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Biomedical subjects

P Shaw

Publications and source records attributed to P Shaw.

At least 91 records · Page 5Linked to original sources
PubMed1997

Molecular cloning of cDNA for guinea pig CYP1A2 comparison with guinea pig CYP1A1.

Guinea pig CYP1A2 cDNA was isolated by RT-PCR from liver tissue of 3,3'-methylcholanthrene-treated guinea pigs. It shares considerable sequence identity with guinea pig CYP1A1 (nt 77%, aa 65%), but differs in levels of constitutive expression, function, and inducibility. Western blot analysis of protein expressed by full-length cDNA in COS-1 cells identified CYP1A2 (56 kDa) and CYP1A1 (53 kDa) proteins in corun liver microsomes. CYP1A2 transfectants metabolized methoxyresorufin and ethoxyresorufin, while CYP1A1 transfectants metabolized only ethoxyresorufin. Constitutive expression of CYP1A2 mRNA (2.0 kb) and protein was much lower than that of CYP1A1 mRNA (2.6 kb) and protein, but the fold induction of CYP1A2 by 3,3'-methylcholanthrene was greater than that of CYP1A1. Changes in splicing of CYP1A2 pre-mRNA occur upon treatment with 3,3'-methylcholanthrene.

Amino Acid Sequence↗
PubMed1997

A novel approach to providing children's dentistry in general dental practice.

Although more dentists are deciding to specialize in one specific area, these specialist subjects tend to deal with adult treatments. Few choose to specialize in children's dentistry. In this article, Dr A Crawford and Mr P Shaw, put forward a system whereby high quality and cost effective dentistry can be provided for children in the practice using the principles of purchaser/provider.

Child↗
PubMed1997

Germ-line mutations of the p16INK4(MTS1) gene occur in a subset of patients with hepatocellular carcinoma.

The molecular mechanisms of hepatocarcinogenesis are poorly understood. Only very recently has there been a suggestion of familial hepatocellular carcinoma (HCC). We have analyzed the status of the p16INK4(MTS1) gene, a cyclin-dependent kinase inhibitor, in 26 patients with HCC of different etiologies. Four patients carried hemizygous germ-line point mutations of the p16INK4(MTS1) gene, suggesting the existence of familial HCC involving this gene. The wild-type allele was lost in the tumor in 2 of these 4 patients. Three of the patients carrying a germ-line mutation had non-cirrhosis-associated HCC. No somatic mutations of p16INK4(MTS1) were observed in the 26 cases of HCC. The most common somatic alteration of the p16INK4(MTS1) gene in HCC was de novo methylation, which was detected in 48% of the cases. Low levels (21%) of p16INK4(MTS1) gene allele loss were observed. Altogether, these results indicate that alteration of the p16INK4(MTS1) gene plays an important role in the genesis of HCC.

Adult↗
PubMed1997

A phase II study of leuprolide in advanced/recurrent endometrial cancer.

In order to determine the efficacy and toxicity of the gonadotrophin-releasing hormone agonist Leuprolide in the management of patients with recurrent or metastatic endometrial cancer, we performed a phase II study. Patients were included if there was clinical or radiological documentation of bidimensionally measurable recurrent or metastatic endometrial cancer that was deemed incurable. Treatment was 7.5 mg i.m. every 28 days, and was to continue for at least 2 courses until evidence of disease progression, patient requested withdrawal, or unacceptable toxicity. Twenty-five patients received Leuprolide for recurrent or metastatic endometrial cancer. The median age at study entry was 62 years, and the median time from initial diagnosis to first course of Leuprolide was 25 months. Six patients had received no systemic or radiotherapy prior to study entry, and 2 of these had not previously undergone hysterectomy. Fifteen patients received prior pelvic radiotherapy and 3 patients received prior whole abdominal radiotherapy. Nine of the 25 patients had received prior progestational agents, and 2 had received prior systemic chemotherapy. There were no responders, 8 patients had stable disease for a median 5 months (range 1-8), 14 patients progressed on therapy, and 3 patients were not evaluable for response due to receiving only 1 treatment. One patient experienced a grade 3 toxicity that was possibly attributable to Leuprolide (deep venous thrombosis). The median survival from study entry was 6 months. Twelve patients received progesterone after discontinuing this study, and none responded. Leuprolide does not appear to be a clinically active agent in the treatment of recurrent or metastatic endometrial cancer.

