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Biomedical subjects

E Lam

Publications and source records attributed to E Lam.

At least 19 recordsLinked to original sources
PubMed2006

Cryptococcosis in apparently immunocompetent patients.

BACKGROUND: Few reports have described the clinical and microbiological features of cryptococcosis in immunocompetent patients. AIM: To compare clinical presentations and outcomes of cryptococcosis in immunocompetent vs. immunocompromised patients. DESIGN: Retrospective case series. METHODS: All culture- or histology-confirmed cases (n = 46) of cryptococcosis in two acute hospitals in Hong Kong (1995-2005) were included. Clinical presentations, rates of fungaemia, cerebrospinal fluid (CSF) parameters and clinical outcomes were recorded. RESULTS: Twenty patients (43.5%) were apparently immunocompetent, 17 (37.0%) had predisposing factors other than HIV infection, and 9 (19.6%) were HIV-positive. Thirty-one (67.4%) presented with meningitis, four (8.7%) with pulmonary cryptococcosis, and 11 (23.9%) with extraneural, extrapulmonary cryptococcosis. Of the immunocompetent patients with retrievable isolates (n = 8), three (37.5%) were Cryptococcus gattii; all isolates (n = 6) from immunocompromised patients were Cryptococcus neoformans var. grubii. Immunocompetent patients more commonly presented with meningitis (80.0% vs. 47.1%, p = 0.03), and tended toward lower rates of fungaemia (10.0% vs. 35.3%, p = 0.06) and mortality (25.0% vs. 52.9%, p = 0.06). Death was associated with fungaemia (p = 0.01) and underlying malignancy (p < 0.01). In cryptococcal meningitis, immunocompetent patients had longer mean time from illness onset to presentation (34.4 vs. 12.6 days, p = 0.02), more intense inflammatory responses (CSF: white blood cells 108 vs. 35 x 10(9)/l, p = 0.03; protein 1.61 g/l vs. 0.79 g/l, p = 0.07), less fungaemia (0% vs. 26.7%, p = 0.04) and more satisfactory clinical outcomes (81.3% vs. 46.7%, p = 0.04). DISCUSSION: A substantial proportion of patients with cryptococcosis are apparently immunocompetent. C. neoformans var. grubii and C. gattii are the common causes. Immunocompetent patients tend to present with localized, indolent neurological disease, with more intense inflammatory responses but better clinical outcomes.

Adult↗
PubMed2001

Detection of chromosomes tagged with green fluorescent protein in live Arabidopsis thaliana plants.

BACKGROUND: Structural and dynamic studies of chromosomes tagged with green fluorescent protein (GFP) in yeast and cultured animal cells have revealed some surprises. Although this technology can be very powerful, only a few studies using this approach with developed multicellular systems have been reported for the study of chromatin behavior in situ. RESULTS: We established vectors and conditions to visualize tagged loci stably inserted in the Arabidopsis genome via GFP fused to a bacterial DNA-binding protein. Using this system, three-dimensional coordinates for tagged loci within nuclei from cells of a live plant can be directly determined with concomitant visualization of the position of the nucleolus. Chromosome polyploidization in epidermal cells at the elongation zone of the root in transgenic plants can be visualized in situ using this technique. CONCLUSION: We have established that GFP fusion with DNA-binding proteins can be used in conjunction with concatameric binding-site arrays to track genomic loci in living Arabidopsis plants. It should now be feasible to study the mechanisms of organization and dynamics of chromatin in specific cell types during various times of plant development, taking advantage of the well developed genetic systems and resources available for Arabidopsis.

Arabidopsis↗
PubMed2001

Programmed cell death, mitochondria and the plant hypersensitive response.

The plant response to attempted infection by microbial pathogens is often accompanied by rapid cell death in and around the initial infection site, a reaction known as the hypersensitive response. This response is associated with restricted pathogen growth and represents a form of programmed cell death (PCD). Recent pharmacological and molecular studies have provided functional evidence for the conservation of some of the basic regulatory mechanisms underlying the response to pathogens and the activation of PCD in animal and plant systems. In animals, the mitochondrion integrates diverse cellular stress signals and initiates the death execution pathway, and studies indicate a similar involvement for mitochondria in regulating PCD in plants. But many of the cell-death regulators that have been characterized in humans, worms and flies are absent from the Arabidopsis genome, indicating that plants probably use other regulators to control this process.

