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Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 667 records · Page 37Linked to original sources

New opportunities for screening and early detection of bladder cancer.

In the United States, over 51,000 new cases of urinary bladder tumors are diagnosed annually. Approximately 75-85% of all newly diagnosed cases are superficial transitional cell carcinomas (TCCs). Incidence is highest (80% of the cases) in the 50-79 year age group. Recent studies have reported that 21-25% of risk for bladder cancer among United States white males is due to occupational exposure. The DuPont Chambers Works in Deepwater, New Jersey, was a major producer of two chemicals now known to be human bladder carcinogens (beta-naphthylamine and benzidine) as well as two suspected human bladder carcinogens [ortho-toluidine and 4,4'-methylene- bis,2-chloroaniline (MOCA)]. Between 1954 and 1982, DuPont screened 1723 exposed employees annually at the Chambers Works using the Papanicolaou test for urinary cytology and microscopic urinalysis. A review of the prior screening program found that employees who developed bladder cancer during this time period were approximately twice as likely to have had hematuria than those comparably exposed who did not develop bladder cancer. Building on this finding, a three-year screening study evaluated a home self-test for microscopic hematuria to aid early detection of treatable urologic conditions among exposed workers at this chemical plant. Every six months, subjects tested their urine at home for 14 consecutive days, for the presence of blood. A high degree of adherence to our protocol (over 92% completed and returned the self-testing record) as well as high compliance with repeat screening (85% returned for screening in subsequent quarters) demonstrated good acceptance and performance of the recommended schedule of self-testing. Through the first 7 periods of screening, two new cases and one recurrence of TCC of the bladder were detected.

Humans↗

Characterization of nicotinic acetylcholine receptors on cultured bovine adrenal chromaffin cells using modified L-[3H]nicotine binding assay.

To characterize the properties of nicotinic acetylcholine receptors (nAChRs) in autonomic ganglia, we examined L-[3H]nicotine binding to membrane fraction prepared from cultured bovine adrenal chromaffin cells, using a modified filtration method. Binding of L-[3H]nicotine to non-treated glass fiber filters interfered with the detection of specific binding to the membrane fraction. Presoaking glass fiber filters in 3% or higher concentrations of polyethyleneimine (PEI) solution (sixty times higher than earlier used concentration) for at least 5 h could reduce the binding of L-[3H]nicotine to the filters to the background level. Specific L-[3H]nicotine binding to the membrane fraction was detected only when the membrane fraction was prepared in Ca(2+)-and Mg2+ (EDTA, EGTA and protease inhibitors were added) -free buffer. Specific binding of L-[3H]nicotine was saturable and reversible. Both computer program and Scatchard analysis revealed a single class of high affinity binding sites with an average Kd of 8.9 nM and a Bmax of 42.5 fmol/mg protein. The Hill coefficient was 0.98. In inhibition studies, both cholinergic agonists (carbachol and L-nicotine) and ganglionic agonists (lobeline and 1,1-dimethyl-4-phenylpiperazinium iodide) were much effective in inhibiting L-[3H]nicotine binding, whereas both neuromuscular blocking (alpha-bungarotoxin and d-tubocurarine) and ganglionic blocking agents were less effective. These results suggest that high affinity nicotinic binding sites on adrenal chromaffin cells are nAChRs of the ganglion-type, which have properties different from nAChRs on the neuromuscular junction but similar to nAChRs in the brain.

Animals↗

Differential sensitivity of cholinergic and GABAergic neurons in chick embryos treated intracerebrally with ethanol at 8 days of embryonic age.

We have shown that in embryos treated with ethanol in ovo during days 1-3, a critical period of neuroembryogenesis, cholinergic neuronal phenotypic expression is decreased whereas GABAergic and catecholaminergic neuronal populations are increased as assessed by neuronal markers choline acetyltransferase (ChAT), glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) respectively. In this study, ethanol was administered intracerebrally to embryos at embryonic day 8, embryos were sacrificed at day 9 and ChAT and GAD activities assayed separately in cerebral hemispheres and remaining brain (diencephalon-midbrain and optic lobes). We found that ChAT activity was enhanced in the cerebral hemispheres only, whereas GAD activity was decreased in both cerebral hemispheres and remaining brain. We have concluded that the differential responses of neuronal phenotypes to ethanol may reflect compensatory mechanisms to ethanol insult. Moreover, these findings emphasize the vulnerability of the GABAergic neuronal phenotypes to ethanol neurotoxicity during early brain development in the chick.

