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Biomedical subjects

L Morris

Publications and source records attributed to L Morris.

At least 37 records · Page 2Linked to original sources
PubMed2001

Improving accessibility: the experience of a Canadian Mental Health Agency.

This article describes the process undertaken by a community mental health organization in Toronto, whose staff are predominantly white and unilingual, to be more accessible and responsive to Toronto's diverse ethnic communities. Board, staff, and consumer input provided guidance for the development of antidiscrimination and antiracism policies, and subsequently for expectations that each program find ways to implement these policies. The article focuses on events and opportunities of one of the programs that led to connections being established between the organization and the Somali community.

Adult↗
PubMed2001

Cellular characteristics of nipple aspiration fluid during the menstrual cycle in healthy premenopausal women.

Cellular characteristics of nipple aspiration fluid during the menstrual cycle in healthy premenopausal women Fifteen healthy premenopausal female volunteers underwent weekly nipple aspiration of ductal fluid from both breasts during two menstrual cycles to investigate the variability of the cellular profile of the ductal fluid. Ductal fluid was successfully obtained using breast massage and nipple-areolar suction from 247/280 (89%) breasts. 83% of samples available for cytological analysis were cellular and 30% of cellular aspirates contained ductal epithelial cells identified using standard morphological criteria. No significant variation in cell number or cell type was identified during the menstrual cycle. All samples tested had an 'H' score of zero for oestrogen receptor. Seven out of 14 women expressed the proliferation marker Mcm-2 in the cells of at least one of the specimens, with no evidence of a menstrual cycle influence on expression. In conclusion, the cellular profile of breast ductal fluid did not vary consistently during the menstrual cycle, permitting future breast cancer screening studies incorporating serial nipple aspirations to be performed independent of the phase of the cycle.

Adult↗
PubMed2001

Indomethacin treatment of infantile cortical periostosis in twins.

Twin girls presented with infantile cortical periostosis (Caffey's disease) at 2 and 3 weeks of age, respectively. This disorder initially involved their upper and lower limbs and resulted in fever, irritability and tenderness. X-rays showed extensive periosteal new bone formation. Multiple relapses occurred in the first year of life and during some of these relapses mandibular and clavicular involvement was noted. Prednisolone, 1 mg/kg per day, was used to treat relapses until 9 months of age. Indomethacin therapy at this age at a dose of 3 mg/kg per day allowed the cessation of prednisolone therapy and disease flares were thereafter infrequent and responsive to indomethacin.

Cyclooxygenase Inhibitors↗
PubMed2001

Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140.

CCR5 serves as a requisite fusion coreceptor for clinically relevant strains of human immunodeficiency virus type 1 (HIV-1) and provides a promising target for antiviral therapy. However, no study to date has examined whether monoclonal antibodies, small molecules, or other nonchemokine agents possess broad-spectrum activity against the major genetic subtypes of HIV-1. PRO 140 (PA14) is an anti-CCR5 monoclonal antibody that potently inhibits HIV-1 entry at concentrations that do not affect CCR5's chemokine receptor activity. In this study, PRO 140 was tested against a panel of primary HIV-1 isolates selected for their genotypic and geographic diversity. In quantitative assays of viral infectivity, PRO 140 was compared with RANTES, a natural CCR5 ligand that can inhibit HIV-1 entry by receptor downregulation as well as receptor blockade. Despite their divergent mechanisms of action and binding epitopes on CCR5, low nanomolar concentrations of both PRO 140 and RANTES inhibited infection of primary peripheral blood mononuclear cells (PBMC) by all CCR5-using (R5) viruses tested. This is consistent with there being a highly restricted pattern of CCR5 usage by R5 viruses. In addition, a panel of 25 subtype C South African R5 viruses were broadly inhibited by PRO 140, RANTES, and TAK-779, although approximately 30-fold-higher concentrations of the last compound were required. Interestingly, significant inhibition of a dualtropic subtype C virus was also observed. Whereas PRO 140 potently inhibited HIV-1 replication in both PBMC and primary macrophages, RANTES exhibited limited antiviral activity in macrophage cultures. Thus CCR5-targeting agents such as PRO 140 can demonstrate potent and genetic-subtype-independent anti-HIV-1 activity.

Amides↗
PubMed2001

Co-existence of nonmuscle-specific and cardiac muscle-specific myosin in myofibrils of cultured adult cardiac muscle cells.

Immunofluorescence microscopy revealed that nonmuscle myosin and cardiac muscle-specific myosin were present in the myofibrils of cultured adult cardiac muscle cells at different stages of redifferentiation including fully redifferentiated cells. Nonmuscle myosin and cardiac muscle-specific myosin were observed in amorphous or fibroamorphous form predominantly in unspread and partially spread cardiac myocytes. Nonmuscle myosin and cardiac muscle-specific myosin were present in the same striated myofibrils of the same fully redifferentiated cells. Nonmuscle myosin was localized in the Z-lines of sarcomeres of myofibrils. In double stained cells, alpha-actinin was colocalized with nonmuscle myosin in the Z-lines. The in vivo adult cardiac muscle cells contained nonmuscle myosin and cardiac muscle-specific myosin in the same myofibrils of the same cells with the localization of nonmuscle myosin in Z-lines and intercalated discs. It is evident that the nonmuscle myosin is an integral part of the sarcomeric structure of myofibrils in cardiac muscle cells.

