Medical phycology 2017 Todd, John R; Matsumoto, Tadahiko; Ueno, Ryohei ...
Medical mycology (Oxford),
2018-Apr-01, 2018-04-01, 20180401, Letnik:
56, Številka:
suppl_1
Journal Article
Recenzirano
In 2014, ISHAM formed a new working group: "Medical Phycology: Protothecosis and Chlorellosis." The purpose of this working group is to help facilitate collaboration and communication among people ...interested in the pathogenic algae, to share ideas and work together. Here we present reports on recent work we have done in five areas. 1. The history of medical phycology as a branch of science. 2. Aspects of the genetics of Prototheca. 3. Aspects of the proteins of Prototheca. 4. Human infections caused by Prototheca. 5. Dairy cow mastitis caused by Prototheca.
A Drosophila Su Gagliani, Ellen K; Gutzwiller, Lisa M; Kuang, Yi ...
PLoS genetics,
08/2022, Letnik:
18, Številka:
8
Journal Article
Recenzirano
Notch signaling is a conserved pathway that converts extracellular receptor-ligand interactions into changes in gene expression via a single transcription factor (CBF1/RBPJ in mammals; Su(H) in ...Drosophila). In humans, RBPJ variants have been linked to Adams-Oliver syndrome (AOS), a rare autosomal dominant disorder characterized by scalp, cranium, and limb defects. Here, we found that a previously described Drosophila Su(H) allele encodes a missense mutation that alters an analogous residue found in an AOS-associated RBPJ variant. Importantly, genetic studies support a model that heterozygous Drosophila with the AOS-like Su(H) allele behave in an opposing manner to heterozygous flies with a Su(H) null allele, due to a dominant activity of sequestering either the Notch co-activator or the antagonistic Hairless co-repressor. Consistent with this model, AOS-like Su(H) and Rbpj variants have decreased DNA binding activity compared to wild type proteins, but these variants do not significantly alter protein binding to the Notch co-activator or the fly and mammalian co-repressors, respectively. Taken together, these data suggest a cofactor sequestration mechanism underlies AOS phenotypes associated with RBPJ variants, whereby the AOS-associated RBPJ allele encodes a protein with compromised DNA binding activity that retains cofactor binding, resulting in Notch target gene dysregulation.
Purpose:
Peripherally inserted central venous catheters are some of the most useful devices for vascular access used globally. Peripherally inserted central venous catheters have a low rate of fatal ...mechanical complications when compared to non-tunnel central venous catheters. However, as peripherally inserted central venous catheter access requires a smaller vein, there is a high risk of thrombosis. The axillary vein (confluence of the basilic and brachial veins) can serve as an access for cannulation. Moreover, as this vein is larger than the basilic or brachial vein, it might be a superior option for preventing thrombosis. The risk of catheter-related bloodstream infection should be considered when the puncture site is at the axillary fossa. The aim of this study was to present our new protocol involving peripherally inserted central venous catheters (non-tunneled/tunneled) and a tunneling technique and assess its feasibility and safety for improving cannulation and preventing thrombosis and infection.
Methods:
The study included 20 patients. The axillary vein in the upper arm was used for peripherally inserted central venous catheters in patients with a small-diameter basilic vein (<3 mm). When the puncture site was in the axillary fossa, a subcutaneous tunnel of about 3 cm was constructed easily using a peripheral venous catheter.
Results:
The observed catheter duration was 645 days (median ± standard deviation, 26 ± 22.22 days). Catheterization was successful in all cases, however, two accidental dislodgements were identified. No fatal or serious complications were observed after catheterization.
Conclusion:
Our new protocol for axillary peripherally inserted central venous catheters/tunneled axillary peripherally inserted central venous catheters use for a small-diameter basilic vein is safe and feasible.
Ciclopirox olamine (CPX), an off-patent fungicide, has recently been identified as a novel anticancer agent. However, the molecular mechanism underlying its anticancer action remains to be ...elucidated. Here we show that CPX inhibits cell proliferation in part by downregulating the protein level of Cdc25A in tumor cells. Our studies revealed that CPX did not significantly reduce Cdc25A mRNA level or Cdc25A protein synthesis, but remarkably promoted Cdc25A protein degradation. This resulted in inhibition of G
-cyclin dependent kinases (CDKs), as evidenced by increased inhibitory phosphorylation of G
-CDKs. Since Cdc25A degradation is tightly related to its phosphorylation status, we further examined whether CPX alters Cdc25A phosphorylation. The results showed that CPX treatment increased the phosphorylation of Cdc25A (S76 and S82), but only Cdc25A-S82A mutant was resistant to CPX-induced degradation. Furthermore, ectopic expression of Cdc25A-S82A partially conferred resistance to CPX inhibition of cell proliferation. Therefore, our findings indicate that CPX inhibits cell proliferation at least in part by promoting Cdc25A degradation.
Cryptotanshinone (CPT), a natural compound isolated from the plant Salvia miltiorrhiza Bunge, is a potential anticancer agent. However, the underlying mechanism is not well understood. Here, we show ...that CPT induced caspase-independent cell death in human tumor cells (Rh30, DU145, and MCF-7). Besides downregulating antiapoptotic protein expression of survivin and Mcl-1, CPT increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK), and inhibited phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2). Inhibition of p38 with SB202190 or JNK with SP600125 attenuated CPT-induced cell death. Similarly, silencing p38 or c-Jun also in part prevented CPT-induced cell death. In contrast, expression of constitutively active mitogen-activated protein kinase kinase 1 (MKK1) conferred resistance to CPT inhibition of Erk1/2 phosphorylation and induction of cell death. Furthermore, we found that all of these were attributed to CPT induction of reactive oxygen species (ROS). This is evidenced by the findings that CPT induced ROS in a concentration- and time-dependent manner; CPT induction of ROS was inhibited by N-acetyl-L-cysteine (NAC), a ROS scavenger; and NAC attenuated CPT activation of p38/JNK, inhibition of Erk1/2, and induction of cell death. The results suggested that CPT induction of ROS activates p38/JNK and inhibits Erk1/2, leading to caspase-independent cell death in tumor cells.
