Search PubMed⌕ Search

Biomedical subjects

A Lee

Publications and source records attributed to A Lee.

At least 163 records · Page 9Linked to original sources
PubMed2001

Evaluation of immunotoxicity induced by single or concurrent exposure to N,N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel.

Approximately 5,000 to 80,000 of the US service personnel involved in the Persian Gulf War have complained of a variety of nonspecific symptoms since their return in 1991. These symptoms have been collectively labeled Gulf War Illness and include muscle fatigue, general malaise, myalgia, impaired cognition, ataxia, headaches, fever, joint pain, skin rash, gastrointestinal disturbances, sleep disturbances, and respiratory difficulties. Exposures of military and service personnel were diverse and included the prescribed anti-nerve gas agent pyridostigmine bromide (PYR), N.N-diethyl-m-toluamide (DEET) insect repellent, and environmental exposures to jet fuel. Thus, studies in our laboratory were undertaken to determine if concurrent exposure to these agents, singly or in combination, would contribute to significant alterations in immunological function and disease susceptibility. To assess immune status, eight-week old B6C3F1 female mice were exposed for 14 days to single compounds or tertiary mixtures of 15.5 mg/kg DEET, 2 mg/kg PYR, and 500 mg/kg JP-8 (termed low dose), or 31 mg/kg DEET, 5 mg/kg PYR, and 1,000 mg/kg JP-8 (termed high dose). Immunosuppression was assessed 24 h after the last exposure. No remarkable alterations were evident in hematological parameters, spleen and thymus organ weight and total cellularity, natural killer (NK) cell activity, cytotoxic T-cell activity, or mitogen-induced lymphocyte proliferation after exposure to either single or tertiary mixtures at low or high doses. A few changes in CD4/CD8 flow cytometric lymphocyte subpopulations were detected after exposure to the tertiary mixture at the high dose. Delayed type hypersensitivity (DTH) was decreased by 88% after exposure to the high-dose mixture, and suppression of antibody-specific IgM immune responses (plaque-forming cell, PFC) occurred after exposure to all single and tertiary mixtures at both dose levels. In the PFC response, antagonism was apparent in the mixture, while coexposure to these agents resulted in a synergistic effect in the DTH response. Susceptibility to B16F10 tumor or Listeria monocytogenes challenge was not affected after single or tertiary exposures. These data suggest that combined exposure to DEET, PYR, and JP-8 does not profoundly alter many immunological endpoints, but does selectively target functional endpoints such as the PFC and DTH response. This should be considered when assessing human health risks in the military environment.

Animals↗
PubMed2001

Impaired mobility in older persons attending a geriatric assessment clinic: causes and management.

OBJECTIVES: To study the profile of older persons with impaired mobility. METHODS: A retrospective observational study that reviewed the case records of patients with impaired mobility at a geriatric assessment clinic. Data on mobility status, duration of decline in mobility, functional status, causes, intervention and short-term outcome (up to 16 weeks) were extracted and analysed. RESULTS: The study included 78 patients (42 males) with the median age of 78 years (61 to 96). About 80% had independent premorbid mobility. At presentation, this declined to 45%. Delayed consultations (more than 2 years) were found in 17% of patients. One third had associated decline in transfer, dressing, toileting or bathing, while 19% also had decline in feeding. In each patient, cause(s), many which were potentially reversible, were identified to have contributed to the immobility. More than one cause was identified in half of the patients. Interventions were prescribed in 88% of these patients. Short-term follow-up (median 7 weeks) showed that 21 had an improvement, 35 had the same and 8 had decline in mobility. There was a significant trend towards better outcome when patient presented early during their course of decline in mobility (p=0.005, linear by linear association = 0.013). CONCLUSION: Impaired mobility is a common pathway for many diseases, and is associated with significant functional decline. With proper evaluation, the offending causes can be identified. Early consultation is important for the application of appropriate intervention and can result in better outcome.

Activities of Daily Living↗
PubMed2001

Risperidone in the treatment of first episode psychosis.

