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Biomedical subjects

Y H Yoon

Publications and source records attributed to Y H Yoon.

At least 19 recordsLinked to original sources

Comparison of diameter and perimeter methods for tumor volume calculation.

PURPOSE: Lesion volume is often used as an end point in clinical trials of oncology therapy. We sought to compare the common method of using orthogonal diameters to estimate lesion volume (the diameter method) with a computer-assisted planimetric technique (the perimeter method). METHODS: Radiologists reviewed 825 magnetic resonance imaging studies from 219 patients with glioblastoma multiforme. Each study had lesion volume independently estimated via the diameter and perimeter methods. Cystic areas were subtracted out or excluded from the outlined lesion. Inter- and intrareader variability was measured by using multiple readings on 48 cases. Where serial studies were available in noncystic cases, a mock response analysis was used. RESULTS: The perimeter method had a reduced interreader and intrareader variability compared with the diameter method (using SD of differences): intrareader, 1.76 mL v 7.38 mL (P < .001); interreader, 2.51 mL v 9.07 mL (P < .001) for perimeter and diameter results, respectively. Of the 121 noncystic cases, 23 had serial data. In six (26.1%) of those 23, a classification difference occurred when the perimeter method was used versus the diameter method. CONCLUSION: Variability of measurements was reduced with the computer-assisted perimeter method compared with the diameter method, which suggests that changes in volume can be detected more accurately with the perimeter method. The differences between these techniques seem large enough to have an impact on grading the response to therapy.

Brain↗

Reconstruction of basement membrane in skin equivalent; role of laminin-1.

To reconstruct the basement membrane in a skin equivalent, the epidermodermal interface was coated with porcine type IV collagen and mouse laminin-1 at various ratios before keratinocyte seeding. Laminin-1, a component of the basement membrane, induced massive infiltration of keratinocytes into the dermal equivalent, while type IV collagen induced discrete demarcation between dermal and epidermal compartments without any infiltrating cells. Immunohistochemical staining indicated that the laminin-induced infiltrating cells expressed endogenous type IV collagens at the cell periphery, which were not incorporated into the basement membrane structure. The infiltrating cells did not express fibronectin receptor alpha5beta1 integrin but showed MMP-9 secretion and cell surface associated MMP-2. However, when laminin-1 was preincubated with type IV collagen, laminin-1-induced keratinocyte infiltration as well as MMP-9 induction were almost completely suppressed to basal levels. Therefore, replenishment of the type IV collagen lattice seemed to cause laminin-stimulated cells to anchor to the lattice, in a similar manner to the basal cells on the basement membrane of normal skin. Our study suggests that the molar ratio of basement membrane components may determine the behavior of basal cells within the wound healing microenvironment, which is probably regulated either by extracellular matrix deposition or degradation.

3T3 Cells↗

The distribution of soiling by coarse particulate matter in the museum environment.

Soiling measurements are needed to address strategies to control dust and determine its sources. There is no widely recognized method for dust monitoring in museums, but we used sticky samplers to collect deposited coarse particulate matter, and both manual microscopic observations and image analysis for determining soiling potential in the museum environment. We adopt fractional area covered by deposited particles as a surrogate for soiling and the covering rate (unit: s-1) as a measure of the rate of soiling. It was clear that visitor flow was a major contributor to soiling, such that soiling mechanisms in different museums could be compared after measurements were normalised on a per capita basis. The proximity of visitors to objects was another important factor with the soiling declining with distance from visitor pathways (a half-distance of about 0.5 m), which suggests soiling of objects on open display could be reduced by increasing the distance from visitors.

Air Pollution, Indoor↗

Depletion of intracellular zinc and copper with TPEN results in apoptosis of cultured human retinal pigment epithelial cells.

