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Biomedical subjects

K K Wong

Publications and source records attributed to K K Wong.

At least 19 recordsLinked to original sources

Breakage of intramedullary femoral guide rod during total knee arthroplasty: a case report.

We report a rare complication during primary total knee arthroplasty. An intramedullary femoral guide rod was broken during insertion. The broken part jammed into the isthmus of the femur. An initial attempt to push the broken rod via the proximal femur by a guide wire to the distal femur was unsuccessful because the broken rod was lodged in the isthmus. Ultimately, the isthmus was opened using a flexible 9-mm end-cutting reamer, and the broken rod was pushed down to the distal femoral entry site in an antegrade fashion under image intensification. Selecting a more medial entry site on the intercondylar notch with a smaller valgus cutting angle and using a shorter guide rod can avoid such a breakage.

Arthroplasty, Replacement, Knee↗

Autoimmune polyendocrinopathy type II in a Chinese patient.

Autoimmune polyendocrinopathy type II is rarely reported in Chinese patients. A 42-year-old Chinese woman with a history of Hashimoto's thyroiditis and hypogonadotropic hypogonadism presented with pneumonia. During hospitalisation, she went into an adrenal crisis and diabetic ketoacidosis. Subsequent dynamic hormonal tests revealed primary and secondary adrenal insufficiency. She also had pernicious anaemia, possible alopecia areata, and myasthenia gravis. This constellation of multiple endocrine and non-endocrine disorders led to the diagnosis of autoimmune polyendocrinopathy type II. As the syndrome can be lethal, it is important to maintain a high index of suspicion, enabling early diagnosis and the appropriate replacement therapy, to ensure a successful outcome.

Adult↗

Recombinant AAV2 transduction of primitive human hematopoietic stem cells capable of serial engraftment in immune-deficient mice.

A recombinant AAV2 (rAAV2) vector encoding antisense RNA to HIV-1 transactivating region (TAR) was evaluated for transduction of human cord blood CD34+CD38- hematopoietic stem cells (HSC) capable of serial engraftment in nonobese diabetic (NOD)/severe combined immunodeficient (SCID) mice. Results revealed long-term multilineage marking in primary and secondary recipients, and significantly, an enrichment of transduced cells in secondary hosts, indicating efficient transduction of multipotential self-renewing HSC. These results were confirmed by the persistence of rAAV marking of clonogenic progenitors in serial analyses of recipient marrow. Upon HIV-1 challenge, the macrophage progeny of transduced CD34+ cells expressed antisense RNA and exhibited sustained and significant inhibition of virus replication as compared with controls in every donor tested, without selective pressure. This study represents a clear in vivo demonstration of efficient rAAV2 transduction of human HSC.

ADP-ribosyl Cyclase↗

Volar fixation of dorsally displaced distal radial fracture using locking compression plate.

PURPOSE: To evaluate the functional and radiological results of treating unstable fractures of the dorsal distal radius with a volar locking plate. METHODS: Dorsally displaced distal radial fractures in 30 patients (11 men and 19 women; mean age, 58.6 years) were fixed by volar locking compression plate and followed up for a minimum of one year. RESULTS: At final functional assessment, 24 patients achieved excellent and 5 achieved good outcomes, with one patient exhibiting fair results. Radiological scores demonstrated 22 excellent and 8 good outcomes. No nonunion or infection occurred. CONCLUSION: Volar locking compression plating is a safe and effective treatment for unstable fractures of the dorsal distal radius.

Adult↗

Performance of large-size superconducting coil in 0.21T MRI system.

A high-temperature superconductor (HTS) was used on magnetic resonance imaging (MRI) receiver coils to improve image quality because of its intrinsic low electrical resistivity. Typical HTS coils are surface coils made of HTS thin-film wafers. Their applications are severely limited by the field of view (FOV) of the surface coil configuration, and the improvement in image quality by HTS coil is also reduced as the ratio of sample noise to coil noise increases. Therefore, previous HTS coils are usually used to image small in vitro samples, small animals, or peripheral human anatomies. We used large-size HTS coils (2.5-, 3.5-, and 5.5-in mean diameter) to enhance the FOV and we evaluated their performance through phantom and human MR images. Comparisons were made among HTS surface coils, copper surface coils, and cool copper surface coils in terms of the signal-to-noise ratio (SNR) and sensitivity profile of the images. A theoretical model prediction was also used to compare against the experimental result. We then selected several human body parts, including the wrist, feet, and head, to illustrate the advantage of HTS coil over copper coil when used in human imaging. The results show an SNR gain of 200% for 5.5-in HTS coil versus same size copper coils, while for 2.5- and 3.5-in coils it is 250%. We also address the various factors that affect the performance of large size HTS coils, including the coil-to-sample spacing due to cryogenic probe and the coil-loading effect.

