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Biomedical subjects

S Y Chan

Publications and source records attributed to S Y Chan.

At least 91 records · Page 5Linked to original sources
PubMed1998

An audit of patient acceptance of one-stop diagnosis for symptomatic breast disease.

AIMS: The impetus for optimizing outpatient provision of breast-care services has come both from the patient and management in order to reduce anxiety and make full use of scarce resources. The one-stop diagnostic clinic for the investigation of symptomatic breast lesions is a relatively recent concept with well-known service benefits. However, acceptance to the patient has not been previously investigated. RESULTS: The results of this prospective audit demonstrate a high level of patient satisfaction with the multi-disciplinary, one-stop breast clinic.

Ambulatory Care↗
PubMed1998

Lipid-mediated gene transfer of viral IL-10 prolongs vascularized cardiac allograft survival by inhibiting donor-specific cellular and humoral immune responses.

The gene encoding the immunosuppressive cytokine viral interleukin-10 (vIL-10) was introduced into BALB/c (H-2d) vascularized cardiac allografts by perfusing the graft vasculature with DNA-liposome complexes, utilizing the experimental cationic lipid gamma AP DLRIE/DOPE and a plasmid encoding vIL-10 under the control of the HCMVie promoter. The DNA to lipid ratio and DNA dose were critical factors in obtaining optimal biologic effects. Gene transfer of vIL-10 with a 3:1 DNA to lipid weight ratio using 375 micrograms DNA significantly prolonged allograft survival in MHC-mismatched C57BL/6 (H-2b) recipients (16.00 days) compared with both unmodified allografts (8.14 days) and vIL-10 antisense controls (8.28 days). Enhanced graft survival was specific to vIL-10 expression since treatment with antisense plasmid or anti-vIL-10 monoclonal antibody (mAb) abrogated the effect. Prolonged survival was associated with a novel histology characterized by a moderate mononuclear infiltrate, edema, and diffuse fibrillar/collagen deposition in the interstitium. Despite these morphologic changes, myocytes remained viable and vessels were patent. Limiting dilution analysis revealed transient infiltration of IL-2 secreting, donor-reactive, helper T lymphocytes (HTL) and cytotoxic T lymphocytes (CTL) in vIL-10 expressing grafts on day 7, that decreased significantly by day 14. Similarly, vIL-10 gene transfer inhibited the accumulation of donor-specific HTL and CTL in the spleen, compared with antisense controls. Prolonged survival was also associated with a marked decrease in IgM and IgG alloantibody production, with little to no IgG isotype switching. These results show that viral IL-10 gene transfer inhibits graft rejection in a clinically relevant model by inhibiting donor-specific cellular and humoral immune responses.

Animals↗
PubMed1998

Up-regulation of lysozyme production in colonic adenomas and adenocarcinomas.

AIMS: The presence of lysozyme protein in some gastric adenomas and adenocarcinomas has been well documented. There have been relatively few studies investigating the presence of lysozyme in tumours of the large intestine and they show contrasting results. We aim to investigate the cellular source and expression of lysozyme in colonic adenomas and adenocarcinomas. METHODS AND RESULTS: We randomly selected 29 and 27 colonic adenomas and adenocarcinomas, respectively. Using in-situ hybridization (ISH) and immunohistochemistry (IHC), we found an up-regulation of lysozyme in the dysplastic epithelium of all the adenomas studied, with more than 80% of cases expressing moderate to strong signals. Although the up-regulation of lysozyme was also observed in adenocarcinomas, only 30% of the cases showed moderate to strong signals, mostly with an uneven distribution. Down-regulation of lysozyme in the severely dysplastic and invasive foci were noted in some cases of adenoma with malignant transformation. Normal colonic glands were consistently negative for lysozyme at both the mRNA and the protein level, but inflamed and immature regenerative colonic epithelium at the crypt base showed positive signals in a similar pattern to those observed in the dysplastic epithelium of the adenomas. CONCLUSIONS: Our results confirm that colonic epithelium can produce lysozyme and its expression is up-regulated in the dysplastic epithelium in adenomas and in invasive cancer cells. It is interesting that regenerative colonic epithelium showed a similar pattern of lysozyme expression as in adenomas. The loss of lysozyme secreting phenotype in most of the invasive tumours suggests that lysozyme may not confer an advantage to tumour progression.

