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Biomedical subjects

C Chu

Publications and source records attributed to C Chu.

At least 19 recordsLinked to original sources
PubMed2005

Integron-associated imipenem resistance in Acinetobacter baumannii isolated from a regional hospital in Taiwan.

We investigated the genetic properties of imipenem-resistant Acinetobacter baumannii collected from a regional hospital in Taiwan. Pulsed-field gel electrophoresis demonstrated that the isolates were genetically diverse. Polymerase chain reaction, DNA sequencing, and DNA-DNA hybridisation showed that the bla(IMP-1) gene resided as a cassette in a plasmid-borne class 1 integron in two isolates. The majority of the resistant isolates were plasmid-less and carried no bla(IMP), bla(VIM) or bla(CFI) genes, indicating that other uncharacterised metallo-beta-lactamases or mechanisms other than enzyme production are involved in carbapenem resistance in this group of A. baumannii. We conclude that multidrug resistance of A. baumannii was a combined effect of lateral gene transfer and clonal spread of multiple resistant clones. Strict measures should be implemented to control the further spread of resistance.

Acinetobacter baumannii↗
PubMed2004

Isolation of Salmonella enterica serotype choleraesuis resistant to ceftriaxone and ciprofloxacin.

Salmonella enterica serotype choleraesuis (S choleraesuis) usually causes systemic infections in man that need antimicrobial treatment. We isolated a strain of S choleraesuis that was resistant to ceftriaxone and ciprofloxacin from a patient with sepsis. Ciprofloxacin resistance was associated with mutations in gyrA and parC, whereas the ampC gene (bla(CMY-2)), responsible for ceftriaxone resistance, was carried by a transposon-like mobile element. This element was found inserted into finQ of a potentially transmissible 140 kb plasmid, with an 8 bp direct repeat flanking the junction regions. The appearance of this resistant S choleraesuis is a serious threat to public health, and thus constant surveillance is warranted.

Ceftriaxone↗
PubMed2003

Image-directed parathyroidectomy under local anaesthesia in the elderly.

BACKGROUND: Surgical morbidity and mortality rates are increased in elderly patients. The aim of this study was to evaluate the outcome of targeted parathyroid operations in patients over the age of 70 years. METHODS: Forty patients aged over 70 years underwent targeted parathyroidectomy for primary hyperparathyroidism (HPT). Data were collected prospectively and reviewed retrospectively. RESULTS: : There were 33 women and seven men with a mean age of 78 (range 70-92) years, all of whom had symptoms attributable to HPT. A solitary parathyroid adenoma was detected by ultrasonography and/or sestamibi scintigraphy before operation in all patients. Six patients had a history of neck surgery, including two with persistent or recurrent HPT. Thirty-three patients underwent neck exploration under local anaesthesia with intravenous sedation. Following parathyroidectomy, intraoperative parathyroid hormone levels normalized in 39 of 40 patients and accurately predicted postoperative eucalcaemia. Intraoperative findings included 37 solitary adenomas, one double adenoma and two carcinomas. One patient with persistent HPT developed severe hypoparathyroidism following targeted parathyroid exploration with autotransplantation. Twenty-nine patients were discharged from hospital on the day of surgery. Nineteen of 21 patients for whom data were available reported an improvement in symptoms. CONCLUSION: A focused neck exploration provides a safe and effective alternative to bilateral neck exploration in elderly patients in whom a solitary parathyroid adenoma has been localized before operation. Targeted parathyroidectomy under local anaesthesia is recommended in most elderly patients with HPT.

Adenoma↗
PubMed2003

What motivates interest in attending a familial cancer genetics clinic?

The motivation of people who seek advice about a family history of cancer was explored in a cross sectional study of new cancer referrals to five regional cancer genetics centres in England: the PACT (patient and clinical team) psychosocial study. One hundred sixty-two people took part. Measures were source of referral, estimated and perceived cancer risk, level of cancer worry, and personal and family-centred reasons for wanting to be seen in clinic. General practitioners referred more people than hospital doctors, and referred a larger proportion of people at low genetic risk of developing cancer. More than half of the participants had been the first to raise the issue of their family history of cancer. Personal motivation for referral is clearly different for those who have had a diagnosis of cancer and for those with children, compared to unaffected and childless people, and is characterised by altruistic concern for other family members rather than a perception of increased personal risk. Men and people from ethnic minorities are very significantly under-represented. Understanding people's motivation may be useful in targeting genetic counselling for people with a family history of cancer.

Adult↗
PubMed2002

Fabrication and characterization of hydroxyapatite reinforced with 20 vol % Ti particles for use as hard tissue replacement.

