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P G Wilson

Publications and source records attributed to P G Wilson.

At least 19 recordsLinked to original sources
PubMed2001

Yeast frameshift suppressor mutations in the genes coding for transcription factor Mbf1p and ribosomal protein S3: evidence for autoregulation of S3 synthesis.

The SUF13 and SUF14 genes were identified among extragenic suppressors of +1 frameshift mutations. SUF13 is synonymous with MBF1, a single-copy nonessential gene coding for a POLII transcription factor. The suf13-1 mutation is a two-nucleotide deletion in the SUF13/MBF1 coding region. A suf13::TRP1 null mutant suppresses +1 frameshift mutations, indicating that suppression is caused by loss of SUF13 function. The suf13-1 suppressor alters sensitivity to aminoglycoside antibiotics and reduces the accumulation of his4-713 mRNA, suggesting that suppression is mediated at the translational level. The SUF14 gene is synonymous with RPS3, a single-copy essential gene that codes for the ribosomal protein S3. The suf14-1 mutation is a missense substitution in the coding region. Increased expression of S3 limits the accumulation of SUF14 mRNA, suggesting that expression is autoregulated. A frameshift mutation in SUF14 that prevents full-length translation eliminated regulation, indicating that S3 is required for regulation. Using CUP1-SUF14 and SUF14-lacZ fusions, run-on transcription assays, and estimates of mRNA half-life, our results show that transcription plays a minor role if any in regulation and that the 5'-UTR is necessary but not sufficient for regulation. A change in mRNA decay rate may be the primary mechanism for regulation.

5' Untranslated Regions↗
PubMed1999

BimC motor protein KLP61F cycles between mitotic spindles and fusomes in Drosophila germ cells.

KLP61F in Drosophila is a member of the BimC family of kinesins and, as for other family members [1], is required for spindle assembly [2] [3]. KLP61F is a bipolar homotetramer that cross-links spindle microtubules [4]. It is not known, however, whether the function of KLP61F is dedicated to mitosis or whether KLP61F interacts exclusively with microtubules. Previous work suggested that KLP61F functions during interphase in proliferating germ cells [3]. Cytokinesis is incomplete in germ cells and a branched cortical structure known as a fusome extrudes through intercellular bridges called ring canals. Here I show that, in germ cells, KLP61F cycles between spindles during mitosis and fusomes during interphase. Inspection of fusome-deficient hu-li tai shao (hts) mutants indicated that KLP61F gains fusome-dependent interactions near telophase that mediate its incorporation into these structures. KLP61F proved to be maintained in fusomes by microtubule-independent, detergent-resistant interactions. Inspection of KLP61F mutants indicated that KLP61F is required to recruit fusome material to spindle midbodies near telophase and for normal fusome organization. These observations suggest that KLP61F is bifunctional in germ cells, with microtubule-dependent functions in spindle assembly and microtubule-independent functions in fusome organization. Cytological analyses with antibodies against phosphorylated Eg5 peptide [4] suggest that cycling of KLP61F might reflect phosphorylation.

Amino Acid Isomerases↗
PubMed1998

Maternally expressed gamma Tub37CD in Drosophila is differentially required for female meiosis and embryonic mitosis.

We report functional analysis of gamma Tub37CD, a maternally synthesized gamma-tubulin that is highly expressed during oogenesis and utilized at centrosomes in precellular embryos. Two gamma Tub37CD mutants contained missense mutations that altered residues conserved in all gamma-tubulins and alpha- and/or beta-tubulins. A third gamma Tub37CD missense mutant identified a conserved motif unique to gamma-tubulins. A fourth gamma Tub37CD mutant contained a nonsense mutation and the corresponding premature stop codon generated a protein null allele. Immunofluorescence analysis of laid eggs and activated oocytes derived from the mutants revealed microtubules and meiotic spindles that were close to normal even in the absence of gamma Tub37CD. Eggs lacking the maternal gamma-tubulin were arrested in meiosis, indicative of a deficiency in activation. Analysis of meiosis with in vitro activation techniques showed that the cortical microtubule cytoskeleton of mature wild-type eggs was reorganized upon activation and expressed as transient assembly of cortical asters, and this cortical reorganization was altered in gamma Tub37CD mutants. In precellular embryos of partial loss of function mutants, spindles were frequently abnormal and cell cycle progression was inhibited. Thus, gamma Tub37CD functions differentially in female meiosis and in the early embryo; while involved in oocyte activation, it is apparently not required or plays a subtle role in formation of the female meiotic spindle which is acentriolar, but is essential for assembly of a discrete bipolar mitotic spindle which is directed by centrosomes organized about centrioles.

