Sequence homology between certain viral proteins and proteins related to encephalomyelitis and neuritis.

Post-infectious or post-vaccinal demyelinating encephalomyelitis and neuritis may be due to immunological cross-reactions evoked by specific viral antigenic determinants (epitopes) that are homologous to regions in the target myelins of the central and peripheral nervous systems. Such homologies have been found by computer searches in which decapeptides in two human myelin proteins were compared with proteins of viruses known to infect humans. These viruses include measles, Epstein-Barr, influenza A and B, and others that cause upper respiratory infections. Several regions identified in myelin basic protein and P2 protein can be related to experimental allergic encephalomyelitis or neuritis in laboratory animals.

Corticospinal conduction studied with magnetic double stimulation in the intact human.

A group of 8 healthy normal subjects (24-36 years old, mean age 29 years) were investigated. Transcranial magnetic double stimulation of the motor cortex was carried out at different interstimulus intervals. With both stimuli suprathreshold, an attenuation of the test response was found at interstimulus intervals of less than 200 msec (target relaxed or contracted). The manifestation of this attenuation correlated with central signs in 31 patients with multiple sclerosis. This phenomenon is (at least at longer intervals) probably not a result of the refractory spinal motoneuron pool, but of a supraspinal inhibitory mechanism or lack of corticospinal drive caused otherwise. At interstimulus intervals between 10 and 30 msec, the test response increases significantly (magnetic double stimulation 10% suprathreshold, target relaxed). This result is also seen with voluntary muscle contraction and with vibration applied to a relaxed target muscle. The facilitatory effect is probably caused by slowly conducted corticospinal volleys enabling summation, with descending impulses generated by the test stimulus. With the conditioning stimulus subthreshold and target muscle relaxed an intracortical inhibition of the test response could be confirmed at short interstimulus intervals.

The multiple causes of multiple sclerosis: the importance of age of infections in childhood.

The geographic distribution of multiple sclerosis (MS) may relate to the age of initial exposure and degree of sensitization to common viruses or bacteria which have proteins with epitopes (antigenic determinants) which are homologous with potentially encephalitogenic peptides in central myelin proteins, such as basic protein and proteolipid protein. Comparable homologies may exist for the as-yet-undefined nonencephalitogenic myelin antigen(s) which evoke demyelinating factors (probably complement-fixing antibodies). Many of these homologous epitopes occur in microorganisms that also possess adjuvant activity for evoking not only the sensitized T-cells but also the antibodies that cross-react with the target antigens in central myelin. If sufficient sensitization to myelin basic protein or proteolipid protein occurs, especially in infections of young adults, the individual develops acute disseminated encephalomyelitis, exactly comparable to ordinary acute experimental allergic encephalomyelitis (EAE). If very young children are infected, however, practically complete resistance develops, and neither acute disseminated encephalomyelitis nor MS follows. In between these two extremes, especially in slightly older children in whom insufficient sensitization occurs to induce acute disseminated encephalomyelitis, the individual may become resistant to acute disseminated encephalomyelitis, but susceptible to chronic relapsing or progressive disseminated encephalomyelitis, otherwise generally recognized as MS. This is exactly comparable to a recently described variant of chronic EAE in which demyelinating antibodies and large subpial plaques of demyelination occur. The similarity of this form of chronic EAE or chronic disseminated encephalomyelitis to one form of MS is emphasized.

Neutron energy spectra from the laser-induced Dd,n3He reaction.

Detailed neutron energy spectra were measured for the D(d,n)3He reaction induced in solid (CD2)(n) targets by irradiation with 50-fs 2 x 10(18) W/cm(2) light pulses from a 10-TW Ti:Sapphire laser. The neutrons were observed at two angles 5 degrees and 112 degrees relative to the incident laser beam. The neutron spectra at the two angles are characterized by peaks with large widths of about 700 keV full width at half maximum and a shift of 300 keV between them. Neutron energies of up to about 4 MeV were observed indicating that deuterons are accelerated up to an energy of 1 MeV in the laser produced plasma. Simulation calculations can describe qualitatively the neutron spectra by assuming isotropic deuteron acceleration and a reduction of the reaction probability by a factor of 1/3 for deuterons emitted from the front of the target. These calculations indicate in particular that it is necessary to assume deuterons moving both into and out of the front of the target in order to describe the neutron energy spectra at the two angles. The highest recorded mean neutron yield was about 10(4) neutrons per pulse. The neutron yield increases with the number of electrons emitted from the front of the target and with the intensity of the prompt gamma flash induced by the bremsstrahlung of energetic electrons.

