Long latency postural reflexes are under supraspinal dopaminergic control

Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by "toe-up" rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild parkinsonism), 8 patients with young-onset Parkinson's disease, and 4 patients with MPTP-induced parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable) perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a "default" response emerged that anticipated the 10 degrees perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic-induced parkinsonism and young-onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP-induced parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.     

Interpretation time of serial chest CT examinations with stacked-metaphor workstation versus film alternator

PURPOSE: Interpretation time of serial staging chest CT cases, which each contained current and previous examinations, with a simple prototype workstation called filmstack was experimentally compared with interpretation time with a film alternator. MATERIALS AND METHODS: The filmstack displayed a "stack" of sections for each examination; user controls allowed rapid selection of preset attenuation windows and both synchronized and unsynchronized scrolling. Eight radiologists were timed as they used the filmstack and the film alternator to interpret four ergonomically complex serial CT cases. RESULTS: All reports dictated on the basis of findings with filmstack and film were of acceptable clinical accuracy. The time to examine a case with filmstack was significantly faster than the time with film, including the time to load and unload the alternator (99% confidence [P = .01]). There was no statistically significant difference in interpretation time between filmstack and prehung film. CONCLUSION: Use of a low-cost stacked CT workstation with a single 1,024 x 1,024 monitor is an effective means of interpreting cases that require comparison of multiple CT examinations.     

The formation of cardiac-electric-field potentials on the surface of the heart and torso in vertebrate animals

The comparative electrophysiological study of excitation process in heart with different types of organization have laid the foundation for solution of the problems of formation of cardioelectric field. It was shown, that the form of extracellular potentials on the epicardium correlated with different types of ventricle myocardial activation. Animals with the "flash" type of myocardial depolarization in most cases have the negative extracellular potentials in the greater part of the epicardial ventricular surface. Animals with the consecutive type of myocardial activation--the positive and biphase potentials. All myocardial layers (epicardial, intramural and endocardial) are electrophysiologically informative.     

The genome of Treponema pallidum: new light on the agent of syphilis

Covert brain activity related to task-free, spontaneous (i.e. unrequested), emotional evaluation of human face images was analysed in 27-channel averaged event-related potential (ERP) map series recorded from 18 healthy subjects while observing random sequences of face images without further instructions. After recording, subjects self-rated each face image on a scale from "liked" to "disliked". These ratings were used to dichotomize the face images into the affective evaluation categories of "liked" and "disliked" for each subject and the subjects into the affective attitudes of "philanthropists" and "misanthropists" (depending on their mean rating across images). Event-related map series were averaged for "liked" and "disliked" face images and for "philanthropists" and "misanthropists". The spatial configuration (landscape) of the electric field maps was assessed numerically by the electric gravity center, a conservative estimate of the mean location of all intracerebral, active, electric sources. Differences in electric gravity center location indicate activity of different neuronal populations. The electric gravity center locations of all event-related maps were averaged over the entire stimulus-on time (450 ms). The mean electric gravity center for disliked faces was located (significant across subjects) more to the right and somewhat more posterior than for liked faces. Similar differences were found between the mean electric gravity centers of misanthropists (more right and posterior) and philanthropists. Our neurophysiological findings are in line with neuropsychological findings, revealing visual emotional processing to depend on affective evaluation category and affective attitude, and extending the conclusions to a paradigm without directed task.     

The crystal structure of a 3D domain-swapped dimer of RNase A at a 2.1-A resolution

