The effect of aging on cognate function and development of immune memory

Immunological memory is one of the central features of the immune system and can be described as the ability of the immune system to respond more efficiently to a second encounter with the same pathogen. The immune system is dramatically affected by age-related changes and it is becoming apparent that immune memory exhibits significant defects as a result of aging. Although immune memory generated during youth functions well into old age, that generated later in life functions poorly. Importantly, age-related defects in the cognate helper function of CD4(+) T cells can potentially influence the development of both humoral and cell-mediated immune memory. These defects ultimately result in aged individuals who exhibit reduced responses to both infections and vaccinations.     

Student's perceptions of a virtual PBL experience.

OBJECTIVE: Our purpose is to present findings regarding student attitudes towards a virtual PBL program used to standardize their pediatric clinical experience. DESCRIPTION: With funding provided by the Fund for the Improvement of Post-Secondary Education, we developed Project LIVE (Learning through Interactive Video Education), a CD-ROM/Web hybrid program that uses digital video cases to conduct "virtual" problem-based learning groups with students doing a clinical rotation in a remote setting. Cases were progressively disclosed by videos of patient/physician encounters on a CD-ROM. Groups of five students and a faculty facilitator collaborated, teaching each other within the discussion section of the program. We conducted a multifaceted evaluation of Project LIVE to study the impact of case modality or distance on student learning and attitudes. We placed students in one of three groups (1) a face-to-face group with a paper case (FFT), (2) a face-to-face group with a video case (FFV), and (3) a virtual group (VG) with the digital video case. We then studied student attitudes about the three teaching formats. Over a six-month period three education specialists, who were not a part of the development team, conducted eight focus groups lasting one hour to assess student attitudes about Project LIVE. No one from the project team was present during these groups, and an independent evaluator analyzed the notes taken by each focus group leader. DISCUSSION: Trends across the groups included the following: (1) Authenticity (video)-Students reported that the authenticity of the case was a critical feature and that, "seeing (videos) made learning more memorable." Virtual and FFV groups reported more confidence in their ability to recognize abnormal findings in their patients. "You can't expect to teach clinical exam skills with a piece of paper." (2) Use of time-Students from all groups believed the cases were a good use of their time and improved their ability to solve clinical problems. They said it gave them an opportunity to "get away from just doing and focus on learning." However, the virtual groups complained of the lack of "a barometer for how much is too much" time. Some students reported spending an average of eight to ten hours per case over the period of a week. (In contrast, face-to-face groups met for three hours.) (3) Modeling clinical reasoning-Students believed the cases were valuable in structuring their knowledge, conceptualizing how to handle difficult situations, distinguishing abnormal from normal physical examination findings, and collaborating with their peers and their mentor to develop critical thinking. "It forced us to be logical" and ". how to think through the process-it mimics the real setting." (4) Technical support-The responsiveness of the Project LIVE staff was essential in assisting students in troubleshooting problems. (5) Distance component-Students preferred to work through the cases in face-to-face groups but agreed that the virtual experience is "good if you are in the middle of nowhere." This program was enjoyed by students and gave us an approach to standardizing experiences across multiple clinical sites.     

Stabilization of neurites in cerebellar granule cells by transglutaminase activity: identification of midkine and galectin-3 as substrates

The formation of covalent isopeptide cross-links between cell surface protein molecules by the enzyme transglutaminase C influences cell adhesion and morphology. Retinoid-inducible cross-linking activity associated with this enzyme is present in the developing rat cerebellar cortex [Perry M. J. M. et al. (1995) Neuroscience 65, 1063-1076]. A monoclonal antibody was used to localize transglutaminase C to granule neurons in the developing cerebellar cortex. The enzyme was inducible by retinoic acid both in granule neurons cultured from postnatal rat cerebellar cortex and in cells of the embryonic dorsal rhombic lip, which contain granule neuron precursors. A possible biological function for transglutaminase activity was investigated in living granule neurons, cultured on a biomatrix substratum, studied by time-lapse cinematographic analysis using the transglutaminase inactivator RS-48373-007. Inhibition of cross-linking activity did not influence the number of neurites formed by granule neurons, but caused the destabilization of neurites during the initial outgrowth period, seen as an increase in the number of growth cone retractions and the onset of premature axon collateral formation (bifurcation). Inactivation of cross-linking activity prevented the formation of fascicles between neurites only when cells were cultured on a biomatrix surface. Two glial proteins involved in cell-extracellular matrix interactions, midkine and galectin-3, were identified as putative substrates for granule neuron transglutaminase.The results suggest that covalent cross-link formation by transglutaminase C or a related enzyme generates multimeric molecular forms of glial-derived proteins, and plays a role in stabilizing newly formed neurites. A possible non-pathological role for transglutaminase in the control of axon collateral branching by developing granule neurons in the cerebellar cortex is discussed.     

