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Biomedical subjects

L E Lim

Publications and source records attributed to L E Lim.

At least 19 recordsLinked to original sources
PubMed2001

Men who commit statutory rape: how are they different from other rapists?

From an original cohort of 63 rapists serving prison sentences for rape in Singapore, two subgroups were identified, one subgroup who raped females 14 years and younger (an offence that is termed 'statutory rape' or 'SR') and another who raped females 14 years and above (which we term 'non-statutory rape' or 'NSR'). The two subgroups were compared across a broad range of variables. Those who committed SR tended to be older, married, Malay men who were more likely to commit rape in their home or in the home of their victims, and who rated the quality of their sexual relationships more unfavourably than the NSRs. The NSRs were more likely to be single men but with concurrent relationships with different females. NSRs were more likely to report dysfunctional family backgrounds, early conduct problems and were more likely to rape their victims outdoors and late into the night. Although in both subgroups the majority of the victims were known to the rapists, relatives (i.e. step-daughters or daughters) were by far the most common victims of the SR rapists.

Adolescent↗
PubMed2001

Men who commit rape in Singapore.

INTRODUCTION: Rape is regarded as one of the most serious forms of sexual assault, yet there has been a lack of clinical information on convicted rapists in Singapore. This paper attempts to confirm the hypotheses that rapists come from disordered backgrounds, from large families and are poorly educated. We further hypothesize that they are more likely to have a history of antisocial behaviour and to have had recent exposure to pornography. METHODS: Rapists serving sentence in a Singapore prison were compared with 2 control groups, one consisting of violent non-sexual offenders and another comprising non-violent non-sexual offenders. RESULTS: Rapists tended to be men in their late thirties who rape women in their early twenties. A large majority of the rapists and their victims are known to each other. Rapists are more likely to come from large, disordered families, attaining low educational levels but seemingly less antisocial when compared with the controls. More rapists and violent controls reported recent viewing of pornography before committing their offenses. CONCLUSION: The demonstrated similarities between rapists and violent controls lend support to the view that rape is an act of violence carried out in a sexual manner rather than a sexual act violently expressed.

Adult↗
PubMed2000

Molecular and genetic characterization of sarcospan: insights into sarcoglycan-sarcospan interactions.

Autosomal recessive limb girdle muscular dystrophies 2C-2F represent a family of diseases caused by primary mutations in the sarcoglycan genes. We show that sarcospan, a novel tetraspan-like protein, is also lost in patients with either a complete or partial loss of the sarcoglycans. In particular, sarcospan was absent in a gamma-sarcoglycanopathy patient with normal levels of alpha-, beta- and delta-sarcoglycan. Thus, it is likely that assembly of the complete, tetrameric sarcoglycan complex is a prerequisite for membrane targeting and localization of sarcospan. Based on our findings that sarcospan is integrally associated with the sarcoglycans, we screened >50 autosomal recessive muscular dystrophy cases for mutations in sarcospan. Although we identified three intragenic polymorphisms, we did not find any cases of muscular dystrophy associated with primary mutations in the sarcospan gene. Finally, we have identified an important case of limb girdle muscular dystrophy and cardiomyopathy with normal expression of sarcospan. This patient has a primary mutation in the gamma-sarcoglycan gene, which causes premature truncation of gamma-sarcoglycan without affecting assembly of the mutant gamma-sarcoglycan into a complex with alpha-, beta- and delta-sarcoglycan and sarcospan. This is the first demonstration that membrane expression of a mutant sarcoglycan-sarcospan complex is insufficient in preventing muscular dystrophy and cardiomyopathy and that the C-terminus of gamma-sarcoglycan is critical for the functioning of the entire sarcoglycan-sarcospan complex. These findings are important as they contribute to a greater understanding of the structural determinants required for proper sarcoglycan-sarcospan expression and function.

Adult↗
PubMed2000

Pharmacological properties of a new aziridinylbenzoquinone, RH1 (2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone), in mice.

