bluuebunny/crossref_metadata_2025 huggingface dataset:
Überprüfung einer deutschen Version der Selbstkonzeptklarheits-Skala von Campbell
Authors: Stucke Tanja S.
Published: May 2003

Zusammenfassung: Die von Campbell et al. (1996) entwickelte Skala zur Erfassung von Selbstkonzeptklarheit wurde ins Deutsche übersetzt und in drei Studien hinsichtlich ihrer Faktorstruktur, Reliabilität und Validität untersucht. In allen drei Stichproben (Studierende im Alter zwischen 18 und 44, Angehörige verschiedener Berufsgruppen zwischen 18 und 61) waren die interne Konsistenz der Skala und die Trennschärfe der Items hoch. Wie in der englischen Version deuteten Faktorenanalysen auf eine Eindimensionalität der Skala hin. Alternative Maße zur Erfassung von Selbstkonzeptklarheit korrelierten mit der Selbstkonzeptklarheits-Skala, was als Hinweis für deren Konstruktvalidität interpretiert werden kann. Überlappungen mit dem Selbstwert der Probanden waren vorhanden, aber nicht zu groß, so dass es sinnvoll erscheint, die Selbstkonzeptklarheit separat zu erfassen. Die Übersetzung der von Campbell et al. (1996) entwickelten Skala scheint aufgrund der vorliegenden Befunde für den deutschen Sprachraum geeignet zu sein.
Prozessdissoziationsprozedur: Quo Vadis?
Authors: Erdfelder Edgar , Buchner Axel
Published: May 2003

Zusammenfassung. Die Prozessdissoziationsprozedur (PDP) ist ein häufig benutztes Instrument zur Erfassung kontrollierter (“bewusster“) und automatischer (“unbewusster“) Gedächtnisprozesse. Die Forschung der letzten zehn Jahre hat jedoch eine Reihe von Problemen im von L. L. Jacoby (1991) vorgeschlagenen Zwei-Prozess-Messmodell aufgezeigt. Dies hat zur Entwicklung von alternativen Modellen geführt, die in dieser Arbeit vorgestellt, systematisiert und bewertet werden. Die Modelle unterscheiden sich auf drei Dimensionen: 1) Modelle mit diskreten vs. kontinuierlichen Prozessvariablen, 2) Modelle mit prüfbaren vs. unprüfbaren Annahmen über die Beziehungen zwischen den Prozessen und 3) Zwei-Prozess-Modelle versus Quellengedächtnismodelle. Für die Zukunft der PDP besonders bedeutsam dürfte sein, dass einige Befunde, die mit Zwei-Prozess-Modellen nur schwer vereinbar sind, plausibel erscheinen, wenn man dieselben Daten im Rahmen von Quellengedächtnismodellen analysiert.
Letter recognition of Germans and Chinese - similarities in attention allocation and differences in encoding
Authors: Lass Uta , Yang Yufang , Fang Yunqiu , Yan Song , Sun Pei , Chen Guopeng , Becker Dietrich , Lüer Gerd
Published: May 2003

Abstract. Germans and Chinese participated in letter recognition experiments based on the Sperling paradigm. They were instructed to report as many items as possible from a briefly exposed two-row matrix of letters from the Latin alphabet. In Experiment 1, the Germans performed better than the Chinese. In addition, a position effect was found in that participants correctly reported more letters from the first row than from the second row. In Experiment 2, the position effect was replicated even though the response mode prompted participants to report items from the bottom row first. In Experiment 3, the instruction as to how to allocate attention influenced the position effect. The performance lead of the Germans, as compared to the Chinese, was independent of these instructions. It is hypothesized that reading habits have influenced the allocation of attention and that language-specific encoding of the letters caused the differences in performance.
Implizites Wissen und Wissensmanagement - Schwierigkeiten und Chancen im Umgang mit einer wichtigen menschlichen Ressource
Authors: Büssing André , Herbig Britta
Published: May 2003

Zusammenfassung. Ausgehend von der Entwicklung der letzten Jahre, in denen dem impliziten Wissen eine immer größere Bedeutung als menschliche Ressource beigemessen wurde, wird zunächst eine Definition impliziten Wissens aus der psychologischen Forschung vorgestellt mit den für das Wissensmanagement und die Personalentwicklung wesentlichen Schwierigkeiten der mangelnden Bewusstheit und möglichen Unangemessenheit dieses Wissens. Im Weiteren wird dargestellt, wie sich diese und andere Probleme für die vier Prozesskategorien des Wissensmanagements (Wissensgenerierung, -repräsentation, -kommunikation und -nutzung) auswirken. Anhand von konkreten Beispielen aus der Praxis werden abschließend der bisherige Umgang mit implizitem Wissen in Organisationen resümiert und Forderungen an die Personalentwicklung diskutiert.
Berufliche Interessentests - Wider die Anwendung geschlechtsspezifischer Normen
Authors: Bergmann Christian
Published: May 2003

