Detection of Legionella pneumophila serogroup 1 in blood cultures from a patient treated with tumor necrosis factor-alpha inhibitor

A 65-year-old man was admitted to our hospital with a temperature of 39.3 °C, cough, sputum, and pharyngeal discomfort that had persisted for 3 days. He had been treated with methotrexate and adalimumab (a tumor necrosis factor-alpha [TNF-α] inhibitor) for rheumatoid arthritis for 2 years, and he had also been treated with S-1 (tegafur, gimeracil, and oteracil potassium) for pancreatic metastasis of gastric cancer for 2 months. Regardless of the underlying pathologies, his general condition was good and he had worked as an electrician until 2 days before admission. However, his appetite had suddenly decreased from the day before admission, and high fever and hypoxia were also evident upon admission. A chest X-ray and computed tomography scan revealed left pleural effusion and consolidation in both lungs. The pneumonia severity index score was 165 and the risk class was V. Accordingly, we started to treat the pneumonia with a combination of levofloxacin and meropenem. Thereafter, we received positive urinary antigen test findings for Legionella pneumophila. After hospitalization, hypoxia was progressed and hypotension was emerged. Despite the application of appropriate antibiotics, vasopressors, and oxygenation, the patient died 8 h after admission. Even after his death, blood cultures were continued to consider the possibility of bacterial co-infection. Although no bacteria were detected from blood cultures, Gimenez staining revealed pink bacteria in blood culture fluids. Subsequent blood fluid culture in selective medium revealed L. pneumophila serogroup 1. Recently, TNF-α inhibitors have been described as a risk factor for Legionnaires’ disease. In consideration of the increased frequency of TNF-α inhibitors, we may need to recognize anew that L. pneumophila might be a pathogen of severe community-acquired pneumonia.     

Low-dose hypersensitivity in nucleus-irradiated V79 cells studied with synchrotron X-ray microbeam

This study aims at elucidating the cellular responses induced by energy deposition in the cell nucleus or cytoplasm in the low-dose (< 1 Gy) region. We compared the survival fraction of V79 cells irradiated with X-ray microbeams of different sizes. Entire cells or cell nuclei were targeted with 5.35 keV monochromatic X-ray microbeams using a synchrotron radiation (SR) X-ray microbeam irradiation apparatus. Using a threshold of 30 cells/colony after 60 h of incubation, conditions that had been proven to give results equivalent to those of the conventional method, we determined the survival fraction of the microbeam-irradiated cells. When cell nuclei were irradiated with 10 x 10 microm (2) X-ray beams, the survival fraction was almost the same as that obtained with 50 x 50 microm (2) beams except in the low-dose region. In the low-dose region irradiated with 10 x 10 microm (2) beams, hyper-radiosensitivity (HRS) was clearly observed in the nucleus-irradiated cells, and the survival curve exhibited a minimum of about 60% at 0.5 Gy. This may be the most distinct HRS reported thus far when an asynchronous population is used. Difference in observed HRS phenomena is solely due to the irradiated part in the cell. These results suggest that energy deposition in the cytoplasm might suppress the HRS.     

Interobserver and intraobserver variation in endoscopic assessment of GERD using the “Los Angeles” classification

Background: A new endoscopic classification of gastroesophageal reflux disease (GERD) has been proposed, and the term mucosal break has been introduced to describe mucosal damage. This new classification was evaluated by endoscopists with different levels of experience. Methods: Fifty endoscopic photographs for each of 20 randomly selected patients with GERD were assessed retrospectively by three groups of seven endoscopists classified by experience: group 1 (100 to 500 procedures), group 2 (500 to 3000), and group 3 (more than 3000). The new classification was modified by adding grade 0 to describe healed mucosal breaks, so that there were five grades. All photographs were assessed twice at an interval of more than 1 week, and κ statistics were used to determine observer variation. Results: Interobserver variation within group 3 (κ = 0.39, n = 21) and between groups 3 and 2 (κ = 0.36, n = 49) was significantly different (p < 0.01) from that between groups 3 and 1 (κ = 0.26, n = 49). Intraobserver variation in group 1 (κ = 0.39, n = 7) was significantly different (p < 0.01) from that in group 2 (κ = 0.51, n = 7) and group 3 (κ = 0.54, n = 7). Conclusions: Observer variation depends on level of endoscopic experience. Only experienced endoscopists should use the new classification for grading of GERD. (Gastrointest Endosc 1999;49:700-4.)     

