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Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 199 records · Page 11Linked to original sources

Implications of prenatal ultrasound screening in the incidence of major genitourinary malformations.

PURPOSE: During the last 3 decades infant mortality has decreased nearly 50%. While neonatal intensive care deserves much of the credit, the recent increase in prenatal ultrasound from 33% of pregnancies in 1980 to 78% in 1987 has improved early detection. We evaluate the impact of prenatal ultrasound on major genitourinary malformations. MATERIALS AND METHODS: Data obtained from the Malformations Surveillance Program at Brigham and Women's Hospital between 1974 and 1994 tracked 163,431 pregnancies and termination rates of fetuses with spina bifida, bladder exstrophy, the prune belly syndrome and posterior urethral valves. RESULTS: Hospital data revealed that pregnancy was electively terminated due to spina bifida in 65% of cases, posterior urethral valves in 46%, the prune belly syndrome in 31% and exstrophy in 25%. CONCLUSIONS: Clearly, surveillance programs and improved accuracy of prenatal ultrasound have allowed early diagnosis of major genitourinary malformations. Many factors influence decision making in these affected fetal cases, including the financial and emotional impact of these major anomalies during lifetime. Future societal decisions and reduction in these anomalies may influence our training programs, manpower needs, medical facility requirements and character of our practices. These findings may have significant implications in the field of pediatric urology.

Abortion, Eugenic↗

Ultrasonographic observation of intestinal mobility of dogs after acupunctural stimulation on acupoints ST-36 and BL-27.

objectives of this study were to observe normal peristalsis and mixing (or segmental movements) and to evaluate an acupuncture stimulation (ST-36 and BL-27) on the intestinal (duodenum) motility in normal dogs using duplex Doppler sonography. Fifteen healthy Beagle dogs were used for this experiment after the administration of warm saline and pellet feeding. The duodenal motility was examined using duplex Doppler sonography. Six hours after the pellet feeding, an electroacupuncture stimulation at ST-36 and BL-27 was applied and the duodenal motility was examined using duplex Doppler sonography pre-stimulation, during the stimulation and post-stimulation. After saline and pellet administration, the duplex Doppler sonograms showed 3 types of peristalsis and a mixing type (or segmental movement) of duodenum motility. In the peristalsis types, most yielded high-amplitude signals which had one high peak (type-1), two high peaks (type-2), and three high peaks (type-3) and lasted more than 1.3 seconds. Mixing type of duodenum motility had weak signals and were lasted more than 1.5 seconds. Among the peristalsis types, the type 1 and type 2 were predominant and the type 3 was rarely observed. The frequency of intestinal motility stimulated by ST-36 acupoint was increased during the acupuncture stimulation (20% increase compared to the basal value) and decreased (7% decrease compared to the basal value) after stimulation. The frequency of intestinal motility stimulated by BL-27 acupoint was decreased during the acupuncture stimulation (31% decrease compared to the basal value) and increased (18% increase compared to the basal value) after stimulation. There was a significant increase between the value found in during and the post-stimulation tests. We conclude that duplex Doppler studies permit a graphic visualization of intestinal movements which can be qualitatively and quantitatively analyzed using this technique, it is possible to evaluate the gastrointestinal motility after an acupuncture

Acupuncture Points↗

Fas-mediated apoptosis and expression of related genes in human malignant hematopoietic cells.

Fas transduces apoptotic signals upon cross-linking with the Fas ligand (FasL), which is experimentally replaced by agonistic anti-Fas monoclonal antibodies (mAb). Of eight human malignant hematopoietic cell lines (HL-60, KG-1, THP-1, K562, U937, Jurkat, IM-9, RPMI-8226) examined by flow cytometric analysis, all, except K562, were found to be positive for surface Fas antigen. However, despite surface Fas expression, the agonistic anti-Fas mAb (7C11) induced apoptosis in only three of seven Fas-expressing cell lines (KG-1, Jurkat and IM-9). This Fas-resistance did not correlated with high levels of mRNA either for DcR3, a decoy receptor for FasL, or for FAP-1, a Fas-associated phosphatase that can block the apoptotic function of Fas. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not show consistent differences in the expression of Bcl-2 and Bax between Fas-sensitive and Fas-resistant cell lines examined. These findings indicated that the presence or absence of mRNA expression of DcR3, FAP-1, Bcl-2 and Bax did not always correlate with relative sensitivity to Fas-mediated apoptosis. Treatment of cells with cycloheximide converted the phenotype of resistant cell lines from Fas-resistant to Fas-sensitive, and enhanced the sensitivity of Fas-sensitive cell lines. These results suggest that the Fas-resistance is dependent on the presence of labile proteins that determine resistance to Fas-mediated apoptosis and the apoptotic machinery is already in place in Fas-resistant cell lines.

