Insulin receptors on leukemia and lymphoma cells

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I- labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.     

Preferential occupancy of Eu3+ and energy transfer in Eu3+ doped Sr2V2O7, Sr9Gd(VO4)7 and Sr2V2O7/Sr9Gd(VO4)7 phosphors

The vanadate-based phosphors Sr₂V₂O₇:Eu³⁺ (SV:Eu³⁺), Sr₉Gd(VO₄)₇:Eu³⁺ (SGV:Eu³⁺) and Sr₉Gd(VO₄)₇/Sr₂V₂O₇:Eu³⁺ (SGV/SV:Eu³⁺) were obtained by solid-state reaction. The bond-energy method was used to investigate the site occupancy preference of Eu³⁺ based on the bond valence model. By comparing the change of bond energy when the Eu³⁺ ions are incorporated into the different Sr, V or Gd sites, we observed that Eu³⁺ doped in SV, SGV or SV/SGV would preferentially occupy the smaller energy variation sites, i.e., Sr4, Gd and Gd sites, respectively. The crystal structures of SGV and SV, the photoluminescence properties of SGV:Eu³⁺, SV, SGV/SV and SGV/SV:Eu, as well as their possible energy transfer mechanisms are proposed. Interesting tunable colours (including warm-white emission) of SGV/SV:Eu³⁺ can be obtained through changing the concentration of Eu³⁺ or changing the relative quantities of SGV to SV by increasing the calcination temperature. Its excitation bands consist of two types of O²⁻ → V⁵⁺ charge transfer (CT) bands with the peaks at about 325 and 350 nm respectively, as well as f–f transitions of Eu³⁺. The obtained warm-white emission consists of a broad photoluminescence band centred at about 530 nm, which originates from the O²⁻ → V⁵⁺ CT of SV, and a sharp characteristic spectrum (⁵D₀–⁷F₂) at about 615 and 621 nm.

The vanadate-based phosphors Sr₂V₂O₇:Eu³⁺ (SV:Eu³⁺), Sr₉Gd(VO₄)₇:Eu³⁺ (SGV:Eu³⁺) and Sr₉Gd(VO₄)₇/Sr₂V₂O₇:Eu³⁺ (SGV/SV:Eu³⁺) were obtained by solid-state reaction.     

Erythrophagocytosis of Lead-Exposed Erythrocytes by Renal Tubular Cells: Possible Role in Lead-Induced Nephrotoxicity

Background: Nephrotoxicity associated with lead poisoning has been frequently reported in epidemiological studies, but the underlying mechanisms have not been fully described.Objectives: We examined the role of erythrocytes, one of the major lead reservoirs, in lead-associated nephrotoxicity.Methods and results: Co-incubation of lead-exposed human erythrocytes with HK-2 human renal proximal tubular cells resulted in renal tubular cytotoxicity, suggesting a role of erythrocytes in lead-induced nephrotoxicity. Morphological and flow cytometric analyses revealed that HK-2 cells actively phagocytized lead-exposed erythrocytes, which was associated with phosphatidylserine (PS) externalization on the erythrocyte membrane and generation of PS-bearing microvesicles. Increased oxidative stress and up-regulation of nephrotoxic biomarkers, such as NGAL, were observed in HK-2 cells undergoing erythrophagocytosis. Moreover, TGF-β, a marker of fibrosis, was also significantly up-regulated. We examined the significance of erythrophagocytosis in lead-induced nephrotoxicity in rats exposed to lead via drinking water for 12 weeks. We observed iron deposition and generation of oxidative stress in renal tissues of lead-exposed rats, as well as the histopathological alterations such as tubulointerstitial lesions, fibrosis, and up-regulation of KIM-1, NGAL, and TGF-β.Conclusions: Our data strongly suggest that erythrophagocytosis and subsequent iron deposition in renal tubular cells could significantly enhance nephrotoxicity following lead exposure, providing insight on lead-associated kidney damages.Citation: Kwon SY, Bae ON, Noh JY, Kim K, Kang S, Shin YJ, Lim KM, Chung JH. 2015. Erythrophagocytosis of lead-exposed erythrocytes by renal tubular cells: possible role in lead-induced nephrotoxicity. Environ Health Perspect 123:120–127; http://dx.doi.org/10.1289/ehp.1408094     

A Study of Mental Health Literacy Among North Korean Refugees in South Korea

Objectives:

This study aimed to investigate North Korean refugees’ knowledge of mental illnesses and treatments and analyze the factors affecting this knowledge.

Methods:

Subjects were selected via a snowball sampling method, and the survey outcomes of 152 North Korean refugee participants were analyzed. The factors affecting knowledge of mental illnesses were analyzed via a regression analysis by constructing a multivariate model with mental illness knowledge score as the dependent variable.

Results:

The North Korean refugees’ mental illness scores ranged from 3 to 24 points, with an average score of 13.0. Regarding the factors that influence mental illness knowledge, the subjects with South Korean spouses and those who had spent more time in South Korea had higher knowledge scores. Furthermore, the subjects who considered the mental health of North Korean refugees to be a serious issue revealed lower knowledge scores than those who did not believe it was a serious issue. The subjects who visit psychiatric clinics showed higher knowledge scores than those who do not. The South Korean subjects who had at least a college education exhibited higher scores than did those without advanced education. The subjects who are satisfied with life in South Korea manifested a higher mental illness knowledge score than those who are not.

