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Biomedical subjects

L Lee

Publications and source records attributed to L Lee.

At least 145 records · Page 8Linked to original sources
PubMed1996

Noninvasive assessment of myocardial viability by positron emission tomography with 11C acetate in patients with old myocardial infarction. Usefulness of low-dose dobutamine infusion.

BACKGROUND: When patients with severely depressed left ventricular function are treated, it is crucial to know in advance how much functional recovery is expected from coronary revascularization. METHODS AND RESULTS: We compared the results of 11C acetate positron emission tomography (PET) with dobutamine infusion with changes in regional wall motion evaluated by left ventriculography in 28 patients with old Q-wave anterior myocardial infarctions. Dysfunctional but viable myocardium (group A, n = 13) was separated from nonviable myocardium (group B, n = 15) by echocardiographic assessments of regional wall motion before and after successful coronary revascularization. 11C acetate PET was performed to characterize normalized myocardial blood flow and oxidative metabolism (the clearance rate constant, k mono). While the baseline k monos of the infarct areas of the two groups were different with overlap, the responses to dobutamine infusion were directionally different. In addition, relative perfusion by 11C acetate PET could predict recovery of left ventricular function as well as or better than dobutamine 11C acetate kinetics. The extent of the increase in k monos of the infarct area with dobutamine infusion correlated well (P < .01) with the degree of the increase in the percentage of systolic segment shortening in the infarct area (left ventriculography) after coronary revascularization. CONCLUSIONS: 11C acetate PET with dobutamine infusion can predict not only the reversibility of dysfunctioning myocardium after coronary revascularization but also the extent of improvement of regional wall motion in patients with old Q-wave infarction.

Acetates↗
PubMed1996

The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator.

Molecular characterization of malignant melanoma of soft parts or soft tissue clear cell sarcoma which shares t(12;22) chromosome translocation revealed fusion of EWS with a transcriptional factor gene ATF-1. The EWS gene, which encodes an RNA binding protein, was also shown to be involved in Ewing sarcoma, related primitive neuroectodermal tumors and desmoplastic small round cell tumors. In order to understand the functional role of EWS-ATF-1 chimeric protein in human solid tumors, we have cloned the aberrant human ATF-1 (EWS-ATF-1) cDNA and studied its DNA binding, transcriptional activation properties and compared with normal ATF-1 protein. Our results demonstrate that EWS-ATF-1 binds weakly to DNA in vitro but functions as an efficient constitutive transcriptional activator unlike the normal ATF-1 which needs to be induced with cAMP. Deletion analysis revealed that EWS-fusion domain functions as a regulatory domain for the transcriptional activation properties of EWS-ATF-1 chimeric protein. Deletion of leucine zipper domain results in a loss of transcriptional activation of EWS-ATF-1 chimeric protein suggesting that protein-protein interaction play a role in the transcriptional activation properties of EWS-ATF-1. We demonstrate that EWS-fusion domain negatively regulates the DNA binding activity of EWS-ATF-1 chimeric protein. Therefore replacement of part of the amino-terminal kinase regulatory domain of ATF-1 protein with EWS regulatory domain results in an altered DNA binding, protein-protein interactions and transcriptional activation properties of EWS-ATF-1 causing deregulated gene expression which may be responsible for the genesis of t(12;22) chromosome translocation-bearing human solid tumors. Targeting the transcriptional cofactors (CBP, etc) by EWS-fusion proteins could be one of the mechanisms of activation of EWS-fusion proteins in human neoplasia.

Activating Transcription Factor 1↗
PubMed1996

Use of enzyme immunoassay for measurement of skeletal troponin-I utilizing isoform-specific monoclonal antibodies.

