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Biomedical subjects

S K Chung

Publications and source records attributed to S K Chung.

At least 73 records · Page 4Linked to original sources

Mouse preproendothelin-1 gene. cDNA cloning, sequence analysis and determination of sites of expression during embryonic development.

Endothelin-1 (ET-1) is a peptide implicated in a wide variety of functions involving vascular and non-vascular systems. We have cloned the cDNA encoding the mouse prepro-endothelin-1 (PPET-1) and determined its nucleotide sequence. The putative PPET-1 peptide processing sites are all conserved and the deduced 21-amino-acid mature ET-1 peptide is identical to that of the rat, human, bovine, porcine and rabbit. Using the cloned cDNA as a probe for in situ hybridization, we detected PPET-1 mRNA in different tissues at different stages of mouse embryonic development. Embryos at a stage as early as 9.5 days postcoitum (E9.5) have very strong expression in the branchial epithelium, optic vesicle and the endothelial cells of large blood vessels, including the dorsal aorta and aortic arches. While the expression level in the branchial epithelium was decreasing towards the later stage of embryogenesis, the expression in the endothelial cells increased with age. At E10.5, PPET-1 mRNA was also detected in the otic vesicle as well as in the developing gut epithelium. At later stage of development, the expression of PPET-1 was primarily found in the vascular endothelial cells, cochlea, eye and the gut, with the highest level of PPET-1 mRNA in the endothelial cells of the lung. These data will be useful for analyzing the function of ET-1 in these organs.

Amino Acid Sequence↗

Tissue-specific expression of two aldose reductase-like genes in mice: abundant expression of mouse vas deferens protein and fibroblast growth factor-regulated protein in the adrenal gland.

Aldose reductase (AR), the first enzyme in the polyol pathway, has been implicated in the pathogenesis of diabetic complications, although its physiological role is unclear. In mice, besides AR, two AR-like proteins, mouse vas deferens protein (MVDP) and fibroblast growth factor-regulated protein (FR-1), have been reported recently. Tissue-specific expression of these two genes was examined using the RNase protection assay method. Contrary to previous reports, MVDP was detected in a variety of tissues besides the vas deferens. High levels of MVDP mRNA were found in the adrenal glands, and low levels of expression were detected in eye, intestine, seminal vesicle, kidney, liver, testis and lung. The major gene expression pattern for FR-1 was slightly different from that of MVDP, with the highest levels of mRNA detected in testis, heart, adrenal gland, and ovary; less was found in the lung and it was barely detectable in eye, intestine, liver and seminal vesicle tissue. Mouse embryos, as early as 10.5 days post coitum, expressed both genes, although the levels of expression were different. Human AR mRNA was found in human vas deferens, although not at the high level found in mice. The localization of both MVDP and FR-1 transcripts in the adrenal cortex by in situ hybridization led to the speculation that these two AR-like proteins could be related to hormone production.

Adrenal Glands↗

Cloning, sequencing, and determination of the sites of expression of mouse sorbitol dehydrogenase cDNA.

Sorbitol dehydrogenase is one of the enzymes in the polyol pathway, which is thought to be implicated in the pathogenesis of diabetic complications. The cDNA encoding mouse sorbitol dehydrogenase was cloned from a liver library and its sequence was determined. The open reading frame encodes a product of 356 amino acids that shares high similarity with the human and rat liver sorbitol dehydrogenases (83% and 93% identity, respectively). The 3'-untranslated region contains a truncated L1Md repeat element inserted in reverse relative to the sorbitol dehydrogenase cDNA. Northern-blot hybridization showed that the testis has the highest level of expression, followed by kidney, liver, and lung. Low levels of expression were also observed in lens, brain, and skeletal muscle. In situ hybridization revealed that in the kidney, the highest concentration of sorbitol dehydrogenase mRNA is observed in the cortex, but is absent from the inner medulla. The parenchymal cells of the liver showed strong expression while the cells of the hepatic vasculature did not hybridize. The sorbitol dehydrogenase expression in the seminiferous tubules was mostly associated with the mature cells of the developing germ cells, confirming the usefulness of sorbitol dehydrogenase as an enzyme indicator for sexual maturation. The seminal vesicle, where most of the seminal fructose is produced, also showed a high level of expression in the epithelial cells. The mouse sorbitol dehydrogenase cDNA will be useful in the studies of the involvement of the polyol pathway in diabetic complications.

Amino Acid Sequence↗

Studies on the promoter of the Arabidopsis thaliana cdc2a gene.