Zusammenfassung. Berufliche Interessenverfahren werden hauptsächlich im Rahmen von berufslaufbahnbezogenen Orientierungsmaßnahmen eingesetzt. In diesem Zusammenhang kann es von entscheidender Bedeutung sein, ob bei der Ermittlung der individuellen Interessenschwerpunkte bzw. des Interessenprofils eines Ratsuchenden geschlechtsunabhängige (gemeinsame) oder geschlechtsspezifische Normen verwendet werden. Im vorliegenden Beitrag wird der Frage nachgegangen, welche Effekte mit der Anwendung von Geschlechtsnormen verbunden sind. Dazu werden theoretische Überlegungen zur Normierungslogik angestellt, die Standards bei prominenten deutschsprachigen Interessenverfahren analysiert und in drei Studien die Auswirkungen der unterschiedlichen Normierungsmöglichkeiten auf die Validität von Interessentests empirisch überprüft. Sowohl theoretische wie auch empirisch gestützte Argumente sprechen gegen die in der deutschsprachigen Interessendiagnostik überwiegend praktizierte Normierung nach Geschlechtern: Offensichtlich vorhandene Interessenunterschiede zwischen den Geschlechtern verschwinden, die konkurrente und prädiktive Validität der Interessen wird eingeschränkt (geringere Übereinstimmung mit Ausbildungs- und Berufswünschen und tatsächlichen -wahlen), die Selbsteinschätzung der Interessen entspricht eher den Interessentestergebnissen, wenn nicht geschlechtsspezifisch normiert wird, etc. Abschließend werden Empfehlungen für bzw. gegen die Verwendung von geschlechtsspezifischen Normen im Rahmen beruflicher Laufbahnberatung und Mindeststandards für die Konstruktion von Interessenverfahren formuliert.
Wissenschafts-Praxis-Forum
Authors: Muck Peter M. , Schuler Heinz , Becker Karlheinz , Diemand Andreas
Published: May 2003

Zusammenfassung. Im Rahmen der Entwicklung eines multimodalen Systems der Leistungsbeurteilung für die Sparkassen-Finanzgruppe wurde ein neuartiges Verfahren zur Beurteilung von Gruppen konstruiert und erprobt. Um der Eigenheit von Gruppen gerecht zu werden, wurde der Fokus auf interindividuelle Aspekte, also auf Gruppenprozesse und -ergebnisse gelegt. Hierzu wurde das normative Modell der Gruppeneffektivität von Hackman (1987 ) mit dem Team Reflexivity-Modell von West (1994 ) verknüpft: Ergebnis sind vier Dimensionen der Beurteilung von Gruppen: Aufgabenbezogene Zusammenarbeit, Leistung, Sozio-emotionales Gruppenverhalten, und Qualität der Beziehungen. Zwei Perspektiven werden unterschieden und als Gruppenselbstbeurteilung und Gruppenfremdbeurteilung bezeichnet. Die vier Dimensionen erhalten eine andere Bedeutung je nach eingenommener Perspektive: Einerseits handelt es sich um Gesichtspunkte innerhalb einer Gruppe, andererseits um solche zwischen miteinander kooperierenden Gruppen. Die Dimensionen wurden über Verhaltensbeobachtungsskalen operationalisiert. Die empirische Überprüfung bestätigte die Verwendbarkeit der Skalen.
Familial predisposition to tufted angioma: identification of blood and lymphatic vascular components
Authors: Tille J‐C , Morris MA , Bründler M‐A , Pepper MS
Published: May 2003

Tufted angioma is a rare benign vascular lesion of unknown etiology which mainly affects children under 5 years. It is characterized by nodules or tufts of capillary‐sized vessels in the dermis. Here we report the second familial occurrence of tufted angioma, with a mode of inheritance compatible with a monogenic autosomal dominant trait with reduced penetrance. A preliminary investigation was performed to exclude association between the predisposition and certain candidate genes including KDR (kinase insert domain receptor), TEK (TEK tyrosine kinase endothelial), ACVRL1 (activin receptor‐like kinase 1), ENG (endoglin) and FLT4 (fms‐like tyrosine kinase 4). KDR, ENG and FLT4 were all compatible with linkage, with haplotypes being shared between three affected individuals and the one obligate carrier available for testing. TEK and ACVRL1 could essentially be excluded. Finally, we provide definitive evidence for the existence of both blood and lymphatic vascular elements in the lesion.
It's only teeth – are there limits to genetic testing?
Authors: Aldred MJ , Crawford PJM , Savarirayan R , Savulescu J
Published: May 2003

Dental genetic disorders can cause severe social and psychological effects in affected individuals. The cost of treatment can be considerable, not only in financial terms but also in time spent during treatment. In theory it is, or will soon be, possible to use advances in molecular genetics for pre‐natal testing, for selection of embryos using in vitro fertilization techniques, and for gene therapy. The questions we pose are whether these approaches are appropriate. We hope that this review will stimulate debate on these issues.
Interaction between SREBP‐1a and APOB polymorphisms influences total and low‐density lipoprotein cholesterol levels in patients with coronary artery disease
Authors: Rios DLS , Vargas AF , Torres MR , Zago AJ , Callegari‐Jacques SM , Hutz MH
Published: May 2003

In this study, we examined the insertion/deletion (Ins/Del) and XbaI polymorphisms of the apolipoprotein B (APOB) gene and the −36delG polymorphism in the sterol regulatory element binding protein‐1a (SREBP‐1a) gene in 298 patients with non‐diabetic angiographically assessed coronary artery disease (CAD), and 188 healthy controls, from a Brazilian population of European descent. Del/X+ haplotype carriers had higher levels of total cholesterol (TC) and low‐density lipoprotein cholesterol (LDL‐C) in patients (TC, p = 0.05; LDL‐C, p = 0.049) and controls (TC, p = 0.004; LDL‐C, p = 0.013). No association was detected between the SREBP‐1a−36delG polymorphism and lipid levels, but a significant interaction effect between APOB and SREBP‐1a polymorphisms was observed in the patient sample on TC (p = 0.005) and on LDL‐C (p = 0.019) levels. Carriers of the APOB Del/X+ haplotype and SREBP‐1a G–G– genotype showed the highest levels of these lipid parameters. This effect of interaction was not observed in the control sample. Despite the associations with lipids, these polymorphisms were not associated with CAD risk or severity in this sample.
Pulmonary involvement in Type 1 Gaucher disease: functional and exercise findings in patients with and without clinical interstitial lung disease
Authors: Miller A , Brown LK , Pastores GM , Desnick RJ
Published: May 2003

