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Biomedical subjects

A Berlin

Publications and source records attributed to A Berlin.

At least 19 recordsLinked to original sources
PubMed2001

Respiratory syncytial virus predisposes mice to augmented allergic airway responses via IL-13-mediated mechanisms.

The development of severe childhood asthma may be influenced by several factors including environmental and infectious stimuli. The causal relationship between infectious viral responses, such as respiratory syncytial virus (RSV), and severe asthma during early childhood is unclear. In these studies, the ability for an initial RSV infection to exacerbate and promote a more severe asthmatic-type response was investigated by combining established murine models of disease. We examined the ability of RSV to induce exacerbation of allergic disease over a relatively long period, leading to development of severe airway responses including airway inflammation and hyperreactivity. The preferential production of IL-13 during a primary RSV infection appears to play a critical role for the exacerbation of cockroach allergen-induced disease. The depletion of IL-13 during RSV infections inhibited the exacerbation and acceleration of severe allergen-induced airway hyperreactivity. This was indicated by decreases in airway hyperreactivity and changes in lung chemokine production. These data suggest that the airway responses during asthma can be greatly affected by a previous RSV infection, even when infection occurs before allergen sensitization. Overall, infection of the airways with RSV can induce an IL-13-dependent change in airway function and promotes an environment that contributes to the development of severe allergic asthmatic responses.

Allergens↗
PubMed2001

Role of bud6p and tea1p in the interaction between actin and microtubules for the establishment of cell polarity in fission yeast.

BACKGROUND: In many cell types, microtubules are thought to direct the spatial distribution of F-actin in cell polarity. Schizosaccharomyces pombe cells exhibit a regulated program of polarized cell growth: after cell division, they grow first in a monopolar manner at the old end, and in G2 phase, initiate growth at the previous cell division site (the new end). The role of microtubule ends in cell polarity is highlighted by the finding that the cell polarity factor, tea1p, is present on microtubule plus ends and cell tips [1]. RESULTS: Here, we characterize S. pombe bud6p/fat1p, a homolog of S. cerevisiae Bud6/Aip3. bud6Delta mutant cells have a specific defect in the efficient initiation of growth at the new end and like tea1Delta cells, form T-shaped cells in a cdc11 background. Bud6-GFP localizes to both cell tips and the cytokinesis ring. Maintenance of cell tip localization is dependent upon actin but not microtubules. Bud6-GFP localization is tea1p dependent, and tea1p localization is not bud6p dependent. tea1Delta and bud6Delta cells generally grow in a monopolar manner but exhibit different growth patterns. tea1(Delta)bud6Delta mutants resemble tea1Delta mutants. Tea1p and bud6p coimmunoprecipitate and comigrate in large complexes. CONCLUSIONS: Our studies show that tea1p (a microtubule end-associated factor) and bud6p (an actin-associated factor) function in a common pathway, with bud6p downstream of tea1p. To our knowledge, bud6p is the first protein shown to interact physically with tea1p. These studies delineate a pathway for how microtubule plus ends function to polarize the actin cytoskeleton through actin-associated polarity factors.

Actins↗
PubMed2001

IL-13-induced airway hyperreactivity during respiratory syncytial virus infection is STAT6 dependent.

Airway damage and hyperreactivity induced during respiratory syncytial virus (RSV) infection can have a prolonged effect in infants and young children. These infections can alter the long-term function of the lung and may lead to severe asthma-like responses. In these studies, the role of IL-13 in inducing and maintaining a prolonged airway hyperreactivity response was examined using a mouse model of primary RSV infection. Using this model, there was evidence of significant airway epithelial cell damage and sloughing, along with mucus production. The airway hyperreactivity response was significantly increased by 8 days postinfection, peaked during days 10-12, and began to resolve by day 14. When the local production of Th1- and Th2-associated cytokines was examined, there was a significant increase, primarily in IL-13, as the viral response progressed. Treatment of RSV-infected mice with anti-IL-13 substantially inhibited airway hyperreactivity. Anti-IL-4 treatment had no effect on the RSV-induced responses. Interestingly, when IL-13 was neutralized, an early increase in IL-12 production was observed within the lungs, as was a significantly lower level of viral Ags, suggesting that IL-13 may be regulating an important antiviral pathway. The examination of RSV-induced airway hyperreactivity in STAT6(-/-) mice demonstrated a significant attenuation of the response, similar to the anti-IL-13 treatment. In addition, STAT6(-/-) mice had a significant alteration of mucus-producing cells in the airway. Altogether, these studies suggest that a primary factor leading to chronic RSV-induced airway dysfunction may be the inappropriate production of IL-13.

Animals↗
PubMed2001

CeMENT: evaluation of a regional development programme integrating hospital and general practice clinical teaching for medical undergraduates. The Community-Based Medical Education in North Thames.

OBJECTIVES: To determine the feasibility and effectiveness of shared hospital and general practice clinical teaching for medical undergraduates. DESIGN: A multifaceted approach employing quantitative and qualitative techniques. SETTING: All medical schools in North Thames Region. SUBJECTS: Students, GP tutors and hospital specialists. RESULTS: The model was successfully adopted in a broad range of clinical specialties in all of the participating medical schools, resulting in a doubling of the involvement of general practice in clinical teaching. Participating students provided an overwhelmingly positive evaluation of the attachments and there was a clear perception of benefit amongst the participating GPs. However, the views of the participating hospital clinicians were less positive and the true nature and extent of the educational impact proved difficult to assess. CONCLUSIONS: This model of collaborative clinical teaching between hospital and general practice can be implemented in accordance with the project's key aims, but the enthusiastic involvement of hospital clinicians may be difficult to secure.

Education, Medical, Undergraduate↗
PubMed2001

SCF-induced airway hyperreactivity is dependent on leukotriene production.

