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Biomedical subjects

T G Wilson

Publications and source records attributed to T G Wilson.

At least 19 recordsLinked to original sources
PubMed2002

A single p450 allele associated with insecticide resistance in Drosophila.

Insecticide resistance is one of the most widespread genetic changes caused by human activity, but we still understand little about the origins and spread of resistant alleles in global populations of insects. Here, via microarray analysis of all P450s in Drosophila melanogaster, we show that DDT-R, a gene conferring resistance to DDT, is associated with overtranscription of a single cytochrome P450 gene, Cyp6g1. Transgenic analysis of Cyp6g1 shows that overtranscription of this gene alone is both necessary and sufficient for resistance. Resistance and up-regulation in Drosophila populations are associated with a single Cyp6g1 allele that has spread globally. This allele is characterized by the insertion of an Accord transposable element into the 5' end of the Cyp6g1 gene.

Alleles↗
PubMed2001

Periodontal considerations in restorative and implant therapy.

The successful integration of periodontal and restorative dentistry for both natural teeth and implants requires knowledge and application of both mechanical and biological principles. In areas of aesthetic concern, an adequate band of attached gingiva can increase patient comfort, reduce the probability of gingival recession following tooth preparation and simplify restorative procedures. While some restorative margins need to be placed at or below the margin of the free gingiva, this should be considered to be a compromise, and margins should not be placed more than 0.5 mm into a healthy gingival sulcus. Approximately 2-3 mm of healthy, natural supra-alveolar tooth surface is needed for attachment of the gingival tissues to the tooth. This dimension is called the biological width. If adequate biological width does not exist, surgical or orthodontic procedures to expose healthy tooth structure are recommended before final restorations are placed. Retraction of soft tissues for impressions is best accomplished with mechanical methods rather than lasers or electrosurgery because of the potentially harmful effects of these devices to the cementum, bone and soft tissues surrounding the teeth. Implants function best and withstand occlusal forces optimally when loaded in a vertical direction. Therefore, planning implant placement is critical for success. Because of increased proprioception, it is suggested that natural teeth be used to guide the occlusion in partially edentulous patients. Cantilevers should be used with caution and with appropriate attention to occlusal forces. While occlusal trauma does not cause periodontal disease, it may contribute to bone loss around teeth and implants. In the opinion of the authors, provisional restorations are an integral part of dental and periodontal therapy. They can be used to establish aesthetic and physiological contours that can be easily cleaned by patients and they can also be used as a guide for any needed surgical tissue modification.

Crown Lengthening↗
PubMed2001

Resistance of Drosophila to toxins.

Insects, including Drosophila, readily respond to toxins such as phytotoxins, metal ions, and insecticides in their environment by evolving resistance. Although Drosophila are seldom targets for insecticides, nevertheless populations worldwide have evolved resistance to a variety of insecticides, and these resistance alleles persist in high frequency. In many cases, Drosophila use the same genetic and biochemical mechanisms that underlie resistance in pest insects, including single-site changes in target molecules resulting from point mutations and upregulation of degradative enzymes, particularly cytochrome P450 enzymes and glutathione S-transferases. However, several types of resistance found in pest insects, such as gene amplification and knock-down resistance, have not been reported in Drosophila field populations. Excellent Drosophila-plant models are being studied to understand the adaptation to phytotoxins; P450 enzymes are clearly involved in phytotoxin resistance in one of these models. The genetic advantages of D. melanogaster, including availability of the sequenced genome, should allow further study of these genes and identification of new ones, particularly regulatory genes, responsible for resistance.

Adaptation, Physiological↗
PubMed2001

Asymptomatic renal neoplasms in the rectal cancer patient.

Although cancers of the rectum and kidney are common malignancies the incidence of coexistent rectal and renal primary tumors is unclear. Our objective was to determine the true incidence of synchronous neoplasms of the rectum and kidney. The computed tumor registry database at the City of Hope National Medical Center was queried for patients with synchronous rectal cancer and renal neoplasms presenting between August 1990 and August 2000. During the 10-year period there were 182 patients presenting for treatment of rectal carcinoma. Of these seven (3.8%) were found to have an asymptomatic renal neoplasm. Four patients underwent synchronous resection. Three patients underwent staged renal and rectal resections. The pathology of the renal lesions included renal cell carcinoma in six and an oncocytoma in one patient. Rectal lesions were all adenocarcinomas and all were within 10 cm of the dentate line. Three patients required abdominoperineal resections and four were treated with low anterior resections. Two patients presented with hepatic metastasis at the time of diagnosis. Five patients remain free of disease. Two patients died of persistent and recurrent disease 6 months and 40 months after operation. With the exception of one patient who required prolonged intubation because of severe Parkinson's disease there were no major complications after simultaneous resection of both renal and rectal disease. Simultaneous asymptomatic renal neoplasms may be found in up to 3.8 per cent of patients with rectal cancer. Synchronous lesions may be treated simultaneously without significant morbidity.

