Search PubMed⌕ Search

Biomedical subjects

C Arnold

Publications and source records attributed to C Arnold.

At least 91 records · Page 5Linked to original sources

Physiology of isolated long-term variability of the fetal heart rate.

Ten singleton third trimester fetuses exhibiting isolated long-term variability of the fetal heart rate were studied with a single Doppler transducer actocardiograph in conjunction with real-time ultrasonography. Each of these studies revealed repetitive clustered bursts of fetal breathing movements during the acceleratory phases and apneic episodes during the deceleratory phases of this fetal heart rate pattern, respectively, in the absence of other fetal movements. This observation may explain the physiology of isolated long-term variability of the fetal heart rate.

Adult↗

Norwalk-like viruses: demonstration of genomic diversity by polymerase chain reaction.

A reverse transcription-polymerase chain reaction (RT-PCR) amplification procedure was developed for the detection of Norwalk-like viruses in fecal specimens. Ninety-nine fecal specimens collected in the United Kingdom and containing small round-structured virus particles as determined by electron microscopy were tested. They came from 50 outbreaks and 16 sporadic cases of viral gastroenteritis. RT-PCR products of the appropriate size for Norwalk virus RNA were detected in 15 specimens from three outbreaks, suggesting that viruses closely related to Norwalk virus have not been circulating widely in the United Kingdom in recent years. From four isolates, the RT-PCR amplification products of two genomic regions were sequenced and the degree of genomic variation was compared. DNA sequencing of the PCR products revealed strong similarities among strains from the United Kingdom (approximately 97% for both regions amplified) but significant differences from Norwalk virus (67 to 78%). All of the viruses detected by RT-PCR were classified as serotype UK2 by solid-phase immune electron microscopy or enzyme-linked immunosorbent assay. These findings provide evidence of a genomic relationship between Norwalk virus and serotype UK2 small round-structured viruses.

Base Sequence↗

Leukotriene B4 transcriptionally activates interleukin-6 expression involving NK-chi B and NF-IL6.

Leukotriene B4 (LTB4) is a notable participant in inflammation and chemotaxis. It is, however, still unclear whether LTB4 acts in this regard directly or indirectly by stimulating the release of chemotactic and inflammatory cytokines. Here we report that LTB4 induces synthesis of interleukin (IL)-6 by human blood monocytes through transcriptional activation of the IL-6 gene. We furthermore demonstrate that this process involves activation of the transcription factor NF-chi B and, to a lesser extent, of NF-IL6, while the activity of the transcription factor AP-1, shown to otherwise confer IL-6 inducibility, appeared to be unaffected by LTB4. Involvement of NF-chi B and NF-IL6 in induction of IL-6 transcription by monocytes was demonstrated using deleted forms of the IL-6 promoter. Activation of the IL-6 promoter by LTB4 was not only associated with accumulation of the respective transcripts but resulted in synthesis of functional IL-6 protein as well. In addition, LTB4 mediated transactivation of a heterologous promoter construct containing the NF-chi B or the NF-IL6 enhancer, but not the AP-1 enhancer. The signaling events mediating this effect appeared to involve the release of H2O2, since LTB4 failed to induce NF-chi B or NF-IL6 in the presence of the scavenger of H2O2, N-acetyl-L-cysteine.

Binding Sites↗

Mesenchyme-mediated effect of dexamethasone on laminin in cocultures of embryonic gut epithelial cells and mesenchyme-derived cells.

Previous studies have shown that glucocorticoids accelerate intestinal maturation and that this process is mediated by the mesenchymal cells. The possible involvement of laminin (LN), a basement membrane component, in this mesenchymal mediation has been analyzed. For this purpose, the influence of dexamethasone (DX) on the synthesis of LN, its chain composition and its cellular distribution has been examined biochemically and immunocytochemically in two different mesenchyme-derived cell populations, fetal intestinal mesenchymal cells and fetal skin fibroblasts, as well as in cocultures of intestinal endodermal cells seeded on top of confluent fetal skin fibroblasts. Neither the amount of metabolically labeled LN purified by affinity chromatography (expressed per mg cell proteins), nor the A versus B chain ratio monitored after separation on gel electrophoresis and immunoblotting, showed significant differences after 5 days of DX treatment. However, glucocorticoids induced a shift from secreted to cell-associated LN molecules paralleling a striking difference in the immunostaining pattern of intracellular and surface LN in the mesenchyme-derived cell monocultures; the granular intracytoplasmic LN staining in the control cultures was replaced by a fibrillar organization of LN molecules concomitantly with an increased accumulation at the cell surface. In 2-day DX-treated cocultures, there was an acceleration of LN deposition at the epithelial-fibroblastic interface, which accompanied the enhanced expression of epithelial cell differentiation markers (brush border digestive enzymes). These DX-induced changes can be blocked by the addition of anti-LN antibodies in the culture medium. These findings further support the concept that glucocorticoid action on intestinal epithelial cells involves alterations in the extracellular microenvironment, assessed here for LN molecules, occurring at the level of the mesenchymal cell compartment. These changes may contribute to an accelerated organization of LN at the epithelial-mesenchymal interface and subsequently to epithelial differentiation.

