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Biomedical subjects

R Lee

Publications and source records attributed to R Lee.

At least 37 records · Page 2Linked to original sources
PubMed2003

Zinc accumulation in N-methyl-N-nitrosourea-induced rat mammary tumors is accompanied by an altered expression of ZnT-1 and metallothionein.

Zinc is essential for cell proliferation. Several human studies have shown that in breast cancer tissues, zinc concentration expressed on a per tissue weight basis is higher than that in normal breast tissues. However, the mechanisms involved are unknown. N-methyl-N-nitrosourea (MNU)-induced rat mammary tumorigenesis is one of the most widely used rodent mammary tumorigenesis models for studying human breast cancer due to their similarities in hormone dependency, pathogenesis, histological classification, and immunocytochemical markers. This study was to establish if there was an accumulation of zinc in MNU-induced rat mammary tumors and, if there was, to explore the possible mechanisms involved. Sprague-Dawley rats were sham-treated or MNU-treated (50 mg/kg; n = 12) for 100 days. In MNU-induced mammary tumors (mammary tumors), zinc concentration expressed on a per dry weight basis was 12 times of that in normal mammary glands. Moreover, the mRNA level of ZnT-1 (a transporter involved in zinc efflux) in mammary tumors was reduced by 55% as compared with that in normal mammary glands. The mRNA level of Nramp2 (a divalent cation importer) and ZnT-4 (another transporter involved in zinc efflux) was unaffected by MNU-induced mammary tumorigenesis. The mRNA and protein levels of metallothionein (a putative zinc storage protein) in mammary tumors were 1.3 and 3.5 times of that in normal mammary glands, respectively. Collectively, our observations showed that zinc is accumulated in MNU-induced rat mammary tumors and this accumulation is accompanied by an altered expression of ZnT-1 and metallothionein, suggesting that zinc homeostasis might be altered in MNU-induced rat mammary tumorigenesis. Because zinc is essential to cell proliferation and cell proliferation is increased in mammary tumors, zinc accumulation is likely a part of an integrated effort to ensure sufficient zinc supply to sustain tumor growth.

Animals↗
PubMed2003

Mitral valve repair in the elderly: operative risk for patients over 70 years of age is acceptable.

AIM: Mitral valve repair for degenerative disease is widely accepted. Because of low risk and excellent late outcomes, surgical intervention is recommended increasingly early when repair appears possible. The place of repair vis a vis continued medical therapy in the elderly, however, is less well defined as there are scant data on their surgical risk. We reviewed our recent results with mitral valvuloplasty for degenerative disease with attention to the influence of age. METHODS: Thirty-day results of mitral valvuloplasty for degenerative disease between January 1996 and April 2000 were examined retrospectively. Patients with ischemic etiology were excluded. Results among those over age 70 years were compared with younger patients. RESULTS: Of 140 patients (78 men and 62 women) aged 27 to 91 (mean 62+/-13) years (44 gs;70 years of age), 61 underwent isolated mitral valvuloplasty, 71 mitral valvuloplasty and coronary artery bypass, and 8 mitral valvuloplasty with other procedures. By multivariate analysis preoperative cardiogenic shock (0.001), but not age, was as a risk factor for death. Among patients stratified by age gs; or <70, there were differences in atrial fibrillation (47.7% vs 29.2%, p=0.03), prolonged ventilation (31.8% vs 15.6%, p=0.03) and hospital stay (median 9.5, range 5-285 vs median 6.5, range 2-36, p=0.001), but not 30-day readmission (15.9% vs 22.9%) or death (5.2% vs 9.1%, p=0.49). CONCLUSION: Operative results for mitral valvuloplasty in the elderly are acceptable. Surgery should not be withheld on the basis of age alone.

Adult↗
PubMed2002

Heating of thin foils with a relativistic-intensity short-pulse laser.

