Metabolism of 2 alpha-propoxy-1 alpha,25-dihydroxyvitamin D3 and 2 alpha-(3-hydroxypropoxy)-1 alpha,25-dihydroxyvitamin D3 by human CYP27A1 and CYP24A1.

Recently, we demonstrated that some A-ring-modified vitamin D3 analogs had unique biological activity. Of these analogs, 2alpha-propoxy-1alpha,25(OH)2D3 (C3O1) and 2alpha-(3-hydroxypropoxy)-1alpha,25(OH)2D3 (O2C3) were examined for metabolism by CYP27A1 and CYP24A1. Surprisingly, CYP27A1 catalyzed the conversion from C3O1 to O2C3, which has 3 times more affinity for vitamin D receptor than C3O1. Thus, the conversion from C3O1 to O2C3 by CYP27A1 is considered to be a metabolic activation process. Five metabolites were detected in the metabolism of C3O1 and O2C3 by human CYP24A1 including both C-23 and C-24 oxidation pathways. On the other hand, three metabolites of the C-24 oxidation pathway were detected in their metabolism by rat CYP24A1, indicating a species-based difference in the CYP24A1-dependent metabolism of C3O1 and O2C3 between humans and rats. Kinetic analysis revealed that the Km and kcat values of human CYP24A1 for O2C3 are, respectively, approximately 16 times more and 3 times less than those for 1alpha,25(OH)2D3. Thus, the catalytic efficiency, kcat/Km, of human CYP24A1 for O2C3 is only 2% of 1alpha,25(OH)2D3. These results and a high calcium effect of C3O1 and O2C3 in animal experiments using rats suggest that C3O1 and O2C3 are promising for clinical treatment of osteoporosis.     

Tumor volume measurements of acoustic neuromas with three-dimensional constructive interference in steady state and conventional spin-echo MR imaging

The purpose was to compare three-dimensional (3D) constructive interference in steady state (CISS) and conventional spin-echo (SE) MR imaging in tumor volume measurements of acoustic neuromas. Twenty-two patients with acoustic neuromas were examined using high-resolution 3D-CISS and SE imaging at a 1.5-T system. Tumor volume determined by SE imaging with the ellipsoid formula was overestimated by 692 mm(3)(35%) on average as compared with that at 3D-CISS with the voxel-count method (the reference standard). Intra- and interobserver variations in SE imaging were poor as compared with 3D-CISS imaging. However, tumor volume results with SE imaging showed a high correlation with those using 3D-CISS imaging (P <. 0001). On the basis of diameters shown on SE images, the tumor volume could be assessed using the following equation (P <.0001): (Tumor volume) = -26.407 + 0.387 x (maximum diameter along the pyramid) x(maximum diameter perpendicular to the pyramid) x (maximum height). J. Magn. Reson. Imaging 2000;12:826-832.     

Takayasu arteritis: diagnosis with breath-hold contrast-enhanced three-dimensional MR angiography

The purpose of the study was to determine the diagnostic accuracy of breath-hold contrast-enhanced three-dimensional (3D) magnetic resonance (MR) angiography in Takayasu arteritis. Thirty patients suspected of having Takayasu arteritis were examined with MR angiography and conventional angiography. Takayasu arteritis was diagnosed in 20 of these patients. MR angiography was performed using a 1.5-T system after bolus injection of 0.1 mmol/kg of gadodiamide. MR angiography clearly depicted various vascular lesions in the aorta and its major branches in all 20 patients with Takayasu arteritis. It also depicted pulmonary artery lesions in 10 (50%) of the 20 patients. MR angiography accurately depicted 323 (98%) of 330 arteries, but 7 (2%) stenotic arteries were overestimated as occluded. The sensitivity and specificity of MR angiography for the diagnosis of Takayasu arteritis were both 100%. Breath-hold contrast-enhanced 3D MR angiography clearly depicts various vascular lesions in both the systemic and pulmonary arteries in Takayasu arteritis, thus allowing a definitive diagnosis of Takayasu arteritis.     

Anisotropic diffusion in kidney: apparent diffusion coefficient measurements for clinical use

The purpose of this study was to evaluate anisotropy of the kidney by measurements of the apparent diffusion coefficient (ADC) using commercially available magnetic resonance (MR) imaging. Fifty-one consecutive patients underwent diffusion-weighted echoplanar MR imaging of the upper abdomen with five different strengths of motion probing gradients (b = 1.51, 55.3, 36.6, 317, and 932 sec/mm2) applied along the z-axis. Four ADC values for the upper pole and central portion of the kidney were calculated from four different b-value ranges and compared. The ADCs for the kidney calculated in the lower b-value ranges were significantly higher than those in the higher ranges. The ADCs for the upper pole portion were significantly higher than those for the central portion except for one in the highest b-value range. Diffusion in the kidney is anisotropic, probably due to the kidney's radially oriented structures such as renal vessels and tubules.     

