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Biomedical subjects

H Morrison

Publications and source records attributed to H Morrison.

At least 37 records · Page 2Linked to original sources

Monograph series on aging-related diseases: X. Prostate cancer.

Prostate cancer is the most commonly diagnosed cancer among Canadian men, excluding non-melanoma skin cancer. Prostate cancer incidence increases almost exponentially with age; most cases are diagnosed in men aged 65 years or older. With the possible exception of animal fat consumption, no known widespread modifiable risk factors have been identified. Although the prognosis is good if appropriate treatment occurs in the early stages of disease, the ability of existing early detection techniques to decrease mortality has not yet been demonstrated. The considerable economic and societal burden of prostate cancer and its treatment, coupled with the projected large increase in the number of new prostate cancer cases as the population ages, make this disease a very important public health issue.

Aged↗

Survival rates among Canadian children and teenagers with cancer diagnosed between 1985 and 1988.

PURPOSE: To describe the survival rates among Canadian children and teenagers with cancer diagnosed between 1985 and 1988 using population-based data, specifically for the more common forms of childhood cancer, and to assess the effect of age at diagnosis and sex as prognostic factors for selected childhood cancers. DESIGN: Retrospective survival study based on incident cases of cancer identified by the National Cancer Incidence Reporting System and follow-up ascertained by computer record linkage to the Canadian Mortality Database. SUBJECTS: A total of 4409 patients with cancer first diagnosed at 19 years of age or younger between 1985 and 1988, and followed up to Dec. 31, 1991. MAIN OUTCOME MEASURES: Survival rates calculated at 1, 3 and 5 years according to the actuarial life table and the proportional hazards models. RESULTS: The 5-year survival rate for all cancers combined was 71%. Females with acute lymphoblastic leukemia and astrocytoma had markedly higher survival rates than their male counterparts (p < 0.05). Age at diagnosis was a significant predictor of survival among children with acute lymphoblastic leukemia or acute nonlymphoblastic leukemia (p < 0.01), infants having a substantially poorer prognosis than older children. Conversely, the survival rate among infants with neuroblastoma was higher than that among older children, 87% surviving for 5 years after diagnosis. CONCLUSIONS: The survival rate among Canadian children and teenagers with cancer is favourable in relation to the rate among adults with cancer. Nonetheless, the 5-year survival rates for several childhood cancers remain poor (i.e., less than 65%). The survival rates among Canadian children with cancer are similar to those among children with cancer in other developed countries.

Adolescent↗

Simultaneous determination of methylene violet, halogenated methylene violet and their photoproducts in the presence of DNA by high-performance liquid chromatography using an internal surface reversed-phase column.

A simple and rapid isocratic high-performance liquid chromatographic method for the analysis of methylene violet, a neutral phenothiazine dye, in the presence of DNA has been developed. These chromatographic conditions are also applicable to its N-demethylated, bromo and iodo analogs. The method utilizes an internal surface reversed-phase column and a mobile phase consisting of 20% acetonitrile in 50 mM phosphate buffer (pH 7.0) and detection at 280 nm. Under these conditions all five dyes are well resolved from one another and from the faster migrating DNA. The effects of organic modifiers, ionic strength and pH of the buffer on the capacity factors of the dyes have been investigated. The method has successfully been applied to detect the photoproducts of methylene violet and its bromo analog in the presence of DNA without removing the biopolymer from the reaction mixture.

Acetonitriles↗

Regulation of tumor antigen presentation by urocanic acid.

