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Biomedical subjects

R K Lee

Publications and source records attributed to R K Lee.

At least 19 recordsLinked to original sources
PubMed2001

Is suicide contagious? A study of the relation between exposure to the suicidal behavior of others and nearly lethal suicide attempts.

This study sought to determine the association between nearly lethal suicide attempts and exposure to the suicidal behavior of parents, relatives, friends, or acquaintances and to accounts of suicide in the media. The authors conducted a population-based case-control study in Houston, Texas, from November 1992 through July 1995. They interviewed 153 victims of attempted suicide aged 13--34 years who had been treated at emergency departments in Houston and a random sample of 513 control subjects. After controlling for potentially confounding variables, the authors found that exposure to the suicidal behavior of a parent (adjusted OR = 1.5; 95% CI: 0.6, 3.6; p = 0.42) or a nonparent relative (adjusted OR = 1.2; 95% CI: 0.7, 2.0; p = 0.55) was not significantly associated with nearly lethal suicide attempts. Both exposure to the suicidal behavior of a friend or acquaintance (adjusted OR = 0.6; 95% CI: 0.4, 1.0; p = 0.05) and exposure to accounts of suicidal behavior in the media (adjusted OR = 0.2; 95% CI: 0.1, 0.3; p = 0.00) were associated with a lower risk of nearly lethal suicide attempts. Exposure to accounts of suicidal behavior in the media and, to a lesser extent, exposure to the suicidal behavior of friends or acquaintances may be protective for nearly lethal suicide attempts, but further research is needed to better understand the mechanisms underlying these findings.

Adolescent↗
PubMed2001

The Mauthner cell and other identified neurons of the brainstem escape network of fish.

This paper reviews the development of our research on the motor consequences of Mauthner cell function and related brainstem neurons. These cells activate fast-start responses such as seen in fishes escaping from predatory attacks. Our goal was to devise a neuroethological theory of fish escape that accurately reconciled the underlying neural function with a correct concept of the motor act. The identified neuron concept of invertebrates greatly influenced the initial studies. Horseradish peroxidase technology allowed us and other workers to identify principal neurons in the brainstem escape system. Digital imaging technology permitted adequate kinematic characterization of the behavior. Resulting experiments showed that Mauthner system demonstrates two general principles of motor organization: (1) the Mauthner cell is a command-like higher order neuron that serially outputs to a lower level central pattern generator; and (2) the Mauthner cell participates in a larger parallel, brainstem escape network. In this network, we showed that the spatio-temporal pattern of activity codes the timing and magnitude of agonist and antagonist trunk muscle contractions during the behavior. Because the approach angle of the stimulus determines these parameters, we were able to discover the overall sensorimotor relationship between stimulus angle and motor output. This relationship is given as a set of descriptive equations written in terms of stimulus angle, magnitude and timing variables of trunk muscle contractions, and resulting escape trajectory. The equations unify the apparent variability of C-start movement patterns into a single, quantitative theory. Recent studies by other workers show how this concept can make accurate predictions about the underlying neural processes, even at the level of the single, identified cell.

Animals↗
PubMed2001

In vivo hatching phenomenon of mouse blastocysts during implantation.

PURPOSE: To determine whether the blastocyst zona shedding process within the murine uterine cornus in vivo is due to a global lytic process caused by uterine proteolytic enzyme, or is triggered by the blastocyst hatching process as observed in vitro. METHODS: Fifty-one female ICR mice aged 5-8 weeks were used for this study. From 8:00 p.m. of the 4th day postcoitus to 7:00 p.m. of the 5th day postcoitus, the uterine cornua of 51 mice were isolated at 30-min intervals. Blastocysts within the uterine cornua were flushed out with a balanced solution under the dissecting microscope. The stages of blastocyst development and the proportion of hatching or hatched blastocysts and the discarded zona pellucida (ZP) were inspected and counted. RESULTS: A total of 672 blastocysts were recovered from the uterine horns of the 51 mice. They were divided into six groups according to the blastocyst developmental stages (before or after ZP escape; before or after the initiation of implantation). Group I represents the earliest embryonic stage and Group VI represents the most advanced blastocyst developmental stage during the peri-implantation period. The empty ZP recovery rates (number of discarded ZP/all hatched blastocysts) were 52.3%, 21.5%, 17.2%, 6.6%, 1.6%, and 0% in Groups I-VI, respectively. Five hatching blastocysts out of 199 embryos in Group I were found and a 100% of ZP recovery rate was obtained from 6 of 19 mice in Groups I and II. CONCLUSIONS: The present study shows that active blastocyst hatching occurs in vivo because both hatching blastocysts and empty ZP can be found within the uterine cornua of ICR mice before implantation. The empty ZP recovery rate declined significantly, along with a progression of embryo development and implantation, implying that intrauterine zona lytic activity occurs during the peri-implantation stage.

