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Biomedical subjects

L H Goldstein

Publications and source records attributed to L H Goldstein.

65 records · Page 4Linked to original sources
PubMed1991

Modulation of neuroendocrine surface antigens in oncogene-activated small cell lung cancer lines.

Small cell lung cancer (SCLC) manifests a number of neuroendocrine differentiation features and antigenic characteristics that distinguish the tumour from non-small cell lung cancer (NSCLC). Several surface antigens on SCLC cells, identified by clusters of monoclonal antibodies (MAbs), distinguish SCLC and other neuroendocrine tumours of NSCLC. Stable transfection of the c-myc proto-oncogene has been reported to confer upon classic SCLC cells the growth properties and morphology of the variant subtype of SCLC (SCLC-v). Furthermore, insertion of the v-Ha-ras oncogene into such SCLC-v cells has been found to induce features typical of NSCLC. We have used classic SCLC cells transfected with c-myc, or co-transformed with c-myc and v-Ha-ras, to examine the expression of characteristics SCLC cluster antigens. Flow cytometric assays reveal that SCLC cells co-transformed with c-myc and v-Ha-ras oncogenes down-modulate SC-1, SC-2 and SC-5A surface antigens to levels approaching, in some cases, those seen with NSCLC cells. The SC-4 surface antigen is not modulated by activation of these oncogenes. These findings support clinical and laboratory observations that important transitions can occur between subtypes of human lung cancer cells, and that these shifts may play a role in the clinical progression of lung cancer.

Adenocarcinoma↗
PubMed1990

Identification of conditioned medium proteins from human cancer cells adapted to serum-free conditions.

Recent studies have shown that human cancer cell lines can be adapted to grow in serum-free, unsupplemented RPMI-1640 (RO) medium. We have developed similar techniques to rapidly identify proteins of interest in serum-free conditioned medium (CM) of human lung cancer cell lines. Classic and variant small cell lung cancer (SCLC) lines were adapted to growth in RO medium. CM from each line was concentrated and fractionated on an anion-exchange column of a fast protein liquid chromatography system. Concentrates of each fraction were loaded onto lanes of minigels of an automated electrophoresis system. Analysis of the chromatograms reveals peaks seen only in CM of the classic SCLC lines. Electrophoretic analysis of the fractions containing these peaks reveal protein bands distinguishing between the subtypes of human SCLC. One protein was purified to homogeneity with subsequent reversed-phase chromatography and identified by protein microsequencing as histone H2B. These automated techniques have general use in the rapid identification of CM proteins associated with the differentiation or progression of the many types of neoplastic cells which can be adapted to growth in RO medium.

Amino Acid Sequence↗
PubMed1990

Behavioural and cognitive-behavioural treatments for epilepsy: a progress review.

Epilepsy is increasingly being viewed as a condition where psychological interventions may offer great potential in bringing about a reduction in the frequency of seizures. Early studies of behavioural interventions (including classical and operant conditioning approaches) designed to reduce seizure frequency were often subject to considerable methodological flaws. The outcome of recent behavioural and cognitive-behavioural treatment trials is reviewed in the light of criticisms of earlier studies. Persisting methodological difficulties are discussed and recommendations made for future studies.

Behavior Therapy↗
PubMed1990

Interaction of recombinant human tumor necrosis factor and etoposide in human lung cancer cell lines.

Studies have suggested that recombinant tumor necrosis factor-alpha (TNF-alpha) may potentiate the killing of murine tumor cells by drugs targeted at DNA topoisomerase II. We have examined the combined cytotoxic effects of the topoisomerase-targeted drug etoposide and TNF in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cell lines using clonogenic assays and a novel flow cytometry technique relying on differential uptake of fluorescein diacetate (FDA) and propidium iodide (PI) by viable and nonviable cells. Good correlation of IC50 determinations for etoposide were noted between clonogenic assays and the FDA/PI technique for both classic and variant SCLC cell lines. The effects of etoposide on the classic SCLC line H209 were potentiated by TNF with a decrease in the IC50 from 3.3 microM to 1.0 microM as determined by FDA/PI. Tumor necrosis factor alone had little effect on the growth or cloning efficiency of H209 cells. Tumor necrosis factor alone stimulated the growth and cloning of variant SCLC line N417, but the cytotoxicity of etoposide was not potentiated by TNF in N417 cells. Tumor necrosis factor alone inhibited the growth and cloning of the NSCLC line H125 but exerted a marked protective effect against higher concentrations of etoposide. It appears that the interaction of TNF with etoposide varies between cell lines and between subclasses of human lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1989

Cognitive mapping after unilateral temporal lobectomy.

