The TOTEM RRMS (Testosterone Treatment on neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis) trial: study protocol for a randomized, double-blind, placebo-controlled trial.

Background: Central nervous system damage in multiple sclerosis (MS) is responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation; however, there is an urgent need for innovative therapies promoting neuroregeneration, particularly myelin repair. It is demonstrated that testosterone can act through neural androgen receptors and several clinical observations stimulated an interest in the potential protective effects of testosterone treatment for MS.

Unveiling the multi-step solubilization mechanism of sub-micron size vesicles by detergents.

The solubilization of membranes by detergents is critical for many technological applications and has become widely used in biochemistry research to induce cell rupture, extract cell constituents, and to purify, reconstitute and crystallize membrane proteins. The thermodynamic details of solubilization have been extensively investigated, but the kinetic aspects remain poorly understood. Here we used a combination of single-vesicle Förster resonance energy transfer (svFRET), fluorescence correlation spectroscopy and quartz-crystal microbalance with dissipation monitoring to access the real-time kinetics and elementary solubilization steps of sub-micron sized vesicles, which are inaccessible by conventional diffraction-limited optical methods.

[Results of a phase I-II clinical trial of Emoxyl, a novel antineoplastic anthracycline].

Emoxyl (ruboxyl) is a product of chemical modification of daunorubicin mediated by a stable free radical. The drug was given to 63 patients with different malignancies stages I-II. Inhibition of hemopoiesis (leukopenia and thrombocytopenia) was identified as the dose-limiting toxicity level.

[Comparative study of cytosolic proteins in normal and neoplastic ovaries by polyacrylamide electrophoresis].

The report discusses the data on cytoplasmic protein occurrence in ovarian tissue (106) obtained by polyacrylamide gel electrophoresis. They were identified in normal ovarian tissue (15), benign tumor (16), primary malignant tumor (55) and tumor tissue after chemotherapy (20). A band was detected in the area of molecular 36 cD in malignant epithelial tumor tissue which was not seen in either normal, benign tumor tissue or after successful chemotherapy.

[The probability of the carcinogenic risk of using nitrosomethylurea for treating cancer patients].

The results of nitrosomethylurea (NMU) chemotherapy in 12 patients suffering Hodgkin's disease were evaluated. Significant effect was seen in 73.3% with 54.

Hofmeister effect in ion transport: reversible binding of halide anions to the roflamycoin channel.

We have studied the anion-dependent gating of roflamycoin ion channels using spectral analysis of noise in currents through multichannel planar lipid bilayers. We have found that in addition to low frequency current fluctuations that may be attributed to channel switching between open and closed conformations, roflamycoin channels exhibit a pronounced higher frequency noise indicating that the open channel conductance has substates with short lifetimes. This noise is well described by a Lorentzian spectrum component with a characteristic cutoff frequency that depends on the type of halide anions according to their position in the Hofmeister series.

The role of cytoplasmic [Ca2+] in glucose-induced inhibition of respiration and oxidative phosphorylation in Ehrlich ascites tumour cells: a novel mechanism of the Crabtree effect.

The effect of Ca2+ on energy-coupling parameters of Ehrlich ascites carcinoma was studied in digitonin-permeabilized cells. In nominally Ca-free medium the permeabilized cells respond to the addition of ADP by increased oxygen uptake with externally added respiratory substrates (succinate or pyruvate), decrease of the mitochondrial membrane potential (delta psi) and alkalinization of the medium. This typical behaviour is drastically changed if Ca2+ is added.

The influence of acetylcholine and atropine on the temporary connection in neuronal populations of the motor cortex.

The activity of neurons of the sensorimotor cortex during the paired combination of stimulations of brain structures (the medial lemniscus, the reticular nucleus of the midbrain tegmentum, and the pyramidal tract), with an interstimulus interval of 1.2 sec, was investigated in awake nonimmobilized rabbits. During the omission of the reinforcing stimulus at a place of its expected delivery, a complicated complex of reorganizations of the impulse activity of the neurons develops, consisting of the reproduction of responses and changes in impulse activity which differ in configuration from them, and which usually appear at later periods.

1H NMR assignments and secondary structure of human beta 2-microglobulin in solution.

Sequence-specific resonance assignments of human beta 2-microglobulin (M(r) 12,000) and its secondary structure are determined by 2D NMR techniques. The protein is found to contain two antiparallel beta-sheets each of four beta-strands with the beta-sheets being connected by a single disulfide linkage. No evidence for any regular helical structure is found.

Interpretation of the X-ray diffraction pattern from relaxed skeletal muscle and modelling of the thick filament structure.

The first part of this paper is devoted to the model-building studies of our high resolution meridional X-ray diffraction patterns (in the region from 1/500 to 1/50 A-1) obtained from relaxed frog muscle. A one-dimensional model of thick filament was proposed which basically consists of two symmetrical arrays of 50 crossbridge crown projections. In the proximate and central zones of the filament the crossbridge crowns are regularly shifted with a 429 A period and appear as triplets with a 130 A distance between crowns, while the crowns in the distal parts of filament are regularly ordered with a 143 A repeat.

Learning of rats under amnesia caused by pentobarbital.

Dissociated learning of rats in the normal state and the state of amnesia produced by pentobarbital (15 mg/kg, ip) was carried out. Rats were trained to approach a shelf where they received food reinforcement. In Group 1 the rats were trained under the influence of pentobarbital to run to the same shelf as in the normal state.

Non-planar structure of nitrous bases and non-coplanarity of Watson-Crick pairs.

