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Biomedical subjects

Y H Tan

Publications and source records attributed to Y H Tan.

At least 19 recordsLinked to original sources

Anisotropy and corotation of galactic cosmic rays.

The intensity of Galactic cosmic rays is nearly isotropic because of the influence of magnetic fields in the Milky Way. Here, we present two-dimensional high-precision anisotropy measurement for energies from a few to several hundred teraelectronvolts (TeV), using the large data sample of the Tibet Air Shower Arrays. Besides revealing finer details of the known anisotropies, a new component of Galactic cosmic ray anisotropy in sidereal time is uncovered around the Cygnus region direction. For cosmic-ray energies up to a few hundred TeV, all components of anisotropies fade away, showing a corotation of Galactic cosmic rays with the local Galactic magnetic environment. These results have broad implications for a comprehensive understanding of cosmic rays, supernovae, magnetic fields, and heliospheric and Galactic dynamic environments.

Journal Article↗

Contemporary results of endopyelotomy for ureteropelvic junction obstruction.

INTRODUCTION: Endopyelotomy is an accepted treatment option for ureteropelvic junction obstruction (UPJO). In this study, we reviewed our 7-year experience with antegrade endopyelotomy for UPJO. MATERIALS AND METHODS: We reviewed the records of 35 consecutive antegrade endopyelotomy for UPJO between 1996 and 2002. Patients were included if they had shown radiographic evidence of UPJO on diuresis urography or intravenous urogram with signs and symptoms or deterioration of renal function. RESULTS: A total of 34 consecutive patients underwent 35 antegrade endopyelotomy procedures in 35 renal units. One patient had bilateral endopyelotomy for bilateral UPJO. Eighteen renal units (51%) had concomitant renal calculi that required percutaneous nephrolithotomy, including 8 renal units with pelvi-ureteric junction stones. Twenty-four renal units (69%) had moderate degree of hydronephrosis whilst 11 renal units (31%) had severe hydronephrosis. The mean operating time for antegrade endopyelotomy was 94 +/- 28 minutes and the mean hospital stay was 4.7 +/- 2.8 days. No patients had conversion to open pyeloplasty and no patient required perioperative blood transfusion. The mean followup was 33 +/- 23 months and the overall success rate following endopyelotomy was 83% (n = 29 renal units). The success rate for primary UPJO was 81%, whilst the success rate for secondary UPJO was 84%. Four renal units (11%) required ancillary procedures for failed endopyelotomy. Two patients required repeat endopyelotomy, and 2 patients needed open pyeloplasty. Two patients were lost to follow-up. CONCLUSION: Endopyelotomy remains a viable approach for UPJO compared to open reconstruction. Careful patient selection can optimise the surgical outcome and minimise endopyelotomy failures.

Adult↗

A Dynamic Interactive Social Chart in Dementia CareAttuning Demand and Supply in the Care for Persons with Dementia and their Carers.

We-centric services may play an important role in the field of care and support for elderly persons with dementia and their carers. They may solve problems, such as fragmentation of care, gaps in the continuum of care and welfare services, and inefficient and uncustomized service delivery to patients and carers. In the FRUX Health Care pilot opportunities for we-centric, context-sensitive service bundles in the field of dementia care will be explored. The service on which we focus in this paper is a dynamic interactive social chart for dementia care (DEM-DISC). The feasibility of DEM-DISC will be investigated from a domain specific content perspective (needs, offerings, information and advice), an ICT perspective (ontology and application), a user perspective (persons with dementia, their carers and professionals/organizations), and an organisational perspective (necessary collaboration, governance and control, business modelling). A first demonstrator (validator) of the DEM-DISC will be designed, built and evaluated. Future possibilities to connect DEM-DISC to actual service delivery will be explored. In this paper we discuss the most important research questions from the different perspectives and the methods used to answer them.

Caregivers↗

Observation by an air-shower array in Tibet of the multi-TeV cosmic-ray anisotropy due to terrestrial orbital motion around the Sun.

We report on the solar diurnal variation of the galactic cosmic-ray intensity observed by the Tibet III air shower array during the period from 1999 to 2003. In the higher-energy event samples (12 and 6.2 TeV), the variations are fairly consistent with the Compton-Getting anisotropy due to the terrestrial orbital motion around the Sun, while the variation in the lower-energy event sample (4.0 TeV) is inconsistent with this anisotropy. This suggests an additional anisotropy superposed at the multi-TeV energies, e.g., the solar modulation effect. This is the highest-precision measurement of the Compton-Getting anisotropy ever made.

Journal Article↗

Routine vascular control using the Hem-o-lok clip in laparoscopic nephrectomy: animal study and clinical application.

