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Biomedical subjects

M Wright

Publications and source records attributed to M Wright.

At least 127 records · Page 7Linked to original sources
PubMed1996

Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer.

We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM than did age and sex-matched controls (19.5% vs 7.5%, P < 0.004). However patients with AEMs do not have occult FAP, as we found no heterozygous adenomatous polyposis coli (APC) gene mutations despite extensive analysis of constitutional DNA. Genome-wide DNA replication errors (RERs) occur in a proportion of colorectal cancers, particularly right-sided lesions and in almost all tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients. As AEMs have been reported in familial colon cancer cases, we investigated the relationship of AEMs to tumour RER phenotype. There was indeed an excess of AEMs in patients with right-sided tumours (30.2% of 53 patients vs 14.7% of 116 patients, P < 0.03) and in those with RER tumours (3 out of 12 patients with RER tumours vs none out of 21 patients with non-RER tumours, P < 0.05). Two patients with AEM were from HNPCC families compared with none of those without AEM (P < 0.05). The association of AEMs with colorectal cancer is intriguing, and we speculate that it may be a manifestation of mutational mosaicism of the APC gene, perhaps associated with a constitutional defect in DNA mismatch pair.

Adenomatous Polyposis Coli↗
PubMed1996

Effects of intermittent pressure-induced strain on the electrophysiology of cultured human chondrocytes: evidence for the presence of stretch-activated membrane ion channels.

1. Cyclical pressurization of cultured chondrocytes results in increases in cyclic AMP and in the rate of proteoglycan synthesis. Intermittent increases in hydrostatic pressure are also associated with hyperpolarization of chondrocyte cell membranes and activation of Ca(2+)-dependent K(+)-ion channels but the physiological basis for this response to mechanical stimulation is unclear. 2. Experiments have been undertaken to better define the types of ion channels involved and to explore the possibility that the hyperpolarization response associated with cyclical pressurization of chondrocytes follows activation of stretch-activated ion channels. 3. The mean membrane potential of chondrocytes in non-confluent monolayer cell culture rose from -15.3 +/- 0.24 mV to -21.1 +/- 0.28 mV (n = 60, P < 0.0001) after intermittent pressurization (0.33 Hz, 16 kPa, 20 min). 4. Strain gauge measurements showed that cyclical pressurization was associated with strain on the base of the culture plate. The amplitude of the hyperpolarization response was proportional to the microstrain to which cells were subjected. 5. Membrane hyperpolarization did not occur when chondrocytes were subjected to cyclical pressurization in rigid glass culture dishes or plastic dishes positioned in the pressurization chamber so as to avoid bending of the base of the culture dish. 6. Indirect evidence that the hyperpolarization response after intermittent pressure-induced strain was associated with stimulation of stretch-activated ion channels was obtained from experiments with gadolinium, amiloride and hexamethylene amiloride, each of which abolished hyperpolarization. 7. Experiments with apamin, charybdotoxin and iberiotoxin showed that the Ca(2+)-activated K+ channels involved in the hyperpolarization response are apamin-sensitive, charybdotoxin- and iberiotoxin-resistant, low-conductance channels. 8. Somatostatin and cadmium chloride, which block L-type calcium channels, abolished strain-induced chondrocyte hyperpolarization. EGTA, which chelates extracellular Ca2+, reduced the response to 48% of control values, and thapsigargin, which raises intracellular Ca2+ by inhibition of Ca(2+)-ATPase in endoplasmic reticulum, caused hyperpolarization independently with further hyperpolarization after pressure-induced strain. These data indicate that chondrocyte hyperpolarization was dependent on intracellular Ca2+ concentrations. 9. Further work is required to determine whether stretch-activated ion channels shown to be associated with chondrocyte hyperpolarization after cyclical pressure-induced strain are also involved in the signal transduction process that leads to increases in proteoglycan synthesis.

Calcium Channels↗
PubMed1996

Phototherapy of cancer and atheromatous plaque with texaphyrins.

Cancer and cardiovascular disease are the leading causes of death in the western world. Photodynamic therapy (PDT) has demonstrated activity in the treatment of superficial cancerous lesions and as an intraoperative adjunct during surgical debulking. Texaphyrins are pure, synthetic water-soluble macrocycles that localize in both cancerous lesions and atheromatous plaque. Lutetium texaphyrin (PCI-0123) is activated by tissue-penetrating far red light (720-760 nm). Patient diagnosis and treatment planning is possible via magnetic resonance imaging (MRI) with the paramagnetic gadolinium texaphyrin (PCI-0120) or via fluorescence imaging using the diamagnetic PCI-0123. In this study it is shown that texaphyrins localize selectively in cancer and atheromatous plaque. PDT with PCI-0123 is found to cause selective photodamage to the diseased tissue. Specifically, PCI-0123 acts to eradicate the SMT-F murine mammary tumors and diet-induced atheromatous plaque in rabbits.