An investigation of the extension of O'KEEFE and NADEL's [The Hippocampus as a Cognitive Map. Oxford University Press, Oxford 1978] theory of hippocampal functioning is described in patients who have undergone unilateral temporal lobectomy for the relief of epilepsy. A new spatial task, incorporating a recall-for-designs test but based on studies of spatial memory and cognitive mapping in animals was devised. Results supported the prediction of temporal lobe structure involvement in the mediation of non-egocentric but not egocentric space, and of the role of right temporal lobe structures in conditions designed to encourage "place" but not "cue" learning strategies. The role of verbal mediation in task performance is also discussed.

Adolescent↗
PubMed1989

Autoshaping in micrencephalic rats.

An autoshaping procedure in which the illumination of a lever was predictive of food reinforcement was used to compare learning in rats with micrencephaly induced by irradiation on the 16th day of gestation and in sham-irradiated controls. Both groups showed equivalent levels of lever-directed activity, and the micrencephalic animals differentiated as well as the control animals between the predictive lever and a nonpredictive lever. The micrencephalic animals were able to redistribute their lever-directed activity when the significance of the levers was reversed and did so more readily than the control animals. Results support the claim that association learning survives either traumatic or developmental neocortical damage and have implications for remedial procedures following both head injury and developmental cerebral pathology in humans.

Animals↗
PubMed1988

Verbal and abstract designs paired associate learning after unilateral temporal lobectomy.

The combined use of a new abstract designs Paired Associates test with the Verbal Paired Associates test of Form 1 of the Wechsler Memory Scale was investigated with respect to eliciting material specific memory deficits after unilateral temporal lobectomy. Although the verbal test differentiated between the memory ability of these two groups more clearly than the abstract designs test, the effectiveness of looking at the difference between total scores on the two tests was demonstrated. The two tests produced similar levels of performance in control subjects.

Analysis of Variance↗
PubMed1987

Visual discrimination in the absence of visual cortex.

Normal rats and rats with devascularization lesions ranging from subtotal removals of striate cortex (Area 17) to complete removal of neocortex were trained in a horizontal/vertical stripe discrimination for a liquid reinforcer. Subgroups of animals were identified on the basis of size and location of lesion (with particular reference to striate cortex) as Subtotal, Striate, Posterior and Decorticate. Some animals in all of the lesion groups were able to acquire the discrimination, but there was a direct relationship between lesion size and number of training trials. Those animals which reached criterion on the original discrimination were trained on a second horizontal/vertical discrimination under either transfer or reversal conditions using 'rotated obliques' stimuli. Performance on this second discrimination indicated that animals from all lesion groups had been using visual stimuli based on stripe orientation in the original problem. Members of all lesion groups solved the rotated obliques problem under the transfer condition, though the speed and completeness with which they did so was again inversely related to lesion size. These data show high levels of visual competence in the absence of visual cortex even when stimuli thought to detect form discrimination are used and thus reinforce the view that superior colliculus may be a more significant visual area for the rat than was previously assumed. They also support other observations that animals do not use residual visual capacities without extensive experience and appropriate motivation.

Animals↗
PubMed1986

Colour versus orientation discrimination in severely brain-damaged and normal adults.

Normal adults and adults with severe, diffuse brain damage were tested on a two-choice simultaneous discrimination where either the colour or orientation of stripes on the stimulus cards was the relevant dimension. There was no overall impairment in discrimination learning by the brain-injured subjects. In the normal subjects, however, the discrimination was produced more readily for line orientation than for colour whereas the converse was true for the brain-damaged group. The present data are compared to those obtained in developmental studies and with other types of cerebral pathology.

Adult↗
PubMed1985

Expected and actual behavioural capacity after diffuse reduction in cerebral cortex: a review and suggestions for rehabilitative techniques with the mentally handicapped and head injured.

Expectations of residual function (and of potential therapeutic outcome) after brain damage are important factors in the selection of rehabilitation programmes. Drawing upon reports of what we call here association learning and memory in humans and animals, it is shown that this type of learning remains intact and may be mediated by subcortical brain structures, despite the often severe cognitive blunting which accompanies diffuse cortical brain damage. In retarded humans the application of association learning-based behaviour modification techniques may lead to the development of an adequate behavioural base-line on which to develop cognitive rehabilitation programmes. The implications of potentially valid neuropsychological extrapolations from animals to man are discussed. Finally suggestions are made concerning the interaction between association learning and more cognitive information-processing strategies, and the implications for behaviour modifications with retarded and head injured are considered.

Anencephaly↗