Delayed treatment with tumor necrosis factor inhibitors in incomplete responders to synthetic disease-modifying anti-rheumatic drugs shows an excellent effect in patients with very early rheumatoid arthritis with poor prognosis factors

We aimed to investigate whether delayed treatment with tumor necrosis factor (TNF) inhibitors in incomplete responders to synthetic disease-modifying anti-rheumatic drugs (DMARDs) was effective among patients with very early rheumatoid arthritis (RA) with poor prognosis factors. We examined 22 patients with very early RA who were positive for anti-cyclic citrullinated peptide antibodies or IgM-rheumatoid factor. The mean disease duration at entry was 14.1 weeks. A treat-to-target strategy, aiming at simplified disease activity index (SDAI) remission, was initiated with synthetic DMARDs. SDAI remission was not achieved in 9 of the 22 patients with synthetic DMARDs alone, and TNF inhibitors were added in these patients. SDAI values in these 9 patients were further examined for the following 6 months. The TNF inhibitors (infliximab 8, etanercept 1) were added at a mean interval of 34.1 weeks after the initiation of synthetic DMARDs. SDAI remission was achieved in 4 of the 9 patients (44.4%) at 3 months and in 8 of the 9 patients (88.9%) at 6 months after the introduction of the TNF inhibitors. Radiographic damage had not progressed in these patients. Delayed treatment with TNF inhibitors is effective and tolerable for patients with very early RA with poor prognosis factors.     

Costimulation of T-cell proliferation by anti-L-selectin antibody is associated with the reduction of a cdk inhibitor p27

In this study, we investigated the costimulatory activity of l-selectin in primary mouse T cells. Proliferation induced by immobilized anti-CD3 antibody was enhanced by immobilized anti-l-selectin antibody. In contrast to the anti-CD28 antibody, anti-l-selectin antibody did not enhance interleukin-2 (IL-2) expression. One of the cyclin-dependent kinase (cdk) inhibitors, p27, was reduced by costimulation with anti-l-selectin antibody, as with anti-CD28 antibody, suggesting that the enhancement of T-cell proliferation is the result of a reduced p27 level. Since anti-l-selectin antibody enhanced the activation of extracellular signal-regulated protein kinase (ERK) induced by anti-CD3 antibody, ERK plays an important role in signal integration during costimulation. These results suggest that the mechanism of T-cell costimulation is at least partially different between CD28 and l-selectin, although the two mechanisms share a common downstream event, a reduction of p27 level, as a critical biochemical event in the cell cycle progression of T cells.     

