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Biomedical subjects

S M Chung

Publications and source records attributed to S M Chung.

At least 55 records · Page 3Linked to original sources

First-pass accumulation of salicylic acid in gut tissue after absorption in anesthetized rat.

PURPOSE: The purpose of this paper is to report the study on the first-pass accumulation kinetics of salicylic acid (SA) in gut tissue after absorption by simultaneously analyzing drug contents in the lumen, gut tissue, and blood in anesthetized rats. METHODS: Sodium salicylate (5.4 mg as SA) in 0.4 ml normal saline was administered into a closed 10-cm jejunal loop. Drained mesenteric blood from the loop area was collected every minute, while lost blood was replaced through infusion of oxygenated blood from donor rats. At 3, 10, 20, 40, or 60 min after dosing, SA remaining in lumen, accumulating in gut tissue, and appearing in blood were analyzed by HPLC. All the data were fitted into a linear two-consecutive (lumen and gut tissue) first-order kinetic model. RESULTS: After absorption, significant amounts of SA accumulated in gut tissue before appearing in blood, e.g., at 3 or 20 min after dosing, 74.4 or 54.4% of absorbed SA accumulated in gut tissue, respectively. Practically all administered SA was recovered. The estimated mean absorption time from the lumen and mean transit time in gut tissue of SA were 20.4 and 18.5 min, respectively. CONCLUSIONS: The above results indicate that gut tissue may act as a reservoir for drug accumulation during the first pass after oral absorption. Thus, the rate of transport of drug into blood circulation after oral administration may significantly differ from the true rate of absorption through the gut membrane. The potential transport resistance from gut tissue to blood should probably be considered in the modeling of GI absorption.

Animals↗

Expression of interleukin-6 in polymorphic reticulosis--immunohistochemical study of 5 cases.

Peripheral T cell lymphoma encompasses lymphomas with a variety of histologic appearances and clinical patterns. Recently, it has been suggested that almost all of the histologic features described under the name of polymorphic reticulosis(PR), lethal midline granuloma, and midline malignant reticulosis can be included in those generally described for malignant lymphomas of peripheral T cell origin(PTCL). There have been few studies of pathogenesis or tissue damage mechanism in PR patients. The need for a precise mechanism for tissue damage has important therapeutic implications. Using immunohistochemical methods with polyclonal anti IL-6 antibody, the authors describe 5 cases of PR with clinically and pathologically typical PR demonstrating a high expression of IL-6. According to classification, 2 cases of grade 1 PR showed the highest expressions, and 2 cases of grade 2 PR with atypical lymphoid cells showed moderate activity, but one case progressed into frank lymphoma(grade 3) and lost IL-6 expression. This strongly implies that some cases of PR have a different mechanism of tissue damage from frank PTCL, despite the one disease spectrum. Further studies on more cases may help clarify the pathogenesis.

Adult↗

Role of endothelin-converting enzyme in the systemic hemodynamics and regional circulatory effects of proendothelin-1 (1-38) and diaspirin cross-linked hemoglobin in rats.

Diaspirin cross-linked hemoglobin (DCLHb) is a promising hemoglobin-based, oxygen-carrying resuscitative solution. DCLHb (400 mg/kg, iv) produces significant cardiovascular effects, along with an increase in plasma endothelin-1 (ET-1) level, when administered to conscious or anesthetized rats. Present studies were performed to determine whether the cardiovascular effects of DCLHb are due to an increase in the conversion of proendothelin-1 (1-38) (proET-1) to ET-1 by endothelin-converting enzyme (ECE). The regional circulatory and systemic hemodynamic effects of proET-1 (20 micrograms/kg, iv) and DCLHb (400 mg/kg, iv) were determined by using a radioactive microsphere technique in control rats and rats pretreated with phosphoramidon (ECE inhibitor). Administration of proET-1 produced an immediate increase in mean arterial pressure (MAP)(52%) and total peripheral resistance (TPR) (55%); stroke volume (SV) and cardiac output were not affected in the initial phase but were decreased subsequently. Heart rate (HR) was not affected after administration of proET-1. A significant increase in blood flow to the heart (39%), brain (46%), kidneys (74%), portal system (40%), and gastrointestinal tract (GIT) (42%) was also observed after administration of proET-1. Vascular resistance was found to be significantly increased in the mesentery and pancreas (168%) and in the musculoskeletal system (147%) and decreased in the kidneys (-11%) after administration of proET-1. Phosphoramidon (4 mg/kg, iv) pretreatment attenuated the increase in MAP and TPR induced by proET-1. Phosphoramidon pretreatment significantly attenuated the proET-1-induced increase in blood flow to the heart, brain, kidneys, portal system, and GIT. The increase in vascular resistance induced by proET-1 in the mesentery and pancreas and in the musculoskeletal system was also attenuated by phosphoramidon. DCLHb increased MAP (63%) and TPR (54%) without affecting HR. DCLHb increased blood flow to the heart (95%), GIT (45%), portal system (43%), and skin (79%) and increased vascular resistance in the musculoskeletal system (58%). In phosphoramidon-treated rats, DCLHb increased MAP (99%), HR (25%), cardiac output (37%), and TPR (60%). DCLHb increased blood flow to the heart (104%), brain (66%), kidneys (49%), GIT (59%), portal system (63%), and skin (100%) when administered to phosphoramidon-treated rats. Phosphoramidon did not attenuate any of the DCLHb-induced cardiovascular effects. It is concluded that proET-1 increases blood flow to various organs and that phosphoramidon, an ECE inhibitor, could block the proET-1-induced increases in regional blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Optic neuropathy, headache, and diplopia with MRI suggestive of cerebral arteritis in relapsing polychondritis.

