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Biomedical subjects

Y D Kim

Publications and source records attributed to Y D Kim.

At least 55 records · Page 3Linked to original sources

Studies in thoracic aortic graft infections: the development of a porcine model and a comparison of collagen-impregnated dacron grafts and cryopreserved allografts.

OBJECTIVE: A porcine model of thoracic aortic graft infection was created, and various anatomic sites and the timing of inoculation of the graft to induce infection were investigated. Ultimately, the ability of cryopreserved allograft to resist infection was compared with that of collagen-impregnated Dacron graft. METHODS: Yorkshire pigs (n = 16) underwent placement of an expanded polytetrafluoroethylene patch graft in the ascending aorta and the left atrial appendage (phase I). Eight animals were immediately given a 50-mL bolus (1 x 10(8) cfu/mL) of Staphylococcus aureus whereas the other 8 received the infusion 24 hours later. Animals were put to death 8 weeks later and the grafts were sterilely explanted and analyzed via microbiologic culture and standard histologic procedures for evidence of infection. The results displayed that the aortic graft and a delay of induced bacteremia of 24 hours were more reliable methods of producing infection. During phase II, 13 pigs were randomized to receive either a collagen-impregnated Dacron graft (n = 6) or a cryopreserved allograft (n = 7) in the ascending aortic position only and infusion of S aureus 24 hours after the operation. The experiment then proceeded to completion. RESULTS: Phase I results displayed that use of an aortic graft and induced bacteremia 24 hours after the operation was a more reliable and reproducible method of producing infection. In phase II, graft infection was present in 38.5% (5/13) of animals, with only 16.7% (1/6) in the collagen-impregnated Dacron graft group and 57.2% (4/7) in the cryopreserved allograft group becoming infected. There was no significant difference between the collagen-impregnated Dacron graft and cryopreserved allograft groups in the incidences of thoracic aortic graft infections (P =.27, Fisher exact test). CONCLUSIONS: This novel porcine model of thoracic aortic graft infection is a reproducible method for the investigation of thoracic aortic graft infections. The phase I study investigated the timing of the induced bacteremia and the most susceptible position of a graft. Phase II demonstrated that collagen-impregnated Dacron grafts are equivalent, if not superior, to cryopreserved allografts in resisting central vascular graft infections in the ascending aorta.

Animals↗

Reduced expression of p27Kip1 protein is associated with poor clinical outcome of breast cancer patients treated with systemic chemotherapy and is linked to cell proliferation and differentiation.

The cyclin-dependent kinase inhibitor p27Kip1 is a negative regulator of cell proliferation. Its expression is known to be altered in a proteasome-dependent manner without changes in DNA level. Reduced expression of p27Kip1 is associated with aggressive behavior in a variety of human cancers. We investigated expression of p27Kip1 protein in human breast cancer using immunohistochemistry to assess its biologic implication along with cell-cycle analysis by flow cytometry. A total of 68 patients with invasive ductal cancer received adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-FU every 3 weeks for six cycles. In epithelial cells of normal and benign breast disease, expression of p27Kip1 was well preserved while its expression markedly decreased in breast cancer (45 of 68). Expression of p27Kip1 is significantly reduced in poorly differentiated cancers and in the advanced stage of the disease. Levels of p27Kip1 expression correlated with cell populations in G0/G1 phase of the cell cycle. In survival analysis, p27Kip1 was useful to predict disease free survival but not overall survival of the patients after adjuvant chemotherapy. In summary, p27Kip1 seems to have a role in the cell proliferation and differentiation process during carcinogenesis of breast cancer. The results of the present study suggest that p27Kip1 can be used in predicting response to systemic chemotherapy in a subset of patients with breast cancer.

Adult↗

Solitary fibrous tumor of the lacrimal sac.

PURPOSE: Solitary fibrous tumor is a rare spindle cell tumor arising in the pleura. We report two cases of this tumor occurring in the lacrimal sac. METHODS: A 23-year-old man and a 34-year-old woman presented with a medial canthal mass. They underwent surgical excision of their tumors. RESULTS: Solitary fibrous tumors were diagnosed by light microscopy, immunohistochemical study, and electron microscopy. Immunohistochemical staining showed that tumor cells were reactive with vimentin and CD34 and demonstrated no smooth muscle or neural differentiation (nonreactive with desmin and S-100 protein). CONCLUSIONS: The findings indicate that solitary fibrous tumor can occur in the lacrimal sac and may recur locally if it is removed incompletely. To our knowledge, these are the first reported cases of solitary fibrous tumors occurring in the lacrimal sac.

