Biomedical subjects

S W Law

Publications and source records attributed to S W Law.

At least 19 recordsLinked to original sources

PubMed2006

A prospective case-control study of ankle fracture in postmenopausal women.

OBJECTIVES: To compare bone mineral density of women with postmenopausal ankle fractures with controls and review patient characteristics, injury mechanisms, and outcomes. DESIGN: Prospective case-control study. SETTING: University teaching hospital, Hong Kong. PARTICIPANTS: Women older than 60 years, admitted with ankle fractures between 2002 and 2003 and controls (age-matched women with femoral neck fractures). MAIN OUTCOME MEASURES: Demographic data, bone mineral density, mechanism of injury, fracture pattern, treatment, and the functional outcome. RESULTS: The mean age of the study group (18 ankle fracture patients) was 74 years. The fractures usually resulted from a low-energy trauma; isolated lateral malleolar fracture was the most common (8/18), whilst six had bimalleolar fractures. Their mean T-score bone mineral density values at the spine and hip were -1.67 and -1.70, respectively; corresponding Z-scores were +0.73 and +0.99. The bone mineral density of the study group was significantly higher than in patients with fractured neck of femur (controls) and the general population (P<0.05). Nine of the study group had diabetes and one had impaired glucose tolerance. Treatment comprised casting in 10 patients and operative fixation in seven. Good functional recovery was achieved; most patients were able to resume their premorbid level of independent daily activities with a good motor functional independence score (85.18/91) 1 year post-injury. CONCLUSION: In this case-control study, postmenopausal ankle fractures were not associated with osteoporosis. Diabetic neuropathy may have been a risk factor for such injury. The functional outcome of such patients was generally satisfactory, provided appropriate treatment was given.

Aged↗

PubMed2005

Management of malignant atlanto-axial tumours.

PURPOSE: To review the management and outcomes of patients with malignant tumours of the atlanto-axial spine treated over a 4-year period at a tertiary hospital. METHODS: A total of 12 patients (9 female and 3 male) with a mean age of 56.5 years (range, 35-71 years) were consecutively enrolled. At the time of presentation, 7 patients had received treatment for a known primary malignancy of the lung (n=4), colon (n=1), nasopharynx (n=1), or breast (n=1). The atlanto-axial spine was the first presentation of malignant disease in the remaining 5 patients, whose subsequent diagnoses were multiple myeloma (n=1), carcinoma of the thyroid (n=1), malignant fibrous histiocytoma (n=2), and adenocarcinoma of unknown origin (n=1). Preoperative, postoperative, and follow-up radiographs and computed tomographic and magnetic resonance imaging scans were analysed with regard to the extent of tumour involvement, other spinal metastases, instability, and evidence of cord compression. Surgeries were performed for surgically fit patients with a life expectancy of more than 3 months. RESULTS: All patients presented with severe suboccipital neck pain. Two had mild neurological deficits (Frankel grade D). Two patients were treated conservatively with rigid neck collars and survived for 3 and 11 months. Surgical stabilisation with posterior instrumentation was performed in 10 patients. One patient received additional anterior surgery for tumour debulking and bone grafting. No neurological complications were recorded in the series. Excellent relief of pain was achieved, and the mean visual analogue scale pain score of the operated patients improved from 9.3 to 1.9. The mean survival of 9 patients after surgery was 13.1 months, while one patient was still living at the time of review (at postoperative 11 months). CONCLUSION: Surgical stabilisation in selected patients provided pain relief and preserved ambulatory status before the deterioration of overall function.

Adult↗

PubMed2001

Enhanced soft tissue repair using locking loop stitch after posterior approach for hip hemiarthroplasty.

Hemiarthroplasty of the hip for displaced fracture of the femoral neck (including Austin-Moore and Thompson arthroplasties) frequently is performed by orthopaedic surgeons. The posterior approach is used despite the slight increase in risk of postoperative dislocation. The outcome after dislocation can be disastrous. We tried to prevent this complication by repairing the posterior capsule and the short external rotators (piriformis, superior and inferior gemellus, obturator internus, and upper part of quadratus femoris) using locking loop stitch as described by Krackow. From January 1998 to April 1999, 205 hips were operated on and followed up for >3 months; no dislocation was found. Using the past records as the comparative group, 28 posterior dislocations (1.9%) were found in 1,483 hip hemiarthroplasties using the posterior approach (P <.05 using exact probability test). Enhanced soft tissue repair with locking loop stitch is an effective way to reduce the incidence of dislocation after hip hemiarthroplasty using the posterior approach.