The 5' flanking (promoter) region of the Arabidopsis thaliana cdc2a gene was cloned and sequenced. A number of putative regulatory motifs were identified including one Myc and three Myb protein binding sequences plus one abscisic acid and two auxin responsive elements. One of the three Myb protein binding sequences is positioned within an auxRE. Promoter-GUS fusions were introduced into plants to study the role of two promoter regions in regulating gene expression. Absence of one Myb binding sequence and the auxRE containing a Myb binding sequence resulted in a significant reduction in expression levels as did a deletion involving the Myc and the third Myb binding sequences along with the second auxRE. However, no changes in expression patterns were observed. The results were quantified using transgenic root cultures.

Abscisic Acid↗

Demonstration that polyol accumulation is responsible for diabetic cataract by the use of transgenic mice expressing the aldose reductase gene in the lens.

Aldose reductase (AR) has been implicated in the etiology of diabetic cataract, as well as in other complications. However, the role of AR in these complications remains controversial because the strongest supporting evidence is drawn from the use of AR inhibitors for which specificity in vivo cannot be ascertained. To settle this issue we developed transgenic mice that overexpress AR in their lens epithelial cells and found that they become susceptible to the development of diabetic and galactose cataracts. When the sorbitol dehydrogenase-deficient mutation is also present in these transgenic mice, greater accumulation of sorbitol and further acceleration of diabetic cataract develop. These genetic studies demonstrated convincingly that accumulation of polyols from the reduction of hexose by AR leads to the formation of sugar cataracts.

Aldehyde Reductase↗

Specificity of the purified inositol (1,3,4,5) tetrakisphosphate-binding protein from porcine platelets.

The specificity of the inositol 1,3,4,5-tetrakisphosphate binding protein purified from porcine platelets [Cullen et al. (1995) Biochem. J. 305, 139-143] was examined using all the isomers of myo-inositol tetrakisphosphate. From the relative potencies of these compounds it appears that phosphorylation of the 1, 3 and 5 positions is essential for high affinity binding, that there is some tolerance of phosphorylation of the 6-hydroxyl, but none of a phosphate in the 2-position, and that phosphorylation of the 4-hydroxyl has very little influence. The binding of Ins(1,3,4,5)P4 was not appreciably altered by physiological Mg2+ concentrations, and the pH dependence of binding under physiological conditions showed a decline from pH 5.5 to pH 9.0.

Animals↗

Influence of peripheral nerve grafts on the expression of GAP-43 in regenerating retinal ganglion cells in adult hamsters.

We have examined the ability of axotomized retinal ganglion cells in adult hamsters, to regenerate axons into a peripheral nerve graft attached to the optic nerve and the expression of GAP-43 by these neurons. We also examined the effect on these events of transplanting a segment of peripheral nerve to the vitreous body. The left optic nerves in three groups of hamsters were replaced with a long segment of peripheral nerve attached to the proximal stump of the optic nerve approximately 2 mm from the optic disc to induce regeneration of retinal ganglion cells into the peripheral nerve. An additional segment of peripheral nerve was transplanted into the vitreous of the left eye in the second group. The animals from the first and second groups were allowed to survive for 1-8 weeks and the number of regenerating retinal ganglion cells was determined by applying the retrograde tracer, Fluoro-Gold to the peripheral nerve graft and the expression of GAP-43 was studied by immunocytochemistry in the same retinas. As a control, a segment of optic nerve was transplanted into the vitreous body of the left eye in the third group of hamsters. These animals were allowed to survive for 4 weeks and the number of regenerating retinal ganglion cells was counted as in Groups 1 and 2. The percentages of the regenerating retinal ganglion cells which also expressed GAP-43 were very high at all time points in Group 1 (with no intravitreal peripheral nerve) and Group 2 (with intravitreal peripheral nerve) and at 4 weeks for the Group 3 (with intravitreal optic nerve) animals. In addition, the number of regenerating retinal ganglion cells, the number of retinal ganglion cells expressing GAP-43 and the number of regenerating retinal ganglion cells which also expressed GAP-43 were much higher in Group 2 than in Group 1 at all the time points and it was also much higher in Group 2 than in Group 3 at 4 weeks whereas there was no significant difference between the results from Groups 1 and 3 at 4 weeks. These data suggested that there was a close correlation between the number of the axotomized retinal ganglion cells regenerating axons into the peripheral nerve graft attached to the optic nerve and the expression of GAP-43.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Structural modeling of differential diagnosis, treatment, and results for allergic rhinitis.

This paper analyzed the relationship among the differential diagnosis, treatment, and results for allergic rhinitis using the covariance structural model. The data were collected from 274 patients with suspected allergic rhinitis who visited the Otorlaryngology Department of the Paik Hospital during 1991-1993. After each patient's characteristics was categorized and combined into several common factors, covariance structure analysis was performed to analyze the structural relationships among the differential diagnosis, treatment, and results of treatment using the significant factors obtained from discriminant analysis. The significant characteristics influenced the diagnosis were the results of skin test from mite/animal, and from mugworts, the results from laboratory tests, rhinorrhea and sneezing, and nasal polyps. The significant characteristics that influenced the method of treatment were: nasal polyps, headache/general symptom, family history/medication, and septal deviation. Headache/general symptom was the only significantly influencing factor for the treatment results.

