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Biomedical subjects

J H Bae

Publications and source records attributed to J H Bae.

At least 55 records · Page 3Linked to original sources

Neuroprotection in relation to retinal ischemia and relevance to glaucoma.

Management of glaucoma is directed at the control of intraocular pressure (IOP), yet it is recognized now that increased IOP isjust an important risk factor in glaucoma. Therapy that prevents the death of ganglion cells is the main goal of treatment, but an understanding of the causes of ganglion cell death and precisely how it occurs remains speculative. Present information supports the working hypothesis that ganglion cell death may result from a particular form of ischemia. Support for this view comes from the fact that not all types of retinal ischemia lead to the pathologic findings seen in glaucomatous retinas or to cupping in the optic disk area. Moreover, in animal experiments in which ischemia is caused by elevated IOP, a retinal abnormality similar to that seen in true glaucoma is produced, whereas after occlusion of the carotid arteries a different pattern of damage is found. In ischemia, glutamate is released, and this initiates the death of neurons that contain ionotropic glutamate (NMDA) receptors. Elevated glutamate levels exist in the vitreous humor of patients with glaucoma, and NMDA receptors exist on ganglion cells and a subset of amacrine cells. Experimental studies have shown that a variety of agents can be used to prevent the death of retinal neurons (particularly ganglion cells) induced by ischemia. These agents are generally those that block NMDA receptors to prevent the action of the released glutamate or substances that interfere with the subsequent cycle of events that lead to cell death. The major causes of cell death after activation of NMDA receptors are the influx of calcium into cells and the generation of free radicals. Substances that prevent this cascade of events are, therefore, often found to act as neuroprotective agents. For a substance to have a role as a neuroprotective agent in glaucoma, it would ideally be delivered topically to the eye and used repeatedly. It is, therefore, of interest that betaxolol, a beta-blocker presently used to reduce IOP in humans, also has calcium channel-blocking functions. Moreover, experimental studies show that betaxolol is an efficient neuro protective agent against retinal ischemia in animals, when injected directly into the eye or intraperitoneally.

Adrenergic beta-Antagonists↗

Long-distance PCR-based screening for large rearrangements of the LDL receptor gene in Korean patients with familial hypercholesterolemia.

BACKGROUND: The LDL receptor is a cell-surface protein that regulates plasma cholesterol by specific uptake of LDL particles from the blood circulation. Familial hypercholesterolemia (FH) results from defective catabolism of LDL, which is caused by mutations in the LDL-receptor gene. METHODS: For the rapid and reliable detection of large rearrangements in the LDL-receptor gene, we established a screening method based on long-distance PCR as an alternative to Southern-blot hybridization. Using long-distance PCR, 45 unrelated Korean subjects heterozygous for FH were screened to assess the frequency and nature of major structural rearrangements in the LDL-receptor gene. RESULTS: Two different deletion mutations, FH6 (same type as FH3 and FH311) and FH 32, were detected in four families by long-distance PCR. Detailed restriction mapping and sequence analysis showed that FH6 was a 5.71-kb deletion extending from intron 8 to intron 12 and that FH32 was a 2-kb deletion extending from intron 6 to intron 7. Sequence analysis for the breakpoints of all deletions detected in Korean FH patients showed that only the left arms of the Alu repetitive sequences were involved in the deletion event. CONCLUSIONS: The screening method based on long-distance PCR provides a powerful strategy for the detection of large rearrangements in the LDL-receptor gene and is a rapid and reliable screening alternative to Southern-blot hybridization.

Base Sequence↗

A case of aortocoronary dissection as a complication during a percutaneous transluminal coronary angioplasty (PTCA).

We report a case of aortocoronary dissection during a percutaneous transluminal coronary angioplasty (PTCA) which resulted from an antegrade and also a progressively retrograde extension of the coronary dissection into the Sinus of Valsalva and the ascending aorta. It was successfully treated with stenting without an operation, resulting in optimal coronary blood flow and diminution of the aortic dissection.

Angioplasty, Balloon, Coronary↗

Brain-derived neurotrophic factor rapidly potentiates synaptic transmission through NMDA, but suppresses it through non-NMDA receptors in rat hippocampal neuron.

Brain-derived neurotrophic factor (BDNF) rapidly enhances synaptic transmission among the hippocampal neurons. In order to examine which component of glutamate receptors participates in synaptic potentiation by BDNF, we have studied the effect of glutamate antagonists on excitatory postsynaptic currents (EPSCs) enhanced by BDNF, using cultured embryonic hippocampal neurons. In the presence of AP5, a N-methyl-D-aspartate (NMDA) antagonist, BDNF depressed the EPSCs. In contrast, BDNF enhanced the EPSCs in the presence of a non-NMDA antagonist CNQX. Our results suggest that BDNF acutely activates synaptic transmission via NMDA, but suppresses it via non-NMDA receptors in the hippocampus.

