Biomedical subjects

H S Teh

Publications and source records attributed to H S Teh.

At least 19 recordsLinked to original sources

PubMed2004

Supernumerary testicle in a case of polyorchidism.

INTRODUCTION: The presence of more than 2 testicles is called polyorchidism. It is a rare anomaly. Less than 100 cases have been reported in the literature. CLINICAL PICTURE: A 51-year-old man complained of a painless right groin lump for a year. Physical examination revealed a discrete ovoid non-tender, firm but mobile lump. No cough impulse was demonstrated. Sonography demonstrated a soft tissue structure within the tunica vaginalis inferior to the deep inguinal ring. It demonstrated similar echotexture and vascular flow as the normal testis, but smaller in size. The findings were compatible with a diagnosis of polyorchidism. TREATMENT: The patient was not keen for surgery and was followed up conservatively. CONCLUSION: Differential diagnosis of a solid extratesticular mass should include polyorchidism.

Choristoma↗

PubMed2004

A case of right loin pain: septic ovarian vein thrombosis due to Campylobacter fetus bacteraemia.

INTRODUCTION: Septic ovarian venous thrombosis is an uncommon condition. Diagnosis is often not immediately apparent clinically and there are many that mimic this condition. We described an unusual case of septic ovarian vein thrombosis associated with Campylobacter fetus (C. fetus) bacteraemia. CLINICAL PICTURE: A 46-year-old female presented with fever and acute right loin pain. Right ovarian venous thrombosis was demonstrated on sonography and confirmed with computed tomography and magnetic resonance imaging. C. fetus was isolated from the blood. TREATMENT AND OUTCOME: The patient was given antibiotics and anticoagulation therapy with good response. CONCLUSION: Septic ovarian vein thrombosis should be considered as a differential diagnosis in female patients presenting with fever associated with lower abdominal pain. C. fetus bacteraemia also predisposes to thrombophlebitis, including septic ovarian vein thrombosis. When they are diagnosed in a timely manner and treated appropriately, the response is good and potential serious complications, including thromboembolism, and death could be averted. Radiological imaging is useful in the diagnostic work-up of this condition.

Bacteremia↗

PubMed2004

The role of computed tomography in clinically-suspected but equivocal acute appendicitis.

INTRODUCTION: To study the role of contrast-enhanced computed tomography (CT) of the abdomen and pelvis in the evaluation of patients with clinically-suspected but equivocal acute appendicitis. METHODS: The medical records of 206 consecutive patients who had CT of the abdomen and pelvis for equivocal signs and symptoms of acute appendicitis were reviewed. 7 mm collimated axial sections from the diaphragm to the iliac crest and 5mm collimated sections of the pelvis with intravenous and oral contrast were obtained. The criteria used to diagnose acute appendicitis were: (a) a thickened appendix of more than 7 mm or (b) inflammatory changes in the periappendiceal fat. The CT findings were correlated with the histological diagnosis at appendectomy. If the CT findings were negative for acute appendicitis and surgery not performed, the results were correlated with other corroborating diagnostic investigations or clinical follow-up. RESULTS: A total of 206 patients were scanned, of which 39 were excluded due to lack of any follow-up. Of the final 167 that were studied, there were 36 true positives, 127 true negatives, 4 false negatives and no false positives, resulting in a sensitivity of 93.9 percent, specificity of 100 percent and accuracy of 98.5 percent. CONCLUSION: We have found CT to be a safe, reliable and accurate modality in the diagnosis of acute appendicitis in patients with equivocal presentation.

Acute Disease↗

PubMed2002

To establish the normal bone mineral density reference database for the Singapore male.

