Water fat separation using the single acquisition "sandwich" type 3-point Dixon method to optimize knee joint scans

In this paper, we tried to evaluate the effect of water-fat separation on and to optimize the scan condition of the newly developed "Sandwiched" 3-point Dixon method at 0.35 Tesla (T), for knee joint imaging. Using a 0.35T superconductive open magnet system with a solenoid type knee coil, one male and two female normal volunteers (27-37 y.o.) underwent knee joint imaging. Each sequence provided good water-fat separated images. At 0.35T, the gradient echo provided a better contrast than the spin echo. Optimal cartilage-marrow and cartilage-fluid contrast could be obtained at a frip angle (FA) of 90 degrees. There was no significant correlation between cartilage-marrow, cartilage-fluid contrast and repetition time (TR) values within the tested range. Cartilage-fluid and cartilage-marrow contrast were both best at an FA of 90 degrees with the gradient echo sequence. TR from 350 ms to 650 ms did not cause any significant contrast difference in the fat suppressed images. This method is useful and could be the only practical choice for obtaining fat suppressed T1 weighted images for joint magnetic resonance (MR) imaging at 0.35T.     

毛穗藜芦中茋类化合物的化学研究

目的：对毛穗藜芦根茎进行化学成分研究。方法：采用柱层析和薄层层析法进行分离，用ＵＶ，ＩＲ，ＭＳ，１ＨＮＭＲ等光谱技术鉴定化合物的结构。结果：得到２个类化合物，为白藜芦醇和２，３′，４，５′四羟基。结论：为首次从该植物中分离得到     

Somatic mutations of epidermal growth factor receptor in colorectal carcinoma.

PURPOSE: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non-small cell lung carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA. EXPERIMENTAL DESIGN: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction and PCR, we examined EGFR mutations by sequencing genomic DNA. RESULTS: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma. CONCLUSIONS: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these tumors may be susceptible to gefitinib treatment.     

A crucial role of uridine/cytidine kinase 2 in antitumor activity of 3'-ethynyl nucleosides.

The antitumor 3'-ethynyl nucleosides, 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine (ECyd) and 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine (EUrd), are potent inhibitors of RNA polymerases and show excellent antitumor activity against various human solid tumors in xenograft models. ECyd is being investigated in phase I clinical trials as a novel anticancer drug possessing a unique antitumor action. ECyd and EUrd require the activity of uridine/cytidine kinase (UCK) to produce the corresponding active metabolite. The UCK family consists of two members, UCK1 and UCK2, and both UCKs are expressed in many tumor cells. It was unclear, however, whether UCK1 or UCK2 is responsible for the phosphorylation of the 3'-ethynyl nucleosides. We therefore established cell lines that are highly resistant to the 3'-ethynyl nucleosides from human fibrosarcoma HT-1080 and gastric carcinoma NUGC-3. All the resistant cell lines showed a high cross-resistance to ECyd and EUrd. As a result of cDNA sequence analysis, we found that UCK2 mRNA expressed in EUrd-resistant HT-1080 cells has a 98-base pair deletion of exon 5, whereas EUrd-resistant NUGC-3 cells were harboring the point mutation at nucleotide position 484 (C to T) within exon 4 of UCK2 mRNA. This mutation was confirmed by genome sequence analysis of the UCK2 gene. Moreover, the expression of UCK2 protein was decreased in these resistant cells. In contrast, no mutation in the mRNA or differences in protein expression levels of UCK1 were shown in the EUrd-resistant HT-1080 and NUGC-3 cells. These results suggest that UCK2 is responsible for the phosphorylation and activation of the antitumor 3'-ethynyl nucleosides.     

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.     

Congenital hyperinsulinism: Global and Japanese perspectives

Over the past 20 years, there has been remarkable progress in the diagnosis and treatment of congenital hyperinsulinism (CHI). These advances have been supported by the understanding of the molecular mechanism and the development of diagnostic modalities to identify the focal form of ATP‐sensitive potassium channel CHI. Many patients with diazoxide‐unresponsive focal CHI have been cured by partial pancreatectomy without developing postsurgical diabetes mellitus. Important novel findings on the genetic basis of the other forms of CHI have also been obtained, and several novel medical treatments have been explored. However, the management of patients with CHI is still far from ideal. First, state‐of‐the‐art treatment is not widely available worldwide. Second, it appears that the management strategy needs to be adjusted according to the patient's ethnic group. Third, optimal management of patients with the diazoxide‐unresponsive, diffuse form of CHI is still insufficient and requires further improvement. In this review, we describe the current landscape of this disorder, discuss the racial disparity of CHI using Japanese patients as an example, and briefly note unanswered questions and unmet needs that should be addressed in the near future.     

Visualization of the photodegradation of a therapeutic drug by chemometric-assisted fluorescence spectroscopy

The fluorescence spectral fingerprint, also known as the excitation-emission matrix (EEM), is used to assess and visualize therapeutic drug photodegradation in combination with chemometrics. Examination of EEM-parallel factor analysis (PARAFAC) data showed that an individual component was easily separated from a mixture of photogenerated products of a heterocyclic pharmacophore, in this case, phenothiazine drugs (PTZs). Detailed investigations of both structure–EEM relationships and kinetics revealed that the components extracted from EEM–PARAFAC could be quantitatively attributed to such photogenerated products as phenothiazine sulfoxide and carbazole derivatives. EEM in combination with principal component analysis (PCA) could be used as a mapping tool to visualize information of the photodegradation process of PTZs. We also assessed the photostability of various types of PTZs containing side chains by using validated EEM–PARAFAC methodology.

Drug quality and assurance changes with time under the influence of a variety of environmental factors, such as light, temperature, and moisture.