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Biomedical subjects

V Ho

Publications and source records attributed to V Ho.

At least 37 records · Page 2Linked to original sources
PubMed1999

Ultraviolet radiation-induced p53 responses in the epidermis are differentiation-dependent.

BACKGROUND: The tumour suppressor, p53, is recognized as a crucial molecule in regulating cellular responses to various DNA-damaging agents. Very early on in the development of nonmelanoma cancers p53 is mutated or lost, suggesting that p53 is crucial in protecting normal keratinocytes from the harmful effects of ultraviolet (UV) radiation. OBJECTIVE: Using two mouse models, one with multiple copies of mutant p53 and the other a p53 "knockout," our laboratory has examined a role for p53 in UV-induced DNA damage and determined if these effects are differentiation dependent. CONCLUSION: We outline in this review a proposed model reflecting differentiation-dependent p53 regulation of UV-induced responses in keratinocytes. After exposure to UV, basal keratinocytes repair damaged DNA, whereas differentiating keratinocytes undergo cell death, both processes are regulated by p53.

Animals↗
PubMed1999

The role of Apligraf in the treatment of venous leg ulcers.

A cultured, allogeneic, bi-layered human skin equivalent has recently become available to help clinicians manage difficult-to-heal venous ulcers. This skin equivalent has an epidermis and dermis similar to human skin. Its living keratinocytes and fibroblasts are from cultured cell banks derived from human neonatal foreskin. Because the skin equivalent is made up of viable human cells, it cannot be terminally sterilized. Safety concerns, which have been addressed, include the risk of possible transmission of infection, immunogenicity, immunological graft rejection, and tumor formation. However, the maternal blood of the neonatal donor and the master cell banks are screened for infectious agents. Additionally, the human skin equivalent is produced under strict aseptic control, with sterility continuously monitored by the Good Manufacturing Processes. This paper reviews the characteristics of this human skin equivalent and provides practice guidelines.

Algorithms↗
PubMed1999

An international perspective on the well being and health care costs for patients with systemic lupus erythematosus. Tri-Nation Study Group.

OBJECTIVE: To compare health care expenditure and health status for patients with systemic lupus erythematosus (SLE) between nations with distinct mechanisms for funding and delivering health care services. METHODS: Seven hundred eight patients with SLE from 2 centers in each of 3 countries (Canada 229, United States 268, United Kingdom 211) underwent physician assessment of disease activity and damage and reported on physical and psychosocial well being, satisfaction, social support, and health resource utilization. To compare overall utilization, constant prices (1997 Canadian dollars) were applied across countries for each service, enabling diverse resources to be collapsed into a single expression. RESULTS: After adjusting for important patient covariates, Canadian, compared to American and British patients, reported significantly superior health status in 3 of 8 Medical Outcome Survey Short Form-36 (SF-36) subscales, the SF-36 physical component summary score, and the visual analog scale of general health status. There was no consistent trend in patient satisfaction. Overall annual resource utilization did not vary significantly, with mean annual per patient expenditures (adjusted for demographics, disease duration, activity, damage, social support, health status, patient satisfaction, and age and sex adjusted country-specific SF-36 general population norms) totalling $4853, $5285, and $4760 for Canada, US, and the UK, respectively. However, within each resource category, differences were observed. Canadians saw more specialists than the British, the British more generalists. Canadians and Americans were more frequent users of the emergency room; Americans of laboratory/imaging procedures. Canadians had higher hospital costs than Americans. CONCLUSION: After adjustment, Canadian patients reported better well being than their counterparts. Despite considerable differences in the mechanisms of health care funding and service mixture, overall resource utilization did not vary significantly between the countries, although there was a trend towards more intense use of inpatient services in Canada and outpatient services in the United States.

Adult↗
PubMed1998

Predictors of delay in starting radiation treatment for patients with early stage breast cancer.

PURPOSE: To describe the factors predicting waiting time for radiation treatment in early breast cancer. MATERIALS AND METHODS: Between January 1992 and December 1993, 739 patients with Stage I and II breast cancer were treated with conservative treatment at three McGill University Hospitals. Waiting time was defined as the interval between the date of surgery and the date of the first radiation treatment. Delay was defined as a waiting time of more than 7 weeks for women who did not receive chemotherapy (Group NC, n = 478), and as a waiting time of more than 24 weeks for those who received chemotherapy (Group C, n = 261). We analyzed predictive factors related to the patient (age, stage, treatment on protocol, income by postal code) and to the referring hospital (university or community hospital). RESULTS: For the entire population, 54% of patients were delayed, 72% in Group NC and 21.4% in Group C. Univariate analysis showed an impact of referring hospital in both groups, and of stage and treatment on protocol in Group C (all p = 0.001). Multivariate analysis showed that delays were significantly less in Group NC for women referred from a community hospital (p = 0.001) and in Group C for women with Stage I disease (p = 0.06), those treated on protocol, and those referred from a university hospital (p = 0.001). CONCLUSION: More than half of patients with early breast cancer waited more than the recommended intervals for radiation therapy. However, lower income breast cancer patients did not wait longer for treatment than higher income patients, possibly a result of the Canadian Medicare system which provides universal access to health care.

