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Biomedical subjects

W L Lee

Publications and source records attributed to W L Lee.

At least 37 records · Page 2Linked to original sources

Expression of the group I metabotropic glutamate receptor in the hippocampus of patients with mesial temporal lobe epilepsy.

Immunocytochemical studies at light and electron microscopic levels in hippocampi of patients with mesial temporal lobe epilepsy showed mGluR1 and mGluR5 immunoreactivity in the molecular layer of the dentate gyrus and CA1 area, especially at the border between stratum oriens and alveus. By electron microscopy, degenerating neuronal elements were found in all areas studied. There were glial filamentous tangles which appeared similar to intranuclear inclusions in astrocytes in all areas studied. Reactive product for mGluR1 was localised only in post-synaptic elements. However, mGluR5 immunoreactivity was demonstrated in both post- and pre-synaptic elements in the molecular layer of the dentate gyrus and CA1 area. Reactive product for mGluR5 was also demonstrated in astrocytes and in the periphery of fibrillary tangles. We postulate that in patients with mesial temporal lobe epilepsy, mGluR1 may increase hippocampal excitability through postsynaptic activation, and mGluR5 may do so through both pre- and post-synaptic mechanisms.

Adolescent↗

Ventilator-induced lung injury and recommendations for mechanical ventilation of patients with ARDS.

Mechanical ventilation is life sustaining and is the standard therapy for acute respiratory failure. The 16th century anatomist Vesalius is often credited for the earliest account of positive-pressure ventilation. In his work De humani corporis fabrica (On the Fabric of the Human Body), he described how an animal could be resuscitated by blowing into a reed inserted into a hole in its trachea. Although positive pressure ventilation using bellows was first used for drowning victims in the 1700s, there were soon concerns that such therapy could in fact be harmful to the lungs. In 1827, Leroy d'Etoille condemned bellows ventilation after discovering that it could lead to emphysema and tension pneumothoraces. Subsequently, positive pressure ventilation would be virtually abandoned for over 100 years. Despite this early concern about the potential for harm from mechanical ventilation, it is only in the last one to two decades that research into so-called ventilator-induced lung injury (VILI) has blossomed. Indeed, although initial studies have focused on which ventilatory parameters are associated with the most (or least) harm, there has been an explosion of research in the last 5 years attempting to delineate the basic cellular mechanisms by which mechanical ventilation injures the lung. Recently, there has been exciting evidence to suggest that lung injury induced by mechanical ventilation may have important systemic consequences, including multi-organ dysfunction. Lastly and most importantly, there is accumulating data from clinical trials in humans that ventilatory strategies designed to avoid VILI can in fact save lives.

Journal Article↗

Demographic and health-related correlates to visits to complementary and alternative medical providers.

OBJECTIVES: The objective of this study was to ascertain the extent to which demographic and health-related variables are related to visits to a complementary or alternative medicine (CAM) practitioner. METHODS: This study reports a secondary analysis of visits to CAM practitioners during the year before the 1996 Medical Expenditure Panel Survey (n = 16,038). RESULTS: Overall visits to CAM providers (9%) were lower than reported in widely cited surveys but quite consistent with a previous Robert Wood Johnson study that used a similar sampling procedure. Gender, education, age, geographic location, and race (Hispanics and African Americans proved to be less likely to visit CAM providers than whites) were statistically significant predictors of visits to CAM providers. Individuals in poorer health and those suffering from mental, musculoskeletal, and metabolic disorders also tended to be more likely to have visited a CAM provider. CONCLUSIONS: Although the choice of alternative versus orthodox treatment appears to be a complex phenomenon, these data suggest that the heaviest users of CAM therapies tend to be individuals with comorbid, non-life-threatening health problems. This finding may help to ameliorate concerns that this type of care is being used in lieu of therapies with more definitive efficacy evidence.

Adolescent↗

Neutrophil activation and acute lung injury.