Animals↗
PubMed2001

Trans-dominant suppression of plant TGA factors reveals their negative and positive roles in plant defense responses.

Salicylic acid (SA) is a key regulator for the induction of systemic acquired resistance (SAR), and NPR1 is a critical mediator for the biological effects of SA. Physical interactions between NPR1 and TGA factors, a conserved family of basic-leucine-zipper (bZip) proteins in plants, have suggested a role for these transcription factors in mediating SAR induction via the regulation of defense genes. To elucidate this function, we constructed a trans-dominant mutant that specifically eliminates DNA-binding activities of this class of bZip proteins in transgenic tobacco plants. Our results demonstrate that the loss of TGA DNA-binding activities is correlated with suppression of two xenobiotic-responsive genes, GNT35 and STR246, and enhanced induction of pathogenesis-related (PR) genes by SA. In addition, these TGA-suppressed plants exhibited higher levels of PR gene induction by pathogen challenge and an enhanced SAR. These results suggest that TGA transcription factors serve both negative and positive regulatory roles in mediating plant defense responses.

Amino Acid Sequence↗
PubMed2000

Nitric oxide and salicylic acid signaling in plant defense.

Salicylic acid (SA) plays a critical signaling role in the activation of plant defense responses after pathogen attack. We have identified several potential components of the SA signaling pathway, including (i) the H(2)O(2)-scavenging enzymes catalase and ascorbate peroxidase, (ii) a high affinity SA-binding protein (SABP2), (iii) a SA-inducible protein kinase (SIPK), (iv) NPR1, an ankyrin repeat-containing protein that exhibits limited homology to IkappaBalpha and is required for SA signaling, and (v) members of the TGA/OBF family of bZIP transcription factors. These bZIP factors physically interact with NPR1 and bind the SA-responsive element in promoters of several defense genes, such as the pathogenesis-related 1 gene (PR-1). Recent studies have demonstrated that nitric oxide (NO) is another signal that activates defense responses after pathogen attack. NO has been shown to play a critical role in the activation of innate immune and inflammatory responses in animals. Increases in NO synthase (NOS)-like activity occurred in resistant but not susceptible tobacco after infection with tobacco mosaic virus. Here we demonstrate that this increase in activity participates in PR-1 gene induction. Two signaling molecules, cGMP and cyclic ADP ribose (cADPR), which function downstream of NO in animals, also appear to mediate plant defense gene activation (e.g., PR-1). Additionally, NO may activate PR-1 expression via an NO-dependent, cADPR-independent pathway. Several targets of NO in animals, including guanylate cyclase, aconitase, and mitogen-activated protein kinases (e.g., SIPK), are also modulated by NO in plants. Thus, at least portions of NO signaling pathways appear to be shared between plants and animals.

Adenosine Diphosphate Ribose↗
PubMed2000

Enzyme biosensor for studying therapeutics of Alzheimer's disease.

An electrochemical method for the investigation and comparison of anti-Alzheimer medications that is based on the inhibition of the acetylcholinesterase is presented. The developed amperometric biosensor determines the in-vitro inhibition of the acetylcholinesterase that is co-immobilized with choline oxidase on the working electrode surface of a three-electrode system using gel entrapment. The sensor has been applied to determine the IC50 values of two known and one newly developed Alzheimer remedy. A simultaneous measurement with the photometric standard method shows the applicability of our method for fast drug screening.

Acetylcholinesterase↗
PubMed2000

Caspase-like protease involvement in the control of plant cell death.

Cell death as a highly regulated process has now been recognized to be an important, if not essential, pathway that is ubiquitous in all multicellular eukaryotes. In addition to playing key roles in the morphogenesis and sculpting of the organs to give rise to highly specialized forms and shapes, cell death also participates in the programmed creation of specialized cell types for essential functions such as the selection of B cells in the immune system of mammals and the formation of tracheids in the xylem of vascular plants. Studies of apoptosis, the most well-characterized form of animal programmed cell death, have culminated in the identification of a central tripartite death switch the enzymatic component of which is a conserved family of cysteine proteases called caspases. Studies in invertebrates and other animal models suggest that caspases are conserved regulators of apoptotic cell death in all metazoans. In plant systems, the identities of the main executioners that orchestrate cell death remain elusive. Recent evidence from inhibitor studies and biochemical approaches suggests that caspase-like proteases may also be involved in cell death control in higher plants. Furthermore, the mitochondrion and reactive oxygen species may well constitute a common pathway for cell death activation in both animal and plant cells. Cloning of plant caspase-like proteases and elucidation of the mechanisms through which mitochondria may regulate cell death in both systems should shed light on the evolution of cell death control in eukaryotes and may help to identify essential components that are highly conserved in eukaryotes.

