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Biomedical subjects

P Lee

Publications and source records attributed to P Lee.

At least 55 records · Page 3Linked to original sources
PubMed2001

Axotomy alters neurotrophin and neurotrophin receptor mRNAs in the vagus nerve and nodose ganglion of the rat.

Neurotrophins and neurotrophin receptors play an important role in survival and growth of injured peripheral nerves. To study the injury-mediated neurotrophic response in autonomic nerves, we investigated changes in mRNA expression of neurotrophins and their receptors in the transected vagus nerve and nodose ganglion. Studies using in situ hybridization histochemistry showed that axotomy of the cervical vagus nerve resulted in increased expression of mRNAs for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and for TrkA, TrkB, and TrkC receptors in non-neuronal cells at both the proximal and distal segments of the transected cervical vagus nerve. Moreover, NGF protein was increased in the distal end, and NT-3 protein was increased in both the proximal and the distal ends of the transected nerve 3 days after axotomy. No change of p75(NTR) mRNA was detected in the transected vagus nerve. The induction of each neurotrophin and Trk receptor mRNA was apparent within 1 day after the axotomy and was sustained at least 14 days. By 45 days after the axotomy, a time when axonal reconnection with target tissue is made (integrity of the nerve-target connection was confirmed by the retrograde transport of FluoroGold from the stomach to vagal cell bodies), the levels of neurotrophin and Trk mRNAs in the vagus nerve declined to pre-axotomy levels. TrkA, TrkC, and p75(NTR) mRNA-containing vagal sensory neurons in the nodose ganglion were reduced in number after cervical vagotomy. Neurotrophin-mRNA-containing neurons were not found in the nodose ganglia from either intact or vagotomized rats. The axotomy-induced up-regulation of neurotrophins and Trk receptors mainly in the non-neuronal cells at or near the site of transection suggests that neurotrophins are involved in the survival and regeneration process of the vagus nerve after injury.

Animals↗
PubMed2001

Differences in antigen recognition and cytolytic activity of CD8(+) and CD8(-) T cells that express the same antigen-specific receptor.

CD8(+) and CD8(-) T cell lines expressing the same antigen-specific receptor [the 2C T cell receptor (TCR)] were compared for ability to bind soluble peptide-MHC and to lyse target cells. The 2C TCR on CD8(-) cells bound a syngeneic MHC (K(b+))-peptide complex 10-100 times less well than the same TCR on CD8(+) cells, and the CD8(-) 2C cells lysed target cells presenting this complex very poorly. Surprisingly, however, the CD8(-) cells differed little from CD8(+) cells in ability to bind an allogeneic MHC (L(d+))-peptide complex and to lyse target cells presenting this complex. The CD8(+)/CD8(-) difference provided an opportunity to estimate how long TCR engagements with peptide-MHC have to persist to initiate the cytolytic T cell response.

Animals↗
PubMed2001

Environmental management in resource-rich Alberta, Canada: first world jurisdiction, Third World analogue?

Economic growth is frequently touted as a cure for environmental ills, particularly for those in Third World countries. Here we examine that paradigm in a case study of Alberta, Canada, a wealthy, resource-rich province within a wealthy nation. Through provincial-scale datasets, we examine the increasing pressures of the forest, petroleum, and agricultural industries upon the ecosystems of Alberta within management, economic, and political contexts. We advance the thesis that economic activity leads to environmental degradation unless ecosystem-based management is integrated into economic decision making. Agricultural lands cover 31.7%, and forest management areas leased to industry cover 33.4% of Alberta; both continue to increase in extent. The rate of logging (focused on old-growth by government policy) continues a decades-long exponential rise. Current Alberta annual petroleum production is 52.5 million m3 crude oil and 117 billion m3 of gas. As of early 1999, there were approximately 199,025 oil and gas wells and a conservative total of approximately 1.5-1.8 million km of seismic lines in Alberta. Fire occurrence data indicate no downward trends in annual area burned by wildfire, which may be characterized as driven by climate and inherently variable. When logging and wildfire are combined, the annual allowable cut in Alberta is unsustainable, even when only timber supply is considered and the effects of expanding agriculture and oil and gas activities are ignored. Ecosystem degradation in Alberta is pervasive and contrasts prominently with a high standard of living. A wealth of ecological data exists that indicates current resource-based economic activities are non-sustainable and destructive of ecosystem health yet these data are not considered within the economic decision making process. Given the complex, compounded, and increasing ecosystem perturbations, a future of unpleasant ecological surprises is likely. We conclude with tentative predictions as to where current trends in Alberta may lead if decisions biased against ecosystems continue.

Agriculture↗
PubMed2001

Clinical features of patients with acute organophosphate poisoning requiring intensive care.

