<Emphasis Type="Italic">GPC5</Emphasis> is a possible target for the 13q31-q32 amplification detected in lymphoma cell lines

Comparative genomic hybridization (CGH) analyses have detected gains of copy number on 13q, especially at 13q31-q32, in cell lines and primary cases of various types of lymphoma. Since amplification of chromosomal DNA is one of the mechanisms that can activate tumor-associated genes, and because 13q amplification had been reported in various other types of tumors as well, we attempted to define by fluorescence in situ hybridization (FISH) a common region at 13q31-q32 in which to explore genes that might be targets for the amplification events. Although the commonly amplified region we defined was relatively large (approximately 4 Mb), only one true gene, GPC5, was found there. GPC5 was over-expressed in lymphoma cell lines that had shown amplification, in comparison with those that had not. Our findings suggest that GPC5 is a likely target for amplification, and that over-expression of this gene may contribute to development and/or progression of lymphomas and other tumors.     

Allicin stimulates lymphocytes and elicits an antitumor effect: a possible role of p21ras

Allicin, the main organic allyl sulfur component in garlic, exhibits immune-stimulatory and antitumor properties. Allicin stimulated [(3)H]thymidine incorporation in mouse splenocytes and enhanced cell-mediated cytotoxicity in human peripheral mononuclear cells. Multiple administration (i.p.) of allicin elicited a marked antitumor effect in mice inoculated with B-16 melanoma and MCA-105 fibrosarcoma. The immune-stimulatory and antitumor effects of allicin are characterized by a bell-shaped curve, i.e. allicin at high, supra-optimal concentrations is less effective or inhibitory. Allicin induced activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in human peripheral mononuclear cells, and also in wild-type Jurkat T-cells. Allicin failed to activate ERK1/2 in Jurkat T cells that express p21(ras), in which Cys118 was replaced by Ser. These cells are not susceptible to redox-stress modification and activation. We postulate that the immune stimulatory effect of allicin is mediated by redox-sensitive signaling such as activation of p21(ras). It is suggested that the antitumor effect of allicin is related to its immune-stimulatory properties.     

Electroconvulsive therapy in adolescent and adult psychiatric inpatients--a retrospective chart design

BACKGROUND: The knowledge available on electroconvulsive therapy (ECT) in adolescents is largely anecdotal, or based on findings from adults. The aim of the present study is to compare the use of ECT in adolescent and adult inpatients. METHODS: We retrospectively analyzed the files of all 36 adolescent (between the ages of 13 and 19) and 57 randomly selected adult inpatients (above the age of 20) treated with ECT in a university-affiliated mental heath center in Israel between 1991 and 1997. RESULTS: Sixty one percent of the adolescents improved by the end of treatment, and 53% were not hospitalized in the subsequent year. The respective percentages among adults were 83% and 49%. Whereas most adults were treated with ECT because of schizophrenic disorders, almost half of the adolescents received ECT for affective disorders. Significantly more adolescents were treated with ECT because of acute life-endangering conditions (catatonia or severe suicidal risk). No significant adverse effects were found in both groups. LIMITATIONS: Our study is based on a retrospective chart review. The adolescent and adult groups are different in psychiatric morbidity, diagnosis and outcome, have not been assessed in a blind manner, and we have not used standardized psychometric batteries for the evaluation of ECT-related memory disturbances. CONCLUSIONS: ECT may be an effective, well-tolerated and safe procedure in both adult and adolescent inpatients.     

A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth

Cyclic AMP (cAMP) promotes neurite outgrowth in a variety of neuronal cell lines through the activation of protein kinase A (PKA). We show here, using both Xenopus laevis embryonic neuronal culture and intact X. laevis embryos, that the nerve growth-promoting action of cAMP/PKA is mediated in part by the phosphorylation of synapsins at a single amino acid residue. Expression of a mutated form of synapsin that prevents phosphorylation at this site, or introduction of phospho-specific antibodies directed against this site, decreased basal and dibutyryl cAMP-stimulated neurite outgrowth. Expression of a mutation mimicking constitutive phosphorylation at this site increased neurite outgrowth, both under basal conditions and in the presence of a PKA inhibitor. These results provide a potential molecular approach for stimulating neuron regeneration, after injury and in neurodegenerative diseases.     

Sequential Measurements of Human Decidua-Associated Protein (hDP) 200 in the Uterine Fluid During the Menstrual Cycle

PROBLEM: To examine the relationship between the concentration of uterine fluid human decidua-associated protein (hDP) 200, identified as a monoclonal rheumatoid factor, and different phases of the menstrual cycle. METHODS: Sequential measurements of hDP 200 concentration in uterine fluid were performed in 11 normal ovulatory women, aged 22–36 years. The samples were collected in early proliferative phase, late proliferative phase, periovulatory period, early secretory phase, and late secretory phase. RESULTS: Consistent fluctuations of hDP 200 levels in uterine fluid were found throughout the menstrual cycle. High levels were found during early proliferative phase and periovulatory period related to significantly lower levels during late proliferative and early luteal phases. CONCLUSION: There is menstrual phase dependent variation in the uterine fluid levels of hDP 200.     

The PapG tip adhesin of P fimbriae protects Escherichia coli from neutrophil bactericidal activity.

Compared with Escherichia coli ORN103, a nonfimbriated K-12 strain, P-fimbriated E. coli ORN103/pPAP5 was found to interact poorly with human neutrophils and resist their bactericidal activity in vitro. PapG, the Gal alpha(1-->4)Gal binding moiety located at the distal end of the P fimbrial filament, appeared to be responsible for this effect because an isogenic PapG- mutant, E. coli ORN103/pPAP24, exhibited binding interactions with neutrophils that were similar to nonfimbriated E. coli ORN103. Although no direct evidence is available, the poor adherence mediated by PapG could be related to its electrostatic properties because the isolated PapG protein had a pI of 5.2, which indicated that in the physiological pH range it possessed a net negative charge. Antibodies against PapG overcame the protective effect of PapG and markedly enhanced the interactions of P-fimbriated E. coli with neutrophils resulting in bacterial killing. When a P-fimbriated clinical E. coli strain or its isogenic PapG- derivative was injected into the peritoneal cavities of mice, a similar number of neutrophils was recruited to the site of injection. After 2 h, the number of P-fimbriated E. coli organisms that survived the neutrophil influx in the mouse peritoneum was approximately four times more than the number of surviving PapG- bacteria. This result demonstrates that the PapG protein, which is strategically located at the distal region of the P-fibrillum structure, protects E. coli from the bactericidal action of neutrophils.     

Modeling pandemic preparedness scenarios: health economic implications of enhanced pandemic vaccine supply

Influenza pandemic planning is a complex, multifactorial process, which involves public health authorities, regulatory authorities, academia and industry. It is further complicated by the unpredictability of the time of emergence and severity of the next pandemic and the effectiveness of influenza epidemic interventions. The complexity and uncertainties surrounding pandemic preparedness have so far kept the various stakeholders from joining forces and tackling the problem from its roots. We developed a mathematical model, which shows the tangible consequences of conceptual plans by linking possible pandemic scenarios to health economic outcomes of possible intervention strategies. This model helps to structure the discussion on pandemic preparedness and facilitates the translation of pandemic planning concepts to concrete plans. The case study for which the model has been used shows the current level of global pandemic preparedness in an assumed pandemic scenario, the health economic implications of enhanced pandemic vaccine supply and the importance of cell culture-based influenza vaccine manufacturing technologies as a tool for pandemic control.