Interferon α and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS

HIV type 1 (HIV-1) not only directly kills infected CD4⁺ T cells but also induces immunosuppression of uninfected T cells. Two immunosuppressive proteins, interferon α (IFNα) and extracellular Tat, mediate this process because specific antibodies against these proteins prevent generation of suppressor cells in HIV-1-infected peripheral blood mononuclear cell cultures. Furthermore, the production of C-C chemokines in response to immune cell activation, initially enhanced by IFNα and Tat, ultimately is inhibited by these proteins in parallel with their induction of immunosuppression. The clinical corollary is the immunosuppression of uninfected T cells and the decline in C-C chemokine release found at advanced stages of HIV-1 infection paralleling rising levels of IFNα and extracellular Tat. We, therefore, suggest that IFNα and Tat may be critical targets for anti-AIDS strategies.     

Evidence for the existence of non-GABAergic, cholinergic interneurons in the rodent hippocampus

Previous studies have revealed a small number of hippocampal interneurons immunoreactive for choline acetyltransferase, the acetylcholine-synthesizing enzyme. It remained an open question, however, whether these neurons represented a subgroup of inhibitory GABAergic neurons co-localizing acetylcholine. In this study, we have combined immunocytochemistry for choline acetyltransferase and in situ hybridization for glutamate decarboxylase messenger RNA, the GABA-synthesizing enzyme. None of the choline acetyltransferase-immunoreactive neurons in the various layers of the hippocampus proper and fascia dentata were found to co-localize glutamate decarboxylase messenger RNA. The lack of an in situ hybridization signal in these neurons is unlikely to result from the combination of the two labeling techniques. When combining in situ hybridization for glutamate decarboxylase messenger RNA with immunostaining for parvalbumin, a calcium-binding protein expressed by many GABAergic hippocampal interneurons, numerous double-labeled cells were observed. These data provide neurochemical evidence for the existence of non-GABAergic, supposedly cholinergic non-principal cells in the hippocampus.     

The Hierarchical Clustering of Clinical Psychology Practicum Competencies: A Multisite Study of Supervisor Ratings

Competency evaluation rating forms are widely used to assess a range of global and specific psychology practitioner competencies during and at the end of clinical placements. Surprisingly, there is little research examining the dimensional structure or the hierarchical clustering of items on these ratings. The current, multisite study examined supervisor ratings of clinical psychology trainees (N = 204) on the Clinical Psychology Practicum Competencies Rating Scale (CΨPRS). Based on the proximity criterion chosen, hierarchical clustering yielded either nine clusters or four super clusters: Good Practitioner Attributes and Conduct, Scientist Practitioner and Professional Management, Assessment and Intervention, and Psychological Testing. The study also tracked the developmental trajectory of competency attainment. CΨPRS ratings differentiated groups between early but not between later stages of training. Measurement issues and implications for training and practice are discussed.     

Plasma levels of asymmetric dimethylarginine in premature neonates: its possible involvement in developmental programming of chronic diseases

Aim: The endothel dysfunction in early life may play a role in developmental programming of cardiovascular morbidity. The changes of dimethylarginines' plasma levels during the first month among preterm infants and their determinants had been investigated in our study.
Methods: Twenty preterm infants of healthy mothers were studied. Mean (±SD) birth weight and gestational age were 919.5 ± 235.5 g and 26.7 ± 1.6 weeks, respectively. Blood samples were taken by venipuncture at the 3rd, 7th, 14th, 21st and 28th days. Plasma concentrations of L-arginine, asymmetric and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-mass spectrometry method, evaluated by multivariate linear regression analysis.
Results: L-arginine (p < 0.001) and asymmetric dimethylarginine (ADMA) levels (p < 0.001) were positively associated with postnatal age. ADMA levels were negatively correlated with gestational age (p = 0.007), dopamine-need on the 3rd day of life (p = 0.015) and late infection (p = 0.038). The higher birth weight was associated with higher L-arginine (p = 0.052) and ADMA (p = 0.002) concentrations. The dopamine-need on the 7th day of life had a significant effect on postnatal elevation of SDMA levels (p = 0.035).
Conclusion: The progressive increase of ADMA levels described by our study among preterm infants suggests that early endothel dysfunction may take part in developmental programming of chronic adult diseases.     

Aspirin acetylation of betaLys-82 of human hemoglobin. NMR study of acetylated hemoglobin Tsurumai

