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Biomedical subjects

S H Lim

Publications and source records attributed to S H Lim.

At least 19 recordsLinked to original sources

Presence and release of immunoreactive atrial natriuretic peptide in granulosa cells of the pig ovarian follicle.

Atrial natriuretic peptide (ANP) has been reported to be locally synthesized in the ovary although its physiological roles are still unknown. To define the origin of ovarian ANP, we demonstrated the presence and release of immunoreactive (ir) ANP in pig granulosa cells and characterized its biochemical properties. Serial dilution curves made with the extracts of pig granulosa cells, their perfusates and follicular fluid were paralleled to the standard curve of ANP. The amount of irANP in the granulosa cell was 2 fg/cell. The total amount of irANP in granulosa cells significantly correlated with the levels of irANP in follicular fluid. Additionally, the total content of irANP in the follicle negatively correlated with the follicular size. On reverse phase HPLC, the major form of irANP in granulosa cells and follicular fluid was high molecular weight but that in perfusate was low molecular weight. In Northern blot analysis, ANP mRNA was detected in the pig granulosa cells. Immunohistochemistry showed ANP prohormone location in granulosa cells of rat ovary. These data strongly suggest that the granulosa cells synthesize and secrete ANP.

Animals

Protein targeting across the three membranes of the Euglena chloroplast envelope.

A system has been developed for the import in vitro of precursor proteins into Euglena chloroplasts, which have three envelope membranes. Preparation of functional chloroplasts with intact envelope membranes has been optimized. Import of the precursor (50 kDa) for the tetrapyrrole biosynthesis enzyme porphobilinogen deaminase (PBGD), and processing to the mature size (40 kDa), occurred at 25 degrees C in the light and the presence of ATP, with an estimated efficiency of 62%. Pretreatment of the chloroplasts with proteases abolished this import, suggesting the involvement of specific protein receptors. The presequence of PBGD was found to be cleaved by Escherichia coli leader peptidase to an intermediate form (46 kDa). A construct in which the first 30 residues of the presequence (presumed to be the region removed by leader peptidase) had been deleted was no longer imported. Neither prePBGD nor the truncated precursor were imported into pea chloroplasts, although both bound to the pea chloroplast envelope. Conversely, a chimeric construct, in which the mature PBGD protein was fused downstream of the transit peptide for pea ferredoxin-NADP reductase, was efficiently imported into pea chloroplasts and processed to the mature size. However, this was not imported into Euglena chloroplasts, although again it bound to them. These results provide preliminary evidence for the possibility of two functional domains within the Euglena PBGD presequence. The implications of these findings with respect to the evolution of Euglena chloroplasts are discussed.

Amino Acid Sequence

Continuous intravenous infusion of high-dose recombinant interleukin-2 for acute myeloid leukaemia--a phase II study.

A group of 13 patients with acute myeloid leukaemia of differing disease status were treated with continuous intravenous infusion of high-dose recombinant interleukin-2 (rIL-2). There was up-regulation of the cellular cytotoxic functions in all these patients following the rIL-2 therapy, with increase in the natural killer (NK) activity, lectin-dependent cellular cytotoxicity, induction of cytotoxicity-linked cytoplasmic serine esterase and lymphocyte activation. However, the clinical response to rIL-2 in these patients was disappointing, especially in patients treated in frank relapse. Although 1 patient treated in early second relapse achieved a third complete remission, the duration of the remission was brief and lasted only 6 months. Adverse reactions among these patients were common. Whether or not lymphokine-activated killer cells are needed to improve the response rate over rIL-2 alone in these patients deserves further investigation.

Adult

Monoclonal antibody (MoAb) therapy in non-Hodgkin's lymphomas.

The advance of monoclonal antibody (MoAb) technology in recent years provides a further treatment modality for cancer therapy. In this review, we discussed the various strategies available for MoAb therapy. We also addressed the problems encountered so far in early clinical trials and suggested possible solutions. We finally reviewed some of the interesting clinical studies conducted so far on the use of MoAbs in patients with non-Hodgkin's lymphomas.

Animals

High-dose mitoxantrone and etoposide conditioning in autologous bone marrow transplantation for relapsed Hodgkin's disease.

We administered high-dose mitoxantrone in combination with etoposide to 6 patients with relapsed Hodgkin's disease as the conditioning regimen for autologous bone marrow transplantation. This regimen was well tolerated and no significant cardiotoxicity was observed. Responses of the Hodgkin's disease to this therapy were favourable but short-lived. Serial measurements of the serum levels of mitoxantrone suggested an open 3-compartment model of drug distribution. The rapid early phase of drug distribution was followed by an intermediate phase and a slow terminal drug-elimination phase. However, mitoxantrone was still detected in the serum of all patients 7 days after the last dose of mitoxantrone and on the day of bone marrow re-infusion. The clinical significance of such findings is unclear but they may suggest a need for the use of other anthracycline-related cytotoxic agents for the conditioning in autologous bone marrow transplantation.

