Arakawa Ward: Urban Growth and Modernization

Paper by Hiroshi Wagatsuma and George A. DeVo

Resolution and Resurgence of Schistosoma haematobium—induced Pathology After Community-based Chemotherapy in Ghana, as Detected by Ultrasound

Community-based treatment is recommended for endemic populations with urinary schistosomiasis; however, the optimal target group for treatment and retreatment interval have not been established. Using ultrasound, this study identified subpopulations whose lesions were most likely to respond to treatment and characterized resurgence of pathology. Ultrasound examination of 1202 infected patients was followed by chemotherapy with praziquantel. A sample of 698 patients was followed for 18 months after treatment. Nearly all types of bladder pathologies resolved after treatment, regardless of patient's age or intensity of initial infection. However, many patients' upper urinary tract pathologies (62.5%) did not resolve. During the 18-month follow-up period, reappearance of severe bladder pathologies was rare, and < 10% of persons had resurgence of mild bladder pathologies. For this population, re-treatment is not needed annually but might be cost effective if given several years later. Confirmation from other areas is required before general policies can be forme

Electronic stress tensor analysis of hydrogenated palladium clusters

We study the chemical bonds of small palladium clusters Pd_n (n=2-9) saturated by hydrogen atoms using electronic stress tensor. Our calculation includes bond orders which are recently proposed based on the stress tensor. It is shown that our bond orders can classify the different types of chemical bonds in those clusters. In particular, we discuss Pd-H bonds associated with the H atoms with high coordination numbers and the difference of H-H bonds in the different Pd clusters from viewpoint of the electronic stress tensor. The notion of "pseudo-spindle structure" is proposed as the region between two atoms where the largest eigenvalue of the electronic stress tensor is negative and corresponding eigenvectors forming a pattern which connects them.Comment: 22 pages, 13 figures, published online, Theoretical Chemistry Account

Significant effect of interfacial spin moments in ferromagnet-semiconductor heterojunctions on spin transport in a semiconductor

Using controlled ferromagnet (FM) -semiconductor (SC) interfaces in SC-based lateral spin-valve (LSV) devices, we experimentally study the effect of interfacial spin moments in FM-SC heterojunctions on spin transport in SC. First-principles calculations predict that the spin moment of FM-SC junctions can be artificially reduced by inserting 3d transition metal V, Cr, or Cu atomic layers between FM and SC. When all-epitaxial FM-SC Schottky-tunnel contacts with a 0.4-0.5-nm-thick V, Cr, or Cu interfacial layer are formed, we find that the spin signals in FM-SC LSV devices are significantly decreased at 8 K. When we increase the interfacial spin moment by inserting an ∼0.3-nm-thick Co layer between FM and SC, the spin signals at 8 K are significantly enhanced again. From these experiments, we conclude that the interfacial spin moments at FM-SC interfaces are one of the important factors to achieve large spin signals even in SC-based spintronic devices.T. Naito, R. Nishimura, M. Yamada, A. Masago, Y. Shiratsuchi, Y. Wagatsuma, K. Sawano, R. Nakatani, T. Oguchi, and K. Hamaya, Significant effect of interfacial spin moments in ferromagnet-semiconductor heterojunctions on spin transport in a semiconductor, Phys. Rev. B 105, 195308

The Combination of Gefitinib With ATRA and ATO Induces Myeloid Differentiation in Acute Promyelocytic Leukemia Resistant Cells

In approximately 15% of patients with acute myeloid leukemia (AML), total and phosphorylated EGFR proteins have been reported to be increased compared to healthy CD34+ samples. however, it is unclear if this subset of patients would benefit from EGFR signaling pharmacological inhibition. pre-clinical studies on AML cells provided evidence on the pro-differentiation benefits of EGFR inhibitors when combined with ATRA or ATO in vitro. despite the success of ATRA and ATO in the treatment of patients with acute promyelocytic leukemia (APL), therapy-associated resistance is observed in 5-10% of the cases, pointing to a clear need for new therapeutic strategies for those patients. In this context, the functional role of EGFR tyrosine-kinase inhibitors has never been evaluated in APL. here, we investigated the EGFR pathway in primary samples along with functional in vitro and in vivo studies using several APL models. we observed that total and phosphorylated EGFR (Tyr992) was expressed in 28% and 19% of blast cells from APL patients, respectively, but not in healthy CD34+ samples. Interestingly, the expression of the EGF was lower in APL plasma samples than in healthy controls. the EGFR ligand AREG was detected in 29% of APL patients at diagnosis, but not in control samples. In vitro, treatment with the EGFR inhibitor gefitinib (ZD1839) reduced cell proliferation and survival of NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. moreover, the combination of gefitinib with ATRA and ATO promoted myeloid cell differentiation in ATRA- and ATO-resistant APL cells. In vivo, the combination of gefitinib and ATRA prolonged survival compared to gefitinib- or vehicle-treated leukemic mice in a syngeneic transplantation model, while the gain in survival did not reach statistical difference compared to treatment with ATRA alone. our results suggest that gefitinib is a potential adjuvant agent that can mitigate ATRA and ATO resistance in APL cells. therefore, our data indicate that repurposing FDA-approved tyrosine-kinase inhibitors could provide new perspectives into combination therapy to overcome drug resistance in APL patients