OBJECTIVE: To determine the serum level of fast skeletal troponin I (fsTnl) resulting from skeletal muscle damage, we have developed a sensitive two-site enzyme immunoassay to measure skeletal troponin I. DESIGN AND METHODS: Twelve monoclonal antibodies were raised against human fsTnl. Of these antibodies, 8 were fsTnl-specific and the remaining 4 reacted with both skeletal and cardiac troponin I (cTnl). Two monoclonals were utilized for a development of this fsTnl immunoassay. Standards were made with purified recombinant human fsTnl for the range of 0-25 micrograms/mL. RESULTS: Total assay variance (CV) ranged from 1.7% to 9.6%. The upper limit of the normal reference range was established as 0.2 microgram/L by determining fsTnl concentration in sera of 108 healthy donors without evidence of muscle damage. Purified human cTnl up to 500 micrograms/L and cTnl-positive clinical serum samples yielded negative results in the fsTnl assay. The serum levels of fsTnl were determined in trauma patients, patients with chronic degenerative muscle disease, and marathon runners. In the study populations, the serum levels of fsTnl were correlated with other biochemical markers that are traditionally used to monitor striated muscle damage. CONCLUSIONS: In the present preliminary studies, measuring the serum levels of fsTnl in patients with various forms of muscle damage is more accurate than using the classical non muscle-specific biochemical markers.

Animals↗
PubMed1996

A recombinant single-chain HLA-A2.1 molecule, with a cis active beta-2-microglobulin domain, is biologically active in peptide binding and antigen presentation.

We have constructed a recombinant single-chain human HLA-A2.1 molecule (from A*0201) with a covalently attached beta 2m. This molecule (MSC beta A2.1) can be detected on the surface of transfected beta 2m- human cells by conformational antibodies W6/32 and BB7.2 and by anti-human beta 2m mAb BM-63. The covalent beta 2m, now a domain of the MSC beta A2.1 molecule, does not rescue endogenous Class I surface expression. Instead, it works in cis to achieve correct folding of the single-chain molecule. Immunoprecipitation shows that MSC beta A2.1 is a 60-kDa molecule with no dissociable beta 2m. The half-life of the MSC beta A2.1 molecule on transfected cell surfaces was as long as that of two-chain HLA-A2.1 molecules. The MSC beta A2.1 molecule was active in presentation of HTLV-I Tax 11-19 peptide and an endogenous peptide to specific CTL. MSC beta A2.1 molecules and wild-type HLA-A2.1 molecules on live cells can bind the HBV core peptide 18-27 with comparable affinities. These results show that MSC beta A2.1 molecules retain the functional ability to present both pulsed and endogenous antigens to the appropriate T cells, and thus may be useful components of antiviral vaccines.

Antigen Presentation↗
PubMed1996

Objective measures of voice production in patients complaining of laryngeal fatigue.

The purpose of this retrospective study is to describe results of acoustic, aerodynamic, and videostroboscopic measures in patients complaining of laryngeal fatigue. Data were collected from 88 patients whose primary complaint was chronic laryngeal fatigue in the absence of visible laryngeal pathologies. The results revealed an abnormally high airflow rate and decreased maximum phonation time. An anterior glottal chink, anterior and posterior glottal chinks, or spindle-shaped glottal closure were found in 61% of the subjects.

Adult↗
PubMed1996

Radiographic features of the mandible in neurofibromatosis: a report of 10 cases and review of the literature.

The radiographs of 10 cases with a diagnosis of neurofibromatosis involving the mandible were evaluated by two reviewers to document common radiographic characteristics. The most common findings included increase in bone density, enlarged mandibular foramen, lateral bowing of the mandibular ramus, increase in dimensions of the coronoid notch, and a decrease in the mandibular angle. The six cases for which computed tomography scans were available, enlargement of the mandibular foramen and concavity of the medial surface of the ramus were seen. In five of these cases, there was no associated tumor mass adjacent to the concavity; instead a soft tissue mass with density of fat was found. This supports the theory that neurofibromatosis may have manifestations of a mesodermal dysplasia.

Adolescent↗
PubMed1996

High-dose chemotherapy supported by peripheral blood progenitor cells in poor prognosis metastatic breast cancer--phase I/II study. Edinburgh Breast Group.

