Biomedical subjects

W P Long

Publications and source records attributed to W P Long.

6 recordsLinked to original sources

PubMed2001

Familial adenomatous polyposis: a case report and review of the literature.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition characterized by diffuse intestinal polyposis, specific gene mutation, and predisposition for developing colon cancer. Left untreated, patients with FAP will develop colorectal carcinoma during early adulthood. Hence, early detection and surgical intervention are of the utmost importance. Colectomy is required and may include an ileal pouch with ileoanal anastomosis, which eliminates the colon and rectal disease while preserving fecal continence and avoidance of a permanent ileostomy. Advances in the treatment of FAP with associated reduction in mortality from colorectal carcinoma make extracolonic manifestations of the disease more common and life-long surveillance is mandatory. The most life-threatening extracolonic manifestations of FAP are periampullary carcinoma and desmoid tumors. The upper gastrointestinal tract should be monitored endoscopically at the time of diagnosis and assessed regularly thereafter. Duodenal adenomas should be resected so as to avoid the devastating effects of invasive periampullary carcinoma. Additionally, the development of desmoid tumors needs to be monitored (by CT or MRI), so as to avoid the severe complications of local invasion. Further research is indicated in the development of effective screening and treatment for this condition.

Adenomatous Polyposis Coli↗

PubMed1999

Lack of an absolute requirement for the native aryl hydrocarbon receptor (AhR) and AhR nuclear translocator transactivation domains in protein kinase C-mediated modulation of the AhR pathway.

Protein kinase C (PKC)-mediated modulation of the aryl hydrocarbon receptor (AhR) pathway was examined in CHOK1-derived L10.I cells stably transfected with the pGUDLUC6.1 reporter; pGUDLUC6.1 is solely controlled by four dioxin-responsive enhancer elements. Co treatment of L10.I cells with 10 nM 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) and 81 nM phorbol 12-myristate 13-acetate (PMA), an activator of sn-1,2-diacylglyerol binding PKCs, enhanced transactivation of the reporter construct several-fold relative to cells treated with a saturating 10 nM TCDD dose alone; this effect was dubbed the "PMA effect." A domain swapping and deletional analysis of the native AhR and AhR nuclear translocator (ARNT) protein transactivation domains (TADs) was performed to determine if these domains are absolutely required for the AhR x ARNT dimer-mediated PMA effect in the L10.I model system; controls demonstrate the suitability of the L10.I model for these analyses and that endogenous AhR and ARNT levels are extremely low in this model. Transient coexpression of the AhR and ARNT-474-FLAG, an ARNT protein lacking the native ARNT TAD, in L10.I cells reveals the native ARNT TAD is not absolutely required for the AhR x ARNT-474-FLAG dimer to mediate the PMA effect. Transient coexpression of AhRDeltaCVP, a chimeric AhR protein in which the native AhR TAD has been replaced with the VP16 (herpes simplex virus protein 16) TAD (which control experiments demonstrate is unaffected by PMA), and ARNT in L10.I cells indicates that the native AhR TAD is not absolutely required for this AhRDeltaCVP x ARNT dimer to mediate the PMA effect. These observations strongly suggest that PKC-mediated modulation of the AhR pathway is not absolutely dependent on coactivators recruited to the AhR. ARNT dimer by the native TADs of the AhR and its heterodimerization partner ARNT.

Animals↗

PubMed1999

Protein kinase C modulates aryl hydrocarbon receptor nuclear translocator protein-mediated transactivation potential in a dimer context.

