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Biomedical subjects

L Lee

Publications and source records attributed to L Lee.

At least 109 records · Page 6Linked to original sources
PubMed1999

Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis.

The records of 239 immunosuppressed patients receiving amphotericin B for suspected or proven aspergillosis were reviewed to determine rates of nephrotoxicity, dialysis, and fatality. The mean and median durations of treatment were 20.4 and 15.0 days, respectively. The creatinine level doubled in 53% of patients and exceeded 2.5 mg/dL in 29%; 14.5% underwent dialysis; and 60% died. A multivariate Cox proportional hazards analysis showed that patients whose creatinine level exceeded 2.5 mg/dL (hazard ratio [HR], 42.02; P<.001), allogeneic bone marrow transplantation (BMT) patients (HR, 6.34; P<. 001), and autologous BMT patients (HR, 5.06; P=.024) were at greatest risk for requiring hemodialysis. Use of hemodialysis (HR, 3. 089; P<.001), duration of amphotericin B use (HR, 1.03 per day; P=. 015), and use of nephrotoxic agents (HR, 1.96; P=.017) were associated with greater risk of death, whereas patients undergoing solid organ transplantation were at lowest risk (HR, 0.46; P=.002). These data indicate that elevated creatinine levels during amphotericin B treatment are associated with a substantial risk for hemodialysis and a higher mortality rate, but the risks vary in different patient groups.

Adolescent↗
PubMed1999

Retinoic acid induces Gpx2 gene expression in MCF-7 human breast cancer cells.

We showed previously that the selenium-dependent glutathione peroxidase, GPX-GI, encoded by the Gpx2 gene, is highly expressed in the epithelium of the gastrointestinal (GI) tract and sporadically in breast tissue. To investigate whether Gpx2 gene expression is epithelium specific, we used in situ hybridization to show that Gpx2 mRNA is highly expressed in the crypt epithelium of human intestine. We also used Northern analysis to study human breast cells and found Gpx2 mRNA in human mammary epithelial cell lines as well as freshly isolated normal breast epithelial cells. Because we identified three putative retinoic acid response elements (RARE) in the Gpx2 gene, we examined the regulation of the Gpx2 gene expression by all-trans retinoic acid (RA) in RA-sensitive MCF-7 cells and RA-resistant HT29 cells. Without RA, MCF-7 cells had very low levels of Gpx2 mRNA and a low level of glutathione peroxidase (GPX) activity (17 mU/mg protein), whereas HT29 cells had a high level of Gpx2 mRNA and GPX activity (200 mU/mg protein). RA treatment increased Gpx2 mRNA level 3- to 11-fold and resulted in a fourfold increase of GPX activity (80 mU/mg protein) in MCF-7 cells. Neither Gpx2 mRNA level nor GPX activity was increased in HT29 cells. These results show that the Gpx2 gene is expressed in both breast and intestinal epithelium cells, and suggest that its expression can be highly regulated by retinoic acid, a known differentiation agent.

Antineoplastic Agents↗
PubMed1999

Effects of environmental tobacco smoke on objective measures of voice production.

OBJECTIVE: The effects of passive smoking on the voice and laryngeal structures of 20 female passive smokers and 20 age-matched nonsmokers were examined. METHODS: The voice evaluation consisted of acoustic, aerodynamic, and videostroboscopic analyses. RESULTS: Three passive smokers displayed mild edema or erythema. Passive smokers had higher mean flow rates and shorter mean maximum phonation times during sustained vowels at comfortable, low-, and high-pitch levels. However, means were only outside normal limits and significantly different from nonsmokers at high pitch. Variables such as the number of years and hours per day subjects were exposed to environmental tobacco smoke were considered. CONCLUSION: The majority of the variables indicated that vocal fold structure and function were not adversely altered by exposure to passive smoke. Differences between these results and clinical observations are highlighted.

Adult↗
PubMed1999

Using a facsimile (fax) as an aid for communication in maxillectomy planning between the prosthodontist and surgeon.

Preoperative communication between the prosthodontist and surgeon is required for properly planning the surgical prostheses that are often indicated for maxillectomy patients. When geography or long distances preclude face-to-face consultation, electronic means of correspondence are necessary to minimize delays in the fabrication of surgical prostheses. This article presents a time-efficient procedure for facilitation of the necessary communication between the prosthodontist and surgeon before maxillectomy surgical procedures.

Communication↗
PubMed1999

Retrospective analysis of the dosage of amphotericin B lipid complex for the treatment of invasive fungal infections.