Aged↗

PubMed1994

Hormonal regulation of hypothalamic gene expression: identification of multiple novel estrogen induced genes.

Estrogen (E) has been shown to play a major role in hypothalamic function and is a prerequisite for progesterone (P) induced sexual behavior in female rats. In the course of studies in search of steroid induced hypothalamic genes, we discovered a surprisingly large number of E-induced genes (21 mRNAs in total). This is the largest number of E-induced genes ever identified in a single organ. Many of these mRNAs exhibit considerable magnitudes of induction and their levels were maintained typically during subsequent P treatment. Among the induced genes, several encode metabolic enzymes and may account for some of the morphological changes observed in hypothalamic neurons in response to E. Since E appears to play a major role in defining the pattern of hypothalamic gene expression in conjunction with its capacity for behavioral modulation, these newly identified cDNAs may serve as genetic markers for correlative studies of E-induced central nervous system behavior.

Animals↗

PubMed1994

Inhibition of rat sexual behavior by antisense oligonucleotides to the progesterone receptor.

To test further the idea that sexual behavior in rodents is mediated via the progesterone receptor (PR) in the ventromedial nucleus of the hypothalamus, antisense and sense oligonucleotides to progesterone receptor were administered intracerebroventricularly into the third cerebral ventricle of ovariectomized estrogen-primed animals. Progesterone-facilitated sexual behavior was inhibited in animals treated with antisense oligonucleotides, with proceptive and receptive responses being minimal or completely suppressed. Sexual behavior was not altered by control sense oligonucleotides. In vitro binding assays of the cytosol progesterone receptors demonstrated a 52.2% reduction of PRs in the hypothalamus of animals that received antisense oligonucleotides, suggesting a reduction in PR synthesis. These data suggest that a threshold level of estrogen-induced hypothalamic PR is critical in the regulation of progesterone-facilitated sexual behavior in female rats.

Animals↗

PubMed1994

Cloning of a novel orphan receptor (GCNF) expressed during germ cell development.

We have cloned a novel member of the nuclear receptor superfamily that has been identified from complementary DNA libraries derived from mouse tissues using a low stringency cross hybridization strategy. The deduced protein sequence contains 495 amino acids and consists of the characteristic DNA-binding and ligand-binding domains of the nuclear receptor superfamily. The primary sequence of this new orphan is distinct from those of previously cloned members and subgroups. Analysis of the DNA-binding properties of the in vitro synthesized protein revealed that this new orphan receptor binds to the sequence TCAAGGTCA that includes the steroidogenic factor-1 half-site and direct repeat with 0 bp spacing elements. Northern blot and ribonuclease protection assays showed that the receptor was predominantly expressed in the testis. Results from in situ hybridization experiments confirmed this observation and showed it to be located in the spermatogenic cells. High level expression was also detected in developing oocytes in the ovary. Thus, high level expression of this gene is restricted to developing germ cells, the oocytes and spermatogenic cells. We speculate that this orphan receptor may be a molecule involved in regulating some aspect of meiosis, and that the major function of this factor is likely to be involved in the regulation of gene expression in germ cell development during gametogenesis. It has been designated germ cell nuclear factor.

Amino Acid Sequence↗

PubMed1994

Molecular cloning of a novel member of the nuclear receptor superfamily related to the orphan receptor, TR2.

We have cloned a novel member (mTR2R1) of the nuclear receptor superfamily of transcription factors from a mouse brain cDNA library. The cDNA sequence predicts a protein primary structure of 629 amino acids with a calculated molecular weight of 68.8 kDa. The amino acid sequence of the protein contains three regions of consensus sequence that are conserved throughout the nuclear receptor superfamily. One of these regions encodes a type II zinc finger DNA binding domain that is characteristic of this family of transcription factors. Comparison of the amino acid sequence of mTR2R1 with other nuclear receptors indicates that it is most closely related to the orphan receptor, hTR2, and suggests that these proteins constitute a novel subfamily within the nuclear receptor superfamily. mTR2R1 is encoded by two mRNAs that show different but overlapping spatial patterns of expression in the adult mouse. The identification of a subfamily of TR2 receptors together with the existence of variant mRNAs for these receptors prompts a close examination of the tissue-specific regulatory role of this subfamily of nuclear receptors.

