The evolutionary relationship among Caucasian MS patients and controls

Previous observations suggest that the mitochondrial (mt)DNA may confer susceptibility to multiple sclerosis (MS). However, the proportion of affected individuals and the range of contributing mtDNA abnormalities are unknown. To help clarify this question, we analyzed the first hypervariable D-loop sequences of the mtDNA in a group of randomly selected Caucasian MS patients, in MS patients with prominent optic neuritis (PON) and in controls. Phylogenetic analysis of these D-loop sequences revealed that individuals in both groups of patients are generally scattered in the Caucasian phylogeny. However, a small cluster of unrelated MS patients identified by this analysis suggests that a maternal lineage with MS relevant mtDNA sequences may exist, and merits a more comprehensive study.     

Neurochemical studies of human narcolepsy: alpha-adrenergic receptor autoradiography of human narcoleptic brain and brainstem

Studies of human and canine narcolepsy-cataplexy syndrome suggest that noradrenergic function may be abnormal. We used quantitative autoradiography to assess noradrenergic alpha-1 and alpha-2 receptors in several regions of seven human narcoleptic and 18 control brains using [3H]prazosin to evaluate alpha-1 receptors, and [3H]UK14304 and [3H]rauwolscine to evaluate alpha-2 receptors. Specific blocking agents were used in combination with the tritiated ligands to assess alpha-1 and alpha-2 receptor subtypes. Although we found few statistically significant differences between narcoleptic and control brains, there were a number of trends. [3H]Prazosin binding to sites in the amygdala, globus pallidus and putamen was reduced by 22-68%, whereas binding was increased by 40% to the inferior olive and by 84% to portions of the dorsal pons. Binding was similar to control values in other regions. In all seven brainstem regions that were evaluated, the ratio of alpha-1b receptor binding to alpha-1a receptor binding was increased. Binding of [3H]UK14304 was increased by 35-74% in the caudate nucleus, putamen and portions of the amygdala and pons. [3H]rauwolscine binding data suggested that increase of alpha-2 receptor binding in the dorsal pons were not due to effects at the imidazole receptor. findings suggest that noradrenergic function may be altered in specific regions of the brain and brainstem in human narcolepsy, although the absence of statistical significance indicates that these trends should be considered preliminary. The trend toward a relative increase of alpha-1b receptor binding in narcoleptic brainstem is consistent with data from studies of canine narcolepsy and suggests that altered activity at this receptor may contribute to the pathogenesis of human narcolepsy. Studies of additional brains will be required to confirm these findings.     

Polysomnographic and subjective sleep predictors of alcoholic relapse

Previous studies indicate that subjectively reported and objectively measured sleep abnormalities at baseline can increase the risk of relapse in treated alcoholics. However, previous studies did not include both subjective and objective sleep measures in the same group of patients. We utilized polysomnography and the Sleep Disorders Questionnaire to determine if baseline polysomnography increased the ability to predict relapse beyond the prediction with subjective measures alone, after controlling for nonsleep variables that were associated with relapse. We followed 74 patients with a DSM-III-R diagnosis of alcohol dependence, of whom 36 relapsed to at least some drinking during an average follow-up interval of 5 months. Univariate analyses revealed that relapsed patients did not differ from abstinent patients at baseline in demographics or psychiatric co-morbidity, but they had more prior treatment episodes for alcoholism, more difficulty falling asleep, more complaints of abnormal sleep, and, on polysomnography, longer sleep latencies, shorter rapid eye movement sleep latencies, and less stage 4 sleep percentage than abstinent patients. With a series of logistic regression analyses, which controlled for age and gender, we demonstrated that sleep measures improved the prediction model compared with nonsleep variables alone, and that polysomnography-measured sleep latency was the most significant predictor variable. We conclude that subjective and objective measures of baseline sleep are predictors of relapse in treated alcoholic patients. These data also suggest that neurophysiological dysfunction contributes strongly to the etiology of relapse. Finally, sleep disturbance warrants clinical attention as a target of alcoholism treatment.     

Effect of electrical stimulation post mortem of bovine muscle on the binding of glycolytic enzymes. Functional and structural implications

The extent of binding of glycolytic enzymes to the particulate fraction of homogenates was measured in bovine psoas muscle before and after electrical stimulation. In association with an accelerated glycolytic rate on stimulation, there was a significant increase in the binding of certain glycolytic enzymes, the most notable of which were phosphofructokinase, aldolase, glyceraldehyde 3-phosphate dehydrogenase and pyruvate kinase. From the known association of glycolytic enzymes with the I-band of muscle it is proposed that electrical stimulation of anaerobic muscle increases enzyme binding to actin filaments. Calculations of the extent of enzyme binding suggest that significant amounts of enzyme protein, particularly aldolase and glyceraldehyde 3-phosphate dehydrogenase, are associated with the actin filaments. The results also imply that kinetic parameters derived from considerations of the enzyme activity in the soluble state may not have direct application to the situation in the muscle fibre, particularly during accelerated glycolysis.     