Adenocarcinoma↗
PubMed1998

Stability of cefazolin sodium eye drops.

OBJECTIVE: Assessing the stability of cefazolin sodium in preservative-free and preservative-containing eye drops. METHOD: Extemporaneous formulations of eye drops were prepared from a commercially-available parenteral product of cefazolin sodium: eye drops 'A' contained 50mg/ml of cefazolin sodium in 0.45% w/v sodium chloride solution, and eye drops 'B' contained 50 mg/ml, 0.005% w/v thiomersal and 1% w/v glycerol in water-for-injection. Cefazolin sodium concentrations in these eye drops were monitored by a stability-indicating HPLC assay method. Measurements of pH and osmolality, as well as tests for microbial contamination, were conducted. RESULTS: The eye drops stored at 4 degrees C were stable for 42 days with minimal changes in pH and osmolality, but eye drops stored at room temperature were only stable for a few days with greater increments in pH and osmolality. None of the samples cultured had bacterial or fungal growth after 7 days of incubation. CONCLUSION: Extemporaneously prepared formulations of cefazolin are unstable at room temperature and should be stored in a refrigerator.

Bacteriological Techniques↗
PubMed1998

DNA diagnosis of FRAXA and FRAXE in Chinese children with neurodevelopmental disorders and fragile X syndrome.

Fragile X (FraX) syndrome is the most common cause of inherited mental retardation. To see whether FRAXA or FRAXE can account for the etiology of some unexplained neurodevelopmental disorders in children, we screened for trinucleotide repeat expansion in a consecutive cohort of 73 Chinese children and their mothers seen in 1995 (group 1) referred for developmental assessment due to developmental delay, language delay, attention deficit hyperactivity disorder, autistic spectrum disorder, mental retardation and/or learning disability. We also screened DNA samples of all five previously diagnosed cytogenetically-positive FraX boys, their mothers and sisters (group 2). A control group of unrelated teenagers and adults were recruited from the community (group 3). In group 1, 3 families (2 mothers and a mother and her son) were found to carry a small premutation allele at FRAXA (premutation frequency = 2%, 3/153 independent X chromosomes), but none had any expansion at FRAXE. In group 2, all 5 FraX boys had full mutation at FRAXA and normal repeat length at FRAXE. In group 3, 1 male has a premutation allele out of 18 males and 59 females tested (premutation frequency of control = 0.7%, 1 out of 136 X chromosomes). For FRAXE screening in group 3, 2 females were carriers (1.5%, 2 out of 136 X chromosomes). Thus, FRAXA and FRAXE cannot account for the etiology of neurodevelopmental disorders in our cohort of Chinese children, and the prevalence of FRAXE mutation in normal Chinese population appears to be higher than reported in the Caucasians.

Adult↗
PubMed1998

Cholelithoptysis: an unusual complication following laparoscopic cholecystectomy.

A 75-year old lady underwent a routine laparoscopic cholecystectomy during which stones were spilled into the peritoneal cavity. Despite peritoneal lavage the patient developed chronic right upper quadrant discomfort and a pleural effusion over several months. Following the production of a pigmented bilirubin stone in her sputum the patient's symptoms resolved. Cholelithoptysis is a rare complication of laparoscopic cholecystectomy, the diagnosis should be considered in patients with prolonged chest symptoms after surgery.

Aged↗
PubMed1998

Association of systemic lupus erythematosus with promoter polymorphisms of the mannose-binding lectin gene.

