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Biomedical subjects

H H Lim

Publications and source records attributed to H H Lim.

At least 37 records · Page 2Linked to original sources

Protective role of superoxide dismutase in rat eustachian tubal mucosa against acute otitis media induced by upper respiratory tract infection.

Superoxide dismutase has been known to play a role as an anti-oxidative system against oxidative injury during acute inflammation. To investigate the role of superoxide dismutase in eustachian tubal mucosa during acute otitis media (AOM), an animal model was made. Sprague-Dawley rats were inoculated with Streptococcus pneumoniae through the nasal cavity following development of virus-induced upper respiratory infection. The animals were divided into three groups according to their tympanic cavity conditions following bacterial inoculation; inoculated animals with no resultant AOM (no-AOM), animals with resultant AOM (AOM) and animals with resolving otitis media (recovery). The changes of superoxide dismutase in each tubal mucosa were compared with that of the normal control using immunohistochemistry and immunoblotting methods. On Western blot, there were little changes of optical density and surface area in no-AOM (213.5 +/- 22.4, 13.2 +/- 0.8 mm2) and recovery group (219.3 +/- 18.7, 14.8 +/- 0.7 mm2) compared to the normal control (223.5 +/- 26.2, 16.7 +/- 0.4 mm2). However, a marked decrease was found in the AOM model (167.6 +/- 19.3, 6.5 +/- 0.9 mm2). These findings suggest that superoxide dismutase may play a role in protecting tubal mucosa from free radical injury during AOM.

Acute Disease↗

The operative treatment of closed tibial fractures.

The tibia is a subcutaneous bone. Operative fixation of tibial fractures is a demanding undertaking. Thirty-five patients with 36 tibial fractures were admitted to our institution between May 1995 and April 1996. The patients were predominantly male (male to female ratio of 4) and the average age of the patients was 31.4 years (range 14 to 67 years). Ten fractures were located in the proximal third, 18 in the middle third and 8 in the distal third. The indications for operation included displaced intra-articular fragments, failed conservative treatment, compartment syndrome, multiple fractures and unstable fracture configuration. Operative procedures included plating in 29 cases and nailing in 7 cases. These patients were reviewed retrospectively and assessed for complications and radiological and functional outcome. The overall results were satisfactory in 88.9% and poor in 11.1%. The complications were reviewed and various factors affecting the incidences analysed. Three deep infections occurred. All were found after discharge from inpatient care. A prolonged interval between admission and surgery as well as high energy of impact are thought to be the main contributing factors.

Adolescent↗

Clinical experiences with acute mastoiditis--1988 through 1998.

The incidence of acute mastoiditis has declined dramatically during the postantibiotic era. Even so, antibiotic-resistant or unusual pathogens can still cause this disease entity. At our hospital, we documented an increase in antibiotic-resistant and atypical pathogens such as Actinomyces spp. and Mycobacterium tuberculosis. In this paper, we discuss the optimal diagnosis and treatment strategy for acute mastoiditis, and we describe our retrospective review of 13 patients with mastoiditis who were treated at our hospital from 1988 through 1998. Eight of these patients recovered following treatment with intravenous antibiotics, with or without myringotomy, and five who had complications of disease were managed surgically. Among these five, one developed chronic otitis media and one developed cholesteatoma 3 years later. For patients with acute mastoiditis, we emphasize the need to be aware of any unusual pathogens that do not respond to empiric antibiotic therapy.

Acute Disease↗

Selective thoracic fusion of King II scoliosis with segmental spinal instrumentation.

Segmental spinal instrumentation with Harrington rod secured to the spine by sublaminar wires was a popular method of scoliosis correction in 1980's. It was gradually replaced by newer rod-hook systems due to concern about neurological complications. However, correction of type II and III curves by selectively fusing the thoracic curves with these new instruments has resulted in poor results in some cases. The aim of this study is to review the result of selective thoracic fusion treated by segmental spinal instrumentation. Between January 1989 to October 1994, 31 patients with King II scoliosis were treated operatively in our unit. These consisted of 29 girls and 2 boys. The mean age of these patients were 11.3 years. The study population consisted of 21 Chinese, 5 Malays and 5 Indians. In one patient, the thoracic curve was convex to the left whilst the thoracic curves in the majority were to the right. The surgery was performed by three surgeons using harrington rods and posterior fusion with autograft. Anterior releases were also required in eight patients to increase flexibility. The curve correction obtained was an improvement from a average preoperative cobb's angle of 71.5 degrees to 39.5 degrees postoperatively. After an average follow-up period of 77.9 months, the correction deteriorated by 22% in the thoracic curve and 59% in the lumbar spine without disturbance to truncal balance. Only one sublaminar wire broke. However, no implant failure or removal has to be performed as yet. This technique appears useful in our institution with minimal morbidity.

