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Biomedical subjects

Kwok-Yung Yuen

Publications and source records attributed to Kwok-Yung Yuen.

At least 19 recordsLinked to original sources

Regular virologic surveillance showed very frequent cytomegalovirus reactivation in patients treated with alemtuzumab.

Ten patients with refractory lymphomas or autoimmune cytopenias were treated with alemtuzumab, and monitored prospectively for cytomegalovirus (CMV) reactivation by antigenemia and polymerase chain reaction. All patients showed virologic CMV reactivation. Two patients developed pneumonitis and hepatitis respectively, necessitating alemtuzumab withdrawal. Eight patients were asymptomatic, and with pre-emptive anti-CMV treatment, alemtuzumab therapy was uninterrupted. All patients ultimately achieved virologic remission. The frequent CMV reactivation was due to a high background seropositivity rate for CMV, severely immunocompromized patients, a sensitive detection method, and the diligence of surveillance. Frequent monitoring for and early treatment of CMV reactivation is necessary during alemtuzumab therapy.

Adult↗

Catabacter hongkongensis gen. nov., sp. nov., isolated from blood cultures of patients from Hong Kong and Canada.

Four bacterial isolates were recovered from the blood cultures of four patients, two of whom were from Hong Kong and two of whom were from Canada. The two Hong Kong strains were isolated from a 48-year-old man with intestinal obstruction and secondary sepsis (strain HKU16T) and from a 39-year-old man with acute appendicitis (strain HKU17), while the two Canadian strains were isolated from a 74-year-old man with biliary sepsis (strain CA1) and from a 66-year-old woman with metastatic carcinoma and sepsis (strain CA2). While the first three patients survived, the last patient died 2 weeks after the episode of bacteremia. All four isolates are strictly anaerobic, nonsporulating, gram-positive coccobacilli that were unidentified by conventional phenotypic tests and commercial identification systems. They grow on sheep blood agar as nonhemolytic pinpoint colonies after 48 h of incubation at 37 degrees C in an anaerobic environment. All are catalase positive and motile, with flagella. They produce acid from arabinose, glucose, mannose, and xylose. They do not produce indole or reduce nitrate. They are sensitive to penicillin, vancomycin, and metronidazole but resistant to cefotaxime. 16S rRNA gene sequence analysis showed 16.0%, 16.8%, and 21.0% base differences from Clostridium propionicum, Clostridium neopropionicum, and Atopobium minutum, respectively. The G+C content of strain HKU16T is 40.2% +/- 2.2%. Based on their phylogenetic affiliation, unique G+C content, and phenotypic characteristics, we propose a new genus and species, Catabacter hongkongensis gen. nov., sp. nov., to describe the bacterium, for which HKU16 is the type strain, and suggest that it be assigned to a new family, Catabacteriaceae. The gastrointestinal tract was probably the source of the bacterium for at least three of the four patients. The isolation of a catalase-positive, motile, nonsporulating, anaerobic gram-positive bacillus in clinical laboratories should raise the possibility of C. hongkongensis. Further studies should be performed to ascertain the epidemiology and other disease associations of this bacterium.

Adult↗

Comparative analysis of twelve genomes of three novel group 2c and group 2d coronaviruses reveals unique group and subgroup features.

Twelve complete genomes of three novel coronaviruses-bat coronavirus HKU4 (bat-CoV HKU4), bat-CoV HKU5 (putative group 2c), and bat-CoV HKU9 (putative group 2d)-were sequenced. Comparative genome analysis showed that the various open reading frames (ORFs) of the genomes of the three coronaviruses had significantly higher amino acid identities to those of other group 2 coronaviruses than group 1 and 3 coronaviruses. Phylogenetic trees constructed using chymotrypsin-like protease, RNA-dependent RNA polymerase, helicase, spike, and nucleocapsid all showed that the group 2a and 2b and putative group 2c and 2d coronaviruses are more closely related to each other than to group 1 and 3 coronaviruses. Unique genomic features distinguishing between these four subgroups, including the number of papain-like proteases, the presence or absence of hemagglutinin esterase, small ORFs between the membrane and nucleocapsid genes and ORFs (NS7a and NS7b), bulged stem-loop and pseudoknot structures downstream of the nucleocapsid gene, transcription regulatory sequence, and ribosomal recognition signal for the envelope gene, were also observed. This is the first time that NS7a and NS7b downstream of the nucleocapsid gene has been found in a group 2 coronavirus. The high Ka/Ks ratio of NS7a and NS7b in bat-CoV HKU9 implies that these two group 2d-specific genes are under high selective pressure and hence are rapidly evolving. The four subgroups of group 2 coronaviruses probably originated from a common ancestor. Further molecular epidemiological studies on coronaviruses in the bats of other countries, as well as in other animals, and complete genome sequencing will shed more light on coronavirus diversity and their evolutionary histories.