Neutrophils are considered to be central to the pathogenesis of most forms of acute lung injury (ALI). For the sake of clarity, neutrophil involvement in ALI can be conceptualized as consisting of sequential stages, beginning with their sequestration in the pulmonary microvasculature, followed by adhesion and activation, and culminating in the production of a microbicidal or "effector" response, such as the generation of reactive oxygen species or release of proteolytic enzymes. Great strides have been made in elucidating these various stages of neutrophil involvement. Recent studies have focused on the intracellular signaling pathways that govern neutrophil activation and have elucidated complex cascades of kinases and other intracellular signaling molecules that allow for amplication of the neutrophil response, yet simultaneously confer specificity of a response. We believe that the inflammatory response in ALI may initially be adaptive, such as the pivotal role played by neutrophils in a bacterial or fungal infection. Ultimately, it is the persistence or the dysregulation of neutrophil activation that may lead to ALI. An increased understanding of how neutrophils function will facilitate the design of therapeutic strategies that retain the beneficial aspects of the inflammatory response, while avoiding unnecessary tissue damage.

Apoptosis↗

Excision of mature teratoma using culdotomy, with and without laparoscopy: a prospective randomised trial.

OBJECTIVE: To compare the results of removing mature teratoma with laparoscopy or without laparoscopy. DESIGN: A prospective, randomised trial. SETTING: Medical centre. PARTICIPANTS: Seventy-nine women with mature teratomas identified using results of ultrasound examinations and biochemical markers. INTERVENTION: Cystectomy with laparoscopic approach or without laparoscopic approach through a culdotomy. METHODS: Patients were randomly assigned to have their cysts removed via vaginal cystectomy without laparoscopy (n = 37, Group A) or laparoscopic cystectomy via culdotomy opening (n = 42, Group B). Inclusion criteria were history of vaginal delivery, no previous abdominal surgery, no history of pelvic inflammatory disease, no medical illness, and no presenting symptoms. Eight women randomised to Group A withdrew before surgery. The laparoscopically resected tumours were each put into a cellulose bag, and tumours without laparoscopic-assistance were removed directly via the vagina. RESULTS: Blood loss in Group A (88 +/- 37 ml) was significantly more than that in Group B (64 +/- 20 ml, P = 0.000). The post-operative recovery times were 20 and 17 hours, respectively (P = 0.030). The rates of successful surgery were 58.6 and 97.6%, respectively (P = 0.002). The spillage rates were 44.8% and 19.0%, respectively (P = 0.006). There were no significant differences in tumour size, patient age, and operative time between groups. CONCLUSION: Cystectomy without assistance of laparoscopy could be applied to manage mature teratoma of the ovary; however, because of the difficulty of this technique, we had high percentages of tumour spillage and more blood loss during operation and a high percentage of patients who required conversion to laparotomy compared with laparoscopic cystectomy. We favoured laparoscopically assisted cystectomy to manage mature teratoma.

Adolescent↗

Successful resuscitation of patient with massive coronary air embolism occluding two vessels during coronary angiography--a case report.

Massive coronary air embolism is usually disastrous although successful resuscitation has been reported previously. To what extent a patient with coronary air embolism can be resuscitated is not known. The authors report a rare case of massive air embolism to the left coronary arteries and successful resuscitation by vigilantly maintaining an effective driving force to dissipate the air lock.

Aged↗

The growth of health-related meta-analyses published from 1980 to 2000.

A MEDLINE search was conducted to estimate trends in the growth of health-related meta-analyses published during the past two decades. Employing a more specific than sensitive search strategy, and not supplementing these results with known sources of published meta-analyses or manual search strategies, 3,025 probable meta-analyses were selected from the 5,128 citations identified. The data showed a definitive upward (and generally linear) trend across time with no evidence for this genre of research either leveling off or decreasing.

Bibliometrics↗

The incidence of coronary artery disease in patients with symptomatic bradyarrhythmias.

