Developmental exposure to pentachlorophenol affects the expression of thyroid hormone receptor β1 and synapsin I in brain, resulting in thyroid function vulnerability in rats

Pentachlorophenol (PCP), a component of biocides and a contaminant in diverse tissue samples from humans from various geographic areas, disrupts regulatory effects of thyroid hormones. Here we examined the effects of developmental exposure of rats to PCP on various aspects of brain development, male reproductive function, and adrenal function, all of which are under thyroid hormones regulation. PCP was administered to dams and their offspring via drinking water (6.6 mg l⁻¹) during gestation and lactation. Tissue samples were obtained from dams, 3-week-old weanling pups, and 12-week-old pups. Gene expressions of thyroid hormone receptor β1 and synapsin I, factors that promote brain growth, was increased in the cerebral cortex of PCP-treated weanling females, whereas plasma concentrations of total thyroxine were decreased in dams and weanling pups, and plasma thyroid-stimulating hormone concentrations were higher in PCP-treated weanling males. PCP caused a decrease in plasma corticosterone concentrations in 12-week-old female rats, but not in male rats or weanling females. PCP-treated male pups had significantly increased testis weight at 12 week of age. No overt signs of toxicity were noted throughout this study. Our results show that PCP exposure during development causes thyroid function vulnerability, testicular hypertrophy in adults, and aberrations of brain gene expression.     

Nestin-positive cells in adult pancreas express amylase and endocrine precursor Cells

The neural precursor cell-specific marker nestin is expressed in fetal and adult pancreas, but its role is not fully understood. Using nestin-enhanced green fluorescent protein (EGFP) transgenic mice and fluorescence activated cell sorter, we characterized nestin-positive cells in adult mice pancreas. EGFP mRNA- and protein-positive cells expressed amylase, a pancreatic exocrine marker. Interestingly, EGFP mRNA-negative and protein-positive cells expressed insulin, glucagon, somatostatin and pancreatic polypeptide, pancreatic endocrine markers. These findings demonstrate that nestin-positive cells comprise a portion of pancreatic exocrine cells and suggest that they can be differentiated into pancreatic endocrine cells.     

High-dose 131I-metaiodobenzylguanidine therapy in patients with high-risk neuroblastoma in Japan

Annals of Nuclear Medicine - The aim of the study was to investigate the outcomes and prognostic factors of high-dose 131I-metaiodobenzylguanidine (131I-MIBG) therapy in patients with refractory or...     

A combination of fludarabine,half-dose cyclophosphamide,and anti-thymocyte globulin is an effective conditioning regimen before allogeneic stem cell transplantation for aplastic anemia

Conditioning regimens consisting of reduced-dose cyclophosphamide (CY) and fludarabine (FDR) have been investigated for use in allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia to reduce the toxicities associated with CY. However, the ideal dose of CY has not been identified. In addition, little information is available regarding donor cell chimerism after allo-HSCT with these regimens. Therefore, we retrospectively analyzed 13 patients who underwent allo-HSCT with half-dose CY (100 mg/kg in total), FDR, and anti-thymocyte globulin at total doses of 2.5–10 mg/kg at our center. All the patients except one, who died due to encephalopathy on day 20, achieved neutrophil engraftment a median of 18.5 days after HSCT with complete donor-type chimerism. Two patients who received a graft from an HLA-matched donor subsequently developed mixed chimerism (MC) associated with transfusion-dependent cytopenia. One became transfusion-independent after donor lymphocyte infusion, but continues to exhibit MC. The other regained complete donor-type chimerism after the cessation of cyclosporine, but remains transfusion-dependent. These findings suggest that a conditioning regimen with half-dose CY and FDR is effective for achieving neutrophil engraftment and complete donor-type chimerism. However, subsequent MC may be observed, especially after HLA-matched HSCT.     

Cardio-ankle vascular index (CAVI) correlates with aortic stiffness in the thoracic aorta using ECG-gated multi-detector row computed tomography

Background

The cardio-ankle vascular index (CAVI) is an arterial stiffness index based on the stiffness parameter β, which is essentially independent of blood pressure. The objective of this study was to determine whether CAVI correlates with the regional stiffness parameter β and pulse wave velocity (PWV) in the thoracic aorta calculated from ECG-gated multi-detector row computed tomography (MDCT).

Methods and results

Forty-nine patients who underwent coronary MDCT for suspicious coronary artery disease were recruited. The largest and smallest vessel luminal cross-sectional areas of the thoracic aorta were measured from MDCT images to calculate PWV and stiffness parameter β of the ascending and descending aorta. CAVI was also measured by VaSera VS-1000.In univariate analysis, CAVI significantly correlated with regional stiffness parameter β and PWV, which was influenced by the inevitable part of the aging process in the ascending (r = 0.485, P < 0.001; r = 0.483, P < 0.001) and descending aortas (r = 0.304, P = 0.034; r = 0.327, P = 0.022), respectively. The regional stiffness parameter β did not correlate with systolic blood pressure (SBP), although the PWV correlated with SBP. In multivariate analysis, CAVI independently correlated with the stiffness parameter β, but not with the PWV.

