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Biomedical subjects

L C Lim

Publications and source records attributed to L C Lim.

At least 55 records · Page 3Linked to original sources
PubMed1995

Abilities of OspA proteins from different seroprotective groups of Borrelia burgdorferi to protect hamsters from infection.

The ability of vaccination with recombinant OspA from six seroprotective groups of Borrelia burgdorferi sensu lato to induce protection against infection with homologous and other Lyme spirochetes was examined in hamsters. Antisera generated against the OspA proteins of B. burgdorferi sensu stricto S-1-10 and C-1-11 (seroprotective groups 1 and 2, respectively), Borrelia afzelii BV1 (seroprotective group 4), and Borrelia garinii LV4 (seroprotective group 5) were able to kill the homologous spirochete in vitro but not other isolates. Surprisingly, antisera against B. afzelii PKo (seroprotective group 6) and B. burgdorferi sensu lato LV5 (seroprotective group 3) OspA proteins were unable to kill the homologous organism, although LV5 OspA antisera killed the heterologous isolates S-1-10 and LV4. In vivo vaccination studies supported the in vitro findings, confirming that vaccination with a single OspA protein does not provide complete protection against challenge with all Lyme disease spirochetes. In addition, OspA antibodies from some isolates may not protect against the homologous isolate. The induction of protective antibodies against other B. burgdorferi proteins may be necessary to insure a comprehensive Lyme disease vaccine.

Amino Acid Sequence↗
PubMed1995

Haemophagocytosis in bone marrow aspirate--a review of the clinical course of 10 cases.

The clinical course of 10 cases where marrow aspirate showed features of haemophagocytosis was reviewed. Eight of these had a fulminant clinical course characterized by high fever, constitutional symptoms, wasting, hepatosplenomegaly with liver dysfunction, sometimes lymphadenopathy, progressive pancytopenia and coagulopathy, like that described as 'malignant histiocytosis' in the past. The remaining 2 cases did not have this classical clinical syndrome. Among the former 8 cases, 4 of them had high-grade lymphoma, 3 of whom were confirmed to be peripheral T cell lymphoma. Three of the remaining 4 had suspicious lymphomatous infiltrate on marrow trephine. In every case an extensive search for viral etiology by serology was negative. The 2 cases which did not have fulminant clinical feature were found to have lymphoma of the diffuse large cell and Ki-1 anaplastic type, respectively. A review of the literature reveal that most cases with haemophagocytic syndrome have a fulminant clinical course and are peripheral T cell lymphoma, which generally has a poor prognosis. In our study, the 8 cases with the classical haemophagocytic syndrome had a median survival of 24 days and a long-term survival of 37.5% at 28 months. Prompt initiation of chemotherapy is a life-saving measure and the only chance of achieving a long-term survival in patients with haemophagocytic syndrome if the underlying lymphoma can be diagnosed early.

Adolescent↗
PubMed1995

Present controversies in the genetics of male homosexuality.

Homosexuality refers to exclusive or predominant sexual attractions for persons of the same sex with or without physical relationship. In 1993, researchers in America identified the region of the X chromosome related to sexual orientation in homosexual men. However, molecular research of homosexuality does present particular problems because of the intense stigmatization some societies accord to these individuals. This paper presents the evidence of a genetic contribution, evaluates the complexity of sexual behaviour, and discusses the implications and challenges ahead if indeed a "gay gene" exists. It is apparent that scientific discoveries do not resolve moral dilemmas. The author believes that it is through debates and discussions that some ethical code can be, and should be formulated to prevent possible abuses.

Genetic Linkage↗
PubMed1994

No evidence of association between dopamine D4 receptor variants and bipolar affective disorder.

Disturbance in the dopamine neurotransmitter system has been implicated in the pathogenesis of affective disorder. In this study, we examine the possibility that functional variants of the recently cloned dopamine D4 receptor gene contribute to the genetic component of manic depression. The polymorphism, a 48 bp tandem repeat coding for part of the third cytoplasmic loop, was detected using a PCR based method. In a first sample of 57 patients and 59 controls, we found allele 7 to be in excess in the patients. In contrast, allele 3 was less frequent in patients. A second, larger sample of 90 patients and 91 controls was utilized to test these hypotheses. Data from the two samples were then pooled together for further analyses. We calculated the power of our samples, and if the frequency of 7 repeat allele obtained from sample 1 is true, i.e., 25% (28/114) for patients and 14% (16/118) for controls, then the power of the combined sample is 62% at 5% (two-tailed) significance level. However, both observations were not replicated; we therefore conclude that variations in this repeat at the DRD4 gene do not contribute to the genetic component of manic depression.