Animals↗
PubMed2001

General pharmacology of IY-81149, a new proton pump inhibitor.

IY-81149 (2-[(4-methoxy-3-methyl)-2-pyridinyl]methylsulfinyl -5-(1H-pyrrol-1-yl)-1H-benzimidazole, CAS 172152-36-2) is a new proton pump inhibitor and expected to be an antiulcer drug. Its general pharmacological effects were studied in this paper. The doses given were vehicle control, 0.3, 1, 3, 100, 300 and 1000 mg/kg and were administered orally. The animals used in this study were mouse, rat, guinea pig and beagle dog. IY-81149 decreased spontaneous locomotor activity at 1000 mg/kg and showed a weak effect in motor performance at 300 and 1000 mg/kg. IY-81149 prolonged the hexobarbital-induced sleeping time dose dependently at 100, 300 and 1000 mg/kg. Oral administration of IY-81149 caused a dose-dependent hypothermic effect up to 300 mg/kg and showed analgesic effect at 1000 mg/kg. IY-81149 produced an antisecretory effect in pylorus ligated rats. The total gastric volume and acidity were significantly decreased at doses ranging from 1 to 3 mg/kg. However, IY-81149 had no effects on general behavior, did not show anticonvulsant activity, and did not affect blood pressure and heart rate, LVP (left ventricular peak systolic pressure), LVEDP (left ventricular end diastolic pressure), LVDP (left ventricular developing pressure), DP (double product), HR (heart rate), CFR (coronary flow rate), smooth muscle contraction, respiration, intestinal transport and renal function. These findings demonstrate that IY-81149 possesses weak central nervous system action and inhibitory effects on microsomal enzymes and gastric secretion after single administration. The results suggest that IY-81149 does not exert any notable pharmacological effects on the cardiovascular system, autonomic nerve system or smooth muscle function at all doses tested.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Alcohol consumption and nearly lethal suicide attempts.

We conducted a case-control study of the association between nearly lethal suicide attempts and facets of alcohol consumption; namely, drinking frequency, drinking quantity, binge drinking, alcoholism, drinking within 3 hours of suicide attempt, and age began drinking. Subjects were 13-34 years of age. In bivariable analyses, all measures were associated with nearly lethal suicide attempts. Odds ratios ranged from 2.4 for alcoholism to 7.0 for drinking within 3 hours of attempt. All exposure variables except age began drinking exhibited a J-shaped relationship between alcohol exposure and nearly lethal suicide attempt. After controlling for potential confounders and other measures of alcohol exposure, drinking within 3 hours of attempt remained most strongly (odds ratios > 6) associated. Alcoholism remained significantly associated in most models, but at lower strength.

Adolescent↗
PubMed2001

The influence of geographic mobility on nearly lethal suicide attempts.

Teenagers and young adults are very mobile and mobility has been identified as a potential risk factor for suicidal behavior. We conducted a population-based, case-control study of nearly lethal suicide attempts with 153 cases and 513 controls. Study participants were asked about changing residence over the past 12 months. Results indicate that moving in the past 12 months is positively associated with a nearly lethal suicide attempt (adjusted odds ratio of 2.1, with 95% confidence interval of 1.4-3.3), as are specific characteristics of the move (e.g., frequency, recency, distance, and difficulty staying in touch). These findings confirm and extend prior ecologic research by demonstrating a relationship, at the individual level, between the geographic mobility of adolescents and young adults and nearly lethal suicide attempts.

Adolescent↗
PubMed2001

An unmatched case-control study of nearly lethal suicide attempts in Houston, Texas: research methods and measurements.