K-shell x-ray spectroscopy of sub-100 nm Al foils irradiated by high contrast, spatially uniform, 150 fs, Ilambda (2)=2 x 10(18) W microm(2)/cm(2), laser pulses is obtained with 500 fs time resolution. Two distinct phases occur: At </=500 fs a broad feature comparable to the resonance transitions occurs due to satellites, and at >/=500 fs the resonance transitions dominate. Initial satellites arise from a large area, high density, low temperature (approximately 100 eV) plasma created by fast electrons. Thus, contrary to predictions, a short, high intensity laser incident on a thin foil does not create a uniform, hot dense plasma.

Journal Article↗
PubMed2002

Volume increase in growth plate chondrocytes during hypertrophy: the contribution of organic osmolytes.

During the differentiation cascade of growth plate chondrocytes, cells undergo as much as a 10-15-fold increase in volume. This volume increase, which occurs to different extents in growth plates growing at different rates, has been demonstrated to be the single most significant variable in understanding the quantitative aspects of the cellular kinetics of long bone growth. Our hypothesis is that this volume increase, which occurs through cell swelling by water imbibition, requires intracellular accumulation of osmolytes through activation or upregulation of membrane transport mechanisms. Significant intracellular accumulation of inorganic osmolytes, such as Na+, K+, and Cl-, is potentially disruptive to normal cellular metabolism, whereas intracellular accumulation of organic osmolytes is considered to be more compatible with metabolic function. Thus, we concentrated on determining the contributions of organic osmolytes--betaine, amino acids, inositol, and sorbitol--to volume increase. Pooled cryostat sections of young bovine growth plates were extracted followed by automated analysis for their content of amino acids. Analysis for betaine and the sugar alcohols was done by extraction and derivatization, followed by high-performance liquid chromatography (HPLC). Parallel stereological analyses correlated osmolyte changes to stages of chondrocytic differentiation, specifically comparing intracellular concentration and amount in proliferative vs. hypertrophic chondrocytes. Calculations demonstrated that, maximally, these organic osmolytes, in total, account for 6%-7% of the intracellular osmolytes required to sustain the volume increase, and that the most significant contribution is from betaine. This suggests that intracellular accumulation of organic osmolytes is not a primary strategy used by growth plate chondrocytes during volume increase of their terminal differentiation. The data also suggest that there is a differential regulation of transporters of these osmolytes such that intracellular concentrations are constantly modified as cells proceed through the differentiation cascade.

Amino Acids↗
PubMed2002

Facial fractures and submental tracheal intubation.

Submental tracheal intubation is a simple, quick and effective alternative to oral and nasal tracheal intubation or tracheostomy in the surgical management of selected patients with craniomaxillofacial injuries. It has a low morbidity and it does not impede the surgical field, allowing for temporary maxillo-mandibular fixation (jaw wiring) intra-operatively, and nasal assessment, manipulation and bone grafting, either simultaneously or as an independent procedure. We report 12 cases utilizing this technique in this retrospective study, this includes 11 patients with mid-facial fractures and associated base of skull fractures, and one patient who underwent an elective Le Fort III advancement. The techniques and indications for submental tracheal intubation are described.

Adolescent↗
PubMed2002

Eliciting a terminology for mammographic calcifications.

AIM: Two studies were carried out to establish, validate and assess descriptors for use in the differential diagnosis for mammographic calcifications. METHODS: In Study 1, eleven radiologists were asked to 'think out loud' as they interpreted 20 sets of calcifications. Participants used 159 terms to describe calcifications. We used this data to design a scheme with 50 descriptors. In Study 2, ten radiologists used the scheme to describe 40 sets of calcifications. We assessed the capacity of the terms to discriminate between benign and malignant calcifications, testing them against radiologists' assessments of malignancy and follow-up data. RESULTS: All descriptors were used by at least 5 radiologists. Five additional descriptors were required. With some exceptions, properties that discriminated between benign and malignant outcomes were highly correlated with radiologists' assessment of risk. Many descriptors have a fairly low sensitivity but high specificity. CONCLUSIONS: Our data suggest that radiologists consider a wide range of features than is included in existing reporting schemes. Our scheme allows a richer characterization of calcifications, potentially improving the reporting and understanding of these abnormalities.