2-Amino-5-phosphonovalerate↗

Reduced dihydroxyacetone sensitivity and normal sensitivity to glyceraldehyde and oxidizing agent of ATP-sensitive K+ channels of pancreatic beta cells in NIDDM rats.

The inhibition of ATP-sensitive K+(KATP) channels in pancreatic beta cells is a key step of insulin secretion induced by glucose. Glucose-induced insulin secretion from the beta cells is selectively impaired in patients with noninsulin-dependent diabetes mellitus (NIDDM) and in animal models of it. In order to clarify the site of this abnormal glucose response, we studied the effects of insulin secretagogues and sulfhydryl oxidizing agent, 2,2'-dithio-bis (5-nitropyridine) (DTBNP), on KATP channels in single beta cells of neonatally streptozotocin-induced NIDDM rats. We used the patch-clamp technique in cell-attached mode (Vpipette = 0 mV). The inhibitory response to glucose of KATP channels was lacking in NIDDM rats, indicating reduced sensitivity to glucose of the channels. Glyceraldehyde (2-5 mM) in the diabetic beta cells elicited the same KATP channel inhibition as that obtained in controls. In contrast, dihydroxyacetone (DHA, 2-10 mM) sensitivity of KATP channels was significantly reduced in the beta cells of NIDDM rats. KATP channels in the diabetic beta cells were rapidly inhibited by 50 microM DTBNP, just as in the normal beta cells, suggesting that KATP channel function was normal. This indicates that one of the sites responsible for impaired glucose-induced insulin secretion in the pancreatic beta cells of NIDDM rats is located in the glycerol phosphate shuttle.

Adenosine Triphosphate↗

Biphasic modifying effect of indole-3-carbinol on diethylnitrosamine-induced preneoplastic glutathione S-transferase placental form-positive liver cell foci in Sprague-Dawley rats.

The biphasic modifying effects of indole-3-carbinol (I3C), a naturally occurring constituent of edible cruciferous vegetables, on the development of glutathione S-transferase placental form (GST-P)-positive liver cell foci were investigated by using a medium-term liver bioassay system and a newborn rat hepatocarcinogenesis system. In Experiment 1, a total of 65 male Sprague-Dawley (SD) rats were divided into 5 groups. Animals were given a single intraperitoneal (i.p.) injection of 200 mg/kg diethylnitrosamine (DEN) dissolved in saline for groups 1, 2, and 3 or a single i.p. injection of saline for groups 4 and 5. Group 1 was given the diet containing 0.25% I3C for 2 weeks prior to DEN initiation and then basal diet for 8 weeks. Group 2 was given basal diet for 4 weeks prior to and after DEN initiation and then the diet containing 0.25% I3C for 6 weeks. The rats of group 3 were placed on basal diet during the experiment. Animals of groups 4 and 5 were treated in the same manner as those of groups 1 and 2 except for injection with saline instead of DEN solution. All rats were subjected to two-thirds partial hepatectomy at week 3 and were killed at week 8 after DEN or saline injection. In Experiment 2, a total of 45 female SD rats were dosed with DEN (100 mg/kg, i.p.) or saline at 24 h after birth. After weaning at week 3, the rats were fed diet containing 0.25% I3C for 9 weeks and then were killed at week 12. In Experiment 1, preinitiation exposure to 0.25% I3C caused a significant decrease in numbers of GST-P-positive liver cell foci (P < 0.05), while postinitiation exposure to 0.25% I3C caused significant increases in both number (No./cm2) and area (mm2/cm2) of GST-P-positive liver cell foci (P < 0.05 or 0.01). In Experiment 2, the relative liver weight in the DEN + I3C group was significantly increased (P < 0.001). The numbers and areas of GST-P-positive liver cell foci in the DEN + I3C group were significantly increased as compared to the values of the DEN-alone group (P < 0.001). These results clearly demonstrated that I3C exerts a promoting effect on the postinitiation stage as well as an inhibitory effect on the preinitiation stage in the medium-term liver bioassay.

Animals↗

Identification of a high-affinity glycine betaine transport system in Staphylococcus aureus.

Staphylococcus aureus accumulates proline and glycine betaine when cells are grown at low water activity. In the present study, we have identified a high-affinity glycine betaine transport system in this bacterium. Optimal activity for this transport system was measured in the presence of high NaCl concentrations, but transport activity was not stimulated by high concentrations of other solutes.

Betaine↗

Search for the heparin antithrombin III-binding site precursor.