Electric Conductivity↗

Significance of the Hygiene Charter towards different sectors in Hong Kong.

The occurrence of SARS in March 2003 has resulted in an increased interest, worldwide in emerging infectious diseases. The SARS experience provided us a lesson on the importance of promoting hygienic practices among individuals and different working sectors. In Hong Kong, a voluntary organization called the UNITE proposed a Hygiene Charter which aimed at taking hygiene to new levels. This action has been supported by individuals and different sectors including the Personal and Family, Management, Buildings, Catering, Education, Finance and Commercial, Industrial, Medical and Health, Public Transportation, Social Welfare, Sports and Culture and Tourism. As promotion and maintenance of environmental health requires input from different sectors, the signing of the Hygiene Charter provides an opportunity for individuals and the public to show their pledge and commitment to good hygiene practices. As a result, with environment improvement and good infectious disease control measures, prevention of epidemics of infectious diseases is deemed to be possible.

Adult↗

Identification of new MHC-restriction elements for presentation of the p210(BCR-ABL) fusion region to human cytotoxic T lymphocytes.

Chronic myelogenous leukemia (CML) is characterized by a t(9;22) translocation resulting in expression of BCR-ABL fusion oncoproteins which are unique to the leukemic cells, necessary for oncogenesis, and potentially immunogenic. We have previously shown that human dendritic cells transduced with an adeno-associated virus vector encoding the fusion region of the b3a2 splice variant (p210(b3a2)) of the BCR-ABL oncoprotein elicit specific T-cell responses in vitro. Two cytotoxic T lymphocyte (CTL) clones generated in this fashion displayed restriction with previously unreported HLA alleles. The first, T1/B9, was CD4(+) and restricted by DRB5*0101 (autologous) or DRB1*1101 (allogeneic). The minimum cytotoxic epitope (MCE) binding to DRB5*0101 for this clone was identified as FKQSSKALQ, overlapping the p210(b3a2) fusion point (boldface). The MCE of DRB1*1101 for this clone differed from DRB5*0101, but also included the fusion point. The clonality of CTL T1/B9 was verified by analyses of TCRalpha/beta chain usage and DNA sequence analyses. To our knowledge, this is the first description of a single clone recognizing both DRB5*0101 and DRB1*1101. The other CTL clone, T1/33, was CD8+ and recognized HLA-B*3501 or B*3503 complexed with an MCE, RPVASDFEP, derived from the c-abl sequence in proximity to the p210(b3a2) fusion point. K562 cells transfected with plasmids encoding HLA-DRA + B5*0101, B*3501, or B*3503 but not controls expressing DRA + DRB1*1501 were lysed by cognate CTL clones, confirming that DRB5*0101 and B*3501/3 could present p210(b3a2) joining region epitopes via endogenous processing. The identification of three additional HLA alleles (DRB5*0101, B*3501, and B*3503) presenting the p210(b3a2) fusion-region antigen will broaden the application of vaccine strategies for targeting CML cells. The findings of single CTL clones cross-recognizing autologous (DRB5*0101 or B*3501) and allogeneic (DRB1*1101 or B*3503) HLA alleles presenting BCR-ABL fusion-region epitopes implies the potential separation of graft-versus-leukemia from graft-versus-host effects.

Adenoviridae↗

Removal of Cu and Pb by tartaric acid modified rice husk from aqueous solutions.

A study on the modification of rice husk by various carboxylic acids showed that tartaric acid modified rice husk (TARH) had the highest binding capacities for Cu and Pb. The carboxyl groups on the surface of the modified rice husk were primarily responsible for the sorption of metal ions. A series of batch experiments using TARH as the sorbent for the removal of Cu and Pb showed that the sorption process was pH dependent, rapid and exothermic. The sorption process conformed to the Langmuir isotherm with maximum sorption capacities of 29 and 108 mg/g at 27 +/- 2 degrees C for Cu and Pb, respectively. The uptake increased with agitation rate. Decrease in sorbent particle size led to an increase in the sorption of metal ions and this could be explained by an increase in surface area and hence binding sites. Metal uptake was reduced in the presence of competitive cations and chelators. The affinity of TARH for Pb is greater than Cu.