Analysis of Variance↗
PubMed1998

The cloning, expression and characterization of a cellobiase gene encoding a secretory enzyme from Cellulomonas biazotea.

A 4.7-kb DNA insert encoding a secretory cellobiase (Cba) was cloned from Cellulomonas biazotea in Escherichia coli using an excretion vector, pM. Host cells transformed with the recombinant construct, designated pBZ4.7, were able to utilize cellobiose as the sole carbon source. Part of the Cba activity encoded by pBZ4.7 could be detected in the periplasm and even in the culture supernatant. The Cba protein was purified from the culture supernatant and analyzed by SDS-PAGE to have an apparent M(r) of 86,000. The insert consisted of two PstI fragments with lengths of 0.75 and 3.95 kb, both of which were found to be crucial for expressing the Cba activity. Sequencing of the first 3.95 kb of the insert revealed that the coding sequence for Cba, designated the cba gene, was 2484 bp long. Comparison of the deduced Cba sequence with those of published beta-glucosidases revealed a potential active site located at the N-terminal portion of the former. The cba gene has a high G + C content of 76.4% and is flanked by a putative ribosome-binding site and potential transcriptional termination signals upstream and downstream from its coding sequence, respectively.

Amino Acid Sequence↗
PubMed1998

Induction of squamous cell carcinoma in p53-deficient mice after ultraviolet irradiation.

Mutations of the p53 gene have been implicated as an important factor in the pathogenesis of ultraviolet light induced skin cancers. To examine the role of p53 in skin carcinogenesis, we observed the development of skin cancers in homozygous p53-deficient (-/-) mice and wild-type p53 (+/+) mice, after chronic ultraviolet B (290-320 nm) exposure. At a dose of 2 J per m2 per s of ultraviolet B for 30 min three times per week, all p53-/- mice developed skin tumors by week 12. All the p53-/- mice developed multiple tumors by week 16. The majority of the tumors occurred on the ears. None of the p53+/+ mice developed skin tumors after 17 wk of UV exposure. Ten p53-/- tumors were examined histologically: five invasive squamous cell carcinomas, four squamous cell carcinomas in situ, and one actinic keratosis. p53-/- mice have a short life-span due to internal tumors or a deficiency in the immune system; however, ultraviolet B exposure did not significantly reduce the life-span of p53-/- mice. These results demonstrate that loss of wild-type p53 function shortens the latent period and predisposes the animals to the development of squamous cell carcinomas after ultraviolet irradiation.

Alleles↗
PubMed1998

Does practice make perfect? Examining the relationship between hospital surgical volume and outcomes for hip fracture patients in Quebec.

OBJECTIVES: Most tests of the practice-makes-perfect hypothesis have used cross-sectional data, which reveal that patients receiving surgery in high-volume hospitals tend to experience better postsurgery outcomes. This study uses longitudinal data to explicitly examine whether any given hospital's patient outcomes change as its surgery volume varies with time. METHODS: Longitudinal data from all hospitals conducting hip fracture surgery in Quebec between 1990 and 1993 were used to examine the relationship between surgery volume and outcomes. The longitudinal data allowed volume to be measured using the actual number of surgeries performed by the admitting hospital in the 12 months before a patient's surgery. Determinants of postsurgery length of stay were assessed using ordinary least squares regression, and the explanators of inpatient mortality were identified using logistic regression. The regressions included fixed effects (hospital-specific dummy variables) to control for systematic differences in outcomes across hospitals that persist with time. Therefore, the coefficient on hip fracture surgery volume in the regression models captured differences in outcomes that were attributable to changes in surgery volume within hospitals with time. RESULTS: The fixed effects were significant explanators of both postsurgery length of stay and inpatient mortality, indicating that there were significant differences in outcomes across hospitals that persisted with time. In regressions that excluded the fixed effects, the coefficient on surgery volume was significant. In contrast, the coefficient on surgery volume was insignificant when the fixed effects were included. CONCLUSIONS: Longitudinal data revealed that after controlling for differences in hospital outcomes that were fixed with time, hospitals performing more surgeries in one period than in another experienced no significant improvement in outcomes. These results do not support the "practice makes perfect" hypothesis. The volume-outcome relationship for hip fracture patients thus appears to reflect fixed differences in quality between high-volume and low-volume hospitals.

