Global folds of highly deuterated, methyl-protonated proteins by multidimensional NMR

The development of 15N, 13C, 2H multidimensional NMR spectroscopy has facilitated the assignment of backbone and side chain resonances of proteins and protein complexes with molecular masses of over 30 kDa. The success of these methods has been achieved through the production of highly deuterated proteins; replacing carbon-bound protons with deuterons significantly improves the sensitivity of many of the experiments used in chemical shift assignment. Unfortunately, uniform deuteration also radically depletes the number of interproton distance restraints available for structure determination, degrading the quality of the resulting structures. Here we describe an approach for improving the precision and accuracy of global folds determined from highly deuterated proteins through the use of deuterated, selectively methyl-protonated samples. This labeling profile maintains the efficiency of triple-resonance NMR experiments while retaining a sufficient number of protons at locations where they can be used to establish NOE-based contacts between different elements of secondary structure. We evaluate how this deuteration scheme affects the sensitivity and resolution of experiments used to assign 15N, 13C, and 1H chemical shifts and interproton NOEs. This approach is tested experimentally on a 14 kDa SH2/phosphopeptide complex, and a global protein fold is obtained from a set of methyl-methyl, methyl-NH, and NH-NH distance restraints. We demonstrate that the inclusion of methyl-NH and methyl-methyl distance restraints greatly improves the precision and accuracy of structures relative to those generated with only NH-NH distance restraints. Finally, we examine the general applicability of this approach by determining the structures of several proteins with molecular masses of up to 40 kDa from simulated distance and dihedral angle restraint tables.     

Dyspnea resulting from phrenic nerve paralysis after interscalene brachial plexus block in an obese male--a case report

While current psychiatric taxonomies recognise a classification of amphetamine dependence, derived from the notion of an alcohol dependence syndrome, little research has validated that such a condition exists for this drug. Current amphetamine users (N = 331), were interviewed using the World Health Organization operationalisation of DSM-III-R substance dependence criteria, and a measure of the psychological components of dependence. Structural analyses indicated that a unidimensional dependence syndrome as assessed by DSM-III-R and DSM-IV criteria exists for amphetamine, and that physiological, psychological and behavioural indicators were all important in accounting for the variance in responses. It was demonstrated that the concept of a dependence syndrome is applicable to amphetamine, and that the inclusion of the amphetamine dependence syndrome in DSM-III-R and DSM-IV is valid.     

Percutaneous fluoroscopic screw fixation of acetabular fractures

Over a 2-year period eight patients underwent percutaneous fluoroscopic fixation of their acetabular fractures. Average patient age was 43 and mean ISS was 27. Mean blood loss was less than 100 ml. There were five transverse fractures, one affecting both columns, one anterior column-posterior hemitransverse and one T-type fracture. There were two ipsilateral femoral and two ipsilateral tibial fractures. Mean follow-up was 15 months. Three broad patient groups were identified. One patient died, one was lost to follow-up, four had full range of motion of the affected hip, one had good range with Brooker II heterotopic ossification and one was wheelchair-bound with Brooker IV heterotopic ossification. The technique, which requires only cannulated screws and fluoroscopy, is described.     

Paracetamol poisoning in the north east of England: presentation, early management and outcome

1. Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2. To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3. There were 400 presentations (attendance rate 1.14/10(3) population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R = 0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4. In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5. One patient died, from arrhythmias caused by co-ingested dothiepin. 6. Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentrations, but those who do often present late and antidotal treatment may be delayed inappropriately.     

Prenatal diagnosis of an extensive fetal lymphangioma using ultrasonography, magnetic resonance imaging and cytology

An unusual case of fetal lymphangioma diagnosed before delivery is reported in a second trimester pregnant woman. The lymphangioma was suspected at 28 weeks on the basis of the ultrasound appearances and progression of the lesions with advancing gestation. MRI was used to evaluate the extent and the tissue characteristics of the lesions. Cytology of the fluid aspirated from the cystic lesions showed abundant lymphocytes and macrophages, confirming the diagnosis of a lymphangioma. The parents opted for a pregnancy termination because of the rapid growth of the lesions and the poor prognosis. It is suggested that the combination of these tests could enable the early diagnosis of these tumours at a stage when the lesion is relatively limited and accessible to therapy in utero.     