Apoptosis↗

Diurnal changes in pore water sulfide concentrations in the seagrass Thalassia testudinum beds: the effects of seagrasses on sulfide dynamics.

The dynamics of the seagrass-sulfide interaction were examined in relation to diel changes in sediment pore water sulfide concentrations in Thalassia testudinum beds and adjacent bare areas in Corpus Christi Bay and lower Laguna Madre, Texas, USA, during July 1996. Pore water sulfide concentrations in seagrass beds were significantly higher than in adjacent bare areas and showed strong diurnal variations; levels significantly decreased during mid-day at shallow sediment depths (0-10 cm) containing high below-ground tissue biomass and surface area. In contrast, diurnal variations in sediment sulfide concentrations were absent in adjacent bare patches, and at deeper (>10 cm) sediment depths characterized by low below-ground plant biomass or when the grasses were experimentally shaded. These observations suggest that the mid-day depressions in sulfide levels are linked to the transport of photosynthetically produced oxygen to seagrass below-ground tissues that fuels sediment sulfide oxidation. Lower sulfide concentrations in bare areas are likely a result of low sulfate reduction rates due to low organic matter available for remineralization. Further, high reoxidation rates due to rapid exchange between anoxic pore water and oxic overlying water are probably stimulated in bare areas by higher current velocity on the sediment surface than in seagrass beds. The dynamics of pore water sulfides in seagrass beds suggest no toxic sulfide intrusion into below-ground tissues during photosynthetic periods and demonstrate that the sediment chemical environment is considerably modified by seagrasses. The reduced sediment sulfide levels in seagrass beds during photosynthetic periods will enhance seagrass production through reduced sulfide toxicity to seagrasses and sediment microorganisms related to the nutrient cycling.

Journal Article↗

Noncovalent thrombin inhibitors incorporating an imidazolylethynyl P1.

A series of noncovalent tripeptidic thrombin inhibitors incorporating a unidazolylethynyl moiety at P1 was investigated. A number of compounds of this series were highly potent and selective versus trypsin, and several compounds demonstrated good oral absorption in rats (F = 58% for compound 19).

Acetylene↗

Identification and purification of an intrinsic human muscle myogenic factor that enhances muscle repair and regeneration.

The limited ability of damaged muscle to regenerate after gross injuries is a major clinical problem. To date, there is no effective therapeutic treatment for muscle injuries. In the present study, we have examined the ability of crude and fractionated human skeletal muscle extracts to promote myogenic cell proliferation and differentiation. It was found that the crude muscle extract could significantly stimulate BrdU incorporation in C2C12 myogenic cell line. In addition, the extract also promoted myogenic cell alignment and fusion. Using electrophoresis techniques, in conjunction with in vitro refolding technique, a protein with molecular weight of approximately 40 kDa was identified that could produce the same effects as the crude muscle exdtract. We also tested the ability of semipurified (30-50 kDa) muscle extract to promote muscle repair in adult rats. Surgical intervention was used to induce muscle damage in the tibialis anterior. The semipurified muscle extract (fraction H) was injected subcutaneously over the tibialis anterior for a period of 5 days. It was found that the damaged muscle fibers were replaced by newly regenerated muscle fibers. These newly regenerated fibers originated from the fusion of differentiated satellite cells as revealed by BrdU-labeling analysis. In contrast, the injury site of muscles treated with BSA control protein contained mainly fibroblasts.

Adult↗

Identification of the self-interaction of rat TCTP/IgE-dependent histamine-releasing factor using yeast two-hybrid system.

