Search PubMed⌕ Search

Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 109 records · Page 6Linked to original sources
PubMed2000

Modulation of human leukocyte antigen and intracellular adhesion molecule-1 surface expression in malignant and nonmalignant human thyroid cells by cytokines in the context of extracellular matrix.

Interactions between malignant cells and their environment are achieved via cell-surface receptors and adhesion molecules. The extracellular matrix (ECM) and ECM-bound cytokines modulate the expression of cell-surface molecules on target malignant cells, which may lead to changes in their susceptibility to cytolysis, in their ability to present antigens, and in the induction of local immune-cell activation and patrol. Eventually, these alterations may culminate in either the destruction, or escape and proliferation, of the tumor. We studied the effects of the ECM and its components in a "naive" form or following binding of the inflammatory cytokines interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) on the surface expression of human leukocyte antigen (HLA) class-I, HLA class-II (HLA-DR), and intracellular adhesion molecule-1 (ICAM-1), on nonmalignant and malignant thyroid cells. The basal expression of HLA class-I molecules was not significantly changed either by naive ECM and its components or by ECM-bound cytokines. ECM synergized with IFNgamma and TNFalpha in inducing HLA-DR molecules on nonmalignant and malignant thyrocytes, with higher HLA-DR levels on the malignant cells. The laminin component, in particular, synergized with IFNgamma. Basal ICAM-1 expression on nonneoplastic cells was not significantly affected by the cytokines when grown in the absence of ECM, but was significantly upregulated when cells were cultured on ECM. In contrast, in malignant thyrocyte cultures, ECM significantly attenuated IFNgamma- and TNFalpha-mediated enhancement of ICAM-1 expression. We concluded that signals derived from ECM-embedded cytokines participate in the regulation of key thyroid cell surface molecules and, thus, may affect the final outcome of human thyroid malignancies.

Animals↗
PubMed2000

Proximal shift of colorectal cancer in the Australian Capital Territory over 20 years.

BACKGROUND: Several studies in other countries have demonstrated a change in subsite distribution of colorectal cancer, with increasing proximal cancers. Confirmation of such a change in Australia would have implications for screening and diagnosis of colorectal cancer. AIMS: To determine whether there has been an increase in the proportion of proximal colorectal cancers in Australia, and whether there have been changes in other clinical and pathological aspects of colorectal cancer. METHODS: A study of the hospital files of patients with colorectal cancer diagnosed and treated at all hospitals in the Australian Capital Territory (ACT) between 1989 and 1995 was compared with data from a published study of patients diagnosed between 1969 and 1976. RESULTS: There was a proximal shift of cancers with a significant increase in the proportion of tumours in the hepatic flexure, ascending colon and caecum, more marked for females than males. There was a corresponding reduction in distal colorectal cancers. Time from onset of symptoms to diagnosis decreased, risk factors for colorectal cancer were noted more frequently, and endoscopy replaced barium enema X-ray as the main diagnostic modality. The resectability of cancers increased, stay in hospital and 30 day mortality declined. Despite apparent earlier presentation and improved surgical resectability, the proportion of patients with localised disease (Dukes' stage A and B) had not changed significantly. CONCLUSIONS: We have detected a number of changes in clinical and pathological aspects of colorectal cancer over a 20 year period in the ACT, including a proximal shift in the subsite distribution of colorectal cancer. These changes suggest that proximal and distal colorectal cancers may have a different aetio-pathogenesis, and have implications for the investigation of patients with suspected colorectal cancer and in screening high-risk groups.

Adenocarcinoma↗
PubMed2000

Assessment of myocardial perfusion by power contrast imaging using a new echo contrast agent.

In a patient with previously documented myocardial infarction, we assessed myocardial perfusion by using power contrast imaging and a newer intravenous echo contrast agent. The images were captured and stored digitally, and various image processing algorithms were used to assess myocardial perfusion. An apical perfusion defect was clearly visualized, and it correlated with radionuclide findings.

Contrast Media↗
PubMed2000

The N-terminal domain of p73 interacts with the CH1 domain of p300/CREB binding protein and mediates transcriptional activation and apoptosis.

The newly identified p53 homolog p73 mimics the transcriptional function of p53. We have investigated the regulation of p73's transcriptional activity by p300/CREB binding protein (CBP). p73-p300 complexes were identified in HeLa cell extracts by cofractionation and coimmunoprecipitation assays. The p73-p300 interaction was confirmed in vitro by glutathione S-transferase-protein association assays and in vivo by coimmunoprecipitating the overexpressed p300 and p73 in human p53-free small-cell lung carcinoma H1299 or osteosarcoma Saos-2 cells. The N terminus but not the N-terminal truncation of p73 bound to the CH1 domain (amino acids [aa] 350 to 450) of p300/CBP. Accordingly, this p73 N-terminal deletion was unable to activate transcription or to induce apoptosis. Overexpression of either p300 or CBP stimulated transcription mediated by p73 but not its N-terminally deleted mutant in vivo. The N-terminal fragment from aa 19 to 597, but not the truncated fragment from aa 242 to 1700 of p300, reduced p73-mediated transcription markedly. p73-dependent transcription or apoptosis was partially impaired in either p300- or CBP-deficient human breast carcinoma MCF-7 or H1299 cells, suggesting that both coactivators mediate transcription by p73 in cells. These results demonstrate that the N terminus of p73 directly interacts with the N-terminal CH1 domain of p300/CBP to activate transcription.

