Biomedical subjects

K Chan

Publications and source records attributed to K Chan.

At least 73 records · Page 4Linked to original sources

PubMed2000

Synthesis, structure-activity relationships, and pharmacological profile of 9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6, 7,1-hi]indoles: discovery of potent, selective phosphodiesterase type 4 inhibitors.

The synthesis, structure-activity relationships, and biological properties of a novel series of potent and selective phosphodiesterase type 4 (PDE4) inhibitors are described. These new aminodiazepinoindoles displayed in vitro PDE4 activity with submicromolar IC(50) values and PDE4 selectivity vs PDE1, -3, and -5. Specifically, one compound (CI-1044, 10e) provided efficient in vitro inhibition of TNFalpha release from hPBMC and hWB with IC(50) values of 0.34 and 0.84 microM, respectively. This compound was found to exhibit potent in vivo activity in antigen-induced eosinophil recruitment in Brown-Norway rats (ED(50) = 3.2 mg/kg po) and in production of TNFalpha in Wistar rats (ED(50) = 2.8 mg/kg po). No emetic side effects at therapeutic doses were observed in ferrets.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2000

Induction of tolerance to immunogenic tumor antigens associated with lymphomagenesis in HOX11 transgenic mice.

Transgenic mice expressing human HOX11 in B lymphocytes die prematurely from lymphomas that initiate in the spleen and frequently disseminate to distant sites. Preneoplastic hematopoiesis in these mice is unperturbed. We now report that expression of the HOX11 transgene does not affect the ability of dendritic cells (DCs) to process and present foreign peptides and activate antigen-specific T cell responses. We also show that nontransgenic DCs presenting peptides derived from the human HOX11 protein are highly efficient stimulators of autologous T cells, whereas transgenic T cells are nonresponsive to peptides derived from the HOX11 transgene and the murine Meis1 protein. HOX11 transgenic mice thus show normal development of tolerance to immunogenic antigens expressed throughout B cell maturation. DCs pulsed with cell lysates prepared from lymphomas, obtained from HOX11 transgenic mice with terminal lymphoma, activate T cells from nontransgenic and premalignant transgenic mice, whereas T cells isolated from lymphomatous transgenic mice are nonresponsive to autologous tumor cell antigens. These data indicate that HOX11 lymphoma cells express tumor-rejection antigens that are recognized as foreign in healthy transgenic mice and that lymphomagenesis is associated with the induction of anergy to tumor antigen-specific T cells. These findings are highly relevant for the development of immunotherapeutic protocols for the treatment of lymphoma.

Animals↗

PubMed2000

Constitutive expression of erbB2 in epidermis of transgenic mice results in epidermal hyperproliferation and spontaneous skin tumor development.

The erbB family of receptor tyrosine kinases, which consists of the epidermal growth factor receptor (EGFr/erbB1), erbB2 (neu), erbB3 and erbB4, has been shown to be important for both normal development as well as neoplasia. The expression of rat erbB2 was targeted to the basal layer of mouse epidermis with the bovine keratin 5 promoter. Overexpression of wild type rat erbB2 in the basal layer of epidermis led to alopecia, follicular hyperplasia and sebaceous gland enlargement as well as hyperplasia of the interfollicular epidermis. Spontaneous papillomas, some of which converted to squamous cell carcinomas, arose in homozygous erbB2 transgenic mice as early as 6 weeks of age with >90% incidence by 6 months. Analysis of several proliferation/differentiation markers indicated that erbB2 overexpression led to epidermal hyperproliferation and a possible delay in epidermal differentiation. Transgenic mice were also hypersensitive to the proliferative effects of the skin tumor promoter, 12-0-tetradecanoylphorbol-13-acetate (TPA) and were more sensitive to two-stage carcinogenesis. Elevations in EGFr and erbB2 protein as well as erbB2:EGFr and erbB2:erbB3 heterodimers were observed in skin of the erbB2 transgenic mice. Phosphotyrosine levels of the EGFr, erbB2 and erbB3 proteins were also elevated. These results indicate an important role for erbB2 signaling in epidermal growth, development and neoplasia. Oncogene (2000) 19, 4243 - 4254

Animals↗

PubMed2000

Interaction of hCLIM1, an enigma family protein, with alpha-actinin 2.

