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Biomedical subjects

S H Lim

Publications and source records attributed to S H Lim.

At least 91 records · Page 5Linked to original sources
PubMed1998

In vitro cytokine-primed leukaemia cells induce in vivo T cell responsiveness in chronic myeloid leukaemia.

We previously showed that in chronic myeloid leukaemia (CML), it is possible to induce costimulatory molecules, CD80/CD86, on leukaemia cells by culturing adherent peripheral blood mononuclear cells from these patients with IL-4 and GM-CSF. In addition to the expression of CD80/CD86 molecules, some of the leukaemia cells also expressed the dendritic cell marker, CD1a. When these leukaemia cells were used in mixed lymphocyte leukaemia reactions, they mediated autologous T cell proliferation not seen when fresh leukaemia cells were used as the stimulator cells. In this study, we showed that reinfusion of these immunogenic leukaemia cells to the autologous hosts resulted in priming in vivo of T cells so that they could respond to subsequent rechallenge in vitro with fresh autologous leukaemia cells. Although cytotoxic T cells against leukaemia cells were not demonstrated, these T cells could proliferate and produce interferon-y when cocultured in vitro with the leukaemia cells. Our findings therefore provide further evidence for the immunogenicity of these cultured leukaemia cells in CML.

Adoptive Transfer↗
PubMed1998

Immunogenicity and cross-reactivity with idiotypic IgA of VH CDR3 peptide in multiple myeloma.

Multiple myeloma idiotypic protein is clone-specific and therefore represents an ideal tumour antigen for immune targeting. In this study we determined whether a synthetic peptide corresponding to the autologous idiotypic VH CDR3 sequence could elicit peptide-specific immune responses in a patient with IgA myeloma. Not unlike B-cell lymphoma, the immune repertoire of the patient contained T cells capable of mounting proliferative and cytotoxic responses to antigen-presenting cells loaded with the CDR3 peptide. Furthermore, the T cells were also able to secrete interferon-gamma upon peptide rechallenge. Antigen recognition by peptide-primed T cells was MHC dependent and could be blocked by antibodies to both monomorphic MHC class I and class II molecules. These results therefore indicate the presence of T-cell epitopes on the VH CDR3 sequence. In addition, CDR3 peptide-primed T cells were also able to mount similar immune responses when rechallenged with the intact IgA idiotypic protein, suggesting that functional T-cell epitopes had been derived from the CDR3 sequence of the idiotypic protein. Our results therefore provide a new perspective to the immunogenicity of the idiotypic protein in myeloma.

Cell Division↗
PubMed1998

In-vivo immune responses to idiotypic VH complementarity-determining region 3 peptide vaccination in B-cell non-Hodgkin's lymphoma.

Idiotypic IgM expressed by B-cell non-Hodgkin's lymphoma (NHL) is clone specific and an ideal tumour antigen for immune targeting. We previously showed that repeated rounds of in vitro stimulation of peripheral blood mononuclear cells (PBMC) with autologous idiotypic heavy variable (VH) complementarity-determining region (CDR)-3 peptide produced T-cell lines able to proliferate, produce Th1 cytokines and kill autologous target cells pulsed with the CDR3 peptide. Furthermore, fresh autologous lymphoma cells were lysed by these T-cell lines, suggesting a potential for the clinical use of the CDR3 peptide for lymphoma vaccination. In this study, we determined the specific immune responses of a patient following vaccination with VH CDR3 peptide to determine if similar immune responses observed in vitro could be elicited in vivo. The patient received three fortnightly subcutaneous injections of idiotypic CDR3 peptide. The injection sites developed inflammation after the second and third vaccinations. Peripheral blood T cells were able to proliferate and produce IFN-gamma upon rechallenge with the CDR3 peptide in vitro. Cytotoxic T lymphocytes (CTLs) for autologous CD3-depleted CDR3-pulsed PBMC were detected, but only after the first vaccination. T-cell lines generated after vaccination could lyse peptide-pulsed autologous target cells. We also detected the production of anti-CDR3 peptide antibodies in the patient's serum. We conclude that naked CDR3 peptide vaccination can result in the generation of potentially beneficial specific immune responses as predicted by in vitro studies.

Antibody Formation↗
PubMed1998

Long-term effect of Helicobacter pylori eradication on gastric metaplasia in patients with duodenal ulcer.

