Increased frequency of rheumatoid factor precursor B lymphocytes after immunization of normal adults with tetanus toxoid.

Vaccination of normal adults with tetanus toxoid induced a two-three-fold rise in the frequency of IgM anti-IgG (rheumatoid factor, RF) B lymphocytes inducible by the polyclonal B cell activator, Epstein-Barr virus. The increase in IgM-RF precursors occurred earlier, was greater in magnitude, and was more sustained than the change in plasma IgM-RF. It was associated with a rise in total IgM levels, and correlated positively with the magnitude of the IgG anti-tetanus antibody response, but not with levels of circulating immune complexes. The ability of apparently innocuous infections and immunizations to increase the frequency of IgM-RF precursor B lymphocytes may be the reason for the previously noted expansion in this autoreactive B cell pool between birth and adulthood.     

A probabilistic approach to measure the strength of bone cell adhesion to chemically modified surfaces

Patterned surfaces with alternating regions of amino silanes [N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS)] and alkyl silanes [dimethyldichlorosilane (DMS)] have been used to alter the kinetics of spatial distribution of cellsin vitro. In particular, we have previously observed the preferential spatial distribution of bone cells on the EDS regions of EDS/DMS patterned surfaces (10). In this study, we examined whether the mechanism of spatial distribution of cells on the EDS regions was adhesion mediated. Homogeneous layers of EDS and DMS were immobilized on quartz substrates and characterized by contact angle, X-ray photoelectron spectroscopy, and spectroscopic ellipsometry. The strength of bone cell attachment to the modified substrates was examined using a radial flow apparatus, within either 20 min or 2 hr of cell incubation in the presence of serum. A Weibull distribution was chosen to characterize the strength of cell-substratum adhesion. Within 20 min of cell exposure, the strength of adhesion was significantly larger on EDS and clean surfaces, compared with DMS surfaces (p<0.0001). Within 2 hr of cell incubation, there was no statistical difference between the strength of cell adhesion to EDS, DMS, and clean surfaces. The results of this study suggest that the surface chemistry mediates adhesion-based spatial cell arrangement through a layer of adsorbed serum proteins.     

Daily stress and mood and their association with pain,health-care use,and school activity in adolescents with sickle cell disease

OBJECTIVE: To determine the extent to which daily stress and mood are associated with pain, health-care use, and school activity in adolescents with sickle cell disease (SCD). METHOD: Adolescents with SCD (n = 37; aged 13 to 17 years) completed daily diaries assessing pain, stress, mood, activity, and health-care use for up to 6 months. Multilevel modeling was used to analyze the data. RESULTS: Daily increases in stress and negative mood were associated with increases in same-day pain, health-care use, and reductions in school and social activity. Increases in positive mood were associated with decreases in pain, less health-care use, and more activity participation. Notably, pain was predictive of higher stress and lower positive mood on subsequent days. CONCLUSION: Pain in adolescents with SCD is stressful and may lead to alterations in mood states. Understanding the way in which these variables relate to health-care use and activity may lead to improved pain management approaches.     

Activation of the skeletal α-actin promoter during muscle regeneration

Little is known conerning promoter regulation of genes in regenerating skeletal muscles. In young rats, recovery of muscle mass and protein content is complete within 21 days. During the initial 5–10 days of regeneration, mRNA abundance for IGF-I, myogenin and MyoD have been shown to be dramatically increased. The skeletal -actin promoter contains E box and serum response element (SRE) regulatory regions which are directly or indirectly activated by myogenin (or MyoD) and IGF-I proteins, respectively. We hypothesized that the skeletal -actin promoter activity would increase during muscle regeneration, and that this induction would occur before muscle protein content returned to normal. Total protein content and the percentage content of skeletal -actin protein was diminished at 4 and 8 days and re-accumulation had largely occurred by 16 days post-bupivacaine injection. Skeletal - actin mRNA per whole muscle was decreased at day 8, and thereafter returned to control values. During regeneration at day 8, luciferase activity (a reporter of promoter activity) directed by –424 skeletal -actin and –99 skeletal -actin promoter constructs was increased by 700% and 250% respectively; however, at day 16, skeletal -actin promoter activities were similar to control values. Thus, initial activation of the skeletal - actin promoter is associated with regeneration of skeletal muscle, despite not being sustained during the later stages of regrowth. The proximal SRE of the skeletal -actin promoter was not sufficient to confer a regeneration-induced promoter activation, despite increased serum response factor protein binding to this regulatory element in electrophoretic mobility shift assays. Skeletal -actin promoter induction during regeneration is due to a combination of regulatory elements, at least including the SRE and E box. © Kluwer Academic Publishers.     

