  • 39
    ISSN: 1432-1440
    Schlagwort(e): Key words Diabetes ; Genetics ; Phosphofructokinase ; Glycogenosis ; NIDDM ; PFK
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is usually explained as a combination of peripheral insulin resistance and impaired beta-cell function. Phosphofructo-1-kinase (PFK1) is a rate limiting enzyme in glycolysis, and its muscle subtype (PFK1-M) deficiency leads to an autosomal recessively inherited disorder known as glycogenosis type VII or Tarui’s disease. It was evaluated whether PFK1-M deficiency leads to NIDDM in humans. A core family of four was evaluated for PFK1-M deficiency by DNA- and enzyme-activity-analyses. All members underwent oral and intravenous glucose tolerance test (oGTT/ivgtt), as well as an insulin sensitivity test (IST) using octreotide. Results: Father (46 years, BMI 22.4 kg/m2) and older son (19 years, BMI 17.8 kg/m5) showed homozygous PFK1-M deficiency, while mother (47 years, BMI 28.4 kg/m5) and younger son (13 years, BMI 16.5 kg/m5) were shown to be heterozygously PFK1-M-deficient on enzyme activity levels. DNA analysis revealed an exon 5-missense-mutation at one allele of all four members, and an exon 22-frameshift-mutation at the other allele of the two homozygously affected individuals. By oGTT the father showed impaired glucose tolerance, and the mother clinical diabetes. By ivGTT both parents and the older son had a decreased first phase insulin secretion, and a diminished glucose disappearance rate. The IST showed marked insulin resistance in both parents and the older son, and moderate resistance in the younger son, previously not described. Conclusion: PFK1-M-deficiency leads to a metabolic state typical for early NIDDM in homozygously affected humans, especially concerning insulin resistance and loss of first phase beta-cell insulin secretion, and may contribute to the manifestation of NIDDM in a subgroup of patients.
    Materialart: Digitale Medien
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    Der Nervenarzt 70 (1999), S. 195-205 
    ISSN: 1433-0407
    Schlagwort(e): Schlüsselwörter Alzheimer-Krankheit ; Genetik ; Risikofaktoren ; Genetische Beratung ; Key words Alzheimer’s disease ; Genetics ; Risk factors ; Genetic counseling
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary A multifactorial etiology underlies the majority of cases of Alzheimer’s disease (AD). Both ill-defined environmental and genetic factors contribute to the development of the disease. Allele ɛ4 of ApoE is a genetic risk factor. Its presence increases the risk of developing AD. However, presence of e4 is neither necessary nor sufficient for the disease to arise. Apart from the common multifactorial forms of the disease, there are rare variants which are inherited as Mendelian traits. To date three genes are known that can be mutated in these rare forms of AD. Of these, mutations in the gene presenilin 1 on chromosome 14 are most frequent. In addition, mutations in the gene presenilin 2 on chromosome 1 and in the amyloid precursor protein gene (APP on chromosome 21) occur in autosomal dominant AD. This article reviews our present knowledge of the genetics of AD and discusses its relevance for patients with AD and their relatives.
    Notizen: Zusammenfassung Der Großteil der Fälle von Alzheimer-Krankheit (AK) hat eine multifaktorielle Ätiologie. Das bedeutet, bisher nicht genauer bekannte Umwelteinflüsse und genetische Faktoren spielen bei der Entwicklung der Krankheit eine wesentliche Rolle. Von seiten der Genetik unterscheidet man bei der AK gegenwärtig genetische Risikofaktroren und Mutationen. Der einzige bisher gesicherte genetische Risikofaktor ist das Allel ɛ4 des Gens für Apolipoprotein E auf Chromosom 19. Dieses Allel erhöht die Wahrscheinlichkeit, an der AK zu erkranken, ist jedoch weder eine notwendige noch eine hinreichende Bedingung. Neben den häufigen Formen mit multifaktorieller Ätiologie kommen seltene Varianten der Krankheit vor, die nach Mendelschen Regeln vererbt werden. Bisher sind 3 Gene bekannt, die bei diesen seltenen, in der Regel früh auftretenden und autosomal dominant vererbten Formen mutiert sein können. Am häufigsten findet sich bei den autosomal-dominanten Fällen eine Mutation im Gen präsenilin 1 auf Chromosom 14, seltener liegen Mutationen im Gen präsenilin 2 auf Chromosom 1 und im Gen des Amyloid- Vorläuferproteins auf Chromosom 21 vor. In diesem Beitrag geben wir eine Übersicht über gegenwärtige Befunde zur Genetik der AK und diskutieren die Bedeutung dieses Wissens für Patienten und deren Verwandte.
    Materialart: Digitale Medien
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    Der Nervenarzt 70 (1999), S. 955-969 
    ISSN: 1433-0407
    Schlagwort(e): Schlüsselwörter Schizophrenie ; Genetik ; Schizophrenes Spektrum ; Kopplungsuntersuchungen ; Assoziationsuntersuchungen ; Key words Schizophrenia ; Genetics ; Schizophrenia spectrum ; Linkage studies ; Association studies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Schizophrenia is a genetic complex disease as it does not follow monogenic transmission while non-familial environmental factors have a strong additional impact. A heterogenous, continuous phenotype is transmitted in families which can now be more precisely characterized. Genes coding for proteins with presumed pathophysiological relevance are apparently not playing a major causal role. However, in the last three years several (currently seven) candidate regions have been identified in a replicable manner by linkage studies. These regions are likely to host susceptibility genes for schizophrenia, but none of them has been identified up to now. Given these findings, polygenic transmission has now become very likely. The candidate regions are currently being narrowed down by various promising techniques.
    Notizen: Zusammenfassung Die Schizophrenie gehört zu den genetisch komplexen Erkrankungen, die keinem monogenen Erbgang folgen und bei denen auch nichtfamiliäre Umgebungsfaktoren eine wichtige Rolle spielen. Dabei wird intrafamiliär ein heterogener, quantitativ variierender Phänotyp übertragen, der zunehmend genauer charakterisiert werden kann. Keines der bekannten Gene mit vermuteter pathophysiologischer Relevanz spielt nach den bisherigen Erkenntnissen eine substantielle Rolle. In den vergangenen drei Jahren ist es aber erstmals durch Kopplungsuntersuchungen gelungen, mehrere replizierbare Kandidatenregionen (derzeit sieben) auf dem Genom zu identifizieren, in denen vermutlich Suszeptibilitätsgene für Schizophrenie liegen. Keines dieser Gene wurde jedoch bislang identifiziert. Mit diesen Befunden ist eine polygene Übertragung der Schizophrenie sehr wahrscheinlich geworden. Verschiedene Techniken zur Eingrenzung der Kandidatenregionen werden derzeit erfolgreich angewandt.
