Haplotype analysis of the human apolipoprotein B mutation associated with familial defective apolipoprotein B100.

Haplotype analysis was conducted on the mutant allele of 14 unrelated subjects heterozygous for a mutation in the codon for amino acid 3500 of human apolipoprotein B100. This mutation is associated with defective binding of low-density lipoprotein to the low-density lipoprotein receptor and with moderate hypercholesterolemia. Ten markers were used for haplotyping: eight diallelic markers within the structural gene and two hypervariable loci flanking the gene. Seven of eight unequivocally deduced haplotypes were identical, and one revealed only a minor difference at one of the hypervariable loci. The genotypes of the six other affected subjects were consistent with this same assigned haplotype. These data are consistent with a common ancestral chromosome and provide no evidence for a recurrent mutation at this potentially hypermutable CG dinucleotide, despite the fact that this mutation is not rare.     

Diagnosis of urogenital Chlamydia trachomatis infection in women based on mailed samples obtained at home: multipractice comparative study.

OBJECTIVE: To compare urine and vaginal flush samples collected by women at home with endocervical and urethral swabs obtained by general practitioners for their efficacy in the diagnosis of urogenital Chlamydia trachomatis infection. DESIGN: Multipractice comparative study. SETTING: 33 general practices and a central department of clinical microbiology in Aarhus County, Denmark. SUBJECTS: 222 women aged 18-25 years who for any reason had a gynaecological examination. INTERVENTIONS: Endocervical and urethral swabs were obtained by the women''s general practitioners. The same women when at home then collected a first void urine sample, a midstream urine sample, and a vaginal flush sample (using a vaginal pipette) and mailed them to the laboratory. MAIN OUTCOME MEASURES: C trachomatis defected by the polymerase chain reaction and the ligase chain reaction. Eight tests for C trachomatis were performed for every woman. When two of the eight yielded positive results the patient was considered infected. RESULTS: The overall prevalence of C trachomatis infection was 11.2% (23/205 women). Test sensitivities in samples obtained by general practitioners, samples obtained at home subjected to polymerase chain reaction, and samples obtained at home subjected to ligase chain reaction were 91%, 96%, and 100% respectively. The corresponding specificities were 100%, 92.9%, and 99.5%. CONCLUSIONS: The diagnostic efficacy of samples obtained by women at home and mailed to the laboratory was as good as for samples obtained by a general practitioner when using the ligase chain reaction. This may have important implications for the practicability of screening for this common, often asymptomatic, and treatable infection.     

A rapid scanning strip for tri- and dinucleotide short tandem repeats.

Oligonucleotides representing 60 trinucleotide (21mers) and four dinucleotide (20mers) tandem repeats were directly synthesized and arrayed onto an aminated polypropylene substrate. DNA samples of different complexities (a CAG-containing 21mer oligonucleotide, PCR fragments of 200 to 3,000 bp, and cosmids with 31 to 35 kb inserts) were radiolabelled and hybridized to the oligonucleotide array at various temperatures. When compared to sequence data available from the test DNAs, the reverse blot system specifically identified various tri- and dinucleotide short tandem repeats (STRs) in every case. Moreover, there was no random or cross hybridization to nonspecific sequences. It was possible to detect as few as three repeated units in a particular location, as shown for (CCT)n, (GCC)n and (CAC)n triplets in cosmid DNA. Varying the hybridization stringency can enhance the detection of STRs. This single-step reverse blot system therefore allows the rapid, specific and sensitive identification of various STRs in DNA sources of different complexity.     

Past,present and future utilisation ofMyrica gale (Myricaceae)

The development ofM. gale oil as an insect repellent has created a requirement for cultivation of the plant. Botanical evidence indicates thatM. gale is likely to thrive on well—aerated acid peatland and could become a valuable crop on land of low agricultural value. Plant growth would be enhanced by the prevention of grazing and could be combined with softwood forestry since the trees would benefit from soil nitrogen enrichment thanks to the symbiotic association ofM. gale andFrankia. The economics of oil production would be improved if additional compounds of value such as pharmacologically active fiavonoids could be extracted from the by-products.     

A review of the effects of dopaminergic agents on humans,animals, and drug-seeking behavior,and its implications for medication development

Medication development for cocaine abuse has focused on potential mechanisms of action related to the abuse of cocaine. The hypothesis that mesolimbic dopamine (DA) is the key neurochemical mediator of cocaine’s addictive and reinforcing effects is well supported by a wide variety of data from animal studies. On the other hand, medications that increase DA or block its actions in humans can produce effects that appear incompatible with this hypothesis. This article reviews these incompatibilities between animal and human data with a focus on the DAergic actions of drugs, including DA reuptake inhibitors, direct DA agonists, DA increasers, and DA antagonists. Possible reasons for these discrepancies are discussed, and the potential role of high-affinity DA uptake inhibitors, such as GBR12909, for pharmacotherapeutic application to treat cocaine abuse is discussed. Since progress in developing pharmacotherapies for treating cocaine addiction in humans is likely to come from understanding its mechanisms of action, it is clear that further research on the effects of cocaine in humans and animals will be critical to the medication development effort. A shortened version of this paper was presented at the Satellite Meeting of the International Society for Neurochemistry on “Cellular and Molecular Mechanisms of Drugs of Abuse: Cocaine and Methamphetamine” held on August 19–20, 1993 in Nice, France.     

Isomerization ofn- andi-butyrate in anaerobic methanogenic systems

Studies of the degradation of the two isomeric forms of butyrate in different anaerobic environments showed isomerization betweenn- andi-butyrate. Degradation rates were similar for the different examined systems and degradation rates forn-butyrate degradation were generally higher than fori-butyrate. Degradation rates forn-butyrate ranged from 0.52 to 1.39 day^–1, while the rates fori-butyrate were from 0.46 to 1.15 day^–1. Production of isomers was not observed when the volatile fatty acid degradation was inhibited by addition of bromoethane sulfonic acid, indicating that isomerization was coupled to the methanogenic degradation of the acid. The degree of isomerization observed duringn-butyrate degradation was similar to the degree duringi-butyrate degradation. Experiments indicated that the isomerization degree was higher for the thermophilic than for the mesophilic inocula.