Metaplasia Of Epithelial Cells Research Articles

Objective assessment of squamous metaplasia of conjunctival epithelial cells as associated with soft contact lens wear versus non-lens wearers.

To objectively assess the morphology of superficial conjunctival surface cells showing squamous metaplasia as seen in contact lens wearers. Impression cytology samples were taken from interpalpebral bulbar conjunctiva from 23 young adult white European women with an average of 6 years of successful daily soft contact lens wear and 23 non-contact-lens-wearing women of the same age. Cell images were graded, and cell and nuclear dimensions and areas were measured by planimetry. The contact lens wearers had a mean squamous metaplasia grade (Nelson) of 2.74 versus 0.35 for the non-lens wearers, with the cell longest dimension (LONG) being 54.4 ± 5.6 μm versus 22.4 ± 2.9 μm, respectively (P < 0.001). Similar differences were found for the cell shortest dimension (SHORT) and cell area values (P < 0.001). The cell nuclei in the contact lens wearers, based on measures of cell nuclear length (NUCLONG), were 12.7 ± 1.7 μm versus 10.0 ± 1.1 μm (P < 0.001) with no evidence of pyknotic (shrunken) nuclei. The nucleo-cytoplasmic ratios had mean values of 3.603 versus 1.282 for the cytoplasm-to-nucleus length (CYT/NUC length) ratio, and 0.075 and 0.319 for the NU/CYT length ratio for contact lens wearers and non-wearers, respectively. As squamous metaplasia develops, at least in long-term soft contact lens wearers, the conjunctival surface cells become considerably enlarged, but the nuclear size of these cells also increases, rather than showing signs of pyknosis.

Phototoxic Effects of an Operating Microscope on the Ocular Surface and Tear Film

We evaluated light exposure-induced dry eye syndrome by investigating the phototoxic effects of an operating microscope on the ocular surface and tear film in rabbits. Sixty eyes of 30 rabbits were divided into 3 groups based on the intensity of light exposure received from an operating microscope: Control group, no exposure to light; group A, 40,000-lx intensity for 30 minutes; and group B, 100,000-lx intensity for 30 minutes. To evaluate the potential damage to the ocular surface and tear film, Schirmer tests, rose bengal staining, and conjunctival impression cytology were performed before the light exposure and at 1, 3, and 5 days afterward. In addition, the expression of interleukin 1-beta was analyzed in tear samples. The expression of mucin 5AC was evaluated using immunofluorescence staining, and periodic acid-Schiff staining was conducted on conjunctival tissues. Corneal and conjunctival tissues were observed by means of electron microscopy. Potential damage to the ocular surface and tear film was found in the light-exposed groups as evidenced by decreased aqueous tear production, devitalized corneal and conjunctival epithelial cells, squamous metaplasia of conjunctival epithelial cells, decreased conjunctival goblet cell density, decreased expression of mucin 5AC, ultrastructural cellular damage to corneal and conjunctival tissues, and increased interleukin 1-beta expression in tears. This damage was more noticeable in group B than in group A (P < 0.05). Light exposure from an operating microscope had phototoxic effects on the ocular surface and tear film in this in vivo experiment. These changes seemed to intensify as the intensity of the light increased. Therefore, excessive light exposure during ophthalmic procedures could be a pathogenic factor in dry eye syndrome after a surgery is performed.

Giant Epidermal Cyst on Posterior Scalp

Giant Epidermal Cyst on Posterior Scalp

Abstract 1880: Role of fatty acid synthase and do novo lipogenesis in liver cancer development in mice.