Urocanic acid (UCA) accumulates in the epidermis after deamination of histidine. UCA isomerizes from the trans to the cis form upon exposure to environmental UV radiation. Cis-UCA is immunosuppressive in several models. Topically applied cis-UCA was reported to enhance the cutaneous tumor yield in chronically UV-irradiated mice, suggesting involvement of cis-UCA in photocarcinogenesis. Since Langerhans cells (LC) are capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor-immune responses, we examined the effects of trans- and cis-UCA on LC tumor Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2a). In this system, induction of immunity requires exposure of LC to granulocyte-macrophage CSF. Naive CAF1 (H-2(a/d)) mice were immunized against S1509a by injection with granulocyte-macrophage CSF-exposed and TAA-pulsed epidermal cells (EC), as assessed by growth inhibition of inoculated tumor cells. Incubation of EC in cis-, but not trans-UCA completely inhibited Ag presentation in this system. Neither histamine antagonists nor indomethacin reversed these effects of cis-UCA. The ability of trans- and cis-UCA to modulate EC presentation of TAA for secondary immune responses was also examined. EC were pulsed with TAA in vitro and then injected into hind footpads of tumor-immune mice. After 24 h, footpad swelling was assessed as a measure of delayed-type hypersensitivity. Incubation with cis-, but again not trans-UCA before TAA exposure significantly inhibited elicitation of delayed-type hypersensitivity. These data indicate that cis-UCA may be an important regulator of LC Ag-presenting function in tumor-immune responses, and thus may play a role in photocarcinogenesis.

Animals↗

Photobiological properties of methylene violet.

The interaction of methylene violet (MV) and 4-bromomethylene violet (BrMV) with calf thymus and supercoiled phi X174 phage RF I DNA is reported. Measurements employing UV-visible absorption spectroscopy and equilibrium dialysis give evidence for the formation of complexes by each dye with DNA in the dark. They covalently bind to DNA, and MV nicks DNA, when the nucleic acid/dye mixtures are irradiated with visible light in a deoxygenated environment. Quantum efficiencies for singlet oxygen formation are 0.27 and 0.25 for MV and BrMV, respectively. A higher value (0.49) is observed for 4-iodomethylene violet (IMV).

Animals↗

Chest teleradiology in a teaching hospital emergency practice.

OBJECTIVE: New standards for hospital accreditation and health care reimbursement may require that faculty subspecialists be more available after regular working hours to supervise residents in academic radiology departments. We designed a receiver operating characteristic study to determine whether a thoracic radiologist who evaluated computed radiography (CR) images of the chest at a home-based teleradiology workstation could add significant value to a junior resident's interpretations of films within the hospital for acutely ill patients. SUBJECTS AND METHODS: Using a hybrid cassette, we obtained analog chest films and CR images simultaneously for each of 252 acutely ill patients in the emergency department and in an intensive care unit. Interpretations of the analog films by three first-year residents were analyzed for 11 parameters deemed critical for patient management. Likewise, CR images of the same chest studies were viewed on a home teleradiology workstation by a faculty thoracic radiologist who analyzed the images for these 11 interpretive parameters. All interpretations by radiology residents and by the home-based thoracic radiologist were then compared with the interpretations of a consensus panel consisting of another thoracic radiologist and a full-time emergency department radiologist. RESULTS: Analysis of the pooled results from the three junior residents as a group failed to show significant differences between their interpretations of chest films and the interpretations of CR images by a thoracic radiologist at a home workstation. However, we observed significant differences for several image interpretation parameters between individual residents and the home-based radiology subspecialist. CONCLUSION: The data confirm that significant value can be added to the interpretations of chest films by individual junior residents when a home-based thoracic radiologist uses teleradiology to provide expert interpretations. Accordingly, it is reasonable to infer that on-line supervision by faculty subspecialists via teleradiology could be used to complement the scheduled visits that are being made now by individual faculty members of our institution to interpret films periodically with a radiology resident during overnight and weekend periods.

Emergency Service, Hospital↗

The passing score in the objective structured clinical examination.

