Birth factors and laterality: Effects of birth order,parental age,and birth stress on four indices of lateral preference

As an alternative to genetic theories of handedness, some theorists have offered an environmental mechanism, associated with birth stress, for the appearance of left-handedness. They suggest that brain damage as a result of birth difficulties can lead to a switch in hand preference from the right side to the left side. Consequently, one should find more left-handers in groups where the probability of the occurrence of birth stress is greater. Three studies are presented which explore the laterality of not only hand but also foot, eye, and ear, in a total of 5161 individuals, in an attempt to assess any relationship to birth stress. Maternal age seems to predict deviations from dextrality, dependent on the sex of the offspring, while paternal age and birth order do not. The use of a direct measure of conditions predisposing toward birth stress suggests that these results depend on prenatal or perinatal environmental trauma rather than chromosomal factors.This research was supported by grants from the Medical Research Council of Canada and from the Natural Sciences and Engineering Research Council of Canada, and represents an equal and shared contribution of both authors.     

Intrauterine death from umbilical cord hematoma

Umbilical cord hematoma is a rare cause of intrauterine morbidity and mortality. There have been many theories about the etiology of this entity, but its cause remains unknown. Intrauterine death occurred in a postmature (44 weeks) fetus and was associated with an umbilical cord hematoma. Histologic examination of the cord showed a thinning of the wall of the umbilical vein with splitting of the elastic membrane.     

Mosaicism in amniotic fluid cell cultures: Classification and significance

The last decade has witnessed increasing application of human cytogenetic technology to prenatal chromosome analysis. However, unlike the rather uniform peripheral blood T-lymphocyte system which has provided most of our experience in human cytogenetics, long-term amniotic-fluid cell cultures display extreme cellular heterogeneity and disproportionate growth of certain cell types as a consequence of clonal amplification. When they enter cell culture, many of these cells are approching the terminal stages of their respective life spans and may have accumulated chromosomal aberrations. Concern about the possibility of true fetal mosaicism seems warranted chiefly in situations were multiple colonies display potentially viable aberrations. Clonal analysis, preferable of multiple clonal types, and attention to details of clonal morphology are likely to minimize diagnostic errors and undue apprehension resulting from mosaicism in amniotic-fluid cell cultures.     

Molecular interactions of fission yeast Skp1 and its role in the DNA damage checkpoint

Skp1 is a central component of the E3 ubiquitin ligase SCF (Skp1-Cullin-1-F-box). It forms an adapter bridge between Cullin-1 and the substrate-determining component, the F-box protein. In order to establish the role of Skp1, a temperature sensitive (ts) screen was carried out using mutagenic PCR (polymerase chain reaction) and 9 independent ts mutants were isolated. Mapping the mutated residues on the 3-D structure of human Skp1 suggested that the mutants would be compromised in binding to F-box proteins but not Cullin-1 (Pcu1). In order to assess the binding properties of ts Skp1, 12 F-box proteins and Pcu1 were epitope-tagged, and co-immunoprecipitation performed. This systematic analysis showed that ts Skp1 retains binding to Pcu1. However, binding to three specific F-box proteins, essential Pof1, Pof3 involved in maintaining genome integrity, and nonessential Pof10, was reduced. skp1ts cells exhibit a G2 cell cycle delay, which is attributable to activation of the DNA damage checkpoint. Intriguingly, contrary to pof3 mutants, in which this checkpoint is required for survival, checkpoint abrogation in skp1(ts) suppresses a G2 delay and furthermore almost rescues the ts phenotype. The activation mechanism of the DNA damage checkpoint therefore differs between pof3Delta and skp1(ts), implicating a novel role for Skp1 in the checkpoint-signalling cascade.     

Persistent tubular conduction in vacuolated amphibian skeletal muscle following osmotic shock

