Orientia tsutsugamushi is obligate intracellular bacterium that grows within the cytoplasm of the eukaryotic host cells. Therefore capability of the attachment, entry into the host cell and intracellular survival should be critical process for oriential infection. In this study we investigated the cellular invasion mechanism of Orientia tsutsugamushi and the role of transmembrane heparan sulfate proteoglycan, which binds diverse components at the cellular microenvironment and is implicated as host cell receptors for a variety of microbial pathogens. First of all Orientia tsutsugamushi can invade a wide range of nonprofessional phagocytic cells including fibroblast, epithelial cells a#nd endothelial cells of various host species, including B and T lymphocytes. Thus, it was postulated that the attachment of O. tsutsugamushi requires the recognition of ubiquitous surface structures of many kinds of host cells. Treatments with heparan sulfate and heparin inhibited the infection of Orientia tsutsugamushi in dose-dependent manner for L cell, mouse fibroblast, whereas other glycosaminoglycans such as chondroitin sulfate had no effect. Collectively, these findings provide strong evidence that initial interaction with heparan sulfate proteoglycan is required for the oriential invasion into host cells.
Animals ; Cellular Microenvironment ; Chondroitin Sulfates ; Cytoplasm ; Endothelial Cells ; Epithelial Cells ; Eukaryotic Cells* ; Fibroblasts ; Glycosaminoglycans ; Heparan Sulfate Proteoglycans ; Heparin ; Heparitin Sulfate ; Mice ; Orientia tsutsugamushi* ; Phagocytes ; T-Lymphocytes

glycosaminoglycans. In this study, tissue sample of pleomorphic adenoma of human salivary gland were obtained from 20 surgical specimens, and all specimens were routinely fixed in 10% formalin and embedded. Serial 4-8 micrometer thick sections were cut from paraffin blocks. The histopathologic evaluation was done with light microscopy. And, with immunohistochemical staining, characteristics of glycosaminoglycan were observed. And, for biochemical analysis of glycosaminoglycan, isolation of crude glycosaminoglycan from tumor tissue and immuno-blot analysis were carried out. With transmission electromicroscopy, tumor cells and biologic behavior of pleomorphic adenoma were observed with distribution and expression of glycosaminoglycan in tumor cells. The results were obtained as follows: 1. In immunohistochemical study, chondroitin 4-sulfate is highly postively stained in myxoid stromal tissue, and chondroitin 6-sulfate is highly positively stained in chondroid mesenchymal tissue, both glycosaminoglycans are positively stained in non-luminal cell of ductal area. 2. Dermatan sulfate and keratan sulfate is positively stained in periductal non-luminal tumor cells. 3. In immunohistochemical study, heparan sulfate is weakly stained in luminal cells and non-luminal cells around duct, and chondroid mesenchymal tissue. 4. In transmission electromicroscopic view, the tumor cells are composed of modified myoepithelial cells, and contain many microfilaments and well developed rough endoplasmic reticulum. 5. In Immuno-Blot analysis, the expression of glycosaminoglycans is expressed mostly in chondroitin 6-sulfate and chondroitin 4-sulfate. From the results obtained in this study, tumor cells of pleomorphic adenoma are composed of modified myoepithelial cells, and glycosaminoglycans of chondroitin 4-sulfate and chondroitin 6-sulfate mostly participate in the development of pleomorphic adenoma, but dermatan sulfate, keratan sulfate and heparan sulfate glycosaminoglycans were expressed variably.]]>
Actin Cytoskeleton ; Adenoma, Pleomorphic ; Bone and Bones ; Chondroitin Sulfates ; Dermatan Sulfate ; Endoplasmic Reticulum, Rough ; Epithelial Cells ; Formaldehyde ; Glycosaminoglycans ; Heparitin Sulfate ; Humans ; Hyalin ; Keratan Sulfate ; Microscopy ; Paraffin ; Parotid Gland ; Phenobarbital ; Salivary Glands ; Sublingual Gland ; Submandibular Gland