RH1 (2,5-diaziridinyl-3-(hydroxylmethyl)-6-methyl-1,4-benzoquinone) has shown preferential activity against human tumour cell lines which express high levels of DTD (EC 1.6.99.2; NAD(P)H:quinone oxidoreductase, NQO1, DT-diaphorase) and is a candidate for clinical trials. EO9 (3-hydroxy-5-aziridinyl-1-methyl-2-[1H indole-4,7-dione]prop-beta-en-alpha-ol) is a known substrate for DTD but clinical trials were disappointing, as a result of rapid plasma clearance and reversible dose-limiting kidney toxicity. It is an obvious concern that RH1 does not exhibit the same limitations. We therefore describe the antitumour activity and pharmacology of RH1 in mice and compare its pharmacological characteristics to those of EO9. Significant antitumour activity (P = 0.01) was seen for RH1 (0.5 mg/kg, i.p.) against the high DTD-expressing H460 human lung carcinoma. Pharmacokinetic analysis of RH1 in mice showed a t1/2 of 23 min with an area under the curve of 43.0 ng hr mL(-1) resulting in a calculated clearance of 5.1 mL min(-1), 10-fold slower than EO9. RH1 was also more stable than EO9 in murine blood, where the breakdown was thought to be DTD-related. NADH-dependent microsomal metabolism of RH1 and EO9 in both liver and kidney was slow (<100 pmol/min/g tissue), reflecting the low microsomal DTD expression (<35 nmol/mg/min). Liver cytosol metabolism was rapid for both compounds (>4500 pmol/min/g tissue), although DTD levels were low (21.4+/-0.6 nmol/mg/min). DTD activity in the kidney cytosol was high (125+/-8.2 nmol/mg/min) and EO9 was rapidly metabolised (4396+/-1678 pmol/min/g), but the metabolic rate for RH1 was 7-fold slower (608+/-86 pmol/min/g), even though RH1 was shown to be an excellent substrate for DTD (Vmax = 800 micromol/min/mg and a Km of 11.8 microM). The two DTD substrates RH1 and EO9 are clearly metabolised differently, suggesting that RH1 may have different pharmacological properties to those of EO9 in the clinic.

Animals↗
PubMed2000

A study of outrage of modesty offenders in a Singapore prison.

Outrage of modesty (OOM) offenders cause considerable annoyance and distress to their victims. The offending behaviours include touching, grabbing or fondling of erogenous or non-erogenous parts of the victim's body. The purpose of this study is to examine a prison cohort of OOM offenders and to compare them with a group of OOM offenders who had been remanded in a state mental hospital. All prisoners serving sentence over a two-year study period were interviewed. They were of similar mean age to the hospital cohort but were better educated, more likely to be married and most were working. Victims tended to be young females with an average age of 19 years. Psychotic disorders were rarely present, although 15% had a dissocial personality disorder. Those with previous OOM convictions were likely to have had past psychiatric consultations and were more likely to be unmarried. However, there were no statistically significant differences between convicted first-time offenders and repeat offenders with respect to age, educational level, nature of offences and alcohol consumption. The prisoners were less inclined to commit their offences in the mornings. Breasts and genitalia were the favoured targets for molest action, irrespective of time or place or whether the offence was committed by a first or repeat offender. The offences were often committed along staircases, corridors and in crowded public places.

Adolescent↗
PubMed2000

The sexual habits of males who molest.

To gain better understanding into the causes of molesting behaviour in males, we examined a prison cohort of molesters and compared them with a control group comprising thieves. The molesters were older, had attained a higher educational level and were more likely to be married. They had their initial sexual intercourse at an older age but tended to have multiple sexual relationships and were less likely to report having viewed pornographic material. Three months prior to committing their offences, molesters seemed to engage in less sexual activity. The implications are that molesters had a need for more explicit sexual contact but were unable to sustain ongoing, stable, intimate sexual relationships.