Amino Acid Sequence↗

Misidentification of a mucoid strain of Salmonella enterica serotype choleraesuis as Hafnia alvei by the Vitek GNI+ card system.

Nontyphoidal salmonellae are among the most common causes of bacterial gastroenteritis worldwide. They are also notable causes of extraintestinal infections, including bacteremia and vascular infections. Salmonella enterica serotype Choleraesuis is typically associated with invasive infections. We report a patient who had an infected intra-abdominal aortic aneurysm due to an unusually mucoid strain of Salmonella enterica serotype Choleraesuis. The isolate was erroneously identified as Hafnia alvei by the Vitek GNI+ card system. A blood culture isolate taken from the same patient 9 months earlier was also identified as H. alvei by the Vitek GNI+ card system. Despite an apparent cure with intravenous amoxicillin-clavulanic acid at that time, the Salmonella infection had not been cleared and manifested as a ruptured infected abdominal aortic aneurysm. Repeated passage of the strain yielded nonmucoid colonies, which were correctly identified by the API and PHOENIX systems. The isolates from the aneurysm and the former bacteremic episode were found to be identical using pulsed field gel electrophoresis. The fallibility of automated bacterial identification systems is highlighted. Such errors are especially important for isolates in which in vitro antibiotic susceptibility testing does not correlate with the clinical success of treatment, as illustrated by Salmonella infections.

Aged↗

Polymorphisms of type I interferon receptor 1 promoter and their effects on chronic hepatitis B virus infection.

BACKGROUND/AIMS: Exposure to HBV leads to a distinct clinical course which is partially pertained to host genetic variability. We aimed to study polymorphisms of type I interferon receptor 1 (IFNAR1) promoter and their potential effects on chronic HBV infection. METHODS: Polymorphisms of IFNAR1 promoter were identified in 320 chronic hepatitis B patients, 148 spontaneously recovered individuals, 148 healthy Chinese donors and 114 Caucasians. Their functional capability in driving reporter gene expression was analyzed. RESULTS: Four polymorphic alleles were identified at loci -568, -408, -77 and -3. Association analysis revealed that carriers of alleles -568G, -408C and their related haplotype I were less susceptible to chronic HBV infection whereas those of alleles -568C, -408T and related haplotype III were significantly associated with higher risk to chronic hepatitis B (P<0.01). In a reporter-driven system, the promoter variants with alleles -408C and -3C could drive higher expression of the reporter gene than those with alleles -408T and -3T (P<0.01). Interestingly, an allele with 9 GT repeats at -77 that was rarely found in Chinese but prevalent in Caucasian exhibited the highest transcriptional ability. CONCLUSIONS: Our results showed that polymorphisms of IFNAR1 promoter may affect, at least in part, the outcomes of HBV infection.

Asian People↗

In silico analysis of 16S ribosomal RNA gene sequencing-based methods for identification of medically important anaerobic bacteria.

This study is the first study that provides useful guidelines to clinical microbiologists and technicians on the usefulness of full 16S rRNA sequencing, 5'-end 527-bp 16S rRNA sequencing and the existing MicroSeq full and 500 16S rDNA bacterial identification system (MicroSeq, Perkin-Elmer Applied Biosystems Division, Foster City, California, USA) databases for the identification of all existing medically important anaerobic bacteria. Full and 527-bp 16S rRNA sequencing are able to identify 52-63% of 130 Gram-positive anaerobic rods, 72-73% of 86 Gram-negative anaerobic rods and 78% of 23 anaerobic cocci. The existing MicroSeq databases are able to identify only 19-25% of 130 Gram-positive anaerobic rods, 38% of 86 Gram-negative anaerobic rods and 39% of 23 anaerobic cocci. These represent only 45-46% of those that should be confidently identified by full and 527-bp 16S rRNA sequencing. To improve the usefulness of MicroSeq, bacterial species that should be confidently identified by full and/or 527-bp 16S rRNA sequencing but not included in the existing MicroSeq databases should be included.

Bacteria, Anaerobic↗

Seasonal and tissue distribution of Laribacter hongkongensis, a novel bacterium associated with gastroenteritis, in retail freshwater fish in Hong Kong.

