Biomedical subjects

S K Tan

Publications and source records attributed to S K Tan.

At least 37 records · Page 2Linked to original sources

PubMed1996

The yeast and mammalian isoforms of phosphatidylinositol transfer protein can all restore phospholipase C-mediated inositol lipid signaling in cytosol-depleted RBL-2H3 and HL-60 cells.

The mammalian phosphatidylinositol transfer proteins (PITP) and the yeast Saccharomyces cerevisiae PITP (SEC14p) that show no sequence homology both catalyze exchange of phosphatidylinositol (PI) between membranes compartments in vitro. In HL-60 cells where the cytosolic proteins are depleted by permeabilization, exogenously added PITPalpha is required to restore G protein-mediated phospholipase Cbeta (PLCbeta) signaling. Recently, a second mammalian PITPbeta form has been described that shows 77% identity to rat PITPalpha. We have examined the ability of the two mammalian PITPs and SEC14p to restore PLC-mediated signaling in cytosol-depleted HL-60 and RBL-2H3 cells. Both PITPalpha and PITPbeta isoforms as well as SEC14p restore G protein-mediated PLCbeta signaling with a similar potency. In RBL-2H3 cells, crosslinking of the IgE receptor by antigen stimulates inositol lipid hydrolysis by tyrosine phosphorylation of PLCgamma1. Permeabilization of RBL cells leads to loss of PLCgamma1 as well as PITP into the extracellular medium and this coincides with loss of antigen-stimulated lipid hydrolysis. Both PLCgamma1 and PITP were required to restore inositol lipid signaling. We conclude that (i) because the PI binding/transfer activities of PITP/SEC14p is the common feature shared by all three transfer proteins, it must be the relevant activity that determines their abilities to restore inositol lipid-mediated signaling and (ii) PITP is a general requirement for inositol lipid hydrolysis regardless of how and which isoform of PLC is activated by the appropriate agonist.

Animals↗

PubMed1996

ARF and PITP restore GTP gamma S-stimulated protein secretion from cytosol-depleted HL60 cells by promoting PIP2 synthesis.

BACKGROUND: In many cell types, including neutrophils and HL60 cells, there is an absolute requirement for a GTP-dependent step to elicit Ca(2+)-regulated secretion. Neutrophils and HL60 cells secrete lysosomal enzymes from azurophilic granules; this secretion is inhibited by 1% ethanol, indicating that phosphatidate (PA) produced by phospholipase D (PLD) activity may be involved. PLD can use primary alcohols in preference to water during the hydrolytic step, generating the corresponding phosphatidylalcohol instead of PA, its normal product. As ARF (ADP-ribosylation factor) proteins regulate PLD activity and are implicated in constitutive vesicular traffic, we have investigated whether ARF is also required for GTP-dependent secretion in HL60 cells. RESULTS: We have used a cell-permeabilization protocol that allows HL60 cells to become refractory to stimulation with GTP gamma S plus 10 microM Ca2+ with regard to secretion and PLD activity. Permeabilization with streptolysin O for 10 minutes permitted the loss of freely diffusable cytosolic proteins, including ARF proteins. Fractions derived from brain cytosol, enriched in ARF proteins, restored secretory function and PLD activity. The major contaminating protein present in these ARF-enriched fractions was identified as phosphatidylinositol transfer protein (PITP). Unexpectedly, PITP was also found to restore GTP gamma S-dependent secretion. Restoration of secretory function was characterized using recombinant proteins, rARF1 and rPITP alpha and rPITP beta. The rARF1 protein restored both secretory function and PLD activity, whereas PITP only restored secretory function. However, both ARF and PITP were capable of stimulating phosphatidylinositol bis phosphate (PIP2) synthesis. CONCLUSIONS: ARF and PITP restore secretory function in cytosol-depleted cells when stimulated with GTP gamma S plus Ca2+. We have previously shown that PITP participates in the synthesis of PIP2. In comparison, ARF1 activates PLD, producing PA, which is a known activator of phosphatidylinositol-4-phosphate 5 kinase, the enzyme responsible for PIP2 synthesis. We propose that ARF and PITP both restore exocytosis by a common mechanism-promoting PIP2 synthesis.

