Search PubMed⌕ Search

Biomedical subjects

L W Lee

Publications and source records attributed to L W Lee.

At least 55 records · Page 3Linked to original sources

Evaluating performance with high-frequency emphasis amplification.

Hearing aid fitting for individuals with high-frequency impairment has been difficult because of the limited gain available at those frequencies. Special high-frequency emphasis hearing aids have been developed in an attempt to alleviate this problem. The insertion-gain responses and changes in speech-recognition performance (in quiet and in noise, aided and unaided) were measured for a commercially available high-frequency emphasis hearing aid, using two types of speech materials (nonsense syllables, monosyllabic words). The maximum obtainable gain observed for high frequencies approximated that prescribed by the NAL-R method, but was considerably lower than that prescribed by other common prescriptive methods. Furthermore, modest improvements in speech recognition were found. When evaluating individuals with high-frequency impairment, speech materials administered in noise appeared to be the most sensitive indication of improved speech recognition. Special high-frequency emphasis speech materials (CUNY NST) were no more sensitive to improvements in performance than conventional clinical word lists (NU6).

Adult↗

Two experiments on the spectral boundary conditions for nonlinear additivity of simultaneous masking.

The present paper describes the results from two experiments which explored the spectral boundaries for the nonlinear additivity of simultaneous masking. The first experiment measured the threshold for detection of a 2-kHz tone in the presence of two 800-Hz-wide bands of noise that had varying degrees of spectral overlap with each other and the 2-kHz signal. Results revealed an abrupt transition from linear to nonlinear additivity of masking as the spectral separation between the two maskers varied from some overlap to none. The second experiment examined alternative explanations for the data. Explanations based on restricted-listening or distortion-product-detection hypotheses were not supported by the results of this experiment. These data indicate that nonlinear additivity of simultaneous masking holds for maskers that do not overlap within the critical band centered on the signal frequency. This interpretation is also consistent with a large body of data on the monaural and binaural summation (additivity) of loudness.

Adult↗

Use of an automated medication storage and distribution system.

The effects of an automated medication storage and distribution system in a hospital setting were evaluated. The Pyxis Medstation system was implemented on two nursing units at a 1000-bed tertiary-care referral hospital. The system, which is designed like an automated bank teller, dispenses items to authorized users and records all transactions. Floor-stock controlled substances and noncontrolled medications, large-volume i.v. solutions, and i.v. administration sets were stocked in the system. The system was evaluated (1) by comparing the mean patient charge capture rates for six months before and for three months after implementation, (2) by measuring nurse and pharmacy technician time required for various tasks before and after implementation, and (3) through questionnaires filled out by nurses and technicians. After the system was installed, nursing personnel spent less time on medication-related activities, charting, and documentation and more time interacting with patients. Pharmacy technicians spent more time on floor-stock activities and less time on billing activities. Nurses indicated positive attitudes toward the system features. Both nurses and pharmacy technicians indicated that the system should remain in use. After implementation, the charge capture rate for noncontrolled medications, i.v. solutions, and i.v. sets increased from 63% to 97%. This increase, extrapolated to the entire hospital, reflects $35,000 in additional revenue over the total costs of implementation of the system. Implementation of an automated medication storage and dispensing system is expected to increase hospital revenue and enable nurses to spend more time interacting with patients at this institution.

Attitude of Health Personnel↗

Clonal cosegregation of tumorigenicity with overexpression of c-myc and transforming growth factor alpha genes in chemically transformed rat liver epithelial cells.