Abstract Aberrant metabolism, including increased de novo lipogenesis, is one of the hallmarks of cancer. Fatty Acid Synthase (Fasn) catalyzes the de novo synthesis of long-chain fatty acids from acetyl-CoA and malonyl-CoA. Increased Fasn expression has been reported in multiple tumor types, and inhibition of Fasn expression has been shown to have tumor-suppressing activity. However, how increased de novo lipogenesis contributes to tumor initiation and progression, especially in vivo, remains unknown. In our previous studies, we showed that overexpression of the activated form of AKT (myr-AKT) induced de novo lipogenesis, hepatocyte proliferation and, eventually, liver cancer formation in mice. The tumorigenesis process could be significantly accelerated via co-expression of activated form of Ras. In the AKTRas tumor model, tumors were predominantly (&amp;gt;80%) hepatocellular carcinoma (HCC), and the remaining (&amp;lt;20%) were intrahepatic cholangiocarcinoma (ICC). The ICCs were induced via hepatocyte-biliary epithelial cell metaplasia in a Notch dependent manner. Intriguingly, fat droplet formation, increased expression of Fasn and other lipogenesis pathway genes were identified in HCC lesions, but not ICC lesions. To define whether Fasn-mediated de novo lipogenesis is a key metabolic event downstream of mTORC1 during AKTRas-induced hepatocarcinogenesis, we utilized Fasn flox/flox mice, and co-expressed AKTRas in the Fasn KO hepatocytes. Of note, we found that ablation of Fasn completely inhibited AKT induced lipogenesis and hepatocyte proliferation in mice. However, loss of Fasn modestly delayed AKTRas-induced liver tumor development. Histological analysis revealed that these tumor lesions were predominantly ICCs. The ICC cells were highly proliferative, and did not express Fasn or any other lipogenic pathway gene. The results suggest that Fasn-mediated de novo lipogenesis is required for AKTRas-induced HCC formation, but this process is dispensable for ICC formation. In summary, our experiments support a critical role for Fasn as a downstream effector of mTORC1 in HCC pathogenesis. However, Fasn-mediated do novo fatty acid synthesis is not required in all tumor types. It is likely that other sources of fatty acids, presumably including those derived from the diet, can be utilized by cancer cells for membrane synthesis during cell proliferation. Citation Format: Xin Chen, Lei Li, Chunmei Wang, Matthias Evert, Diego F. Calvisi, Clay F. Semenkovich. Role of fatty acid synthase and do novo lipogenesis in liver cancer development in mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1880. doi:10.1158/1538-7445.AM2013-1880 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

Preexisting epithelial diversity in normal human livers: A tissue-tethered cytometric analysis in portal/periportal epithelial cells

Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BECs). Considerable epithelial diversity, however, arises during disease states when a variety of hepatocyte-BEC hybrid cells appear. This has been attributed to activation and differentiation of putative hepatic progenitor cells (HPC) residing in the canals of Hering and/or metaplasia of preexisting mature epithelial cells. A novel analytic approach consisting of multiplex labeling, high-resolution whole-slide imaging (WSI), and automated image analysis was used to determine if more complex epithelial cell phenotypes preexist in normal adult human livers, which might provide an alternative explanation for disease-induced epithelial diversity. "Virtually digested" WSI enabled quantitative cytometric analyses of individual cells displayed in a variety of formats (e.g., scatterplots) while still tethered to the WSI and tissue structure. We employed biomarkers specifically associated with mature epithelial forms (HNF4α for hepatocytes, CK19 and HNF1β for BEC) and explored for the presence of cells with hybrid biomarker phenotypes. The results showed abundant hybrid cells in portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes. These bipotential cells likely serve as a reservoir for the epithelial diversity of ductular reactions, appearance of hepatocytes in bile ducts, and the rapid and fluid transition of BEC to hepatocytes, and vice versa. Novel imaging and computational tools enable increased information extraction from tissue samples and quantify the considerable preexistent hybrid epithelial diversity in normal human liver. This computationally enabled tissue analysis approach offers much broader potential beyond the results presented here.

