Notch1 and Notch3 Instructively Restrict bFGF-Responsive Multipotent Neural Progenitor Cells to an Astroglial Fate

AbstractNotch1 has been shown to induce glia in the peripheral nervous system. However, it has not been known whether Notch can direct commitment to glia from multipotent progenitors of the central nervous system. Here we present evidence that activated Notch1 and Notch3 promotes the differentiation of astroglia from the rat adult hippocampus-derived multipotent progenitors (AHPs). Quantitative clonal analysis indicates that the action of Notch is likely to be instructive. Transient activation of Notch can direct commitment of AHPs irreversibly to astroglia. Astroglial induction by Notch signaling was shown to be independent of STAT3, which is a key regulatory transcriptional factor when ciliary neurotrophic factor (CNTF) induces astroglia. These data suggest that Notch provides a CNTF-independent instructive signal of astroglia differentiation in CNS multipotent progenitor cells

Extensive genomic diversity and selective conservation of virulence determinants in enterohemorrhagic Escherichia coli strains of O157 and non O157 serotypes

Background: Enterohemorrhagic Escherichia coli (EHEC) O157 causes severe food-borne illness in humans. The chromosome of O157 consists of 4.1 Mb backbone sequences shared by benign E. coli K-12, and 1.4 Mb O157-specific sequences encoding many virulence determinants, such as Shiga toxin genes (stx genes) and the locus of enterocyte effacement (LEE). Non-O157 EHECs belonging to distinct clonal lineages from O157 also cause similar illness in humans. According to the "parallel" evolution model, they have independently acquired the major virulence determinants, the stx genes and LEE. However, the genomic differences between O157 and non-O157 EHECs have not yet been systematically analyzed. Results: Using microarray and whole genome PCR scanning analyses, we performed a whole genome comparison of 20 EHEC strains of O26, O111, and O103 serotypes with O157. In non-O157 EHEC strains, although genome sizes were similar with or rather larger than O157 and the backbone regions were well conserved, O157-specific regions were very poorly conserved. Around only 20% of the O157- specific genes were fully conserved in each non-O157 serotype. However, the non-O157 EHECs contained a significant number of virulence genes that are found on prophages and plasmids in O157, and also multiple prophages similar to, but significantly divergent from, those in O157. Conclusion: Although O157 and non-O157 EHECs have independently acquired a huge amount of serotype- or strain-specific genes by lateral gene transfer, they share an unexpectedly large number of virulence genes. Independent infections of similar but distinct bacteriophages carrying these virulence determinants are deeply involved in the evolution of O157 and non-O157 EHECs

“Cheese wire” fenestration of a chronic aortic dissection flap for endovascular repair of a contained aneurysm rupture

A 70-year-old man presented with a contained aortic rupture above the aortic bifurcation in the setting of a chronic type B aortic dissection. The celiac and right iliac arteries were supplied by the false lumen, and the superior mesenteric, left iliac, and bilateral renal arteries were supplied by the true lumen. An open repair was not possible due to right-sided heart failure. The “cheese wire” maneuver is a technique used to fenestrate an intimal flap, alleviating malperfusion in aortic dissection. In our modification, a Glidewire (Terumo Medical, Somerset, NJ) was passed across the intimal flap using a Ross Modified Colapinto needle (Cook Medical, Bloomington, Ind) and pulled downward to shear through the membrane to the aortic bifurcation. The fenestration was followed by a unibody endograft stent repair across the contained rupture

Pancreatic β Cell–specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes

The cytotoxicity of reactive oxygen intermediates (ROIs) has been implicated in the destruction of pancreatic β cells in insulin-dependent diabetes mellitus (IDDM). Thioredoxin (TRX), a redox (reduction/oxidation)-active protein, has recently been shown to protect cells from oxidative stress and apoptosis. To elucidate the roles of oxidative stress in the development of autoimmune diabetes in vivo, we produced nonobese diabetic transgenic mice that overexpress TRX in their pancreatic β cells. In these transgenic mice, the incidence of diabetes was markedly reduced, whereas the development of insulitis was not prevented. Moreover, induction of diabetes by streptozotocin, an ROI-generating agent, was also attenuated by TRX overexpression in β cells. This is the first direct demonstration that an antioxidative and antiapoptotic protein protects β cells in vivo against both autoimmune and drug-induced diabetes. Our results strongly suggest that oxidative stress plays an essential role in the destruction of β cells by infiltrating inflammatory cells in IDDM

Nosocomial Infection with Serratia marcescens: Comparison of Bacteriocin Types and Antibiograms between Two University Hospitals