Tumorigenicity was correlated with levels of expression of the genes for transforming growth factor alpha (TGF-alpha), epidermal growth factor receptor, c-myc, c-H-ras, and c-K-ras in a series of 16 clonally derived transformed liver epithelial cell lines. The clonal lines, which varied in tumorigenicity from 0 to 97%, were established from a phenotypically heterogeneous population produced by repeated exposure of diploid WB-F344 (WB) cells to N-methyl-N'-nitro-N-nitrosoguanidine. Segregation of gene expression with tumorigenicity among clonal lines was determined by correlating rank orders of gene expression by clones relative to expression by wild-type WB cells. Only the expression of the c-myc gene correlated with tumorigenicity among all transformed clones. TGF-alpha gene expression was not correlated with tumorigenicity among all clones, but it was highly correlated with tumorigenicity among clones that expressed the c-myc gene above the median level for all clones (greater than 5-fold the level of expression by WB cells). Even high levels of expression of the TGF-alpha gene (up to 60-fold the level of expression by WB cells) were not correlated with tumorigenicity among the clones expressing the c-myc gene at levels less than 5-fold the level of expression by WB cells. Clones which simultaneously overexpressed both c-myc and TGF-alpha genes at levels above the median levels for all clones were significantly more tumorigenic than were clones which expressed either or both genes at lower than median levels. These results suggest that overexpressed c-myc and TGF-alpha genes cooperate in their association with tumorigenicity. Most of the highly tumorigenic clones that overexpressed c-myc and TGF-alpha also overexpressed the c-H-ras and/or the c-K-ras genes; clones that overexpressed neither of the c-ras genes nor the genes for c-myc and TGF-alpha were not very tumorigenic, while clones that expressed one or both c-ras genes (but not both c-myc and TGF-alpha) were variably tumorigenic over an intermediate range.

Animals↗

The primary structures of four subunits of the human, high-molecular-weight proteinase, macropain (proteasome), are distinct but homologous.

Macropain (proteasome) is a high-molecular-weight proteinase complex composed of at least 13 electrophoretically distinct subunits. Previous work, including peptide mapping and limited amino acid sequencing, suggested that most of the subunits belong to an evolutionarily related group of different gene products (Lee et al. (1990) Biochim. Biophys. Acta. 1037, 178-185). In order to define the extent and pattern of subunit relatedness, and to determine the structural basis for possible similarities and differences in subunit functions, we are deducing the primary structures of macropain subunits by cDNA cloning and DNA sequence analysis. We report here the primary structures of four subunits. The data clearly demonstrate that the proteins represent different, but homologous gene products. Surprisingly, no evidence for homology with any other protein, including proteinases, was obtained. These results suggest that macropain is comprised of a previously unidentified family of evolutionarily related polypeptides. Because biochemical data indicate that macropain contains several different proteinase activities, the current results raise the possibility that the macropain complex is composed of a group of novel proteinases, distinct from those of other structurally identifiable proteinase families.

Amino Acid Sequence↗

Clonal analysis of neoplastic transformation in cultured diploid rat liver epithelial cells.

Expression of TGF-alpha mRNA, which correlates well with the ability of cells to condition medium with an EGF-like activity, clonally segregates best with tumorigenicity among the several single phenotypes considered in this study. The results of unreported studies in which we have analyzed the quantitative relationships between the expression of selected phenotypes and tumorigenicity, suggest that the elevated expression of myc and TGF-alpha mRNAs interact in their associations with tumor yield. These results suggest that elevated myc expression sensitizes hepatic epithelial cells to the possible tumorigenic action of TGF-alpha. This observation may explain why the correlation between the qualitative expression of TGF-alpha and tumorigenicity, described here, is not perfect. Conventionally applied markers of transformation in hepatocytes in vivo and in cultured liver epithelial cells in vitro that we studied -histochemical expression of GGT, ability to grow in medium containing low levels of calcium, and ability to grow in soft agar- clonally segregated with tumorigenicity poorly in liver epithelial cells transformed in vitro. We conclude that these phenotypes are not adequate markers for determining the lineage of hepatic epithelial neoplasms (including, probably hepatocellular cancers arising in vivo). This study appears to be the first to attempt to analyze clonally the association of these markers with tumorigenicity, and to quantify the sensitivity, specificity, and predictive value of the associations. Our study suggests that the relatively weak associations of these phenotypes with tumorigenicity may be related only to their stronger associations with expression of TGF-alpha, or to some other property that is strongly associated with tumorigenicity. Expression of TGF-alpha is more strongly associated with expression of GLC, for example, than is the GLC phenotype with tumorigenicity. At least for GLC, autocrine stimulation by TGF-alpha is likely, since EGF increases growth of WB cells in low calcium medium. This observation may explain the perfect correlation between expression of TGF-alpha and GLC. EGF also stimulates lactate dehydrogenase, pyruvate kinase, and glucose 6-phosphate dehydrogenase in WB cells. However, quantitative correlation between GGT activity and TGF-alpha is less strong. Thus, our data from these studies suggest that the tumorigenic phenotype of cultured hepatic epithelial cells is intimately dependent on the expression of the TGF-alpha gene, possibly producing autocrine stimulation of growth via the cells' EGF receptors. This is the most simple view of the potential relationship between TGF-alpha expression and tumorigenicity in liver epithelial cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Idiopathic orthostatic hypotension, midodrine, and anaesthesia.

