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Biomedical subjects

M Moscovitch

Publications and source records attributed to M Moscovitch.

At least 109 records · Page 6Linked to original sources

Visual processing deficits as assessed by spatial frequency contrast sensitivity and backward masking in normal ageing and Alzheimer's disease.

Visual functions of patients with senile dementia of the Alzheimer type were compared with those of young people and age-matched controls. Visual acuity and spatial frequency contrast sensitivity did not differ significantly between Alzheimer patients and normal elderly subjects, although both were impaired in comparison with young subjects. Alzheimer patients required more time than ageing controls to identify letters and were susceptible to the interfering effects of a backward pattern mask on letter recognition over a longer interval. The spatial extent over which the pattern mask was effective, as well as the time interval over which a homogeneous mask interfered with letter recognition, were equivalent in normal old people and Alzheimer patients. In all the masking tasks, young people performed better than the old. It is suggested that Alzheimer's disease affects later central visual functions more than early relatively peripheral ones.

Adult↗

Lateralization of peripherally and centrally masked words in young and elderly people.

Twenty three-letter, vertical words were presented to the right or left visual fields followed by either a flash, a visual noise, or a pattern mask at various stimulus onset asynchronies. For both young and elderly adults, target identification decreased from the flash to the pattern mask condition, whereas the magnitude of the right visual advantage increased. Although the elderly people identified fewer targets than the young, especially in the pattern mask condition, the magnitude of the right visual field advantage did not vary with age. The results argue against the hypothesis that the cerebral hemispheres deteriorate at different rates with age.

Adult↗

Memory CTL-hybridoma: a model system to analyze the anamnestic response of cytolytic T lymphocytes.

We have previously described monoclonal CTL-hybridomas growing continuously in culture in the absence of a known antigenic stimulus or growth-promoting factor(s), exhibiting specific anti-H-2Db killing activity in vitro after a distinct 2-hr lag period before the onset of lysis. Here we provide evidence indicating that the hybridoma Md 26.15 represents "memory" CTL, and we examine the mechanism whereby they respond to antigen/mitogen. The brief period (2 to 3 hr) required for stimulation suggests that expression of potentiated effector function(s) after stimulation requires no cell replication. The frequency of effector hybridoma cells capable of specific binding to target cells before and after stimulation is the same, as determined in a direct hybridoma-target cell conjugation test, although cytolytic activity is markedly enhanced. On the other hand, kinetic and cell dispersion assays indicate that the potentiation of cytolytic activity can be attributed to shortening of the lag period of killing as well as to a small enhancement in the recycling ability of cytolytic effectors. We suggest that shortening of the lag period involves activation of potential effectors, which is manifested at a post-binding stage of effector-target interaction. The CTL hybridoma described herein provides a unique model system for studying CTL reactivation.

Animals↗

Anti-tumor effects of allogeneic bone marrow transplantation in (NZB X NZW)F1 hybrids with spontaneous lymphosarcoma.

Untreated female (NZB X NZW)F1 hybrid mice (B/W F1) were found to develop lymphosarcoma spontaneously as they aged. Tumor incidence was evaluated in B/W F1 mice immunosuppressed with total lymphoid irradiation (TLI) and in TLI-conditioned B/W F1 mice reconstituted with 3 X 10(7) BALB/c bone marrow (BM) cells. BALB/C leads to B/W F1 chimerism (79 to 89% BALB/c-type cells) was confirmed by typing peripheral blood lymphocytes with specific alloantisera and complement by using a microcytotoxicity assay. Chimeras showed no clinical signs of graft-vs-host disease (GVHD). TLI-treated mice seemed to show a slightly accelerated onset of lymphosarcoma as compared with untreated controls, but the difference was not significant (p = 0.08). BALB/c leads to B/W F1 chimeras reconstituted at 1 to 3 mo of age (25 mice) developed no tumors for an observation period of 18 mo after transplantation. In contrast, tumors developed in 24/130 of age-matched controls, and in 13/57 of TLI-treated nonreconstituted age-matched B/W F1 mice. Tumor incidence in BALB/c leads to B/W F1 chimeras transplanted at an older age (9 to 11 mo) was similar to that observed in age-matched TLI-treated B/W F1 mice and age-matched untreated controls. The data suggests that the high naturally occurring incidence of lymphosarcoma could be reversed by reconstituting TLI-treated mice with BM cells (p = 0.027). Thus, allogeneic BM transplantation may exert potent graft-vs-tumor effects (GVT) when tumor susceptible hosts are reconstituted at an early age, whereas GVT is relatively ineffective at an advanced age, which probably correlates with an advanced stage of tumor development. Allogeneic BM transplantation should be additionally explored as a potential clinical tool for eradication of certain solid tumors in adjunct to high-dose radiochemotherapy, inasmuch as GVT seems to be independent of GVHD.

Aging↗

Successful treatment of autoimmune manifestations in MRL/l and MRL/n mice using total lymphoid irradiation (TLI).

