Kreatin-Phosphokinase-Aktivität im Serum bei Konduktorinnen der progressive Muskeldystrophie vom Typ Duchenne

Zusammenfassung Bei 148 weiblichen Verwandten von 33 Patienten mit Duchennescher Muskeldystrophie in 21 Sippen sowie bei 25 Kontrollpersonen ist die Kreatin-Phosphokinase bestimmt worden. Die Getesteten befanden sich im Alter zwischen 6 Monaten und 79 Jahren. Erhöhte CPK-Werte fanden wir bei 7 (88%) von 8 sicheren und wahrscheinlichen Genträgerinnen.Von den 30 möglichen Konduktorinnen der Gruppe A — bei denen das statistische Risiko der Heterozygotie bekannt ist — wiesen 17 (52%) über die Norm erhöhte CPK-Werte auf. Die Zahl der als Heterozygote identifizierten Personen entsprach der statistischen Erwartung von 13. Von den 14 Müttern isoliert erkrankter Patienten wurden bei 10 (71,5%) erhöhte CPK-Aktivitäten nachgewiesen.In der Gruppe B der möglichen Trägerinnen, bei denen das statistische Risiko, heterozygot zu sein, nicht bekannt ist, konnten bei insgesamt 110 weiblichen Verwandten bei 32 Personen (29%) erhöhte CPK-Aktivitäten gemessen werden.In den 4 Sippen der genetisch sicheren Konduktorinnen können wir auf Grund unserer Befunde nicht bestimmen, zu welchem Zeitpunkt die Neumutation auftrat. Das gleiche gilt für weitere 9 Sippen, während bei den restlichen 8 der Mutationszeitpunkt diskutiert wird.Die CPK-Bestimmung zur Identifizierung von Heterozygoten hat sich als bester Indicator erwiesen. Die ca. 25% falsch-negativen Werte sind durch Mehrfachbestimmungen zu mindern. Mögliche Ursachen der falsch-negativen Werte sind intraindividuelle Schwankungen, meßtechnische Fehler und die Mosaikstruktur heterozygoter Gene gemäß der Lyon-Hypothese.

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Serum creatine-phosphokinase activity in female carriers of muscular dystrophy (type Duchenne)

Summary Serum creatine-phosphokinase activity has been investigated in 148 female relatives of 33 patients with progressive muscular dystrophy (type Duchenne) and in 25 controls. The age of the relatives ranged from 6 months to 79 years. Elevated creatine kinase activity was found in 7 (88%) of 8 definite and probable carriers. Among 30 possible carriers in whom the risk of heterozygosity could be calculated, 17 subjects were identified as carriers, in close agreement with the expectation of 13. — Among 110 other possible carriers, in whom the risk of heterozygosity could not be determined, 32 carriers were identified. Of the 14 mothers of sporadic cases, included in this group, high CK activity was found in 10. — In the 4 families of the definite carriers it was not possible to determine at which time the new mutation took place. In 8 families of possible carriers data supporting the appearance of the mutation in some subjects are discussed. — For genetic prognosis, an elevated CK value in a relative of a Duchenne patient is regarded as reliable evidence of heterozygosity, but if the CK value is within the normal range there is an appreciable risk that it is a false negative and that the subject is actually a carrier. Possible causes of false negative observations are technical difficulties, decline of CK levels with increasing age, heterozygote variability consequent to lyonization of an X-chromosome, and genetic heterogeneity.

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Benutzte Abkürzungen ADP Adenosindiphosphat - ADK Adenylatkinase (Myokinase) - ALD Aldolase - ATP Adenosin-5-Triphosphat - CPK Kreatinphosphatkinase - EDTA Äthylendiamintetraessigsäure - GOT Glutamat-Oxalacetat-Transaminase - GPT Glutamat-Pyruvat-Transaminase - GSH reduziertes Glutathion - LDH Lactatdehydrogenase - MgSO₄ Magnesiumsulfat - NAD Nicotinadenindinucleotid - NADH Nicotin-adenindinucleotid, reduzierte Form - NaOH Natronlauge - PEP Phosphoenolpyruvat - PK Pyruvatkinase - PMD progressive Muskeldystrophie - P Phosphat - TRAP Triäthanolaminpuffer     

Transient Dissociation between Infectious HIV-1 Titer and Viral RNA during the Early Phase of AZT Treatment

The short-term kinetics of infectious HIV titers, HIV copy numbers and p24-antigen during the first 28 days of AZT monotherapy were evaluated. In three of four patients, infectious HIV was culturable and infectious titers rose 2- and 4-fold compared to baseline values. This increase was neither associated with mutations conferring resistance to AZT nor a switch from NSI to SI phenotypes. Two patients showed an increase of plasma infectivity associated with a reduction of HIV copies and p24-antigen. We conclude that transient dissociations of plasma infectivity and HIV copy numbers occur during early AZT monotherapy.     

