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PubMed2004

Communications. Zap it to 'em.

Communication is something all trusts do, whether they know it or not. Reputation management involves proactively controlling how your organisation is, and will be, perceived. Patient choice and a move away from a waiting-list focus is changing the messages trusts need to get across.

Communication↗
PubMed2005

Zapping cancer cells.

Explore the source record for details and available documents.

Academic Medical Centers↗
PubMed2005

Zeta-chain associated protein 70 and CD38 combined predict the time to first treatment in patients with chronic lymphocytic leukemia.

BACKGROUND: Zeta-chain associated protein (ZAP)-70 has been proposed as a surrogate marker for immunoglobulin heavy-chain variable region (IgVH) mutation in chronic lymphocytic leukemia (CLL), but it is still not clear whether it is an independent prognostic factor. METHODS: The authors evaluated ZAP-70 expression by flow cytometry in 201 untreated patients and correlated ZAP-70 levels with CD38 expression, genetic abnormalities detected by fluorescence in situ hybridization (FISH), and the time from diagnosis to first treatment. RESULTS: Fifty-seven patients (28%) were positive for ZAP-70 (> or = 20%). Positive ZAP-70 status was associated with advanced disease stage, atypical morphology, CD38-positive status, trisomy 12, del(6q), or no detectable abnormalities; negative ZAP-70 status was correlated with del(13q) as a sole abnormality. The treatment-free interval (TFI) was 17.7 months for ZAP-70-positive patients and 44.6 months for ZAP-70-negative patients (P < 0.001). Multivariate analysis in 117 patients identified advanced stage, CD38 > or = 7%, and the absence of del(13q) as a sole abnormality as independent factors for short TFI. Excluding FISH, ZAP-70 status acquired independent prognostic value along with CD38 status. The authors proposed a risk model that combines ZAP-70 and CD38 to identify patients who are likely to progress. When both markers were positive, the TFI was 12 months; when both were negative, the median TFI was 54 months; a median TFI of 26 months was observed in patients who had discordant results (P < 0.00001). CONCLUSIONS: The current findings suggested that both ZAP-70 and CD38 should be tested prospectively in all patients with early-stage CLL.

ADP-ribosyl Cyclase 1↗
PubMed2000

Phosphodiesterase type 5 inhibition enhances vasorelaxation caused by nitroprusside in guinea pig intact heart and isolated aorta.

Increased vascular smooth muscle cyclic guanine monophosphate (cGMP) results in vascular relaxation. The vascular effects of stimulating cGMP production with 10(-8)-10(-4) M nitroprusside (NP) and inhibiting cGMP hydrolysis with 10(-8)-10(-4) M zaprinast (ZAP), a selective type V inhibitor of cGMP phosphodiesterase (PDE), were assessed in isolated guinea pig hearts and aortic rings. Coronary flow (CF) IC50 values for NP and ZAP, respectively, were 0.8+/-0.1 x 10(-6) M and 3.6+/-0.1 x 10(-6) M; for coronary sinus pO2 IC50 values were 0.7+/-0.1 x 10(-6) M and 3.7+/-0.1 x 10(-6) M. CF increased by 13+/-2% with 10(-6) NP, and by 12+/-2% with 10(-5) M ZAP; percentage O2 extraction (%O2E) decreased by 17+/-3% with NP and 28+/-4% with ZAP. Together, 10(-6) M NP + 10(-5) M ZAP augmented the increased in CF to 23+/-3% of control, and the decrease in percentage O2 extraction (%O2E) to 40+/-4% of control. Other cardiac effects of NP and ZAP were minimal. In norepinephrine preconstricted aortic rings, the IC50 for relaxation was elicited at 0.4+/-0.1 x 10(-6) M NP and 6.1+/-0.1 x 10(-6) M ZAP. NP given with ZAP gave a logarithmic relation so that IC50 [NP] = -(57 log10 [ZAP]) + 416; R2 = 0.95. NP, 3 x 10(-7) M; ZAP, 3 x 10(-6) M; and NP + ZAP combined increased aortic tissue cGMP by eight-, nine-, and 15-fold, respectively. Inhibiting cGMP hydrolysis may be an effective approach to augment vasorelaxation elicited by cGMP synthesis in the heart.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Zeta-chain-associated protein-70 molecule is essential for the proliferation and the final maturation of dendritic epidermal T cells.

Adult murine epidermis contains members of the epithelial gammadelta T-cell family called dendritic epidermal T cells (DETCs). Their development and maturation have been the subjects of investigations, but the details are still unclear. T-cell receptor (TCR) zeta-chain-associated protein-70 (ZAP-70), one of the protein tyrosine kinases required for TCR signaling, plays a pivotal role in the development of alphabeta T cells. In mice lacking ZAP-70, thymic development of alphabeta T cells was completely arrested at the immature CD4(+)CD8(+) TCR(low) stage. Here, we examined whether or not the development and maturation of DETCs were altered in ZAP-70-deficient mice. Immunohistochemical analyses of epidermal sheets revealed that the number of DETCs was reduced and their characteristic dendrites were lost or markedly shortened in ZAP-70(-/-) mice. In flow cytometric analyses, the expression levels of gammadelta TCR and Thy-1.2 on the ZAP-70(-/-) DETCs were lower than those on ZAP-70(+/-) DETCs. The expression of a very early activation antigen, CD69, was not detected on ZAP-70(-/-) DETCs, whereas CD69 was expressed on ZAP-70(+/-) DETCs. Furthermore, ZAP-70(-/-) DETCs showed markedly reduced proliferation and no IL-2 gene expression in response to anti-CD3epsilon or concanavalin A stimulation. These results suggest that ZAP-70 is essential for TCR signaling which induces the proliferation and the final maturation of DETCs in the epidermis.

Animals↗
PubMed1992

Screening of a Babesia bigemina cDNA library with monoclonal antibodies directed to surface antigens.

A Babesia bigemina cDNA library prepared in lambda ZAP bacteriophage vector was immunoscreened to detect clones expressing surface-exposed epitopes of B. bigemina. A nonradioactive indirect plaque-lift immunoassay was used to detect the positive clones. The primary antibody consisted of a pooled sample of six monoclonal antibodies (mAb) specific for B. bigemina that recognizes various parasite surface antigens of different molecular mass. Screening of approximately 300,000 plaque-forming units from the lambda ZAP cDNA expression library resulted in the identification of five positive clones. The five recombinant clones were immunoscreened individually with each of the six mAb. All five independently obtained clones consisted of lambda ZAP recombinants expressing B. bigemina components recognized by mAb C2F3G3 and B1B3C4. Restriction enzyme digests of rescued recombinant phagemids showed that only four clones contained B. bigemina cDNA. One clone (lambda ZAP Bbi1) contained an insert of approximately 0.6 kBp whereas the other three clones (lambda ZAP Bbi2, lambda ZAP Bbi3, and lambda ZAP Bbi5) carried a cDNA insert of approximately 1.7 kBp. Immunoblotting of protein extracts from recombinants lambda ZAP Bbi2, lambda ZAP Bbi3, and lambda ZAP Bbi5 with mAb C2F3G3 and B1B3C4 demonstrated the expression of a recombinant B. bigemina polypeptide of 55 kDa in E. coli.

Animals↗