OBJECTIVE: To evaluate the efficacy and safety of risperidone in Singapore patients with first-episode psychosis in an eight-week open label prospective study. METHOD: Previously untreated male and female patients aged 18 - 65 with DSM IV schizophreniform disorder or DSM IV schizophrenia for no longer than 12 months were recruited from Woodbridge Hospital and Geylang Psychiatric Outpatient Clinic. Patients were treated with risperidone for 56 days. Outcome was assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression scale (CGI). Safety was assessed by monitoring of vital signs and by comparing the frequency of adverse events (AEs) before and after treatment. RESULTS: 24 patients with a mean age of 33.29+/-9.12 years and a mean duration of illness of 166.5+/-111.4 days (median 180 days) were included. The mean risperidone dosage was 2.7 mg +/- 1.0 at day 56. Mean PANSS total scores reduced by 50.21% from 88.29+/-21.55 at baseline to 43.96+/-7.5 at endpoint (p < 0.001). The responder rate (> or = 20% reduction in the total PANSS score) was 87.5%. 13 patients (54.2%) exhibited a 50% or greater reduction in total PANSS score. Except for item G5 (mannerisms and posturing) all single PANSS items were reduced significantly. The CGI scores of all patients improved at endpoint. No serious adverse events were reported. CONCLUSIONS: Overall the therapy of first-episode psychosis patients with risperidone was effective and safe.

Adult↗
PubMed2001

Morbidity patterns of non-urgent patients attending accident and emergency departments in Hong Kong: cross-sectional study.

OBJECTIVES: To study the morbidity patterns of non-urgent patients utilising accident and emergency services and compare these patients with 'true' accident and emergency cases. To analyse the morbidity pattern of non-urgent cases over different time periods, and across different age groups. DESIGN: A cross-sectional study completed over a 1-year period. SETTING: Four accident and emergency departments in Hong Kong. PATIENTS: Two thousand, four hundred and ten patients randomly selected from four accident and emergency departments. MAIN OUTCOME MEASURES: The morbidity patterns by body system, according to the International Classification of Primary Care, were tabulated and analysed for 'true' accident and emergency cases versus non-urgent cases. The ten most frequent diagnoses for the 'true' accident and emergency and non-urgent cases were also compared. Further analysis of accident and emergency service utilisation was conducted comparing different age groups, and also different time periods. RESULTS: Significantly more cases presenting to the accident and emergency service with respiratory and digestive problems were found to be non-urgent, rather than appropriate accident and emergency cases. In contrast, significantly more cases presenting with circulatory and neurological problems were appropriate cases for accident and emergency department management. The morbidity pattern for the ten most frequent diagnoses seen in non-urgent cases was noted to be similar to the Hong Kong general practice morbidity pattern for self-limiting conditions. Utilisation of accident and emergency services for acute self-limiting conditions was more marked in the late evening, and also among children and the younger population in general. CONCLUSION: The utilisation of accident and emergency services by patients requiring a general practice service only, reflects problems in the primary health care delivery system. These may be solved by appropriate interfacing between general practitioners and other service providers, with the aim of providing seamless health care. Without revision of primary health care services, accident and emergency departments will continue to be used inappropriately by patients as an alternative to general practice care.

Accidents↗
PubMed2001

Anticancer effect of a lentiviral vector capable of expressing HIV-1 Vpr.

A lentiviral vector capable of expressing the HIV-1 vpr gene (Vpr lentiviral vector) was constructed, and its in vivo anticancer effect was determined against cutaneous tumors derived from the AT-84 oral cancer cells in immunocompetent mice. A single intratumoral injection of the Vpr lentiviral vector not only significantly reduced the primary tumor volume but also completely regressed tumors in >40% of animals. More interestingly, the mice of which the primary tumors were completely regressed by the Vpr lentiviral vector were additionally protected from a secondary challenge of AT-84 cells. These data suggest that the Vpr lentiviral vector elicits its anticancer activity in part by the activation of the immune system. The above suggestion is additionally supported by the failure of the lentiviral vector to demonstrate anticancer activity in immunocompromised nude or SCID mice. The Vpr lentiviral vector offers a powerful new strategy for cancer gene therapy and may be useful for the control of solid tumors, such as human oral squamous cell carcinomas.

Animals↗
PubMed2000

The human renal sodium sulfate cotransporter (SLC13A1; hNaSi-1) cDNA and gene: organization, chromosomal localization, and functional characterization.