The objective structured clinical examination (OSCE) now has an established place in the assessment of the medical undergraduate. While much has been written about the reliability of the OSCE, empirical work on the determination of the passing score which represents competence on the OSCE is rarely encountered. If the OSCE is to play its role in the 'high stakes' testing of clinical competence, it is important that this passing score be set reliably and defensibly. This article illustrates how a two-session modified Angoff standard-setting procedure is used to set the passing score on a 14 station Obstetrics and Gynaecology OSCE used to assess final year students at The Queen's University of Belfast. The Angoff methodology harnesses the professional judgement of expert judges to establish defensible standards. Four university teachers, five non-academic consultants and six junior clinical staff took part in a two-session Angoff standard-setting procedure. In the first session, the judges (individually and in silence) used their professional judgement to estimate the score which a minimally competent final year obstetrics and gynaecology student should achieve on each tested element of the OSCE. In the second session they revised their session 1 judgements in the light of the OSCE scores of real students and the opportunity for structured discussion. The passing score for the OSCE is reported together with the statistical measures which assure its reliability.

Clinical Competence↗

On the roles of urocanic acid in photoimmunosuppression: attempted photorepair of urocanic acid-DNA cyclobutane adducts with DNA photolyase.

It has been reported that UV-induced immunosuppression can be reversed by photoreactivation or exposure to T4 endonuclease V, two treatments that can repair cyclobutane pyrimidine dimers. These observations, together with the known role of urocanic acid (UA) in UV-induced immune suppression, prompted us to study the ability of DNA photolyase to repair UA-DNA cyclobutane photoadducts in single-stranded calf thymus DNA. We did not detect any release of UA, with a sensitivity implying that photolyase is at least 2900 times less active toward UA-DNA adducts than toward cis-syn thymine-thymine dimers. This indicates that any reversal of photoimmunosuppression by photoreactivation cannot significantly involve cleavage of UA-DNA cyclobutane adducts.

Animals↗

Epigenetic control of mammalian centromere protein binding: does DNA methylation have a role?

Chromosome 1 of the inbred mouse strain DBA/2 has a polymorphism associated with the minor satellite DNA at its centromere. The more terminal block of satellite DNA sequences on this chromosome acts as the centromere as shown by the binding of CREST ACA serum, anti-CENP-B and anti-CENP-E polyclonal sera. Demethylation of the minor satellite DNA sequences accomplished by growing cells in the presence of the drug 5-aza-2'-deoxycytidine results in a redistribution of the CENP-B protein. This protein now binds to an enlarged area on the more terminal block and in addition it now binds to the more internal block of minor satellite DNA sequences on chromosome 1. The binding of the CENP-E protein does not appear to be affected by demethylation of the minor satellite sequences. We present a model to explain these observations. This model may also indicate the mechanism by which the CENP-B protein recognises specific sites within the arrays of minor satellite DNA on mouse chromosomes.

Animals↗

Analysis of loss of inactive X chromosomes in interphase cells.

We have developed a method that allows, for the first time, a specific analysis of the inactive X chromosome (Xi) in interphase cells. By combining immunolabeling of acetylated histone H4 with specific antisera and FISH with an X-chromosome centromere-specific DNA probe, micronucleated whole Xis in human female cells may be identified by their lack of histone H4 acetylation. As one example of the potential applications of this methodology in genetic studies in humans, an artifact-free X-chromosome aneuploidy detection in lymphocytes of women of different ages has been performed. Our results indicate that not only the Xi but also the active X chromosome is preferentially lost during aging, indicating that the high frequency of sex-chromosome aneuploidy in human females cannot be explained solely by a lack of negative selection of Xi aneuploid cells. Further applications of the proposed methodology in genetic studies are discussed.

Adult↗

Photoaquation of cis-dichlorobis-(1,10-phenanthroline)chromium(III) and the photochemical and thermal reactions of this complex with native calf-thymus DNA.