Adult↗
PubMed1997

Aging and prospective memory: the influence of increased task demands at encoding and retrieval.

A feature of prospective memory tasks is that they tend to be embedded into other background activities. Two experiments examined how the demands of these background activities affect age differences in prospective memory. The first experiment showed that increasing the demands of the background activities (by adding a digit-monitoring task) significantly reduced prospective memory performance. Planned comparisons revealed that age differences in prospective memory were reliable only in the more demanding background condition. The second experiment revealed significant prospective memory declines when the demands were selectively increased at encoding for both younger and older adults. When the demands were selectively increased at retrieval, older adults were particularly affected. The authors propose a model that relies on both automatic retrieval processes and working memory resources to explain prospective memory remembering.

Adult↗
PubMed1997

Developmental instability and cerebral lateralization.

On the basis of prior studies of handedness, it was predicted that variations from modal asymmetry scores on cognitive tasks, in either direction from the mean, would be associated with an elevated incidence of classic markers of developmental instability (minor physical anomalies and fluctuating anatomic asymmetries). University students (N = 146) were administered 4 tasks that typically reveal functional asymmetries: the fused rhymed words dichotic listening task, the line bisection task, the chimeric faces task, and the cartoon faces task. A composite measure of developmental instability was computed from minor physical anomalies and fluctuating asymmetries. Participants with greater evidence of developmental instability had more atypical lateralization scores, deviating more from the sample mean, in either direction. Directional asymmetries were unrelated to developmental instability. These results suggest that developmental instability influences variation in the lateralization of cognitive skills as well as handedness.

Adolescent↗
PubMed1997

Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer.

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for reliable prognostic markers to assist clinicians in making management decisions. Although a variety of factors have been tested, only tumor stage, grade, size, hormone receptor status, and S-phase fraction are used on a routine basis. The cell cycle is governed by a family of cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by phosphorylation. p27Kip1, a cyclin-dependent kinase inhibitor, regulates progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27Kip1 protein levels and/or activity are upregulated by growth inhibitory cytokines including transforming growth factor-beta (TGF-beta) and, thus, provide an important link between extracellular regulators and the cell cycle. Loss of p27Kip1, a negative cell-cycle regulator, may contribute to oncogenesis and tumor progression. However, p27Kip1 mutations in human tumors are extremely rare. We have demonstrated by immunohistochemistry that p27Kip1 protein levels are reduced in primary breast cancers and that this is associated with tumor progression in both in situ and invasive lesions. This was confirmed by western analysis, reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to be regulated posttranscriptionally by in situ hybridization. Furthermore, on multivariate analysis, low p27Kip1 is a predictor of reduced disease-free survival. This simple and reliable immunohistochemical assay may become a routine part of breast cancer evaluation and may influence patient management.

Biomarkers, Tumor↗
PubMed1997

Oesophageal ECG in a child for burns surgery.

Continuous monitoring of heart rate and rhythm are regarded as minimal standards of monitoring during anaesthesia. However, when the thoracic area is exposed for surgery as for debridement of burns and split skin grafting then placement of surface electrodes for electrocardiographic (ECG) monitoring is not possible. We report the intraoperative use of an old technique, oesophageal ECG (OesECG) in a child presenting for major burns surgery. The positioning of the probe, electrical safety and P-QRS morphology, are discussed.

