How a Medical Association Can Make a Difference in a Crisis Situation

Non peer reviewe

The Life Span Determinant p66Shc Localizes to Mitochondria Where It Associates with Mitochondrial Heat Shock Protein 70 and Regulates Trans-membrane Potential

P66Shc regulates life span in mammals and is a critical component of the apoptotic response to oxidative stress. It functions as a downstream target of the tumor suppressor p53 and is indispensable for the ability of oxidative stress-activated p53 to induce apoptosis. The molecular mechanisms underlying the apoptogenic effect of p66Shc are unknown. Here we report the following three findings. (i) The apoptosome can be properly activated in vitro in the absence of p66Shc only if purified cytochrome c is supplied. (ii) Cytochrome c release after oxidative signals is impaired in the absence of p66Shc. (iii) p66Shc induces the collapse of the mitochondrial trans-membrane potential after oxidative stress. Furthermore, we showed that a fraction of cytosolic p66Shc localizes within mitochondria where it forms a complex with mitochondrial Hsp70. Treatment of cells with ultraviolet radiation induced the dissociation of this complex and the release of monomeric p66Shc. We propose that p66Shc regulates the mitochondrial pathway of apoptosis by inducing mitochondrial damage after dissociation from an inhibitory protein complex. Genetic and biochemical evidence suggests that mitochondria regulate life span through their effects on the energetic metabolism (mitochondrial theory of aging). Our data suggest that mitochondrial regulation of apoptosis might also contribute to life span determination

Dendritic cell generation for leukemia immunotherapy

[No abstract available

Retinal Plasticity

Brain plasticity is a well-established concept designating the ability of central nervous system (CNS) neurons to rearrange as a result of learning, when adapting to changeable environmental conditions or else while reacting to injurious factors. As a part of the CNS, the retina has been repeatedly probed for its possible ability to respond plastically to a variably altered environment or to pathological insults. However, numerous studies support the conclusion that the retina, outside the developmental stage, is endowed with only limited plasticity, exhibiting, instead, a remarkable ability to maintain a stable architectural and functional organization. Reviewed here are representative examples of hippocampal and cortical paradigms of plasticity and of retinal structural rearrangements found in organization and circuitry following altered developmental conditions or occurrence of genetic diseases leading to neuronal degeneration. The variable rate of plastic changes found in mammalian retinal neurons in different circumstances is discussed, focusing on structural plasticity. The likely adaptive value of maintaining a low level of plasticity in an organ subserving a sensory modality that is dominant for the human species and that requires elevated fidelity is discussed

Developmental approaches in immunological control of acute myelogenous leukaemia

After many years of hope and disillusionment, the possibility of utilizing immune-mediated approaches to control neoplastic clones has become a reality in various haematological malignancies. This is largely a consequence of the continuous advances in knowledge and the progressive development of more refined technologies that have led to a better understanding of the biology of the malignant cells and of the host immune system, to a more precise definition of disease entities and to the design of innovative therapeutic programmes. In this chapter, we will review different immunological strategies that have reached clinical practice in patients with acute myelogenous leukaemia (AML), the focus of this volume, and discuss preclinical developments that may in the near future translate into the design of new immunotherapeutic protocols for the management of AML. Treatment of AML with antibody directed therapy will also discussed

Revisiting the association between hypnotisability and blink rate

Blink rate (BR), which is considered an index of the dopaminergic tone, has been studied in 41 subjects with high (highs), medium (mediums) and low (lows) hypnotisability scores in resting conditions. It has been found higher in highs; relaxation (indicated by skin conductance), anxiety and the proneness to absorption in tasks (assessed by questionnaires) were not responsible for the observed difference. In contrast, the BR difference did not survive controlling for mind wandering (MW questionnaire) whose variability could account for contrasting earlier reports, although no significant hypnotisability-related difference has been observed in MW scores. Findings do not allow to exclude that mechanisms other than dopaminergic ones may be involved in the observed difference in BR. In particular, we suggest that one of the mechanisms possibly sustaining the highs' higher BR may be a reduced cerebellar inhibition. In fact, cerebellar impairment is associated with higher BR and several studies of sensorimotor integration indicate different cerebellar controls in the highs' and lows' behavior

Multisensory Integration is modulated by hypnotizability

This study investigated multisensory integration in 29 medium-to-high (mid-highs) and 24 low-to-medium (mid-lows) hypnotizable individuals, classified according to the Stanford Hypnotic Susceptibility Scale, Form A. Participants completed a simultaneity judgment (SJ) task, where an auditory and a visual stimulus were presented in close proximity to their body in a range of 11 stimulus onset asynchronies. Results show that mid-highs were prone to judge audiovisual stimuli as simultaneous over a wider range of time intervals between sensory stimuli, as expressed by a broader temporal binding window, when the visual stimulus precedes the auditory one. No significant difference was observed for response times. Findings indicate a role of hypnotizability in multisensory integration likely due to the highs' cerebellar peculiarities and/or sensory modality preference

Autologous bone marrow transplantation in 44 patients with aggressive non-Hodgkin's lymphoma at University ''La Sapienza'' of Rome

High dose therapy followed by infusion of autologous bone narrow has become a major treatment option for an increasing number of poor prognosis non-Hodgkin's lymphoma (NHL) patients. In our study we analyzed the outcome of autologous bone marrow transplantation (ABMT) in 44 high grade NHL patients transplanted at our institution between 1985 and 1992. Median age was 31 years (range 12-61); nineteen were in partial remission (PR) after first line chemotherapy and 25 in sensitive relapse (SR). Of the 25 patients transplanted in SR, 14 relapsed after a median time of 5.5 months (range 1-26), 8 are in complete remission after a median follow up of 41.5 months and three died from toxicity. Of the 19 patients grafted in PR, 11 are alive and progression free after a median follow up of 52 months, while 8 relapsed at a median time of 5 months. The overall progression free survival (PFS) projected at 6 years is 35% with a 47% PFS for patients transplanted in PR and 28% for patients in SR. In conclusion, high dose therapy and ABMT has achieved widespread use as salvage therapy for patients with relapsed/refractory high grade NHL. In particular, our experience confirms that myeloablative treatment is a safe and well tolerated procedure for patients in PR, that may be easily applied as early salvage therapy without major toxicities

Blink reflex in subjects with different hypnotizability: New findings for an old debate

Hypnotizability is associated with attentional characteristics whose neurophysiological bases are still under debate. Aim of the study was the assessment of possible hypnotizability-related differences in blink reflex (BR) which has a nociceptive component, is sensitive to attentional-emotional traits and states and is modulated by the brain dopamine content. In 10 high (highs) and 10 low hypnotizable participants (lows) BR was induced by electrical nociceptive stimulation of the right supraorbital nerve in the absence (noW) and in the presence of a visual cue preceding the electrical stimulation by 0.1 ms (W01) and by 1 ms (W1). The studied variables were: the amplitude of BR components (R1, R2, R3), the amplitude of the quick change (TO) of heart rate ("turbulence") induced by stimulation and its recovery slope (TS), the role of the Behavioral Inhibition/Activation System (BIS/BAS) in the variability BR and cardiac turbulence. Repeated measures ANOVA did not show any significant difference between highs and lows in blink reflex. TO indicated stimulation related HR increase in highs and decrease in lows, TS was larger in highs. BIS and BAS accounted for the warning effects on the BR amplitude and modulated the hypnotizability and warning effects on TO and TS. Findings do not support dopamine based hypnotizability-related attentional abilities. In contrast, they indicate that hypnotizability modulates the short-lasting cardiac response to electrical nociceptive stimulation