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Biomedical subjects

S Chu

Publications and source records attributed to S Chu.

At least 19 recordsLinked to original sources
PubMed2005

Parametric amplification of matter waves in periodically translated optical lattices.

We observe the sudden growth of small classes of Bloch waves from atomic Bose-Einstein condensates held in periodically translated optical lattices. The effect is explained by narrowband parametric amplification of Bloch waves from noise, due to phase-matched scattering of atom pairs out of the condensate. Amplification occurs above a well-defined modulation threshold, described by dynamic shaping of single-particle band structure.

Journal Article↗
PubMed2003

Direct measurement of acid permeation into rat oesophagus.

BACKGROUND AND AIMS: The early responses of the oesophageal mucosa to acid perfusion may predict subsequent pathology. Mucosal responses to luminal acid may result either from acid permeating through the mucosa or from other unknown transduction mechanisms. In order to better understand the dynamics of acid permeation into the oesophageal mucosa, we measured interstitial pH (pH(int)) of the oesophageal basal epithelial layer, pre-epithelial layer thickness, and blood flow in rats in vivo during luminal acid challenge. A novel confocal microscopic technique was used in vitro to measure pH(int) from defined cellular sites in response to luminal and basolateral acidification. METHODS: 5-(and-6)-Carboxyfluorescein (CF) and carboxy-seminapthorhodofluor-1 (SNARF-1) fluorescence was used to measure pH(int) by conventional and confocal microscopy, respectively, in urethane anaesthetised rats. Pre-epithelial layer thickness was measured optically with carbon particles as markers. Blood flow was measured with laser Doppler flowmetry. RESULTS: Luminal acidification failed to alter pH(int) in vivo and in vitro, but pH(int) was lowered by modest serosal acidification. Pre-epithelial layer thickness and blood flow increased significantly during luminal surface acid perfusion. Indomethacin had no effect on any acid related response. CONCLUSION: In this first dynamic measurement of oesophageal acid permeation and pre-epithelial layer thickness, pH(int) was preserved in spite of high luminal acidity by two complementary techniques. Despite the apparent permeability barrier to acid permeation, oesophageal blood flow and thickness responded to luminal acid perfusion.

Acids↗
PubMed2002

FSH-regulated gene expression profiles in ovarian tumours and normal ovaries.

Development, growth and function of the ovary are controlled by endocrine and paracrine signals. These may also influence the development of ovarian cancer. The aim of this study was to identify the key molecular markers of the unregulated growth and hormone synthesis seen in ovarian tumours, particularly in granulosa cell tumours (GCT). Genes used in this study were chosen on the basis of our understanding of growth and differentiation in the normal ovary. We sought to define the patterns of gene expression in a panel of epithelial and stromal ovarian tumours. Expression was determined by RT-PCR using gene-specific primers for the FSH receptor (FSHR); the FSH early response genes: regulatory subunit of protein kinase A (RII-beta), cyclin D2 (cycD2) and sgk; and late response markers: cyclooxygenase-2 (COX-2) and the LH receptor (LHR). The GCT had high expression of FSHR compared with normal ovaries and the other tumours. cycD2 and RII-beta and COX-2 genes were also highly expressed in the GCT. sgk and LHR expression was lower in all of the tumours than in normal ovaries. Serous cystadenocarcinomas also had an unexpectedly high expression of COX-2. Comparison of the gene expression profiles between each tumour group suggests a molecular phenotype for GCT that is similar to that reported for FSH stimulated pre-ovulatory granulosa cells.

Adult↗
PubMed2001

The inhibins and ovarian cancer.