Eccrine squamous syringometaplasia secondary to cutaneous extravasation of docetaxel: report of three cases

Eccrine squamous syringometaplasia is characterized by the metaplasia of cuboidal epithelial cells of the eccrine sweat ducts into squamous epithelial cells. It has been associated with several conditions including chemotherapy-related bilateral dermatitis, an entity that can take place in body areas rich in eccrine glands, as well as in acral erythema related to chemotherapy. Only a few cases because of cutaneous extravasation of chemotherapy have been previously reported. We report three cases of eccrine squamous syringometaplasia secondary to extravasation of docetaxel.

Alimentary factors in the development of gastric intestinal metaplasia in functional dyspeptic patients

Intestinal metaplasia of the stomach is a lesion in which metaplasia of gastric epithelial cells occurs for an intestinal phenotype. Gastric intestinal metaplasia is a lesion associated with an increase in the risk of gastric carcinoma development. Epidemiologic studies indicate a relation between dietary habits and stomach cancer development, some habits increasing the risk for it, and others have a protective effect, suggesting that antioxidants, such as vitamins A, C, and E, decrease the risk of this type of cancer. The relationship of these alimentary factors and intestinal metaplasia is unknown. It is a case-control, observational study in which 320 patients with functional dyspepsia, divided in two groups, were assessed. The case I group (individuals with intestinal metaplasia) had their dietary pattern compared to that of the control group, constituted of individuals similar to those in the case group but without intestinal metaplasia, through a food frequency questionnaire. The analysis of the dietary pattern of functional dyspeptic patients with intestinal metaplasia, and its comparison with those without intestinal metaplasia, showed a higher frequency of canned and smoked foods consumption in the first group and, on the other hand, a higher consumption of fruits and vegetables in patients without intestinal metaplasia. No effect of salt consumption was detected. The results obtained in this study suggest changes in the diet, with a decrease in the consumption of smoked and canned foods, and an increase in the consumption of fruits and vegetables, can lead to a diminution of gastric intestinal metaplasia cases.

IFNγ contributes to the development of gastric epithelial cell metaplasia in Huntingtin interacting protein 1 related (Hip1r)-deficient mice

Huntingtin interacting protein 1 related (Hip1r) is an F-actin- and clathrin-binding protein involved in vesicular trafficking that is crucial for parietal cell function and epithelial cell homeostasis in the stomach. Gastric parietal cells in Hip1r-deficient mice are lost by apoptotic cell death, which leads to a progressive epithelial cell derangement, including glandular hypertrophy, zymogenic cell loss and expansion of a metaplastic mucous cell lineage known as spasmolytic polypeptide-expressing metaplasia (SPEM). The epithelial cell changes are associated with infiltration of inflammatory cells. As inflammatory mediators, such as IFNγ, have been shown to contribute to the development of the gastric epithelial cell metaplasia after Helicobacter infection, we tested whether IFNγ played a role in the spontaneous progressive epithelial metaplasia observed in Hip1r-deficient mice. Hip1r-deficient mice were crossed with IFNγ-deficient mice and single- and double-mutant mice were analyzed at 3 and 12 months of age. Histopathology scoring showed that loss of IFNγ tempered the spontaneous development of metaplastic lesions in Hip1r-deficient mice. Loss of IFNγ was observed to abrogate the glandular hypertrophy evident in Hip1r mutant stomach, although increased epithelial cell proliferation and elevated gastrin levels were not affected by the presence or absence of this pro-inflammatory cytokine. An analysis of cell lineage markers in the double-mutant mice demonstrated that IFNγ specifically affected the development of metaplastic mucous cells in the neck region, whereas the parietal cell, surface mucous cell and zymogenic cell alterations remained similar to the histopathology in the Hip1r mutant. Morphometric analysis showed that IFNγ was required for the mucous cell hypertrophy and hyperplasia observed in Hip1r-deficient mice. Together, these findings demonstrate that IFNγ is critical for the development of the gastric epithelial cell metaplasia that results from parietal cell atrophy in the Hip1r-deficient mice.

