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Biomedical subjects

K Chua

Publications and source records attributed to K Chua.

17 recordsLinked to original sources
PubMed2003

Urinary incontinence after traumatic brain injury: incidence, outcomes and correlates.

OBJECTIVES: To document the incidence and outcome of urinary incontinence (UI) and urinary retention (UR) during acute traumatic brain injury (TBI) rehabilitation and determine associated clinical variables. METHODS: Retrospective case series. RESULTS: Eighty-four patients (mean age 44.7 +/- 17.9 years; 66 males, 18 females) with first-ever TBI within 6 weeks of injury. On admission, UI was present in 52 (62%). UR defined as post-void residual urine volumes of > 100 mls was present in eight (9.5%). Forty-six (54.8%) needed external collecting devices and six (7.1%) used indwelling catheters. Bilateral lesions, diabetes mellitus and faecal impaction were present in 70.2, 10.7 and 6.0%, respectively. UI was associated with poorer functional status (measured by the modified Barthel index) and presence of bilateral lesions (p < 0.01). UR was associated with diabetes mellitus and faecal impaction (p < 0.01). On discharge, 31 (36.9%) remained incontinent. CONCLUSION: UI is common after acute TBI and is associated with poorer functional outcome.

Adolescent↗
PubMed2002

Aerobic demands of the dance simulation game.

The purpose of this study was to assess the intensity and energy cost of dance simulation in relation to the American College of Sports Medicine (ACSM) recommendations on the quantity and quality of exercise for developing and maintaining cardiorespiratory fitness, and to assess its safety. Forty subjects (21 males and 19 females, age 17.5 +/- 0.7 years) had their heart rate (HR) and oxygen consumption (.VO(2)) measured during maximal treadmill exercise and during a dance simulation game at a self-selected level of difficulty. They were monitored for injuries during and after the study. The results showed a mean HR of 137 beats x min(-1) (139 beats x min(-1) for males and 136 beats x min(-1) for females) and a mean .VO(2) of 24.6 ml x kg(-1) x min(-1) (25.3 ml x kg(-1) x min(-1) for males and 23.8 ml x kg(-1) x min(-1) for females) during the dance simulation game test, with an estimated energy expenditure of 480 W (550 W for males and 410 W for females). The dance intensity only just meets the minimum ACSM guidelines, so dancer-players will need to play for extended periods to improve or maintain cardiorespiratory fitness or to lose weight. No injuries occurred during 201 hours of dance time.

Adolescent↗
PubMed2001

An upstream AG determines whether a downstream AG is selected during catalytic step II of splicing.

Specific mechanisms must exist to ensure fidelity in selecting the AG dinucleotide that functions as the 3' splice site during the second transesterification step of splicing. Here we show that the optimal location for this AG is within a narrow distance (19 to 23 nucleotides [nt]) downstream from the branch point sequence (BPS). Contrary to previous expectations, AGs located less than 23 nt from the BPS are always recognized, even when a second AG located more optimally downstream is used in the transesterification reaction. Indeed, the AG closest to the BPS actually dictates the precise location of the AG that engages in the reaction. This mechanism, in which the AG is identified by a general localization step followed by a precise localization step, may be used to achieve fidelity while allowing flexibility in the location of 3' splice sites.

Cell Nucleus↗
PubMed2000

Activated self-MHC-reactive T cells have the cytokine phenotype of Th3/T regulatory cell 1 T cells.

In the present study, we show that human self-MHC-reactive (autoreactive) T cell clones are functionally distinct from Ag-specific T cell clones. Self-MHC-reactive T cells exhibited helper function for B cell Ig production when cultured with non-T cells alone, and they exhibit suppressor function when cultured with PWM- or rCD40 ligand (rCD40L)-activated non-T cells, whereas tetanus toxoid (TT)-specific clones exhibited only helper function in the presence of TT with or without PWM or rCD40L. Addition of neutralizing Abs to the cultures showed that the suppression was mediated by TGF-beta but not by IL-10 or IFN-gamma. The self-MHC-reactive clones also inhibited proliferation of primary CD4+ T cells and TT-specific T cell clones, but in this case the inhibition was mediated by both IL-10 and TGF-beta. In further studies, the interactions between self-MHC-reactive T cell clones and non-T cells that led to suppressor cytokine production have been explored. We found that prestimulation of non-T cells for 8 h with PWM or for 48 h for rCD40L results in non-T cells capable of inducing self-MHC-reactive T cell to produce high levels of TGF-beta and IL-10. In addition, these prestimulation times coincided with peak induction of HLA-DR and costimulatory B7 molecule (especially CD86) expression on B cells. Finally, addition of CTLA-4/Fc or blocking F(ab')2 anti-CTLA-4 mAb, plus optimally stimulated non-T cells, to cultures of self-MHC-reactive clones inhibited the induction of TGF-beta but not IL-10 or IFN-gamma production. In summary, these studies show that activated self-MHC-reactive T cells have the cytokine phenotype of Th3 or T regulatory cell 1 and thus may be important regulatory cells that mediate oral and peripheral tolerance and prevent the development of autoimmunity.