A patient with idiopathic orthostatic hypotension receiving chronic oral midodrine therapy required anaesthesia for coronary artery bypass grafting. A perioperative infusion of phenylephrine was substituted for midodrine, an alpha-2 agonist, enabling hypotension resulting from low systemic vascular resistance to be controlled easily. Anticipated adrenergic receptor denervation hypersensitivity was noted. The only significant perioperative problem was one episode of syncope from orthostatic hypotension during the reambulation period.

Anesthesia, Intravenous↗

Relationships among the subunits of the high molecular weight proteinase, macropain (proteasome).

An analysis of the subunits of the high molecular weight proteinase, macropain (multicatalytic proteinase or proteasome) from human erythrocytes has been conducted using N-terminal amino acid sequencing, gel electrophoresis and reverse-phase peptide mapping. This analysis provided evidence for the existence of 13 subunits of different primary structure. Five subunits were susceptible to the Edman degradation and yielded unique N-terminal sequences. Similarities among these sequences, however, indicated that the subunits are homologous. Two-dimensional gel electrophoresis discriminated 10 major components, which included two of the subunits for which N-terminal sequences had been determined and eight N-terminally blocked subunits. Tryptic peptide mapping indicated that all 10 of these components have a different amino acid sequence. Tryptic peptides from some of the subunits were subjected to amino acid sequence analysis, and the data indicated that all the subunits tested in this way are related by common ancestry. The data suggest that at least nine of the total of 13 subunits are encoded by members of the same gene family; the remaining four subunits have not yet been investigated in sufficient detail to establish their relationships. No evidence for a close relationship with any previously investigated proteinase family has been found. Finally, through a comparison of the 'latent' and 'active' forms of macropain, the study established a close similarity in the subunit composition of these catalytically very different species, although proteolytic degradation of selected subunits appears in the active form of the enzyme.

Amino Acid Sequence↗

Pulmonary artery pressures with tension pneumothorax.

Five hours following an uneventful coronary artery bypass graft operation, an otherwise healthy 54-yr-old man developed a pneumothorax while his lungs were being ventilated in the recovery room. Neither arterial blood gas analysis, ventilatory variables, nor clinical examination had suggested this diagnosis, which was made subsequent to a chest radiograph taken as part of the assessment of hypotension. At the same time, the waveform of the pressure tracing from his pulmonary artery catheter changed inexplicably while attempting balloon inflation as part of the assessment of the hypotensive episode. In retrospect, the changes in the pressure tracing most likely were due to alterations in the pulmonary vasculature associated with the pneumothorax. These changes can be explained in terms of a well-known physiological model. If such changes are encountered in similar circumstances, a tension pneumothorax should be suspected.

Coronary Artery Bypass↗

[A evaluation of chlorhexidine as an endosonic irrigan].

