Two novel mutations in the prothrombin gene cause severe bleeding in a compound heterozygous patient

Hypoprothrombinemia is a rare hereditary coagulation defect characterized by low levels of biologically active prothrombin. In this paper we report the laboratory and genetic analysis of a patient with a severe hypoprothrombinemia and some of her relatives. Laboratory analysis showed very low levels of prothrombin antigen. Molecular analysis of the prothrombin genes of the patient resulted in the identification of two novel sequence variations in heterozygous state, a 20079 G to A transition, which predicts a Trp 569-->Stop mutation, and a 1261C-->G change within intron B near the acceptor splice site. A cosegregation of prothrombin deficiency in family members with the two genetic defects was observed.     

Gamma-globin gene promoter elements required for interaction with globin enhancers

The solution structure of ganglioside G(M1) carbohydrate moiety at the surface of a 102-kDa lipid-modified-G(M1) micelle is investigated by high-resolution 1H-NMR in H2O. The micellar surface can be considered a cluster-like lateral distribution of the gangliosides, each single monomer being anchored in a carbohydrate-enriched model membrane matrix. 1H NOESY measurements at short mixing times reveal a rigid trisaccharide core -beta-GalNAc-(1-4)-[alpha-Neu5Ac-(2-3)]-beta-Gal- and a more flexible beta-Gal-(1-3)-beta-GalNAc- terminal glycosidic bond. In the lipid-modified G(M1) ganglioside micellar system, there is no evidence that intermolecular side-by-side carbohydrate interactions modulate, or alter in any way, the head-group spatial arrangement. Possible intermonomer interactions at the level of the branched trisaccharide portion were further investigated on mixed micelles of natural N-glycolyl- and N-acetylneuraminic acid containing G(M1) in D2O, taking advantage of the different NMR features of N-glycolyl- and N-acetylneuraminic acids, which allow discrimination between sialic acid ring proton signals. Measurements of the water/ganglioside-OH proton chemical exchange rates suggest hydroxyl group involvement at position 8 of sialic acid in strong intramolecular interaction processes.     

A nuclear genetic lesion affecting Saccharomyces cerevisiae mitochondrial translation is complemented by a homologous Bacillus gene

A novel Bacillus gene was isolated and characterized. It encodes a homolog of Saccharomyces cerevisiae Pet112p, a protein that has no characterized relative and is dispensable for cell viability but required for mitochondrial translation. Expression of the Bacillus protein in yeast, modified to ensure mitochondrial targeting, partially complemented the phenotype of the pet112-1 mutation, demonstrating a high degree of evolutionary conservation for this as yet unidentified component of translation.     

Editorial: Multiple loci for human globin genes

It is often suggested that when z-scores are used for linkage estimation, a maximum z-score of 3 (or maximum antilod score, M = 1000) is good evidence for the presence of linkage. It is pointed out that a better formula, applicable if nothing more is known about the loci concerned, would be that the probability that linkage is present is roughly 1--4/Msigma, whereas sigma is the standard error, i.e. square root(2-3 X downward curvature of z curve at peak). A consideration of typical cases suggests that a value M = 1000 would imply something like a 90% chance of linkage. It would seem simpler to use the formula, probability of linkage approximately to 1--H/20, where H is the average height of the antilod curve.     

Factors affecting epirubicin pharmacokinetics and toxicity: evidence against using body-surface area for dose calculation

PURPOSE: An exploratory study to test whether body-surface area (BSA) should be used for the calculation of epirubicin dose. PATIENTS AND METHODS: The relationship between pretreatment characteristics and the effects of epirubicin were investigated in 20 chemotherapy-naive patients. Measurements of body size, renal and hepatic function, and other factors were correlated with epirubicin pharmacokinetics (PK) and epirubicin-induced neutropenia. All patients received 150 mg of epirubicin infused continuously over 120 hours, regardless of body size. Factors were analyzed by univariate and multivariate linear regression. RESULTS: There were no correlations between BSA or weight with any PK parameter or with the degree of neutropenia. In multivariate analysis, indicators of liver function were the only factors that correlated with neutropenia and epirubicin PK. Thus, correlations for neutropenia were seen with antipyrine clearance (P = .003), activated partial thromboplastin time (APTT) (P = .005) and serum transferrin (P = .01). Further, the area under the concentration-time curve (AUC) for epirubicin correlated with prothrombin index (P < .01), antipyrine clearance (P < .01), and serum bile salt concentration (P = .03), and there were similar correlations for epirubicin steady-state concentration (CpSS). Epirubicin clearance correlated with antipyrine clearance (P = .02). PK parameters for dihydroepirubicin correlated with prothombin index, serum transferrin, and bile salt concentrations (P < .001 for all correlations). Because of the number of statistical examinations performed, some of these correlations may be spurious. However, some are likely to be real, since the same variables repeatedly correlated with different epirubicin-associated outcomes. There were no correlations between epirubicin PK indices or neutropenia and serum aminotransferase levels or other biochemical liver function tests, creatinine, or any of the clinical factors examined. CONCLUSION: These results led us to question the use of BSA for epirubicin dose calculation. In contrast, quantitative liver function tests may give a better indication of drug handling and toxicity and may be useful to determine more accurate methods for dose calculation of epirubicin.     

