Creativity in older adults: a plethora of possibilities

Aging continues to be an important topic of study. For many older adults, the elder years can be a challenging, if not difficult, time. Creativity interventions have been shown to positively affect mental and physiological health indicators. The process of creating and one's attitude toward life may be more important than the actual product or tangible outcome. While many activities are those typically thought of as creative, such as painting, there are also a number of useful interventions that are not traditionally identified as creative ones, but that are, in fact, creative activities. This paper describes recent work with creativity in older adults, including research and clinical projects, and earlier works that could be refined as creative interventions. Recommendations for further investigation of creativity also are presented.     

Retinoids and activation of PKC induce tissue‐type plasminogen activator expression and storage in human astrocytes

Summary. Background: Emerging data demonstrate important roles for tissue‐type plasminogen activator (t‐PA) in the central nervous system (CNS). In contrast to endothelial cells, little is known about the regulation of t‐PA gene expression and secretion in astrocytes. Objectives: The aims of the present study were to investigate whether t‐PA gene expression is regulated by retinoids and the protein kinase C (PKC) activator phorbol 12‐myristate 13‐acetate (PMA) in human astrocytes, and to study whether t‐PA is stored and subject to regulated release from these cells, as with endothelial cells. Methods: Native human astrocytes were treated with RA and/or PMA. mRNA was quantified by real‐time RT‐PCR and protein secretion determined by ELISA. Intracellular t‐PA immunoreactivity in astrocytes was examined by immunocyto‐ and histochemistry. Results: RA and/or PMA induced a time‐dependent increase in t‐PA mRNA and protein levels in astrocytes, reaching 10‐fold after combined treatment. This was associated with increased amounts of t‐PA storage in intracellular granular structures. Both forskolin and histamine induced regulated release of t‐PA. The presence of t‐PA in reactive astrocytes was confirmed in human brain tissue. Conclusions: These data show that RA and PKC activation induce a strong up‐regulation of t‐PA expression in astrocytes, and increased intracellular storage pools. Moreover, a regulated release of t‐PA can be induced from these cells. This raises the possibility that astrocytes contribute to the regulation of extracellular t‐PA levels in the CNS.     

Treosulfan and Fludarabine Conditioning for Hematopoietic Stem Cell Transplantation in Children with Primary Immunodeficiency: UK Experience

We previously published results for 70 children who received conditioning with treosulfan and cyclophosphamide (n = 30) or fludarabine (n = 40) before undergoing hematopoietic stem cell transplantation (HSCT) for primary immunodeficiency (PID). Toxicity was lower and T cell chimerism was better in the patients receiving fludarabine, but cohort numbers were relatively small and follow-up was short. Here we report outcomes of 160 children who received homogeneous conditioning with treosulfan, fludarabine, and, in most cases, alemtuzumab (n?=?124). The median age at transplantation was 1.36 years (range, .09 to 18.25 years). Donors included 73 matched unrelated, 54 1 to 3 antigen-mismatched unrelated, 12 matched sibling, 17 other matched family, and 4 haploidentical donors. Stem cell source was peripheral blood stem cells (PBSCs) in 70, bone marrow in 49, and cord blood in 41. Median duration of follow-up was 4.3 years (range, .8 to 9.4 years). Overall survival was 83%. No patients had veno-occlusive disease. Seventy-four patients (46%) had acute GVHD, but only 14 (9%) greater than grade II. Four patients underwent successful retransplantation for graft loss or poor immune reconstitution. Another patient experienced graft rejection and died. There was no association between T cell chimerism?>95% and stem cell source, but a significant association was seen between myeloid chimerism?>95% and use of PBSCs without an increased risk of significant GVHD compared with other sources. All 11 patients with severe combined immunodeficiency diagnosed at birth were alive at up to 8.7 years of follow-up. Long-term studies are needed to determine late gonadotoxic effects, and pharmacokinetic studies are needed to identify whether specific targeting is advantageous. The combination of treosulfan, fludarabine, and alemtuzumab is associated with excellent results in HSCT for PID.     

The immune response of allophenic mice to 2,4-dinitrophenyl (DNP)-bovine gamma globulin. I. Allotype analysis of anti-DNP antibody

The question of whether or not lymphoid cells can cooperate across a histocompatibility difference barrier has been studied in several laboratories. Using an adoptive transfer system, Katz et al. (1) first showed that T cells from (low responder × high responder) F(1) mice, primed to the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT), could collaborate with 2,4-dinitrophenyl (DNP)-primed B cells from a high responder, but not a low responder strain, in response to DNP-GLT. The response to GLT is under H- 2-1inked Ir gene control. In contrast, studies with mouse bone marrow chimeras have shown that T cells can interact with H-2-histoincompatible B cells in response to antigens not under Ir gene control (2-4). Another type of chimera, the allophenic mouse, has been used to study possible histoincompatible cell interactions to a number of antigens, including DNP-L- glutamic acid, L-lysine, L-alanine; L-glutamic acid, L-alanine, L-tyrosine; L-glutamic acid, L-lysine, L-phenylalanine; and poly-L (Tyr, Glu)-poly D,L- Ala-poly-L-Lys[T,G)-A-L] (5-9). The response to each of these antigens is under H-2-1inked Ir gene control. It was initially reported (8, 9) that in allophenic mice containing both high and low responder cells, the antibody to (T,G)-A-L was of both the high and low responder allotype. This was interpreted to mean that high responder T cells had cooperated with low responder B cells across a histocompatibility difference barrier in the environment of the allophenic mice. However, Press and McDevitt (10) have recently reported that additional and more accurate analyses of these allophenic mouse sera failed to detect any anti-(T,G)-A-L antibody of the low responder allotype. Moreover, in an experiment using bone marrow chimeras, there was no low responder allotype antibody produced in response to (T,G)-A- L(10). The present study was undertaken to test the immune response of allophonic mice to an antigen, DNP-bovine gamma globulin (DNP(56)BGG), known to be controlled by genes both inside and outside the H-2 complex (11, 12).(1) When high and low responder cells to DNP(56)BGG are present in allophenic mice, only antibody of the high responder allotype is produced. The results suggest that cell cooperation in allophenic mice cannot occur across a histocompatibility difference barrier in response to an antigen whose genetic control is at least partially within the H-2 complex.     