Stem cell factor (SCF) is directly involved in the induction of airway hyperreactivity during allergen-induced pulmonary responses in mouse models. In these studies, we examined the specific mediators and mechanisms by which SCF can directly induce airway hyperreactivity via mast cell activation. Initial in vitro studies with bone marrow-derived mast cells indicated that SCF was able to induce the production of bronchospastic leukotrienes, LTC(4) and LTE(4). Subsequently, when SCF was instilled in the airways of naive mice, we were able to observe a similar induction of LTC(4) and LTE(4) in the bronchoalveolar lavage (BAL) fluid and lungs of treated mice. These in vivo studies clearly suggested that the previously observed SCF-induced airway hyperreactivity may be related to the leukotriene production after SCF stimulation. To further investigate whether the released leukotrienes were the mediators of the SCF-induced airway hyperreactivity, an inhibitor of 5-lipoxygenase (5-LO) binding to the 5-LO activating protein (FLAP) was utilized. The FLAP inhibitor MK-886, given to the animals before intratracheal SCF administration, significantly inhibited the release of LTC(4) and LTE(4) into the BAL fluid. More importantly, use of the FLAP inhibitor nearly abrogated the SCF-induced airway hyperreactivity. In addition, blocking the LTD(4)/E(4), but not LTB(4), receptor attenuated the SCF-induced airway hyperreactivity. In addition, the FLAP inhibitor reduced other mast-derived mediators, including histamine and tumor necrosis factor. Altogether, these studies indicate that SCF-induced airway hyperreactivity is dependent upon leukotriene-mediated pathways.

Animals↗
PubMed2001

Critical role for the chemokine MCP-1/CCR2 in the pathogenesis of bronchiolitis obliterans syndrome.

Bronchiolitis obliterans syndrome (BOS) is the major limitation to survival after lung transplantation. Acute rejection, its main risk factor, is characterized by perivascular/bronchiolar leukocyte infiltration. BOS is characterized by persistent peribronchiolar leukocyte recruitment leading to airway fibrosis and obliteration. The specific mechanism(s) by which these leukocytes are recruited are unknown. Because MCP-1, acting through its receptor CCR2, is a potent mononuclear cell chemoattractant, we hypothesized that expression of this chemokine during an allogeneic-response promotes persistent recruitment of leukocytes and, ultimately, rejection. We found that elevated levels of biologically active MCP-1 in human bronchial lavage fluid (BALF) were associated with the continuum from acute to chronic allograft rejection. Translational studies in a murine model of BOS demonstrated increased MCP-1 expression paralleling mononuclear cell recruitment and CCR2 expression. Loss of MCP-1/CCR2 signaling, as seen in CCR2(-/-) mice or in WT mice treated with neutralizing antibodies to MCP-1, significantly reduced recruitment of mononuclear phagocytes following tracheal transplantation and led to attenuation of BOS. Lymphocyte infiltration was not reduced under these conditions. We suggest that MCP-1/CCR2 signaling plays an important role in recruitment of mononuclear phagocytes, a pivotal event in the pathogenesis of BOS.

Animals↗
PubMed1996

Perihepatic abscess formation in diabetes: a complication of silent gallstones.

Perforation of the gallbladder is a serious complication of acute cholecystitis, with significant morbidity and mortality rates. We present the case of a diabetic adult in whom the usual signs and symptoms of acute cholecystitis were obscured. A high index of suspicion at the time of admission prompted emergent evaluation. Computerized axial tomography revealed a large perihepatic abscess extending from a perforated gallbladder. Fourteen hundred milliliters of malodorous brown fluid were drained by ultrasound-guided percutaneous aspiration from the collection. Early clinical suspicion combined with conservative surgical management may prevent serious morbidity and/or mortality in diabetic patients with complicated cholecystitis.

Cholecystitis↗
PubMed1994

Information about patients' deaths: general practitioners' current practice and views on receiving a death register.

BACKGROUND: Although general practitioners are involved in the care of most dying patients, they do not routinely receive information about their deceased patients for whom they did not complete the death certificate, and often they rely upon informal communication channels. AIM: This study set out to assess how general practitioners obtained, recorded and used information about deceased patients and to determine their views on receiving a death register. METHOD: A questionnaire was sent to all 305 general practitioners in the Newcastle upon Tyne and Sunderland Family Health Services Authority areas. RESULTS: A total of 225 questionnaires were returned (response rate 74%). General practitioners usually first learnt about their patients' deaths from hospital discharge summaries (54%) and patients' relatives (46%) and less commonly from newspaper obituary columns (20%) and hospital telephone calls (9%). Two thirds of respondents recorded information about decreased patients, mainly listing personal details and the immediate cause of death. One third or fewer of those recording information listed contributory causes. The information was used mainly for following up bereaved relatives and notifying hospitals and other agencies. CONCLUSION: Current informal systems for handling information about patients' deaths are inadequate. General practitioners need and would welcome prompt, accurate and comprehensive information about all their deceased patients.

Death↗
PubMed1993

Creating a death register for general practice.

General practitioners complete approximately 26% of death certificates themselves but have considerable difficulty obtaining prompt and accurate information about their other patients who die. A random survey of district health authorities in England revealed that all were able to compile death lists but none included general practitioner details. This paper reviews the flow of information on patient deaths and describes a project to assess the feasibility of providing Newcastle general practitioners with comprehensive death registers. With the collaboration of the family health services authority and the district health authority, and with data from the regional perinatal mortality survey the creation each week of complete lists of patient deaths, broken down by general practitioner, is feasible. Death registers allow general practitioners to undertake audit of the quality of death certification and of the care of the recently deceased, and to improve the continuing care of the bereaved.

Cause of Death↗