OBJECTIVE: To investigate the distribution of promoter variants of the mannose-binding lectin (MBL) gene and correlations between the promoter variants and serum MBL concentrations in Chinese patients with systemic lupus erythematosus (SLE) and in healthy Chinese controls. METHODS: We studied the serum MBL levels and codon 54 mutation in 112 Chinese patients with SLE and 110 healthy controls. Genotyping of promoter variants of the MBL gene were done by polymerase chain reaction and allele-specific oligonucleotide hybridization. RESULTS: We found significant differences in the distribution of the 2 pairs of promoter polymorphisms, H/L and Y/X, between SLE patients and controls (P=0.018 and P=0.019, respectively). Analysis of the correlation between promoter haplotypes and serum MBL levels revealed HY as the highest-producing, LY as the intermediate-producing, and LX as the lowest-producing haplotypes. The LX haplotype was present at a frequency of 0.259 in SLE patients and 0.154 in controls and was significantly associated with SLE (P=0.019, odds ratio 1.79, 95% confidence interval 1.12-2.85). CONCLUSION: The low-producing promoter polymorphism of the MBL gene is associated with SLE, and a low serum MBL level is a risk factor for SLE. Even allowing for promoter polymorphisms and structural mutations of the MBL gene, serum MBL levels in SLE patients are still lower than those in controls, suggesting a trans-factor in regulating serum MBL levels.

Adolescent↗
PubMed1997

Phylogenetic analysis of the human papillomavirus type 2 (HPV-2), HPV-27, and HPV-57 group, which is associated with common warts.

Human papillomavirus types 2 (HPV-2), HPV-27, and HPV-57, are three closely related viruses within the phylogenetic supergroup formed by the remotely related genital papillomaviruses. In contrast to this phylogenetic association, these three viruses are most often found in common warts at nongenital sites, but also occasionally in genital warts and mucosal lesions of the nasopharyngeal cavity. We studied the genomic diversity of HPV sequences in skin warts presumably caused by these viruses. These biopsies were sampled from 75 patients living in Germany, Japan, or Singapore. Among 27 warts with HPV-2, we found seven new genomic variants and among 32 with HPV-57, eight new variants. In both cases, we did not detect the original prototype genomes. In contrast, 13 of 16 warts with HPV-27 contained the prototype genome, and only one new variant was found in three patients. We did not find variants clearly intermediate between any two types, although HPV-2 and HPV-27 are among the most closely related of the extent HPV types. We also did not detect novel HPV types, although the samples were examined with polymerase chain reaction protocols that would have detected remotely related HPVs. So we propose that the phylogenetic group formed by HPV-2, HPV-27, and HPV-57 has no or only very are additional members. One of the HPV-57 variants found, HPV-57-G44, was most likely identical to the subtype HPV-57b, previously proposed to be associated with nasal neoplasia, but found here frequently in common skin warts. Our publication establishes a foundation for pathological and phylogenetic comparisons of HPV types in skin warts.

Base Sequence↗
PubMed1997

Effects of ingredients on stability of captopril in extemporaneously prepared oral liquids.

The stability of captopril in several extemporaneously prepared oral liquid formulations was studied. Captopril 1-mg/mL oral liquid formulations were prepared from either powder or tablets in two grades of water, syrup, methylcellulose, and edetate disodium. The liquids were stored at 5 degrees C in amber glass containers, and samples were removed at intervals up to 30 days for assay of captopril concentration by stability-indicating high-performance liquid chromatography. The pH of the formulations remained fairly stable for 30 days. In general, captopril was more stable in formulations containing captopril from tablets than from powder. Captopril in formulations in which the only vehicle was highly purified water was slightly but not significantly more stable than in formulations made with sterile water for irrigation. Formulations made with undiluted syrup were more stable than formulations in which water was used to dilute syrup or formulations containing methylcellulose. The formulations containing edetate disodium were much more stable than those that lacked this component. The stability of captopril 1 mg/mL in oral liquid formulations was influenced by the captopril source (tablets versus powder) and by the presence of syrup, methylcellulose, and edetate disodium. Captopril in a preparation made with tablets and undiluted syrup was stable for 30 days at 5 degrees C, and the formulation should be palatable.

Captopril↗
PubMed1997

Stability of phenoxybenzamine hydrochloride in various vehicles.