Diagnosis, Differential↗

Use of absorbable mesh as an aid in abdominal wall closure in the emergent setting.

A surgeon has many options available to aid in the closure of abdominal wall defects in the elective setting. In the emergent setting, active infection or contamination increases the likelihood of infection of permanent prosthetic material and limits the surgical options. In such settings, we have used absorbable mesh (Dexon) as an adjunct to fascial closure until the acute complications resolve. To evaluate the effectiveness of this technique, we reviewed the outcome of such closures in 26 critically ill patients. Between July 1987 and June 1993, 26 patients were identified who had placement of absorbable mesh as part of an emergent laparotomy at a major urban trauma center. Through a retrospective chart review, the incidence of complications and outcome of the closure were tabulated. Seven patients were initially operated on for trauma. Two of the patients had mesh placement at their initial procedure secondary to fascial loss from trauma. The remainder of the patients hd mesh placement during a subsequent laparotomy for complications related to their initial procedure. Indications for these laparotomies included combinations of wound dehiscence, intra-abdominal abscess, anastomotic disruption, and perforation. Mesh placement in patients with intra-abdominal infection created effectively open abdominal wounds that allowed continued abdominal drainage, but required extensive wound care. Despite the absorbable nature of the mesh and often prolonged hospital stay in these ill patients, none of them required reoperation for dehiscence, recurrence of intra-abdominal abscess, or infection of the mesh.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Abscess↗

Bone pathologic correlation of multimodality imaging in Paget's disease.

The pagetic bones in the active phase of the disease with brisk lysis and sclerosis manifest intense tracer uptake on planar bone and SPECT images. Intense tracer uptake, however, can occur also in infections, dysplasias and metastases. Pinhole bone scintigraphy has been shown to portray specific diagnostic signs in a number of skeletal diseases. In an effort to identify useful bone scan signs, we prospectively carried out 99mTc-oxidronate pinhole bone scintigraphy of the skull, vertebrae, ribs, humerus, sacrum and ilium in two patients with Paget's disease of the bone. The pinhole bone scintigraphy findings correlated with radiographic, CT and MRI findings and in the vertebra with the pathological study. Interestingly enough, pinhole bone scintigraphy revealed intense tracer uptake preferentially in the bone cortex and the rim of the affected bones. Thus, the cranial inner table, humeral cortex and vertebral endplates and rims were the seats of characteristic tracer uptake, respectively creating a scintigraphic version of the radiographic "cotton wool" sign, "casket" sign and "picture frame" sign. The pagetic lesions in the sacrum and ilium also showed intense cortical and rim uptake. Correlation of pinhole bone scintigraphy with radiography, CT and MRI indicated that such cortical or rim uptake is characteristic of Paget's disease.

Bone and Bones↗

Synthesis and biological activities of (4,6-di-O-phosphonato-beta-D-mannopyranosyl)-methylphosphonate as an analogue of 1L-myo-inositol 1,4,5-trisphosphate.

The synthesis of the alpha and beta anomers of the title compound (1) was accomplished from D-mannose. In the key step, the phosphonate analogues of the mannopyranosyl phosphates were prepared by a direct Wadsworth-Emmons condensation of a protected mannose derivative (8) with tetraethyl methylenebisphosphonate under two-phase conditions. In vitro bioassays have shown that the beta anomer (1a) is a potent inhibitor of Ins(1,4,5)P3 3-kinase and inhibits other enzymes.

Animals↗

Pinhole skeletal scintigraphic manifestations of Tietze's disease.

Tietze's disease (TD) is a self-limited, non-specific, inflammatory condition of the upper costochondral junction (CCJ). Unlike in many other skeletal diseases, radiography plays a relatively minor role in TD because radiographic changes are frequently obscured by physiological costochondral calcifications. Bone scanning is a sensitive test for TD, but its specificity is low. The present study has been conducted to assess prospectively whether pinhole scintigraphy (PS) can enhance diagnostic specificity in TD. Both planar and PS bone images were obtained in seven ribs of five patients with TD. Scans alterations were analyzed and compared with the radiographic findings. Planar scans showed "hot" areas in the region of the CCJ in all seven ribs, these hot areas lacking textural patterns. However, the magnified PS images of the CCJ showed two characteristic uptake patterns: drumstick-like uptake in acute cases and C- or inverted C-shaped uptake in chronic cases. Radiographically, chondritic sclerosis could be seen when physiological chondral calcifications were minimal or absent, but was observed when the calcification was prominent. The correlation of PS and radiographic findings revealed that C- or inverted C-shaped uptake indeed faithfully reflected the inflammatory process in the CCJ, the medial border of which is concave. The further correlation of magnetic resonance and PS images of two lesions in one patient in whom histological examination was performed showed that C- or inverted C-shaped uptake is closely associated with hypervascularity of TD. Differential diagnosis between TD, fracture and metastasis is discussed.

