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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 577 records · Page 32Linked to original sources
PubMed1999

Comparison of the structures of beta amyloid peptide (25-35) and substance P in trifluoroethanol/water solution.

The three-dimensional structure of beta amyloid peptide (25-35) in aqueous solution with 50% (vol/vol) 2,2,2-trifluoroethanol was determined by NMR spectroscopy. Beta amyloid peptide(Abeta) is the major component of senile plaques found in the brain of patient of Alzheimer's disease. Abeta25-35 is biologically active fragment of Abeta and exhibits some sequence homology with the tachykinin family. In this study, we present the structural similarity between Abeta25-35 and substance P which is a member of tachykinin family in order to examine the possibility of sharing pathways mediated by tachykinin receptors. Both peptides have alpha-helical structures in their C-terminal regions and aromatic rings or hydrophobic side chains in the center of the helix protrude outside. These conformational features are expected to be the key for the interaction with the receptors.

Amyloid beta-Peptides↗
PubMed1999

Changes in the pattern of growth in stature related to prenatal exposure to ionizing radiation.

PURPOSE: To examine the pattern and spurt in growth and development of prenatally exposed atomic-bomb survivors and to determine whether a statistically significant radiation-related growth retardation exists. MATERIALS AND METHODS: The stature of 1566 individuals exposed prenatally to the atomic bombings has been employed to study the effect of such exposure on growth. Among these survivors, 30 were severely mentally retarded, and 66 individuals on whom no physical measurements between ages 9 and 19 exist were excluded from this study. Thus this analysis rests on the measurements obtained on 1470 survivors 9 to 19 years of age at the time of examination. RESULTS: When the > or =0.50 Sv group was compared to the other two prenatally exposed groups, a significant retardation of growth was observed only among those survivors exposed in the first trimester of gestation. The onset of the growth spurt among males in the three exposure groups was at approximately the same age, 11.34 years, but this was not true in females. The maximum velocity in growth for males was at 14.38 years of age, but for females no clear peak velocity was demonstrable. CONCLUSION: A radiation-related growth retardation was demonstrable in this longitudinal study of the stature of individuals prenatally exposed. It is further demonstrated that among these survivors the growth velocity was faster in the high-dose group than in the low-dose group for both males and females.

Adolescent↗
PubMed1999

Characterization of the human CR1 gene promoter.

The human CR1 is a single chain membrane glycoprotein that is a member of the group of regulators of the complement activation system. In order to clarify the regulatory mechanisms of human CR1 gene expression, the 5'-flanking region of the human CR1 gene was isolated and its promoter was characterized. The CR1 expression was found to be transcriptionally up-regulated in HL60 cells by stimulation with DMSO. The cloned CR1 gene promoter was sequenced and computer analyzed. The potential promoter region lacks a distinct TATA box sequence. The transcription initiation site was determined by primer extension and several possible regulatory elements for transcription were found in the promoter region.

Base Sequence↗
PubMed1999

Gene knockouts reveal separate functions for two cytoplasmic dyneins in Tetrahymena thermophila.

In many organisms, there are multiple isoforms of cytoplasmic dynein heavy chains, and division of labor among the isoforms would provide a mechanism to regulate dynein function. The targeted disruption of somatic genes in Tetrahymena thermophila presents the opportunity to determine the contributions of individual dynein isoforms in a single cell that expresses multiple dynein heavy chain genes. Substantial portions of two Tetrahymena cytoplasmic dynein heavy chain genes were cloned, and their motor domains were sequenced. Tetrahymena DYH1 encodes the ubiquitous cytoplasmic dynein Dyh1, and DYH2 encodes a second cytoplasmic dynein isoform, Dyh2. The disruption of DYH1, but not DYH2, resulted in cells with two detectable defects: 1) phagocytic activity was inhibited, and 2) the cells failed to distribute their chromosomes correctly during micronuclear mitosis. In contrast, the disruption of DYH2 resulted in a loss of regulation of cell size and cell shape and in the apparent inability of the cells to repair their cortical cytoskeletons. We conclude that the two dyneins perform separate tasks in Tetrahymena.

Amino Acid Sequence↗
PubMed1999

A novel Ras-interacting protein required for chemotaxis and cyclic adenosine monophosphate signal relay in Dictyostelium.

