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Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 397 records · Page 22Linked to original sources
PubMed1998

Expression of C/EBP alpha, beta and delta in fetal and postnatal subcutaneous adipose tissue.

The C/EBP (CCAAT/enhancer binding protein) family of transcription factors (C/EBP alpha, beta, and delta) has been implicated in the development and the metabolic regulation of adipocytes from in vitro studies, yet the function of these factors, particularly CEBP beta and delta, in vivo has not been characterized. To assess the role of these factors in vivo, subcutaneous adipose, tissue from fetal and postnatal pigs was examined for C/EBP alpha, beta, and delta expression in developing and mature adipocytes. Western blot analysis of fetal adipose tissue showed a progressive increase of C/EBP alpha expression in 50, 75 and 95 day old fetuses. C/EBP beta and delta proteins were not observed in fetal adipose tissue. These results were confirmed with immunohistochemical studies of fetal adipose showing enhanced C/EBP alpha expression in the nuclei of adipocytes and cells closely associated with adipose cell clusters from 75 and 95 day old fetuses. For the same tissues only light background staining with no differential enhancement was found for C/EBP beta and delta. In postnatal adipose tissue C/EBP alpha and C/EBP beta protein were expressed in both 8 day old postnatal and mature (180 day) pigs. C/EBP delta reactive products were found in postnatal tissues however, their molecular weights were lower than that found in fetal pig liver. Our data suggest that adipose cell terminal differentiation proceeds in the pig fetus without the expression of C/EBP beta and delta and that these factors may have a more important role in fully differentiated adipose cells in postnatal tissue.

Adipose Tissue↗
PubMed1998

Children's use of triadic eye gaze information for "mind reading".

Five experiments examined children's use of eye gaze information for "mind-reading" purposes, specifically, for inferring another person's desire. When presented with static displays in the first 3 experiments, only by 4 years of age did children use another person's eye direction to infer desires, although younger children could identify the person's focus of attention. Further, 3-year-olds were capable of inferring desire from other nonverbal cues, such as pointing (Experiment 3). When eye gaze was presented dynamically with several other scaffolding cues (Experiment 4), 2- and 3-year-olds successfully used eye gaze for desire inference. Scaffolding cues were removed in Experiment 5, and 2- and 3-year-olds still performed above chance in using eye gaze. Results suggest that 2-year-olds are capable of using eye gaze alone to infer about another's desire. The authors propose that the acquisition of the ability to use attentional cues to infer another's mental state may involve both an association process and a differentiation process.

Attention↗
PubMed1998

The still-face effect in Chinese and Canadian 3- to 6-month-old infants.

Studies conducted in China examining cross-cultural differences in 3- to 6-month-olds used the still-face paradigm. In each study, 20 infants were in the experimental group (normal, still-face, normal interactions) and 20 in the control (3 normal periods). In Study 1, infants interacted with either their mother or their father; they looked and smiled less to the still-face of both parents. In Study 2, infants interacted with both their mother and a stranger, with order counterbalanced. Experimental groups showed similar still-face effects to both adults. The control group responded similarly to the stranger in both orders but responded less to their mother when she interacted 2nd. The data were compared with archival data from Canadian infants. Although Chinese infants took longer to begin smiling, responding was similar in both cultures, despite differences in mothers' behavior: Chinese mothers played with the infants' arms; Canadian mothers played with the legs.

Adult↗
PubMed1998

Coverage of bone marrow transplant patients: a survey of American and Canadian institutions.

