Invasive mucinous adenocarcinoma mimicking organizing pneumonia associated with Mycobacterium fortuitum infection.

We herein report the case of a 68-year-old man diagnosed with invasive mucinous adenocarcinoma of the lungs. Chest computed tomography showed subpleural ground-glass opacity and small nodules with cavitation. A culture of the bronchoalveolar lavage fluid resulted in the detection of Mycobacterium fortuitum.

Cathepsin E deficiency impairs autophagic proteolysis in macrophages.

Cathepsin E is an endosomal aspartic proteinase that is predominantly expressed in immune-related cells. Recently, we showed that macrophages derived from cathepsin E-deficient (CatE(-/-)) mice display accumulation of lysosomal membrane proteins and abnormal membrane trafficking. In this study, we demonstrated that CatE(-/-) macrophages exhibit abnormalities in autophagy, a bulk degradation system for aggregated proteins and damaged organelles.

(-)-Xanthatin induces the prolonged expression of c-Fos through an N-acetyl-L-cysteine (NAC)-sensitive mechanism in human breast cancer MDA-MB-231 cells.

We reported that (-)-xanthatin, a xanthanolide sesquiterpene lactone present in the Cocklebur plant, exhibited potent anti-proliferative effects on human breast cancer cells, in which GADD45γ, a novel tumor suppressor gene, was induced. Mechanistically, topoisomerase IIα (Topo IIα) inhibition by (-)-xanthatin was shown to be the upstream trigger that stimulated the expression of GADD45γ mRNA and concomitantly produced reactive oxygen species (ROS) to maintain this expression. Since the anti-cancer drug etoposide, a selective Topo IIα inhibitor, has also been shown to induce intracellular ROS, (-)-xanthatin may exert its anti-proliferative effects on cancer cells in a similar manner to those of etoposide.

Δ(9)-Tetrahydrocannabinol disrupts estrogen-signaling through up-regulation of estrogen receptor β (ERβ).

Δ(9)-Tetrahydrocannabinol (Δ(9)-THC) has been reported as possessing antiestrogenic activity, although the mechanisms underlying these effects are poorly delineated. In this study, we used the estrogen receptor α (ERα)-positive human breast cancer cell line, MCF-7, as an experimental model and showed that Δ(9)-THC exposures markedly suppresses 17β-estradiol (E2)- induced MCF-7 cell proliferation. We demonstrate that these effects result from Δ(9)-THC's ability to inhibit E2-liganded ERα activation.

Induction of the fatty acid 2-hydroxylase (FA2H) gene by Δ(9)-tetrahydrocannabinol in human breast cancer cells.

To investigate gene(s) being regulated by ∆(9)-tetrahydrocannabinol (∆(9)-THC), we performed DNA microarray analysis of human breast cancer MDA-MB-231 cells, which are poorly differentiated breast cancer cells, treated with ∆(9)-THC for 48 hr at an IC50 concentration of approximately 25 µM. Among the highly up-regulated genes (> 10-fold) observed, fatty acid 2-hydroxylase (FA2H) was significantly induced (17.8-fold).

(-)-Xanthatin up-regulation of the GADD45γ tumor suppressor gene in MDA-MB-231 breast cancer cells: role of topoisomerase IIα inhibition and reactive oxygen species.

Previously, we reported that (-)-xanthatin, a naturally occurring xanthanolide present in the Cocklebur plant, exhibits potent anti-proliferative effects on human breast cancer cells, accompanied by an induction of the growth arrest and DNA damage-inducible gene 45γ (GADD45γ), recognized recently as a novel tumor suppressor gene. However, the mechanisms mediating this activation were unknown. Topoisomerase IIα (Topo IIα) inhibition has been reported to produce a cell death response accompanied by an atypical DNA laddering fragmentation profile, similar to that noted previously for (-)-xanthatin.

Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration.

Cannabidiol (CBD), a major non-psychotropic constituent of fiber-type cannabis plant, has been reported to possess diverse biological activities, including anti-proliferative effect on cancer cells. Although CBD is obtained from non-enzymatic decarboxylation of its parent molecule, cannabidiolic acid (CBDA), few studies have investigated whether CBDA itself is biologically active. Results of the current investigation revealed that CBDA inhibits migration of the highly invasive MDA-MB-231 human breast cancer cells, apparently through a mechanism involving inhibition of cAMP-dependent protein kinase A, coupled with an activation of the small GTPase, RhoA.