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  • 42
    ISSN: 1434-0879
    Schlagwort(e): Key words Transitional cell carcinoma ; Cisplatin resistance ; Cross-resistance ; Methotrexate ; Metallothioneins ; Capillary electrophoresis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Cisplatin is one of the most potent cytotoxic drugs and in chemotherapy has ameliorated numerous tumors. Nevertheless, resistance to cisplatin is a problem that is encountered in the chemotherapy of urologic tumors, especially transitional cell carcinomas. In order to improve definition of the mechanisms of cisplatin-resistance we established a series of cisplatin-resistant sublines from the cell line RT 112 in increasing concentrations of cisplatin. The most resistant subline CP3 is approximately 10 times more resistant than the parental line and shows a 10-fold cross-resistance against methotrexate, whereas vinblastine and doxorubicin are equally effective in the parental and sublines. Combined treatment of CP3 cells with cisplatin and buthionine sulfoximine (BSO) does not result in enhanced cell kill, thereby ruling out glutathione as a resistance mechanism. However, in comparison with parental cells, CP3 cells are about 1.5 times more resistant against cadmium. On the protein level, the cisplatin-resistant cells reveal an enhanced expression of metallothionein II (MTII), but not MTI, suggesting that the cisplatin resistance we observed in these sublines is at least partly mediated by MTII. These sublines will in the future serve as valuable tools for the analysis of cisplatin resistance, especially in view of metallothionein-mediated resistance mechanisms.
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  • 43
    ISSN: 1432-0533
    Schlagwort(e): Key words Frontotemporal dementia ; Genetics ; Progressive supranuclear palsy ; Tauopathy ; Exon ; amplifcation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Recently intronic and exonic mutations in the Tau gene have been found to be associated with familial neurodegenerative syndromes characterized not only by a predominantly frontotemporal dementia but also by the presence of neurological signs consistent with the dysfunction of multiple subcortical neuronal circuitries. Among families, the symptomatology appears to vary in quality and severity in relation to the specific Tau gene mutation and often may include parkinsonism, supranuclear palsies, and/or myoclonus, in addition to dementia. We carried out molecular genetic and neuropathological studies on two patients from a French family presenting, early in their fifth decade, a cognitive impairment and supranuclear palsy followed by an akinetic rigid syndrome and dementia. The proband died severely demented 7 years after the onset of the symptoms; currently, his brother is still alive although his disease is progressing. In both patients, we found a Tau gene mutation in exon 10 at codon 279, resulting in an asparagine to lysine substitution (N279K). Neuropathologically, widespread neuronal and glial tau accumulation in the cortex, basal ganglia, brain stem nuclei as well as in the white matter were the hallmark of the disease. These deposits were shown by immunohistochemistry and immunoelectron microscopy, using a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes present in multiple tau regions. In the neocortex, tau-immunopositive glial cells were more numerous than immunopositive neurons; the deeper cortical layers as well as the white matter adjacent to the cortex contained the largest amount of immunolabeled glial cells. In contrast, some brain stem nuclei contained more neurons with tau deposits than immunolabeled glial cells. The correlation of clinical, neuropathological and molecular genetic findings emphasize the phenotypic heterogeneitiy of diseases caused by Tau gene mutations. Furthermore, to test the effect of the N279K mutation and compare it with the effect of the P301L exon 10 mutation on alternative splicing of Tau exon 10, we used an exon amplification assay. Our results suggest that the N279K mutation affects splicing similar to the intronic mutations, allowing exon 10 to be incorporated more frequently in the Tau transcript.
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    Annals of hematology 78 (1999), S. 485-494 
    ISSN: 1432-0584
    Schlagwort(e): Key words Mantle cell lymphoma ; Classification ; Pathology ; Prognosis ; Immunology ; Genetics ; Antineoplastic agents ; Combined ; Therapeutic use ; Radiotherapy ; Hematopoietic stem cell transplantation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
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  • 45
    ISSN: 1432-0584
    Schlagwort(e): Key words Acute leukemia ; Genetics ; Sex ; ABO Blood group
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Acute leukemia is more common in males at almost every age, and this fact remains unexplained. A study was carried out in northeast peninsular Malaysia, where the population is predominantly Malay, to examine whether there was a difference in ABO blood group distribution between males and females with acute leukemia (AL). The ABO blood groups of 109 male and 79 female patients with AL (98 ALL, 90 AML) were compared with those of 1019 controls. In the control population, 39.7% were group O. Among males with AL, 39.4% were group O, whereas among females with AL, the proportion was 24.1% (p=0.03). The same trend to a lower proportion of group O among females was seen if the group was divided into adult/pediatric or lymphoblastic/myeloblastic groups, though these differences were not statistically significant. If these findings can be confirmed, they suggest the presence of a "sex-responsive" gene near to the ABO gene locus on chromosome 9, which relatively protects group O women against AL, at least in our population. The existence of such a gene might also partly explain why acute leukemia, and possibly other childhood cancers, are more common in males.
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  • 46
    ISSN: 1423-0127
    Schlagwort(e): Tax ; HTLV-1 ; Trans-activation ; Phosphorylation ; Mutagenesis ; Transcription ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The human T cell leukemia virus type 1 (HTLV-1) Tax is a phosphoprotein, however, the contribution of phosphorylation to Tax activity is unknown. Previous studies have shown that phosphorylation of Tax occurs on serine residue(s), within one tryptic fragment, in response to 4β-phorbol-12β-myristate-13α-acetate, in both mouse and human cells. Studies were conducted in multiple cell lines to identify the specific phosphorylated serines as a prelude to functional analysis. The phosphorylation pattern of Tax was found to be different in 293T and COS-7 cells in comparison with MT-4 and Px-1 cells. However, one tryptic fragment remained consistent in comigration analyses among all cell lines. Using selected Tax serine mutants a tryptic fragment containing a serine at residue 113 believed to be the site of phosphorylation of Tax did not comigrate with the common phosphorylated tryptic fragment. Analysis of selected Tax mutants for ability totrans-activate the cytomegalovirus promoter demonstrated mutation of serine 77 to alanine reducedtrans-activation by 90% compared to wild-type Tax. However, examination of the phosphorylation pattern of the serine 77 mutant demonstrated that it is not the site of phosphorylation. These studies demonstrate the importance of using relevant cell lines to characterize the role of phosphorylation in protein function.
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  • 47
    ISSN: 1432-1963
    Schlagwort(e): Schlüsselwörter Rhadomyosarkom ; Klassifizierung ; Immunhistochemie ; Genetik ; Prognose ; Key words Rhabdomyosarcoma ; Classification ; Immunohistochemistry ; Genetics ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary Rhabdomyosarcoma (RMS) is the most important and a very heterogeneous group of malignant soft tissue tumors of childhood and adolescence.The two major subtypes (embryonal and alveolar) share a common myogenic differentiation, but seem to be histogenetically not related. The so-called ’International Classification of Rhabdomyosarcoma’ includes, besides the two major subtypes, the botryoid and leiomyomatous subtypes of embryonal RMS which are associated with a better prognosis and are treated less aggressively according to current protocols. In addition, the solid variant of alveolar RMS is included in the alveolar group of RMS. The identification of the various subtypes is necessary and important because the treatment with the current protocols is also related to histology. Using conventional stains and immunohistochemistry, these subtypes are distinguishable. Genetic analysis can be helpful in the demonstration of t(2;13) or t(1;13) translocations in alveolar RMS. The identification of alveolar RMS with t(1;13) translocation might become important in the future, because this type of translocation seems to be related to a better prognosis as compared to tumors with a t(2;13) translocation.
