A case of unicuspid aortic valve associated with a single coronary artery and ventricular septal defect

The patient was a 26-year-old man who had undergone patch closure of a ventricular septal defect at 2 years of age. After this surgery, his condition was satisfactory until he visited our hospital for treatment of paroxysmal supraventricular tachycardia in November 2000. Echocardiography revealed moderate to severe aortic valve regurgitation and dilatation of the left ventricle and ascending aorta. These echocardiographic abnormalities were attributed to a bicuspid aortic valve. Coronary angiography suggested the presence of a single coronary artery originating from the left Valsalva sinus. We performed Bentall’s operation in January 2003. The intraoperative findings revealed that the aortic valve consisted of an extensively calcified single cusp, and there was a single coronary artery originating from the left Valsalva sinus. Because adult patients with a unicuspid aortic valve are rare, and no cases of unicuspid aortic valve associated with a single coronary artery have been reported, we herein report this case with a review of the literature.This paper was presented at the 19th meeting of the Chubu Chapter of the Japan Society of Ultrasonics in Medicine.     

An enzymatic method for the measurement of glycated albumin in biological samples

BACKGROUND: In order to determine glycated albumin more easily and rapidly, we developed a new enzymatic method for glycated albumin in blood samples. METHODS: The method involves use of albumin-specific proteinase, ketoamine oxidase and serum albumin assay reagent. In the assay, glycated albumin is hydrolyzed to glycated amino acids by proteinase digestion, and ketoamine oxidase oxidizes the glycated amino acids to produce hydrogen peroxide, which is quantitatively measured. Glycated albumin is calculated as the percentage of glycated albumin in total albumin. RESULTS: The calibration curve for glycated albumin concentration was linear (r(p)=0.999) between 0.0 and 50.0 g/l and that for albumin concentration was linear (r(p)=0.999) between 0.0 and 60.0 g/l. The analytical recoveries of exogenous glycated albumin added to serum were 100-102.5%. The within-run and between-run CVs were 0.45-0.67% and 1.09-1.26%, respectively. This method was free from interference by bilirubin, chyle, glucose, globulins and labile intermediate. Weak interference by hemoglobin and ascorbic acid was observed. Glycated albumin detected by the present method was significantly correlated with glycated albumin detected by high-performance liquid-chromatographic (HPLC) method (serum: r(s)=0.989, plasma: r(p)=0.992). CONCLUSIONS: This new enzymatic method is simple, rapid, allows multiple determinations and enables quantitative analysis of glycated albumin.     

Expression of epithelial cancer-related antigens in hematologic malignancies applicable for peptide-based immunotherapy

Recent advances in tumor immunology have resulted in identification of many epithelial cancer-related antigens and peptides applicable to specific immunotherapy. The authors investigated whether these peptides, which are being studied clinically, could be appropriate target molecules for treatment of patients with hematologic malignancies. The majority of hematologic malignant cells studied expressed five different epithelial cancer-related antigens. Cytotoxic T lymphocyte (CTL) precursors reactive to these antigen-derived peptides were detected in peripheral blood mononuclear cells (PBMCs) of the majority of HLA-A24 patients, and the mean number of peptides recognized by CTL precursors was 2.4 per patient, ranging from 0 to 8 among the 10 peptides tested. These peptide-stimulated PBMCs exhibited HLA-A24-restricted cytotoxic activity against hematologic malignant cells but not against blastoid T cells. More importantly, these peptide-stimulated PBMCs exhibited cytotoxicity against freshly prepared autologous malignant cells in an HLA-A24-restricted manner. These results may provide a scientific basis for the use of these peptides from epithelial cancer-related antigens in specific immunotherapy for patients with hematologic malignancies.     

Potent plasmodicidal activity of a heat-induced reformulation of deoxycholate-amphotericin B (Fungizone) against Plasmodium falciparum

The emergence and spread of drug-resistant Plasmodium falciparum continue to pose problems in malaria chemotherapy. Therefore, it is necessary to identify new antimalarial drugs and therapeutic strategies. In the present study, the activity of a heat-treated form of amphotericin B (HT-AMB) against P. falciparum was evaluated. The efficacy and toxicity of HT-AMB were also compared with those of the standard formulation (AMB). HT-AMB showed significant activity against a chloroquine-resistant strain (strain K-1) and a chloroquine-susceptible strain (strain FCR-3) in vitro. The 50% inhibitory concentrations of HT-AMB were 0.32 +/- 0.03 mug/ml for strain K-1 and 0.33 +/- 0.03 mug/ml for strain FCR-3. In the presence of 1.0 mug of HT-AMB per ml, only pyknotic parasites were observed after 24 h of incubation of early trophozoites (ring forms). However, when late trophozoites and schizonts were cultured with 1.0 mug of HT-AMB per ml, those forms multiplied to ring forms but the number of infected erythrocytes did not increase. These results indicate that HT-AMB possesses potent antiplasmodial activity and that the drug is more effective against the ring-form stage than against the late trophozoite and schizont stages. HT-AMB was observed to have little cytotoxic effect against a human liver cell line (Chang liver cells). In conclusion, the results suggest that HT-AMB has promising properties and merits further in vivo investigations as a treatment for falciparum malaria.     