[Signet ring cell carcinoma of the bile duct: a case report].

A 72-year-old man was admitted with obstructive jaundice. Computed tomography revealed a 4cm tumor with multiple cystic components obstructing the common bile duct. Endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography and intraductal ultrasonography demonstrated the tumor, which derived from the lower bile duct, grew into the bile duct lumen.

Role of the transcription factor Sp1 in regulating the expression of the murine cathepsin E gene.

Cathepsin E (CE) is an intracellular aspartic proteinase that is exclusively expressed in cells of the gastrointestinal tracts, lymphoid tissues, urinary organs and red blood cells. However, the molecular mechanism by which CE is predominantly expressed in these cells remains unknown. Here, we report the identification of several transcription start sites of the CE gene and their regulatory factors in gastric adenosarcoma cells.

Cannabidiol-2',6'-dimethyl ether as an effective protector of 15-lipoxygenase-mediated low-density lipoprotein oxidation in vitro.

15-Lipoxygenase (15-LOX) is one of the key enzymes responsible for the formation of oxidized low-density lipoprotein (ox-LDL), a major causal factor for atherosclerosis. Both enzymatic (15-LOX) and non-enzymatic (Cu(2+)) mechanisms have been proposed for the production of ox-LDL. We have recently reported that cannabidiol-2',6'-dimethyl ether (CBDD) is a selective and potent inhibitor of 15-LOX-catalyzed linoleic acid oxygenation (Takeda et al.

(--)-Xanthatin selectively induces GADD45γ and stimulates caspase-independent cell death in human breast cancer MDA-MB-231 cells.

exo-Methylene lactone group-containing compounds, such as (--)-xanthatin, are present in a large variety of biologically active natural products, including extracts of Xanthium strumarium (Cocklebur). These substances are reported to possess diverse functional activities, exhibiting anti-inflammatory, antimalarial, and anticancer potential. In this study, we synthesized six structurally related xanthanolides containing exo-methylene lactone moieties, including (--)-xanthatin and (+)-8-epi-xanthatin, and examined the effects of these chemically defined substances on the highly aggressive and farnesyltransferase inhibitor (FTI)-resistant MDA-MB-231 cancer cell line.

The role of cathepsin E in terminal differentiation of keratinocytes.

Cathepsin E (CatE) is predominantly expressed in the rapidly regenerating gastric mucosal cells and epidermal keratinocytes, in addition to the immune system cells. However, the role of CatE in these cells remains unclear. Here we report a crucial role of CatE in keratinocyte terminal differentiation.

Quantum chemical molecular dynamics simulation of single-walled carbon nanotube cap nucleation on an iron particle.

The atomic scale details of single-walled carbon nanotube (SWNT) nucleation on metal catalyst particles are elusive to experimental observations. Computer simulation of metal-catalyzed SWNT nucleation is a challenging topic but potentially of great importance to understand the factors affecting SWNT diameters, chirality, and growth efficiency. In this work, we use nonequilibrium density functional tight-binding molecular dynamics simulations and report nucleation of sp(2)-carbon cap structures on an iron particle consisting of 38 atoms.

Rapid growth of a single-walled carbon nanotube on an iron cluster: density-functional tight-binding molecular dynamics simulations.

Continued growth of a single-walled carbon nanotube (SWNT) on an Fe cluster at 1500 K is demonstrated using quantum chemical molecular dynamics simulations based on the self-consistent-charge density-functional tight-binding (SCC-DFTB) method. In order to deal with charge transfer between carbon and metal particles and the multitude of electronic states, a finite electronic temperature approach is applied. We present trajectories of 45 ps length, where a continuous supply of carbon atoms is directed toward the C-Fe boundary between a 7.

Impaired chemotaxis and cell adhesion due to decrease in several cell-surface receptors in cathepsin E-deficient macrophages.

Cathepsin E is an endo-lysosomal aspartic proteinase exclusively present in immune system cells. Previous studies have shown that cathepsin E-deficient (CatE(-/-)) mice display aberrant immune responses such as atopic dermatitis and higher susceptibility to bacterial infection. However, the mechanisms underlying abnormal immune responses induced by cathepsin E deficiency are still unclear.

Direct metagenomic detection of viral pathogens in nasal and fecal specimens using an unbiased high-throughput sequencing approach.

With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a "next-generation" parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.

[The program of Founding Research Centers for Emerging and Reemerging Infectious Diseases: the present status and future prospects].