    Notizen: Zusammenfassung Rhabdomyosarkome stellen eine heterogene Gruppe von ganz verschiedenartigen, histogenetisch wohl nicht zusammengehörenden Tumoren dar. Nach der heute verwendeten „Internationalen Klassifikation” der Rhabdomyosarkome werden neben der Unterteilung in embryonalen und alveoläre Rhabdomyossarkome auch Subtypen des embryonalen RMS identifiziert (botryoider und leiomyomatöser Subtyp), die durch eine günstigere Prognose und durch die Notwendigkeit einer weniger aggressive Therapie gekennzeichnet sind. Durch Einsatz von verschiedenen histologischen und immunhistochemischen Färbungen ist die Identifizierung der verschiedenen Typen der RMS heute möglich und auch zwingend notwendig, da die einzelnen Entitäten nach ganz unterschiedlichen Therapieprotokollen behandelt werden. Der Nachweis typischer molekulargenetischer Veränderungen kann in der Unterscheidung insbesondere von embryonalen und alveolären RMS hilfreich sein. In der Regel ist die Abgrenzung zwischen diesen beiden Entitäten auch an konventionell gefärbten Schnittpräparaten möglich. Die Identifizierung von alveolären RMS mit einer t(1;13)-Translokation könnte in Zukunft eine große Bedeutung haben, da diese genetische Veränderung möglicherweise mit einer günstigeren Prognose assoziert sein könnte als die t(2;13)-Translokation.
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  • 48
    Digitale Medien
    Digitale Medien
    Springer
    European journal of pediatrics 158 (1999), S. 302-307 
    ISSN: 1432-1076
    Schlagwort(e): Key words Congenital heart disease ; Pulmonary atresia and ventricular septal defect ; Genetics ; Monosomy 22q11.2
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The purpose of our study was to describe the prevalence and the clinical spectrum of monosomy 22q11.2 in a population of patients with pulmonary atresia and ventricular septal defect. We examined all 44 patients with this conotruncal cardiac malformation who presented to our institution from January 1994 until December 1997. The type of collateral lung perfusion was recorded including anomalies of the pulmonary arteries as well as facial and immunological abnormalities. Molecular-cytogenetic testing for a 22q11.2 microdeletion was performed using the probes D22S75 and cHKAD26. Statistical differences were evaluated with the Fisher's Exact Test. Monosomy 22q11.2 was present in ten children (23%) with major aortopulmonary collateral arteries (group 1). The remaining 13 children (29%) with major aortopulmonary collateral arteries (group 2) and all 21 children (48%) with ductus arteriosus (group 3) were negative for this microdeletion. All children in group 1 had facial anomalies, six had mild immunological abnormalities including decreased CD 4+ or CD 8+ cells. Anomalies of the pulmonary vascular bed were significantly more frequent in children of group 1 (9/10) than in children of group 2 (4/13) or group 3 (0/21). Due to these pulmonary vascular anomalies, corrective surgery had been accomplished in fewer children with monosomy 22q11.2 (none in group 1) as compared to 7/13 children in group 2 and 14/21 children in group 3. Conclusion In children with pulmonary atresia and ventricular septal defect, monosomy 22q11.2 is preferentially associated with major aortopulmonary collateral arteries. Due to the higher incidence of pulmonary arterial abnormalities, successful surgical repair will require a different therapeutic approach in most patients with this microdeletion.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    Current genetics 35 (1999), S. 571-584 
    ISSN: 1432-0983
    Schlagwort(e): Key words Cytokinesis ; Kinase ; Mitosis ; Schizosaccharomyces pombe ; Cell division ; Phosphatase ; Mutant ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The fission yeast Schizosaccharomyces pombe provides a simple eukaryotic model for the study of cytokinesis. S. pombe cells are rod-shaped, grow mainly by elongation at their tips, and divide by binary fission after forming a centrally placed division septum. Analysis of mutants has begun to shed light upon how septum formation and cytokinesis are regulated both spatially and temporally. Some of the proteins involved in these events have been functionally conserved throughout eukaryotic evolution, suggesting that aspects of this control will be common to all eukaryotic cells.
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neurology 246 (1999), S. 1140-1144 
    ISSN: 1432-1459
    Schlagwort(e): Key words Amyotrophic lateral sclerosis ; Genetics ; Glutamate transporter gene
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder characterised by degeneration of upper and lower motor neurons. Whilst the primary pathogenic trigger is unknown in most cases, evidence is mounting to implicate a role for glutamate-mediated neurotoxicity in the disorder. Recent studies have shown reduced levels of the mainly astroglial glutamate transporter EAAT2 in ALS motor cortex and spinal cord and multiple abnormal EAAT2 mRNA species in ALS brain tissue. One cause of the low EAAT2 levels may be that point mutations in the EAAT2 gene, EAAT2, result in an abnormal unstable protein. To test this hypothesis we analysed EAAT2 in 128 sporadic and 23 familial European ALS cases. No variants within the coding sequence of EAAT2 to affect the protein sequence nor in the consensus splice sites of the flanking intronic sequences were found in any cases, similar to findings in other reports. Frequent polymorphisms within the flanking intronic sequences of both exons 2 and 4 were seen but at similar frequencies in controls. Mechanisms other than mutations within the coding region of EAAT2 must therefore be responsible for the low levels of EAAT2 seen in most cases of ALS.
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    International journal of colorectal disease 14 (1999), S. 2-9 
    ISSN: 1432-1262
    Schlagwort(e): Key words Inflammatory bowel disease ; Crohn's disease ; Ulcerative colitis ; Epidemiology ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Inflammatory bowel diseases (IBD) are complex disorders. While the exact etiology of these diseases remains unknown, recent progress in the epidemiology and genetics of IBD has clearly demonstrated both environmental and genetic factors to play a role in the development of the disease, and it is expected that some risk factors are common for both Crohn's disease (CD) and ulcerative colitis (UC). The environmental factor(s) are associated with the Western way of life in the second half of the twentieth century. Cigarette smoking is presently the best known environmental factor. However, the effect of tobacco is opposite in CD and UC. A familial history of IBD is the most important risk factor for developing the disease, suggesting a genetic predisposition to IBD. This hypothesis has recently been confirmed by the localization of at least two susceptibility loci on chromosomes 12 and 16. These genes seem to play a role in both CD and UC. They must now to be identified.
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    Child's nervous system 15 (1999), S. 676-680 
    ISSN: 1433-0350
    Schlagwort(e): Key words Craniosynostosis ; Genetics ; FGFR ; Msx2 ; Development ; Skull
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The genetic studies of syndromic craniosynostoses lead to the characterisation of genes that regulate the correct development of the bones of the skull. From these studies, it appears that FGF/FGFR signalling has a crucial role in this problem. Numerous mutations affecting the genes coding for FGFR1, 2 or 3 are responsible for these syndromes. It is interesting to note that some identical mutations produced various different phenotypes, suggesting that other genes modulate the phenotypic expressivity. The other involved genes in these syndromes code for such proteins as Msx2 or Twist that interact in the cellular pathways responsible for FGF action. From these genetic studies, it is now important to establish the role of these proteins during the development of the skull. Msx2 plays a repressive role in osteogenesis, whereas FGFRs act as promoting proteins. In the near future, it will be very important to improve our understanding of these phenomena in order to test specific treatments to prevent the development of such syndromes.