The dimer of bovine pancreatic ribonuclease A (RNase A) discovered by Crestfield, Stein, and Moore in 1962 has been crystallized and its structure determined and refined to a 2.1-A resolution. The dimer is 3D domain-swapped. The N-terminal helix (residues 1-15) of each subunit is swapped into the major domain (residues 23-124) of the other subunit. The dimer of bull seminal ribonuclease (BS-RNase) is also known to be domain-swapped, but the relationship of the subunits within the two dimers is strikingly different. In the RNase A dimer, the 3-stranded beta sheets of the two subunits are hydrogen-bonded at their edges to form a continuous 6-stranded sheet across the dimer interface; in the BS-RNase dimer, it is instead the two helices that abut. Whereas the BS-RNase dimer has 2-fold molecular symmetry, the two subunits of the RNase A dimer are related by a rotation of approximately 160 degrees. Taken together, these structures show that intersubunit adhesion comes mainly from the swapped helical domain binding to the other subunit in the "closed interface" but that the overall architecture of the domain-swapped oligomer depends on the interactions in the second type of interface, the "open interface." The RNase A dimer crystals take up the dye Congo Red, but the structure of a Congo Red-stained crystal reveals no bound dye molecule. Dimer formation is inhibited by excess amounts of the swapped helical domain. The possible implications for amyloid formation are discussed.     

Protein kinase C-dependent in vivo phosphorylation of prourokinase leads to the formation of a receptor competitive antagonist

We recently reported that in vivo phosphorylation of urokinase-type plasminogen activator on Ser138/303 prevents its catalytic-independent ability to promote myelomonocytic cell adherence and motility. We now show that Ca2+ activated, phospholipid-dependent protein kinase C from rat brain phosphorylates in vitro a peptide corresponding to prourokinase residues 133-143 (DGKKPSSPPEE) and the full-length molecule on Ser138/139. The in vivo involvement of the protein kinase C isoenzyme family is supported by the finding that inhibition of kinase C activity prevents prourokinase phosphorylation on Ser138/303 in A431 human carcinoma cells. Conversely, a short treatment of A431 cells with phorbol myristate acetate increases the extent of phosphorylated prourokinase and, concomitantly, affects its function; under these conditions, the capability of prourokinase to up-regulate U937 monocyte-like cell adherence is severely impaired, although receptor binding is unaltered. By the aid of a "phosphorylation-like" variant (Ser138 to Glu) we show that modification of Ser138 is sufficient to confer to prourokinase the antagonistic properties observed following in vivo stimulation of protein kinase C activity. These observations provide the first evidence that protein kinase C directs the formation of a receptor competitive antagonist by regulating the in vivo phosphorylation state of prourokinase.     

Cancer predisposition, radiosensitivity and the risk of radiation-induced cancers. IV. Prediction of risks in relatives of cancer-predisposed individuals

Individuals carrying cancer-predisposing germline mutations are known to be at a higher risk for cancers than those who do not carry them. This is also true of their biological relatives because they have a higher probability of being carriers of such mutant genes than unrelated individuals in the population. Further, there are now sufficient grounds for assuming that cancer-predisposed individuals may also be at a higher risk for cancers induced by ionizing radiation. In our earlier work, we examined the impact of this heterogeneity (with respect to cancer predisposition and radiosensitivity differentials) on risks of radiation-induced cancer at the population level. This paper is focused on the question of risks of radiation-induced cancer in relatives of cancer-predisposed individuals. Using an autosomal dominant model of cancer predisposition and radiosensitivity developed earlier and applying it to breast cancer risks associated with mutations in the BRCA1 gene, we show that: (1) The risk ratio (i.e. the ratio of risk of radiation-induced cancer in relatives to that in unrelated individuals) in the population increases with the degree of biological relatedness of the relative, being higher for close than for distant relatives; incomplete penetrance of the mutant gene "dilutes" this risk ratio. (2) The proportion of excess radiation-induced cancers in relatives (i.e. the attributable fraction) is higher than in unrelated individuals. (3) In relatives, the proportion of excess cancers due to radiosensitivity differentials alone depends on the strength of predisposition, the radiosensitivity differentials assumed, the radiation dose, the proportion of cancers due to predisposition, the mutant gene frequency and the penetrance of the mutant gene. This is in contrast to the situation for unrelated individuals, for whom the above-mentioned proportion is dependent on the first three but not on the last three of these factors. Further, even when the proportion of excess cancers is small, most of it is due to radiosensitivity differential alone both in unrelated individuals and in relatives. (4) For values of predisposition strength and radiosensitivity differential <10, even when the estimated frequency of a mutant BRCA1 gene is 0.0047 and the proportion of breast cancers due to these mutations is 38% (as is the case for Ashkenazi Jewish women under age 30), the increase in breast cancer risks is only marginal even for first-degree relatives. (5) These findings support the conclusion that increases in radiation risks to relatives (compared to those in unrelated individuals), to be detectable epidemiologically, will occur only when the mutant alleles are common and the strength of predisposition and radiosensitivity differentials are conjointly dramatic.     