The stability of phenoxybenzamine hydrochloride in various oral liquids was studied. Phenoxybenzamine hydrochloride powder or capsules were combined with various vehicles to prepare 10-mL formulations with a drug concentration of 2 mg/mL and a 20-mL stock solution containing 10 mg/mL. All formulations were prepared in triplicate and stored at 4 degrees C. A 1.0-mL sample of each of the 2-mg/mL formulations was withdrawn on days 0, 1, 2, 3, and 4, and samples of selected formulations were taken on days 7 and 10. Samples of the stock solution were withdrawn on days 0, 2, 4, 7, 10, 14, and 30. All samples were analyzed by high-performance liquid chromatography. Phenoxybenzamine hydrochloride 2 mg/mL was stable for a longer time in 1% propylene glycol, 0.15% citric acid, and water than in a similar vehicle in which syrup was used in place of water. The concentrations of the drug in both the 10-mg/mL stock solution and stock solutions diluted to 2 mg/mL were > 90% of the initial drug concentration for 30 days. Phenoxybenzamine hydrochloride 2 mg/mL in 1% propylene glycol and 0.15% citric acid in distilled water was stable for 7 days at 4 degrees C. A stock solution of phenoxybenzamine hydrochloride 10 mg/mL in propylene glycol was stable for 30 days at 4 degrees C and, after dilution with 66.7% sucrose in distilled water to a concentration of 2 mg/mL, for up to one hour at 4 degrees C.

Chromatography, High Pressure Liquid↗
PubMed1997

Genital papillomaviruses (PVs) and epidermodysplasia verruciformis PVs occur in the same monkey species: implications for PV evolution.

Portions of the genome from two different papillomaviruses (PVs) of the Abyssinian Colobus monkey were sequenced and phylogenetically analyzed. This revealed that the major evolutionary separation between genital PVs and epidermodysplasia verruciformis-associated PVs (EV-PVs) hitherto found only in human papillomaviruses (HPVs) also exists in animal PVs. The sequence of the long control region (LCR) of Colobus monkey PV type 2 (CgPV-2) reveals a small size and an arrangement of potential cis-responsive elements typical of the EV-HPVs; namely four binding sites for the viral E2 protein, with one of them being located within the L1 gene, a cluster of nuclear factor I (NFI)- and AP-1-binding sites and a 50-bp sequence upstream of the E6 gene consisting only of the nucleotides A and T. This level of conservation of functional elements within the highly variable LCR suggests that CgPV-2 could be adopted as a model for studying human skin cancer associated with EV-HPVs. Although isolated from the same monkey species, the other Colobus monkey PV, CgPV-1, is a typical genital PV as shown by E1 and L1 sequence comparisons. The presence of these two major phylogenetic divisions of PVs in both human and monkey hosts strongly suggests that this diversification predated the evolutionary split between monkeys and apes. In other words, at least two different groups of PVs have been evolving separately in their respective primate hosts for more than 22 million years with only moderate sequence changes since their genesis.

Animals↗
PubMed1997

Differential effects of IL-12 receptor blockade with IL-12 p40 homodimer on the induction of CD4+ and CD8+ IFN-gamma-producing cells.

The role of IL-12 role in regulating Th1/Th2 balance is attributed in part to the ability of this cytokine to induce IFNgamma production by NK and Th1 cells, which in turn promotes Th1 and inhibits Th2 development. In the present study, the requirement for IL-12 in the development of alloantigen-reactive Th1 was assessed by adding neutralizing anti-IL-12 Abs or the IL-12 receptor antagonist p40 homodimer to primary MLC. The resulting cell populations were assessed for Th1 development by measuring IFN-gamma production upon restimulation with alloantigens. While the addition of anti-IL-12 Abs to primary MLC did not influence subsequent cytokine production, addition of p40 homodimer markedly enhanced, rather than decreased, Th1 development. To determine which T cell population produced enhanced levels of IFN-gamma in response to p40 homodimer, CD4+ or CD8+ T cells were depleted from the MLC. While p40 homodimer was inhibitory to selected CD4+ Th1 development, it enhanced IFN-gamma production by CD8+ T cells. To test the in vivo relevance of these findings, mouse heterotopic cardiac allograft recipients were treated with either p40 homodimer, anti-CD8 mAb, or with both p40 homodimer and anti-CD8 mAb. Treatment of allograft recipients with p40 homodimer had no effect on the in vivo sensitization of IFN-gamma-producing cells and resulted in accelerated allograft rejection relative to unmodified recipients. However, p40 homodimer markedly prolonged allograft survival in mice depleted of CD8+ T cells. Hence, p40 homodimer stimulates CD8+ Th1 development in vitro but inhibits CD4+ T cell function both in vitro and in vivo.