PURPOSE: Although zinc deficiency may contribute to the pathogenesis of age-related macular degeneration, how it leads to retinal pigment epithelium (RPE) degeneration is unknown. To investigate this, cultured human RPE cells were rendered zinc depleted with a membrane-permeant metal chelator, N,N,N',N-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), and the resultant cytopathic changes were examined. METHODS: RPE cell degeneration was examined with light microscopy, TdT-mediated dUTP nick end labeling (TUNEL) staining, Hoechst dye staining, and electron microscopy and quantified with cell counting or lactate dehydrogenase release assay. The effect of sublethal zinc depletion on the vulnerability of RPE cells to UV irradiation or hydrogen peroxide (H(2)O(2)) exposure, was studied in cultures without or with pretreatment with low-concentration TPEN. RESULTS: Exposure to 1 to 4 microM TPEN for 48 hours induced RPE cell death in a concentration-dependent manner. Features of apoptosis such as membrane blebbing, chromatin condensation, nuclear fragmentation, and caspase-3 activation, accompanied the TPEN-induced cell death. Addition of equimolar zinc or copper completely reversed TPEN-induced apoptosis, whereas addition of iron had no effect. As in apoptosis of several other cell types including neurons, a protein synthesis inhibitor as well as caspase inhibitors blocked TPEN-induced apoptosis. On the contrary, at sublethal concentrations, TPEN increased the vulnerability of RPE cells to subsequent UV irradiation but not to H(2)O(2) exposure. CONCLUSIONS: The present results suggest that depletion of intracellular zinc and copper, but not copper alone, may be harmful to RPE cells, directly inducing apoptosis or indirectly increasing vulnerability of RPE cells to UV injury. The present culture model may be useful for gaining insights into the mechanisms of zinc depletion-associated RPE cell degeneration.

Apoptosis↗

Depletion of intracellular zinc induces macromolecule synthesis- and caspase-dependent apoptosis of cultured retinal cells.

Although zinc deficiency may contribute to age-related macular degeneration (ARMD), the pathogenic mechanism is as yet uncertain. In light of evidence that cellular zinc depletion induces apoptosis in cortical neurons and thymocytes, in the present study, we examined the possibility that the same phenomenon occurs also in retinal cells. Exposure of primary retinal cell cultures to 1-3 microM of a cell membrane-permeant zinc chelator TPEN for 24 h induced concentration-dependent death of neurons, photoreceptor cells, and astrocytes. Addition of zinc or copper reversed TPEN toxicity to all cell components, indicating the particular involvement of zinc chelation in cell death. Consistent with apoptosis, oligonucleosomal DNA fragmentation and chromatin condensation accompanied, and the protein synthesis inhibitor cycloheximide blocked the TPEN-induced retinal cell death. During TPEN-induced retinal cell apoptosis, cleavage/activation of procaspase-1, but little of procaspase-3, was observed. Consistent with this finding, a broad-spectrum caspase inhibitor (zVAD-fmk) was significantly more protective than a caspase-3-selective inhibitor (DEVD-fmk). The present study has demonstrated that depletion of intracellular zinc is sufficient to induce macromolecule synthesis- and caspase-dependent apoptosis of cultured retinal cells. In light of the possibility that zinc depletion may contribute to the pathogenesis of ARMD, the current culture model may be a useful tool for the investigation of the mechanism of zinc depletion-induced retinal cell death.

Age Factors↗

Ethambutol-induced vacuolar changes and neuronal loss in rat retinal cell culture: mediation by endogenous zinc.

Ethambutol is an efficacious antituberculosis agent. However, its use has been limited by the occurrence of ocular toxicity. To investigate characteristics and possible mechanisms of ethambutol ocular toxicity, we used primary rat retinal cultures as a model. Primary rat retinal cultures were obtained from newborn Sprague-Dawley rats and used for experiments after maturation (DIV > or = 10). Cytopathologic changes were examined under light and electron microscopes. Thy-1 (a membrane glycoprotein expressed by retinal ganglion neurons)-containing neurons and gamma-aminobutyric acid (GABA)-ergic neurons were identified immunocytochemically. Exposure of retinal cultures for 24-48 h to ethambutol induced cytoplasmic vacuolar changes and neuronal loss. Vacuolar changes were partially reversible with the termination of ethambutol exposure. Of neurons, Thy-1(+) ganglion neurons were more vulnerable than GABA(+) neurons. Glutamate antagonists, an antioxidant (trolox), or cycloheximide, did not attenuate either vacuolar changes or neuronal loss. A cell-permeant zinc chelator N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) markedly attenuated vacuolar degeneration and neuronal loss, while the addition of zinc augmented both. In rat retinal cultures, ethambutol induces reversible vacuolar degeneration as well as irreversible neuronal loss, more preferentially of Thy-1(+) ganglion neurons. Contrary to the current theories, ethambutol-induced retinal cytotoxicity in the present study is mediated not by excitotoxicity or zinc deficiency but by a mechanism requiring intracellular zinc. In addition, features of the ethambutol-induced cell death were not consistent with those of apoptosis.