Single motor unit myoelectric signal analysis with nonstationarydata

The information content of the myoelectric signal (MES) is commonly revealed by statistical measures in the time or frequency domain. Empirical analyses of the MES from a single motor unit have generally assumed that features are invariant with time. Theoretical and experimental work has been done to demonstrate how nonstationary behavior in the discharge statistics of a motor neuron may affect estimates of features extracted from the motor unit's contribution to the MES. Specifically, it has been shown that nonstationary behavior can markedly influence estimates of features describing motor neuron firing behavior and consequently, the low-frequency portion of the MES power spectral density. These results may help to explain the discrepancies in the literature which report empirical models of motor neuron firing statistics     

The HLD (CalMod) index and the index question

Twenty free-ranging guanaco (Lama guanicoe) in Chubut Province, Argentina, were immobilized for health evaluations. All but two animals appeared to be in good condition. Hematology, serum chemistry, and vitamin and mineral levels were measured, and feces were evaluated for parasites. Serology tests included bluetongue, brucellosis, bovine respiratory syncitial virus, bovine viral diarrhea/mucosal disease, equine herpesvirus 1, infectious bovine rhinotracheitis, Johne's disease (Mycobacterium paratuberculosis), foot and mouth disease, leptospirosis (17 serovars), parainfluenza-3, and vesicular stomatitis. Blood samples from 20 domestic sheep (Ovis aries) maintained in the same reserve with the guanaco were also collected at the same time for serology tests. No guanaco had positive serologic tests. Sheep were found to have antibody titers to bovine respiratory syncytial virus, Johne's disease, leptospirosis, and parainfluenza-3. There was no apparent difference in external appearance or condition, or statistical difference in blood test values, between the animals that were positive or negative for parasite ova.     

Visualization of plasma turbulence

We have developed a three-dimensional toroidal gyrokinetic particle simulation to study tokamak turbulence. The gyrokinetic equations are a reduced set derived from the Vlasov-Maxwell equations by phase averaging over the ion gyromotion and keeping only the time and space scales relevant for describing tokamak plasmas. These large-scale simulations in complex geometry can produce gigabytes of data consisting of large 3D arrays evolving in time. Visualization plays a critical role in going from the raw nonlinear solution of these complex equations to a simplified theoretical model explaining the essential underlying physics     

Metabolic factors have a major impact on kidney allograft survival

BACKGROUND: At the present time, late graft loss is the major cause of kidney failure after transplantation. However, the influence of metabolic factors on this process is ill-defined. METHODS: To identify the impact of lipid metabolism, glucose metabolism, and blood pressure and their prognostic value for graft survival, data for all recipients of a kidney allograft with a potential graft survival of >15 years and a minimum graft survival of 1 month were analyzed retrospectively. Recipients of kidney grafts functioning more than 15 years (n=32) were compared with those with a graft function of less than 10 years (n=152, controls) and evaluated in a multivariate analysis. RESULTS: Low levels of serum cholesterol, triglycerides, and glucose, before and after transplantation, were accompanied by a prolonged graft survival. Prognostic factors for early graft failure included serum triglycerides >300 mg/dl, cholesterol >250 mg/dl before transplantation, serum creatinine >4.0 mg/dl 1 month after transplantation, and donor age above 45 or less than 10 years. Additionally, systolic and, particularly, diastolic blood pressure was lower in the group with a prolonged graft function as compared with controls immediately before and after transplantation. In addition, the incidence of primary graft function was lower and the incidence of acute rejection episodes higher in controls. Cold and warm ischemic time, body mass index, recipient age, and gender did not differ significantly. CONCLUSIONS: Our data suggest that metabolic parameters play an important role in the process of late graft loss after kidney transplantation.