Adult

Gifted children.

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Child

Lying in children.

Lying is a common problem in children. The causes of lying are numerous. With proper management including good parental role models, minimising or preventing contributing factors, and appropriate discipline, most children outgrow the tendency to lie.

Adolescent

Stealing in children.

Stealing is a common behavioural problem in children. The causes of stealing include a desire for possession, attention-seeking behaviour, revenge, a lack of discipline, poor parental role models, or significant psychological or psychiatric problems. With proper management, the tendency to steal resolves in most children.

Child

Teicoplanin and prophylaxis of Hickman catheter insertions.

A total of 88 patients with haematological malignancies who required Hickman catheters for intensive chemotherapy, were randomized to receive either a single bolus intravenous injection of teicoplanin, or no teicoplanin, immediately before insertion of a double lumen Hickman catheter. There was a lower incidence of catheter-related Gram-positive sepsis in patients receiving prophylactic teicoplanin. This benefit was particularly clear in patients who were already neutropenic at the time of catheter insertion. Prophylactic teicoplanin may, therefore, be useful as a routine procedure during the insertion of Hickman catheters for this group of patients.

Adult

Counseling parents about childhood discipline.

Traditional disciplinary methods include rewards to reinforce good behavior and punishment for unacceptable behavior. Rewards may take the form of verbal praise, a smile, special attention or activities, physical affection, extra privileges or material benefits. Punishment may include verbal disapproval, an unhappy look, ignoring the behavior (extinction), temporary isolation ("time-out") or temporary removal of a privilege. Rewards are more effective than punishment. Discipline should be consistent, reasonable and appropriate to the child's age. Rules should be as few and as clear as possible. Parents should be exemplary role models for their children. Punishment, when required, should be immediate and inevitable. Punishment should be just and directed toward the undesired behavior rather than the child. Parents should discipline their children with love, understanding, patience and tolerance.

Child

Use of intracranial neurophysiologic recording techniques in the evaluation for epilepsy surgery in children.

Resective surgery is an accepted treatment modality for medically intractable focal epilepsy in children as well as in adult. During the presurgical evaluation processes, intracranial neurophysiologic recording of epileptiform abnormalities have been used much more commonly in adults and older adolescents than in infants and children. However, as infants and children are increasingly referred for early surgery in many centres, it may be necessary to study complex cases in some children with invasive electrodes in order to plan a safe and effective resection. This article gives first an overview of the rationale and indications, with case illustrations, for using these techniques. This is followed by general discussions on individual electrodes and their use in infants and children.

Adolescent

Etiologic factors for unitemporal vs bitemporal epileptiform discharges.

We compared the etiologic factors and clinical characteristics of 30 patients with unitemporal vs those of 30 patients with bitemporal independent (minimum 20% from one side) interictal epileptiform discharges on extracranial electroencephalograms. Febrile seizures occurred significantly more frequently in the unitemporal (40%) than in the bitemporal (17%) group. Mass lesions were more common in the bitemporal group, and seven of 10 patients with mass lesions showed bitemporal interictal epileptiform discharges. There were no statistically significant differences in age at onset, frequency of seizures, duration of epilepsy, and history of central nervous system infection or trauma between the two groups. A history of febrile seizures or central nervous system infection that may be expected to cause diffuse cerebral injury does not appear to be the major factor predisposing to the development of bitemporal interictal epileptiform discharges.

Adolescent

Lymphocyte activation in patients with acute myeloid leukaemia. Evidence for the presence of myeloblast antigen?

A group of 27 patients with acute myeloid leukaemia (AML), 15 with active disease and 12 in complete remission, were investigated for evidence of T cell activation. The parameters of T cell activation measured were the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules and the proportions of T cells expressing the cytotoxicity-linked cytoplasmic serine esterase. All patients studied with active disease had elevated sIL-2R and sCD8 molecules and an elevated proportion of T cells expressing serine esterase. Patients studied in complete remission also had elevated sIL-2R. sCD8 and serine-esterase-positive T cells, but values were lower than those studied in active disease. These patients were all studied in the absence of any ongoing or recent infection or exposure to homologous blood products, either of which could potentially affect these parameters. In the absence of any obvious alternative cause, we suggest these data indicate that AML leukaemia blast cells may be immunogenic and lead to the activation of cytotoxic T cells.

Acute Disease

Lymphocyte activation and serine-esterase induction following recombinant interleukin-2 infusion for lymphomas and acute leukaemias.