The transverse (T-)tubules primarily function in conducting the action potentials that initiate excitation– contraction coupling in skeletal muscle but may additionally subserve longer-term roles in volume regulation, membrane fusion and other trafficking processes. Osmotic shock thus both electrically detaches the T-tubules from surface membrane (‘detubulation’) and produces tubular vacuolation. The present experiments separated these effects. An established, reference osmotic shock protocol that exposed muscles to Ca²⁺/Mg²⁺-Ringer and gradual cooling to 10°C after 18 min in glycerol–Ringer accomplished significant detubulation (77.5 ± 13.15%, mean ± SEM; n = 4). In contrast, a test protocol conducted entirely at room temperature using Mg²⁺-rather than Ca²⁺/Mg²⁺-Ringer yielded reduced (P < 0.05, post hoc Duncan's multiple range test) detubulation indices (1.67 ± 1.67%, n = 6) statistically indistinguishable from findings in fibres spared osmotic shock. Yet both osmotic shocks caused a formation of closed vacuoles, demonstrated by Sulphorhodamine B trapping, that occupied statistically similar fractions of total fibre volume (reference procedure: 14.38 ± 2.7%, n = 6; test procedure: 13.36 ± 2.00%, n = 22) in turn higher than determinations in control fibres (P < 0.05). The findings reconcile reports associating detubulation with vacuolation in osmotically shocked muscle [S. Nik-Zainal et al. (1999) J Muscle Res Cell Motil 20: 45–53; K.N. Khan et al. (2000) J Muscle Res Cell Motil 21: 79–90] with the persistence of tubular electrical activity in extensively vacuolated amphibian fibres following fatigue [J. Lannergren and H. Westerblad (1987) Acta Physiol Scand 129: 311–318; J. Lannergren et al. (1999) J Muscle Res Cell Motil 20: 19–32]. Furthermore test protocols produced higher densities of open vacuoles (13.38 ± 2.33%, n = 9) than did reference protocols (6.66 ± 1.63%, n = 20) contrary to their possible involvement in the electrophysiological changes. Abolition of tubular electrophysiological activity thus either follows or is independent of tubular vacuolation whilst sharing some of its underlying osmotic mechanisms. This revised version was published online in July 2006 with corrections to the Cover Date.     

Measurement of changes in cytochrome oxidase redox state during obstructive sleep apnea using near-infrared spectroscopy

STUDY OBJECTIVES: To use near-infrared spectroscopy to investigate the effect of obstructive sleep apnea on cytochrome oxidase, the terminal enzyme of the mitochondrial respiratory chain. DESIGN: Observational study. SETTING: Teaching hospital sleep unit. PATIENTS: Subjects with diagnosed moderate to severe obstructive sleep apnea were recruited from the sleep clinic. INTERVENTIONS: Subjects were invited to attend 2 daytime sleep-study sessions, which included near-infrared monitoring of cerebral oxygenation and cytochrome-oxidase oxidation state. In addition, in study session 1, full polysomnography was performed (8 subjects, 303 apneas), and in study session 2, arterial oxygen saturation, cerebral blood flow velocity, and blood pressure were monitored (7 subjects, 287 apneas). MEASUREMENTS AND RESULTS: In study session 1, mean (+/- SD) cytochrome-oxidase changes ranged from 0.48 +/- 0.08 microM to 0.13 +/- 0.05 microM. The magnitude of cytochrome-oxidase change correlated significantly with the magnitude of change in the cerebral tissue oxygenation index (P < .001). In study session 2, there were significant correlations between arterial oxygen-saturation changes and cytochrome-oxidase redox changes and between Doppler cerebral blood flow velocity changes and cytochrome-oxidase redox changes (P < .001 and P = .001, respectively). CONCLUSIONS: Changes in directly measured cerebral tissue saturation and changes in arterial saturation and cerebral blood flow velocity (the 2 main factors affecting cerebral oxygenation) are associated with changes in cytochrome-oxidase oxidation state. The reduced cerebral oxygenation that occurs during obstructive sleep apnea is associated with changes in the intracellular redox state.     

Short term performance evaluation of a perfluorocopolymer coated gas exchanger for arteriovenous CO2 removal

A new perfluorocopolymer coating for micropore hollow fiber gas exchangers was developed to improve gas exchange, reduce plasma leakage, and reduce blood-surface interactions. The present authors evaluated gas exchanger performance using this new coating in a prospective, randomized, controlled, unblinded, large animal model of CO2 retention. Adult sheep (30-40 kg), under general anesthesia, underwent cannulation of the carotid artery (12 F) and jugular vein (14 F). The perfluorocopolymer coated (n = 5) and uncoated (n = 5) gas exchangers were attached to an arteriovenous CO2 removal (AVCO2R) circuit. Blood gases, CO2 removal, and hemodynamics were monitored throughout the 6 hour study. Average CO2 removal was 107.6 +/- 15.6 ml/min (coated) vs. 93.0 +/- 13.9 ml/min (uncoated; p < 0.01). PaCO2 and CO2 removal for both coated and uncoated did not deteriorate significantly over the study. Average AVCO2R blood flow was 1,130 +/- 25 ml/min (coated) versus 1,101 +/- 79 ml/min (uncoated; p = not significant). Likewise, cardiac output and AVCO2R blood flow did not change over the duration of the study. No significant differences in the pressure gradient or resistance between devices (coated, 6.89 +/- 1.14 mm Hg/L/min; uncoated, 6.42 +/- 0.23 mm Hg/L/min) was noted. The authors concluded that the new perfluorocopolymer coated gas exchanger improved CO2 removal without compromising hemodynamics in an acute performance evaluation.     

Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, alpha-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for alpha-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant alpha-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.