INTRODUCTION: The objective of this study was to establish the normal bone mineral density (BMD) reference curve for the Asian Singapore male. MATERIALS AND METHODS: Three hundred and eighty-three male subjects were enrolled; comprising of 309 Chinese, 44 Malays and 30 Indians resident in Singapore. Bone mineral density was measured at the lumbar spine and left hip using a Hologic QDR 4500 Elite dual-energy X-ray absorptiometry (DXA) scanner. RESULTS: The mean peak BMD for the average lumbar spine and the neck of femur was 1.006 g/cm2 and 0.97 g/cm2, respectively. The mean peak BMD was taken at the 20 to 24 years age group at both the hip and spine based on data distribution for the various age groups. The BMD corresponding to -2.5 standard deviations from the peak adult value was 0.719 g/cm2 for the average lumbar spine and 0.655 g/cm2 for the neck of femur. CONCLUSION: This Asian male BMD reference database, which is 10% and 5% lower than corresponding values from the Caucasian reference database, allows for more accurate diagnosis of osteoporosis in Asian males.

Absorptiometry, Photon↗

PubMed2002

Penile colour duplex ultrasonography as a screening tool for venogenic erectile dysfunction.

INTRODUCTION: Vasculogenic impotence is one of the major causes of erectile dysfunction. Cavernosometry and cavernosography is traditionally the gold standard for evaluation of venogenic impotence. However, it is invasive and there are potentially significant complications. Penile colour flow Doppler imaging (PCDI) is non-invasive and can be used to assess venous incompetence. MATERIALS AND METHODS: One hundred and sixty-eight patients were referred for PCDI assessment from March 1998 to February 2001. Forty-three of these also had cavernosogram and cavernosometry done and were included in the study. RESULTS: The sensitivity was 93.9%, the specificity was 90.0%, the accuracy was 93.0% with a negative predictive value of 81.8% and a positive predictive value of 96.9%. Kappa value of 0.81 was obtained, indicating excellent agreement between PCDI and cavernosogram and cavernometry. CONCLUSIONS: Penile colour flow Doppler imaging is accurate in the assessment of venogenic erectile dysfunction. It can replace cavernometry and cavernosogram as a screening tool. Cavernometry and cavernosogram should only be done in cases when PCDI suggests venogenic impotence, and when surgery is contemplated.

Adult↗

PubMed2001

TNF type 2 receptor (p75) lowers the threshold of T cell activation.

T cell activation requires a threshold amount of TCR-mediated signals, an amount that is reduced by signals mediated through costimulatory molecules expressed on the T cell surface. Here the role of TNFR2 (p75) as a putative costimulatory receptor for T cell activation was examined. It was found that p75 deficiency in CD8(+) T cells increased the requirements for TCR agonist approximately 5-fold. Furthermore, p75(-/-) T cells display a marked reduction in the proliferative response to TCR agonist. This hypoproliferative response was associated with delayed kinetics of induction of the acute activation markers CD25 and CD69 as well as a marked decrease in the production of IL-2 and IFN-gamma. The net result is that very few cells are recruited into the dividing population. Interestingly, CD28 costimulation was only partially effective in rescuing the proliferative defect of p75(-/-)CD8(+) T cells. Thus, p75 provides an important costimulatory signal in addition to that provided by CD28 toward optimal T cell proliferation.

Animals↗

PubMed2001

TCR/self-antigen interactions drive double-negative T cell peripheral expansion and differentiation into suppressor cells.

Mature CD4-CD8- alphabeta+ T cells (DNTC) in the periphery of TCR transgenic mice are resistant to clonal deletion in cognate Ag-expressing (Ag+) mice. Previously, we have characterized DNTC populations bearing the alloreactive 2C TCR in Ag-free (Ag-) and Ag+ mice. Despite appearing functionally anergic when challenged with cognate Ag in vitro, Ag-experienced DNTC exhibit markers of activation/memory, a lowered threshold of activation, ex vivo cytolytic activity, and the ability to rapidly secrete IFN-gamma. Remarkably, these memory-like DNTC also possess potent immunoregulatory properties, competing effectively for bystander-produced IL-2 and suppressing autoreactive CD8+ T cell proliferation via a Fas/FasL-dependent cytolytic mechanism. The fact that DNTC recovered from Ag+ mice possess markers and attributes characteristic of naive CD8+ T cells that have undergone homeostasis-induced proliferation suggested that they may be derived from a similar peripheral expansion process. Naive DNTC adoptively transferred into Ag-bearing hosts rapidly acquire markers and functional attributes of DNTC that have continually developed in the presence of Ag. Thus, the peripheral selection and maintenance of such autoreactive cells may serve to negatively regulate potential autoimmune T cell responses.

