Telomerase activity in oral lichen planus

The purpose of this study was to determine the expression of telomerase in refractory oral lichen planus. Using a polymerase chain reaction-based telomerase activity assay, we investigated telomerase activity in 20 oral lichen planus specimens (erosive 9, atrophic 11). Telomerase activity was detected in 14 cases (erosive 7, atrophic 7). Furthermore, 13 cases of lichen planus with mild dysplasia proved telomerase-positive in eight specimens and six of seven cases devoid of dysplasia were also positive in the telomerase assay. The data indicate that, in general, telomerase activity might be frequently detectable in OLP. The data also suggest that telomerase activity might not be particularly associated with the premalignant phenotype in OLP.     

Epidermolysis Bullosa Associated with Congenital Localized Absence of Skin,Fetal Abdominal Mass,and Pyloric Atresia**

Abstract: 2320-g male infant was delivered at 35 weeks gestation to a mother who had polyhydramnios. He had a combination of congenital localized absence of skin, unilateral hydronephrosis, and hydroureterdue to ureterovesical obstruction, and nonbilious vomiting due to pyloric atresia. Blistering of the skin developed after birth. Epidermolysis bullosa simplex was confirmed by electron microscopy of a skin biopsy specimen. We describe this patient, who had three unusual manifestations of epidermolysis bullosa.     

A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting.

ONYX-015 is an oncolytic virus untested as a treatment for malignant glioma. The NABTT CNS Consortium conducted a dose-escalation trial of intracerebral injections of ONYX-015. Cohorts of six patients at each dose level received doses of vector from 10(7) plaque-forming units (pfu) to 10(10) pfu into a total of 10 sites within the resected glioma cavity. Adverse events were identified on physical exams and testing of hematologic, renal, and liver functions. Efficacy data were obtained from serial MRI scans. None of the 24 patients experienced serious adverse events related to ONYX-015. The maximum tolerated dose was not reached at 10(10) pfu. The median time to progression after treatment with ONYX-015 was 46 days (range 13 to 452 + days). The median survival time was 6.2 months (range 1.3 to 28.0 + months). One patient has not progressed and 1 patient showed regression of interval-increased enhancement. With more than 19 months of follow-up, 1/6 recipients at a dose of 10(9) and 2/6 at a dose of 10(10) pfu remain alive. In 2 patients who underwent a second resection 3 months after ONYX-015 injection, a lymphocytic and plasmacytoid cell infiltrate was observed. Injection of ONYX-015 into glioma cavities is well tolerated at doses up to 10(10) pfu.     

Poland-Möbius syndrome and cocaine abuse: a relook at vascular etiology

This report presents a severe case of Poland-M?bius syndrome with central apnea at birth, ventilator-dependent, and with brainstem calcifications. The newborn had unilateral defect of the right pectoralis muscle, breast, and limb. He manifested bilateral paralysis of the cranial nerves resulting in shallow respiration, apnea, and dysphagia. He finally required tracheostomy and gastrostomy. Maternal history revealed multiple uses of cocaine during the first 3 months of pregnancy. The patient supports the Poland-M?bius combination and the possibility of vascular disruption sequence.     

Effects of the etonogestrel-releasing implant Implanon and a nonmedicated intrauterine device on the growth of breast-fed infants

The study objectives were to compare the effects of an etonogestrel-releasing implant (Implanon) and a nonmedicated intrauterine device (IUD) on parameters of lactation in breast-feeding women and on the growth of their breast-fed infants over a 3-year period. Healthy lactating women (28-56 days postpartum) chose either the implant (n=42) or the IUD (n=38). Infant growth during a 3-year follow-up period is reported here. Total duration of breast-feeding coinciding with the mothers' treatment was 421.0 and 423.4 days in the Implanon and IUD groups, respectively. There were no differences between the infant groups in terms of body length, biparietal head circumference and body weight. No abnormalities were reported in psychomotor development or during physical examination. No treatment-related side effects were observed in either group. In conclusion, there were no differences in the growth of breast-fed infants of women treated with Implanon or a nonmedicated IUD. Implanon, therefore, appears to be a safe contraceptive option for breast-feeding women and their infants.     