The autoimmune manifestations of MRL-+/+ (MRL/n) and MRL/Mp-lpr/lpr (MRL/l) murine models of systemic lupus erythematosus (SLE) were successfully reversed following total lymphoid irradiation (TLI) therapy consisting of 8-12 daily fractions of 200 rad. Following radiotherapy the characteristic lymphadenopathy of MRL/l disappeared, proteinuria was 334 mg% compared to a peak of 2272 mg% in untreated controls, and the median survival time was prolonged to 423 days compared to 214 days in untreated mice. The albuminuria of TLI-treated MRL/n mice was 194 mg% compared to 1180 mg% in untreated controls. The survival of treated MRL/n mice was prolonged to a median of 389 as compared to 190 days in untreated controls. The effect of TLI on antiDNA antibodies in both MRL/l and MRL/n was less remarkable. However, the antiDNA activity reached normal levels in most long-living mice. The most impressive finding was complete reversal and/or prevention of the SLE-like glomerulonephritis in MRL/l mice as documented by light and electron microscopy. Immunomanipulation with TLI should be further evaluated as a possible treatment modality in intractable human autoimmune disorders.

Animals↗

Hemispheric specialization and the perception of emotion: evidence from right-handers and from inverted and non-inverted left-handers.

Right-handers and inverted and non-inverted left-handers viewed emotional expressions in one hemifield and, simultaneously, a neutral expression of the same poser in the other hemifield. Subjects were required to identify the side containing the affective face. Happy faces with open (i.e. salient) and closed mouth smiles and sad faces were used as stimuli. For right-handers and inverters reaction time was faster to right hemifield presentations for happy faces and to left hemifield presentations for sad faces. Non-inverters showed the reverse pattern. The saliency of the happy expressions had no effect on the magnitude and direction of asymmetry for any group. The data support the hypothesis of differential hemispheric specialization for positive and negative emotion and demonstrate opposite patterns of asymmetry in affect perception for inverted and non-inverted left-handers.

Adult↗

Modified general cavity theory applied to the calculation of gamma dose in 60Co thermoluminescence dosimetry.

Burlin's general cavity theory for intermediate sized cavities incorporated two weighting factors: d, the average reduction in the electron fluence from the medium inside the cavity, and 1 - d, the average fractional build-up to equilibrium of the cavity-generated electron spectrum--both calculated for an average path length g of electrons crossing the cavity. A new weighting factor d' has been introduced expressing the fact that average path length for medium- and cavity-generated electrons are not equal and this leads to a modified general cavity expression. The new expression is applied to 60Co thermoluminescence dosimetry experimental results of other workers. For LiF TLD in all the media agreement with experiment is improved. There is a significant dependence of the theoretical results on the effective mass attenuation coefficient, indicating the need for further studies.

Cobalt Radioisotopes↗

Paired-associate learning in institutionalized and noninstitutionalized old people: an analysis of interference and context effects.

Groups of old people were impaired, relative to young adults, on a test of negative transfer involving lists of paired-associate words. Susceptibility to interference effects were greater in old people living in institutions than in old people living in their own homes. The effects of varying contextual cues on performance on this task were also assessed. All participants, regardless of age, benefitted from manipulations that were intrinsic to the task (e.g., relatedness of paired associates), but only the institutionalized aged responded to extrinsic contextual manipulations (e.g., environmental changes). In general, the performance of institutionalized old people resembled that of brain-damaged amnesic patients tested under similar conditions; old people living at home generally behaved more like normal, young people. The results were discussed in terms of specific age differences in cognitive function, declining brain function, and possible selective effects of institutionalization.

Adult↗

Regulation of the immune response in experimental models of autoimmune disorders. II. Induction of suppressor cells of the mixed lymphocyte culture in adult (NZB x NZW)F1 mice using total lymphoid irradiation.

Kinetic studies were done on mixed lymphocyte reaction suppressor cells generated in female (NZB x NZW)F1 hybrid mice (B/WF1) treated with total lymphoid irradiation (TLI) and in stable BALB/c leads to B/WF1 bone marrow chimeras prepared with TLI (8 daily fractions of 200 rads followed by either whole body irradiation 400 rads (WBI) or intravenous cyclophosphamide (CY) 100--200 mg/kg). All chimeras maintained intact BALB/c skin grafts (greater than 500 days) and showed no signs of graft vs host disease (GVHD). Radioresistant alloantigen-nonspecific suppressor cells were apparent in the spleen immediately following TLI (78--88% suppression of 3H-thymidine incorporation by co-cultured spleen cells using unrelated stimulator and responder cells in one way MLR). The suppressive capacity was of a relatively short duration since suppression became inapparent within 15--30 days following TLI. Nonspecific radioresistant suppressor cells were maintained in stable BALB/c leads to B/WF1 chimeras for longer periods of time (7 months in chimeras prepared with TLI and CY and 11 months of chimeras prepared with TLI and WBI). On the other hand, specific suppressor cells blocking host type (B/WF1 chimeras. The data suggest that the impaired suppressive immunoregulatory functions of B/WF1 mice can be corrected by normal stem cells even though maturation occurs in the B/WF1 lymphoid milieu.