Amino Acid Sequence↗
PubMed1998

Acute pancreatitis as a model of sepsis.

Severe acute pancreatitis has many similarities to sepsis syndrome and septic shock. The haemodynamic features of cardiovascular instability, reduced ejection fraction and decreased systemic vascular resistance are indistinguishable in each of these conditions. In addition there are many striking similarities in the cytokine and inflammatory mediator profiles, suggesting that the haemodynamic abnormalities may result from the same pathogenic mechanisms, albeit as a result of different inflammatory stimuli. Although septic complications of severe acute pancreatitis do arise these are usually late features and in the early phase of a severe attack there is sterile pancreatic necrosis. Evidence suggests that the important cytokines in the development of complications and multiple organ failure in severe acute pancreatitis are tumour necrosis factor-alpha, interleukin-1, interleukin-6 and interleukin-8. In addition, endotoxin and other important inflammatory mediators including platelet activating factor and phospholipase A2 are implicated in the development of complications in both severe acute pancreatitis and sepsis. Patients with severe acute pancreatitis are not an entirely homogeneous group but in terms of pathogenesis and complications of their disease they have much more in common with each other than the patients who are collected under the unifying diagnosis of 'sepsis'. The similar clinical and biochemical features between severe acute pancreatitis and sepsis make the former an excellent model for studying the pathogenesis of the sepsis syndrome.

Acute Disease↗
PubMed1997

Differential expression of two gamma-tubulin isoforms during gametogenesis and development in Drosophila.

Previous work identified a gamma-tubulin gene, gamma Tub23C, in Drosophila (Zheng et al., 1991). We now report identification of a second gamma-tubulin gene, gamma Tub37CD. Immunoblot analysis and immunolocalization show that gamma Tub37CD and gamma Tub23C are differentially expressed during gametogenesis and development. During oogenesis, gamma Tub23C was detected at centrosomes and in the cytoplasm of mitotic germ cells, but was not detected in germ cells following completion of mitosis. Conversely, gamma Tub37CD was not detected in proliferating germ cells, but appeared to accumulate in germ cells during egg chamber development. Neither gamma-tubulin isoform was detected at the anterior or posterior poles of developing oocytes. During spermatogenesis, only gamma Tub23C was detected at centrosomes, where it showed cell cycle- and differentiation-dependent organization. During the transition into the first meiotic division, gamma Tub23C became organized as a corpuscular focus at centrioles until completion of meiosis II. During postmeiotic spermatid differentiation, gamma Tub23C was detected first as a rod and then as a collar-like structure near the juncture of the nucleus and the elongating flagellum, but was not detected in bundles of mature sperm. The germline-specific CDC25 encoded by twine is required for organization of gamma Tub23C into corpuscular focus in spermatocytes, but not for separation of centriole pairs in M-phase or postmeiotic organization of gamma Tub23C at centrioles. Following reconstitution of a canonical centrosome at fertilization, only gamma Tub37CD was detected at centrosomes in syncytial embryos, but both gamma Tub37CD and gamma Tub23C were detected at centrosomes in cellularized embryos. Colocalization of these two isoforms suggests that gamma Tub23C and gamma Tub37CD both contain structural features of gamma-tubulins essential for localization to centrosomes.

Amino Acid Sequence↗
PubMed1997

Evolution of the multi-tubulin hypothesis.

Microtubules are organized into diverse cellular structures in multicellular organisms. How is such diversity generated? Although highly conserved overall, variable regions within alpha- and beta-tubulins show divergence from other alpha- and beta-tubulins in the same species, but show conservation among different species. Such conservation raises the question of whether diversity in tubulin structure mediates diversity in microtubule organization. Recent studies probing the function of beta-tubulin isotypes in axonemes of insects suggest that tubulin structure, through interactions with extrinsic proteins, can direct the architecture and supramolecular organization of microtubules.

Animals↗
PubMed1997

Home-based behavioral treatments for chronic benign headache: a meta-analysis of controlled trials.

