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Biomedical subjects

C Chan

Publications and source records attributed to C Chan.

At least 55 records · Page 3Linked to original sources
PubMed2001

Cooperative enhancement of specificity in a lattice of T cell receptors.

Two of the most important models to account for the specificity and sensitivity of the T cell receptor (TCR) are the kinetic proofreading and serial ligation models. However, although kinetic proofreading provides a means for individual TCRs to measure accurately the length of time they are engaged and signal appropriately, the stochastic nature of ligand dissociation means the kinetic proofreading model implies that at high concentrations the response of the cell will be relatively nonspecific. Recent ligand experiments have revealed the phenomenon of both negative and positive crosstalk among neighboring TCRs. By using a Monte Carlo simulation of a lattice of TCRs, we integrate receptor crosstalk with the kinetic proofreading and serial ligation models and discover that receptor cooperativity can enhance T cell specificity significantly at a very modest cost to the sensitivity of the response.

Cell Line↗
PubMed2001

Giant coronary aneurysms with multiple vascular aneurysms: a rare manifestation of hyperhomocysteinemia.

Hyperhomocysteinemia is associated with accelerated atherosclerosis, which leads to an increased incidence of premature vascular disease. Although multiple vascular aneurysms have been linked to hyperhomocysteinemia, coronary artery aneurysms have not. We report a case of giant coronary artery aneurysm associated with multiple peripheral vascular aneurysms in a patient with hyperhomocysteinemia.

Aged↗
PubMed2001

Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate: potential rational drug design lead frameworks.

By introducing cationic charge sites novel peptide lead inhibitor structures for trypanothione reductase have been designed using molecular modelling methods. The inhibitors showed reversible, linear competitive inhibition and the strongest peptide inhibitor to date was found to be N-benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-beta-naphthylamide with a Ki value of 2.4 microM and a selectivity for parasitic enzyme (trypanothione reductase) over the host enzyme (human glutathione reductase) of over 3 orders of magnitude.

Drug Design↗
PubMed2001

Improved reduction in pain in chronic pancreatitis with combined intraoperative celiac axis plexus block and lateral pancreaticojejunostomy.

PURPOSE:Severe abdominal pain secondary to chronic pancreatitis is often multifactorial in origin. Lateral pancreaticojejunostomy (LPJ) is currently the accepted surgical treatment of choice when the main pancreatic duct is dilated. Chemical ablation of the celiac plexus for the treatment of intractable pain in chronic pancreatitis has been used without clear benefit. The aim of this study is to compare treatment outcomes of 2 groups of patients with the diagnosis of chronic pancreatitis and intractable abdominal pain (LPJ alone versus LPJ with intraoperative alcohol celiac ablation).Between 1994 and 1997, 34 patients underwent LPJ to control intractable pain secondary to chronic pancreatitis. These patients were divided into 2 groups, group 1 was LPJ only (16 patients) and group 2 was LPJ and intraoperative celiac ablation with 50% absolute alcohol (18 patients). Preoperative diagnosis and treatment criteria were similar for both groups. The clinical characteristics and outcome of both groups were retrospectively analyzed. Fisher exact test was used for statistical analysis.Demographic characteristics were similar in both groups. Pain control at short- and long-term follow-up was significantly improved in group 2 compared with group 1 (p < 0.035).Intraoperative celiac ablation in addition to LPJ appears to have a better response than does LPJ alone. Even though the number of patients is small, these results provide a basis for pursuing a prospective, randomized study to definitively answer this question.

Journal Article↗
PubMed2001

Microsporidial keratoconjunctivitis in a healthy contact lens wearer without human immunodeficiency virus infection.

PURPOSE: To present a rare case of microsporidial keratoconjunctivitis in an otherwise healthy contact lens wearer without human immunodeficiency virus infection who responded to treatment with systemic albendazole and topical fumagillin. DESIGN: Interventional case report. METHOD: A cornea epithelial scraping from a man with unilateral keratoconjunctivitis previously treated with topical steroids was evaluated by modified trichome staining. MAIN OUTCOME MEASURES: The patient was evaluated for his symptoms, visual acuity, clinical observations, and pathologic examination of corneal scrapes. RESULTS: Modified trichome staining of an epithelial corneal scraping revealed pinkish to red organisms characteristic of microsporidia. Results of a human immunodeficiency virus (HIV) enzyme-linked immunosorbent assay test were negative. The symptoms of ocular discomfort and clinical signs of keratoconjunctivitis resolved after 2 months of treatment with albendazole and topical fumagillin. CONCLUSIONS: Ocular infection with microsporidia, although classically occurring in patients with HIV infection, may occur rarely in healthy individuals, especially if previously treated with systemic immune suppression or topical steroids. Microsporidial keratoconjunctivitis should be considered in the differential diagnosis of a contact lens wearer with atypical multifocal diffuse epithelial keratitis.