Interest in inhibin as a marker of ovarian malignancy was stimulated by the description of elevated immunoreactive inhibin levels in the sera of patients with granulosa cell tumours. Several groups have confirmed the value of serum inhibin in the diagnosis and follow-up of patients with this uncommon malignancy. Immunoreactive inhibin levels are also frequently elevated in patients with mucinous cystadenocarcinoma and less frequently in other forms of ovarian tumour. Assay of sera using the specific dimeric inhibin assays has shown that ovarian tumours are able to secrete dimeric inhibin particularly inhibin B. The less specific alpha-subunit directed assays, however, most frequently show elevated concentrations. Used in combination with CA125 as a dual tumour marker, it appears in principle that inhibin can be a useful diagnostic agent. Immunohistochemistry for the inhibin subunits has been reported with increasing frequency as a helpful method to assess suspected ovarian stromal cell tumours. Its diagnostic accuracy for other types of ovarian adenocarcinoma appears less reliable. Expression of the inhibin subunit mRNAs has been demonstrated in a variety of ovarian malignancies. The observation that inhibin levels are elevated in ovarian cancer has stimulated studies of their relevance to the molecular pathogenesis of these malignancies. Findings to date have been largely negative with no evidence for activating mutations of the FSH receptor or of the post-receptor signalling pathway proteins.

Biomarkers, Tumor↗
PubMed2001

The epithelium-specific ETS protein EHF/ESE-3 is a context-dependent transcriptional repressor downstream of MAPK signaling cascades.

Exon trapping and cDNA selection procedures were used to search for novel genes at human chromosome 11p13, a region previously associated with loss of heterozygosity in epithelial carcinomas. Using these approaches, we found the ESE-2 and ESE-3 genes, coding for ETS domain-containing transcription factors. These genes lie in close proximity to the catalase gene within a approximately 200-kilobase genomic interval. ESE-3 mRNA is widely expressed in human tissues with high epithelial content, and immunohistochemical analysis with a newly generated monoclonal antibody revealed that ESE-3 is a nuclear protein expressed exclusively in differentiated epithelial cells and that it is absent in the epithelial carcinomas tested. In transient transfections, ESE-3 behaves as a repressor of the Ras- or phorbol ester-induced transcriptional activation of a subset of promoters that contain ETS and AP-1 binding sites. ESE-3-mediated repression is sequence- and context-dependent and depends both on the presence of high affinity ESE-3 binding sites in combination with AP-1 cis-elements and the arrangement of these sites within a given promoter. We propose that ESE-3 might be an important determinant in the control of epithelial differentiation, as a modulator of the nuclear response to mitogen-activated protein kinase signaling cascades.

Base Sequence↗
PubMed2001

[Linkage analysis of candidate genes for glucose and lipid metabolism with essential hypertension].

OBJECTIVE: To identify the genetic loci responsible for susceptibility to essential hypertension (EH) in chromosomal regions containing candidate genes involved in the regulation of glucose and lipid metabolism. METHODS: Linkage analysis of EH were performed in 95 Chinese nuclear families with 477 subjects using the technique of fluorescence-based gene scan with microsatellite markers. Markers were selected in 11 chromosomal regions containing 18 candidate genes regulating blood glucose and lipid metabolism. The two-locus, non-parametric linkage analysis (NPL), maximum LOD score and transmission/disequilibrium test (TDT) with GENEHUNTER program were used in this study. RESULTS: No significant linkages were found by NPL and LOD score analysis (P > 0.05 or LOD score < 1) at all loci. The results of TDT showed significant linkage with EH at D8S261 and D11S1347 (chi(2) = 11.92, P < 0.001 and chi(2) = 7.37, P < 0.01, respectively). Near these loci, there were a few candidate genes including lipoprotein lipase (LPL) and a cluster of apolipoprotein (apoA1-C3-A4). CONCLUSION: TDT suggests significant linkage with EH at D8S261 and D11S1347. Whether the genes located at or near the two loci, such as LPL and apoA1-C3-A4, are susceptibility genes of EH need to be verified.

Adult↗
PubMed2001

Computerised clinical pathway management systems and the implications.