Apoptosis↗
PubMed2000

NPR1 differentially interacts with members of the TGA/OBF family of transcription factors that bind an element of the PR-1 gene required for induction by salicylic acid.

NPR1 is a critical component of the salicylic acid (SA)-mediated signal transduction pathway leading to the induction of defense genes, such as the pathogenesis-related (PR)-1 gene, and enhanced disease resistance. Using a yeast two-hybrid screen, we identified several NPR1-interacting proteins (NIPs). Two of these NIPs are members of the TGA/OBF family of basic leucine zipper (bZIP) transcription factors; this family has been implicated in the activation of SA-responsive genes, including PR-1. Six TGA family members were tested and shown to differentially interact with NPR1: TGA2 and TGA3 showed strong affinity for NPR1; TGA5 and TGA6 exhibited weaker affinity; and TGA1 and TGA4 displayed little or no detectable interaction with NPR1, respectively. Interestingly, the amino-termini of these factors were found to decrease their stability in yeast and differentially affect their apparent affinity toward NPR1. The interacting regions on NPR1 and the TGA factors were also defined. Each of four point mutations in NPR1 that disrupt SA signaling in Arabidopsis completely blocked interaction of NPR1 with TGA2 and TGA3. TGA2 and TGA3 were also found to bind the SA-responsive element of the Arabidopsis PR-1 promoter. These results directly link NPR1 to SA-induced PR-1 expression through members of the TGA family of transcription factors.

Amino Acid Sequence↗
PubMed2000

Clinical study of lamotrigine and valproic acid in patients with epilepsy: using a drug interaction to advantage?

Lamotrigine (LTG) is one of the newer antiepileptic drugs which has been shown to have a spectrum of drug interactions (including with other epilepsy drugs) that can have a pronounced effect on LTG kinetics. The present study examined the LTG metabolic inhibition dose-response relationship with valproic acid (VPA) in eight patients with epilepsy with a view to using this to benefit the patient. This could benefit the patient not only by attaining higher plasma LTG concentrations with "standard" dosages of LTG, but also possibly by achieving better seizure control through providing a less variable peak-to-trough fluctuation in LTG concentrations as a result of extending the half-life of LTG. The dosages of VPA trialed were 0, 200, 500, and 1,000 mg/d which resulted in a mean increase in LTG area under the curve of 83.7 +/- 14.7% at 200 mg VPA/d, to and 160 +/- 37.9% at 1,000 mg VPA/d. The presence of concomitant enzyme inducers in some patients did not influence the percentage increase from baseline in half-life observed, although clearly those on inducers started from a lower absolute half-life as a result of the induction. The effect was shown to be quite variable, particularly at the highest dosage of VPA tested (1,000 mg/d), suggesting that this effect could be best applied with the support of the therapeutic drug monitoring laboratory determining plasma LTG concentrations to allow individualization of the LTG dosage.

Adult↗
PubMed1999

Nonspecific inhibition of myogenic tone by PD98059, a MEK1 inhibitor, in rat middle cerebral arteries.

Activation of MAP kinase kinase, also called ERK kinase (MEK), may lead to desinhibition of thin filament regulatory proteins and we therefore investigated the acute effects of the potent MEK inhibitor, PD98059 on the contractile properties of pressurized rat middle cerebral arteries. Cerebral arteries (diameter 100-150 microm) were mounted on a pressure myograph and PD98059 (10 microM, 40 microM) significantly inhibited (15% and 64%) myogenic tone (P < 0.001). At these concentrations, PD98059 also significantly reduced the vasopressin (0.1 microM)- and KCl (60 mM)-induced tone. Cumulative addition of exogenous Ca2+ (0.4-1.6 mM) increased myogenic tone to approximately 50% of constriction at 80 mmHg. This effect was inhibited by PD98059 (P < 0.001). These results demonstrate that pressure-induced myogenic tone is inhibited by PD98059 at the concentrations that have been reported to be selective for inhibition of MEK and the MAP kinase cascade. However, our results also demonstrate that PD98059 may have nonspecific effects on voltage-sensitive Ca2+ entry in vascular smooth muscle.

Animals↗
PubMed1999

Die and let live - programmed cell death in plants.