Adult↗
PubMed2001

Nutritional assessment of the lung transplant patient: body mass index as a predictor of 90-day mortality following transplantation.

BACKGROUND: It is well documented that malnourished and/or obese surgical patients have increased morbidity and mortality post-operatively. Only a few studies investigating the effect of nutritional status on mortality are available pertaining to the transplant population. Since limited data are available on the nutritional status and its effects on mortality in the lung transplant population, we sought to ascertain whether there is an association between mortality and preoperative nutritional status. METHODS: We examined mortality during the first 3 months after transplantation. Patients were grouped by body mass index (BMI) categories as < 17 kg/m(2), 17 to < 20 kg/m(2), 20 to 25 kg/m(2) (reference group), > 25 to 27 kg/m(2), and > 27 kg/m(2). Additional risk factors retrieved from the pre-transplant records included age, gender, diagnosis, energy requirements, protein requirements, protein and caloric intake, and weight history. Logistic regression for univariate and multivariate analysis for mortality used recipient age, gender, disease category, pre-transplant cytomegalovirus (CMV) serology, transplant type (single or bilateral), and donor age, gender, and CMV serology. RESULTS: The likelihood estimates or odds ratios (ORs) of the risk of death within 90 days of lung transplantation for the BMI categories compared to the reference group were 3.7 for BMI < 17 kg/m(2) (p = 0.085), 1.6 for BMI < 17 to 20 kg/m(2) (p = 0.455), 3.5 for BMI > 25 to 27 kg/m(2) (p = 0.069), and 5.0 for BMI > 27 kg/m(2) (p = 0.003). CONCLUSIONS: In patients with a pre-transplant BMI < 17 kg/m(2) or > 25 kg/m(2) the risk of dying within 90 days post-transplant was increased. In patients with a pre-transplant BMI of > 27 kg/m(2) the risk was significantly higher in than the reference group.

Adult↗
PubMed2001

Immunocytochemical localization of apolipoprotein D in oligodendrocyte precursor-like cells, perivascular cells, and pericytes in the human cerebral cortex.

Apolipoprotein D, a lipocalin transporter of small hydrophobic molecules including sterols, steroid hormones and arachidonic acid, is a widely expressed protein in peripheral and neural tissues. It has been shown to be upregulated in the context of neural injury, and with neuronal degeneration and regeneration. Here we have used light and electron microscopic immunocytochemistry with immunogold labeling to delineate the pattern of expression of apoD in the human brain. Our results confirm previous observations that apoD is a predominantly glial protein in the nervous system. In addition we have found that apoD is present in the cytosol and outer membrane of the nuclear envelope of glial cells in the neuropil. The labeled glial cells were putatively identified as a population of oligodendrocyte precursor cells. Immunoreactivity was also associated with the cytosol of perivascular cells, and lysosomes of pericytes, in the walls of blood vessels. These observations suggest a potential role for glial cells and apoD, in the transport of sterols and small hydrophobic molecules to, or from, blood vessels in the cortex.

Adult↗
PubMed2001

Melanoma-associated retinopathy: does autoimmunity prolong survival?

PURPOSE: To discuss the autoimmune basis of melanoma-associated retinopathy (MAR) and its implications for management and prognosis. METHODS: An unusual history of a woman with melanoma-associated retinopathy is presented in detail. A review of published reports and a summary of 19 reported cases of MAR provide a basis for discussion. RESULTS: This case report and other published reports highlight a number of points regarding MAR including the male predominance, prolonged survival in several patients and lack of response to immunosuppression. CONCLUSIONS: Melanoma-associated retinopathy may prolong the survival of patients with metastatic melanoma through the autoimmune response. Therefore, treatment of visual symptoms with immunosuppression needs to be considered carefully.

Adult↗
PubMed2001

Cervical assessment at the routine 23-week scan: standardizing techniques.