Enigma proteins are proteins that possess a PDZ domain at the amino terminal and one to three LIM domains at the carboxyl terminal. They are cytoplasmic proteins that are involved with the cytoskeleton and signal transduction pathway. By virtue of the two protein interacting domains, they are capable of protein-protein interactions. Here we report a study on a human Enigma protein hCLIM1, in particular. Our study describes the interaction of the human 36 kDa carboxyl terminal LIM domain protein (hCLIM1), the human homologue of CLP36 in rat, with alpha-actinin 2, the skeletal muscle isoform of alpha-actinin. hCLIM1 protein was shown to interact with alpha-actinin 2 by yeast two-hybrid screening and immunochemical analyses. Yeast two-hybrid analyses also demonstrated that the LIM domain of hCLIM1 binds to the EF-hand region of alpha-actinin 2, defining a new mode of LIM domain interactions. Immunofluorescent study demonstrates that hCLIM1 colocalizes with alpha-actinin at the Z-disks in human myocardium. Taken together, our experimental results suggest that hCLIM1is a novel cytoskeletal protein and may act as an adapter that brings other proteins to the cytoskeleton.

Actinin↗

PubMed2000

Surgical validation and implications for transcatheter closure of quantitative echocardiographic evaluation of atrial septal defect.

Accurate evaluation of secundum atrial septal defect (ASD) is important for the success of transcatheter closure. The purpose of this study was (1) to describe a quantitative evaluation by transthoracic (TTE) and transesophageal (TEE) echocardiography of the various morphologic features of ASD that might be important for patient selection for transcatheter closure, and (2) to assess the reliability of these 2 methods by surgical findings. Preoperative TTE and TEE were used to evaluate the ASD of 27 children undergoing surgical closure. Measurements included the diameters of ASD and the atrial septal lengths in the transverse and longitudinal axis, and the width of the superior, inferior, anteroinferior, and posterior septal margins. The shape and location of the ASD and the adequacy of the septal margins for anchoring occluding devices were determined. Echocardiographic data were compared with corresponding surgical measurements. No significant difference occurred in the means of all the parameters measured with the 3 methods, except for the transverse ASD diameter (p <0.05). Good agreement occurred between TTE and TEE and surgical data, except for the transverse ASD diameter, transverse atrial septal length, and the posterior septal margin on TTE. Intraclass correlations between TTE and TEE and surgical measurements of all parameters were good, except for the transverse ASD diameter. The accuracy in determining shape and location of the ASD by TTE and TEE were 100%, whereas that for determining the adequacy of septal margins was 98% and 97%, respectively. In conclusion, TTE and TEE are reliable methods for quantitative evaluation of ASD.

Cardiac Catheterization↗

PubMed2000

Depressive symptoms decline among persons on HIV protease inhibitors.

OBJECTIVE: To ascertain whether initiation of protease inhibitors was associated with a change in depressive symptoms among persons infected with HIV. METHODS: Study subjects included men and women who were enrolled in the HIV/AIDS Drug Treatment Program and who had completed an annual participant survey before and after initiating triple combination therapy with a protease inhibitor. Depressive symptoms were assessed using the Centre for Epidemiologic Studies-Depression scale (CES-D). Statistical analyses to determine the change in CES-D total and subscale scores before and after protease inhibitor use were conducted using parametric and multivariate methods. RESULTS: Our analysis was restricted to 453 participants. Of these 234 (52%) were depressed at baseline (CES-D score > or = 16). Compared with nondepressed participants, depressed participants were slightly younger (p = .048), less likely to be employed (p < .001) and more likely to have an annual income less than $10,000 per annum (p < .001). After adjusting for CD4 count, employment status, income, age, and CES-D total or subscale score at baseline, we found a significant improvement in total scale score (p = .001) and depressive mood (p = .002), positive affects (p = .005), and somatic symptoms (p = .011) subscale scores at follow-up. There was no significant change in the interpersonal relations score over the study period. CONCLUSION: Our findings indicate that in addition to conferring impressive clinical benefits, protease inhibitor use is associated with a significant improvement in HIV-positive individuals' mental health.