Laribacter hongkongensis, a recently discovered bacterium associated with community-acquired gastroenteritis, has been found in the intestines of freshwater fish. To better understand the epidemiology and ecology of the bacterium, we carried out a surveillance study to investigate possible seasonal variation in the recovery of L. hongkongensis and its distribution in various organs in retail freshwater fish in Hong Kong. Forty whole freshwater fish of two species (20 grass carps and 20 bighead carps), and intestines from 120 grass carps were sampled during a one-year period. L. hongkongensis was isolated from 11 (55%) of the 20 grass carps and 6 (30%) of the 20 bighead carps; and the intestines of 49 (41%) of 120 grass carps. Seasonal variation in the recovery of L. hongkongensis from both whole fish and intestines was observed, with higher isolation rates in spring and summer than in fall and winter. There was also positive correlation between temperature and the isolation rates. When L. hongkongensis was cultured in vitro at different temperatures, shorter lag time and higher growth rate were observed at higher temperatures, with 37 degrees C being optimal among the tested temperatures. L. hongkongensis was commonly found in the gills, stomachs and intestines in both grass carps and bighead carps, and on the skin surface of one fish, but not in other organs. Proper handling of freshwater fish for cooking, especially the gills and gut, is recommended to prevent acquisition of L. hongkongensis, and other freshwater fish related infections.

Animals↗

Molecular epidemiology and household transmission of community-associated methicillin-resistant Staphylococcus aureus in Hong Kong.

This study evaluated the clinical and epidemiologic features of individuals with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Hong Kong from January 2004 through December 2005. Twenty-four episodes of skin and soft tissue infections and 1 episode of meningitis due to CA-MRSA were identified. CA-MRSA infections or carriage was found in 6 (13%) of 46 household contacts. A total of 29 isolates were analyzed by the Staphylococcus cassette chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing. In addition, polymerase chain reaction detection of the genes encoding Panton-Valentine leukocidin was also carried out. It was observed that 24 had SCCmec IV/IVA and 5 had SCCmec V, and 23 were pvl positive. PFGE analysis clustered all except 1 isolate into 3 pulsed-field types (PFTs), HKU100 through HKU300. The HKU100 isolates had genotype ST30-IV identical to the Southwest Pacific clone. The HKU200 isolates belonged to ST59-V and were multiresistant, including an ermB-mediated macrolide resistance trait, which is characteristic of the predominant CA-MRSA clone in Taiwan. The HKU300 isolates had unique features (ST8, Panton-Valentine leukocidin negative, and SCCmec IVA) typical of CA-MRSA in Japan. In conclusion, CA-MRSA has a propensity to spread within families. Our findings showed that CA-MRSA strains in Hong Kong have diverse genetic backgrounds.

Adolescent↗

Recombinant adeno-associated virus expressing the receptor-binding domain of severe acute respiratory syndrome coronavirus S protein elicits neutralizing antibodies: Implication for developing SARS vaccines.

Development of an effective vaccine for severe acute respiratory syndrome (SARS) remains to be a priority to prevent possible re-emergence of SARS coronavirus (SARS-CoV). We previously demonstrated that the receptor-binding domain (RBD) of SARS-CoV S protein is a major target of neutralizing antibodies. This suggests that the RBD may serve as an ideal vaccine candidate. Recombinant adeno-associated virus (rAAV) has been proven to be an effective system for gene delivery and vaccine development. In this study, a novel vaccine against SARS-CoV was developed based on the rAAV delivery system. The gene encoding RBD was cloned into a pAAV-IRES-hrGFP plasmid. The immunogenicity induced by the resulting recombinant RBD-rAAV was evaluated in BALB/c mice. The results demonstrated that (1) a single dose of RBD-rAAV vaccination could induce sufficient neutralizing antibody against SARS-CoV infection; (2) two more repeated doses of the vaccination boosted the neutralizing antibody to about 5 times of the level achieved by a single dose of the immunization and (3) the level of the antibody continued to increase for the entire duration of the experiment of 5.5 months. These results suggested that RBD-rAAV is a promising SARS candidate vaccine.

Animals↗

Accelerated evolutionary rate may be responsible for the emergence of lineage-specific genes in ascomycota.

The evolutionary origin of "orphan" genes, genes that lack sequence similarity to any known gene, remains a mystery. One suggestion has been that most orphan genes evolve rapidly so that similarity to other genes cannot be traced after a certain evolutionary distance. This can be tested by examining the divergence rates of genes with different degrees of lineage specificity. Here the lineage specificity (LS) of a gene describes the phylogenetic distribution of that gene's orthologues in related species. Highly lineage-specific genes will be distributed in fewer species in a phylogeny. In this study, we have used the complete genomes of seven ascomycotan fungi and two animals to define several levels of LS, such as Eukaryotes-core, Ascomycota-core, Euascomycetes-specific, Hemiascomycetes-specific, Aspergillus-specific, and Saccharomyces-specific. We compare the rates of gene evolution in groups of higher LS to those in groups with lower LS. Molecular evolutionary analyses indicate an increase in nonsynonymous nucleotide substitution rates in genes with higher LS. Several analyses suggest that LS is correlated with the evolutionary rate of the gene. This correlation is stronger than those of a number of other factors that have been proposed as predictors of a gene's evolutionary rate, including the expression level of genes, gene essentiality or dispensability, and the number of protein-protein interactions. The accelerated evolutionary rates of genes with higher LS may reflect the influence of selection and adaptive divergence during the emergence of orphan genes. These analyses suggest that accelerated rates of gene evolution may be responsible for the emergence of apparently orphan genes.