Adult↗
PubMed2000

A review of offenders remanded in a State Psychiatric Hospital.

Patients remanded over a two-year period to Woodbridge Hospital by Court Order were studied retrospectively. Schizophrenia was the most common diagnosis, theft and robbery the most prevalent offences. Males greatly outnumbered females. There were important gender differences, with males tending to commit sexual offences and females, theft and mischief. Males were less likely to be acquainted with their victims but those who caused hurt were more likely to know their victims. Outrage of modesty and theft were more likely to be committed against strangers. The reconviction rate was 26%, with repeat offenders more likely to commit sexual offences and theft. Patients who had previous psychiatric hospitalisation were more likely to be attending follow-up prior to and after release from remand and were more likely to have schizophrenia. Those assessed to be fit to plead were either fined or given jail sentences. Unsoundness of mind and unfitness to plead were associated with further remand in this hospital.

Adult↗
PubMed1999

Minimum requirements for efficient transduction of dividing and nondividing cells by feline immunodeficiency virus vectors.

The development of gene delivery vectors based on feline immunodeficiency virus (FIV) is an attractive alternative to vectors based on primate sources for the delivery of genes into humans. To investigate the requirements for efficient transduction of dividing and nondividing cells by vector particles based on FIV, a series of packaging and vector constructs was generated for which viral gene expression was minimized and from which unnecessary cis-acting sequences were deleted. Pseudotyped vector particles produced in 293T cells were used to transduce various target cells, including contact-inhibited human skin fibroblasts and growth-arrested HT1080 cells. FIV vectors in which the U3 promoter was replaced with the cytomegalovirus promoter gave rise to over 50-fold-higher titers than FIV vectors containing the complete FIV 5' long terminal repeat (LTR). Comparison of the transduction efficiencies of vectors containing different portions of the FIV Gag coding region indicates that at least a functional part of the FIV packaging signal (Psi) is located within an area which includes the 5' LTR and the first 350 bp of gag. Transduction efficiencies of vectors prepared without FIV vif and orf2 accessory gene expression did not differ substantially from those of vectors prepared with accessory gene expression in either dividing or nondividing cells. The requirement for FIV rev-RRE was, however, demonstrated by the inefficient production of vector particles in the absence of rev expression. Together, these results demonstrate the efficient transduction of nondividing cells in vitro by a multiply attenuated FIV vector and contribute to an understanding of the minimum requirements for efficient vector production and infectivity. In addition, we describe the ability of an FIV vector to deliver genes in vivo into hamster muscle tissue.

Animals↗
PubMed1998

Progressive muscular dystrophy in alpha-sarcoglycan-deficient mice.

Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mutations in the alpha-sarcoglycan gene. To determine how alpha-sarcoglycan deficiency leads to muscle fiber degeneration, we generated and analyzed alpha-sarcoglycan- deficient mice. Sgca-null mice developed progressive muscular dystrophy and, in contrast to other animal models for muscular dystrophy, showed ongoing muscle necrosis with age, a hallmark of the human disease. Sgca-null mice also revealed loss of sarcolemmal integrity, elevated serum levels of muscle enzymes, increased muscle masses, and changes in the generation of absolute force. Molecular analysis of Sgca-null mice demonstrated that the absence of alpha-sarcoglycan resulted in the complete loss of the sarcoglycan complex, sarcospan, and a disruption of alpha-dystroglycan association with membranes. In contrast, no change in the expression of epsilon-sarcoglycan (alpha-sarcoglycan homologue) was observed. Recombinant alpha-sarcoglycan adenovirus injection into Sgca-deficient muscles restored the sarcoglycan complex and sarcospan to the membrane. We propose that the sarcoglycan-sarcospan complex is requisite for stable association of alpha-dystroglycan with the sarcolemma. The Sgca-deficient mice will be a valuable model for elucidating the pathogenesis of sarcoglycan deficient limb-girdle muscular dystrophies and for the development of therapeutic strategies for this disease.