Cloning of a human platelet-activating factor receptor gene: evidence for an intron in the 5''-untranslated region

Twenty-four chickens were randomly assigned to one of three treatments (ketamine, 30 mg/kg; thiopental, 20 mg/kg; saline, 0.8 mL). Baseline data (heart rate, respiratory rate, systolic blood pressure, and cloacal temperature) were recorded before ulnar intraosseous cannulation and administration of drug treatment and for 30 minutes after administration. One investigator, unaware of the treatment administered, assessed the reaction to cannulation, number of attempts per cannulation, reaction to injection, time to induction and recovery, and quality of induction and recovery. Respiratory rate increased significantly (p < .05) from baseline after thiopental. Other parameters did not vary within groups or between groups. Most birds did not react or had a mild reaction to cannulation and injection, and on average fewer than two attempts were necessary. Quality of recovery was significantly (p < .05) better after thiopental. Time to recovery was significantly (p < .05) shorter after thiopental. No major histopathologic changes were noted in bone marrow samples from the injection site. This study demonstrates that the intraosseous route may be used to induce anesthesia in chickens, and that minimal changes in the variables studied were produced by ketamine and thiopental.     

Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23

Transient neonatal diabetes mellitus (TNDM) is a rare form of childhood diabetes which usually resolves in the first 6 months of life but which predisposes to type 2 diabetes of adult onset. We recently reported paternal uniparental isodisomy of chromosome 6 (UPD6) in two children with TNDM and proposed that there may be an imprinted gene important in the aetiology of diabetes on chromosome 6. We now describe two unrelated families which independently suggest that the gene is imprinted, is paternally expressed and maps to 6q22-q23. One family has a duplication while the other, with familial TNDM, shows linkage to a marker in this region.     

Preparation for undergoing an invasive medical procedure: interacting effects of information and coping style

Four reagent formulations (three provided by a manufacturer; one prepared in-house by mixing equal volumes of two commercial reagents) are used for the assay of phencyclidine (PCP) in urine samples. Performance characteristics evaluated included assay precision and sensitivity at and near the assay cutoff concentration. Data resulting from the reagent prepared in-house are better than those using then commercially available formulations, and are comparable with those obtained using the recently available new commercial formulation.     

No evidence for an association of AChR beta-subunit gene (CHRNB1) with myasthenia gravis

Using a polymorphic dinucleotide repeat, we have investigated the contribution of the gene encoding the beta-subunit of the muscle acetylcholine receptor (CHRNB1), the target autoantigen, to the susceptibility to myasthenia gravis (MG). We have combined a case-control study (comparing 143 patients and 162 controls) and a transmission-disequilibrium test bearing on 35 simplex families with heterozygous parents. There was no evidence for an association of CHRNB1 with MG, even after subgrouping patients according to thymus histology, or other clinical criteria. Interestingly however, the shortest four variants of the CHRNB1 microsatellite were seen only in patients with thymus hyperplasia and in none of the control subjects (P < 0.0025).     

The rectal tube: an excellent catheter for severe clot retention

PURPOSE: We describe the use of an alternative catheter for clot irrigation. MATERIALS AND METHODS: Six patients with severe clot retention that could not be treated successfully with irrigation using large bore urethral catheters were subsequently treated with a fenestrated 28 to 32F Rusch red rubber rectal catheter. RESULTS: All clots were successfully evacuated. Cystoscopic evaluation the following day in 4 patients with hematuria confirmed the absence of clots. The other 2 patients did not undergo cystoscopy but continuous bladder irrigation was completely clear for the next 24 hours and the catheters were removed without further sequelae. CONCLUSIONS: Irrigation through a rectal tube can provide immediate relief of clot retention and consequently avoid emergency endoscopic intervention in the operating room.     

CAMs and the FGF receptor: an interacting role in axonal growth

Red howling monkeys, Alouatta seniculusin the central Amazonian basin move to specific sites before defecating. Differences in the vegetation profile of behavioural sites, defecation sites and random sites within the ranging area of howler groups were examined. The defecation sites used differed in the number of leaf intercepts at the levels of the forest the monkeys used for foraging and travelling. Defecating in areas free of underlying vegetation decreases the likelihood of contaminating potential food sources or arboreal pathways. This defecation behaviour may be an important parasite avoidance strategy of red howling monkeys.