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Biomedical subjects

Y S Jang

Publications and source records attributed to Y S Jang.

35 records · Page 2Linked to original sources

Coronary stenting (Cordis) without anticoagulation.

We evaluated the effect of antithrombotic regimens on subacute thrombosis and short-term clinical courses after successful implantation of the Cordis coronary stent, which is a flexible, balloon expandable, radiopaque tantalum stent. Two hundred seventy-five consecutive patients with 290 lesions were treated with 356 Cordis stent implantations. According to poststent antithrombotic regimen, patients were divided into 3 groups; 165 patients with 175 lesions received aspirin 200 mg/day, ticlopidine 500 mg/day, and warfarin for 1 month (group 1), 66 patients with 69 lesions received aspirin and ticlopidine (group 2), and 44 patients with 46 lesions received aspirin alone (group 3) after successful Cordis stenting. The overall procedural success rates were 97.7% in group 1, 98.6% in group 2, and 100% in group 3. More than 65% of the patients were eligible for elective stenting. The overall rate of stent thrombosis was 1.8%: 1.2% in patients assigned to the treatment with aspirin, ticlopidine, and warfarin; 0% in patients with aspirin and ticlopidine; and 6.8% in patients assigned to the treatment with aspirin alone. In conclusion, the Cordis coronary stent is an effective endovascular stent in various clinical indications including unstable angina and acute myocardial infarction. Antiplatelet therapy using aspirin and ticlopidine after successful Cordis coronary stenting is a promising alternative to anticoagulation therapy to overcome the drawbacks of stenting. However, poststent antithrombotic therapy with aspirin alone is associated with a significant rate of stent thrombosis.

Anticoagulants↗

Role of a C-terminal residue of an immunodominant epitope in T cell activation and repertoire diversity.

In the present study, the extent of heterogeneity in the high responder T cell response to the predominant epitope region of hen egg white lysozyme (HEL46-61) was examined. Through analyses of T cell proliferation and precursor frequency, the C3H T cell response is shown not to be limited to peptides containing the previously defined minimal epitope of residues 52-61, but rather is quite heterogeneous, encompassing much of the 46-61 sequence. Further characterization using a panel of T cell hybridoma clones revealed T cell recognition of diverse minimal epitopes within this region. Interestingly, these T hybridomas could be grouped into three distinct categories based on the ability to respond to peptides with or without the native arginine residue at position 61 (61-required, 61-inhibitory, dual responders). Using analogue peptides containing single amino acid substitutions at position 61, further heterogeneity within these hybridoma groups was identified, suggesting the presence of an extremely diverse T cell repertoire for the epitope region. The charge and/or size of the C-terminal residue appears to be a critical factor for certain clones; replacement of the native arginine residue with aspartic acid or glutamic acid enabled a nonstimulatory ligand to specifically antagonize a T cell hybridoma response. Collectively, these results strongly suggest that the C-terminal residue of the predominant epitope in high responder mice plays a critical role in T cell diversity and activation.

Amino Acid Sequence↗

Colorectal cancer in familial adenomatous polyposis.

PURPOSE: This study was performed to determine the relationship among surgical treatment, colorectal cancer, and outcome in patients with familial adenomatous polyposis (FAP). METHODS: Records of 115 patients with FAP who underwent surgery at The Mount Sinai Medical Center between 1947 and 1994 were retrospectively reviewed. Patients without cancer were compared with those with colorectal cancer at initial surgery and with patients who developed rectal cancer following colectomy. RESULTS: Thirty-one patients (27 percent) had colorectal cancer at the time of initial surgery (colon = 24; rectal = 7). Another 11 patients (26 percent) developed rectal cancer after colectomy with ileorectal anastomosis (IRA). Mean age of patients with colorectal cancer at initial surgery was significantly higher than those without cancer (P < 0.01). Patients who developed rectal cancer after IRA were significantly older than patients with colorectal cancer at initial surgery (P < 0.01). All patients with rectal cancer after IRA had advanced disease with either nodal or distant metastases at the time of diagnosis. CONCLUSIONS: Colorectal cancer remains a major problem in the treatment of patients with FAP. Nearly one-fourth of these patients have colorectal cancer at initial operation, and one-fourth of patients with IRA develop rectal cancer after a mean follow-up of 13 years. Patients with rectal cancer following IRA are more likely to have advanced tumors than patients with colorectal cancer at initial operation. The high incidence and late stage of rectal cancer detected while under surveillance after IRA supports excision of the entire colorectal mucosa as the treatment of choice for most patients with FAP.