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neurology 246 (1999), S. 69-72 
    ISSN: 1432-1459
    Schlagwort(e): Key words Alzheimer’s disease ; Genetics ; Genetic counseling ; Predictive testing ; Diagnosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Alzheimer’s disease (AD) has a significant genetic background manifested as autosomal dominant inheritance in some early-onset families and as familial risk in late-onset cases. Three genes responsible for early-onset autosomal dominant AD have been identified, and one gene, apolipoprotein E, has been confirmed as a susceptibility gene for late-onset forms of the disorder. These findings raise the possibility of genetic testing, either for early diagnosis or prediction. For early-onset autosomal dominant AD genetic testing will have a limited but useful role in confirming diagnosis in established cases and in predictive counselling for relatives; a situation analogous to that for Huntington’s disease. For late-onset AD significant problems remain to be overcome before the advances in molecular genetics have a direct clinical application
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  • 54
    ISSN: 1432-5233
    Schlagwort(e): Key words Mitochondrial DNA ; Genetics ; Maternally inherited diabetes mellitus ; Deafness ; np 3243 mutation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Mitochondrial DNA (mtDNA) gene defects may play a role in the development of maternally inherited diabetes mellitus and deafness (MIDD). A family from Southern Italy who showed maternal transmission of type 2 diabetes mellitus with three individuals affected is described. A 10.4 kb deletion and mutations at nucleotide positions (np) 3243, 7445 and 11778 in the mtDNA of six relatives were sought. The mitochondrial np 3243 mutation of the tRNA Leu (UUR) gene was identified in a boy affected by optic atrophy and mental retardation, as well as in his diabetic mother. No other mutations or deletions were found. Our study points out the variable phenotypic expression of the np 3243 mtDNA mutation. This may suggest the presence of other mitochondrial or nuclear mutations required to modulate the phenotype. A clinical and metabolic follow-up of all family members was necessary to understand the role of the np 3243 mutation, especially in one child affected by optic atrophy and mental retardation. Further studies will be aimed at investigating the prevalence of mutations and deletions of mtDNA in type 2 diabetes mellitus.
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  • 55
    ISSN: 1432-2242
    Schlagwort(e): Key words Passiflora ; Self-incompatibility ; Genetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  The self-incompatibility in yellow passion fruit was previously described as homomorphic sporophytic with monofactorial inheritance. Five progenies were obtained by bud-selfing. The plants of these progenies were selfed, reciprocally crossed within each progeny and crossed with known incompatible phenotypes to identify their phenotypic group. Fruit set was evaluated at the 7th day after pollination. Two progenies consisted of two self-incompatible groups, the other three formed three suck groups. The groups were identified as S1, S2, S3, S4, S5 and S6. The results provide evidence that the self-incompatibility of passion fruit is controlled by two loci, the S-gene and another, whose expression needs to be investigated.
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  • 56
    ISSN: 1432-2242
    Schlagwort(e): Key words Simple sequence repeat (SSR) ; Microsatellites ; Molecular markers ; Genetics ; Fingerprinting
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  We report the sequences of 17 primer pairs of microsatellite loci, which we have cloned and sequenced from two genomic libraries of peach [Prunus persica (L) Batsch] ‘Redhaven’, enriched for AC/GT and AG/CT repeats respectively. For ten of these microsatellite loci we were able to demonstrate Mendelian inheritance in a segregating back-cross population; the remainder did not segregate. The polymorphism of the microsatellites was evaluated in a panel of ten peach genotypes, including true-to-type peaches, nectarines and one canning-peach. Fifteen microsatellites (88%) were polymorphic showing 2–4 alleles each. The mean heterozygosity, averaged over all loci, was 0.32 and significantly higher than that reported in the literature for isozymes and molecular markers, such as RFLPs and RAPDs. We have also assayed the cross-species transportability and found that ten microsatellite (59%) gave apparently correct amplification in all Prunus species surveyed, namely P. domestica (European plum), P. salicina (Japanese plum), P. armeniaca (apricot), P. dulcis (almond), P. persica var. vulgaris (peach), P. persica var. laevis (nectarine), P. avium (sweet cherry) and P. cerasus (sour cherry), with three of them also being amplified in Malus (apple). The remaining microsatellites gave less-extensive amplification. Because of their appreciable polymorphism and wide cross-species transportability, most of these new markers can be integrated into the linkage maps which are currently being constructed in peach, as well as in other stone fruit crops, such as almond, apricot, cherry and plum.
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    Theoretical and applied genetics 99 (1999), S. 800-810 
    ISSN: 1432-2242
    Schlagwort(e): Key words Almond ; Compatibility ; Genetics ; Prunus dulcis ; Ribonucleases
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  Six almond progenies, each the product of a cross between a self-compatible and a self-incompatible parent, were analysed for stylar ribonucleases. Proteins were extracted and separated using non-equilibrium pH gradient electrofocusing (NEPHGE), and the gels were stained for ribonuclease activity. Most seedlings showed either two principal bands, interpreted as corresponding to two incompatibility alleles, or a single band. The seedlings were also bagged in the field at flowering time to determine fruit set after selfing, and some were also examined for the growth of pollen-tubes in selfed styles using UV fluorescence microscopy. With very few exceptions, those seedlings showing single-banded zymograms were found to be self-compatible according to field and microscope studies, and those with two bands were found to be self-incompatible. We conclude that the allele for self-compatibility in almond does not code for ribonuclease activity and that the ribonuclease isoenzyme assay is a convenient technique for predicting self-compatibility in segregating progenies. A novel band in two derivatives of ’Ferrastar’ was ascribed to a new incompatibility allele, S 10 .
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    Behavioral ecology and sociobiology 46 (1999), S. 171-179 
    ISSN: 1432-0762
    Schlagwort(e): Key words Honeybee ; Apis mellifera ; Division of labor ; Genetics ; Pollen foraging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  A fundamental requirement of task regulation in social groups is that it must allow colony flexibility. We tested assumptions of three task regulation models for how honeybee colonies respond to graded changes in need for a specific task, pollen foraging. We gradually changed colony pollen stores and measured behavioral and genotypic changes in the foraging population. Colonies did not respond in a graded manner, but in six of seven cases showed a stepwise change in foraging activity as pollen storage levels moved beyond a set point. Changes in colony performance resulted from changes in recruitment of new foragers to pollen collection, rather than from changes in individual foraging effort. Where we were able to track genotypic variation, increases in pollen foraging were accompanied by a corresponding increase in the genotypic diversity of pollen foragers. Our data support previous findings that genotypic variation plays an important role in task regulation. However, the stepwise change in colony behavior suggests that colony foraging flexibility is best explained by an integrated model incorporating genotypic variation in task choice, but in which colony response is amplified by social interactions.
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  • 59
    ISSN: 1612-1112
    Schlagwort(e): Review ; Capillary electrophoresis ; DNA ; Oligonucleotides ; Pluronic polymers ; Liquid crystals ; Micelles
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary The liquid crystalline gel phases of solutions of Pluronic F127, a triblock copolymer, were recently introduced as an alternative to disordered solutions of random coil polymers as replaceable media for capillary gel electrophoresis (CGE). Pluronic F127, from BASF, is a copolymer of poly(ethylene oxide) and poly(propylene oxide) with the approximate formula (EO)106 (PO)70 (EO)106. Polymer chains aggregate into spherical micelles in aqueous solutions, with poly(propylene oxide) chains creating a hydrophobic core surrounded by brushes of hydrated poly(ethylene oxide) tails. Crowding at high concentrations promotes ordering of micelles. Solutions in the range of about 14–24 % polymer are self-supporting, gel-like cubic liquid crystals at 25–30°C, but when cooled they become low viscosity liquids that are easily loaded into capillaries. This article reviews applications of Pluronic F127 media for capillary gel electrophoresis separations of nucleic acids of several types including oligonucleotides, double stranded DNA fragments, and supercoiled plasmid DNAs.