Breast Diseases↗
PubMed2002

Application of semiological seizure classification to epileptic seizures in children.

To better define seizure characteristics and to examine whether semiological seizure classification (SSC) can be appropriately applied to the seizures of infants and children, we studied 152 videotaped seizures recorded in 133 children. Seizure semiology was described on the basis of a series of behavioural, sensory, and motor phenomena according to SSC. Special emphasis was placed on whether one semiology can be representative of a patient's whole semiology sequence. If one semiology was able to represent the whole sequence, the seizure was classified according to SSC. Ninety of 152 seizures (59.2%) could be classified as a single seizure type by SSC. However, only 19 of 53 seizures (35.9%) consisting of two semiologies, three of 24 seizures (12.5%) consisting of three semiologies, and one of eight seizures (12.5%) consisting of four semiologies could be classified according to SSC. Although SSC is very efficient, it is more accurately a descriptive terminology for clinical ictal events than a classification system.

Adolescent↗
PubMed2002

Significance of fractionated irradiation for the biological therapeutic gain of carbon ions.

It is well established that the RBE (relative biological effectiveness) for cell killing depends on LET (linear energy transfer), and that a maximum RBE is observed at approximately 150 keV.micron-1. However, the therapeutic gain depends on the ratio of the RBEs for the effects on the cancer cell population and the effects on normal tissues. The RBE of a given radiation quality depends not only on LET but also on dose, biological system and effect, and irradiation conditions. There is no data available to answer the question: which LET is suitable to improve the biological therapeutic gain of carbon ions? Here, three different LET values of 290 MeV/u carbon ions were selected, and the relative biological effectiveness was compared between tumour-growth retardation and skin damage using a murine transplantable tumour. Larger RBE values for tumours after than the skin type were obtained when carbon ions of intermediate LET were delivered daily for 2 to 5 fractions. The biological therapeutic gain would be high for the carbon ion SOBP if the number of fractions were correctly selected in clinical trials.

Animals↗
PubMed2001

Guided medication dosing for inpatients with renal insufficiency.

CONTEXT: Usual drug-prescribing practices may not consider the effects of renal insufficiency on the disposition of certain drugs. Decision aids may help optimize prescribing behavior and reduce medical error. OBJECTIVE: To determine if a system application for adjusting drug dose and frequency in patients with renal insufficiency, when merged with a computerized order entry system, improves drug prescribing and patient outcomes. DESIGN, SETTING, AND PATIENTS: Four consecutive 2-month intervals consisting of control (usual computerized order entry) alternating with intervention (computerized order entry plus decision support system), conducted in September 1997-April 1998 with outcomes assessed among a consecutive sample of 17 828 adults admitted to an urban tertiary care teaching hospital. INTERVENTION: Real-time computerized decision support system for prescribing drugs in patients with renal insufficiency. During intervention periods, the adjusted dose list, default dose amount, and default frequency were displayed to the order-entry user and a notation was provided that adjustments had been made based on renal insufficiency. During control periods, these recommended adjustments were not revealed to the order-entry user, and the unadjusted parameters were displayed. MAIN OUTCOME MEASURES: Rates of appropriate prescription by dose and frequency, length of stay, hospital and pharmacy costs, and changes in renal function, compared among patients with renal insufficiency who were hospitalized during the intervention vs control periods. RESULTS: A total of 7490 patients were found to have some degree of renal insufficiency. In this group, 97 151 orders were written on renally cleared or nephrotoxic medications, of which 14 440 (15%) had at least 1 dosing parameter modified by the computer based on renal function. The fraction of prescriptions deemed appropriate during the intervention vs control periods by dose was 67% vs 54% (P<.001) and by frequency was 59% vs 35% (P<.001). Mean (SD) length of stay was 4.3 (4.5) days vs 4.5 (4.8) days in the intervention vs control periods, respectively (P =.009). There were no significant differences in estimated hospital and pharmacy costs or in the proportion of patients who experienced a decline in renal function during hospitalization. CONCLUSIONS: Guided medication dosing for inpatients with renal insufficiency appears to result in improved dose and frequency choices. This intervention demonstrates a way in which computer-based decision support systems can improve care.