Sulfate plays an essential role during growth, development, bone/cartilage formation, and cellular metabolism. In this study, we have determined the structure of the human Na+-sulfate cotransporter (hNaSi-1) cDNA (Human Genome Nomenclature Committee-approved symbol SLC13A1) and gene (NAS1). hNaSi-1 encodes a protein of 595 amino acids with 13 putative transmembrane domains. hNaSi-1 mRNA expression was exclusive to the human kidney. Expression of hNaSi-1 protein in Xenopus oocytes demonstrated a high-affinity Na+-sulfate cotransporter that was inhibited by selenate, thiosulfate, molybdate, tungstate, citrate, and succinate. Antisense inhibition experiments suggest hNaSi-1 to represent the major Na+-sulfate cotransporter in the human kidney. NAS1 was localized on human chromosome 7, mapped to 7q31-q32, near the sulfate transporter genes, DRA and SUT-1. The NAS1 gene contains 15 exons, spanning over 83 kb in length. Knowledge of the structure, function, and chromosomal localization of hNaSi-1 will permit the screening of NAS1 mutations in humans with disorders in renal sulfate reabsorption and homeostasis.

Amino Acid Sequence↗
PubMed2000

Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

Arabidopsis↗
PubMed2000

Consumption of tomato products with olive oil but not sunflower oil increases the antioxidant activity of plasma.

Health benefits of lycopene from tomato products have been suggested to be related to its antioxidant activity. Dietary fat may influence the absorption and hence the plasma levels and antioxidant activity of lycopene. In the present study, we have compared the effect of consumption of tomato products with extra-virgin olive oil vs. tomato products plus sunflower oil on plasma lycopene and antioxidant levels. Results show that the oil composition does not affect the absorption of lycopene from tomato products because similar levels of plasma lycopene (mean +/- SD) were obtained on feeding tomatoes (providing approximately 46 mg lycopene/d) for 7 d with either olive oil (0.66 +/- 0.26 vs 1.20 +/- 0.20 micromol/l, p <.002) or sunflower oil (0.67 +/- 0.27 vs. 1.14 micromol/l, p <.001). However, consumption of tomato products with olive oil significantly raised the plasma antioxidant activity (FRAP) from 930 +/- 150 to 1118 +/- 184 micromol/l, p <.01) but no effect was observed when the sunflower oil was used. The change (supplementation minus start values) in FRAP following the consumption of tomato products with oil was significantly higher for olive oil (190 +/- 101) than for sunflower oil (-9.6 +/- 99, p <. 005). In conclusion, the results of the study show that consumption of tomato products with olive oil but not with sunflower oil improves the antioxidant activity of the plasma.

Adult↗
PubMed2000

Patient characteristics and patterns of use for lumbar spine radiographs: results from the Veterans Health Study.

STUDY DESIGN: Longitudinal data from the Veterans Health Study, an observational study of male patients receiving Veterans Administration ambulatory care, were analyzed. OBJECTIVE: To identify patient characteristics that predict different patterns in the use of lumbar spine radiographs. SUMMARY AND BACKGROUND DATA: In this study, 401 patients with low back pain receiving ambulatory care services in four Veterans Administration outpatient clinics in the greater Boston area were followed for 12 months. METHODS: Participants were mailed the Medical Outcome Study Short Form Health Survey and participated in scheduled interviews that included the completion of a low back questionnaire, a comorbidity index, and a straight leg raising test. Four groups of patients were defined according to the patterns of use for lumbar spine radiographs: prior use, repeat use, no use, and new use of lumbar spine radiographs. These groups were compared in terms of sociodemographics, comorbid conditions, low back pain intensity, radiating leg pain, straight leg raising, Medical Outcome Study Short Form Health Survey scores, and low back disability days. RESULTS: The patients with new lumbar spine radiographs showed worse physical and psychological distress than the participants in the other three groups. In contrast, the patients with no lumbar spine radiographs reported minor physical impairment. Compared with patients who had no repeat radiographs, patients with repeat lumbar spine radiographs had similar scores on physical health, but they showed worse scores of mental health. CONCLUSIONS: Both physical and psychological factors contribute to having new radiographic examinations, whereas psychological factors have increased importance in the repeat use of roentgenographic examinations. Repeat radiographs appear to be overused, judging by the severity of physical impairment as measured by low back pain intensity, the Medical OutcomeStudy Short Form Health Survey, and disability days.

Ambulatory Care↗
PubMed2000

Ca2+/calmodulin-dependent facilitation and inactivation of P/Q-type Ca2+ channels.