Pulmonary disease is a well‐known complication of Type 1 Gaucher disease (GD), although its incidence is not well established and its severity varies. The purpose of this study was to determine the frequency and extent of pulmonary involvement in patients with GD. Pulmonary involvement was assessed by history, physical examination and chest radiograph in 150 consecutive patients with Type 1 GD presenting at a specialized center for genetic diseases. Five patients were noted to have clinical evidence of pulmonary involvement. Full pulmonary function tests were performed in these five patients and in an additional 13 patients randomly selected from the remaining 145. Many of the 18 patients also underwent radionuclide body imaging with 67Gallium citrate and 111Indium‐tagged leucocyte scans, as well as incremental cardiorespiratory exercise tests. Lung biopsies were available in two patients with lung disease, and a second examination of lung tissue was performed in one of these two patients post‐mortem. Clinical lung disease was detected in five patients. All five had dyspnea, diffuse infiltrates, restrictive impairment and low single breath CO diffusing capacity (DLCOSB). Two of these patients underwent exercise testing and showed abnormalities consistent with lung disease (ventilatory limitation, excessive ventilation and increased dead space) as well as decreased VO2 max. and anaerobic threshold (AT). In contrast, in the other 13 patients, physical examination, chest radiographs and pulmonary function were normal (except for a low DLCOSB in one patient). Responses on exercise testing (performed in six of the 13 patients) were consistent with a circulatory impairment (decreased VO2 max. and AT). Our study found that <5% of patients with Type 1 GD have clinical interstitial lung disease. In addition, we found that some patients, without evident lung involvement, may experience limitations in physical exertion and are easily fatigued; this is attributable to impaired circulation.
APOA5‐1131T>C polymorphism is associated with triglyceride levels in Chinese men
Authors: Baum L , Tomlinson B , Thomas GN
Published: May 2003

A new apolipoprotein gene, APOA5, was recently discovered near the APOA1/C3/A4 gene cluster. Transgenic mice overexpressing the homologous gene, apoa5, showed reduced plasma triglyceride levels, while knockout mice had greatly increased triglycerides, suggesting that human genetic variants affecting expression of the protein product, APOAV, might affect triglyceride levels. Polymorphisms in the APOA5 gene were indeed found to be associated with triglyceride levels in men, though not in women. We sought to confirm the association of the APOA5‐1131T>C polymorphism with triglyceride levels in 167 Chinese men chosen for having either high (≥1.7 mm, n = 82) or low (≤1.2 mm, n = 85) triglycerides. More subjects with high triglycerides had one or two copies of the minor (C) allele of the polymorphism (67%) than did low triglyceride subjects (48%), and combining all subjects showed that those with one or two C alleles had higher triglyceride levels [1.67 ± 2.20 (geometric mean ± SD)] than those without (1.22 ± 2.08 mm, p = 0.01), confirming the reported effect in a different ethnic group. The C allele is more common in Chinese than in Caucasians (26–40% vs. 8% of alleles), suggesting that the impact of this polymorphism on triglyceride levels in the population and therefore on public health is greater among Chinese.
Five new subjects with ring chromosome 22
Authors: Ishmael HA , Cataldi D , Begleiter ML , Pasztor LM , Dasouki MJ , Butler MG
Published: May 2003

Ring chromosome 22, a rare cytogenetic finding, was first described by Weleber et al. in 1968. Since then approximately 50 patients have been reported in the medical literature. We describe five previously unreported subjects with ring chromosome 22 syndrome, summarize the clinical findings of reported patients from the literature and discuss the involvement of the ring chromosome and clinical outcome. Our subjects demonstrated the prominent features of this syndrome including mental retardation, hypotonia, motor delay, lack of speech, full eyebrows, and large ears. In addition, two of our subjects had central nervous system malformations and regression. The lack of consistent physical abnormalities in our subjects further supports no consistent phenotype manifestations in this cytogenetic syndrome. The variable clinical manifestations seen in ring chromosome 22 subjects may be associated with loss of chromosome 22 sequences near the telomere or attributed to the genetic background of each subject. Similarly, recessive alleles unmasked by the deletion could also contribute to the phenotype.
Congenital universal hypertrichosis with deafness and dental anomalies inherited as an X‐linked trait
Authors: Tadin‐Strapps M , Salas‐Alanis JC , Moreno L , Warburton D , Martinez‐Mir A , Christiano AM
Published: May 2003

We report a large Mexican kindred with a variant form of congenital universal hypertrichosis that is inherited in an apparent X‐linked recessive manner. In addition to the generalized hypertrichosis, the affected individuals have dental malformations and deafness. Males are more severely affected than females who exhibit only mild hypertrichosis, but not deafness or dental anomalies. Haplotype analysis in this pedigree revealed linkage to a 13‐cM region on chromosome Xq24‐q27.1 between markers GATA198A10 and DXS8106. Localization of the gene underlying this form of hypertrichosis is the initial step in identifying genes on the X chromosome that are involved in the control of hair growth and development.
Triple A syndrome: genotype–phenotype assessment
Authors: Prpic I , Huebner A , Persic M , Handschug K , Pavletic M
Published: May 2003

The triple A or Allgrove syndrome is an autosomal‐recessive disease (MIM*231550) characterized by the triad of achalasia, alacrima and adrenocorticotropic hormone (ACTH)‐resistant adrenal insufficiency. Associated features of the syndrome are neurological and dermatological abnormalities. Until the discovery of the AAAS gene as the responsible gene in triple A syndrome, the diagnosis was based on characteristic clinical features. Here we present the clinical and molecular genetic data which demonstrated the marked phenotypic variability in three unrelated patients with triple A syndrome. The final diagnosis of triple A syndrome was confirmed by molecular analysis. In one patient with isolated achalasia, the diagnosis of triple A syndrome could only be made on the basis of the molecular genetic analysis of the AAAS gene. We therefore suggest that the diagnosis of triple A syndrome should be considered in patients who exhibit only one or two of the main symptoms (i.e. alacrima, achalasia or adrenal insufficiency). These patients require careful neurological investigation, and mutation analysis of the AAAS gene should be performed.
Evaluation of a Tay‐Sachs Disease screening program
Authors: Gason AA , Sheffield E , Bankier A , Aitken MA , Metcalfe S , Barlow Stewart K , Delatycki MB
Published: May 2003