OBJECTIVES: To describe the clinical features of organophosphate poisoning (OPP), to evaluate the Acute Physiology and Chronic Health Evaluation (APACHE) II score as an alternative index for measuring OPP severity, and to assess cholinesterase levels for predicting successful weaning from mechanical ventilation (MV). DESIGN AND SETTING: Retrospective medical record review in a medical intensive care unit of an acute general hospital. PATIENTS: Twenty-three adults with OPP between 1995 and 1999. All cases were due to malathion poisoning. Muscarinic features were the predominant clinical manifestations (83%), followed by central nervous system (78%) and nicotinic manifestations (17%). RESULTS: MV was required by 74% of patients because of bronchial secretions (83%), altered conscious level (78%), pneumonia (78%), and flaccid paralysis (57%). Five patients (22%) had features of intermediate syndrome. ICU mortality was 13% and the mean ICU stay was 9.1 +/- 6.0 days. The mean APACHE II score was 17.4 +/- 7.4 and it correlated with mortality, severity of OPP, length of MV, and cholinesterase level. An APACHE II score of 26 or higher was predictive of mortality, with 95% sensitivity and 100% specificity. Threshold levels of serum and red blood cell cholinesterase for successful weaning from MV were 2,900 U/l and 7,500 U/l, respectively. CONCLUSIONS: The APACHE II score may be used as an alternative index of severity in patients with OPP; a score of 26 or higher is a good predictor of mortality. Cholinesterase levels are useful in predicting successful weaning of patients from MV.

APACHE↗
PubMed2001

Factors associated with clinical assessment of overactive bladder and selection of treatment.

BACKGROUND: Overactive bladder (OAB) affects >17 million individuals in the United States, but the symptoms of OAB are frequently underreported by patients and therefore untreated by physicians. OBJECTIVE: The purpose of this observational study was to investigate the demographic and clinical factors associated with the decision to treat OAB pharmacologically and identify factors associated with physicians' assessment of symptom severity. METHODS: We studied 31 physicians treating 217 patients with OAB and collected data on patient demographic characteristics, OAB symptoms, previous management strategies, physicians' assessments of OAB severity, and treatment prescribed. Stepwise logistic regression was used to identify factors associated with selecting pharmacologic treatment and with physician assessment of severity of OAB symptoms. RESULTS: The mean age of the patients was 61.3 years; approximately 82% were female, and approximately 73% were white. Participants with urinary incontinence were significantly (P < 0.001) more likely to be treated with medication than were those with only symptoms of nocturia or urinary frequency. Other significant factors associated with pharmacologic treatment were being white (odds ratio [OR], 9.5; 95% CI, 2.9-30.8); being black (OR, 5.9; 95% CI, 1.2-29.7); physician's clinical assessment of OAB as moderate (OR, 3.5; 95% CI, 1.5-8.2) or severe (OR, 3.8; 95% CI, 1.1-13.7); previous use of medication (OR, 2.9; 95% CI, 1.1-8.1); and number of incontinence episodes in the last 24 hours (OR, 1.2; 95% CI, 1.0-1.5). Factors associated with physician assessment of OAB severity included distress due to OAB symptoms (OR, 2.1; 95% CI, 1.3-3.2), number of incontinence episodes in the last 24 hours (OR, 1.2; 95% CI, 1.1-1.4), and use of previous treatment(s) (OR, 0.4; 95% CI, 0.2-0.8). CONCLUSIONS: Both demographic and clinical symptoms of OAB were associated with the decision to treat OAB with medication, whereas physicians' assessment of OAB severity was associated only with clinical symptoms. Urinary incontinence was the key symptom associated with the decision to treat patients with medication and with the assessment of OAB symptom severity.

Aged↗
PubMed2001

Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia.

Based on the use of Scutellaria baicalensis for the treatment of stroke in traditional Oriental medicine, the current study was carried out to evaluate neuroprotective effects of S. baicalensis after transient global ischemia using rat 4-vessel occlusion model. Methanol extracts from the dried roots of S. baicalensis (0.1-10 mg/kg) administered intra-peritoneally significantly protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated by measuring the density of neuronal cells stained with Cresyl violet. Methanol extract of S. baicalensis inhibited microglial tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production, and protected PC12 cells from hydrogen peroxide-induced toxicity in vitro.

Animals↗
PubMed2001

Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation.

Cytosine methylation of mammalian DNA is essential for the proper epigenetic regulation of gene expression and maintenance of genomic integrity. To define the mechanism through which demethylated cells die, and to establish a paradigm for identifying genes regulated by DNA methylation, we have generated mice with a conditional allele for the maintenance DNA methyltransferase gene Dnmt1. Cre-mediated deletion of Dnmt1 causes demethylation of cultured fibroblasts and a uniform p53-dependent cell death. Mutational inactivation of Trp53 partially rescues the demethylated fibroblasts for up to five population doublings in culture. Oligonucleotide microarray analysis showed that up to 10% of genes are aberrantly expressed in demethylated fibroblasts. Our results demonstrate that loss of Dnmt1 causes cell-type-specific changes in gene expression that impinge on several pathways, including expression of imprinted genes, cell-cycle control, growth factor/receptor signal transduction and mobilization of retroelements.