Adult↗

PubMed2000

Two novel myogenic factors identified and isolated by sequential isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

A number of environmental factors were used experimentally to enhance myogenesis during muscle regeneration; however, many hormones and growth factors have been shown to have the ability to increase the rate of satellite cell division, but they only work on satellite cells that are already active in many animal experiments. Recently, the crushed muscle extract (CME) of rats was found to be able to trigger dormant adult rat satellite cells to re-enter the cell mytogenic cycle; however, the identity of the active factors present in rat CME remains unknown. In the present study, the CME was fractionated by the strategy of sequential isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) coupled with functional analysis by myoblast culture. Two satellite cell-specific myogenic factors were identified and purified from CME by this strategy. One of the factors has a molecular mass of around 7 kDa and another about 39 kDa. The factor of 39 kDa could be retained in heparin-Sepharose column and eluted with phosphate-buffered saline (PBS) containing 1 M NaCl, but the 7 kDa factor did not bind to the heparin column. These two purified myogenic factors could synergistically trigger the proliferation and differentiation of dormant satellite cells, whose progenies subsequently fuse in vitro, or fuse to pre-existing partially damaged muscle fibers to form full repair of the damaged muscle fibers or to form new myotubes to replace the completely damaged muscle fibers during the cascade of muscle healing and regeneration in vivo. The identities of these two myogenic factors are under study.

Animals↗

PubMed2000

Age-related changes of aqueous protein profiles in rat fast and slow twitch skeletal muscles.

Two-dimensional electrophoresis was used to generate the aqueous protein expression patterns of rat extensor digitorum longus muscle (EDL, fast twitch muscle) and solues muscle (SOL, slow twitch muscle) of different ages. Two specific protein spots, S1 and S3, were identified from EDL muscles at the ages of 12 and 18 months onward respectively. In the EDL muscles of aged rat (24 months) after intensive exercise training, S3 was still detected while S1 disappeared. In addition, diaphragm muscle (DIA, fast twitch muscle), which retains physically active throughout the life span, was used as nondisuse control. The results showed that the expressions of S1 and S3 in 24-month DIA muscle were identical with the trained aged EDL muscle. It is suggested that exercise might delay the onset of S1 expression. However, the expression of S3 over age seemed to be progressive and exercise independent. Another protein spot, S2 was identified to express only in young EDL and SOL muscles, but its expression decreased over age. Furthermore, exercise has no effect on S2 expression since S2 could not be detected in aged DIA as well as trained aged EDL and SOL muscles. These results indicated that aqueous protein expression patterns of skeletal muscle undergo changes during aging. Some of these changes such as S2 and S3 appear progressively, and some such as S1 could be delayed by exercise. S3 was identified as ubiquitin, which might play an important role in protein degradation during skeletal muscle aging process.

Aging↗

PubMed2000

Impaired estrogen priming of progesterone receptors in uterus of MRL/MP-lpr/lpr mice, a model of systemic lupus erythematosus (SLE).