Nosocomial distribution of Serratia marcescens at two university hospitals was studied by bacteriocin typing and antibiogram from January 1981 to July 1983, and the results were compared. The 126 strains isolated from Medical College Hospital of Oita (MCHO) consisted mainly of bacteriocin types 4 (29%), 9 (23%), 52 (19%) and 42 (6%) , and the 86 from Nagasaki University Hospital (NUH) were mainly of types 14 (20%) , 4 (17%), 9 (12%) and 26 (12%); these four types amounted to 77% and 61% respectively. Types 4 and 9 which formed a high proportion of isolates at both hospitals were apparently the most common bacteriocin types. Using 154 strains of the bacteriocin types 4 , 9, 14, 26, 42 and 52 of S. marcescens, antibiogram with 13 antimicrobial agents was tested. The strains isolated from MCHO were found to be more resistant than those from NUH. The isolates of S. marcescens at each hospital showed characteristic , different distribution in bacteriocin type and antibiogram. The close relation was not always observed between antibiograms and bacteriocin types

Clinicopathological Study of 50 Cases of Lung Cancer Associated with Silicosis

To clarify any causal relationship between lung cancer and silicosis, we studied clinicopathological findings in 50 men, mainly tunneling workers, aged from 47 to 85 years with both diseases. The histological types were : squamous cell carcinoma, 29 cases; small cell carcinoma, 10; adenocarcinoma, 6 ; large cell carcinoma, 4 ; and adenosquamous carcinoma, 1. The high frequency of cancer, particularly squamous and small cell cancer, in sites of silicotic fibrosis suggested a causal relationship, perhaps via a carcinogen. If a weak carcinogen accumulastes in fibrotic leasions, its prolonged presence may induce cancer. We believe that silica alone is rarely carcinogenic, but it may interact with polycyclin aromatic hydrocarbons from cigarette smoking or from pyrolysis, or with other substances encountered in occupational environments

Evaluation of an Experimental Animal Model for Estimating the Pathogenicity and the Efficacy of Antibiotic Treatment in Bacterial Infection

An experimental model of intracutaneous infection in the guinea pig, which was based on the study of MILES et al. (Br. J. Exp. Path. 38: 79-96, 1957) :and MASKELL (J. Med. Microbiol. 14: 131-140, 1981), was used to investigate the pathogenicity and the effect of chemotherapy with lincomycin, using 36 strains of the genus Bacteroides. The pathogenicity was estimated by intracutaneous injection of 0.1-ml quantities of bacterial suspension into guinea pigs and the value was expressed as the number of inoculated organisms required to induce a skin lesion 10 mm in diameter 24 hours after injection. Bacteroides fragilis was, on average, three times as pathogenic as non-B. fragilis strains (p<0.1). Two intramuscular injections of lincomycin were more effective than a single one against the intracutaneous infection, and the lower was the MIC value, the greater was the effect (p<0.001). This experimental animal model was simple and convenient for estimating the pathogenicity and efficacy of antimicrobial agents. However, the skin lesions were often not clear if the bacteria with low virulence were inoculated and the induced infection is not natural

Effects of substitutions of glycine and asparagine for serine132 on activity and binding of human lipoprotein lipase to very low density lipoproteins

AbstractFor studying the role of Ser132 in the putative catalytic site of human lipoprotein lipase (LPL), mutant LPL cDNAs expressing LPLs with amino acid substitutions of Gly or Asn for Ser132 were obtained by site-directed mutagenesis, and were expressed in COS-1 cells. Considerable amounts of LPL enzyme protein mass were detected in the culture medium of COS-1 cells transfected with wild-type LPL, LPL-Gly132, or LPL-Asn132. LPL-Gly132 hydrolyzed Triton X-100-triolein and tributyrin as effectively as wild-type LPL, whereas LPL-Asn132 showed no activity. LPL-Asn132 bound to very low density lipoproteins as effectively as wild-type LPL

Variability Time Scales of TeV Blazars Observed in the ASCA Continuous Long-Look X-ray Monitoring

Three uninterrupted, long (lasting respectively 7, 10, and 10 days) ASCA observations of the well-studied TeV-bright blazars Mrk 421, Mrk 501 and PKS 2155-304 all show continuous strong X-ray flaring. Despite the relatively faint intensity states in 2 of the 3 sources, there was no identifiable quiescent period in any of the observations. Structure function analysis shows that all blazars have a characteristic time scale of ~ a day, comparable to the recurrence time and to the time scale of the stronger flares. On the other hand, examination of these flares in more detail reveals that each of the strong flares is not a smooth increase and decrease, but exhibits substructures of shorter flares having time scales of ~10 ks. We verify via simulations that in order to explain the observed structure function, these shorter flares ("shots") are unlikely to be fully random, but in some way are correlated with each other. The energy dependent cross-correlation analysis shows that inter-band lags are not universal in TeV blazars. This is important since in the past, only positive detections of lags were reported. In this work, we determine that the sign of a lag may differ from flare to flare; significant lags of both signs were detected from several flares, while no significant lag was detected from others. However, we also argue that the nature of the underlying component can affect these values. The facts that all flares are nearly symmetric and that fast variability shorter than the characteristic time scale is strongly suppressed, support the scenario where the light crossing time dominates the variability time scales of the day-scale flares.Comment: 29 pages, 12 figures, accepted for publication in Ap