MicroRNAs Up-Regulated by CagA of Helicobacter pylori Induce Intestinal Metaplasia of Gastric Epithelial Cells

CagA of Helicobacter pylori is a bacterium-derived oncogenic protein closely associated with the development of gastric cancers. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs, many of which are involved in cell growth, cell differentiation and tumorigenesis. The relationship between CagA protein and miRNAs is unclear. Using mammalian miRNA profile microarrays, we found that miRNA-584 and miRNA-1290 expression was up-regulated in CagA-transformed cells, miRNA-1290 was up-regulated in an Erk1/2-dependent manner, and miRNA-584 was activated by NF-κB. miRNA-584 sustained Erk1/2 activities through inhibition of PPP2a activities, and miRNA-1290 activated NF-κB by knockdown of NKRF. Foxa1 was revealed to be an important target of miRNA-584 and miRNA-1290. Knockdown of Foxa1 promoted the epithelial-mesenchymal transition significantly. Overexpression of miRNA-584 and miRNA-1290 induced intestinal metaplasia of gastric epithelial cells in knock-in mice. These results indicate that miRNA-584 and miRNA-1290 interfere with cell differentiation and remodel the tissues. Thus, the miRNA pathway is a new pathogenic mechanism of CagA.

Primary squamous cell carcinoma of the liver: A case report and review of the literature

Primary squamous cell carcinoma of the liver is rare. It has a high malignancy rate and poor prognosis, and survival is typically no longer than one year. The pathogenesis of the disease is unclear, but is generally considered to be correlated with the long-term inflammation or metaplasia of biliary epithelial cells and congenital cyst of the liver. The current viewpoint is that surgical resection of the tumor, preoperative or postoperative subsidiary chemoembolization, radiotherapy and generalized chemotherapy may extend a patient's survival. In the present case study, a patient suffered from biliary calculosis for over 20 years. We theorized that the mechanism of carcinomatous change was correlated with the persistent stimulation of chronic biliary infection induced by calculus of the intrahepatic duct. However, the transformation mechanism from cholangiocellular carcinoma to squamous carcinoma is undetermined and further studies are needed.

Glucose uptake mediated by glucose transporter 1 is essential for early tooth morphogenesis and size determination of murine molars

Glucose is an essential source of energy for body metabolism and is transported into cells by glucose transporters (GLUTs). Well-characterized class I GLUT is subdivided into GLUTs1–4, which are selectively expressed depending on tissue glucose requirements. However, there is no available data on the role of GLUTs during tooth development. This study aims to clarify the functional significance of class I GLUT during murine tooth development using immunohistochemistry and an in vitro organ culture experiment with an inhibitor of GLUTs1/2, phloretin, and Glut1 and Glut2 short interfering RNA (siRNA). An intense GLUT1-immunoreaction was localized in the enamel organ of bud-stage molar tooth germs, where the active cell proliferation occurred. By the bell stage, the expression of GLUT1 in the dental epithelium was dramatically decreased in intensity, and subsequently began to appear in the stratum intermedium at the late bell stage. On the other hand, GLUT2-immunoreactivity was weakly observed in the whole tooth germs throughout all stages. The inhibition of GLUTs1/2 by phloretin in the bud-stage tooth germs induced the disturbance of primary enamel knot formation, resulting in the developmental arrest of the explants and the squamous metaplasia of dental epithelial cells. Furthermore, the inhibition of GLUTs1/2 in cap-to-bell-stage tooth germs reduced tooth size in a dose dependent manner. These findings suggest that the expression of GLUT1 and GLUT2 in the dental epithelial and mesenchymal cells seems to be precisely and spatiotemporally controlled, and the glucose uptake mediated by GLUT1 plays a crucial role in the early tooth morphogenesis and tooth size determination.