Animals↗

A review of physical exercises recommended for VDT operators.

This paper presents an evaluation of exercises that have been recommended for the prevention of musculoskeletal discomfort among VDT/office workers. 127 individual exercises were analysed for their suitability for performance in VDT workplaces. Additionally, each exercise was judged in terms of its safety and its compliance with principles of physiotherapy. Results showed that, in the majority of cases, the prepared instructions for the exercises were satisfactory and the exercises could be readily performed at the workstation. However, over a third of the exercises were conspicuous and potentially embarrassing to perform, and half would significantly disrupt the work routine. Additionally, a number of the exercises posed potential safety hazards, exacerbated biomechanical stresses common to VDT work, or were contraindicated for persons with certain health problems. These findings suggest a need for greater attention to both the practical and the therapeutic aspects of exercises promoted for VDT users.

Journal Article↗

Improving nursing practice: the provision of equipment.

The quality of nursing care depends not only on the knowledge and skill of practitioners, but also on the equipment provided for their use. The availability and storage of urinary catheters was recorded in two "point prevalence" surveys in one District Health Authority. The numbers of catheters available in different locations were not related to the prevalence or "predicted incidence" of catheterized patients. The second survey documented evidence of improvements in practice, in particular a reduction in excessive and/or out-of-date stocks; a reduction in damaged stock; an increased availability of catheters with small balloons; and a greater awareness of those considerations important to a judicious choice of catheter for each individual patient. Equipment audits improve practice by raising awareness of clinical issues; by providing objective evidence of unnecessary expenditure; and by monitoring indirectly certain aspects of care such as the provision of standards and guidelines.

Catheters, Indwelling↗

Induction of apoptosis in CD4+ prolymphocytic leukemia by deoxyadenosine and 2'-deoxycoformycin.

The leukemic cells of a patient with CD4+ prolymphocytic leukemia were treated in vitro with 5 microM deoxyadenosine and 60 microM 2'-deoxycoformycin (dCF), an inhibitor of adenosine deaminase (ADA). Following treatment, the leukemic cell dATP level increased to 378 pmol/10(6) cells on day 3, after which the level plateaued. Apoptosis was apparent following 4 h of incubation, and by day 8 34% of the chromatin was fragmented. Apoptosis also occurred in control cells, but to a lesser extent than in drug-treated cells. When the patient was treated with dCF, 4 mg/M2 i.v. the leukemic cell ADA activity was inhibited 24 h following treatment, and the lymphocyte dATP content increased to 303 pmol/10(6) cells by day 6. The lymphocyte count fell 60% in 1 week, but during this time there was no evidence of apoptosis in these cells. Thus, if dCF induces apoptosis in vivo, the effete cells may be rapidly cleared from the circulation and thus elude detection.

Adenosine Deaminase Inhibitors↗

Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and beta 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients.

Quinolinic acid (QUIN) is an neurotoxic N-methyl-D-aspartate receptor agonist and an L-tryptophan metabolite of the kynurenine pathway. Increased concentrations of QUIN occur in both cerebrospinal fluid (CSF) and blood of patients infected with human immunodeficiency virus (HIV)-1, particularly those with neurologic disturbances. In the present study of HIV-1 infected patients in Walter Reed stages 4, 5 and 6, reductions in L-tryptophan accompanied proportional increases in L-kynurenine and QUIN in both serum and CSF. Further, close inter-correlations exist between QUIN kynurenic acid and L-kynurenine with both beta 2-microglobulin and neopterin in CSF and serum. These correlations support the hypotheses that the kynurenine pathway is activated in association with inflammation and induction of indoleamine-2,3-dioxygenase. There were no relationships between CSF QUIN, L-kynurenine or kynurenic acid with the ratio of serum:CSF albumin concentrations, which indicates that the increases in CSF QUIN, L-kynurenine or kynurenic acid were not dependent on a breakdown of the blood-brain barrier. Kynurenic acid is also a kynurenine pathway metabolite that can attenuate the excitotoxic effects of QUIN when present in higher molar concentrations. While CSF kynurenic acid levels were increased in HIV-1-infected patients, the magnitude of the increases were smaller than those of QUIN and the molar concentrations of kynurenic acid were consistently lower than QUIN by at least one order of magnitude. We conclude that immune activation increases the levels of neuroactive kynurenines within the central nervous system of HIV-1-infected patients secondary to activation of indoleamine-2,3-dioxygenase.

