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Biomedical subjects

L Mylin

Publications and source records attributed to L Mylin.

17 recordsLinked to original sources
PubMed2001

Role of CTL host responses and their implication for tumorigenicity testing and the use of tumour cells as vaccine substrate.

Viral oncogenes, mutated cellular oncogenes, or other adventitious agents that might contaminate vaccine preparations on inoculation of the host will encounter a T cell-mediated immune response which will play a determining role in the progression of neoplastic events or replication of contaminating viral agents. Using SV40 T antigen tumour systems as a model we discuss the regions of the oncoprotein that have an impact on tumourigenicity and the role of CD8 T lymphocyte immune responses in eliminating potential tumour cells. In addition, we discuss measures that counteract T cell immune responses to abrogate T cell-mediated immunosurveillance.

Animals↗
PubMed1998

Cytotoxic T lymphocyte recognition sequences as markers for distinguishing among tumour antigens encoded by SV40, BKV and JCV.

Simian virus 40 (SV40) has been shown to be associated with a number of human tumours. Two other human papova viruses, BKV and JCV, infect humans at a relatively high frequency and are activated upon immune suppression. The T antigens of both of these viruses share considerable homologies with the transforming protein T antigen of SV40. We have used SV40 T antigen specific cytotoxic T lymphocyte (CTL) clones to discriminate among the T antigens of SV40, BKV and JCV. These CTL clones directed to four distinct CTL epitopes serve as specific probes and can differentiate subtle alterations or deletions in the CTL epitopes relative to SV40 T antigen. Using this strategy, we have been able to authenticate three SV40 viruses isolated from humans as all four distinct CTL epitopes in the T antigens encoded by these three SV40 human isolates (SVCPC, SVMEN, and SVPML-1) were found to be identical to prototype SV40. We have further identified a 198 amino acid deletion T antigen variant of SVCPC. The finding of a deletion mutant in the SVCPC virus population suggests that the cellular immune response may play a role in the selection of antigenic loss variants.

Amino Acid Sequence↗
PubMed1997

A simian virus 40 large T-antigen segment containing amino acids 1 to 127 and expressed under the control of the rat elastase-1 promoter produces pancreatic acinar carcinomas in transgenic mice.

The simian virus 40 large T antigen induces tumors in a wide variety of tissues in transgenic mice, the precise tissues depending on the tissue specificity of the upstream region controlling T-antigen expression. Expression of mutant T antigens that contain a subset of the protein's activities restricts the spectrum of tumors induced. Others showed previously that expression of a mutant large T antigen containing the N-terminal 121 amino acids (T1-121) under control of the lymphotropic papovavirus promoter resulted in slow-growing choroid plexus tumors, whereas full-length T antigen under the same promoter induced rapidly growing CPR tumors, T-cell lymphomas, and B-cell lymphomas. In those instances, the alteration in tumor induction or progression correlated with inability of the mutant large T antigen to bind the tumor suppressor p53. In the study reported here, we investigated the capacity of an N-terminal T antigen segment (T1-127) expressed in conjunction with small t antigen under control of the rat elastase-1 (E1) promoter to induce pancreatic tumors. The results show that pancreases of transgenic mice expressing T1-127 and small t antigen display acinar cell dysplasia at birth that progresses to neoplasia. The average age to death in these mice is within the range reported for transgenic mice expressing full-length T antigen under control of the E1 promoter. These results indicate that sequestering p53 by binding is not required for the development of rapidly growing acinar cell carcinomas. In addition, we provide evidence that small t antigen is unlikely to be required. Finally, we show that the p53 protein in acinar cell carcinomas is wild type in conformation.

Animals↗
PubMed1995

Modality dependent changes in event-related potentials correlate with specific cognitive functions in nondemented patients with Parkinson's disease.

The relationship between event-related potentials (ERPs) and cognitive functioning was studied in patients with Parkinson's Disease (PD) but without dementia. Auditory and visual stimuli were used; 30 subjects participated in the auditory study and 20 in the visual study. Patient groups did not differ with respect to gender, age, education, illness duration, and level of cognitive functioning. Visual stimuli were 2.3 cpd sinusoidal grating patterns randomly presented in an oddball paradigm (oblique vs. vertical spatial orientation). Auditory stimuli were tones presented at 70 dB SPL at a rate of 1.1/second, also using the oddball paradigm (1.5K vs. 1K tones). All patients were given neuropsychological tests to measure verbal fluency, memory, visual spatial perception, and abstract reasoning. P300 and N200 abnormalities correlated with a number of these measures, such that longer ERP latencies were related to lower scores on tests of cognitive functioning. Patterns of results suggest that auditory and visual ERPs correlate with different subsets of neuropsychological functions in nondemented PD patients and that N200 may provide a new metric for clinical use.