There have been conflicting reports on the effect of Helicobacter pylori eradication on gastric metaplasia in the duodenal bulb (DGM). In the present study, we have investigated the relationships between DGM and H. pylori by examining whether or not H. pylori-positive patients had more DGM than H. pylori-negative patients with nonulcer dyspepsia (NUD) or duodenal ulcer (DU), and by examining the effect of eradication of H. pylori on the prevalence and the extent of DGM during the long-term up to 4 years. Fifty H. pylori-positive and seven H. pylori-negative patients with DU and 23 H. pylori-positive and 23 H. pylori-negative NUD subjects were studied. Two duodenal bulb biopsy specimens were taken for histologic evaluation and the presence and the extent of DGM were evaluated. The extent of DGM was classified as none (grade 0), focal (grade 1), multifocal (grade 2), and diffuse type (grade 4). In H. pylori-positive patients with DU, follow-up gastroscopy was conducted 4 weeks, 1 year, and 4 years after H. pylori eradication. DGM was significantly (p < 0.001) more common (DU: 93%, NUD: 22%) and significantly (p < 0.001) greater in extent for patients with DU than for NUD subjects (DU: 1.89, NUD: 0.28). Neither the prevalence nor the extent of DGM was affected by H. pylori status in patients with DU or NUD; the prevalence (extent) of DGM of H. pylori-positive and -negative patients with DU were 96% (1.94) and 71% (1.57), respectively. In the 43 "H. pylori-eradicated" group, initial prevalence of DGM was 95% and those of 4 weeks, 1 year, and 4 years after eradication were 91%, 96%, and 79%, respectively. The initial extent of DGM was 1.93, and those of 4 weeks, 1 year, and 4 years after eradication were 1.90, 1.88, and 1.57, respectively. In conclusion, the prevalence and the extent of DGM were not related to H. pylori in patients with DU or NUD. In addition, the prevalence and the extent of DGM did not change until 1 year after H. pylori eradication in patients with DU, and decreased to the initial level of the H. pylori-negative DU group but without statistical significance after 4-year follow-up.

Adolescent↗
PubMed1998

Helicobacter pylori reinfection rate and duodenal ulcer recurrence in Korea.

In the short term, the eradication of Helicobacter pylori in patients with duodenal ulcer (DU) is deemed to be clearly effective; the long-term effectiveness apparently depends on the H. pylori reinfection rate. We conducted the present study to investigate the rates of H. pylori reinfection and DU recurrence in 45 patients previously cured of DU in whom H. pylori had been eradicated. These patients underwent gastroscopy and tests for H. pylori at least 1 year after eradication. In a control group comprising 31 patients with DU who were not treated with H. pylori eradication regimen, the DU recurrence rate was checked annually for 4 years. Twenty of 45 patients (44.4%) in whom the mean follow-up period was 3.5 years were again found to be H. pylori positive, and the reinfection rate was 12.8% per year. DU recurred in 8 of these 20 (40%) but not in any nonreinfected patients. In the control group, the DU recurrence rate was 61% within 1 year, 81% within 2 years, 84% within 3 years, and 90% within 4 years. The respective recurrence rates in the 45 patients in whom the bacteria had been eradicated were 0%, 4%, 13%, and 18%. The H. pylori reinfection rate was as high as 12.8% per year in Korea, but in that the DU recurrence rate is significantly lower (p < 0.01; odds ratio, 129.5) in the H. pylori-eradicated group than in the control group, the eradication of H. pylori in DU patients is effective over the long term (at least 4 years).

Adolescent↗
PubMed1998

Group B Streptococcal septicaemia/meningitis in neonates in a Singapore teaching hospital.

Our aims were to establish the incidence and clinical characteristics of early and late onset Group B Streptococcal (GBS) septicaemia in neonates in our hospital over a period of 1 year. Routine screening for maternal GBS was not standard practice in the hospital. GBS was isolated from high vaginal swabs (HVS) obtained antenatally or postnatally for risk factors as determined by the obstetrician or neonatologist in charge. Data obtained were analyzed separately and these did not form part of the study. By a system of clinical case review and follow-up, mail, telephone and home visits, the outcome of all 15,062 livebirths in the hospital over a 1-year period were verified and reported. Our results show a low incidence of GBS infection in neonates in the hospital: early onset disease was 0.265 per 1,000 livebirths and late onset a quarter of that. The majority of our cases of early onset GBS disease were in premature infants. Because of our low incidence, prophylaxis schedules would have to ensure an acceptably smaller number of mothers exposed to antibiotics over and above the current level and the cooperation of our obstetricians. We have devised a schedule incorporating a current PROM (prelabour premature rupture of membranes) protocol which would result in only an additional 2.2% of mothers requiring prophylactic antibiotics.