This is the second paper of the two-part series. Part 1 of the series (Reconceptualising Clinical Pathway System Design) reported defects existed in the paper clinical pathways and proposed a set of design premises to guide the development of a computerised clinical pathway management system (CCPMS). This paper provides an overview of a robust CCPMS that was designed to accurately map patients' changing clinical states and support dynamic modification of the clinical pathway structure and associated interventions. This electronic system provides clinicians with real time outcome feedback on care delivered and generates alerts on out of range assessment results, deteriorating trends and potential problems such as drug interactions. It has been rated by clinicians who participated in an evaluative study as a highly useful information management and decision support tool. However, the introduction of a power tool like the clinical pathway management system has raised very important issues such as the need for work practice redesign, education of clinicians and more research to maximise the benefits of the tool and achieve better process quality improvement. It also generates serious concerns about legal liabilities and the potential threat of the cost cutting strategies taken by senior management in search of paybacks after their implementation. These issues and their implications are also explored in this paper.

Critical Pathways↗
PubMed2001

Reconceptualising clinical pathway system design.

Increased patient throughput and patient acuity resulting from the introduction of prospective funding mechanisms, such as Case Mix (based on the Diagnosis Related Groups) for in-patient acute care, raised serious concerns about compromising quality of care delivered to patients. The paper clinical pathway has been introduced as a tool to streamline documentation, implement standardised clinical management protocols and improve quality of care provided to patients. However, the checklist format and its lack of connection to clinical data reflecting changes in patient status have imposed severe limitations on the ability of clinical pathway to be used as an effective information management and decision support tool. This is the first of two papers reporting on a research effort that was undertaken to identify, validate and address the limitations of paper clinical pathways. A set of functional specifications and a functional model were developed following the initial exploratory study. The work led to a set of reconceptualised system (CCPMS) design guidelines for the development of a robust computerised clinical pathway management system that could provide dynamic information management and decision support to clinicians in response to changing patient clinical status. The second paper will report on the features and benefits demonstrated by the CCPMS prototype. Implications to nursing brought about by the introduction of such a tool will also be explored.

Australia↗
PubMed2001

Knowledge representation and retrieval using conceptual graphs and free text document self-organisation techniques.

Hospitals generate and store a large amount of clinical data each year, a significant portion of which is in free text format. Conventional database storage and retrieval algorithms are incapable of effectively processing free text medical data. The rich information and knowledge buried in healthcare records are unavailable for clinical decision-making. We examined a number of techniques for structuring and processing free text documents to effective and efficient for information retrieval and knowledge discovery. One critical success criterion is that the complexity of the techniques must be polynomial both in space and time for them to be able to cope with very large databases. We used conceptual graphs (CG) to capture the structure and semantic information/knowledge contained within the free text medical documents. Ordering and self-organising techniques (lattice techniques and knowledge space) were used to improve organisation of concepts from standard medical nomenclatures and large sets of free text medical documents. Pair-wise union of CG was performed to identify the common generalisation structure and a lattice structure of these CG documents. A combination of all three techniques allowed us to organise a set of 9000 discharge summaries into a generalisation hierarchy that supported efficient and rich information/knowledge retrieval.

Classification↗
PubMed2001

Decrease in rat taste receptor cell intracellular pH is the proximate stimulus in sour taste transduction.

Taste receptor cells (TRCs) respond to acid stimulation, initiating perception of sour taste. Paradoxically, the pH of weak acidic stimuli correlates poorly with the perception of their sourness. A fundamental issue surrounding sour taste reception is the identity of the sour stimulus. We tested the hypothesis that acids induce sour taste perception by penetrating plasma membranes as H(+) ions or as undissociated molecules and decreasing the intracellular pH (pH(i)) of TRCs. Our data suggest that taste nerve responses to weak acids (acetic acid and CO(2)) are independent of stimulus pH but strongly correlate with the intracellular acidification of polarized TRCs. Taste nerve responses to CO(2) were voltage sensitive and were blocked with MK-417, a specific blocker of carbonic anhydrase. Strong acids (HCl) decrease pH(i) in a subset of TRCs that contain a pathway for H(+) entry. Both the apical membrane and the paracellular shunt pathway restrict H(+) entry such that a large decrease in apical pH is translated into a relatively small change in TRC pH(i) within the physiological range. We conclude that a decrease in TRC pH(i) is the proximate stimulus in rat sour taste transduction.

Acetic Acid↗
PubMed2001

Intragastric pH regulates conversion from net acid to net alkaline secretion by the rat stomach.

