Biofeedback and applied psychophysiology at the crossroads

Biofeedback and applied psychophysiology, as tools, as objects of scientific inquiry, and as clinical interventions, have progressed from speculative experiment to data-based research, from trial clinical intervention to efficacy studies and accountability. These are multidisciplinary approaches, crossing the boundary between traditional professions such as medicine, psychology, physical therapy, occupational therapy, and other health care related fields. Along the way we as an Association, our members both scientists and practitioners, have encountered the many hurdles and stumbling blocks that stand in the way of developing new technologies. How we deal with these obstacles shapes us as a group and shapes the perceptions of others who view us. An attempt will be made to place the current development of the field within the context of the rapidly changing health care environment, and to address the challenges, and sometimes conflicting demands, of experimental science and clinical practice.     

Morphological and cytoskeletal changes caused by non-membrane damaging cytotoxin of Vibrio cholerae on Int 407 and HeLa cells

End-group mediated conjugation of bacterial polysaccharides (PSs) to carrier proteins containing T-helper cell epitopes renders such polysaccharides immunogenic also in young infants. Optimal construction of such conjugate vaccines requires fragmentation of the PS prior to the coupling reaction. In the present study a general simple and inexpensive method for the fragmentation of PSs is presented. It is based on the irradiation of isolated PSs in an electron beam accelerator. Exposure of isolated pneumococcal capsular polysaccharides (PnPSs) to ionizing radiation resulted in their partial depolymerization in a radiation dose-dependent manner. Radiation, unlike sonication, generated PnPS fragments of molecular size lower than 50 kDa and as small as 1.5 kDa when high radiation doses were used. These PnPS fragments have terminal reducing groups that can be easily used for chemical activation and subsequent coupling to any chosen carrier protein. The radiation-produced PnPS fragments retained their antigenic epitopes, when compared to native, full-size PnPSs as determined by enzyme-linked immunoassay.     

Imagerie des azoospermies d’origine excrétoire

Obstruction of the seminal tract is observed in 10 to 15% of men presenting with azoospermia or severe oligozoospermia (sperm count <1 million/ml) and with a normal FSH level. When ejaculate volume is normal, scrotal ultrasonography can detect, when clinical examination is unconclusive, enlarged hypoechoic epididymis or dilatation of the epididymal head. When biochemical markers are normal (carnitine and a1-4 glucosidase) a very proximal obstacle, located in the efferent cones can be responsible for the azoospermia; in this case, only sonography can detect dilatation of the rete-testis. Azoospermia with low, volume ejaculate and marked decrease of the fructose level in the semen, are related to a distal stenosis. Transrectal ultrasonography (TRUS) and endorectal MRI, performed in selected cases, show abnormalities which have to be interpreted according to the clinical setting. In case of bilateral absence of the vas deferens, scrotal ultrasonography is helpful if clinical examination is unconclusive; it shows a dilatation of the rete-testis and of the efferent ductules. The epididymal head can have a cystic-like appearance (spermatocele). TRUS shows the agenesia of the ampullae and agenesia or abnormalties of the seminal vesicles in 95% cases. In case of unilateral absence of the scrotal vas deferens, TRUS shows an ipsi-lateral agenesia of the ampulla and contralateral abnormalities suggesting a distal stenosis of the ejaculatory ducts. In case of bilateral palpable scrotal vas deferens, TRUS shows abnormalitites suggesting a distal obstruction of the ejaculatory ducts. The most frequent causes are congenital median cysts (Mullerian or Wolffian origin) and inflamatory stenosis of the ejaculatory ducts, which can occasionally be related to a ductal stone. TRUS is now routine part of the investigation of azoospermic patients with low volume ejaculate. Endorectal MRI better assesses than TRUS the relationships of the abnormality with the veru-montanum, which is useful when surgery is planned. Likewise, scrotal ultrasonography is useful when clinical examination is unconclusive and/or when biochemical sperm markers levels do not confirm an otherwise clinically suspected obstruction.     