Tay‐Sachs Disease (TSD) is an autosomal recessive neurodegenerative disorder. TSD is prevalent in the Ashkenazi Jewish population, and carrier screening programs have been implemented worldwide in these communities. A screening program initiated in 1997 involving the Melbourne Jewish community (Australia) incorporated education, counselling and carrier testing of high‐school students aged 15 to 18 years. This study aimed to assess the participation rates, level of knowledge obtained and predicted feelings and attitudes of the students involved. Seven hundred and ten students participated, there was a 67% uptake for testing with a carrier rate of 1 in 28 determined. The level of knowledge of the students following education was high and of relative importance in regard to decision making, as were their feelings and attitudes about genetic testing for carrier status. A significant impediment to test uptake was the need for blood sampling, resulting in a recommendation for the introduction of DNA analysis on cheek brush samples. The evaluation of this program has given a wider scope for further development as well as providing valuable information for the implementation of community screening programs.
Exclusion of PTPN11 mutations in Costello syndrome: further evidence for distinct genetic etiologies for Noonan, cardio–facio–cutaneous and Costello syndromes
Authors: Tartaglia M , Cotter PD , Zampino G , Gelb BD , Rauen KA
Published: May 2003

Costello syndrome (CS) is a rare, multiple congenital anomaly syndrome with characteristic dysmorphic features, cardiac anomalies and a tendency to develop certain cancers. Phenotypically there is some overlap with other genetic disorders, notably cardio–facio–cutaneous (CFC) syndrome and Noonan syndrome (NS), suggesting that these syndromes may be allelic. We recently identified PTPN11, which encodes the non‐receptor protein tyrosine phosphatase, SHP‐2, as a major NS disease gene. In this report, we screened a cohort of 27 patients, with the clinical diagnosis of CS, for PTPN11 mutations using denaturing high performance liquid chromatography analysis. No mutations of the PTPN11 gene were found in the CS patients. Common polymorphisms in introns 6 and 7 and exon 8 were identified in four individuals. With our previous exclusion of PTPN11 mutations in CFC syndrome, these data suggest distinct genetic etiologies for Noonan, CFC and Costello syndromes.
Vascular malformations: localized defects in vascular morphogenesis
Authors: Brouillard P , Vikkula M
Published: May 2003

Vascular anomalies are localized defects of the vasculature, and usually affect a limited number of vessels in a restricted area of the body. They are subdivided into vascular malformations and vascular tumours. Most are sporadic, but Mendelian inheritance is observed in some families. By genetic analysis, several causative genes have been identified during the last 10 years. This has shed light into the pathophysiological pathways involved. Interestingly, in most cases, the primary defect seems to affect the characteristics of endothelial cells. Only mutations in the glomulin gene, responsible for hereditary glomuvenous malformations, are thought to directly affect vascular smooth‐muscle cells.
Allelic variation of the inducible costimulator (ICOS) gene: detection of polymorphisms, analysis of the promoter region, and extended haplotype estimation
Authors: Haaning Andersen A.D. , Lange M. , Lillevang S.T.
Published: May 2003

Abstract: The human chromosome region 2q33 including the three costimulatory molecules CD28, CTLA‐4 and ICOS, has been subject to much attention due to its linkage to a number of autoimmune diseases. The search for the causal relationship of this linkage has revealed several polymorphisms, but no variations in the amino acid sequences, except for one polymorphism in the leader sequence of CTLA‐4. In the present study, we examined the ICOS gene of an unrelated group of healthy donors from the Danish population. We were able to report 16 intronic SNP, one intronic G‐insert and two repeat regions in intron 4, consistent with the [T]n and the [GT]n regions reported in a Japanese study. Putative haplotypes for the established SNP and repeat polymorphisms have been estimated by computational analysis. Sequencing of ∼3500 bp of the upstream region of ICOS revealed an additional eight SNP of which two resided in putative NF‐kB and Sp1 sites. In accordance with previous studies we detected no variations in the coding regions except for a rare polymorphism that was found in one donor in the last codon of exon 5, which lead to a heterozygous genotype, but no amino acid change. This suggests that regulation of transcription rather than protein structure could be a possible mechanism in the explanation of linkage.
Additional factor in some HLA DR3/DQ2 haplotypes confers a fourfold increased genetic risk of celiac disease
Authors: Bolognesi E. , Karell K. , Percopo S. , Coto I. , Greco L. , Mantovani V. , Suoraniemi E. , Partanen J. , Mustalahti K. , Mäki M. , Momigliano‐Richiardi P.
Published: May 2003

Although HLA‐DQ genes are the major celiac disease (CD) susceptibility genes, results from Finnish families suggest that not all DQ2‐encoding haplotypes confer equal susceptibility to CD, implying the effect of other gene(s) in the HLA region. The aim of the present work was to extend and confirm the aforementioned results in a southern European population ( Italian) and to better localize the additional risk factor/s. The association of nine loci spanning the HLA region from DR to HFE, 4.5‐Mb telomeric of HLA‐A, was tested. The analysis was performed by comparing marker frequencies in DR3‐DQ2 haplotypes transmitted and non‐transmitted to the affected offspring in 156 Italian CD families selected for having at least one DR3‐positive parent. The same analysis was performed independently in 101 Finnish CD families selected with the same criteria. Three alleles, MICA‐A5.1, MICB‐CA24 and MIB‐350, all characteristic of the B8‐DR3 extended haplotype, showed a significantly increased frequency in DR3 transmitted haplotypes in the Italian families. DR3 haplotypes carrying the combination of these alleles conferred an approximate fourfold increased CD risk. B8‐DR3 transmitted haplotypes were significantly more conserved telomerically down to the MIC‐Class I region. Similar results were seen in the Finnish families. The major conclusion that holds true in both populations is that, while DQ2 is an absolute requirement for the development of CD, the presence of an additional genetic factor within the MIC‐Class I region confers an approximate 4‐fold increased risk of the disease.
Immunogenetics of two new HLA alleles: A*0108 and B*4031
Authors: Street J. , Downing J. , Hammond L. , Thompson J. , Darke C.
Published: May 2003