Asymmetric hindwing foldings in rove beetles

Foldable wings of insects are the ultimate deployable structures and have attracted the interest of aerospace engineering scientists as well as entomologists. Rove beetles are known to fold their wings in the most sophisticated ways that have right–left asymmetric patterns. However, the specific folding process and the reason for this asymmetry remain unclear. This study reveals how these asymmetric patterns emerge as a result of the folding process of rove beetles. A high-speed camera was used to reveal the details of the wing-folding movement. The results show that these characteristic asymmetrical patterns emerge as a result of simultaneous folding of overlapped wings. The revealed folding mechanisms can achieve not only highly compact wing storage but also immediate deployment. In addition, the right and left crease patterns are interchangeable, and thus each wing internalizes two crease patterns and can be folded in two different ways. This two-way folding gives freedom of choice for the folding direction to a rove beetle. The use of asymmetric patterns and the capability of two-way folding are unique features not found in artificial structures. These features have great potential to extend the design possibilities for all deployable structures, from space structures to articles of daily use.Artful wing folding of insects has attracted the interest of aerospace engineering scientists as well as entomologists. Foldable hindwings are the ultimate deployable structures. They have sufficient strength and stiffness to tolerate 20–1,000 beats per second in the flight position, although they can be folded and unfolded instantly, depending on the situation. It is well known that many species of insects are equipped with deployable wings. Simple examples are found in the longitudinally folded forewing of ants and bees (Hymenoptera) (1) and in the fanlike folding of locusts (Orthoptera) and praying mantises (Dictyoptera) (2). These types of deployable wings have simple crease patterns and can be folded and unfolded by relatively easy mechanisms; however, their storage efficiencies are not large. Earwigs (Dermaptera) are known to use advanced fanlike folding (3). Their fan frames have additional bending points, and earwigs achieve more extensive folding by refolding the closed fan. This folding can confer high storage efficiency but requires external support by the cercus for deployment, and the wings cannot be opened quickly. The most highly diverse wing folding patterns and mechanisms are found in beetles (Coleoptera) (4–13) (SI Text). Among these examples, the most sophisticated wing folding is found in rove beetles (Coleoptera: Staphylinidae) (7–9, 13), from the perspective of both deployment capability and storage efficiency. In addition to their performance as a deployable structure, the wings have a strange feature that is not observed in other beetles: The right and left wings use different folding patterns. Compared with other typical beetles, elytra of most rove beetles are reduced, and the projecting abdomen is exposed and freely movable (Fig. 1 and Fig. S1). At the expense of protection of the abdomen, rove beetles have highly maneuverable bodies that can move rapidly through narrow and curved spaces and can extend their wide range of microhabitats, especially into leaf litter layer and soil. The most remarkable feature of their survival strategy is that they have never lost their flight wings, despite the reduction of dorsal storage space (with some minor exceptions in soil- and cave-dwelling species). The strategy is achieved by their extraordinary right–left asymmetric wing folding. As a result, rove beetles became highly diverse group, such that they account for 15% (i.e., nearly 60,000 species) of all known species of Coleoptera.Open in a separate windowFig. 1.Cafius vestitus (Sharp). (A) Overall view (length of body, 6.1 mm). Elytra of most rove beetles are reduced, and the projecting abdomen is exposed and freely movable. (B) Wings in the folded position. Elytra are removed in this image. (C) Wing venation. The anterior margin (pterostigma) is strongly sclerotized. The wing membrane is supported mainly by two median veins. The terminologies are derived from ref. 7.Despite the great potential of the process for engineering applications, few studies have been undertaken revealing the details of this asymmetric wing folding. The wings of a rove beetle have two different crease patterns, but previous studies have described only one side. It is already known that the movement of the abdomen plays a central role in the wing folding (9), but the detailed folding process remains unexplained. A major obstacle to investigation is the difficulty of detailed observation of the folding processes. The wing-folding movement of a rove beetle consists of multiple sequences, and a series of movements is accomplished very smoothly and quickly. The aforementioned problem cannot be solved without careful investigation of this movement. This article is a detailed report on wing folding in rove beetles, including specific crease patterns of respective wings. A high-speed camera was used for the first time to the authors’ knowledge to reveal the details of wing folding movements. Specimens were Cafius vestitus (Sharp) and were captured in the coastal region of Japan. The results clarify the highly efficient wing-folding mechanism.     

A morphologic analysis of'naked'islets of Langerhans in lobular atrophy of the pancreas

The 'naked' islets of Langerhans (NIL) in randomly selected autopsy cases and In cases of chronic alcoholic pancreatitis, cystic fibrosis, and pancreatic carcinoma were studied histopathologically. The NIL were found in 55 of 164 randomly selected cases, with age-related frequency, in 21 of 30 cases of chronic alcoholic pancreatitis, in 2 of 2 cases of cystic fibrosis, and in 25 of 32 cases of pancreatic carcinoma. The NIL were frequently accompanied by ductal alterations: epithelial metaplasia and hyperplasia in randomly selected cases, protein plugs in chronic alcoholic pancreatitis, mucus plugs in cystic fibrosis, and obliterated ducts in pancreatic carcinoma. The NIL in randomly selected cases may have been formed by ductal alterations that caused stenosis of the lumen, those in chronic alcoholic pancreatitis and cystic fibrosis were the result of protein or mucus plugging, and those in pancreatic carcinoma were a result of neoplastic involvement of the distal pancreatic duct. Therefore, the common factor in the development of NIL is thought to be obstruction of the pancreatic duct system, and in cases of NIL that have a multilobular distribution and interinsular fibrosis, a diagnosis of chronic pancreatitis can usually be made.     

Usefulness of Intraductal Ultrasonography (IDUS) for Diagnosing Mucin-producing Pancreatic Tumors

Abstract: While it is very important to detect protruded lesions in order to determine the optimal treatment modality for mucin-producing tumors of the pancreas (MPT), it can be very difficult to discriminate between mucinous substance and tumor. Intraductal ultrasonography (IDUS) (2.0 mm diameter, 15 or 20 MHz) was performed in five MPT cases. The sizes of the tumors were 2, 5, 12, 12 and 30 mm. Histological findings of the resected specimens demonstrated adenocarcinoma in two cases, adenoma in one, and hyperplasia in one. IDUS visualized all tumors, i. e. the visualization rate was 100%. The visualization rate for US and CT was 40% with 12 and 30 mm tumors, and that for EUS was 60% with 2, 12, and 30 mm tumors. We found IDUS to be a very useful method for visualizing small protruded lesions in MPT.