Alleles↗
PubMed2001

Vulnerability to health problems in female informal caregivers of persons with HIV/AIDS and age-related dementias.

The health of informal caregivers is often studied from the perspective of caregivers' and care receivers' personal and interpersonal characteristics. This study offers an alternative explanation based on a vulnerable populations framework and considers the role of resource availability to the health status of informal caregivers (n=76). Caregivers in a convenience sample were females of diverse ethnicity and socioeconomic status, and care recipients were diagnosed with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) or age-related dementias (ARD). Personal interviews using structured instruments were conducted with caregivers who were attending outpatient clinics at a public hospital and a VA hospital. Instruments included the Center for Epidemiologic Studies Depression-Scale (CES-D), the Global Health Assessment (GHA), the Activities of Daily Living Scale (ADL), the Memory and Behavior Problems Checklist (MBPC) and items from the Symptom Checklist-90 (SCL-90) measuring anger, anxiety and loneliness. Caregivers were experiencing both physical and mental health problems. Regression analyses were used to examine the relationships among resources available to caregivers, conditions that put caregivers at risk for poorer health, and health status itself. Analyses were conducted for each group of caregivers separately (HIV and ARD) and for the total group, using depressive symptoms and perception of physical health as dependent variables. In caregivers of people with HIV/AIDS (PWHIV), caregiver distress over care recipient symptoms, anxiety and education were related to depressive symptoms. Depressive symptoms, anger and functional status of the PWHIV were related to caregivers' perception of poorer physical health. In caregivers of people with ARD, there were no significant predictors for depressive symptoms or perception of physical health. In the total group of caregivers, lower income and more anger were related to depressive symptom score. When perception of physical health was the dependent variable, minority ethnicity and depressive mood were related to worse perception of physical health. These findings support the relationship of a lack of resources to health status. A community-based programme of resources and health care services for the caregiver-care receiver dyad is recommended.

Adult↗
PubMed2001

Rapid loss of microvascular integrin expression during focal brain ischemia reflects neuron injury.

The integrity of cerebral microvessels requires the close apposition of the endothelium to the astrocyte endfeet. Integrins alpha1beta1 and alpha6beta4 are cellular matrix receptors that may contribute to cerebral microvascular integrity. It has been hypothesized that focal ischemia alters integrin expression in a characteristic time-dependent manner consistent with neuron injury. The effects of middle cerebral artery occlusion (MCAO) and various periods of reperfusion on microvasclar integrin alpha1beta1 and alpha6beta4 expression were examined in the basal ganglia of 17 primates. Integrin subunits alpha1 and beta1 colocalized with the endothelial cell antigen CD31 in nonischemic microvessels and with glial fibrillary acidic protein on astrocyte fibers. Rapid, simultaneous, and significant disappearance of both integrin alpha1 and beta1 subunits and integrin alpha6beta4 occurred by 2 hours MCAO, which was greatest in the region of neuron injury (ischemic core, Ic), and progressively less in the peripheral (Ip) and nonischemic regions (N). Transcription of subunit beta1 mRNA on microvessels increased significantly in the Ic/Ip border and in multiple circular subregions within Ic. Microvascular integrin alpha1beta1 and integrin alpha6beta4 expression are rapidly and coordinately lost in Ic after MCAO. With loss of integrin alpha1beta1, multiple regions of microvascular beta1 mRNA up-regulation within Ic suggest that microvessel responses to focal ischemia are dynamic, and that multiple cores, not a single core, are generated. These changes imply that microvascular integrity is modified in a heterogeneous, but ordered pattern.

Animals↗
PubMed2001

Lansoprazole treatment of patients with chronic idiopathic laryngitis: a placebo-controlled trial.