HeLa cells as a model to study the invasiveness and biology of Legionella pneumophila

HeLa cells were established as a model system to study the invasiveness and biology of Legionella pneumophila. In this model, invasion could be distinguished from adherence; virulent strains of L. pneumophila were adherent and invasive, whereas nonvirulent strains were adherent but poorly invasive. Invasion was rapid and did not require de novo bacterial protein synthesis, suggesting that the invasion factor is constitutively expressed by virulent strains. Entry into HeLa cells required actin polymerization and an intact microtubule cytoskeleton and was only moderately inhibited by the presence of 100 mM glucose or galactose. Intracellular replication of virulent L. pneumophila took place in ribosome-studded complex endosomes and led to the formation of free bacteria-laden vesicles presumably released from lysed HeLa cells. These free vesicles (referred to as mature vesicles) were isolated in continuous density gradients of Percoll. The bacteria contained in the isolated mature vesicles had a unique envelope structure and were highly adherent to HeLa cells, characteristics that correlated with a bright red appearance after the Giménez stain (Giménez positive). Plate-grown legionellae and replicating legionellae, harboured in complex endosomes, displayed a typical Gram-negative envelope and stained green after the Giménez stain (Giménez negative). Chronically infected cultures of HeLa cells were also established that may be a useful tool for studying long-term interactions between virulent L. pneumophila and mammalian cells. HeLa cells constitute a valuable model system that offers unique opportunities to study parasite-directed endocytosis, as well as stage specific-parasite interactions.     

Information exchange and governance structures in US and JapaneseR&D consortia: institutional and organizational influences

We examine institutional and organizational influences upon information exchange and governance structures within R&D consortia in the United States and Japan. We hypothesized that national differences in institutional environments would lead to less active governance and information-exchange activities within Japanese R&D consortia relative to their US counterparts. At the consortium level, we expected that internal consortium diversity would increase information exchange and governance requirements, and that structures stabilizing relations between consortium members would reduce information exchange and governance requirements. We tested these hypotheses on 39 US and 54 Japanese multifirm R&D consortia, involving, respectively, 1801 US member organizations and 1647 Japanese member organizations. Controlling for organizational age, size, and strategic focus, we found that internal diversity and interorganizational relations are both associated with information-exchange and governance mechanisms. Our model has much greater explanatory power for the United States than for Japan     

Tumor necrosis factor alpha and interleukin 6 release induced by antibiotic killing of Pseudomonas aeruginosa and Staphylococcus aureus

OBJECTIVE: The purpose of this study was to determine the depth that implants may be safely placed into the distal femoral epiphysis (DFE) for the repair of distal femoral physeal fractures. STUDY DESIGN: The depth of the DFE was related to the radiographic thickness of the patella in this experimental study. ANIMALS OR SAMPLE POPULATION: Twenty immature canine cadavers. METHODS: Patella thicknesses were measured from lateral radiographs. Actual DFE depths were determined for pins driven in normograde fashion and for pins driven retrograde from the central depression between the metaphyseal pegs and from the cranial pegs. The association of DFE depth and patella thickness was evaluated using linear regression analysis. Using 95% confidence intervals, rules for estimating the safe depth of implant placement into the DFE were determined. RESULTS: DFE depth had significant correlation with patella thickness for pins placed in retrograde fashion from the central depression between the metaphyseal pegs (r2 = .83) and from the cranial pegs (r2 = .82) and for pins placed in normograde fashion (r2 = .65). CONCLUSIONS: Based on 95% confidence intervals, pins placed in retrograde fashion from the central depression between the metaphyseal pegs may be safely driven into the DFE a distance equal to 140% of patella thickness. Pins placed from the cranial metaphyseal pegs may be driven to a depth equal to 80% of patella thickness, and pins placed in normograde fashion may be driven to a depth equal to 30% of patella thickness. CLINICAL RELEVANCE: Measurement of patella thickness assists the surgeon in determining the approximate depth that pins may be driven into the DFE without penetrating the articular surface of the stifle joint.     

Prevalence of malaria in Dakar, Senegal. Comparative study of the plasmodial indices in pregnant and non-pregnant women

One hundred ASA I orthopaedic surgical patients (four randomized groups) were anaesthetized using continuous propofol and intermittent fentanyl (TIVA), with controlled ventilation via a tracheal tube in groups 1 and 2, and a laryngeal mask airway (LMA) in groups 3 and 4. Neuromuscular blockers were used in groups 1 and 3 only. There were no significant differences between groups in total anaesthetic requirements, as assessed by cardiovascular variables and movement. Coughing interfered with surgery and made controlled ventilation difficult to manage. In contrast, movement not associated with coughing did not impair surgery or ventilation. Patients in group 2 (tracheal tube, no neuromuscular blocker) required more interventions for coughing than the other groups, while patients in group 4 (LMA, no neuromuscular blocker) needed more boluses for movement than groups 1 and 3. Groups 1 and 2 (tracheal tube) had significantly higher heart rates and mean arterial pressures than groups 3 and 4 for varying periods up to 5 min after insertion of the airway management device. There was no correlation between mean arterial pressure and plasma concentrations of catecholamines related to insertion of either the tracheal tube or LMA. The LMA was found to be a highly effective device for controlled ventilation in TIVA and easier to manage than the tracheal tube in the absence of neuromuscular blockers.