Amino Acid Sequence↗
PubMed1998

Beta-sarcoglycan: genomic analysis and identification of a novel missense mutation in the LGMD2E Amish isolate.

The sarcoglycan complex is involved in the etiology of four autosomal recessive limb-girdle muscular dystrophies (LGMD2C-F). A missense mutation (T151R) in the beta-sarcoglycan gene on chromosome 4q12 has been shown to cause a mild form of LGMD2E in 11 families from a Southern Indiana Amish community sharing a common haplotype. We now report that two sibs from another Amish family with mild LGMD2E are compound heterozygotes for chromosome 4q12 markers. In order to characterize the genetic defect in this new family, we determined the genomic organization of the beta-sarcoglycan gene. A second missense mutation (R91C) has now been identified in this LGMD2E Amish family. This mutation is also present in the homozygous state in another family of probable Amish ancestry. Finally, analysis of all the components of the dystrophin-glycoprotein complex was performed for the first time on a biopsy from a patient homozygous for the beta-sarcoglycan mutation (T151R). Interestingly, in addition to the loss of the entire sarcoglycan complex, we detected a reduction of alpha-dystroglycan which suggests a role for the sarcoglycan complex in stabilizing alpha-dystroglycan at the sarcolemma.

Adolescent↗
PubMed1998

Functional rescue of the sarcoglycan complex in the BIO 14.6 hamster using delta-sarcoglycan gene transfer.

Four types of limb-girdle muscular dystrophy (LGMD) are known to be caused by mutations in distinct sarcoglycan genes. The BIO 14.6 hamster is a model for sarcoglycan-deficient LGMD with a deletion in the delta-sarcoglycan (delta-SG) gene. We investigated the function of the sarcoglycan complex and the feasibility of sarcoglycan gene transfer for LGMD using a recombinant delta-SG adenovirus in the BIO 14.6 hamster. We demonstrate extensive long-term expression of delta-sarcoglycan and rescue of the entire sarcoglycan complex, as well as restored stable association of alpha-dystroglycan with the sarcolemma. Importantly, muscle fibers expressing delta-sarcoglycan lack morphological markers of muscular dystrophy and exhibit restored plasma membrane integrity. In summary, the sarcoglycan complex is requisite for the maintenance of sarcolemmal integrity, and primary mutations in individual sarcoglycan components can be corrected in vivo.

Adenoviridae↗
PubMed1998

The sarcoglycan complex in limb-girdle muscular dystrophy.

The involvement of the sarcoglycan complex in the pathogenesis of muscular dystrophy is becoming increasingly clear. Sarcoglycan gene mutations lead to four forms of autosomal recessive limb-girdle muscular dystrophy. Recent progress has been made with the identification of novel mutations and their correlations with disease. Through this research, a better understanding the molecular pathogenesis of limb-girdle muscular dystrophy has been gained. Finally, animal models are now being used to study viral-mediated gene transfer for the future treatment of this disease.

Animals↗
PubMed1997

A review of outrage of modesty offenders remanded in a state mental hospital.

Minor sexual offences have been increasing over the years. These include parasexual offences such as exhibitionism, frotteurism and its variant. In Singapore, a common minor sexual offence which involves touching, grabbing, kissing or fondling is known as outrage of modesty or molestation. To date no known studies have been made on this subtype of sexual offender. This is a five-year retrospective study looking into the profile of 157 outrage of modestry offenders remanded to Woodbridge Hospital, a state mental hospital. Results showed that schizophrenia was the predominant psychiatric diagnosis amongst the offenders (45.3%) followed by mental retardation (21.7%). Only 28.7% of those suffering from a mental illness experienced active psychiatric symptoms at the time of the sexual offence. Touching, stroking or fondling were the most frequently reported type of molestation (60.5%). The majority of the offences took place between 6 am and 6 pm. Only 15.3% had a past history of sexual offences and the majority (94.9%) were of sound mind at the time of the offence. There were no statistically significant differences between first time and repeat offenders with regard to age, ethnic group, educational level, marital status, diagnoses, place of offence, time and type of offence, soundness of mind and fitness to plead.