Protein kinase C (PKC)- and protein kinase A (PKA)-mediated modulation of the transactivation potential of human aryl hydrocarbon receptor nuclear translocator (hARNT), a basic helix-loop-helix (bHLH)-PAS transcription factor, and the bHLH-ZIP transcription factors USF-1 (for upstream regulatory factor 1) and c-Myc were examined. An 81 nM dose of the PKC activator phorbol-12-myristate-13-acetate (PMA), shown here to specifically activate PKC in COS-1 cells, or a 1 nM dose of the PKA activator 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP) results in 2. 6- and 1.9-fold enhancements, respectively, in hARNT-mediated transactivation of the class B, E-box-driven reporter pMyc3E1bLuc relative to identically transfected, carrier solvent-treated COS-1 cells. In contrast, 81 nM PMA and 1 nM 8-Br-cAMP did not enhance transactivation of pMyc3E1bLuc-driven by USF-1 and c-Myc expression relative to identically transfected, carrier-treated COS-1 cells. Co-transfection of pcDNA3/ARNT-474-Flag, expressing a hARNT carboxyl-terminal transactivation domain deletion, and pMyc3E1bLuc does not result in induction of reporter activity, suggesting PMA's effects do not involve formation of unknown hARNT-protein heterodimers. Additionally, PMA had no effect on hARNT expression relative to Me2SO-treated cells. Metabolic 32P labeling of hARNT in cells treated with carrier solvent or 81 nM PMA demonstrates that PMA does not increase the overall phosphorylation level of hARNT. These results demonstrate, for the first time, that the transactivation potential of ARNT in a dimer context can be specifically modulated by PKC or PKA stimulation and that the bHLH-PAS and bHLH-ZIP transcription factors are differentially regulated by these pathways in COS-1 cells.

Animals↗

PubMed1998

Protein kinase C activity is required for aryl hydrocarbon receptor pathway-mediated signal transduction.

The role of protein kinase C (PKC) in the human aryl hydrocarbon receptor (hAhR) signal transduction pathway was examined in cell lines stably transfected with pGUDLUC6.1, in which luc+ is solely controlled by four dioxin-responsive elements (DREs). These cell lines, P5A11 and HG40/6, were derived from HeLa and HepG2 cells respectively. Simultaneous treatment of these cells with 2,3,7,8, -tetrachlorodibenzo-p-dioxin (TCDD) and phorbol-12-myristate-13-acetate (PMA) enhanced trans-activation of the reporter construct several-fold relative to cells treated with TCDD alone. PKC inhibitors block the PMA effect and hAhR-mediated signal transduction, demonstrating these processes require PKC activity. Examination of other independently generated, HeLa-derived cell lines stably transfected with pGUDLUC6.1 demonstrates the PMA effect in P5A11 cells is not a clonal artifact. Transient transfections indicate the PMA effect is not due to a luciferase message/gene product stabilization mechanism or stimulation of the basal transcription machinery. Examination of cytosolic preparations demonstrates PKC stimulation or inhibition does not alter hAhR and hAhR nuclear translocator protein levels or TCDD-induced down-regulation of hAhR levels. Similarly, examination of nuclear extracts indicated PKC stimulation or inhibition does not alter nuclear AhR levels or hAhR/hAhR nuclear translocator protein heterodimer DRE-binding activity as assessed by electrophoretic mobility shift assay. These results demonstrate a PKC-mediated event is required for the hAhR to form a functional transcriptional complex that leads to trans-activation and that the DRE is the minimal DNA element required for PMA to enhance AhR-mediated trans-activation.

Alkaloids↗

PubMed1998

Recurrent malignant acrospiroma. Treatment by chest wall excision.

Malignant acrospiroma is an uncommon tumor of the eccrine sweat gland. In contrast to its relatively more common benign counterpart, malignant acrospiroma is highly invasive, often with significant lymphatic and distant metastasis. The establishment of this diagnosis is difficult on both clinical and histopathologic grounds. After diagnosis, wide surgical excision is warranted to completely extirpate these lesions. We report the case of a 66-year-old female with a recurrent malignant acrospiroma. This patient's tumor was removed by wide radical resection, including chest wall excision, followed by reconstructive surgery and radiotherapy. After 16 months there is no evidence of local recurrence or distant metastasis.

Acrospiroma↗

PubMed1997

Chest wall resection for extrapulmonary tumor.

Despite progress in early detection of breast cancer, a minority of women continue to present with extensive disease which may necessitate chest wall resection. Between 1992 and 1996, 14 patients were treated by surgical resection of the chest wall and reconstruction by the LSU Sections of Surgical Oncology and Plastic Surgery. Indications included resection of primary tumor, resection of recurrent tumor, and resection of radiation therapy induced damage to the chest wall. We report chest wall excision and reconstruction with no operative mortality and minor surgical morbidity in 21% of cases. Local control was achieved in 13 of 14 cases. Additionally we report uniform success in the palliation of ulcerating, painful, or infected chest wall lesions. Approximately 25% of patients treated for breast cancer and followed up for more than 6 months have remained free of disease. Chest wall resection is a useful modality in selected patients with extensive disease.

Aged↗