A National Institutes of Health Workshop Report. Cellular and molecular mechanisms for suppression and reversion of tumorigenicity. A Chemical Pathology Study Section workshop

A workshop organized by the Chemical Pathology Study Section was convened to discuss recent findings on the suppression and/or reversal of neoplastic transformation. The existence of specific genes involved in suppressing tumorigenicity has been clearly demonstrated by molecular and cytogenetic analyses of tumor and normal cells from individuals predisposed to develop specific malignancies and by studies of hybrids between normal and neoplastic cells. The malignancy of tumor cells can be suppressed in hybrids with normal cells despite the continued expression of activated oncogenes. Reversal of the malignant state can also be affected by placing tumor cells in certain embryonic environments, such as the mouse blastocyst, or in response to differentiation inducing factors. The numerous examples of suppression and reversal of malignancy indicate that this is an important area for future study which may lead to new methods to control cancer.     

Mental object rotation in Parkinson's disease.

Deficits in visual-spatial ability can be associated with Parkinson's disease (PD), and there are several possible reasons for these deficits. Dysfunction in frontal-striatal and/or frontal-parietal systems, associated with dopamine deficiency, might disrupt cognitive processes either supporting (e.g., working memory) or subserving visual-spatial computations. The goal of this study was to assess visual-spatial orientation ability in individuals with PD using the Mental Rotations Test (MRT), along with other measures of cognitive function. Non-demented men with PD were significantly less accurate on this test than matched control men. In contrast, women with PD performed similarly to matched control women, but both groups of women did not perform much better than chance. Further, mental rotation accuracy in men correlated with their executive skills involving mental processing and psychomotor speed. In women with PD, however, mental rotation accuracy correlated negatively with verbal memory, indicating that higher mental rotation performance was associated with lower ability in verbal memory. These results indicate that PD is associated with visual-spatial orientation deficits in men. Women with PD and control women both performed poorly on the MRT, possibly reflecting a floor effect. Although men and women with PD appear to engage different cognitive processes in this task, the reason for the sex difference remains to be elucidated.     

Patients' recollections of therapeutic paralysis in the intensive care unit.

BACKGROUND: Neuromuscular blocking agents used for therapeutic purposes, such as facilitating mechanical ventilation and relieving life-threatening agitation, paralyze patients but leave them fully conscious. Aggressive sedation or analgesia is necessary to reduce awareness, relieve fear, produce comfort, decrease anxiety, induce unconsciousness, and minimize possible complications such as posttraumatic stress syndrome. Little information is available on the extent to which patients experience awareness during therapeutic paralysis. OBJECTIVES: To determine and describe the remembered experiences of critical care patients who were given neuromuscular blocking agents and sedatives and/or analgesics to facilitate mechanical ventilation, improve hemodynamic stability, and improve oxygenation. METHODS: A phenomenological approach with in-depth interviews with 11 patients was used. Data were analyzed by using the constant comparative approach. RESULTS: A total of 4 themes and 3 subthemes were identified. The first theme was back and forth between reality and the unreal, between life and death; the subtheme was having weird dreams. The second theme was loss of control; the 2 subthemes were (1) fighting or being tied down and (2) being scared. The third theme was almost dying, and the fourth theme was feeling cared for. CONCLUSIONS: Patients can remember having both negative and positive experiences during neuromuscular blockade. Steps to improve the experiences of patients receiving neuromuscular blockers include improving assessment parameters, developing and using sedation/analgesia guidelines, and investing in quality improvement programs to provide assessment of awareness during therapeutic paralysis and follow-up and referral as necessary. Ways to decrease the use of neuromuscular blockers would also be useful.     

Cortical potential shifts preceding voluntary movement are normal in parkinsonism

We have recorded movement-related cortical potentials (MRCPs) preceding voluntary finger extension from 10 subjects with Parkinson's disease and compared the results with those obtained from groups of young and old subjects described in the previous paper in this volume (Barrett et al. 1986). Three separate potential shifts preceding voluntary movement were identified in the wave forms of all subjects. There were no differences between the healthy aged subjects and those with Parkinson's disease in terms of the onset latencies or gradients of these potential shifts. The potential shift associated with the final phase of preparation (NS') was significantly less widespread over central scalp for the older subjects compared with the young. Equivalent results for a 35-year-old subject with Parkinson's disease were indistinguishable from those obtained from the young subjects suggesting that this restriction in the distribution of NS' is related to normal ageing rather than the disease process of parkinsonism. There were no differences within the group of parkinsonian subjects with respect to potential shifts associated with differing degrees of movement disability between the two hands. Our results contradict previous reports of abnormal MRCPs in Parkinson's disease (Deecke et al. 1977; Deecke and Kornhuber 1978; Shibasaki et al. 1978). We attribute this primarily to an improved method of recording MRCP which compensates for time jitter between EMG onset and the production of a trigger pulse for averaging (Barrett et al. 1985).     

Intestinal permeability and orocaecal transit time in elderly patients with Parkinson's disease.

The aetiology of weight loss in patients with Parkinson''s disease is likely to be multifactorial. We studied 15 patients with Parkinson''s disease and 15 age- and sex-matched controls and looked for evidence of malabsorption due to small bowel bacterial overgrowth or alteration of intestinal permeability. There was a marked increase in orocaecal transit time in the patients with Parkinson''s disease, although lactulose hydrogen breath testing did not show evidence of small bowel bacterial contamination. Intestinal permeability measured by the differential sugar absorption test was also deranged. There was reduced absorption of mannitol in patients with Parkinson''s disease while lactulose absorption was similar in both groups, suggesting decreased non-mediated uptake across the enterocyte brush border membrane in patients with Parkinson''s disease.     

The assessment of mood and affect in developmentally disabled children and adolescents: the Emotional Disorders Rating Scale

There is an unmet need for a reliable method of evaluating disorders of mood and affect in developmentally disabled children and adolescents. Such a measure is required for both accurate diagnosis and treatment monitoring in this population. An extensive review of existing assessment techniques confirms that: (a) current techniques for the evaluation of emotional disorders in cognitively normal individuals are inappropriate for most children with developmental disabilities; and (b) current instruments designed for the assessment of developmentally disabled children pay inadequate attention to affective symptoms. In this paper, the preliminary version of a new instrument, the "Emotional Disorders Rating Scale for Developmental Disabilities" (EDRS-DD), designed to evaluate mood and affect in children and adolescents with developmental disabilities, is presented. A pilot study indicates that interrater agreement is good.     

Event-related potentials and the semantic matching of faces

Event-related brain potentials (ERPs) were recorded while subjects determined whether two sequentially presented famous faces depicted individuals belonging to the same or to different occupational categories. During the 1.56 sec interval between the onset of the faces, ERPs recorded from right hemisphere electrodes were more negative-going than those from electrodes over the left hemisphere. The ERPs evoked by the second face on each trial differed as a consequence of whether or not the person depicted belonged to the occupational category specified by the first face. This difference took the form of a bilaterally-distributed negative-going shift in the ERPs evoked by non-matching as opposed to matching faces. This negativity was maximal around 450 msec post-stimulus. The ERP asymmetries during the inter-stimulus interval are interpreted as evidence for the engagement of cognitive processes lateralized to the right hemisphere. The match/non-match differences are considered to reflect the modulation of an "N400" component similar to that evoked by words, and thus suggest that such components can be modulated by associative priming between non-linguistic stimuli.