Estrogens exacerbate the autoimmune disease SLE and progesterone is immunoprotective. Estrogens increase synthesis of progesterone receptors (PR) and it is hypothesized that this physiological balance may be impaired in SLE. To test this, cytosolic PR were measured in hypothalamus, thymus and uterus from 6-week-old female ovariectomized BALB/c and MRL/MP-lpr/lpr mice 48 h after s.c. injection of estradiol benzoate (3.2 microg/0.1 ml; OB) in peanut oil or 0.1 ml peanut oil alone. PR were measured using [(3)H]ORG 2058, which does not bind to corticosteroid-binding globulin (CBG), and bound and free ligand were separated using minicolumns of Sephadex LH20 at 0 degrees C. PR were measured in cytosols from hypothalamus and uterus of oil-treated BALB/c mice, but were undetectable in thymus, whereas receptors were measurable in all three tissues of MRL mice. There was a significantly greater priming effect of OB on PR in uterus of BALB/c mice, but not in hypothalamus, and PR became detectable in thymus cytosols from BALB/c mice. Also, the apparent affinity of the binding reaction between [(3)H]ORG 2058 and PR was significantly higher than those measured in other tissues in hypothalamic cytosols of both strains. These results suggest that there is an impairment of estrogen priming of progesterone receptors in uterus and perhaps thymus of MRL mice.

Animals↗

PubMed2000

The end of the line: has rapid transit contributed to the spatial diffusion of HIV in one of Canada's largest metropolitan areas?

The objective of this study is to describe the relationship between socio-demographic characteristics and the geographic distribution of persons with HIV in the metropolitan area surrounding Vancouver, British Columbia. Specifically, we sought to determine the location of persons with HIV and the population based characteristics related to the rate of anti-HIV medication use. In addition, we investigated the relationship between the distribution of persons on anti-HIV medications and the city's monorail "SkyTrain" route. The residences of persons on anti-HIV therapy were linked to Census Tracts. Data from the most recent census were used to create a socio-demographic profile of each geographic area. The spatial relationship between the distribution of persons on anti-HIV therapy and the path of the monorail was assessed by digitizing the SkyTrain route over a digital Census Tract map. Statistical analyses were used to determine the characteristics of Census Tracts associated with the rate of anti-HIV medication use. The overall rate of anti-HIV medication use in the Census Tracts that are within 1 km of SkyTrain was 66 per 100,000 population, whereas the rate was only 22 in the non-proximal Census Tracts. Multivariate analyses indicated that persons on anti-HIV therapy were significantly less likely to reside where there is a higher proportion of the population female, and were more likely to reside in areas with a higher proportion of the population of First Nations or Aboriginal descent, a higher population density, and in areas within 1 km of the SkyTrain route. Our analyses suggest that neither migration, nor a heightened access to therapy explain these findings. The environment surrounding the SkyTrain may have been conducive to the spatial diffusion of HIV, and could be the focus of targeted public health interventions. The mechanisms responsible for the clustering of persons on anti-HIV medications around the SkyTrain require further investigation.

Adult↗

PubMed2000

The analgesic and anti-inflammatory effects of Portulaca oleracea L. subsp. Sativa (Haw.) Celak.

Many ethnic groups have used different species of Portulaca oleracea L., a member of the Family Portulacaceae, as vegetable and also herbal medicine against several diseases for many centuries. A review of the records in both folkloric and scientific literature indicates that Portulaca has many medicinal uses. After our previous preliminary screening of three species of the family for analgesic and anti-inflammatory properties, Portulaca oleracea L. subsp. sativa (Haw.) Celak. (a cultivar) was chosen for further work due to its abundant availability from reliable sources. The 10% ethanolic extract of the aerial parts (dried leaves and stem) showed significant anti-inflammatory and analgesic after intraperitoneal and topical but not oral administration when compared with the synthetic drug, diclofenac sodium as the active control. Results indicate this cultivar species of Portulaca also possesses some of the claimed traditional uses of the wild species in the relief of pain and inflammation.

Analgesics↗

PubMed2000

Designing an amperometric thick-film microbial BOD sensor.