To further understand the biological function of translationally controlled tumor protein (TCTP), also known as IgE-dependent histamine-releasing factor (HRF), the yeast two-hybrid system was used to screen interacting molecules. We isolated cDNA clones coding for TCTP/HRF, suggesting that it may have a self-interacting property. Domain mapping of the interaction revealed that the C-terminal region of residue 126-172 is involved in self-interaction. The self-interacting property of TCTP/HRF was further supported by FPLC gel-filtration chromatography and coimmunoprecipitation analysis from transfected COS-7 cells. Our data suggests that TCTP/HRF may have a potential to self-interact through the C-terminal region, and the self-interaction property may be related to its biological function.

Animals↗

Analysis of the MRP4 drug resistance profile in transfected NIH3T3 cells.

BACKGROUND: Multidrug resistance-associated protein (MRP) 1 and canalicular multispecific organic anion transporter (cMOAT or MRP2) are adenosine triphosphate-binding cassette transporters that confer resistance to anticancer agents. In addition to these two transporters, there are at least four other human MRP subfamily members (MRP3 through MRP6). We and others reported previously that MRP3 is capable of conferring resistance to certain anticancer agents. In this study, we investigated whether MRP4 (MOAT-B), whose transcript accumulates to the highest levels in prostate tissue, has the capacity to confer drug resistance. METHODS: MRP4-transfected NIH3T3 cells were generated, and their drug sensitivity was analyzed. The subcellular localization of MRP4 was assessed by immunohistochemical analysis in transfected cells and in prostate tissue. Statistical tests were two-sided. RESULTS: MRP4 was detected as a 170-kd protein that was localized in the plasma membrane and cytoplasm of transfected cells. The MRP4 transfectants displayed 5.5-fold increased resistance to methotrexate in short-term drug-exposure assays (P=.022) and exhibited decreased cellular accumulation of this agent at 4 hours (P=.006) and 24 hours (P<.001). In continuous-exposure assays, however, the MRP4 transfectants did not display increased resistance for either methotrexate or natural product cytotoxic agents (anthracyclines, etoposide, vinca alkaloids, and paclitaxel [Taxol]). However, the transfectants did show increased resistance (2.3-fold) for the anti-acquired immunodeficiency syndrome nucleoside analogue 9-(2-phosphonylmethoxyethyl)adenine (PMEA) (P=.022) in continuous-exposure assays. Consistent with MRP4's plasma membrane localization in transfected cells, analysis of prostate tissue showed that MRP4 protein was localized primarily in the basolateral plasma membranes of tubuloacinar cells. CONCLUSIONS: These results indicate that MRP4 confers resistance to short-term methotrexate and continuous PMEA treatment. Given its structure, drug resistance profile and subcellular localization, MRP4 probably functions as an amphipathic anion efflux pump whose substrate range includes glutamate and phosphate conjugates.

3T3 Cells↗

Synthesis of Highly Charged, Monodisperse Polystyrene Colloidal Particles for the Fabrication of Photonic Crystals.

We have developed a series of emulsion polymerization recipes for the synthesis of highly charged, monodisperse polystyrene colloids of diameters between 100-400 nm. These spherical colloidal particles were crosslinked with divinyl benzene and functionalized with 1-allyloxy-2-hydroxypropane sulfonate. These highly charged, monodisperse colloidal particles readily self-assemble into robust three-dimensionally ordered crystalline colloidal arrays (CCAs). These CCAs operate as photonic crystals that Bragg diffract light in the ultraviolet, visible, and infrared regions of the spectrum. Copyright 2000 Academic Press.

Journal Article↗

The endoribonuclease activity of mammalian IRE1 autoregulates its mRNA and is required for the unfolded protein response.

