Wnt activation disturbs cell competition and causes diffuse invasion of transformed cells through NF-κB-MMP21 pathway.

Normal epithelial cells exert their competitive advantage over RasV12-transformed cells and eliminate them into the apical lumen via cell competition. However, the internal or external factors that compromise cell competition and provoke carcinogenesis remain elusive. In this study, we examine the effect of sequential accumulation of gene mutations, mimicking multi-sequential carcinogenesis on RasV12-induced cell competition in intestinal epithelial tissues. Consequently, we find that the directionality of RasV12-cell extrusion in Wnt-activated epithelia is reversed, and transformed cells are delaminated into the basal lamina via non-cell autonomous MMP21 upregulation. Subsequently, diffusively infiltrating, transformed cells develop into highly invasive carcinomas. The elevated production of MMP21 is elicited partly through NF-κB signaling, blockage of which restores apical elimination of RasV12 cells. We further demonstrate that the NF-κB-MMP21 axis is significantly bolstered in early colorectal carcinoma in humans. Collectively, this study shows that cells with high mutational burdens exploit cell competition for their benefit by behaving as unfit cells, endowing them with an invasion advantage.

Clinical characteristics of healthcare-associated pneumonia in a public hospital in a metropolitan area of Japan.

Healthcare-associated pneumonia (HCAP) is a new category that is essential in the present aging society. Knowing the different characteristics and outcomes between patients with HCAP and community-acquired pneumonia (CAP) would help physicians manage and treat HCAP patients. Although HCAP is thought to be heterogeneous in regions, there are no reports from a metropolitan area in Japan. We retrospectively reviewed the clinical findings of all consecutive pneumonia patients who required hospitalized care in our hospital between April 2006 and March 2010. There were 184 (35.0%) patients with HCAP and 342 (65.0%) patients with CAP. Previous hospitalization within 90 days of the infection was the most common criterion for HCAP (63.0%). HCAP patients were significantly older than CAP patients (82.5 vs. 70.0 years, P < 0.001). The percentage of patients with poor functional status was higher in HCAP than CAP (64.0% vs. 26.6%, P < 0.001). Hospital mortality was significantly higher in HCAP patients than in CAP patients (15.8% vs. 5.0%, P < 0.001). Low levels of serum albumin (odds ratio, 0.126; 95% CI, 0.025-0.640; P = 0.012) and high scores in the ADROP (age, dehydration, respiratory failure, orientation, and blood pressure) system (odds ratio, 2.846; 95% CI, 1.449-5.587; P = 0.002) were the risk factors for HCAP mortality. In conclusion, patients with HCAP have different epidemiological characteristics compared with those with CAP in a metropolitan area of Japan. Outcomes and risk factors for mortality of patients with HCAP included poor nutritional status and high severity scores on the pneumonia severity scoring system.

[A case of sarcoidosis with an endobronchial polypoid lesion].

A 59-year-old woman complained of impaired vision. She visited an ophthalmologist and glaucoma was diagnosed. In July 200X, she was admitted to our hospital for further examination. Chest radiography and CT showed lymphadenopathy in the mediastinum and bilateral hilum. Bronchofiberscopy revealed mucosal hypervascularity and a polypoid lesion at the orifice of the left B8a. A transbronchial biopsy specimen of the polypoid lesion showed non-caseating epithelioid cell granuloma. On bronchoalveolar lavage, both the proportion of lymphocytes and the CD 4/8 ratio had increased. We diagnosed sarcoidosis with an endobronchial polypoid lesion. The patient has been observed without therapy since, and after a year the polypoid lesion is the same size on 3D CT scans. This is a very rare case of endobronchial sarcoidosis presenting as a polypoid lesion.

[Pulmonary non-tuberculous mycobacteriosis (Mycobacterium intracellulare) with cavities developing in a non-small cell lung cancer patient during chemotherapy].

A 70-year-old man was admitted to our hospital for examination of an abnormal shadow found on a chest radiograph. Chest CT showed a nodular shadow in the left upper lobe S1+2. We diagnosed non-small cell lung cancer (squamous cell carcinoma) clinical stage T4N2M1. Chemotherapy consisting of carboplatin and weekly paclitaxel was begun. After the second course of chemotherapy, another nodular shadow with small cavities in the left lower lobe S6 was seen, and which then increased in size. Bronchial lavage revealed a diagnosis of non-tubercular mycobacteriosis (Mycobacterium intracellulare). Anti-NTM chemotherapy consisting of rifampicin, ethambutol and clarithromycin was started in addition to anticancer chemotherapy, without severe side effects. Although there are some reports of the co-occurrence of lung cancer and non-tuberculous mycobacteriosis, this apparently rare case involved the appearance of a solitary nodule with a cavity caused by pulmonary non-tuberculous mycobacteriosis during anticancer chemotherapy.

Direct hemoperfusion with polymyxin-B-immobilized fiber columns improves septic hypotension and reduces inflammatory mediators in septic patients with colorectal perforation.

PURPOSE: Although some studies have reported favorable effects of direct hemoperfusion with polymyxin-B-immobilized fiber columns (PMX) for the treatment of septic shock, few studies have demonstrated the efficacy of PMX in studies with a uniform case definition and without any other blood purification techniques. MATERIALS AND METHODS: Fifty-two patients with severe sepsis or septic shock secondary to colorectal perforation were treated with PMX. Hemodynamic alterations and plasma concentrations of endotoxin, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, and IL-10 were evaluated following PMX treatment. RESULTS: We observed a significant reduction in plasma endotoxin in the nonsurvivors immediately after PMX treatment compared to before treatment. Systolic blood pressure was markedly increased and circulating levels of IL-1beta, IL-1Ra, and IL-8 were significantly reduced during a 2-h interval of PMX. CONCLUSIONS: Our findings suggested that PMX treatment appears to adsorb endotoxin and also modulates circulating cytokine during a 2-h interval of direct hemoperfusion in septic patients with such condition.