Aldose reductase deficiency in mice protects from ragweed pollen extract (RWE)-induced allergic asthma

BackgroundChildhood hospitalization related to asthma remains at historically high levels, and its incidence is on the rise world-wide. Previously, we have demonstrated that aldose reductase (AR), a regulatory enzyme of polyol pathway, is a major mediator of allergen-induced asthma pathogenesis in mouse models. Here, using AR null (AR-/-) mice we have investigated the effect of AR deficiency on the pathogenesis of ragweed pollen extract (RWE)-induced allergic asthma in mice and also examined the efficacy of enteral administration of highly specific AR inhibitor, fidarestat.MethodsThe wild type (WT) and AR-/- mice were sensitized and challenged with RWE to induce allergic asthma. AR inhibitor, fidarestat was administered orally. Airway hyper-responsiveness was measured in unrestrained animals using whole body plethysmography. Mucin levels and Th2 cytokine in broncho-alveolar lavage (BAL) were determined using mouse anti-Muc5A/C ELISA kit and multiplex cytokine array, respectively. Eosinophils infiltration and goblet cells were assessed by H&E and periodic acid Schiff (PAS)-staining of formalin-fixed, paraffin-embedded lung sections. T regulatory cells were assessed in spleen derived CD4+CD25+ T cells population.ResultsDeficiency of AR in mice led to significantly decreased PENH, a marker of airway hyper-responsiveness, metaplasia of airway epithelial cells and mucus hyper-secretion following RWE-challenge. This was accompanied by a dramatic decrease in infiltration of eosinophils into sub-epithelium of lung as well as in BAL and release of Th2 cytokines in response to RWE-challenge of AR-/- mice. Further, enteral administration of fidarestat significantly prevented eosinophils infiltration, airway hyper-responsiveness and also markedly increased population of T regulatory (CD4+CD25+FoxP3+) cells as compared to RWE-sensitized and challenged mice not treated with fidarestat.ConclusionOur results using AR-/- mice strongly suggest the role of AR in allergic asthma pathogenesis and effectiveness of oral administration of AR inhibitor in RWE-induced asthma in mice supports the use of AR inhibitors in the treatment of allergic asthma.

The Role of Mindbomb 1 in Gastric Epithelial Cell Differentiation and Metaplasia

The Role of Mindbomb 1 in Gastric Epithelial Cell Differentiation and Metaplasia

Eyelid Alterations in Involutional Ectropion

Purpose: To describe the histological features of eyelid tissue in involutional ectropion carriers. Methods: An interventional case series study was performed evolving 52 involutional eyelid ectropion carriers submitted to Tarsal strip surgery. A full-thickness eyelid fragment was evaluated by light microscope and results were statistical analyzed. Results: The conjunctival substantia propria had an inflammatory mononuclear process. Meibomian glands and eyelash follicles were enlarged. Inflammatory cells permeated the glands and eyelashes follicles. Orbicularis muscle fibers were replaced by fibrosis in some areas. Solar elastosis and epithelial squamous cell metaplasia were also observed in the skin epithelium. Conclusion: Eyelid ectropion is associated with important lid margin alterations affecting the glands, eyelashes, and orbicularis muscle. Inflammation and fibrosis compromise and disturb eyelid function.

Aldose reductase inhibition prevents metaplasia of airway epithelial cells.