Adolescent↗

Identification and characterization of a putative C. elegans potassium channel gene (Ce-slo-2) distantly related to Ca(2+)-activated K(+) channels.

Two putative homologues of large conductance Ca(2+)-activated K(+) channel alpha-subunit gene (slowpoke or slo) were revealed by C. elegans genome sequencing. One of the two genes, F08B12.3 (Ce-slo-2), shows a relatively low amino acid sequence similarity to other Slo sequences and lacks key functional motifs, which are important for calcium and voltage sensing. However, its overall structure and regions of homology, which are conserved in all Slo proteins, suggest that Ce-SLO-2 should belong to the Slo channel family. We have cloned a full-length cDNA of the Ce-slo-2, which encodes a protein containing six putative transmembrane segments with a K(+)-selective pore and a large C-terminal cytosolic domain. Green fluorescent protein (GFP) and whole-mount immunostaining analyses revealed that Ce-slo-2 is specifically expressed in neuronal cells at the nerve ring, at the ventral nerve cord of the mid-body, and at the tail region. We have also identified a putative human counterpart of Ce-slo-2 from a human brain EST database, which shows a stretch of highly conserved amino acid residues. Northern blot and mRNA dot blot analyses revealed a strong and specific expression in brain and skeletal muscle. Taken together, our data suggest that Ce-slo-2 may constitute an evolutionarily conserved gene encoding a potassium channel that has specific functions in neuronal cells.

Amino Acid Sequence↗

Expression of vascular endothelial growth factor in otitis media.

Increased vascular permeability and endothelial cell growth are important in the pathogenesis of otitis media with effusion (OME) and the vascular endothelial growth factor (VEGF) is known to play an important role in the increased vascular permeability and angiogenesis. To date, at least five isoforms of the VEGF family have been identified as VEGF transcripts, encoding polypeptides of 206, 189, 165, 145 and 121, but their physiological roles are unclear. The purpose of this study was to investigate the expression of VEGF, in both endotoxin-induced OME of the rat and human otitis media. We instilled endotoxin and saline as a control into the middle ear cavity of the rat. Middle ear mucosa were taken at 0 h, 1 h, 3 h, 6 h, 12 h, 1 day, 3 days, 7 days and 14 days and the expression of VEGF mRNA and VEGF protein was evaluated using semi-quantitative RT-PCR and immunohistochemistry. Expression of VEGF164 mRNA and VEGF120 mRNA was first identified 1 h after endotoxin instillation and was dramatically increased over the period 6 h-1 day and then progressively decreased by day 7. The level of expression of VEGF120 mRNA was slightly higher than that of VEGF164 mRNA and that of VEGF164 mRNA was much higher than that of VEGF188 mRNA. Immunostaining revealed expression of VEGF during 6 h to day 3 and its expression was localized to ciliated cells and some inflammatory cells. We also performed RT-PCRs of cDNA from middle ear fluids of 8 human OME patients and middle ear mucosa of 4 chronic otitis media patients for the identification of VEGF mRNA expression. VEGF121 mRNA was highly expressed in all samples compared with VEGF165 mRNA. These results suggest that VEGF may be primarily responsible for increased vascular permeability and endothelial cell growth in OME and that VEGF seems to play a significant role in the pathogenesis of OME.

Animals↗

External quality assurance in Malaysia.