Abstract: Two new alleles, HLA‐A*0108 and B*4031, were identified in north‐western European Caucasoid subjects. A*0108 differed from A*010101 by a single substitution (C to T) at position 216 in exon 3, resulting in an amino acid difference of Arg to Trp at position 163. It was present on a haplotype with B*1501/60/70/71; Cw*0303; DRB1*1301; DRB3*0202; DQA1*0103; DQB1*0603 and its product reacted as a normal HLA‐A1 specificity. B*4031 differed from B*4001 by two nucleotides in exon 3 (positions 20 (G to C) and 69 (A to G)) resulting in two amino acid differences (Arg to Ser at position 97 and Asn to Asp at position 114). It was found on a haplotype with HLA‐A*03; Cw*0304; DRB1*0404/32; DRB4*0101/3/5; DQA1*03; DQB1*0302 and has the HLA‐B60 specificity. Both alleles have frequencies of < 0.0002 in the largely north‐western European Caucasoid blood donor population resident in Wales.
A single round PCR method for genotyping human surfactant protein (SP)‐A1, SP‐A2 and SP‐D gene alleles
Authors: Pantelidis P. , Lagan A.L. , Davies J.C. , Welsh K.I. , Du Bois R.M.
Published: May 2003

Abstract: The genes coding for the human surfactant proteins (SP)‐A and SP‐D are located on chromosome 10q22‐q23.1. SP‐D is the product of a single gene whereas SP‐A is the product of two highly homologous genes SP‐A1 and SP‐A2. Several single nucleotide polymorphisms (SNP) are present in the SP‐A1, SP‐A2 and SP‐D genes. Because of this high degree of sequence homology between the SP‐A1 and SP‐A2 genes, current genetic analysis studies employ a nested PCR/radioactive hybridization or restriction fragment length polymorphism approach to initially isolate the genes and subsequently to detect the SNP in these isolates. In this manuscript, we report the primers and conditions of a sequence specific primer‐PCR methodology that enables the identification of SP‐A1, SP‐A2 and SP‐D gene allelic variants directly on genomic DNA material.
Genetic affinities among Mongol ethnic groups and their relationship to Turks
Authors: Machulla H.K.G. , Batnasan D. , Steinborn F. , Uyar F.A. , Saruhan‐Direskeneli G. , Oguz F.S. , Carin M.N. , Dorak M.T.
Published: May 2003

Abstract: The central Asian country Mongolia is home to more than 20 tribes and ethnic groups, some of which are related to neighboring Turkic populations. The main Mongolian people, Khalkha, live in central and eastern Mongolia while the Tsaatan minority lives in the north of the country. The Oold minority is from the western Altai mountain region and live in close proximity with Turkic people. We have typed the HLA‐A, ‐B, ‐Cw, ‐DRB1 and ‐DQB1 loci by PCR‐SSP in these three Mongolian populations as well as a sample of the German population. To examine their genetic relationships, a sample of the Turkish population already typed at the HLA‐A, ‐B and ‐DRB1 loci were used. Altogether five populations were analyzed: Khalkha (n = 100), Tsaatan (n = 72), Oold (n = 52), German (n = 260) and (Anatolian) Turkish (n = 498). Nei's unbiased genetic identity (GI) and genetic distance (GD) were estimated from genotypes using PopGene v1.31, and dendrograms were constructed using phylip. The results suggested a close relationship of the Khalkha to the Tsaatan. The Turks and Germans were equally distant to all three Mongolian populations. These results confirmed the lack of strong genetic relationship between the Mongols and the Turks despite the close relationship of their languages (Altaic group) and shared historical neighborhood. This study has provided useful population data for genetic and anthropologic studies bridging eastern and western populations.
Expression defect of an HLA‐A*24 allele associated with DNA methylation in a normal individual
Authors: Lee K.W. , Shin J.‐Y. , Lee J.‐Y.
Published: May 2003

Abstract: Non‐expressed HLA alleles become a potential problem in the transition of the HLA typing methodology from serologic typing to more accurate DNA typing. In this study, a novel nonexpressed A*24 allele identified from two members of a Korean family was characterized. At the DNA sequence level, the nonexpressed allele (A*24023) is apparently normal; the complete genomic sequence was identical to HLA‐A*2402101, from the 5′‐upstream region to the 3′‐downstream region, except for a single silent substitution at codon 211 (GCG→GCA) in exon 4. A DNA methylation analysis using methylation‐sensitive restriction enzymes, however, showed that the nonexpressed A*24023 allele from an apparently normal individual was highly methylated in regions covering exons and introns as well as the 5′‐upstream region. This result suggests that hypermethylation of the HLA‐A gene may induce gene inactivation in the normal individuals.
Observations on the HLA‐A2403 specificity
Authors: Street J. , Hammond L. , Downing J. , Thompson J. , Darke C.
Published: May 2003