This article details the research methods and measurements used in conducting a population-based, case-control study of nearly lethal suicide attempts among persons aged 13-34 years, residing in Houston, Texas. From November 1992 to July 1995, we interviewed 153 case subjects presenting at one of three participating hospital emergency departments and used random digit dialing to identify 513 control subjects residing in the same catchment area in which cases were enlisted. Unlike most research in this area, this study was designed to extend our understanding of suicidal behavior and prevention activities beyond identification and treatment of depression and other mental illnesses. We discuss the overall strengths and weaknesses of our study design and conclude that this methodology is well suited for studying rare outcomes such as nearly lethal suicide.

Adolescent↗
PubMed2000

Identification of a novel platelet-derived growth factor-like gene, fallotein, in the human reproductive tract.

We isolated the cDNA of a novel platelet-derived growth factor-like gene from human endometrium. The gene was named fallotein; it was 3007 bases in length, and encoded a protein of 345 amino acids. Antiserum against the fallotein protein can recognize a specific protein in the fallopian tube, with a molecular size in accordance with the anticipated size of fallotein. Fallotein mRNA is expressed in two molecular sizes, 3.8 and 2.9 kb, with the former being more abundant. High expression of the gene was found in the prostate, testis, and uterus. A weaker expression signal was found in the spleen, thymus, and small intestine, but expression of fallotein in the colon and peripheral blood leukocytes was negligible.

Amino Acid Sequence↗
PubMed2000

Amyloid precursor protein and membrane phospholipids in primary cortical neurons increase with development, or after exposure to nerve growth factor or Abeta(1-40).

We examined the relationships between membrane phospholipid levels, the secretion and expression of the amyloid precursor protein (APP), and the responses of both to nerve growth factor (NGF), Abeta(1-40) or Abeta(40-1) in developing cortical neurons cultured from rat embryos. Neuronal membrane phospholipid levels per cell, and phosphatidylcholine, phosphatidylserine, phosphatidylinositol and phosphatidylethanolamine increased individually between the first and seventh days of culturing. The amounts of APP holoprotein and APP mRNAs in the cells, as well as the amounts of soluble APP (APPs) secreted by them, also increased during neuronal development in vitro. The increases in APPs exceeded the increases in APP which, in turn, exceed those in phospholipid levels. The levels of APP holoprotein, but not of phospholipids, increased when neurons were grown in a choline-free medium, suggesting that increases in APP are not sufficient to stimulate changes in membrane phospholipids. Treatment of neuron cultures for four days with NGF or Abeta(1-40), but not with Abeta(40-1), dose-dependently increased membrane phospholipids, tau and GAP-43, as well as APP holoprotein and secreted APPs. These results indicate that agents, like NGF or Abeta(1-40), which enhance membrane phospholipid levels may promote neurite formation, APP expression and APPs secretion in primary neuronal cultures.

Amyloid beta-Peptides↗
PubMed2000

Choline plus cytidine stimulate phospholipid production, and the expression and secretion of amyloid precursor protein in rat PC12 cells.

The amyloid precursor protein (APP) is a transmembrane protein anchored in the membrane lipid bilayer. Choline and cytidine are major precursors of cell membranes, and are regulatory elements in membrane biosynthesis. We examined the levels of cellular APP holoprotein and secreted APPs when rat PC12 cells are stimulated to undergo increase in membrane phospholipids by choline+cytidine (2+2, 5+5, 10+10 or 50+50 microM) treatment. We now show that as phospholipids levels are increased by supplemental choline and cytidine treatment, the levels of cell-associated APP also rise stoichiometrically; these treatments also caused major (up to 6. 8-fold) increases in the amounts of secreted APP released into the cell medium, and also stimulated increased process formation. These results show that choline plus cytidine increase both phospholipid levels, and the expression and secretion in PC12 cells. It appears that agents that stimulate cellular membrane biosynthesis may be used to stimulate the secretion of neurotrophic APPs and neurite formation in neurodegenerative disorders such as Alzheimer's disease.

Alzheimer Disease↗
PubMed2000

Embryonic dormancy phenomenon in obstructed healthy mouse fallopian tubes.