The photoaquation of the title compound [cis-Cr(phen)2CL+2] has been studied using high performance liquid chromatography. Both monoaquo [cis-Cr(phen)2Cl(OH2)2+2] and diaquo [cis-Cr(phen)2(OH2)3+2] products are formed, and the quantum efficiency for the loss of starting material in Tris buffer (pH 7) under argon and oxygen is 0.010 +/- 0.001 and 0.0026 +/- 0.0002, respectively. The presence of deoxyguanosine (dG) increases the rate of loss, as much as twofold under argon, but only the rate of diaquo product formation is enhanced by the nucleoside. The dG effect is attributed to reductive quenching of the cis-Cr(phen)2Cl+2 excited state by the base. Equilibrium dialysis studies indicate that both cis-Cr(phen)2Cl+2 and cis-Cr(phen)2(OH2)3+2 minimally associate with calf-thymus DNA. However, photolyses of cis-Cr(phen)2Cl+2 with the nucleic acid yield a mixture of unidentified covalent adducts. The diaquo complex also forms covalent adducts with DNA in the absence of light. Photolyses of the cis-Cr(phen)2Cl+2 with polyribonucleotides indicate a clear preference for covalent binding to the purines.

Animals↗

Mutations in the p53 gene are not limited to classic 'hot spots' and are not predictive of p53 protein expression in high-grade non-Hodgkin's lymphoma.

We have investigated the relationship between the p53 genotype and phenotype in a series of 22 high-grade non-Hodgkin's lymphomas (NHLs) in which we sequenced the p53 gene open reading frame (exons 2-11). Immunostaining for p53 was already available for these cases. Mutations were found in 10/22 cases (45%) and 3/10 were in exons 4 or 10 outside the classic 'hot spot' regions (exons 5-8). Comparison with immunostaining indicated that, besides cases with the 'expected' patterns (in which gene mutation and protein detection were either both present or both absent) there were also cases in which p53 protein was detected in the absence of any mutation and those with a mutant gene in which the protein was undetectable. These data show that: (1) in high-grade NHLs mutations frequently occur outside the classic hot spot regions and (2) staining for p53 is not predictive of the status of the gene, i.e. whether or not a mutation is present. Therefore in order to document p53 involvement in lymphoid tumours it is necessary both to sequence at least the whole translated open reading frame of the gene and to show evidence of protein expression by immunostaining.

Amino Acid Sequence↗

Photosensitized inactivation of infectious DNA by urocanic acid, indoleacrylic acid and rhodium complexes.

Naked, infectious single-stranded (ss) and double-stranded (ds) DNA from phages S13 and G4 were irradiated with 308 nm UV radiation in the absence and presence of several photobiologically active compounds: E- and Z-urocanic acid (E- and Z-UA), their methyl esters (E- and Z-MU), E- and Z-indoleacrylic acid (E- and Z-IA), cis-dichloro-bis(1,10-phenanthroline)rhodium(III) chloride (cDCBPR) and tris(1,10-phenanthroline)rhodium (III) perchlorate (TPR). E-urocanic acid protects against cyclobutane pyrimidine dimer formation in ssDNA but concomitantly photosensitizes the formation of other lesions that inactivate ssDNA. Z-urocanic acid also protects ssDNA against such dimerization but without the associated sensitized damage. The methyl ester isomers behave similarly. There is no such differential activity observed for the IA isomers, both of which sensitize the inactivation of ssDNA. Photostationary state mixtures of both UA and IA efficiently sensitize the inactivation of dsDNA, and cDCBPR strongly protects ssDNA from UV damage, while TPR is a significant sensitizer. Both of these metal complexes sensitize the inactivation of dsDNA slightly. For all compounds, cyclobutane pyrimidine dimers were the predominant lethal lesions produced by sensitization of the dsDNA, but they were not the major lethal lesions created by sensitization of the ssDNA. In the case of dsDNA, both UA and IA created pyrimidine dimers with a high degree of potential for mutagenesis, as determined by an assay that monitors the frequency of mutations following the spontaneous deamination of cytosine in photodimers.

Coliphages↗

An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration.