AIDS Dementia Complex↗

Commitment reversion model of unrestricted cell growth.

Through the analysis of accumulated experimental data of cell growth, a model of unrestricted cell growth is presented here. This model is based hypothetically on the cellular commitment to senescence as in the previously presented commitment theory. Cells are divided into 3 types, namely uncommitted cells, committed cells and terminal cells. The division of an uncommitted cell produces an uncommitted cell itself and a committed cell of the first generation. This committed cell goes through a limited number of cell divisions until the cells become non-dividing terminal cells. It is hypothesized that during a committed cell division, there is a very small probability that an uncommitted cell may be generated. With computer simulations, it is estimated that a committed cell of the first generation may divide around 30 times until they become non-dividing terminal cells, and that the probability of an uncommitted cell regeneration for each committed cell division may be 2(-H). This hypothesis may possibly clarify some aspects of the biological phenomena of cell growth, which can not be explained by the previous commitment theory, such as the growth pattern of cultured diploid cells, cancer initiation and promotion, and cancer progression and metastasis.

Animals↗

Differences in neuronal and glial cell phenotypic expression in neuron-glia cocultures: influence of glia-conditioned media and living glial cell substrata.

Neuron-glia cocultures were prepared using, as a source for glial cells, either C6 glia (2B clone) of early (2B23) or late (2B111) passages or advanced passages of glial cells derived from primary cultures prepared from aged mouse cerebral hemispheres (MACH). Six-day-old chick embryo cerebral hemispheres (E6CH) were the source of neuron-enriched cultures. Glutamine synthetase (GS) activity was used as a marker for astrocytes and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity was used as a marker for oligodendrocytes. GS activity was markedly enhanced in cocultures of E6CH neurons and 2B23 glioblastic cells, whereas GS activity was reduced in cocultures of E6CH neurons and 2B111 astrocytic glia. In contrast, CNP activity was enhanced in cocultures of C6 glial cells with E6CH neurons. Glial cells from aged mouse brain did not respond to coculturing with E6CH neurons. It appears from these findings that neuronal input enhances the differentiation of glioblastic cells to either astrocytic or oligodendrocytic expression, whereas it decreases the activity of committed astrocytes. In contrast, glial cells from aged mouse brain do not respond to neuronal input. Choline acetyltransferase (ChAT) activity, a marker for cholinergic neurons, was enhanced only when E6CH cultures were grown in conditioned medium (CM) from 2B23 glioblastic cells. In contrast, ChAT activity was markedly diminished when E6CH neurons were cocultured with MACH glial cells but not when grown in CM from MACH glial cells. Thus, humoral factors from immature glial cells appear to enhance cholinergic neuronal phenotypic expression whereas cell-cell membrane contacts with aged glial cells diminish cholinergic phenotypic expression. The findings present supportive evidence that neuron-glia interrelationships are age dependent.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

Confronting the issues of patient safety and investigator conflict of interest in an international clinical trial of myocardial reperfusion. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) Steering Committee.

The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial is a large scale international trial of new myocardial reperfusion strategies. The primary hypothesis is that early and sustained coronary artery recanalization will be associated with a significant reduction in mortality. The four regimens that are being tested are 1) streptokinase with subcutaneous heparin; 2) streptokinase with intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) with intravenous heparin; and 4) combination streptokinase, rt-PA and intravenous heparin. The planned recruitment of 41,600 patients in 1,500 sites from 15 countries is expected to be completed by December 1992 and will enable detection of a 15% reduction or 1% absolute difference in mortality compared with that associated with standard therapy (streptokinase and subcutaneous heparin). In designing the trial, two important issues were directly addressed. First, a strategy was developed to provide assurance of patient safety during large scale investigational use of an aggressive thrombolytic regimen. This includes fascimile transmission of a one-page safety summary form to the Data Coordinating Center within 24 h of death or discharge, acceptance of the concept of "net clinical benefit" and close surveillance of the trial's progress by the independent Data and Safety Monitoring Committee. Second, to avoid potential conflict of interest beyond elimination of any position of financial equity, the Steering Committee unanimously voted to prohibit any honoraria for speaking engagements, payment for consultancy or travel or reimbursement of any kind from any of the five corporate sponsors until 1 year after publication of the results. Incorporation of these approaches may facilitate the design of future large scale randomized trials in cardiovascular medicine.