Animals↗

Consultation and capital works: a recipe for implementing change.

When the Royal Children's Hospital launched into a $50 million building/refurbishment program in 1987/88, there was a clear recognition of the need to establish appropriate consultation mechanisms with unions and employees. Little documentation existed on major capital works consultation models. As Monash Medical Centre and Western Hospital were involved in major projects, discussions took place between the three hospitals and the Health Department Victoria, which resulted in a model (based largely on Monash's existing arrangements), capable of being applied across the hospital field. This model was subsequently ratified by the Victorian Trades Hall Council on behalf of the unions, and implemented (with minor differences in each case) at the three hospitals. The purpose of this paper is to document this consultation model. Highlighted is the importance of tight project management, regular communication, and substantial involvement by staff affected in the area(s) under development in 'user groups'. As the model has been agreed by the Trades Hall Council for use in Victorian public hospitals, it is hoped that this paper may provide a useful basis for other hospitals contemplating major capital works.

Decision Making, Organizational↗

Vectorette PCR: a novel approach to genomic walking.

Vectorette PCR (or chemical genetics) is a method that enables the amplification of specific DNA fragments in situations where the sequence of only one primer is known. Thus, it extends the application of PCR to stretches of DNA where the sequence information is only available at one end. In this report, we describe the chemical genetics method and demonstrate its use in one specific application. In addition, we demonstrate how fragments generated by this procedure can be sequenced rapidly and simply using methods that have the potential for automation.

Chlamydia trachomatis↗

An assembly defect as a result of an attenuating mutation in the capsid proteins of the poliovirus type 3 vaccine strain.

The molecular basis of the temperature-sensitive (ts) phenotype of P3/Sabin, the type 3 vaccine strain of poliovirus, was investigated in light of the known correlation between ts and attenuation phenotypes. A phenylalanine at residue 91 of the capsid protein VP3 was a major determinant of both phenotypes, and attenuation and ts could be reverted by the same second-site mutations. The ts phenotype was due to a defect early in the assembly process that inhibited the formation of 14S pentamers, empty capsids, and virions. It was further shown that capsid proteins that were not incorporated into higher-order structures had short half-lives at the nonpermissive temperature.

Capsid↗

MRI measurements of left ventricular systolic wall thickening compared to regional myocardial perfusion as determined by 201Tl SPECT in patients with coronary artery disease.

Magnetic resonance imaging (MRI) of the left ventricle (LV) is an excellent method of measuring systolic wall thickening (SWT). The aim of the present study was (a) to describe a new approach for measurement of SWT and (b) to define the relationship between SWT and regional myocardial perfusion as determined by 201Tl SPECT. 79 patients -51 with and 28 without history of earlier myocardial infarction - underwent SPECT and, within the next two weeks. MRI. End-diastolic and end-systolic spin echo images were obtained by a reduced permutation technique. For MRI measurements, only long-axis sections through the LV in the equatorial plane were used. Slice orientation was selected according to the findings of SPECT, imaging the infarcted wall segment by single or double angulation. At 7 equidistant points around the LV wall SWT was measured and compared with the corresponding regional myocardial uptake values from SPECT in percent of maximal perfusion. Wall thickness of the anterior wall was normal. Because the majority of myocardial infarctions were posterior-inferior (55%), thickness of the posterior wall was markedly decreased. A close relationship of perfusion to SWT was found. Higher perfusion areas (greater than 50% of maximal TI uptake) corresponded with normal SWT (greater than 3.0 mm), a marked decrease of SWT (less than 1 mm) was found in areas with perfusion deficits (less than 40%). Thus, a 201TI uptake value at rest of 41-50% of the respective myocardial maximum acts as a threshold by discriminating normal from severely reduced SWT.

Adult↗

Inheritance and effect on ripening of antisense polygalacturonase genes in transgenic tomatoes.