Animals↗
PubMed2001

HIV-1 drug resistance and mother-to-child transmission.

The use of antiretroviral drug therapies in HIV-1 infected pregnant women and their infants has resulted in significant reductions in the rates of mother-to-child transmission of HIV-1. A number of drugs that target the reverse transcriptase enzyme have been tested either alone or in combination in short-course regimens tailored for use in developing countries. The drug of choice is nevirapine, which is cheap, easy to administer and highly effective even following a single dose to mother and child. However, this regimen is associated with the selection of mutations associated with drug resistance. While these mutations do not compromise the ability of nevirapine to prevent mother-to-child transmission there is some concern that they may compromise future treatment options. Here we review the current data on HIV-1 drug resistance mutations and what they might mean in terms of efficacy of antiretroviral therapies to prevent mother-to-child transmission.

Anti-HIV Agents↗
PubMed2000

Tuberculosis control and molecular epidemiology in a South African gold-mining community.

BACKGROUND: Gold miners have very high rates of tuberculosis. The contribution of infections imported into mining communities versus transmission within them is not known and has implications for control strategies. METHODS: We did a prospective, population-based molecular and conventional epidemiological study of pulmonary tuberculosis in a group of goldminers. Clusters were defined as groups of patients with Mycobacterium tuberculosis isolates with identical IS6110 DNA fingerprints. We compared the frequency of possible risk factors in the clustered and non-clustered patients whose isolates had fingerprints with more than four bands, and re-interviewed members of 45 clusters. FINDINGS: Of 448 patients, ten were excluded because they had false-positive cultures. Fingerprints were made in 419 of 438, of which 371 had more than four bands. 248 of 371 were categorised into 62 clusters. At least 50% of tuberculosis cases were due to transmission within the community. Patients who had failed treatment at entry to the study were more likely to be in clusters (adjusted odds ratio 3.41 [95% CI 1.25-9.27]). Patients with multidrug-resistant isolates were more likely to have failed treatment but were less likely to be clustered than those with a sensitive strain (0.27 [0.09-0.83]). HIV infection was common (177 of 370 tested) but not associated with clustering. INTERPRETATION: Despite a control programme that cures 86% of new cases, most tuberculosis in this mining community is due to ongoing transmission. Persistently infectious individuals who have previously failed treatment may be responsible for one third of tuberculosis cases. WHO targets for cure rates are not sufficient to interrupt transmission of tuberculosis in this setting. Indicators that are more closely linked to the rate of ongoing transmission are needed.

Adult↗
PubMed2000

Acampomelic campomelic dysplasia with SOX9 mutation.

Acampomelic campomelic dysplasia is a rare clinical variant of the more commonly encountered campomelic dysplasia (CMD1), characterized by absence of long bone curvature (acampomelia). We present a patient with acampomelic CMD1 with a de novo SOX9 missense mutation and report his clinical course to age one year, thereby contributing to genotype-phenotype correlation in CMD1. 2000.

High Mobility Group Proteins↗
PubMed2000

Regulation of E2F transcription by cyclin E-Cdk2 kinase mediated through p300/CBP co-activators.

The E2F proteins form a family of transcription factors that regulate the transition from the G1 to the S phase in the cell cycle. E2F activity is regulated by members of the retinoblastoma protein (pRb) family, ensuring the tight control of E2F-responsive genes. During the G1 phase, phosphorylation of pRb by cyclin-dependent kinases (CDKs), most notably cyclin D-CDK complexes, releases pRb from E2F, facilitating cell-cycle progression by the timely induction of E2F-targeted genes such as cyclin E. However, it is not known whether E2F proteins are directly targeted by CDKs. Here we show that E2F-5 is phosphorylated by the cyclin E-Cdk2 complex, which functions in the late G1 phase, but not by the early-G1-phase-acting cyclin D-CDK complex. A phosphorylation site in the trans-activation domain of E2F-5 stimulates transcription and cell-cycle progression by the recruitment of the p300/CBP family of co-activators, whose binding to E2F-5 is stabilized upon phosphorylation by cyclin E-Cdk2. These results indicate that E2F activity may be directly regulated by cyclin E-Cdk2, and imply an autoregulatory mechanism for cell-cycle-dependent transcription through the CDK-stimulated interaction of E2F with p300/CBP co-activators.

Animals↗
PubMed2000

Evidentiary challenges to evidence-based medicine.

The evidence-based medicine (EBM) movement has exerted a strong influence on contemporary medicine. It has been used to define the hierarchy of knowledge in clinical medicine by classifying clinical findings according to the perceived relevance and validity of the respective methodologies of studies from which evidence was collected. In the spectrum of theories of knowledge, EBM predominantly relies on findings obtained from population-derived clinical research. This reliance on knowledge obtained from population studies sharply contrasts with a physiologic model of clinical knowledge advocated by basic science researchers and many clinicians. An apparent schism between proponents of physiologic and population models in the approach to the practice of medicine has been created. This dichotomy between practising physicians and EBM physicians in the approach to clinical knowledge should not be irreconcilable. We advocate a consilient approach to the interpretation of evidence and the integration of medical knowledge. This approach relies on 'linking of facts and fact-based theory across various disciplines to create a common groundwork of explanation'.

Decision Making↗