BACKGROUND AND PURPOSE: During laparoscopic nephrectomy (LPN), a stapling device is often used for vascular control, especially of the renal vein. Herein, we report our experience using a polymer clip (Hem-o-lok) for routine control of the vessels during LPN in the animal and clinical setting. PATIENTS AND METHODS: Fifty ablative and fifteen live-donor nephrectomies were performed in domestic pigs. Hem-o-lok clips (10 mm; Weck Closure System, Research Triangle Park, NC) were routinely used for vascular control. In addition, from January 2001 to July 2002, 46 patients underwent hand-assisted laparoscopic (HAL) (N=40) or laparoscopic (N=6) nephrectomy for renal disease or donor nephrectomy. Venous control was achieved solely by the Hem-o-lok clips where at least two clips were applied on the patient side. Arterial control was obtained by the Hem-o-lok clips either alone or in combination with the metal clips. The technical difficulty in obtaining vascular control, transfusion requirement, and clinical outcome were evaluated. RESULTS: In the animal study (total 65 nephrectomies), individual vascular control was obtained by the Hem-o-lok clip in all cases except two, where vascular injury during dissection necessitated endoscopic stapling of renal hilum or open conversion. The warm ischemic time for animal donor kidney harvest was uniformly <2 minutes. In the clinical study, arterial control was obtained mostly by a combination of Hem-o-lok and metal clips. Venous control using the Hem-o-lok was successful in all 46 cases without any slipping of clips or uncontrolled bleeding. The mean operating time was 148 minutes. No open conversion was required. The transfusion rate was 6.5% (N=3), with none of the transfusions being related to inadequacy of vascular control using the Hem-o-lok. Major complications included deep vein thrombosis and postoperative retroperitoneal hemorrhage (same patient) and acute respiratory distress syndrome (N = 1). The mean postoperative stay was 5.2 days (range 1-20 days). CONCLUSION: The Hem-o-lok is a reliable and economical device for vascular control in laparoscopic renal surgery.

Animals↗

Cellular RNA helicase p68 relocalization and interaction with the hepatitis C virus (HCV) NS5B protein and the potential role of p68 in HCV RNA replication.

Chronic infection by hepatitis C virus (HCV) can lead to severe hepatitis and cirrhosis and is closely associated with hepatocellular carcinoma. The replication cycle of HCV is poorly understood but is likely to involve interaction with host factors. In this report, we show that NS5B, the HCV RNA-dependent RNA polymerase (RdRp), interacts with a human RNA helicase, p68. Transient expression of NS5B alone, as well as the stable expression of all the nonstructural proteins in a HCV replicon-bearing cell line (V. Lohmann, F. Korner, J.-O. Koch, U. Herian, L. Theilmann, and R. Bartenschlager, Science 285:110-113), causes the redistribution of endogenous p68 from the nucleus to the cytoplasm. Deletion of the C-terminal two-thirds of NS5B (NS5BDeltaC) dramatically reduces its coimmunoprecipitation (co-IP) with endogenous p68, while the deletion of the N-terminal region (NS5BDeltaN1 and NS5BDeltaN2) does not affect its interaction with p68. In consistency with the co-IP results, NS5BDeltaC does not cause the relocalization of p68 whereas NS5BDeltaN1 does. With a replicon cell line, we were not able to detect a change in positive- and negative-strand synthesis when p68 levels were reduced using small interfering RNA (siRNA). In cells transiently transfected with a full-length HCV construct, however, the depletion (using specific p68 siRNA) of endogenous p68 correlated with a reduction in the transcription of negative-strand from positive-strand HCV RNA. Overexpression of NS5B and NS5BDeltaN1, but not that of NS5BDeltaC, causes a reduction in the negative-strand synthesis, indicating that overexpressed NS5B and NS5BDeltaN1 sequesters p68 from the replication complexes (thus reducing their replication activity levels). Identification of p68 as a cellular factor involved in HCV replication, at least for cells transiently transfected with a HCV expression construct, is a step towards understanding HCV replication.

Cell Nucleus↗

An anti-HIV-1 gp120 antibody expressed as an endocytotic transmembrane protein mediates internalization of HIV-1.

In this study, we used HIV-1 as a model to demonstrate a novel approach for receptor-independent cell entry of virus. The heavy chain of an anti-HIV-1 gp120 antibody was engineered with endocytotic and transmembrane motifs from either the cation-independent mannose 6-phosphate receptor or the low-density lipoprotein receptor. Flow cytometry and immunofluorescence studies showed that the chimeric antibodies were expressed on the cell surface and can undergo rapid internalization. Furthermore, one of the chimeric antibodies was able to bind and internalize HIV-1. Using a luciferase reporter HIV-1, we further showed that internalized viruses could undergo replication. Therefore, we have demonstrated a proof-of-principle of a novel method that can be used to internalize virus into cells, without prior knowledge of the cellular receptor for the virus. We propose that this approach would be particularly useful for studying viruses whose cellular receptor(s) is not known.

