ATP-dependent proteolysis in mitochondria. m-AAA protease and PIM1 protease exert overlapping substrate specificities and cooperate with the mtHsp70 system

To analyze protein degradation in mitochondria and the role of molecular chaperone proteins in this process, bovine apocytochrome P450scc was employed as a model protein. When imported into isolated yeast mitochondria, P450scc was mislocalized to the matrix and rapidly degraded. This proteolytic breakdown was mediated by the ATP-dependent PIM1 protease, a Lon-like protease in the mitochondrial matrix, in cooperation with the mtHsp70 system. In addition, a derivative of P450scc was studied to which a heterologous transmembrane region was fused at the amino terminus. This protein became anchored to the inner membrane upon import and was degraded by the membrane-embedded, ATP-dependent m-AAA protease. Again, degradation depended on the mtHsp70 system; it was inhibited at non-permissive temperature in mitochondria carrying temperature-sensitive mutant forms of Ssc1p, Mdj1p, or Mge1p. These results demonstrate overlapping substrate specificities of PIM1 and the m-AAA protease, and they assign a central role to the mtHsp70 system during the degradation of misfolded polypeptides by both proteases.     

Typology of prolonged anxious-phobic disorders with agoraphobia

There were studied 23 schizophrenic and cyclothymic patients with stable agoraphobia in the structure of anxiousphobic disorders (APD). No absolute correlation was found between stability of agoraphobia and severity of panic disorder (frequency and intensity of panic attacks). It was established that APD with manifestations of agoraphobia had been, perhaps, conditioned by the presence of comorbid disturbances in their structure which had determined peculiarities of the patients' behavior. Two types of prolonged APD with agoraphobic phenomena were recognized. Retention of agoraphobic disturbances in conditions of the first type was related to symptoms of generalized somatic disorder (generalized somatic anxiety) in clinical pattern of APD. Manifestations similar to panphobias prevailed, agoraphobic avoidance included all the situations in which the patient could find himself without help. In the states of the second type retention of agoraphobic disorders was conditioned by comorbidity of APD with asthenohypochondriac manifestations with somato-psychic fragility in their structure. Anxiety of expectation was formed in situations with emotional or physical tension. Agoraphobic avoidance in conditions of this type had displayed the character of preventive measures and one of manifestations of hypochondriac development of personality. The presence of pronounced anxiety (intensive panic attacks, generalized anxiety) in clinical pattern of prolonged agoraphobic conditions can serve a predictor of a favourable development of the disease.     

Menstruation, menarche, and sexuality in the public school curriculum: school nurses' perceptions

Nurses employed by schools and health departments have varying responsibilities for curricula related to menstruation, menarche, and sexuality. Nevertheless, the school nurse is usually a source of information on these subjects whether employed full-time in school health or also participating in other nursing roles in the community. This survey examines the involvement of school nurses in curricula related to human reproduction including contraception. Data about their involvement in these classroom topics provides a basis for evaluating their roles and making recommendations for subsequent continuing education programs for school health nurses.     

Spontaneous spectral changes of the reduced cytochrome bd

Suramin inhibits the growth of non-small cell lung cancer (NSCLC) and breast cancer in vitro by blocking the action of most known growth factors. The clinical efficacy of suramin was evaluated in patients with unresectable or relapsed NSCLC (n = 16) and advanced breast cancer (ABC) resistant to conventional therapies (n = 12). A plasma level > or = 200 micrograms/ml was maintained by three times weekly administrations using adaptive control with feedback. Treatment was continued until documented progression of disease or unacceptable toxicity. No clinical responses were observed in any patient. Median overall survival was 4.5 months in NSCLC and 9 months in ABC patients. Mean treatment duration was 6.6 weeks in NSCLC patients and 15.9 weeks in ABC patients. Treatment was discontinued due to disease progression in 14 patients, unacceptable adverse effects in 11 patients, while three patients refused to continue therapy. We cannot recommend this drug for further clinical trials in NSCLC and ABC.     