BackgroundGoblet cell metaplasia that causes mucus hypersecretion and obstruction in the airway lumen could be life threatening in asthma and chronic obstructive pulmonary disease patients. Inflammatory cytokines such as IL-13 mediate the transformation of airway ciliary epithelial cells to mucin-secreting goblet cells in acute as well as chronic airway inflammatory diseases. However, no effective and specific pharmacologic treatment is currently available. Here, we investigated the mechanisms by which aldose reductase (AR) regulates the mucus cell metaplasia in vitro and in vivo.Methodology/FindingsMetaplasia in primary human small airway epithelial cells (SAEC) was induced by a Th2 cytokine, IL-13, without or with AR inhibitor, fidarestat. After 48 h of incubation with IL-13 a large number of SAEC were transformed into goblet cells as determined by periodic acid-schiff (PAS)-staining and immunohistochemistry using antibodies against Mucin5AC. Further, IL-13 significantly increased the expression of Mucin5AC at mRNA and protein levels. These changes were significantly prevented by treatment of the SAEC with AR inhibitor. AR inhibition also decreased IL-13-induced expression of Muc5AC, Muc5B, and SPDEF, and phosphorylation of JAK-1, ERK1/2 and STAT-6. In a mouse model of ragweed pollen extract (RWE)-induced allergic asthma treatment with fidarestat prevented the expression of IL-13, phosphorylation of STAT-6 and transformation of epithelial cells to goblet cells in the lung. Additionally, while the AR-null mice were resistant, wild-type mice showed goblet cell metaplasia after challenge with RWE.ConclusionsThe results show that exposure of SAEC to IL-13 caused goblet cell metaplasia, which was significantly prevented by AR inhibition. Administration of fidarestat to mice prevented RWE-induced goblet cell metaplasia and AR null mice were largely resistant to allergen induced changes in the lung. Thus our results indicate that AR inhibitors such as fidarestat could be developed as therapeutic agents to prevent goblet cell metaplasia in asthma and related pathologies.

Molecular Mechanism of Proinflammatory Cytokine-Mediated Squamous Metaplasia in Human Corneal Epithelial Cells

The cornified envelope protein small proline-rich protein 1B (SPRR1B) is a biomarker for squamous metaplasia. Proinflammatory cytokines IL-1beta and IFN-gamma are potent inducers of ocular surface keratinization and SPRR1B expression. Here the molecular mechanisms controlling SPRR1B gene expression in response to IL-1beta and IFN-gamma are elucidated. A 3-kb fragment of the SPRR1B gene 5'-flanking region was amplified from human chromosome 1, sequentially deleted, and cloned into a luciferase vector. Constructs were transiently transfected into human corneal epithelial cells, and activity was assessed in response to IL-1beta, IFN-gamma, or basal medium. Functional cis-elements responding to IL-1beta and IFN-gamma were characterized by site-directed mutagenesis and gel mobility shift assay. Effects of mitogen-activated protein kinases p38, ERK, and JNK were assessed using inhibitors and dominant-negative mutants. Results were validated by real-time RT-PCR. The first 620 bp of the SPRR1B 5'-flanking region regulated constitutive expression and increased promoter activity in response to IL-1beta and IFN-gamma. Corresponding cis-elements for IL-1beta and IFN-gamma were bound by cAMP response element binding protein (CREB) and zinc-finger E-box binding homeobox 1 (ZEB1), respectively. Inhibition of p38 abolished the stimulatory effects of IL-1beta and IFN-gamma on SPRR1B, whereas inhibition of JNK and ERK had no effect. Dominant-negative mutants targeting p38alpha and p38beta2 blocked cytokine-induced SPRR1B promoter activity and mRNA expression. SPRR1B is upregulated by the proinflammatory cytokines IL-1beta and IFN-gamma via p38 MAPK-mediated signaling pathways that lead to the activation of transcription factors CREB and ZEB1, respectively. These results identify key intracellular signaling intermediates involved in the pathogenesis of immune-mediated ocular surface squamous metaplasia.