Adsorption↗

Immune responses to adeno-associated virus and its recombinant vectors.

Recombinant adeno-associated virus (rAAV) vectors have emerged as highly promising for use in gene transfer for a variety of reasons, including lack of pathogenicity and wide host range. In addition, all virus-encoded genes have been removed from standard rAAV vectors, resulting in their comparatively low intrinsic immunogenicity. For gene replacement strategies, transgenes encoded by rAAV vectors may induce less robust host immune responses than other vectors in vivo. However, under appropriate conditions, host immune responses can be generated against rAAV-encoded transgenes, raising the potential for their use in vaccine development. In this review, we summarize current understanding of the generation of both undesirable and beneficial host immune responses directed against rAAV and encoded transgenes, and how they might be exploited for optimal use of this promising vector system.

Animals↗

Immunogenicity of a p210(BCR-ABL) fusion domain candidate DNA vaccine targeted to dendritic cells by a recombinant adeno-associated virus vector in vitro.

Chronic myelogenous leukemia (CML) is characterized by a t(9;22) translocation, which results in the expression of chimeric BCR-ABL fusion oncoproteins that are necessary for oncogenesis, unique to the leukemic clones, and represent enticing targets for immunotherapy. As a strategy for the immunotherapy of CML, we constructed a recombinant adeno-associated virus vector encoding the p210(BCR-ABL) b3a2 variant fusion region with flanking sequences (CWRBA) and used it to express the BCR-ABL fusion region within primary human dendritic cells (DCs), the most potent antigen-presenting cells currently known. Peripheral blood mononuclear cells from healthy donors were primed and restimulated in vitro with autologous DCs transduced with purified CWRBA, CWRAP (negative control), or pulsed with a peptide corresponding to the fusion domain (positive control). No specific responses were generated using DCs transduced with CWRAP. In contrast, CWRBA-transduced DCs primed autologous T cells in an antigen-specific, MHC-restricted fashion to levels comparable with the positive control. CWRBA-transduced DCs elicited both cytotoxic CD4+/Th1 and CD8+ responses, although the former were more readily detected in this system. Cytotoxicity against a tumor cell line endogenously expressing the p210(BCR-ABL) b3a2 variant fusion region was also demonstrable. In addition, HLA-DRB5(*)0101+DRA (DR2a) was identified as a new restriction element capable of presenting the b3a2 BCR-ABL fusion region epitope. Thus, the construct developed herein may serve as a candidate vaccine for gene-based antigen-specific immunotherapy of CML and may serve as a paradigm for the use of DCs transduced with recombinant adeno-associated virus vectors encoding multiepitope immunogens for vaccine development.

Amino Acid Sequence↗

Prevalence of snoring and sleep-disordered breathing in a group of commercial bus drivers in Hong Kong.

OBJECTIVES: To assess the prevalence of sleep-disordered breathing (SDB) and its associated symptoms in a group of commercial bus drivers in Hong Kong. METHODS: Two hundred and sixteen of 410 bus drivers from three different shifts were interviewed with the Sleep & Health Questionnaire (SHQ) and the Epworth sleepiness scale (ESS) at a Hong Kong bus depot. Seventeen subjects from each shift were then randomly selected for at-home sleep study using the Mesam IV device (Madaus Medizin-Elektronik, Freiburg, Germany). RESULTS: There were 207 men and nine women (mean age 42.4 +/- 7.5 years; body mass index (BMI) 25.4 +/- 4.5 kg/m2; ESS 5.3 +/- 4.2). From the SHQ it was discovered that: (i) daytime sleepiness was reported by 87 subjects (40%), (ii) snoring > or = 3 times per week was reported by 80 subjects (37%), (iii) witnessed apnoea was reported by 17 subjects (7.9%) and (iv) 29 subjects (13.4%) reported having fallen asleep during driving. Among the 51 subjects who underwent the at-home sleep study: (i) 31 subjects (61%) had respiratory disturbance index (RDI) > or = 5 per hour of sleep, (ii) 21 subjects (41%) had RDI > or = 10 per hour of sleep, (iii) 12 subjects (24%) had RDI > or = 15 per hour of sleep and (iv) 35 subjects (68.6%) snored objectively > or = 10% of the night. Ten subjects (20%) had RDI > or = 5 and sleepiness at work, while five subjects (9.8%) had RDI > or = 5 and ESS > 10. No significant differences were noted in the SHQ responses, ESS, objective snoring or RDI among the three groups. Multiple regression analysis showed that BMI and witnessed apnoea were the only positive independent predictors of RDI. CONCLUSIONS: This study showed a high prevalence of objective snoring and SDB in a group of commercial bus drivers. Neither self-reported sleepiness nor the ESS could identify subjects with SDB.