Animals↗

PubMed2001

The affinity/avidity and length of exposure to the deleting ligand determine dependence on CD28 for the efficient deletion of self-specific CD4+CD8+ thymocytes.

Whether the CD28/B7 signaling pathway is essential for the negative selection of immature CD4+CD8+ (DP) thymocytes expressing self-specific alphabeta TCRs is a controversial issue. In this study we examined the role of CD28 in the deletion of thymocytes that express either the H-Y or the 2C transgenic TCR. In H-2(b) male mice that expressed the H-Y TCR, negative selection of DP H-Y TCR+ thymocytes occurred very efficiently and this deletion was unaffected by the CD28(-/-) mutation. In H-2(b) 2C mice, where the deletion of DP 2C TCR+ thymocytes occurred less efficiently, the CD28(-/-) mutation led to a higher recovery of DP thymocytes. Using an in vitro deletion assay, a requirement for the CD28 signaling pathway in the deletion of DP H-Y TCR+ thymocytes was evident at low, but not high, densities of the antigenic ligand. Similar results were also observed in an in vivo assay for the deletion of these thymocytes. Intraperitoneal administration of an anti-CD3epsilon mAb led to the intrathymic deletion of DP H-Y TCR+ thymocytes in a CD28-dependent manner at the 24-h time point. However, the CD28 dependence was less evident at the 40-h time point. These results indicate that the dependence on CD28 for the efficient deletion of self-specific thymocytes is determined by the concentration, affinity/avidity, and length of exposure to the deleting ligand.

Abatacept↗

PubMed2001

p59fyn (Fyn) promotes the survival of anergic CD4-CD8- alpha beta TCR+ cells but negatively regulates their proliferative response to antigen stimulation.

T cell anergy is characterized by alterations in TCR signaling that may play a role in controlling the unresponsiveness of the anergic cell. We have addressed questions regarding the importance of the Src kinase p59(fyn) (Fyn) in this process by using Fyn null mice. We demonstrate that a mature population of CD4(-)CD8(-) alphabeta TCR(+) anergic T cells lacking Fyn have a substantial recovery of their proliferation defect in response to Ag stimulation. This recovery cannot be explained by ameliorated production of IL-2, and the improved proliferation correlates with an enhanced ability of the Fyn(-/-) anergic T cells to up-regulate the high affinity IL-2 receptor. We also observe that anergic CD4(-)CD8(-) alphabeta TCR(+) T cells have a heightened survival ability that is partially dependent on the elevated levels of Fyn and IL-2 receptor beta-chain expressed by these cells. The enhanced survival correlates with an increased capacity of the anergic cells to respond to IL-15. We conclude that Fyn plays an important role in aspects of T cell anergy pertaining to TCR signaling and to cell survival.

Animals↗

PubMed2001

The p38 mitogen-activated protein kinases can have opposing roles in the antigen-dependent or endotoxin-stimulated production of IL-12 and IFN-gamma.