Amino Acid Sequence↗

PubMed1993

Identification of two mPPAR related receptors and evidence for the existence of five subfamily members.

Two additional forms of mouse peroxisome proliferator activated receptor have been identified from cDNA libraries derived from mouse tissues using a low stringency cross-hybridization screening method. One is mNUCI, which has 97% amino acid sequence identity with hNUCI in its DNA binding domain. The other one is mPPAR gamma. The full-length cDNA of mPPAR gamma encodes a protein of 470 amino acids in length. The overall amino acid sequence identity is 75% as compared with xPPAR gamma, with the highest homology in the DNA binding region and ligand binding region, 97% and 86% identity, respectively. The discovery of two new forms of mPPAR and the recent cloning of hPPAR provide evidence for the existence of at least five different forms of receptor in the peroxisome proliferator activated receptor subfamily.

Amino Acid Sequence↗

PubMed1992

Identification of a new brain-specific transcription factor, NURR1.

We have identified and cloned a novel member of the nuclear receptor superfamily. The cDNA was isolated from a mouse brain cDNA library and encodes a protein 598 amino acids in length with a predicted mol wt of 66 kilodaltons. The amino acid sequence of the protein is closely related to an additional family member and immediate early gene product, Nur77, and the novel factor is referred to as Nurr1 (Nur-related factor 1). The relationship between Nurr1 and Nur77 suggests that these proteins constitute an additional subfamily within the nuclear receptor superfamily. Like Nur77, the expression of Nurr1 is induced by membrane depolarization of PC12 cells. However, while Nur77 shows an early transcriptional response to nerve growth factor stimulation, the failure of Nurr1 to respond to this agent suggests a differential selectivity of the two proteins in terms of their transcriptional responses to specific stimuli. Finally, both proteins are differentially expressed during development and in tissues of the adult mouse. Unlike Nur77, Nurr1 appears to be predominantly located in brain tissue, suggesting a primary role for this putative transcription factor in regulation of gene expression in the central nervous system.

Action Potentials↗

PubMed1992

Reported reasons for retirement: a study of recently retired workers.

The normal retirement age in the United States is gradually increasing from 65 to 67 (by the year 2027) as provided by the 1983 Amendments to the Social Security Act. One can raise the question, "Who will be the most affected by this change?" This article presents the findings from a study that investigated the relationship between the primary reason given by recently retired workers for their retirement and their economic and demographic backgrounds. A logistic regression analysis was performed using data from the 1982 New Beneficiary Survey concerning involuntary reasons. A major finding was that economically disadvantaged workers tended to retire for involuntary reasons. Therefore, policymakers need to consider the establishment of policies that would protect such workers from the adverse financial impact of the increase in the normal retirement age.

Age Distribution↗

PubMed1991

Expression and characterization of the N-terminal half of antistasin, an anticoagulant protein derived from the leech Haementeria officinalis.

Antistasin, a 15-kDa anticoagulant protein isolated from the salivary glands of the Mexican leech Haementeria officinalis, has been shown to be a potent inhibitor of factor Xa in the blood coagulation cascade. Antistasin possesses a twofold internal homology between the N- and C-terminal halves of the molecule, suggesting a gene duplication event in the evolution of the antistasin gene. This structural feature also suggests that either or both halves of the protein may possess biological activity if expressed as separate domains. Because the N-terminal domain contains a factor Xa P1-reactive site, we chose to express this domain in an insect cell baculovirus expression system. Characterization of this recombinant half antistasin molecule reveals that the N-terminal domain inhibits factor Xa in vitro, with a K(i) of 1.7 nM.

Amino Acid Sequence↗

PubMed1989

Effect of low density lipoproteins, high density lipoproteins, and cholesterol on apolipoprotein A-I mRNA in Hep G2 cells.

We have utilized the human hepatocellular carcinoma cell line, Hep G2, to study the effects of low density lipoproteins (LDL), high density lipoproteins (HDL), and free cholesterol on apolipoprotein (apo) A-I mRNA levels. Incubation of the Hep G2 cells with LDL and free cholesterol led to a significant increase in the cellular content of cholesterol without any effect on the yield of total RNA or in the cellular protein content. Our studies established that incubation with LDL or free cholesterol increased the relative levels of apoA-I mRNA in the Hep G2 cells. In contrast with cholesterol loading, HDL had the effect of lowering the levels of apoA-I mRNA. These results indicate the LDL and HDL pathways as well as intracellular cholesterol may be important in apoA-I gene expression and regulation.