Adult↗

Selective cytotoxicity of gemcitabine in bladder cancer cell lines.

We have examined the cytotoxic effect of gemcitabine in intravesical therapy using an in vitro co-cultured spheroid model composed of transitional cell carcinoma (TCC) and fibroblasts from both human and rat species. Immunohistochemistry analysis of the co-cultured spheroids, using cytokeratin-13 and vimentin antibodies against TCC and fibroblasts, respectively, showed the central location of fibroblasts within the spheroid, whereas TCC formed the peripheral layers. Spheroids composed of human TCC and fibroblasts (MGH-U3/CRL-1120 or RT-112/CRL-1120) as well as rat TCC and their corresponding fibroblasts (AY-27/RF-Ed1) displayed the same drug tolerance profile after an exposure of 0, 1, 3, 5, 7 and 14 days. As confirmed by time-lapse photography, MTT essay and vital dye staining, gemcitabine selectively killed the human and rat bladder cancer cell lines, but did not affect un-transformed human and rat fibroblast lines.

Animals↗

Immunogenic issues concerning recombinant adeno-associated virus vectors for gene therapy.

Recombinant adeno-associated virus (rAAV) vectors have emerged as highly promising for use in gene transfer for a variety of reasons, including lack of pathogenicity and wide host range. In addition, all virus-encoded genes have been removed from standard rAAV vectors, resulting in their comparatively low intrinsic immunogenicity. For gene replacement strategies, transgenes encoded by rAAV vectors may induce less robust host immune responses than other vectors in vivo. However, under appropriate conditions, host immune responses can be generated against rAAV encoded transgenes, raising the potential for their use in vaccine development. In this review, we have summarized current understanding of the generation of both undesirable and beneficial host immune responses directed against rAAV and encoded transgenes, and how they might be exploited for optimal use of this promising vector system.

Antibody Formation↗

A returned traveller with persistent fever due to murine typhus.

Murine (endemic) typhus is a notifiable disease in Hong Kong, but its diagnosis can be difficult. We report a case of murine typhus in a middle-aged man who presented with persistent fever, headache, and skin rash 2 weeks after returning from a visit to China. The diagnosis of murine typhus requires a high index of suspicion for a febrile patient with a history of potential exposure to the disease vector (rat flea) in an endemic area. The importance of early recognition lies in the potential for early therapeutic intervention, leading to decreases in morbidity and duration of stay in hospital.

Anti-Bacterial Agents↗

Inactivation of pyruvate formate-lyase by dioxygen: defining the mechanistic interplay of glycine 734 and cysteine 419 by rapid freeze-quench EPR.

Pyruvate formate-lyase from Escherichia coli (EC 2.3.1.54; PFL) catalyzes the reversible anaerobic conversion of pyruvate and CoA into acetyl-CoA and formate. Active PFL contains a novel alpha-carbon centered glycyl radical at G734 that is required for its catalytic activity. Two adjacent cysteine residues, C418 and C419, are essential for PFL activity according to site-directed mutagenesis studies. Upon exposure to air, active PFL loses its activity with the concomitant loss of the glycyl radical. Previous EPR studies of dioxygen inactivation of PFL revealed protein-based peroxyl and sulfinyl radicals during the manual mixing and quenching process [Reddy et al. (1998) Biochemistry 37, 558-563]. To probe the mechanism of this process, we carried out experiments using rapid freeze-quench EPR spectroscopy. Upon mixing of active wild type or C418A PFL with oxygenated solution, a short-lived radical intermediate appears at the earliest time point (10 ms), followed by the appearance of a long-lived sulfinyl radical. The axial EPR spectrum of this short-lived radical (g = 2.034, 2.007) is characteristic of a peroxyl radical. When C419A PFL or the double mutant [C418A/C419A] PFL was mixed with oxygenated solution, the peroxyl radical was also observed at 10 ms but in this case persisted over 12 s. These observations provide compelling evidence to support a proposed mechanism in which dioxygen quenches the glycyl radical in the active enzyme and the resulting peroxyl radical may react further with the sulfhydryl group of the C419 residue to form the sulfinyl radical.

Acetylation↗