Inhibition of Ly-6A antigen expression prevents T cell activation

Antisense oligonucleotides complementary to the 5' end of the mRNA encoding the Ly-6A protein were used to block the expression of that protein. Using this approach we could inhibit the expression of Ly-6A by 60-80% in antigen-primed lymph node (LN) T cells as well as in the D10 T cell clone. Inhibition of Ly-6 expression resulted in the inability to restimulate in vitro, antigen-primed T cells. It also blocked the activation of normal spleen cells by Con A, monoclonal antibody (mAb) to CD3, and mAb to Ly-6. In contrast, stimulation of normal spleen cells with the pharmacological agents PMA + ionomycin were unaffected by the inhibition of Ly-6 expression. Similar results were obtained with the D10 T cell clone; stimulation with Con A + interleukin 1 (IL-1), antigen-presenting cells (APC), or the clonotypic antibody + IL-1 was greatly reduced in the presence of antisense oligonucleotides to Ly-6. Stimulation with PMA + ionomycin was again unaffected. We also studied the effect of antisense oligonucleotides on stimulation of preactivated D10 cells. Preactivation of D10 cells with Con A + IL-1 renders them receptive to secondary stimulation by other lymphokines. In this case, antisense oligonucleotides to Ly-6 had no effect on secondary activation with IL-2, IL-4 + IL-1, or PMA + ionomycin. We conclude from these studies that Ly-6 expression is required for T cell receptor (TCR)-mediated T cell activation.     

Marked hyperamylasemia associated with carcinoma of the lung.

We present a case of marked hyperamylasemia associated with undifferentiated small cell carcinoma of the lung. The serum alpha-amylase had an electrophoretic mobility similar to that of salivary gland enzyme (s-type), and that in tissue extracts from the lung tumor and metastatic skin nodules showed similar migration. No evidence of a salivary or pancreatic cause of hyperamylasemia was found at autopsy, and macroamylasemia was excluded. We suggest that the strikingly increased serum alpha-amylase activity was a result of ectopic production of this enzyme by tumor. We compare results for this case to other published reports.     

Outcome of hematopoietic stem cell transplantation in severe combined immune deficiency with central nervous system viral infection

BACKGROUND: Patients with severe combined immunodeficiency and preexisting viral pneumonitis formally had a poor outcome from hematopoietic stem cell transplantation. With inhaled steroid and antitumor necrosis factor alpha antibody treatment, results improved. The poor outcome of patients with viral central nervous system infection prompted this retrospective single center review. RESULTS: Eight of 71 patients with severe combined immunodeficiency transplanted since 1987 were identified with viral central nervous system infection (adenovirus [1], cytomegalovirus [2], Epstein-Barr virus [2], parvovirus [1], varicella zoster virus [1], human herpesvirus 6 [1]). Nonspecific neurologic symptoms included drowsiness, irritability, head lag, fisting and floppiness. Later symptoms included unresponsiveness, apnea, posturing, hypotonia, hyperreflexia and seizures. All had neuroradiologic investigations. Only one had an initially normal computed tomography scan. Magnetic resonance image abnormalities included cerebral atrophy, basal ganglia changes, diffuse leukoencephalopathy, and multifocal mass lesions. Five patients had virus identified from cerebrospinal fluid by polymerase chain reaction and brain tissue examination from 3 patients identified human herpesvirus 6, adenovirus type 41 and varicella zoster virus. Three children remain alive, 2 received replete marrow and one remains untransplanted. Others who received T cell depleted marrow died of neurologic sequelae. CONCLUSION: Outcome of viral central nervous system infection after hematopoietic stem cell transplantation for severe combined immunodeficiency is poor, particularly associated with T cell depleted marrow.     

Departmental audit of tonsillectomy haemorrhage rates: pitfalls in interpretation

Concerns that a largely anecdotal increase in post tonsillectomy haemorrhage rates was related to the introduction of disposable instruments have prompted much investigation. The result has been, rather, to highlight other variables influencing this risk, but especially to insist on the following: 1. Training in traditional 'cold' techniques. 2. Regular departmental audit of haemorrhage rates. 3. Presentation of such data to patients to ensure informed consent. This audit demonstrates the pitfalls in interpretation of crude data, unadjusted for case-mix, in predicting individual patient risk and in national ranking of unit performance.