Trains of action potentials cause Ca(2+)-dependent facilitation and inactivation of presynaptic P/Q-type Ca(2+) channels that can alter synaptic efficacy. A potential mechanism for these effects involves calmodulin, which associates in a Ca(2+)-dependent manner with the pore-forming alpha(1A) subunit. Here, we report that Ca(2+) and calmodulin dramatically enhance inactivation and facilitation of P/Q-type Ca(2+) channels containing the auxiliary beta(2a) subunit compared with their relatively small effects on channels with beta(1b). Tetanic stimulation causes an initial enhancement followed by a gradual decline in P/Q-type Ca(2+) currents over time. Recovery of Ca(2+) currents from facilitation and inactivation is relatively slow (30 sec to 1 min). These effects are strongly inhibited by high intracellular BAPTA, replacement of extracellular Ca(2+) with Ba(2+), and a calmodulin inhibitor peptide. The Ca(2+)/calmodulin-dependent facilitation and inactivation of P/Q-type Ca(2+) channels observed here are consistent with the behavior of presynaptic Ca(2+) channels in neurons, revealing how dual feedback regulation of P/Q-type channels by Ca(2+) and calmodulin could contribute to activity-dependent synaptic plasticity.

Action Potentials↗
PubMed2000

Genes controlling circadian rhythm are widely distributed in cyanobacteria.

The kaiABC gene cluster is important for maintaining circadian rhythms in the cyanobacterium Synechococcus PCC 7942. An extensive PCR-based survey of phylogenetically diverse cyanobacteria was conducted using degenerate primers designed to identify the presence of the kaiC gene. Hybridization and sequence analyses showed that the observed amplification products had a high degree of similarity to kaiC. Forty cyanobacterial strains possessed kaiC related sequences, suggesting that a clock system is universal among cyanobacteria.

Amino Acid Sequence↗
PubMed2000

Correlation of intellectual impairment in Parkinson's disease with FDG PET scan.

This study investigated the relationship between regional glucose metabolism with intellectual impairment in patients with Parkinson's disease using statistical parametric mapping. Regional cerebral glucose metabolism using [18F]deoxyglucose (FDG) PET scans were performed on 10 patients with Parkinson's disease. We used the intellectual impairment score from the UPDRS. PET scans were analyzed with SPM96. Patients showed significant positive correlations with left limbic structures such as the cingulate gyrus, parahippocampal gyrus, and medial frontal gyrus. Patients showed significant negative correlations with associative neocortical posterior structures such as bilateral parietal and occipital gyrus. There were significant relationships between regional glucose metabolism and intellectual impairment.

Aged↗
PubMed2000

Further development of the Helicobacter pylori mouse vaccination model.

Immunisation against Helicobacter infection in mouse models has thus far produced neither complete protection against the bacteria, nor a complete prevention of the associated gastritis. This study aimed firstly to compare the sensitivities of the various methods used to assess H. pylori infection in the mouse model, and secondly to develop the experimental design to induce a more effective immunity, aimed at further reducing bacterial burden in the gastric tissue. Various mouse strains were prophylactically immunised with whole bacterial sonicate and cholera toxin before challenge with H. pylori-SS1. The relative sensitivities of the urease assay, histological assessment and the colony forming assay to detect levels of H. pylori colonisation were compared. Comparisons of different antigen doses and different timecourses of immunisation were performed. The colony forming assay was found to be far more sensitive than either the urease assay or histological assessment for determining the protective efficacies of immunisation. Mice which had 10(5) H. pylori per gram of stomach by colony assay were negative by histology and urease. Lower doses of whole cell sonicate were more protective than high doses and more effective immunisation was achieved by leaving at least 3 weeks between immunisation instead of weekly immunisations. In conclusion, for assessment of H. pylori colonisation in the mouse model, the colony forming assay should be used. The experimental protocol for immunisation has been altered to produce a significant improvement in protection. However, full protection has still not yet been achieved and more work is still required.

Animals↗
PubMed2000

GFAP-positive and myelin marker-positive glia in normal and pathologic environments.