Adult↗

Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium.

Expression of innate immune response proteins, including IL-1beta, TNF, and the cytokine-inducible isoform of nitric oxide synthase (iNOS), have been documented in the hearts of humans and experimental animals with heart failure regardless of etiology, although the proximal events leading to their expression are unknown. Noting that expression of a human homologue of Drosophila Toll, a proximal innate immunity transmembrane signaling protein in the fly, now termed human Toll-like receptor 4 (hTLR4), appeared to be relatively high in the heart, we examined TLR4 mRNA and protein abundance in isolated cellular constituents of cardiac muscle and in normal and abnormal murine, rat, and human myocardium. TLR4 expression levels in cardiac myocytes and in coronary microvascular endothelial cells could be enhanced by either LPS or IL-1beta, an effect inhibited by the oxygen radical scavenger PDTC. Transfection of a constitutively active TLR4 construct, CD4/hTLR4, resulted in activation of a nuclear factor-kappaB reporter construct, but not of an AP-1 or an iNOS reporter construct, in cardiac myocytes. In normal murine, rat, and human myocardium, TLR4 expression was diffuse, and presumably cytoplasmic, in cardiac myocytes. However, in remodeling murine myocardium remote from sites of ischemic injury and in heart tissue from patients with idiopathic dilated cardiomyopathy, focal areas of intense TLR4 staining were observed in juxtaposed regions of 2 or more adjacent myocytes; this staining was not observed in control myocardium. Increased expression and signaling by TLR4, and perhaps other Toll homologues, may contribute to the activation of innate immunity in injured myocardium.

Amino Acid Sequence↗

c-Myc expression is related with cell proliferation and associated with poor clinical outcome in human gastric cancer.

We underwent protein assay for Myc expression in 76 human gastric cancer tissues using immunohistochemistry. Expression of Myc protein was analyzed according to proliferative indices measured by flow cytometry. Levels of Myc protein expression was evaluated by correlating with biologic and clinical parameters. In 36 (47.4%) of 76 primary gastric cancers, overexpression of Myc was observed. We could observe expression of Myc protein in a significant portion of early gastric cancer (42.9%). Expression of Myc protein was demonstrated to be more frequent in poorly differentiated cancer cells (p=0.043). However, expression of Myc protein had little influence over progress or extent of the disease. Expression of Myc protein was significantly correlated with increased proliferative activity (p=0.032) and patients with high levels of Myc expression had poor disease-free survival. In a certain proportion of human gastric cancer, Myc protein may function as a regulator of cancer cell growth and expression of Myc may represent an aggressive phenotype of gastric cancer.

Adult↗

Non-anticoagulant heparin increases endothelial nitric oxide synthase activity: role of inhibitory guanine nucleotide proteins.

Heparin, which is widely used clinically, has recently been shown to have specific properties affecting the vascular endothelium. We hypothesized that heparin stimulates endothelial nitric oxide synthase (eNOS) activity by a mechanism independent of its anticoagulant properties and dependent on an inhibitory guanine nucleotide regulatory protein (Gi). We determined the effect of both heparin and N-acetyl heparin (Non-Hep), a heparin derivative without anticoagulant properties, on eNOS activity in cultured bovine aortic endothelial cells and on endothelium-dependent relaxation in isolated vascular rings. The eNOS activity was determined by measuring both citrulline and nitric oxide (NO) metabolite formation. Heparin and Non-Hep dose-dependently increased basal eNOS activity (ED50 1.0 microgram/ml or 0.15 U/ml), an effect that was significantly inhibited by pertussis toxin (100 ng/ml), a Gi-protein inhibitor. Agonist-stimulated (acetylcholine, 10 microM) eNOS activity was potentiated following pre-treatment with both heparin and Non-Hep and reversed by pertussis toxin. Heparin and Non-Hep induced a dose-dependent relaxation in preconstricted thoracic aortic rings, an effect that was significantly inhibited by pertussis toxin, endothelial inactivation (following treatment with sodium deoxycholate) and NG-nitro-L-arginine-methyl ester (L-NAME). We conclude that heparin and non-anticoagulant heparin induce endothelium-dependent relaxation following activation of eNOS by a mechanism involving a Gi-protein. Administration of heparin derivatives without anticoagulant properties may have therapeutic implications for the preservation of eNOS in conditions characterized by endothelial dysfunction.

