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Biomedical subjects

Peter Watson

Publications and source records attributed to Peter Watson.

At least 37 records · Page 2Linked to original sources
PubMed2004

Coupling of ER exit to microtubules through direct interaction of COPII with dynactin.

Transport of proteins from the endoplasmic reticulum (ER) to the Golgi is mediated by the sequential action of two coat complexes: COPII concentrates cargo for secretion at ER export sites, then COPI is subsequently recruited to nascent carriers and retrieves recycling proteins back to the ER. These carriers then move towards the Golgi along microtubules, driven by the dynein/dynactin complexes. Here we show that the Sec23p component of the COPII complex directly interacts with the dynactin complex through the carboxy-terminal cargo-binding domain of p150(Glued). Functional assays, including measurements of the rate of recycling of COPII on the ER membrane and quantitative analyses of secretion, indicate that this interaction underlies functional coupling of ER export to microtubules. Together, our data suggest a mechanism by which membranes of the early secretory pathway can be linked to motors and microtubules for subsequent organization and movement to the Golgi apparatus.

Animals↗
PubMed2004

The health of alternative education students compared to secondary school students: a New Zealand study.

AIM: To describe the health and wellbeing of alternative education (AE) students from the Northland and Auckland regions of New Zealand and compare these AE students with secondary school students of similar age from the same region. METHODS: All 36 AE schools in the region were surveyed in the year 2000. A total of 268 AE students completed a youth health questionnaire using laptop computers. Regional data from a 2001 national secondary school survey that used the same methodology was used for comparison with the AE student data. RESULTS: This study found that compared to secondary school students, AE students are more likely to come from disadvantaged backgrounds, with proportionally more AE students reporting socioeconomic difficulty and less parental connection. AE students were more likely to be vulnerable to behaviours that endanger their health, such as drug and alcohol use, risky sexual behaviours and risky motor vehicle use than secondary school students. AE students were also more likely to suffer from high levels of depressive symptoms indicative of significant psychopathology. CONCLUSIONS: Findings from this study support the need for specific policies and programs for alternative secondary school students to address urgent and serious threats to their health and wellbeing.

Adolescent↗
PubMed2004

Phospho-serine-118 estrogen receptor-alpha expression is associated with better disease outcome in women treated with tamoxifen.

PURPOSE: The purpose of this research was to determine whether estrogen receptor alpha specifically phosphorylated at Ser(118) is associated with clinical outcome in primary breast tumors from estrogen receptor-positive and node-negative breast cancer patients. EXPERIMENTAL DESIGN: Estrogen receptor alpha specifically phosphorylated at Ser(118) was determined by immunohistochemistry in 117 primary breast tumors from node-negative patients who were subsequently treated with adjuvant tamoxifen. The relationship of estrogen receptor alpha specifically phosphorylated at Ser(118) expression to disease-free survival and overall survival was determined. RESULTS: Estrogen receptor alpha specifically phosphorylated at Ser(118) was limited to estrogen receptor alpha ligand binding assay-positive tumors and among this subset was expressed in 70 (62%) of these tumors. Estrogen receptor alpha specifically phosphorylated at Ser(118) expression was more frequently observed in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors (chi(2) test, P = 0.012, n = 113). A significant correlation was also seen between estrogen receptor alpha specifically phosphorylated at Ser(118) and progesterone receptor levels (Spearman r = 0.236, P = 0.0118, n = 113). Kaplan-Meier outcome analysis showed that patients whose primary tumors expressed estrogen receptor alpha specifically phosphorylated at Ser(118) had a longer disease-free survival (P = 0.0018, n = 113) and a trend toward better overall survival, but this was not statistically significant. Among the subset of progesterone receptor-positive tumors, progesterone receptor-positive/estrogen receptor alpha specifically phosphorylated at Ser(118)-positive patients had a significantly longer disease-free survival that progesterone receptor-positive/estrogen receptor alpha specifically phosphorylated at Ser(118)-negative patients (P = 0.0041). CONCLUSIONS: Our data suggest that estrogen receptor alpha specifically phosphorylated at Ser(118) is a marker of a functional, intact ligand-dependent estrogen receptor signaling pathway in breast cancer and that estrogen receptor alpha specifically phosphorylated at Ser(118) status has the potential to provide a more precise biomarker of responsiveness to endocrine therapy in conjunction with estrogen receptor alpha and progesterone receptor status.