We have identified a novel Ras-interacting protein from Dictyostelium, RIP3, whose function is required for both chemotaxis and the synthesis and relay of the cyclic AMP (cAMP) chemoattractant signal. rip3 null cells are unable to aggregate and lack receptor activation of adenylyl cyclase but are able, in response to cAMP, to induce aggregation-stage, postaggregative, and cell-type-specific gene expression in suspension culture. In addition, rip3 null cells are unable to properly polarize in a cAMP gradient and chemotaxis is highly impaired. We demonstrate that cAMP stimulation of guanylyl cyclase, which is required for chemotaxis, is reduced approximately 60% in rip3 null cells. This reduced activation of guanylyl cyclase may account, in part, for the defect in chemotaxis. When cells are pulsed with cAMP for 5 h to mimic the endogenous cAMP oscillations that occur in wild-type strains, the cells will form aggregates, most of which, however, arrest at the mound stage. Unlike the response seen in wild-type strains, the rip3 null cell aggregates that form under these experimental conditions are very small, which is probably due to the rip3 null cell chemotaxis defect. Many of the phenotypes of the rip3 null cell, including the inability to activate adenylyl cyclase in response to cAMP and defects in chemotaxis, are very similar to those of strains carrying a disruption of the gene encoding the putative Ras exchange factor AleA. We demonstrate that aleA null cells also exhibit a defect in cAMP-mediated activation of guanylyl cyclase similar to that of rip3 null cells. A double-knockout mutant (rip3/aleA null cells) exhibits a further reduction in receptor activation of guanylyl cyclase, and these cells display almost no cell polarization or movement in cAMP gradients. As RIP3 preferentially interacts with an activated form of the Dictyostelium Ras protein RasG, which itself is important for cell movement, we propose that RIP3 and AleA are components of a Ras-regulated pathway involved in integrating chemotaxis and signal relay pathways that are essential for aggregation.

Adenylyl Cyclases↗
PubMed1999

Analysis of electret ion chamber radon detector response to 222Rn and interference from background gamma radiation.

Environmental radon (222Rn) monitors that incorporate electret detectors are confounded by background gamma radiation, which may cause the electret to discharge by as much as 7.5 volts per mR. Although background gamma corrections were formerly made by multiplying the known background gamma exposure rate with a constant conversion factor, this research demonstrates that doing so introduces an error ranging up to about 20%, especially in high gamma background areas. A new, more accurate method of background gamma correction has been developed that uses an average, voltage-dependent discharge factor, Dgamma (V Kg C(-1)). This factor and its coefficients were experimentally determined by separately exposing groups of electret radon detectors to photons from 60Co and 137Cs. Statistical analysis shows that Dgamma is independent of the orientation of the electret during irradiation but that some dependency on dose rate or energy of the irradiating photons may be expected. The discharge of the electret due only to gamma irradiation, Vgamma is determined by multiplying the total integrated gamma exposure by Dgamma. The discharge of the electret during a radon measurement can then be corrected for background gamma radiation by subtracting Vgamma from the total discharge of the electret resulting in a net discharge due solely to radon. A new equation has also been developed in this study for the radon discharge factor, D(Rn)(V m3 Bq(-1) s(-1)), that is entirely consistent with the gamma discharge factor and was thoroughly evaluated by exposing the electret radon detectors to known concentrations of radon.

Air Pollution, Radioactive↗
PubMed1999

A long-term, controlled-outcome analysis of in utero versus neonatal cleft lip repair using an ovine model.