Cognition↗
PubMed1993

The effect of levo-acetyl-carnitine on visual cognitive evoked potentials in the behaving monkey.

We studied acute and chronic effects of levo-acetyl-carnitine (LAC) on event-related potentials (ERPs) in 3 monkeys trained in a "go"/"no-go" visual "oddball" discrimination task. The stimuli were 2.5 cpd sinusoidal gratings differing in their respective orientation only (0 degrees or 45 degrees). Each monkey was trained to release a lever during a prespecified time window. Target stimulus presentation probabilities were between 0.25 and 0.5. ERPs had comparable mean latencies and amplitudes in all monkeys. Primary evoked potentials recorded to either the target or non-target stimulus did not change significantly as a result of LAC treatment. On the other hand, P300 latency decreased following LAC administration, with a maximum occurring in 15-20 min. The major effects of LAC were consistent within each animal and for all three of them.

Acetylcarnitine↗
PubMed1990

The auditory P 300 correlates with specific cognitive deficits in Parkinson's disease.

An abnormally prolonged latency of the P 300 event-related potential has been reported in several types of dementing illnesses, including Parkinson's disease (PD). While some PD patients have dementia, a significant number of PD patients have less severe cognitive impairments. We examined the relationship between the auditory P 300 and a neuropsychological battery of 11 tasks in 43 PD patients. The quantitative relationship between the individual neuropsychological measures and the P 300 was examined using partial correlation and analysis of covariance techniques which controlled for age, education, and illness duration. The strongest correlations were between P 300 and both short-term memory and visual perception. Global cognitive deficits do not appear to relate to the abnormal P 300 responses in PD: instead, specific aspects of cognitive decline accounted for the electrophysiological abnormalities. An abnormally long or absent P 300 correlated with deficits on select cognitive tasks: those involving memory, visual perception, and abstract reasoning. The interactions between anatomical and neurochemical abnormalities in PD are discussed in light of the pattern of deficits seen in this study.

Adult↗
PubMed1987

Delayed visual evoked potentials are independent of pattern orientation in macular disease.

Visual evoked potentials (VEPs) and contrast sensitivity (CS) were studied in patients affected by maculopathy. VEP delays and CS reduction were demonstrated in each affected eye. In distinction to patients affected by multiple sclerosis (MS), in maculopathy patients VEP latency is independent of the orientation of the grating stimulus. It is proposed that stimulating with more than one pattern orientation is useful in the differential diagnostic use of VEPs.

Adult↗
PubMed1987

Plasticity of monocular and binocular vision following cerebral blindness: evoked potential evidence.

Using monocular and dynamic random dot correlogram (DRDC) stimuli, sequential visual evoked potentials changes were demonstrated in 2 patients following cerebral blindness. The recovery of binocular vision was delayed in comparison to the recovery of monocular vision. The results are not due to simple acuity impairment or convergence deficiency, and thus provide evidence for the vulnerability of postsynaptic cortical mechanisms of human binocular vision.

Adult↗
PubMed1987

Visual dysfunction in Parkinson's disease. Loss in spatiotemporal contrast sensitivity.

Flicker sensitivity and spatial contrast sensitivity (CS) were examined in a total of 99 patients with Parkinson's disease (PD). All patients were undergoing treatment with dopaminergic agents. Specific losses in sensitivity observed in PD were (1) a loss in flicker sensitivity which was most pronounced around the peak of the function (8 Hz) and (2) a loss near the peak of the spatial CS curve, often with no noticeable low frequency attenuation. Several PD patients affected by the 'on-off' syndrome were tested in both 'on' and 'off' phases, and the results show that the CS function switches in parallel with motor symptoms of the disease. These data suggest that not only is the visual system affected in PD, but that dopamine may have an essential role in receptive field organization in human vision.