Antineoplastic Agents, Hormonal↗
PubMed2004

Acne prevalence in secondary school students and their perceived difficulty in accessing acne treatment.

AIMS: To describe the epidemiology of acne in New Zealand adolescents and their access to acne treatment. METHODS: Secondary analysis of data collected in the 'Youth2000' survey. A random sample of 12,934 Year 9-13 students, from 133 secondary schools across New Zealand, was invited to participate. The survey included items asking about self-perceived acne and access to acne treatment. RESULTS: The 'Youth2000' school response rate was 85.7%, the student response rate 75.0%, and the overall response rate 64.3%. Of the 9570 students who completed the questions on acne, 67.3% reported having acne. 'Problem acne' was reported by 14.1% of students and was more frequently reported by female, Pacific, and older students. Students with 'problem acne' (as well as female, Maori, and Pacific students) were significantly more likely to report difficulty accessing medical treatment for acne (46.0% vs 13.3%; OR 5.29). These differences persisted after controlling for socioeconomic factors. CONCLUSIONS: Acne is perceived as a significant health problem by nearly 1 in 7 adolescents. For those with 'problem acne,' effective treatment is available but not necessarily accessible. There are also disparities in access to treatment, particularly for females, Maori, and Pacific ethnic groups. This important youth health issue needs to be addressed.

Acne Vulgaris↗
PubMed2004

Phospho-serine-118 estrogen receptor-alpha detection in human breast tumors in vivo.

PURPOSE: To determine whether estrogen receptor (ER)-alpha specifically phosphorylated at Ser(118) is detectable in multiple human breast cancer biopsy samples. To gain insight into possible roles for P-Ser(118)-ERalpha in human breast cancer in vivo. EXPERIMENTAL DESIGN: A specific antibody for P-Ser(118)-ERalpha was validated for immunohistochemistry (IHC), and Western blot analysis confirmed IHC results. IHC was used to determine the relationship of P-Ser(118)-ERalpha to known prognostic markers and active mitogen-activated protein kinase (MAPK; erk1/2) expression. RESULTS: P-Ser(118)-ERalpha was significantly correlated with the expression of total ER, determined by ligand binding assay (r = 0.442, P = 0.002), but not with progesterone receptor expression or nodal status. P-Ser(118)-ERalpha was inversely correlated with histological grade (r = -0.34, P = 0.023), reflecting a similar trend for total ER (r = -0.287, P = 0.056). Categorical contingency analysis confirmed that P-Ser(118)-ERalpha was more frequently associated with lower than higher grade breast tumors (P = 0.038). In addition P-Ser(118)-ERalpha was significantly associated with detection of active MAPK (Erk1/2; Spearman r = 0.649, P < 0.0001; Fisher's exact test, P = 0.0004). CONCLUSIONS: P-Ser(118)-ERalpha detection is associated with a more differentiated phenotype and other markers of good prognosis in human breast cancer. P-Ser(118)-ERalpha is correlated with active MAPK in human breast tumor biopsies, suggesting the possibility that active MAPK either directly or indirectly has a role in the regulation of P-Ser(118)-ERalpha expression in vivo. These data provide evidence for a role of P-Ser(118)-ERalpha in human breast cancer in vivo.

Biomarkers, Tumor↗
PubMed2004

BAG-1 expression correlates with Bcl-2, p53, differentiation, estrogen and progesterone receptors in invasive breast carcinoma.

BAG-1, a recently identified anti-apoptotic protein, is overexpressed in the majority of invasive breast carcinomas. Overexpression of BAG-1 is important for both multi-step oncogenesis and resistance of cancer cells to apoptosis induced by DNA-damaging alkylating agents. BAG-1 protein species are localized differentially; nuclear expression may be associated with a shorter disease-free and overall survival in early stage breast cancer, while cytoplasmic expression has been associated with longer survival in non-small cell lung cancer. Growing evidence suggests that Bcl-2 and p53 are also involved in the oncogenesis of breast cancer. Since BAG-1 interacts with Bcl-2 and is upregulated by mutant p53 in vitro, it would be interesting to determine if their expressions are correlated with each other and with other clinical prognostic factors in invasive breast cancer. To address this question we conducted a large scale retrospective study of BAG-1, Bcl-2 and p53 in 185 breast cancer patients. Our study again showed that BAG-1 is overexpressed in the majority of breast cancer patients. In addition, it demonstrated that the expression of BAG-1 correlates with that of Bcl-2, p53, differentiation, estrogen and progesterone receptors. Our clinical study supports the preclinical finding of the interaction between BAG-1 and Bcl-2, p53 and estrogen and progesterone receptors. Further experiments to explore the prognostic and therapeutic role of BAG-1 in breast cancer are warranted.

