Successful Pregnancy and Lactation Outcome in a Patient With Gaucher Disease Receiving Enzyme Replacement Therapy, and the Subsequent Distribution and Excretion of Imiglucerase in Human Breast Milk

Background: Enzyme replacement therapy (ERT) with imiglucerase is a well-established, effective treatment for Gaucher disease. However, there have been no published reports regarding the excretion of imiglucerase into human breast milk and its effects on the nursing infant. Objective: This letter reports on the successful pregnancy and lactation of a patient with Gaucher disease receiving treatment with imiglucerase, and the subsequent distribution and excretion of imiglucerase in human breast milk. Methods: A 39-year-old Japanese female (height, 164 cm; weight, 55 kg) with Gaucher disease had 2 successful pregnancies and continued ERT through both. The study was conducted 6 months after the first delivery. She was administered a 1-hour infusion of imiglucerase 60 U/kg that coincided with her regular every-2-week regimen. Serum and breast-milk samples were obtained before and up to 24 hours after administration. Breast-milk samples were also obtained from 10 nursing mothers with galactorrhea as controls. Results: The preinfusion level of breast-milk beta-glucocerebrosidase was 0.008 nmol/h/mL. The peak of serum beta-glucocerebrosidase activity (0.119 nmol/h/mL) was obtained at the end of the 1-hour infusion period. Slightly increased enzymatic activity (0.016 nmol/h/mL) was observed in the first breast milk sampled after imiglucerase infusion. Conclusions: We report a case of successful pregnancy and breastfeeding in a Japanese patient with Gaucher disease. A small amount of imiglucerase was found to be excreted into human breast milk, but only in the first milk produced after infusion. (Clin Ther. 2010;32:2048-2052)ArticleCLINICAL THERAPEUTICS. 32(12):2048-2052 (2010)journal articl

Suzaku observation of Jupiter's X-rays around solar maximum

We report on results of imaging and spectral studies of X-ray emission from Jupiter observed by Suzaku. In 2006 Suzaku had found diffuse X-ray emission in 1\unicode{x2013}5 keV associated with Jovian inner radiation belts. It has been suggested that the emission is caused by the inverse-Compton scattering by ultra-relativistic electrons ($\sim 50$ MeV) in Jupiter's magnetosphere. To confirm the existence of this emission and to understand its relation to the solar activity, we conducted an additional Suzaku observation in 2014 around the maximum of the 24th solar cycle. As a result, we successfully found again the diffuse emission around Jupiter in 1\unicode{x2013}5 keV and also point-like emission in 0.4\unicode{x2013}1 keV. The luminosity of the point-like emission which was probably composed of solar X-ray scattering, charge exchange, or auroral bremsstrahlung emission increased by a factor of $\sim 5$ with respect to 2006, most likely due to an increase of the solar activity. The diffuse emission spectrum in the 1\unicode{x2013}5 keV band was well-fitted with a flat power-law function ($\Gamma = 1.4 \pm 0.1$) as in the past observation, which supported the inverse-Compton scattering hypothesis. However, its spatial distribution changed from $\sim 12 \times 4$ Jovian radius (Rj) to $\sim 20 \times 7$ Rj. The luminosity of the diffuse emission increased by a smaller factor of $\sim 3$. This indicates that the diffuse emission is not simply responding to the solar activity, which is also known to cause little effect on the distribution of high-energy electrons around Jupiter. Further sensitive study of the spatial and spectral distributions of the diffuse hard X-ray emission is important to understand how high-energy particles are accelerated in Jupiter's magnetosphere.Comment: 17 pages, 4 figures, 1 tabl

Poorer prognosis with ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia: a single-center case-control study.

In ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia (PTCP), automated platelet counts are lower than actual counts because of EDTA-induced aggregation. Factors contributing to the incidence of EDTA-PTCP are unknown, and no study has assessed the prognosis of EDTA-PTCP patients. This retrospective study assessed characteristics in EDTA-PTCP patients and matched controls to determine differences in prognosis. A retrospective case-control study was designed. From the University of Tokyo Hospital database, we identified patients diagnosed with EDTA-PTCP between 2009 and 2012, and performed 1:2 case:control matching for age and sex. A control group of sex- and age-matched patients was selected at random from the same database. We investigated differences in the frequency of complications, medication history, and blood transfusion history between the groups at the time of blood collection. Prognosis was evaluated using multivariate Cox regression analysis adjusting for age, sex, autoimmune disease, liver disease, and malignant tumor. We identified 104 EDTA-PTCP patients and 208 matched controls. The median age was 69.0 years (interquartile range: 54-76), with men comprising 51%. EDTA-PTCP patients had a higher frequency of malignant tumor and a lower frequency of hypertension and diabetes than controls. After adjustment for background factors, prognosis of EDTA-PTCP patients was significantly poorer than controls (hazard ratio, 11.8; 95% confidence intervals, 2.62-53.54). In conclusion, EDTA-PTCP patients had higher mortality, and EDTA-PTCP may need to be recognized as an indicator of worse prognosis

A consortium study of Antarctic micrometeorites recovered from the Dome Fuji Station

Deposits in the water tank at the Dome Fuji Station were collected by the 37th Japanese Antarctic Research Expedition team in 1996. We recovered 233 micrometeorites from the deposits. A consortium study was started in late 1998 to investigate mineralogy, petrology, bulk chemistry, and isotopic compositions of the micrometeorites. This is the first case of an organized study of micrometeorites in Japan, in order to establish the methods to investigate micrometeorites routinely. Consortium results on mineralogy, petrology, minor and trace element compositions, isotopic compositions of noble gases of the micrometeorites are reported in this volume. We also found a sequence of mineralogical and compositional changes of micrometeorites experienced from frictional heating during atmospheric entry. INAA and ion probe studies are now in progress

Experimental model for the irradiation-mediated abscopal effect and factors influencing this effect

Radiotherapy (RT) is the primary treatment for cancer. Ionizing radiation from RT induces tumor damage at the irradiated site, and, although clinically infrequent, may cause regression of tumors distant from the irradiated site-a phenomenon known as the abscopal effect. Recently, the abscopal effect has been related to prolongation of overall survival time in cancer patients, though the factors that influence the abscopal effect are not well understood. The aim of this study is to clarify the factors influencing on abscopal effect. Here, we established a mouse model in which we induced the abscopal effect. We injected MC38 (mouse colon adenocarcinoma) cells subcutaneously into C57BL/6 mice at two sites. Only one tumor was irradiated and the sizes of both tumors were measured over time. The non-irradiated-site tumor showed regression, demonstrating the abscopal effect. This effect was enhanced by an increase in the irradiated-tumor volume and by administration of anti-PD1 antibody. When the abscopal effect was induced by a combination of RT and anti-PD1 antibody, it was also influenced by radiation dose and irradiated-tumor volume. These phenomena were also verified in other cell line, B16F10 cells (mouse melanoma cells). These findings provide further evidence of the mechanism for, and factors that influence, the abscopal effect in RT

Combination treatment with highly bioavailable curcumin and NQO1 inhibitor exhibits potent antitumor effects on esophageal squamous cell carcinoma

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most intractable cancers, so the development of novel therapeutics has been required to improve patient outcomes. Curcumin, a polyphenol from Curcuma longa, exhibits various health benefits including antitumor effects, but its clinical utility is limited because of low bioavailability. Theracurmin® (THC) is a highly bioavailable curcumin dispersed with colloidal submicron particles. Methods: We examined antitumor effects of THC on ESCC cells by cell viability assay, colony and spheroid formation assay, and xenograft models. To reveal its mechanisms, we investigated the levels of reactive oxygen species (ROS) and performed microarray gene expression analysis. According to those analyses, we focused on NQO1, which involved in the removal of ROS, and examined the effects of NQO1-knockdown or overexpression on THC treatment. Moreover, the therapeutic effect of THC and NQO1 inhibitor on ESCC patient-derived xenografts (PDX) was investigated. Results: THC caused cytotoxicity in ESCC cells, and suppressed the growth of xenografted tumors more efficiently than curcumin. THC increased ROS levels and activated the NRF2–NMRAL2P–NQO1 expressions. Inhibition of NQO1 in ESCC cells by shRNA or NQO1 inhibitor resulted in an increased sensitivity of cells to THC, whereas overexpression of NQO1 antagonized it. Notably, NQO1 inhibitor significantly enhanced the antitumor effects of THC in ESCC PDX tumors. Conclusions: These findings suggest the potential usefulness of THC and its combination with NQO1 inhibitor as a therapeutic option for ESCC