Aged↗
PubMed2000

Biological complications with dental implants: their prevention, diagnosis and treatment.

Biofilms form on all hard non-shedding surfaces in a fluid system, i.e. both on teeth and oral implants. As a result of the bacterial challenge, the host responds by mounting a defence mechanism leading to inflammation of the soft tissues. In the dento-gingival unit, this results in the well-described lesion of gingivitis. In the implanto-mucosal unit, this inflammation is termed "mucositis". If plaque is allowed to accumulate for prolonged periods of time, experimental research has demonstrated that "mucositis" may develop into "periimplantitis" affecting the periimplant supporting bone circumferentially. Although the bony support may be lost coronally, the implant still remains osseointegrated and hence, clinically stable. This is the reason why mobility represents an insensitive, but specific diagnostic feature of "periimplantitis". More sensitive and more reliable parameters of developing and existing periimplant infections are "bleeding on probing", "probing depths" and radiographic interpretation of conventional or subtraction radiographs. Depending on the diagnosis made continuously during recall visits, a maintenance system termed Cumulative Interceptive Supportive Therapy (CIST) has been proposed.

Animals↗
PubMed2000

Chemical and gamma-ray mutagenesis of the white gene in Aedes aegypti.

A molecular understanding of an insect gene can be facilitated by analysing the phenotypes of mutants for that gene. Protocols were developed for both chemical and gamma-ray mutagenesis in Aedes aegypti using the white (w) gene as an assay. Wild-type adult males were subjected to varying doses of either ethyl methanesulphonate (0. 1%, 0.5% or 1%) or gamma rays (1500 R or 3000 R), mated to females homozygous for the recessive w mutation, and progeny screened for the w phenotype, indicating non-complementation. The expression of newly induced w alleles was either complete or mosaic. Gamma-ray mutagenesis resulted in high (1.65 or 6.39%, depending on dose) induction of mutant alleles for the w gene, but not for a different gene, red-eye (0.15%). Gamma-ray-induced w alleles did not revert at a reasonable frequency following additional irradiation, suggesting that the high rate of gamma-ray-induced w mutagenesis is not due to a transposon insertion event.

Aedes↗
PubMed2000

Simplified technique with short and long-term followup of conversion of an ileal conduit to an Indiana pouch.

PURPOSE: We report a simplified technique for converting an existing conduit to an Indiana pouch as well as short and long-term results. MATERIALS AND METHODS: From May 1988 to February 1998 we evaluated short and long-term outcome and complications in 23 patients 14 to 82 years old (average age 51.8) who underwent conversion of a conduit to an Indiana pouch. When no obstruction of the existing ureteroileal anastomoses was identified, the conduit was freed from the abdominal wall and surrounding bowel. The proximal conduit and ureteral anastomoses were not dissected. The conduit was opened along the antimesenteric wall proximal to the ureteral anastomoses and attached to 25 to 28 cm. of detubularized right colon as a refluxing Studer limb. The pouch was completed in the usual fashion and the stoma was matured at a virgin site. RESULTS: Surgical indications included stomal complications in 10 patients, an infected nonfunctioning kidney in 2 and patient preference in 11. There were no perioperative deaths although 3 patients died of cancer progression. Average operative time was 6.6 hours, estimated blood loss 518 cc and length of stay 7.8 days. Average followup after conversion was 4.7 years (range 0.2 to 11.0). Six late complications developed in 4 cases, including pyelonephritis in 2, severe pouchitis in 1, dehydration in 1 and stomal revision in 2. Renal function was well preserved with an average preoperative and postoperative creatinine of 0.91 and 1.14 mg./dl., respectively. CONCLUSIONS: This technique simplifies conversion and decreases bowel requirements. The low complication rate and stable serum creatinine support the finding that conversion of a conduit to an Indiana pouch is a safe, viable procedure.

Adolescent↗
PubMed2000

NCCN Practice Guidelines for Prostate Cancer.

Systemic therapies for prostate cancer are likely to improve, and as they do, they will have enormous impact on the treatment of high-risk and locally advanced cancers. Further technical improvements in radiotherapy and alternative local modalities, such as cryoablation, are also likely, and will bring even more options for local control. It is certain these guidelines will continue to evolve.

Evidence-Based Medicine↗
PubMed1999

A modification of isolated Roux loop reconstruction after pancreaticoduodenectomy.

