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Biomedical subjects

M K Hong

Publications and source records attributed to M K Hong.

144 records · Page 8Linked to original sources

Clinical significance of distal embolization after transluminal extraction atherectomy in diffusely diseased saphenous vein grafts.

Standard balloon angioplasty of degenerated saphenous vein graft lesions may be complicated by distal embolization, particularly in the presence of intragraft thrombus. Transluminal extraction atherectomy may be useful in this setting because of its ability to remove particulate debris. This study was designed to identify the incidence and prognostic significance of distal embolization after transluminal extraction atherectomy in high-risk saphenous vein graft lesions. To address these issues the clinical course of 65 consecutive patients (86 high-risk saphenous vein graft lesions) was reviewed after extraction atherectomy. Distal embolization occurred in 11 (12.8%) of 86 high-risk lesions. The majority (63.6%) of these episodes occurred after adjunct balloon dilatation following uncomplicated use of the extraction atherectomy catheter. Correlates of distal embolization included patient age and the presence of intragraft thrombus. Major in-hospital complications developed more often in patients with distal embolization (46% vs 2% in those without distal embolization, p < 0.001), resulting in a reduced procedural success rate in this group (55% vs 91%, p = 0.01). We conclude that the risk of distal embolization after saphenous vein graft angioplasty, although potentially reduced, is not eliminated with transluminal extraction atherectomy, particularly in lesions with superimposed thrombus.

Aged↗

Inhibition of platelet deposition and lysis of intracoronary thrombus during balloon angioplasty using urokinase-coated hydrogel balloons.

BACKGROUND: Conventional balloon angioplasty of intracoronary thrombus is associated with a high incidence of abrupt closure, distal embolization, and no-reflow phenomenon. The purpose of this study was to assess a new technique for treating intracoronary thrombus consisting of the local delivery of urokinase directly to the angioplasty site with urokinase-coated hydrogel balloons. METHODS AND RESULTS: We assessed local urokinase delivery using hydrogel balloons in four protocols. First, we evaluated the pharmacokinetics of urokinase delivery in vitro using 125I-labeled urokinase to measure drug loading onto hydrogel balloons, drug retention by the hydrogel polymer during blood exposure, and drug transfer from the balloon surface to the arterial wall during balloon dilatation. Second, we measured 125I-urokinase washoff from the hydrogel balloon in the intact circulation and intramural drug delivery during in vivo balloon angioplasty in 10 anesthetized New Zealand rabbits. Third, we assessed the effect of local urokinase delivery on 111In-labeled platelet deposition after balloon angioplasty in vivo in 13 porcine carotid or iliac arteries dilated with urokinase-coated balloons and compared them with contralateral control arteries dilated with saline-coated balloons. Finally, we determined the clinical efficacy of urokinase-coated balloons in 15 patients with intracoronary thrombus, including 7 who demonstrated abrupt thrombotic closure after conventional angioplasty. Between 241 and 1509 U urokinase could be loaded onto hydrogel balloons ranging in size from 2 to 8 mm. In vitro and in vivo studies demonstrated that hydrogel balloons absorbed significantly more urokinase and demonstrated less drug wash-off than nonhydrogel balloons (P < .01). Similarly, both in vitro and in vivo studies demonstrated urokinase transfer from the hydrogel to the arterial wall during balloon angioplasty, with greater intramural drug deposition with larger balloons (P < .01). Local urokinase delivery after in vivo porcine angioplasty decreased 111In-labeled platelet deposition by 47% compared with contralateral control vessels (P = .03). Use of urokinase-coated balloons in patients with intracoronary thrombus resulted in thrombus dissolution and reversal of abrupt closure in all cases, without evidence of distal embolization. CONCLUSIONS: With the use of hydrogel-coated balloons, urokinase can be delivered locally to an angioplasty site. This technique decreases platelet deposition after in vivo balloon angioplasty and is efficacious in treating intracoronary thrombus in patients, including those with abrupt thrombotic closure.

Adult↗

Acute myocardial infarction in the young adults.