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 49 (1999), S. S79 
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Diagnosis of myelomatosis ; Metabolic disorders ; Serum proteins ; CE-MS
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary CE is used both for routine clinical analysis and for specialized clinical investigations. CE analysis of serum proteins is fast and reliable, with immunosubtraction for identification of immunoglobulins. This method was used to show the appearance of a pathological protein many years prior to the diagnosis of myelomatosis. CE with diode array detector and CE-MS were suitable for the diagnosis of a number of metabolic disorders. Online analyte concentrators are sometimes required to enhance the concentration sensitivity of CE.
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 49 (1999), S. S87 
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Electrospray-ionization ; Ion trap mass spectrometry ; Separation of compounds
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary Capillary electrophoresis (CE) coupled with mass spectrometry (MS) has proven a powerful alternative to conventional chromatographic separation techiques. Here the analysis of various compounds with a novel CE ESI sprayer and an ion trap mass analyzer is described.
    Materialart: Digitale Medien
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  • 62
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Anions ; System peaks
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary This study deals with the simultaneous analysis of UV-transparent anions by capillary electrophoresis with indirect UV-detection. With a background electrolyte (BGE) based on UV-absorbing chromate and UV-transparent borate, the interference of system peaks with those of sample anions (chloride, sulfate, citrate, phosphate) is shown. The existence of such system peaks, and their position in relation to the peaks of the sample anions, are explained on the basis of the eigenpeak theory proposed by Poppe [1]. With this BGE the system peaks were manifested as a negative peak followed by a positive peak. Their shapes depended on the relative mobilities of the analyte and BGE anions and their areas depended on the amount of sample. The mobility of the system peak depends on the borate/boric acid mobility, which was adjusted by slight variation of the pH close to its pK a-pH is the key factor governing system-peak mobility. When the locations of the system peaks are optimized, the quantification of citrate can be achieved; this was successfully used for determination of anions in milk.
    Materialart: Digitale Medien
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 49 (1999), S. 343-346 
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Frontal analysis ; Binding constants ; Basic drugs ; Human serum albumin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary The applicability of capillary electrophoresis/frontal analysis (CE/FA) for determining the binding constants of the drugs propranolol (PRO) and verapamil (VER) to human serum albumin (HSA) was investigated. After direct hydrodynamic injection of a drug-HAS mixture solution into a coated capillary (32 cm × 50 μm i.d.), the basic drug was eluted as a zonal peak with a plateau region under condition of phosphate buffer (pH 7.4; ionic strength 0.17) at 12 kV positive running voltage. The unbound drug concentrations measured from the plateau peak heights had good correlation coefficients,r〉0.999. Employing the Scatchard plot, the Klotz plot and nonlinear regression, the drug protein binding parameters, the binding constant and the number of binding sites on one protein molecule, were obtained. The binding constant obtained was compared to a reported equilibrium dialysis result and they are basically in good agreement.
    Materialart: Digitale Medien
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 49 (1999), S. 379-384 
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Nucleotides ; Cadmium complexation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary The CE separation of twelve nucleotides (5′-mono-, di-, triphosphates of adenosine, guanosine, cytidine and uridine) was improved by adding cadmium ion to the ammonium citrate/citric acid buffer (pH 5, ionic strength 100 mM). Cadmium ion acts as a complexing agent for some nucleotides (ATP, CTP, GTP, UTP, GDP). In order to accelerate the separation, the electroosmotic flow was reversed by flushing the fused-silica capillary with 0.2 % aqueous solution of the polycationic surfactant hexadimethrine bromide. A good separation of the twelve nucleotides studied was then achieved on a dynamically coated capillary in less than 5 min by using an ammonium citrate/citric acid buffer (pH 5, ionic strength 100 mM) to which 2 mM cadmium ion has been added. High peak efficiencies were obtained (210 000 theoretical plates) and the resolution between two adjacent peaks was always greater than 1.5.
    Materialart: Digitale Medien
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  • 65
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 49 (1999), S. 406-410 
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Pharmaceutical Analysis ; Lactose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary A CE method has been validated for the analysis of batches of lactose used as a pharmaceutical raw material. This method was shown to be selective for lactose and was found to be quantitative. The separation was achieved due to on-capillary chelation of the lactose with borate ion. The resulting complex was detected at 195nm. An internal standard is employed to improve injection precision and detector linearity. A system peak occurred in the separation and was systematically investigated to show that it was not sample related. The method was validated and successfully submitted to regulatory authorities and is now in routine use in a number of our quality control laboratories.
    Materialart: Digitale Medien
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 49 (1999), S. 28-34 
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Membrane proteins ; Serine receptor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary Capillary zone electrophoresis (CZE) was applied to the characterization of the transmembrane serine receptor in biosynthetic samples. The serine receptor, otherwise known as Tsr (taxis to serine and repellents), is a ∼ 60,000 Dalton intrinsic membrane protein whose periplasmic domain (ligand binding domain) reversibly binds the amino acid serine. In general, the electrophoresis of intrinsic membrane proteins is difficult due to severe solubility problems and adsorption which occurs during the electrophoretic run. This is due to the tendency of these types of proteins to undergo aggregation, self-aggregation and precipitation in aqueous environments. The addition of percentage levels of the surfactant, sodium dodecyl sulfate (SDS), to a tetraborate run buffer was shown to be effective both in enhancing the solubility of intact Tsr and in preventing the adsorption of intact Tsr to the fused-silica capillary wall during electrophoretic analysis. Critical separation parameters such as run buffer concentration, surfactant concentration and surfactant type were optimized to give the best separation profiles.
    Materialart: Digitale Medien
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  • 67
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Micellar electrokinetic capillary chromatography ; Nonaqueous media ; Tropane alkaloids ; Hyoscyamine and scopolamine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary The potential of nonaqueous capillary electrophoresis has been investigated for the separation of structurally similar tropane alkaloids. The effects of the organic solvent and of electrolyte composition on separation selectivity, migration times, and efficiency are described. The addition of trifluoroacetic acid to the separation buffer was found beneficial for manipulation of the order of migration of the two positional isomers littorine and hyoscyamine. Replicate injections under nonaqueous conditions gave migration time and peak area data of excellent precision. The application of the optimized conditions to the analysis of hyoscyamine and scopolamine in genetically transformed root cultures ofDatura candida x D. aurea is presented.
    Materialart: Digitale Medien
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 49 (1999), S. 71-74 
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Serum analysis ; Total iron binding capacity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary A capillary electrophoresis (CE) technique for determining total iron binding capacity (TIBC) of serum has been developed. The optimum serum pretreatment involves the following major steps: at first, saturate serum transferrin with Fe+3; then, dissociate them completely after removing excess unbound Fe. Finally, complex the released iron with phenanthroline, a chromophore, to make suitable for the CE analysis. Ammonium acetate (pH=5.0) was used as CE background electrolyte solution. In this system, a good linear correlation coefficient was maintained over the range 0.5≈10 μM (r=0.9979,n=12). Seven adult serum samples were studied and the TIBC parameters measured. In the present system, 10≈30 μL serum is sufficient for determination. The study shows that the CE technique described is a powerful method for rapid, efficient, sensitive and reliable analysis and hence particularly suitable for clinical application.