Acetylation of hemoglobin by aspirin and other compounds has been of interest for the development of agents useful for the treatment of sickle cell disease. In the present study, we have used 2D NMR methods in combination with [1-(13)C-acetyl]salicylic acid to probe the acetylation sites of hemoglobin A and hemoglobin Tsurumai, a mutant human hemoglobin characterized by a betaLys-82-Gln substitution. In contrast to earlier studies by Klotz and coworkers (e.g. Shamsuddin M, Mason RG, Ritchey JM, Honig GR and Klotz KM, Proc Natl Acad Sci USA 71: 4693-4697, 1974) in which it was concluded that betaLys-144 is the principal target residue acetylated by aspirin, the present study confirms our previous but less conclusive demonstration (Xu ASL, Macdonald JM, Labotka RJ and London RE, Biochim Biophys Acta 1432: 333-349, 1999) that betaLys-82 is the primary acetylation site of aspirin and related agents. The present studies also provide conclusive evidence that acetylation of betaLys-82 produces multiple resonances, probably as a consequence of additional acetylation of other sites, particularly betaLys-82' on the second beta chain. The present results also resolve the apparent discrepancy between the targets of modification by aspirin and double-headed aspirin analogs, and provide an explanation for the changes in oxygen affinity and aggregation threshold of aspirin-modified hemoglobin previously observed under in vitro conditions. In light of the present identification of the principal site of acetylation, the potential therapeutic benefit of aspirin in the treatment of sickle cell disease is discussed.     

Synthesis and antitumor activity of 1,5,6-substituted E-3-(2-chloro-3-indolylmethylene)-1,3-dihydroindol-2-ones

Synthesis and antitumor activity of new E-3-(2-chloro-3-indolylmethylene)-1,3-dihydroindol-2-ones are described. All compounds prepared were active in the primary test (three human cell lines) and entered the second level (60 human cell lines). The most active antitumor derivatives bear the same substituents in the chloroindole ring and are not CDK1 inhibitors. A COMPARE analysis showed that they could act as tubulin binders. In most cell lines, E-3-(2-chloro-5-methoxy-6-methyl-3-indolylmethylene)-1,3-dihydroindol-2-one was a growth inhibitor more potent than vincristine.     

Methotrexate-induced acral erythema with bullous reaction

Chemotherapy-induced acral erythema (CIAE), a toxic reaction to a number of different chomotherapeutic agents, causes a symmetrical, painful erythema of both the palms and soles which is self-limiting. The association of this syndrome with methotrexate is unusual; only nine cases have been reported in the literature. We describe the tenth case of this syndrome associated with methotrexate, which is also the third case of the bullous variant of methotrexate-induced acral erythema. Our case is unusual in that the acral erythema was present only on the soles of the feet and in that it was associated with the presence of diffuse maculopapular lesions over the legs and trunk.     

Mean blood flow velocities in posterior cerebral arteries during visual stimulation

Changes of mean blood flow velocities (MBFV) in the posterior cerebral arteries (PCA) recorded during visual stimulation in a group of 51 healthy, right-handed volunteers are presented. There were 27 (52.9%) males and 24 (47.1%) females, aged 20-59 years (mean age: 36.98 years). Measurements were performed with a hand-held 2 MHz transcranial Doppler (TCD) probe through the temporal window, with the subjects' eyes open and closed, and while they were looking at constant and at flashing white light. In half of the subjects, first the right PCA was insonated and then the left PCA, while in the other half the reverse procedure was used. Statistical analysis was done using Wilcoxon's matched-pair signed-rank test. Mean MBFV value in the left PCA was 41.2+/-8.6 cm/s (mean +/- SD) with eyes open, 27.8+/-8.5 cm/s with eyes closed, 42.3+/-9.1 cm/s while looking at constant white light, and 43.0+/-9.6 cm/s while looking at flashing white light. Mean MBFV value in the right PCA was 41.7+/-8.9 cm/s with eyes open, 28.2+/-9.1 cm/s with eyes closed, 42.4+/-8.8 cm/s while looking at constant white light, and 43.4+/-9.2 while looking at flashing white light. Value differences for the left PCA, between eyes open and closed and between looking at constant white light and looking at flashing white light were statistically significant (p<0.001, z= -6.2146, and p<0.001, z= -3.4836, respectively). For the right PCA, a value difference between eyes open and closed, and between looking at constant and flashing white light was statistically significant (p<0.001, z= -6.2146 and p<0.001, z= -3.6928), but there was no significant difference between eyes open and constant white light (p=0.03, z= -2.1693). The results showed that simple visual stimulation had an effect on blood flow velocities in PCA and that it could be measured with TCD.     

Assessing Quality of Life in Adult Cancer Survivors (QLACS)

This article describes development of a quality of life measure designed to assess issues relevant to long-term cancer survivors. In-depth semi-structured interviews were conducted with 58 long-term cancer survivors to identify domains most relevant to long-term survivors ( 5 years post-diagnosis). Self-report items were developed from these interviews and administered to a second sample of 242 long-term survivors. Domains and items were selected from the item pool by a combination of factor analysis and criterion-based item selection. Five cancer-specific domains were identified (appearance concerns, financial problems, distress over recurrence, family-related distress, and benefits of cancer) along with seven generic QOL domains (negative feelings, positive feelings, cognitive problems, sexual problems, physical pain, fatigue, and social avoidance). Cronbachs was 0.72 or greater for each domain. Correlations between domain scores and criterion measures were 0.72 or higher in all but one generic domain (social avoidance), but somewhat lower on cancer-specific domains. The new multidimensional measure has good internal consistency and validity and is appropriate for comparisons between cancer and non-cancer populations, as well as long-term follow-up of cancer patients.