Alleles↗
PubMed1994

Detection of borreliacidal antibodies by flow cytometry. An accurate, highly specific serodiagnostic test for Lyme disease.

BACKGROUND: Borreliacidal antibodies can be detected in serum samples from patients with early or late Lyme disease symptoms. When these serum samples are incubated with Borrelia burgdorferi and complement, spirochetes are rapidly killed. Detection of these antibodies can be used as a serodiagnostic test. METHODS: Individual serum samples containing IgM or IgG borreliacidal antibodies were Used to develop a method for detection using flow cytometry. An additional 10 case-defined Lyme disease serum samples and 10 normal serum samples were used to confirm appropriate flow cytometric parameters. To determine specificity, 157 normal serum samples and 104 potential cross-reactive serum samples were tested for borreliacidal activity and antibodies to B burgdorferi using indirect fluorescent antibody or enzyme immunoassay. RESULTS: Flow cytometry can be used to detect borreliacidal activity within 16 to 24 hours after incubation of B burgdorferi organisms. Lyme disease serum, and complement. Significant borreliacidal activity was detected in all Lyme disease serum samples. The percentages of positive normal serum samples were comparable (6% to 10%) using all three assays. In addition, the indirect fluorescent antibody and enzyme immunoassay identified 41 (39%) and 47 (45%) potential cross-reactive serum samples as positive, respectively. In contrast, significant borreliacidal activity was not detected in any potential cross-reactive serum samples. CONCLUSION: Detection of borreliacidal antibody, unlike indirect fluorescent antibody and enzyme immunoassay, is an accurate, highly specific serodiagnostic test for detection of Lyme disease.

Antibodies, Bacterial↗
PubMed1994

Seroprotective groups of Lyme borreliosis spirochetes from North America and Europe.

Five distinct seroprotective groups among North American and European isolates of Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii have been identified using the in vitro borreliacidal assay. The predominant North American seroprotective group comprised isolate 297 and B. burgdorferi isolates from California, Illinois, Wisconsin, New York, and Texas. A second group was represented by isolate C-1-11. The majority of European isolates belonged to a seroprotective group composed of B. garinii. Another European group contained isolates classified genetically as genospecies group VS461 (B. afzelii). A fifth group, represented by isolate LV5, could kill both North American and European isolates of B. burgdorferi sensu lato. These results suggest that combinations of immunogenic protective proteins of spirochetes will be necessary to provide a comprehensive vaccine.

Animals↗
PubMed1994

Detection of borreliacidal antibody by using acridine orange and flow cytometry.

Borreliacidal antibody has been shown to be important for the serodiagnosis of Lyme disease and determination of immune status. Our results show that borreliacidal antibody can be rapidly and accurately detected by flow cytometry. Acridine orange was added to normal and immune sera containing Borrelia burgdorferi organisms in the presence and absence of complement prior to data acquisition by flow cytometry. The flow cytometric parameters of side scatter and detection of acridine orange fluorescence were used to determine events per minute (number of labeled spirochetes), percent shift in fluorescence (number of dead spirochetes), and mean channel fluorescence (intensity of fluorescence-labeled spirochetes) of acridine orange-labeled spirochetes. Borreliacidal antibody was detected as early as 4 h, with optimal detection 16 to 24 h after incubation of B. burgdorferi organisms with immune serum and complement. Our results also showed that complement was necessary for detection of borreliacidal antibody. Flow cytometry with acridine orange-labeled spirochetes provides a rapid means for detection of borreliacidal antibody.

Acridine Orange↗
PubMed1994

Differentiation of borreliacidal activity caused by immune serum or antimicrobial agents by flow cytometry.

We demonstrated that borreliacidal activity caused by immune serum and complement can easily be differentiated by flow cytometry from killing activity caused by antimicrobial agents that are commonly used for the treatment of Lyme disease. Assay suspensions containing normal or immune serum were incubated with Borrelia burgdorferi in the presence or absence of ceftriaxone, doxycycline, penicillin, and phosphomycin for 2, 8, 16, and 24 h. Samples containing killing activity were identified by using flow cytometry and acridine orange. In 30 min, the effects of immune serum and complement were easily distinguished from the killing of spirochetes by antimicrobial agents by adding fluorescein isothiocyanate-conjugated goat anti-hamster immunoglobulin. This simple procedure greatly enhanced the usefulness of the borreliacidal assay by eliminating a major source of false-positive reactions.