Animals↗

Myositis ossificans of the chest wall simulating malignant neoplasm.

Myositis ossificans originating from the chest wall is extremely rare. We report a case of myositis ossificans occurring in a young woman with progressive painful swelling in the chest wall. Preoperative examination suggested a malignant neoplasm originating from soft tissue. Although rare, myositis ossificans is one of the potential causes of painful swelling in the chest wall, and can be mistaken for a malignant neoplasm.

Adolescent↗

Needle thoracic sympathectomy for essential hyperhidrosis: intermediate-term follow-up.

BACKGROUND: Essential hyperhidrosis is a condition with excessive sweating localized to certain part of the body. A definitive cure can be obtained by upper thoracic sympathectomy. METHOD: Between June and October 1997, 117 patients with essential hyperhidrosis underwent needle thoracoscopic sympathectomy. Of the 94 patients, 42 were men and 52 women. Their ages ranged from 14 to 63 years, with a mean age of 23 years. RESULTS: There were no mortality or life-threatening complications. Symptomatic improvement was found in 95.7%. Compensatory hyperhidrosis was found in 71.2% of the patients, but in these compensatory hyperhidrosis were mostly tolerable. CONCLUSIONS: This therapeutic procedure is minimally invasive and very effective. Further development of the new device and surgical technique are expected to follow.

Adolescent↗

Management of persistent or recurrent pneumothorax with a two millimeter mini-videothoracoscope.

The aim of this study was to assess whether a 2 mm mini-videothoracoscope could be used as a conventional videothoracoscope in the management of pneumothorax. Thirty patients of ages from 15 to 35 years with recurrent or persistent pneumothorax were involved in this study. The subjects consisted of 27 males and three females. The indications for videothoracoscopic surgery were ipsilateral recurrent pneumothorax in 12 (40%), persistent air leakage in 15 (50%), visible bullae in 2 (6%), and 1 bilateral pneumothorax (3%). The mean operation time was 42.9+/-12.9 min. The average number of uses for Endo-GIA was 1.9+/-1.3 times and chest tube indwelling time was 3.8+/-2.7 days. The average amount of keptoprofen (100 mg/2 mL/ampule) used on the first postoperative day was 1.2+/-1.1 ampules. No parenteral opioids were given to the patients for pain control after the procedures. After a follow up of 8 to 20 months, there was only one recurrence among the patients. In conclusion, a 2 mm videothoracoscope, in selective cases, can be successfully used as conventional videothoracoscope to manage persistent or recurrent pneumothorax with cosmetically excellent results.

Adolescent↗

High vulnerability of GABA-immunoreactive neurons to kainate in rat retinal cultures: correlation with the kainate-stimulated cobalt uptake.