Animals↗
PubMed1997

Intrachain disulfide bond in the core hinge region of human IgG4.

IgG is a tetrameric protein composed of two copies each of the light and heavy chains. The four-chain structure is maintained by strong noncovalent interactions between the amino-terminal half of pairs of heavy-light chains and between the carboxyl-terminal regions of the two heavy chains. In addition, interchain disulfide bonds link each heavy-light chain and also link the paired heavy chains. An engineered human IgG4 specific for human tumor necrosis factor-alpha (CDP571) is similar to human myeloma IgG4 in that it is secreted as both disulfide bonded tetramers (approximately 75% of the total amount of IgG) and as tetramers composed of nondisulfide bonded half-IgG4 (heavy chain disulfide bonded to light chain) molecules. However, when CDP571 was genetically engineered with a proline at residue 229 of the core hinge region rather than serine, CDP571 (S229P), or with an IgG1 rather than IgG4 hinge region, CDP571(gamma 1), only trace amounts of nondisulfide bonded half-IgG tetramers were observed. Trypsin digest reversephase HPLC peptide mapping studies of CDP571 and CDP571(gamma 1) with on-line electrospray ionization mass spectroscopy supplemented with Edman sequencing identified the chemical factor preventing inter-heavy chain disulfide bond formation between half-IgG molecules: the two cysteines in the IgG4 and IgG1 core hinge region (CPSCP and CPPCP, respectively) are capable of forming an intrachain disulfide bond. Conformational modeling studies on cyclic disulfide bonded CPSCP and CPPCP peptides yielded energy ranges for the low-energy conformations of 31-33 kcal/mol and 40-42 kcal/mol, respectively. In addition, higher torsion and angle bending energies were observed for the CPPCP peptide due to backbone constraints caused by the extra proline. These modeling results suggest a reason why a larger fraction of intrachain bonds are observed in IgG4 rather than IgG1 molecules: the serine in the core hinge region of IgG4 allows more hinge region flexibility than the proline of IgG1 and thus may permit formation of a stable intrachain disulfide bond more readily.

Alkylation↗
PubMed1997

Does a hypertonic saline load predict fluid retention in pacing induced heart failure?

OBJECTIVE: We examined the response to hypertonic saline challenge (SC) as a potential predictor of fluid retention during heart failure induced by rapid ventricular pacing. METHODS: Twelve dogs (22 +/- 4 kg) were given an intra-arterial bolus of 30 ml of 20% saline after establishing baseline fluid intake and urine output (24 h). Dogs were classified according to whether they drank more (Group A) or less (Group B) than the amount required to dilute the s.c. to isotonicity. Fluid retention was then assessed during heart failure after rapid ventricular pacing according to a graded ordinal scale and correlated with the responses to s.c.. RESULTS: No difference was noted in baseline fluid intake (1112 +/- 236 ml in Group A vs. 809 +/- 129 ml in Group B). Five hours after s.c. cumulative water intake was significantly greater in Group A than in Group B (1018 +/- 136 vs. 591 +/- 17 ml) (P < 0.01). Urine sodium concentration was 113 +/- 11 and 124 +/- 28 mmol/l at baseline in Group A and B, respectively; increased to 190 +/- 21 and 295 +/- 59 mmol/l at 5 h and remained elevated 24 h after s.c., 177 +/- 60 and 274 +/- 55 mmol/l (both P < 0.01 for within-group comparisons vs. baseline). Urine sodium concentration was less in Group A than in Group B at 5 and 24 h (P < 0.05). The fluid retention score was greater in Group A (3.6 +/- 0.5) than in Group B (0.8 +/- 0.4) (P < 0.01). Fluid retention in heart failure correlated with water intake after the pre-pacing s.c. (r = 0.68, P < 0.025) and inversely with urine concentrating ability (r = -0.58, P < 0.05). Furthermore, water intake and urine concentrating ability following the s.c. were inversely related (r = -0.67, P < 0.02). CONCLUSIONS: We conclude that normal dogs may be classified according to their fluid intake after s.c.. Those dogs that drank excessively and produced a dilute urine were more likely to retain fluid during pacing-induced heart failure. Hence, fluid intake and the ability to excrete a concentrated urine after a saline challenge may be useful variables to predict fluid retention in pacing-induced heart failure.