STUDY OBJECTIVE: To understand the relationship between dosage and therapeutic response of amphotericin B lipid complex (ABLC) by analyzing underlying diseases, types of infections, and therapeutic outcomes with different dosages as second-line antifungal therapy. DESIGN: Retrospective analysis of low-dose (initial dose < or = 3 mg/kg) ABLC from three open-label, clinical, second-line treatment studies. SETTING: Centers in the United States (204), Canada (3), Australia (1), Mexico (1), and The Netherlands (1). PATIENTS: Five hundred fifty-one patients (5 enrolled twice) with invasive fungal infections, of whom 289 failed and 267 were intolerant to conventional antifungal therapy. INTERVENTIONS: Patients were to receive the recommended dosage of ABLC 5 mg/kg/day, with dosage reduction for markedly increased serum creatinine. The duration of treatment was 4 weeks; therapy could be extended if the investigator considered additional treatment necessary. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients (13%) received ABLC 3 mg/kg/day (low dosage) instead of the protocol-recommended 5 mg/kg/day Response was 65% and 56%, respectively. Logistic regression analysis revealed that the following patients are most likely to start therapy at the lower dosage: those with candidiasis and other yeast infections, patients with nephrotoxicity due to prior amphotericin B, and those with underlying conditions other than hematologic malignancy. CONCLUSION: These results suggest that ABLC 3 mg/kg/day may be effective in treating patients with candidiasis who do not have hematologic malignancy.

Adolescent↗
PubMed1999

Access to multiple sclerosis diagnosis for Canadian neurologists.

BACKGROUND: Access to multiple sclerosis (MS) diagnosis in Canada has never been assessed. This study was designed to examine the pattern of MS diagnosis in Canada, including neurologists' diagnostic approach and waiting times for investigations. METHODS: A mail survey was forwarded to every registered neurologist in Canada (n = 479) in late 1996. Questions included their diagnostic approach to MS including perceived waiting times for various investigations including MRI. Actual MRI waiting periods were separately obtained from booking clerks or neuroradiologists from every MRI unit in Canada. RESULTS: 153 responses were received. Neurological assessment is obtained, on average, 1 month after referral. MRI is routinely ordered by 92% of neurologists for suspected MS followed by evoked potentials (EP) (36%) and lumbar puncture (LP) (17%). The perceived waiting period for EP and LP is less than one month but 3 months for MRI. This is very similar to the actual waiting periods obtained from the MRI units surveyed (mean of 101 days). There is a trend for longer waiting periods as one moved east to west (Eastern provinces--mean of 62 days, Ontario--95 days, Quebec--102 days and 122 days in the Western provinces). Private MRI units have appeared in the Western provinces and have the shortest waiting periods (2 weeks maximum). The current MRI/million population ratio in Canada is 1.8, far below the ratios of other developed nations. CONCLUSIONS: Canadian neurologists prefer MRI of the brain to confirm an MS diagnosis and desire greater access to it. Access to neurological assessment, EP and LP is probably adequate but the average wait for MRI of 3 months is relatively long. The perceived average waiting period for MRI is similar to the actual waiting times of 3 months, with the Western provinces of Canada having the longest waits. Canada continues to have one of the lowest MRI/population ratios in the developed world.

Adult↗
PubMed1998

Fli-1b is generated by usage of differential splicing and alternative promoter.

The proto-oncogene Fli-1, a member of Ets family is rearranged or activated through proviral integration in erythroleukemias, induced by Friends' Murine Leukemia Virus. The DNA binding domain (ETS domain) of Fli-1 is fused to the RNA binding domain of EWS by t(11q24:22q12) chromosomal translocation in Ewing's sarcoma and primitive neuroectodermal tumors. Screening of human cDNA libraries has identified two different 5'-termini and alternatively spliced forms of the human Fli-1 gene (Fli-1b), suggesting the possible existence of two independent promoters. The genomic sequence adjacent to the alternate exon of human Fli-1b gene shows functional promoter activity when cloned in promoter-less CAT expression vector and transfected into QT-6 cells. The transcription initiation (CAP) site and minimum promoter region necessary for function were localized. The 5'-flanking regions of human Fli-1b and mouse Fli-1 show 80% homology suggesting conserved promoter regulatory elements. The Fli-1b 5'-flanking sequence lacks canonical TATA or CCAAT boxes but contains a partially conserved TATA-like sequence at position 242. Several transcription factor binding sequences like ATF/CREB, E2A-PBX1, EBP, PEA-3, ETS-2, Sp-1, c-Myc, TBP, GATA-1 and Oct-3 were conserved in the promoter sequence. Functional promoter assays revealed that Fli-1b promoter shows very strong transcriptional activation compared to Fli-1 promoter. We also showed that variant Fli-1b has transcriptional activation properties similar to those of Fli-1. Fli-1b and Fli-1 show differential expression in various hematopoietic cell lines. This differential expression and promoter activities of Fli-1 and Fli-1b suggests that several mechanisms are involved in Fli-1 gene regulation which are mediated by many transcription factors.

