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Models of visuospatial and verbal memory across the adult life span.

The authors investigated the distinctiveness and interrelationships among visuospatial and verbal memory processes in short-term, working, and long-term memories in 345 adults. Beginning in the 20s, a continuous, regular decline occurs for processing-intensive tasks (e.g., speed of processing, working memory, and long-term memory), whereas verbal knowledge increases across the life span. There is little differentiation in the cognitive architecture of memory across the life span. Visuospatial and verbal working memory are distinct but highly interrelated systems with domain-specific short-term memory subsystems. In contrast to recent neuroimaging data, there is little evidence for dedifferentiation of function at the behavioral level in old compared with young adults. The authors conclude that efforts to connect behavioral and brain data yield a more complete understanding of the aging mind.

Adult↗

Regulation of adhesion molecule expression by CD8 T cells in vivo. I. Differential regulation of gp90MEL-14 (LECAM-1), Pgp-1, LFA-1, and VLA-4 alpha during the differentiation of cytotoxic T lymphocytes induced by allografts.

A variety of adhesion molecules regulate the traffic and tissue localization of lymphocytes in vivo by mediating their binding to vascular endothelial cells. The homing receptor gp90MEL-14 (gp90), also known as LECAM-1 or L-selectin, mediates the adhesion of lymphocytes to specialized high endothelial venules in lymph nodes (LN) and is the primary molecule regulating lymphocyte recirculation and homing to LN, whereas other adhesion molecules have a major role in the localization of lymphocytes in inflammatory sites. We used four-color flow cytometric analysis to examine the regulation of adhesion receptor expression on LN CD8 T cells responding to skin allografts in vivo. In normal mice, greater than 95% of LN CD8 T cells are gp90+, being either gp90+Pgp1- (Population (Pop.) 1 or gp90+Pgp-1+ (Pop.2). Allografting induces the down-regulation of gp90 and up-regulation of Pgp-1 on a subset of cells, resulting in the appearance of CD8+gp90-Pgp-1hi (Pop. 3) cells. Pop. 3 cells also express high levels of LFA-1, ICAM-1, and ICAM-2, and a subset of them are VLA-4 alpha-positive. Purified Pop. 3 cells have potent cytolytic activity directed against donor alloantigen, whereas no such activity is present in Pop. 1 or 2 cells. Correlating with this is the high granzyme activity in Pop. 3 cells. In addition, Pop. 3 lymphocytes, but not Pop. 1 or 2, secrete a large amount of IFN-gamma in response to Ag. Finally, the CD8 T cells that infiltrate sponge matrix allografts are markedly enriched for the Pop. 3 subset. These results show that, during the immune response to alloantigen in vivo, a small subset of CD8 T cells down-regulates the LN homing receptor while increasing the expression of other adhesion molecules, as they differentiate into highly active cytolytic T lymphocytes. Thus, the differential regulation of LN homing receptors and receptors for peripheral vascular endothelium provides a mechanism that would redirect the traffic of activated effector cells away from lymphoid tissue and to sites of Ag deposition, where they would participate in the inflammatory response.

Animals↗

Recent research on multiple personality disorder.

The last decade has seen the emergence of solid research on MPD and the dissociative disorders, particularly in the area of diagnosis and clinical phenomenology. A number of other areas have been opened up or advanced considerably. The most notable of these include child and adolescent dissociative disorders; investigation of dissociative memory disturbances; studies of differential alter personality psychophysiology and switching; cross-cultural comparisons of MPD, possession, and dissociative states; and the contribution of pathologic dissociation to the symptomatology of other psychiatric disorders. Yet to be attempted, however, are prospective clinical trials and treatment outcome studies. In addition to clinical and theoretical insights, recent research provides strong evidence for the validity of the diagnosis of MPD. The repeated replication of a core clinical phenomenology demonstrates a construct validity equal to or superior to that demonstrated for most DSM-III/IIIR disorders. The ability of several independently developed instruments to blindly discriminate MPD patients from nondissociative disorder patients with high rates of accuracy supports both the construct and discriminant validity of the diagnosis; and as the astute clinical observations of the last century continue to be confirmed, MPD manifests an historical validity absent in most modern era diagnoses. In the future, arguments about the "reality" of MPD cannot confine themselves merely to attacking one aspect of the disorder but rather must confront the broad range of evidence supporting the validity and reliability of the diagnosis. The future belongs to multicenter studies, although intensive single-case and personal-case series will continue to make important contributions in some areas. The essential elements necessary to begin prospective multicenter studies are rapidly coming together. Already one multicenter structured interview study of clinical phenomenology has been completed and other studies are underway or near publication. As these collaborative research networks mature, even more ambitious studies will be attempted. Adequate funding remains the principal obstacle and must be creatively addressed in this era of budgetary shortfalls, particularly as several research networks cross international boundaries. Exceptionally gratifying is the burgeoning interest of large numbers of psychiatric residents and psychology graduate students in the dissociative disorders. Thanks to a decade of hard work, the next generation of clinicians and researchers will know a great deal more about these patients than the last.