Conclusions:

This study is significant as being the first study to ever measure and evaluate the level of North Korean refugees’ knowledge of mental illnesses. In addition, the evaluations of North Korean refugees’ mental illness knowledge and influencing factors while residing in South Korea created basic data that formed the foundation of an effort to enhance mental health literacy and provide proper mental health services. The results of this study can be utilized to solve mental health problems that might frequently occur during the unification process of North and South Korea in the future.     

Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

AIM: rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer. However, a sustained and high protein delivery is required to achieve the desired therapeutic effects. We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS: rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines. To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin, Western blotting and ELISA were performed. The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor, etoposide, were evaluated in a mouse liver tumor model. RESULTS: Topoisomerase inhibitors, including camptothecin and etoposide, were found to increase the endostatin expression level in vitro. The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active. In animal experiments, the combined therapy of topoisomerase inhibitor, etoposide with the rAAV-endostatin vector had the best tumor-suppressive effect and tumor foci were barely observed in livers of the treated mice. Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice. Finally, the mice treated with rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION: rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.     

Anomalous subaortic position of the brachiocephalic vein (innominate vein): an echocardiographic study

In 24 (0.98%) of 2457 patients with congenital heart disease the brachiocephalic vein was in an anomalous position below the aortic arch. This is a much higher proportion of such cases than reported so far. This high frequency may arise from differences in the study population and the method of diagnosis. This venous anomaly was more common in patients with tetralogy of Fallot or ventricular septal defect with pulmonary atresia. Patients with the venous anomaly were more likely to have a right aortic arch. The anomalous course of the brachiocephalic vein from the neck to the junction of the superior vena cava was shown by cross sectional echocardiography. In doubtful cases, Doppler study usually clarified the anatomical arrangement.     

Composite neuroendocrine and adenocarcinoma of the common bile duct associated with Clonorchis sinensis: a case report

The biliary tract has neuroendocrine cells of endoderm origin similar to the gastrointestinal tract, however neuroendocrine tumors of the biliary tract are rare. We report a composite glandular-endocrine cell carcinoma of the common bile duct in a 64-year-old Korean man which was associated with Clonorchis sinensis. The patient complained of right upper quadrant abdominal pain. Several parasites of Clonorchis sinensis were removed during the percutaneous transbiliary drainage. Endoscopic retrograde cholangiopancreatography revealed a polypoid mass (3 x 3 cm) with central ulceration in the common bile duct. Pancreaticoduodenectomy was performed. Microscopic examination of the tumor revealed a composite small cell neuroendocrine carcinoma and adenocarcinoma. The small cell carcinoma component showed positive reaction to chromogranin A and neuron-specific enolase and it was located mainly in the deeper portion of the mass. The well-differentiated adenocarcinoma component showed a positive reaction to carcinoembryonic antigen and it was situated in the superficial portion of the mass. Exclusively, the small cell component metastasized to the lymph node. It is suggested that this tumor could arise from a multipotential stem cell and showed neuroendocrine and glandular differentiation and that Clonorchis sinensis could be a predisposing factor, as in cholangiocarcinoma.     

Effects of APOE ɛ4 on brain amyloid,lacunar infarcts,and white matter lesions: a study among patients with subcortical vascular cognitive impairment

The relationship between the apolipoprotein E ?4 allele (APOE4) and factors associated with vascular cognitive impairment (VCI) is unclear. We aimed to examine the effects of APOE4 on brain amyloid beta using Pittsburg compound B (PiB) and subcortical cerebrovascular disease, as assessed by lacunes and white matter hyperintensities (WMH) in subcortical VCI (SVCI) patients. We recruited 230 subjects with normal cognition, 111 subjects with cognitive impairment due to clinically defined Alzheimer’s disease (ADCI), and 134 subjects with clinically defined SVCI. A PiB retention ratio greater than 1.5 was considered to be PiB positive. Logistic regression analysis was performed to investigate whether APOE4 increased the risk for each cognitive impairment group. Multiple linear regression analysis was performed to investigate whether APOE4 was associated with brain amyloid beta, lacunes, and WMH. APOE4 did not increase the risk of PiB(−) SVCI (odds ratio [OR], 1.50; 95% confidence interval [CI], 0.79–2.84), whereas APOE4 increased the risk of PiB(+) SVCI (OR, 4.52; 95% CI, 1.70–11.97) and PiB(+) ADCI (odds ratio, 4.84; 95% CI, 2.54–7.91). In SVCI patients, APOE4 was positively associated with PiB retention ratio, whereas APOE4 was not associated with the number of lacunes or with WMH volume. Our results suggest that amyloid beta burden can occur in patients with and without subcortical cerebrovascular disease, and that it is associated with APOE4. However APOE4 might be independent of subcortical cerebrovascular disease.