OBJECTIVE: To examine the frequency of curvature of the cervix and to establish the degree of curvature with increasing cervical length. To assess the significance of this phenomenon in terms of the classification of patients as high risk for pre-term delivery. METHOD: Cervical length was measured prospectively by transvaginal sonography in 301 women at 23 weeks of gestation. The distance between the internal and external os was measured both as a straight line and also as a curved line along the endocervical canal. In addition, a search of our database was made to identify all women who had undergone cervical assessment as part of a policy of routine screening. In those with cervical length of less than 26 mm the thermal images of the cervix were used to obtain straight and curved measurements. The frequency of curved cervix was calculated and the relationship between the ratio of straight to curved measurement to the curved one was determined. RESULTS: In the prospective study curvature of the cervix was observed in 143 (48%) of the 301 women. Curvature was observed in 51% (135 of 267) with cervical length of 26-55 mm, 25% (8 of 32) with length of 16-25 mm, and none of the two with length of 1-15 mm. The ratio of the straight to the curved measurement decreased with increasing cervical length (r = -0.27, P = 0.001). In the retrospective study curvature of the cervix was found in 72 (15%) of 471 with length of 16-25 mm and in none of the 76 with length of 1-15 mm. CONCLUSION: Cervical length is influenced by the degree of cervical curvature. The disparity of measurements between the internal and external os taken as a straight line or along the cervical canal increases with cervical length. However, this disparity may not have any clinical implications because at short cervical length (less than 16 mm) the cervix appears to be always straight.

Cervix Uteri↗
PubMed2001

Macrolide resistance in Streptococcus pneumoniae in Hong Kong.

Erythromycin resistance rates among penicillin-susceptible Streptococcus pneumoniae were 38 and 92% among penicillin-intermediate and -resistant S. pneumoniae isolates from Hong Kong, respectively, and 27% (43 of 158) of the isolates showed the MLS(B) phenotype, and the majority carried the ermB gene; 73% (115 of 158) displayed the M phenotype, and all possessed the mef gene. The MLS(B) phenotype was predominant in penicillin-susceptible, macrolide-resistant isolates and in penicillin-nonsusceptible isolates of serotype 6B, whilst the M phenotype was predominant in penicillin-intermediate or -resistant isolates belonging to serotype 23F or 19F. Extensive spread of clones of drug-resistant pneumococci has led to the widespread presence of macrolide resistance in S. pneumoniae in Hong Kong.

Anti-Bacterial Agents↗
PubMed2001

Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation.

As a result of concern over excessive mortality after lung transplantation, many transplant programs refuse to accept cystic fibrosis (CF) patients infected with Burkholderia cepacia. As a significant proportion of patients with CF in our community are infected with this organism, we have continued to provide lung transplantation as an option. A retrospective review was conducted of medical records of all patients with CF transplanted between March 1988 and September 1996. Fifty-six transplant procedures were performed in 53 recipients with CF between March 1988 and September 1996. Twenty-eight had B. cepacia isolated pretransplant and 25 remaining positive post-transplant. Of the 53 recipients, 19 have died (15 of 28 [54%] B. cepacia positive and 4 of 25 [16%] B. cepacia negative). B. cepacia was responsible for or involved in 14 deaths. Nine of the deaths occurred in the first 3 mo post-transplantation. One-year survival was 67% for B. cepacia positive patients and 92% for B. cepacia negative patients. Recent modifications in antimicrobial and immunosuppressive therapy since 1995 have resulted in no deaths early post-transplant in the last five patients transplanted. We conclude that early mortality in patients with CF infected with B. cepacia is significantly higher than in those not infected with B. cepacia. Modifications in post-transplant medical therapy may improve outcome.

Adult↗
PubMed2001

Ceramide-mediated apoptosis in lung epithelial cells is regulated by glutathione.