Age of Onset↗
PubMed1998

Difficult pulmonary artery catheterization in a patient with persistent left superior vena cava.

A persistent left superior vena cava is an uncommon congenital abnormality. It arises when the left anterior cardinal vein fails to regress during the embryonic period. Although such patients are usually asymptomatic, they may have associated cardiovascular abnormalities. The anaesthetist may encounter difficulty in the insertion of pulmonary artery catheters. Other implications in the management of these patients in the operating theatre or intensive care unit are discussed.

Aged↗
PubMed1998

Cryptococcal prostatic abscess in an immunocompromised patient: a case report and review of the literature.

A case of cryptococcal prostatic abscess in a 65-year-old Chinese man with immunosuppression from treatment of myasthenia gravis is presented. The patient was diagnosed to have cryptococcaemia when he presented with fever and urinary symptoms. Further investigations confirmed cryptococcal meningitis and imaging studies showed a hypodense lesion in the prostate. This proved to be an abscess and it was deroofed transurethrally. Histology of the prostatic tissue revealed the presence of Cryptococcus. The prostate can be a site of persistent cryptococcal infection and may take the form of an abscess. It should be drained transurethrally to prevent relapse.

Abscess↗
PubMed1998

Comparison of treatment of supraventricular tachycardia by Valsalva maneuver and carotid sinus massage.

STUDY OBJECTIVE: To compare the efficacy of the Valsalva maneuver with that of carotid sinus massage (CSM) in terminating paroxysmal supraventricular tachycardia (SVT) in the ED. METHODS: This prospective, randomized case study was performed in the ED of a tertiary care institution. Patients were at least 10 years of age with regular narrow complex tachycardia and had an ECG diagnosis of SVT. Patients with regular narrow complex tachycardia were randomly assigned to undergo either the Valsalva maneuver or CSM. If the tachycardia was not terminated by the method chosen by randomization, then the alternative method of vagal maneuver was used. If the tachycardia was not converted by both methods of vagal stimulation, patients would undergo either synchronized electrical cardioversion or a pharmacologic method of conversion at the discretion of the treating physician, depending on the patient's hemodynamic status. RESULTS: One hundred forty-eight instances of SVT were studied Sixty-two patients underwent Valsalva maneuver first with conversion in 12 (success rate of 19.4%). Eighty-six underwent CSM first with conversion in 9 (success rate 10.5%). Carotid sinus massage was used in the 50 cases of SVT in which conversion was not achieved with the Valsalva maneuver. Conversion occurred in 7 cases (success rate 14.0%). For the 77 cases of SVT in which initial CSM did not achieve conversion, conversion occurred in 13 with the Valsalva maneuver (success rate 16.9%). The Valsalva maneuver and CSM achieved conversion in a total of 41 instances of SVT (success rate 27.7%). CONCLUSION: Vagal maneuvers are efficacious in terminating about one quarter of spontaneous SVT cases. There is no detectable difference in efficacy between the Valsalva maneuver and CSM.

Adult↗
PubMed1998

Idiotypic protein-pulsed adherent peripheral blood mononuclear cell-derived dendritic cells prime immune system in multiple myeloma.

Adherent peripheral blood mononuclear cell-derived dendritic cells pulsed with autologous idiotypic protein (Id) were given to a patient with advanced-stage refractory myeloma. Potentially beneficial antimyeloma Id-specific immune responses were produced, characterized by MHC-dependent T-cell-proliferative responses with cytokine release and the production of anti-Id antibodies. A T-cell line generated after vaccination was also able to lyse autologous Id-pulsed targets and recognize fresh autologous myeloma cells. The immune responses were associated with a transient minor fall in the serum Id level and were not ablated by high-dose myeloablative chemotherapy. This report therefore demonstrates the clinical use of adherent peripheral blood mononuclear cell-derived dendritic cells for vaccination in cancer and the persistence of immune responses after high-dose chemotherapy. Such a therapeutic approach may be useful in reducing the relapse rate in patients who have minimal residual disease after chemotherapy.