Adult↗
PubMed1986

Temporal frequency-dependent VEP changes in Parkinson's disease.

We recorded steady-state (4.19 and 8.41 Hz) VEPs in 17 Parkinson's Disease (PD) patients and 18 control observers using on-off temporal modulation of a 2.3 c/deg sinusoidal grating. With 4.19 Hz, 20 out of 33 PD patient eyes had abnormal VEPs. However, only 8 of 33 eyes were abnormal with 8.41 Hz. "Routine" (counterphase) transient VEPs revealed delayed VEPs for only 7 out of 24 eyes of the patients. These findings suggest an "input" temporal frequency-dependent abnormality in the foveal pathway.

Adult↗
PubMed1983

Pattern electroretinograms and visual-evoked potentials in glaucoma and multiple sclerosis.

Steady-state visual-evoked potentials and electroretinograms were simultaneously recorded in four patients with glaucoma and in five patients with multiple sclerosis. The stimuli included a homogenous field and a 2.3 cycles per degree sinusoidal grating that were counter-phase modulated at the rate of 7.5 Hz. We used narrow bandwidth spectral analysis to measure the response amplitudes and signal-to-noise ratios. Transient pattern visual-evoked potentials (1 Hz) were also measured for latency in each eye. We found abnormal pattern electroretinograms, based on the absence of a significant second harmonic component, in three of the four glaucomatous eyes although the homogenous field electroretinograms were normal. In the patients with multiple sclerosis, the pattern electroretinograms were abnormal in two eyes, but the transient visual-evoked potential latency had the highest diagnostic yield (seven of ten eyes).

Adult↗
PubMed1983

On the possible role of temporal delays of afferent processing in Parkinson's disease.

Visual evoked potential (VEP) latency is one measure of afferent delays in Parkinson's disease. New aspects of temporal processing were studied in the VEP of 7 patients and 10 normals. For this analysis the patterned stimulus was simultaneously modulated at two temporal frequencies. Phase shifts of non-linear VEP components in patients, compared to normals, revealed that an abnormality of temporal processing in this disease must be caused by altered neuronal interactions, not only by simple conduction defects.

Adult↗
PubMed1983

Flicker threshold and pattern VEP latency in ocular hypertension and glaucoma.

Latency of the pattern visual-evoked potential (PVEP) was measured in 24 ocular hypertensive (OHT) patients, eight open-angle glaucoma (OAG) patients, and 37 control subjects. The PVEP stimulus was a 2.3 cycle/degree sinusoidal grating, counterphase-modulated at 1 Hz. Field size was 9 degrees and mean luminance 1.7 log ft-lamberts. For 22 of the 32 patients, a psycholphysical measure of dynamic contrast sensitivity at 8 Hz (DRC) was obtained with a 4 degrees diameter stimulus, by determining the mean value for the contrast sensitivities to a homogeneous flickering field and to a 1.2 cycle/degree counterphase-flickering grating. Patient DRC values were compared with previously published control data from 21 subjects. Mean PVEP latencies of both the OHT and the OAG patients were greater than normal (P less than 0.001), with the OAG value larger than the OHT value (P less than 0.001). Mean DRCs were lower than normal (P less than 0.002) for both patient groups, with the OAG value lower than the OHT value (P less than 0.025). DRC correlated with PVEP latency for these patients (r = -0.66, P less than 0.001).

Evoked Potentials, Visual↗
PubMed1982

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.

Adult↗
PubMed1982

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.

Brain↗
PubMedDate not supplied

N70 and P100 can be independently affected in multiple sclerosis.

We have studied the relationship between N70 and P100 of the pattern visual evoked potential in 98 patients with multiple sclerosis and in 59 controls. In patients with multiple sclerosis, P100 was either absent or had prolonged latency in 121 eyes (61.7%), while N70 was absent or prolonged in 97 eyes (49.5%). The total number of eyes with either N70 and/or P100 abnormalities was 137 (69.9%). Eighty eyes (40.8%) had abnormal latency of both P100 and N70, while 41 eyes showed P100 delays without corresponding N70 changes. Seventeen eyes had abnormal N70, but normal P100 latency. N70 and P100 appear to be more often absent in the definite rather than in the possible multiple sclerosis group. These data show that N70 and P100 can be independently affected in patients with MS.

Adolescent↗