Integrin α11 in non–small cell lung cancer is associated with tumor progression and postoperative recurrence

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11β1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non–small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT‐PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence‐free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.     

Urinary excretions of lipocalin-type prostaglandin D2 synthase predict the development of proteinuria and renal injury in OLETF rats.

BACKGROUND: Otsuka Long-Evans Tokushima Fatty (OLETF) rats genetically develop diabetes which is associated with hypertension. In preliminary studies, urinary excretions of L-PGDS (lipocaline-type prostaglandin D synthase) increase before diabetic nephropathy obviously develops, and this may predict progression of renal injury following diabetes. In the present study, we attempted to define whether urinary excretions of L-PGDS behave as the predictor of development of diabetic nephropathy in OLETF rats. METHODS: We investigated alterations of urinary L-PGDS excretions during the establishment of diabetes and assessed the relationship between the L-PGDS excretions and renal function in OLETF rats. Furthermore, we treated OLETF rats with troglitazone and analysed the effects on L-PGDS metabolisms. Urinary L-PGDS was measured by immunoenzyme assay and the occurrence of L-PGDS and its mRNA in the kidney was assessed by immunohistochemistry and a PCR method. RESULTS: Urinary excretions of L-PGDS were significantly higher in OLETF rats than non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. The excretions age-dependently increased in OLETF and this increase appeared to be due to increased glomerular permeability to L-PGDS. Messenger RNA and antigenicity of L-PGDS were demonstrated in renal tissue; however, the de novo synthesis of L-PGDS mRNA seemingly contributed to urinary L-PGDS excretions much less than glomerular filtration. Multiple regression analysis revealed that urinary L-PGDS was determined by urinary protein excretions, and not by high blood pressure per se. Conversely, urinary proteinuria in the established diabetic nephropathy was predicted by urinary L-PGDS excretions in the early stage of diabetes. CONCLUSIONS: Urinary excretions of L-PGDS are likely to reflect the underlying increase in glomerular permeability. This property may be useful to predict forthcoming glomerular damage following diabetes in OLETF rats.     

Epilepsy and Recursive Consciousness with Special Attention to Jackson's Theory of Consciousness

Summary: John Hughlings Jackson's theory of consciousness has been reconsidered. The author stressed that his uniqueness as a neuroscientist lay in his keen interest in the recursive nature of human consciousness. Two clinical symptoms of interest to Jackson were discussed: recurrent utterances and mental diplopia. Recurrent utterances were believed to represent an exceptional state, in which the unconscious process in speech production, otherwise destined to be swept away automatically, became manifest and observable. Jackson regarded mental diplopia as a revelation of otherwise inaccessible duality of all healthy mental actions. Therefore, he supposed that the essence of recursive consciousness resided in a transformation of multiple, multidirectional, unconscious processes into a linear, unidirectional process     

Effects of suramin on metastatic ability,proliferation, and production of urokinase-type plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12C-PM6

Effects of suramin, a polysulfonated naphthylurea compound, on metastatic ability, proliferation, and production of plasminogen activators and plasminogen activator inhibitors were studied using the highly metastatic human renal cell carcinoma cell line, SN12C-PM6. After renal subscapular implantation of tumor cells in nude mice, suramin significantly inhibited metastasis of tumor cells to the lungs and liver. In vitro growth of tumour cells was inhibited by suramin in a dose-dependent manner, at relatively low doses (ID₅₀ = 105 µg/ml). Plasminogen activator inhibitor type 2 (PAI-2) production by tumor cells was enhanced by suramin (100 µg/ml), whereas urokinase-type plasminogen activator (uPA) production was suppressed. Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin. Therefore suramin may be beneficial for the treatment of patients with an early stage of renal cancer with potential risk of metastasis.     

Polymorphous low-grade adenocarcinoma of submandibular gland origin

A case of polymorphous low-grade adenocarcinoma (PLGA) in the submandibular gland is reported. A 72 year old woman presented with a 5 year history of a gradually expanding tumor in the submandibular region. The surgical specimen revealed a relatively well demarcated tumor, 35 × 35 × 20 mm in size. Macroscopically, necrosis and hemorrhage were not seen in the solid tumor. Histologically, the tumor growth pattern was variable, composed of tubular, papillary, solid, trabecular and cribriform structures. Immunohistochemically, some tumor cells were positive for epithelial membrane antigen (EMA), S-100 protein, keratin, and carcino-embryonic antigen (CEA). Electron microscopically, prominent microvilli projected into the luminal spaces, and basal lamina and hemidesmosomes were seen in the tumor cells adjacent to the connective tissues. The submandibular gland is an extremely rare location for PLGA. To the authors' knowledge, this is the first case of its kind reported in the English literature.     