Apolipoprotein A-I↗

PubMed1989

Cloning and expression of cDNA encoding antistasin, a leech-derived protein having anti-coagulant and anti-metastatic properties.

As a factor Xa inhibitor, antistasin is a potent anti-coagulant and anti-metastatic agent that is found in the salivary gland of the Mexican leech Haementaria officinalis. cDNA clones that encode antistasin have been isolated. Subsequent sequence analysis and comparison with the amino acid sequence of the mature protein indicates that antistasin is produced as a pre-protein containing a 17-amino acid signal peptide. Antistasin exists as at least two variants. By sequence analysis of multiple cDNA clones, we found two additional sites for amino acid substitutions, confirming variants that differ from each other by amino acid changes at a minimum of four residues. These sequence variations appear to be the result of allelic variation rather than gene duplication as deduced from DNA blot analyses. Sequence data suggest that antistasin may have evolved from a smaller ancestral gene by a duplication event giving rise to a two-fold structural homology between the N- and C-terminal halves of the molecule. Insect cells transfected with a recombinant baculovirus expressed antistasin which was biologically active and had an electrophoretic mobility identical to that of the native molecule.

Amino Acid Sequence↗

PubMed1988

Tissue-specific expression of apolipoprotein A-I (ApoA-I) is regulated by the 5'-flanking region of the human ApoA-I gene.

We have isolated and characterized a 2.5-kilobase pairs genomic DNA fragment which includes the 5'-flanking region and the first and second exons of the human apolipoprotein (apo) A-I gene. The major transcriptional start site was determined by primer extension analysis and is 235 base pairs (bp) upstream from the AUG translational start codon in liver and 234 bp upstream in the intestine. TATA box-like and CAT box-like sequences and two GC box sequences are present in the intestine 30, 108, 220, and 440 bp upstream, respectively, from the transcriptional start site. Fragments of 570 bp (-487 to +71) and 2.15 kilobase pairs (-2067 to +99) containing the 5'-flanking region of the apoA-I gene were fused upstream to the bacterial chloramphenicol acetyltransferase (CAT) gene. These constructs, designated pA-I(0.6)CAT and pA-I(2.2)CAT, respectively, were introduced into human oral epithelial cells (KB), mouse NIH 3T3 cells, Chinese hamster ovary (CHO) cells, human hepatoma cells (Hep G2), human duodenal epithelial cells (Hutu 80), and human colonic epithelial cells (Caco-2) by calcium phosphate coprecipitation. When compared with control vectors, highly efficient CAT expression of both the pA-I(0.6)CAT and pA-I(2.2)CAT constructs were observed only in cells derived from the liver (Hep G2) and intestine (Caco-2), which is consistent with the tissue specificity of expression of the native gene. Analysis of deletion mutants of the human apoA-I 5'-flanking region revealed that: 1) the region from -250 to -199 bp, from -487 to -413 bp, and -1021 to -691 bp upstream from the transcriptional start site contain sequences required for maximum gene expression; and 2) the regions from -2067 to -1476 bp and -199 to -80 bp contain the sequences required for tissue-specific repression of apoA-I gene expression in non-apoA-I producing cells.

Animals↗

PubMed1988

Human apolipoprotein B (apoB) mRNA: identification of two distinct apoB mRNAs, an mRNA with the apoB-100 sequence and an apoB mRNA containing a premature in-frame translational stop codon, in both liver and intestine.

