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Biomedical subjects

J Lee

Publications and source records attributed to J Lee.

At least 577 records · Page 32Linked to original sources

Immobile vocal fold secondary to thyroid abscess: a case report.

Vocal fold paralysis as a result of a thyroid abscess is extremely rare. In this article, we report only the second documented case of such a finding. The paralysis was discovered after our patient, a 40-year-old woman, had come to the office with a complaint of discomfort in the right lower neck. Computed tomography confirmed the presence of an abscess in the posterior thyroid gland. Fine-needle aspiration did not identify any inflammatory or suspicious cells. The abscess was treated with hemithyroidectomy, and the paralysis resolved 3 weeks later. There has been no recurrence after 4 years.

Abscess↗

Incidence of ischaemic heart disease and stroke in Chinese, Malays and Indians in Singapore: Singapore Cardiovascular Cohort Study.

INTRODUCTION: This is the first prospective cohort study in Singapore to describe the incidence of ischaemic heart disease (IHD) and stroke among Chinese, Malays and Asian Indians. MATERIALS AND METHODS: The Singapore Cardiovascular Cohort Study is a longitudinal follow-up study on a general population cohort of 5920 persons drawn from 3 previous cross-sectional surveys. Morbidity and mortality from IHD and stroke were ascertained by record linkage using a unique identification number with the death registry, Singapore Myocardial Infarct Registry and in-patient discharge databases. RESULTS: There were 193 first IHD events and 97 first strokes during 52,806 person-years of observation. The overall incidence of IHD was 3.8/1000 person-years and that of stroke was 1.8/1000 person-years. In both males and females, Indians had the highest IHD incidence, followed by Malays and then Chinese. For males after adjusting for age, Indians were 2.78 times (95% CI 1.86, 4.17; P < 0.0001) and 2.28 times (95% CI 1.34, 3.88; P = 0.002) more likely to get IHD than Chinese and Malays respectively. For females after adjusting for age, Indians were 1.97 times (95% CI 1.07, 3.63; P = 0.03) and 1.37 times (95% CI 0.67, 2.80; P = 0.39) more likely to get IHD than Chinese and Malays respectively. For stroke, male Chinese and Indians had higher incidence than Malays (though not statistically significant). However, in females, Malays had the highest incidence of stroke, being 2.57 times (95% CI 1.31, 5.05; P = 0.008) more likely to get stroke than Chinese after adjustment for age. CONCLUSIONS: This prospective study of both mortality and morbidity has confirmed the higher risk of IHD in Indians. It has also found that Malay females have a higher incidence of stroke, which deserves further study because of its potential public health importance.

Adult↗

ARK-1 inhibits EGFR signaling in C. elegans.

A screen for synthetic enhancers of sli-1 identified ark-1 (forAck-related tyrosine kinase), a novel inhibitor of let-23 EGFR signaling in C. elegans. An ark-1 mutation synergizes with mutations in other negative regulators of let-23, resulting in increased RAS signaling. Genetic analysis suggests that ARK-1 acts upstream of RAS and is dependent upon SEM-5. ARK-1 inhibits LET-23-mediated ovulation, a RAS-independent function. ARK-1 physically interacts with SEM-5 in the yeast two-hybrid assay. We find that sem-5 also has a negative function in let-23-mediated ovulation and suggest that this negative function is mediated by the recruitment of inhibitors such as ARK-1.

Amino Acid Sequence↗

Spiny keratoderma.

Spiny keratoderma is a descriptive term used to encompass a variety of unusual, disparate keratodermas. Spiny keratoderma has been associated with lipid abnormalities and has been limited to the palms and soles in some individuals. We describe an acquired case of spiny keratoderma in which an adult woman developed filiform lesions predominating on the trunk and proximal extremities. Treatment with topical emollients and keratolytic agents was unsuccessful, but topical tazarotene led to long periods of resolution. She has had no other associated abnormalities. The clinical features and differential diagnosis of spiny keratoderma are reviewed.