The pathogenesis of central nervous system disease in relapsing polychondritis (RPC) is unknown but may be related to cerebral arteritis. Previous reports have described clinical and histopathologic evidence of cerebral vasculitis in RPC; however, a neuroimaging correlate has not been reported. We present a 36-year-old man with neuro-ophthalmic features of RPC whose magnetic resonance imaging revealed multifocal gray- and white-matter high intensities. This pattern is consistent with cerebral arteritis as described in other systemic vasculitides.

Adult↗

Nonarteritic ischemic optic neuropathy. The impact of tobacco use.

BACKGROUND: Numerous associations to anatomic variation and systemic vascular disease have been made to anterior ischemic optic neuropathy (AION) but exogenous agents have not been emphasized. The authors studied the effect that smoking had in the development of AION. The relevance of other intraocular and systemic vascular disease to AION also is discussed. METHODS: Over a 10-year period (January 1980-May 1990), nonarteritic AION was diagnosed in 148 patients, 137 of whom were included in this analysis. FINDINGS: Of the 137 patients identified with nonarteritic AION, 28 smokers were statistically younger, at 51 years of age, compared with 83 nonsmokers whose mean age was 64 years (P = 0.005). CONCLUSIONS: Cigarette smoking is an important risk factor in the development of AION. Cessation of smoking appears to reduce the risk of AION to that of the nonsmoking population.

Adult↗

Quantitative assessment of normal and stenotic aortic valve using transesophageal three-dimensional echocardiography.

The present study demonstrates the feasibility of transesophageal three-dimensional reconstruction of normal, sclerotic, and stenotic aortic valves using a computed tomographic ultrasound system. The study also shows the potential clinical usefulness of this technique in delineating aortic valve morphology (extent and severity of valve thickening and calcification and size and number of cusps) and assessing aortic orifice areas by direct planimetry of the three-dimensional images.

Aged↗

Effects of vanadate on vascular contractility and membrane potential in the rabbit aorta.

Isolated rabbit aortic ring with intact endothelial cell preparations precontracted with NE (10(-7) M) were relaxed by vanadate in a dose dependent manner (from 0.2 to 2 mM). Application of vanadate and ACh during the tonic phase of high K+(100 mM)-induced contraction showed a slight relaxation in contrast to that in NE-induced contraction, but sodium nitroprusside (10 microM) more effectively relaxed the aortic ring preparations in high K+ contraction than that of vanadate. Vanadate-induced relaxation in NE-contracted aortic rings was reversed by application of BaCl2 (50 microM) or glibenclamide (10 microM). Furthermore, Vanadate hyperpolarized membrane potential of smooth muscle cells in endothelium-intact aortic strips and this effect was abolished by application of glibenclamide. The above results suggest that vanadate release EDHF (Endothelium-Derived Hyperpolarizing Factor), in addition to EDRF (Endothelium-Derived Relaxing Factor) from endothelial cell. This EDHF hyperpolarize the smooth muscle cell membrane potential via opening of the ATP-sensitive K+ channel and close a voltage dependent Ca++ channel. So it is suggested that the vanadate-induced relaxation of rabbit thoracic aortic rings may be due to the combined effects of EDRF and EDHF.

Animals↗

Bilateral internuclear ophthalmoplegia in a patient with Wernicke's encephalopathy.