Symptomatic bradyarrhythmia occurs most often in aged patients. Most of these patients have multiple coronary risk factors and present with angina-like symptoms. The coexistence of CAD not only has major effects on their prognosis but also influences the long-term care. This study was designed to evaluate the incidence of coexistent CAD in patients with symptomatic bradyarrhythmias and its relationship to conventional coronary risk factors in Chinese people. From May 1996 to April 1998, we prospectively studied all consecutive patients admitted to our institution for symptomatic bradyarrhythmias requiring permanent pacemaker implantation. Coronary angiographies were performed non-selectively at the same session of pacemaker implantation. Based on the presence or absence of CAD, patients were divided into two groups for analysis. Multivariate logistic regression analysis was performed to determine independent predictors of CAD including sex, age, diabetes mellitus (DM), hypertension, hypercholesterolemia, and smoking. The odds-ratio (OR) and 95% confidence interval (CI) were determined. A total of 113 patients [68 males and 45 females, mean age 70.4+/-8.2 years old (range 45-86)] were included in our study. The diagnosis was sick sinus syndrome in 69 patients (61%) and atrioventricular block in 44 patients (39%). The incidence of CAD based on coronary angiography was 20%. The nodal-related artery was seldom involved among patients with coexistent CAD and symptomatic bradyarrhythmias (9%), and most patients had significant stenosis over LAD (74%). The baseline characteristics and presenting symptoms were not different statistically between patients with or without CAD. Hypercholesterolemia (OR 6.6, 95% CI 2.0-22.2, p=0.002) and DM (OR 4.7, 95% CI 1.3-17.2, p=0.020) were the two most significant independent predictors of CAD. In our patients with symptomatic bradyarrhythmias requiring permanent cardiac pacing, the incidence of CAD was 20% as determined by coronary angiography (CAG). Hypercholesterolemia and DM were the two most significant independent predictors for CAD in these patients. The nodal artery was seldom involved in patients with coexistent CAD and symptomatic bradyarrhythmias.

Aged↗

Agents for the treatment of glycosphingolipid storage disorders.

We have developed a series of inhibitors of glucosylceramide synthase that are structurally based on the parent compound D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP). These inhibitors provide useful tools for manipulating glycosphingolipid levels in cells and for elucidating questions associated with sphingolipid signaling. Recently, two highly active glucosylceramide synthase inhibitors, D-threo-3', 4'-ethylenedioxy-1-phenyl-2-palmitoylamino-3- pyrrolidino-1-propanol and D-threo-4'-hydroxy-1-phenyl-2-palmitoylamino-3- pyrrolidino-1-propanol, were designed, synthesized, and studied. These inhibitors markedly reduced glycosphingolipid levels in MDCK cells without any accumulation of intracellular ceramide and associated growth inhibition. Subsequently, each inhibitor was evaluated for its ability to lower glycolipid levels in virally transformed lymphoblasts from a patient with alpha-galactosidase A deficiency. Both compounds significantly reduced neutral glycosphingolipid levels in the lymphoblasts without any morphological changes and growth inhibition. Furthermore, the inhibitors were applied to a mouse knockout model of Fabry disease. Inhibitor treatment blocked accumulation of globotriaosylceramide (Gb3) in the kidney, liver and heart of mice. In contrast to another glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin, this treatment was not associated with any significant change in body weight or organ weight and without immunodepletion. These results suggest that these newest PDMP homologues are promising as therapeutic agents for the treatment of glycosphingolipid storage disorders.

Animals↗

Antimutagenicity of extracts of Hericium erinaceus.

Hericium erinaceus is valuable in the diet and in medical treatment. It contains water-soluble polysaccharides that have been found to enhance immunity and which show anti-artificial pulmonary metastatic tumor effects. In this study, water and ethanol extracts of the mycelium and fruiting body of Hericium erinaceus were examined by the Ames test using Salmonella typhimurium TA98 to screen for antimutagenic effects against 5 mutagens: AFB1, B[a]P, Glu-P-1, NQNO, and Trp-P-1. We found that both extracts have the strongest antimutagenic activity against Trp-P-1, followed by Glu-P-1, B[a]P-1, AFB1, and finally NQNO. In addition, the antimutagenicity of the extracts was produced in a concentration-dependent manner. At a concentration of 200 ppm, both extracts showed the highest inhibitory action. However, the linear correlation indicated that concentration-activity relationship was not significant (p > 0.05). In addition, extracts showed less antimutagenicity after heat treatment (p < 0.05). This suggests that the antimutagenicity of the extracts is heat-labile. The ethanol extract from mycelium or fruiting body had better antimutagenic effects than did the water extract (p < 0.05). Also, the extract from the fruiting body had better antimutagenic effects than did that from the mycelium.

Antimutagenic Agents↗

Torsion of benign serous cystadenoma of the fallopian tube: a challenge in differential diagnosis of abdominal pain in women during their childbearing years--a case report.