Decision Support Systems, Clinical↗
PubMed2001

Regulation of cell survival by secreted proneurotrophins.

Neurotrophins are growth factors that promote cell survival, differentiation, and cell death. They are synthesized as proforms that can be cleaved intracellularly to release mature, secreted ligands. Although proneurotrophins have been considered inactive precursors, we show here that the proforms of nerve growth factor (NGF) and the proforms of brain derived neurotrophic factor (BDNF) are secreted and cleaved extracellularly by the serine protease plasmin and by selective matrix metalloproteinases (MMPs). ProNGF is a high-affinity ligand for p75(NTR) with high affinity and induced p75NTR-dependent apoptosis in cultured neurons with minimal activation of TrkA-mediated differentiation or survival. The biological action of neurotrophins is thus regulated by proteolytic cleavage, with proforms preferentially activating p75NTR to mediate apoptosis and mature forms activating Trk receptors to promote survival.

Animals↗
PubMed2001

Characterization of NR13-related human cell death regulator, Boo/Diva, in normal and cancer tissues.

Mouse Boo/Diva is an ovary-specific member of the Bcl-2 family identified through homology with the avian cell death antagonist NR13. We identified a human orthologue of Boo/Diva, which is highly conserved between mouse and human and related to avian NR13. Human Boo/Diva is also expressed in human liver and kidney in addition to the ovary. We found that green fluorescence protein (EGFP)-tagged Boo/Diva was not exclusively localized to mitochondria before the induction of apoptosis. However, EGFP-Boo/Diva translocated to mitochondria in the process of apoptosis induced by vincristine, a microtubule-interfering agent. Overexpression of human Boo/Diva promoted cell death in HeLa and 293 cells. The cell death antagonist Bcl-XL interacts with Boo, but is unable to protect 293 cells from Boo/Diva-induced cell death. Finally, we mapped human Boo/Diva to chromosome 15q21, a locus known to be related to human cervical cancer. Moreover, we found that genomic DNAs of three of 24 human cervical cancer samples display deletions within their Boo/Diva genes. This result suggests a role for human Boo/Diva in the pathogenesis of cervical cancer.

Amino Acid Sequence↗
PubMed2001

Erythropoietin (Epo) and EpoR expression and 2 waves of erythropoiesis.

Erythropoiesis occurs in 2 distinct waves during embryogenesis: the primitive wave in the extra-embryonic yolk sac (YS) followed by the definitive wave in the fetal liver and spleen. Even though progenitors for both cell types are present in the YS blood islands, only primitive cells are formed in the YS during early embryogenesis. In this study, it is proposed that erythropoietin (Epo) expression and the resultant EpoR activation regulate the timing of the definitive wave. First, it was demonstrated that Epo and EpoR gene expressions are temporally and spatially segregated: though EpoR is expressed early (embryonic days 8.0-9.5) in the yolk sac blood islands, no Epo expression can be detected in this extra-embryonic tissue. Only at a later stage can Epo expression be detected intra-embryonically, and the onset of Epo expression correlates with the initiation of definitive erythropoiesis. It was further demonstrated that the activation of the EpoR signaling pathway by knocking-in a constitutively active form of EpoR (R129C EpoR) can lead to earlier onset of definitive erythropoiesis in the YS. Thus, these results provide the first in vivo mechanism as to how 2 erythroid progenitor populations can coexist concurrently in the YS yet always differentiate successively during embryogenesis.