Amino Acid Sequence↗

The regulation of retina specific expression of rhodopsin gene in vertebrates.

Rhodopsin genes in most vertebrate species, with the exception of teleost fishes, contain introns. Despite differences in the gene structure, similar regulatory motifs have been identified in fish, amphibian and mammalian rhodopsin promoters, suggesting that rhodopsin gene regulation may be conserved in vertebrates. However, there is no direct evidence to support this notion. To address this, the rhodopsin promoter from the pufferfish, Fugu rubripes, was isolated and tested in transgenic mice and frogs. A 6.5 kb Fugu genomic fragment containing the rhodopsin gene and 4.5 kb 5' flanking region was able to direct expression of the Fugu rhodopsin gene to the retina of transgenic mice. In transgenic tadpoles, photoreceptor rod cell-specific expression of a reporter gene was achieved using only 500 bp Fugu rhodopsin promoter fragment. Mutagenesis of this promoter fragment revealed that a conserved NRE-like motif is crucial for the retina-specific expression. Our investigation suggests that the regulation of retinal specific expression is conserved in the pufferfish, frog and mouse and that the ancestral intron-containing rhodopsin gene has been displaced by an intronless copy in teleosts.

Animals↗

CD81 engineered with endocytotic signals mediates HCV cell entry: implications for receptor usage by HCV in vivo.

Although CD81 has been shown to bind HCV E2 protein, its role as a receptor for HCV remains controversial. In this study, we constructed two CD81 chimeras by linking the cytoplasmic domains of recycling surface receptors, low-density lipoprotein receptor (LDLR), and transferrin receptor (TfR), respectively, to CD81 and compared their internalization properties to wild-type CD81. Binding experiments with anti-hCD81 antibody showed that cell-surface CD81 chimeric receptors were internalized much more efficiently than wild-type CD81. In addition, CD81 chimeras, but not wild-type CD81, could internalize recombinant E2 protein and E2-enveloped viral particles from the serum of HCV-infected patients into Huh7 liver cells. The latter resulted in persistent positive-strand viral RNA and accumulation of replication intermediates, negative-strand viral RNA, in the infected cells, suggesting that the internalized viruses have undergone replication. Therefore, it appeared that CD81, possibly in association with a liver-specific endocytotic protein(s), represents one of the pathways by which HCV can infect hepatocytes.

Antigens, CD↗

A 12-year experience in the surgical management of vesicovaginal fistulae.

INTRODUCTION: Vesicovaginal fistulae are largely iatrogenic and represent therapeutic dilemmas in surgical approach and timing of repairs. AIM: We have reviewed our surgical management of vesicovaginal fistulae over a 12-year period to determine whether the outcome is dependent on surgical approach and timing of repair. PATIENTS AND METHODS: From January 1990 to September 2001, 23 patients were referred to our department of whom 20 have retrievable records. Fourteen of these 20 patients had gynaecological operations as the primary cause for their fistulas whilst the remaining six had varied causes ranging from forceps delivery to recurrent pelvic malignancies. RESULTS: Of 20 patients, four underwent transvaginal repair, seven transvesical repair, eight supravesical repair and one required an ileal conduit diversion. There was an 85% success after first repair with only three fistula recurrences, two of whom underwent a successful second repair and one was treated conservatively and successfully with urethral catheterisation. There were no further recurrences at mean follow-up of 23 months for our cohort. Earlier repair seemed to be associated with a higher recurrence rate (33% of six patients within six weeks) compared with delayed operations (7% of remaining 14 operated after six weeks). CONCLUSION: Vesicovaginal fistulae can be successfully managed surgically. Although the type of approach did not affect outcome, the timing of the repair may affect the success of the operation.

Adult↗

Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes.

The compact genome of Fugu rubripes has been sequenced to over 95% coverage, and more than 80% of the assembly is in multigene-sized scaffolds. In this 365-megabase vertebrate genome, repetitive DNA accounts for less than one-sixth of the sequence, and gene loci occupy about one-third of the genome. As with the human genome, gene loci are not evenly distributed, but are clustered into sparse and dense regions. Some "giant" genes were observed that had average coding sequence sizes but were spread over genomic lengths significantly larger than those of their human orthologs. Although three-quarters of predicted human proteins have a strong match to Fugu, approximately a quarter of the human proteins had highly diverged from or had no pufferfish homologs, highlighting the extent of protein evolution in the 450 million years since teleosts and mammals diverged. Conserved linkages between Fugu and human genes indicate the preservation of chromosomal segments from the common vertebrate ancestor, but with considerable scrambling of gene order.