Dissociative Disorders↗

Effects of hippocampal kindled afterdischarges and complex partial seizures on previously established avoidance response in cats.

The performance of well established avoidance response was tested in cats with developed, kindled, bioelectric hippocampal epileptic focus and complex partial and secondarily generalized seizures. The animals were trained before kindling to perform foreleg movement in response to clicks (conditioning stimulus) in order to avoid an unconditioned stimulus - electric shocks, applied to the same forepaw. In addition, two animals were trained to differentiate between different frequencies of clicks. There was no deficit in reflex performance and differentiatimon if the conditioning stimulus was presented during intensive uni- or bilateral spontaneous interictal limbic spiking, occurring before or after hippocampal afterdischarges and complex partial seizures. After repeated secondary generalized tonic-clonic seizures the performance was, however, completely abolished. Presentation of the conditioning stimulus during afterdischarges and partial seizures resulted in 75 percent correct responses during afterdischarges shorter than 10s and 25 percent correct responses during afterdischarges longer than 10 s. Correct responses were observed in cases when conditioning stimulus was applied not later than 6 s after the termination of hippocampal electrical stimulation. The results suggest that the functional integrity of the hippocampal formation is of no critical importance for the retrieval and for performance of the previously established avoidance response and differentiation. A deficit in memory retrieval and/or performance of the avoidance response during afterdischarges and partial seizures may be related to indirect effects caused by the afterdischarges in remote, other than limbic structures.

Animals↗

Clinical similarities and differences between Alzheimer's disease and Parkinson's disease.

Dementia and extrapyramidal signs combine in both Alzheimer's disease (AD) and Parkinson's disease (PD) to produce various degrees of clinical overlap between the two diseases. Rest tremor, positive motor response to dopaminergic drugs, bradyphrenia and disproportionate deficits in visuospatial function, dating capacity, recency discrimination, sequencing and set-shifting are specific features of PD; myoclonus, orofacial dyskinesia, aphasia and rapidly progressive global dementia favours AD. A clearer analysis of the underlying brain-behaviour relationships is necessary to advance our understanding of the origin of cognitive and motor impairment and its treatment.

Alzheimer Disease↗

[Probability analysis of elements of rat behavior after sudden and signalled interruption of food reinforcement].

Probability analysis was carried out of the appearance of single elements of rats behaviour in the process of extinction of a conditioned alimentary motor reflex. The dynamics of effector behavioural components at a sudden cessation of reinforcement (usual schedule of extinction) was compared with cessation of reinforcement signalled by a previously differentiated signal and with reinforcement cessation preceded by a stimulus initially unknown to the animal. If the reinforcement cessation is signalled by a previously differentiated (negative) stimulus, in response to its action the animals "loose the aim", what is revealed in a rapid complete reduction of all elements of the goal-directed alimentary behaviour. Obviously differentiation signal actualises the memory trace of "nonreinforcement" which was formed in the previous negative experience of the animal; this is revealed in accelerated inhibition of the alimentary motor reflex under extinction.

Animals↗

Affinity maturation in Lyn kinase-deficient mice with defective germinal center formation.

Lyn kinase-deficient (lyn-/-) mice show several abnormalities such as reduced numbers of circulating B cells, hyper-IgM, and low proliferative responses induced by CD40 ligand. Lyn-/- mice also develop splenomegaly, produce autoreactive Abs with age, and finally develop glomerulonephritis. Another abnormality observed in lyn-/- mice is that their disability to form germinal centers (GCs). It has been considered that GCs play an important role in affinity maturation and differentiation to B cell memory upon immunization with thymus-dependent Ag. Since Lyn kinase has been thought to be downstream of the signals from the B cell Ag receptor as well as CD40, we studied whether or not lyn-/- mice could exhibit normal Ag-specific class switching and affinity maturation following somatic hypermutation. The mice were immunized with (4-hydroxy-3-nitrophenyl)acetyl-chicken gamma-globulin (NP-CG). Production of NP-specific IgG1 Abs was slightly reduced but clearly detectable. The affinity of Abs produced was comparable to that in wild-type mice. Furthermore, somatic hypermutation occurred in the heavy-chain variable region at the same level as that in wild-type mice. Therefore, we conclude that isotype switching and affinity maturation occur normally in lyn-/- mice without the formation of GCs. The results lead to a speculation that Lyn may not play a role in induction of isotype switching or affinity maturation, despite being downstream of the signals from the B cell Ag receptor complex and CD40, and that GC architecture may not be absolutely essential for affinity maturation.

Amino Acid Sequence↗

Neurofibroma.

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Diagnosis, Differential↗