We discuss the non-planar structural stability of the NH2-group in formamide, cytosine, adenine, guanine and aniline molecules. Based on the microwave data available on small amino derivatives and on the results of PCILO conformation study it is shown that the slope of the amino group HNH plane to the molecular plane in nitrous bases should be close to 40 degrees. One of the main consequences of the non-planar structure of bases is a comparatively large (approximately equal to 15 degrees) propeller twisting of purine and pyrimidine planes in the complementary adenine-thymine and guanine-cytosine pairs.

Photophysical processes in the NADH-alcohol dehydrogenase complex.

Fluorescent analysis showed the high sensitivity of the NADH-alcohol dehydrogenase complex to UV irradiation. The complex reacts to UV illumination with "photoresponse," a rapid decrease in NADH fluorescence intensity to some stationary level. No such decrease was found in the NADH solution without the protein.

Interaction of cupric ion with parvalbumin.

Cod parvalbumin, a calcium-binding protein, possesses a specific Zn2+ (or Cu2+) binding site per molecule. This work employed fluorescence energy transfer techniques to measure the distance between the Zn2+ (Cu2+) site and the stronger Ca(2+)-binding site in parvalbumin. Specifically, the distance between Tb3+ bound at the Ca2+ site and Co2+ bound to the Zn2+ (Cu2+) binding site was 10.

Effects of pH, Ca2+ and lanthanides on conformation of the sarcoplasmic reticulum Ca(2+)-ATPase catalytic site.

The conformational changes at the ATP-catalytic site of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase have been studied by the fluorescence of the fluorescein 5-isothiocyanate (FITC) bound to the adenine subsite. The FITC-SR fluorescence parameters have been examined in the pH range 5.7-8.

Bursting responses of Lymnea neurons to microwave radiation.

Microelectrode and voltage-clamp techniques were modified to record spontaneous electrical activity and ionic currents of Lymnea stagnalis neurons during exposure to a 900-MHz field in a waveguide-based apparatus. The field was pulse-modulated at repetition rates ranging from 0.5 to 110 pps, or it was applied as a continuous wave (CW).

Binding of Zn(II) ions to alpha-lactalbumin.

The binding of Zn(II) ions to human and bovine alpha-lactalbumin has been studied by fluorescence, scanning microcalorimetry, and proteolytic digestion. The intrinsic tryptophan fluorescence spectrum of Ca(II)-loaded alpha-lactalbumin is insensitive to Zn(II) binding to the strong cation binding sites (Zn:protein ratios up to 20), yet the thermal denaturation transition, as detected by intrinsic fluorescence, is shifted toward lower temperatures. On the other hand, low concentrations of Zn(II) ([Zn]:[protein] less than 1) shift heat sorption curves toward lower temperatures.

A new philosophy of medical imaging.

In general, the traditional approach to medical imaging is based on the solution of the inverse problem of deducing the characteristics of tissues within the body from the received field resulting from probing radiation. Ambiguities and lack of complete data, and physical limitations such as diffraction, field non-uniformity and so on, prevent the image from being an exact representation of what would be seen if the imaged part of the patient were to be exposed to direct vision or drawn by an artist. Much more exact representation could be produced, however, if the philosophy of imaging were to be changed to involve the solution of the forward problem in which the received field is iteratively compared with that calculated to be produced by a computer-simulated model of the object from a knowledge base of anatomy, pathology, histology, physical properties of tissues etc.

Survey of small molecule and ion binding to beta 2-microglobulin--possible relation to BEN.

Using a new method which permits rapid detection of ligand binding to cross linked protein films and crystals, we evaluated a spectrum of ligand binding to cross linked amorphous films of beta 2-microglobulin purified from urine of Balkan endemic nephropathy patients. Among more than 50 substances studied, including amino acids, fatty acids, sugars, nucleotides, nucleosides, and different inorganic ions, only polyvalent cations, such as Cu2+, Ca2+, Zn2+, Be2+ and La3+, were found to strongly bind to human beta 2-microglobulin with dissociation constants in the range 10(-6) to 10(-4) M. These cations can release beta 2-microglobulin from HLA complexes leading to an increased beta 2-microglobulin level in serum.

Endothelial cell population dynamics in rat brain after local irradiation.

The dynamics of the endothelial cell population was investigated in the rat brain after local irradiation with different doses of X rays. A fluorescent-histochemical technique was used for the visualization of the cells. A decrease in endothelial cell number was observed within 1 day of irradiation with doses of 5-200 Gy.

Vertebrate muscle Z-line structure: an electron microscopic study of negatively-stained myofibrils.

Structural features of the Z-lines of rabbit psoas muscle myofibrils have been studied in the electron microscope with a negative staining technique. The results obtained suggest the presence of about 20 nm periodicity in the structural organization of the Z-line region: a band pattern of five bands of extra density spaced about 20 nm apart was revealed in the Z-region and the Z-filaments connecting actin filaments from neighbouring sarcomeres often appeared to be positioned at intervals of 17-20 nm. An electron microscopic investigation of the interaction in vitro of two major Z-line proteins, alpha-actinin and F-actin, indicated that the positions of alpha-actinin bridges between actin filaments are defined by relative azimuthal positions of actin subunits.

The spatial organization of the cytoskeleton in crayfish stretch receptor.

An electron microscopic study of the cytoskeleton of the crayfish stretch receptor was carried out. Longitudinal sections of the sensory neuron axons and dendrites showed wave-like arrays of microtubules with a period of about 5 microns. Transverse sections showed that the microtubules displayed no regularity in the arrays.