Cistite glandular evoluindo com uropatia obstrutiva

INTRODUCAO: Cistite glandular e um processo proliferativo benigno e infrequente da mucosa vesical, caracterizado por proliferacao do epitelio e, em alguns casos, formacao de glândulas intestinais. Alteracoes metaplasicas na cistite glandular sao bem documentadas na literatura, embora sua etiologia nao seja totalmente esclarecida. RELATO DO CASO: Relatamos um caso de cistite glandular em um paciente de 55 anos, apresentando sintomas miccionais irritativos e obstrutivos persistentes sem resposta a terapia com alfabloqueadores. Ultrassonografia evidenciou lesao vegetante no trigono vesical e o paciente foi submetido a resseccao endoscopica por duas vezes e evoluiu com ureterohidronefrose bilateral. Dado o extenso acometimento vesical e a persistencia dos sintomas, o paciente foi submetido a cistoprostatectomia e neobexiga ileal com boa evolucao pos-operatoria. DISCUSSAO: Ha duas formas de cistite glandular: tipica e intestinal. A forma tipica e a mais comum e a intestinal e marcada pela producao de mucina, mais frequentemente associada ao adenocarcinoma de bexiga. A maioria dos casos de cistite glandular e assintomatica, sendo que os pacientes sintomaticos normalmente apresentam hematuria, sintomas urinarios irritativos e tipicos de cistite cronica. Ha controversias sobre o tratamento precoce agressivo, sendo que varios estudos propoem a resseccao transuretral e o acompanhamento com biopsias.

Angiogenesis in asthma

Asthma is a chronic inflammatory disease of the airways characterized by infiltration and activation of inflammatory cells and by structural changes, including subepithelial fibrosis, smooth muscle cells hypertrophy/hyperplasia, epithelial cell metaplasia and angiogenesis. These structural changes are thought to correlate with asthma severity and to account for the development of progressive lung function deterioration. The mechanism underlying airway angiogenesis in asthma and its precise clinical relevance have not yet been completely elucidated. This review provides recent data showing the contribution of allergic inflammation in increased airway vascularity and potential therapeutical approaches in asthma treatment by acting on bronchial microvascular changes.

Is Lymphocytic (Hashimoto) Thyroiditis Associated With Suicide?

The histologic diagnosis of lymphocytic (Hashimoto) thyroiditis requires lymphocytic inflammation of the thyroid gland in combination with Hourthle cell metaplasia of follicular epithelial cells. Clinically, this autoimmune process has been associated with hypothyroidism and psychiatric conditions including depression. This retrospective study was designed to quantify the incidence and severity of lymphocytic thyroiditis in a series of nonconsecutive suicides compared with a cohort of motor vehicle accident victim controls. Eighty-one suicide victims (61 male, 20 female; age range 13-79 years, average 43) were compared with 88 age and gender matched controls (64 males, 24 females; age range 19-85 years, average 36). The degree of lymphocytic inflammation of the thyroid gland was graded on a scale of 0 to 3 (0 = no inflammation, 1 = mild inflammation, 2-3 moderate-to-marked inflammation with Hourthle cell metaplasia). Slides from each case were reviewed while blinded to the cause and manner of death in each case. Of these 169 total cases, 8 (4.7%) received a score of 3, whereas additional 7 (4.1%) received a grade of 2. Eighty-six percent of all of the cases showed no significant inflammation and recorded a score of 0. Of the 81 suicides, 3 had a score of 3, and 3 had a score of 2 (combined incidence of 7.4%). Within the control group, 5 of 88 cases scored 3 and another 4 scored 2 (combined incidence = 10.2%). Three males and 5 females scored 3 with an age range of 23 to 63 years, average 42. Incidental data tabulated showed that 19% of suicide victims were on psychoactive medications compared with 6% in the motor vehicle accident control group. No one on this study was on thyroid hormone replacement therapy. Depression is strongly linked to suicide and lymphocytic thyroiditis may be a cause of depression. Based on this study, however, the presence of lymphocytic thyroiditis cannot be used as a histologic adjunct to discriminate between suicide and accident in problematic cases (ie, overdose deaths). This diagnosis is rendered with essentially equal frequency in suicide victims versus controls.