Urinary cadmium and serum levels of estrogens and androgens in postmenopausal Japanese women.

BACKGROUND: Recent laboratory studies have suggested that cadmium is an estrogenic compound and may be a potential risk factor for breast cancer. METHODS: We investigated the relationship between urinary cadmium concentrations and serum concentrations of estrone, testosterone, and dehydroepiandrosterone sulfate in 164 postmenopausal Japanese women. RESULTS: There was a significant positive association between the urinary cadmium and serum testosterone levels after controlling for age and body mass index. The mean testosterone level was 28% higher in women with high urinary cadmium (> or = 3.00 microg/g creatinine) than in those with low urinary cadmium (< 2.00 microg/g creatinine). Urinary cadmium was not significantly associated with serum estrone and dehydroepiandrosterone sulfate levels. Additional adjustment for smoking, alcohol and reproductive factors including known risk factors for breast cancer did not substantially alter the results. CONCLUSION: Data suggested that cadmium exposure is associated with increased testosterone levels. As high testosterone levels have been associated with the risk of breast cancer, the involvement of cadmium exposure in breast cancer risk should be evaluated in future studies.     

Atypical Shone's Complex Diagnosed at 70 Years Old: Presenting with Double-orifice Mitral Valve,Bicuspid Aortic Valve,and Aortic Coarctation

Atypical Shone''s complex is a rare congenital anomaly involving a left-sided obstructive lesion of two or three cardiovascular levels. A 70-year-old man with dyspnea on exertion was diagnosed with severe aortic stenosis (AS) with a bicuspid valve, complicated by severe aortic coarctation (CoA) and a double-orifice mitral valve. He underwent surgery for AS and CoA in one session. It is important to search for complicated malformations, even in cases of bicuspid aortic valve found in old age.     

Morvan Syndrome Converted from Isaacs' Syndrome after Thymectomy with Positivity for Both Anti-LGI1 and Anti-CASPR2 Antibodies

Anti-voltage-gated potassium channel complex antibodies-mediated disorder includes Isaacs'' syndrome, which is characterized by neuromyotonia, and Morvan syndrome, which is characterized by neuromyotonia, encephalopathy and autonomic dysfunction. We herein report a patient with Morvan syndrome that converted from Isaacs'' syndrome after thymectomy. The patient first presented with myospasm in all extremities and positivity for both anti-leucine-rich glioma inactivated 1 (LGI1) and anti-contactin-associated protein like 2 (CASPR2) antibodies and subsequently developed encephalopathy after thymectomy, which was successfully improved by immunotherapy. This is the first case of Morvan syndrome wherein thymectomy worsened Isaacs'' syndrome, suggesting that immunotherapy should be considered for Isaacs'' syndrome accompanied by positivity for both anti-LGI1 and anti-CASPR2 antibodies to prevent worsening to Morvan syndrome.     

Partial Substitution of Glucose with Xylitol Prolongs Survival and Suppresses Cell Proliferation and Glycolysis of Mice Bearing Orthotopic Xenograft of Oral Cancer

Many types of cancer have metabolic alterations with increased glycolysis. Identification of alternative sweeteners that do not fuel cancer is a novel approach to cancer control. The present study aimed to investigate the effects of xylitol on tumor growth and survival of mice bearing orthotopic xenograft of tongue cancers. The results showed that partial substitution of glucose with xylitol (glucose 0.35 g plus xylitol 2.06 g/kg body weight) non-significantly reduced tumor volume, and significantly prolonged the median survival time from 19 days in the control to 30.5 days in the xylitol group. Immunohistochemical data of the tongue tissue shows significantly lower intense-to-mild staining ratios of the proliferation marker Ki-67 in the xylitol than those of the control group (p = 0.04). Furthermore, the xylitol substitution significantly reduced the expression of the rate-limiting glycolytic enzyme, phosphofructokinase-1 (PFK-1) (p = 0.03), and showed a non-significant inhibition of PFK activity. In summary, partial substitution of glucose with xylitol at the equivalent dose to human household use of 10 g/day slows down tumor proliferation and prolongs survival of mice bearing an orthotopic oral cancer xenograft, possibly through glycolytic inhibition, with minimal adverse events. The insight warrants clinical studies to confirm xylitol as a candidate sweetener in food products for cancer survivors.