Adult↗
PubMed1997

Panic disorder in Singapore: clinical features and comparisons with generalised anxiety disorder.

Fifty-eight outpatients with panic disorder (PD) were examined to determine their clinical features in comparison with a cohort of 52 patients with generalised anxiety disorder (GAD). Both groups were of comparable age, sex, educational level, marital status and ethnicity. PD patients were more likely to complain of palpitations, breathlessness, chest pain, numbness, choking sensations and especially fear of dying. GAD patients tended to complain of feeling tense, insomnia, headaches, weakness, restlessness and muscle aches. PD patients had greater comorbidity especially with agoraphobia and depression. Contrary to other reports, there were more males than females in both groups but alcohol dependence and suicide attempts were relatively rare. PD symptoms seemed more distressing, caused more social and occupational disruption, led to more requests for medical investigations and earlier psychiatric consultations. These factors seemed to suggest that panic disorder is a more severe illness than generalised anxiety disorder.

Adult↗
PubMed1995

Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12.

beta-Sarcoglycan, a 43 kDa dystrophin-associated glycoprotein, is an integral component of the dystrophin-glycoprotein complex. We have cloned human beta-sarcoglycan cDNA and mapped the beta-sarcoglycan gene to chromosome 4q12. Pericentromeric markers and an intragenic polymorphic CA repeat cosegregated perfectly with autosomal recessive limb-girdle muscular dystrophy in several Amish families. A Thr-to-Arg missense mutation was identified within the beta-sarcoglycan gene that leads to a dramatically reduced expression of beta-sarcoglycan in the sarcolemma and a concomitant loss of adhalin and 35 DAG, which may represent a disruption of a functional subcomplex within the dystrophin-glycoprotein complex. Thus, the beta-sarcoglycan gene is the fifth locus identified (LGMD2E) that is involved in autosomal recessive limb-girdle muscular dystrophy.

Amino Acid Sequence↗
PubMed1995

Why patients fail to attend psychiatric outpatient follow-up: a pilot study.

Patients who failed to attend psychiatric outpatient follow-up were compared with a group of comprising regular attenders. There were 71 defaulters out of 1,664 appointments given during the study period. Schizophrenia was the most common diagnosis. The defaulters did not differ from the controls in terms of age, sex, ethnicity, occupational or marital status. The unemployed were not more likely to be regular, instead, the better educated, shorter intervals between appointments and those given morning appointments were. Those solely on oral medication were more likely to default. The largest proportion gave reasons of work commitments and of not being free to attend; others claimed they had forgotten their appointments or had lost their appointment cards. Patients who said they did not come because they felt well or still had medication were cause for concern because of possible lack of insight and non-compliance with their medication.

Adult↗
PubMed1994

Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy.

Adhalin, the 50 kDa dystrophin-associated glycoprotein, is deficient in skeletal muscle of patients having severe childhood autosomal recessive muscular dystrophy (SCARMD). In several North African families, SCARMD has been linked to chromosome 13q, but SCARMD has been excluded from linkage to this locus in other families. We have now cloned human adhalin cDNA and mapped the adhalin gene to chromosome 17q12-q21.33, excluding it from involvement in 13q-linked SCARMD. However, one allelic variant of a polymorphic microsatellite located within intron 6 of the adhalin gene cosegregated perfectly with the disease phenotype in a large family. Furthermore, missense mutations were identified within the adhalin gene that might cause SCARMD in this family. Thus, the adhalin gene is involved in at least one form of autosomal recessive muscular dystrophy.

Amino Acid Sequence↗