Chromosome mapping of human cell surface molecules: Monoclonal anti-human lymphocyte antibodies 4F2, A3D8, and A1G3 define antigens controlled by different regions of chromosome 11

Monoclonal antibodies 4F2, A3D8, and A1G3, directed against cell surface antigens present on subsets of human cells, were used to identify the human chromosome regions that code for the antigenic determinants. Human fibroblasts expressed all three antigens, and no cross-reactivity with Chinese hamster or mouse cells was found. Fourteen rodent x human somatic cell hybrids, derived from six different human donors and from two different Chinese hamster and one mouse cell line, were studied simultaneously for human chromosome content and for antibody binding as detected by indirect immunofluorescence. Concordancy with binding of all three antibodies was observed only for human chromosome 11. All other chromosomes were excluded by three or more discordant hybrid clones. Data from six hybrids containing three different regions of chromosome 11 indicate that it is the long arm of chromosome 11 which is both necessary and sufficient for expression of the human antigen defined by 4F2 while the antigen(s) defined by A3D8 and A1G3 map to short arm.     

Synthèse de polysiloxanes téléchéliques, 2. Synthèse de diamines aromatiques

Telechelic aromatic diamines ( 11 ) containing an oligo- or polysiloxane chain were prepared in a 4-step synthesis. In the first step 1-allyloxy-4-nitrobenzene ( 6 ) was synthesized and subsequently hydrosilylated with chlorodimethylsilane. In the third step the product ( 7 ) was hydrolyzed or condensed with α-hydro-β-hydroxyoligo- or polydimethylsiloxane ( 9a or 9b ). In the last step the nitro groups were reduced into amino groups. The steps were controlled by means of ¹H and ²⁹Si NMR spectroscopy.     

Demonstration of phenotypic abnormalities of thymic epithelium in thymoma including two cases with abundant Langerhans cells.

A panel of monoclonal antibodies that phenotypically define stages of normal human thymic epithelial (TE) cell maturation was used to compare thymic epithelium of nine thymomas with hyperplastic thymic epithelium in myasthenia gravis (MG) and thymic epithelium of normal thymuses. It has been shown previously that normal thymic epithelial cells express antigens of early TE cell maturation (A2B5, TE-4) throughout thymic ontogeny and acquire antigens 12/1-2, TE8, and TE-15 at 14 to 16 weeks of fetal gestation. Hyperplastic MG thymic epithelial cells expressed TE antigens in phenotypic patterns similar to that seen in normal postnatal thymus, ie, TE in subcapsular cortex and medulla was TE4+, A2B5+, and 12/1 - 2+ and Hassall's bodies were reactive with antibodies TE8 and TE15. In contrast, thymic epithelium in primary mediastinal thymomas was TE4+, A2B5+, TE8-, and greater than 75% of thymoma epithelium was 12/1 - 2-, a thymic epithelial phenotype similar to that seen on normal fetal thymic epithelium at 14 to 16 weeks fetal gestation. In one subject with a mature epithelial histologic pattern, thymoma epithelium was found to be strongly TE8+, a phenotype suggestive of a later stage of TE maturation. Lymphocytes in five of seven thymomas with immature thymic epithelial cells predominantly expressed immature thymocyte phenotype while two thymomas with immature epithelial phenotype showed a predominance of Langerhans cells and surrounding lymphocytes expressing a mature phenotype. Lymphocytes in the thymoma with differentiated epithelial cells expressed a mature thymocyte phenotype. Thus, in thymomas of varying histologic types, phenotypic abnormalities of thymic epithelium are present; these phenotypic abnormalities may reflect abnormal thymic epithelial maturation.     

Serum-catalyzed hydrolysis of metronidazole amino acid esters

Glycine (Gly), alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), phenylalanine (Phe), and lysine (Lys) esters of metronidazole were synthesized using dicyclohexylcarbodiimide (DCC) coupling or a mixed-anhydride route, using tert-butyloxycarbonyl (tert-Boc) amino acids. Human serum-catalyzed hydrolysis of these esters at 37 degrees C give half-lives varying from 4.5 min for the Phe ester to 96 h for the Ile ester. Also determined was the pH-rate profile for hydrolysis in aqueous buffers at 25 degrees C. A linear relationship was observed between the logarithmic value of the hydrolysis rate constant in serum and that of the OH- -catalyzed hydrolysis of cationic esters. This finding may indicate that the esters studied are "equally" poor substrates for binding to the enzymes in serum and, thus, the difference observed in the serum-catalyzed hydrolysis rate is solely derived from the chemical lability of an ester bond. Interestingly, the extent of chemical activation observed in the buffer system appears to be amplified in the serum-catalyzed hydrolysis.     

Treatment Options in Severe Psychotic Depression

In our sample of 15 hospitalized patients with severe psychotic depression, six responded to therapy with tricyclic antidepressants combined with neuroleptics. Of the nine nonresponders, eight showed an excellent clinical response to electroconvulsive therapy (ECT). The clinical outcome after 6 months of treatment was similar in both groups. We recommend that protracted, complicated trials of pharmacotherapy be reevaluated in psychotic depression. A prospective comparative study of ECT and pharmacotherapy is needed to define the optimal treatment for psychotic depression.