Effect of the electric field in the space-charge layer on the efficiency of short-wave photoelectric conversion in GaAs Schottky diodes

A study is reported of the quantum efficiency of the short-wave photoelectric effect as function of the reverse bias applied to GaAs Schottky diodes when the light absorption length is much shorter than the width of the space charge region. The quantum efficiency of photoelectric conversion is found to depend strongly on the contact electric field and the photon energy. The field independence of the quantum efficiency is interpreted in terms of a fluctuational trap model. The model can also be used to determine the loss factor for hot photocarriers, which is found to increase in a stepwise manner with increasing photon energy. This effect is explained in terms of the formation of excitons in X-and L-valleys of the semiconductor. Fiz. Tekh. Poluprovodn. 31, 1225–1229 (October 1997)     

Magnetoencephalographic evidence for non-geniculostriate visual input to human cortical area V5

The aim of this study was to establish whether there is non-geniculostriate input to the extrastriate motion-sensitive area V5 in humans. Responses were measured with a SQUID neuro-magnetometer to motion stimuli presented within the blind hemifield of GY, a well-documented subject with a complete absence of the left primary visual cortical area V1. The motion stimulus was a 0.5c/deg, rapidly drifting (16Hz) achromatic sinusoidal grating. With this stimulus, the magnetic responses recorded over the temporo-parieto-occipital region in normals are well modelled by localized current sources in areas V1 and V5 (Anderson, S. J. et al., Proceedings of the Royal Society, London, Series B, 1996, 263, 423-431). As a control, evoked responses were measured to a 1.0 c/deg, stationary, photometrically isoluminant red/green sinusoidal grating. With the chromatic stimulus, the principal component of the magnetic responses recorded over the occipital pole in normals is well modelled by a current source in area V1 (Fylan, F. et al., Investigative Ophthalmology and Visual Science, 1995, 36, s1053). Both stimuli subtended 4 deg vertically by 6 deg horizontally, positioned such that the stimulus extended beyond the area of macular sparing into the lower field quadrant of the blind (or sighted) hemifield. Chromatic stimuli failed to evoked responses from GY's blind (contralateral) hemifield, consistent with there being no V1 activity in his left cortical hemisphere. However, motion stimuli did evoke responses from GY's blind hemifield, originating from a location consistent with activity in area V5. We further observed that both colour and motion stimuli evoked responses from GY's sighted (ipsilateral) hemifield. We conclude that there is non-geniculostriate input to extrastriate motion-sensitive areas in the human visual system, and that this pathway subserves the residual visual sensitivity to motion in the blind hemifield that has been demonstrated psychophysically in observer GY.     

FcalphaRI (CD89) as a novel trigger molecule for bispecific antibody therapy

Promising results from clinical trials with unconjugated antibodies stimulated renewed interest in immune effector mechanisms of monoclonal antibodies (MoAbs). We investigated the potential of IgA as antibody isotype for cell- or complement-mediated tumor cell lysis and assessed the potential of its myeloid Fc receptor, FcalphaRI (CD89), as trigger molecule for bispecific antibody (BsAb)-mediated immunotherapy. Comparing hapten-directed antibodies of human IgA2 with IgG1 or IgG3 isotypes, we found all three to mediate effective killing of sensitized tumor target cells in whole blood assays. Analysis of effector mechanisms showed IgG-mediated lysis to be predominantly complement-dependent, whereas IgA-dependent killing was primarily effector cell-mediated. A comparison of effector cell populations in antibody-dependent cell-mediated cytotoxicity (ADCC) showed neutrophils to be most important for IgA-dependent tumor cell killing, involving FcalphaRI as shown with Fc receptor blocking antibodies. Reverse ADCC experiments against target cells sensitized with Fc receptor antibodies, or assays with FcalphaRI-directed bispecific antibodies confirmed FcalphaRI as effective trigger molecule in polymorphonuclear neutrophil (PMN)-mediated lysis. During granulocyte colony-stimulating factor (G-CSF ) therapy, (FcalphaRI x HER-2/neu) bispecific antibodies induced enhanced killing of HER-2/neu positive SK-BR-3 breast cancer cells in whole blood assays. This enhanced cytotoxicity was paralleled by increased PMN counts, which lead to higher effector to target cell ratios in G-CSF-primed blood. Furthermore, bispecific antibodies, directed to FcalphaRI and Candida albicans, enhanced neutrophils' phagocytosis of fungi. In summary, these results identify IgA as an effective antibody isotype for immunotherapy, working primarily via FcalphaRI on neutrophils. They suggest FcalphaRI-directed bispecific antibodies and G-CSF to be an attractive combination for malignant or infectious diseases.     

The laboratory diagnosis of spring-summer infections in Yekaterinburg in the epidemic season for tick-borne encephalitis

The authors propose a comprehensive approach to laboratory diagnosis of seasonal transmissible infections, based on modern methods permitting etiological deciphering of disease. A universal diagnostic algorithm notably accelerated the laboratory diagnosis due to cutting the period between collection of material from a patient and consecutive screening for antibodies to agents of tick-borne encephalitis, Lyme disease, and California encephalitis.