A novel AMPA receptor antagonist, YM872, reduces infarct size after middle cerebral artery occlusion in rats

The neuroprotective effect of YM872 ([2.3-dioxo-7-(1H-imidazol-1-yl) 6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]acetic acid monohydrate), a novel α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist with improved water solubility, was examined in a rat focal cerebral ischemia model. Rats were subjected to permanent middle cerebral artery (MCA) occlusion using the intraluminal suture occlusion method for 24 h. YM872 was intravenously infused for 4 h (20 and 40 mg/kg/h) or 24 h (10 and 20 mg/kg/h), starting 5 min after the MCA occlusion, to investigate the effect of prolonged duration of the treatment on infarct volume. In the 4 h infusion study, YM872 reduced the cortical infarct volume by 48% at a dose of 40 mg/kg/h. YM872 did not significantly reduce the infarct at 20 mg/kg/h for 4 h. In the 24 h infusion study, however, YM872 markedly reduced the cortical infarct volume by 62%, even at 20 mg/kg/h. The present study indicates that the neuroprotective effect of YM872 is enhanced by extending the duration of treatment, and demonstrates the benefit of the prolonged treatment with AMPA antagonists following focal cerebral ischemia. YM872, a highly water soluble compound, is applicable to investigate the role of AMPA receptors in ischemic models without concern about nephrotoxicity and could be useful in the treatment of human stroke.     

The intensity of continuous theta burst stimulation,but not the waveform used to elicit motor evoked potentials,influences its outcome in the human motor cortex

Background

Responses to continuous theta burst stimulation (cTBS) applied to the human primary motor cortex are highly variable between individuals. However, little is known about how to improve the after-effects of cTBS by adjusting the protocol characteristics.

Surgical resection of gastrointestinal stromal tumor of esophagus following preoperative imatinib treatment: a case report

We report a case of esophagectomy after a primary esophageal gastrointestinal stromal tumor (GIST) was preoperatively treated with imatinib mesylate. A 71-year-old woman was diagnosed with an esophageal submucosal tumor by upper gastrointestinal endoscopy at her health checkup. The tumor was located at the lower thoracic esophagus immediately above the esophagogastric junction and measured 4.5 cm in size. It was diagnosed as GIST of the esophagus for reasons of its high susceptibility to imatinib mesylate. Preoperative treatment with imatinib was performed in an attempt to preserve the esophagus. Although the tumor size was decreased by 36% after the 6-month treatment, transhiatal esophagectomy was required for complete resection, and esophageal preservation could not be accomplished.     

Air pollutants and cough

Epidemiological studies have shown that exposure to air pollution is associated with respiratory symptoms and decreases in lung function. This paper reviews recent literature showing that exposure to particulate matter, irritant gases, environmental tobacco smoke (ETS), mixed pollutants, and molds is associated with an increase in cough and wheeze. Some pollutants, like particulate matter and mixed pollutants, appear to increase cough at least as much as wheeze. Others, like irritant gases, appear to increase wheeze more than cough. For ETS, exposure during childhood is associated with cough and wheeze in adulthood, suggesting that the pollutant permanently alters some important aspect of the lungs, immune system or nervous system. We have shown in animal studies that pollutants change the neural control of airways and cough. Second hand smoke (SHS) exposure lengthened stimulated apnoea, increased the number of stimulated coughs, and augmented the degree of stimulated bronchoconstriction. The mechanisms included enhanced reactivity of the peripheral sensory neurones and second-order neurones in the nucleus tractus solitarius (NTS). NTS effects were due to a substance P mechanism at least in part. Ozone and allergen increased the intrinsic excitability of second-order neurones in the NTS. The animal studies suggest that the cough and wheeze experienced by humans exposed to pollutants may involve plasticity in the nervous system.     

Simple method for the identification of oxidative fibers in skeletal muscle

Skeletal muscle is composed of several different types of myofiber: slow oxidative (SO), fast glycolytic oxidative and fast glycolytic. However, the classification is usually determined by myosin heavy chain typing rather than by metabolic index. In this study, the oxidative metabolic index was investigated as a possible method of myofiber typing. Myoglobin, which is involved in oxygen transport and storage in myofibers, and mitochondria, which are the central organelles for oxidative metabolism, were studied. High levels of myoglobin and mitochondria are believed to exist in SO fibers, but the current study showed that they are considerably richer in some fast type fibers. As myofiber typing using the oxidative metabolic index is important physiologically, an attempt was made to find a simple method for this purpose. Some mitochondrial proteins have been observed to auto-fluoresce but until now this effect was too faint to detect easily. Owing to the recent advances in cooling charge-coupled device technology, such auto-fluorescence can now be used for myofiber typing, and the simple and rapid method for doing so is reported here.     