BACKGROUND: Different techniques of reconstruction following pancreaticoduodenectomy have been described. A new modification using an isolated Roux-en-Y loop is reported. METHODS: The isolated loop is taken up to bile duct rather than pancreas as previously described. RESULTS: Seventeen patients have undergone this procedure. Two pancreatic fistulae developed, both following postoperative abscess formation. There was no operative mortality. CONCLUSION: This reconstruction provides separation of biliary and pancreatic fluid but adds two further benefits: the wide jejunal lumen allows for an easier pancreaticojejunal anastomosis, particularly when operating on a soft pancreas, and separation of gastric and biliary anastomoses prevents the efflux of bile into stomach.

Aged↗
PubMed1999

The relationship between the interleukin-1 periodontal genotype and implant loss. Initial data.

BACKGROUND: This study investigated the relationship of the interleukin-1 (IL-1) genotype, smoking status, and the patient's age to the survival of osseointegrated dental implants. METHODS: Twenty-seven patients with 33 implants that had been lost or who had at least 50% bone loss on radiographs were compared to a group of 38 patients who had experienced no bone or implant loss. All lost implants in a private practice were included in the data, except those that had fractured with no previous bone loss. RESULTS: Smoking was demonstrated to increase the risk of implant failure by a factor of almost 2.5. CONCLUSIONS: Statistical testing failed to provide evidence of an increased risk for implant failure for patients who are positive for the IL-1 genotype. There was no apparent relationship between the patient's age at the time of placement and implant loss. This study raises several questions concerning the etiology of implant loss and the comparative biology of tissues surrounding implants when compared to those surrounding natural teeth.

Adult↗
PubMed1999

Immunotherapy of bladder cancer targeting P53.

PURPOSE: Superficial bladder cancer is often responsive to immunotherapy with bacillus Calmette-Guerin (BCG). However, some tumors progress despite BCG treatment, and most of these have mutations in the p53 tumor suppressor gene resulting in its over-expression. Overexpressed p53 is therefore a potential target for immunotherapy. The objective of this study was to demonstrate whether human bladder cancer xenografts in SCID mice could be eliminated by cytotoxic T cells (CTL) which recognize over-expressed p53. MATERIALS AND METHODS: Murine CTL which are specific for human p53 were previously generated in our laboratory by peptide immunization of HLA A2.1 transgenic mice. These CTL recognize and lyse human tumor cell lines which over-express p53 in the context of HLA A2.1. The p53 over-expressing HLA A2.1+ human bladder cancer cell line J82 was used to establish subcutaneous or intravesicular tumors in SCID mice. The mice were then administered tail vein injections of 5 x 10(7) p53-specific CTL, control CTL, or phosphate buffered saline (PBS). RESULTS: The subcutaneous tumor mean volume at 5 weeks for the p53-specific CTL treatment group was significantly lower than for both the control CTL or the PBS group (32 mm.3 versus 185 mm.3, p = 0.04 and 32 mm.3 versus 418 mm.3, p = 0.0001). In the mice with intravesicular tumors, a reduction to nonpalpable tumor size in vivo was seen with specific CTL therapy (14% palpable) versus control CTL treatment (86% palpable), the final tumor volume at necropsy was 127 mm.3 versus 246 mm.3 (N.S.). CONCLUSION: The overall response of the human bladder tumors in the SCID mouse model suggests the possibility of targeting p53 in patients with bladder cancer.

Animals↗
PubMed1999

Using risk assessment to customize periodontal treatment.

In recent years, understanding of the multifactorial nature of periodontal disease has taken great strides. Periodontal disease is initiated and sustained by the presence of bacteria, but disease progression is significantly modified by the body's response to the bacteria. This article highlights the emerging evidence regarding which risk factors are predominant in influencing the disease process and how the incorporation of prognostic risk factors in overall diagnosis can help facilitate treatment planning. These factors appear to be smoking, genetic susceptibility, compliance, and diabetes. The first three factors mentioned are the focus of this article. Each is discussed with regard to their role in amplifying the disease process and how this information can be used in clinical practice. By acknowledging the importance of these factors, dentists can consider their patients' risk to allow for more cost-effective planning and treatment. The opportunity to identify high-risk patients and treat them more proactively is significant; the challenge rests with dentists' willingness and ability to embrace the change before them.

Disease Progression↗
PubMed1998

Insecticide resistance resulting from an absence of target-site gene product.

Genetic changes in insects that lead to insecticide resistance include point mutations and up-regulation/amplification of detoxification genes. Here, we report a third mechanism, resistance caused by an absence of gene product. Mutations of the Methoprene-tolerant (Met) gene of Drosophila melanogaster result in resistance to both methoprene, a juvenile hormone (JH) agonist insecticide, and JH. Previous results have demonstrated a mechanism of resistance involving an intracellular JH binding protein that has reduced ligand affinity in Met flies. We show that a gamma-ray induced allele, Met27, completely lacks Met transcript during the insecticide-sensitive period in development. Although Met27 homozygotes have reduced oogenesis, they are viable, demonstrating that Met is not a vital gene. Most target-site resistance genes encode vital proteins and thus have few mutational changes that permit both resistance and viability. In contrast, resistance genes such as Met that encode nonvital insecticide target proteins can have a variety of mutational changes that result in an absence of functional gene product and thus should show higher rates of resistance evolution.

