Clinical implications of telomerase activity and inactivation of the tumor suppressor gene p16 (CDKN2A) in head and neck cancer.
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Biomedical subjects
Publications and source records attributed to C Theuer.
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The p16INK4A (CDKN2A/MTS1) putative tumor suppressor gene encodes a cyclin dependent kinase inhibitor which plays an important role in the regulation of the G1/S phase cell cycle checkpoint. A high frequency of various p16 gene alterations were consequently observed in many primary tumors. P16 can be inactivated by different mechanisms: i) homozygous deletion, ii) methylation of the promoter region or iii) point mutation. In order to investigate p16 alterations in head and neck cancer (HNC) we analyzed 70 primary tumors of the larynx, pharynx and oral cavity including their corresponding normal mucosa for mutation inactivation by direct sequencing exon 2. We detected only one so far undescribed transversion G to T at position 322 (Asp108Tyr) and a known polymorphism (Ala148Thr) in five cases. The methylation status of the p16 promoter region was analyzed by an improved highly sensitive methylation-specific PCR protocol. P16 methylation inactivation was found in 16 of 55 cases (29%). Our data indicate that p16 point mutations in HNC are less frequent, but inactivation by methylation of the promoter region could be involved in genesis and progression of HNC.
Blunt tracheobronchial injuries may be difficult to diagnosis at presentation but can pose major airway difficulties. We present a patient with a tracheal transection who underwent intubation with the tip of the endotracheal tube exiting the trachea and terminating in the mediastinum adjacent to the distal trachea. He underwent surgical repair of the injury with end-to-end anastomosis. Although intubation over a flexible fiberoptic bronchoscope is desirable in cases of suspected tracheobronchial injury, it may not be feasible. In cases of suspected tracheobronchial injuries with blind endotracheal intubation, the possibility of false intubation should always be entertained.
The translocation of PE from the extracytosolic compartment to the cytosol during the intoxication of mammalian cells is mediated by domain II of the toxin. We have shown previously that within domain II amino acids 280-313 of PE promote their own export from mammalian microsomes following signal sequence-directed membrane insertion. In this study, we attempted to target full-length PE into mammalian microsomes using the preprocecropin signal sequence, but found that translocation was arrested to generate a transmembrane protein. "Stop transfer" required the presence of amino acids 280-313 of PE, and the first 313 amino acids of PE were sufficient to generate a transmembrane protein (N-terminus-in/C-terminus-out). The mechanism of stop transfer appears to be different from that described previously because amino acids 280-313 of PE are not highly hydrophobic and do contain many charged residues. In addition, the transmembrane segment appeared to be influenced by the cytoplasmic domain of the transmembrane proteins.
The charts of all patients with colonic volvulus at the University of Louisville Hospitals between 1983 and 1988 were reviewed. A total of 45 patients were identified, and there were 17 with cecal volvulus and 29 with sigmoid volvulus (1 had both). Two-thirds of the patients were either demented, bedridden, or used constipating drugs. Initial nonoperative decompression was achieved in 26 of 29 patients with sigmoid volvulus but in only three of nine patients in which it was attempted with cecal volvulus. Two of these recurred, and 16 of the 17 cecal volvulus patients underwent operation. One-third of the sigmoid volvulus patients had at least one recurrent episode on the index admission. Fourteen of the 29 had an operation, and half of these patients died following surgery. Fifteen sigmoid volvulus patients chosen to be treated with successive nonoperative treatment had no mortality. Mortality was higher following emergent (4 of 5) than elective (2 of 9) operation for sigmoid volvulus, and one of three died after operation for a successfully decompressed first episode. Mortality for nonoperative reduction of an early recurrence was zero of four patients, while operative mortality for recurrence was two of seven (all had successful preoperative deflation). There was no mortality or recurrence in four patients with cecal volvulus treated by cecopexy alone, but all three patients died in whom tube cecostomy was performed. Two of nine patients died following right hemicolectomy. These data suggest that if an elective operation is to be performed for sigmoid volvulus, it should be done following one or more recurrences and that nonoperative decompression can be safely performed on successive occasions.(ABSTRACT TRUNCATED AT 250 WORDS)
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