Personnel involved in supportive care of bone marrow transplant (BMT) patients include fellows (F), medical house-staff (HS), nurse practitioners (NP), physician assistants (PA), and moonlighting physicians (MP). We have obtained surveys from 108 American and Canadian transplant centers on the composition of inpatient support teams. Eighty-seven percent of institutions responding to the survey were university-based programs. Eighty-eight percent of the centers performed both allogeneic and autologous transplants, and 60% performed unrelated donor grafts. The mean number of transplants performed annually at each center was 101 (range 4-515). For daytime coverage, the percent of programs involving F, HS, NP, PA, or MP was 57, 50, 35, 25, and 0%, respectively, and for nighttime coverage, the composition was 50, 56, 7, 6, and 13%, respectively. Medical HS were incorporated into the care of BMT patients at some level in 93% of the programs. Involvement by HS included full 24-hour coverage (44%), full nighttime coverage (8%), stat coverage (18%), and code blue only coverage (21%). HS involvement was similar in small and large transplant programs. HS were more involved in university-based programs. Programs on the East Coast had more HS involvement, with 54% of the programs reporting full 24-hour coverage by HS compared with 32% of the programs in the Pacific region. Coverage of transplant patients varies throughout the country, and nonphysician providers are often used. HS are more active in university-based programs, and their role is similar in both large and small programs.

Bone Marrow Transplantation↗
PubMed1998

Impact of residential nitrogen dioxide exposure on personal exposure: an international study.

Nitrogen dioxide (NO2) concentrations were measured during two-day winter periods in indoor and outdoor environments, and these concentrations were compared with simultaneously measured personal exposures in 18 cities in 15 countries around the world. Information was also gathered on activity patterns and household characteristics in order to determine the influences of these factors on personal exposures. All NO2 measurements were taken using passive filter badges. Personal exposures were found to vary greatly among the array of cities, with mean concentrations ranging between 11.0 ppb and 51.5 ppb. Personal NO2 exposures were more strongly correlated with indoor concentrations (r = 0.75) than with outdoor concentrations (r = 0.57) when all countries were considered simultaneously. Use of a gas stove in the home was the dominant activity influencing NO2 concentrations, with a 67% increase in mean personal NO2 exposure and an increase in indoor-outdoor ratios from 0.7 to 1.2 for participants using gas stoves, although preliminary evidence indicates the importance of combustion space heaters as well. These associations indicate the global nature of the correlation between personal NO2 exposures and indoor NO2 sources such as gas stoves or space heaters, demonstrating that this relationship is not dependent on country-specific parameters.

Air Pollution, Indoor↗
PubMed1998

The Boston residential nitrogen dioxide characterization study: classification and prediction of indoor NO2 exposure.

Many epidemiological studies have used house characteristics associated with indoor sources as simplified proxies for personal nitrogen dioxide (NO2) exposure. Stove type and presence of a pilot light often been used as the two key characteristics, but significant overlaps have remained in the NO2 concentrations in the exposed and unexposed groups. This has contributed to inconsistencies in epidemiological findings, due to potential misclassification of exposure. In this study, other possible proxies were analyzed by cross-table analyses and were investigated in terms of improvements in both classification and predictive power. Adding building type to the above two proxies resulted in 0-5% of households with concentrations overlapping the observed range for the opposing stratum, compared with 22-42% for the two-proxy model. In spite of this performance, the predictive power of regression models for indoor NO2 was not improved by the addition of the third proxy, and the potential sample population was significantly limited. Using these analytical methods to choose descriptive proxies and evaluate the tradeoffs in their implementation can help epidemiological studies improve their designs and therefore optimize the robustness of their conclusions.

Air Pollution, Indoor↗
PubMed1998

Functional dissection of yeast Hir1p, a WD repeat-containing transcriptional corepressor.

The HIR1 gene product is required to repress transcription of three of the four histone gene loci in Saccharomyces cerivisiae, and like its counterpart, the HIR2 protein, it functions as a transcriptional corepressor. Although Hir1p and Hir2p are physically associated in yeast, Hir1p is able to function independently of Hir2p when it is artificially recruited to the histone HTA1 promoter. A deletion analysis of HIR1 has revealed two separate repression domains: one in its N terminus, where seven copies of the beta-transducin or WD40 motif reside, and the second in the remaining C-terminal amino acids. Overexpression of the WD repeats in a hir1delta strain complemented its Hir- phenotype, while overexpression of the C terminus in a wild-type strain caused both Hir- and Spt- phenotypes. The Hir1p C terminus physically interacted in vivo with Hir2p, and both Hir1p repression domains interacted with full-length Hir1p. It was additionally found that the Hir1p WD repeats functionally interacted with the SPT4, SPT5, and SPT6 gene products, suggesting that these repeats may direct Hir1p to different protein complexes.