Adenomatous Polyposis Coli↗

T cell epitope recognition involved in the low-responsiveness to a region of hen egg lysozyme (46-61) in C57BL/6 mice.

The predominant T cell epitope of hen egg lysozyme (HEL) in high-responder C3H mice has been previously identified as the HEL 46-61 region. In contrast, this region is poorly recognized by T cells from low-responder C57BL/6 mice upon immunization with HEL. In previous studies, we have demonstrated that several C57BL/6 derived T cell hybridomas reactive to this epitope and other HEL epitopes preferentially recognize phosphorylcholine (PC)-conjugated HEL over unconjugated HEL. To understand the mechanisms involved in this difference of T cell recognition, we have further analysed the reactivity of T cells and T cell hybridomas from low-responder C57BL/6 mice. T cells from HEL-immunized mice were preferentially reactive to HEL 47-60. These results suggest a potential deficiency in generating an appropriate T cell epitope from the 46-61 region of native HEL in low-responder C57BL/6 mice. The minimal T cell epitope of this region was defined as HEL 51-60 using the PCH4.1 T hybridoma clone. This minimal epitope represents a single amino acid shift from the minimal epitope of HEL high-responder C3H mice (HEL 52-61). Various peptides representing this region were synthesized with single alanine substitutions at each position. The residues at positions 51, 52, 53 and 57 of HEL appear to be involved in Ia binding and the residues at 55 and 56 in contracting the TCR. T cell reactivity to HEL 51-61 peptides with various substitutions at position 61 strongly suggest that primarily the size of the C-terminal residue interferes with binding to the Ia molecules of low-responder mice. In addition, substitutions of the TCR contacting residues at positions 55 and 56 with similar residues (isoleucine-->leucine or leucine-->isoleucine) significantly increased the T cell reactivity, suggesting a low reactivity with the native residues. Therefore, the requirement of many residues in the T cell epitope for interaction with Ia, the necessity for additional Ag processing to facilitate Ia binding, and the low affinity of the TCR contacting residues may together render C57BL/6 mice unresponsive to the HE 46-61 region.

Animals↗

Collateral circulation in total occlusion of the left anterior descending or right coronary artery.

The functional significance of the collateral circulation was evaluated in 125 patients with total coronary occlusion. Patients were classified into two groups. Group 1:patients with angina pectoris (AP), Group 2:patients with a first transmural myocardial infarction (MI) within 3 months of the symptom onset. Clinical variables, resting and exercise electrocardiogram (EKG) were analyzed with angiographic findings. Collateral fillings were graded from 0 to 3: 0 = none; 1 = filling of side branches only; 2 = partial filling of the epicardial segment; 3 = complete filling of epicardial segment. The wall motion of each segment was scored from 1 to 5: 1 = normal; 2 = mild to moderate hypokinesia; 3 = severe hypokinesia; 4 = akinesia; 5 = dyskinesia. The scores of the 5 segments were added to yield a total LV score. There was a higher prevalence of good collaterals and multi-vessel disease in patients with AP than in those with MI (83% vs 53%, 54% vs 30%, respectively, p < 0.005). The left ventricular ejection fraction (LVEF), left ventricular end-diastolic pressure (LVEDP) and segmental wall motion score were significantly better in patients with AP than in those with MI (68.9 +/- 13.4%, vs 50.5 +/- 12.6%, 15.0 +/- 7.3 mmHg vs 20.3 +/- 8.8 mmHg, 6.5 +/- 2.2 vs 9.6 +/- 2.3, respectively, p < 0.05). In spite of total coronary occlusion, 61% of AP patients had normal resting EKG but (96% of AP patients who underwent treadmill test proved positive. The proportions of well-developed collaterals in 3 groups divided according to the interval between onset of MI and angiography (within 1 day, 2 to 14 days, 15 days to 3 months) were 13%, 54% and 60%. There were no significant differences in LVEF, segmental wall motion score and LVEDP in MI patients with poorly-developed collaterals and well-developed collaterals (49.1 +/- 15.7% vs 46.4 +/- 10.1%, 11.1 +/- 2.2 vs 10.9 +/- 1.4 and 24.3 +/- 9.7 mmHg vs 20.3 +/- 7.0 mmHg, p = NS). The degree of collateral development was higher in MI with right coronary artery occlusion compared with that of left anterior descending artery occlusion (1.1 +/- 1.0 vs 2.0 +/- 1.0, p < 0.05). In conclusion, collateral circulation can prevent myocardial ischemia and preserve myocardial function in a significant number of patients with AP but do not provide protection against exercise-induced myocardial ischemia in the majority of patients with AP.(ABSTRACT TRUNCATED AT 400 WORDS)

