Isolation and primary cultures of human intrahepatic bile ductular epithelium

A technique for the isolation of human intrahepatic bile ductular epithelium, and the establishment of primary cultures using a serum- and growth-factor-supplemented medium combined with a connective tissue substrata is described. Initial cell isolates and monolayer cultures display phenotypic characteristics of biliary epithelial cells (low molecular weight prekeratin positive; albumin, alphafetoprotein, and Factor VIII-related antigen negative). Ultrastructural features of the cultured cells show cell polarization with surface microvilli, numerous interepithelial junctional complexes and cytoplasmic intermediate prekeratin filaments. © 1988 Tissue Culture Association, Inc

Methylated DNA recognition during the reversal of epigenetic silencing is regulated by cysteine and cerine residues in the Epstein-Barr Virus lytic switch protein

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with various malignancies, including Burkitt's lymphoma and nasopharyngeal carcinoma. Like all herpesviruses, the EBV life cycle alternates between latency and lytic replication. During latency, the viral genome is largely silenced by host-driven methylation of CpG motifs and, in the switch to the lytic cycle, this epigenetic silencing is overturned. A key event is the activation of the viral BRLF1 gene by the immediate-early protein Zta. Zta is a bZIP transcription factor that preferentially binds to specific response elements (ZREs) in the BRLF1 promoter (Rp) when these elements are methylated. Zta's ability to trigger lytic cycle activation is severely compromised when a cysteine residue in its bZIP domain is mutated to serine (C189S), but the molecular basis for this effect is unknown. Here we show that the C189S mutant is defective for activating Rp in a Burkitt's lymphoma cell line. The mutant is compromised both in vitro and in vivo for binding two methylated ZREs in Rp (ZRE2 and ZRE3), although the effect is striking only for ZRE3. Molecular modeling of Zta bound to methylated ZRE3, together with biochemical data, indicate that C189 directly contacts one of the two methyl cytosines within a specific CpG motif. The motif's second methyl cytosine (on the complementary DNA strand) is predicted to contact S186, a residue known to regulate methyl-ZRE recognition. Our results suggest that C189 regulates the enhanced interaction of Zta with methylated DNA in overturning the epigenetic control of viral latency. As C189 is conserved in many bZIP proteins, the selectivity of Zta for methylated DNA may be a paradigm for a more general phenomenon

Between feminism and anorexia: An autoethnography

Critical feminist work on eating disorders has grown substantially since its establishment in the 1980s, and has increasingly incorporated the use of anorexic stories, voices and experiences. Yet rarely do such accounts offer the anorexic a space to respond to the now established feminist conceptions of the problem which structure the books or articles in which they appear. Anorexic, or recovered anorexic, voices are used by the researcher to interpret the role played by gender, even whilst the subjects are invited to respond to and critique, medical and popular discourses on the disorder. This lack of dialogue is all the more striking in the context of the feminist aim to fight ‘back against the tendency to silence anorexic women’s’ own interpretations of their starving, treatment and construction (Saukko, 2008: 34). As someone who suffered from anorexia for 20 years, this article offers an autoethnographic account of my experience of encountering the feminist literature on anorexia in a bid to speak back, or enter into a dialogue between feminist politics and eating disorder experience

A retrospective review and multi-specialty, evidence-based guideline for the management of necrotising otitis externa

BACKGROUND: Necrotising otitis externa is a progressive infection of the external auditory canal which extends to affect the temporal bone and adjacent structures. Progression of the disease process can result in serious sequelae, including cranial nerve palsies and death. There is currently no formal published treatment guideline.OBJECTIVE: This study aimed to integrate current evidence and data from our own retrospective case series in order to develop a guideline to optimise necrotising otitis externa patient management.METHODS: A retrospective review of necrotising otitis externa cases within NHS Lothian, Scotland, between 2013 and 2018, was performed, along with a PubMed review.RESULTS: Prevalent presenting signs, symptoms and patient demographic data were established. Furthermore, features of cases associated with adverse outcomes were defined. A key feature of the guideline is defining at-risk patients with initial intensive treatment. Investigations and outcomes are assessed and treatment adjusted appropriately.CONCLUSION: This multi-departmental approach has facilitated the development of a succinct, systematic guideline for the management of necrotising otitis externa. Initial patient outcomes appear promising.</p

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie

A randomised crossover trial comparing Thai and Swedish massage for fatigue and depleted energy

Background: The aim of this study was to compare the efficacy and social constructions of Thai massage (TM) and Swedish massage (SM) for patients experiencing fatigue or depleted energy. Method: Twenty participants were randomised to receive three once-weekly TM treatments and three once-weekly SM treatments, with crossover after three massages. Symptom checklists were administered at three time points and included Activation-Deactivation Adjective Check List and VAS Scale. Qualitative data were collected through semi-structured interviews and participants’ diary entries. Results: Both massage types enhanced physical, emotional and mental wellbeing through improved sleep, relaxation, relief of stress and relief of muscular tension. TM alone showed specific energising and psychological stimulation results, along with carry-over effect and longer lasting benefits. Ninety-five percent of participants found relief from their initial reason presenting symptoms. Conclusion: TM or SM can relieve symptoms of fatigue or low energy by releasing stress, promoting relaxation, relieving muscular aches and pains and improving energy. SM results in a larger effect in relaxation and improved sleep whereas TM results in a larger effect in energising, rejuvenating and mentally stimulating effects

The Effect of Real and Sham Acupuncture on Thermal Sensation and Thermal Pain Thresholds

Objective: To compare the effect of real and sham acupuncture and a control intervention on thermal sensation and thermal pain thresholds. Design: Single-blind, randomized controlled, repeated-measures trial. Setting: Laboratory. Participants: Eighteen acupuncture naive, healthy subjects with no history of upper-limb pathology or acupuncture contraindications. Intervention: Subjects were randomly assigned (blind card allocation) to 1 of 6 possible orders of application of the interventions, which consisted of 25 minutes each of control, real, and sham acupuncture. Main Outcome Measures: Thermal sensation and thermal pain thresholds measured with a thermal sensory analyzer before and after each intervention. Results: There were increases in cold and hot pain and cold sensation thresholds with real acupuncture. The level of increase did not differ significantly from the changes that occurred with sham acupuncture and control interventions. Conclusions: Although we observed a trend toward a decreased sensitivity to thermal pain and thermal sensation with real acupuncture, this trend did not differ significantly from the changes with control or sham interventions. Therefore, no support was provided for analgesic or placebo effects of acupuncture. The trend, combined with the relatively low power of the inferential tests applied does, however, suggest that further research is merited