Alternative Splicing↗
PubMed1998

A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy.

We have used adenoviral-mediated gene transfer of a constitutively active (V12rac1) and dominant negative (N17rac1) isoform of rac1 to assess the role of this small GTPase in cardiac myocyte hypertrophy. Expression of V12rac1 in neonatal cardiac myocytes results in sarcomeric reorganization and an increase in cell size that is indistinguishable from ligand-stimulated hypertrophy. In addition, V12rac1 expression leads to an increase in atrial natriuretic peptide secretion. In contrast, expression of N17rac1, but not a truncated form of Raf-1, attenuated the morphological hypertrophy associated with phenylephrine stimulation. Consistent with the observed effects on morphology, expression of V12rac1 resulted in an increase in new protein synthesis, while N17rac1 expression inhibited phenylephrine-induced leucine incorporation. These results suggest rac1 is an essential element of the signaling pathway leading to cardiac myocyte hypertrophy.

Adenoviridae↗
PubMed1998

Targeted disruption of the acid alpha-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II.

We have used gene targeting to create a mouse model of glycogen storage disease type II, a disease in which distinct clinical phenotypes present at different ages. As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter. By 3.5 weeks of age, these mice have markedly reduced mobility and strength. They grow normally, however, reach adulthood, remain fertile, and, as in the human adult disease, older mice accumulate glycogen in the diaphragm. By 8-9 months of age animals develop obvious muscle wasting and a weak, waddling gait. This model, therefore, recapitulates critical features of both the infantile and the adult forms of the disease at a pace suitable for the evaluation of enzyme or gene replacement. In contrast, in a second model, mutant mice with deletion of exon 6 (Delta6/Delta6), like the recently published acid alpha-glucosidase knockout with disruption of exon 13 (Bijvoet, A. G., van de Kamp, E. H., Kroos, M., Ding, J. H., Yang, B. Z., Visser, P., Bakker, C. E., Verbeet, M. P., Oostra, B. A., Reuser, A. J. J., and van der Ploeg, A. T. (1998) Hum. Mol. Genet. 7, 53-62), have unimpaired strength and mobility (up to 6.5 months of age) despite indistinguishable biochemical and pathological changes. The genetic background of the mouse strains appears to contribute to the differences among the three models.

Alleles↗
PubMed1998

Evoked potential abnormality scores are a useful measure of disease burden in relapsing-remitting multiple sclerosis.

Fifty patients with relapsing-remitting multiple sclerosis were examined and studied with serial evoked potential and magnetic resonance imaging (MRI) measurements as part of a clinical trial. An evoked potential abnormality score (EPAS) for each testing session was calculated consisting of the total number of abnormal tests. The EPAS correlated well with Expanded Disability Status Scale (EDSS) at years 0, 1, and 2, with Spearman correlation coefficient scores of 0.68, 0.66, and 0.72, respectively. MRI lesion volume correlations ranged from 0.27 to 0.34 for the EDSS. EPAS are a potentially useful surrogate measure of clinical disability in relapsing-remitting multiple sclerosis.

Disability Evaluation↗
PubMed1998

Bcl-2 regulates nonapoptotic signal transduction: inhibition of c-Jun N-terminal kinase (JNK) activation by IL-1 beta and hydrogen peroxide.

We have explored the role of bcl-2 as a potential modulator of intracellular signal transduction. Stable expression of bcl-2 in fibroblasts inhibited the activation of the c-jun amino terminal kinase (JNK) by the nonapoptotic cytokine interleukin-1 beta (IL-1 beta). This effect appeared to be selective for JNK activation as bcl-2 did not appear to alter the other aspects of IL-1 beta signal transduction. Similarly, bcl-2 did not inhibit all all activators of JNK as it had no effect on JNK activation by the protein synthesis inhibitor anisomycin. Treatment with nonlethal concentrations of H2O2, which resulted in the simultaneous stimulation of mitogen-activated protein kinase (MAPK) and JNK, demonstrated that bcl-2 appeared to alter the balance of activation of these two kinase cascades. The pathway by which bcl-2 inhibits JNK activation is demonstrated to be independent of the rac1 GTPase. In contrast, the reduction in JNK activity in cells expressing bcl-2 can be restored by costimulation with a calcium ionophore. This suggests that bcl-2 can regulate certain nonapoptotic signaling pathways. Such results therefore expand the functions of bcl-2 and may have important implication in the understanding of the role of this protein in a variety of human diseases.

