Plakoglobin (PG) is a paralog of β-catenin with similar adhesive, but contrasting signalling functions. Although β-catenin has well-known oncogenic function, PG generally acts as a tumor/metastasis suppressor by mechanisms that are just beginning to be deciphered. Previously, we showed that PG interacted with wild type (WT) and a number of mutant p53s, and that its tumor/metastasis suppressor activity may be mediated, at least partially, by this interaction. Here, carcinoma cell lines deficient in both p53 and PG (H1299), or expressing mutant p53 in the absence of PG (SCC9), were transfected with expression constructs encoding WT and different fragments and deletions of p53 and PG, individually or in pairs. Transfectants were characterized for their in vitro growth, migratory and invasive properties and for mapping the interacting domain of p53 and PG. We showed that when coexpressed, p53-WT and PG-WT cooperated to decrease growth, and acted synergistically to significantly reduce cell migration and invasion. The DNA-binding domain of p53 and C-terminal domain of PG mediated p53/PG interaction, and furthermore, the C-terminus of PG played a central role in the inhibition of invasion in association with p53.
This pilot study shows, for the first time, increased capillary blood flow in the duodenum of UC patients that was unrelated to inflammatory markers or disease activity. Thus, early vascular changes can be assessed using pCLE during endoscopy.
40-year-old woman, originally from Armenia, presented to the emergency department with a three-day history of fever, malaise, myalgia and nonproductive cough, followed by a rash that began on her face and spread downwards to her trunk and arms. She had delivered her first child nine weeks earlier with no complications. Ten days before onset of symptoms, she had received both mumps-measles-rubella (MMR) (MMR II, Merck Frosst Canada) and tetanus-diphtheria vaccinations. The patient lacked childhood immunization records and reported that she had not received all of her childhood vaccinations in Armenia owing to an allergic reaction, which remained unrecognized on her immigration to Canada. Apart from prior subacute thyroiditis, the patient was healthy and was taking no active medications. She had no recent travel or known sick contacts. She had immigrated to Canada seven years prior, was married to a monogamous male partner and worked as an accountant. On initial examination, she was alert and oriented. She was normotensive, but tachycardic at 116 beats/min. She was febrile with a maximum temperature of 39.3°C. A mild conjunctival injection was noted. She had a diffuse blanchable erythematous maculopapular rash involving her face, trunk and proximal upper extremities (Figure 1). The rest of her examination was noncontributory. Laboratory investigations showed mild leukopenia (leukocytes 2.6 [normal 4.0-11.0] × 10 9 /L) and elevated lactate dehydrogenase (320 [normal 100-235] U/L). Chest radiography was unremarkable. An acute respiratory viral infection, along with the possibility of measles, was considered based on the fever and rash presentation. A nasopharyngeal swab and urine sample were sent for respiratory viruses and measles virus testing. On admission, the patient was placed in an airborne isolation room, along with additional precautions. On postadmission day one, the respiratory viral panel came back negative for the following: influenza A and B; respiratory syncytial virus; parainfluenza virus 1, 2, 3 and 4; adenovirus; coronaviruses 229E, NL63, OC43 and HKU1; and the enterovirus/ rhinovirus group. Both the nasopharyngeal and urine samples tested positive for measles virus by real-time polymerase chain reaction (PCR), which targets the hemagglutinin and nucleoprotein genes of the virus. 1 Differentiation between the wild-type
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