Animals↗

Regulation of the immune response in experimental models of autoimmune disorders: I. Immunocompetence and transplantation tolerance in female (NZB X NZW)F1 hybrid mice immunosuppressed with total lymphoid irradiation and in reconstituted bone marrow chimeras.

Female (NZB X NZW)F1 (B/WF1) mice treated with fractionated total lymphoid irradiation (TLI) and TLI conditioned BALB/c leads to B/WF1 bone marrow (BM) chimeras were studied to determine the effects of TLI and reconstitution with normal BM on in vivo and in vitro immune reactivity. TLI treated B/WF1 females showed limited increased retention of semiallogeneic skin grafts (2 1/2 times as long as untreated) and allogeneic skin grafts (twice as long as untreated). In vitro proliferative responses to allogeneic lymphocytes were severely depressed at 5 days after TLI with partial recovery as early as 15 days post TLI. Proliferative responses to phytohemmagglutinin, concanavalin A and lipopolysaccharide were similarly depressed in the immediate post TLI period with gradual subsequent recovery. Nine out of eleven B/WF1 mice transplanted with semiallogeneic, BALB/c BM after TLI conditioning were stable chimeras without evidence of graft vs host disease and were permanently tolerant to BALB/c skin allografts in vivo and BALB/c alloantigens in vitro. BALB/c leads to B/WF1 chimeras showed BALB/c type in vitro proliferative mitogen responses without the age related decline in reactivity characteristic of untreated B/WF1. In contrast, adult B/WF1 mice were resistant to induction of completely allogeneic BM chimerism. The significance of these findings as they relate to the impaired immune status of female B/WF1 mice is discussed.

Animals↗

T lymphocyte-mediated cytolysis. III. Delineation of mechanisms whereby mitogenic and non-mitogenic lectins mediate lymphocyte-target interaction.

We have investigated the mechanism(s) by which mitogenic (concanavalin A [Con A], phytohaemagglutinin [PHA] and Lens culinaris agglutinin [LCA]) and non-mitogenic (soybean agglutinin, peanut agglutinin, wheat-germ agglutinin and pokeweed mitogen) lectins mediate, non-specifically, lectin-dependent lymphocytotoxicity (LDCC). We show that non-mitogenic lectins are ineffective mediators of LDCC, due to their inability to mediate effective binding of effector cytotoxic T cells (EC) and target cells (TC), and not to their failure to 'activate' TC-bound EC, as proposed before. Evidence is presented that in LDCC Con A and PHA exert their primary effect(s) by affecting the TC rather than the EC. Although the lectin LCA, unlike Con A and PHA, is equally reactive with either EC or TC, a direct comparison is difficult since the presence of LCA, but not Con A or PHA, during the entire assay is required for optimal kill. Furthermore, all three LDCC-supportive lectins (PHA, Con A and LCA) show a similar TC preference when tested in a EC-TC conjugation assay. Taken together, these results are inconsistent with the theory that lectins mediate LDCC by 'bridging' EC and TC through lectin-binding receptors followed by 'activation' of the TC-bound EC. We would like to suggest that the potential of mitogenic lectins to mediate EC-TC interaction is related to their modification of TC-surface constituents, possibly major histocompatibility complex determinants, rendering them recognizable, non-specifically by EC.

Animals↗

Regulation of the immune response in experimental models of autoimmune disorders: resistance of (NZB X NZW)F1 mice to tolerance induction in vivo.

Studies were carried out to test whether tolerance to alloantigens and to heterologous proteins could be induced in (NZB X NZW)F1 (B/W) female mice, compared with females of various other mouse strains, including BALB/c, C3H/eb, C57Bl/Ka and (BALB/c X C57Bl/6)F1. Untreated BALB/c and B/W mice were resistant to tolerance induction by deaggregated BSA, while all other strains were susceptible, as indicated by their lack of response to antigen challenge. Tolerance induction to BSA was further potentiated in all mouse strains including BALB/c with the exception of B/W, following prior conditioning of the mice with total lymphoid irradiation (TLI). Similarly, specific and permanent tolerance to H-2 incompatible alloantigens was successfully induced in TLI conditioned BALB/c, C3H/eb, (BALB/c X C57Bl/6)F1 injected with bone marrow cells, however, B/W mice were resistant. Stable chimeras could be established in TLI treated B/W mice only across a semi-allogeneic combination (BALB/c--greater than B/W). No graft vs host disease (GVHD) was observed in any of the chimeras including B/W mice. We conclude that B/W mice are resistant to tolerance induction to heterologous proteins and alloantigens, even after TLI conditioning. We postulate that this phenomenon is a function of both the intrinsic properties of the haemopoietic stem cells, including their differentiated progeny, as well as characteristics of their cellular microenvironment.

Animals↗

Processing the intensity of dichotic syllables.

Subjects were required to match the intensity levels of the left- and right-ear members of dichotically presented nonsense syllables. When subjects matched the overall average intensities of a sequence of differing dichotic pairs no ear differences were observed. When repetitions of single dichotic pairs were matched right-ear syllables were judged louder than left-ear syllables. The results support a model predicting left-hemisphere superiority in a task permitting higher-level encoding of speech input.

Cerebral Cortex↗