Our previous report showed gastric mucosal surface pH was determined by alkali secretion at intragastric luminal pH 3 but by acid secretion at intragastric pH 5. Here, we question whether regulation of mucosal surface pH is due to the effect of luminal pH on net acid/base secretions of the whole stomach. Anesthetized rats with a gastric cannula were used, the stomach lumen was perfused with weakly buffered saline, and gastric secretion was detected in the gastric effluent with 1) a flow-through pH electrode and 2) a fluorescent pH-sensitive dye (Cl-NERF). During pH 5 luminal perfusion, both pH sensors reported the gastric effluent was acidic (pH 4.79). After perfusion was stopped transiently (stop-flow), net acid accumulation was observed in the effluent when perfusion was restarted (peak change to pH 4.1-4.3). During pH 3 luminal perfusion, both pH sensors reported gastric effluent was close to perfusate pH (3.0-3.1), but net alkali accumulation was detected at both pH sensors after stop-flow (peak pH 3.3). Buffering capacity of gastric effluents was used to calculate net acid/alkaline secretions. Omeprazole blocked acid secretion during pH 5 perfusion and amplified net alkali secretion during pH 3 perfusion. Pentagastrin elicited net acid secretion under both luminal pH conditions, an effect antagonized by somatostatin. We conclude that in the basal condition, the rat stomach was acid secretory at luminal pH 5 but alkaline secretory at luminal pH 3.

Alkalies↗
PubMed2001

Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas.

Previous studies indicated that a new member of the human kallikrein (KLK) gene family, KLK4, was expressed in prostate, breast, and endometrial carcinoma cell lines and may have potential as a tumor marker. The aim of this study was to examine the expression of KLK4 in the normal ovary and ovarian tumors of different histology, stage, and differentiation and to determine its association with ovarian tumor progression. Using reverse transcription-PCR, Southern blot, and densitometry analyses, we found the level of KLK4 expression was higher in late stage serous (SER) epithelial-derived ovarian carcinomas than in normal ovaries, mucinous epithelial tumors, and granulosa cell tumors. KLK4 was highly expressed in all of the SER ovarian carcinoma cell lines (eight of eight), SER epithelial carcinomas (11 of 11), and two adenomas, whereas it was expressed at a lower level (or not at all) in normal ovaries (four of six), mucinous epithelial tumors (three of four), endometrioid carcinomas (four of five), clear cell carcinomas (two of three), or granulosa cell tumors (three of six). Of particular interest, KLK4 mRNA variants were detected in SER ovarian carcinoma cell lines and primary cultured ovarian tumor cells, but they were not present in normal ovaries. In situ hybridization analysis showed that KLK4 mRNA transcripts are localized to adenocarcinoma cells of ovarian tumor tissues. Similarly, immunohistochemical staining of ovarian carcinoma sections showed immunoreactivity to KLK4 protein product (hK4) antipeptide antibodies. In addition, intracellular hK4 levels, as detected on Western blot analysis, were induced by 100 nM estrogen treatment of the estrogen receptor positive ovarian carcinoma cell line OVCAR-3, >8-24 h. Our results show that the level of KLK4 expression and expression of KLK4 mRNA variants are associated with progression of ovarian cancer, particularly late stage SER adenocarcinomas. Moreover, hK4 may be a candidate marker for the diagnosis and/or monitoring of ovarian epithelial carcinomas.

Amino Acid Sequence↗
PubMed2001

Computerised clinical pathway as process quality improvement tool.

Experiences from other industries show that process quality improvement (PQI) is far more effective than product quality assurance in ensuring quality outputs and cost savings. The PQI approach is becoming more important to the healthcare industry as healthcare professionals struggle to cope with increasing demands for productivity gains, the raising patient acuity and need to curtail the large number of adverse medical events. This paper presents a continuous process quality improvement operational model for healthcare quality improvement and operationalization of the model through the implementation of a computerised clinical pathway management system (CCPMS). It also reports on a small-scale evaluative study conducted to assess the effectiveness of the PQI approach using the CCMPS prototype.

Attitude of Health Personnel↗