Hydroxyapatite(HA)-based composite reinforced with 20 vol % titanium (Ti) particles was fabricated by hot pressing based on the studies of the structural stability of HA phase in HA-Ti composite by means of FTIR spectrometry and X-ray diffractometry. The mechanical properties and biological behaviors of the composite were investigated by mechanical and in vivo studies. The existence of Ti metal phase can promote the dehydration and decomposition of HA ceramic phase into the more stable calcium phosphate phases, such as alpha-Ca(3)(PO(4))(2) (alpha-TCP) and Ca(4)O(PO(4))(2) at high temperatures. Comparing with pure HA ceramic manufactured under the same conditions, HA-20 vol % Ti composite with higher fracture toughness (0.987 MPa m(1/2)), bending strength (78.59 MPa), work of fracture (12.8J/m(2)), porosity (9.8%) and lower elastic modulus (75.91 GPa) is more suitable for use as hard tissue replacement. Crack deflection is the chief toughening mechanism in the composite. Histological evaluation by light microscope shows HA-20 vol % Ti composite implant could be partially integrated with newborn bone tissues after 3 weeks and fully osteointegrated at 12 weeks in vivo. The excellent biological properties of HA-20 vol % Ti composite may be contributed to the coexistence of high porosity and the decomposition products of HA phase in the composite.

Journal Article↗
PubMed2002

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS).

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS) is in progress. The study design, accrual to date, and related research projects are described. Revised accrual rates and expected recruitment are given. 15 cancers have been detected to date, from a total of 1236 screening measurements. This event rate and the tumour grades reported are compared with recent reports from other studies in women at high risk of breast cancer.

Adult↗
PubMed2001

Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase.

Cyclin E binds and activates the cyclin-dependent kinase Cdk2 and catalyzes the transition from the G1 phase to the S phase of the cell cycle. The amount of cyclin E protein present in the cell is tightly controlled by ubiquitin-mediated proteolysis. Here we identify the ubiquitin ligase responsible for cyclin E ubiquitination as SCFFbw7 and demonstrate that it is functionally conserved in yeast, flies, and mammals. Fbw7 associates specifically with phosphorylated cyclin E, and SCFFbw7 catalyzes cyclin E ubiquitination in vitro. Depletion of Fbw7 leads to accumulation and stabilization of cyclin E in vivo in human and Drosophila melanogaster cells. Multiple F-box proteins contribute to cyclin E stability in yeast, suggesting an overlap in SCF E3 ligase specificity that allows combinatorial control of cyclin E degradation.

Amino Acid Motifs↗
PubMed2001

Potential cost-effectiveness of one-time screening for lung cancer (LC) in a high risk cohort.

The development of low-dose helical computed-tomography (CT) scanning to detect nodules as small as a few mm has sparked renewed interest in lung cancer (LC) screening. The objective of this study was to assess the potential health effects and cost-effectiveness of a one-time low-dose helical CT scan to screen for LC. We created a decision analysis model using baseline results from the Early Lung Cancer Action Project (ELCAP); Surveillance, Epidemiology and End Results (SEER) registry public-use database; screening program costs estimated from 1999 Medicare reimbursement rates; and annual costs of managing cancer and non-cancer patients from Riley et al. (1995) [Med Care 1995;33(8):828-841] and Taplin et al. (1995) [J Natl Cancer Inst 1995;87(6):417-26]. The main outcome measures included years of life, cost estimates of baseline diagnostic screening and follow up, and cost-effectiveness of screening. We found that in a very high-risk cohort (LC prevalence of 2.7%) of patients between 60 and 74 years of age, a one-time screen appears to be cost-effective at $5940 per life year saved. In a lower risk general population of smokers (LC prevalence of 0.7%), a one-time screen appears to be cost-effective at $23100 per life year. Even when a lead-time bias of 1 year is incorporated into the model for a low risk population, the cost-effectiveness is estimated at $58183 per life year. Based on the assumptions embedded in this model, one-time screening of elderly high-risk patients for LC appears to be cost-effective.

Aged↗
PubMed2001

Comparison of spiral CT angiography with conventional digital subtraction angiography in the evaluation of renal transplant donors: a pilot study.

Conventional digital subtraction renal arteriography (IA-DSA) has been traditionally used as the preoperative imaging modality for assessment of renal vascular anatomy for renal transplant donors. This study evaluates the potential use of spiral CT angiography in replacing IA-DSA in the preoperative assessment of this group of patients. Seven patients underwent both spiral CT angiography and IA-DSA between October 1997 and April 1998. It is concluded that spiral CT angiography can demonstrate the number, length and location of renal arteries and it is suggested that spiral CT angiography can potentially replace IA-DSA in the preoperative assessment of renal donors.

Adult↗
PubMed2001

Differences in mesenchymal tissue repair.