The role of the cell wall hydrolase polygalacturonase (PG) during fruit ripening was investigated using novel mutant tomato lines in which expression of the PG gene has been down regulated by antisense RNA. Tomato plants were transformed with chimaeric genes designed to express anti-PG RNA constitutively. Thirteen transformed lines were obtained of which five were analysed in detail. All contained a single PG antisense gene, the expression of which led to a reduction in PG enzyme activity in ripe fruit to between 5% and 50% that of normal. One line, GR16, showed a reduction to 10% of normal PG activity. The reduction in activity segregated with the PG antisense gene in selfed progeny of GR16. Plants homozygous for the antisense gene showed a reduction of PG enzyme expression of greater than 99%. The PG antisense gene was inherited stably through two generations. In tomato fruit with a residual 1% PG enzyme activity pectin depolymerisation was inhibited, indicating that PG is involved in pectin degradation in vivo. Other ripening parameters, such as ethylene production, lycopene accumulation, polyuronide solubilisation, and invertase activity, together with pectinesterase activity were not affected by the expression of the antisense gene.

Food Technology↗

Dietary evaluation of patients with smell and/or taste disorders.

The impact of smell and taste disorders on dietary habits and nutritional status has received limited research attention. This paper reports findings obtained from questionnaires and diet records completed by 40 healthy subjects and 118 patients with chemosensory dysfunction. Chemosensory disorders were frequently associated with decreases in food acceptability. Although dietary responses to these dysfunctions varied greatly, patients with distorted or phantom smell and/or taste sensations tended to report weight loss whereas those with simple sensory loss were more likely to report weight gain. Indices derived from diet records did not indicate that either group of patients was at substantial nutritional risk, but food frequency responses and estimates of body mass index were consistent with patient reports of changes in dietary patterns and weight. In addition, marked weight change and aberrant dietary practices were noted in individual patients. Thus, there were indications that chemosensory dysfunction may be associated with nutritionally important dietary alterations.

Adult↗

Smooth muscle actin expression during rat gut development and induction in fetal skin fibroblastic cells associated with intestinal embryonic epithelium.

Cytodifferentiation of smooth muscle cells has been analyzed immunocytochemically during rat intestinal development and in chimaeric intestines by using monoclonal antibodies reacting specifically with smooth muscle actin species (CGA7 [10] and anti-alpha SM-1 [40]). As development proceeds, the various intestinal muscle layers differentiate in the following order: (1) cells expressing smooth muscle actin appear within the mesenchyme of the 15-day fetal rat intestine, in the circular muscle-forming area, the differentiation of cells in the presumptive longitudinal muscle layer starting with a 48-h delay; (2) smooth muscle fibers appear within the connective tissue core of the villi shortly after birth, in parallel with a progressive formation of the muscularis mucosae, which becomes clear-cut only in the course of the 2nd week after birth; (3) a distinct cell layer in the innermost part of the circular muscle layer arises during the perinatal period. Thereafter, the fluorescence pattern remains unchanged until the adult stage. Chimaeric intestines were constructed by the association of 14-day fetal intestinal epithelium and cultured fetal rat or human skin fibroblasts. These fibroblastic cells did not express actin at the time at which they were associated. The immunocytochemical analysis of smooth muscle actin in the hybrid intestines, which had developed as intracoelomic grafts for 12 days, revealed that the skin fibroblastic cells had been induced by the intestinal epithelial cells to differentiate into smooth muscle cells. Such a result was also obtained with allantoic endoderm. It was not obvious in cocultures of intestinal epithelium with skin fibroblastic cells. However, when intestinal epithelial cells were cocultured with intestinal mesenchymal cells, actin expression was stimulated in the latter cell population.

Actins↗

Performance indicators--can you afford not to have them? Royal Children's Hospital--a structured approach.

