Safety and usefulness of a novel eMotion electric mesh nebulizer in children with asthma.

BACKGROUND: A new electronic mesh nebulizer, eMotion is known to have higher performance compared to conventional nebulizers. However, there are some concerns about whether too much delivered dose might cause side effects with higher frequency. METHODS: To evaluate the safety and usefulness of the nebulizer, we measured changes in heart rates and lung functions of 73 asthmatic children when they inhaled 1 microg/kg of procaterol with eMotion or a conventional nebulizer, Junior BOY. RESULTS: In 34 children with mild asthma exacerbation, physical findings, lung function and transcutaneous oxygen saturation levels were improved after inhalation using both nebulizers. No adverse effects including significant increase of heart rate were found. Improvements in the rates of the parameters were comparable. When response to beta2-agonist inhalation was checked in 39 children in stable condition, similar degrees of improvement in lung function were observed, and heart rates did not change after inhalation with either nebulizers. CONCLUSIONS: Safety and efficacy was comparable between eMotion and a conventional nebulizer when it was used to administer beta2-agonists in asthmatic children. However, from the fact that eMotion needs only 3-4 minutes to inhale 2 mL solution, eMotion could be more useful for most children who usually do not prefer longer inhalation time with conventional compressor nebulizers.     

Formation and distribution of the sural nerve based on nerve fascicle and nerve fiber analyses

The formation and distribution of the sural nerve are presented on the basis of an investigation of 31 legs of Japanese cadavers using nerve fascicle and fiber analyses. Nerve fibers constituting the medial sural cutaneous nerve were designated as 'T', whereas those constituting the peroneal communicating branch were designated as 'F'. In 74.2% of cases (23/31), the T and F fibers joined each other in the leg, whereas in 9.7% of cases (3/31) they descended separately. In 16.1% of cases (5/31), the sural nerve was formed of only the T fibers. The sural nerve gave off lateral calcaneal branches and medial and lateral branches at the ankle. The lateral calcaneal branches always contained T fibers. The medial branches consisted of only T fibers, whereas most of the lateral branches consisted of only F fibers (71.0%; 22/31). In addition to the T and F fibers, P fibers, which derived from the superficial and deep peroneal nerves, formed the dorsal digital nerves. The P fibers were entirely supplied to the medial four and one-half toes. However, they were gradually replaced by the T and F fibers in the lateral direction. The 10th proper dorsal digital nerve consisted of T fibers only (38.7%; 12/31), of F fibers only (19.4%; 6/31) or of both T and F fibers (38.7%; 12/31). These findings suggest that the T fibers are essential nerve components for the skin and deep structures of the ankle and heel rather than the skin of the lateral side of the fifth toe. The designation of the medial sural cutaneous nerve should be avoided and only the T fibers are appropriate components for naming as the sural nerve.     

Immunoelectron Microscopic Study of Podoplanin Localization in Mouse Salivary Gland Myoepithelium

We have recently reported that salivary gland cells express the lymphatic endothelial cell marker podoplanin. The present study was aimed to immunohistochemically investigate the expression of the myoepithelial cell marker α-smooth muscle actin (SMA) on podoplanin-positive cells in mouse parotid and sublingual glands, and to elucidate podoplanin localization in salivary gland myoepithelial cells by immunoelectron microscopic study. The distribution of myoepithelial cells expressing podoplanin and α-SMA was examined by immunofluorescent staining, and the localization of reaction products of anti-podoplanin antibody was investigated by pre-embedded immunoelectron microscopic method. In immunohistochemistry, the surfaces of both the mucous acini terminal portion and ducts were covered by a number of extensive myoepithelial cellular processes expressing podoplanin, and the immunostaining level with anti-podoplanin antibody to myoepithelial cells completely coincided with the immunostaining level with anti-α-SMA antibody. These findings suggest that podoplanin is a salivary gland myoepithelial cell antigen, and that the detection level directly reflects the myoepithelial cell distribution. In immunoelectron microscopic study, a number of reaction products with anti-podoplanin antibody were found at the Golgi apparatus binding to the endoplasmic reticulum in the cytoplasm of myoepithelial cells between sublingual gland acinar cells, and were also found at the myoepithelial cell membrane. These findings suggest that salivary gland myoepithelial cells constantly produce podoplanin and glycosylate at the Golgi apparatus, and transport them to the cell membrane. Podoplanin may be involved in maintaining the homeostasis of myoepithelial cells through its characteristic as a mucin-type transmembrane glycoprotein.     

The topoisomerase II alpha gene status in primary breast cancer is a predictive marker of the response to anthracycline-based neoadjuvant chemotherapy

This study aimed at evaluating the usefulness of topoisomerase II alpha (TOP2A) for predicting the effect of anthracycline-based neoadjuvant chemotherapy in breast cancer. The TOP2A status was examined using fluorescent in situ hybridization (FISH) in 14 pre-chemotherapeutic breast cancer tissues, and was also assessed by immunohistochemistry (IHC) in 14 pairs of pre- and post-chemotherapeutic breast cancer specimens. TOP2A gene aberration by IHC tended to show a correlation with pathological responses but this was not statistically significant (p=0.060). On the other hand, the low TOP2A/CEP17 ratio correlated with good pathological responses (p=0.012). TOP2A overexpression was not significantly associated with response (p=0.580). Our results thus suggest that the TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer.     