A review was done on 631 patients with acute myocardial infarction who underwent coronary angiography within 30 days after onset of myocardial infarction at Yonsei University Severance Hospital from January, 1985, to August, 1993. The incidence of acute myocardial infarction in patients under 40 years of age was 10.3% (65/631). Acute myocardial infarction below the fourth decades was the predominant disease of men. Risk factor analysis revealed a history of cigarette smoking and hypercholesterolemia were more frequently found in the young patients, but a history of hypertension and diabetes were more frequently found in the elderly patients. Angiographically, the incidence of one vessel disease and normal or minimal lesion coronary anatomy were more frequent in the young patients and incidence of multi-vessel disease were more frequent in the elderly patients. Of the 65 patients under 40 with acute myocardial infarction, the patients with multi-vessel disease tended to have a history of diabetes mellitus in comparison with those with normal coronary anatomy or one vessel disease.

Adult↗

Feasibility and drug delivery efficiency of a new balloon angioplasty catheter capable of performing simultaneous local drug delivery.

BACKGROUND: Local drug delivery at angioplasty treatment sites may improve acute and long-term results after angioplasty. A new dual-purpose balloon angioplasty catheter containing intramural channels and exterior pores ('channeled balloon') was designed to allow local drug delivery at low pressure without jet streams during simultaneous balloon angioplasty. METHODS: Acute feasibility studies were performed in normal ex-vivo and in-vivo arteries (three canine arteries and three rabbits with normal iliac arteries), in which 2 ml of marker agents were locally infused at 2 atm during simultaneous angioplasty at 6 atm with the channeled balloon. Histology, radioactive counting, and autoradiography were performed to determine the intramural localization of the delivered markers. The in-vitro efficiency of acute local drug delivery was estimated in seven normal canine arteries by infusing 3H-heparin and radioactive counting. RESULTS: Histology revealed the presence of markers in the inner third of the media in all ex-vivo samples, and markers in all in-vivo iliac arteries except for one, whereas control segments had no intramural staining. Autoradiography documented transmural radioactive granules. Radioactive counts were 40- to 263-fold higher in those locally treated with the radioactive marker agent. Efficiency of the acute local delivery was estimated by dividing the actual counts by the expected counts; it ranged from 24 to 48%. CONCLUSION: This study demonstrates that the channeled balloon is capable of delivering drugs locally at low pressure in adequate concentrations during simultaneous high-pressure balloon angioplasty in normal arteries.

Angioplasty, Balloon, Coronary↗

The effect of porous infusion balloon-delivered angiopeptin on myointimal hyperplasia after balloon injury in the rabbit.

BACKGROUND: Angiopeptin, a synthetic somatostatin analogue, reduces myointimal hyperplasia after experimental balloon angioplasty when given subcutaneously. The feasibility and efficacy of a single dose of angiopeptin delivered locally via the Wolinsky porous balloon on myointimal hyperplasia were studied. METHODS AND RESULTS: Three rabbits received 125I-angiopeptin in the mid abdominal aorta via the Wolinsky balloon at 5 atm for 1 minute after balloon injury. Thirty minutes later, autoradiography demonstrated radioactivity in the media and the adventitia. Forty rabbits were divided equally into one control group receiving saline and three angiopeptin groups receiving 1, 10, or 100 micrograms/mL of angiopeptin delivered locally at 5 atm for 1 minute via the Wolinsky balloon into the mid abdominal aorta after balloon injury of the entire abdominal aorta. On day 21, the abdominal aortas were fixed in situ and harvested. There was no statistical difference in the amount of myointimal hyperplasia in the locally treated aorta in the angiopeptin groups compared with the control group. However, in the lower abdominal aorta, where balloon injury without local delivery was performed, there was a significant reduction of myointimal hyperplasia in the highest-concentration angiopeptin group (P < .001 versus the control group). Electron microscopy showed that the control animals had a pseudointima of smooth muscle cells throughout the aorta, whereas in all the angiopeptin-treated animals, endothelial cells were present at both locations. CONCLUSIONS: Angiopeptin can be delivered intramurally via the Wolinsky porous balloon and reduces myointimal hyperplasia only in the area distal to the local drug delivery site (downstream effect), possibly by healing the injured endothelium, by transport via the vasa vasora, and/or by systemic effect.

Amino Acid Sequence↗

Effects of estrogen replacement therapy on serum lipid values and angiographically defined coronary artery disease in postmenopausal women.