Acetylcholine↗

Heparin preserves nitric oxide activity in coronary endothelium during ischemia-reperfusion injury.

BACKGROUND: Brief episodes of ischemia followed by reperfusion adversely affect endothelial vasomotor function. We hypothesized that heparin may impart a protective effect on the coronary endothelium during ischemia-reperfusion injury possibly via the nitric oxide pathway. METHODS: Eighteen anesthetized dogs were randomly assigned to one of two treatment groups: saline solution or bovine heparin (6.0 mg x kg intravenously). A flow probe and cannula were placed in the left anterior descending artery. Functional recovery of the coronary endothelium was assessed after 15 minutes of ischemia and during 120 minutes of reperfusion after acetylcholine and nitroprusside challenge. In a separate group (n = 10), nitric oxide activity was measured as nitrate/nitrite levels and cyclic guanosine monophosphate levels in the left anterior descending artery. RESULTS: Control dogs displayed a significant decrease in percent change of left anterior descending artery flow at 15, 30, and 60 minutes of reperfusion (67%+/-8%, 76% +/-11%, and 84%+/-8%) when compared with preischemic values (108+/-6; p < 0.01). Heparinized dogs, however, showed preservation of coronary endothelial function after acetylcholine challenge throughout reperfusion. Heparin-treated dogs also displayed a significant increase in nitrate/nitrite levels during reperfusion (37.3+/-4.1 micromol/L) when compared with the saline group (24.3+/-0.8 micromol/L; p < 0.03). Left anterior descending artery levels of cyclic guanosine monophosphate were also significantly increased after heparin administration (3.0+/-0.3 pmol/mg) when compared with ischemia-reperfusion alone (0.7+/-0.1 pmol/mg; p < 0.03). CONCLUSIONS: Heparin preserves the vasoregulatory function of the coronary endothelium during brief episodes of ischemia-reperfusion injury, in part, via the nitric oxide pathway. Administration of heparin may have important therapeutic implications in the prevention of coronary endothelial dysfunction associated with reperfusion injury.

Animals↗

Heparin and nonanticoagulant heparin preserve regional myocardial contractility after ischemia-reperfusion injury: role of nitric oxide.

OBJECTIVES: These studies were performed to determine the effect of heparin and nonanticoagulant heparin on myocardial function after ischemia-reperfusion and to further evaluate the role that the nitric oxide-cyclic guanosine monophosphate pathway plays in mediating the effect of heparin. METHODS: Fifteen dogs were subjected to 15 minutes ischemia followed by 120 minutes reperfusion and pretreated with either saline solution, bovine heparin (6.0 mg/kg intravenously), or N-acetyl heparin (6.0 mg/kg intravenously), a heparin derivative without anticoagulant properties. The left anterior descending artery was occluded for 15 minutes and regional systolic shortening, a unitless measure of myocardial contractility, assessed during reperfusion. To evaluate the role of nitric oxide, the inhibitor N(omega)-nitro-L-arginine, 1.5 mg/kg intracoronary, was given before heparin administration. Myocardial levels of cyclic guanosine monophosphate, the second messenger of nitric oxide, were also measured in the N-acetyl heparin group using radioimmunoassay. RESULTS: Regional systolic shortening was significantly decreased in the saline group during 60 and 120 minutes compared with before ischemia (9.2 +/- 1.0 and 9.0 +/- 0.9 vs 12.2 +/- 1.2, p < or = 0.0003). Heparin and N-acetyl heparin-treated dogs, however, showed preservation of systolic shortening throughout reperfusion. Administration of nitro-L-arginine significantly attenuated the protective effect of heparin (9.2 +/- 1.2 vs 12.7 +/- 1.1, p < or = 0.0001) and N-acetyl heparin (9.3 +/- 0.3 vs 12.8 +/- 0.4, p < or = 0.0001) during 120 minutes reperfusion. Myocardial levels of cyclic guanosine monophosphate were also significantly increased in the N-acetyl heparin group compared with saline (199.1 +/- 7.1 vs 103.5 +/- 4.5 pmol/mg, p < or = 0.0001). CONCLUSIONS: Heparin preserves myocardial contractility after ischemia-reperfusion independent of its anticoagulant properties. Furthermore, the protective effects of heparin during ischemia-reperfusion are mediated, at least in part, through a nitric oxide-cyclic guanosine monophosphate pathway.