Ascomycota↗

Distribution of amantadine-resistant H5N1 avian influenza variants in Asia.

We examined the distribution of genetic mutations associated with resistance to the M2 ion channel-blocking adamantane derivatives, amantadine and rimantadine, among H5N1 viruses isolated in Vietnam, Thailand, Cambodia, Indonesia, Hong Kong, and China. More than 95% of the viruses isolated in Vietnam and Thailand contained resistance mutations, but resistant mutants were less commonly isolated in Indonesia (6.3% of isolates) and China (8.9% of isolates), where human infection was recently reported. The dual mutation motif Leu26Ile-Ser31Asn (leucine-->isoleucine at aa 26 and serine-->asparagine at aa 31) was found almost exclusively in all resistant isolates from Vietnam, Thailand, and Cambodia, suggesting the biological selection of these mutations.

Amantadine↗

Clinical isolates of Streptococcus iniae from Asia are more mucoid and beta-hemolytic than those from North America.

Streptococcus iniae, a widely distributed fish pathogen, is known to cause rare cases of human infection. We describe 2 cases of invasive S. iniae infection, one with septic arthritis complicating chronic gout and the other with bacteremic cellulitis. Both patients were Chinese and have been regularly handling fresh fish for cooking. Both isolates were unidentified or misidentified by 3 commercially available identification system and were only identified by 16S rRNA gene sequencing. When compared with a clinical isolate of S. iniae from Canada, their colonies were larger, more beta-hemolytic, and microcoid. Although bacteremic cellulitis has been described as the most common infection associated with S. iniae, the bacterium has not been reported to cause exacerbations of gouty arthritis previously. Clinical laboratories should be aware of the possibility of different colony morphology of S. iniae from Asia. More accurate identification of nongroupable beta-hemolytic streptococci, especially from patients with epidemiologic linkage to fresh fish, may uncover more cases of S. iniae infection. The Asian population and handlers of fresh fish should be informed of the risk of acquiring S. iniae infection.

Aged↗

Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals.

Most of the SARS-CoV-infected patients spontaneously recovered without clinical intervention while a small percentage succumbed to the disease. Here, we characterized temporal changes in N protein-specific and S glycoprotein-specific neutralizing antibody (Nab) responses in infected patients who have either recovered from or succumbed to SARS-CoV infection. Recovered patients were found to have higher and sustainable levels of both N protein-specific and S glycoprotein-specific Nab responses, suggesting that antibody responses likely play an important role in determining the ultimate disease outcome of SARS-CoV-infected patients.

Antibodies, Viral↗

False-negative cerebrospinal fluid cryptococcal antigen test due to small-colony variants of Cryptococcus neoformans meningitis in a patient with cystopleural shunt.

This is the first report of a small-colony variant Cryptococcus neoformans isolated from the cerebrospinal fluid of a patient with cystopleural shunt associated chronic meningitis. Cryptococcal antigen testing of the cerebrospinal fluid and the serum were both negative. The atypical morphology and the false-negative test may lead to delay of diagnosis and treatment.

Antigens, Fungal↗

Diagnostic application of genotypic identification of mycobacteria.

This study evaluated conventional methods, GLC and three molecular tests, including 16S rRNA sequencing, for the identification of mycobacteria, and the experiences of the authors with the integration of these methods into a diagnostic clinical laboratory were also recorded. Of 1067 clinical isolates of mycobacteria identified by conventional tests, 365 were tested by Accuprobe hybridization assays and PCRs specific for Mycobacterium tuberculosis (MTB) complex or Mycobacterium avium complex (MAC), 202 were tested by 16S rRNA sequencing, and 142 were tested by GLC. Three runs of all tests were performed on a weekly basis. The identifications for 209 MTB complex and 118 MAC isolates obtained by species-specific PCR were in complete agreement with AccuProbe hybridization and conventional test results. The 16S rRNA sequence-based identification, at a similarity of > or =99 %, for 132 of 142 isolates was concordant with the identifications made by the biochemical methods, and for 134 isolates was concordant with the identifications made by GLC at species, group or complex level. 16S rRNA sequencing resulted in fewer incorrectly identified or unidentified organisms than GLC or conventional tests. For the slowly growing non-tuberculous mycobacteria, the mean turnaround times for identification were 4-5 days for 16S rRNA sequencing, 14-29 days for GLC and 22-23 days for conventional methods. Considering the large proportion of some species among clinical isolates, a strategy of initial screening with species-specific PCR (or AccuProbe assays) for the MTB complex and MAC, followed by direct sequencing of the strains that yield negative results, should make 16S rRNA sequencing more affordable for routine application in diagnostic laboratories.

Algorithms↗