Apoptosis↗
PubMed2000

Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET.

Age-related decline in working memory figures prominently in theories of cognitive aging. However, the effects of aging on the neural substrate of working memory are largely unknown. Positron emission tomography (PET) was used to investigate verbal and spatial short-term storage (3 sec) in older and younger adults. Previous investigations with younger subjects performing these same tasks have revealed asymmetries in the lateral organization of verbal and spatial working memory. Using volume of interest (VOI) analyses that specifically compared activation at sites identified with working memory to their homologous twin in the opposite hemisphere, we show pronounced age differences in this organization, particularly in the frontal lobes: In younger adults, activation is predominantly left lateralized for verbal working memory, and right lateralized for spatial working memory, whereas older adults show a global pattern of anterior bilateral activation for both types of memory. Analyses of frontal subregions indicate that several underlying patterns contribute to global bilaterality in older adults: most notably, bilateral activation in areas associated with rehearsal, and paradoxical laterality in dorsolateral prefrontal sites (DLPFC; greater left activation for spatial and greater right activation for verbal). We consider several mechanisms that could account for these age differences including the possibility that bilateral activation reflects recruitment to compensate for neural decline.

Adult↗
PubMed2000

Pupils' causal attributions for difficult classroom behaviour.

BACKGROUND: Studies of causal attributions within educational contexts have tended to concentrate on academic performance. There have been a smaller number of investigations of teachers' attributions for pupils' behaviour in school. AIMS: The present study examines the causal attribution made by pupils for difficult behaviour in classrooms. It reveals the structure of these attributions and serves as a comparison with the teacher studies. SAMPLE: The participants were 105 pupils (52 males and 53 females) in the first year of secondary schooling, all drawn from the same inner city school. METHOD: Four initial small group interviews were used to identify a wide range of factors that pupils viewed as being causes of difficult classroom behaviour in the 18 primary schools they had previously attended. A questionnaire was then constructed incorporating items from these discussions and administered to the whole of the year group of pupils, but omitting the participants in the initial group discussions. RESULTS: The results of a factor analysis indicated that pupils' attributions for misbehaviour at school were best represented by four factors: (1) 'fairness of teacher's actions', (2) 'pupil vulnerability', (3) 'adverse family circumstances' and (4) 'strictness of classroom regime'. While there were no gender differences, pupils saw the 'fairness of teacher's actions' and 'pupil vulnerability' as more significant contributors to pupil misbehaviour than either 'adverse family circumstances' or 'strictness of classroom regime'. CONCLUSION: The attributions by pupils for difficult classroom behaviour differ markedly from those obtained in studies of teachers. Policy and practice initiatives which do not attend to conflicting attributional styles are unlikely to succeed in improving levels of pupil behaviour in schools.

Child↗
PubMed2000

Changes in cortical bone mineralization in the developing mandible: a three-dimensional quantitative computed tomography study.

Quantitative computed tomography (QCT) was completed in 34 subjects between the ages of 9 and 33 years with symmetrical mandibles in order to investigate the three-dimensional cortical bone mineral density (BMD) distribution in the mandible. The number and distribution of the pixels were determined at three levels: (1) representing the entire mandibular bone; (2) the cortical bone at 60% above the baseline defined as the segmentation level (around 1050 mg/cm3) and representative of only cortical bone; and (3) the highest mineralized cortical bone (>1250 mg/cm3). The geometrical distribution of the highest mineralized areas was evaluated by three-dimensional reconstruction of the images. The total number of pixels for the entire mandible increased significantly at each time point represented at four increasing ages groups (9-11 years of age, 12-14 years of age, 15-17 years of age, and >18 years of age). The male and female subjects had a similar total number of pixels for the entire mandible before the age of 11, but the male subjects showed a significantly larger total number of mandibular pixels after that age. Comparison of the number of pixels for pure cortical bone (60% segmentation level) and the highest mineralized cortical bone indicated a significant increase with maturation with the greatest change occurring between the 13-year and 16-year age groups. However, the ratio of cortical bone/total bone increased at a more rapid rate in the male subjects and reached a plateau by the 16-year age group, showing distinct differences in mineralization of the mandible between the sexes.

Adolescent↗
PubMed2000

A sequence-ready map for human chromosome 12q15-21.