Abstract: We found HLA‐A*2423 in a subject possessing the HLA‐A2403 specificity. Consequently we delineated the A*24 alleles of 41 subjects previously assigned as ‘A2403’ by serology and/or ‘low‐resolution’ PCR‐SSP (allele group: A*2403/10/18/22/23/33) and found that 36 were A*2403, 3 were A*2410 and 2 were A*2433. The A*2410 and A*2433 subjects also typed as A2403. Several likely A*2410/23/33‐bearing haplotypes were identified and the frequency of the A*2403/10/18/22/23/33 alleles was determined in 26,826 Welsh blood donors. We suggest that HLA‐A9/A24 antibodies against epitope(s) involving 166D and 167G will fail to react with all A*2403/10/18/22/23/33 products. As it is this ‘short’ A9/A24 serological reactivity that defines HLA‐A2403 all these products will be serologically designated as HLA‐A2403.
HFE, the MHC and hemochromatosis: Paradigm for an extended function for MHC class I
Authors: Cardoso C.S. , De Sousa M.
Published: May 2003

Abstract: HFE was discovered as the hereditary hemochromatosis (HH) gene. It is located on chromosome 6 (6p21.3), 4Mb telomeric to the HLA‐A locus, and its product has a structure similar to MHC class I molecules. HFE encodes two frequent mutations: C282Y and H63D. One of these (C282Y) is present in a large proportion of Caucasian HH patients. HFE has a tissue distribution compatible with a role in iron absorption (intestine), recycling (macrophages) and transport to the fetus (placenta).
Solution structure of a novel ETB receptor selective agonist ET1–21[Cys(Acm)1,15, Aib3,11, Leu7] by nuclear magnetic resonance spectroscopy and molecular modelling
Authors: Hewage C.M. , Jiang L. , Parkinson J.A. , Ramage R. , Sadler I.H.
Published: May 2003

The solution structure of a biologically active modified linear endothelin‐1 analogue, ET1–21[Cys(Acm)1,15, Aib3,11, Leu7], has been determined for the first time by two‐dimensional nuclear magnetic resonance spectroscopy in a methanol‐d3/water solvent mixture. Out of approximately one hundred linear peptide analogues tested by biological assay, this peptide, together with a dozen others, showed significant ETB selective agonist activity. Here we report the solution structure of an ETB selective agonist of a full‐length, synthetic linear endothelin analogue. The calculated structures indicate that the peptide adopts an α‐helical conformation between residues Ser5–His16, whilst both N‐ and C‐termini show no preferred conformation. These results suggest that the disulphide bridges normally associated with endothelin and sarafotoxin peptides may not necessarily be important for either ETB receptor binding activity or the formation of a helical conformation in solution.
Ion‐binding and pharmacological properties of Tyr6 and Tyr9 antamanide analogs
Authors: Ruzza P. , Calderan A. , Biondi B. , Borin G. , Tancredi T. , Carrara M.
Published: May 2003

Abstract: In order to investigate the antiproliferative properties of antamanide, we have synthesized and studied two antamanide analogs where the phenylalanine residue in positions 6 or 9 is substituted by tyrosine, their corresponding linear forms and the cyclic and linear des Phe5,Phe6–Tyr9–analogs. Antamanide and its biologically active synthetic analogs are able to form highly stable complexes with metal ions, particularly Na+, K+ and Ca2+. We studied the ion‐binding properties of the Tyr–antamanide analogs by CD and Tb3+‐mediated fluorescence in acetonitrile. In this medium the far‐and near‐UV CD spectra of the neat Tyr6–antamanide analog are very similar to that of the parent cyclic decapeptide. Substantial differences occur on the contrary in the CD spectra of the neat Tyr9–antamanide, particularly in the regions at 220 nm and 270–290 nm. In acetonitrile, as already found for antamanide, the interaction with the above‐mentioned metal ions always produces evident changes in the far‐ and near‐UV CD spectra of both analogs. On the contrary, the CD spectra of the linear deca‐ and octa‐ and of the cyclic octa‐analogs are affected by the presence of metal ions only in the near‐UV region. In the same solvent the Tb3+‐mediated fluorescence spectra of all the synthetic peptides are remarkably affected by the addition of ions. On the basis of the spectral total changes, by using either or both the spectroscopic techniques, it has been possible to determine the ion binding constants for all the linear and cyclic Tyr–antamanide analogs and to compare them with that of the parent peptide. The antitoxic and antiproliferative activities of these antamanide analogs have been tentatively correlated to their ion‐binding properties. A preliminary account of this work was given in (1).
Structure–activity studies of normal and retro pig cecropin–melittin hybrids
Authors: Juvvadi P. , Vunnam S. , Yoo B. , Merrifield R.B.
Published: May 2003

Chimeric analogs of cecropin P1 and melittin with normal and retro sequences were synthesized to explore the effect of sequence, amide bond direction (helical dipole), charge, amphipathicity and hydrophobicity on their antibacterial activity and channel‐forming ability. When viewed from the opposite end by rotation in the plane 180° retro analogs have the same sequence as the parent with reversed amide bond and helical dipole directions. The expected activities were related to the important structural features and a series of assumptions were made. Retro analogs are expected to be inactive if both sequence and amide bond direction make critical contributions to the activity. CP1(1–10)M(2–9) amide, (SWLSKTAKKLIGAVLKVL), showed a broad antibacterial spectrum with high activity against the two Gram‐negative and three Gram‐positive bacteria tested. Retro‐CP1(1–10)M(2–9) was less active compared to its normal peptide. CP1(1–9)M(1–8) and CP1(1–9)M(2–8) amides were found to be active against Gram‐negative Escherichia coli and also Gram‐positive Streptococcus pyogenes, but inactive against the other test organisms. The corresponding retro analogs were inactive against all the five bacteria tested. These results suggest that both sequence and amide bond direction (helix dipole) are important structural requirements for the activity of CP1‐M hybrids. Acetylation of the N‐terminal amine in both normal and retro analogs lowered their activity, indicating the contribution of free amine to the activity. These analogs form ion‐conducting channels in lipid bilayers. The action of the peptides may be explained by self‐aggregation and formation of ion‐conducting pores across bacterial membranes. Conformational analysis obtained from CD measurements showed that all analogs form amphipathic α‐helices in presence of 12–20% hexafluoro isopropanol. The retro CP1(1–10)M(2–9) amide showed higher helicity and is more potent compared to other retro analogs synthesized. These studies show the effect of small sequence modifications on the biological activity of the peptides and on their α‐helical conformation in HFIP, the structure‐inducing organic solvent.
A Lewisy epitope mimicking peptide induces anti‐Lewisy immune responses in rabbits and mice
Authors: Lou Q. , Pastan I.
Published: May 2003