Burns↗
PubMed1997

Increased survival of patients treated with a vaccinia melanoma oncolysate vaccine: second interim analysis of data from a phase III, multi-institutional trial.

OBJECTIVE: The efficacy of vaccinia melanoma oncolysate (VMO) vaccine to increase overall survival and disease-free survival of patients with surgically resected International Union Against Cancer (UICC) stage II melanoma was studied in a phase III, randomized, multi-institutional trial. SUMMARY BACKGROUND DATA: Phase I and II trials with VMO showed minimal toxicity and clinical efficacy in patients with melanoma. In a recently completed phase III VMO trial, the first interim analysis performed in April 1994 showed an increasing trend in the survival of patients treated with VMO. The second interim analysis was performed in April 1995. METHODS: Patients with surgically resected stage II (UICC) melanoma were treated with VMO (N = 104) or placebo vaccinia vaccine virus (V) (N = 113) once a week for 13 weeks and then once every 2 weeks for a total of 12 months. Patients' clinical data were collected as of May 1995 and analyzed for survival. RESULTS: In this second interim analysis, the mean follow-up time is 42.28 months. No survival difference was observed between VMO and V treatments. However, in a retrospective subset analysis, a subset of males between the ages of 44 and 57 years and having one to five positive nodes (at 2-, 3-, and 5-year intervals, 13.6%, 15.9%, and 20.3% difference insurvival in favor of VMO [N = 20] when compared to V [N = 18] [p = 0.037]) and another subset of patients with clinical stage I (at 3- and 5-year intervals, 30% and 7% difference in survival in favor of VMO [N = 20] when compared to V [N = 23], [p = 0.05]) showed significant survival advantage with VMO. CONCLUSIONS: Although VMO vaccine therapy in surgical adjuvant setting did not produce a significant survival benefit to all patients with melanoma, patients from the above two subsets had significant survival benefit.

Adult↗
PubMed1997

Complications of central venous access devices in children with and without cancer.

OBJECTIVE: Complications of indwelling central venous access devices (CVAD) were assessed in 63 children with cancer and 35 without cancer. METHODOLOGY: Central venous access devices placed surgically in 1991 were reviewed for complications. RESULTS: In cancer patients, the median CVAD duration was 211 days (range 9-924), compared to 37 days (range 3-339) in the non-cancer patients. Although significantly more CVAD, 41 of 72 (57%), were infected in the cancer patients compared to 14 of 40 (35%) CVAD in the non-cancer patients (OR = 2.46, 95% CI 1.03-5.93), the rate of line infection in cancer patients was lower: 2.8 per 1000 catheter days compared with 7.6 per 1000 in non-cancer patients (P = 0.0014). Infection was significantly more common in intensive chemotherapy cancer patients (P = 0.0002). CONCLUSIONS: Treating infected CVAD with antibiotics or hydrochloric acid (HCl), clearing occluded lines with streptokinase/HCl and repairing fractured lines, when successful, resulted in a considerable gain in the number of days of use for the CVAD.

Adolescent↗
PubMed1997

[Identification of herba taraxaci and its adulterants in Hong Kong market by DNA fingerprinting with random primed PCR].

DNA fingerprinting for Taraxacum mongolicum and its adulterants of six species of Compositae was demonstrated with random-primed polymerase chain reaction (PCR) including arbitrarily-primed PCR (AP-PCR) and random-amplified polymorphic DNA(RAPD). Distinctive genomic fingerprints from DNA of Taraxacum mongolicum and its adulterants were generated with two long (20-24 mer) and one short (10 mer) random-chosen primers Taraxacum mongolicum can be distinguished from six adulterants according to the banding patterns of their amplified DNA on agarose gels. Moreover, that Taraxacum mongolicum and its adulterant are unrelated. The Similarity Indexes values of the genomic fingerprints. Results showed AP-PCR and RAPD might be used for identifying Chinese drugs.

Asteraceae↗
PubMed1997

Airborne particles from latex gloves in the hospital environment.