Successful open repair of a cleft lip in utero has the advantage of scarless wound healing in the fetus. Unfortunately, no long-term outcome studies have been performed to evaluate the efficacy of these repairs. Moreover, no study to date has compared the long-term results of an in utero cleft lip repair to a similar, control-matched, newborn cleft repair. This study was performed to evaluate the 9-month outcome of in utero cleft lip surgery compared with an identical cleft lip repair performed on infant lambs. In utero epithelialized cleft lips were created through an open hysterotomy in sixteen 65-day-old fetal lambs (term = 140 days) using methods described by Longaker et al. Eight of 16 animals underwent subsequent in utero repair of these clefts at 90 days gestational age. The repair of the remaining eight animals was delayed until 1 week postpartum. At 9 months, the animals were analyzed for changes in lip contour and for the degree of scarring by hematoxylin and eosin and Masson's trichrome collagen staining. Two animals in each group died from preterm labor. Of the animals that survived to term, all repaired lips had some degree of abnormality postoperatively. One of six lips repaired in utero dehisced before delivery. Three of six neonatal repairs dehisced in the first postoperative month. In the remaining animals with intact lip repairs, the vertical lip height on the repaired side was an average of 9 to 12 mm shorter than the normal lip in both the in utero and neonatally repaired animals. Phenotypically, the postnatally repaired animals had more lip distortion and visible notching. Histologically, the in utero repair was scarless and the neonatal repairs had scar throughout the entire vertical height of the lip with an associated loss of hair in this region. Maxillary growth was also evaluated. There was no inhibition of maxillary growth in the animals that underwent in utero cleft lip repair. However, in the neonatal repair group, significant maxillary retrusion was evident. Compared with the cleft side of the maxilla, horizontal growth was decreased by 11 percent (p = 0.01). Compared with the intrauterine repair group, there was a 17-percent decrease in horizontal maxillary width (p = 0.01). Straight-line in utero repair of a cleft lip produces a better long-term result in terms of maxillary growth than a similar repair performed postnatally in the ovine model. There was no diminution in maxillary growth in the animals treated in utero. Histologically, in utero repair of clefts was indeed scarless. However, both lip repairs produced lips that were significantly shorter than their contralateral noncleft sides. This degree of lip shortening would require a secondary lip revision, thereby defeating the purpose of performing an intrauterine repair. Comparisons now need to be made between in utero and neonatal repairs using a Millard-type rotation advancement technique before intrauterine treatment can be considered to be more beneficial than our current treatment modalities.

Animals↗
PubMed1999

Multistability analysis of phase locking patterns in an excitatory coupled neural system.

We quantitatively analyze the multistability of dynamic patterns of a bursting neural system with diffusive coupling. Through effective coupling analysis, we show that the system is not in-phase locking but exhibits various phase locking patterns, each of which corresponds to the stable fixed points of the effective coupling. The simulation proves the validity of the effective coupling method in analyzing the multistability of neural systems which presents complicated dynamic patterns such as bursting.

Computer Simulation↗
PubMed1999

Effects of time-delayed interactions on dynamic patterns in a coupled phase oscillator system.

We investigate the effects of time delayed interactions in the network of neural oscillators. We perform the stability analysis in the vicinity of a synchronized state at vanishing time delay and present a related phase diagram. In the simulations it is shown that time delay induces various phenomena such as clustering where the system is spontaneously split into two phase locked groups, synchronization, and multistability. Time delay effects should be considered both in the natural and artificial neural systems whose information processing is based on the spatiotemporal dynamic patterns.

Journal Article↗
PubMed1999

Oligogalacturonic acid and chitosan reduce stomatal aperture by inducing the evolution of reactive oxygen species from guard cells of tomato and Commelina communis.

Stomatal opening provides access to inner leaf tissues for many plant pathogens, so narrowing stomatal apertures may be advantageous for plant defense. We investigated how guard cells respond to elicitors that can be generated from cell walls of plants or pathogens during pathogen infection. The effect of oligogalacturonic acid (OGA), a degradation product of the plant cell wall, and chitosan (beta-1,4-linked glucosamine), a component of the fungal cell wall, on stomatal movements were examined in leaf epidermis of tomato (Lycopersicon esculentum L.) and Commelina communis L. These elicitors reduced the size of the stomatal aperture. OGA not only inhibited light-induced stomatal opening, but also accelerated stomatal closing in both species; chitosan inhibited light-induced stomatal opening in tomato epidermis. The effects of OGA and chitosan were suppressed when EGTA, catalase, or ascorbic acid was present in the medium, suggesting that Ca(2+) and H(2)O(2) mediate the elicitor-induced decrease of stomatal apertures. We show that the H(2)O(2) that is involved in this process is produced by guard cells in response to elicitors. Our results suggest that guard cells infected by pathogens may close their stomata via a pathway involving H(2)O(2) production, thus interfering with the continuous invasion of pathogens through the stomatal pores.

Ascorbic Acid↗
PubMed1999

Acoustics of children's speech: developmental changes of temporal and spectral parameters.