Conclusion

These data suggest that CAVI, which correlated with stiffness parameter β in the thoracic aorta, has a potential role in evaluating integrated arterial stiffness including that of the central aorta.     

Evaluation of multiwave pulse total-hemoglobinometer during general anesthesia

The purpose of this prospective study was to evaluate the accuracy and trending ability of a four-wavelength pulse-total hemoglobinometer that continuously and noninvasively measures hemoglobin in surgical patients. With IRB approval and informed consent, spectrophotometric hemoglobin (SpHb) was measured with a pulse-total hemoglobinometer manufactured by Nihon Kohden Corp (Tokyo, Japan) and compared to the CO-oximeter equipped with blood gas analyzer. Two hundred twenty-five samples from 56 subjects underwent analysis. Bland–Altman analysis revealed that the bias ± precision of the current technology was 0.0 ± 1.4 g/dl and ?0.2 ± 1.3 g/dl for total samples and samples with 8 < Hb < 11 g/dl, respectively. The percentages of samples with intermediate risk of therapeutic error in error grid analysis and the concordance rate of 4-quadrant trending assay was 17 % and 77 %, respectively. The Cohen kappa statistic for Hb < 10 g/dl was 0.38, suggesting that the agreement between SpHb and CO-oximeter-derived Hb was fair. Collectively, wide limits of agreement, especially at the critical level of hemoglobin, and less than moderate agreement against CO-oximeter-derived hemoglobin preclude the use of the pulse-total hemoglobinometer as a decision-making tool for transfusion.     

Quantitative estimation of DNA damage by photon irradiation based on the microdosimetric-kinetic model

The microdosimetric-kinetic (MK) model is one of the models that can describe the fraction of cells surviving after exposure to ionizing radiation. In the MK model, there are specific parameters, k and y_D, where k is an inherent parameter to represent the number of potentially lethal lesions (PLLs) and y_D indicates the dose-mean lineal energy in keV/μm. Assuming the PLLs to be DNA double-strand breaks (DSBs), the rate equations are derived for evaluating the DSB number in the cell nucleus. In this study, we estimated the ratio of DSBs for two types of photon irradiation (6 MV and 200 kVp X-rays) in Chinese hamster ovary (CHO-K1) cells and human non-small cell lung cancer (H1299) cells by observing the surviving fraction. The estimated ratio was then compared with the ratio of γ-H2AX foci using immunofluorescent staining. For making a comparison of the number of DSBs among a variety of radiation energy cases, we next utilized the survival data in the literature for both cells exposed to other photon types, such as ⁶⁰Co γ-rays, ¹³⁷Cs γ-rays and 100 kVp X-rays. The ratio of DSBs based on the MK model with conventional data was consistent with the ratio of γ-H2AX foci numbers, confirming that the γ-H2AX focus is indicative of DSBs. It was also shown that the larger y_D is, the larger the DSB number is. These results suggest that k and y_D represent the characteristics of the surviving fraction and the biological effects for photon irradiation.     

Pediatricians’ Practice Location Choice—Evaluating the Effect of Japan’s 2004 Postgraduate Training Program on the Spatial Distribution of Pediatricians

Objectives

To explore determinants of change in pediatrician supply in Japan, and examine impacts of a 2004 reform of postgraduate medical education on pediatricians’ practice location choice.

Methods

Data were compiled from secondary data sources. The dependent variable was the change in the number of pediatricians at the municipality (“secondary tier of medical care” [STM]) level. To analyze the determinants of pediatrician location choices, we considered the following predictors: initial ratio of pediatricians per 1000 children under five years of age (pediatrician density) and under-5 mortality as measures of local area need, as well as measures of residential quality. Ordinary least-squares regression models were used to estimate the associations. A coefficient equality test was performed to examine differences in predictors before and after 2004. Basic comparisons of pediatrician coverage in the top and bottom 10% of STMs were conducted to assess inequality in pediatrician supply.

Results

Increased supply was inversely associated with baseline pediatrician density both in the pre-period and post-period. Estimated impact of pediatrician density declined over time (P = 0.026), while opposite trends were observed for measures of residential quality. More specifically, urban centers and the SES composite index were positively associated with pediatrician supply for the post-period, but no such associations were found for the pre-period. Inequality in pediatrician distribution increased substantially after the reform, with the best-served 10% of communities benefitting from five times the pediatrician coverage compared to the least-served 10%.

Conclusions

Residential quality increasingly became a function of location preference rather than public health needs after the reform. New placement schemes should be developed to achieve more equity in access to pediatric care.Key words: human resources, physician distribution, postgraduate medical training program, Japan