The p38 mitogen-activated protein kinases (p38 MAPK) are activated in lymphocytes and acessory cells during innate and antigen-specific responses. We show that an inhibitor of two isoforms of p38 MAPK, SB 203580, inhibited the antigen-initiated production of IL-12, and IFN-gamma by cultures of splenic APC and naive CD4(+) T cells. Paradoxically, SB 203580 enhanced the LPS plus IFN-gamma-initiated production of IL-12 by peritoneal exudate macrophages, and the LPS-initiated of the production of both IL-12 and IFN-gamma by non-T non-B (scid) splenocytes. The enhancing effect of SB 203580 on the production of IL-12 by peritoneal exudate macrophages stimulated by LPS and IFN-gamma was dose dependent (EC(50) 0.3 microM), was only seen at lower concentrations of IFN-gamma and was due, at least in part, to a dose-dependent (IC(50) 0.3 microM) inhibition of the production of IL-10. These results indicate first, that p38 MAP kinase activity is required for the production of IL-10, as well as that of proinflammatory cytokines such as IL-12 and IFN-gamma, and, second, that the net effects of SB 203580 on the production of IL-12 and IFN-gamma can be positive or negative, depending on stimuli, cell populations, and levels of cytokines such as IFN-gamma and IL-10.

Animals↗

PubMed2001

Tight skin mouse subcutaneous hypertrophy can occur in the absence of alphabeta T cell receptor-bearing lymphocytes.

OBJECTIVE: The tight skin (TSK) mouse has been proposed to be a murine model for heritable fibrotic disorders, and studies have implicated immune dysregulation in TSK pathogenesis. We evaluated the core features of TSK cutaneous pathology to ascertain whether cutaneous features were altered in TSK mice deficient in alphabeta T cell receptor (TCR)-bearing lymphocytes. METHODS: Blinded qualitative evaluations of cutaneous and subcutaneous tissues were performed to determine the effect of the TSK mutation and whether the TCR-alpha-/- mutation had any influence on TSK mediated pathology. RESULTS: Analysis by light microscopy revealed no difference in the thickness or any obvious changes in dermal architecture in 2 to 4-month-old TSK mice compared to age and sex matched littermate controls. The most consistent feature of TSK dermatohistopathology is the substantially expanded superficial fascia with accentuated "lamellar" architecture. We found that this reliable pathological marker and the characteristic skin tightness were not abrogated when the TSK mutation was crossed onto the TCR-alpha-/- background. CONCLUSION: The results dispute assertions that cutaneous and subcutaneous sclerosis in the TSK mouse are dependent upon the presence of CD4+ cells and that skin tightness can be dissociated from these pathological changes.

Animals↗

PubMed2001

Flank pain: is Intravenous Urogram necessary?

AIMS: To determine the diagnostic yield of Intravenous Urogram (IVU) and the values of plain radiograph of kidney, ureter and bladder (KUB) and urinalysis as screening tests, with the objective to improve the cost effectiveness, in the management of patients presenting with flank pain due to urinary lithiasis. PATIENTS AND METHODS: All Intravenous Urogram (IVU) request forms and reports for the month of February 1998 were audited. The case notes, urinalysis, KUB and IVU films were traced and reviewed. RESULTS: There were 110 patients investigated, 61.8% (68) had normal IVU, 38.2% (42) had abnormal IVU. The sensitivity and specificity of KUB alone was 79.4% and 90%. The sensitivity using urinalysis alone was 90.9% and its specificity 33.8%. The sensitivity of combined KUB and urinalysis was 100% and its specificity 26%, with a negative predictive value of 100%. All the patients with both negative KUB and urinalysis in our study were found to have negative IVU. CONCLUSION: Our study shows that in patients with both negative KUB and urinalysis, the yield of IVU is very low and may not be necessary. This is important, as an IVU examination is not without risk. A combination of KUB with urinary analysis and careful evaluation of clinical symptoms will improve the cost-effectiveness of patient management.

Adolescent↗

PubMed2000

TNF receptor 2-deficient CD8 T cells are resistant to Fas/Fas ligand-induced cell death.