The differential diagnosis of abdominal pain in women during their childbearing years is still a challenge. Abdominal pain caused by isolated tubal torsion is extremely rare. In the report, we presented a case of isolated tubal torsion caused by benign serous cystadenoma. A 28-year-old married woman (G0) having lower abdominal pain and nausea was referred to our Emergency Room with suspicion of ovarian mass. Physical examination, transvaginal ultrasound and computed tomography showed a 4-cm right adnexal cystic mass. Other laboratory data were all within normal limits. She was managed by laparoscopic examination due to a lack of improvement in her clinical symptoms and inclusive diagnosis after 48-hours' conservative treatment. Laparoscopy showed isolated torsion of right fallopian tube but the right ovary was normal without torsion. Initially, detorsion was performed but necrotic change of the fallopian tube persisted because of permanent darkened color tube without blood flow redistribution, so salpingectomy was performed 30 minutes later. Final pathology showed benign serous cystadenoma of fallopian tube. The present case is the first case of benign serous cystadenoma with resultant necrotic tubal torsion. We reported this case to emphasize the possible value of early performance of laparoscopy in aiding an accurate diagnosis.

Abdominal Pain↗

Attempted suicide and polymorphism of the serotonin transporter gene in Chinese patients with schizophrenia.

Abnormalities of serotonin synthesis and metabolism may be associated with suicidality. The serotonin transporter gene (5-HTT) is one of the important genes involved in the regulation of serotonin neurotransmission. We examined the association of suicidal behavior in Chinese schizophrenic patients with a functional polymorphism of the promoter region of the 5-HTT gene (5-HTTLPR). The 5-HTTLPR genotype was determined by polymerase chain reaction for 76 suicidal and 262 non-suicidal patients with a diagnosis of schizophrenia (DSM-IV criteria). All subjects were unrelated to each other, and all were Chinese. There was no significant genotypic or allelic association of the 5-HTTLPR polymorphism with history of attempted suicide. From our results, this 5-HTTLPR polymorphism is unlikely to have a major effect on suicidal behavior in Chinese patients with schizophrenia.

Adult↗

Expression of constitutively active phosphatidylinositol 3-kinase inhibits activation of caspase 3 and apoptosis of cardiac muscle cells.

Apoptosis of cardiac muscle cells contributes to the development of cardiomyopathy. Recent studies showed that insulin-like growth factor I (IGF-I) inhibits apoptosis of cardiac muscle cells and improves myocardial function in experimental heart failure. This study was carried out to elucidate the role of phosphatidylinositol 3-kinase (PI 3-kinase) in the anti-apoptotic actions of IGF-I in cardiomyocytes and to explore whether expression of constitutively active PI 3-kinase can inhibit apoptosis in cardiomyocytes. Apoptosis of primary cardiomyocytes was induced by doxorubicin treatment and serum withdrawal. Transduction of cardiomyocytes with constitutively active PI 3-kinase specifically lead to serine phosphorylation of Akt, whereas phosphorylation of IGF-I receptor, IRS1/2 and p44/42 mitogen-activated protein kinase were not increased. In the cardiomyocytes transduced with constitutively active PI 3-kinase, activation of the pro-apoptotic caspase 3 was attenuated and fragmentation of DNA was reduced. Preincubating cells with PI 3-kinase inhibitor LY294002 was associated with loss of anti-apoptotic actions of IGF-I and PI 3-kinase. Neither IGF-I nor constitutively active PI 3-kinase lead to serine phosphorylation of Bad, suggesting that the anti-apoptotic effects of PI 3-kinase are not mediated through Bad phosphorylation in cardiac muscle cells. To determine whether activation of caspase 3 is sufficient to induce apoptosis in cardiomyocytes, an engineered TAT-caspase 3 protein was introduced to cardiomyocytes. Significant reduction of cell viability occurred in the cardiomyocytes transduced with active caspase 3, indicating that activation of caspase 3 is sufficient to cause cardiomyocyte death. These findings indicate the existence of an IGF-I receptor-PI 3-kinase-caspase 3 pathway in cardiomyocytes that plays an important role in the anti-apoptotic actions of IGF-I in heart. Moreover, these data suggest that modulation of PI 3-kinase activities may represent a potential therapeutic strategy to counteract the occurrence of apoptosis in cardiomyopathy.

Animals↗

Fission yeast myosin-I, Myo1p, stimulates actin assembly by Arp2/3 complex and shares functions with WASp.