An activity supportive of the MOH QA Programme, the National EQAS for clinical chemistry monitors for analytical performance in core routine biochemical testing by the pathology laboratories, with unsatisfactory performance scores serving to alert against deficiencies or problems and the scores in subsequent challenges providing the feedback of effectiveness of remedial actions taken. While unacceptable individual analyte performance score (variance index score, VIS) indicated problems in instruments, reagent and calibrators, or the use of inherently poorer methods, repeated occurrence of unsatisfactory OMRVIS was traceable to generally poor laboratory management of usually inadequately-equipment small laboratories. The outcome has been one of slow but gradual improvement in the overall performance of participating laboratories, with a move towards methods upgrading and standardization to achieve greater concordance of results. Presently, the programme is limited to 61 government and 4 private hospital laboratories in the country for 12 commonly assayed clinical biochemistry analytes. It is hoped that the NEQAS could be extended to the other private laboratories and that of academic institutions. However, this is dependent to a large extent on the manpower and financial support obtainable by the organizing body of the programme in the future. Belk and Sunderman, 1947 demonstrated that laboratories participating in an quality assessment scheme could rapidly and dramatically improve their analytical performance. In some countries, participation has become mandatory, and acceptable performance is a requirement in laboratory accreditation. The need and value of the NEQAP is, therefore, evident. While there may be limitations in the national programme. efforts are being made at improving the programme within the means and resources of the organising body. The goals of the NEQAP are not just to monitor performance but also to educate. On this, matters related to and supportive of these goals have also been pursued. The annual workshop/forum on quality controls had allowed exchange of information between representatives of participating laboratories and the organising body. Recently in the 1997 MOH Quality Improvement evaluation, Quality Control has been evaluated together with the other 17 such activities. The study on knowledge, attitude and practice has provided the necessary feedback and will be used for future planning in making efforts at increasing the effectiveness and benefits of the all QC activities including this NEQAP for clinical chemistry. In addition, there is a need to look into areas such as selection of methods and test systems, and improvement of continuing education, training as well as research in quality improvement as suggested by the Quality Improvement evaluation.

Clinical Chemistry Tests↗

Asbestosis in Malaysia: report on first two cases.

The first two cases of asbestosis in Malaysia are reported. Both had considerable occupational exposure to asbestos dust in the past, with a long latency period exceeding 30 years. One case presented with distinctive clinical and radiological features, while the other case was only confirmed by histological diagnosis. The usefulness of modern investigation techniques such as CT scan in the diagnosis of asbestosis is also illustrated.

Asbestosis↗

Scoliosis in a patient with lipodystrophy--treatment difficulties and literature review.

A 12 year-old Chinese schoolgirl presented with left-sided scoliosis at the age of 9 years. She has a rare defect in lipid metabolism, which is not known to be associated with spinal deformity. Her scoliotic curve deteriorated despite bracing. We report a rare occurrence of scoliosis in patient with lipodystrophy and the difficulty of using instrumented fusion in treating this condition.

Adolescent↗

Cdc20 is essential for the cyclosome-mediated proteolysis of both Pds1 and Clb2 during M phase in budding yeast.

Chromosome separation during the cell-cycle transition from metaphase to anaphase requires the proteolytic destruction of anaphase inhibitors such as Pds1 [1-3]. Proteolysis of Pds1 is mediated by a ubiquitin-protein ligase, the anaphase-promoting complex (APC) or cyclosome [4,5]. The APC is also necessary for the ubiquitin-dependent degradation of mitotic cyclins in late telophase as cells exit mitosis [6-9]. Although phosphorylation seems to be involved [10], it is not clear what activates the APC at the onset of anaphase. In Saccharomyces cerevisiae, chromosome segregation also requires the CDC20 gene, whose product contains WD40 repeats [11,12]. We have investigated the functional relationship between the APC and the Cdc20 protein. We present evidence that strongly suggests that Cdc20 is an essential regulator of APC-dependent proteolysis such that in the absence of Cdc20, cells are unable to degrade either Pds1 at the onset of anaphase or the mitotic cyclin Clb2 during telophase. This notion is consistent with our observations that Cdc20 is localized in the nucleus and co-immunoprecipitates with an APC component, Cdc23.

Anaphase-Promoting Complex-Cyclosome↗

Uncemented total hip replacements using the Mecron acetabular cup--a prospective study.