Image-analysis-based assessment of the effects of the "Ca2+-jump" technique on sarcomere uniformity

A new image analysis-based technique was used to quantitatively examine the effects of the "Ca2+-jump" activation protocol on the maintenance of fiber quality in skinned rabbit psoas muscle fiber segments. Specifically, contractions in pCa 4.6 were preceded by short-duration "preactivation" soaks in a solution in which EGTA was replaced with the low-Ca2+ buffering capacity analog hexamethylenediamine-N, N, N', N'-tetraacetate, which facilitated rapid Ca2+ equilibration within the fiber segments. Fiber quality was assessed by examining the Fourier spectra of the muscle fiber images before, during, and after activation. Segment lengths were typically below 500 micrometer, thus allowing the majority of the sarcomeres to be visualized in the field of view (x200 and x400 magnification). The preactivation protocol resulted in less deterioration of fiber quality with repetitive activation. In addition, there was also a significant reduction in the time required to reach the 50% level of maximum tension, with no significant change in the maximum tension level.     

Preoperative anxiety and fear: a comparison of assessments by patients and anesthesia and surgery residents

We sought to compare self-assessment of preoperative anxiety levels and selection of worst fears by surgical patients with the assessments made by the anesthesia and surgery residents providing intraoperative care for those patients. One hundred inpatients at a Veterans Affairs hospital (Group 1) and 45 patients at a University hospital (Group 2) were asked to complete a brief questionnaire; the residents were asked to complete the same questionnaire. Group 1 results showed that median patient visual analog scale (VAS) scores were lower for anxiety about anesthesia compared to surgery (16 vs 22, P < or = 0.05). Anesthesia resident VAS scores were higher than patient or surgery resident scores. Neither type of resident was able to predict their individual patient's VAS score (Kendall's tau). The fear chosen with the greatest incidence by Group 1 patients and residents was "whether surgery would work". A significant number of residents (34%, anesthesia or surgery, P < or = 0.05) matched their patient's fear choice. Residents commonly chose fears related to their specialty (e.g., anesthesia residents chose anesthesia-related fears more often than surgery residents, 50% vs 28%, P < or = 0.001). In Group 2, residents demonstrated an improved ability to predict patient scores. For instance, both surgery and anesthesia residents were able to predict individual University patient VAS scores (P < or = 0.01). The fear chosen with the greatest frequency by Group 2 patients was "pain after the operation". Sixty percent of anesthesia residents matched their patients' fear choice (P < or = 0.001). This study indicates a variable ability of anesthesia and surgery residents to predict patient anxiety and fear which may be due, in part, to difficulty in understanding a Veterans Affairs hospital patient population.     

The lateral retromalleolar groove: a radio-anatomic study]

The anatomy of the malleolar peroneal groove is presented. The results are based on a coupled osteological and CTscan study of 20 samples of fibulae. The average distal fibular torsion was 64 degrees. The peroneal groove was oriented posteriorly (mean value: 78 degrees). Three types of morphological variations were found: concave, flat, convex (the convex shaped groove was the most frequent one: 70%). The average width of the groove was 9 mm. These morphometric results were compared to "clinical" ones performed on patients with a peroneal tendons dislocation syndrome: CTscan study showed an osseous dysplasia concerning the groove depth (flat or convex) and/or a torsional insufficiency. Hypothesis of a bone dysplasia in peroneal dislocation syndrome is discussed.