Chlorhexidine has been utilized as a root canal irrigant since 1971. It is a broad-spectrum antimicrobial agent with minimal toxicity and residual long-term antibacterial capability. Although a sodium hypochlorite solution has been shown to have a better antimicrobial effect than chlorhexidine, its corrosive effect has prevented its further use especially since the in vitro antimicrobial effect of chlorhexidine has been shown to not be much less. However, the efficacy of chlorhexidine as an endodontic irrigant and intracanal medicament, requires further research in vivo. Therefore, in this study, the clinical effects of chlorhexidine were evaluated by comparing its antimicrobial properties with other endodontic irrigants. One hundred and fifty teeth were selected and evenly divided into 6 groups according to their pathological status. The root cancals were prepared with conventional hand filing or ultrasonic filing, respectively, and were rinsed singly with either chlorhexidine, EDTA or distilled water. The contents of each root canal before or after debridement were cultured in an incubator. The results showed that chlorhexidine with hand filing in one week and with endosonics in 48 hours had a better antimicrobial effect than did EDTA. As compared with the control group (distilled water), chlorhexidine showed marked antimicrobial effect in both hand and endosonic filing. It is concluded that chlorhexidine has an antibacterial effect as an endodontic irrigant in clinical applications.

Bacteria↗

Phaeochromocytoma and mitral valve replacement.

A phaeochromocytoma was diagnosed following a mitral valve replacement and coronary artery bypass in a patient with progressive mitral regurgitation. Despite a previous adverse reaction to anaesthesia, this was not predicted perhaps due to his cardiac disease. Fever, leucocytosis and confusion were also prominent features. Haemodynamic control was achieved with the aid of labetalol.

Adrenal Gland Neoplasms↗

Emergence of neoplastic transformants spontaneously or after exposure to N-methyl-N'-nitro-N-nitrosoguanidine in populations of rat liver epithelial cells cultured under selective and nonselective conditions.

Many studies have shown that cultured rat liver epithelial cells can be neoplastically transformed by repeated or long-continued exposure to chemical carcinogens. These cells also may transform spontaneously in the absence of carcinogen treatment after long-term, continuous passage in culture or after chronic maintenance in a confluent state in vitro. In this study, we have compared the times of emergence and rates of accumulation of transformed cells in populations of rat hepatic epithelial cells exposed either to a single dose of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 3 micrograms/ml culture medium for 30 minutes) or to acetone vehicle alone (3 microliters/ml culture medium for 30 minutes). Transformation was compared in cell populations that were passaged continuously once a week as they attained a confluent density (nonselective growth conditions), or that were maintained at a confluent density for 3 weeks between passages once a month (selective growth conditions). Emergence of both spontaneous transformants and transformants induced by MNNG was facilitated by selective growth conditions, as compared with non-selective growth conditions. Transformants were detected both in cultures exposed to MNNG and in cultures exposed only to acetone (solvent controls), but they always emerged earlier in cultures exposed to MNNG (nine population doublings earlier when grown under selective growth conditions and 22 population doublings earlier when grown under nonselective growth conditions). Once transformants were detected, they replaced the nontransformed population more quickly under selective than under nonselective conditions of culture. Cells possessing the ability to grow in soft agar and to produce tumors in syngeneic rats were detected (at about 12 population doublings after treatment) under selective conditions much earlier than under nonselective growth conditions (at about 90 population doublings after treatment). Among MNNG-treated cultures, the fraction of aneuploid cells in the population was correlated significantly with tumorigenicity. In contrast, among acetone-treated control populations, aneuploidy and tumorigenicity were not correlated; populations of aneuploid acetone-treated cells often were not tumorigenic. These observations suggest that MNNG treatment produced a specific type of aneuploidy that was associated with tumorigenicity.

Animals↗

Induction of foci of morphologically transformed cells in synchronized populations of 10T1/2 cells by N-methyl-N'-nitro-N-nitrosoguanidine and the effect of spontaneous transformation on calculated transformation frequency.