To examine the effects of estrogen replacement on lipids and angiographically defined coronary artery disease (CAD) in postmenopausal women, lipid profiles were obtained in 90 consecutive postmenopausal women undergoing diagnostic coronary angiography. Eighteen women (20%) were receiving estrogen and 72 (80%) were not. CAD (defined as greater than or equal to 25% luminal diameter narrowing in a major coronary artery) was present in only 22% of women (4 of 18) receiving estrogen and in 68% (49 of 72) who were not (p less than 0.001), with an odds ratio of 0.13. Mean high-density lipoprotein (HDL) cholesterol level was significantly higher (63 +/- 6 vs 48 +/- 2; p less than 0.01) and mean total/HDL cholesterol ratio significantly lower in women receiving estrogen than in those who were not (4.2 +/- 0.5 vs 5.1 +/- 0.2; p less than 0.05). The other lipid values were similar in both groups. On multiple logistic regression analysis, absence of estrogen use was the most powerful independent predictor of the presence of CAD (p less than 0.001), with total/HDL cholesterol ratio as the only other variable selected (p less than 0.01). Thus, among 90 consecutive postmenopausal women undergoing diagnostic coronary angiography, estrogen replacement therapy was associated with an 87% reduction in the prevalence of CAD, and those receiving estrogen had a significantly higher mean HDL cholesterol level and lower mean total/HDL cholesterol ratio.

Aged↗

Usefulness of the total cholesterol to high-density lipoprotein cholesterol ratio in predicting angiographic coronary artery disease in women.

To investigate the relation between lipids and angiographic coronary artery disease (CAD) in women, fasting lipid profiles were obtained on 108 women undergoing coronary angiography (group I). CAD, defined as greater than or equal to 25% luminal diameter narrowing in a major coronary artery, was present in 57 (53%). Neither serum total cholesterol nor triglyceride levels correlated with the presence of CAD. Mean total/high-density lipoprotein (HDL) cholesterol ratio was higher among women with than without CAD (5.5 +/- 0.3 vs 4.2 +/- 0.2, p less than 0.0001). Multiple regression analyses identified a higher total/HDL cholesterol ratio as the variable most predictive of the presence (p less than 0.001), extent (number of narrowed arteries) (p less than 0.0001), and severity (% maximum stenosis) (p less than 0.001) of CAD. Age and lack of estrogen use were also independently associated with the presence of CAD, age and low-density lipoprotein cholesterol level were additional indicators of extent, and age was the only other discriminator of severity of CAD. In 56 women with total cholesterol less than 200 mg/dl (group II), mean total/HDL cholesterol ratio was higher in women with (n = 24) than without CAD (4.3 +/- 0.2 vs 3.5 +/- 0.2, p = 0.01). Higher total/HDL cholesterol ratio was the variable most predictive of the presence of CAD (p = 0.01), and the lone variable associated with severity (p less than 0.001) after adjustment for other risk factors. Age was independently associated with presence and extent, and hypertension was also independently related to extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Conformational substates and motions in myoglobin. External influences on structure and dynamics.

Myoglobin, a simppe dioxygen-storage protein, is a good laboratory for the investigation of the connection between protein structure, dynamics, and function. Fourier-transform infrared spectroscopy on carbon-monoxymyoglobin (MbCO) shows three major CO bands. These bands are excellent probes for the investigation of the structure-function relationship. They have different CO binding kinetics and their CO dipoles form different angles with respect to the heme normal, implying that MbCO exists in three major conformational substates, A0, A1, and A3. The entropies and enthalpies of these substates depend on temperature above approximately 180 K and are influenced by pH, solvent, and pressure. These results suggest that even a protein as simple as Mb can assume a small number of clearly different structures that perform the same function, but with different rates. Moreover, protein structure and dynamics depend strongly on the interaction of the protein with its environment.

Fourier Analysis↗

Inhomogeneous broadening in spectral bands of carbonmonoxymyoglobin. The connection between spectral and functional heterogeneity.