DNA Mutational Analysis↗
PubMed1998

KCB-328: a novel class III antiarrhythmic agent with little reverse frequency dependence in isolated guinea pig myocardium.

The effects of 1-(2-amino-4-methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxypheneth yl)-N-methylamino] ethane hydrochloride (KCB-328), in comparison with those of dofetilide, were studied on the action potentials (APs) of isolated guinea pig papillary muscles. KCB-328 (0.003-3 microM) concentration-dependently prolonged the AP duration at 90% repolarization (APD90) at 1- and 3-Hz pacing, and the concentration-response relations at 1 and 3 Hz resemble each other. Dofetilide (0.001-1 microM) also produced the concentration-dependent prolongation of APD90 but more pronouncedly at 1 than at 3 Hz, demonstrating the reverse frequency-dependent effect. KCB-328 at 0.03, 0.1, 0.3, and 1 microM increased APD90 by 11 +/- 1, 19 +/- 1, 25 +/- 1, and 29 +/- 1% at 3 Hz and by 9 +/- 1, 19 +/- 2, 27 +/- 2, and 33 +/- 2% at 1 Hz, respectively. Prolongation of the effective refractory period (ERP) by each drug is parallel to those of APD90 at each pacing frequency. KCB-328 modified neither the maximal velocity of depolarization, amplitude of AP, and resting membrane potential in the fast APs, nor any parameters of the slow APs. In a separate experiment, the effects of KCB-328 on the ERP of contractile response (ERPc) of excised guinea-pig papillary muscles also were studied at 1 and 3 Hz. KCB-328 (0.01-10 microM) lengthened the ERPc in a concentration-dependent and frequency-independent manner as in the electrophysiologic results. This frequency-independent ERPc prolongation by KCB-328 was not influenced by increased extracellular K+ concentration from 4 to 10 mM. These results suggest that KCB-328 might be a selective class III agent with effects that are relatively frequency independent.

Action Potentials↗
PubMed1998

Cardiovascular effects of nepicastat (RS-25560-197), a novel dopamine beta-hydroxylase inhibitor.

Nepicastat (RS-25560-197) is a novel, selective, and potent inhibitor of dopamine beta-hydroxylase, which modulates catecholamine levels (reduces norepinephrine and elevates dopamine) in cardiovascular tissues. This study was designed to evaluate the cardiovascular effects of nepicastat. Acute oral administration of nepicastat (0.3, 1, 3, 10, and 30 mg/kg) produced attenuation of the pressor and positive chronotropic responses to preganglionic sympathetic nerve stimulation (about twofold to sixfold shift in the frequency-response curve) in pithed spontaneously hypertensive rats (SHRs). In inactin-anesthetized SHRs, the antihypertensive effects of nepicastat (3 mg/kg, i.v.) were accompanied by a significant decrease in renal vascular resistance (38%), a tendency toward an increase in renal blood flow (22%), and no adverse effects on urine output and Na/K excretion. In conscious, unrestrained, telemetry-implanted SHRs, nepicastat (30 and 100 mg/kg/day for 30 days) produced dose-dependent decreases in mean arterial blood pressure (peak decrease of 20 and 42 mm Hg, respectively) without evoking reflex tachycardia. Long-term, concurrent administration of nepicastat (30 mg/kg/day, p.o.) and a subthreshold dose of enalapril (1 mg/kg/day, p.o.) produced greater antihypertensive effects than those produced by nepicastat alone. In normal dogs, nepicastat (5.0 mg/kg, p.o., b.i.d., for 4.5 days) blunted the positive chronotropic and pressor response to tyramine. These findings suggest that nepicastat functionally modulates sympathetic drive to cardiovascular tissues and may be of value in the treatment of cardiovascular disorders associated with overactivation of the sympathetic nervous system such as hypertension and congestive heart failure.