Current treatments for metastatic breast cancer are not associated with significant survival benefits despite response rates of over 50%. High-dose therapy with autologous bone marrow transplantation (ABMT) has been investigated, particularly in North America, and prolonged survival in up to 25% of women has been reported, but with a significant treatment-related mortality. However, in patients with haematological malignancies undergoing autologous transplantation, haematopoietic reconstruction is significantly quicker and mortality lower than with ABMT, when peripheral blood progenitor cells (PBPCs) are used. In 32 women with metastatic breast cancer, we investigated the feasibility of PBPC mobilisation with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) after 12 weeks' infusional induction chemotherapy and the subsequent efficacy of the haematopoietic reconstitution after conditioning with melphalan and either etoposide or thiotepa. PBPC mobilisation was successful in 28/32 (88%) patients, and there was a rapid post-transplantation haematopoietic recovery: median time to neutrophils > 0.5 x 10(9) l-1 was 14 days and to platelets > 20 x 10(9) l-1 was 10 days. There was no procedure-related mortality, and the major morbidity was mucositis (WHO grade 3-4) in 18/32 patients (56%). In a patient group of which the majority had very poor prognostic features, the median survival from start of induction chemotherapy was 15 months. Thus, PBPC mobilisation and support of high-dose chemotherapy is feasible after infusional induction chemotherapy for patients with metastatic breast cancer, although the optimum drug combination has not yet been determined.

Adult↗
PubMed1996

Does the NAIP classification predict length of stay in rehabilitation, geriatrics and palliative care?

The Australian National Non-Acute Inpatient Project (NAIP) reported its findings on casemix in rehabilitation and slow stream geriatric medicine in October 1992. It proposed a per diem NAIP classification of 19 classes using six major clinical groups and the resource utilisation groups version three activities of daily living index (RUG III ADL index). Weightings were determined based on time spent by clinical staff in treating these patients. A quality management study was undertaken in the rehabilitation, geriatrics, and palliative care wards of the Illawarra Area Health Service for three months in 1993, analysing length of stay and cost against the predictive weights of the NAIP classification. The study concluded that this classification was an acceptable predictor of per diem costs of care in these wards of the Illawarra but was not a good predictor of length of stay.

Activities of Daily Living↗
PubMed1996

Clinicians as managers: organisational change at the Illawarra Regional Hospital.

In 1990 a decision was made to merge the Port Kembla (160 beds) and Wollongong (290 beds) Hospitals into the Illawarra Regional Hospital and to change the traditional functional management structure to one of product line institute management, with medical officers as part-time clinical directors. This transformation in health care management had been occurring in other sections of the Illawarra Area Health Service, with medical directors of programs and with allied health and nursing heads of departments throughout the system. A survey was conducted among 22 clinician managers for their impressions of the 'new' management organisation. The respondents felt that the change had been a positive one and that it had particularly improved communication and accountability among clinicians.

Communication↗
PubMed1996

Pictorial superiority during verbal learning tasks in moderate to severe closed head injury: additional evidence.

Evidence for picture superiority in verbal learning following moderate to severe closed head injury (CHI) was found in a study involving 31 participants with CHI and 31 noninjured participants. A multitrial free-recall paradigm was implemented incorporating three modalities: Auditory, visual, and simultaneous auditory plus visual. Participants with moderate to severe CHI learned fewer words and at a slower rate than the noninjured participants. The visual presentation of objects (with or without the simultaneous auditory presentation of names) resulted in better learning than the auditory presentation alone.

Adolescent↗
PubMed1996

Peroxynitrite modification of glutathione reductase: modeling studies and kinetic evidence suggest the modification of tyrosines at the glutathione disulfide binding site.