Lewisy carbohydrate antigens are abundant on the surface of many carcinomas. Mab B3 directed against this carbohydrate antigen has been used to make an immunotoxin that is very cytotoxic to cancer cells expressing the Lewisy antigen. Mab B3 was also used to screen a phage‐displayed peptide library and identified a peptide mimicking the Lewisy epitope. In this report, we demonstrate that the Lewisy epitope‐mimicking peptide induces anti‐Lewisy immune responses in both rabbits and mice. In addition, Lewisy antigens induce anti‐peptide immune responses. These results indicate that carbohydrate‐mimicking peptides provide a novel strategy to elicit immune responses for tumor‐associated carbohydrates.
Coupling difficulty following replacement of Tyr with HOTic during synthesis of an analog of an EGF B‐loop fragment
Authors: Ötvös F. , Murphy R.F. , Lovas S.
Published: May 2003

During Fmoc synthesis of an analog, [Abu20,31, HOTic22]hEGF(20–31), of a fragment, Cys‐Met‐Tyr‐Ile‐Glu‐Ala‐Leu‐Asp‐Lys‐Tyr‐Ala‐Cys, of the B‐loop of human EGF, conductivity measurements showed that increased time was necessary for coupling and complete deprotection of the residues Met21 and Abu20 which followed the HOTic22. Use of different active ester‐forming reagents, including HOBt and BOP, did not increase the yield. Use of symmetrical anhydride with extended coupling time increased the yield but did not complete the coupling. It appears that inclusion of HOTic in place of Tyr to introduce conformational constraint to peptide analogs can cause or augment a tendency towards conformations with increasing occlusion of N‐terminal amino groups and result in the need for altered coupling strategies for completion of analog synthesis.
Helix‐enhancing propensity of fluoro and alkyl alcohols: influence of pH, temperature and cosolvent concentration on the helical conformation of peptides
Authors: Kumaran S. , Roy R.P.
Published: May 2003

We have analyzed the effects of trifluoroethanol (TFE) and three other alcohols(1‐propanol, 2‐propanol and hexafluoro‐2‐propanol) on S‐peptide (residues 1–20) of ribonuclease A, an analog of S‐peptide (QHM → AAA, Sa‐peptide) and TC‐peptide (residues 295–316) of thermolysin to assess the helix‐enhancing propensity of fluoro and alkyl alcohols under different environmental conditions of cosolvent concentration, pH and temperature by circular dichroism (CD). The dependence of cosolvent concentration on helix‐induction showed a plateauing effect in all cases. 1‐Propanol and 2‐propanol were as effective as TFE in all the three peptides. Hexafluoro‐2‐propanol (HFIP) was a better helix enhancer in all cases however, the relative effectiveness varied with the peptide sequence. The alcohol transitions were analyzed assuming a two‐state transition. The free energy decreased linearly in the cosolvent concentration range of 0–5 m for all the three peptides. The m‐value (constant of proportionality) varied between peptides but was similar for any given peptide for TFE, 1‐propanol or 2‐propanol. The m‐values of HFIP for all three peptides was much higher compared to other cosolvents. The isothermal cosolvent helix‐induction curves for the three peptides exhibited similar features of shape and character for 1‐propanol, 2‐propanol and TFE. The additivity of cosolvent‐induced helix formation was observed for different blends of alkyl and/or fluoro cosolvents. The pH‐dependence of helix formation was observed in both TFE and 1‐propanol solutions for S‐peptide and TC‐peptide, respectively, while in Sa‐peptide, which was designed to perturb the pH‐effect, helix formation was unaffected. The overall results provide some insight into the mechanism of cosolvent‐mediated helix‐enhancement in protein segments and are likely to facilitate optimization of conditions for cosolvent usage in chemistry and biology.
Syntheses and biological activities of potent bombesin receptor antagonists
Authors: Llinares M. , Devin C. , Chaloin O. , Azay J. , Noel‐Artis A.M. , Bernad N. , Fehrentz J.A. , Martinez J.
Published: May 2003

Bombesin receptor antagonists are potential therapeutic agents due to their ability to act as inhibitors of cellular proliferation. On the basis of our hypothesis concerning the mechanism of action of gastrin associating an activating enzyme to the receptor and on the results reported in the literature, we have synthesized bombesin analogs which have been modified in the C‐terminal part. Potent bombesin receptor antagonists were obtained by replacement of Leu‐13 with a statyl residue or with a residue bearing an hydroxyl group in place of the carbonyl function of Leu‐13. Several inhibitors were able to recognize the bombesin receptor on rat pancreatic acini and antagonized bombesin stimulated amylase secretion in the nanomolar range. These compounds were also able to recognize the bombesin receptor and to inhibit [3H] thymidine incorporation in 3T3 cells with the same potency.
Chiral recognition in dipeptides containing 1‐aminocyclopropane carboxylic acid or α‐aminoisobutyric acid: NMR studies in solution
Authors: Ghosh Sunil K.
Published: May 2003