Explosion characteristics of intense femtosecond-laser-driven water droplets.

An efficient acceleration of energetic ions is observed when small heavy-water droplets of approximately 20 microm diameter are exposed to ultrafast (approximately 40 fs) Ti:sapphire laser pulses of up to 10(19) W/cm2 intensity. Quantitative measurements of deuteron and neutron spectra were done, allowing one to analyze the outward and inward directed deuteron acceleration from the droplet. Neutron spectroscopy based on the D (d,n) fusion reaction was accomplished in four different spatial directions. The energy shifts of those fusion neutrons produced inside the exploding droplet reflect a remaining deuteron acceleration inside the irradiated droplet along the axis of the incident laser beam. The overall neutron yield of the microdroplets is relatively small as a result of the dominant outward directed acceleration of the deuterons with 1200 neutrons/shot. Relying on the "explosion-like" acceleration of such spherical droplet targets we have developed a spray target consisting of heavy-water microspheres with diameters of 150 nm . Both the high deuteron energies of up to 1 MeV resulting from the irradiation intensity of approximately 10(19) W/cm2 as well as the collisions between the deuterons and the surrounding spray delivered about one order of magnitude more neutrons than the single-droplet system. The approximately 6 x 10(3) neutrons per laser pulse from the spray can be attributed to an efficient deuteron release from a significantly smaller laser excited volume as from deuterium-cluster targets.

The causes of the syndromes of Landry (1859) and of Guillain, Barré and Strohl (1916).

Post-infectious and post-vaccinal peripheral neuritis or encephalomyelitis have frequently been considered the human equivalents of experimental allergic neuritis (EAN) or encephalomyelitis (EAE). The major basis for these comparisons between diseases in humans and experimental animals rests on the classical observations of "paralytic accidents" of Pasteur-type vaccination against rabies. These old observations in humans injected with brain tissue indicate a remarkable heterogeneity of periphéral as well as central nervous system syndromes, quite in contrast with the remarkable specificity for either peripheral or central involvement in most experimental animals. The syndromes of Landry (1859) and of Guillain, Barré and Strohl (1916) differ clinically and pathologically, the latter a purely peripheral neuritis and the former a mixture of transverse myelitis and facial neuritis. Each can be caused by many different factors, including 1) direct infection by wild or attenuated rabies virus, 2) direct auto-sensitization by myelin antigens in the vaccine and 3) indirect or cross-reactive sensitization by viral or bacterial antigenic determinants (epitopes) with sufficient chemical homology with aminoacid sequences in central or peripheral myelin antigens to be recognized as immunological homologies.

Olfactory function in patients with idiopathic Parkinson's disease: effects of deep brain stimulation in the subthalamic nucleus.

Decrease of olfactory function in patients with Parkinson's disease (PD) is a well-investigated fact. The present study aimed to investigate olfaction in PD patients with a specific focus on the effects of deep brain stimulation in the subthalamic nucleus. Eleven patients (age 42-67 years) participated in this study. Using the "Sniffin' Sticks", olfactory function was assessed based on butanol odor thresholds and the patients' ability to discriminate odors. Measures were taken with the stimulator being switched ON and OFF, respectively. While deep brain stimulation had no effect on odor thresholds, in hyposmic PD patients odor discrimination was found to be significantly higher during the ON period. This may indicate that deep brain stimulation has a positive effect on the cognitive processing of olfactory information in PD patients.

Fast decision in favor of the slow fission process.

The fission probability P(f) of highly excited targetlike nuclei produced in reactions of 2.5 GeV protons on Au, Bi, and U was studied as a function of excitation energy E* whereby E* is deduced eventwise from the multiplicity of evaporated light particles. At the highest E* of 1000 MeV P(f) amounts to approximately 30% with all 3 target nuclei irrespective of the initial fissility. Statistical-model calculations satisfactorily reproduce the observed evolution of P(f) with E*--provided that no extra transient delay is introduced. Fission thus is decided upon very fast and early in the long deexcitation chain towards scission which comprises as much as approximately 80% of all evaporated alpha particles.

Comparison of the Mg2+ and Ca2+ binding properties of troponin complexes P1-TI2C and TI2C.