PURPOSE: A mouse model of unilateral oviductal obstruction was designed to study whether healthy oviducts can support embryo development in an advanced stage toward blastocyst hatching and implantation when the embryos in the contralateral side normally move into the uterine cavity. METHODS: The oviducts of 80 female ICR mice (aged 5-8 weeks) were ligated unilaterally 12-40 hr postcoitus. The ligated oviducts were isolated from day 4 to 19.5 postcoitus. Embryos within the ligated oviducts were then flushed out to record the developmental stage and compared with the conceptuses in the contralateral uterine horns with unligated oviducts. Embryos recovered from ligated oviducts were then cultured in vitro to observe their potential for further development. RESULTS: In 33 mice, 53.4% (163/305) and 86.1% (241/280) of the morphologically normal blastocysts had hatched from the zona pellucida within the obstructed tube and contralateral uterine horns, respectively, on the 5th day postcoitus. The data demonstrated that the hatching process could take place within the obstructed fallopian tube, but the timing was delayed. From 5.5 to 19.5 days postcoitus, a total of 362 implanted embryos were obtained in unligated control uterine horns, but none of the 404 embryos in the artificially obstructed oviducts were implanted. The embryos within the ligated tubes were dormant in the hatched blastocyst stage as demonstrated by their ability to continue growing (98.2%) when removed from the oviduct to an in vitro environment. CONCLUSIONS: In this study, we demonstrate that mouse embryos can hatch, although delayed, in obstructed healthy oviducts. Tubal pregnancy is not likely to happen in artificially obstructed healthy mouse fallopian tubes, since all the viable embryos were dormant at the hatched blastocyst stage.

Animals↗
PubMed2000

The effects of brief gamete co-incubation in human in vitro fertilization.

PURPOSE: To investigate whether very short exposure of mature oocytes to sperm in vitro may affect the fertilization rates, embryo cleavage rates, and embryo quality between sibling oocytes in the same patient. METHODS: Sibling oocytes of the same patient from 23 oocyte collection cycles were randomly allocated to the study group, with a 1-hr or 3-hr sperm-oocyte incubation, or the control group with the standard overnight gamete co-incubation. The fertilization rates, cleavage rates, and subsequent embryo quality were evaluated. RESULTS: Our results showed no statistically significant differences in fertilization rates, embryo cleavage rates, and quality of the embryos between the study group and the control group. CONCLUSIONS: Since the present study showed that long exposure of the oocyte to sperm has no advantage over short exposure, we prefer shortening the oocyte-sperm incubation period for reducing the negative effect induced by nonphysiologically high concentrations of spermatozoa.

Female↗
PubMed2000

Regulation of APP synthesis and secretion by neuroimmunophilin ligands and cyclooxygenase inhibitors.

We and others previously showed that both the synthesis of the amyloid precursor protein (APP) and its processing (i.e., to amyloidogenic A beta peptides; soluble nonamyloidogenic APPs; and other APP fragments) are regulated by neurotransmitters. Transmitters that elevate cellular cAMP levels (like norepinephrine and prostaglandins, which act on beta-adrenergic receptors and prostaglandin E2 receptors respectively) enhance APP synthesis and the formation of amyloidogenic APP holoprotein. Transmitters that stimulate phosphatidylinositol hydrolysis (by activating muscarinic m1 or m3 receptors, serotoninergic 5HT2a or 5HT2c receptors, or metabotropic glutamate receptors of subtypes 1 or 5) increase the conversion of APP to soluble APPs, and decrease the formation of A beta. These findings suggest that drugs that regulate the activity of neurotransmitter receptors might be useful in preventing the excessive formation of A beta or other amyloid precursors in Alzheimer's disease. We now show that neuroimmunophilin ligands (like cyclosporin A or FK-506) and nonsteroidal antiinflammatory agents (NSAIDs), including cyclooxygenase (COX)-2 inhibitors, can also prevent APP overexpression and the overproduction of amyloidogenic peptides. We observe that the enhancement of APP overexpression by prostaglandin E2 is inhibited by neuroimmunophilin ligands like cyclosporin A or FK-506 (tacrolimus). We also find that the NSAIDs, which reduce prostaglandin synthesis by inhibiting COX-1 and -2 enzymes, might also be expected to lower APP levels. Our present data confirm that these drugs, as well as drugs that selectively inhibit COX-2, reduce the levels of amyloidogenic APP holoprotein in cultured neurons or in cultured astrocytes. We previously showed that elevations in cAMP, perhaps generated in response to prostaglandins, can suppress APPs secretion. The NSAIDs and COX inhibitors also increased levels of soluble APPs in the media of cultured astrocytes and neurons, perhaps acting by inhibition of prostaglandin production. Since APP holoprotein can be amyloidogenic, while APPs may be neurotrophic, our findings suggest that some neuroimmunophilin ligands, NSAIDs and COX-2 inhibitors might suppress amyloid formation and enhance neuronal regeneration in Alzheimer's disease.