Administration, Topical↗

Serum selenium and subsequent risk of prostate cancer.

It is suspected that selenium is protective against prostate cancer. To test this hypothesis, we conducted a nested case-control study in a cohort of 9345 Japanese-American men examined between 1971 and 1977. At the time of examination, a blood specimen was obtained, and the serum was frozen. After a surveillance period of more than 20 years, 249 tissue-confirmed incident cases of prostate cancer were identified. Their stored sera and those of 249 matched controls were measured for selenium levels. Odds ratios for prostate cancer, based on quartiles of serum selenium levels, were determined using the General Estimating Equations approach. The multivariate odds ratio for the highest quartile was 0.5 (95% confidence interval, 0.3-0.9) with a two-sided P for trend of 0.02. The inverse association was more notable for cases with advanced disease and for cases diagnosed 5-15 years after phlebotomy. However, the association was mainly present in current or past cigarette smokers rather than nonsmokers, which leads to caution in the interpretation of the results.

Aged↗

A rare complication of PTCS: ruptured balloon with retained broken catheter.

This report describes a rare situation in which a retained ruptured balloon with broken catheter was caught in an incompletely opened stent during a percutaneous transluminal coronary stenting (PTCS) procedure in a 84 year old gentleman. A short, warm heart bypass and single cross clamping coronary artery bypass grafting procedure was performed.

Aged↗

Longitudinal change in the treatment of nausea and vomiting of pregnancy in Ontario.

BACKGROUND: Health problems associated with untreated nausea and vomiting of pregnancy (NVP) include maternal weight loss, dehydration, and electrolyte and acid-base disturbances. Negative social consequences include the deterioration of domestic, social and occupational function of the affected women. In 1994 it was documented that most physicians in Ontario tended not to treat women with NVP pharmacologically. PURPOSE: To investigate the longitudinal change in therapeutic practice of physicians, with respect to the treatment of NVP. SUBJECTS AND METHODS: A questionnaire was distributed to a randomly selected sample of physicians that included community-based family physicians, hospital-based family physicians, obstetricians and physicians who called the Motherisk Program for information. The participants were questioned about their choices in the pharmacological treatment of NVP. The data from the survey were compared with those from a previously published survey conducted in 1994. RESULTS: In 1999, 90.2% of physicians surveyed reported to have used pharmacological means to treat NVP. In 1999, 95% of the physicians surveyed reported to have prescribed doxylamine succinate-pyridoxine hydrochloric acid (Diclectin), and 11% prescribed dimenhydrinate (Gravol) to treat NVP. These results are significantly different from those found in 1994 (90% prescribed Gravol as the first choice). CONCLUSIONS: In 1999, temporally related to various educational efforts, physicians offered treatment for NVP more readily, including the drug recommended by the regulatory agency. These changes may explain in part the recently documented decrease in hospitalizations due to NVP in Canada.

Chi-Square Distribution↗

TAK1 regulates multiple protein kinase cascades activated by bacterial lipopolysaccharide.

During inflammation the balance between cell activation and cell death is determined by the tight regulation of multiple intracellular enzyme cascades. Key regulatory steps often involve protein kinases. We show that the prototypical pro-inflammatory molecule, bacterial lipopolysaccharide, activates multiple protein kinases such as p38, JNK, IKK-beta, and PKB/Akt via transforming growth factor beta-activated kinase-1 (TAK1). We also show that TAK1 plays an important role in similar activation pathways triggered by interleukin-1. Thus TAK1 must be considered as an important component of intracellular pathways in cells involved in host responses to physiological and/or environmental stress signals during inflammation.

Androstadienes↗

The ontogeny of conditioned odor potentiation of startle.