Changes in magnitude and variability of duration, fundamental frequency, formant frequencies, and spectral envelope of children's speech are investigated as a function of age and gender using data obtained from 436 children, ages 5 to 17 years, and 56 adults. The results confirm that the reduction in magnitude and within-subject variability of both temporal and spectral acoustic parameters with age is a major trend associated with speech development in normal children. Between ages 9 and 12, both magnitude and variability of segmental durations decrease significantly and rapidly, converging to adult levels around age 12. Within-subject fundamental frequency and formant-frequency variability, however, may reach adult range about 2 or 3 years later. Differentiation of male and female fundamental frequency and formant frequency patterns begins at around age 11, becoming fully established around age 15. During that time period, changes in vowel formant frequencies of male speakers is approximately linear with age, while such a linear trend is less obvious for female speakers. These results support the hypothesis of uniform axial growth of the vocal tract for male speakers. The study also shows evidence for an apparent overshoot in acoustic parameter values, somewhere between ages 13 and 15, before converging to the canonical levels for adults. For instance, teenagers around age 14 differ from adults in that, on average, they show shorter segmental durations and exhibit less within-subject variability in durations, fundamental frequency, and spectral envelope measures.

Adolescent↗
PubMed1999

Receptor-mediated Moloney murine leukemia virus entry can occur independently of the clathrin-coated-pit-mediated endocytic pathway.

To investigate receptor-mediated Moloney murine leukemia virus (MoMuLV) entry, the green fluorescent protein (GFP)-tagged ecotropic receptor designated murine cationic amino acid transporter (MCAT-1) (MCAT-1-GFP) was constructed and expressed in 293 cells (293/MCAT-1-GFP). 293/MCAT-1-GFP cells displayed green fluorescence primarily at the cell membrane and supported wild-type levels of MoMuLV vector binding and transduction. Using immunofluorescence labeling and confocal microscopy, it was demonstrated that the surface envelope protein (SU) gp70 of MoMuLV virions began to appear inside cells 5 min after virus binding and was colocalized with MCAT-1-GFP. However, clathrin was not colocalized with MCAT-1-GFP, suggesting that MoMuLV entry, mediated by MCAT-1, does not involve clathrin. Double immunofluorescence labeling of SU and clathrin in 293 cells expressing untagged receptor (293/MCAT-1) gave the same results, i.e., SU and clathrin did not colocalize. In addition, we examined the transduction ability of MoMuLV vector on HeLa cells overexpressing the dominant-negative GTPase mutant of dynamin (K44A). HeLa cells overexpressing mutant dynamin have a severe block in endocytosis by the clathrin-coated-pit pathway. No significant titer difference was observed when MoMuLV vector was tranduced into HeLa cells overexpressing either wild-type or mutant dynamin, while the transduction ability of vesicular stomatitis virus glycoprotein pseudotyped vector into HeLa cells overexpressing mutant dynamin was decreased significantly. Taken together, these data suggest that MoMuLV entry does not occur through the clathrin-coated-pit-mediated endocytic pathway.

3T3 Cells↗
PubMed1999

Transcription-dependent nuclear-cytoplasmic trafficking is required for the function of the von Hippel-Lindau tumor suppressor protein.

Mutation of the von Hippel-Lindau tumor suppressor gene (vhl) causes the von Hippel-Lindau cancer syndrome as well as sporadic renal clear cell carcinoma. To pursue our study of the intracellular localization of VHL protein in relation to its function, we fused VHL to the green fluorescent protein (GFP) to produce the VHL-GFP fusion protein. Like VHL, VHL-GFP binds to elongins B and C and Cullin-2 and regulates target gene product levels, including levels of vascular endothelial growth factor and glucose transporter 1. VHL-GFP localizes predominantly to the cytoplasm, with some detectable nuclear signal. Inhibition of transcription by actinomycin D or 5,6-dichlorobenzimidazole riboside (DRB) causes VHL to be redistributed to the nucleus. A cellular fusion assay was used to demonstrate that inhibition of transcription induces a decrease in the nuclear export rate of VHL. The dependence of transcription for trafficking is lost with a deletion of exon 2, a region with a mutation causing a splice defect in the VHL gene in sporadic renal clear cell carcinoma. Addition of a strong nuclear export signal (NES) derived from the Rev protein results in complete nuclear exclusion and abrogates the redistribution of VHL-GFP-NES into the nucleus upon inhibition of transcription. Leptomycin B, which inhibits NES-mediated nuclear export, reverts the distribution of VHL-GFP-NES to that of VHL-GFP and restores sensitivity to actinomycin D and DRB. Uncoupling of VHL-GFP trafficking to transcription either by an exon 2 deletion or fusion to NES abolishes VHL function. We suggest that VHL function requires not only nuclear or cytoplasmic localization, but also exon 2-mediated transcription-dependent trafficking between these two cellular compartments.