BACKGROUND: Impaired renal function may contribute to development of stroke and small vessel pathology in the brain. We investigated whether stroke subtype, initial stroke severity, early neurologic outcomes, time to cerebral infarction occurrence, and the presence of small vessel pathology in the brain are different between patients with end stage renal disease (ESRD) and those with renal transplantation (RT). METHODS: A total of 57 consecutive de novo RT patients (RT group) and 120 patients undergoing dialysis due to ESRD (ESRD group) who developed a first-ever acute cerebral infarction were enrolled. We compared stroke subtypes based on the Trial of Org 10172 in Acute Stroke Treatment classification, the presence of small vessel pathology (cerebral microbleed, leukoaraiosis and silent lacunar infarction) on MRI, stroke severity based on the National Institutes of Health Stroke Scale (NIHSS) and in-hospital mortality between the groups. RESULTS: The stroke subtypes, NIHSS scores at admission and in-hospital mortality were not different between the two groups. On multivariate analysis, the presence of high grade periventricular white matter changes tended to be more frequently detected in the ESRD group than the RT (P=0.078). The time from starting dialysis to stroke was longer in the RT group (129.9+/-60.9 months) than in the ESRD group (51.1+/-46.1 months). CONCLUSIONS: The stroke patterns, severity and short term outcomes were not different between RT and ESRD. The risk of cerebral infarction and high grade periventricular white matter changes may be reduced after RT in patients with ESRD.
Brain ; Cerebral Infarction ; Chondroitin Sulfates ; Dermatan Sulfate ; Dialysis ; Glycosaminoglycans ; Heparitin Sulfate ; Hospital Mortality ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation ; Leukoaraiosis ; Multivariate Analysis ; National Institutes of Health (U.S.) ; Stroke

Adenoid cystic carcinoma is malignant tumor in salivary gland, and its behavior is very invasive. Of all malignant tumor adenoid cystic carcinoma is occured in frequency of 4.4% in major salivary gland, and 1.29% in minor salivary gland. Histopathologically, adenoid cystic carcinoma is characterized by a cribriform appearance, and tubular form and solid nest type tumor can be seen. The tumor cell structure composed of modified myoepithelial cell, and basaloid cell. Extracellular matrix of this tumor cell contains variable ground substance with basement membrane component. Basement membrane matrix composed of collagen fibers, glycoproteins, proteoglycans, and its function is well known that it participate in differentiation, proliferation, and growth of tumor cell. Basement membrane molecule is essential for invasion of peripheral nerve, blood vessel, skeletal muscle in tumor cell of adenoid cystic carcinoma. In many studies, the tumor cell of adenoid cystic carcinoma containing modified myoepithelial cell participate in synthesis of proteoglycan. In this study, tissue sample of adenoid cystic carcinoma of human salivary gland were obtained from 15 surgical specimen, and all specimen were routinely fixed in 10% formalin and embedded. Serial 4-micrometer thick sections were cut from paraffin blocks. the histopathologic evaluation was done with light microscopy. And, the immunohistochemical staining, characteristics of glycosaminoglycan were observed. For biochemical analysis of glycosaminoglycan, isolation of crude glycosaminoglycan from tumor tissue and Western bolt analysis were carried out. With transmission electomicroscopy, tumor cell were observed. Biologic behavior of adenoid cystic carcinoma was observed with distribution and expression of basement membrane of glycosaminoglycan in tumor cells, The results obtained were as follows: 1. In immunohistochemical study, chondroitin sulfate is postively stained in tumor cell and interstitial space, dermatan sulfate is weakly stained in ductal cell. But keratan sulfate is negatively stained. 2. In immunohistochemical study, heparan sulfate is strong positive stained in tumor cell and basement membrane, especially in invasion area to peripheral nerve tissue. 3. In transmission electromicroscpic view, the tumor cells are composed modifed myoepithelial cells, and contains many microvilli and rough endoplasmic reticulum. 4. In Western blot analysis, the expression of glycosaminoglycan is expressed mostly in heparan sulfate. From the results obtained in this study, tumor cell of adenoid cystic carcinoma is composed modified myoepithelial cell, and glycosaminoglycan of basement membrane molecule of heparan sulfate and chondroitin sulfate mostly participate in the development and invasiveness of adenoid cystic carcinoma by immunohistochemical study and western blot analysis.
Adenoids* ; Basement Membrane ; Blood Vessels ; Blotting, Western ; Carcinoma, Adenoid Cystic* ; Chondroitin Sulfates ; Collagen ; Dermatan Sulfate ; Endoplasmic Reticulum, Rough ; Extracellular Matrix ; Formaldehyde ; Glycoproteins ; Heparitin Sulfate ; Humans ; Keratan Sulfate ; Microscopy ; Microvilli ; Muscle, Skeletal ; Paraffin ; Peripheral Nerves ; Proteoglycans ; Salivary Glands ; Salivary Glands, Minor