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↗

Initial clinical experience of intracoronary coil (Gianturco-Roubin) stents for management of acute dissection after balloon angioplasty.

Dissections after percutaneous transluminal coronary angioplasty (PTCA) are risk factors for acute or subacute vessel closures. Intracoronary stenting was developed to avoid these complications by pressing the intimal and medial flaps against the vessel wall, thus reducing the risk of acute closure from thrombus formation. Thirty three coil (Gianturco-Roubin) stents were implanted into the coronary arteries of 32 patients with dissections after PTCA during the period of March 1993 to December 1993. The indications for stent implantation were acute closure in 6 (18.8%), threatened closure in 6 (18.8%) and suboptimal result in 20 (62.4%) patients. Stent insertion were successful in 30 (94%) patients. The diameter stenosis in an immediate angiographic findings after stenting was decreased from 87% to 18% by caliper estimation. Emergency coronary artery bypass graft surgery was required in 1 (3%) patient. A non-Q wave myocardial infarction occurred in 1 (3%) patient. Complications included hematoma of the arterial access site requiring blood transfusion in 4 (12.5%) patients and hemopericardium in 1 (3%) patient. Our initial clinical experience of flexible coil coronary stent imply that stenting is efficacious treatment for acute dissections that are causing acute or threatened closure following angioplasty. The long term follow-up result in all groups of patient who received coronary stents is needed for better evaluation of new devices and prognosis.

Acute Disease↗

Percutaneous mitral balloon valvuloplasty in patients with restenosis after surgical commissurotomy: a comparative study.

We performed percutaneous mitral balloon valvuloplasty (PMV) in 367 patients to compare the effectiveness of PMV between patients with mitral restenosis after surgical commissurotomy (group 1) and patients with unoperated mitral stenosis (group 2). Twenty-two had undergone closed or open mitral commissurotomy 11.2 years before. There were no significant differences in clinical profiles between the two groups. The mitral valve area was increased from 1.0 +/- 0.8 to 1.8 +/- 0.6 cm2 in group 1 and 0.9 +/- 0.3 to 2.0 +/- 0.7 cm2 in group 2 (p > 0.05). The mitral gradient was decreased from 14 +/- 5.9 to 6 +/- 2.6 mmHg in group 1 and 18 +/- 7.0 to 7 +/- 5.3 mmHg in group 2 (p > 0.05). The increment of mitral regurgitation and significant left to right shunt after PMV were not significantly different (10% versus 14.7%, 5% versus 10.4% respectively). Optimal results were attained in 75% of the patients in group 1 and in 84.3% of the patients in group 2 (p > 0.05). These results suggest PMV in mitral restenosis after surgical commissurotomy may be safe in selected patients and may be equally effective as in unoperated mitral stenosis.

Adult↗

Constraints in antigen processing result in unresponsiveness to a T cell epitope of hen egg lysozyme in C57BL/6 mice.