Animals↗
PubMed1999

Determination of resonance frequency of the respiratory system in respiratory distress syndrome.

AIM: To measure tidal volume delivery produced by high frequency oscillation (HFO) at a range of frequencies including the resonance frequency. METHODS: Eighteen infants with respiratory distress syndrome were recruited (median gestation 28.7 weeks). Each was ventilated at frequencies between 8 and 30 Hertz. Phase analysis was performed at various points of the respiratory cycle. HFO was provided by a variable speed piston device. Resonance frequency was determined from the phase relation between the cyclical movements of the piston and pressure changes at the airway opening. Tidal volume was measured using a jacket plethysmograph. RESULTS: The results were most reproducible when analysis was performed at the end of inspiration (within 1 Hz in nine out of 10 cases). Comparison between tidal volume delivery at 10 Hz and resonance frequency was made in 10 subjects. Delivery was significantly higher at resonance than at 10 Hertz (mean percentage increase 92%, range 9-222%). CONCLUSIONS: These preliminary findings suggest that there is improved volume delivery at resonance frequency.

Airway Resistance↗
PubMed1999

Assessment of effect of nasal continuous positive pressure on laryngeal opening using fibre optic laryngoscopy.

AIM: To assess the effect of nasal continuous positive airways pressure (CPAP) on the dimensions of the laryngeal opening. METHODS: Nine preterm infants who had previously received ventilatory support for respiratory distress syndrome (RDS) were studied. All were receiving nasal CPAP. The laryngeal opening was visualised using a fibre optic video camera system. The ratio of width to length of the opening was measured on and off CPAP. RESULTS: In eight of the infants the width: length ratio increased on CPAP; mean change for group +24.4% (95% CI +11.9 to +37.9). CONCLUSIONS: Nasal CPAP seems to dilate the larynx. This may explain the selective beneficial effects of CPAP on mixed and obstructive apnoea.

Apnea↗
PubMed1999

Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion.

PURPOSE: Donor lymphocyte infusion (DLI) can restore complete remission in patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell-depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of salvage treatment for patients with DLI after TCD allogeneic BMT prompted an evaluation of overall outcome after CD6+ -TCD allogeneic BMT for patients treated during the time when DLI has been available. PATIENTS AND METHODS: We performed a retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic BMT for stable-phase CML and compared these outcomes with those of 40 patients who underwent non-TCD allogeneic BMT. All subjects were patients at one of two neighboring institutions during a period when DLI was available. All patients received marrow from HLA-identical sibling donors, underwent similar myeloablative regimens, and had similar pretreatment characteristics. RESULTS: After BMT, the TCD group had a lower incidence of grade 2 to 4 acute (15% v 37%, P = .026) and chronic graft-versus-host disease (GVHD) (18% v 42%, P = .024) than did the non-TCD group. The 1-year treatment-related mortality rates for the TCD group and the non-TCD group were 13% and 29%, respectively (P = .07). The estimated 3-year probability of relapse (cytogenetic or hematologic) was higher for patients in the TCD group than for patients in the non-TCD group (62% v 24%, P = .0003). Twenty-three patients (20 in the TCD group and three in the non-TCD group) received and were assessable for response to DLI. After DLI, 17 of 20 patients in the TCD group and two of three patients in the non-TCD group achieved complete remission. Donor lymphocyte infusion induced GVHD in nine of 23 patients. Thirty (65%) of 46 patients in the TCD group and 27 (69%) of 39 assessable patients in the non-TCD group remained alive without evidence of disease. The estimated 3-year overall survival rates were similar for the TCD group and the non-TCD group (72% v 68%, respectively; P = .38). At last follow-up, there was no difference in the overall prevalence of GVHD or the proportion of patients requiring immunosuppressive agents between groups. CONCLUSION: These results suggest that the combination of T-cell depletion and post-BMT DLI is a viable treatment option for patients undergoing allogeneic BMT for CML and should be prospectively compared with traditional forms of GVHD prophylaxis.

Adult↗