Cysteine and serine proteases are prominent players in the control of developmental and pathogen-activated cell deaths in plants. Ethylene, salicylic acid, the small G-protein Rac, calcium and reactive oxygen species are recurring mediators of death signaling. Lastly, the mitochondrion has emerged in both plant and animal systems as a 'central depot' that interprets multiple signals and in some instances determines the fate of the cell.

Apoptosis↗
PubMed1999

Signals controlling the expression of cytosolic ascorbate peroxidase during pathogen-induced programmed cell death in tobacco.

In plants ascorbate peroxidase (APX) is an important H2O2-detoxifying enzyme. The expression of APX is rapidly induced in response to stresses that result in the accumulation of reactive oxygen species (ROS). We have recently reported that the steady-state level of transcripts encoding cytosolic APX (cAPX) is dramatically induced during the hypersensitive response (HR) of tobacco plants infected with tobacco mosaic virus (TMV). Because cAPX expression is closely linked to the production of ROS in plant cells, studying the regulation cAPX mRNA can reveal some of the signal transduction events associated with ROS metabolism during the HR. Analysis of cAPX mRNA induction during the HR suggested that the expression of cAPX is under the control of the HR signal transduction pathway. The activation of cAPX expression followed signaling events such as changes in protein phosphorylation and induction of ion fluxes. Expression of cAPX was suppressed under conditions of low oxygen pressure, and could only be mimicked by enhancing the intracellular generation of ROS. Interestingly, salicylic acid (SA), which is thought to be involved in ROS metabolism during the HR, did not affect the induction of cAPX mRNA during TMV-induced HR. Using cAPX expression as a marker for the production of ROS, it is suggested that SA may not be involved in the formation of ROS during the HR of tobacco to TMV, and that ROS may not be involved in the induction of the pathogenesis-related protein, PR-1, during this process.

Anti-Infective Agents↗
PubMed1999

Markers for hypersensitive response and senescence show distinct patterns of expression.

Controlled cellular suicide is an important process that can be observed in various organs during plant development. From the generation of proper sexual organs in monoecious plants to the hypersensitive response (HR) that occurs during incompatible pathogen interactions, programmed cell death (PCD) can be readily observed. Although several biochemical and morphological parameters have been described for various types of cell death in plants, the relationships existing between those different types of PCD events remain unclear. In this work, we set out to examine if two early molecular markers of HR cell death (HIN1 and HSR203J) as well as a senescence marker (SAG12) are coordinately induced during these processes. Our result indicates that although there is evidence of some cross-talk between both cell death pathways, spatial and temporal characteristics of activation for these markers during hypersensitive response and senescence are distinct. These observations indicate that these markers are relatively specific for different cell death programs. Interestingly, they also revealed that a senescence-like process seems to be triggered at the periphery of the HR necrotic lesion. This suggests that cells committed to die during the HR might release a signal able to induce senescence in the neighboring cells. This phenomenon could correspond to the establishment of a second barrier against pathogens. Lastly, we used those cell death markers to better characterize cell death induced by copper and we showed that this abiotic induced cell death presents similarities with HR cell death.

Apoptosis↗
PubMed1998

Caspases and programmed cell death in the hypersensitive response of plants to pathogens.

The hypersensitive response (HR) is induced by certain plant pathogens and involves programmed cell death (PCD) to restrict the spread of pathogens from the infection site [1]. Concurrent with the induction of cell death, the host activates a defense response [2]. The cell death associated with the HR in several plant-pathogen systems has morphological similarities to animal apoptosis [3,4], which suggests that cell death mechanisms in plants and animals may share common components that lead to similar cellular events. Caspases are conserved cysteine proteases that regulate animal PCD [5]; caspase activity or an involvement of caspases in cell death has yet to be reported in plants. In this work, we investigated the participation of caspases in HR cell death. Caspase-specific peptide inhibitors, Ac-YVAD-CMK [6] and Ac-DEVD-CHO [7], could abolish bacteria-induced plant PCD but did not significantly affect the induction of other aspects of HR, such as the expression of defense genes. This result confirmed our previous model that cell death can be uncoupled from defense gene activation during HR [8]. Caspase-like proteolytic activity was detected in tobacco tissues that were developing HR following infection with tobacco mosaic virus (TMV). Our results provide evidence for the presence of caspase-like plant protease(s) that participate in HR cell death.

Amino Acid Chloromethyl Ketones↗