Inhibition of Oncogenic and Activated Wild-Type ras–p21 Protein-Induced Oocyte Maturation by Peptides from the Guanine-Nucleotide Exchange Protein, SOS, Identified from Molecular Dynamics Calculations. Selective Inhibition of Oncogenic ras–p21

In the preceding paper we performed molecular dynamics calculations of the average structures of the SOS protein bound to wild-type and oncogenic ras–p21. Based on these calculations, we have identified four major domains of the SOS protein, consisting of residues 631–641, 676–691, 718–729, and 994–1004, which differ in structure between the two complexes. We have now microinjected synthetic peptides corresponding to each of these domains into Xenopus laevis oocytes either together with oncogenic (Val 12)-p21 or into oocytes subsequently incubated with insulin. We find that the first three peptides inhibit both oncogenic and wild-type p21-induced oocyte maturation, while the last peptide much more strongly inhibits oncogenic p21 protein-induced oocyte maturation. These results suggest that each identified SOS region is involved in ras–stimulated signal transduction and that the 994–1004 domain is involved uniquely with oncogenic ras–p21 signaling.     

The lingual (root analogue) and the labial (crown analogue) mouse incisor dentin promotes ameloblast differentiation

Previous studies have suggested that mouse molar ameloblast differentiation was triggered by the predentin-dentin. Knowing that enamel is absent on the lingual surface of the mouse incisor, the aim of this study was to compare in heterotopic tissue recombinations the behavior of mouse molar inner dental epithelium associated with lingual or labial mouse incisor dentin. It was shown that root-analogue and crown-analogue incisor dentin promotes ameloblast differentiation of competent molar inner dental epithelium.     

A novel form of vitamin B-12 and its derivatives

A new isomeric form of cobalamins is reported. The conversion of cobalamin to cobalamin′ (the new form) is achieved by substituting the benzimidazole base by a less bulky group like H₂O of CN^? and modest thermal treatment. The back conversion of adenosylcobalamin′ to the corresponding regular form occurs in the ‘base-off’ form at room temperature. It seems that the corrin ring becomes quite flexible in the ‘base-off’ form and the freer axial movement of the cobalt atom flips the corrin ring into a different conformation. The change in conformation is borne out by subtle changes in the proton magnetic resonances on the corrin ring and the base, and very marked variation in the emission Mössbauer spectra. The latter is indicative of appreciable changes in the spatial conformation in the immediate vicinity of the central metal atom.The ultraviolet-visible and infrared spectra of a cobalamin′ are indistinguishable from those of its corresponding regular form.The new conformational isomeric species is present as an impurity in all commercially available cobalamins (including pharmaceutical preparations). It raises the question whether the cobalamins′ constitute the real biologically active anti-anemic factor in humans     

Stabilization of Thermolysin Induced by a Decrease in the PH and Dielectric Constant of the Reaction Medium Resulting from a Temperature Increase in Z-Phe-Phe-OMe Synthesis

Thermolysin was stabilized by increasing the reaction temperature from 90°C to 110°C during peptide synthesis of N-(benzyloxycarbonyl)-_L-phenylalanyl-_L-phenylalanine methyl ester (Z-Phe-Phe-OMe). The stabilization energy was acquired from the drop in both pH and dielectric constant due to the temperature increase. The acquired stabilization energy was as high as ca. 42 kJ/mol (corresponding to 20°C). This acquired stabilization energy did not result from a single event such as a change in electrical charges. It was evaluated as the overall stabilization energy at and around the active site area of the enzyme using an electrostatic potential equation.     

Inhibition of Oncogenic and Activated Wild-Type ras-p21 Protein-Induced Oocyte Maturation by Peptides from the ras-Binding Domain of the raf-p74 Protein, Identified from Molecular Dynamics Calculations

In the preceding paper we found from molecular dynamics calculations that the structure of the ras-binding domain (RBD) of raf changes predominantly in three regions depending upon whether it binds to ras-p21 protein or to its inhibitor protein, rap-1A. These three regions of the RBD involve residues from the protein–protein interaction interface, e.g., between residues 60 and 72, residues 97–110, and 111–121. Since the rap-1A–RBD complex is inactive, these three regions are implicated in ras-p21-induced activation of raf. We have therefore co-microinjected peptides corresponding to these three regions, 62–76, 97–110, and 111–121, into oocytes with oncogenic p21 and microinjected them into oocytes incubated in in insulin, which activates normal p2l. All three peptides, but not a control peptide, strongly inhibit both oncogenic p21- and insulin-induced oocyte maturation. These findings corroborate our conclusions from the theoretical results that these three regions constitute raf effector domains. Since the 97–110 peptide is the strongest inhibitor of oncogenic p21, while the 111–121 peptide is the strongest inhibitor of insulin-induced oocyte maturation, the possibility exists that oncogenic and activated normal p21 proteins interact differently with the RBD of raf.