Fission yeast myo1(+) encodes a myosin-I with all three tail homology domains (TH1, 2, 3) found in typical long-tailed myosin-Is. Myo1p tail also contains a COOH-terminal acidic region similar to the A-domain of WASp/Scar proteins and other fungal myosin-Is. Our analysis shows that Myo1p and Wsp1p, the fission yeast WASp-like protein, share functions and cooperate in controlling actin assembly. First, Myo1p localizes to cortical patches enriched at tips of growing cells and at sites of cell division. Myo1p patches partially colocalize with actin patches and are dependent on an intact actin cytoskeleton. Second, although deletion of myo1(+) is not lethal, Deltamyo1 cells have actin cytoskeletal defects, including loss of polarized cell growth, delocalized actin patches, and mating defects. Third, additional disruption of wsp1(+) is synthetically lethal, suggesting that these genes may share functions. In mapping the domains of Myo1p tail that share function with Wsp1p, we discovered that a Myo1p construct with just the head and TH1 domains is sufficient for cortical localization and to rescue all Deltamyo1 defects. However, it fails to rescue the Deltamyo1 Deltawsp1 lethality. Additional tail domains, TH2 and TH3, are required to complement the double mutant. Fourth, we show that a recombinant Myo1p tail binds to Arp2/3 complex and activates its actin nucleation activity.

Actin-Related Protein 2↗

Crucial role of kainate receptors in mediating striatal kainate injection-induced decrease in acetylcholine M(1) receptor binding in rat forebrain.

We investigated the roles of kainate-, alpha-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA)- and N-methyl-D-aspartate (NMDA)-receptors in mediating striatal kainate injection-induced decrease in the binding of acetylcholine M(1) receptors in rat forebrain. After unilateral intrastriatal injection of kainate (4 nmol), the bindings of [3H]kainate (10 nM), [3H]MK-801 (4 nM) and [3H]pirenzepine (4 nM) to the rat ipsilateral forebrain membranes declined, reaching the lowest on day 2 to 4 and recovering on day 8. Saturation binding studies, performed on day 2 post-injection, showed that kainate (1, 2, 4 nmol) dose-dependently decreased B(max) and K(d) of the three ligands. (+)-5-Methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), a selective NMDA receptor channel blocker, antagonised (from a dose of 4 nmol) kainate-induced decreases in the bindings of [3H]kainate (up to approximately 20%), [3H]MK-801 (up to approximately 90%) and [3H]pirenzepine (up to approximately 70%). In contrast, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective non-NMDA receptor antagonist, almost completely abolished (from a dose of 12 nmol) kainate-induced decreases in the bindings of all the three ligands (up to approximately 95-98%). Cyclothiazide, a selective potentiator that enhances AMPA receptor-mediated responses, significantly enhanced (from a dose of 4 nmol) kainate-induced decrease in the binding of [3H]kainate but not that of [3H]pirenzepine or [3H]MK-801. In summary, these results indicate that striatal kainate injection-induced decrease in the binding of acetylcholine M(1) receptors in rat forebrain is dependent on activation of kainate receptors and, to a certain extent, a consequent involvement of NMDA receptors. These and previous studies provide some evidence showing that kainate receptors might play a crucial role in regulating excitatory amino acids (EAA)-modulated cholinergic neurotransmission in the central nervous system (CNS).

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Coagulation inhibitors in sepsis and disseminated intravascular coagulation.

Sepsis is a syndrome that is increasing in frequency and continues to be associated with an unacceptably high mortality. DIC is an important and common sequel of sepsis, is implicated in the development of multiple organ failure, and has been shown repeatedly to connote a poor prognosis. Increasing understanding of the pathogenesis of DIC has suggested several novel therapies designed to correct deficiencies in inhibitors of coagulation. To date, small randomized, controlled studies of antithrombin III concentrates in sepsis and DIC have shown a trend to increased survival, but have not achieved statistical significance. Currently, a large randomized controlled trial of antithrombin III in sepsis is being conducted. Until more data are available, important questions remain as to its proper place in the treatment of sepsis, septic shock, and DIC. Similarly, therapy with protein C and tissue factor-pathway inhibitor has been beneficial in animal models of sepsis and DIC. The results of controlled clinical trials in humans are eagerly awaited.

Animals↗