Apoptotic cell death plays a fundamental role in the maintenance of tissue homeostasis in complex biological systems. It is also a major mechanism for keeping immune reactions in check. Members of the TNF family of receptors and cytokines are implicated in the regulation of apoptotic signals that shape the immune system. In this study, we have examined the role of three members of the TNFR family, Fas (CD95), TNFR1 (p55), and TNFR2 (p75), in inducing cell death in Con A-activated CD4 and CD8 T cells. It was found that Con A-activated p55(-/-) CD4 or CD8 T cells were highly resistant to TNF-induced cell death. By contrast, although activated p75(-/-) CD4 or CD8 T cells were killed by TNF, they were more resistant to TNF-induced killing when compared with p75(+/+) cells, particularly at higher concentrations of TNF. We also determined whether activated p55(-/-) and p75(-/-) T cells differ in their sensitivity to cell death induced by TCR cross-linking. We found that activated p55(-/-) CD4 or CD8 T cells were equally susceptible to TCR-induced cell death. More interestingly, the loss of the p75 receptor conferred resistance to TCR-induced death in activated CD8, but not CD4 T cells. This resistance to TCR-induced death in activated p75(-/-) CD8 T cells correlated with the resistance of these cells to Fas/Fas ligand-induced cell death.

3T3 Cells↗

PubMed2000

A population of in vivo anergized T cells with a lower activation threshold for the induction of CD25 exhibit differential requirements in mobilization of intracellular calcium and mitogen-activated protein kinase activation.

Chronic exposure of mature T cells with specificity for self-Ags can lead to the induction of a nonfunctional state which is referred to as T cell anergy. It is unclear whether anergic T cells are destined for cell death and thereby harmless or whether they can contribute to the induction of autoimmunity and/or regulation of anti-self reactivity. We have begun to address this issue. In a recent study, we showed that a population of mature CD4-CD8- T cells that express a transgenic TCR specific for the Ld MHC class I molecule are rendered anergic in Ld-expressing mice. In this study, we show that this population of anergic T cells possess a lower activation threshold for the induction of CD25 and CD69 in response to stimulation by antigenic ligands. Furthermore, these anergic T cells undergo extensive proliferation when stimulated with a low-affinity ligand in the presence of an exogenous source of IL-2. Biochemical analysis of the early intracellular signaling events of these in vivo anergized T cells showed that they have a signaling defect at the level of ZAP-70 and linker for the activation of T cell (LAT) phosphorylation. They also exhibit a defect in mobilization of intracellular calcium in response to TCR signaling. However, these anergic T cells demonstrate no defect in SLP-76 phosphorylation and extracellular signal-regulated kinase 1/2 activation. These biochemical characteristics of the anergic T cells were associated with an elevated level of Fyn, but not Lck expression. The potential contributions of these anergic T cells in the induction and/or regulation of autoimmune responses are discussed.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Retroperitoneal Castleman's disease in the perinephric space--imaging appearance: a case report and a review of the literature.

INTRODUCTION: Castleman's disease (CD) is a rare lymphoid tumour usually found in the mediastinum. Extrathoracic sites are uncommon. Its radiological findings may be similar to other retroperitoneal tumours, making diagnosis difficult. CLINICAL PICTURE: A 54-year-old female was found to have an incidental hypoechoic mass in the left posterior perinephric space on routine ultrasound. Abdominal computed tomography (CT) scan demonstrated an isodense mass which enhanced brightly with intravenous contrast. Angiogram confirmed a hypervascular mass. TREATMENT: The retroperitoneal mass was excised. OUTCOME: Histology revealed CD of hyaline-vascular type. CONCLUSION: CD should be considered in the differential diagnosis of a retroperitoneal mass, which demonstrates homogeneous and intense enhancement.

Biopsy, Needle↗

PubMed1999

A role for T helper 2 cells in mediating skin fibrosis in tight-skin mice.