Biomedical Research↗

Late-onset atypical psychosis: a case involving neuroleptic drug toxicity and autoimmune serological abnormalities.

Serious or significant neuroleptic toxicity (Kurlan et al. 1984; Lazarus 1985; Levenson 1985; Pearlman 1986) may complicate the diagnosis and management of patients who develop acute medical problems while under treatment with neuroleptics (Levenson and Simpson 1986). We have found that in some cases it is difficult, if not impossible, to determine whether neuroleptics have contributed to the cause of an acute medical illness, or if the occurrence of acute medical problems precipitated the signs of neuroleptic toxicity by altering the disposition or the pharmacologic effects of the drugs.

Autoimmune Diseases↗

The effect of dairy products on iron availability.

Many researchers report substantial reductions in iron availability when dairy products are consumed with solutions of iron. Yet other studies indicate that dairy products have little effect on iron availability when added to complex meals. The conflicting data may be due to differences in the technique used to measure availability, species of animal used, form of iron in the diet, and meal composition. Human studies show superior bioavailability of iron in human milk when compared with cow's milk. Definitive causes for the differences between human and cow's milk have not been identified. Human milk contains lower amounts of casein, phosphate, and calcium, components thought to inhibit iron absorption. More work is needed to identify the factors that influence iron-dairy interactions. The nutritional benefits provided by dairy products outweigh the slight inhibitory effect they may have on iron availability.

Animals↗

Characterization of transforming growth factor-beta (TGF-beta) receptors on BeWo choriocarcinoma cells including the identification of a novel 38-kDa TGF-beta binding glycoprotein.

Transforming growth factor-beta (TGF-beta) is a potential mediator of placental trophoblast functions, including differentiation, hormone production, endometrial invasion, and immunosuppression. Equilibrium binding and affinity-labeling assays were used to investigate the binding characteristics of TGF-beta 1 and TGF-beta 2 on an established human choriocarcinoma trophoblastic cell line (BeWo). The equilibrium binding experiments indicated that the BeWo cells exhibited similar average affinities and total number of binding sites for TGF-beta 1 and TGF-beta 2. The Kd values obtained from Scatchard analyses were approximately 65 pM for 125I-TGF-beta 1 and approximately 40 pM for 125I-TGF-beta 2, with 70,000 and 85,000 sites per cell, respectively. Competitive equilibrium binding experiments indicated that TGF-beta 1 and TGF-beta 2 were equipotent (apparent half maximal inhibition [IC50] approximately 70 pM) and that all binding sites were capable of recognizing both isoforms. Affinity-labeling studies with 125I-TGF-beta 1 and 125I-TGF-beta 2 and the chemical cross-linking agent bis(sulfosuccinimidyl)suberate (BS3) revealed a predominant type III/betaglycan receptor, a low level of apparently heterogeneous type I and II receptors and an additional novel 38-kDa TGF-beta binding glycoprotein that was present both under reducing and nonreducing conditions on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Affinity-labeling saturation and competition studies indicated that the type III/betaglycan component appears to have a 7-fold higher capacity for TGF-beta 1 than for -beta 2 yet exhibits a 5- to 10-fold higher affinity for TGF-beta 2 than for -beta 1. The 38-kDa TGF-beta binding component, an N-linked glycoprotein, exhibits a higher affinity for TGF-beta 2 than for -beta 1 that is strikingly similar to that of the type III/betaglycan receptor. This 38-kDa binding protein appears to be upregulated after methotrexate-induced differentiation of the BeWo cells.

Affinity Labels↗

Ischemia-induced loss of brain calcium/calmodulin-dependent protein kinase II.

Forebrain ischemia in gerbils, produced by brief bilateral carotid occlusion, induced the dramatic loss of Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) as determined by both kinase activity assays and western blot analysis. In cortex and hippocampus, cytosolic CaM-kinase II was completely lost within 2-5 min of ischemia. Particulate CaM-kinase II was more stable and decreased in level approximately 40% after 10 min of ischemia followed by 2 h of reperfusion. CaM-kinase II in cerebellum, which does not become ischemic, was not affected. The rapid loss of CaM-kinase II within 2-5 min was quite specific because cytosolic cyclic AMP kinase and protein kinase C in hippocampus were not affected. These data indicate that cytosolic CaM-kinase II is one of the most rapidly degraded proteins after brief ischemia. Because the multifunctional CaM-kinase II has been implicated in the regulation of numerous neuronal functions, its loss may destine the neuronal cell for death.

Animals↗