The catalytic properties of glutathione reductase for its substrate, glutathione disulfide, were altered following a 60 s exposure to a 100-fold molar excess of peroxynitrite; the K(M) value was increased by approximately 2.5-fold and the V(max) value was decreased by approximately 1.7-fold. The kinetic alterations are thought to result from nitrotyrosine formation as the intrinsic Tyr fluorescence is diminished. The UV-visible spectrum of glutathione reductase exhibited absorbance at approximately 423 nm, characteristic of nitrotyrosine. In addition, the presence of nitrotyrosine has been detected by Western immunoblots with an anti-nitrotyrosine antibody. The peroxynitrite-induced inactivation is not observed in the presence of excess glutathione disulfide. However, excess NADPH offered no protection against peroxynitrite-induced inactivation. These observations suggest that the modification of approximately 1.8 Tyr per subunit, at or near the glutathione disulfide binding domain, probably results in the observed catalytic alterations. To test this hypothesis, the two tyrosines closest to the glutathione disulfide binding domain (Tyr114 and Tyr106), as indicated by the X-ray crystallographic data [Karplus and Schulz (1989) J. Biol. Chem., 210, 163-180], were each converted to nitrotyrosines by molecular modeling and the structure energy was minimized. These theoretical calculations indicate that the bond lengths between Tyr114-O and the Gly-N and Cys II-N of glutathione disulfide bound to glutathione reductase (Karplus and Schulz, 1989) increased by 3.0 and 4.3 A, respectively, upon nitration. In the case of Tyr106 the 0-Cys II-N distance also increases by approximately 1.6 A. The loss of these hydrogen bonding contacts is likely to result in the observed catalytic alterations upon reaction with peroxynitrite.

Animals↗
PubMed1996

Novel DNA binding specificities of a putative herpesvirus bZIP oncoprotein.

Marek's disease virus is a highly oncogenic herpesvirus that can cause T lymphomas and peripheral nerve demyelination in chickens. meq, a candidate oncogene of Marek's disease virus, encodes a basic leucine zipper (bZIP) transcription factor which contains a large proline-rich domain in its C terminus. On the basis of its bZIP structural homology, meq is perhaps the only member of the jun-fos gene family completely viral in origin. We previously showed that Meq's C-terminal domain has potent transactivation activity and that its bZIP domain can dimerize with itself and with c-Jun also. In an effort to identify viral and cellular targets of Meq, we have determined the optimal binding sites for Meq-Jun heterodimers and Meq-Meq homodimers. By a PCR-based approach using cyclic amplification of selected targets, Meq-Jun heterodimers were found to optimally bind tetradecanoylphorbol acetate response element (TRE) and cyclic AMP response element (CRE) consensus sequences. This result was consistent with the results of our previous functional analysis implicating Meq-Jun heterodimers in the transactivation of the Meq promoter through a TRE- or CRE-like sequence. Interestingly, Meq-Meq homodimers were found to bind two distinct motif elements. The first [GAGTGATG AC(G)TCATC] has a consensus which includes a TRE or CRE core flanked by additional nucleotides critical for tight binding. Methylation interference and mutational analyses confirmed the importance of the flanking residues. The sequences of a subset of TRE and CRE sites selected by Meq-Meq are closely related to the binding motif of Maf, another bZIP oncoprotein. The second putative Meq binding site (RACACACAY) bears a completely different consensus not shared by other bZIP proteins. Binding to this consensus sequence also requires secondary structure characteristics associated with DNA bending. CACA motifs are known to promote DNA curvature and function in a number of special biological processes. Our results lend further weight to the increasing importance of DNA bending in transcriptional regulation and provide a baseline for the identification of Meq-responsive targets.

Amino Acid Sequence↗
PubMed1996

A radiological analysis of chronic sclerosing osteomyelitis of the mandible.

OBJECTIVE: To determine the frequency of specific characteristics of chronic sclerosing osteomyelitis (CSO) of the mandible in plain films compared with CT scans. METHODS: After calibration, three observers studied 13 cases of plain films and 11 sets of separated and masked CT scans from the same cases. Controls consisted of cases of fibro-osseous disease with a similar appearance. Comparison with the results of nuclear scans of eight of the cases was made. RESULTS: Periosteal new bone formation, sclerosis and bone enlargement were the most common characteristics. When the CT scans were analysed, detection of sequestra improved from 45 to 91%. There was greater agreement between observers when analysing CT scans compared with plain films. The results of the gallium scans supported the diagnosis in only two of the eight cases. CONCLUSION: In this study, the CT scans were the most reliable imaging method for revealing characteristics such as sequestra which are useful for the diagnosis of CSO.

Chronic Disease↗
PubMed1996

Diagnostic risk adjustment for Medicaid: the disability payment system.