Animals↗
PubMed1998

A cadaveric and clinical evaluation of endoscopically assisted zygomatic fracture repair.

An endoscopic method of malar arch repair without a bicoronal incision has been recently described. To determine the effectiveness of this new technique, a cadaver study was performed to evaluate the capacity of this technique to (1) restore the anatomic position of a fractured malar arch, (2) rigidly fixate the arch, and (3) avoid injury to the frontal branch of the facial nerve. The technique of endoscopically assisted fracture repair was then applied to a clinical series of consecutive patients presenting with displaced zygomatic fractures with comminution at the malar arch. All cadaveric specimens repaired with this endoscopic technique demonstrated anatomic reduction and rigid fixation of the arch without disruption of the frontal branch of the facial nerve. In all clinical cases, four-point rigid plate fixation (zygomaticofrontal, infraorbital, malar arch, and zygomaticomaxillary buttress) was achieved endoscopically with limited access incisions. All clinical cases demonstrated excellent skeletal restoration of the zygoma on postoperative computed tomography scans. On clinical examination, facial symmetry and normal facial nerve function were observed in all patients after operation.

Cadaver↗
PubMed1998

Endoscopic subcondylar fracture repair: functional, aesthetic, and radiographic outcomes.

An endoscopic method of mandibular subcondylar fracture repair has been described recently. To determine the effectiveness of this new technique, we longitudinally studied functional, aesthetic, and radiographic parameters following endoscopic repair of 22 subcondylar fractures in 20 patients. Restoration of mandibular function was achieved without postoperative maxillomandibular fixation. Premorbid occlusion was restored. Clinical jaw motion was found to progressively increase with a mean interincisal jaw opening of 43 mm achieved after the eighth postoperative week. Patients were pleased with the aesthetic restoration of their chin projection,jaw line, and the symmetric midline movement of the chin point onjaw opening. Anatomic fracture reduction with rigid plate fixation was confirmed on early postsurgical radiographs. Late radiographs showed fracture union without remodeling of the condylar head. Endoscopic subcondylar fracture repair was efficacious at functional, aesthetic, and radiographic restoration of the mandible.

Adult↗
PubMed1998

Isolation and characterization of toluene-sensitive mutants from the toluene-resistant bacterium Pseudomonas putida GM73.

To understand the mechanism underlying toluene resistance of a toluene-tolerant bacterium, Pseudomonas putida GM73, we carried out Tn5 mutagenesis and isolated eight toluene-sensitive mutants. None of the mutants grew in the presence of 20% (vol/vol) toluene in growth medium but exhibited differential sensitivity to toluene. When wild-type cells were treated with toluene (1% [vol/vol]) for 5 min, about 2% of the cells could form colonies. In the mutants Ttg1, Ttg2, Ttg3, and Ttg8, the same treatment killed more than 99.9999% of cells (survival rate, <10(-6)). In Ttg4, Ttg5, Ttg6, and Ttg7, about 0.02% of cells formed colonies. We cloned the Tn5-inserted genes, and the DNA sequence flanking Tn5 was determined. From comparison with a sequence database, putative protein products encoded by ttg genes were identified as follows. Ttg1 and Ttg2 are ATP binding cassette (ABC) transporter homologs; Ttg3 is a periplasmic linker protein of a toluene efflux pump; both Ttg4 and Ttg7 are pyruvate dehydrogenase; Ttg5 is a dihydrolipoamide acetyltransferase; and Ttg7 is the negative regulator of the phosphate regulon. The sequences deduced from ttg8 did not show a significant similarity to any DNA or proteins in sequence databases. Characterization of these mutants and identification of mutant genes suggested that active efflux mechanism and efficient repair of damaged membranes were important in toluene resistance.