The program of Founding Research Centers for Emerging and Reemerging Infectious Diseases was commenced in 2005 with an outline for Japanese universities and research institutions to establish bilateral collaboration research bases in countries where emerging and reemerging infections are breaking out or will likely break out. So far, six universities and two institutions are participating in the program and ten collaboration bases have been established in six countries (five in Asia and one in Africa). Each research base aims to contribute to the security and safety of the partner and own countries by facilitating better understanding of infectious diseases, technology innovation in diagnosis, therapy and prevention, and human resources development.

Cathepsin E prevents tumor growth and metastasis by catalyzing the proteolytic release of soluble TRAIL from tumor cell surface.

The aspartic proteinase cathepsin E is expressed predominantly in cells of the immune system and highly secreted by activated phagocytes, and deficiency of cathepsin E in mice results in a phenotype affecting immune responses. However, because physiologic substrates for cathepsin E have not yet been identified, the relevance of these observations to the physiologic functions of this protein remains speculative. Here, we show that cathepsin E specifically induces growth arrest and apoptosis in human prostate carcinoma tumor cell lines without affecting normal cells by catalyzing the proteolytic release of soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from the cell surface.

Cathepsin E deficiency induces a novel form of lysosomal storage disorder showing the accumulation of lysosomal membrane sialoglycoproteins and the elevation of lysosomal pH in macrophages.

Cathepsin E, an endolysosomal aspartic proteinase predominantly expressed in cells of the immune system, has an important role in immune responses. However, little is known about the precise roles of cathepsin E in this system. Here we report that cathepsin E deficiency (CatE(-/-)) leads to a novel form of lysosome storage disorder in macrophages, exhibiting the accumulation of the two major lysosomal membrane sialoglycoproteins LAMP-1 and LAMP-2 and the elevation of lysosomal pH.

Cathepsin E-deficient mice show increased susceptibility to bacterial infection associated with the decreased expression of multiple cell surface Toll-like receptors.

Cathepsin E, an intracellular aspartic proteinase, is predominantly localized in the endosomal compartments of immune system cells. In the present study, we investigated the role of cathepsin E in immune defense systems against bacterial infection. Cathepsin E-deficient (CatE(-/-)) mice showed dramatically increased susceptibility to infection with both the Gram-positive bacterium Staphyrococcus aureus, and the Gram-negative bacterium Porphyromonas gingivalis when compared with syngeneic wild-type mice, most likely due to impaired regulation of bacterial elimination.

No high-mass protostars in the silhouette young stellar object M17-SO1.

The birth of very massive stars is not well understood, in contrast to the formation process of low-mass stars like our Sun. It is not even clear that massive stars can form as single entities; rather, they might form through the mergers of smaller ones born in tight groups. The recent claim of the discovery of a massive protostar in M17 (a nearby giant ionized region) forming through the same mechanism as low-mass stars has therefore generated considerable interest.

An early extrasolar planetary system revealed by planetesimal belts in beta Pictoris.

beta Pictoris (beta Pic) is a main-sequence star with an edge-on dust disk that might represent a state of the early Solar System. The dust does not seem to be a remnant from the original protoplanetary disk, but rather is thought to have been generated from large bodies like planetesimals and/or comets. The history and composition of the parent bodies can therefore be revealed by determining the spatial distribution, grain size, composition and crystallinity of the dust through high-resolution mid-infrared observations.

Association of cathepsin E deficiency with development of atopic dermatitis.

Atopic dermatitis (AD) is a pruritic inflammatory skin diseases associated with a family history of atropy. Here we show that mice lacking the endolysosomal aspartic proteinase cathepsin E spontaneously develop skin lesions similar to those of humans with AD when reared under conventional conditions but not under specific pathogen-free conditions. These mice showed the increase in the ratio of CD4+/CD8+ T cells, the strong polarization of naïve T cells to T helper 2 cells, and the systemic accumulation of IL-18 and IL-1beta accompanied by a marked increase in IL-4, IL-5, and IgE.

[Recovery of intersubjectivity and empathy in schizophrenics: through a characteristic type of friendship "frolicking"].

The author has noticed a characteristic form of close, frolicsome friendship between recovering adolescent schizophrenic patients. It occurs in groups of young patients in a psychiatric clinic and in a day-care institution. Through this type of friendship, their intersubjectivity, ability for empathy and human relations develop, essential changes for the amelioration of schizophrenia.