This article describes a system of diagnostic categories that Medicaid programs can use for adjusting capitation payments to health plans that enroll people with disability. Medicaid claims from Colorado, Michigan, Missouri, New York, and Ohio are analyzed to demonstrate that the greater predictability of costs among people with disabilities makes risk adjustment more feasible than for a general population and more critical to creating health systems for people with disability. The application of our diagnostic categories to State claims data is described, including estimated effects on subsequent-year costs of various diagnoses. The challenges of implementing adjustment by diagnosis are explored.

Adolescent↗
PubMed1996

Perception and use of insect repellent among soldiers in the Singapore Armed Forces.

The Singapore Armed Forces currently uses the 75% DEET formulation insect repellent. To study the perception, use, and acceptability of this insect repellent, a survey was carried out on servicemen who had participated in field exercises. Although over 80% of the servicemen knew the proper use of the insect repellent and brought along the army-issued repellent in the field, less than half used this repellent frequently while on exercise. Eighty-three percent felt that the army repellent was only effective sometimes and that it lasted for 4 hours or less. Skin irritation was a common side effect when using the repellent. About 70.4% had used commercial insect repellents and perceived them to be more long lasting and with fewer side effects. The results from our study indicate that the army-issued insect repellent currently used is not totally acceptable to our servicemen. Thus, there is a pressing need to develop or acquire a better insect repellent that is more or just as effective, has fewer side effects in terms of smell and skin irritation, and with an improved mode of delivery, such as aerosol or pump spray.

Adolescent↗
PubMed1996

Randomized trial of periportal peritoneal bupivacaine for pain relief after laparoscopic cholecystectomy.

The aim of this study was to determine whether injection of a long-acting local anaesthetic, in relation to the port sites at the level of the parietal peritoneum, would reduce postoperative pain following laparoscopic cholecystectomy. Patients were entered into a randomized, prospective, double-blind study comparing the effects of a standard technique, in which bupivacaine (total of 20 ml, 0.5 per cent) was injected into the subcutaneous periportal tissue around the four port sites, and a technique in which bupivacaine (total of 20 ml, 0.25 per cent) was injected into the subcutaneous periportal tissue as above with the addition of periportal parietal peritoneal injection of bupivacaine (total of 20 ml, 0.25 per cent). Two scores for pain, with the patient at rest, and on movement, were assessed 6 and 18 h after surgery using a visual analogue pain scale. Median pain score was significantly higher in patients who received standard technique (n = 40) than in those given peritoneal injection (n = 40) at both 6 (rest = 3.0 versus 1.0, movement = 5.0 versus 2.9) and 18 h (rest = 1.9 versus 0, movement = 3.2 versus 1.2). Both opiate and oral analgesic requirements were reduced in patients administered peritoneal injection, although this was not statistically significant. The addition of periportal injection of bupivacaine at the level of the parietal peritoneum, performed under direct vision, reduces pain after laparoscopic cholecystectomy.

Adult↗
PubMed1995

Identification of an essential cysteinyl residue in the ArsC arsenate reductase of plasmid R773.

The ArsC protein encoded by the arsenical resistance operon of plasmid R773 catalyzes the reduction of arsenate to arsenite in Escherichia coli. The reductase has been shown to require glutathione and glutaredoxin, suggesting that thiol chemistry might be involved in the reaction mechanism. The ArsC arsenate reductase has two cysteinyl residues, Cys12 and Cys106. By a combination of random and site-specific mutagenesis, Cys12 was altered to four other amino acid residues. Cells expressing any of those arsC genes were sensitive to arsenate. The ArsCC12S protein was purified and found to be catalytically inactive. Cys106 was altered separately to seryl, glycyl, and valyl residues. Cells expressing arsCC106S, arsCC106G, and arsCC106V genes retained arsenate resistance, and the purified C106S and C106G proteins had reductase activity. Both wild-type ArsC and C106S proteins were inactivated by iodoacetate. In the native enzyme only Cys12 was alkylate by iodoacetate; Cys106 was alkylated only if the enzyme was first denatured. In the presence of the substrate, arsenate, or competitive inhibitors, phosphate or sulfate, the rate of alkylation was reduced. Reductase activity was inhibited by N-ethylmaleimide and could be protected by arsenate. These results suggest Cys12 is an active-site residue essential for catalysis by the arsenate reductase.

Adenosine Triphosphatases↗