Background Translation initiation factor eIF4E unwinds long 5′-untranslated regions of certain tightly regulated mRNAs and, thereby, facilitates their translation into proteins. eIF4E has been shown ...to be overexpressed in a majority of solid tumors, including head and neck cancers. To exploit this dysregulation, a long 5′-untranslated region was spliced upstream of a thymidine kinase (Tk) gene to enhance translation of this “suicide” gene within cells overexpressing eIF4E. We investigated the efficacy of therapy with an adenovirus incorporating this novel suicide gene (Ad-HSV-UTk) following cytoreductive tumor surgery in improving disease-free and overall survival in a mouse soft-tissue metastasis model for head and neck squamous cell carcinoma. Materials and methods SCC-7 (orally-derived mouse SCCa) cells were treated with Ad-HSV-Tk, Ad-HSV-UTk, Ad-null, or saline and characterized for eIF4E and Tk levels by Western blot analysis. Cytotoxicities for cells treated with Ad-HSV-Tk, Ad-HSV-UTk, or Ad-null were quantified by MTS assay. Mice bearing SCC-7-induced tumors received cytoreduction followed by Ad-HSV-UTk + ganciclovir (GCV) or control treatment and were followed for disease-free and overall survival. Results SCC-7 cells showed uniformly high levels of eIF4E but elevated Tk for Ad-HSV-Tk- and Ad-HSV-UTk-treated cells over Ad-null-treated cells. Cytotoxicities for Ad-HSV-Tk- and Ad-HSV-UTk-treated cells were, correspondingly, observed to be 100-fold more sensitive than Ad-null-treated cells to GCV treatment. Cytoreduced mice receiving Ad-HSV-UTk + GCV treatment showed significantly longer disease-free survival ( P = 0.0045) than control arm mice. Conclusions Ad-HSV-UTk suicide gene therapy prolonged disease-free survival in a mouse minimal residual soft-tissue head and neck squamous cell carcinoma metastasis model.
Background:
Totally implantable venous access devices are valuable tools for total parenteral nutrition, chemotherapy, and long-term intravenous therapy. However, late catheter fracture is a ...well-known complication of totally implantable venous access device, particularly in Groshong silicone catheter. Recently, a specific type of totally implantable venous access device made with Groshong silicone has been introduced to facilitate power injection of contrast medium for enhanced computed tomography.
Cases description:
We reported three cases of catheter fracture in power-injectable Groshong silicone totally implantable venous access device. From May 2012 to August 2014, 66 patients underwent power-injectable Groshong silicone totally implantable venous access device implantation at our institution, with a median follow-up of 20.1 (range 0.2–58.1) months. The catheters in all patients were inserted into the internal jugular vein under ultrasound guidance and were connected to the port implanted in the upper chest through the subcutaneous tunnel. Chemotherapy was administered using these routes. Fractures of all three cases specifically showed a torn catheter section: smooth surface on one side, and a rough edge on the other side of the catheter, suggesting that long-term repeated stretch force may be related with the mechanism of fracture.
Conclusion:
Totally implantable venous access devices with Groshong silicone catheters, if inserted via the internal jugular vein, have a potential risk for late catheter fracture.
ETO (MTG8) was first described due to its involvement in the (8;21) translocation frequently observed in acute myeloid leukemias. In the t(8;21) the AML1 gene on chromosome 21 is fused to ETO on ...chromosome 8. The resultant hybrid protein is comprised of the DNA binding domain of AML-1 and the majority of ETO. This study examines the subnuclear distributions of ETO, AML-1B and AML-1/ETO proteins fused to green fluorescence protein in living cells using fluorescence microscopy. Further, we identified a 40 amino acid portion of ETO (amino acids 241-280) that was sufficient to cause nuclear import of green fluorescent protein. Mutational analysis demonstrated that lysine 265 and/or arginine 266 were required for nuclear import of ETO, but that the surrounding basic residues were not critical. ETO interacted with the nuclear import proteins importin-alpha and beta in vitro, and mutations in ETO that abolish nuclear localization also abolished the in vitro interaction with importin-alpha and beta. These data suggest that ETO enters the nucleus via an importin-mediated pathway. Additionally, ETO and AML-1/ETO co-localized to punctate nuclear bodies distinct from those containing promyelocytic leukemia protein. Nuclear body formation was dependent upon a region of ETO N-terminal to the nuclear localization signal. Thus, ETO and AML-1/ETO reside in potentially novel subnuclear compartments.
We present a Prototheca wickerhamii wound infection case that failed treatment with ketoconazole but was cured with amphotericin-B plus tetracycline. The patient was immunocompetent but had had local ...steroid injections. We reviewed another 159 cases from the literature. Prototheca has infected many areas of the human body, but most often skin, olecranon bursa, or wounds. Prior treatment with steroids and immune deficiencies are contributing factors. Itraconazole and fluconazole are reasonable initial treatments for patients with mild infections. For serious infections, or for infections that have failed azole treatment, amphotericin-B is the treatment of choice.
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