Enantioselective Alkylation of Hydrophobic Vitamin B12 Bearing a Binaphthyl Moiety

The enantioselective alkylation of hydrophobia vitamin B12 derivatives at the β-axial site was examined in methanol with various alkyl bromides, and those B12 analogues bearing a peripheral binaphthyl moiety showed the highest S-selectivity toward enantiomeric alkyl bromides among vitamin B12 models as caused by a steric effect of the peripheral substituent

Evaluation of liver function parameters by Tc-99m-GSA using multivariate analysis: a study of 47 clinical cases.

To investigate the correlation between nuclear medicine parameters determined by technetium-99m-DTPA-galactosyl-human serum albumin (Tc-99m-GSA) and liver function tests, canonical correlation analysis was performed. Tc-99m-GSA studies were performed on 47 patients with hepatocellular carcinoma (HCC) who had undergone transcatheter arterial embolization (TAE). The nuclear medicine parameters LU15, HH15 and LHL15, which are results of nuclear imaging tests, were chosen in combination with the following liver function tests: the serum bilirubin level (T.Bil), the serum albumin level (Alb), serum cholinesterase activity (Ch-E), the clearance rate of indocyanine green (KICG), the hepaplastin test (HPT) and the prothrombin time (PT). The canonical correlation coefficient was 0.7345 and the upper tail probability was 0.00167. A significant correlation was observed between the two sets of variables. The high structural coefficients of Ch-E, KICG and HPT indicated a close relationship with the nuclear medicine parameters, supporting the notion that these nuclear medicine parameters are useful for the estimation of liver damage. The structural coefficients of the nuclear medicine parameters were also high, with LU15 being a parameter as useful as both HH15 and LHL15. T.Bil may evaluate a liver function that is not measured by nuclear imaging techniques, so we should take T.Bil results into account before considering TAE.</p

Quantitative evaluation of 99mTc-GSA in the rat liver after ischemia-reperfusion injury.

99mTc-DTPA-galactosyl human serum albumin (Tc-GSA) is a new liver-imaging agent which binds specifically to hepatic binding protein. The purpose of this study was to evaluate the usefulness of Tc-GSA in quantitatively evaluating hepatic ischemia-reperfusion injury in the rat. Regional hepatic ischemia was induced by clamping the left hepatic artery and the left portal vein for 5 to 45 min. A hepatic accumulation index (t90) was obtained on the basis of the dynamic data. A significant difference of this index was observed between all ischemic groups and the control. In conclusion, 99mTc-GSA appears useful for evaluating the hepatic ischemia-reperfusion injury.&#60;/P&#62;</p

Hydrophobic Vitamin B12. XI. Preparation, Characterization, and Enantioselective Alkylation of Hydrophobic Vitamin B12 Bearing a Binaphthyl Moiety

Hydrophobic vitamin B12 derivatives bearing a chiral binaphthyl moiety, hexamethyl 71-decarboxy-71-[(R)-2′-methoxy-1,1′-binaphthyl-2-carboxymethyl]cobyrinate perchlorate [B12–BINAP(R)] and hexamethyl 71-decarboxy-71-[(S)-2′-methoxy-1,1′-binaphtyl-2-carboxymethyl]cobyrinate perchlorate [B12–BINAP(S)], were prepared from cyanocobalamin. These complexes were characterized by means of electronic and circular dichroism spectroscopy as well as by cyclic voltammetry in comparison with those data for a hydrophobic vitamin B12 without a binaphthyl moiety. The enantioselective alkylation of hydrophobic vitamin B12 derivatives at the β-axial site was examined in methanol with various 3-bromo-2-methylpropionic esters by means of 1H NMR spectroscopy. All the hydrophobic vitamin B12 derivatives used here, the one bearing methoxycarbonyl groups as peripheral substituents without a binaphthyl moiety, B12–BINAP(R), and B12-BINAP(S), were found to bind (S)-2-methylpropionates more favorably than the corresponding R-enantiomers; the highest S-selectivity was observed with the latter two derivatives, 65% e.e. The cause of such S-enantioselectivity was discussed with attention to stereochemical configurations of the peripheral substituents placed in the corrin ring

Renal Outcome of Immunoglobulin A Nephropathy With Mild Proteinuria

We determined the natural history of immunoglobulin A nephropathy (IgAN) among patients who presented with mild proteinuria (0.2 to 0.4 g/day), and factors associated with development of adverse clinical events, defined as proteinuria 竕ｧ 1.0g/day, blood pressure > 130/80mmHg, serum creatinine 竕ｧ 1.4mg/dl. We did analyzed data from 27 patients(mean age 30 ﾂｱ 12 years) with IgAN accompanied by mild proteinuria between 1990 and 1998. We also evaluated semiquantitave scores of glomerulosclerosis, tubulointerstitial injury, hyaline arteriosclerosis, and IgAN classification. The median duration of follow-up was 51 months. During followup, at least one adverse clinical event affected 15 patients (56%): among who eight (53%) developed proteinuria. And one of 8 developed impaired renal function and 7 (47%) became hypertensive. Another 12 patients (44%) were not affected by adverse clinical events. The clinical findings were not significantly different between the adverse events and no evens group. The scores of glomerulosclerosis and tubulointerstitial injury reveled significant differences between events. The only renal histological parameters of glomerulosclerosis and adverse clinical events were statistically correlated with renal survival. We concluded that IgAN with mild proteinuria frequently follows a slow by progressive course and that the severity of glomerulosclerosis may be predictable prognostic factor in patients who have IgAN with by mild proteinuria

Characterisation of Ppy-lineage cells clarifies the functional heterogeneity of pancreatic beta cells in mice

Aims/hypothesis Pancreatic polypeptide (PP) cells, which secrete PP (encoded by the Ppy gene), are a minor population of pancreatic endocrine cells. Although it has been reported that the loss of beta cell identity might be associated with beta-to-PP cell-fate conversion, at present, little is known regarding the characteristics of Ppy-lineage cells. Methods We used Ppy-Cre driver mice and a PP-specific monoclonal antibody to investigate the association between Ppy-lineage cells and beta cells. The molecular profiles of endocrine cells were investigated by single-cell transcriptome analysis and the glucose responsiveness of beta cells was assessed by Ca2+ imaging. Diabetic conditions were experimentally induced in mice by either streptozotocin or diphtheria toxin. Results Ppy-lineage cells were found to contribute to the four major types of endocrine cells, including beta cells. Ppy-lineage beta cells are a minor subpopulation, accounting for 12–15% of total beta cells, and are mostly (81.2%) localised at the islet periphery. Unbiased single-cell analysis with a Ppy-lineage tracer demonstrated that beta cells are composed of seven clusters, which are categorised into two groups (i.e. Ppy-lineage and non-Ppy-lineage beta cells). These subpopulations of beta cells demonstrated distinct characteristics regarding their functionality and gene expression profiles. Ppy-lineage beta cells had a reduced glucose-stimulated Ca2+ signalling response and were increased in number in experimental diabetes models. Conclusions/interpretation Our results indicate that an unexpected degree of beta cell heterogeneity is defined by Ppy gene activation, providing valuable insight into the homeostatic regulation of pancreatic islets and future therapeutic strategies against diabetes