The rebinding kinetics of CO to myoglobin after flash photolysis is nonexponential in time below approximately 180 K; the kinetics is governed by a distribution of enthalpic barriers. This distribution results from inhomogeneities in the protein conformation, referred to as conformational substates. Hole-burning experiments on the Soret and IR CO-stretch bands test the assumption that an inhomogeneous distribution of conformational substates results in inhomogeneously broadened spectra. CO was slowly photolyzed at different wavelengths in the Soret band at 10 K. Both the Soret band and the CO-stretch band A1, centered at 1,945 cm-1, shift during photolysis, demonstrating that different wavelengths excite different parts of the distributed population. We have also done kinetic hole-burning experiments by measuring peak shifts in the Soret and A1 bands as the CO molecules rebind. The shifts indicate that the spectral and enthalpic distributions are correlated. In the A1 band, the spectral and enthalpic distributions are highly correlated while in the Soret the correlation is weak. From the peak shifts in the spectral and kinetic hole-burning experiments the inhomogeneous broadening is estimated to be approximately 15% of the total width in the Soret band and approximately 60% in A1. We have previously measured the tilt angle alpha between the bound CO and the heme normal (Ormos, P., D. Braunstein, H. Frauenfelder, M. K. Hong, S.-L. Lin, T. B. Sauke, and R. D. Young. 1988. Proc. Natl. Acad. Sci. USA. 85:8492-8496) and observed a wave number dependence of the tilt angles within the CO-stretch A bands. Thus the spectral and enthalpic distributions of the A bands are coupled to a heterogeneity of the structure.

Binding Sites↗

Orientation of carbon monoxide and structure-function relationship in carbonmonoxymyoglobin.

Fourier transform infrared spectroscopy of the CO stretch bands in carbonmonoxymyoglobin (MbCO) reveals three major bands implying that MbCO exists in three major substates, A0, A1, and A3. After photolysis at low temperatures the CO is in the heme pocket, and the resulting CO stretch bands represent the B substates. Photoselection experiments determine the orientation of CO in the A (bound) and B (photolyzed) substates: Small fractions of MbCO are photolyzed at 10 K with linearly polarized light at 540 nm. The resulting linear dichroism in the A and B IR bands yields the tilt angle between the heme normal and CO. The average angles are as follows: alpha (A0) = 15 degrees +/- 3 degrees; alpha (A1) = 28 degrees +/- 2 degrees, and alpha (A3) = 33 degrees +/- 4 degrees. The A bands are inhomogeneously broadened; the angle alpha shows a wavenumber dependence within the A bands. The wavenumber dependence is interpreted as a distribution of the tilt angle within the individually inhomogeneous A substates, thus providing a structural parameter to characterize the distribution of the conformational substates. The B substates exhibit no induced linear dichroism; in the photolyzed substates the ligand is randomly oriented with respect to the heme plane. The present results together with earlier data on static and kinetic properties of CO binding to Mb establish relations among spectroscopic, structural, energetic, and functional parameters.

Carbon Monoxide↗

Ligand binding to synthetic mutant myoglobin (His-E7----Gly): role of the distal histidine.

Low-temperature flash photolysis with IR and visible spectroscopy was used to probe the influence of the distal histidine His-64(E7) of sperm-whale myoglobin (Mb) on the orientation of bound carbon monoxide (CO) and on the kinetics of CO rebinding. The synthesis and high-level expression of a sperm-whale myoglobin gene in Escherichia coli permits the efficient substitution of the distal histidine through site-directed mutagenesis. Substitution of His-E7 with glycine [GlyE7]Mb bound with CO (CO[GlyE7]Mb) results in one broad bound-CO IR stretch band, v(C-O), centered at 1973 cm-1 at 10 K, in contrast to three distinct bands for native and synthetic wild-type MbCO at 1966, 1945, and 1929 cm-1. After flash photolysis at 10 K, the unbound state of CO[GlyE7]Mb exhibits two CO stretch bands, whereas MbCO has three. Fourier transform IR spectroscopy measurements of the linear dichroism after photoselective flash photolysis of CO bound to [GlyE7]Mb at 10 K reveals the bound CO to be oriented at an angle of alpha = 20 degrees +/- 2 degrees with respect to the heme normal. Flash photolysis data from 10 to 300 K provide evidence for a larger distal pocket and a smaller enthalpy barrier (by approximately 4 kJ/mol) for [GlyE7]MbCO as compared with wild-type MbCO. These results reinforce the notion that the dominant control of the binding step at the heme iron comes from the proximal side through the protein structure.

Animals↗

Rebinding and relaxation in the myoglobin pocket.