Animals↗
PubMed1996

Are physiological effects of sleep deprivation in the rat mediated by bacterial invasion?

Recent reports have indicated that rats subjected to total sleep deprivation (TSD) by the disk-over-water method and sacrificed when death appeared imminent showed aerobic bacteria in their blood. Yoked control rats did not. Extrapolating from these results, it has been suggested that the late body temperature declines and eventual deaths of TSD rats are caused by septicemia, and that other, earlier-appearing effects of TSD-including weight loss, increased energy expenditure, and regulation of temperature at a higher level-might be mediated by impaired host defenses against bacterial invasion. Three measures of aerobic bacterial invasion were used to evaluate these hypotheses: bacteremia, bacterial colonization in major organs of filtration (liver, kidney, and mesenteric lymph nodes), and adherence of bacteria to the cecal wall. Experiment 1 showed nonsignificant trends toward more bacterial invasion in 4-day TSD rats compared to yoked control rats and no relationship between the bacterial indicators and the early TSD effects. Experiment 2 showed that the elimination of aerobic bacterial infection by antibiotic treatment did not prevent the early TSD effects in 4-day TSD rats. Experiment 3 showed that the elimination of aerobic bacterial invasion in TSD rats did not eliminate the late temperature decline or the progression towards death. The results showed no significant evidence of aerobic bacterial invasion early in TSD and no indication that the major effects of TSD were dependent upon aerobic bacterial invasion.

Animals↗
PubMed1996

Lutetium texaphyrin (PCI-0123): a near-infrared, water-soluble photosensitizer.

Lutetium texaphyrin, PCI-0123, is a pure, water-soluble photosensitizer with a large broad absorption band centered at 732 nm. The compound was tested for photodynamic therapy (PDT) effectiveness in a murine mammary cancer model. The texaphyrin macrocycle as illustrated by magnetic resonance imaging and 14C-radiolabeled texaphyrin studies was shown to be tumor selective; a tumor-to-muscle ratio of 10.55 was seen after 5 h. Lutetium texaphyrin, at a drug dose of 20 mumol/kg with irradiation 5 h postinjection at 150 J/cm2 and 150 mW/cm2, had significant efficacy (P < 0.0001) in treating neoplasms of moderate size (40 +/- 14 mm3) and also had significant efficacy (P < 0.0001) in treating larger neoplasms (147 +/- 68 mm3). The PDT efficacy was correlated with the time interval between PCI-0123 administration and light exposure. A 100% cure rate was achieved when photoirradiation took place 3 h postinjection compared to 50% for 5 h using 10 mumol/kg and 150 J/cm2 at 150 mW/cm2. The PDT efficacy was attributable to the selective uptake/retention of the texaphyrin photosensitizer in addition to the depth of light penetration achievable at the 732 nm laser irradiation.

Animals↗
PubMed1996

Molecular characterization of an Aspergillus parasiticus dehydrogenase gene, norA, located on the aflatoxin biosynthesis gene cluster.

An Aspergillus parasiticus cDNA library was screened with monoclonal antibody raised against a purified A. parasiticus 43-kDa protein demonstrating norsolorinic acid reductase (NOR) activity. One immunopositive clone contained a cDNA insert of 1,418 bp. DNA sequence analysis of this cDNA identified an open reading frame of 1,167 bp that represented the norA gene. The deduced amino acid sequence of the norA coding region consisted of 388 residues capable of encoding a polypeptide of 43.7 kDa. Southern blot analysis of genomic DNA from A. parasiticus indicated that there may be an additional copy of norA. Western blot (immunoblot) analysis of crude protein extracts of A. parasiticus mycelia demonstrated a band of reactivity at 43 kDa only when the fungus was grown in a medium conducive to aflatoxin biosynthesis. Northern (RNA) blot analysis of total RNA from the fungus demonstrated a band of hybridization at about 1.5 kb. As observed with the fungal NORA protein, the norA transcript was present only when the fungus was grown in medium conducive to aflatoxin biosynthesis. Hybridization of the norA cDNA with cosmid DNAs known to encompass a major portion of the A. parasiticus and Aspergillus flavus aflatoxin biosynthetic pathway gene cluster placed the norA gene coding region just upstream of the ver-1 gene. The deduced amino acid sequence of norA had 49% amino acid identity with that of an aryl-alcohol dehydrogenase (aad) gene from Phanerochaete chrysosporium.

Aflatoxins↗
PubMed1996

FISH studies in a patient with sporadic aniridia and t(7;11) (q31.2;p13).