T cell hybridoma clones were derived after fusion of BW-5147 parent cells with lymphocytes from C57BL/6 mice injected with phosphorylcholine (PC)-hen egg lysozyme (HEL) conjugates. Several T cell hybridomas were preferentially reactive with PC-HEL over unconjugated HEL, and a particular clone (PC-H4.1) was further analyzed. This T cell hybridoma clone could respond to its maximal level toward unconjugated HEL only when the dose of HEL was increased to 5-10-fold of the PC-HEL concentration. Interestingly, this clone was not stimulated by unfolded HEL (by S-carboxymethylation) to the level of PC-HEL. A synthetic peptide representing the amino acid position 47-61 of HEL, which is known to be non-immunogenic upon HEL injection in C57BL/6 mice, was able to stimulate the hybridoma only to a level comparable to that induced by unconjugated HEL. The T cell response to this synthetic peptide required an additional antigen-processing step, based on its inability to stimulate T cells after treatment of antigen-presenting cells with leupeptin, chloroquine or paraformaldehyde. Deletion of a single C-terminal amino acid residue of HEL 47-61 (arginine) significantly enhanced (10-100-fold of HEL 47-61) the T cell reactivity and abrogated the necessity of further antigen processing. These results suggest that the lack of a T cell response to a certain epitope may not be due to the lack of a T cell repertoire reactive to the epitope. In some cases, the unresponsiveness may be due to the difficulty in generating the particular epitopes. Taken together, modification of the lysozyme molecule with PC conjugation may facilitate further antigen processing of HEL to generate an optimal epitope for the nonresponder mice.

Animals↗

Comparison of outcome among double, bifoil and Inoue balloon techniques for percutaneous mitral valvuloplasty in mitral stenosis.

The efficacy and complications of three different methods of percutaneous mitral valvuloplasty (PMV) were evaluated in 245 patients with mitral stenosis (MS). Eight six patients (35%) had severe MS defined in the mitral valve area (MVA) less than 1.0 cm2 (0.8 +/- 0.2) and Echoscore greater than or equal to 8(8.9 +/- 1.1). The results including post MCA greater than or equal to 1.5cm2 and complications, i.e, increment of mitral regurgitation (MR) greater than or equal to +1 and atrial septal defect (ASD) with Qp/Qs greater than or equal to 1.5 were compared in overall and in severe MS groups. There was no statistically significant difference in size of MVA before and after PMV between overall patients group and severe mitral stenosis group (0.8 +/- 0.1 vs 1.7 +/- 0.4cm2 in the double technique, 0.8 +/- 0.2 vs 1.5 +/- 0.3cm2 in the Bifoil technique and 0.7 +/- 0.2 vs 1.8 +/- 0.3cm2 in the Inoue technique. p: NS). However, a significantly larger number of patients in the severe MS group had better MVA with the double than the Bifoil technique [MVA greater than or equal to 1.5cm2; 42 (72%) vs 6 (46%), p less than 0.005] whereas higher complications were observed with the Bifoil than the Inoue technique (MR greater than or equal to +1; 9 (69%) vs 4 (27%), ASD (Qp/Qs greater than or equal to 1.5' 6 (46%) vs 2 (13%) p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Analysis of T cell reactivities to phosphorylcholine-conjugated hen egg lysozyme in C57BL/6 mice: hapten-conjugate specificity reflects an altered expression of a major carrier epitope.

We have selected several different T cell hybridoma clones reactive to hen egg lysozyme (HEL) conjugated to phosphorylcholine (PC) after fusion of PC-HEL-primed C57BL/6 lymphocytes with BW5147 parent cells. These hybridoma clones preferentially recognize PC-HEL over unconjugated HEL, but not other carrier molecules conjugated with the same hapten. All the PC-HEL-reactive clones are similarly responsive to not only p-azobenzenearsonate (ABA)-conjugated HEL (ABA-HEL) but also to a variety of other diazotized hapten-HEL conjugates. However, these clones are not stimulated by fluoresceinated or dinitrophenylated HEL beyond the level of HEL carrier alone. Therefore, the type of hapten linkage (diazonium) to the carrier molecule appears to affect T cell recognition. The hybridoma clones apparently recognize the carrier molecule alone, although the level of stimulation is relatively low compared to that induced by either PC-HEL or ABA-HEL. Interestingly, HEL unfolded by S-carboxymethylation is capable of stimulating the hybridomas to a level comparable to that obtained with PC-HEL. T cell recognition of the unfolded HEL is independent of antigen processing, which is different from that of PC-HEL. The peptide sequence corresponding to the amino acids 81-93 of HEL appears to contain the epitope region for the hybridoma clones based on testing stimulation activity with synthetic peptides. Previously, the peptides including this region (81-96) have been reported as the determinant recognized by T cells derived from C57BL/6 mice after immunization with an HEL peptide (HEL 13-105) but not with native HEL. These results suggest that a hapten conjugation via diazonium linkage modifies antigen presentation and consequently the presentation of the major T cell epitopes similar to that of the HEL fragment.

Animals↗