Cancers, Vol. 9, Pages 23: Photodynamic Detection of Peritoneal Metastases Using 5-Aminolevulinic Acid (ALA)

In the past, peritoneal metastasis (PM) was considered as a terminal stage of cancer. From the early 1990s, however, a new comprehensive treatment consisting of cytoreductive surgery and perioperative chemotherapy has been established to improve long-term survival for selected patients with PM. Among prognostic indicators after the treatment, completeness of cytoreduction is the most independent predictors of survival. However, peritoneal recurrence is a main cause of recurrence, even after complete cytoreduction. As a cause of peritoneal recurrence, small PM may be overlooked at the time of cytoreductive surgery (CRS), therefore, development of a new method to detect small PM is desired. Recently, photodynamic diagnosis (PDD) was developed for detection of PM. The objectives of this review were to evaluate whether PDD using 5-aminolevulinic acid (ALA) could improve detection of small PM.

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Heterogeneity in phenotype of hyperinsulinism caused by activating glucokinase mutations: a novel mutation and its functional characterization

Abstract

Background

Mutations in the GCK gene lead to different forms of GCK-disease, activating mutations cause hyperinsulinemic hypoglycemia while inactivating mutations cause monogenic diabetes. Hyperinsulinism (HI) is a heterogeneous condition with a significant genetic component. The major causes are channelopathies, the other forms are rare and being caused by mutations in genes such as GCK.

Objective

To describe the clinical and genetic presentation of four families with activating GCK mutations, and to explore the pathogenicity of the novel mutation identified through functional studies.

Results

Four cases of HI with mutations in GCK were identified. These include one novel mutation (p.Trp99Cys). Functional analysis of the purified mutant fusion protein GST-GCK-p.Trp99Cys demonstrated that p.Trp99Cys is an activating mutation since it induces a higher affinity for glucose and increases the relative activity index more than 11 times. Moreover, the thermal stability of the mutant protein was similar to that of its wild-type. All patients were responsive to diazoxide treatment. One of the mutations arose de novo, and two were dominantly inherited, although only one of them from an HI affected parent. The age of presentation in our cases varied widely from the neonatal period to adulthood.

Conclusion

The clinical phenotype of the GCK activating mutation carriers was heterogeneous, the severity of symptoms and age at presentation varied markedly between affected individuals, even within the same family. The novel activating GCK mutation (p.Trp99Cys) has a strong activating effect in vitro although it has been identified in one case of a milder and late-onset form of HI.

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Analysis of Spatiotemporal Evolution of Isolated Rainstorm Events in Huai River Basin, China

Because of the impacts of extreme climate, the severity, areal extent, and frequency of rainstorm events are rapidly increasing, especially in the Huai River Basin of China. This article is based on hourly precipitation data of 229 meteorological stations from 1951 through 2012, combined with statistical and meteorological theory. We used the Mann-Kendall mutation test, moving -test, and inverse distance weighting spatial interpolation to analyze the spatiotemporal evolution of precipitation, duration, intensity, and frequency of isolated rainstorm events under climate change. The main results are as follows: () isolated rainstorm events were obviously bimodal and their occurrence moved backward in time. Their average duration and time of maximum intensities changed dramatically, without a significant increasing trend. The period since the 2000s has seen an increase of rainstorms and their temporal regression across the entire basin. () The intensity of isolated rainstorm events in the study area decreased, but precipitation, its duration, areal extent, and frequency had increasing trends basin-wide. () Four rainstorm event indices were examined for the period of 1990–2000. Relative to the years before 2003, the average precipitation increased by 2.1%, the average total duration by 8.1%, and the average frequency of occurrence by 25.5%. All indices show smaller minimum and larger maximum values. Overall, the isolated rainstorm events tended to increase.

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SuperSonic features Aixplorer updates at ECR 2017

Ultrasound technology developer SuperSonic Imagine is showing updates to its...

Read more on AuntMinnieEurope.com

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Bleeding near brain is linked to increased use of anti-clotting drugs, study finds

The risk of subdural haematoma is associated with antithrombotic drug use, particularly a vitamin K antagonist, a large Danish study has found.1Although use of antithrombotic drugs has long been...

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Non-invasive prenatal screening should be banned for sex selection, says ethics report

Testing a fetus to determine its sex should be banned, and the marketing practices of manufacturers and private companies offering the tests should be more closely monitored, a report has...

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Activity of human kallikrein-related peptidase 6 (KLK6) on substrates containing sequences of basic amino acids. Is it a processing protease?

Publication date: Available online 28 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Roberta N. Silva, Lilian C.G. Oliveira, Carolina B. Parise, Juliana R. Oliveira, Beatrice Severino, Angela Corvino, Paola di Vaio, Piero A. Temussi, Giuseppe Caliendo, Vincenzo Santagada, Luiz Juliano, Maria A. Juliano
Human kallikrein 6 (KLK6) is highly expressed in the central nervous system and with elevated level in demyelinating disease. KLK6 has a very restricted specificity for arginine (R) and hydrolyses myelin basic protein, protein activator receptors and human ionotropic glutamate receptor subunits. Here we report a previously unreported activity of KLK6 on peptides containing clusters of basic amino acids, as in synthetic fluorogenic peptidyl-Arg-7-amino-4-carbamoylmethylcoumarin (peptidyl-ACC) peptides and FRET peptides in the format of Abz-peptidyl-Q-EDDnp (where Abz=ortho-aminobenzoic acid and Q-EDDnp = glutaminyl- N-(2,4-dinitrophenyl) ethylenediamine), in which pairs or sequences of basic amino acids (R or K) were introduced. Surprisingly, KLK6 hydrolyzed the fluorogenic peptides Bz-A-R^↓R-ACC and Z-R^↓R-MCA between the two R groups, resulting in non-fluorescent products. FRET peptides containing furin processing sequences of human MMP-14, nerve growth factor (NGF), Neurotrophin-3 (NT-3) and Neurotrophin-4 (NT-4) were cleaved by KLK6 at the same position expected by furin. Finally, KLK6 cleaved FRET peptides derived from human proenkephalin after the KR, the more frequent basic residues flanking enkephalins in human proenkephalin sequence. This result suggests the ability of KLK6 to release enkephalin from proenkephalin precursors and resembles furin a canonical processing proteolytic enzyme. Molecular models of peptides were built into the KLK6 structure and the marked preference of the cut between the two R of the examined peptides was related to the extended conformation of the substrates.



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