The infrared stretching bands of carboxymyoglobin (MbCO) and the rebinding of CO to Mb after photodissociation have been studied in the temperature range 10-300 K in a variety of solvents. Four stretching bands imply that MbCO can exist in four substates, A0-A3. The temperature dependences of the intensities of the four bands yield the relative binding enthalpies and and entropies. The integrated absorbances and pH dependences of the bands permit identification of the substates with the conformations observed in the X-ray data (Kuriyan et al., J. Mol. Biol. 192 (1986) 133). At low pH, A0 is hydrogen-bonded to His E7. The substates A0-A3 interconvert above about 180 K in a 75% glycerol/water solvent and above 270 K in buffered water. No major interconversion is seen at any temperature if MbCO is embedded in a solid polyvinyl alcohol matrix. The dependence of the transition on solvent characteristics is explained as a slaved glass transition. After photodissociation at low temperature the CO is in the heme pocket B. The resulting CO stretching bands which are identified as B substates are blue-shifted from those of the A substates. At 40 K, rebinding after flash photolysis has been studied in the Soret, the near-infrared, and the integrated A and B substates. All data lie on the same rebinding curve and demonstrate that rebinding is nonexponential in time from at least 100 ns to 100 ks. No evidence for discrete exponentials is found. Flash photolysis with monitoring in the infrared region shows four different pathways within the pocket B to the bound substates Ai. Rebinding in each of the four pathways B----A is nonexponential in time to at least 10 ks and the four pathways have different kinetics below 180 K. From the time and temperature dependence of the rebinding, activation enthalpy distributions g(HBA) and preexponentials ABA are extracted. No pumping from one A substate to another, or one B substate to another, is observed below the transition temperature of about 180 K. If MbCO is exposed to intense white light for 10-10(3) s before being fully photolyzed by a laser flash, the amplitude of the long-lived states increases. The effect is explained in terms of a hierarchy of substates and substate symmetry breaking. The characteristics of the CO stretching bands and of the rebinding processes in the heme pocket depend strongly on the external parameters of solvent, pH and pressure. This sensitivity suggests possible control mechanisms for protein reactions.

Carbon Monoxide↗

Fourier-transform infrared difference spectroscopy of rhodopsin and its photoproducts at low temperature.

Fourier-transform infrared difference spectroscopy has been used to detect the vibrational modes in the chromophore and protein that change in position or intensity between rhodopsin and the photoproducts formed at low temperature (70 K), bathorhodopsin and isorhodopsin. A method has been developed to obtain infrared difference spectra between rhodopsin and bathorhodopsin, bathorhodopsin and isorhodopsin, and rhodopsin and isorhodopsin. To aid in the identification of the vibrational modes, we performed experiments on deuterated and hydrated films of native rod outer segments and rod outer segments regenerated with either retinal containing 13C at carbon 15 or 15-deuterioretinal. Our infrared measurements provide independent verification of the resonance Raman result that the retinal in bathorhodopsin is distorted all-trans. The positions of the C = N stretch in the deuterated pigment and the deuterated pigments regenerated with 11-cis-15-deuterioretinal or 11-cis-retinal containing 13C at carbon 15 are indicative that the Schiff-base linkage is protonated in rhodopsin, bathorhodopsin, and isorhodopsin. Furthermore, the C = N stretching frequency occurs at the same position in all three species. The data indicate that the protonated Schiff base has a C = N trans conformation in all three species. Finally, we present evidence that, even in these early stages of the rhodopsin photosequence, changes are occurring in the opsin and perhaps the associated lipids.

Animals↗

Novel application of breath-hold turbo spin-echo T2 MRI for detection of acute myocardial infarction.

To assess the clinical utility of the breath-hold turbo spin-echo T2-weighted MRI in patients with acute myocardial infarction, the results of MRI were compared with those of electrocardiography, coronary angiography, and thallium-201 single photon emission tomography (SPECT) in 23 patients and 5 healthy volunteers. To compare MRI and thallium-SPECT, the left ventricle was divided into five segments, and the presence of myocardial infarction was determined in each segment. MRI demonstrated an abnormally bright signal in 49 of 140 segments (five segments each from 23 patients and 5 volunteers); thallium-SPECT showed a fixed perfusion defect in 52 segments, for an 85% diagnostic concordance rate. The size of the myocardial infarction measured on MRI corresponded well to that measured on thallium-SPECT (r = .70, P < .01). Breath-hold turbo spin-echo T2 MRI can be used for detection of acute myocardial infarction in conjunction with thallium-SPECT, especially when accurate localization of lesion, increased spatial resolution, and anatomic landmarks are needed.