Dvl regulates endo- and exocytotic processes through binding to synaptotagmin

Dvl, an important component of the Wnt signalling pathway, is thought to be involved in synaptogenesis. In this study, we investigated whether Dvl regulates neurotransmitter release. Knockdown of Dvl in PC12 cells suppressed K(+)-induced dopamine release, and this phenotype was restored by expression of Dvl-1. We identified synaptotagmin (Syt) I, which is involved in neurotransmitter release, as a Dvl-binding protein. Dvl directly bound to the C2B domain of Syt I. Dvl colocalized with Syt I at the tip of neurites of differentiated PC12 cells and of neurons in the rat dorsal root ganglion. Dvl and Syt I was located in large dense-core vesicles, which contain dopamine. In addition, endocytosis of vesicles containing Syt I was suppressed in Dvl knockdown PC12 cells. Dvl inhibited the binding of Syt I to the complex consisting of syntaxin-1A and SNAP-25. Furthermore, micro2-adaptin of AP-2, which is known to play a role in endocytosis, formed a complex with Dvl and Syt I. Taken together, these results suggest that Dvl is involved in endo- and exocytotic processes through the binding to Syt I.     

Bilateral subclavian arteries passing in front of the scalenus anterior muscles

Herein, we present a very rare case of bilateral subclavian arteries passing in front of the scalenus anterior muscles in a cadaver. This abnormality was observed in a 73-year-old Japanese male cadaver during a dissection session for students in 2004 at Osaka Dental University. The bilateral scalenus anterior muscle originated from the anterior tubercle of the transverse processes of the fifth and sixth cervical vertebrae and inserted into the scalene tubercle of the first ribs. The right scalenus minimus muscle was observed, but no left scalenus minimus muscle was observed. The aortic arch was a type A according to Adachi's classification. The origin of the internal thoracic artery was distal to that of the thyrocervical trunk. The bilateral brachial plexuses was formed by the union of the ventral rami from the fifth cervical to the first thoracic nerves and passed between the scalenus anterior and the scalenus medius muscles. To our knowledge, such a case has not been reported previously.     

Association study between the cholecystokinin A receptor gene and schizophrenia in the Japanese population

Cholecystokinin A receptor (CCK-AR) has been implicated in the pathophysiology of schizophrenia through its mediation of dopamine-release in the central nervous system. Several studies have observed the association between the CCK-AR gene and schizophrenia. Especially, the association has been repeatedly observed between the 779T/C polymorphism and auditory hallucinations or positive symptoms of schizophrenia. In this study, we investigated the association between the 779T/C polymorphism of the CCK-AR gene and schizophrenia in 290 Japanese patients with schizophrenia and 290 controls. As a result, no significant difference was observed in genotypic distributions or allelic frequencies between the patients and controls, although there was a trend for the association between the C allele of the polymorphism and hallucination (P=0.024) or hallucinatory-paranoid state (P=0.049). In conclusion, the present results may not provide evidence for the association between the CCK-AR gene and schizophrenia in the Japanese population.     

FDA's decisions in oncology drug product approvals from 2006 to 2016

Objective

Under the circumstances that several oncology drugs have been approved under expedited programs in the US, this study aimed to analyze the relationship between the expedited programs and characteristics of approvals in the recent decade, and the attitude of the Food and Drug Administration (FDA) toward the development and review of oncology drugs.

Neurospheres from human adipose tissue transplanted into cultured mouse embryos can contribute to craniofacial morphogenesis: a preliminary report

Adipose-derived stromal cells (ASCs) are one of the most promising stem cell populations that differentiate into the mesodermal as well as neural lineages in vitro. In this study, we examined the neural differentiating potential of human ASCs by a neurosphere culture method. Neurospheres derived from human ASCs expressed Nestin and Musashi-1 genes, which are marker genes for neural stem cells. When these cells were labeled with green fluorescent protein gene transfection by Sendai virus vector and transplanted into the head region of mouse embryos using a whole embryo culture system, these cells were incorporated into the craniofacial development. Some transplanted cells appeared to migrate along the second branchial arches, implicating some similarity to the cranial neural crest cells. Although preliminary, our results support an idea that ASC-derived neurospheres have properties of neural progenitors in vitro and in vivo.