Comorbidity↗
PubMed1998

Chemotherapy-induced apoptosis in melanoma cells is p53 dependent.

Metastatic melanomas are often resistant to chemotherapy. To study whether the p53 mutational status affects chemosensitivity, we compared the responses to chemotherapy of four melanoma cell lines containing the wild-type p53 and four cell lines carrying the mutant p53. Cisplatin, at 10 microM, virtually killed all the cells in the wild-type p53 cell lines, while 57-95% of the cells in the mutant p53 cell lines survived (P = 0.005). After treatment with 100 nM of vincristine, on average 18% of the wild-type p53 melanoma cells survived compared with 55% of the mutant p53 cells (P = 0.04). After treatment with 40 nM, 200 nM or 1 microM of camptothecin the survival rates were, on average, 16%, 8% and 4% for the wild-type p53 melanoma cells, compared with 89%, 67% and 38% for the mutant p53 cells, respectively (P = 0.00004, P = 0.003 and P = 0.04, respectively). The anticancer agents were not toxic to normal melanocytes at doses inducing cytotoxicity in wild-type p53 melanoma cells. The main mechanism of cytotoxicity appears to be drug-induced apoptosis. Cisplatin, camptothecin and vincristine all induced apoptosis in wild-type p53 melanoma cells, but not in mutant p53 cells. Our results suggest that chemotherapy-induced apoptosis in melanoma cells is p53 dependent, and mutation of the p53 gene is an indicator of drug resistance in melanoma.

Antineoplastic Agents↗
PubMed1997

Erythropoietin gene regulation depends on heme-dependent oxygen sensing and assembly of interacting transcription factors.

Studies on erythropoietin (Epo) gene expression have been useful in investigating the mechanism by which cells and tissues sense hypoxia. Both in vivo and in Hep3B cells. Epo production is induced not only by hypoxia but also by certain transition metal (cobalt and nickel) and by iron chelation. When Hep3B cells were incubated in an iron deficient medium, Epo mRNA expression was enhanced fourfold compared to Hep3B cells in iron enriched medium. Epo induction by cobalt was inversely related to iron concentration in the medium, indicating competition between the two metals. Under hyperbaric oxygen, cobalt induction of erythropoietin mRNA was modestly suppressed while nickel induction was markedly enhanced. These recent observations support the proposal that the oxygen sensor is a heme protein in which cobalt and nickel can substitute for iron in the porphyrin ring. The up-regulation of Epo gene transcription by hypoxia depends on at least two known DNA binding transcription factors, HIF-1 and HNF-4, which bind to cognate response elements in a critical approximately 50 bp 3' enhancer. Hypoxia induces HIF-1 binding. HNF-4, an orphan nuclear receptor constitutively expressed in kidney and liver, binds downstream of HIF-1 and cooperates with HIF-1, contributing importantly to high level and perhaps tissue specific expression. The C-terminal activation domain of HNF-4 binds to the beta subunit of HIF-1. The C-terminal portion of the alpha subunit of HIF-1 binds specifically to p300, a general transcriptional activator. Hypoxic induction of the endogenous Epo gene in Hep3B cells as well as an Epo-reporter gene was fully inhibited by E1A, an adenovirus protein that binds to and inactivates p300, but only slightly by a mutant E1A that fails to bind to p300. Moreover, overexpression of p300 enhanced hypoxic induction. Thus, it is likely that in hypoxic cells, p300 or a related family member plays a critical role in forming a macromolecular assembly with HIF-1 and HNF-4, enabling transduction from the Epo 3' enhancer to the apparatus on the promoter responsible for the initiation of transcription.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1996

Sweet's syndrome in a patient with oral cancer associated with radiotherapy.

Approximately 10-20% of the reported patients with acute febrile neutrophilic dermatosis (Sweet's syndrome) have an associated neoplasm. Oral findings of Sweet's syndrome are rarely reported, and no cases in patients with oral cancer have been reported to date. This report describes the clinico- and histopathological findings of Sweet's syndrome in a patient with oral cancer, treated with radiotherapy. After 10 fractions of external beam radiotherapy, treatment was interrupted because of severe oral mucositis which extended beyond the radiation fields. Two days later the patient developed multiple tender skin lesions and the diagnosis Sweet's syndrome was made. Skin and oral lesions resolved without additional treatment and did not recur upon resuming radiotherapy. As suggested in previous case reports, tumour antigens might play a role in the development of Sweet's syndrome. In this case, irradiation therapy may also have been a trigger for this syndrome.