    Materialart: Digitale Medien
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 49 (1999), S. S12 
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Field-amplified sample stacking ; Water plug ; Drugs in biological fluids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary Strategies to improve the sensitivity of drug monitoring in microliter amounts of biological fluids by capillary electrokinetic methods are currently being explored in our laboratory. Head-column field-amplified sample stacking is the most effective method of sensitivity enhancement—this approach is robust and highly reproducible when applied correctly. For analysis of opioids as standards or in plasma extracts by binary capillary electrophoresis with ethylene glycol, the data presented in this work unambiguously demonstrate that the water plug initially inserted at the column inlet is essential for establishing a steady current during separation, and thus the highest reproducibility. Internal calibration shows thatRSD imprecision values otherwise up to approximately 30% are reduced to values significantly below 10%. The water plug also results in higher detector responses at elevated solute levels (≥100 ng mL−1) and leads to increased sensitivity when the sample (standards and extracts of body fluids) is dissolved in water. The water plug does not, however, furnish higher sensitivity in the analysis of opioids as standards or in plasma extracts that are prepared in the optimized sample solvent or buffer. The optimum length of the water plug cannot, furthermore, be obtained merely by dipping the capillary inlet into water (insertion of water by capillary action). The water zone obtained in this way must be elongated by approximately 0.6 mm by deliberate hydrodynamic introduction of additional water from a different vial. These head-column field-amplified sample-stacking conditions are shown in operation on two different commercial instruments. As an illustration, data are presented depicting the analysis of dihydrocodeine and nordihydrocodeine in plasma and urine specimens of individuals to which dihydrocodeine was administered.
    Materialart: Digitale Medien
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  • 70
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Anion exchange chromatography ; Carbohydrate ; Derivatization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary The derivatization process of malto-oligosaccharides by means of reductive amination for the subsequent separation by capillary electrophoresis (CE) is investigated. Aminonaphthalene-disulfonic acid was used as derivatization agent for this purpose. The molecular weight distribution found by CE differed significantly from that measured by anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD). While the proportion of maltodextrins with lower molecular weight was higher in CE than in HPAEC-PAD, the opposite hold for oligomers with higher molecular weights. An investigation of the derivatization process provided strong indications that degradation of higher molecular weight oligomers could be the reason for these differences. The derivatization process was optimized with respect to minimal degradation expressed as the peak area ratio of maltose to maltoheptaose at simultaneously maximal reaction rate expressed as the peak area of maltoheptaose by using a Box-Behnken design. It was found that only a compromise allowed both sufficient reaction turnover and low degradation of the oligomers. This technique could be employed successfully to analyze maltodextrins and oligomannans in coffee.
    Materialart: Digitale Medien
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  • 71
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Coelectroosmotic flow ; Osmotic modifiers ; Aromatic sulphonate compounds ; Organic solvents
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary Coelectroosmotic capillary zone electrophoresis (CZE) has been investigated as a means of rapid analysis of twelve aromatic sulphonate compounds. The main factors affecting reversal of electroosmotic flow (EOF)—type of osmotic modifier and concentration-were studied. Two types of osmotic modifier, an alkylammonium salt (cetyltrimethylammonium bromide, CTAB) and a cationic polyelectrolyte (hexadimentrine bromide, HDB) were investigated. The composition of the running buffers was optimized according to the characteristics of each osmotic modifier. A concentration of HDB as low as 0.0001% (w/v) was used successfully to provide a stable and reversed EOF.
    Materialart: Digitale Medien
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  • 72
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 49 (1999), S. 299-305 
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Column technology ; Deactivation ; Polyethyleneoxides ; Ribonucleotides
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary In this study, a variety of fused silica capillaries with different combinations and sequences of treatments with HMDS and polyethylene oxide were prepared in order to develop an optimized column modification method for analysis of ribonucleotides. The 12 most common ribonucleotides (UTP, CTP, ATP, GTP, UDP, CDP, ADP, GDP, UMP, CMP, AMP, and GMP) in human cells were used as test solutes. Column performance measurements, including electroosmotic flow (EOF), solute migration speed and retention, column efficiency, peak shape, and resolution were investigated. By analyzing solute migration speed and retention of various hydrophilic/hydrophobic solutes, the column wall effects (EOF and adsorption) can be distinguished. This analysis method can give guidance in optimizing polymer coating properties (hydrophilicity/hydrophobicity) for CE columns. By studying the performance of these columns after various surface treatments, we were able to improve the separation of ribonucleotides from real samples to within 16 minutes with high efficiency and stability (over 300 analyses) using columns first deactivated with hexamethyldisilazane, and then coated with polyethylene oxide.
    Materialart: Digitale Medien
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  • 73
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Ion chromatography ; Carbon disulphide in air ; Alkyl xanthogenates
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary A simple and sensitive method is presented for the measurement of carbon disulphide in air without interference from other gaseous sulphides. The procedure is based on the collection of CS2 in an ethanolic solution of KOH, where it is converted to potassium ethyl xanthogenate (PEX). The latter is determined by high-performance ion chromatography (HPIC) and/or capillary zone electrophoresis (CZE). Laboratory and field determination of detection limit, reproducibility and linearity, and specific advantages over other gas chromatographic and wet chemical methods, are discussed. Quantitative measurements of CS2 in air can be performed after sampling for 1 h with limits of detection as low as 15 ppb by HPIC and ca 0.1 ppm by CZE.
    Materialart: Digitale Medien
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  • 74
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Nonaqueous electrolytes ; N-Methylformamide ; UV-detection ; Pyridinyl-methyl-sulfinyl-benzimidazoles
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary A screening method using nonaqueous capillary electrophoresis (NACE) has been developed for purity analysis of pyridinyl-methyl-sulfinyl-benzimidazoles (PMSB). Eight different polar organic solvents were tested as background electrolytes.N-Methylformamide (NMF) was found to have the best properties in respect of both electrophoretic behavior and high solubility of five different model compounds. Optimization of the CE separation with regard to the effects of addition of various electrolyte modifiers is reported. An additional feature of amide solvents, rarely utilized in CE, is their intrinsic basic nature; this is of particular interest for analysis of compounds such as the PMSB, the degradation of which is acid-catalyzed. It is shown here that these compounds are stable at room temperature for weeks in NMF solution. Results from quantitative application of the NACE method were highly precise (typically 1.8%RSD for normalized peak area); linearity was good and detection limit in drug purity determination was low (∼0.05 area % relative to the drug compound).
    Materialart: Digitale Medien
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    Chromatographia 49 (1999), S. S73 
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Electrospray-ionization ; Mass spectrometry ; Orthogonal spray ; Peptides
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary Capillary electrophoresis (CE) with tandem UV and MS detection is increasingly being used for the analysis of complex mixtures. Here the analysis of peptides by CE-ESI-MS with a fully automated system is described.
    Materialart: Digitale Medien
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  • 76
    ISSN: 1612-1112
    Schlagwort(e): Capillary electrophoresis ; Chiral separation ; Neutral cyclodextrins ; Clorprenaline and other chiral drugs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Summary Neutral cyclodextrin (CD)-modified capillary zone electrophoresis (CZE) has been applied to the chiral separation of four basic drugs— clorprenaline, benzhexol, esmolol and terazosin. Selector screening and concentration optimization experiments were performed. The resolution was 3.9 for clorprenaline, 2.3 for benzhexol, 3.1 for esmolol and 1.2 for terazosin when the running electrolyte was 60 mM hydroxypropyl-β-CD, 15 mM heptakis (2,3,6-Tri-O-methyl)-β-CD, 60 mM γ-CD and 60 mM heptakis (2,6-di-O-methyl)-β-CD, respectively, in 50 mM, pH 2.5 sodium phosphate buffer.