The uncemented threaded cup gained some popularity over the past decade, firstly as a revision and then as a primary procedure. We elected to test the Mecron acetabular threaded cup system as a routine hip replacement. As there was no matched femoral component, we decided to use an uncemented femoral stem of the Ring system of the hip prosthesis. All patients were logged on to the study at the outset although this is not a controlled comparison with another system. Patients were assessed annually for up to 4-years at the time of reporting. There were 104 primary total hip replacements in 99 patients between 1987 and 1991. The mean follow-up for this report was 22.5 months (range 12 to 48 months). The mean age was 76.3 years (range 24 to 88 years) and the female to male sex ratio was 3.3:1. Within the study period, 5 hips required revision, all for acetabular loosening. Patients were assessed by the modified Harris score annually and 60.6% of the cases had an excellent or good short-term result. Poor results were observed in 18.3% of cases. Radiographic studies of the acetabular component were undertaken annually and measured. Migration and tilting of the acetabular cup was observed in all cases. Heterotropic bone formation occurred in 10 patients. As a result of these poor results, the prosthesis was abandoned in 1991. The cohort of patients continues to be followed. Failure of the Mecron acetabular cup in our series was mainly due to tilting and migration and not untwisting.

Acetabulum↗

Cdc20, a beta-transducin homologue, links RAD9-mediated G2/M checkpoint control to mitosis in Saccharomyces cerevisiae.

In the budding yeast Saccharomyces cerevisiae, the DNA damage-induced G2 arrest requires the checkpoint control genes RAD9, RAD17, RAD24, MEC1, MEC2 and MEC3. These genes also prevent entry into mitosis of a temperature-sensitive mutant, cdc13, that accumulates chromosome damage at 37 degrees C. Here we show that a cdc13 mutant overexpressing Cdc20, a beta-transducin homologue, no longer arrests in G2 at the restrictive temperature but instead undergoes nuclear division, exits mitosis and enters a subsequent division cycle, which suggests that the DNA damage-induced G2/M checkpoint control is not functional in these cells. This is consistent with our observation that overexpression of CDC20 in wild-type cells results in increased sensitivity to UV irradiation. Overproduction of Cdc20 does not influence the arrest phenotype of the cdc mutants whose cell cycle block is independent of RAD9-mediated checkpoint control. Therefore, we suggest that the DNA damage-induced checkpoint controls prevent mitosis by inhibiting the nuclear division pathway requiring CDC20 function.

Cdc20 Proteins↗

Spindle pole body separation in Saccharomyces cerevisiae requires dephosphorylation of the tyrosine 19 residue of Cdc28.

In eukaryotes, mitosis requires the activation of cdc2 kinase via association with cyclin B and dephosphorylation of the threonine 14 and tyrosine 15 residues. It is known that in the budding yeast Saccharomyces cerevisiae, a homologous kinase, Cdc28, mediates the progression through M phase, but it is not clear what specific mitotic function its activation by the dephosphorylation of an equivalent tyrosine (Tyr-19) serves. We report here that cells expressing cdc28-E19 (in which Tyr-19 is replaced by glutamic acid) perform Start-related functions, complete DNA synthesis, and exhibit high levels of Clb2-associated kinase activity but are unable to form bipolar spindles. The failure of these cells to form mitotic spindles is due to their inability to segregate duplicated spindle pole bodies (SPBs), a phenotype strikingly similar to that exhibited by a previously reported mutant defective in both kinesin-like motor proteins Cin8 and Kip1. We also find that the overexpression of SWE1, the budding-yeast homolog of wee1, also leads to a failure to segregate SPBs. These results imply that dephosphorylation of Tyr-19 is required for the segregation of SPBs. The requirement of Tyr-19 dephosphorylation for spindle assembly is also observed under conditions in which spindle formation is independent of mitosis, suggesting that the involvement of Cdc28/Clb kinase in SPB separation is direct. On the basis of these results, we propose that one of the roles of Tyr-19 dephosphorylation is to promote SPB separation.

Amino Acid Sequence↗

Dephosphorylation of threonine 169 of Cdc28 is not required for exit from mitosis but may be necessary for start in Saccharomyces cerevisiae.