Adult↗
PubMed2004

Antifeedant compounds from three species of Apiaceae active against the field slug, Deroceras reticulatum (Muller).

Extracts of volatiles from foliage of three plants in the Apiaceae, Conium maculatum L. (hemlock), Coriandrum sativum L. (coriander), and Petroselinum crispum Mill. (Nym.) (parsley), previously shown to exhibit antifeedant activity in assays with the field slug, Deroceras reticulatum (Muller) (Limacidae: Pulmonata), were studied further to identify the active components. Coupled gas chromatography-mass spectrometry (GC-MS) and neurophysiological assays using tentacle nerve preparations resulted in the identification of 11 active compounds from the three extracts. Wheat flour feeding bioassays were used to determine which of these compounds had the highest antifeedant activity. One of the most active compounds was the alkaloid gamma-coniceine, from C. maculatum. The role of potentially toxic alkaloids as semiochemicals and the potential for using such compounds as crop protection agents to prevent slug feeding damage is discussed.

Alkaloids↗
PubMed2004

Developmental changes in insulin-like growth factor I receptor gene expression in the mouse mammary gland.

The insulin-like growth factor I receptor (IGF-IR), which mediates the mitogenic action of IGF-I, has been shown to play an essential role in normal growth and development. However, the precise role of IGF-IR in the growth and differentiation of the mammary gland has not been elucidated. This study examines the profile of the IGF-IR gene and protein expression during normal postnatal mammary gland development in order to gain further insight into the role of the IGF-I/IGF-IR during mammary gland morphogenesis. Gene and protein expression were examined in developing mouse mammary glands (virgin, pregnant, lactating, involuting) by real time PCR analysis and Western blotting. Both IGF-IR gene and protein expression levels were high during early pregnancy. Interestingly, the level of gene expression was significantly down-regulated during late pregnancy (5.4 fold) and lactation (9-13 fold) and significantly up-regulated (3.9 fold) during late involution, to the level observed in the virgin mammary gland. By in situ hybridization, the IGF-IR transcripts were localized to the proliferating ductal epithelium of the mammary glands of virgin mice and to the differentiating ductal and alveolar epithelium of the mammary glands during pregnancy and lactation. In the involuting gland, the transcripts were localized to the regressing ductal epithelium. These data are direct evidence that IGF-IR expression is important for alveolar cell proliferation and suggest that the progression of involution may require the down-regulation of IGF-IR gene expression. Altogether, these results demonstrate that a developmental IGF-IR gene expression pattern exists in the mouse mammary gland and that increases in gene expression at specific phases of development may reflect an important role for IGF-I/IGF-IR at those phases of development.

Animals↗
PubMed2004

Intracranial metastatic parathyroid carcinoma. Case report and review of the literature.

Parathyroid carcinoma (PTC) is a rare pathological entity, with fewer than 400 reported cases. Intracranial metastasis of a PTC is exceptional; only five other cases have been identified in the English literature. The authors present a unique case of a patient with a solitary intracerebral metastasis of a PTC in an individual presumed to have hereditary hyperparathyroidism who had concomitant papillary and follicular carcinomas of the thyroid. The literature relevant to the management of these rare lesions is reviewed and discussed.

Brain Neoplasms↗
PubMed2003

Expression of the cell death genes BNip3 and NIX in ductal carcinoma in situ of the breast; correlation of BNip3 levels with necrosis and grade.