ADP-Ribosylation Factor 1↗

PubMed1996

Regulation of topoisomerase II expression during the VM-26 induced differentiation of IW32 murine erythroleukemia cells.

The effect of VM-26, a topoisomerase II targeting drug, on IW32 murine erythroleukemia cells was investigated. The VM-26 induced IW32 cells to differentiate at a non-toxic but cytostatic concentration (0.01 microgram/ml). More than 40% of the cells were induced to synthesize hemoglobin, and cells were arrested in G2/M phase of the cell cycle. Levels of beta-globin mRNA also increased significantly. Cells became committed to erythroid maturation after 16 h of continuous drug exposure. Replacement with fresh VM-26 after 48 h of drug treatment further increased the hemoglobin containing cells to greater than 80%. Unlike other drug induced erythroleukemia cell differentiation, c-myc mRNA expression was not affected by VM-26. Inhibition of topoisomerase II activity was observed during the first 12 h of VM-26 treatment; however, elevated enzyme activity was found thereafter. Northern blot analysis showed significant increase in the expression of topoisomerase IIalpha mRNA at 12 and 24 h after VM-26 addition. These findings indicate that VM-26 inhibited the activity of topoisomerase II and promoted the committed differentiation of IW32 cells along the erythroid pathway. In addition, a parallel increase in mRNA and activity levels of topoisomerase II in differentiated cells suggests that regulation of the enzyme expression occurred in the VM-26 induced erythroid maturation.

Animals↗

PubMed1996

Comparison of various interpositional materials in the prevention of transphyseal bone bridge formation.

Various interpositional materials, except muscle, have been used to prevent transphyseal bone bridge formation after resection of the damaged physeal plate. In this animal model, muscle was used as an interpositional material, and its effectiveness was compared with that of 3 known materials (fat, physeal allograft, and iliac apophyseal autograft). Five experiments were done on the distal femoral physis of 40 skeletally immature 3-month-old New Zealand white rabbits. The rabbits were divided into 5 groups, each containing 8 rabbits. A standard defect was created in the lateral distal physis of the left femur in all the rabbits. In Group A, there was no interpositional material. Vastus lateralis muscle, groin fat, physeal allograft, and iliac apophyseal autograft were inserted into the femoral defect in Groups B, C, D, and E, respectively. The right femur served as a sham control for the animals. The animals were sacrificed at 12 weeks after surgery. The results of limb length discrepancy and angular deformity of the groups with interpositional material were compared with those of Group A (experimental control). Muscle, fat, and iliac apophyseal autografts had less severe limb length discrepancy and angular deformity. These differences were statistically significant, whereas the differences between allograft and experimental control were statistically insignificant.

Adipose Tissue↗

PubMed1996

Comparing staple fixation to buttress plate fixation in high tibial osteotomy.

A retrospective study was made between July 1988 and March 1992, of 171 patients (223 knees) who had high tibial osteotomy at the Singapore General Hospital. Seventy-four cases (97 knees) had buttress plate fixation and 97 cases (126 knees) had staple fixation. The mean postoperative Hospital for Special Surgery Knee Score was 87.0 for the buttress plate group and 87.4 for the staple group. The difference was statistically not significant (P > 0.05). The hospitalisation stay was shorter in the staple fixation group as compared to the buttress plate group (P < 0.05). However, the mean rehabilitation time was shorter in the buttress plate group as compared to the staple fixation group (P < 0.05). The incidence of wound infection was higher among those fixed with buttress plate (9 cases) as compared to those fixed with staple (1 case). The difference was statistically significant (P < 0.05). Buttress plate fixation did not seem to eliminate the risk of non-union of the osteotomy (4 out of 126 osteotomies compared to 3 out of 97 in the staple group), neither did it prevent recurrence of varus deformity (2 out of 126 osteotomies). Overall it would appear that buttress plating did not have any significant advantage over staple fixation for high tibial osteotomy.

Female↗

PubMed1996

Arthroscopic treatment of osteochondral lesion of the talus.

