Biomedical subjects
C Johnston
Publications and source records attributed to C Johnston.
Cervical adenocarcinoma in situ: a persistent clinical dilemma.
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Toronto centre hopes to cash in on growing demand for private health services.
When the CMA held its 1996 annual meeting, part of the debate on the future of health care involved the "appropriate balance of the roles of the public and private sectors" in delivering health care. The King's Health Centre in Toronto is now doing its own balancing act: providing publicly funded care to Canadians, and private care to non-Canadians and Canadians who can afford it. This article discusses some of the niche markets King's is attempting to develop.
Stress, maternal distress, and children's adjustment following immigration: the buffering role of social support.
This study examined, in the context of a stress-buffering model, the relationship of certain family-level variables to children's adjustment after immigration. Immigrant Chinese mothers from Hong Kong completed questionnaires regarding postmigration stress, personal distress, perceived social support, and their child's adjustment. Another adult also provided child behavior ratings. Analyses revealed that, for boys, family stress and maternal distress were significant predictors of child problems and that maternal support buffered the association between family stress and child problems. Contrary to expectation, the relationship between maternal distress and boys' problems was stronger at higher levels of maternal support. For families of girls, although there were significant relationships between the predictors and child behavior, no stress buffering was evident. Cultural explanations are discussed.
The epidermal nerve fibre network: characterization of nerve fibres in human skin by confocal microscopy and assessment of racial variations.
As a first line of defence, the skin is equipped with a complex and interactive nerve fibre system to detect irritants and maintain homeostasis. The dermal component of this fibre network has been well characterized and fibres are known to extend throughout the viable epidermis as free nerve endings. To date, this epidermal component remains poorly characterized. We have visualized human volar forearm epidermal nerve fibres by laser-scanning confocal microscopy using the pan-neuronal marker, protein gene-product 9.5 and specific antibodies to substance P. calcitonin gene-related peptide and nerve growth factor. In addition to the varicose free nerve endings, there is a 3-D fibre network in normal human epidermis, with frequent branching of fibres. Branching can be seen to converge on a central trunk apparently extending to the dermis. Thin unmyelinated fibres can be seen in all layers of the viable epidermis. Substance P staining is rarely observed and is much less intense than the protein gene-product 9.5 staining. Calcitonin gene-related peptide and nerve growth factor were not detected in volar forearm epidermis by this method. Pretreatment of the skin in vivo with the neuropharmacological agent, capsaicin, resulted in loss of epidermal fibre staining indicating that these are sensory fibres of the primary C-afferent type. Epidermal innervation in racial and ethnic skin types was also assessed. No apparent difference in innervation was observed between European caucasian and Japanese/Chinese skin at the architectural or biochemical level, i.e. the presence, properties and biochemical content of fibres was similar in all cases tested.
Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease.
The allelic frequency of the gene for the K variant of butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age > 65 years) histopathologically diagnosed Alzheimer's disease (AD), which was higher than the frequencies in 104 elderly control subjects (0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed cases of other dementia (0.10). The association of BCHE-K with late-onset AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E gene (APOE), among whom the presence of BCHE-K gave an odds ratio of confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene for late-onset AD.
Pathways to scaling-up in community based rehabilitation agencies.
Scaling-up is the expansion or development of organizational activities to achieve a greater impact. Scaling-up among non-government organizations (NGOs) involved in community based rehabilitation (CBR) is a recent phenomenon. Case study materials from NGOs in India, Canada, and Indonesia are used to illustrate four pathways to scaling-up in CBR and the use of collaboration strategies in these efforts. Discussion focuses on differences between scaling-up in industrialized and less developed countries and on structural characteristics of organizations which influence their pathways.
Kinematics and kinetics of the carpus.