The thought of performance assessment may send chills through even the most experienced hospital manager. It conjures up the worst facets of negativeness, failure, being 'watched', funding cuts and being 'on trial'. Yet the constructive use of performance indicators is undoubtedly an essential tool to all levels of management within a hospital. Performance indicators are as important to health agencies as they are to B.H.P. Stringent financial restraints, calls from 'shareholders' to demonstrate performance and to be more accountable are placing management under increasing scrutiny. Overseas work points to the use and abuse of indicators, and the difficulty in arriving at appropriate and meaningful performance indicators. A computer search of Australian literature reveals a dearth of papers on the subject of health service performance indicators. Perhaps the cultural norm of reticence towards formal performance appraisal is reflected by this dearth. Within individual agencies, however, performance indicators are being utilised in varying degrees. The Royal Children's Hospital, Melbourne, has compiled a structured set of performance indicators for two purposes--firstly, as a means of monitoring performance on a regular basis, and secondly, as a quality assurance tool. The hospital's chosen indicators cover not only throughput, but attempt to shed some light on efficiency and effectiveness. They are designed to highlight areas/trends which diverge from the 'norm', which act as warning signals to investigate further. Whilst some measures relate specifically to the activities and objectives of the Royal Children's Hospital, many are sufficiently general to the hospital field to be worth considering by any hospital interested in a more structured, formal review of its performance. It may also be possible to obtain many of the measures shown without necessarily having in place extensive/comprehensive computer information systems. Introduction of measures may therefore be undertaken progressively.

Australia↗

Sucrase-isomaltase expression and enterocytic ultrastructure of human colorectal tumors.

We report the relative frequency of sucrase-isomaltase (SI) antigen expression in human colonic adenocarcinoma (22/57), in peritumoral mucosa taken next to the tumor (31/41) or distant from it (29/42) as well as in 21/23 polyps. Our results are based on indirect immunofluorescence with a monoclonal antibody (MAb) specific for human intestinal SI. A regular and intense expression of SI occurred only in 6 tumor specimens. In the remaining 16 SI-positive tumor samples, labelling was heterogeneous, i.e., scattered over more or less extensive areas. A similar irregular staining pattern was also found in polyps and in peritumoral mucosa, irrespective of its distance from the tumor. Electron microscopic examination of 19 carcinomas mostly revealed altered brush-border membrane features, irrespective of histological SI staining pattern. Brush-border enzyme activities of sucrase, alkaline phosphatase and maltase showed no difference between tumor specimens and peritumoral mucosa, but aminopeptidase was depressed in the former. Sucrase activity was extremely low (mean values 1.1 to 1.8 mU/mg protein) and rose only exceptionally to 17.5 mU/mg prot.

Adenocarcinoma↗

Control and manipulation of gene expression during tomato fruit ripening.

Ripening is a complex developmental process involving changes in the biochemistry, physiology and gene expression of the fruit. It is an active process characterised by changes in all cellular compartments. cDNA cloning has been used as an approach to analyse changes in gene expression during fruit ripening. This has revealed that several genes are switched on specifically during fruit ripening, including one encoding polygalacturonase (PG), a major cell wall protein. These cDNA clones have been used to study the expression of the genes in normal and ripening mutant fruits, and under environmental stress conditions. The PG gene has been isolated and it has been demonstrated that 1450 bases 5' of the coding region are sufficient for the tissue- and development-specific expression of a bacterial marker gene in transgenic tomatoes. Antisense RNA techniques have been developed to generate novel mutant tomatoes in which the biochemical function of this enzyme and its involvement in fruit softening has been tested.

Cloning, Molecular↗

Reversion of the attenuated and temperature-sensitive phenotypes of the Sabin type 3 strain of poliovirus in vaccinees.

Isolates of type 3 poliovirus from vaccine-recipients were characterized in terms of virulence, sensitivity of growth to high temperatures, and differences in genome structure from the Sabin type 3 vaccine strain. These included point mutations in the region of the genome coding for the structural proteins and in the 5' noncoding region, and the presence of type 1 or type 2 poliovirus genomic sequences resulting from intertypic recombination. Isolates from healthy vaccinees resembled those from vaccine-associated cases of poliomyelitis in all of these properties. Suppression of the temperature-sensitive phenotype was strictly correlated with reversion to virulence in nonrecombinant type 3 strains. Recombinant isolates were more attenuated than expected, even when they had lost all mutations known to attenuate the type 3 vaccine strain.

Base Sequence↗

The effect of oral nutritional supplements on head and neck cancer.

Fifty ambulatory patients with head and neck cancer treated by definitive radiation therapy at the Fox Chase Cancer Center were prospectively studied to determine the effect of oral nutritional supplements on both nutritional status and treatment response. Nutritional supplements maintained serum albumin during and post treatment. Nutritional supplements were shown to increase total protein and total calorie intake rather than displace these nutrients in usual food intake. Equal weight loss occurred in both the supplemented and non-supplemented groups during the observation period of 6 months, with the same or greater amount of weight loss registered 10 weeks after the start of treatment. Food supplements did not affect treatment response or complications, nor did they offer any survival advantage.

Adult↗