A retrospective study of the arthroscopic treatment of osteochondral lesions of the talus in 25 patients was conducted. The follow-up period ranged from 1 to 4 years with an average of 2 years. Of the 25 patients, 20 could recall a history of injury. The diagnosis could be made by standard anteroposterior and lateral X-rays in 22 out of 25 patients. The standard anteromedial and anterolateral portals were usually sufficient. Patients with stage I and II lesions did well uniformly. In the 16 patients with stage III and IV lesions, good results were obtained in 12 and fair in 4. Morbidity was minimal.

Ankle Injuries↗

PubMed1996

Factors affecting healing of below knee amputation.

Between January and December 1992, 54 diabetic patients with 60 below knee amputations performed in the Department of Orthopaedic Surgery O, Singapore General Hospital were available for evaluation. The average follow-up period was 16.3 months with a range of 13 to 24 months. Five patients had stump necrosis and above knee amputation was performed. Eight patients had partial stump necrosis and required debridement with or without secondary procedures. The other patients had uneventful stump healing which was defined as healing of the stump wound without complications and remained intact for at least 6 months after surgery. Absence of popliteal pulse, presence of central cardiovascular disease and absence of intraoperative skin flap bleeding were found to be associated with higher incidence of stump necrosis.

Adult↗

PubMed1996

Popliteal artery pseudoaneurysm caused by an osteochondroma--a traditional medicine massage sequelae.

We report an unusual case of a popliteal aneurysm complicating a distal femoral osteochondroma caused by the repeated massages of a traditional medicine practitioner (sinseh). Management was by excision of the exostosis and reconstruction of the damaged arterial segment by a reversed long saphenous vein graft. We advice against massage over an osteochondroma on the distal medial aspect of the femur and suggest prophylactic removal of such lesions because of this potential complication.

Adolescent↗

PubMed1995

Congenital perforations of the triangular fibrocartilage of the wrist.

A cadaveric study of the triangular fibrocartilage of the wrist in the foetus and infant revealed a high incidence of congenital perforation. In the second half of the study, wrist arthrography in foetal and infant cadavers with crown-rump length of more than 20 cm followed by dissection of the wrist joints showed good correlation between the two. In 60 cadavers there were 11 with bilateral perforations and five had unilateral perforation. This gave a total of 27 perforations in 120 wrist joints studied.

Arthrography↗

PubMed1995

Effect of growth hormone on bone marrow grafts in fracture healing--an experimental study in rabbits.

The lack of effectiveness of growth hormone in stimulating the healing of fresh fractures has been attributed to the presence of insufficient precursor osteogenic cells at the fracture site for the growth hormone to exert its influence. We tested the effect of growth hormone on healing in a rabbit non-union model after injection of autogenous marrow cells into the fracture gap. Two millilitres of bone marrow were injected percutaneously into 1 cm diaphyseal defects of rabbit radii. The test group was given subcutaneous human recombinant growth hormone at 0.3 IU/kg/day in divided doses for 2 weeks, while the control group received subcutaneous saline injections. Biomechanical, radiological and callus calcium content assessments were carried out at 4 and 7 weeks. There was significantly increased tensile strength and callus calcium concentration in the group given growth hormone both at 4 and 7 weeks but there was no significant difference in stiffness or in callus volume in the 2 groups. These data suggest that growth hormone can enhance the osteogenic potential of bone marrow as a graft in the treatment of fracture non-union.

Animals↗

PubMed1995

Infection in diabetic patients with ankle fractures.

Between January 1992 to June 1993, 93 ankle fractures underwent surgical treatment, of which, 10 patients were diabetic and 83 were non-diabetic. Infection occurred in 5 patients and all belonged to the diabetic group. The average follow-up period of the infected cases was 16.2 months. Wound infection occurred in 4 patients treated with open reduction and internal fixation. An infected pressure sore developed in the other patient treated initially in a below-knee cast for which arthrodesis of the ankle was performed. Infection was resistant to treatment in 2 patients and they ended up with below-knee amputation. Infection resolved in 3 patients with treatment. Of these, 1 developed neuropathic ankle joint and the other 2 achieved fracture union.

