Activation of apoptosis associated with enforced myc expression in myeloid progenitor cells is dominant to the suppression of apoptosis by interleukin-3 or erythropoietin

The inappropriate expression of c-myc in cells deprived of growth factors has recently been implicated in the activation of programmed cell death (apoptosis). The studies described here examine the ability of interleukin-3 (IL-3) or erythropoietin (Epo) to suppress apoptosis that occurs in association with enforced myc expression during cell cycle arrest of a murine IL-3-dependent myeloid progenitor cell line, 32D. G1 arrest was observed when culturing 32D cells to high density in medium supplemented with IL-3, or at subconfluent densities in medium supplemented with Epo. Under both conditions, endogenous c-myc expression was downregulated and viability was maintained. In clones of cells in which c-myc is constitutively expressed from a retroviral vector, enforced c-myc expression was associated with the activation of apoptosis at high cell densities. Similarly, enforced c-myc expression was deleterious to cell survival when these cells were cultured in Epo, as apoptosis was evident within 6 hours. The results support the concept that inappropriate c-myc expression activates apoptosis and that neither IL-3 nor Epo can suppress this program under these conditions.     

Characterization of endometrial T lymphocyte subpopulations in spontaneous early pregnancy loss

T lymphocyte subpopulations were compared in normal first trimester human decidua and in decidua associated with spontaneous abortion. Cryostat sections were labelled using a panel of monoclonal antibodies specific for CD3, CD8, CD4 and for the alphabeta and gammadelta heterodimers of the T cell receptor using an avidin-biotin complex peroxidase method. All the endometrial T cell subsets which have been demonstrated in normal early pregnancy were detected in similar numbers and proportions in spontaneous abortion. The findings suggest that adverse pregnancy outcome is not influenced by altered proportions of T cell subpopulations; nevertheless, the possibility remains that these cells may have an altered antigenic phenotype in spontaneous abortion which could contribute to pregnancy success or failure.      

p53 and MDM2 expression in odontogenic cysts and tumours

OBJECTIVE: The aim of this report was to assess p53 and MDM2 expression in odontogenic cysts and tumours, as they are known to play important roles in cell proliferation and tumorigenesis. MATERIALS AND METHODS: The expression of p53 and MDM2 proteins was determined immunohistochemically in 51 formalin-fixed, paraffin embedded specimens of odontogenic cysts and tumours.RESULTS: No positivity to p53 was found in the cases studied. MDM2 expression in ameloblastoma was higher than in radicular cysts, but lower than that observed in odontogenic keratocysts. No difference was observed between MDM2 expression in radicular cyst and adenomatoid odontogenic tumour. The clear-cell odontogenic ameloblastoma presented strong immunoreaction to this antigen.CONCLUSIONS: The results suggest that MDM2 overexpression may be involved in the pathogenesis of some odontogenic lesions.     

Complications of automatic implantable cardioverter defibrillators: radiographic, CT, and echocardiographic evaluation

Automatic implantable cardioverter defibrillators (AICDs) were studied in three groups: (a) Serial radiographs were reviewed in 51 clinic patients. Twenty of 96 (21%) AICD patches distorted with time. (b) Thirty-six postoperative computed tomographic (CT) scans of asymptomatic patients revealed that pericardial fluid collections were frequent during the month after surgery but rare beyond that. Echocardiography was insensitive for these collections. CT also demonstrated dense fibrosis around some distorted patches, months after surgery. (c) Five other patients with pericardial infection had distorted patches, and the four studied with CT had fluid beneath their patches. (d) A case of constrictive pericarditis had distorted patches but was not diagnosed with CT. The authors conclude that distorted patches may indicate postoperative complications and that CT is the imaging modality of choice.     

Tongue and tonsil cancer: staging with US

A prospective study on the value of ultrasound (US) for the staging of 70 cases of cancer of the tongue and tonsil was performed. A real-time, high-frequency transducer was used, and the examination was often coupled with endobuccal palpation. US did not visualize the tumor in nine of 42 cases of tongue cancer (seven stage T1 and two anterior stage T2 tumors); US accurately defined tumor size in 33 cases. The degree of in-depth extension and the location with respect to the median line (only four false results) were evaluated correctly. With regard to 28 tonsil cancers, US depicted extension from the tonsillar fossa to the tongue in all cases but one (13 of 14 cases). US is valuable for the detection of cervical lymph nodes associated with both tongue and tonsil tumors and is a safe and helpful technique for the follow-up of medium-size lesions. The major limitations of US include the nonvisualization of superficial lesions, reduced accuracy for evaluation of the extension of large tumors, and analysis of posterior pharyngeal extension.     

Recurrence of primary sclerosing cholangitis after liver transplantation – analysing the European Liver Transplant Registry and beyond

Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4–18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9–9.1) and patient survival (HR 2.3; 95% CI 1.5–3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7–4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival.     

Haplotype and interspersion analysis of the FMR1 CGG repeat identifies two different mutational pathways for the origin of the fragile X syndrome

To understand the origins of the fragile X syndrome and factors predisposing alleles to instability and hyperexpansion, we have compared the haplotype (using markers FRAXAC1, FRAXAC2, and DXS548) and AGG interspersion patterns of the FMR1 CGG repeat for 214 normal and 16 premutation chromosomes. Association testing between interspersion pattern and haplotype reveals a highly significant (P < 0.002) non- random distribution, indicating that all three markers are useful in phylogenetic reconstruction of mutational change. Parsimony analysis of the FMR1 CGG repeat substructure predicts that loss of AGG interruptions has occurred independently on many haplotypes associated with the fragile X syndrome, partially explaining the haplotype diversity of this disease. Among haplotypes found in linkage disequilibrium with the fragile X mutation, two different modes of mutation and predisposition to instability have been identified. One pathway has involved the frequent and recurrent loss of AGG interruptions from rare asymmetrical ancestral array structures. Intergenerational transmission studies suggest that these predisposed chromosomes progress relatively rapidly to the disease state. In contrast, the second mutational pathway involves a single haplotype which has maintained two AGG interruptions. Parsimony analysis of CGG repeat substructure within this haplotype suggests that larger alleles have been generated by gradual increments of CGG repeats distal to the most 3' interruption. Pedigree analysis of the intergenerational stability of alleles of this haplotype confirms a gradual progression toward instability thresholds. As a result, a large reservoir of chromosomes carrying large repeats on this haplotype exists. These chromosomes are predisposed to disease. The present data support a model in which there are at least two different mutational pathways predisposing alleles to instability and hyperexpansion associated with the fragile X syndrome.