GENOME: a rapid coalescent-based whole genome simulator

Summary: GENOME proposes a rapid coalescent-based approach tosimulate whole genome data. In addition to features of standardcoalescent simulators, the program allows for recombinationrates to vary along the genome and for flexible population histories.Within small regions, we have evaluated samples simulated byGENOME to verify that GENOME provides the expected LD patternsand frequency spectra. The program can be used to study thesampling properties of any statistic for a whole genome study. Availability: The program and C++ source code are availableonline at http://www.sph.umich.edu/csg/liang/genome/ Contact: lianglim{at}umich.edu Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Martin Bishop     

Within-plant distribution and emission of sesquiterpenes from Copaifera officinalis

Copaifera officinalis, the diesel tree, is known for massive production of oleoresin, mainly composed of sesquiterpene hydrocarbons. In this study, composition of these sesquiterpenes and their concentrations in leaves, stems and roots of C. officinalis at two developmental stages, including the three-week old (TW) seedlings and two-year old (TY) trees, were determined. The leaves of TW seedlings and TY trees contained similar number of sesquiterpenes, which also had comparable concentrations. The stems of TW seedlings had higher concentrations of sesquiterpenes than those of TY trees. In contrast, the number of sesquiterpene species and their concentrations in the roots of TW seedlings were much lower than those in the roots of TY trees. Cluster analysis of sesquiterpenes estimated that there are at least four terpene synthase genes involved in the production of sesquiterpenes in C. officinalis. Because sesquiterpenes are highly volatile, emissions of sesquiterpenes from healthy and wounded TW seedlings were examined using headspace analysis. Whereas very low emission of sesquiterpenes was detected from undamaged plants, the physically injured seedlings emitted a large number of sesquiterpenes, the quality and the relative quantity of which were similar to those in leaves determined using organic extraction. The implications of our findings to the biosynthetic pathways leading to the production of sesquiterpenes as well as their biological roles in C. officinalis are discussed.     

Improved hidden Markov models for molecular motors, part 2: extensions and application to experimental data

Unbiased interpretation of noisy single molecular motor recordings remains a challenging task. To address this issue, we have developed robust algorithms based on hidden Markov models (HMMs) of motor proteins. The basic algorithm, called variable-stepsize HMM (VS-HMM), was introduced in the previous article. It improves on currently available Markov-model based techniques by allowing for arbitrary distributions of step sizes, and shows excellent convergence properties for the characterization of staircase motor timecourses in the presence of large measurement noise. In this article, we extend the VS-HMM framework for better performance with experimental data. The extended algorithm, variable-stepsize integrating-detector HMM (VSI-HMM) better models the data-acquisition process, and accounts for random baseline drifts. Further, as an extension, maximum a posteriori estimation is provided. When used as a blind step detector, the VSI-HMM outperforms conventional step detectors. The fidelity of the VSI-HMM is tested with simulations and is applied to in vitro myosin V data where a small 10 nm population of steps is identified. It is also applied to an in vivo recording of melanosome motion, where strong evidence is found for repeated, bidirectional steps smaller than 8 nm in size, implying that multiple motors simultaneously carry the cargo.     

The molecular basis of host plant selection in Melaleuca quinquenervia by a successful biological control agent

Melaleuca quinquenervia (Cav) S.T. Blake (broadleaf paperbark) is an Australian tree that has become a serious weed in many places around the world. Two insects Oxyops vitiosa (the melaleuca weevil), and Boreioglycaspis melaleucae (the melaleuca psyllid), which were introduced to Florida as part of a biological control programme, have been very effective in reducing survival and reproduction of this weed. There are two terpene chemotypes of M. quinquenervia; one rich in the sesquiterpene E-nerolidol whereas the other is rich in viridiflorol. Viridiflorol is a strong feeding deterrent for the melaleuca weevil and retards larval development. The larvae therefore avoid the viridiflorol-rich chemotype, in contrast, female melaleuca psyllids prefer to oviposit on these leaves. To identify the molecular basis of these preferences, we isolated and characterised two terpene synthases from the viridiflorol-rich chemotype, both of which utilise farnesyl pyrophosphate and have the same product profile. Chemotypic variation in terpenes in M. quinquenervia is under strong genetic control and the reproductive potential of each chemotype is limited by a different insect. These insects could, therefore, be selective agents for the maintenance of chemotypic variation in M. quinquenervia.