Amino Acid Sequence↗
PubMed1998

Role of the liver in long-term control of drinking behavior, Na+ balance, and arterial pressure in Dahl rats.

The role of postabsorptive mechanisms in long-term control of drinking behavior, Na+ balance, and arterial pressure was examined in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. NaCl (0.15 M) was infused (0.5 ml/h) into either the inferior vena cava (IVC) or the portal vein (PV) for 7 days, and then 1.5 M NaCl was infused for 10 days. During 1.5 M infusion, the IVC group retained more Na+ than the PV group. Furthermore, in DS rats, mean arterial pressure was higher in the IVC group than in the PV group. Regardless of the strain and infusion route, 1.5 M infusion had no effect on volume of daily saline consumption. However, when the data for light and dark periods were analyzed separately, dark period saline consumption in the PV group was decreased by 1.5 M infusion but was not changed in the IVC group. These results indicate that, in Dahl rats, the postabsorptive mechanism plays a significant role in controlling long-term saline drinking behavior and Na+ balance and has a significant role in controlling arterial pressure in DS, but not DR, rats.

Animals↗
PubMed1998

Heterogeneity among cells that express osteoclast-associated genes in developing bone.

In the present study, we characterized the phenotype of cells in the osteoclast lineage by in situ hybridization, using antisense complementary RNA probes that encode three genes typically expressed by osteoclasts, tartrate-resistant acid phosphatase (TRAP), type IV collagenase (matrix metalloproteinase-9), and c-fms, the receptor for macrophage colony-stimulating factor. By using complementary RNA probes labeled with 35S, digoxygenin, or a combination of the two labeling methods (dual labeling in situ hybridization), we found that each of these genes exhibited a distinct expression pattern during early stages of endochondral bone development [embryonic day 15 (ED15) to ED17] in fetal mouse hind limbs. Type IV collagenase messenger RNA (mRNA) was first expressed in or just outside of the cellular layers that define perichondrium/periosteum, earlier than transcripts for TRAP or c-fms appeared at the same sites (ED15). Although transcripts for TRAP and c-fms colocalized within the skeleton, c-fms was also found in surrounding soft tissue, whereas TRAP mRNA was never detected outside the skeleton (ED16). Type IV collagenase mRNA was uniquely distributed at the chondro-osseous border, being distinct from the distribution of TRAP or c-fms (ED17). At later stages of skeletal development (ED18 to 15-day-old postnatal bone), however, there was more overlap among TRAP, type IV collagenase, and c-fms mRNAs in cells throughout bone, except at the chondro-osseous junction, where type IV collagenase continued to be uniquely localized to some cells at all developmental stages. Whereas the levels of type IV collagenase mRNA expression was most intense at the chondro-osseous margin, the levels of c-fms and TRAP mRNA expression appeared to be more uniform throughout the developing bone. The results indicate that there is considerable heterogeneity among cells expressing osteoclast-associated genes, particularly during early stages of endochondral bone development, but that this difference becomes less pronounced later in the more mature skeleton. Distinct expression patterns of these markers may represent different stages of osteoclastogenesis. Alternatively, type IV collagenase-positive and TRAP/c-fms-positive cells may represent distinct subpopulations of cells of the osteoclast lineage.

Acid Phosphatase↗
PubMed1998

Identification, functional characterization, and developmental expression of two nonallelic parathyroid hormone (PTH)/PTH-related peptide receptor isoforms in Xenopus laevis (Daudin).