A 2 year old female presenting with bilateral sporadic aniridia was found to have an apparently balanced reciprocal translocation with a chromosome 11 breakpoint within band p13. Fluorescence in situ hybridisation (FISH) studies with distal 11p13 specific cosmids showed that the chromosome 11 breakpoint lay between the aniridia (PAX6) locus and a region approximately 100 kb distal to PAX6 defined by the cosmid FO2121. Although this patient did not have a detectable deletion within PAX6, her aniridia may have resulted from a disruption of the distal chromatin domain containing either enhancers or regulators for PAX6. This case may therefore be another example of aniridia caused by a position effect as recently described in two familial aniridia patients in which the phenotype cosegregated with chromosome abnormalities with 11p13 breakpoints.

Aniridia↗
PubMed1996

A single gamma-tubulin gene and mRNA, but two gamma-tubulin polypeptides differing by their binding to the spindle pole organizing centres.

Cells of eukaryotic organisms exhibit microtubules with various functions during the different developmental stages. The identification of multiple forms of alpha- and beta-tubulins had raised the question of their possible physiological roles. In the myxomycete Physarum polycephalum a complex polymorphism for alpha- and beta-tubulins has been correlated with a specific developmental expression pattern. Here, we have investigated the potential heterogeneity of gamma-tubulin in this organism. A single gene, with 3 introns and 4 exons, and a single mRNA coding for gamma-tubulin were detected. They coded for a polypeptide of 454 amino acids, with a predicted molecular mass of 50,674, which presented 64-76% identity with other gamma-tubulins. However, immunological studies identified two gamma-tubulin polypeptides, both present in the two developmental stages of the organism, uninucleate amoebae and multinucleate plasmodia. The two gamma-tubulins, called gamma s- and gamma f-tubulin for slow and fast electrophoretic mobility, exhibited apparent molecular masses of 52,000 and 50,000, respectively. They were recognized by two antibodies (R70 and JH46) raised against two distinct conserved sequences of gamma-tubulins. They were present both in the preparations of amoebal centrosomes possessing two centrioles and in the preparations of plasmodial nuclear metaphases devoid of structurally distinct polar structures. These two gamma-tubulins exhibited different sedimentation properties as shown by ultracentrifugation and sedimentation in sucrose gradients. Moreover, gamma s-tubulin was tightly bound to microtubule organizing centers (MTOCs) while gamma f-tubulin was loosely associated with these structures. This first demonstration of the presence of two gamma-tubulins with distinct properties in the same MTOC suggests a more complex physiological role than previously assumed.

Amino Acid Sequence↗
PubMed1996

An exploration of the quality of peer review group activities within Australasia.

OBJECTIVE: To describe a two-phase study of the structure of Australasian psychiatrist peer review groups. METHOD (Phase one): Initially, information was sought from chairs/coordinators of psychiatrist peer review groups regarding the nature and organisation of their group. RESULTS (Phase one): One hundred and three questionnaires were returned describing a number of models of peer review. Three principal models were identified: a teaching hospital model, a private practice model, and a private institution model. METHOD (Phase two): The second-phase questionnaire sought information on the quality of the review, using six proposed standards developed by the Quality Assurance Committee of the Royal Australian and New Zealand College of Psychiatrists. RESULTS (Phase two): Many groups indicated that four of the proposed standards (those relating to documentation, having clear goals, reviewing actual clinical cases, and rigorous protection of confidentiality) were either already being followed or would be relatively easy to implement. The remaining two proposed standards (including structure, process and outcome dimensions of health care in the case discussion, and the use of explicit criteria) presented more difficulty. CONCLUSION: The application of such standards to peer review group meetings should assist groups to provide a forum for presentation and evaluation of clinical work where participants know they will be challenged in an environment which is both supportive and educational.

Attitude of Health Personnel↗
PubMed1996

To whom do you refer? A referrer satisfaction study.

OBJECTIVE: To report the development of a referrer satisfaction measure. METHOD: Urban and rural general practitioners, physicians, neurologists, as well as obstetricians and gynaecologists rated 36 items in terms of their judged importance to the respondent's satisfaction with a psychiatric service. Responses of the whole sample and component practitioner sub-groups were ranked. RESULTS: We established a high level of agreement across the several subgroups suggesting that we had identified general rather than idiosyncratic variables contributing to referrer satisfaction. Referrers prioritised as most important the immediacy of initial appointment, the psychiatrist reporting at the beginning and end of any treatment course, and ready verbal communication between the referrer and the psychiatrist. Items accorded low priority were the psychiatrist's billing arrangements, the psychiatrist being 'perfect' (in either having a high 'cure' rate or making a definitive diagnosis initially), or the psychiatrist taking complete responsibility for difficult patients. A principal components analysis identified four factors underpinning the item set, and we again established that scores on these factors were not influenced by the particular referrer sub-group. CONCLUSIONS: Such findings suggest that only minor modifications would need to be made to the item set in developing a referrer satisfaction measure for quality assurance activities.

Family Practice↗
PubMed1996

The development of a patient satisfaction measure for psychiatric outpatients.