Animals↗

Psychoneuroendocrinology and brain imaging in depression.

In the past three decades, psychoneuroendocrinologic investigations have generated a great volume of information, particularly in the field of affective disorders, which has formed the basis for designing studies with newer tools such as anatomic and functional imaging. In this article, the authors focus on endocrine imaging in psychiatry and attempt to relate morphometric findings to physiologic neuroendocrine dysfunction in depression.

Anorexia Nervosa↗

The effect of propofol on isolated human pregnant uterine muscle.

BACKGROUND: Propofol is an alternative to thiopental as an intravenous induction agent for cesarean section. Because it has relaxant effects on vascular and other smooth muscles, the authors set out to determine whether propofol has any effect on pregnant human uterine smooth muscle in an isolated preparation. METHODS: Myometrial specimens were excised from 10 parturients undergoing elective cesarean section. The muscle strips were suspended in tissue baths and isometric tension was recorded. After establishment of rhythmic contractions in the buffer solution as a control, propofol (0.5 to 10 microg/ml) in fat emulsion was applied cumulatively to the bath. The effect of the fat emulsion at equivalent concentrations was also examined. RESULTS: Propofol concentrations of 2.7 x 10(-6) M (0.5 microg/ml) and 1.1 x 10(-5) M (2 microg/ml) had no significant effect on the active tension developed by muscle contraction. However, propofol at concentration of 5.5 x 10(-5) M (10 microg/ml) reduced the active tension by 45% (P < 0.02) compared with the control value. The fat emulsion had no effects on the active tension. CONCLUSIONS: These results imply that the decline in the active tension of muscle contraction was most likely caused by propofol and not by the fat emulsion. However, the propofol concentrations needed to produce a significant reduction in the uterine muscle tension appear to be much greater than the free propofol concentrations reported by others during cesarean section.

Adult↗

17-Beta estradiol regulation of myocardial glutathione and its role in protection against myocardial stunning in dogs.

We studied the effect of 2-week treatment with estradiol 17beta on myocardial glutathione concentration in dogs and isolated perfused rat heart subjected to brief coronary ischemia and reperfusion. Estradiol protected against ischemia/reperfusion-induced myocardial systolic shortening and malonylaldehyde production and increased myocardial glutathione concentration and glucose-6-phosphate dehydrogenase enzyme activity. Reduction of myocardial glutathione with buthionine sulfoximine to levels seen in the absence of estrogen reversed the protective effect of estradiol against myocardial dysfunction and lipid peroxidation associated with ischemia/reperfusion. These results suggest that the antioxidant effect of estradiol in ischemia/reperfusion may be mediated by regulation of myocardial glutathione metabolism.

Animals↗

Transcanalicular laser-assisted revision of failed dacryocystorhinostomy.

BACKGROUND AND OBJECTIVE: Despite the high success rate of external dacryocystorhinostomy (DCR), recurrent tearing after DCR can be troublesome. The authors performed transcanalicular revision in 6 patients with failed DCR. PATIENTS AND METHODS: With the use of a continuous wave Nd:YAG laser with a sclerostomy probe, the internal ostium was reopened by a transcanalicular approach. The authors applied 0.4 mg/ml of mitomycin-C around the opening for 5 minutes intranasally and inserted a silicone tube as a stent. RESULTS: A total of 7 operations were performed in 6 patients. The operation was successful after the first revision in 5 of the 6 patients, but 1 of the patients required a second procedure. CONCLUSIONS: The transcanalicular laser-assisted revision has several advantages. It is simple and fast, skin incision is avoided, there is good hemostasis, it is less traumatic, and there is less postoperative morbidity.

Adult↗

Mutations of the STK11 gene in sporadic gastric carcinoma.

Gastric carcinoma may occur sporadically or in association with hereditary diseases, such as Peutz-Jehgers syndrome (PJS). The PJS gene (named STK11 or LKB1) was mapped to 19p13.3 and recently cloned. Germ-line mutations of the gene have been detected in familial PJS patients and are predicted to predispose STK11 carriers to the development of a wide range of gastrointestinal and other neoplasms. To elucidate the etiological role of the STK11 gene in sporadic gastric carcinoma tumorigenesis, we analyzed 28 gastric carcinomas (22 of intestinal type and 6 of diffuse type) for STK11 gene mutations. STK11 gene mutations were detected in 3 of 28 gastric carcinomas but were not seen in the corresponding germ-line DNA sequence. In one tumor, a missense mutation, C-to-T transition, was detected at codon 324 resulting in proline to leucine substitution; in the other two, silent mutations were detected at codons 106 and 350, respectively. While these results suggest that somatic STK11 mutations are not common in sporadic gastric carcinomas, they may occur in a subset of these tumors.