Variations in certain mesenchymal tissue healing processes are not widely recognized. The current review summarizes key differences in healing mechanisms and healing potential after injury to soft tissues having different healing outcomes.

Animals↗
PubMed2001

Large drug resistance virulence plasmids of clinical isolates of Salmonella enterica serovar Choleraesuis.

Salmonella enterica serovar Choleraesuis generally causes systemic human salmonellosis without diarrhea, and therefore, antimicrobial treatment is essential for such patients. The drug resistance information on this organism is thus of high value. Serovar Choleraesuis usually harbors a virulence plasmid (pSCV) of 50 kb in size. Of the 16 clinical isolates identified to be serovar Choleraesuis, all except one harbored a pSCV and seven of them carried a pSCV of more than 125 kb in size. A pSCV was defined as a plasmid carrying spvC and characteristic deletions detected by PCR and by DNA-DNA hybridization (for the former criterion). The results of PCR, restriction fragment profiles, and Southern DNA-DNA hybridizations of the profiles all indicated that such larger pSCVs were derived from the 50-kb plasmid recombined with non-pSCVs found in some clinical isolates. Fifteen of the 17 strains, including a laboratory strain, were then tested for drug resistance against 16 antibiotics with E-test and the dilution method. The laboratory strain, which harbored a 50-kb pSCV and a 6-kb non-pSCV, was resistant only to sulfonamides (SUL), and its resistance gene, sulII, checked with PCR and DNA-DNA hybridization, was located on the 6-kb non-pSCV. All 14 clinical strains were resistant to multiple drugs. Of the 14, 7 were resistant to SUL, and the resistance gene was located on a plasmid. The sulII gene, but not bla(TEM-1), was carried only on the 6-kb non-pSCV. Of the remaining six large plasmids, three of 90 kb, two of 136 kb, and one of 140 kb, the last three were pSCVs and carried the other SUL gene (sulI) and the bla(TEM-1) gene. The six strains were also resistant to trimethoprim-sulfamethoxazole. None of the 50-kb pSCVs carried resistance genes. These drug resistance genes on the large pSCVs were apparently also acquired through recombination.

Bacterial Proteins↗
PubMed2001

Safety and immunogenicity of improved Shigella O-specific polysaccharide-protein conjugate vaccines in adults in Israel.

Data suggest that the O-specific polysaccharide (O-SP) domain of the lipopolysaccharide (LPS) of Shigella species is both an essential virulence factor and a protective antigen and that a critical level of serum immunoglobulin G (IgG) to this antigen will confer immunity to shigellosis. Because covalent attachment of polysaccharides to proteins increases their immunogenicity, especially in infants and in young children, the O-SP of Shigella species were bound to medically useful proteins, and the safety and immunogenicity of the resultant conjugates were confirmed in adults and 4- to 7-year-old children. Succinylation of the carrier protein improved the immunogenicity of Shigella conjugates in mice and increased their yield. Based on these results, a clinical trial of O-SP conjugates of Shigella sonnei and Shigella flexneri 2a bound to succinylated mutant Pseudomonas aeruginosa exotoxin A (rEPAsucc) or native or succinylated Corynebacterium diphtheriae toxin mutant (CRM9 or CRM9succ) was conducted in healthy adults. The conjugates were safe and immunogenic. S. sonnei-CRM9, S. sonnei-CRM9succ, and S. sonnei-rEPAsucc elicited significant rises of geometric mean (GM) IgG anti-LPS within 1 week of injection (P < 0.001). At 26 weeks, the GM anti-LPS levels elicited by these three conjugates were similar and higher than their prevaccination levels (P < 0.0001). GM IgG anti-LPS levels elicited by S. flexneri 2a-rEPAsucc were significantly higher than those elicited by S. flexneri 2a-rCRM9succ at all intervals after injection. At 26 weeks, the levels of IgG anti-LPS in vaccinees were higher than their prevaccination levels (P < 0.0001). The serum antibody responses were specific, as there was no significant rise of anti-LPS to the heterologous O-SP in any vaccinee. Both conjugates elicited statistically significant rises of serum antibodies to the injected carrier protein. At 6 months, these five Shigella conjugates elicited higher fold rises than similar conjugates (D. N. Taylor et al., Infect. Immun. 61:3678-3687, 1993). Based on these data, we chose S. sonnei-CRM9 and S. flexneri 2a-rEPAsucc for evaluation in children.

Adolescent↗
PubMed2000

Identification of the E2A gene products as regulatory targets of the G1 cyclin-dependent kinases.