Adult↗
PubMed1998

Reduction of nosocomial infection in a neonatal intensive care unit (NICU).

UNLABELLED: New measures aimed at reducing nosocomial infection in our neonatal intensive care unit (NICU) were introduced over a 3-month period from 1 July to 30 September 1994. OBJECTIVE: The aim of this study was to evaluate the impact of these measures on the incidence of nosocomial infection in our NICU. METHODS: The new measures introduced were: 1. grouping of all blood investigations to allow for fewer blood samplings per baby per day; 2. reduction of routine blood investigations after the acute illness has stabilised, and 3. a system of aseptic delivery of drugs through a central venous catheter, thereby reducing the need for peripheral intravenous lines. Nosocomial infections were defined according to the criteria spelt out in the Centres for Disease Control (CDC) guidelines. Data for the study was obtained from the ongoing surveillance carried out by the hospital's infection control team. Period 1 (1 year duration) was prior to the implementation of the new measures. Period 2 (1 year duration) was after implementation of the new measures. RESULTS: The overall nosocomial infection patient rates (expressed as number of infections per 100 intensive care unit patients) were 17.6 for Period 1 and 7.5 for Period 2. The overall nosocomial infection patient-day rates (expressed as number of infections per 1000 patient-days) were 13.5 and 6.1 respectively (p < 0.01). When the infants' birth weights were stratified as < 1500 g, 1500-2500 g, and > 2500 g, the greatest decline in both the overall nosocomial infection patient rate and nosocomial infection patient-day rate was seen in infants weighing < 1500 g. There was also a significant decline in the rates of blood-stream infections in infants weighing < 1500 g (from 7.5 to 2.8 per 1000 patient-days) (p < 0.05). Ventilator associated pneumonias also showed a decline from 3.3 to 1.0 pneumonia per 1000 ventilator days. The organisms responsible for the majority of blood stream infections in Period 1 were methicillin-resistant Staphylococci Aureus (MRSA), coagulase-negative staphylococci, gram-negative bacilli and candida. In Period 2, coagulase-negative staphylococci was the predominant organism. CONCLUSION: We conclude that there was a reduction in nosocomial infection rates. The new measures introduced may have contributed to this reduction.

Bacteremia↗
PubMed1997

Chronic myeloid leukemia as an immunological target.

Various clinical observations have implicated T cells in the control of chronic myeloid leukemia (CML). These observations have in recent years been supported by laboratory results indicating the presence of CML-specific T cells in the lymphocyte repertoire of both normal healthy individuals and disease-bearing patients. Both MHC-unrestricted and MHC-restricted immune effector mechanisms are involved. Donor lymphocyte infusion has produced encouraging GvL effects. However, future adoptive immunotherapy may depend on the isolation and generation of leukemia-specific T cells. Although many proteins may potentially act as leukemia antigens in CML for MHC-restricted cytotoxicity, the bcr-abl fusion protein has been most extensively investigated. There is now much evidence to suggest that the bcr-abl junctional peptides are capable of eliciting both CD4 and CD8 responses in normal healthy donors and CML patients. Furthermore, the T-cell lines generated react with autologous or HLA-matched fresh CML cells, suggesting that the bcr-abl fusion protein can be processed in vivo so that the joining segment is bound to HLA molecules in a configuration and concentration similar to those of the immunizing peptide for antigen recognition by the antigen-specific T-cell receptor. These results also indicate that the bcr-abl junctional peptides may be used for immunotherapy of CML. Other strategies available for immunotherapy of CML include immunologically or genetically manipulated donor T-cell infusion, the use of cytokines, adoptive immunotherapy with leukemia-reactive T-cells expanded ex vivo, and immune gene therapy. Novel and rational immunotherapy may therefore play an important adjuvant role in future in the management of patients with CML.

CD4-Positive T-Lymphocytes↗
PubMed1997

T cells recognize the VH complementarity-determining region 3 of the idiotypic protein of B cell non-Hodgkin's lymphoma.