Reactive oxygen species (ROS) are mediators of lung injury, and glutathione (GSH) is the major nonprotein antioxidant that protects the cell from oxidative stress. We have recently shown that H(2)O(2) induces ceramide-mediated apoptosis in human lung epithelial cells. We hypothesized that ROS-mediated depletion of GSH plays a regulatory role in ceramide generation, and thus in the induction of apoptosis. Our present studies demonstrate that GSH at physiologic concentrations (1 to 10 mM) inhibits ceramide production in a time- and dose-dependent manner in A549 human alveolar epithelial cells. On the other hand, buthionine-sulfoximine-mediated depletion of intracellular GSH induces elevation of ceramide levels and apoptosis. In addition, GSH blocks H(2)O(2)-mediated induction of intracellular ceramide generation and apoptosis. These effects were not mimicked by oxidized GSH (GSSG) or other thiol antioxidants, such as dithiothreitol and 2-mercaptoethanol. Moreover, increase of intracellular H(2)O(2), mediated by inhibition of catalase by aminotriazole, also induces ceramide generation and apoptosis. These effects were blocked by N-acetylcysteine. Our results suggest that GSH depletion may be the link between oxidative stress and ceramide-mediated apoptosis in the lung.

Acetylcysteine↗
PubMed2001

A body-mind-spirit model in health: an Eastern approach.

Under the division of labor of Western medicine, the medical physician treats the body of patients, the social worker attends to their emotions and social relations, while the pastoral counselor provides spiritual guidance. Body, mind, cognition, emotion and spirituality are seen as discrete entities. In striking contrast, Eastern philosophies of Buddhism, Taoism and traditional Chinese medicine adopt a holistic conceptualization of an individual and his or her environment. In this view, health is perceived as a harmonious equilibrium that exists between the interplay of 'yin' and 'yang': the five internal elements (metal, wood, water, fire and earth), the six environmental conditions (dry, wet, hot, cold, wind and flame), other external sources of harm (physical injury, insect bites, poison, overeat and overwork), and the seven emotions (joy, sorrow, anger, worry, panic, anxiety and fear). The authors have adopted a body-mind-spirit integrated model of intervention to promote the health of their Chinese clients. Indeed, research results on these body-mind-spirit groups for cancer patients, bereaved wives and divorced women have shown very positive intervention outcomes. There are significant improvements in their physical health, mental health, sense of control and social support.

Adult↗
PubMed2001

The role of early tracheostomy in critically ill neurosurgical patients.

OBJECTIVE: To determine the value of early tracheostomy (within 7 days) in ventilated neurosurgical patients. METHODS: Retrospective review of intubated patients in the neurosurgical intensive care unit (NICU) who underwent elective open tracheostomies for prolonged ventilation. RESULTS: Thirty patients over a 2-year period were analysed. There were 19 males and 11 females, mean age 53.9 +/- 18.1 years (range 14 to 89), and mean Glasgow Coma Scale (GCS) score on admission 7.1 +/- 3.8 (range 3 to 15). The underlying disease aetiology was cerebrovascular disease in 53% of patients, head trauma in 33% and tumour or infection in 13%. Tracheostomy was performed after a mean period of 8.5 +/- 3.5 days (range 2 to 18), with patients requiring ventilation for a mean duration of 13.5 +/- 6.3 days (range 3 to 31). Complications were minimal; 1 wound infection (3.3%) and 4 tube obstructions (13.3%). Patients who underwent elective early tracheostomy (Group 1 = within 7 days) had poorer GCS on admission (6.3 +/- 2.9 versus 7.7 +/- 4.3 in Group 2, P = 0.271). Tracheostomy was performed after a mean of 5.3 +/- 1.7 days in Group I vs. 10.6 +/- 2.7 days in Group 2. Group 1 patients had faster recovery from nosocomial pneumonia (12.3 +/- 6.2 versus 17.9 +/- 12.5 days, P = 0.168), shorter duration of ventilation (9.8 +/- 5.9 versus 16.0 +/- 5.4 days, P = 0.007), and reduced incidence of multibacterial tracheobronchial colonisation (42% versus 72%, P = 0.098). The most prevalent organisms were Acinetobacter baumanii (43.3%), Pseudomonas (40%), methicillin-resistant Staphylococcus aureus (MRSA) (33%), Klebsiella (30%) and Staphylococcus aureus (26.7%). CONCLUSION: Early tracheostomy in selected neurosurgical patients with poor GCS scores was associated with reduced incidence of tracheobronchial colonisation by multiple pathogens, improvement in chest infections, and rapid weaning from ventilatory support.

Adolescent↗
PubMed2000

DsbD-catalyzed transport of electrons across the membrane of Escherichia coli.