Acridine Orange↗
PubMed1994

Development of destructive arthritis in vaccinated hamsters challenged with Borrelia burgdorferi.

We present the first direct evidence that adverse effects, particularly severe destructive arthritis, can develop in vaccinated hamsters after challenge with Borrelia burgdorferi sensu lato isolates. Hamsters were vaccinated with a whole-cell preparation of Formalin-inactivated B. burgdorferi sensu stricto isolate C-1-11 in adjuvant. A severe destructive arthritis was readily evoked in vaccinated hamsters challenged with the homologous B. burgdorferi sensu stricto isolate C-1-11 before high levels of protective borreliacidal antibody developed. Once high levels of C-1-11 borreliacidal antibody developed, hamsters were protected from homologous challenge and development of arthritis. Vaccinated hamsters, however, still developed severe destructive arthritis when challenged with other isolates of the three genomic groups of B. burgdorferi sensu lato (B. burgdorferi sensu stricto isolate 297, Borrelia garinii isolate LV4, and Borrelia afzelii isolate BV1) despite high levels of C-1-11 specific borreliacidal antibody. Vaccines that contained whole spirochetes in adjuvant induced destructive arthritis, but this effect was not dependent on the isolate of B. burgdorferi sensu lato or the type of adjuvant. These studies demonstrate that caution is necessary when employing whole spirochetes in adjuvant for vaccination to prevent Lyme borreliosis. Additional studies are needed to identify the antigen(s) responsible for the induction and activation of arthritis and to define the immune mechanisms involved.

Adjuvants, Immunologic↗
PubMed1994

Ability of canine Lyme disease vaccine to protect hamsters against infection with several isolates of Borrelia burgdorferi.

We used flow cytometry to determine levels of borreliacidal antibodies in hamsters after vaccination with a commercially available canine Lyme disease vaccine. In addition, we evaluated the ability of vaccinated hamsters to resist infection with several isolates of Borrelia burgdorferi. Borreliacidal antibodies could be detected 1 week after a primary vaccination, peaked at weeks 3 to 5, and then rapidly declined. One week after a booster vaccination, borreliacidal activity was detected at a dilution of 1:10,240, and it decreased fourfold by week 10 after the booster vaccination. Vaccinated hamsters were protected against infection with < or = 10(6) B. burgdorferi 297 organisms during the peak borreliacidal response (5 weeks after primary vaccination or 2 weeks after booster vaccination). However, hamsters were not fully protected from development of Lyme arthritis when the titer of borreliacidal antibodies was < 1:5,120. In addition, no significant borreliacidal activity was induced against B. burgdorferi C-1-11, LV4, or BV1, which belong to three other seroprotective groups. These studies demonstrate that vaccination with the canine Lyme disease vaccine induces protective antibodies against B. burgdorferi 297. However, significant levels of borreliacidal antibodies are not produced until 5 weeks after vaccination, and protection is short-lived. In addition, no borreliacidal activity was induced against other isolates of B. burgdorferi. Because of this, the incorporation of multiple isolates or protein subunits may be necessary to increase the effectiveness of future vaccines.

Animals↗
PubMed1994

Use of low molecular weight heparin in the treatment of venous thrombosis in a patient with anti-thrombin III deficiency: a case report.

This paper describes the use of a low molecular weight heparin (LMWH) in the treatment of a thrombotic episode in a patient with anti-thrombin III deficiency. Subcutaneous Fraxiparine, a low molecular weight heparin, was successfully used in the initial treatment of a second thrombotic episode in this patient with good results--no clot extension and an almost complete resolution of pulmonary emboli. This case demonstrates the advantages of using LMWH over conventional unfractionated heparin (UFH) which include ease of administration and the rapid achievement of optimal anticoagulation in conjunction with a diminished need for laboratory monitoring.

Adult↗
PubMed1993

Linkage between tyrosine hydroxylase gene and affective disorder cannot be excluded in two of six pedigrees.