Exposure of synchronized C3H10T1/2 (clone 8) cell populations of various sizes to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at a concentration of 2 micrograms/ml for 30 min at 24 h after release from confluence-induced arrest of proliferation produced neoplastic transformation (formation of foci of morphologically altered cells) by a random but episodic process in a small fraction of the cells at risk soon after treatment. The fraction of dishes that contained type II or type III foci increased as the number of cells at risk increased. In contrast, the development of spontaneous foci is a stochastic process that depends on the number of new cells that form during population growth and is independent of the number of cells that are plated (J. W. Grisham et al., Cancer Res., 48: 5969-5976,1988). When there were small numbers of cells at risk, spontaneous formation of foci was a source of considerable error in evaluating MNNG-induced transformation frequency. In surviving cell populations of less than 1000-3000 cells/100-mm dish, the frequency of induction of foci by MNNG could not be distinguished statistically from the frequency with which foci were expected to form spontaneously. When the fraction of MNNG-treated dishes that contained foci was adjusted for the fraction of pooled control dishes that contained foci, the number of foci induced by a uniform dose of MNNG was found to vary with the number of surviving cells. However, the MNNG-induced transformation frequencies calculated by the Poisson method were independent of the size of the population of cells at risk, provided the population of cells at risk was of sufficient size to allow spontaneous and induced transformation to be distinguished statistically. The results of this study show that the frequency of MNNG-induced transformation can be quantitated in cultures of 10T1/2 cells that contain varying but sufficient numbers of cells at risk when spontaneous transformation is considered. Furthermore, these observations suggest that MNNG-induced transformation of 10T1/2 cells occurs with the frequency and characteristics of a mutation-like change involving a single gene.

Animals↗

Spontaneous formation of foci of morphologically transformed cells in populations of C3H 10T1/2 (clone 8) cells.

Spontaneous formation of morphologically altered foci of types II and III (neoplastic transformation) was examined in populations of C3H 10T1/2 (10T1/2) cells. Initial surviving cell densities ranged from 3 to 3 x 10(5) cells/100-mm dish and the final cell density was approximately 2 x 10(6) cells/dish, yielding widely differing numbers of population doublings but similar numbers of cell births from the time of cell plating to the attainment of confluence. Spontaneous formation of foci was independent of the initial surviving cell densities (and, therefore, of the number of population doublings) but was related to the number of cell divisions (cell births) between the time the cell population was plated and when suppression of proliferation of wild-type cells occurred in confluent cultures. In 418 pooled asynchronously proliferating cultures in 100-mm dishes the 95% confidence limits for the fraction of dishes containing foci was 0.041-0.089 for type II foci and 0.008-0.036 for type III foci; for cell populations in 2041 pooled cultures in 100-mm dishes, the proliferation of which was synchronized by release from confluence-induced arrest of proliferation, the 95% confidence limits for the fraction of dishes containing foci were 0.150-0.166 for type II foci and 0.017-0.032 for type III foci. Using the Poisson method, the 95% confidence limits for rates of spontaneous transformation in asynchronously proliferating populations of 10T1/2 cells were 1.4-3.2 x 10(-8)/cell/division for type II foci and 0.28 to 1.3 x 10(-8)/cell/division for type III foci; in populations in which proliferation was initially synchronized by release from confluence-induced arrest, spontaneous transformation rates were 5.6-6.3 x 10(-8)/cell/division for type II foci and 0.59-1.1 x 10(-8)/cell/division for type III foci. Spontaneous transformation occurred in populations of wild-type 10T1/2 cells at the rates and with the characteristics expected of the mutation of a single gene locus.

Animals↗

Epidermal growth factor (EGF) and hormones stimulate phosphoinositide hydrolysis and increase EGF receptor protein synthesis and mRNA levels in rat liver epithelial cells. Evidence for protein kinase C-dependent and -independent pathways.

