Developmental alterations in N-methyl-D-aspartate stimulated [3H]norepinephrine release in rat brain cortex and hippocampus

Developmental alterations in N-methyl-D-aspartate (NMDA)-stimulated[3H]norepinephrine release from rat brain cortical and hippocampal slices were studied. NMDA (10-1000 microM) resulted in a concentration-dependent increase in [3H]norepinephrine efflux; maximal responses (% released) in the cortex were: (1.53 +/- 0.12, 3.68 +/- 0.20, 2.94 +/- 0.20, 4.60 +/- 0.28 and 5.28 +/- 0.33) and the hippocampal responses were: (1.90 +/- 0.18, 3.84 +/- 0.23, 3.60 +/- 0.28, 5.16 +/- 0.38 and 5.81 +/- 0.45) at varying postnatal ages (1, 7, 14, 21 and 90 days) respectively. Cortical tissue from 7-day-old pups exhibited a transient increase in maximal efflux and a decrease in EC50. These results indicated that developmental alterations in the NMDA receptor appear to be translated into differences in NMDA stimulated [3H]norepinephrine release.     

The American Indian Holocaust: healing historical unresolved grief

American Indians experienced massive losses of lives, land, and culture from European contact and colonization resulting in a long legacy of chronic trauma and unresolved grief across generations. This phenomenon, labeled historical unresolved grief, contributes to the current social pathology of high rates of suicide, homicide, domestic violence, child abuse, alcoholism and other social problems among American Indians. The present paper describes the concept of historical unresolved grief and historical trauma among American Indians, outlining the historical as well as present social and political forces which exacerbate it. The abundant literature on Jewish Holocaust survivors and their children is used to delineate the intergenerational transmission of trauma, grief, and the survivor's child complex. Interventions based on traditional American Indian ceremonies and modern western treatment modalities for grieving and healing of those losses are described.     

A study of patient-related characteristics and outcome after moderate injury

The purpose of all injury care is to restore patients' pre-injury functioning and to facilitate the return to normal activities. The aim of this prospective study was to describe and analyse psychiatric factors and other patient-related characteristics which influence long-term results after moderate injuries. One hundred and sixty-nine injured patients were randomized to go through a comprehensive psychosocial research protocol and to participate in the 12 month follow up. The 49 patients lost to follow-up differed significantly from all other patients. They were more often single, blue-collar workers with a lower educational level and had a less favourable psychosocial background, including alcohol abuse. The 120 patients who completed the follow-up were divided in two groups: the non-recovered group (NR, N = 58), patients reporting limitations in performing their work and/or limitations in carrying out housework and/or in social life, and the recovered group (R, N = 62), patients reporting full recovery or only minor limitations in exercise or sports 12 months after the injury. The NR patients were older (P < 0.05), had a slightly higher injury Severity Score (P < 0.01) and showed signs of depression both during the acute post-injury period and at 1 year follow up (P < 0.001). The multivariate analysis showed that measurements of pain and depression during the acute post-injury period were associated with the functional outcome after 12 months. Co-operation between injury and psychiatric units should be developed to identify patients needing psychosocial or psychiatric support during the early phase of rehabilitation.     

Experimental evaluation of a multivariable adaptive nonlinear predictive controller

A new multivariable adaptive nonlinear predictive controller is designed using a general nonlinear input-output model and variable transformations. The controller is similar in form to typical linear predictive controllers can be tuned analogously or by specifying a single parameters for each controlled variable. In addition, the design procedure is computationally efficient. The new controller is compared to a multi-loop proportional-integral (PI) controller with one-way static decoupling and to an adaptive linear predictive controller through tests on a simulated nonlinear distillation column. The new controller performed well in an experimental application to a multicomponent distillation column.     

DNA recognition by the EcoK methyltransferase. The influence of DNA methylation and the cofactor S-adenosyl-L-methionine

The methyltransferase of the EcoK type I restriction/modification system is trimeric, M2S1, where the S subunit determines the sequence specificity of the enzyme. The methyltransferase has a strong preference for hemimethylated substrate DNA and, therefore, we have investigated the effect of the methylation state of DNA on binding by the enzyme, together with the effects on binding of the cofactor S-adenosyl-L-methionine. Our results indicate that the methyltransferase has two non-interacting S-adenosyl-L-methionine binding sites, each with a dissociation constant of 3.60 (+/- 0.42) microM determined by equilibrium dialysis, or 2.21 (+/- 0.29) microM determined by the displacement of a fluorescent probe. Ultraviolet light-induced crosslinking showed that S-adenosyl-L-methionine binds strongly only to the modification (M) subunits. Changes in the sedimentation velocity of the methyltransferase imply a protein conformational change due to S-adenosyl-L-methionine binding. Gel retardation results show that the binding of S-adenosyl-L-methionine to the methyltransferase enhances binding to both specific and non-specific DNAs, but the enhancement is greater for the specific DNA. Differences in binding affinities contribute to the recognition of the specific nucleotide sequence AAC(N)6GTGC by the methyltransferase in preference to a non-specific sequence. In contrast, although the complexes of unmodified and hemimethylated DNAs with the methyltransferase have different mobilities in non-denaturing gels, there appears to be no contribution of binding affinity to the distinction between these two substrates. Therefore, the preference for a hemimethylated substrate must be due to a difference in catalysis.     

Apoptosis as a cause of death in measles virus-infected cells

To determine the mechanism of measles virus-induced cell death, we studied the infection of Vero cells and monocytic cell lines with wild-type (Chicago-1) and vaccine (Edmonston) strains of measles virus. DNA fragmentation indicative of apoptosis was apparent by flow cytometry, agarose gel electrophoresis, and electron microscopy. Within syncytia, DNA strand breaks were demonstrated by end labeling with terminal transferase and then by visualization.