Construction of sequence-ready clone map is an essential step toward sequencing the human genome. We chose a region that is frequently amplified in liposarcoma between D12S350 and D12S106 in chromosome 12q15-21 to build a PAC/BAC clone contig map. This region was spanned by 4 YACs and contained 30 STS on the YAC and radiation hybrid (RH) framework maps, providing an average STS spacing of 160 kb if each YAC is approximately 1.2 Mb in size. To convert a STS-based YAC map to a STS-based contig map of bacterial clones, 22 non-polymorphic STS markers were used as probes to screen the high density gridded arrays of PAC and BAC clones by filter hybridizations, followed by assembly of clones into contigs by marker content. Contigs have been extended and joined by direct end sequencing of appropriate clones, generating new STSs and rescreening the library as necessary. Using these approaches, we have constructed 5 contigs covering the region with the largest single contig being 1.4 Mb and a final size estimation of 3.6 Mb. The map is comprised of 17 YACs, 187 PACs, 160 BACs, and 17 cosmids; onto this, 6 polymorphic, 97 non-polymorphic, 24 ESTs, and 4 gene-based markers are now placed in a unique order, providing an average resolution of approximately 28 kb. Of a total of 131 markers, 97 were developed in the present study. The sequence-ready map should provide a framework to generate complete DNA sequence and ultimately gene map of this segment of chromosome 12.

Base Sequence↗
PubMed2000

Rapid diagnosis of massive pulmonary embolism in a district general hospital.

Effective treatment of massive pulmonary embolism is more likely if diagnostic tests are rapidly available, including during out-of-hours. An agreed protocol was implemented in November 1997, which allowed initiation of thrombolysis by junior doctors within an hour of clinical suspicion of the diagnosis of massive pulmonary embolism in six patients in the subsequent year. A similar approach could be considered by other acute hospitals.

Aged↗
PubMed2000

[Immunosuppressive mechanisms for immunoglobulin function].

The article reviews the evidence supporting and explaining suppressive activity of intravenous immunoglobulin (IVIG) preparations towards human immune system. Besides basic mechanisms also clinical applications and effects in various autoimmune disorders such as idiopathic thrombocytopenia, Guillain-Barré syndrome and others are described. This evidence supports novel application of IVIG as convenient alternative to other immunosuppressive therapies with many more adverse effects.

Autoimmune Diseases↗
PubMed1999

Discovery and structure-activity relationships of imidazole-containing tetrahydrobenzodiazepine inhibitors of farnesyltransferase.

2,3,4,5-Tetrahydro-1-(imidazol-4-ylalkyl)-1,4-benzodiazepines were found to be potent inhibitors of farnesyltransferase (FT). A hydrophobic substituent at the 4-position of the benzodiazepine, linked via a hydrogen bond acceptor, was important to enzyme inhibitory activity. An aryl ring at position 7 or a hydrophobic group linked to the 8-position through an amide, carbamate, or urea linkage was also important for potent inhibition. 2,3,4, 5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2-(t rifluo romethoxy)benzoyl]-1H-1,4-benzodiazepine (36), with an FT IC(50) value of 24 nM, produced 85% phenotypic reversion of Ras transformed NIH 3T3 cells at 1.25 microM and had an EC(50) of 160 nM for inhibition of anchorage-independent growth in soft agar of H-Ras transformed Rat-1 cells. Selected analogues demonstrated ip antitumor activity against an ip Rat-1 tumor in mice.

3T3 Cells↗
PubMed1999

Antigen-specific signaling by a soluble, dimeric peptide/major histocompatibility complex class II/Fc chimera leading to T helper cell type 2 differentiation.

Interaction between a T cell receptor (TCR) and various ligands, i.e. , anti-TCR antibodies, superantigens, peptides, or altered peptide ligands in the context of major histocompatibility complex (MHC) molecules can trigger different T helper cell (Th) effector functions. Herein, we studied the T cell response induced by a soluble, dimeric peptide/MHC class II chimera, namely hemagglutinin (HA)110-120/I-E(d)alphabeta/Fcgamma2a (DEF). We have previously demonstrated that the soluble DEF molecule binds stably and specifically to HA110-120-specific TCRs expressed by a T cell hybridoma. Administration of DEF in vivo induced differentiation of resting and activated peptide-specific T cells toward a Th2 response, as indicated by the increase of interleukin (IL)-4, IL-10, and specific immunoglobulin (Ig)G1 antibodies and decrease of IL-2, specific IgG2a antibodies, and cytotoxic T lymphocyte activity. In contrast to HA110-120 peptide presented by the DEF molecule to T cells, the nominal synthetic peptide induced a predominant Th1 response, and the PR8 virus-derived HA110-120 peptides induced a mixed Th1/Th2 response. Independent of antigen processing, soluble DEF was almost 2 logs more potent in stimulating cognate T cells than the nominal peptide. Polarization of cognate T cells toward the Th2 response occurred upon interaction of soluble DEF with TCR and CD4 molecules followed by early activation of p56(lck) and ZAP-70 tyrosine kinases, and negative signaling of the signal transducer and activator of transcription (STAT)4 pathway of Th1 differentiation. DEF-like molecules may provide a new tool to study the mechanisms of signaling toward Th2 differentiation and may also provide a potential immunotherapeutic approach to modulate autoreactive T cells toward protective Th2 immune responses.

Animals↗