Gingival fibroblasts are embedded in an extracellular matrix. The matrixs have influence on the development, polarity, and behavior of nearby cells. The major component of periodontal extracellular matrix is a glycosaminoglycan. The glycosaminoglycan are large carbohydrates that are composed of repeating disaccharide units and exist in three main form: dermatan sulfate, chondrotitin sulfate, heparan sulfate. The purpose of present study is to examine the biologic effects of glycosaminoglycan on human gingival fibroblast. Human gingival fibroblasts were supplemented with each glycosaminoglycan, and cellular attachment and proliferation was determined by MTT assay. Dermatan sulfate and chondroitin sulfate did not stimulate the attachment and proliferation of human gingival fibroblasts, but heparan sulfate increased the proliferation and attachment in a time- and dose- dependent manner. These results indicated that heparan sulfate seems to have a high potential for gingival regeneration and root surface attachment.
Carbohydrates ; Chondroitin Sulfates ; Dermatan Sulfate ; Extracellular Matrix ; Fibroblasts* ; Heparitin Sulfate ; Humans* ; Regeneration

OBJECTIVE: We evaluated whether serum total bilirubin levels were related to large artery atherosclerosis (LAA), classified by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and stroke severity at admission in acute ischemic stroke. METHODS: We analyzed clinical features, laboratory tests, and radiologic findings such as brain MRI and MR angiography of patients admitted to our hospital within 24 hours of the onset of ischemic stroke between January 2004 and June 2007. By TOAST classification, 237 patients [115 with LAA and 122 with small artery occlusion (SAO)] were selected. We divided serum total bilirubin levels into three groups: Low (<0.6 mg/dL), Middle (0.6~0.9 mg/dL), and High (1.0~1.2 mg/dL). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) at admission. We divided NIHSS scores into three groups: Mild (0-6), Moderate (7-15), and Severe group (>15). RESULTS: Total bilirubin levels were significantly higher in the Mild group than other groups, and high-sensitivity C reactive protein (hsCRP) levels were significantly higher in the Severe group than other groups in LAA. There were no differences for these factors in SAO. We found a significant correlation between total bilirubin levels and stroke severity in LAA (p=0.005). CONCLUSION: Higher serum total bilirubin levels were associated with lower stroke severity at admission in LAA but not SAO.
Angiography ; Arteries ; Atherosclerosis ; Bilirubin ; Brain ; C-Reactive Protein ; Chondroitin Sulfates ; Dermatan Sulfate ; Heparitin Sulfate ; Humans ; National Institutes of Health (U.S.) ; Stroke

BACKGROUND: Although levels of D-dimer and fibrinogen/fibrin degradation products (FDP) are low in the circulation of healthy individuals, their levels are significantly elevated in patients with thromboembolic diseases. The aim of this study was to investigate the clinical utilities of D-dimer and FDP in the early diagnosis of stroke subtypes and the prediction of early prognosis. METHODS: Hospitalized patients due to acute ischemic stroke underwent measurement of plasma levels of D-dimer and FDP within 12 hours after admission. Stroke severity was assessed on admission and 2 weeks later using the National Institutes of Health Stroke Scale (NIHSS). Stroke subtypes were classified according to the criteria of the Trial of ORG 10172 in Acute Stroke Treatment criterion. RESULTS: D-dimer and FDP levels were significantly higher in the cardioembolic group than in the atherosclerotic and lacunar groups. There was independent correlation between the level of FDP and cardioembolism. Ninety-six patients showed clinical improvement that was defined by a reduction of more than 4 points on the NIHSS two weeks later compared with that on admission. The level of D-dimer was higher in patients with clinical improvement than in patients without improvement (p=0.032). However, there was no correlation between the level of D-dimer and early improvement. CONCLUSIONS: These results show that measurement of FDP in acute ischemic stroke could be helpful in subtype classification. However, D-dimer and FDP were not related with early prognosis.
Cerebral Infarction ; Chondroitin Sulfates ; Dermatan Sulfate ; Early Diagnosis ; Fibrin Fibrinogen Degradation Products ; Formycins ; Heparitin Sulfate ; Humans ; National Institutes of Health (U.S.) ; Plasma ; Ribonucleotides ; Stroke ; Thromboembolism