Abatacept↗
PubMed2000

Bacteremia and skin/bone infections in two patients with X-linked agammaglobulinemia caused by an unusual organism related to Flexispira/Helicobacter species.

Two patients with Bruton's X-linked agammaglobulinemia are described with bacteremia and skin/bone infection due to an organism which by 16S rRNA gene sequence analysis was most closely related to "Flexispira" rappini (and thus designated a Flexispira-like organism, FLO) and more distantly related to the Helicobacter species. The organism required microaerobic conditions and, supplemental H(2) gas for growth and was reliably stained with acridine orange. In common with Helicobacter cinaedi infections, the focus of the FLO infection was in one case in the blood vessels or lymphatics of an extremity and in the other case in the skin and adjacent bone of an extremity. In both cases, prolonged IV antibiotic therapy was necessary to clear the infection. The susceptibility of XLA patients to FLO infection appears to be related to the fact that XLA is associated with severe B cell (humoral) immunodeficiency and thus these patients have difficulty with intravascular or intralymphatic infection. These findings elucidate the nature of FLO infections in humans and point the way to their detection and treatment.

Adult↗
PubMed1999

The RNA splicing factor hSlu7 is required for correct 3' splice-site choice.

The production of correctly spliced messenger RNA requires two catalytic splicing steps. During step II, exon 1 attacks an adenine-guanine (AG) dinucleotide at the 3' splice site. This AG is usually located between 18 and 40 nucleotides downstream from the branch site, and closer AGs are skipped in favour of AGs located more optimally downstream. At present, little is understood about how the correct AG is distinguished from other AGs. Here we describe a metazoan splicing factor (hSlu7) that is required for selection of the correct AG. In the absence of hSlu7, use of the correct AG is suppressed and incorrect AGs are activated. We investigated this loss of fidelity by analysing spliceosomes assembled in the absence of hSlu7. These studies reveal that exon 1 is loosely associated with these spliceosomes. Thus, the improperly held exon cannot access the correct AG, but can attack other AGs indiscriminately. We conclude that hSlu7 is required to hold exon 1 tightly within the spliceosome for attack on a prespecified AG.

Adenine↗
PubMed1999

Human step II splicing factor hSlu7 functions in restructuring the spliceosome between the catalytic steps of splicing.

The spliceosome catalyzes pre-mRNA splicing in two steps. After catalytic step I, a major remodeling of the spliceosome occurs to establish the active site for step II. Here, we report the isolation of a cDNA encoding hSlu7, the human homolog of the yeast second step splicing factor Slu7. We show that hSlu7 associates with the spliceosome late in the splicing pathway, but at a stage prior to recognition of the 3' splice site for step II. In the absence of hSlu7, splicing is stalled between the catalytic steps in a novel complex, the CDeltahSlu7 complex. We provide evidence that this complex differs significantly in structure from the known spliceosomal complexes, yet is a functional intermediate between the catalytic steps of splicing. Together, our observations indicate that hSlu7 is required for a structural alteration of the spliceosome prior to the establishment of the catalytically active spliceosome for step II.

Adenoviridae↗
PubMed1999

Sequence analysis and expression of a cDNA clone encoding a 98-kDa allergen in Dermatophagoides farinae.

BACKGROUND: The important dust mite allergens identified to date are of molecular weights ranging from 14 to 60 kDa. Our previous protein study indicated that the 98-kDa native paramyosin in Dermatophagoides farinae mite showed IgE reactivity with 82% of the mite-sensitive asthmatic patients suggesting that it is a novel major mite allergen. This study described the isolation and characterization of the cDNA clone encoding the 98-kDa mite allergen. METHODS: A Dermatophagoides farinae cDNA library was constructed in lambda ZAPII vector and the library was immunoscreened with a monoclonal antibody 642. The cDNA insert was sub-cloned into M13 sequencing vector for single-stranded sequencing. The whole cDNA insert was expressed in pGEX-2T Escherichia coli expression system as a fusion protein with GST. The allergenicity of the recombinant peptides was tested by skin tests and IgE immunoassay. The IgE and IgG immunoassays were performed with sera from 20 mite-allergic patients. RESULTS: The cDNA clone Df642 was 2134 bp long, coding for a polypeptide of 711 amino acid residues. Protein sequence analysis and alignment confirmed that the deduced polypeptide is a mite paramyosin which is truncated slightly at the N- and C-terminuses. In vivo skin tests and in vitro IgE-binding study showed that 62% (13/21) and 50% (10/20) of the mite-sensitive asthmatic patients reacted positively with the recombinant Dermatophagoides farinae paramyosin, respectively. CONCLUSION: The study indicated that 98-kDa mite paramyosin is an important allergen.

Adolescent↗
PubMed1998

Phosphorylation of spliceosomal protein SAP 155 coupled with splicing catalysis.