In this study we investigated the pattern of T lymphocyte changes in 16 adult patients with acute myeloid leukaemia (8), non-Hodgkin's lymphoma (4) and Hodgkin's disease (4) treated with continuous infusion of recombinant interleukin-2 (rIL-2). Effects indicative of lymphocyte activation occurred even prior to any rIL-2 therapy in these patients, being most prominent in patients with active diseases. Following each course of cytokine therapy, there were further changes in these parameters. Significant rebound lymphocytoses occurred with a concomitant increase in the cytotoxic functions and induction of the cytotoxicity-linked cytoplasmic serine esterase. Hence, both the natural killer and lectin-dependent cellular cytotoxicity activities were up-regulated. There were also increases in the serum sIL-2 receptor, sCD4 and sCD8 levels. More CD3+ lymphocytes, especially cells bearing CD4, were also recruited to the pool of potential effector cells, as demonstrated by the greater proportion of cells expressing the cytoplasmic serine esterase.

Adult

Cellular cytotoxic function and potential in acute myelogenous leukaemia.

Twenty-seven adult AML patients (13 with active disease and 14 in complete remission) were investigated for their cellular cytotoxic potential and function. All AML patients, whether with active disease or in complete remission, showed increased percentage of CD3+ lymphocytes expressing the cytotoxicity-linked cytoplasmic serine esterase, suggesting a higher than normal cytotoxic potential. However, when the cytotoxic function in these patients were analysed in terms of the natural killer and lectin-dependent cellular cytotoxicity, all AML patients, whether with active disease or in complete remission, had impaired target cell lytic activity. This paradox of cytotoxicity is most likely due to the immunosuppressive effect of the serum factor elaborated by leukaemia myeloblasts.

Adult

Continuous intravenous infusion of high dose recombinant interleukin 2 for advanced lymphomas--a phase II study.

The prognosis of patients with advanced refractory lymphoma remains poor. We have carried out a Phase II study of continuous high dose intravenous recombinant interleukin 2 alone without LAK cells in this group of patients. Eight patients have so far been treated, 4 with non-Hodgkins lymphoma and 4 with Hodgkins disease. Of the 7 evaluable patients, the maximum response observed was stable disease in 2 patients (1 with NHL and 1 with HD). The other patients' diseases progressed in the face of immune activation following the rIL-2 infusion. Adverse reactions were common but no life-threatening occurred. These results are disappointing. Whether or not lymphokine-activated killer (LAK) cells are needed to improve response rate deserve further investigations.

Adult

Production of tumour-derived suppressor factor in patients with acute myeloid leukaemia.

In an attempt to investigate the underlying cause of impaired cellular cytotoxic functions in patients with acute myeloid leukaemia and the relative ineffectiveness of immunotherapy with recombinant interleukin 2 (IL-2), normal donor lymphocytes were incubated in AML sera and in supernatant of myeloblasts. There was significant inhibition of both the natural killer activity and the lectin dependent cellular cytotoxicity of the normal donor lymphocytes compared to when incubation took place in autologous or normal allogeneic sera or marrow supernatant. This inhibition was time-related and partially reversible by washing of the normal lymphocytes immediately before the cytotoxicity assay. The suppressor factor, however, did not inhibit the IL-2 induced lymphocyte proliferation or affect the cytotoxicity-linked cytoplasmic serine esterase expression in the normal lymphocytes. This suppressor phenomenon was of myeloblast origin. Chronic exposure to the tumour-derived suppressor factor may be responsible for the impaired cellular cytotoxic functions observed in patients with acute myeloid leukaemia. It may also suppress the in vivo cytotoxic functions of IL-2 activated lymphocytes in patients treated with recombinant IL-2, hence leading to the disappointing results of immunotherapy so often encountered in clinical setting.

Cytotoxicity, Immunologic

A prospective randomized study of prophylactic teicoplanin to prevent early Hickman catheter-related sepsis in patients receiving intensive chemotherapy for haematological malignancies.

Eighty-eight patients with haematological malignancies requiring Hickman catheters for intensive chemotherapy were randomized to receive either one single bolus intravenous injection of teicoplanin or no teicoplanin immediately before insertion of a double lumen Hickman catheter. There were lower incidences of catheter-related Gram-positive sepsis in patients receiving prophylactic teicoplanin. There were less exit site infections, tunnel infections and catheter-related Gram-positive septicaemia. The benefit of prophylactic teicoplanin was observed especially among patients who were already neutropenic at the time of catheterization. All Gram-positive organisms isolated from the infected skin sites or from blood cultures taken from the Hickman catheters were sensitive to teicoplanin. No adverse reaction was reported in any of the patients in the prophylactic group. Prophylactic teicoplanin therefore may be used routinely for patients requiring insertion of Hickman catheters for intensive chemotherapy to reduce the early incidence of catheter-related sepsis, especially during the associated period of neutropenia following chemotherapy.

Adult