Gene Expression Regulation, Neoplastic↗

Seroimmunological characteristics of Korean workers exposed to toluene diisocyanate.

Since type I allergy caused by specific IgE antibodies may play principal roles and IgG antibody-mediated reactions have been thought to be involved in some parts of the pathogenesis, this study was performed to investigate the role of IgE- or IgG-mediated hypersensitivity reactions in development of toluene diisocyanate (TDI) asthma in Korean workers. For 81 TDI spray painters, self-administrative questionnaires and direct interviews on respiratory symptoms, chest auscultation, and measurements of forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1.0) were performed. The TDI concentration in their working environments was measured. Levels of serum IgE and IgG specific to TDI were estimated by radioallergosorbent test (RAST) and ELISA using p-tolyl isocyanate-human serum albumin (TMI-HSA) as the antigen. When sputum, cough, and dyspnea aggravated by work or wheezing existed, when FVC or FEV1.0 was less than 80% of the normal reference value, or when IgE RAST for TDI was positive, the peak expiratory flow rate (PEFR) was recorded four times per day for over 2 weeks. If decrease of PEFR was over 20% of baseline PEFR and changing pattern of PEFR was closely related to workshift in time, then a diagnosis of TDI asthma was made. Changing patterns of PEFR of 8 (9.9%) workers corresponded to the diagnostic criteria of TDI-related occupational asthma. Levels of the specific IgE were increased in 9 (11.1%) of the 81 subject workers and in 3 (37.5%) of the 8 PEFR-positive workers. Levels of the specific IgG were increased in 9 (11.1%) workers, and in only 1 (12.5%) of the asthmatics sensitive to TDI. Neither elevated TDI-specific IgE levels nor PEFR test positivities were associated with increased IgG levels. The mean titer of the PEFR-test-positive workers was slightly lower than that of the PEFR-negative workers and that of the IgE RAST-positive workers lower than that of the test-negative workers, but there was no statistical significance. These results suggest that IgG is not deeply involved in the pathogenesis of TDI-induced occupational asthma in Korean workers.

Adult↗

Distribution of nitric oxide in the nasal mucosa of the rat: a histochemical study.

We evaluated the distribution of nitric oxide (NO) in the rat nasal mucosa using nicotineamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry. The NADPH-diaphorase positive nerve fibers in the nasal mucosa were observed around blood vessels and submucosal glands and in sphenopalatine ganglions. Strong positive reactions for NADPH-diaphorase were observed in ganglions as compared with the other tissues. In septal and turbinate mucosa, positive reactions for NADPH-diaphorase were mainly seen in the anterior portion, and a few positive reactions were observed in the posterior portion. No positive reactions for NADPH-diaphorase were demonstrated in the sinus mucosa. These results suggest that NO may be related to regulation of blood flow, glandular secretion and neurotransmission, and also that NO may play an important role in the defense mechanism of the upper airway system against external environments.

Animals↗

Breath pentane concentrations during labor and the effect of epidural analgesia on the pentane concentration.

Increased lipid peroxidation has been observed in pregnancy and particularly in preeclampsia. Pentane, a by-product of lipid peroxidation, can be measured in exhaled breath, and its measurement is considered a non-invasive method of assessing lipid peroxidation in vivo. We measured pentane levels in the breath of 36 healthy parturient women and examined the effect of epidural analgesia on the pentane level. Single-expiratory breath samples were analyzed by gas chromatography. The breath pentane level was higher during labor (4.88 parts per billion [p.p.b.], 95% confidence interval 3.25-6.51 p.p.b.) than before the induction of labor (3.10 p.p.b., 95% confidence interval 2.01-4.19 p.p.b.). There was a significant decrease in the pentane level after the institution of epidural analgesia (2.27 p.p.b., 95% confidence interval 1.43-3.11 p.p.b.). Our results suggest that labor may be accompanied by an increase in lipid peroxidation, and epidural analgesia reverses this increase.

Journal Article↗