The U2 snRNP component SAP 155 contacts pre-mRNA on both sides of the branch site early in spliceosome assembly and is therefore positioned near or at the spliceosome catalytic center. We have isolated a cDNA encoding human SAP 155 and identified its highly related Saccharomyces cerevisiae homolog (50% identity). The carboxy-terminal two-thirds of SAP 155 shows the highest conservation and is remarkably similar to the regulatory subunit A of the phosphatase PP2A. Significantly, SAP 155 is phosphorylated concomitant with or just after catalytic step one, making this the first example of a protein modification tightly regulated with splicing catalysis.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Spinal injury rehabilitation in Singapore.

Traumatic spinal cord injuries (SCI) are often preventable. In order to determine the characteristics and rehabilitation outcome of our spinal injured, we carried out a retrospective study of SCI patients admitted between January 1990 and December 1995 to the only spinal rehabilitation centre in Singapore. There was a total of 231 patients with ages between 14 and 82 years. The majority (73.6%) were below the age of 50. There was a male preponderance (83.1%) and a significant proportion of foreigners (20.3%). The most common causes of injuries were falls (50.7%) and road traffic accidents (37.2%). Damage to the cervical spine predominated (53.7%), followed by the thoracolumbar junction (23.4%). At the end of rehabilitation, the number of patients who were Frankel D/E improved significantly from 61 to 136. Sixty-eight patients were able to ambulate independently without aid and total independence in activities of daily living was achieved in 45 patients. The majority (87.9%) were discharged to their own homes. Of those who returned for follow-up, 86.3% were gainfully employed at the time of injury but only 21.6% had returned to some form of vocation within 1 year.

Accidental Falls↗
PubMed1998

Cyclin E associates with components of the pre-mRNA splicing machinery in mammalian cells.

Cyclin E-cdk2 is a critical regulator of cell cycle progression from G1 into S phase in mammalian cells. Despite this important function little is known about the downstream targets of this cyclin-kinase complex. Here we have identified components of the pre-mRNA processing machinery as potential targets of cyclin E-cdk2. Cyclin E-specific antibodies coprecipitated a number of cyclin E-associated proteins from cell lysates, among which are the spliceosome-associated proteins, SAP 114, SAP 145, and SAP 155, as well as the snRNP core proteins B' and B. The three SAPs are all subunits of the essential splicing factor SF3, a component of U2 snRNP. Cyclin E antibodies also specifically immunoprecipitated U2 snRNA and the spliceosome from splicing extracts. We demonstrate that SAP 155 serves as a substrate for cyclin E-cdk2 in vitro and that its phosphorylation in the cyclin E complex can be inhibited by the cdk-specific inhibitor p21. SAP 155 contains numerous cdk consensus phosphorylation sites in its N terminus and is phosphorylated prior to catalytic step II of the splicing pathway, suggesting a potential role for cdk regulation. These findings provide evidence that pre-mRNA splicing may be linked to the cell cycle machinery in mammalian cells.

Amino Acid Sequence↗
PubMed1997

The splicing factor BBP interacts specifically with the pre-mRNA branchpoint sequence UACUAAC.

The yeast splicing factor BBP (branchpoint bridging protein) interacts directly with pre-mRNA at or very near the highly conserved branchpoint sequence UACUAAC within the commitment complex. We also show that the recombinant protein recognizes the UACUAAC sequence. Therefore, BBP is also an acronym for branchpoint binding protein. The mammalian splicing factor SF1 is a BBP ortholog (mBBP) and an E complex component, and also has branchpoint sequence specificity. The relative conservation of this region in yeast and mammals correlates well with the RNA-binding differences between BBP and mBBP, suggesting that BBP contributes to branchpoint sequence definition in both systems.

Binding Sites↗
PubMed1994

B cell differentiation defects in common variable immunodeficiency are ameliorated after stimulation with anti-CD40 antibody and IL-10.

In these studies we show that although purified B cells of patients with common variable immunodeficiency (CVI) have a normal capacity to proliferate, they manifest differentiation defects at multiple levels. Compared with controls, circulating CVI B cell populations contain reduced numbers of sIgG+ and sIgA+ cells with a commensurate increase in sIgM+ B cells, suggesting an in vivo defect in isotype switch. In addition, CVI B cells manifest Ig secretion defects on stimulation with either anti-CD40 and IL-10 or SAC and IL-2 and IL-10, which are of increasing severity for IgM, IgG, and IgA, respectively. These Ig secretion defects are not overcome by addition of a variety of cytokines, including TGF-beta, to anti-CD40-driven cultures. In further studies we show that despite the above abnormalities, CVI B cells are induced to express normal or near-normal levels of C mu, C gamma, and C alpha mRNA after 7 days of stimulation with anti-CD40 and IL-10. That this CH mRNA expression represents a recovery of CVI B cell differentiation is supported by studies of Ig secretion in which CVI B cells that are first stimulated for 7 days with anti-CD40 and IL-10 and then restimulated in coculture with activated normal allogeneic T cells and IL-10, secrete substantial levels of IgM and IgG and increased amounts of IgA. Overall, therefore, CVI B cell function can be significantly improved by maintenance in culture. These data suggest the abnormalities of B cell differentiation in CVI are reversible and that the defect is a form of B cell anergy.

Adult↗