The structure of human metaphase chromosomes: its histological perspective and new horizons by atomic force microscopy

Studies on the structure of the human chromosome were reviewed from the histological perspective and discussed in connection with our recent findings obtained mainly by atomic force microscopy (AFM). In this paper, we introduce several hitherto known models of the high-order structure of the metaphase chromosome and discuss the actual structure of chromosomes in relation to such structures as spiral chromatids, chromosome bands, and chromosome scaffolds. In chromosomes treated with Ohnuki's hypotonic solution, the chromosome arms were elongated and showed a characteristic spiral pattern of chromatid fibers. On the other hand, alternating transverse ridges and grooves were clearly observed on the surface of chromosomes treated with 0.025% trypsin for G-banding, and these ridges and grooves corresponded to the dark and pale bands of G-banded chromosomes. Similar findings were also found in chromosomes treated with quinacrine mastards for Q-banding. Fibers bridging the gap between the sister chromatids were often observed in G/Q-banded chromosomes; these fibers tended to be restricted within the G/Q-positive portions, suggesting the presence of chromatin fibers bridging these regions. Based on these findings in conjunction with previous studies, we outlined the high-order structure of the human chromosome. Recent advances in nanotechnology have provided new AFM techniques for the imaging and handling of materials at nano-scale resolution. Application of these techniques to chromosome research is expected to provide valuable information on the chromosome structure in relation to its function.     

Direct clipping of a large basilar trunk aneurysm via the posterior petrosal (extended retrolabyrinthine presigmoid) approach--case report

A 53-year-old female presented with an unruptured, large basilar trunk aneurysm manifesting only as headache with no neurological deficits, including absence of cranial nerve dysfunction. Cerebral angiography disclosed a large aneurysm with a wide neck arising from the midbasilar artery. We treated the aneurysm surgically via the posterior petrosal approach. Five angled clips were applied sequentially to the aneurysm and the basilar artery was successfully reconstructed. Electrophysiological monitoring was continued during the operation and showed no changes. Following the operation, the patient suffered from transient right abducens nerve palsy, which persisted for 3 months. Postoperative angiography showed that the aneurysm was obliterated, and the patency of the basilar artery was preserved.     

Non-N-methyl-D-aspartate glutamate receptors mediate oxygen--glucose deprivation-induced oligodendroglial injury

Cells of oligodendroglial lineage are susceptible to oxygen and glucose deprivation. When oligodendrocyte-like cells differentiated from CG-4-immortalized rat O-2A progenitor cells were exposed to hypoxia alone or glucose deprivation alone for 48 h, release of lactate dehydrogenase (LDH) into the culture medium did not increase. However, when cells were deprived of both oxygen and glucose for 6 or 12 h preceding reoxygenation for 2 h, LDH release increased. Adding glucose to the medium protected against cell death and increased lactate production in a concentration-dependent manner. Cell damage induced by deprivation of oxygen and glucose was prevented by calcium-free medium or by non-N-methyl-D-aspartate glutamate receptor (GluR) antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione or LY293558, but not by the voltage-dependent calcium channel blocker, nimodipine, or by the N-methyl-D-aspartate GluR antagonist, MK-801. The glutamate concentration in the medium from cells exposed to oxygen-glucose deprivation for 12 h was 49.70+/-3.04 microM/l, which is sufficient to activate GluRs during deprivation of oxygen and glucose. Apoptotic cells detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) or Hoechst 33258 staining did not increase in cells exposed to oxygen-glucose deprivation for 12 h and subsequent reoxygenation for 2 h. No DNA laddering was detected by agarose gel electrophoresis from cells exposed to deprivation of oxygen and glucose. Neither acetyl-YVAD-CHO, an inhibitor of caspase-1-like proteases, nor acetyl-DEVD-CHO, an inhibitor of caspase-3-like proteases, prevented oxygen-glucose deprivation-induced injury. Thus, oxygen and glucose deprivation causes calcium-influx-induced necrotic cell damage in cells of oligodendroglial lineage via non-N-methyl-D-aspartate GluR channels.     

Guidelines for treatment of ulcerative colitis in children

This paper introduces the guidelines for treatment of ulcerative colitis in children, created by the working group of the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (Chair: Yuichiro Yamashiro) and the Japanese Society for Pediatric Inflammatory Bowel Disease (IBD) (Chair: Akio Kobayashi). The ideas of the working group, with regard to the fundamental differences in medical treatment between children and adults, included: (1) for children, intensive medical treatment including appropriate systemic management is important during the acute phase of illness. (2) Treatment with steroids, which can cause growth disturbances, should not be continued for long periods of time. (3) Pulsed steroid therapy, selective removal of blood cells, and intravenous infusion of cyclosporin should be included in the therapeutic option for severe and fluminant cases.