The data herein demonstrate that in addition to the well-characterized myelin marker-positive, glial fibrillary acidic protein (GFAP)-negative, membrane sheet-bearing oligodendrocytes, another type of myelin marker-positive, process-bearing glia exists in normal and pathologic conditions. This second type of myelin marker-positive glia expresses GFAP, and therefore these cells have been referred to as mixed phenotype glia. Although mixed phenotype glia have been documented previously, their identity and function have remained a mystery. The goal of this immunocytochemical study was to further characterize these cells. Using the MBPlacZ transgenic mouse in which beta-galactosidase is under the control of the myelin basic protein (MBP) gene promoter, GFAP-positive/beta-galactosidase-positive and myelin/oligodendrocyte-specific protein (MOSP)-positive/beta-galactosidase-positive cells were detected in subcortical white matter and in perivascular locations within cerebral white and gray matter. In cultures prepared from highly enriched myelin marker-positive immature glia, mixed phenotype glia were detected that were GFAP-positive and either MOSP-, MBP-, O1-, and O4-positive. The expression of multiple myelin markers by mixed phenotype glia may suggest that these cells are of oligodendrocyte origin. Increased numbers of MOSP-positive/GFAP-positive mixed phenotype glia were detected in sections from adult hypomyelinated brain from shiverer, quaking, and PKU mice compared to myelinated control adult mouse brain. Similarly, cultures from control brain exposed to elevated pH for 2-3 weeks showed dramatically increased numbers of mixed phenotype glia (80%) compared to control (<10%). Increased numbers of mixed phenotype glia also were detected in shiverer cultures (40%). Since increases in the number of mixed phenotype glia occur in shiverer, quaking, and PKU mouse brain, these data suggest that mixed phenotype glia contribute to gliosis in pathologic white matter.

Animals↗
PubMed2000

The Variability of Seyfert 1.8 and 1.9 Galaxies at 1.6 Microns.

We present a study of Seyfert 1.5-2.0 galaxies observed at two epochs with the Hubble Space Telescope (HST) at 1.6 µm. We find that unresolved nuclear emission from nine of 14 nuclei varies at the level of 10%-40% on timescales of 0.7-14 months, depending upon the galaxy. A control sample of Seyfert galaxies lacking unresolved sources and galaxies lacking Seyfert nuclei show less than 3% instrumental variation in equivalent aperture measurements. This proves that the unresolved sources are nonstellar and associated with the central parsecs of active galactic nuclei. Unresolved sources in Seyfert 1.8 and 1.9 galaxies are not usually detected in HST optical surveys; however, high angular resolution infrared observations will provide a way to measure time delays in these galaxies.

Journal Article↗
PubMed2000

Stabilization and remodeling of the membrane skeleton during lens fiber cell differentiation and maturation.

Actin filaments are integral components of the plasma membrane-associated cytoskeleton (membrane skeleton) and are believed to play important roles in the determination of cell polarity, shape, and membrane mechanical properties, however the roles of actin regulatory proteins in controlling the assembly, stability, and organization of actin filaments in the membrane skeleton are not well understood. Tropomodulin is a tropomyosin and actin-binding protein that stabilizes tropomyosin-actin filaments by capping their pointed ends and is associated with the spectrin-actin membrane skeleton in erythrocytes, skeletal muscle cells, and lens fiber cells, a specialized epithelial cell type. In this study, we have investigated the role of tropomodulin and other membrane skeleton components in lens fiber cell differentiation and maturation. Our results demonstrate that tropomodulin is expressed concomitantly with lens fiber cell differentiation and assembles onto the plasma membrane only after fiber cells have begun to elongate and form apical-apical contacts with the undifferentiated epithelium. In contrast, other membrane skeleton components, spectrin, actin, and tropomyosin, are constitutively expressed and assembled on the plasma membranes of both undifferentiated and differentiated fiber cells. Tropomodulin, but not other membrane skeleton components, is also enriched at a novel structure at the apical and basal ends of newly elongated fiber cells at the fiber cell-epithelium and fiber cell-capsule interface, respectively. Once assembled, tropomodulin and its binding partners, tropomyosin and actin, remain membrane-associated and are not proteolyzed during fiber cell maturation and aging, despite proteolysis of alpha-spectrin and other cytoskeletal filament systems such as microtubules and intermediate filaments. We propose that actin filament stabilization by tropomodulin, coupled with partial proteolysis of other cytoskeletal components, represents a programmed remodeling of the lens membrane skeleton that may be essential to maintain plasma membrane integrity and transparency of the extremely elongated, long-lived cells of the lens. The unique localization of tropomodulin at fiber cell tips further suggests a new role for tropomodulin at cell-cell and cell-substratum contacts; this may be important for cell migration and/or adhesion during differentiation and morphogenesis.

Actins↗