Single-tube multiplex PCR using type-specific E6/E7 primers and capillary electrophoresis genotypes 21 human papillomaviruses in neoplasia

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) <it>E6/E7 </it>type-specific oncogenes are required for cervical carcinogenesis. Current PCR protocols for genotyping high-risk HPV in cervical screening are not standardized and usually use consensus primers targeting HPV capsid genes, which are often deleted in neoplasia. PCR fragments are detected using specialized equipment and extra steps, including probe hybridization or primer extension. In published papers, analytical sensitivity is typically compared with a different protocol on the same sample set.</p> <p>A single-tube multiplex PCR containing type-specific primers was developed to target the <it>E6/E7 </it>genes of two low-risk and 19 high-risk genotypes (HPV6, 11 and 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82) and the resulting short fragments were directly genotyped by high-resolution fluorescence capillary electrophoresis.</p> <p>Results</p> <p>The method was validated using long oligonucleotide templates, plasmid clones and 207 clinical samples of DNA from liquid-based cytology, fresh and formalin-fixed specimens and FTA Microcards^®imprinted with cut tumor surfaces, swabbed cervical cancers or ejected aspirates from nodal metastases of head and neck carcinomas. Between one and five long oligonucleotide targets per sample were detected without false calls. Each of the 21 genotypes was detected in the clinical sample set with up to five types simultaneously detected in individual specimens. All 101 significant cervical neoplasias (CIN 2 and above), except one adenocarcinoma, contained <it>E6/E7 </it>genes. The resulting genotype distribution accorded with the national pattern with HPV16 and 18 accounting for 69% of tumors. Rare HPV types 70 and 73 were present as the sole genotype in one carcinoma each. One cervical SCC contained DNA from HPV6 and 11 only. Six of twelve oropharyngeal cancer metastases and three neck metastases of unknown origin bore <it>E6/E7 </it>DNA; all but one were HPV16. One neck aspirate contained atypical squames with HPV26.</p> <p>Analytical sensitivity in dilute plasmid mixes was variable.</p> <p>Conclusions</p> <p>A primer-rich PCR readily detects the <it>E6/E7 </it>oncogenes of 21 HPV types in cellular and fixed tissue specimens. The method is straightforward, robust and reproducible and avoids post-PCR enzymatic and hybridization steps while detecting HPV with high clinical sensitivity in significant HPV-related neoplasia regardless of specimen type.</p

The Combination of Gefitinib With ATRA and ATO Induces Myeloid Differentiation in Acute Promyelocytic Leukemia Resistant Cells

In approximately 15% of patients with acute myeloid leukemia (AML), total and phosphorylated EGFR proteins have been reported to be increased compared to healthy CD34(+) samples. However, it is unclear if this subset of patients would benefit from EGFR signaling pharmacological inhibition. Pre-clinical studies on AML cells provided evidence on the pro-differentiation benefits of EGFR inhibitors when combined with ATRA or ATO in vitro. Despite the success of ATRA and ATO in the treatment of patients with acute promyelocytic leukemia (APL), therapy-associated resistance is observed in 5-10% of the cases, pointing to a clear need for new therapeutic strategies for those patients. In this context, the functional role of EGFR tyrosine-kinase inhibitors has never been evaluated in APL. Here, we investigated the EGFR pathway in primary samples along with functional in vitro and in vivo studies using several APL models. We observed that total and phosphorylated EGFR (Tyr992) was expressed in 28% and 19% of blast cells from APL patients, respectively, but not in healthy CD34(+) samples. Interestingly, the expression of the EGF was lower in APL plasma samples than in healthy controls. The EGFR ligand AREG was detected in 29% of APL patients at diagnosis, but not in control samples. In vitro, treatment with the EGFR inhibitor gefitinib (ZD1839) reduced cell proliferation and survival of NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. Moreover, the combination of gefitinib with ATRA and ATO promoted myeloid cell differentiation in ATRA- and ATO-resistant APL cells. In vivo, the combination of gefitinib and ATRA prolonged survival compared to gefitinib- or vehicle-treated leukemic mice in a syngeneic transplantation model, while the gain in survival did not reach statistical difference compared to treatment with ATRA alone. Our results suggest that gefitinib is a potential adjuvant agent that can mitigate ATRA and ATO resistance in APL cells. Therefore, our data indicate that repurposing FDA-approved tyrosine-kinase inhibitors could provide new perspectives into combination therapy to overcome drug resistance in APL patients

Influence of INF-gamma gene polymorphism in HTLV-1 proviral load

Financial Support FAPESP, CNPq, CTC/FUNDHERP and INCTC