Aged↗

PubMed1995

Surgical treatment of symptomatic accessory navicular.

The accessory navicular is a known cause of foot pain. When symptomatic and conservative measures have failed, surgical intervention may be required. Simple excision of the ossicle or the Kidner procedure with transplantation of tibialis posterior tendon to the undersurface of the navicular bone may be done. Eighteen patients with symptomatic accessory navicular were reviewed at the Singapore General Hospital, Department of Orthopaedic Surgery 'O' Unit. All 18 patients had foot pain and restriction of activities. Thirteen noticed a prominence on the medial side of the affected foot and 7 had difficulty with shoe fitting. Nine underwent simple excision of the ossicle while the other 9 had the Kidner procedure done. The average follow-up period was 3.1 years. Both the simple excision and the Kidner procedure were equally successful in relieving symptoms in 15 out of the 18 cases. The Kidner procedure did not confer any particular advantage over simple excision.

Adolescent↗

PubMed1995

Vascular assessment in the neuropathic diabetic foot.

Diabetic foot infections, a common source of morbidity and mortality, often have been related to vasculopathy and neuropathy in its etiopathogenesis, especially in the elderly person with diabetes. However, blood flow in the neuropathic diabetic foot has not been evaluated extensively, and there is evidence of abnormal blood flow patterns in the neuropathic diabetic foot unrelated to ischemia. The authors studied young persons with diabetes, with varying degrees of neuropathy, to assess the extent of vasculopathy in their lower limbs. Twelve young persons with insulin-dependent (Type I) diabetes (mean age, 36.1 +/- 1.975 years) and peripheral neuropathy, all of whom had previous surgery for diabetic foot infections, were identified. Confirmatory evidence of neuropathy was made using electromyographic studies and clinical tests that showed severe peripheral neuropathy. The results of vascular assessment of both lower limbs did not reveal any change in the pulse wave velocities from the popliteal to the digital vessels of the big toe as compared with correspondingly matched controls. There also was no significant stenosis in any of the vessels studied as far as the level of the dorsalis pedis and posterior tibial vessels. The normal triphasic pattern of arterial blood flow was lost. A monophasic pattern was present in all patients with prolonged diastolic flow at the level of the dorsalis pedis and posterior tibial arteries and distally. The pulsatility index was 3.14 +/- 0.81 as compared with 9.85 +/- 4.2. Mean toe pressures in the patient with diabetes was 64.17 +/- 20.87 mm Hg as compared with 98.23 +/- 10.12 mm Hg in controls. A linear correlation of decreasing toe pressures with increasing severity of neuropathy was seen (R = 0.7). The data suggest that changes exist in the blood flow patterns in young patients with diabetes and neuropathy, even in the absence of lower limb ischemia.

Adult↗

PubMed1995

Long-term results of free vascularized fibular graft. A clinical and radiographic evaluation.

Seven patients who had free vascularized fibular grafts for bone defects > 6 cm (mean, 16.6 cm) were studied retrospectively. There were 5 cases of tumor, 1 pseudoarthrosis, and 1 chronic osteomyelitis. The average followup period was 9.2 years (range, 5.2-11.3 years). Of the 5 patients with grafts to the lower limb, 1 showed a 30% reduction in bone width as seen on anteroposterior radiographs, whereas 4 patients had increases ranging from 44% to 100% (average, 66%). There were 4 graft stress fractures, of which 1 developed eventual shortening of 2.5 cm. One graft had pseudoarthrosis involving the proximal graft-host junction that required secondary procedures with autogenous cancellous bone grafting, with eventual limb-length shortening of 5 cm. All other graft-recipient junctions healed primarily. The Functional Evaluation Score ranged from 60% to 100% of normal function (mean, 85%). Three patients were able to return to sports participation. Mild weakness of the extensor hallucis longus in the donor limb was observed in 5 patients. Two patients had mild loss of plantar flexion, and 4 had limitation of dorsiflexion affecting the ankle of the donor limb.