Ductal carcinoma in situ (DCIS) of the breast is an early, non-invasive lesion and the prognosis is associated with the extent of necrosis and cell death within the tumour. Two cell death genes, BNip3 and NIX, are up-regulated in response to hypoxia in breast carcinoma cells, although any involvement of either gene in disease progression is currently unknown. This study has analysed the expression of BNip3 and NIX in 56 samples of breast DCIS, as well as in adjacent benign and invasive breast tissue. Both genes are strongly expressed in the epithelial component of a subset of DCIS and invasive disease. The data show a correlation between high expression of BNip3 in the DCIS cells and a high-grade, necrotic lesion that is likely to be associated with invasive tumour. BNip3 was present in tumour-associated macrophages and in apocrine metaplastic lesions. Expression of NIX did not correlate with any of the parameters investigated.

Breast Neoplasms↗
PubMed2003

Helicobacter pylori infection and dyspepsia in pregnancy.

OBJECTIVE: To investigate the relationship of Helicobacter pylori infection with dyspeptic symptoms in early and late pregnancy. Infection with H pylori and pregnancy outcome were also assessed. METHODS: H pylori seropositivity was determined in 416 antenatal patients at 10 to 14 weeks' gestation. Dyspeptic symptoms were recorded at 10 to 14 weeks' gestation and at 30 to 32 weeks' gestation by means of a well-validated questionnaire. Details of pregnancy outcome were recorded from patients' case notes. RESULTS: The incidence of H pylori infection in our population was 41.8% (164 of 404). Patients infected with H pylori were no more likely than controls to experience dyspepsia at 10 to 14 weeks' or at 30 to 32 weeks' gestation (P =.75 and.43, respectively). CONCLUSION: H pylori infection was not associated with preterm delivery, non reassuring fetal status in labor, or birth weight less than the 10th centile (P =.17,.57, and.19, respectively).H pylori infection is not associated with an increase in dyspepsia or with maternal or neonatal morbidity.

Adult↗
PubMed2003

New insights into estrogen receptor function in human breast cancer.

An important new concept associated with estrogen receptor (ER) function in breast cancer is that ER status/ phenotype is multifaceted. In particular, the two full-length, ligand binding ERs (ER-alpha and ER-beta) and possibly multiple variant isoforms of ER must be considered. In addition, cross-talk factors that can influence ER activity in a ligand independent fashion and factors downstream of the ER, including coactivators and corepressors, clearly have important roles in ER function. Their careful evaluation in addition to ER status will be necessary to more fully understand the etiology of breast cancer and the changes occurring in estrogen signaling during breast tumorigenesis and breast cancer progression. Such knowledge is necessary to have a significant impact on better prevention and treatment strategies for human breast cancer.

Breast Neoplasms↗
PubMed2002

Characterization of a tissue-specific CDP/Cux isoform, p75, activated in breast tumor cells.

Two isoforms of the CCAAT-displacement protein/cut homeobox (CDP/Cux) transcription factor have been characterized thus far. The full length protein, p200, which contains four DNA binding domains, transiently binds to DNA and carries the CCAAT-displacement activity. The p110 isoform is generated by proteolytic processing at the G1-S transition and is capable of stable interaction with DNA. Here we demonstrate the existence of a shorter CDP/Cux isoform, p75, which contains only two DNA binding domains, Cut repeat 3 and the Cut homeodomain, and binds more stably to DNA. CDP/Cux p75 was able to repress a reporter carrying the promoter for the cyclin-dependent kinase inhibitor p21 gene and to activate a DNA polymerase alpha gene reporter. Expression of CDP/Cux p75 involved a novel mechanism: transcription initiation within intron 20. The intron 20-initiated mRNA (I20-mRNA) was expressed at higher level in the thymus and in CD4+/CD8+ and CD4+ T cells. I20-mRNA was expressed only weakly or not at all in normal human mammary epithelial cells and normal breast tissues but was detected in many breast tumor cells lines and breast tumors. In invasive tumors a significant association was established between higher I20-mRNA expression and a diffuse infiltrative growth pattern (n = 41, P = 0.0137). In agreement with these findings, T47D breast cancer cells stably expressing p75 could not form tubule structures in collagen but rather developed as solid undifferentiated aggregates of cells. Taken together, these results suggest that aberrant expression of the CDP/Cux p75 isoform in mammary epithelial cells may be associated with the process of tumorigenesis in breast cancer.

3T3 Cells↗