Controlled clinical trials have consistently demonstrated that behavioral treatments for chronic benign headache produce clinically beneficial outcomes both post-treatment and at follow-up. Given these results there is interest in cost-reduction and redesign of these treatments to improve their accessibility. One promising approach in this regard is home-based headache treatment. These treatments seek to provide the same amount of treatment as clinic-based treatments; however, some of the material typically presented to the patient by a clinician is presented through home-study materials (e.g., manuals, audiotapes). To date, the published literature contains 20 controlled clinical trials which have examined the outcomes produced by home-based treatments. This article presents the first comprehensive meta-analysis of these clinical outcome studies. Results of the quantitative analyses suggest that home-based treatments produce comparable, or with certain outcome measures, superior results to clinic-based treatments. Moreover, costeffectiveness scores of home-based treatments were found to be more than five times larger than those of clinic-based therapies. Methodological analyses are also presented along with suggestions for future research.

Adolescent↗
PubMed1997

Monastral bipolar spindles: implications for dynamic centrosome organization.

Implicit to all models for mitotic spindle assembly is the view that centrosomes are essentially permanent structures. Yet, immunofluorescence revealed that spindles in larval brains of urchin mutants in Drosophila were frequently monastral but bipolar; the astral pole contained a centrosome while the opposing anastral pole showed neither gamma tubulin nor a radial array of astral microtubules. Thus, mutations in the urchin gene seem to uncouple centrosome organization and spindle bipolarity in mitotic cells. Hypomorphic mutants showed a high frequency of monastral bipolar spindles but low frequencies of polyploidy, suggesting that monastral bipolar spindles might be functional. To test this hypothesis, we performed pedigree analysis of centrosome distribution and spindle structure in the four mitotic divisions of gonial cells. Prophase gonial cells showed two centrosomes, suggesting cells entered mitosis with the normal number of centrosomes and that centrosomes separated during prophase. Despite a high frequency of monastral bipolar spindles, the end products of the four mitotic divisions were equivalent in size and chromatin content. These results indicate that monastral bipolar spindles are functional and that the daughter cell derived from the anastral pole can assemble a functional bipolar spindle in the subsequent cell cycle. Cell proliferation despite high frequencies of monastral bipolar spindles can be explained if centrosome structure in mitotic cells is dynamic, allowing transient and benign disorganization of pericentriolar components. Since urchin proved to be allelic to KLP61F which encodes a kinesin related motor protein (Heck et al. (1993) J. Cell Biol. 123, 665-671), our results suggest that motors influence the dynamic organization of centrosomes.

Alleles↗
PubMed1997

Outcome of surgery for chronic pancreatitis.

BACKGROUND: In patients with chronic pancreatitis, surgery is indicated for the management of intractable pain or for the treatment of complications. METHODS: Sixty-three consecutive patients (49 men and 14 women of median age 40 (range 20-72) years) who had undergone surgery over an 8-year interval for chronic pancreatitis were studied. The mortality and morbidity rates associated with surgery were assessed and quality of life was reviewed based on relief of symptoms, analgesic use, employment and long-term sequelae. RESULTS: Forty-four patients (70 per cent) had alcoholic chronic pancreatitis. In 60 patients the principal indication for surgery was intractable pain. Eighteen patients had a duodenum-preserving resection of the pancreatic head (Beger operation); the other surgical procedures were Whipple resection (15), left-sided resection (13), total pancreatectomy (seven), pseudocystjejunostomy (five), pancreaticojejunostomy (one) and bypass procedures (four). The median inpatient stay was 12 days; 23 patients had postoperative complications including one death (2 per cent). There was improved pain control (P < 0.001), a reduction in opiate analgesia use, increase in percentage weight gain (P < 0.01 at 2 years) and return to employment following surgery. Although there was an increase in diabetes mellitus and need for enzyme supplementation these were easily controlled. CONCLUSION: Surgery is an effective treatment in carefully selected patients with chronic pancreatitis but must be tailored to the pattern of disease in each individual.

Adult↗
PubMed1996

Duodenal gangliocytic paraganglioma presenting as an ampullary tumor.