The most common cause of bilateral internuclear ophthalmoplegia is multiple sclerosis. Wernicke's encephalopathy has been reported as a cause of unilateral internuclear ophthalmoplegia but not of bilateral internuclear ophthalmoplegia. In this report, we present the case of a patient with a history of alcohol abuse and acute onset of bilateral internuclear ophthalmoplegia whose clinical course and diagnostic studies are most consistent with a diagnosis of Wernicke's encephalopathy.

Adult↗

Management of the hearing-impaired adults in Singapore.

A preliminary study to investigate that the pure-tone air-conduction hearing threshold level which is not an accurate index of amplification need profile applies to the hearing-impaired population in Singapore. Results obtained from a sample of twenty users of monaural amplification indicate that the hearing-impaired patients showed a significant reduction in communication difficulties with their hearing aids and are overall satisfied with their monaural amplification despite certain problems with background noise, regardless of the severity of their hearing losses.

Adult↗

Characterization of a cathepsin L-like enzyme secreted from human pancreatic cancer cell line HPC-YP.

Spent culture medium from the human pancreatic carcinoma cell line HPC-YP, which can propagate in a protein-free, chemically defined medium without any other supplements, was analyzed for the presence of the cysteine protease, cathepsin L. The secreted form of cathepsin L was distinguished from the lysosomal form by its increased stability at alkaline pH, by its strong thermostability, and by its larger molecular size. HPC-YP cathepsin L was still stable at pH 7.4 and at 56 degrees C after 60-min preincubation. The molecular weight of this enzyme was estimated to be 68,000, compared with a molecular weight of 29,000 for normal liver cathepsin L. By Western blot analysis, HPC-YP enzyme was found to be composed of two components, one with a molecular weight of 37,000 and the other of 31,000. This result suggests that HPC-YP enzyme in the spent medium may be a complex of the proenzyme (in the case of liver proenzyme; Mr 39,000) and the mature enzyme (in the case of liver mature enzyme; Mr 29,000). Interestingly, an intrinsic inhibitor was also separated from the spent medium by gel filtration. The molecular weight of this inhibitor was estimated to be approximately 13,000. The cathepsin L of HPC-YP proved more resistant toward leupeptin than did liver cathepsin L. On the other hand, the former was more sensitive than the latter toward the diazomethane inhibitors, Z-Phe-Phe-CHN2 and Z-Phe-Ala-CHN2. These results indicate that cathepsin L secreted from cancer cell lines may play a role in the destruction of basal lamina, invasion of tissue, and formation of metastasis.

Blotting, Western↗

Variant cathepsin L activity from gastric cancer tissue.

Cathepsin L activity was partially purified by S-Sepharose FF chromatography, concanavalin-A Sepharose chromatography, phenyl-Superose column chromatography, Mono S column chromatography, and TSK G3000SWXL column chromatography from gastric cancer tissue. The optimal pH of cathepsin L from gastric cancer tissue was 7.4, and the activity was retained even at alkaline pH. Heat stability tests showed that cathepsin L from gastric cancer tissue was heat stable; that is, 65% activity was retained after incubation at 56 degrees C for 60 min. The molecular weight of cathepsin L from gastric cancer tissue was estimated as 115 kD by gel filtration or 110 kD by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme showed a different affinity for wheat germ agglutinin-Sepharose than cathepsin L from gastric normal mucosa. These results suggest that cathepsin L from gastric cancer tissue may play an important role in gastric cancer invasion through the destruction of the surrounding extracellular matrix by its proteolytic activity.

Cathepsin L↗

[Protease activities in gastric and colon cancer tissues].

Activities of cathepsin B, cathepsin L, and plasminogen activators (urinary type plasminogen activator and tissue type plasminogen activator) were assayed in homogenates of cancer tissue, normal tissue closely surrounding the cancer tissue, and normal tissue distant from the cancer tissue from 30 patients undergoing surgery for gastric cancers and 10 patients undergoing surgery for colon cancers. Activities of those proteases were also assayed in homogenates of adenoma tissue from 10 patients undergoing polypectomy for colon polyps. In the gastric cancer tissue homogenates, the activities of cathepsin B, cathepsin L and tissue type plasminogen activator were significantly higher than in normal tissues. By contrast, the activities of urinary type plasminogen activator of gastric cancer tissues were significantly lower than normal tissues. In the colon cancer tissue homogenates, the activities of cathepsin, B, cathepsin L, and urinary type plasminogen activator were significantly higher than in normal tissues. On the other hand, the activities of tissue type plasminogen activator of cancer tissues were significantly lower than normal tissues. But there were no significant differences in the activities of plasminogen activators between the cancer tissues and adenoma tissues. These results suggest that cathepsin B and cathepsin L play an important role in gastric and colon cancer proliferation and evolution, although the roles of plasminogen activators in gastric and colon cancer proliferation and evolution and in the colon adenoma-carcinoma sequence are still unknown.