Animals↗
PubMed1998

Insect juvenile hormone resistance gene homology with the bHLH-PAS family of transcriptional regulators.

Juvenile hormone analog (JHA) insecticides are relatively nontoxic to vertebrates and offer effective control of certain insect pests. Recent reports of resistance in whiteflies and mosquitoes demonstrate the need to identify and understand genes for resistance to this class of insect growth regulators. Mutants of the Methoprene-tolerant (Met) gene in Drosophila melanogaster show resistance to both JHAs and JH, and previous biochemical studies have demonstrated a mechanism of resistance involving an intracellular JH binding-protein that has reduced ligand affinity in Met flies. We cloned the Met+ gene by transposable P-element tagging and found reduced transcript level in several mutant alleles, showing that underproduction of the normal gene product can lead to insecticide resistance. Transformation of Met flies with a Met+ cDNA resulted in susceptibility to methoprene, indicating that the cDNA encodes a functional Met+ protein. MET shows homology to the basic helix-loop-helix (bHLH)-PAS family of transcriptional regulators, implicating MET in the action of JH at the gene level in insects. This family also includes the vertebrate dioxin receptor, a transcriptional regulator known to bind a variety of environmental toxicants. Because JHAs include a diverse array of chemicals with JH activity, a mechanism whereby they can exert effects in insects through a common pathway is suggested.

Amino Acid Sequence↗
PubMed1998

A juvenile hormone agonist reveals distinct developmental pathways mediated by ecdysone-inducible broad complex transcription factors.

Juvenile hormone (JH) is an important regulator of insect development that, by unknown mechanisms, modifies molecular, cellular, and organismal responses to the molting hormone, 20-hydroxyecdysone (20E). In dipteran insects such as Drosophila, JH or JH agonists, administered at times near the onset of metamorphosis, cause lethality. We tested the hypothesis that the JH agonist methoprene acts by interfering with function of the Broad Complex (BRC), a 20E-regulated locus encoding BTB/POZ-zinc finger transcription factors essential for metamorphosis of many tissues. We found that methoprene, administered by feeding or by topical application, disrupts the metamorphic reorganization of the central nervous system, salivary glands, and musculature in a dose-dependent manner. As we predicted, methoprene phenocopies a subset of previously described BRC defects; it also phenocopies Deformed and produces abnormalities not associated with known mutations. Interestingly, methoprene specifically disrupts those metamorphic events dependent on the combined action of all BRC isoforms, while sparing those that require specific isoform subsets. Thus, our data provide independent pharmacological evidence for the model, originally based on genetic studies, that BRC proteins function in two developmental pathways. Mutations of Methoprene-tolerant (Met), a gene involved in the action of JH, protect against all features of the "methoprene syndrome." These findings have allowed us to propose novel alternative models linking BRC, juvenile hormone, and MET.

Animals↗
PubMed1998

Expression of insulin-like growth factor (IGF)-II in human prostate, breast, bladder, and paraganglioma tumors.

Insulin-like growth factors (IGFs) are potent mitogens for a variety of cancer cells in vitro. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. Information on cell-type-specific IGF-II expression in vivo in the breast and prostate is, however, limited. Thus, cell types expressing IGF-II mRNA and protein in tumors were identified by in situ hybridization and immunohistochemistry. Of 36 prostate, 17 breast, and 10 bladder cancers, and 9 paraganglioma tissues examined, IGF-II was expressed in more than 50% of prostate, breast, and bladder tumors, and in 100% of paraganglioma tumors. Expression levels of IGF-II were highest in the paraganglioma and bladder followed by prostate and breast tumors. In all the tumors expressing IGF-II, both mRNA and protein were localized to malignant cells, expression in the stroma being minimal. Since previous studies had indicated that an incompletely processed form of 15-kDa IGF-II exhibited higher mitogenic potency than the completely processed 7.5-kDa IGF-II form, the quantity and size of IGF-II proteins expressed in these tumors were analyzed by Western immunoblotting. Greater expression of 15-kDa IGF-II relative to the 7.5-kDa IGF-II form was clearly demonstrated in all six prostate cancers and in half of the two breast and four bladder cancers examined. The results are consistent with the hypothesis that the 15-kDa form of IGF-II expressed in cancerous cells contributes to autocrine cancer cell growth in vivo.

Breast Neoplasms↗