Proteomic analysis of mechanisms of hypoxia-induced apoptosis in trophoblastic cells

Preeclampsia is often accompanied by hypoxia of the placenta and this condition induces apoptosis in trophoblastic cells. The aim of this study was to characterize global changes of apoptosis-related proteins induced by hypoxia in trophoblastic cells so as to clarify the mechanism of hypoxia-induced apoptosis by using the PoweBlot, an antibody-based Western array. Human choriocarcinoma cell line JAR was cultured for 24 hours under aerobic and hypoxic conditions. Hypoxia induced apoptosis accompanied by increased expression of Bcl-x, Caspase-3 and -9, Hsp70, PTEN, and Bag-1. Bad, pan-JNK/SAPK-1, Bcl-2, Bid, and Caspase-8 showed decreased expression. Hypoxia-induced apoptosis was increased with the transfection of a bag-1 antisense oligonucleotide. The bag-1 antisense oligonucleotide affected the expression of Bid, Bad, Bcl-2, JNK, and phosphorylated JNK, although expression of PTEN and Bcl-X did not change. Bag-1 may inhibit apoptosis by suppressing the expression of Bid and Bad. It may also enhance apoptosis by inhibiting the expression of Bcl-2 and by modulating phosphorylation of JNK. Both mitochondrial and stress-activated apoptosis pathways played important roles in the hypoxia induced cell death of trophoblastic cells. These findings will contribute to establish new approach to detect hypoxic stress of the placenta, which leads to preeclampsia and other hypoxia-related obstetrics complications.     

Formation and distribution of the sural nerve based on nerve fascicle and nerve fiber analyses

The formation and distribution of the sural nerve are presented on the basis of an investigation of 31 legs of Japanese cadavers using nerve fascicle and fiber analyses. Nerve fibers constituting the medial sural cutaneous nerve were designated as 'T', whereas those constituting the peroneal communicating branch were designated as 'F'. In 74.2% of cases (23/31), the T and F fibers joined each other in the leg, whereas in 9.7% of cases (3/31) they descended separately. In 16.1% of cases (5/31), the sural nerve was formed of only the T fibers. The sural nerve gave off lateral calcaneal branches and medial and lateral branches at the ankle. The lateral calcaneal branches always contained T fibers. The medial branches consisted of only T fibers, whereas most of the lateral branches consisted of only F fibers (71.0%; 22/31). In addition to the T and F fibers, P fibers, which derived from the superficial and deep peroneal nerves, formed the dorsal digital nerves. The P fibers were entirely supplied to the medial four and one-half toes. However, they were gradually replaced by the T and F fibers in the lateral direction. The 10th proper dorsal digital nerve consisted of T fibers only (38.7%; 12/31), of F fibers only (19.4%; 6/31) or of both T and F fibers (38.7%; 12/31). These findings suggest that the T fibers are essential nerve components for the skin and deep structures of the ankle and heel rather than the skin of the lateral side of the fifth toe. The designation of the medial sural cutaneous nerve should be avoided and only the T fibers are appropriate components for naming as the sural nerve.     

Analysis of mRNA with microsomal fractionation using a SAGE-based DNA microarray system facilitates identification of the genes encoding secretory proteins

In the regulation of host defense responses such as inflammation and immunity, the secretory proteins, including membrane proteins, play central roles. Although many secretory proteins have been identified by using methods such as differential display, random screening, or the signal sequence trap method, each method suffers from poor reproducibility, low sensitivity, or time-consuming or laborious work. Therefore, the strategy for facilitating the selection of the genes encoding the secretory proteins is desired. In this paper, we describe a system for isolating the genes encoding secretory proteins by analyzing mRNAs with microsomal fractionation on serial analysis of gene expression (SAGE)-based DNA microarray system. This system succeeded in discriminating the genes encoding secretory proteins from ones encoding nonsecretory proteins with 80% accuracy. We applied this system to human T lymphocytes. As a result, we were able to identify the genes that are not only encoding secretory proteins but also expressing selectively in a specific subset of T lymphocytes. The SAGE-based DNA microarray system is a promising system to identify the genes encoding specific secretory proteins.     

Gastric carcinosarcoma presenting as a huge epigastric mass

Gastric carcinosarcoma often presents with an elevated lesion or increased thickness of the stomach wall. Histological diagnosis is achieved using conventional hematoxylin and eosin staining to confirm the coexistence of both epithelial and mesenchymal elements. We report a case of gastric carcinosarcoma presenting as a large mass in the epigastric region. Specimens obtained by endoscopic biopsy and surgical excision showed diffuse proliferation of atypical cells in sheet formation. No mucus production or glandular structures were apparent, but immunoreactivity for both epithelial and mesenchymal markers was noted. These findings led to a definitive diagnosis of gastric carcinosarcoma. Immunohistochemical analysis is useful for the early diagnosis and treatment of gastric carcinosarcoma.