Tipranavir resistance associated mutations in protease inhibitor-na?ve patients with HIV-1 subtype A/E infection

BACKGROUND: Tipranavir-resistance associated mutations (TPV-RAMs) are often observed among patients with HIV-1 subtype A/E infection. Data regarding TPV resistance in subtype A/E is still limited. OBJECTIVES: To determine the prevalence of TPV-RAMs among protease inhibitor-na?ve, HIV-1 subtype A/E infected patients. STUDY DESIGN: Genotypic resistance testing was conducted among HIV-1-infected patients who were PI-na?ve. RESULTS: We studied 112 patients (mean age, 40.7 years; 58% male). Median CD4 cell count and HIV-1 RNA were 192cells/mm(3) and 4.2logcopies/mL, respectively. Ninety-three patients (83%) infected with subtype A/E; the others had subtype B. The most common TPV-RAMs were M36I (88%), H69K (61%), and I13V (48%). Median number of TPV-RAMs was 3 mutations. Patients with subtype A/E had higher prevalence of I13V (54% vs. 21%, P=0.011), M36I (96% vs. 53%, P<0.001), H69K (68% vs. 26%, P=0.001), and >2 TPV-RAMs (62% vs. 21%, P=0.002). In multivariate analysis, only subtype A/E was associated with the occurrence of >2 TPV-RAMs (OR 9.83; 95%CI, 1.95-39.57; P=0.006). CONCLUSIONS: TPV-RAMs previously described by IAS-USA are commonly observed in PI-na?ve patients with HIV-1 subtype A/E infection. Further studies to define virologic response of subtype A/E to TPV and clinical validation of TPV-RAMs in HIV-1 subtype A/E are essentially needed.     

Endometrial progesterone and estrogen receptors and bleeding disturbances in depot medroxyprogesterone acetate users

BACKGROUND: Depot medroxyprogesterone acetate (DMPA) is a very popular hormonal contraceptive. Unpredictable bleeding disturbances are the main reasons for discontinuation and may be mediated through endometrial hormone receptors. This study was aimed to compare the expression of progesterone and estrogen receptors in the endometrium of bleeding DMPA users with that of amenorrhoeic DMPA users. METHODS: Subjects were recruited between April 2000 and January 2001. On the day of the third DMPA injection, 42 amenorrhoeic DMPA users and 42 DMPA users who had frequent or prolonged endometrial bleeding and were bleeding on that day were matched by age and body mass index. Endometrial biopsies were collected for immunohistochemical study of progesterone receptor A plus B (PRAB) and B alone (PRB) and estrogen receptor alpha (ERalpha) and beta (ERbeta) expression. RESULTS: There were 23 adequate endometrial samples from each group. There were no differences in any of a series of comparisons of PRAB, PRB, ERalpha and ERbeta expression in glands or stroma between the groups. Serum estradiol and progesterone levels were also not different between the groups. CONCLUSIONS: Endometrial PRAB, PRB, ERalpha and ERbeta expression in glands and stroma was not different between DMPA users who had frequent or prolonged bleeding and amenorrhoeic DMPA users.     

Lipid rafts and nonrafts mediate tumor necrosis factor related apoptosis-inducing ligand induced apoptotic and nonapoptotic signals in non small cell lung carcinoma cells

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is capable of inducing apoptosis in non-small cell lung carcinoma (NSCLC). However, many of the human NSCLC cell lines are resistant to TRAIL, and TRAIL treatment of the resistant cells leads to the activation of nuclear factor-kappaB (NF-kappaB) and extracellular signal-regulated kinase 1/2 (ERK1/2). TRAIL can induce apoptosis in TRAIL-sensitive NSCLC cells through the induction of death-inducing signaling complex (DISC) assembly in lipid rafts of plasma membrane. In the DISC, caspase-8 is cleaved and initiates TRAIL-induced apoptosis. In contrast, TRAIL-DISC assembly in the nonraft phase of the plasma membrane leads to the inhibition of caspase-8 cleavage and NF-kappaB and ERK1/2 activation in TRAIL-resistant NSCLC cells. Receptor-interacting protein (RIP) and cellular Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (c-FLIP) mediates the DISC assembly in nonrafts and selective knockdown of either RIP or c-FLIP with interfering RNA redistributes the DISC from nonrafts to lipid rafts, thereby switching the DISC signals from NF-kappaB and ERK1/2 activation to caspase-8-initiated apoptosis. Chemotherapeutic agents inhibit c-FLIP expression, thereby enhancing the DISC assembly in lipid rafts for caspase-8-initiated apoptosis. These studies indicate that RIP and c-FLIP-mediated assembly of the DISC in nonrafts is a critical upstream event in TRAIL resistance and thus targeting of either RIP or c-FLIP may lead to the development of novel therapeutic strategies that can overcome TRAIL resistance in human NSCLC.