Genetic linkage between manic depression and DNA markers on the short arm of chromosome 11 was first reported in 1987 but not supported by further analyses. However, genetic markers at the tyrosine hydroxylase (TH) gene located within this region have been reported to show allelic association with the affective disorder phenotype. We present the results of a linkage analysis using polymorphic DNA segments within the TH gene and the nearby dopamine D4 receptor (DRD4) gene in 6 families multiply affected with affective disorder. Small positive Lod scores were obtained in 2 of 6 pedigrees with the TH polymorphism which may be indicative of genetic heterogeneity.

Female↗
PubMed1993

Characterization of the molecularly cloned murine alpha-globin transcription factor CP2.

We recently cloned human and murine cDNAs that encode CP2, a transcription factor that interacts with the murine alpha-globin promoter. In this report, we exploited our ability to express CP2 in bacteria and eukaryotic cells to further investigate factor activities in vitro and in vivo. CP2 expressed in bacteria was significantly enriched and used in a series of DNase I footprinting and electrophoretic gel shift assays. The results suggest that CP2 binds a hyphenated recognition sequence motif that spans one DNA helix turn. In addition, the enriched bacterial protein activated transcription of alpha-globin promoter templates approximately 3- to 4-fold in vitro. We then tested the effect of elevating CP2 levels 2.5- to 5.5-fold in vivo using both transient and stable transformation assays. When a reporter construct comprised of the intact murine alpha-globin promoter driving the bacterial chloramphenicol acetyltransferase (CAT) gene was introduced into these overexpressing cells, we observed a 3- to 6-fold increase in CAT activity when compared to cells expressing normal levels of CP2. These results define the CP2 factor binding site in more detail and help characterize the activities of the factor in vivo.

Animals↗
PubMed1993

Induction of interleukin-1 release by high- and low-passage isolates of Borrelia burgdorferi.

Low-passage isolates of Borrelia burgdorferi induced arthritis when injected into the hind paws of irradiated hamsters, while high-passage isolates did not. To examine a possible mechanism for induction of arthritis, peritoneal exudate cells were coincubated with high- and low-passage isolates of B. burgdorferi, and the resultant conditioned medium was assayed for interleukin-1 (IL-1) activity. Comparable amounts of IL-1 activity were detected in culture supernatants generated by high- and low-passage spirochetes and were dependent on the number of spirochetes added. Live B. burgdorferi stimulated greater release of IL-1 activity than did heat-killed organisms. No evidence of release of IL-1 due to shedding of soluble components from spirochetes was obtained. A recombinant human IL-1 receptor antagonist blocked the proliferative activity of conditioned medium in a murine thymocyte assay for IL-1 activity. The greater ability of low-passage spirochetes to survive in vivo may be more important than the ability to induce IL-1 production in the pathogenesis of Lyme arthritis.

Animals↗
PubMed1993

Seroprotective groups among isolates of Borrelia burgdorferi.

We demonstrated that different seroprotective groups exist among isolates of Borrelia burgdorferi and Borrelia garinii. The major group was composed of isolates 297, B31, S-1-10, MMTI, IPT, and ATCC 35211 and 21 isolates obtained from California, Illinois, New York, Texas, and Wisconsin. A second group was composed of European isolates PBi and G25. A third group was composed of a single isolate, C-1-11. These groupings were supported by Western immunoblot findings. In addition, the seroprotective groups were confirmed by passive transfer of immune sera and challenge of recipient hamsters with the homologous isolate or other isolates of B. burgdorferi or B. garinii. These studies demonstrate that a monovalent vaccine will not provide complete protection against infection with all isolates of B. burgdorferi.

Animals↗
PubMed1993

Mortality of public mental health patients: a Singapore experience.

This study reports the Standardised Mortality Ratio (SMR) by age and sex among public mental health patients in Singapore. The authors also examine the differences between those who were classified as "inpatient deaths" and those who were classified as "outpatient deaths". Mortality was 5.1 times that of the general population and the SMR was most accentuated in the younger, female patients. Of the 217 deaths documented over two years, schizophrenia was the most common diagnosis. Inpatient deaths (N = 120) occurred in older patients with prior physical illness who died of natural causes. In contrast, outpatient deaths (N = 97) involved younger patients with no previous illness and the majority jumped to their deaths. Mortality studies are necessary in monitoring the efficacy of mental health provisions.

Adolescent↗