Coronary Angiography↗

Detection of human papillomavirus (HPV) in sinonasal inverted papillomas using polymerase chain reaction (PCR).

Paraffin-embedded tissues of 42 sinonasal inverted papillomas were subjected to polymerase chain reaction using type-specific primers pairs of HPV 6, 11, 16, 18, and 33. Two cases of HPV 11 and one of HPV 6 were amplified in 36 samples of benign inverted papilloma, and two cases of HPV 16 were amplified in five samples of inverted papilloma with co-existing squamous cell carcinoma. Inverted papillomas recurred in 1 (16%) of 6 cases exhibiting dysplasia, and in 3 (10%) of 30 cases not exhibiting dysplasia. Inverted papillomas also recurred in 2 (66%) of 3 cases positive for HPV, and in 2 (6%) of 33 cases negative for HPV. These results suggest that HPV may be involved in the pathogenesis of inverted papillomas, may cause malignant transformation of inverted papillomas, and that there may be an apparent relationship between HPV infection and the recurrence of sinonasal inverted papillomas.

Adult↗

[Stent coated with bovine pericardium: in vitro evaluation, in animals, and initial results in humans].

Covering a stent with a membrane (stent graft) allows treatment of diverse coronary abnormalities such as aneurysms, rupture and fistulas (which, until recently, required surgical therapy). A stent graft could also reduce embolic complications associated with angioplasty of saphenous vein grafts. The objective of this study is to evaluate bovine pericardium as a graft for conventional stents. In vitro testing of the bovine pericardium disclosed an elasticity of 15% and a resistance to rupture of 0.22 kg/mm2, well above the pressure commonly used during stent deployment. In 18 pigs, 29 of 32 (90.63%) attempts to implant stent grafts were successful. Histology of acute porcine studies revealed correct apposition of the stent graft to the vessel wall, subacute and chronic (10 days and 1 month) samples showed adequate endothelization and exclusion of proliferative media. Twenty stents were placed in 15 patients with a 100% success rate. Seven patients had coronary aneurysms and in all a complete exclusion of the aneurysm was obtained without complications. Fourteen patients have a follow-up of 6 or more months with evidence of clinical restenosis in 2 (14.28%), whereas angiographic follow-up in 9 patients, which included the 2 cases with recurrent angina, evidenced restenosis in 3 of 14 stents (21.4%), two of which were overlapped in the LAD of one patient and one corresponded to a series of 9 stents (in 5 patients) placed in saphenous vein grafts. It is concluded that bovine pericardium is a suitable material for stent-grafts and its efficacy to seal coronary aneurysms was demonstrated. These results warrant a larger comparative study to better define its restenosis rate and further delineate its usefulness in the treatment of diseased saphenous vein grafts.

Animals↗

Analysis of 2,2,2-trifluoroethyl derivatives of carboxylic acid herbicides by gas chromatography with mass-selective and electron capture detection.

A method for derivatizing carboxylic acid herbicides with 2,2,2-trifluoroethanol (TFE) in preparation for gas chromatographic (GC) analysis was developed. Esterification efficiency was determined by GC with electron capture detection (ECD), and esters were identified by GC with mass-selective detection (MSD). On the basis of reaction temperature for optimum esterification efficiency, 13 common carboxylic acid herbicides were separated into 2 groups before reaction with TFE. TFE derivatization was optimized for simultaneous analyses by altering reaction temperature, re action time, and concentration of sulfuric acid in reaction solutions. The method is simple, safe, and economical, and it gives good resolution without a laborious cleanup. Recovery of 13 analytes from water, taken from a pesticide residue well, was greater than 80% for all except 2 analytes. The well-water was fortified with analytes at the lower microgram-per-liter concentrations required for detection of pesticide residues in potable water systems. The method can simultaneously determine multiple herbicide residues in water samples with a high degree of accuracy and precision.

Carboxylic Acids↗