EDITORIAL

We start this issue with the first of a set of two ‘Year-in-Review’ papers, highlighting important findings in respiratory medicine from articles published in Respirology in 2007. The first paper by Professor Bardin and Professor Ruffin reviews the clinical science publications in Respirology in 2007. The second ‘Year-in-Review’ paper, which will appear in the next issue, will review the respiratory science publications reported in the Journal in 2007. This issue features the last review in the Presidents' Series by the immediate past-President of the American College of Chest Physicians, Professor Mark Rosen. In his review ‘Pulmonary Complications of HIV Infection’, Professor Rosen discusses the incidence of different pulmonary disorders associated with HIV infection, and their diagnosis and treatment. Professor Rosen is Chief of the Divisions of Pulmonary, Critical Care and Sleep Medicine at North Shore University Hospital and Long Island Jewish Medical Center. His research interests include pulmonary disease and critical care in patients with HIV infection, respiratory failure and medical ethics. He has published extensively on the subject of pulmonary disease in patients with HIV infection and is co-editor of the textbook ‘HIV and the Lung’. I highly recommend this paper to you as it is a comprehensive review of the topic and should be of great interest. We regret to announce the cancellation of the Presidents' Review by Dr Nan Zhong from the APSR owing to unforeseen circumstances. Our next Presidents' Series with reviews by the new Presidents of the major respiratory societies will commence in a later issue this year. Three highlights in this issue are articles studying the role of mitogen-activated protein kinase pathways in airway epithelial cells. The first of these articles ‘Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells’ by Dr Fujisawa et al. (pp. 191–202), demonstrates that the p38 MAPK pathway is involved in IL-13-induced mucous cell metaplasia and MUC5AC mRNA regulation in mouse tracheal epithelial cells and that phosphorylation of p38 MAPK may require STAT6-dependent de novo protein synthesis induced by IL-13. The same study also shows that the ERK1/2 pathway is not directly activated by IL-13. The article ‘Analysis of gene expression in human bronchial epithelial cells upon influenza virus infection and regulation by p38 MAP kinase and JNK’ by Dr Hayashi et al. (pp. 203–214) reports on the role of p38 MAPK in gene expression in human bronchial epithelial cells following influenza virus infection. In ‘Erythromycin attenuates MUC5AC synthesis and secretion in cultured human tracheal cells infected with RV14’ (pp. 215–220), Dr Inoue et al. examine the inhibitory effect of erythromycin on RV14-induced p44/42 MAPK activation and MUC5AC protein production and hypersecretion in human tracheal cells, suggesting a link between the two. Another highlight in this issue is the article by Dr Long et al. entitled ‘Rapid non-genomic effects of glucocorticoids on oxidative stress in a guinea pig model of asthma’ (pp. 227–232). In this study, the authors identify a rapid non-genomic mechanism whereby glucocorticoids reduce oxidative stress in ‘asthmatic’ guinea pigs. These findings may contribute to future developments in the clinical treatment of asthma. The article by Dr Bu et al.‘Effects of independent lung ventilation and lateral position on cytokine markers of inflammation after unilateral lung acid injury in dogs’ (pp. 233–239) compared the effects of different mechanical ventilation settings and lateral body position on inflammatory markers in an animal model of unilateral lung acid injury. Their results suggest that the release of pro-inflammatory cytokines in the injured lung is attenuated by independent lung ventilation and lateral positioning. Early initiation of this type of mechanical ventilation may be of benefit in patients with severe unilateral lung injury. Finally, the Short Communication by Dr Koh et al.‘Vascular endothelial growth factor in epithelial lining fluid of patients with acute respiratory distress syndrome’ (pp. 281–284) demonstrates that elevated levels of vascular endothelial growth factor in lung epithelial lining fluid may predict a better outcome in patients with acute lung injury and acute respiratory distress syndrome. Professor Chong-Kin Liam from the University of Malaya, Malaysia has decided to retire early from his role as Associate Editor of Respirology. Professor Liam joined the Journal in April 2006. His contribution over the past year and a half has been greatly appreciated and we are very grateful for his assistance. Professor Liam will continue to be involved with Respirology as an Editorial Board member. I hope you enjoy this issue of Respirology.