The unfolded protein response (UPR) is a signal transduction pathway that is activated by the accumulation of unfolded proteins in the endoplasmic reticulum (ER). In Saccharomyces cerevisiae the ER transmembrane receptor, Ire1p, transmits the signal to the nucleus culminating in the transcriptional activation of genes encoding an adaptive response. Yeast Ire1p requires both protein kinase and site-specific endoribonuclease (RNase) activities to signal the UPR. In mammalian cells, two homologs, Ire1 alpha and Ire1 beta, are implicated in signaling the UPR. To elucidate the RNase requirement for mammalian Ire1 function, we have identified five amino acid residues within IRE1 alpha that are essential for RNase activity but not kinase activity. These mutants were used to demonstrate that the RNase activity is required for UPR activation by IRE1 alpha and IRE1 beta. In addition, the data support that IRE1 RNase is activated by dimerization-induced trans-autophosphorylation and requires a homodimer of catalytically functional RNase domains. Finally, the RNase activity of wild-type IRE1 alpha down-regulates hIre1 alpha mRNA expression by a novel mechanism involving cis-mediated IRE1 alpha-dependent cleavage at three specific sites within the 5' end of Ire1 alpha mRNA.

Amino Acid Sequence↗

Expression of translationally controlled tumor protein mRNA in human colon cancer.

The translationally controlled tumor protein (TCTP) was first identified as a tumor-associated protein. Here we described the expression profile of TCTP mRNA using a panel of normal human tissues. We also investigated the cell-cycle-dependent expression of the TCTP mRNA using synchronized cultures of Saccahromyces cerevisiae. The TCTP gene was constantly expressed through the yeast cell cycle. The expression of TCTP mRNA from three human colon carcinoma cell lines and their tumors xenografted in a nude mouse was studied. Our data imply that the TCTP is a housekeeping gene and that its deregulation may be involved in the tumor development of colon carcinoma.

Adenocarcinoma↗

Effects of mutation at a conserved N-glycosylation site in the bovine retinal cyclic nucleotide-gated ion channel.

Bovine retinal cyclic nucleotide-gated (CNG) ion channel contains an evolutionary conserved N-glycosylation site in the external loop between the fifth transmembrane segment and the pore-forming region. The effect of tunicamycin treatment and the site-specific mutation suggested that the channel is glycosylated when expressed in Xenopus oocytes. To test the role of glycosylation in this channel, N-glycosylation was abolished by mutation, and the detailed permeation and the gating characteristics of the mutant channel were investigated. The charge contribution turned out to be detectable, although the mutation of the N-glycosylation site did not affect expression and functionality of the CNG channel in oocytes.

Amino Acid Sequence↗

Characteristics of levan fructotransferase from Arthrobacter ureafaciens K2032 and difructose anhydride IV formation from levan.

A microorganism producing levan fructotransferase was isolated from sugar-disclosed soil and it was identified as Arthrobacter ureafaciens. The major product from levan by enzyme reaction was identified as di-D-fructofuranose 2,6':6,2' dianhydride by mass spectrometry, nuclear magnetic resonance, and chemical analyses. Small amounts of several oligosaccharides and free fructose were also formed by enzyme reaction. An extracellular enzyme that produces di-D-fructofuranose 2,6':6,2' dianhydride from levan was purified from the culture broth of A. ureafaciens K2032. The enzyme had optimum activity around pH 5.8 and 45 degrees C and had a dimeric form in solution. The N-terminal amino acid residues of the purified enzyme were SAPGSLRAVYHMTPPSGXLXDPQ. The enzyme has narrow substrate range and converts the levan to di-D-fructofuranose 2,6':6,2' dianhydride with around 62.5% conversion yield.

Journal Article↗

Interconnected feedback loops in the Neurospora circadian system.

In Neurospora crassa, white collar 1 (WC-1), a transcriptional activator and positive clock element, is rhythmically expressed from a nonrhythmic steady-state pool of wc-1 transcript, consistent with posttranscriptional regulation of rhythmicity. Mutations in frq influence both the level and periodicity of WC-1 expression, and driven FRQ expression not only depresses its own endogenous levels, but positively regulates WC-1 synthesis with a lag of about 8 hours, a delay similar to that seen in the wild-type clock. FRQ thus plays dual roles in the Neurospora clock and thereby, with WC-1, forms a second feedback loop that would promote robustness and stability in this circadian system. The existence also of interlocked loops in Drosophila melanogaster and mouse clocks suggests that such interlocked loops may be a conserved aspect of circadian timing systems.

Amino Acid Sequence↗