Entry into mitosis requires activation of cdc2 kinase brought on by its association with cyclin B, phosphorylation of the conserved threonine (Thr-167 in Schizosaccharomyces pombe) in the T loop, and dephosphorylation of the tyrosine residue at position 15. Exit from mitosis, on the other hand, is induced by inactivation of cdc2 activity via cyclin destruction. It has been suggested that in addition to cyclin degradation, dephosphorylation of Thr-167 may also be required for exit from the M phase. Here we show that Saccharomyces cerevisiae cells expressing cdc28-E169 (a CDC28 allele in which the equivalent threonine, Thr-169, has been replaced by glutamic acid) are able to degrade mitotic cyclin Clb2, inactivate the Cdc28/Clb2 kinase, and disassemble the anaphase spindles, suggesting that they exit mitosis normally. The cdc28-E169 allele is active with respect to its mitotic functions, since it complements the mitosis-defective cdc28-1N allele. Whereas replacement of Thr-169 with serine affects neither Start nor the mitotic activity of Cdc28, replacement with glutamic acid or alanine renders Cdc28 inactive for Start-related functions. Coimmunoprecipitation experiments show that although Cdc28-E169 associates with mitotic cyclin Clb2, it fails to associate with the G1 cyclin Cln2. Thus, an unmodified threonine at position 169 in Cdc28 is important for interaction with G1 cyclins. We propose that in S. cerevisiae, dephosphorylation of Thr-169 is not required for exit from mitosis but may be necessary for commitment to the subsequent division cycle.

Alleles↗

Age-related changes of IgA immunocytes and serum and salivary IgA after tonsillectomy.

For determining treatment options of tonsillar diseases, the authors compared immunohistochemical differences for IgA immunocytes and measured the changes in concentrations of the serum immunoglobulin A and salivary secretory immunoglobulin A before and after tonsillectomy according to age in 126 cases (60 control cases, 66 tonsillectomy cases). The serum IgA and salivary SIgA concentrations of the control group reached to adult's level at the age of 11 to 13. In the tonsillectomies, the serum IgA concentrations below the age of 10 were higher than that of controls and were decreased to the levels of the controls after tonsillectomy in all ages and the salivary SIgA concentrations were decreased to the levels of the controls at the 30th postoperative day, especially at the age of 5 to 7 and 8 to 10. Morphometric features of tonsils in the group below the age of 8 were more active than those in the group above the age of 8 in the controls. In the tonsillectomies, morphometric features of the tonsils were similar to those in the group above the age of 8, but the reticular part of the crypt epithelium remained significantly. Total number of IgA immunocytes was the highest at the age of 5 to 7 with a decline by age, especially at the age of 19 in the controls. In the tonsillectomy group, the number of IgA immunocytes of the extrafollicular area and the reticular part of crypt epithelium decreased below the levels of the control group. In conclusion, tonsils in preschool children are important as a local immunologic defense mechanism, but no significant changes in the immunologic system occurs after tonsillectomy.

Adolescent↗

Review of results of ankle fracture fixation in Alexandra Hospital (Singapore) between January 1987-April 1990.

In 67 consecutive cases of ankle fracture treated operatively in Alexandra Hospital in Singapore, 35 ankles (53.7%) were available for review of the post-operative results. Thirteen fractures were of AO type A, 13 were type B and 9 type C. These patients had a minimum follow-up period of 16 months. They were assessed subjectively with a questionnaire and objectively by measuring the ankle movements. Good or excellent subjective results were obtained in 71% of the patients, while functional ankle scores were good or excellent in 88.5% of cases. Some restriction of ankle motion was present in 33.9% of patients. Difficulty in squatting was the most common complaint.

Adolescent↗

Bilateral acute haemangioma of the knee.

Recurrent knee swelling is a common orthopaedic problem which sometimes can be a diagnostic enigma. We report a case of bilateral haemangioma of the knee, which presented clinically after trauma, as an unusual cause of knee swelling. This case demonstrates the therapeutic difficulties in surgical treatment of an haemangioma and emphasises the need for complete excision of this lesion. We further postulate that the aetiology of these lesions was possibly a result of trauma initiated growth of pre-existing haemangiomata.

Adult↗