OBJECTIVE: To describe the first stage of development of a patient satisfaction form designed for psychiatric outpatients. METHOD: An initial 62-item questionnaire was completed by 172 patients, who were asked to assess the importance of a number of practice and practitioner features in contributing to their satisfaction. RESULTS: Mean scores prioritized the psychiatrist respecting the rights of the patient; appointment and billing arrangements were of intermediate importance, while amenity issues were rated as unimportant. When rankings across the several practices were examined, very high levels of agreement were demonstrated, supporting the likely validity of the overall rankings. Four underlying domains were identified by factor analysis, the principal one being defined by respect for confidentiality, by support and adequate communication. The three remaining factors were contributed to more by practice (e.g. billing arrangements, amenities) than by practitioner features. CONCLUSION: We consider how a refined and modified version of the measure might be developed for use by both individual practitioners and group practices, as well as being used as a formal QA component activity.

Australia↗
PubMed1996

Clinical practice issues in consultation-liaison psychiatry.

OBJECTIVE: To overview and highlight the issues currently challenging and confronting consultation-liaison (C-L) psychiatry and to present them for discussion in a wider forum. METHOD: Following preliminary discussions, the authors (members of the New South Wales C-L Interest Group) undertook to selectively review a number of issues relevant to C-L psychiatry. A preliminary paper was prepared and then presented to the membership of the interest group. Feedback from this meeting was incorporated into the final version of the paper. RESULTS: Issues selected as a nidus for further discussion include economic issues, changing models of C-L practice, service issues as well as ethical, issues. In addition, recognition of C-L psychiatry as a true subspeciality is foreshadowed. CONCLUSION: This paper highlights some of the challenges for C-L psychiatry both now and in the future. Intuitive beliefs in our efficacy will not suffice in this era of economic rationalisation. Disciplined and focused research substantiating our value is imperative. Subspeciality recognition is likely to ensure uniformity of standards as well as providing the structure and direction required to consolidate C-L psychiatry's future.

Australia↗
PubMed1996

Interest among occupational therapy managers in measuring workload for case costing.

OBJECTIVES: Interest in costing health care delivery on an individual case basis has increased in recent years as concern with overall health care costs has heightened. Costing exercises have been largely oriented around medical classification systems. Measures to incorporate the contributions of allied health activities such as occupational therapy are relatively recent. The objective of this study was to examine the attitudes and opinions of senior occupational therapy managers toward workload measurement on the basis of case mix. METHOD: A survey was sent to all 198 senior occupational therapy managers in accredited Canadian facilities, which was completed by 182 respondents for a response rate of 92%. The questionnaire asked about workload measurement system(s) currently used, satisfaction with the system(s), and needs and expectations of workload systems in general. RESULTS: The majority of respondents were using a time recording workload measurement system and expressed relatively low levels of satisfaction with it. Current systems were unable to provide costing data, which respondents ranked as very important for themselves as managers. The majority of respondents believed that it would be useful or very useful to be able to cost occupational therapy services by a diagnostic grouping system and to establish standard protocols per diagnosis, standard times per procedure per institution, and standard times per procedure for the profession. CONCLUSION: There is support for developing or expanding current methods of measuring workload. Senior occupational therapy managers would like to be able to predict their workload prospectively, a step that will accommodate the move toward case costing and program management.

Attitude of Health Personnel↗
PubMed1996

Gamma-tubulin is permanently associated with basal bodies in ciliates.

Ciliates are of special interest owing to the multiplicity and diversity of their microtubule organizing centers (MTOCs). The subcellular localization of gamma-tubulin in these protozoa has not been extensively studied. The cloning of a gamma-tubulin gene in Euplotes (Liang, A., K. Heckmann, Gene 136, 319-322 (1993) led us to examine the localization of this protein. We used three polyclonal antibodies, JH46, R58 and R70. They had been raised against peptides common to mammalian and Aspergillus gamma-tubulins. These regions had 69%, 95%, and 75% identity with the corresponding regions of Euplotes gamma-tubulin. Immunoblotting (R70) revealed a polypeptide corresponding to the molecular mass of Euplotes gamma-tubulin. In Euplotes octocarinatus, gamma-tubulin was detected by immunofluorescence (R70) in the basal bodies, the micronucleus and the macronucleus throughout the cell cycle. The presence of gamma-tubulin in basal bodies and micronuclei was confirmed with the other two antibodies JH46 and R58. The permanent association of gamma-tubulin with basal bodies was also observed in Tetrahymena thermophila and Paramecium tetraurelia, two ciliates distantly related to Euplotes. These results not only extend to ciliates the finding that gamma-tubulin is permanently associated with ciliary basal bodies, but also demonstrate that gamma-tubulin is present in unconventional MTOCs.

Amino Acid Sequence↗