A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression

Transgenic expression of activated AKT1 in the murine prostate induces prostatic intraepithelial neoplasia (PIN) that does not progress to invasive prostate cancer (CaP). In luminal epithelial cells of Akt-driven PIN, we show the concomitant induction of p27(Kip1) and senescence. Genetic ablation of p27(Kip1) led to downregulation of senescence markers and progression to cancer. In humans, p27(Kip1) and senescence markers were elevated in PIN not associated with CaP but were decreased or absent, respectively, in cancer-associated PIN and in CaP. Importantly, p27(Kip1) upregulation in mouse and human in situ lesions did not depend upon mTOR or Akt activation but was instead specifically associated with alterations in cell polarity, architecture, and adhesion molecules. These data suggest that a p27(Kip1)-driven checkpoint limits progression of PIN to CaP.     

Effectiveness of inactivated influenza vaccine for prevention of otitis media in children

OBJECTIVE: The objective of this study was to evaluate the effectiveness of inactivated influenza vaccine in preventing acute otitis media (AOM) and otitis media with effusion (OME) in children aged 6 to 60 months who attend day care. STUDY DESIGN: This prospective, single-blind study was conducted in 8 day care centers in Ankara, Turkey. One hundred nineteen (61 vaccinated and 58 unvaccinated against influenza) healthy children were examined at study entry and at 6-week intervals for 6 months by the same 2 otorhinolaryngologists who were blinded about the vaccination status of the children. The frequency of AOM and OME is compared between the 2 groups and the effect of influenza season on frequency of episodes was evaluated. Based on national influenza laboratory data, the influenza season was determined to be the period between December 15, 2003, and January 31, 2004. RESULT: The frequencies of AOM, OME and total otitis media episodes in vaccinated children were 2.3%, 22.8% and 25.2%, respectively, and these frequencies were 5.2%, 31.1% and 36.3% in the unvaccinated group. The difference was statistically significant (P < 0.01). This difference was especially prominent in the influenza season (P < 0.05). CONCLUSION: Influenza vaccine is effective in reducing AOM and OME episodes in 6- to 60-month-old day care children, especially during influenza season.     

Expression of matrix metalloproteinases (MMP-2, MMP-3, and MMP-9) and fibronectin in lichen planus

BACKGROUND: Keratinocyte damage and lichenoid-interface reaction are the two major pathologic findings in lichen planus (LP). Matrix metalloproteinases (MMPs) are proteinases that participate in extracellular matrix (ECM) degradation and may play an important role in basal membrane (BM) damage in LP. Fibronectin (FN) mediates a variety of cellular interactions with ECM and plays important roles in cell adhesion, migration, growth and differentiation. OBJECTIVE: To determine MMP-2, MMP-3, MMP-9 and FN expressions in LP and discuss the possible associations. MATERIALS AND METHODS: Skin biopsy samples of 55 patients with LP and 11 normal skin were investigated. Five discoid lupus erythematosus (DLE) and 5 chronic dermatitis (CD) samples were also examined for comparison. Immunochemical stainings were performed for MMP-2, MMP-3, MMP-9 and fibronectin. RESULTS: Weak or absent expressions of MMP-2 and MMP-3 in epidermis; and dense MMP-9 expression in dermal inflammatory infiltrate cells were detected in LP. FN expression was lost in epidermal basal layer and papillary dermis. CONCLUSION: Loss of MMP-2, MMP-3 and FN in LP can be explained with the destruction of the epidermal basal layer. Similar expressions of MMP-2 and MMP-3 both in LP and DLE implied that these MMPs may be involved in the pathogenesis of interface dermatitis.     

Examination of bcl-2 and p53 expressions and apoptotic index by TUNEL method in psoriasis

BACKGROUND: Psoriasis is characterised by hyperproliferation and by aberrant differentiation. Blockage of the normal apoptotic process is one of the factors implicated in the pathogenesis. OBJECTIVE: To determine the apoptotic features by using TUNEL method and also bcl-2 and p53 expressions in psoriatic epidermis. MATERIALS AND METHODS: Biopsies of 35 patients with psoriasis vulgaris and 14 normal skin were evaluated. Apoptotic cells were detected using the dUTP nick-end labelling assay; bc1-2 and p53 expressions were assessed by using immunohistochemical techniques. A semi-quantitative grading system (HSCORE) was used for comparison. RESULTS: Bcl-2 was strongly expressed in basal keratinocytes of normal skin, while no expression was observed in 13 (37.2%) of the psoriatic samples and it was weakly expressed in the spinous cell layer of 22 (62.8%) samples. Moderate p53 expression was observed in the psoriasis group, while it was weak in the control. The percentage of TUNEL positive cells were significantly increased in the psoriasis group (65+/-2.30) when compared with the control (32.84+/-7.16). CONCLUSION: Apoptotic index besides bc1-2 and p53 expressions in psoriasis differ from normal epidermis. Down-regulation of bc1-2 is consistent with the dynamics of psoriasis but increased TUNEL positive cells and p53 expression has not been fully elucidated yet. Gündüz K, Demireli P, Vatansever S, Inanir I. Examination of bcl-2 and p53 expressions and apoptotic index by TUNEL method in psoriasis.     

Is dissection of levels 4 and 5 justified for cN0 laryngeal and hypopharyngeal cancer?

CONCLUSION: Dissecting levels 2 and 3 and sparing the dissection of level 4 and the contralateral neck when frozen section results are negative are reasonable options for the selective dissection of cN0 necks. Our findings show that dissection of level 5 is considered unnecessary, unless there is overt metastasis. OBJECTIVE: The level of node involvement and recurrence rates were assessed in cN0 laryngeal and hypopharyngeal carcinoma patients in order to develop appropriate guidelines for the treatment of the neck. MATERIALS AND METHODS: A total of 328 cN0 necks operated with selective dissection were reviewed retrospectively. Patients were monitored for at least 24 months and regional recurrences were evaluated. RESULTS: The prevalence of level 4 occult metastases was 3.4%; 1.5% of them were isolated to level 4. We observed regional recurrence in 5.6% of the necks. No case of metastasis or regional relapse was observed in level 5.     

Rubral tremor after thalamic infarction in childhood

The occurrence of tremor after thalamic lesions is well known. Delayed rubral tremor secondary to bilateral thalamic infarction is a rare finding and has not been reported previously in childhood. We present two children with a combined resting-postural-kinetic tremor caused by bithalamic infarction. The first child was a male 14 months of age, and the second was a male 9 years of age. These children come from unrelated families. On hospital admission of the first patient, generalized seizures and routine electroencephalogram (EEG) findings with diffuse spike-wave discharges predominantly over the left frontal area were clinically observed, leading to the initial diagnosis of epilepsia partialis continua. However, clinical observation and video-EEG monitoring of the movements revealed nonepileptiform accompaniments, favoring the diagnosis of rubral tremor. In the second patient, EEG revealed no paroxysmal activity and was within normal limits for age. In both patients, cranial magnetic resonance imaging revealed ischemic lesions in thalami bilaterally but failed to reveal any mesencephalic lesion. These patients demonstrate that thalamic infarction can cause rubral tremor in childhood.