The phosphoserine present in troponin T of freshly isolated skeletal muscle troponin P1-TI2C was dephosphorylated by alkaline phosphatase and the resulting troponin TI2C characterized by phosphorous content and gel electrophoresis in presence of sodium dodecylsulfate. Both complexes bind Ca2+ in an identical manner with a K0.5 of 5.3 X 10(-9) M for the Ca2+/Mg2+ binding sites and of 1.1 X 10(-6) M for the Ca2+-specific sites. 3.5 mM Mg2+ lowers the K0.5 value at the Ca2+/Mg2+ binding sites of 1.3 X 10(-7) M in the phospho-troponin P1-TI2C and leaves nearly unchanged the value of the dephosphorylated troponin TI2C at 1.2 X 10(-8) M. At 10 mM Mg2+ only one dissociation constant of about 1.0 X 10(-6) M is determined with both complexes. In analogy dephosphorylation of troponin P1-TI2C reduces the affinity for Mg2+ at the Ca2+/Mg2+ binding sites from 6.7 X 10(-5) M to 2.0 X 10(-3) M. Again the Mg2+-specific sites are uninfluenced. The possibility is discussed that removal of the phosphate group from troponin T allows the interaction of the N-terminal domain of troponin T with other amino acid side chains of troponin.

Ca2+ and Mg2+-dependent complex formation of tropomyosin with phosphotroponin (P1TI2C) or dephosphotroponin (TI2C).

The reduced viscosity of troponin and dephosphotroponin is independent of the protein concentration in both states, either metal-free or with troponin C saturated with Ca2+ or Mg2+; that of tropomyosin increases linearly as function of the protein concentration, indicating aggregation. Addition of troponin to tropomyosin increases the reduced viscosity over the expected value being maximal at a 1:1 molar ratio of both proteins. The reduced viscosity of a 1:1 molar mixture of phosphotroponin-Mg4 or dephosphotroponin-Mg3 increases in two phases as function of the total protein concentration, indicating the formation of two kinds of troponin-tropomyosin complexes. In the first phase, troponin and tropomyosin form a non-aggregating 1:1 complex, which is characterized by a value of 0.45 dl/g for the intrinsic viscosity and a sedimentation coefficient of 3.6 S. Employing these two values a molecular weight of 150 000 can be calculated, which is in the range of the sum of molecular weights for troponin and tropomyosin (156 000). In the second phase the troponin-tropomyosin complex aggregates further, a process described by:n (troponin-tropomyosin) leads to (troponin-tropomyosin)n. This further aggregation occurs upon saturation of the Ca2+-specific sites in troponin C. A model is discussed which explains the shortening of 1.5 nm per tropomyosin molecule upon the shift of tropomyosin from the periphery into the groove of the actin filament by tropomyosin aggregation.

The acyl-carrier protein in Neurospora crassa mitochondria is a subunit of NADH:ubiquinone reductase (complex I).

We determined the primary structure of a 9.6-kDa subunit of the respiratory chain NADH:ubiquinone reductase (complex I) from Neurospora crassa mitochondria and found a close relationship between this subunit and the bacterial or chloroplast acyl-carrier protein. The degree of sequence identity amounts to 80% in a region of 19 residues around the serine to which the phosphopantetheine is bound. The N-terminal presequence of the subunit has the characteristic features of a mitochondrial import sequence. We cultivated the auxotroph pan-2 mutant of N. crassa in the presence of [14C]pantothenate and recovered all radioactivity incorporated into mitochondrial protein in the 9.6-kDa subunit of complex I. We cultivated N. crassa in the presence of chloramphenicol to accumulate the nuclear-encoded peripheral arm of complex I. This pre-assembled arm also contains the 9.6-kDa subunit. These results demonstrate that an acyl-carrier protein with pantothenate as prosthetic group is a constituent part of complex I in N. crassa.

The 49 K subunit of NADH: ubiquinone reductase (complex I) from Neurospora crassa mitochondria: primary structure of the gene and the protein.

The primary structure of the 49 K subunit of the respiratory chain NADH:ubiquinone reductase (complex I) from Neurospora crassa was determined by sequencing cDNA, genomic DNA and the N-terminus of the mature protein. The sequence lengths correlate to a molecular mass of 54,002 daltons for the preprotein and 49,239 daltons for the mature protein. The presequence consists of 42 amino acids of typical composition for sequences which target nuclear-encoded proteins into mitochondria. The mature protein consists of 436 amino acids and shows 64% similarity to a 49 K subunit of bovine heart NADH:ubiquinone reductase and 33% to a predicted translation product of an open reading frame in the chloroplast DNAs of Marchantia polymorpha and Nicotiana tabacum. Evidence for an iron-sulfur cluster in the subunit is discussed.