Peritoneal implantation of meningeal melanosis via ventriculoperitoneal shunt: A case report and review of the literature

Systemic spread of primary intracranial neoplasms is rare and may be due to ventriculoperitoneal shunt (VPS). The most common tumors to metastasize via VPS are germinoma of the pineal gland and medulloblastoma. We report a case of 16-yr-old girl with central nervous system malignant melanosis who developed subsequent peritoneal implants via VPS. To the best of our knowledge, this patient represents the third reported case of meningeal melanosis or melanoma which metastasized to the peritoneal cavity via VPS. The VPS should be considered as possible mode of systemic spread in patients with primary cranial malignancy. © 1995 Wiley-Liss, Inc.     

Changes in muscle recruitment patterns during skill acquisition

The control of movement is predicated upon a system of constraints of musculoskeletal and neural origin. The focus of the present study was upon the manner in which such constraints are adapted or superseded during the acquisition of motor skill. Individuals participated in five experimental sessions, in which they attempted to produce abduction-adduction movements of the index finger in time with an auditory metronome. During each trial, the metronome frequency was increased in eight steps from an individually determined base frequency. Electromyographic (EMG) activity was recorded from first dorsal interosseous (FDI), first volar interosseous (FVI), flexor digitorum superficialis (FDS), and extensor digitorum communis (EDC) muscles. The movements produced on the final day of acquisition more accurately matched the required profile, and exhibited greater spatial and temporal stability, than those generated during initial performance. In the early stages of skill acquisition, an alternating pattern of activation in FDI and FVI was maintained, even at the highest frequencies. In contrast, as the frequency of movement was increased, activity in FDS and EDC was either tonic or intermittent. As learning proceeded, alterations in recruitment patterns were expressed primarily in the extrinsic muscles (EDC and FDS). These changes took the form of increases in the postural role of these muscles, shifts to phasic patterns of activation, or selective disengagement of these muscles. These findings suggest that there is considerable flexibility in the composition of muscle synergies, which is exploited by individuals during the acquisition of coordination.     

The dynamics of isometric bimanual coordination

Eight right-handed subjects performed rhythmic isometric applications of torque in the directions of pronation and supination of the forearm, in single limb and bimanual conditions. Bimanual movements were executed in either in-phase (homologous muscles simultaneously active) or anti-phase (non-homologous muscles active simultaneously) modes of coordination, in self-paced and frequency-scaled conditions. In the inphase (frequency-scaled) condition, subjects were required to synchronise (applications of torque) with each beat of a metronome, either in the direction of pronation or supination. In the anti-phase (frequency-scaled) condition, subjects were required to synchronise (applications of torque) with each beat of the metronome, either to the left or to the right. Departures from the anti-phase mode of coordination were observed as pacing frequency was increased. However, these departures were of short duration and the anti-phase mode was always re-established. These findings are in marked contrast to those obtained when there is free motion of the limbs. There also existed systematic differences between the stability of the pronation and supination phases of torque application. These differences were, in turn, modified through coincidence with the pacing signal. These results are discussed with reference to the constraints imposed upon the coordination dynamics by the intrinsic properties of the neuromuscular-skeletal system.     

Regulation of Epstein-Barr virus infection by recombinant interferons. Selected sensitivity to interferon-gamma

Interferons (IFN) are antiviral proteins that may be important in mediating cellular defenses against Epstein-Barr virus (EBV) infection. However, the means by which IFN-alpha, -beta and -gamma modify EBV infectivity are not clear. We have evaluated the effects of purified recombinant preparations of all three classes of IFN on EBV-induced B lymphocyte proliferation and Ig secretion. When added early after EBV infection, all three recombinant IFN reduced B cell outgrowth and Ig secretion. IFN-gamma exerted a 7-10-fold more potent antiviral effect than IFN-alpha or -beta. All three types of IFN act directly on B cells. Monocytes and natural killer cells are not necessary for the anti-EBV activity. Of the three recombinant IFN, only IFN-gamma reduced EBV-induced proliferation and Ig secretion when added 3-4 days after virus infection; IFN-alpha/beta were only effective up to 24 h. B lymphoblastoid lines already transformed by EBV are insensitive to the anti-proliferative actions of all three types of IFN. On the basis of these findings, we propose three phases of regulation during EBV infection. In the early phase, EBV-infected cells can be regulated by all IFN. Subsequently, there is an intermediate period where only IFN-gamma is capable of directly affecting EBV-induced B cell responses. In the third phase, B lymphocytes become insensitive to direct actions of all IFN and are now subject to regulation only by cytotoxic cells.