Animals↗

Interferon-beta administration confers a beneficial outcome in a rabbit model of thromboembolic cerebral ischemia.

We demonstrate that treatment with the cytokine human interferon-beta (IFN-beta) resulted in a beneficial outcome in a rabbit model of thromboembolic cerebral ischemia. Rabbits administered subcutaneously with IFN-beta prior to (pre-treatment) or after (post-treatment) the introduction of an autologous blood clot into the middle cerebral artery have consistently smaller subcortical infarct volumes compared to control (untreated) counterparts. The average subcortical infarct volume of pre-treatment rabbits is 46.3+/-9.3 mm(3) (n=4), and that of post-treatment rabbit is 40.0+/-23.1 mm(3) (n=4). Both are significantly lower (P=0.003 and P=0.004, respectively) than the average subcortical infarct volume of control rabbits (121.6+/-32.9 mm(3), n=5). Although the precise mechanism responsible for the beneficial effect of IFN-beta on stroke is not yet clear, our results are in line with the known anti-inflammatory potential and anti-apoptotic function of IFN-beta.

Animals↗

Conserved regulation of the lymphocyte-specific expression of lck in the Fugu and mammals.

The lck gene encodes a lymphocyte-specific protein-tyrosine kinase that is implicated in T cell maturation and signaling. In mammals, the transcription of the lck gene is regulated by two independent promoters, the proximal promoter, which is active in thymocytes, and the distal promoter, which dominates in mature T cells. In the human and mouse lck gene loci, the two promoter elements are separated by at least 40 kb and 10 kb, respectively. In this study, we have cloned and sequenced 60 kb from the pufferfish (Fugu rubripes) lck locus. The promoter region of the Fugu lck spans only 4.2 kb and contains a proximal and a distal promoter in the 2.3-kb region adjacent to the coding sequence. By generating transgenic mice, we have demonstrated that the compact promoter of the Fugu lck contains regulatory elements that direct expression to lymphoid organs of mice. We were able to localize the regulatory elements to a short region of 830 bp without losing specificity to cultured human T cell line. These results show that the basic mechanisms that mediate lymphocyte-specific expression are conserved between teleosts and mammals. The short promoter of the Fugu lck isolated by us offers a powerful tool for labeling T cells, targeting expression, and manipulating T cell activity in fishes as well as in mammals.

Amino Acid Sequence↗

Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci.

Fierce (frc) mice are deleted for nuclear receptor 2e1 (Nr2e1), and exhibit cerebral hypoplasia, blindness, and extreme aggression. To characterize the Nr2e1 locus, which may also contain the mouse kidney disease (kd) allele, we compared sequence from human, mouse, and the puffer fish Fugu rubripes. We identified a novel gene, c222389, containing conserved elements in noncoding regions. We also discovered a novel vertebrate gene conserved across its length in prokaryotes and invertebrates. Based on a dramatic upregulation in lactating breast, we named this gene lactation elevated-1 (LACE1). Two separate 100-bp elements within the first NR2E1 intron were virtually identical between the three species, despite an estimated 450 million years of divergent evolution. These elements represent strong candidates for functional NR2E1 regulatory elements in vertebrates. A high degree of conservation across NR2E1 combined with a lack of interspersed repeats suggests that an array of regulatory elements embedded within the gene is required for proper gene expression.

Alternative Splicing↗

Comparison of laparoscopic and open adrenalectomy--a Singapore experience.

OBJECTIVE: We present our experience with laparoscopic adrenalectomy for benign adrenal diseases and compare clinical outcomes with the conventional open approach. METHODS: Between 1990 and 2001, two consecutive series of patients who underwent adrenalectomy for small, benign adrenal diseases were reviewed retrospectively. Patients with large tumours(> 7 cm), cancer and phaeochromocytoma were excluded. Fifty-eight patients underwent laparoscopic adrenalectomy and 48 patients had open surgery for benign adrenal diseases. Perioperative and postoperative records of both approaches were reviewed. RESULTS: The two groups were comparable in terms of patient age, sex, weight and side of lesion.The common indications for surgery were Conn's syndrome and Cushing's syndrome. The sizes of tumour were comparable between the laparoscopic and open groups (mean, 2.1 cm vs 2.4 cm). Despite the longer operating time (mean, 128 minutes vs 87 minutes), the postoperative morbidity, parenteral analgesic requirement and length of postoperative hospital stay (3.2 days vs 7.2 days) were less inpatients undergoing laparoscopic adrenalectomy. Patients also enjoyed earlier return to oral intake and ambulation. There were fewer complications in the laparoscopic group. There was no conversion to open surgery. CONCLUSION: Laparoscopic adrenalectomy is safe and has become the treatment of choice for small, benign adrenal lesions at our institution.

Adrenal Gland Diseases↗