Complementary DNAs encoding two nonallelic PTH/PTH-related peptide (PTHrP) receptor (PPR) isoforms, xPPR-A and xPPR-B, were isolated from a kidney complementary DNA library of the tetraploid African clawed frog Xenopus laevis. Both isoforms differ in their coding region by 19 amino acids, and lack the region corresponding to the mammalian exon E2. When expressed in mammalian COS-7 cells, both receptor isoforms bound radiolabeled PTH-(1-34) and PTHrP-(1-36) analogs with comparable affinity, and both unlabeled peptides equivalently stimulated the accumulation of cAMP. xPPR-A also mediated inositol phosphate turnover in COS cells and stimulated channel-mediated current changes in voltage clamp experiments after injection into oocytes. Using ribonuclease protection analysis, significant xPPR-A messenger RNA expression was first detected in neurula stage embryos, which subsequently increased approximately 30-fold during tadpole development. Expression reached a maximum at the metamorphotic climax, when isoform B also became detectable at significant levels, and subsequently declined in postmetamorphotic froglets. In the adult frog, xPPR-A was prominently expressed in lung, brain, small bowel, and skin, whereas isoform B was highest in lung, heart, and brain. Using an xPPR-A antisense riboprobe for in situ hybridization, expression appeared during metamorphosis at all sites of chondrogenesis, specifically in the maturing zone of the amphibian growth plate. xPPR-A expression was also seen in a subpopulation of mononuclear cells, possibly representing osteoblasts that line perichondral bone and diaphyseal bone trabeculae. Our findings suggest that xPPRs serve a prominent role in amphibian skeletal development and possibly other functions during embryonal and early larval development.

Aging↗
PubMed1998

Randomized trial of pamidronate in patients with thyroid cancer: bone density is not reduced by suppressive doses of thyroxine, but is increased by cyclic intravenous pamidronate.

Patients taking suppressive doses of T4 are thought to have accelerated bone loss and increased risk of osteoporosis. We therefore randomize 55 patients taking suppressive doses of T4 to treatment with pamidronate (APD) 30 mg i.v. every 3 months for 2 yr (APD/T4), or placebo (placebo/T4). Patients had measurements of bone mineral density (BMD) of the spine, hip, radius, and total body every 6 months for 2 yr. There was no significant bone loss at any site in the placebo/T4 group. Ninety five percent confidence intervals excluded a rate of bone loss > 0.89%/yr for the spine and > 0.31%/yr at the total hip. When men were excluded from the analysis, there still was no significant bone loss for the placebo/T4 group, and confidence intervals did not change. The APD/T4 group showed increases in spine (4.3%, P = 0.0001), total hip (1.4%, P < 0.05), and trochanteric (3.0%, P = 0.0001) BMDs. In conclusion, premenopausal women and men on suppressive therapy with T4 do not lose bone rapidly, and are not at increased risk of developing osteoporosis. A regimen of 30 mg APD given every 3 months for 2 yr causes significant suppression of bone resorption and increases in BMD, and may be an acceptable alternative treatment for osteoporosis in patients who cannot tolerate oral bisphosphonates.

Adult↗
PubMed1998

Determinants of nitrogen dioxide concentrations in indoor ice skating rinks.

OBJECTIVES: The combination of poor ventilation and fuel-powered ice resurfacers has resulted in elevated nitrogen dioxide (NO2) concentrations in many indoor ice skating rinks. This study examined the factors influencing concentrations and the effects of various engineering controls in ice rinks with different resurfacer fuels. METHODS: Indoor NO2 concentrations were measured in 19 enclosed ice skating rinks over 3 winters by means of passive samplers, with 1-week average measurements during the first winter pilot study and single-day working-hour measurements in the final 2 winters. Personal exposures to drivers also were assessed during the last winter. RESULTS: Rinks in which propane-fueled resurfacers were used had a daily mean indoor NO2 concentration of 206 ppb, compared with 132 ppb for gasoline-fueled and 37 ppb for electric-powered resurfacers. Engineering controls, such as increased ventilation and resurfacer tuning, reduced NO2 concentrations by 65% on average, but outcomes varied widely, and concentrations increased in subsequent months. CONCLUSIONS: Electric ice resurfacers, increased ventilation, or emission control systems are recommended to protect the health of workers and patrons, with surveillance programs proposed to track implementation and maintain an observer effect.

Air Pollutants, Occupational↗