Animals↗
PubMed2001

The toxicity of styrene to the nasal epithelium of mice and rats: studies on the mode of action and relevance to humans.

Inhaled styrene is known to be toxic to the nasal olfactory epithelium of both mice and rats, although mice are markedly more sensitive. In this study, the nasal tissues of mice exposed to 40 and 160 ppm styrene 6 h/day for 3 days had a number of degenerative changes including atrophy of the olfactory mucosa and loss of normal cellular organisation. Pretreatment of mice with 5-phenyl-1-pentyne, an inhibitor of both CYP2F2 and CYP2E1 completely prevented the development of a nasal lesion on exposure to styrene establishing that a metabolite of styrene, probably styrene oxide, is responsible for the observed nasal toxicity. Comparisons of the cytochrome P-450 mediated metabolism of styrene to its oxide, and subsequent metabolism of the oxide by epoxide hydrolases and glutathione S-transferases in nasal tissues in vitro, have provided an explanation for the increased sensitivity of the mouse to styrene. Whereas cytochrome P-450 metabolism of styrene is similar in rats and mice, the rat is able to metabolise styrene oxide at higher rates than the mouse thus rapidly detoxifying this electrophilic metabolite. Metabolism of styrene to its oxide could not be detected in human nasal tissues in vitro, but the same tissues did have epoxide hydrolase and glutathione S-transferase activities, and were able to metabolise styrene oxide efficiently, indicating that styrene is unlikely to be toxic to the human nasal epithelium.

Alkynes↗
PubMed2001

Overview of the Third International Workshop on Swine Leukocyte Differentiation Antigens.

The aim of the Third International Workshop on Swine Leukocyte Differentiation Antigens (CD workshop), supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS), was to standardize the assignment of monoclonal antibodies (mAb) reactive with porcine leukocyte differentiation antigens and to define new antibody clusters, using nomenclature in accordance with human and ruminant CD nomenclature, as agreed at the summary meeting of the Second International Swine CD Workshop in Davis, 1995: only mAb with proven reactivity for the orthologous porcine gene product or cross-reactivity for the human gene products, were given the full CD nomenclature, all other allocations were prefixed with "w". As in previous workshops, the overall organization was entrusted to the chair and first author, with support by the chair of the previous workshop and second author. In addition to the existing 26 pig leukocyte CD/SWC determinants established in previous workshops, this workshop established/confirmed another 11 CDs for pig leukocytes, identified by a total of 21 mAb: CD11R1 (2 mAb), CD11R2 (1 mAb), CD11R3 (4 mAb), wCD40 (1 mAb), wCD46 (4 mAb), wCD47 (3 mAb), wCD49d (1 mAb), CD61 (1 mAb), wCD92 (1 mAb), wCD93 (1 mAb) and CD163 (2 mAb).

Animals↗
PubMed2001

Summary of the first round analyses of the Third International Workshop on Swine Leukocyte Differentiation Antigens.

The reactivity of 155 monoclonal antibodies submitted to the Third International Workshop on Swine Leukocyte Differentiation Antigens, together with 41 internal standards, was analysed by flow cytometry on 29 different pig cell targets as well as two human cell targets as a means of establishing suitable panels of monoclonal antibodies for more detailed clustering analyses by the various subsections of the workshop. Results were collected either without further gating, with gating based on FS/SS characteristics or with gating based on the co-expression of a reference antibody in two-colour flow cytometry. The CD or SWC reactivity of the internal standards had been established in previous workshops. Data sets were subsequently analysed by statistical clustering using the Leucocyte Typing Database IV software. The resulting 18 cluster groups were allocated to the appropriate second round sections of the workshop, after reviewing the overall cellular reactivity of each cluster as well as the specificity of known standards which clustered in a group.

Animals↗