Lipoteichoic acid may affect the pathogenesis of bile duct damage in primary biliary cirrhosis

AIM: Intrahepatic bile ducts are the targets for inflammation in primary biliary cirrhosis (PBC), but their pathogenesis is not known. Gram-positive bacterial DNA was detected recently in gallbladder bile of PBC patients. In the present study, we assessed the possible pathological role of lipoteichoic acid (LTA), the gram-positive bacterial cell wall component, in PBC. METHODS: Liver samples, obtained from 20 patients with PBC (stage 1-2 with CNSDC: stage 3-4 with loss of bile ducts = 10:10) and from 13 patients with chronic hepatitis due to hepatitis C virus (CH-C) with lymphocytic cholangitis, were subjected to immunohistochemical staining with polyclonal rabbit anti-LTA as the primary antibody. Serum reactivities to LTA were studied by ELISA. After 1 microg of purified LTA was placed in a 96-well microplate as an antigen, an antibody capture assay was carried out using serum samples from PBC (n = 20), CH-C (n = 13) and healthy subjects (n = 11). RESULTS: LTA was localized around the sites of chronic non-suppurative destructive cholangitis (CNSDC) in the portal area in stage 1-2 PBC but was not detected in the portal area in CH-C. In stage 3-4 PBC, LTA was localized around sites of ductular proliferation at the periphery of portal tracts. IgM class anti-LTA serum titers were significantly higher in PBC than in CH-C. IgA class anti-LTA serum titers were significantly higher in PBC than in healthy subjects. CONCLUSIONS: In the PBC livers, the profile of immunoreactivity to LTA changed markedly as the disease progressed. Sera from PBC showed higher levels of anti-LTA titers than CH-C (IgM) or from healthy subjects (IgA). The LTA-mediated immune system might affect the initiation and/or progression of PBC.     

Phosphorylation status of epidermal growth factor receptor is closely associated with responsiveness to gefitinib in pulmonary adenocarcinoma

Twenty-one cases of primary lung carcinoma were analyzed for correlations between the presence of somatic mutations of the epidermal growth factor receptor (EGFR) gene and the phosphorylation status of EGFR, which was analyzed by immunohistochemistry with antibodies recognizing the phosphorylated form of EGFR. Somatic mutations were detected in 11 (52.4%) of the 21 cases. Immunohistochemistry with an antibody recognizing EGFR phosphorylated at tyrosine (pEGFR-tyr) 992 and an antibody recognizing EGFR phosphorylated at tyrosine 1173 (pEGFR-tyr1173) revealed that 12 (57.1%) and 21 (100%) of the 21 cases were positive, respectively. Interestingly, the mutation status of the EGFR gene was strongly correlated with immunoreactivity for pEGFR-tyr992 (P = .0019). pEGFR-tyr992 immunoreactivity was significantly correlated with clinical responsiveness to gefitinib (P = .0011). These findings suggest that immunohistochemical evaluation with anti-pEGFR-tyr992 antibody is useful for prediction of responsiveness to gefitinib.     

Identification of mutations in the Bruton's tyrosine kinase gene,including a novel genomic rearrangements resulting in large deletion,in Korean X-linked agammaglobulinemia patients

Mutations in the Bruton's tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA). We identified BTK mutations in six patients with presumed XLA from unrelated Korean families. Four out of six mutations were novel: two missense mutations (P565T, C154Y), a point mutation in a splicing donor site (IVS11+1G>A), and a large deletion (a 6.1-kb deletion including BTK exons 11–18). The large deletion, identified by long-distance PCR, revealed Alu-Alu mediated recombination extended from an Alu sequence in intron 10 to another Alu sequence in intron 18, spanning a distance of 6.1 kb. The two known mutations consisted of one missense (G462D) mutation, and a point mutation in a splicing acceptor site (IVS7−9A>G). This study suggests that large genomic rearrangements involving Alu repeats are few but an important component of the spectrum of BTK mutations.     

Bcl‐3 induced by IL‐22 via STAT3 activation acts as a potentiator of psoriasis‐related gene expression in epidermal keratinocytes

IL‐22 induces STAT3 phosphorylation and mediates psoriasis‐related gene expression. However, the signaling mechanism leading from pSTAT3 to the expression of these genes remains unclear. We focused on Bcl‐3, which is induced by STAT3 activation and mediates gene expression. In cultured human epidermal keratinocytes, IL‐22 increased Bcl‐3, which was translocated to the nucleus with p50 via STAT3 activation. The increases in CXCL8, S100As and human β‐defensin 2 mRNA expression caused by IL‐22 were abolished by siRNA against Bcl‐3. Although CCL20 expression was also augmented by IL‐22, the knockdown of Bcl‐3 increased its level. Moreover, the combination of IL‐22 and IL‐17A enhanced Bcl‐3 production, IL‐22‐induced gene expression, and the expression of other psoriasis‐related genes, including those encoding IL‐17C, IL‐19, and IL‐36γ. The expression of these genes (except for CCL20) was also suppressed by the knockdown of Bcl‐3. Bcl‐3 overexpression induced CXCL8 and HBD2 expression but not S100As expression. We also compared Bcl‐3 expression between psoriatic skin lesions and normal skin. Immunostaining revealed strong signals for Bcl‐3 and p50 in the nucleus of epidermal keratinocytes from psoriatic skin. The IL‐22‐STAT3‐Bcl‐3 pathway may be important in the pathogenesis of psoriasis.     

Radiotherapy for Japanese elderly patients with cervical cancer: preliminary survival outcomes and evaluation of treatment-related toxicity

Purpose  

To examine the preliminary survival outcomes and treatment-related toxicity for elderly patients with cervical cancer treated with radiotherapy (RT).     

The Long Elusive IgM Fc Receptor,FcμR

IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both pre-immune “natural” and antigen-induced “immune” IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed but fail to fully account for the IgM-mediated protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (FcμR). We have recently identified a bona fide FcμR in both humans and mice. In this article we briefly review what we have learned so far about FcμR.