A case of pseudoxanthoma elasticum with proliferative diabetic retinopathy.

BACKGROUND: To report the case of a patient with pseudoxanthoma elasticum (PXE) and proliferative diabetic retinopathy (PDR), and discuss the relationship between PXE and diabetic retinopathy (DR). CASE PRESENTATION: A 47-year-old man with PXE presented with angioid streaks and DR in both eyes, and bilateral panretinal photocoagulation was performed for treatment. Vitrectomy had previously been performed in his right eye for vitreous hemorrhage due to PDR. Systemic findings included multiple, discrete, symmetrical, small yellow papules bilaterally in the axilla and inguinal region. Examination on presentation showed vitreous hemorrhage in his left eye, and vitrectomy was performed for treatment. Intraoperative findings showed fibrovascular membrane around the optic disc and vascular arcade. A mottled fundus (peau d'orange appearance) associated with angioid streaks was also present, yet there was no evident choroidal neovascularization (CNV). The postoperative course was satisfactory, and corrected visual acuity improved from 0.02 to 0.7 diopters. CONCLUSION: Despite the peau d'orange appearance in both eyes of this case, no CNV was evident. The vitreous hemorrhage was thus attributed to PDR. Moreover, we reviewed the published literature and discuss the relationship between PXE and DR.

The Effect of 5-Aminolevulinic Acid on Cytochrome P450-Mediated Prodrug Activation.

Of late, numerous prodrugs are widely used for therapy. The hemeprotein cytochrome P450 (CYP) catalyzes the activation of prodrugs to form active metabolites. Therefore, the activation of CYP function might allow the use of lower doses of prodrugs and decrease toxicity. We hypothesized that the addition of 5-aminolevulinic acid (ALA), a precursor in the porphyrin biosynthetic pathway, enhances the synthesis of heme, leading to the up-regulation of CYP activity. To test this hypothesis, we treated a human gastric cancer cell line with ALA and determined the effect on CYP-dependent prodrug activation. For this purpose, we focused on the anticancer prodrug tegafur, which is converted to its active metabolite 5-fluorouracil (5-FU) mainly by CYP2A6. We show here that ALA increased CYP2A6-dependent tegafur activation, suggesting that ALA elevated CYP activity and potentiated the activation of the prodrug.

The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid.

Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC) with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects.

Interactions between histidine kinase NblS and the response regulators RpaB and SrrA are involved in the bleaching process of the cyanobacterium Synechococcus elongatus PCC 7942.

Cyanobacteria have developed a light-harvesting antenna complex known as the phycobilisome. When cells are starved for nutrients or exposed to high light, the phycobilisome is rapidly degraded (bleaching). It has been suggested that in the cyanobacterium Synechococcus elongatus PCC 7942, the bleaching process is regulated by a two-component histidine kinase, NblS. To clarify the signaling pathway involving NblS, we identified the NblS-interacting response regulators RpaB and SrrA. In vitro assays using recombinant proteins showed that both RpaB and SrrA can receive phosphoryl groups from autophosphorylated NblS; the NblS-interacting protein SipA clearly enhances the phosphotransfer activity from NblS to RpaB and SrrA. In addition, NblS prefers SrrA over RpaB as the phosphotransfer target with or without SipA. Gel mobility shift assay revealed that both RpaB and SrrA can bind to the upstream region of nblA, a major regulatory factor in the bleaching process. nblA transcript accumulates in nblS or rpaB mutants even under normal growth conditions, while in the srrA disruptant the nblA transcripts are slightly up-regulated under stress conditions. These observations suggest that the bleaching signal transduction pathway via NblS is regulated by RpaB and that SrrA is partially involved.

Analysis of the sarcomere protein gene mutation on cardiomyopathy - Mutations in the cardiac troponin I gene.

Developments in the molecular genetic studies of cardiomyopathy (CM) have led to discovery of a large number of mutations in the genes encoding the sarcomeric proteins. In this study, comprehensive screening of TNNI3 was performed in 36 consented autopsy cases diagnosed as CM, in order to evaluate the prevalence of gene mutations in sudden death caused by CM. In DCM cases, a new missense mutation Pro16Thr was detected. A single nucleotide polymorphism at -8 position of intron 3 (IVS 3 -8 T>A) was identified, which had a significant difference in allele frequency between DCM and control cases. From these results, it was indicated that this study contribute to genetic based diagnosis, risk stratification and prevention of sudden death caused by CM.

Synthesis of multisubstituted furans, pyrroles, and thiophenes via ynolates.

An efficient synthetic method for the preparation of multisubstituted furans, thiophenes, and pyrroles using ynolates was developed. This novel formal [4 + 1] annulation by C2-C3 and C3-C4 bond formations includes cycloaddition, cyclization, decarboxylation, and dehydration as key steps.

Palladium-catalyzed diastereoselective coupling of propargylic oxiranes with terminal alkynes.

[reaction: see text] A diastereoselective coupling of propargylic oxiranes with terminal alkynes has been developed with use of a palladium catalyst. The stereochemistries of the resulting 4-alkynyl-substituted 2,3-allenols have been altered depending on the palladium catalyst. An optically active anti-substituted allene was synthesized from the reaction of an enantiomerically enriched propargylic oxirane without loss of chirality.