During development, conditioned responses usually occur first to olfactory, then to auditory, and finally to visual cues. The authors of the present study report that fear potentiation of startle to an olfactory conditioned stimulus emerges relatively late in development (i.e., at 23 days of age; Experiments 1 and 2). The failure to observe conditioned odor potentiation of startle (OPS) in younger rats was not due to a failure to either acquire or remember the odor-shock association (Experiment 3). Surprisingly, the authors also found that rats trained at 16 but tested at 23 days of age failed to exhibit the OPS effect even though they did exhibit pronounced odor avoidance (Experiment 4). The results are discussed in terms of (a) sensory-specific sequential emergence of learned fear, (b) the neural circuit involved in fear potentiation of startle, and (c) the concept that conditioned responding is appropriate to the animal's age at the time of training rather than its age at testing.

Aging↗

Modest increases in the titers of helper virus-free herpes simplex virus 1 (HSV-1) vectors by packaging in a cell line with inducible expression of HSV-1 VP16 or by treatment with N,N'-hexamethylene-bis-acetamide.

A recently developed helper virus-free HSV-1 vector system has potential for both gene therapy and physiological studies, but relatively low vector titers have complicated use of this system. In this report, we explored improving the vector titers by isolating a Vero cell line that uses the tetracycline-regulated promoter system to induce HSV-1 VP16 at the beginning of the packaging procedure. We isolated the required cell line and demonstrated that it supports enhanced expression from a HSV-1 immediate early (IE) promoter. However, use of this cell line in helper virus-free vector packaging results in only a modest, approximately 2-fold increase in the vector titers. Additionally, treating the packaging cells with N,N'-hexamethylene-bis-acetamide (HMBA), which is known to induce HSV-1 IE promoters, also supports only modest increases in the vector titers. These results suggest that the lack of VP16 is not the rate limiting factor in the packaging procedure.

Acetamides↗

Direct, preparative enantioselective chromatography of propranolol hydrochloride and thioridazine hydrochloride using carbon dioxide-based mobile phases.

In this paper, we describe the direct, preparative enantioselective chromatography of racemic (rac)-propranolol hydrochloride (HCI) and rac-thioridazine.HCl using Chiralpak AD chiral stationary phase and mobile phase systems containing carbon dioxide and methanol without the use of basic or acidic additives. Isolated fractions of propranolol.HCl were positively identified by mass spectrometry, Beilstein flame test, melting point, and chemical analysis to be HCI enantiomers of propranolol-HCl salts exhibited characteristic mass spectra peaks at 36 and 38 mass-to-charge ratio in the expected 3:1 isotopic ratio for the solute that were absent in the mass spectra for the free-base forms. To our knowledge, the direct, preparative enantioselective isolation of HCI enantiomeric salts of rac-propranolol and of rac-thioridazine have not been previously demonstrated and published.

Adrenergic beta-Antagonists↗

Toward creation of a universal NMR database for the stereochemical assignment of acyclic compounds: the case of two contiguous propionate units.

[formula: see text] Using triol 1 as a representative example of natural products containing two contiguous propionate units, 13C and 1H NMR databases for the stereochemical assignment of acyclic compounds have been created. Chemical shift increments due to the presence of additional functional groups as well as solvent effects are discussed.

Databases, Factual↗

Caenorhabditis elegans mediator complexes are required for developmental-specific transcriptional activation.

Mediator proteins are required for transcriptional regulation of most genes in yeast. Mammalian Mediator homologs also function as transcriptional coactivators in vitro; however, their physiological role in gene-specific transcription is not yet known. To determine the role of Mediator proteins in the development of complex organisms, we purified putative Mediator complexes from Caenorhabditis elegans and analyzed their phenotypes in vivo. C. elegans Mediator homologs were assembled into two multiprotein complexes. RNA interference assays showed that the CeMed6, CeMed7, and CeMed10/CeNut2 gene products are required for the expression of developmentally regulated genes, but are dispensable for expression of the ubiquitously expressed genes tested in this study. Therefore, the gene-specific function of Mediator as an integrator of transcriptional regulatory signals is evolutionarily conserved and is essential for C. elegans development.