The last step of heparin biosynthesis is thought to involve the action of 3-O-sulfotransferase resulting in the formation of an antithrombin III (ATIII) binding site required for heparin's anticoagulant activity. The isolation of a significant fraction of heparin chains without antithrombin III-binding sites and having low affinity for ATIII suggests the presence of a precursor site, lacking the 3-O-sulfate group. Porcine mucosal heparin was depolymerized into a mixture of oligosaccharides using heparin lyase. One of these oligosaccharides was derived from heparin's ATIII-binding site. In an effort to find the ATIII-binding site precursor, the structures of several minor oligosaccharides were determined. A greater than 90% recovery of oligosaccharides (on a mole and weight basis) was obtained for both unfractionated and affinity-fractionated heparins. An oligosaccharide arising from the ATIII-binding site precursor was found that comprised only 0.8 mol % of the oligosaccharide product mixture. This oligosaccharide was only slightly enriched in heparin having a low affinity for ATIII and only slightly disenriched in high affinity heparin. The small number of these ATIII-binding site precursors, found in unfractionated and fractionated heparins, suggests the existence of a low ATIII affinity heparin may not simply be the result of the incomplete action of 3-O-sulfotransferase in the final step in heparin biosynthesis. Rather these data suggest that some earlier step, involved in the formation of placement of these precursor sites, may be primarily responsible for high and low ATIII affinity heparins.

Animals↗

Identification of two proline transport systems in Staphylococcus aureus and their possible roles in osmoregulation.

The food-borne pathogen Staphylococcus aureus is distinguished from other food-borne pathogens by its ability to grow at water activity values below 0.90. Previous studies have indicated that proline accumulation mediated by transport represents a primary osmoregulatory strategy utilized by this bacterium (C. B. Anderson and L. D. Witter, Appl. Environ, Microbiol. 43:1501-1503, 1982; I. Koujima, H. Hayashi, K. Tomochika, A. Okabe, and Y. Kanemasa, Appl. Environ. Microbiol. 35:467-470, 1978; K. J. Miller, S. C. Zelt, and J.-H. Bae, Curr. Microbiol. 23:131-137, 1991). In this study, we demonstrate the presence of two proline transport systems within whole cells of S. aureus, a high-affinity transport system (Km, 7 microM) and a low-affinity transport system (Km, 420 microM). Our results indicate that the low-affinity proline transport system is osmotically activated and is the primary system responsible for the accumulation of proline by this pathogen during growth at low water activity.

Betaine↗

A simple noninvasive measurement of stenotic mitral valve area: an alternative approach using M-mode and Doppler echocardiography.

Doppler echocardiography is a widely used noninvasive technique to examine the mitral valve area (MVA) by obtaining mitral pressure half-time (PHT) and to assess the severity of the stenosis. However, several hemodynamic factors influence the PHT and may render the PHT data inaccurate in any measurement of MVA under certain conditions. Using a simple echo-Doppler (E-D) method, we assessed the MVA in a physiological equation. The mitral flow volume (MFV) is represented by MVA x transmitral mean flow velocity (mV) x diastolic filling time (DFT). Thus, the formula can be restated as MVA (cm2) = MFV (cm3)/mV (cm/sec) x DFT (sec). We measured MFV by M-mode, and mV and DFT by continuous wave Doppler echocardiography. This formula was tested in 43 patients with isolated mitral stenosis. MVA was obtained by the PHT and E-D methods, and the data obtained were validated against the results of cardiac catheterization. The results obtained using the E-D method showed much better correlation (r = 0.82) with those of catheterization than those with the PHT method (r = 0.52). The inter- and intraobserver variabilities were checked. The results obtained with the E-D method were found to be reproducible. To further validate the accuracy of the E-D method, MVA was measured by both methods at different R-R intervals after exercise and the results were compared. The MVA obtained by the PHT method showed marked variations; whereas, that obtained by the E-D method remained nearly constant. Similarly, in a patient with atrial fibrillation, the MVA assessed by the PHT method varied from beat to beat; whereas, the fluctuations in MVA were minimal using the E-D method. We concluded that the E-D method can be reliable and clinically easily applicable for the accurate assessment of MVA.

Adult↗

Modifying responses of allyl sulfide, indole-3-carbinol and germanium in a rat multi-organ carcinogenesis model.

The modifying potential of allyl sulfide (AS), indole-3-carbinol (I3C) and carboxyethylgermanium sesquioxide (GE) on lesion development was examined in a wide-spectrum initiation model. Groups 1-4 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, i.p., single dose), N-methylnitrosourea (MNU) (20 mg/kg, i.p., four doses at days 2, 5, 8 and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Groups 5-7 received vehicles without carcinogens during the initiation period. Group 8 served as the untreated control. After this initiating procedure, groups 2-7 were administered a diet containing 0.5% AS or I3C and 0.05% GE. All surviving animals were killed 40 weeks after the beginning of the experiment and the target organs were examined. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with all three compounds. AS treatment significantly decreased the incidence of hepatic hyperplastic nodules, adenoma of the lung and thyroid, and papillary or nodular hyperplasia of the urinary bladder. Administration of GE also significantly inhibited the development of hepatic nodules and adenoma of the lung and thyroid. However, I3C only inhibited the hyperplastic nodules of the liver. These results demonstrated that this multi-organ initiation model could be useful in confirming organ-specific modification potential and, in addition, the inhibitory effect of AS, I3C and GE on liver, lung, thyroid and urinary bladder carcinogenesis.