The E2A gene products, E12 and E47, are multifunctional transcription factors that as homodimers regulate B cell development, growth, and survival. In this report, the E2A gene products are shown to be targets for regulation by the G1 cyclin-dependent kinases. Two novel G1 cyclin-dependent kinase sites are identified on the N-terminal domain of E12/E47. One site displays homology to a preferential D-type cyclin-dependent kinase site (serine 780) on the retinoblastoma susceptibility gene product (pRB) and, consistent with this homology, is more efficiently phosphorylated by cyclin D1-CDK4 than by the other cyclin-dependent kinases (CDK) that were tested. The second kinase site is phosphorylated by both cyclin D1-CDK4 and cyclin A/E-CDK2 complexes. Mutation studies indicated that phosphorylation of the cyclin D1-CDK4 site, or more potently, of both the cyclin D1-CDK4 and cyclin A/E-CDK2 sites, negatively regulates the growth suppressor function associated with the N-terminal domain of E12/E47. Transient expression studies showed that ectopic expression of cyclin D1 or E negatively regulates sequence-specific activation of gene transcription by E12/E47. Analysis of site mutants, however, indicated that inhibition of E12/E47 transcriptional activity did not require the N-terminal G1 cyclin-dependent kinase sites. Together, the results suggest that the growth suppressor and transcriptional activator functions of E12/E47 are targets for regulation by G1 cyclin-dependent kinases but that the mechanisms of regulation for each function are distinct.

Animals↗
PubMed2000

Linkage analysis of systemic lupus erythematosus induced in diabetes-prone nonobese diabetic mice by Mycobacterium bovis.

Systemic lupus erythematosus induced by Mycobacterium bovis in diabetes-prone nonobese diabetic mice was mapped in a backcross to the BALB/c strain. The subphenotypes-hemolytic anemia, antinuclear autoantibodies, and glomerular immune complex deposition-did not cosegregate, and linkage analysis for each trait was performed independently. Hemolytic anemia mapped to two loci: Bah1 at the MHC on chromosome 17 and Bah2 on distal chromosome 16. Antinuclear autoantibodies mapped to three loci: Bana1 at the MHC on chromosome 17, Bana2 on chromosome 10, and Bana3 on distal chromosome 1. Glomerular immune complex deposition did not show significant linkage to any genomic region. Mapping of autoantibodies (Coombs' or antinuclear autoantibodies) identified two loci: Babs1 at the MHC and Babs2 on distal chromosome 1. It has previously been reported that genes conferring susceptibility to different autoimmune diseases map nonrandomly to defined regions of the genome. One possible explanation for this clustering is that some alleles at loci within these regions confer susceptibility to multiple autoimmune diseases-the "common gene" hypothesis. With the exception of the H2, this study failed to provide direct support for the common gene hypothesis, because the loci identified as conferring susceptibility to systemic lupus erythematosus did not colocalize with those previously implicated in diabetes. However, three of the four regions identified had been previously implicated in other autoimmune diseases.

Anemia, Hemolytic↗
PubMed2000

Lack of evidence of an association between the carriage of virulence plasmid and the bacteremia of Salmonella typhimurium in humans.

The involvement of the virulence plasmid (pSTV) of Salmonella typhimurium in human salmonellosis was examined. Most of the 224 clinical strains isolated from the blood (53) and nonblood samples (171) contained a 90 kb or larger plasmid, most of which were pSTV. The rates of pSTV carriage in the isolates showed no statistically significant difference between those derived from the blood and those from other sources (87% vs. 83%; chi2=0.49, 0.1<P<0.9), suggesting that pSTV may not play a critical role in promoting S. typhimurium bacteremia in humans. Nine strains with representative plasmid profiles were tested for the mouse virulence. The result revealed that these clinical isolates contained all three virulent types known: the avirulent, the highly virulent when a pSTV was present, and the moderately virulent regardless of the presence or absence of pSTV. This indicated that mouse virulence of S. typhimurium did not correlate their virulence in humans. Clinical data showed that most patients with primary bacteremia had underlying immunosuppressive diseases, whereas only a few patients with secondary bacteremia had preexisting diseases (87% vs. 13%; chi2=22.73, P<0.005). It is suggested that the contribution of pSTV to S. typhimurium bacteremia in humans is likely to be limited, and both the host factor and the microbial virulence determinants on the chromosome are more important than virulence plasmid in predisposing patients to bacteremia.

Aged↗
PubMed1999

Biopharmaceutics of transmucosal peptide and protein drug administration: role of transport mechanisms with a focus on the involvement of PepT1.

Non-invasive delivery of peptide and protein drugs will soon become a reality. This is due partly to a better understanding of the endogenous transport mechanisms, including paracellular transport, endocytosis, and carrier-mediated transport of mucosal routes of peptide and protein drug administration. This paper focuses on work related to the elucidation of structure-function, intracellular trafficking, and regulation of the intestinal dipeptide transporter, PepT1.

Biological Transport↗