pH-sensitive GaInAsP photonic crystal fractal band-edge laser.

The light emission characteristics of GaInAsP semiconductors in aqueous solutions are modified by the surface charge, depending on the balance between radiative and nonradiative recombination. This Letter demonstrates the application of a GaInAsP photonic crystal band-edge laser in sensing a solution pH, which reflects the surface charge. The sensitivity is enhanced by a hybrid of fractal honeycomb and close-packed structures with a large surface-to-volume ratio and a high quality factor (Q), which allows a low threshold carrier density. We experimentally obtained a maximum pH sensitivity of 1.9 dB/pH near the threshold and a signal-to-noise ratio of 52/pH (pH resolution of 0.019) at a pump power 2.4 times the threshold where the intensity noise diminished.

A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo.

In many repeat diseases, such as Huntington's disease (HD), ongoing repeat expansions in affected tissues contribute to disease onset, progression and severity. Inducing contractions of expanded repeats by exogenous agents is not yet possible. Traditional approaches would target proteins driving repeat mutations. Here we report a compound, naphthyridine-azaquinolone (NA), that specifically binds slipped-CAG DNA intermediates of expansion mutations, a previously unsuspected target. NA efficiently induces repeat contractions in HD patient cells as well as en masse contractions in medium spiny neurons of HD mouse striatum. Contractions are specific for the expanded allele, independently of DNA replication, require transcription across the coding CTG strand and arise by blocking repair of CAG slip-outs. NA-induced contractions depend on active expansions driven by MutSß. NA injections in HD mouse striatum reduce mutant HTT protein aggregates, a biomarker of HD pathogenesis and severity. Repeat-structure-specific DNA ligands are a novel avenue to contract expanded repeats.

Label-free and spectral-analysis-free detection of neuropsychiatric disease biomarkers using an ion-sensitive GaInAsP nanolaser biosensor.

The emission intensity of GaInAsP semiconductors that show an ion sensitivity is altered by the surface charge. In this study, we propose a biosensing technique using GaInAsP photonic crystal nanolasers based on this principle. Here, simple and rapid detection of collapsin response mediator protein 2 (CRMP2) is demonstrated, which is a promising biomarker candidate for neuropsychiatric diseases existing in peripheral white blood cells. We prepared CRMP2 as a standard protein and introduced sodium dodecyl sulfate (SDS) as an anionic surfactant to enhance the net negative charge of the protein. The nanolaser was modified in advance with an anti-CRMP2 antibody and then photopumped at a constant power. The laser emission intensity was monitored during the antibody-antigen reaction. Consequently, CRMP2 was detected as a decrease in the emission intensity. We achieved a lower limit for detection of 3.8 µg/mL that satisfies the requirement for clinical biomarker testing. Without the requirements of any kind of labels and spectral analyses, this technique allows for simple, rapid, and low-cost biomarker detection.

Naphthyridine-Benzoazaquinolone: Evaluation of a Tricyclic System for the Binding to (CAG)n Repeat DNA and RNA.

The expansion of CAG repeats in the human genome causes the neurological disorder Huntington's disease. The small-molecule naphthyridine-azaquinolone NA we reported earlier bound to the CAG/CAG motif in the hairpin structure of the CAG repeat DNA. In order to investigate and improve NA-binding to the CAG repeat DNA and RNA, we conducted systematic structure-binding studies of NA to CAG repeats. Among the five new NA derivatives we synthesized, surface plasmon resonance (SPR) assay showed that all of the derivatives modified from amide linkages in NA to a carbamate linkage failed to bind to CAG repeat DNA and RNA. One derivative, NBzA, modified by incorporating an additional ring to the azaquinolone was found to bind to both d(CAG)9 and r(CAG)9 . NBzA binding to d(CAG)9 was similar to NA binding in terms of large changes in the SPR assay and circular dichroism (CD) as well as pairwise binding, as assessed by electron spray ionization time-of-flight (ESI-TOF) mass spectrometry. For the binding to r(CAG)9 , both NA and NBzA showed stepwise binding in ESI-TOF MS, and NBzA-binding to r(CAG)9 induced more extensive conformational change than NA-binding. The tricyclic system in NBzA did not show significant effects on the binding, selectivity, and translation, but provides a large chemical space for further modification to gain higher affinity and selectivity. These studies revealed that the linker structure in NA and NBzA was suitable for the binding to CAG DNA and RNA, and that the tricyclic benzoazaquinolone did not interfere with the binding.