    Materialart: Digitale Medien
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  • 77
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 22 (1999), S. 33-38 
    ISSN: 0935-6304
    Schlagwort(e): Capillary electrophoresis ; chiral separation ; negatively charged chiral selectors ; capillary filling methods ; dual systems ; Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: ---Data on the use of two chiral selectors, namely 18-crown-6 tetracarboxylic acid and a negatively charged cyclodextrin derivative (sulfated-β-cyclodextrin or carboxymethyl-β-cyclodextrin), in the same background electrolyte are presented. The use of such dual systems has a considerable influence on the resolution, as illustrated for the separation of tryptophan derivatives. Reduction of the consumption of chiral selector without significant loss in resolution was obtained by only partly filling the capillary and applying a run buffer without selector. This is illustrated for the chiral separation of tryptophan hydroxamate and the diastereomeric and enantiomeric separation of the dipeptide α/b-AspPhe-OMe.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
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  • 78
    ISSN: 0935-6304
    Schlagwort(e): Capillary electrophoresis ; interfacing ; sample treatment ; serum ; solid-phase extraction ; sulfonamides ; urine ; Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: ---No abstract
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
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  • 79
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 22 (1999), S. 449-453 
    ISSN: 0935-6304
    Schlagwort(e): Capillary electrophoresis ; experimental design ; cyclodextrin ; chiral separation ; Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: ---Orthogonal design and uniform design were used for the optimization of separation of enantiomers using 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD) as a chiral selector by capillary zone electrophoresis. The concentration of DM-β-CD, buffer pH, running voltage, and capillary temperature were selected as variable parameters, their different effects on peak resolution were studied by the design methods. It was concluded that orthogonal design offers a rapid and efficient means for testing the importance of individual parameters and for determining the optimum operating conditions. However, for a large number of both factors and levels, uniform design is more efficient. The effect of addition of methanol and citric acid buffer on the separation of enantiomers was also examined.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
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  • 80
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 22 (1999), S. 39-42 
    ISSN: 0935-6304
    Schlagwort(e): Capillary electrophoresis ; CE ; chemical migration ; food contact plastics ; dihydroxybenzenes ; packaging ; Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: ---A capillary electrophoresis method has been developed to determine 1,2-dihydroxybenzene and 1,3-dihydroxybenzene in the food simulants distilled water, 3% acetic acid, 15% ethanol, and olive oil. Both substances, used as monomers and additives to make food packaging plastics, could be analyzed within 15 min. The 1,4-dihydroxybenzene isomer was unretained and eluted with the electroosmotic flow, and so the CE method can give only a semi-quantitative estimate of this isomer if it is present as a migrant. The analytical recovery for the 1,2- and 1,3-isomers from spiked simulants was good at 87% to 98% except for 1,2-dihydroxybenzene which could only be recovered to the extent of 58% from olive oil. Calibration graphs were linear and the limit of detection for each substance was 0.6 mg/kg, which is well below migration limits for these substances. It is concluded that CE offers a rapid and reliable analysis for the control of migration from plastics intended for food contact which employ 1,2-dihydroxybenzene or 1,3-dihydroxybenzene during manufacture, and offers a screening method for 1,4-dihydroxybenzene migration.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
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  • 81
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 22 (1999), S. 79-82 
    ISSN: 0935-6304
    Schlagwort(e): Capillary electrophoresis ; thickeners ; monosaccharides ; PMMA capillaries ; Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: ---Gelling agents based on polysaccharides have become extremely important in the food industry. As more and more products like soups and sauces have become available in lyophilized form, thickeners have to be added to give a controlled consistency to the finished meal. A capillary electrophoretic method has been developed to investigate the monosaccharide composition of hydrolyzed thickeners. 2-Aminoanthracene was used as a derivatization reagent to allow sensitive fluorescence detection. This system was applied to a set of standard thickeners as well as to food samples.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
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  • 82
    ISSN: 0935-6304
    Schlagwort(e): Capillary electrophoresis ; conductivity detection ; inorganic anions ; organic acids ; electrodipcoats ; Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: ---No abstract
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
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  • 83
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 4-4 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Materialart: Digitale Medien
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  • 84
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 6-11 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: Irgendwie wird niemand mehr richtig glücklich mit der Wissenschaft, so erfolgreich sie auch ist und so sehr unsere alltäglichen Verrichtungen von ihren Ergebnissen und Lieferungen auch abhängen. Das Verständnis der öffentlichen Beobachter nimmt trotz aller Bemühungen nicht zu, sondern ab, und die professionellen Betreiber sehen sich unentwegt nach ihrer Verantwortung gefragt und in ethische Debatten verstrickt. Die ursprüngliche Idee, daß Wissenschaft nur gut sein kann, hat massiv an Überzseugungskraft verloren, und dieser Verlust tritt deshalb besonders deutlich hervor, weil man spürt, wie die alte Basis der Rationalität brüchig geworden ist, ohne einen neuen Grund zu erkennen, auf den man in Zukunft bauen kann. Dabei übersehen wir ein Fundament, auf dem Menschen immer schon gestanden haben und zu dem sie also auch zu jeder Zeit wieder zurückkommen können.
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
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  • 85
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 18-25 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: Gallmücken (Cecidomyiidae) sind unter den Insekten die häufigsten Verursacher von Vergallungen an Pflanzen. Diese morphologischen Veränderungen von Pflanzenteilen sind die Folge begrenzter Wachstumsreaktionen des Pflanzegewebes (Hypertrophien). Gallen sind nicht nur Lebensräume des Gallinsektes, sondern stellen Mikroökkosysteme dar, in denen sich Beziehungen zwischen dwen beteiligten Organismen abspielen können.Eine sowohl für Entomologen als auch für Mykologen besonders interessante Sonderform dieser Lebensgemeinschaften sind Pflanzengallen, in denen neben dem Gallerreger regelmäßig das Mycel bestimmter Pilze zu finden ist (Abbildungen 1a und b). Untersuchungen an der Fruchtgalle der Gallmücke Asphondylia melanopus an Wiesen-Hornklee (Lotus corniculatus) deuten darauf hin, daß das Zusam menleben von Insekt und Pilz alles andere als zufällig ist.
    Zusätzliches Material: 9 Ill.