Epidermal growth factor (EGF) stimulated the rapid accumulation of inositol trisphosphate in WB cells, a continuous line of rat hepatic epithelial cells. Since we previously had shown that EGF stimulates EGF receptor synthesis in these cells, we tested whether hormones that stimulate PtdIns(4,5)P2 hydrolysis would increase EGF receptor protein synthesis and mRNA levels. Epinephrine, angiotensin II, and [Arg8]vasopressin activate phospholipase C in WB cells as evidenced by the accumulation of the inositol phosphates, inositol monophosphate, inositol bisphosphate, and inositol trisphosphate. A 3-4-h treatment with each hormone also increased the rate of EGF receptor protein synthesis by 3-6-fold as assessed by immunoprecipitation of EGF receptor from [35S]methionine-labeled cells. Northern blot analyses of WB cell EGF receptor mRNA levels revealed that agents linked to the phosphoinositide signaling system increased receptor mRNA content within 1-2 h. A maximal increase of 3-7-fold was observed after a 3-h exposure to EGF and hormones. The phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), which activates protein kinase C also stimulated EGF receptor synthesis. Pretreatment of WB cells for 18 h with high concentrations of TPA "down-regulated" protein kinase C and blocked TPA-directed EGF receptor mRNA synthesis. In contrast, the effect of EGF on EGF receptor mRNA levels was not significantly decreased by TPA pretreatment. Epinephrine-induced increases in EGF receptor mRNA were reduced from 4- to 2-fold. Similarly, 18 h TPA pretreatment abolished the effect of TPA on EGF receptor protein synthesis but did not affect EGF-dependent EGF receptor protein synthesis. The 18-h TPA pretreatment diminished by 30-50% the induction of receptor protein synthesis by epinephrine or angiotensin II. We conclude that in WB cells EGF receptor synthesis can be regulated by EGF and other hormones that stimulate PtdIns(4,5)P2 hydrolysis. In these cells, EGF receptor synthesis appears to be regulated by several mechanism: one pathway is dependent upon EGF receptor activation and can operate independently of protein kinase C activation; another pathway is correlated with PtdIns(4,5)P2 hydrolysis and is dependent, at least in part, upon protein kinase C activation.

Angiotensin II↗

[A clinical evaluation of antimicrobial effectiveness of EDTA as an endosonic irrigant].

Recently the chelating agent EDTA has gained increasing attention by dentists, in view of the facts that it does not produce deleterious or corrosive effect when used as an irrigant for root canal debridement. However, the efficacy of EDTA as an irrigant in clinical practice is still not clear. Therefore, in this study EDTA was adopted as an irrigant alone to evaluate its antimicrobial effect as a reference for subsequent clinical application. One hundred single-root teeth were selected and evenly divided into 4 groups. The root canals were prepared with conventional hand filing or ultrasonic filing respectively and the canals were rinsed singly with either EDTA or distilled water for contrast. The contents of each root canal before and after debridement were cultured in an incubator. The results showed that EDTA with hand filing in 48 hours and with endosonics in both 48 hours and one week had better antimicrobial effect than did distilled water. The results also indicated that EDTA combined with endosonics manifested the best antimicrobial effect among the four groups in this experiment. The above-mentioned differences were statistically significant at the level of p less than 0.05 by Fisher's exact test.

Bacteria↗

Epidermal growth factor (EGF) stimulates EGF receptor synthesis.

Epidermal growth factor (EGF) binds to the extracellular domain of a specific 170,000-dalton transmembrane glycoprotein; this results in rapid removal of both ligand and receptor from the cell surface. In WB cells, a rat hepatic epithelial cell line, ligand-directed receptor internalization leads to receptor degradation. We tested whether the EGF receptor was replenished at a constitutive or enhanced rate following EGF binding by immunoprecipitating biosynthetically labeled EGF receptor from cells cultured with [35S]methionine. EGF stimulated receptor synthesis within 2 h in a dose-dependent manner; this was particularly evident when examining the nascent form of the receptor. To determine the site of EGF action, total WB cell RNA was transferred to nitrocellulose paper after electrophoresis and was hybridized to cDNA probes from both the external and cytoplasmic coding regions of the human EGF receptor. EGF increased receptor mRNA by 3-5-fold. Therefore, at least in some cells, the surface action of EGF that leads to EGF receptor degradation is counterbalanced by a positive effect on receptor synthesis.

Animals↗