Like other areas of the central nervous system, the retina is highly vulnerable to ischemia. In particular, neurons in the inner nuclear layer, including gamma-amino butyric acid (GABA)-ergic amacrine neurons, are highly vulnerable. Since excitotoxicity is likely a major mechanism of ischemic retinal injury, using rat retinal cell culture, we examined whether GABAergic retinal neurons are differentially vulnerable to particular excitotoxins. The neuronal population as a whole, identified by anti-microtubule associated protein-2 (MAP-2) immunocytochemistry, was equally vulnerable to kainate, but more resistant to N-methyl-d-aspartate (NMDA) than cultured cortical neurons. Compared to Thy-1 immunoreactive neurons, GABA immunoreactive neurons were more vulnerable to kainate, but more resistant to NMDA neurotoxicity. Double staining of cultures with anti-GABA immunocytochemistry and the kainate-stimulated cobalt uptake method, revealed a close correlation between the two. However, unlike in other neuronal cells, there was no clear correlation between GluR2 immunoreactivity and the cobalt staining. The heightened vulnerability of GABAergic neurons to kainate, as compared to the general neuronal population, may be due to the calcium-permeable AMPA/kainate receptors they have, as identified functionally by the kainate-stimulated cobalt uptake staining. Since these neurons are preferentially injured in ischemia, AMPA/kainate receptor-mediated neurotoxicity may contribute significantly to ischemic retinal injury.

Animals↗

An unusual type of cancer-associated retinopathy in a patient with ovarian cancer.

We studied a case of unusual retinopathy in a 35-year-old woman who presented with bilateral visual deterioration due to retinal pigmentary mottling and serous elevation in the posterior pole. Two years before, she had undergone hysterectomy and bilateral salphingo-oophorectomy for ovarian cancer. Her electroretinogram became subnormal, and her fluorescein angiogram exhibited multiple deep retinal pigment epithelial leakages and subretinal dye pooling in both eyes. Corticosteroid therapy failed to prevent visual loss. She was found to possess antibodies against retinal 45 kd protein. This led to a diagnosis of cancer-associated retinopathy with atypical protein profile. We report a rare variety of cancer-associated retinopathy in a patient with-ovarian cancer.

Adenocarcinoma↗

The effects of solutes on the freezing properties of and hydration forces in lipid lamellar phases.

Quantitative deuterium nuclear magnetic resonance is used to study the freezing behavior of the water in phosphatidylcholine lamellar phases, and the effect upon it of dimethylsulfoxide (DMSO), sorbitol, sucrose, and trehalose. When sufficient solute is present, an isotropic phase of concentrated aqueous solution may coexist with the lamellar phase at freezing temperatures. We determine the composition of both unfrozen phases as a function of temperature by using the intensity of the calibrated free induction decay signal (FID). The presence of DMSO or sorbitol increases the hydration of the lamellar phase at all freezing temperatures studied, and the size of the increase in hydration is comparable to that expected from their purely osmotic effect. Sucrose and trehalose increase the hydration of the lamellar phase, but, at concentrations of several molal, the increase is less than that which their purely osmotic effect would be expected to produce. A possible explanation is that very high volume fractions of sucrose and trehalose disrupt the water structure and thus reduce the repulsive hydration interaction between membranes. Because of their osmotic effect, all of the solutes studied reduced the intramembrane mechanical stresses produced in lamellar phases by freezing. Sucrose and trehalose at high concentrations produce a greater reduction than do the other solutes.

Biophysical Phenomena↗

Development and progression of diabetic retinopathy in Koreans with NIDDM.

OBJECTIVE: To determine the incidence and risk factors for the development and progression of diabetic retinopathy in Korean patients with NIDDM. RESEARCH DESIGN AND METHODS: A total of 186 patients with NIDDM who did not have proliferative diabetic retinopathy (PDR) at baseline were prospectively studied for 5.3 +/- 1.0 years in an outpatient clinic of a university hospital. The incidence and progression of diabetic retinopathy was determined by annual funduscopic examination by an ophthalmologist. RESULTS: Of the 130 patients who were free of diabetic retinopathy at baseline, 30 developed it, giving an incidence of 44.4/1,000 person-years. Age and known duration of diabetes, mean fasting plasma glucose, and HbA1 levels during the follow-up period were higher in the patients who developed diabetic retinopathy. Of the 56 patients who had nonproliferative diabetic retinopathy at baseline, 11 developed PDR, giving an incidence of 37.5/1,000 person-years. The patients who progressed to PDR during follow-up (progressors) had a higher change of BMI and urinary albumin excretion rate at baseline and a higher mean HbA1 during the follow-up period than the nonprogressors. Cox proportional hazards analysis revealed that mean HbA1 was the only independent risk factor for both the development and progression of diabetic retinopathy. CONCLUSIONS: The incidence of PDR in Korean NIDDM patients is comparable to that reported in other populations. Poor glycemic control is the most important risk factor for both the development and progression of diabetic retinopathy in NIDDM patients.