The idiotypic protein expressed by B lymphoma cells is a clone-specific tumor antigen which may be suitable for immune targeting by T cells. In this study, we cloned the immunoglobulin heavy chain variable gene (VH) of the idiotypic protein from a patient with B cell lymphoma and used a synthetic peptide of 22 amino acids corresponding to the VH complementarity-determining region (CDR)-3 of the idiotypic protein to investigate whether autologous T cells could recognize this unique peptide. We demonstrated that autologous T cells possessing both CD4+ and CD8+ phenotypes could be propagated. The T cells were able to proliferate, secrete cytokines, and lyse autologous cells presensitized with the specific peptide in a major histocompatibility complex-dependent manner. Moreover, these CDR3 peptide-primed T cells were also able to kill autologous lymphoma cells. Our results therefore offer new perspectives for specific therapeutic vaccination for the treatment of B cell lymphoma.

Amino Acid Sequence↗
PubMed1997

Cyclosporin A/alpha interferon-induced autologous graft-versus-host disease following peripheral blood stem cell transplant for chronic myeloid leukaemia: a clinico-pathological study.

Autologous GVHD was induced using CsA and alpha-IFN in a patient undergoing autologous PBSCT for accelerated phase CML. We demonstrated that the autologous mixed lymphocyte reactions were extremely sensitive and specific for the detection of the GVHD when compared to skin biopsy. The resultant autologous GVHD was associated with an in vitro GVL effect, suggesting a potential clinical benefit of this therapeutic manoeuvre. The post-PBSCT period was associated with an improvement in normal haemopoiesis and reduction in the proportion of blood cells expressing the Philadelphia chromosome.

Antineoplastic Agents↗
PubMed1997

Cytokine enhancement of immunogenicity in chronic myeloid leukaemia.

Various clinical and laboratory observations suggest that the leukaemia cells in chronic myeloid leukaemia (CML) are potentially immunogenic. Whilst the ability of the leukaemia cells to elicit an anti-leukaemic immune response in the allogeneic setting is established, it remains unclear why such anti-leukaemic response does not occur in vivo in the autologous setting. We previously demonstrated the presence of leukaemia-reactive T cells in a patient with CML. However, we found that the T cells were normally anergic unless pre-incubated in vitro in high-dose recombinant interleukin-2. We speculated that the T cell anergy was the result of a lack of the appropriate immune costimulatory molecules on the leukaemia cell surface. In this study, we confirm the absence of immune costimulatory molecules, CD80 (B7-1) and CD86 (B7-2), on leukaemia cells and demonstrated that these costimulatory molecules on the leukaemia cells can be upregulated by a combination of GM-CSF and IL-4. There was an associated restoration of leukaemia cell immunogenicity to autologous T cells in mixed lymphocyte leukaemia reactions, suggesting a possible enhancement of anti-leukaemic reaction. More importantly, T cells primed with 'activated' leukaemia cells were able to recognise fresh cytokine-naive leukaemia cells. Furthermore, leukaemia cells expressing the dendritic cell marker, CD1a, were also generated. Our findings therefore suggest the opportunity in future to use these combination cytokines in vivo or these leukaemia cells which have been activated in vitro for leukaemia immunotherapy.

Cytokines↗
PubMed1997

T-cell receptor V beta usage by lesional lymphocytes in oral lichen planus.

To determine whether the T-cell inflammatory infiltrate in oral lichen planus (OLP) represents a selective activation and expansion of a limited repertoire of T-cell receptor (TCR) specific T-cells, V beta gene expression was investigated in lesional T-lymphocytes in OLP. A reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used to amplify the 24 major V beta gene sub-families of infiltrating mucosal lymphocytes and peripheral blood mononuclear cells (PMNC) in seven patients with reticular OLP and four healthy control patients. Specificity of amplified products was confirmed by Southern blotting with a C beta internal probe. TCR V beta usage by lesional T-cells in OLP was markedly heterogeneous 5-23 V beta sub-families). In 6/8 patients with OLP, V beta usage was restricted with < or = 20/25 sub-families detected; only one of the V beta sub-families (V beta 8) was present in all of the OLP patients demonstrating TCR V beta restriction. In contrast, TCR V beta usage was unrestricted in PMNC from OLP patients and controls (> or = 23/ 25 sub-families detected). In three patients, certain V beta sub-families (V beta 13, V beta 14 & V beta 15) were present in the lesional T-cell population but were under-represented in PMNC. These results suggest a selective V beta gene usage by lesional infiltrating T-cells in oral lichen planus. The non-uniformity of V beta restriction in lesional T-cells does not support the concept of a common superantigen in OLP and reflects the heterogeneity of the disease.

Adult↗