A short latency cortical component of the foveal VEP is revealed by hemifield stimulation.

Transient evoked potentials were recorded simultaneously over 5 electrodes placed in a horizontal row across the occiput. A range of spatial frequencies were presented as either full-field or hemifield stimuli. Subjects were 11 normal observers and 5 patients with lesions causing a homonymous hemianopic field defect. The shortest latency peak response was at approximately 70 msec, a negative potential (N70). For all spatial frequencies, full-field stimuli evoked a lower amplitude N70 at the midline than the sum of N70 amplitudes to two hemifield stimuli, suggesting partial cancellation. The latency and amplitude of N70 increased as spatial frequency increased. N70 and P100 differed in respect to their response to spatial frequency and field size, further suggesting that they may not be subsets of a unitary response. For hemifield stimulation, N70 had an ipsilateral maximum and attenuated or completely reversed in polarity across the midline. Consistent with the data of normals using hemifield stimuli, in 5 patients a full-field stimulus elicited an N70 lateralized contralaterally to the homonymous hemianopia, i.e., the ipsilateral N70 was absent. The absolute amplitude difference between the left and right electrodes was significant for hemifield stimulation in normals and full-field stimulation in the patients, but not for full-field stimulation in normals. Our results imply that the evaluation of N70 hemispheric distribution is useful for the evaluation of paramacular visual field defects.     

Species-dependent variations in erythrocyte membrane skeletal proteins

Two mammalian species (porcine and murine) have erythrocytes that are being widely used to study membrane protein synthesis and red cell aging. Erythrocytes of these species however, are significantly smaller than those of the human. Before results obtained from study of these red cells can be applied to human cells, the membrane skeleton of these species must be investigated to determine if the skeletal elements are equivalent. Both pig and mouse bands 4.1b were of lower molecular weight than human 4.1b, and the a/b ratio was lower. In each species, 4.1a and b were sequence-related phosphoproteins, and yielded substantially different one-dimensional peptide maps. Band 3 of pig and mouse erythrocytes had a higher molecular weight than human band 3 and also had differing one-dimensional peptide maps after limited proteolytic cleavage with three different enzymes. In each species, free band 3 and band 3 bound to the membrane skeleton had identical peptide maps. Other major membrane skeletal components (spectrin, actin, and bands 2.1 and 4.2) seem to be very similar in molecular weight in various species. These results demonstrate that the molecular weights and relative proportions of the membrane skeletal elements are species dependent.     

AC480, formerly BMS-599626, a pan Her inhibitor,enhances radiosensitivity and radioresponse of head and neck squamous cell carcinoma cells in vitro and in vivo

Purpose: The present study investigated the effect of AC480, a small molecule pan-HER tyrosine kinase inhibitor, on in vitro radiosensitivity and in vivo radioresponse of a human head and neck squamous cell carcinoma cell line. Methods: HN-5 cells were exposed to γ-radiation with and without AC480 and assayed for proliferation, clonogenic survival, apoptosis, cell cycle distribution, and DNA damage. The cells were analyzed by immunoprecipitation and western blotting for proteins involved in apoptosis, cell cycle regulation, and the EGFR pathway. The effect of AC480 on tumor radioresponse was assessed by tumor growth delay assay using HN5 tumor xenografts generated in nude mice. Results: At the molecular level, in HN-5 cells the agent inhibited the expression of pEGFR, pHER2, cyclins D and E, pRb, pAkt, pMAPK, pCDK1 and 2, CDK 6, and Ku70 proteins. The drug also induced accumulation of cells in the G1 cell cycle phase, inhibited cell growth, enhanced radiosensitivity, and prolonged the presence of γ-H₂AX foci up to 24 h after radiation. AC480 did not increase the percentage of cells undergoing radiation-induced apoptosis. The drug given before and during irradiation improved the radioresponse of HN5 tumors in vivo. Conclusion: AC480 significantly enhanced the radiosensitivity of HN-5 cells, expressing both EGFR and Her2. The mechanisms involved in the enhancement included cell cycle redistribution and inhibition of DNA repair. Both in vitro and in vivo data from our study suggest that AC480 has potential to increase tumor response to radiotherapy.     

Visual evoked potential diagnosis of field defects in patients with chiasmatic and retrochiasmatic lesions.

Visual evoked potentials were studied in 18 patients with visual field defects assessed by perimetry. Stimuli were reversing checkerboard and grating patterns of 13', full field and hemifield. Two reversal rates were studied: 1 Hz (transient VEPs) and 8 Hz (steady-state VEPs). Using monocular hemifield stimulation the "paradoxical lateralisation" of transient but not of steady-state VEPs was confirmed. Diagnostic yield was 90% using transient, but less than 20% using steady-state stimuli.     

Topographical analysis of the onset VEP in the detection of paracentral visual field defects.

Transient visual evoked potentials (VEP) were recorded simultaneously from 16 electrodes evenly placed over posterior scalp locations covering the occipital, posterior parietal and temporal areas. Interhemispheric amplitude difference of the N70 deflection was established across 6 homologous lateral electrode pairs in 15 normal controls and 32 patients with chiasmatic or retrochiasmatic cerebral lesions. Twenty-three of these had known homonymous or bitemporal field defects while 9 had normal fields on routine perimetry. Significant interhemispheric asymmetry of any single electrode pair occurred in 55% of the 32 patients with known pathology, while the cumulative yield of all electrode pairs was over 80 percent. The diagnostic yield of individual electrode pairs was significantly different: the electrode pair placed over the temporo-parietal junction detected the highest number of abnormalities. The cumulative abnormality taken over all lateral electrode pairs could be described with a curve well fitted with a probability summation function. It is inferred that the contribution of several independent generator sources is reflected in the N70 of the pattern onset VEP. The results suggest that multichannel recording of the interhemispheric amplitude distribution of the N70 of the onset VEP is useful for the evaluation of paracentral visual field defects.     

Dopaminergic deficiency and delayed visual evoked potentials in humans

Abnormal delay in visual evoked potential (VEP) could be normalized in 9 of 14 previously untreated parkinsonian patients under the influence of levodopa/carbidopa therapy. In 6 of 11 previously untreated schizophrenic patients the VEP latency became abnormal following therapy with agents known to cause dopaminergic blockade. Besides defects in retrobulbar conduction secondary to demyelination, synaptic dysfunction due to neurotransmitter deficiency or receptor blockade must also be considered as a mechanism underlying VEP delays in humans.