Protected dipeptides containing 1‐aminocyclopropane carboxylic acid (Ac3c) or α‐aminoisobutyric acid (Aib) residues at theC‐terminus and Phe, Val or Ala residues at theN‐terminus displayed different proton NMR spectra for the pure enantiomers and the racemic mixtures in deuterochloroform (CDCl3) solution. An unequal mixture of enantiomers showed two sets of resonances (NMR nonequivalence), one corresponding to major and the other to minor enantiomer. The NMR nonequivalence was originated by the presence of theC‐terminal Ac3c or Aib residues, which have been known for their unique spatial preferences in avoiding an extended (C5) conformation. When a C5conformation favoring residue such as glycine was incorporated in place of Ac3c or Aib, negligible NMR nonequivalence was observed. The magnitude of the NMR nonequivalence depended on the side chain as well as on the protecting groups atN‐terminus α‐amino acid. For the same peptide, the magnitude of nonequivalence increased with increasing solution concentration and/or with decreasing the solution temperature. The NMR nonequivalence disappeared in polar solvent‐like deuterated dimethylsulfoxide (DMSO‐d6). A preference for hetero‐chiral recognition leading to dimeric association under fast exchange conditions had been invoked to explain the observed phenomenon. The dipeptides thus prepared could well serve as ‘model peptides’ for the evaluation of any preparative methods.
Cyclic enkephalin analogs that are hybrids of DPDPE‐related peptides and Met‐enkephalin‐Arg‐Gly‐Leu: prohormone analogs that retain good potency and selectivity for δ opioid receptors
Authors: Bartosz H. , Bechowski ‐ , Hruby V.J. , Davis P. , Slaninova J. , Malatynska E. , Stropova D. , Porreca F. , Yamamura H.I.
Published: May 2003

We report here on the binding affinity and bioassay results of cyclic enkephalin analogs comprising a cyclic moiety and C‐terminal fragment of MERGL, where ME denotes methionine enkephalin. MERGL (YGGFMRGL) has been suggested to be cleaved enzymatically by membrane‐bound enkephalinase 24.11 to leave ME and the tripeptide RGL. In our study we have synthesized hybrids of DPDPE or DPLCE and the C‐terminal tripeptide RGL in order to mimic a prohormone able to cross the blood–brain barrier. The study has shown that of the homologs presented here, analogs of DPLCE often are more potent at delta opioid receptors both in binding affinity and in bioactivity at the MVD, than DPDPE. Our hypothesis that hybrids (consisting of the drug and the spacer for the carrier) could be designed which would either have no opioid activity or, alternatively, be by themselves very active, has been verified.
Suppression of epimerization by cupric (II) salts in peptide synthesis using free amino acids as amino components
Authors: Ryadnov M.G. , Klimenko L.V. , Mitin Y.V.
Published: May 2003

An epimerization‐free system for coupling N‐protected peptides with free amino acids was developed. A number of inorganic substances were tested as epimerization suppressant additives during the coupling by various methods (carbodiimide plus additives, uronium salts, Woodward’s reagent‐K, isobutyl‐chloroformate, etc.). Some of them (ZnCl2, RbClO4, LiCl, SnCl4, AlCl3, etc.) in combination with some coupling methods can guarantee coupling with minimal epimerization (D‐epimer < 1%). But only a simultaneous use of 1‐hydroxybenzotriazole and Cu2+ ions as additives in carbodiimide‐mediated peptide couplings appeared to give a standard result (D‐epimer < 0.1%). There was no epimerization even in the case when N‐methyl amino acid (sarcosine) was used as an amino component, while in the absence of Cu2+ ions an unacceptable level of epimerization was observed (D‐epimer, 22% for carbodiimide with the 1‐hydroxybenzotriazole method). So far it has been considered that Cu2+ ions prevent obtaining peptides in high yields (< 90%) by various coupling methods. We have found that the use of 1‐hydroxybenzotriazole, CuCl2 and 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide instead of dicyclohexylcarbodiimide provides a possible method for obtaining the desired peptides in 90–99% yields without epimerization. All these results were shown by employing several model peptide couplings with free amino acids as amino components dissolved in an effective solvent system which readily dissolved them.
Homologation of α‐amino acids to β‐amino acids using Fmoc‐amino acid pentafluorophenyl esters
Authors: Suresh Babu V.V. , Gopi H.N. , Anandi K.
Published: May 2003

The homologation of α‐amino acids to β‐amino acids by the two‐step Arndt–Eister method is achieved by using Fmoc‐α‐amino acid pentafluorophenyl esters for the acylation of diazomethane, synthesizing the key intermediates Fmoc‐aminoacyldiazomethanes as crystalline solids in good yields and purity.
Detection of nascent polyproline II helices in solution by NMR in synthetic insect kinin neuropeptide mimics containing the X‐Pro‐Pro‐X motif
Authors: Moyna G. , Williams H.J. , Scott A.I. , Nachman R.J.
Published: May 2003

The conformations of three synthetic peptide analogs containing the dPro‐dPro‐dXaa motif (dXaa=dThr, dGlu, dAsn) in aqueous solution were studied by a combination of NMR and molecular modeling simulations. The three compounds were identified from a random d‐amino acid tripeptide library on the basis of their ability to either mimic or block the diuretic activity of neuropeptides of the insect kinin family. TOCSY and ROESY correlations, as well as abnormal secondary chemical shifts for protons on the d‐proline residues were employed to obtain conformational ensembles consistent with the experimental NMR data for the three analogs using an in vacuo simulated annealing protocol. Similar secondary structures were found for the three molecules after refinement, in agreement with the similarities observed between their NMR spectra. Unrestrained molecular dynamics simulations with explicit water representation indicate that the structural motifs found in vacuo are stable in aqueous solution. The three analogs can be considered initiators of right‐handed poly d‐proline II helices, mirror images of the poly l‐proline II left‐handed helical motifs normally found in proline‐rich proteins. The role of these secondary folds on binding of the analogs to the kinin receptors is discussed.