The sequestration of parasitized erythrocytes in the microvasculature of vital organs is central to the pathogenesis of severe Plasmodium falciparum malaria. This process is mediated by specific interactions between parasite adherence ligands and host receptors on vascular endothelium such as intercellular adhesion molecule-1 (ICAM-1) and CD36. Using immunohistochemistry we have examined the distribution of putative sequestration receptors in different organs from fatal cases of P. falciparum malaria and noninfected controls. Receptor expression and parasite sequestration in the brain were quantified and correlated. Fatal malaria was associated with widespread induction of endothelial activation markers, with significantly higher levels of ICAM-1 and E-selectin expression on vessels in the brain. In contrast, cerebral endothelial CD36 and thrombospondin staining were sparse, with no evidence for increased expression in malaria. There was highly significant co-localization of sequestration with the expression of ICAM-1, CD36, and E-selectin in cerebral vessels but no cellular inflammatory response. These results suggest that these receptors have a role in sequestration in vivo and indicate that systemic endothelial activation is a feature of fatal malaria.

Adult↗

Cellular aspects of the development of diarthrodial joints and articular cartilage.

There have been many reports on the histological development of mammalian diarthrodial or synovial joints. While these are useful for comparative purposes, they tell us little of the cellular basis of joint morphogenesis which must underlie a number of morphogenetic defects. The process of joint morphogenesis is complex and can be subdivided into a number of facets and this report will focus on 2 of them. First, the process of joint cavitation in the chick metatarsophalangeal joint, where we propose that the selective secretion of hyaluronan into the presumptive cavity plays a central role. Secondly, the development of articular cartilage where we have used the South American opossum Monodelphis domestica as a model for mammalian development. Like most marsupials, the young are born at a much earlier developmental stage than eutherian mammals. Using antibodies which detect proliferating chondrocytes and those synthesising insulin-like growth factors 1 and 2 and insulin-like growth factor 1 binding protein, we report that the majority of growth (as assessed by these indicators) appears appositional.

Animals↗

A novel internal antigen which distinguishes germinal centre cells from other B-cell types.

A new monoclonal antibody, 4KB51, is described which labels the majority of B cells in blood and in mantle and marginal zones but not germinal centre lymphocytes or plasma cells. Antibody 4KB51 also stains monocytes, neutrophils and the majority of T cells. It recognizes an intracellular antigen of 160,000 MW (unreduced) and 68,000 MW (reduced). Antibody 4KB51 labels the tumour cells in all cases of hairy cell leukaemia and in four of the 16 cases of centrocytic B-cell lymphoma studied. No labelling of the other lymphomas (114 cases) or lymphoid leukaemias (13 cases) tested was seen. Antibody 4KB51 may be of value in defining B-cell subsets and in the differential diagnosis of hairy cell leukaemia and centrocytic lymphomas. The pattern of reactivity of 4KB51 suggests that its target antigen may play a functional role, possibly involved in lymphocyte homing.

Antibodies, Monoclonal↗

Farming and prostate cancer mortality.

Although farmers appear to be at an increased risk of prostate cancer, the specific exposures which produce the excess risk remain unexplained. This study was based on a retrospectively assembled cohort of male Manitoba, Saskatchewan, and Alberta, Canada, farmers age 45 years or older identified in the 1971 Canadian censuses of population and agriculture. The cohort was linked to the Canadian National Mortality Database using an iterative computer record linkage system for the period June 1971 to the end of 1987. A total of 1,148 prostate cancer deaths and 2,213,478 person-years were observed. Using Poisson regression, the study examined the relation between the risk of dying from prostate cancer and various farm practices as identified on the 1971 Census of Agriculture, including exposure to chickens, cattle, pesticides, and fuels. A weak, but statistically significant, association was found between number of acres sprayed with herbicides in 1970 and risk of prostate cancer mortality. When the analysis was restricted to farmers believed to be subject to the least amount of misclassification, the risk associated with acres sprayed with herbicides increased (rate ratio (RR) = 2.23 for 250 or more acres sprayed; 95% confidence interval (CI) 1.30-3.84; test for trend, p < 0.01). No other farm exposure examined was associated with any detectable pattern of increased or decreased risk. These findings encourage further research to examine the effects of herbicides on prostate cancer.

Aged↗