This study investigated the kinematics and kinetics of the carpus during the stance phase. Five Standardbred horses trotted on a treadmill at 8.9 m/s. The kinematics of the horses were filmed and hoof reaction forces (HRF) were recorded. The carpus was overextended throughout most of the stance. There were 2 periods of overextension, a more rapid period in the beginning of the stance and second directly following the first period. Maximal overextension occurred slightly before the second minimum of the braking horizontal HRF. The metacarpal and antebrachial segments rotated counter-clockwise for most of the stance. The angular velocities of these segments attained absolute and local extremes that were concurrent. The absolute maxima in the longitudinal and the transversal acceleration of the proximal metacarpus were coincident in time with the minimal horizontal braking force. The moment of force about the carpus was extending throughout most of the stance, with a short period of flexion near the end of the stance. The results show that horizontal braking of the hoof results in impulsive loading followed by maximal overextension of the carpus. The second phase of overextension is suggested to be related to the tension or active roll of the flexor tendons of the distal limb. The carpus is, therefore, subjected to rapid and high loading in both the longitudinal and transversal directions, as well as large moments and forces.
Unsuspected thyrotoxicosis and hyperemesis gravidarum in Asian women.
This report describes three women with hyperemesis gravidarum caused by previously undiagnosed thyrotoxicosis. All three women were eight weeks pregnant and only one woman had typical features of thyrotoxicosis. Hyperemesis could not be controlled by anti-emetics. The patients were successfully treated with antithyroid drugs. Anti-thyroid treatment does not need to be continued once resolution of symptoms and thyrotoxicosis have occurred.
Particulate-cell interactions and pulmonary cytokine expression.
The type II cell plays an important role in the response of the alveolar epithelium after lung injury through its synthesis and secretion of pulmonary surfactant, and by acting as the stem cell for the replacement of damaged type I epithelial cells. The nonciliated bronchiolar epithelial (Clara) cell is thought to play a similar role during repair of the bronchiolar epithelium. Recent evidence has suggested that epithelial cells may participate in aspects of the inflammatory response and regulation of fibroblast growth during pulmonary fibrosis through the production of and response to specific growth factors and cytokines. The cellular and molecular responses of epithelial cells and how they lead to the progression of events that defines the pulmonary parenchymal response to a class of particles is unclear. We used particles differing in size, chemical composition, and fibrogenicity in vivo and in vitro to elucidate early changes in proinflammatory and profibrotic cytokine and antioxidant gene expression in lung cells. Early increases in mRNA and protein for the proinflammatory cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha have been observed in epithelial cells following exposure. These are accompanied by changes in specific epithelial genes including surfactant protein C and Clara cell secretory protein. The data indicate that effects on the epithelium are due to direct interactions with particles, not a result of macrophage-derived mediators, and suggest a more significant role in the overall pulmonary response than previously suspected. These results suggest that type II cell growth factor production may be significant in the pathogenesis of pulmonary fibrosis.
Evidence for reduced Th1 function in normal pregnancy: a hypothesis for the remission of rheumatoid arthritis.
OBJECTIVE: The mechanisms underlying the pregnancy induced remission of rheumatoid arthritis (RA) remain unclear. We assessed the hypothesis that it reflects systemic physiologic changes in immune response during gestation. METHODS: We used in vitro whole blood culture systems stimulated with either lipopolysaccharide or phytohemagglutinin to assess cytokine secretion of cells from healthy pregnant and control donors. RESULTS: Interleukin 2 (IL-2) production was decreased during pregnancy, more so in the 3rd trimester, and soluble tumor necrosis factor (TNF) receptor p55 and p75 was increased, again most significantly in the 3rd trimester. TNF-alpha and IL-1 beta were unchanged. CONCLUSION: These findings are consistent with the hypothesized downregulation of Th1 responses during pregnancy. Further studies to assess the relationship with fetal/maternal HLA class II disparity, and eventually the presence or absence of remission in actual patients with RA, are required.
Psychiatrist says counselling via e-mail may be yet another medical use for Internet.
The head of the Personality Disorders Clinic at the University of Michigan recently told the annual meeting of the American Psychiatric Association that he has used "e-mail counselling" to treat seriously ill patients. He provided some advice about the possible use of e-mail to supplement face-to-face sessions in the psychiatrist's office.