Allyl Compounds↗

Different modifying responses of capsaicin in a wide-spectrum initiation model of F344 rat.

The modifying potential of capsaicin (CAP) on lesion development was examined in a rat multiorgan carcinogenesis model. Groups 1 and 2 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, ip, single dose at commencement), N-methylnitrosourea (MNU) (20 mg/kg, ip, 4 doses at days 2, 5, 8, and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Group 3 received vehicles without carcinogens during the initiation period. Group 4 served as the untreated control. After this initiating procedure, Groups 2 and 3 were administered a diet containing 0.01% CAP. All surviving animals were killed 20 weeks after the beginning of the experiment and the target organs examined histopathologically. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with CAP. CAP treatment significantly decreased the incidence of adenoma of the lung but increased the incidence of papillary or nodular (PN) hyperplasia of the urinary bladder. The tumor incidence of other organs, such as the kidney and thyroid, was not significantly different from the corresponding controls. These results demonstrated that concurrent treatment with CAP not only can inhibit carcinogenesis but can also enhance it depending on the organ. Thus, this wide-spectrum initiation model could be used to confirm organ-specific modification potential and, in addition, demonstrate different modifying effects of CAP on liver, lung, and bladder carcinogenesis.

Animals↗

The frequency distribution of cardiovascular diseases in 13 hospital admitted patients in Korea. Korean Society of Circulation.

The frequency distribution of cardiovascular disease are changing recently due to the development of living environment. Unfortunately there are few epidemiological studies of cardiovascular diseases in general population, we tried to estimate the recent trend of cardiovascular diseases studying hospitalized patients in nationwide 13 large hospitals during a year of 1985. The hypertensive disease (24.1%) was the most common cardiovascular disease and the next were cerebrovascular disease (15.8%), arrhythmias (12.2%), ischemic heart disease (9.7%), congenital heart disease (9.1%), and rheumatic heart disease (5.4%) in order. This results showed that hypertensive disease and cerebrovascular disease are still the major cardiovascular disease and ischemic heart disease and arrhythmias are increased. But chronic rheumatic heart disease is declined compared with previous studies in hospitalized patients.

Adolescent↗

In vitro study of the pressure-velocity relation across stenotic orifices.

In a hand-driven, pulsatile in vitro model, the pressure-velocity relation across stenotic orifices was studied from simultaneous measurements recorded over a wide range of pressure and across different-sized orifices, individually and paired. Velocity spectra were recorded with continuous-wave Doppler ultrasound. In a rigid, noncompliant system, integrated instantaneous maximal velocities precisely register simultaneous integrated pressure gradients without measureable phase shift. Across stenotic orifices of 5 to 10 mm in diameter, the pressure-velocity relation is independent of orifice size for pressures extending from -30 to +240 mm Hg. The relation is quadratic and crosses 0. In this model, application of the simplified Bernoulli equation transforms the relation from curvilinear to linear with a bias toward the derived-pressure axis. In the presence of 2 different-sized orifices, the pressure-velocity relation remains constant, with a given pressure producing 2 identical velocities.

Animals↗

Left ventricular stroke volume determinations from radionuclide ventriculograms: the effects of photon attenuation.

To improve the accuracy of scintigraphic ventricular volume determination, which is limited by photon attenuation between the heart and the gamma camera, a method was developed for directly measuring the photon attenuation of radioactivity delivered as a bolus through a Swan-Ganz catheter into the right atrium. Comparison of the count rate recovered from this bolus with the total ex vivo measured activity determined by imaging an aliquot of the administered activity allowed calculation of the attenuation factor. Left ventricular stroke volumes determined scintigraphically by the count method in gated blood pool studies and then corrected with this attenuation factor correlated well with stroke volumes determined from thermodilution cardiac output and heart rate (r = 0.92; SEE, 6.1 ml). The agreement between the two measurements was markedly less when an average attenuation factor was employed for correction of scintigraphic volumes (r = 0.52; SEE, 14.8 ml). The results indicate that correction for photon attenuation is needed for accurate measurement of left ventricular volumes. Correction of left ventricular counts based on body weight or body surface area improves the accuracy of volume estimates.

Adult↗