Thick film oxygen electrodes manufactured by screen print method have been used as a transducer for a biochemical oxygen demand (BOD) sensor. The kinetics of the immobilized yeast, Arxula adeninivorans (Arxula) has been studied. The apparent KM of immobilized Arxula (> 100 microM) is higher than free cells of Arxula (70 microM). The increase in KM caused by the effect of immobilization extends the linear range of the sensor. End-point measurement and quasi-kinetic measurement have been studied comparatively as measurement procedures with a good correlation. The Vmax for end-point measurement is 790.7 microM/s and that for quasi-kinetic measurement is 537.3 microM/s. The limit of detection is calculated 1.24 mg/l BOD. Using the quasi-kinetic measurement, instead of end-point measurements, the measuring time can be reduced from 5-30 min to 100 s. The sensor layer thickness or increase in the layer of covering gel can increase the KM that is accompanied with the extension of the linear range of the sensor. Nevertheless, increase in the layer of covering gel will not increase the saturation signal. Domestic wastewater was checked by the thick film BOD sensor and the results are satisfactory.

Bacteria↗

PubMed2000

Psychometric evaluation of the fatigue severity scale for use in chronic hepatitis C.

Evidence exists demonstrating that infection with hepatitis C virus impairs health-related quality of life, but less is known about the effect of fatigue, a common symptom, on everyday life. The psychometric properties of the fatigue severity scale (FSS) were explored to determine suitability as an outcome measure in clinical trials. The FSS includes nine items developed to measure disabling fatigue and a visual analog scale (VAS) to measure overall fatigue. Using baseline data from three clinical trials (n = 1225) involving chronic hepatitis C patients, scaling and psychometric characteristics of the FSS were assessed. The SF-36 was also used in the trials. Item response theory analysis demonstrated that the FSS items can be placed along a single homogenous domain, fatigue. Internal consistency reliability was 0.94. Test-retest reliability was 0.82 for the total score and 0.80 for the VAS. The total score and the VAS were significantly correlated with the SF-36 vitality subscale (r = -0.76 and r = -0.76 respectively). Correlations with other SF-36 subscales were moderate (r = -0.46 to r = -0.67, all p < 0.0001). In summary, the FSS possesses good psychometric properties.

Adolescent↗

PubMed2000

Health related quality of life among persons with HIV after the use of protease inhibitors.

OBJECTIVE: This study was conducted to determine the effect of the use of HIV protease inhibitors on the quality of life among persons infected with HIV. METHODS: Subjects were participants in the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program who had completed two annual participant surveys, one prior to initiating therapy with a protease inhibitor and one after. Quality of life was measured using the Medical Outcomes Study Short Form Health Survey (MOS-SF). Statistical analyses were conducted using parametric and multivariate methods. RESULTS: Our analysis was based on 179 HIV-positive individuals. Compared to quality of life at baseline, we found no statistically significant changes in the health perception, pain, physical, role and social functioning MOS-SF subscale scores at follow-up. The measure of mental health was the only component to decline significantly over time. Subanalyses found significant increases in the measures of health perception (p = 0.004), physical (p = 0.037), role (p < 0.001) and social functioning (p = 0.053) for individuals with a low baseline quality of life. For those with a higher quality of life before starting a protease inhibitor containing regimen we observed a significant decline in the subscales of mental health (p = 0.001), physical (p = 0.007), role (p = 0.021) and social functioning (p = 0.003) over the study period. CONCLUSIONS: Our findings indicate that despite strict dosage requirements and adverse side effects associated with protease inhibitor use patients are on the whole maintaining their quality of life after starting on a protease inhibitor containing regimen. Continued follow-up of this cohort will be required to determine the long term implications of these observations.

Adult↗

PubMed2000

Enhanced safety and efficacy of live attenuated SIV vaccines by prevaccination with recombinant vaccines.

The only vaccines shown to be protective against intravenous challenge with virulent virus in the simian immunodeficiency virus (SIV)/macaque model are attenuated live SIVs. However, these vaccines have several disadvantages: 1) they persist indefinitely in vaccinated macaques; 2) they are pathogenic to neonatal macaques; and 3) they are lethal in some adult macaques. To enhance the safety and efficacy of these vaccines, we immunized macaques first with recombinant vaccines and then inoculated the animals with SIV(delta(nef)). In the first experiment, preimmunized macaques advanced to disease slower than controls after challenge with virulent SIV; five animals survived for 3 years without disease and only the vaccine virus (SIV(delta(nef)) could be isolated at this time. In the second experiment, preimmunized animals had lower virus loads and no disease compared to controls.