Cathepsin B↗

Variant cathepsin B activity secreted from human pancreatic cancer cell lines into protein-free chemically defined medium.

Cathepsin B activity was found in serum-free spent media of human pancreatic cancer cell lines, Panc-1 and MiaPaca. Cathepsin B activity was partially purified by gel filtration on TSK G3000SW, Con-A Sepharose chromatography, Phenyl-Superose column chromatography, and Mono S column chromatography. The optimal pH of cathepsin B was 7.4, and the activity was retained even at alkaline pH. Heat stability test showed that the enzyme was heat stable; that is, 50% activity was retained after incubation at 56 degrees C for 60 min. These results suggest that cathepsin B secreted from human pancreatic cancer cell is a variant type and may play an important role in pancreatic cancer invasion or metastasis through destruction of the surrounding extracellular matrix by its proteolytic activity.

Cathepsin B↗

Characterization of variant gamma-glutamyl transpeptidase produced by pancreatocholangiocarcinoma cell lines in a protein-free, chemically defined medium.

Four pancreatocholangiocarcinoma cell lines (HPC-Y1, HPC-YT, MIA PaCa-2, and HChol-Y1) were established to propagate in a protein-free, chemically defined medium. High gamma-glutamyl transpeptidase (GGTP) activities were showed in their spent media (designated as the secreted (GGTP). Their GGTP activities in the spent media were 125, 85, 110, and 153 IU/L/mg of lyophilized spent media, whereas GGTP activities extracted from their cancer cell lines with bromelain were 105, 37, 86, and 112 IU/L/1 x 10(6) cells, respectively. The chemical characteristics of the GGTPs in the spent media from these cell lines resembled one of the GGTPs, sialic acid-rich GGTP, extracted from normal human pancreas with bromelain treatment as follows: the GGTPs secreted from the cancer cell lines bound to an anion exchange column moved fast on electrophoresis and then showed decreased electrophoretic mobility with neuraminidase treatment, showed a high affinity for concanavalin A and lentil lectin columns, and had an acidic isoelectric point. However, the elution patterns of erythroagglutinating phytohemagglutinin (E-PHA) column chromatography and thermostability tests demonstrated clear differences between the carcinoma GGTPs both in the spent media and cell lines and the sialic acid-rich GGTP of normal pancreas, namely the carcinoma GGTPs treated with neuraminidase showed affinity to E-PHA columns, and, in addition, the GGTPs in the spent media showed an apparent heat resistance at 56 degrees C. These findings indicate that the carcinoma GGTPs have a different oligosaccharide structure from that in normal pancreatic GGTPs.

Adenoma, Bile Duct↗

Purification of human pancreatic gamma-glutamyltranspeptidase by lectin affinity chromatography.

Two types of pancreatic gamma-glutamyltranspeptidase (GGTP) (EC 2.3.2.2), sialic acid poor and sialic acid rich, were purified by the following: anion-exchange chromatography, wheat germ agglutinin (WGA)-Sepharose chromatography, gel filtration chromatography, phenyl-Superose chromatography, and hydroxylapatite chromatography. Among these, WGA-Sepharose chromatography helped to increase the specific activity of the GGTPs by approximately 20-30-fold in one effort. On dodecyl sulfate polyacrylamide gel electrophoresis, the two pancreatic GGTPs had different molecular weights. Sialic acid-rich GGTP had two subunits of Mr 67,000 and 27,000; however, the sialic acid-poor type had two subunits of Mr 72,000 and 29,000. The pI value of the sialic acid-poor GGTP was 5.9, and that of the sialic acid-rich GGTP 3.6.

Chromatography, Affinity↗

Management of pregeniculate anterior visual pathway gliomas.

Gliomas of the pregeniculate anterior visual pathways comprise about 5% of all intracranial tumors that occur in the first decade of life. Gliomas are the most common primary optic nerve tumor. Diagnosing a glioma of the anterior visual pathways is much easier since the advent of computerized tomography (CT) and magnetic resonance imaging (MRI); the continuing problem is appropriate management. Improved guidelines for management are suggested based on a review of the literature and the authors' experience. These guidelines include both the need to characterize accurately the location of the tumor and its clinical and radiologic progression, and the imperative to employ active intervention only when there is a specific therapeutic goal that can be used for measuring the success of the treatment.

Child↗