    Materialart: Digitale Medien
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  • 86
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 26-35 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: Alle höheren Wirbeltiere besitzen ein ausgefeiltes Immunsystem, das im wesentlichen zwei Aufgaben hat: den Organismus vor Infektionen durch Krankheitserreger zu Schützenund den Organismus von entarteten Tumorzellen zu befreien.Um diese Aufgabe zu bewältigen, hält das Immunsystem die weißen Blutkörperchen oder Leukozyten parat: Makrophagen und Granulozyten vernichten eingedrungene Erreger. Lymphozyten produzieren Antikörper (B-Zellen), welche die Erreger neutralisieren; sie sezernieren Zytokine (T-Helferzellen), welche die Immunreaktion gergen den Erreger koordinieren, oder sie wirken als Killerzellen (T-Killerzellen), die in virusinfizierten Zellen und Tumorzellen den programmierten Zelltod (Apoptose) auslösen.Aus ihrem Aufenthaltsort - die Leukozyten zirkulieren passiv im Blutgefäßsystem - ergibt sich ein prinzipielles Problem. I nfektionen oder Zellentartungen entstehen in den meisten Fällen nicht in den Blutgefäßen, sondern in den Geweben des Organismus. Um den Ort der Infektion zu erreichen, müssen die Leukozyten die Blutgefäße verlassen und in das betroffene Gewebe einwandern. Gleichzeitig muß gewährleistet werden, daß nur diejenigen Leukozyten das Gewebe infiltrieren, die dort auch gebraucht werden; würden alle Leu kozytentypen unkontrolliert in ein bestimmtes Gewebe einwandern, käme es zu unerwünschten Nebeneffekten, wie Autoimmunreaktionen oder chronischen Entzündungen. Das Auswandern von Leukozyten muß also sehr genau reguliert werden.In der jüngsten Vergangenheit hat sich herausgestellt, daß den Leukozyten die notwendige Information von den Endothelzellen - den Zellen, welche die innere Oberfläche der Blutgefäße auskleiden - vermittelt wird. Über eine Kaskade von Zell-Zell-Interaktionen, vermittelt durch Zelladhäsionsmoleküle, werden die richtigen Leukozyten am richtigen Ort festgehalten und zum Auswandern in das Gewebe veranlaßt. Durch die Aufklärung der molekularen Mechanismen beginnt sich nun eine Antwort au f die Frage abzuzeichnen, wie verschiedene Leukozyten ihren Weg in die verschiedenen Kompartimente des Organismus finden. Die Kenntnis dieser molekularen Mechanismen bietet Ansatzpunkte für Therapien von Krankheiten, die durch eine fehlregulierte Entzündungsreaktion ausgelöst werden.
    Zusätzliches Material: 9 Ill.
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  • 87
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    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 56-57 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
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  • 88
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    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 60-60 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Materialart: Digitale Medien
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  • 89
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 68-68 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 90
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999) 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 91
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 70-78 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: Die gezielte Veränderung von Genen, in der Fachsprache als “homologe Rekombination” bezeichnet, stellt heute eine der grundlegendsten Methoden dar, um Informationen über die Funktion dieser Gene zu erlangen. 1987 wurde das erste Gen ausgeschaltet [6]. Seit dieser Zeit steigt die Zahl der durch homologe Rekombination erzeugten “Knock-Out”-Mäuse mit mehreren hundert Stämmen pro Jahr Zunehmend an. Knock-Out-Mäuse tragen Genmutationen, die in einem Ausfall des betroffenen Gens resultieren. Mit den bisher durchgeführten Methoden werden diese Mutationen schon in die Zellen der Keimbahn der Maus eingeführt.Dies hat zur Auswirkung, daß der gesamte daraus entstehende Organismus, jede einzelne seiner Zellen, die Genveränderung aufweist. Handelt es sich bei dem veränderung aufweist. Handelt es sich bei dem veränderten Gen um ein lebensnotwendiges Gen, welches zum Beispiel in der Embryonalentwiclung eine tragende Rolle spielt, so kann sein Ausschalten zu schwerwiegenden Störungen in der Entwicklung des Embryos oder sogar zu seinem Absterben im Mutterleib führen. Obwohl diese Mutationen sehr dazu beigetragen haben, unser Verständnis über die Funktion dieser Gene in der frühen Entwicklung des Embryos zu verbessern, erlauben sie es nicht, ihre Funktion während späterer Stadien oder im erwachsenen Tier zu untersuchen. Gerade dies ist aber oft wünschenswert, um menschliche Erbkrankheiten oder die Entstehung von Krebs am Mausmodell studieren zu können. 1994 gelang es zum ersten Mal, gezielte Genmutationen auf einen bestimmten Zelltyp zu beschränken. Rajewsky und seine Mitarbeiter bedienten sich dabei der Eigenschaften des Cre/LoxP-Rekombinationssystems. Mäuse, welche das DNA-Polymerase β-Gen (polβ) auf herkömmlichem Weg verloren ahtten, erwiesen sich als nicht labensfähig, und Fragen betreffend der Funktion dieses Proteins blieben unbeantwortet.Unter Verwendung der Cre/LoxP-Technologie gelang es den Forschern, den polβ-Knock-Out auf ein einziges Gewebe zu beschränken. Der die Mutation tragende Organismus war labensfähig un d Funktionsanalysen konnten unternommen werden, zum Beispiel die Rolle der Polymerase bei der somatischen Rekombination ‘;4’. Inzwischen ist es mittels Cre/LoxP möglich, jedes beliebige Gen in jedem beliebigen Gewebe oder Zelltyp und zu jedem gewünschten Zeitpunkt zu verändern.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
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  • 92
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 98-109 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: Seen mit Wasser, so sauer wie verdünnte Essigsäure, so sauer wie manche Kraterseen, gibt es solche Seen in Deutschland? Ja, sie gibt es, und zwar sogar recht zahlreich in den alten und vor allem in den neuen Bundesländern. Alle diese Seen sind künstlicher Natur und treten im Zusammenhang mit dem Abbau von Bodenschätzen auf. Durch diesen Vorgang werden tiefere Schichten des Deckgebirges belüftet und mit Wasser versorgt, so daß eine chemische und vor allem mikrobiologische Oxidation von reduzierten Schwefelkver bindungen (Sulfiden) einsetzen kann. Dieselben Vorgänge laufe auch auf und in den Abraumhalden ab. Sulfide sind sehr häufige Begleiter von Braun- oder Steinkohlevorkommen. Ein wesentlicher Teil der Wasserkontaminationen im mitteldeutschen und Lausitzer Raum ist in der Tat mit der Braunkohleförderung verbunden. Ferner sind die meisten, abbauwürdigen Metallvorkommen ebenfalls in sulfidischen Erzen zu finden, so daß deren Abbau zu denselben Oxidation führt, die international als Als Mine Drainage bezeichnet werden.
    Zusätzliches Material: 9 Ill.
    Materialart: Digitale Medien
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  • 93
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 117-117 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
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  • 94
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    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 118-120 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: Die Vielfalt des Lebens zu beschreiben, zu verstehen und zu bewahren gehört zu den wichtigsten Herausforderungen des 21. Jahrhunderts. Dies ist mittlerweile auch auf allen Ebenen, regional, national wie international, erkannt und wird prioritär behandelt. Senckenberg ist in Deutschland eines der größten Institute, das diese Aufgabe mit neuem Schwung angeht. Die dabei entwickelte Infrastruktur steht getreu den Grundsätzen der “Blaue-Liste-Finanzierung” dem ganzen Land zur Verfügung.
    Zusätzliches Material: 3 Ill.
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  • 95
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    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 247-249 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: Goethes eigenständige Untersuchungen zur Pflanzenchemie verknüspfen seine botanischen Studien mit seinen Arbeiten zur Farbenlehre. Bereits im Sommer 1796 begann er unter dem Einfluß von Alexander von Humboldt, die Wirkung des Lichts auf Pflan zen zu untersuchen. Zwanzig Jahre später protokollierte er die Experimente mit Pflanzenextrakten in seinem Notizbuch. Ergebnisse dieser Untersuchungen wurden erst als nachgelassene Schriften 1906 veröffentlicht.
    Zusätzliches Material: 2 Ill.
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  • 96
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    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 255-255 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
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  • 97
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    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 256-256 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: No Asbstract.
    Materialart: Digitale Medien
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    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 258-258 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Materialart: Digitale Medien
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  • 99
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    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 260-260 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Materialart: Digitale Medien
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  • 100
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    Digitale Medien
    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 29 (1999), S. 266-266 
    ISSN: 0045-205X
    Schlagwort(e): Life and Medical Sciences
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Materialart: Digitale Medien
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