Mice heterozygous for the tight-skin (Tsk) mutation develop skin fibrosis. Previous studies have implicated a role for the immune system and, specifically, CD4(+) T cells, in the etiology of skin fibrosis in Tsk/+ mice. We have recently shown that the administration of neutralizing anti-IL-4 antibodies to Tsk/+ mice prevented the development of skin fibrosis in these mice. Since IL-4 is a major cytokine produced by T helper 2 (Th2) cells, we investigated the role of Th2 cells in mediating skin fibrosis in Tsk/+ mice. Previous studies have shown that the development of Th2 cells in non-Tsk mice is abrogated in mice with null mutation for either the IL-4 or the Stat6 gene. In this study we showed that the polarization of CD4(+) T cells from Tsk/+ mice toward the Th2 lineage is also dependent on a functioning IL-4 or Stat6 gene. More importantly, the development of skin fibrosis in Tsk/+ mice was abrogated by the IL4(-/-) or the Stat6(-/-) mutation. We also determined whether alteration of the TCR repertoire in Tsk/+ mice, achieved by the introduction of TCR transgenes, was able to prevent the development of skin fibrosis in Tsk/+ mice. We found that the exclusive usage of the Vbeta8.2 gene segment by T cells was sufficient to prevent skin fibrosis in Tsk/+ mice. This result suggests that the exclusive use of this Vbeta gene segment by T cells may have prevented the development of fibrosis-causing Th2 cells.

Animals↗

PubMed1999

Functional similarity and differences between selection-independent CD4-CD8- alphabeta T cells and positively selected CD8 T cells expressing the same TCR and the induction of anergy in CD4-CD8- alphabeta T cells in antigen-expressing mice.

In TCR-alphabeta transgenic mice, CD4-CD8- TCR-alphabeta+ (alphabeta DN) cells arise in the absence of positively selecting MHC molecules and are resistant to clonal deletion in Ag-expressing mice. In this study the activation requirements and functional properties of alphabeta double-negative (DN) cells were compared with those of positively selected CD8+ cells expressing equivalent levels of the same MHC class I-restricted transgenic TCR. We found that positively selected CD8+ cells required a lower density of the antigenic ligand for optimal proliferative responses compared with alphabeta DN cells derived from nonpositively selecting mice. However, when the CD8 coreceptor on CD8+ cells was blocked with an anti-CD8 mAb, both alphabeta DN and CD8+ cells exhibited the same dose-response curve to the antigenic ligand and the same dependence on CD28/B7 costimulation. Positively selected CD8+ cells also differed from alphabeta DN cells in that they differentiated into more efficient killers and IL-2 producers after Ag stimulation, even after CD8 blockade. However, Ag-activated alphabeta DN and CD8+ cells were equally efficient in producing IFN-gamma, suggesting that this functional property is independent of positive selection. We also found that alphabeta DN cells recovered from the lymph nodes of Ag-expressing mice were functionally anergic. This anergic state was associated with defective proliferation and IL-2 production in response to Ag stimulation. These observations indicate that alphabeta DN cells can be anergized in vivo by physiological levels of the antigenic ligand.

Animals↗

PubMed1998

Specific antiviral activity demonstrated by TGTP, a member of a new family of interferon-induced GTPases.

The GTPase superfamily includes a diversity of molecules whose functions are regulated through the binding and hydrolysis of GTP. This superfamily can be segregated into families of functionally related molecules that typically share amino acid sequence similarity within and around the nucleotide-binding domains. A new family of putative GTPases, including IRG-47, LRG-47, IGTP, and TGTP/Mg21, has recently emerged that share significant sequence identity (25-40%). Expression of these molecules has been shown to be selectively induced by IFN-gamma and in some cases by IFN-alpha beta or bacterial LPS. This induction pattern implicates these putative GTPases as part of the innate defense of cells to infection, but their role in such defense has not yet been defined. We have previously described the cloning of TGTP and now confirm its intrinsic activity as a GTPase. We found that TGTP is strongly induced by endogenous IFN-alpha beta produced in response to standard lipofection of plasmid DNA or polyinosinic polycytidylic acid. The ability of endogenously produced IFN-alpha beta to efficiently induce expression of TGTP under these conditions suggested that TGTP might participate in defense against viral infection. This proposal was borne out when TGTP-transfected L cells displayed relative resistance to plaque formation by vesicular stomatitis virus but not herpes simplex virus. This observation places TGTP among a small family of innate antiviral agents and has implications for the functions of other members of this family of GTPases.

Animals↗