Animals↗

PubMed2000

Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre-and postmenopausal women.

OBJECTIVE: The use of topically applied micronised ('natural') progesterone as a substitute for synthetic oestrogens and progestogen preparations is controversial. The aim of this study was to examine the changes in blood and salivary concentrations of progesterone following a single topical application of a progesterone cream. PATIENTS AND MEASUREMENTS: We investigated six premenopausal women in the luteal phase and six postmenopausal women to determine the short-term changes in serum, urinary and salivary progesterone concentrations following a single 64 mg topical application of micronised progesterone. RESULTS: Serum progesterone concentrations did not increase during the first 3 hours after application of progesterone cream, however, salivary values rose significantly in both premenopausal and postmenopausal women, consistent with the view that progesterone is absorbed and transported through the body. Salivary progesterone concentrations were significantly elevated above basal levels by 30-60 minutes and reached peak levels at 1-4 h, with mean levels approximately fivefold higher in premenopausal, than in menopausal women. CONCLUSIONS: Salivary progesterone measurements confirm that topically applied progesterone is absorbed, despite the lack of change in serum progesterone concentrations. However, at the dose administered, serum progesterone levels do not reach those observed after oral or vaginally delivered progesterone preparations. Higher doses may be required to induce biological responses within the endometrium.

Absorption↗

PubMed2000

Effects of basic fibroblast growth factor (bFGF) on early stages of tendon healing: a rat patellar tendon model.

We studied the effects of basic fibroblast growth factor (bFGF) on cell proliferation, type III collagen expression, ultimate stress and the pyridinoline content in the early stages of healing in rat patellar tendon. 96 male Sprague Dawley rats were injected with increasing doses of basic fibroblast growth factor (bFGF) at 3 days after a "window defect" was induced in the mid-part of the patellar tendon. They were killed at 7 and 14 days after the injury. A dose-dependent increase in the number of proliferating cells and the level of expression of type III collagen was demonstrated at only 7 days post-injury. On the other hand, we found no effects of bFGF on ultimate stress and the pyridinoline content of healing tendons. Only time significantly affected both strength-associated parameters. We showed that in vivo supplementation with bFGF affected the initial events of healing such as cell proliferation and type III collagen expression.

Amino Acids↗

PubMed2000

An international comparison of childhood injuries in Hong Kong.

OBJECTIVES: This study describes 7813 childhood injuries in Shatin, Hong Kong. Supplementary analyses include developmental specificity of external causes and comparison with international childhood injury data. METHODS: Children aged 0-15 attending the accident and emergency (A&E) department of the Prince of Wales Hospital in Hong Kong were recruited for the study. Attendance records of participants from the A&E department were analyzed. Details concerning the injury, including the International Classification of Diseases, ninth revision, external cause of injury (E code), nature of injury (N code), abbreviated injury scale, and injury severity scale constitute core measurements, along with participants' age, gender, and respective A&E procedural data. RESULTS: Males (65.7%) and fall related injuries (44.2%) predominate, while contusion (34.6%) is the prevailing nature of injury. Two age external cause dimensions are derived from a correspondence analysis. Children 0-1 years old are associated with falls, poisoning, scalds, and machinery related injury. Adolescents aged 12-15 are associated with motor related injury, animal related injury, and cuts/piercings. In comparison with international data, unintentional child injuries in Hong Kong comprised more falls but fewer poisonings and burns. CONCLUSION: A large proportion of falls, along with low proportion of poisonings and burns, are characteristics of childhood injury profile in Hong Kong. From the results of age external cause correspondence analysis, prevention strategies for different external cause should be developmentally specific.

Adolescent↗