OBJECTIVE: Previous uncontrolled studies suggested a therapeutic benefit for treating gastroesophageal reflux disease (GERD) among patients with laryngitis. The present study is the first randomized, placebo-controlled, double-blind study of gastric acid suppression among patients with laryngitis in the United States. METHODS: Patients diagnosed with idiopathic chronic laryngitis were randomized to receive either lansoprazole 30 mg p.o. b.i.d. or a matching placebo for 3 months. Before randomization, all patients underwent upper endoscopy, dual probe ambulatory 24-h esophageal pH-metry, and laryngoscopy, as well as completing a symptom questionnaire for GERD and laryngitis. The primary outcome of treatment was the complete resolution of laryngeal symptoms. RESULTS: A total of 22 patients with symptoms and signs of chronic laryngitis were enrolled, 20 of whom completed the study. At baseline, there were no significant differences between the two groups with regards to GERD symptoms, erosive esophagitis, proximal and distal esophageal pH-metry, or laryngeal signs and symptoms. In an intention-to-treat analysis, six patients in the lansoprazole group (50%) and only one patient (10%) in the placebo group achieved a complete symptomatic response, p = 0.04. Apart from receiving lansoprazole, there were no significant differences between responders and nonresponders in any of baseline esophageal or laryngeal signs and symptoms. CONCLUSIONS: Empirical treatment with lansoprazole is efficacious in relieving symptoms of laryngitis compared to placebo. Such treatment can be considered as a first-line option in managing patients with idiopathic chronic laryngitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Gastroesophageal reflux disease is a risk factor for laryngeal and pharyngeal cancer.

OBJECTIVE: Gastroesophageal reflux disease (GERD) is a proposed risk factor for developing laryngeal and pharyngeal cancers. No controlled study has examined this association. METHODS: A case-control-study was performed using the computerized hospitalization and outpatient databases of the US Department of Veterans Affairs. All patients, who were veterans, had been identified as being hospitalized with laryngeal or pharyngeal during 1991 to 1997. In addition, all persons diagnosed with laryngeal or pharyngeal cancer in 1999 in the outpatient files were identified. From the same patient populations, four nonmatched control subjects were randomly assigned for each case. The medical history for cases and controls was retrospectively searched for GERD diagnoses, tobacco use, and alcohol dependence. Multivariable logistic regression analyses were performed to assess the risk factors for laryngeal and pharyngeal cancers. RESULTS: A total of 8,228 hospitalized patients with laryngeal cancers and 1,912 with pharyngeal cancers were compared to 32,912 and 7,648 hospitalized controls, while 9,292 outpatients with laryngeal cancer and 2,769 outpatients with pharyngeal cancer were compared with 37,168 and 11,076 outpatient controls without cancer. Among hospitalized persons, the prevalence of GERD was higher among patients with laryngeal cancer (8.9 vs 4.0%, p < 0.0001) and pharyngeal cancer (6.2 vs 3.8%, p < 0.0001). In a multivariable logistic regression analysis that was controlled for age, gender, ethnicity, smoking, and alcohol, GERD was associated with an adjusted odds ratio (OR) of 2.40 for laryngeal cancer among hospitalized patients (95% CI 2.15-2.69, p < 0.0001) and an adjusted OR of 2.38 (95% CI 1.87-3.02, p < 0.0001) for pharyngeal cancer. For outpatients, GERD was associated with an adjusted OR = 2.31 (95% CI 2.10-2.53) for laryngeal cancer and adjusted OR = 1.92 (95% CI 1.72-2.15). CONCLUSIONS: Among US veterans, the risk for laryngeal or pharyngeal cancers is modestly increased in the presence of GERD. This effect seems to be independent of age, gender, smoking, and alcohol intake.

Aged↗
PubMed2001

Staphylococcus lugdunensis endocarditis.

A case of Staphylococcus lugdunensis endocarditis is presented with low back pain suggesting a secondary bone focus of infection. An umbilical skin lesion may have been an additional embolic phenomenon. The case highlights the aggressive nature of S lugdenensis endocarditis compared with other coagulase negative staphylococci and its association with native heart valves. In addition the importance of full identification of coagulase negative staphylococci isolated from patient samples in a case of suspected S lugdenensis infection is emphasised. Antibiotic treatment may be insufficient alone in the treatment of S lugdenensis endocarditis and early recourse to surgical intervention and valve replacement should therefore be considered.

Aged↗
PubMed2001

Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation.

The potential role of caveolin-1 in apoptosis remains controversial. Here, we investigate whether caveolin-1 expression is proapoptotic or antiapoptotic using a well-defined antisense approach. We show that NIH/3T3 cells harboring antisense caveolin-1 are resistant to staurosporine-induced apoptosis, as assessed using cell morphology, DNA content, caspase 3 activation, and focal adhesion kinase cleavage. Importantly, sensitivity to apoptosis is recovered when caveolin-1 levels are restored. Conversely, recombinant stable expression of caveolin-1 in T24 bladder carcinoma cells sensitizes these cells to caspase 3 activation. Consistent with the observations using NIH/3T3 cells, downregulation of caveolin-1 in T24 cells substantially diminishes caspase 3-like activity. Loss of sensitivity to apoptotic stimulation is recovered by inhibition of the phosphatidylinositol 3-kinase pathway using LY-294002, suggesting a possible mechanism for the sensitizing effect of caveolin-1. Thus our results suggest that caveolin-1 may act as a coupling or sensitizing factor in signaling apoptotic cell death in both fibroblastic (NIH/3T3) and epithelial (T24) cells.

3T3 Cells↗