Activating Transcription Factor 2↗
PubMed1998

Nucleotide sequence of a resistance breaking mutant of southern bean mosaic virus.

SBMV-S is a resistance-breaking mutant of an Arkansas isolate of the bean strain of southern bean mosaic virus (SBMV-BARK) that is able to move systemically in Phaseolus vulgaris cvs. Pinto and Great Northern, whereas the wild-type SBMV-BARK causes local necrotic lesions and is restricted to the inoculated leaves of these hosts. Sequence analysis of the 4136 nucleotide genomes of SBMV-BARK and SBMV-S revealed seven nucleotide differences, but only four deduced amino acid changes. A single amino acid change occurred in the C-terminal region of the putative RNA-dependent RNA polymerase and three differences were identified in the N-terminal portion of the virus coat protein. SBMV-BARK and SBMV-S were compared with other sobemoviruses and were found to contain a high level of nucleotide sequence identity (91.3%) to SBMV-B. Unlike SBMV-B however, SBMV-BARK and SBMV-S contained four putative overlapping open reading frames, making them more similar in genome organization to the cowpea strain, SBMV-C. The possibility exists that mutations or even errors, that resulted in mis-identification of open reading frames, occurred in previously published information on nucleotide sequence and genomic organization for SBMV-B.

Amino Acid Sequence↗
PubMed1998

Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases.

The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were evaluated in 556 cases of invasive fungal infection treated through an open-label, single-patient, emergency-use study of patients who were refractory to or intolerant of conventional antifungal therapy. All 556 treatment episodes were evaluable for safety. During the course of ABLC therapy, serum creatinine levels significantly decreased from baseline (P < .02). Among 162 patients with serum creatinine values > or = 2.5 mg/dL at the start of ABLC therapy (baseline), the mean serum creatinine value decreased significantly from the first week through the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases evaluable for therapeutic response, there was a complete or partial response to ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of 42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and 82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern of invasive fungal infection, underlying condition, and reason for enrollment (intolerance versus progressive infection). These findings support the use of ABLC in the treatment of invasive fungal infections in patients who are intolerant of or refractory to conventional antifungal therapy.

Adult↗
PubMed1998

Can a clinical score aid in early diagnosis and treatment of various stroke syndromes?

BACKGROUND: Accurate and timely diagnosis of hemorrhagic and nonhemorrhagic strokes helps in patient management. Neuroimaging studies are useful in diagnosis and distinction of hemorrhagic (HS) and nonhemorrhagic (NHS) strokes. The use of clinical variables, such as Siriraj stroke scores (SSS), has shown good sensitivity, specificity and predictive values (distinguishing stroke types). The aim of our study was to evaluate the use of SSS in a U.S. population and assess whether it could aid to expedite treatment decisions. METHODS: Levels of consciousness, vomiting, headache and atheroma markers used in SSS were applied to patients who met the criteria for stroke. RESULTS: Of the 302 patients identified, the SSS classified 254 with sensitivity of 36% (HS) and 90% (NHS) and positive predictive values of 77% and 61%, respectively. CONCLUSION: Our results suggest that SSS is not reliable in distinguishing stroke types (in a US population). Definite neuroimaging studies are needed prior to thrombolytic therapy.

Aged↗
PubMed1998

Evaluation of dyspnea during physical and speech activities in patients with pulmonary diseases.

STUDY OBJECTIVES: Dyspnea is most commonly assessed by questioning patients about their subjective perception of shortness of breath during physical exertion. Although speech production is altered by pulmonary disease, it has not been included in current dyspnea assessment tools. A questionnaire was developed to address reports of dyspnea during (1) physical activity, (2) speech activity, and (3) simultaneous speech and physical activity. DESIGN: An equal number of self- and experimenter-administered 30-item questionnaires was given to 203 patients with restrictive and obstructive pulmonary diseases. Their responses were analyzed statistically. RESULTS: The questionnaire had high internal consistency for individual items within each of the three sections. The sections were highly correlated but provided separate and distinct information. Factors extracted from each section were related to severity of dyspnea. Pairwise t tests demonstrated highly significant differences in subject responses to the three sections. The least dyspnea was experienced during speech activities, more during physical activities, and the most when speech and physical activities were combined. CONCLUSIONS: The questionnaire proved to be a quickly administered tool for providing information about the effect of dyspnea on activities of daily living. Because of the emphasis on dyspnea during speech production, it may be particularly useful for assessing patients who rely extensively on speaking ability for their livelihood.

Activities of Daily Living↗