OBJECTIVE: To investigate the correlation between the pulse pressure (PP) and functional outcome in acute middle cerebral arterial (MCA) ischemic stroke. METHOD: We reviewed the medical records of 52 first-ever hemiplegic MCA ischemic stroke patients (age 61.5+/-9.7 years; 35 men, 17 women). Functional outcomes were evaluated with Korean-modified Barthel index (K-MBI), functional independence measure (FIM), Korean-national institutes of health stroke scale (K-NIHSS), and Korean-mini mental state examination (K-MMSE) on 3 days and 3 months after the onset of stroke in all the subjects. The PP was measured six times within initial 24 hours after stroke onset and then the highest PP was selected for the analysis. RESULTS: The degree of PP elevation revealed the significant correlations with male gender, over the age of 55 years, diabetes mellitus, and current smoking history, respectively (p<0.05). In TOAST (Trial Org 10172 in Acute Stroke Treatment) classification, the large artery atherosclerosis group showed significantly the higher PP rather than the other groups (p<0.05). There were inverse correlations between the PP and each of FIM and K-MBI scores on 3 months after stroke onset (p=0.000, 0.009; r=- 0.479, -0.358). There was an inverse correlation between the PP and the change of FIM (p=0.000, r=-0.532). CONCLUSION: The PP within initial 24 hours after stroke onset revealed significant correlation with functional outcome. The management for the proper PP gives the favorable effect on the functional outcome in acute MCA territory ischemic stroke.
Academies and Institutes ; Arteries ; Atherosclerosis ; Blood Pressure ; Chondroitin Sulfates ; Dermatan Sulfate ; Diabetes Mellitus ; Hemiplegia ; Heparitin Sulfate ; Humans ; Male ; Medical Records ; Middle Cerebral Artery ; Smoke ; Smoking ; Stroke

Sulodexide is composed of two glycosaminoglycans (fast-moving heparin 80%, dermatan sulfate 20%) that are capable of preventing diabetic nephropathy by correcting abnormal glycosaminoglycan metabolism. Considering heparin-like propertyof sulodexide, side effect profiles of sulodexide are expected to be similar with those of heparin. Among those side effects, we remarked on heparin-induced hyperkalemia and hereby report a case of severe hyperkalemia during the use of sulodexide. A 52-year-old man with diabetic nephroapthy and hypertension was admitted to our hospital because of severe hyperkalemia up to 7.5 meq/L. His clinical condition was stable and medications including losartan and furosemide had not been changed for last 6 months except the addition of sulodexide, which was started 30 days prior to admission. Despite intensive use of Kayexalate and immediate discontinuation of losartan, hyperkalemia aggravated up to 8.0 meq/L. After recognition of possible sulodexide-induced hyperkalemia, sulodexide was discontinued, which resulted in rapid correction of hyperkalemia. In view of the above discussed clinical consideration, we suspect sulodexide as a major cause of hyperkalmia and report this case with a review of literature.
Dermatan Sulfate ; Diabetic Nephropathies ; Furosemide ; Glycosaminoglycans ; Heparin ; Humans ; Hyperkalemia ; Hypertension ; Losartan ; Middle Aged ; Polystyrenes

Chondroitin sulfate (CS) in corneal preservation medium can porolong corneal preservation time. The solutions used in the experimental chambers were made of TC-199 (GIB Co.) either by itself of by adding 1% CS (Sigma) to the TC-199. The evaliation of the viability of corneas can be made by monitoring their physiological parameter. Thus, we monitored the transendothelial electrical potential difference (p.d.) across deepithelialized rabbit corneas. We found that TC-199 containing 1% CS maintained higher p.d.'s than the same solution without CS.
Chondroitin Sulfates* ; Chondroitin* ; Cornea*