Dsb proteins catalyze folding and oxidation of polypeptides in the periplasm of Escherichia coli. DsbC reduces wrongly paired disulfides by transferring electrons from its catalytic dithiol motif (98)CGYC. Genetic evidence suggests that recycling of this motif requires at least three proteins, the cytoplasmic thioredoxin reductase (TrxB) and thioredoxin (TrxA) as well as the DsbD membrane protein. We demonstrate here that electrons are transferred directly from thioredoxin to DsbD and from DsbD to DsbC. Three cysteine pairs within DsbD undergo reversible disulfide rearrangements. Our results suggest a novel mechanism for electron transport across membranes whereby electrons are transferred sequentially from cysteine pairs arranged in a thioredoxin-like motif (CXXC) to a cognate reactive disulfide.

Cell Membrane↗
PubMed2000

Use of an additional hydrophobic binding site, the Z site, in the rational drug design of a new class of stronger trypanothione reductase inhibitor, quaternary alkylammonium phenothiazines.

Improved rationally designed lead drug structures against African trypanosomiasis, Chagas disease, and leishmaniasis were obtained against trypanothione reductase from Trypanosoma cruzi. Substituted-benzyl [3-(2-chloro-4a, 10a-dihydrophenothiazin-10-yl)propyl]dimethylammonium salts, synthesized by Menschutkin quaternization of the tertiary alkylamine omega-nitrogen atom of chlorpromazine, were linear, competitive inhibitors of recombinant trypanothione reductase from T. cruzi, with either trypanothione disulfide or N-benzyloxycarbonyl-L-cysteinylglycyl 3-dimethylaminopropylamide disulfide as substrate. The permanent positive charge on the distal nitrogen atom of the tricyclic side chain contribution to binding was estimated as >/=5.6 kcal.mol(-1) by comparison with the analogue with the cationic nitrogen atom of the quaternary replaced by an ether oxygen atom. A further major contribution to improving K(i) values and inhibition strength was the hydrophobic natures and structures of the N-benzyl substituents. The strongest inhibitor, the [3-(2-chloro-4a,10a-dihydrophenothiazin-10-yl)propyl](3, 4-dichlorobenzyl)dimethylammonium derivative (K(i) 0.12 microM), was approximately 2 orders of magnitude more inhibitory than the parent chlorpromazine. Several of these quaternary phenothiazines completely inhibited T. brucei parasite growth in vitro at <1 microM. Antiparasite activity was not solely determined by inhibition strength against trypanothione reductase, there being a strong contribution from hydrophobicity (for example, benzhydryl-quaternized chlorpromazime had ED(50) < 1 microM). Although active against Leishmania donovani, none of the analogues showed major improvement in this activity relative to chlorpromazine or other nonquaternized phenothiazines. The p-tert-butylbenzyl-quaternized analogue very strongly inhibited (ED(50) < 1 microM) growth of the amastigote stage of T. cruzi.

Animals↗
PubMed2000

The activation state of alphavbeta 3 regulates platelet and lymphocyte adhesion to intact and thrombin-cleaved osteopontin.

Cleavage of osteopontin by thrombin has been reported to enhance cell adhesion. We asked whether thrombin could regulate the alpha(v)beta(3)-mediated adhesion of platelets and B lymphocytes to this substrate. Although there was no difference in the extent or the avidity of thrombin- and ADP-stimulated platelet adhesion to intact or thrombin-cleaved human osteopontin, both the extent and avidity of phorbol ester-stimulated B cell adhesion to thrombin-cleaved osteopontin was significantly increased. Thus, these data suggest that the ability of alpha(v)beta(3) to recognize osteopontin can be differentially regulated in a cell-specific manner. To localize the alpha(v)beta(3) binding site on osteopontin, we measured cell adhesion to the two thrombin cleavage products of osteopontin and to a series of nested RGD-containing osteopontin peptides cross-linked to albumin. Whereas ADP-stimulated platelets adhered to the amino-terminal but not the carboxyl-terminal osteopontin fragment and to the osteopontin peptide RGDSVVYGLR, phorbol ester-stimulated B cells did not adhere to this peptide, although they did so in the presence of 1 mm Mn(2+). Thus, our data confirm that thrombin cleavage enhances the accessibility of the binding motif for alpha(v)beta(3) on osteopontin, but this enhancement is also a function of the activation state of alpha(v)beta(3). Moreover, they indicate that the sequence RGDSVVYGLR contains sufficient information to specify activation-dependent alpha(v)beta(3)-mediated platelet and lymphocyte adhesion.

Adenosine Diphosphate↗