Alzheimer Disease↗
PubMed1999

Azidothymidine and interferon-alpha induce apoptosis in herpesvirus-associated lymphomas.

Lymphoproliferative diseases that occur in immunocompromised patients are frequently associated with herpesviruses. These patients often fare poorly after treatment with conventional chemotherapy. We reported previously that patients with AIDS-related Burkitt's lymphoma (BL) responded to parenteral azidothymidine (AZT) and IFN-alpha. We found that EBV-positive lymphoma cells derived from these patients cultured with AZT express CD95 and undergo apoptosis. AZT-mediated apoptosis was caspase dependent and occurred despite Fas receptor blockade. In contrast, EBV-negative lymphomas were resistant to AZT-induced apoptosis, as were EBV-positive lymphomas that expressed high levels of bcl-2. Primary effusion lymphoma (PEL) cell lines infected with human herpesvirus type 8 required IFN-alpha to potentiate AZT-induced apoptosis. IFN-alpha did not up-regulate CD95 in BL or PEL but did induce expression of the death receptor ligand, CD95 ligand. AZT-sensitive lymphomas also accumulated significantly higher intracellular AZT monophosphate than did resistant lymphomas. Our data demonstrated distinct apoptotic responses to AZT and IFN-alpha in herpesvirus-associated lymphomas. EBV-positive BL cells that expressed low BCL-2 levels were sensitive to AZT alone; PEL cells required the addition of IFN-alpha to enhance apoptosis, and EBV-negative lymphomas were insensitive to both agents. AZT-sensitive BL cells transfected with BCL-2 became resistant. Susceptibility to antivirus-mediated apoptosis may be exploited to improve the therapy of certain herpesvirus-associated lymphomas.

Apoptosis↗
PubMed1999

Intracellular and cell-surface distribution of amyloid precursor protein in cortical astrocytes.

Amyloid peptides that aggregate to form plaques in Alzheimer's disease are derived from secretory processing of the amyloid precursor protein (APP). Transport of APP to the cell surface may be prerequisite for non-amyloidogenic APP processing and the secretion of soluble APP (APPs), while missorting or reinternalization of APP to intracellular compartments can promote amyloid formation. In cultured astrocytes, APP mRNA and holoprotein are increased by elevations in cAMP levels, and 8-Bromo-cAMP promotes process formation on these cells. We now report that treatment of cultured astrocytes with 8-Bromo-cAMP increased intracellular and cell surface APP in the soma and perinuclear region as detected by immunolabeling with monoclonal antibody 22C11 and polyclonal antibody Kunitz-type protease inhibitor (KPI) (against the N-terminus and KPI domain of APP, respectively) and led to intense but discontinuous labelling of APP on the surface of astrocytic processes. Northern and Western blot analyses confirmed that 8-Bromo-cAMP treatment of cultured astrocytes also increased APP mRNA and KPI-containing APP holoprotein, implying that the intense APP immunolabeling observed in 8-Bromo-cAMP treated astrocytes was not derived from truncated forms of APP (e.g., APPs), but reflected high levels of APP holoprotein containing intact amyloid peptides. Discontinuous cell surface staining in process-bearing astrocytes may be caused by miscompartmentalization of APP related to rearrangement of the cytoskeleton. Inasmuch as intracellular APP is not accessible for non-amyloidogenic processing, we suggest that the increased immunoreactivity of intracellular APP in process-bearing astrocytes may predispose the cells to increased amyloid production.

8-Bromo Cyclic Adenosine Monophosphate↗