Human apolipoprotein B (apoB) is present in plasma as two separate isoproteins, designated apoB-100 (512 kDa) and apoB-48 (250 kDa). ApoB is encoded by a single gene on chromosome 2, and a single nuclear mRNA is edited and processed into two separate apoB mRNAs. A 14.1-kilobase apoB mRNA codes for apoB-100, and the second mRNA, which codes for apoB-48, contains a premature stop codon generated by a single base substitution of cytosine to uracil at nucleotide 6538, which converts the translated CAA codon coding for the amino acid glutamine at residue 2153 in apoB-100 to a premature in-frame stop codon (UAA). Two 30-base synthetic oligonucleotides (nucleotides 6523-6552 of apoB mRNA), designated apoB-Stop and apoB-Gln, were synthesized containing the complementary sequence to the stop codon (UAA) and glutamine codon (CAA), respectively. Analysis of intestinal apoB mRNA by hybridization with apoB-Stop and apoB-Gln probes and sequence analysis of apoB clones in two independent human small intestinal cDNA libraries established that intestinal apoB mRNA contained both the apoB mRNA that codes for apoB-100 and the apoB mRNA containing the premature in-frame stop codon, which codes for apoB-48. Investigation of hepatic apoB mRNA and two hepatic cDNA libraries by hybridization with the apoB-Stop and apoB-Gln synthetic probes as well as by cDNA sequencing revealed that liver apoB mRNA also contains both the apoB-100 mRNA and the apoB-48 mRNA containing the stop codon. The combined results from these studies establish that both human intestine and liver contain the two distinct apoB mRNAs, an mRNA that codes for apoB-100 and an apoB mRNA that contains the premature stop codon, which codes for apoB-48. The premature in-frame stop codon is not tissue specific and is present in both human liver and intestine.

Apolipoprotein B-100↗

PubMed1988

Homozygous hypobetalipoproteinemia: a disease distinct from abetalipoproproteinemia at the molecular level.

apoB DNA, RNA, and protein from two patients with homozygous hypobetalipoproteinemia (HBL) were evaluated and compared with normal individuals. Southern blot analysis with 10 different cDNA probes revealed a normal gene without major insertions, deletions, or rearrangements. Northern and slot blot analyses of total liver mRNA from HBL patients documented a normal size apoB mRNA that was present in greatly reduced quantities. ApoB protein was detected within HBL hepatocytes utilizing immunohistochemical techniques; however, it was markedly reduced in quantity when compared with control samples. No apoB was detectable in the plasma of HBL individuals with an ELISA assay. These data are most consistent with a mutation in the coding portion of the apoB gene in HBL patients, leading to an abnormal apoB protein and apoB mRNA instability. These results are distinct from those previously noted in abetalipoproteinemia, which was characterized by an elevated level of hepatic apoB mRNA and accumulation of intracellular hepatic apoB protein.

Apolipoproteins B↗

PubMed1987

Identification of a novel in-frame translational stop codon in human intestine apoB mRNA.

Human apolipoprotein (apo) B exists in plasma as two isoproteins designated apoB-100 and apoB-48. ApoB-100 (512 kDa) and apoB-48 (250 kDa) are synthesized by the liver and intestine respectively. Analysis of apoB cDNA clones isolated from a human intestinal cDNA library revealed that the intestinal apoB mRNA contains a new in-frame translational stop codon. This premature stop codon is generated by a single base substitution of a 'C' to 'T' at nucleotide 6538 which converts the codon 'CAA' coding for the amino acid glutamine residue 2153 to an in-frame stop codon 'TAA'. The generation of a stop codon in the intestinal apoB mRNA appears to be tissue specific since it has not been reported in cDNA clones isolated from human liver cDNA libraries which code for the 4536 amino acid apoB-100. A potential polyadenylation signal sequence 'AATAAA' was also identified 390 bases downstream from the new stop codon. The new stop codon in the human intestinal apoB mRNA provides a potential mechanism for the biosynthesis of intestinal apoB-48.

Amino Acid Sequence↗

PubMed1987

The human apoB-100 gene: apoB-100 is encoded by a single copy gene in the human genome.

Northern blot analysis of human liver and intestine mRNA revealed two separate apoB mRNA of 14.1 and 7.5 kb in the intestine, and a single 14.1 kb apoB mRNA in the liver. cDNA probes which encode for the 5', middle, and 3' regions of the human apoB-100 mRNA have been utilized to evaluate the number of apoB genes present in the human genome by Southern blot hybridization analysis. Comparison of restriction enzyme digestions of high molecular weight leukocyte DNA and a known apoB genomic clone with cDNA probes for the 5', middle and 3' regions of the apoB-100 mRNA were consistent with only a single apoB gene per human haploid genome. Further analysis with synthetic oligonucleotides definitively established that there is a single apoB-100 gene. The two mRNA species observed in the intestine must be derived from a single nuclear apoB RNA transcript.

Apolipoprotein B-100↗