Animals↗
PubMed1997

Locally advanced breast cancer: early results of a randomised trial of multimodal therapy versus initial hormone therapy.

The aim of this study was to investigate initial treatment of locally advanced breast cancer. Patients were randomised to "multimodal" therapy (pre-operative chemotherapy, Patey mastectomy, flap irradiation and adjuvant hormone therapy) (n = 55), or initial "hormone" therapy (n = 53) with further therapy upon tumour progression. The objective response to chemotherapy was 57% (31/54) after four cycles. Of patients on hormone therapy, 36% (19/53) had an objective response and 32% (17/53) disease stasis at a 6 month assessment. At a median 30 months follow-up, there was no notable difference in development of metastases or survival: only 6 patients have uncontrolled loco-regional relapse (4 "hormonal", 2 "multimodal"). The number of treatments per patient required for this loco-regional control was lower in the "hormone" group (mean 2.13 versus 4.20 in the "multimodal" group). This small study has shown that the use of consecutive therapies, with the aim of tumour control, does not appear to compromise outcome in comparison with initial "multi-modal" therapy. Adopting such a policy may allow some patients to avoid unnecessary treatments.

Adult↗
PubMed1997

Colorectal carcinoma in Hong Kong: epidemiology and genetic mutations.

The incidence of colorectal carcinoma is rising at an alarming pace in Asian urban societies such as Hong Kong. Detailed examination of the epidemiological pattern and genetic mutation of colorectal cancer in the Hong Kong Chinese population is overdue. We compared the reported age incidence of colorectal carcinoma in Hong Kong with that of Scotland and other countries. Hong Kong showed a much higher incidence of colorectal carcinoma among the young age groups. By comparison with other countries, this raised incidence among the young appeared to be related to southern Chinese societies. The recent dramatic rise in colorectal cancer in Hong Kong was largely attributable to an increase in the over 50 years age group, while the young incidence remained unchanged. We also defined the mutation spectrum of p53 and Ki-ras in 67 unselected cases by direct DNA sequencing. Interestingly, insertion/deletion mutations in p53 from colorectal carcinoma in Hong Kong showed a significantly higher frequency (17.2%) than the Scottish data (0%) and the world database (6.6%), although the overall frequency of p53 mutation (43%) in Hong Kong was similar to others. The high incidence of colorectal carcinoma in young people and the raised proportion of frameshift mutations in p53 encourage further search for a genetic basis for susceptibility to this disease in the Hong Kong Chinese population.

Adolescent↗
PubMed1997

Inhibition of the alloantibody response by CD95 ligand.

We investigated the effect of Fas/APO1-ligand (CD95L) gene transfer on allogeneic immune responses in vivo. A colon carcinoma cell line from BALB/c mice, CT26, was stably transfected with a vector encoding mouse CD95L and was inoculated into C57BL/6 mice. CD95L expression markedly reduced allogeneic cytotoxic T lymphocyte and helper T lymphocyte activity directed toward CT26. Strikingly, expression of CD95L on these allogeneic tumors completely inhibited the generation of alloantibodies of both IgM and IgG subclasses. Thus, CD95L inhibited alloantibody production and conferred localized immune suppression through this mechanism. These results provide insight into the role of CD95L in regulating the alloantibody response and the generation of local immune responses.

Animals↗