CONCLUSION: We report a case of a duodenal gangliocytic paraganglioma that had an unusual clinical presentation and atypical immunohistochemical features. BACKGROUND: Duodenal gangliocytic paragangliomas are rare tumors of the gastrointestinal tract with approx 70 cases reported in the literature. The most common presentation is with gastrointestinal bleeding, whereas obstructive jaundice is very uncommon. Immunohistochemistry typically shows positive epithelial cell staining for somatostatin, pancreatic polypeptide, and other neuroendocrine markers. METHODS: A 56-yr-old man presented with intermittent episodes of epigastric pain, vomiting, and obstructive jaundice. Upper gastrointestinal endoscopy revealed a pedunculated ampullary tumor that was subsequently confirmed by computed tomography. At operation, there was marked secondary obstructive chronic pancreatitis in the remaining pancreas necessitating a pylorus-preserving total pancreatectomy. RESULTS: Histology confirmed typical features of a duodenal gangliocytic paraganglioma, but immunohistochemistry demonstrated negative staining for somatostatin and other polypeptides, which is in contrast to most other reported cases. Two years after surgery, the patient remains alive and well on medical treatment with no evidence of recurrent tumor.

Ampulla of Vater↗
PubMed1996

Coordinate developmental control of the meiotic cell cycle and spermatid differentiation in Drosophila males.

Wild-type function of four Drosophila genes, spermatocyte arrest, cannonball, always early and meiosis I arrest, is required both for cell-cycle progression through the G2/M transition of meiosis I in males and for onset of spermatid differentiation. In males mutant for any one of these meiotic arrest genes, mature primary spermatocytes with partially condensed chromosomes accumulate and postmeiotic cells are lacking. The arrest in cell-cycle progression occurs prior to degradation of cyclin A protein. The block in spermatogenesis in these mutants is not simply a secondary consequence of meiotic cell-cycle arrest, as spermatid differentiation proceeds in males mutant for the cell cycle activating phosphatase twine. Instead, the arrest of both meiosis and spermiogenesis suggests a control point that may serve to coordinate the male meiotic cell cycle with the spermatid differentiation program. The phenotype of the Drosophila meiotic arrest mutants is strikingly similar to the histopathological features of meiosis I maturation arrest infertility in human males, suggesting that the control point may be conserved from flies to man.

Alleles↗
PubMed1995

Interaction of persons with severe mental retardation and their nondisabled co-workers in integrated work settings.

This investigation matched 23 workers with severe mental retardation to 23 workers without disabilities by job type and minimal duration of employment (at least 6 months) to determine if co-worker relations differed between the two groups of employees. Results indicated that, compared to workers with severe mental retardation, nondisabled workers were more likely to receive information, to receive training, and to interact as friends outside the workplace.

Adult↗
PubMed1994

Matched-pairs analysis of co-worker interactions in relation to opportunity, type of job, and placement approach.

Workers with and without disabilities (n = 85) were studied in an effort to determine whether co-worker relations differed between these employees. Few differences were found. Interactions of co-workers without disabilities with their supported co-workers who had disabilities were remarkably similar to their interactions with other co-workers without disabilities in eight of the nine interaction categories investigated. In the ninth category (befriending off the job), co-workers without disabilities interacted more among themselves. Considering only workers with disabilities, those employed individually in light industry occupations experienced less physical integration than did those employed either in groups or in any other occupation. These findings were discussed in relation to available research.

Employment↗
PubMed1993

Awareness and knowledge of fragile X syndrome among special educators.

A questionnaire to assess awareness and knowledge of various syndromes was mailed to a random sample of elementary special education teachers in Colorado. Approximately half of the questionnaires were completed and returned. Results indicate that significantly more respondents had knowledge of Down syndrome than of fetal alcohol or fragile X syndromes. Respondents' level of education, date of most recent degree, and years of experience were not associated with greater awareness nor knowledge of fragile X syndrome. Respondents expressed interest in a broad array of fragile X in-service training topics.

Adult↗
PubMed1992

Strategies to increase exercise-report correspondence by boys with moderate mental retardation: collateral changes in intention-exercise correspondence.

Correspondence between verbal and nonverbal behavior in an exercise room was taught to 4 13-year-old boys diagnosed with moderate mental retardation. Participants were asked prior to each exercise session which exercise machine(s) they intended to use. No contingencies on stating intentions (promising) were applied. Following the exercise session, participants were asked to say (report) which machine(s) they had used. Following the baseline condition, do-report correspondence training was introduced sequentially across participants. During do-report correspondence training, accurate reporting was reinforced. High rates of both do-report and promise-do correspondence were observed. Data were analyzed via a multiple baseline across subjects design and contingency-space analysis. Results are discussed with regard to observed changes in promise-do correspondence subsequent to observed changes in do-report correspondence.

Adolescent↗