Adolescent↗

PubMed1995

Failed back surgery syndrome: differentiating epidural fibrosis and recurrent disc prolapse with Gd-DTPA enhanced MRI.

The failed back surgery syndrome (FBSS) is a difficult diagnostic problem. Two of the more common causes of FBSS are epidural fibrosis and recurrent disc prolapse. Forty-five gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhanced magnetic resonance (MR) scans were performed on 43 patients to evaluate the effectiveness in differentiating recurrent disc prolapse from epidural fibrosis. Operative findings were available in 11 patients and they confirmed the pre-operative radiological diagnosis of recurrent disc prolapse in 6, epidural fibrosis in 4 and facet joint hypertrophy in 1 patient. Although the number of surgically verified cases is small, our initial experience of 100% diagnostic accuracy reflects the tremendous potential of this investigative tool. Separating epidural fibrosis from recurrent disc prolapse is crucial as patients with the former are expected to benefit from further surgery. Patients with epidural fibrosis, on the other hand, generally do not gain relief from another operation.

Adult↗

PubMed1995

Tarsometatarsal (Lisfranc's) injuries--results of open reduction and internal fixation.

Injuries of the tarsometatarsal (Lisfranc's) joint are uncommon and are potentially associated with chronic disability. The aim of our study was to review retrospectively the results of open reduction with Kirschner wire internal fixation of tarsometatarsal injuries. In this study, 12 patients with Lisfranc's injuries treated between January 1986 and March 1993 were reviewed at an average of 36 months after the injuries. Majority of the patients suffered from type B injuries (Hardcastle's classification, 1982). There were 9 closed and 3 open injuries. All were high energy injuries sustained in motor vehicle accidents, fall from a height or crush force. All were treated with open reduction and internal fixation with Kirschner wires. Anatomical reduction was achieved and maintained. There was no postoperative redisplacement. During follow-up, most patients developed radiological evidence of post-traumatic osteoarthritic changes. However, majority of the patients were pain-free or had very little foot pain, and were able to return to their previous occupation. Our study showed that open reduction with Kirschner wire internal fixation offered satisfactory anatomical and functional results.

Accidental Falls↗

PubMed1994

Social aspects in patients following proximal femoral fractures.

Between January 1989 and December 1990, a study was conducted on the social aspects of 123 patients admitted to the Singapore General Hospital, Department of Orthopaedic O, with proximal femoral fractures. Twenty-three patients passed away, leaving 100 patients for review at 2 years post-fracture. Of the 20 social functions evaluated, less than 60% improvement was observed in 6 lower limb dependent activities. Before fracture, 82 patients were independent and 83 were ambulating without aids. After fracture, improvement occurred progressively and reached a plateau at 1 year with 62 (75.6%) patients independent and 41 (49.4%) patients ambulating normally. All the patients stayed in their own home before fracture and 90 (90%) patients returned to their home after their discharge. Of the 59 patients who were unable to ambulate without aids, 21 had visual problems, 9 had cerebrovascular accident and 8 had both problems.

Accidental Falls↗

PubMed1994

Torsional performance of canine femoral osteotomy union.

This study allows the establishment of a protocol for standardizing the technical methodology of canine surgery for mechanical testing. Twenty mongrels were divided into 4 groups of 5 dogs each. All dogs had one femur selected as the test bone and the contralateral as paired control. The test femur was osteotomized and plated. The dogs were sacrificed at 7, 10, 13 and 16 weeks according to their group designation to determine healing of the osteotomy. Both test and control femora were tested to fracture in torsion using a computerized torsion machine. Various mechanical parameters were studied with the age of osteotomy union. The study found that all bones sustained spiral fractures through the osteotomy site. The maximum torque capacity and stiffness increased with age of union. There is an apparent biphasic pattern in the remodelling process. Up till the 13th week there was a decline in the polar moment of inertia and a rise in the torsional stress with an increase in strength. We postulate that this was due to a reduction of the outer diameter of the external bridging callus. After the 13th week, there was a reversal in the process and the outer diameter of the callus increased. The findings provide a baseline reference for future studies involving osteotomy healing as is necessary in bone allograft reconstruction and bone transport.

Animals↗