Mild cytological atypia in women with HIV infection.
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Apolipoprotein-E genotyping in diagnosis of Alzheimer's disease.
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Identification and characterization of a unique chondrocyte gene involved in transition to hypertrophy.
The character of differentiating chondrocytes in growing long bones has been defined by altered expression of a limited number of genes. To expand this set we have applied differential display to identify genes expressed in either mineralizing or nonmineralizing chondrocytes. One such gene, Band 17, has the following characteristics: (1) Band 17 expression is predominantly found in cartilage destined for mineralization. Band 17 mRNA is undetectable in articular cartilage and undetectable or weak in all other tissues tested. (2) Band 17 expression is spatially restricted to the lower proliferative/upper hypertrophic zone of chondrocytes in the growth plate of long bones and embryonic vertebrae. (3) Induction of a hypertrophic phenotype in progenitor sternal chondrocytes by treatment with ascorbate increases expression of Band 17. (4) Induction of hypertrophy in growth plate chondrocytes in short-term monolayer cultures correlates with a rapid but transient rise in Band 17 message. Our interpretation of these findings is that Band 17 expression is associated with the transition to hypertrophy, not maintenance of the hypertrophic phenotype. Molecular analysis of the 3' end of Band 17 cDNAs and genomic structure has shown that Band 17 is a single copy gene transcribed into four messages. Alternative splicing of these messages is predicted to result in two proteins that differ at the C-terminal by 131 amino acids. The longer protein contains a C-terminal consensus sequence that potentially targets this protein to the lumen of the endoplasmic reticulum. There is a Band 17 homologue in humans, suggesting conservation of Band 17 function in mammals. In summary, the pattern of expression and the predicted primary structure identify Band 17 as unique among all previously known chondrocyte genes.
Suicide totals for MDs sad reminder of stresses facing medicine, conference told.
A recent conference on physician health cosponsored by the CMA and American Medical Association provided some sobering news. One physician reported on the suicides of physicians practising in the US. Another reported that inroads being made by managed health care is affecting physician morale. "Physicians' lifetime calling of caring for the sick is being called into question," said Dr. Patricia Tighe. "They have become like factory workers who can't take pride in their work and are denied a sense of belonging. They are part of a corporate enterprise, to be dispensed with when they are not profitable, and subjected to penalties if their work doesn't measure up".
Characterization of a Ku86 variant protein that results in altered DNA binding and diminished DNA-dependent protein kinase activity.
Three proteins known to play a critical role in mammalian DNA double-strand break repair and lymphoid V(D)J recombination are the autoantigens Ku86 and Ku70 and a 465-kDa serine/threonine protein kinase catalytic subunit (DNA-PKcs). These proteins physically associate to form a complex (DNA.PK) with DNA-dependent protein kinase activity. In this study, we demonstrate using electrophoretic mobility shift assays (EMSAs) that the nuclear DNA end-binding activity of Ku is altered in the human promyelocytic leukemic HL-60 cell line. Western blot and EMSA supershift analyses revealed that HL-60 cells expressed both full-length and variant Ku86 proteins. However, a combined EMSA and immunoanalysis revealed that the Ku heterodimers complexed with DNA in HL-60 cells contained only the variant Ku86 proteins. Finally, UV cross-linking experiments and DNA.PK assays demonstrated that the Ku complexes containing variant Ku86 had a greatly reduced ability to interact with DNA-PKcs and that consequently HL-60 cells had severely diminished DNA.K activity. These data provide important insights into the interaction between Ku and DNA-PKcs and into the role of DNA.PK in DNA double-strand break repair.
Would you recommend a medical career to your children?
Physicians are frustrated by cutbacks, threats to their practices, income restrictions and government interference. However, in spite of complaints from practising physicians medicine remains an attractive career option for Canada's best and brightest, with four to five candidates for every first-year position in medical school.