Carcinoma, Squamous Cell↗
PubMed1995

Use of a marked erythropoietin gene for investigation of its cis-acting elements.

To examine the function of conserved noncoding regions in the erythropoietin (Epo) gene, we have prepared clones and pools of Hep3B cells stably transfected with a marked 4.1-kilobase Epo gene and deletions thereof. The marked transcripts had single base substitutions at three sites in the coding portion of Exon 5, enabling them to be distinguished from endogenous Epo mRNA by ribonuclease protection and competitive polymerase chain reaction. The basal expression and hypoxic induction of the marked Epo gene that had no deletions were indistinguishable from that of the endogenous Epo gene. Likewise, deletion of conserved intervening sequence 1 had minimal effect on hypoxic induction. In contrast, a 3'-deletion that included the conserved 3'-enhancer element resulted in a substantial, but not complete, suppression of hypoxic induction while a 3'-deletion downstream of the enhancer resulted in enhancement. A 188-base pair deletion of a conserved 3'-untranslated region in Exon 5 had minimal effect on hypoxic induction. However, the truncated Epo mRNA had a markedly prolonged half-life (15 h) in comparison to the endogenous Epo mRNA (2.0 h) or the marked full-length Epo mRNA (2.1 h). Further deletions in the 3'-UTR showed that a relatively small region of approximately 50 bases is responsible for the relatively rapid turnover of Epo mRNA. These experiments provide information on cis-acting elements of the Epo gene that cannot be obtained from conventional reporter gene transfection experiments.

Base Sequence↗
PubMed1995

Marginal capacity: the dilemmas faced in assessment and declaration.

Ontario is adopting informed-consent legislation that reflects increasing emphasis on patient autonomy and self-determination. Capacity assessment and declaration by physicians and other health care professionals are pivotal under the new legislation. While grossly capable or incapable patients provide few management difficulties, marginally capable patients provide a challenge for physicians who must assess capacity, and decisions concerning them emphasize the ethical dilemma involved in any declaration of incapacity. Our 1994 Logie Medical Ethics Essay first-prize winner, Vincent Ho, examines the issues that clinicians must consider when assessing marginally capable patients.

Humans↗
PubMed1995

Illness characteristics and psychosocial and demographic correlates of illness severity at onset of insulin-dependent diabetes mellitus among school-age children.

To verify empirically the most prevalent physical signs and symptoms of diabetes at onset among school-age children, document the distribution of illness-severity, and examine psychosocial and demographic correlates of initial illness severity, the authors analyzed data on 95 school-age children whose diabetes had been newly diagnosed. The most common presenting symptoms were generally consistent with descriptions in the clinical literature. Only 22% of the children presented with severe illness on admission. Children who lived in single-parent households tended to be more ill on admission than children who lived in two-parent households.

Adolescent↗
PubMed1995

Criterion and predictive validity of the diagnosis of adjustment disorder: a prospective study of youths with new-onset insulin-dependent diabetes mellitus.

OBJECTIVE: The authors examined the criterion and predictive validity of the diagnosis of adjustment disorder in a pediatric study group. METHOD: Ninety-two school-age children with new-onset insulin-dependent diabetes mellitus were evaluated repeatedly and were diagnosed by using DSM-III. The criteria for adjustment disorder were further operationalized by requiring four clinically significant symptoms or signs; the time frame for its onset was extended to 6 months after the diagnosis of insulin-dependent diabetes. Predictive validity was assessed in terms of new psychiatric disorders other than adjustment disorder during the next 5 years. RESULTS: Of the 92 children, 33 developed adjustment disorder and five developed other psychiatric disorders in response to the diagnosis of insulin-dependent diabetes mellitus. Mean time from diabetes diagnosis to onset of adjustment disorder was 29 days, the average episode length was 3 months, and the recovery rate was 100%. Among youths with adjustment disorder in response to the medical diagnosis, the 5-year cumulative probability of a new psychiatric disorder was 0.48, compared to 0.16 among the other youths. CONCLUSIONS: The findings generally support the criterion validity of the diagnosis of adjustment disorder. However, episode duration and the predictive validity of the diagnosis appear to be functions of the study group being examined. In nonpsychiatrically referred pediatric patients, early problems in adaptation to the stress of changed health status, as evidenced by adjustment disorder, appear to signal vulnerability to later psychopathology.

Adaptation, Psychological↗