Amino Acid Sequence↗

Baculovirus-based genetic screen for antiapoptotic genes identifies a novel IAP.

The prototype baculovirus, Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) expresses p35, a potent anti cell-death gene that promotes the propagation of the virus by blocking host cell apoptosis. Infection of insect Sf-21 cells with AcMNPV lacking p35 induces apoptosis. We have used this pro-apoptotic property of the p35 null virus to screen for genes encoding inhibitors of apoptosis that rescue cells infected with the p35 defective virus. We report here the identification of Tn-IAP1, a novel member of the IAP family of cell death inhibitors. Tn-IAP1 blocks cell death induced by p35 null AcMNPV, actinomycin D, and Drosophila cell-death inducers HID and GRIM. Given the conserved nature of the cell death pathway, this genetic screen can be used for rapid identification of novel inhibitors of apoptosis from diverse sources.

Amino Acid Sequence↗

Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana.

Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2.

Arabidopsis↗

Structural studies of the detergent-solubilized and vesicle-reconstituted insulin receptor.

Insulin binding to the insulin receptor initiates a cascade of cellular events that are responsible for regulating cell metabolism, proliferation, and growth. We have investigated the structure of the purified, functionally active, human insulin receptor using negative stain and cryo-electron microscopy. Visualization of the detergent-solubilized and vesicle-reconstituted receptor shows the alpha(2)beta(2) heterotetrameric insulin receptor to be a three-armed pinwheel-like complex that exhibits considerable variability among individual receptors. The alpha-subunit of the receptor was labeled with an insulin analogue.streptavidin gold conjugate, which facilitated the identification of the receptor arm responsible for insulin binding. The gold label was localized to the tip of a single receptor arm of the three-armed complex. The beta-subunit of the insulin receptor was labeled with a maleimide-gold conjugate, which allowed orientation of the receptor complex in the membrane bilayer. The model derived from electron microscopic studies displays a "Y"-like morphology representing the predominant species identified in the reconstituted receptor images. The insulin receptor dimensions are approximately 12.2 nm by 20.0 nm, extending 9.7 nm above the membrane surface. The beta-subunit-containing arm is approximately 13.9 nm, and each alpha-subunit-containing arm is 8.6 nm in length. The model presented is the first description of the insulin receptor visualized in a fully hydrated state using cryo-electron microscopy.

3T3 Cells↗

Protein isoaspartyl methyltransferase protects from Bax-induced apoptosis.

Protein L-isoaspartyl methyltransferase (Pimt) is a highly conserved enzyme utilising S-adenosylmethionine (AdoMet) to methylate aspartate residues of proteins damaged by age-related isomerisation and deamidation. We have been particularly interested in this enzyme since addition of the compound CGP3466 to primary rat astroglia cell cultures resulted in an upregulation of Pimt at the mRNA level, as shown here by semi-quantitative RT-PCR. CGP3466 is a compound related to the anti-Parkinson's drug R-(-)-deprenyl, which has been shown to protect from neural apoptosis induced by trophic factor withdrawal [Tatton et al., 1994. J. Neurochem. 63, 1572]. The pro-apoptotic gene Bax is required in the cascade of events following withdrawal [Deckwerth et al., 1996. Neuron 17, 401]. We therefore investigated whether Pimt overexpression was able to affect Bax-induced apoptosis in primary mouse cortical neurons. Our results show that Pimt is indeed able to protect from Bax-induced apoptosis. Furthermore, this activity is not restricted to brain-specific cell types, since the same effect is also demonstrated in COS1 cells. In addition, mutational analysis suggests that the protective effect is dependent on the adenosine methionine-binding motif, which is well conserved in protein methyltransferases, and that a mutation destroying this motif crucially affects cytoskeletal structures of the cell.

Animals↗