Effect of mycobacteria on sensitivity to the cytotoxic effects of tumor necrosis factor

Unlike Mycobacterium leprae, Mycobacterium tuberculosis is not found inside cells other than macrophages and polymorphonuclear cells in vivo, yet previous work has revealed that in vitro it readily enters all cell lines tested. Moreover, these cells are not killed by the intracellular mycobacteria. We report here that when fibroblasts take up live (but not killed) M. tuberculosis H37Rv, they develop greatly increased sensitivity to the toxic effects of tumor necrosis factor (TNF) whether the cell line is inherently sensitive to TNF or not. Ultrasonically disrupted M. tuberculosis also has this property. The increased sensitivity is seen in the absence of metabolic inhibitors, although addition of emetine, an inhibitor of protein synthesis, causes the effect to manifest itself earlier and at a lower concentration of TNF. In contrast, infection with Mycobacterium bovis bacillus Calmette-Guérin induces little or no increased sensitivity to TNF, whereas Mycobacterium avium and M. tuberculosis H37Ra have intermediate sensitivities. We discuss the possibility that virulent tuberculosis strains produce a factor which distorts the normal protective function of TNF, rendering it toxic to host tissues and leading to the classical immunopathology of tuberculous lesions.     

Correlation of neuropsychological and MRI findings in chronic/progressive multiple sclerosis

Sixty patients with chronic/progressive MS received a newly assembled neuropsychological screening battery (NSB) and a brain MRI. A neuroradiologist blinded to NSB findings quantified cerebral lesions on MRI. We developed weighted brain area lesion scores according to number and size of cerebral lesions. Patients who were impaired on NSB testing had a significantly higher mean bihemispheric lesion score (X = 26.1) than those who were unimpaired (X = 17.4); this MRI lesion rating score correlated significantly with the cognitive summary score of the NSB (r = 0.35, p less than 0.01). However, we did not find a significant correlation between the Kurtzke Expanded Disability Status Scale and any MRI or NSB summary measures. Compared with the Mini-Mental State Exam (MMSE), the NSB cognitive summary score yielded a prevalence estimate for cognitive impairment that is more consistent with previous findings in chronic/progressive MS. The NSB is a useful screening test for cognitive dysfunction in chronic/progressive MS because of its relationship to cerebral lesions on MRI and its greater sensitivity than the frequently used MMSE.     

Education provides no protection against Alzheimer's disease

It has been suggested that educational achievement confers protection against dementia. We examined educational level and age of onset in 28 patients with Alzheimer's disease, and assessed the progression of dementia over a mean period of 28 months using both a measure of neurobehavioral status and an index of functional impairment. No protective effect of education was found in either early- or late-onset dementia.     

Toluene abuse causes diffuse central nervous system white matter changes

We describe the findings of magnetic resonance imaging (MRI) of the brain in 6 chronic toluene vapor abusers and the neuropathological findings in 1 abuser not studied by MRI. MRI in 6 chronic toluene abusers revealed the following abnormalities: (1) diffuse cerebral, cerebellar, and brainstem atrophy; (2) loss of differentiation between the gray and white matter throughout the central nervous system; and (3) increased periventricular white matter signal intensity on T2-weighted images. Another chronic toluene abuser (MRI not performed) died as a result of acute toluene overdose. The brain displayed diffuse, ill-defined myelin pallor, maximal in cerebellar, periventricular, and deep cerebral white matter. Neurons were preserved throughout, axonal swelling or beading was not seen, gliosis was minimal, and occasional, scant perivascular macrophage collections were seen. Taken in concert, these findings suggest that the pathological and MRI abnormalities are due to either increased water content of the white matter or subtle toluene-induced metabolic changes in myelin.     

An investigation of the Venetian blind effect

When a rectangular wave grating is binocularly viewed with a neutral density filter over one eye, an illusory rotation resembling that of a partially opened Venetian blind is perceived (Cibis and Haber, 1951). Using a binary classification task, in the first experiment, the probability of perceiving a rotation in a given direction was measured as a function of a factorial combination of inter-ocular contrast (see Note 1) and luminance ratios. The probability of a rotation in a given direction decreased monotonically with the luminance of the brighter bars when the grating contains a less than unity contrast. This result is inconsistent with (i) the model of the Venetian blind effect proposed by Cibis and Haber (1951), (ii) a mechanism based on irradiation with a compressive non-linearity (von Helmholtz, 1911/1924, pp. 186-193) and (iii) contemporary stereo-energy/cross-correlation models of stereopsis. In the second and third experiments, we tested the prediction that irradiation combined with an early compressive non-linearity in response implies a positive relationship between both the threshold contrast or average luminance disparity to perceive rotation and the magnitude of perceived rotation, and the blur width at the bar's edge. No support was found for the prediction. We propose an intensity difference model of the probability of perceiving a rotation in a given direction as a function of the interocular difference in luminance or contrast.     

The neuroendocrine effects of traumatic brain injury

Neuroendocrine dysfunction after traumatic brain injury (TBI) is under-diagnosed, under-treated, and may adversely affect the rate of recovery. Single or multiple pituitary-target hormone disruption occurs in up to two-thirds of persons with TBI, most commonly affecting the gonadal and growth hormone axes. The time course of decline in and recovery of pituitary function in relation to cognitive dysfunction and rehabilitation progress are not well described. This article reviews the clinical spectrum of neuroendocrine deficits after TBI and their underlying mechanisms. Future studies of the effects of hormonal replacement on recovery are recommended.