Blood Glucose↗

High serum lipoprotein(a) levels in Korean type 2 diabetic patients with proliferative diabetic retinopathy.

OBJECTIVE: To examine the possible association between serum lipoprotein(a) [Lp(a)] concentration and proliferative diabetic retinopathy (PDR) in Korean patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 412 Korean outpatients with type 2 diabetes were examined. Diabetic retinopathy was determined by an ophthalmologist using fundoscopic examination. Serum Lp(a) levels were measured by two-site sandwich enzyme-linked immunosorbent assay. RESULTS: The patients with PDR had higher serum Lp(a) levels than those with no diabetic retinopathy or with nonproliferative diabetic retinopathy (NPDR). Multiple logistic regression analysis showed that high serum Lp(a) levels and the presence of diabetic nephropathy were independent variables having a statistically significant association with PDR. CONCLUSIONS: Korean type 2 diabetic patients with PDR had higher serum Lp(a) levels versus those with no diabetic retinopathy or with NPDR. Although these results suggest that Lp(a) might play a role in the occlusion of retinal capillaries leading to PDR, further prospective studies are required to prove the causal relationship.

Blood Glucose↗

Iron-induced cytotoxicity in cultured rat retinal neurons.

Oxidative stress has been proposed as a major injury mechanism in the central nervous system including the retina. In this study, as an initial attempt to study the mechanism of oxidative injury in the retina, we developed a cell culture model by utilizing the iron exposure paradigm. Exposure of rat retinal cultures for 24 hours to 10-40 MicroM ferrous or ferric chloride induced a concentration-dependent death of retinal neurons but not of photoreceptors or astrocytes. An antioxidant, trolox effectively attenuated the iron-induced death of neurons and photoreceptors in a dose-dependent manner whereas neither glutamate receptor antagonists nor cycloheximide were protective. Of retinal interneurons, GABAergic neurons were more vulnerable to the iron toxicity than calbindin (+) horizontal neurons. These findings show that iron exposure induces anti-oxidant-sensitive neuronal injury in retinal culture, independent of the excitotoxic or the apoptotic mechanisms. Of retinal neurons, different cell types exhibit differential vulnerabilities to the iron-induced oxidative injury. This simplified culture model system may be useful in elucidating mechanisms of oxidative injury in the retina.

Animals↗

Construction of a Helicobacter pylori-Escherichia coli shuttle vector for gene transfer in Helicobacter pylori.

In this study, a Helicobacter pylori-Escherichia coli shuttle vector was constructed for transferring DNA into H. pylori. The smallest cryptic plasmid (1.2 kb), pHP489, among those harbored by 77 H. pylori isolates was selected as a base replicon for constructing vectors. HindIII-digested pHP489 was ligated with a kanamycin resistance gene [aph(3')-III], which originated from Campylobacter jejuni, to produce the recombinant plasmid pHP489K. pHP489K was efficiently transformed into and stably maintained in H. pylori strains. The shuttle vector pBHP489K (3.6 kb) was constructed by the recombination of pHP489, ColE1, and aph(3')-III sequences. pBHP489K was reciprocally transformed into and maintained in both H. pylori and E. coli. Introduction of the shuttle vector clone DNA (pBHP489K/AB; 6.7 kb), containing the ureA and ureB genes of H. pylori, into urease-negative mutants of H. pylori led to the restoration of their urease activity. The transformants were confirmed to contain the incoming plasmid DNA. pBHP489K satisfied the requirements for an H. pylori-E. coli shuttle vector, implying that it might be a useful vector for investigating pathogenicity and restriction-modification systems of H. pylori.

Cloning, Molecular↗