[Clinical statistics of outpatients investigated for asbestos-related lung diseases at a general hospital in Tokyo].

We evaluated 122 outpatients who visited our hospital for examination of asbestos-related diseases between November, 2005 and October, 2006. Patients were divided into three groups; occupational exposure, non-occupational exposure and non-exposure groups. The occupational exposure group showed a significantly higher rate of asbestos-related abnormal findings than the non-occupational exposure plus the non-exposure group (33% vs. 5%, respectively; P = 0.001). Pleural plaque was the most common abnormal finding related to asbestos. Only four of 24 patients with pleural plaques could obtain personal health records for workers enjoyed in dangerous work, whereas the rest of them were not able to mainly because they were self-employed. A health support system is necessary to also cover non-employees.

[A case of bird related hypersensitivity pneumonitis had a progressive course].

A 50-year-old woman was admitted due to productive cough continuing for 3 years. A chest computed tomography showed appearance of nonspecific interstitial pneumonia (NSIP). Thoracoscopic lung biopsy specimens showed mainly a pattern of NSIP with multinucleated cells and cholesterol clefts. She was not a bird fancier, but had indirect exposure to birds in her living environment, and had been using feather-filled duvets for a long time. We established a diagnosis of bird-related hypersensitivity pneumonitis based on antibodies in serum positive to pigeon dropping extracts. She was treated by coadministration of corticosteroids and immunosuppressants, and avoidance of bird-related antigens, but had a progressive course and died of respiratory failure.

Association between embryonic loss and damage to the zona pellucida by invasive micromanipulation during oviductal transfer of early-stage embryos in pigs.

The aim of this study was to examine the impact of zona pellucida damage, which might arise during somatic cell nuclear transfer (SCNT), on the development and survival of transferred embryos. The zonae pellucidae of in vitro matured oocytes were either punctured with 8- to 10-microm square-ended nuclear injection pipettes and piezo pulses or slit with 35- to 40-microm enucleation pipettes. Intact oocytes were used as controls. These oocytes were electroactivated to induce parthenogenesis and transferred to the oviducts of estrus-synchronized recipient gilts. After 5 to 7 days, the recipient uteri were flushed to collect embryos, and embryonic development (morula-blastocyst stage embryos/collected embryos) and survival (viable embryos/collected embryos) were determined. In total, 221 zona-punctured, 129 zona-slitted and 57 intact embryos were transplanted into four, two and two gilts, respectively. The efficiency of embryo recovery was similar in all groups (64.3 to 79.1%). However, the zona-penetrated and incised embryos exhibited unstable development and survival compared with the controls; development and survival of the control embryos were 94.7 and 87.7%, whereas those of the zona-punctured embryos were 69.0 and 47.9% (P<0.01) and those of the zona-slit embryos were 64.7 and 50.0% (P<0.01). Cells with large foci that appeared to be macrophage giant cells were observed at the surface or inside the degenerated zona-damaged embryos. These results indicate that the recipient's immune response to damage to the zona pellucida may impair embryonic development after transplantation to the oviduct. This may be one of the factors causing the reduced efficiency of live progeny production by SCNT.

Dermoscopic features of mucinous carcinoma of the skin.

BACKGROUND: Dermoscopic features of nonpigmented skin lesions are seldom reported; dermoscopy might be useful in speculating pathologic features in the upper dermis. OBJECTIVE: The objective was to identify additional dermoscopic criteria. METHODS: Dermoscopy of the mucinous carcinoma of the skin occurring on the cheek of a 69-year-old man was performed. RESULTS: We have shown characteristic dermoscopic features of whitish network and light-brown globules and they correspond to the pathologic findings of fibrous septum and mucinous deposition, respectively. DISCUSSION: Dermoscopic examination seemed useful as an adjunct to the diagnosis of this rare nonpigmented malignant neoplasm.

A randomized clinical trial comparing transjugular intrahepatic portosystemic shunt with endoscopic sclerotherapy in the long-term management of patients with cirrhosis after recent variceal hemorrhage.

The aim of this study was to compare the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with that of endoscopic sclerotherapy (ES) in the long-term management of patients with cirrhosis after variceal bleeding. Seventy-eight consecutive cirrhotic patients with recent variceal bleeding were randomly allocated to either TIPS (n=38) or ES (n=40). All patients were in good condition at randomization. The mean follow-up was 1116+/-92 days in the TIPS group and 1047+/-102 days in the ES group. Differences in rebleeding from any source (18.4% vs. 32.5%) and esophageal variceal rebleeding (15.7% vs. 27.5%) were not significantly different between the two groups (P>0.05). The mortality rates were similar in both treatment groups. Shunt dysfunction was noted in 27 patients (71%) in the TIPS group. There were more numbers of rehospitalization during follow-up in the TIPS group than in the ES group (2.6+/-0.4 vs. 1.1+/-0.2) (P<0.01). TIPS and ES are equally effective in the prevention of variceal rebleeding. However, TIPS is associated with high incidence of shunt dysfunction, which lead to more rehospitalization. Therefore, TIPS may not be a first-line treatment for the prevention of variceal rebleeding in cirrhotic patients who are in stable condition.