Air sampling studies are described which show high levels of airborne starch powder contamination in areas where powdered latex gloves are used. Furthermore, culture of collected samples show a clear association between starch particles and bacterial colonies in an experimental system suggesting that airborne particles could act as a vector for pathogens in the hospital environment.

Air Microbiology↗
PubMed1997

Frequent p16INK4 (MTS1) gene inactivation in testicular germ cell tumors.

The molecular mechanisms responsible for the development of testicular germ cell tumors (GCTs) have not as yet been elucidated. The aim of the present study was to determine whether genetic alterations of p16INK4 (MTS1) and/or cyclin-dependent kinase 4 (CDK4) occur in the genesis of these tumors. We have analyzed these two genes in 29 testicular GCTs, seminomas, and nonseminomas. None of the tumors showed either p16INK4 or CDK4 mutations. Only 1 of the 29 GCTs displayed loss of heterozygosity of the p16INK4 gene. No homozygous deletions of p16INK4 were detected. Evidence of hypermethylation of p16INK4 exon 1, however, was demonstrated in 13 of the 26 (50%) GCTs analyzed. Tumor samples having exon 1 of p16INK4 methylated expressed significantly lower levels of p16INK4 mRNA, as analyzed by reverse transcriptase polymerase chain reaction. These results suggest that p16INK4 inactivation plays a role in the genesis of GCTs.

Adolescent↗
PubMed1996

Regulation of specific DNA binding by p53: evidence for a role for O-glycosylation and charged residues at the carboxy-terminus.

The carboxy-terminus of p53 contains a basic region which represses DNA binding, and this repression can be relieved by PAb421, an antibody against the basic region. The EB-1 human cell line contains wild type p53 protein which fails to express the PAb421 epitope and is highly active both in biological assays and in DNA binding assays. We show by wheat germ agglutinin chromatography and galactosyl-transferase labelling that this p53 is O-glycosylated, and that at least one of the sugar residues masks the PAb421 epitope, as demonstrated by recovery of reactivity with PAb421 after digestion of Western blots of EB-1 cell extract with hexosaminidase. A minor population of p53 molecules in EB-1 cells lacks the modification, and there is a correlation between the ability to bind DNA with high affinity and masking of the PAb421 epitope. We also show that strongly positively charged peptides, including short peptides from the basic region of p53, can derepress DNA binding, probably by disruption of an intramolecular interaction involving the basic region. We propose that any intervention which prevents this intramolecular interaction, including addition of bulky residues such as sugar groups, can activate DNA binding by p53.

Amino Acid Sequence↗
PubMed1996

Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway.

Cell cycle regulation is critical for maintenance of genome integrity. A prominent factor that guarantees genomic stability of cells is p53 (ref. 1). The P53 gene encodes a transcription factor that has a role as a tumour suppressor. Identification of p53-target genes should provide greater insight into the molecular mechanisms that mediate the tumour suppressor activities of p53. The rodent Pc3/Tis21 gene was initially described as an immediate early gene induced by tumour promoters and growth factors in PC12 and Swiss 3T3 cells. It is expressed in a variety of cell and tissue types and encodes a remarkably labile protein. Pc3/Tis21 has a strong sequence similarity to the human antiproliferative BTG1 gene cloned from a chromosomal translocation of a B-cell chronic lymphocytic leukaemia. This similarity led us to speculate that BTG1 and the putative human homologue of Pc3/Tis21 (named BTG2) were members of a new family of genes involved in growth control and/or differentiation. This hypothesis was recently strengthened by the identification of a new antiproliferative protein, named TOB, which shares sequence similarity with BTG1 and PC3/TIS21 (ref. 7). Here, we cloned and localized the human BTG2 gene. We show that BTG2 expression is induced through a p53-dependent mechanism and that BTG2 function may be relevant to cell cycle control and cellular response to DNA damage.

3T3 Cells↗