Lymphoepithelial cyst of the pancreas that was difficult to distinguish from branch duct-type intraductal papillary mucinous neoplasm: report of a case.

A 58-year-old woman was admitted to our hospital to optimize the management of her diabetes mellitus. A computed tomography (CT) scan showed a 30-mmdiameter, multilocular cyst in the head of the pancreas. The tumor markers, including DUPAN 2, SPAN-1, and carbohydrate antigen 19-9, were within the normal ranges. A contrast-enhanced CT scan showed a nonenhanced, multilocular cyst. Abdominal magnetic resonance imaging showed a multilocular cyst. Endoscopic retrograde cholangiopancreatography showed that the main pancreatic duct was normal. Based on these findings, we suspected a branch duct type intraductal papillary mucinous neoplasm. A distal pancreatectomy with a splenectomy was performed, since more of the mass was located on the dorsolateral side, inconsistent with the preoperative imaging results. On the resected specimen, a 4-cm-diameter, multilocular cyst containing serous fluid was found. Pathologically, the cyst wall was lined with squamous epithelium surrounded by abundant lymphoid tissue with follicles, consistent with a lymphoepithelial cyst of the pancreas, which is an unusual benign cyst.

Hepatobiliary cystadenoma exhibiting morphologic changes from simple hepatic cyst shown by 11-year follow up imagings.

BACKGROUND: A long-term follow up case of hepatobiliary cystadenoma originating from simple hepatic cyst is rare. CASE PRESENTATION: We report a case of progressive morphologic changes from simple hepatic cyst to hepatobiliary cystadenoma by 11 - year follow up imaging. A 25-year-old man visited our hospital in 1993 for a simple hepatic cyst. The cyst was located in the left lobe of the liver, was 6 cm in diameter, and did not exhibit calcification, septa or papillary projections. No surgical treatment was performed, although the cyst was observed to gradually enlarge upon subsequent examination. The patient was admitted to our hospital in 2004 due to epigastralgia. Re-examination of the simple hepatic cyst revealed mounting calcification and septa. Abdominal CT on admission revealed a hepatic cyst over 10 cm in diameter and a high-density area within the thickened wall. MRI revealed a mass of low intensity and partly high intensity on a T1-weighted image. Abdominal angiography revealed hypovascular tumor. The serum levels of AST and ALT were elevated slightly, but tumor markers were within normal ranges. Left lobectomy of the liver was performed with diagnosis of hepatobiliary cystadenoma or hepatobiliary cystadenocarcinoma. The resected specimen had a solid component with papillary projections and the cyst was filled with liquid-like muddy bile. Histologically, the inner layer of the cyst was lined with columnar epithelium showing mild grade dysplasia. On the basis of these findings, hepatobiliary cystadenoma was diagnosed. CONCLUSION: We believe this case provides evidence of a simple hepatic cyst gradually changing into hepatobiliary cystadenoma.

Giant pulmonary cyst associated with congenital pericardial defect.

Congenital defects of the pericardium are rare. This report describes a young woman with a congenital complete pericardial defect who developed a giant pulmonary cyst. After operation the patient experienced chest pain caused by myocardial ischemia due to cardiac displacement. It is important to note that heart lability in patients with congenital pericardial defects may cause grave complications after thoracotomy associated with volume loss of the residual lung.

[A case of rectal cancer treated by preoperative chemoradiation].

Fifty-one-year-old male visited our hospital suffering from anal pain and subileus. Further examination revealed that advanced rectal cancer which invaded to presacral space (Ai, N 0, P 0, H 0, M(-), stage IIIa) caused such symptom. We administered neo-adjuvant chemoradiotherapy for fear of non curative resection of the rectum. The regimen was once weekly administration of intravenous CPT-11 40 mg, plus daily oral administration of UFT-E 600 mg/day and Uzel 75 mg/day for 4 weeks. In addition we underwent radiation 2.4 Gy/day and intravenous low-dose cisplatin (CDDP) 5 mg/day, 5 days/week for 3 weeks. Four weeks after the first administration, a partial response was confirmed on CT, and so we carried out an abdominoperineal resection. The postoperative course is almost uneventful without a little perineal infection. The specimen revealed that no malignant lesion remained, which changed to necrotic tissue. The side effects were not so severe. For example, diarrhea, nausea, and mucosal dysfunction were each less than grade 2, and there was much tolerate for renal, liver, and bone marrow function. This combination chemoradiotherapy is considered to be effective for locally advanced rectal cancer.