Adult↗

Pinhole scintigraphic sign of chondromalacia patellae in older subjects: a prospective assessment with differential diagnosis.

UNLABELLED: Chondromalacia patellae (CP) is an important cause of anterior knee pain. Two clinical types are known: one that typically affects young subjects and the one that affects older patients. The primary diagnostic approach is radiography reinforced with arthrography. A 99mTc-MDP bone scan is invaluable in the study of bone diseases especially when augmented with pinhole scintigraphy (PS). In this study previously unknown, specific sign of CP demonstrated by PS in six middle-aged and elderly patients is described. METHODS: Noting an increased patellar uptake in a planar spot view, a medial PS scan of the patella was taken to detail the uptake pattern using a 3-mm or 4-mm aperture pinhole collimator. The uptake pattern was analyzed in terms of location, definition, mode, grade and other associated changes, and correlated with radiographic and CT scan alterations. RESULTS: The planar views showed patellar uptake to be diffuse and nonlocalizing in five patients and ill-defined and spotty in the remaining patient. In contrast, PS revealed small, spotty uptake well localized in the central retropatellar facet in all but one patient in whom uptake was segmental. A control PS study of 16 patients with their patellas involved by osteoarthritis (n = 6), rheumatic arthritis (n = 5) and Reiter's syndrome (n = 5) also revealed retropatellar uptake with or without anterior patellar uptake in every patient. The CP with localized osteolysis or osteopenia accumulated tracer intensely, whereas those without showed mild to moderate uptake. CONCLUSION: Spotty tracer uptake occurring exclusively in the central retropatellar facet without other knee joint alteration appears pathognomonic of CP in older patients.

Adult↗

Primary common bile duct closure following exploration: an effective alternative to routine biliary drainage.

Primary closure of the common bile duct following exploration has been safely and effectively performed, as advocated by Halsted, provided no evidence of pancreatitis, cholangitis, or ampullary obstruction exists. Using this precedent, the operative management and clinical course of 29 patients undergoing common bile duct exploration (CBDE) for choledocholithiasis from 1986 to 1992 were reviewed. Ten patients had primary closure of the common bile duct (CBD) following choledochotomy and exploration, and 17 patients had t-tube placement. Two patients had CBDE through an enlarged cystic duct that was then ligated. Patients were selected for t-tube placement if they had pancreatitis, ascending cholangitis, evidence of retained stones, or ampullary obstruction. Two patients in this series died. No patient with primary closure of the CBD suffered a biliary complication including retained stones, biliary fistula, pancreatitis, or bile peritonitis. Serious systemic complications were comparable in both groups. The results of this series support the safety of primary common bile duct closure in selected cases.

Cholecystectomy↗

Dexamethasone decreases somatostatin mRNA levels in the periventricular nucleus of the rat hypothalamus.

Glucocorticoid excess inhibits somatic growth in man and laboratory animals. While the mechanism involved is likely to be multifactorial, indirect evidence suggesting the role of an enhanced endogenous somatostatin (SS) tone has been reported. However, there has been no direct evidence indicating an increased synthesis or secretion of hypothalamic SS. In this study, we investigated the effects of glucocorticoids on hypothalamic SS expression by measuring the peptide and mRNA content of SS in whole hypothalamic blocks of male Sprague-Dawley rats sacrificed 4 weeks after adrenalectomy or sham operation. Adrenalectomy decreased the SS content in the rat hypothalamus (p < 0.05), an effect which was reversed by dexamethasone treatment for 10 days. On the other hand, total hypothalamic SS mRNA levels were unaffected by adrenalectomy, but became significantly decreased following dexamethasone treatment (p < 0.05). Using in situ hybridization, this reduction in SS gene expression was shown to occur consistently in the periventricular nucleus and in the parvocellular subdivision of the paraventricular nucleus. The effects of adrenalectomy and dexamethasone on SS mRNA levels were further quantitated in hypothalamic fragments containing predominantly the periventricular and paraventricular nuclei. Somatostatin mRNA levels in these tissue fragments were marginally increased by adrenalectomy (p < 0.05), but showed a 50% reduction following dexamethasone treatment (p < 0.0001). In conclusion, our findings suggest that the inhibitory effect of glucocorticoids on somatic growth is probably not mediated via an effect on hypothalamic SS gene expression.

Adrenalectomy↗

Distributions of the calcitonin gene-related peptide and substance P in the monkey larynx.

The distribution of calcitonin gene-related peptide (CGRP)- and substance P (SP)-like immunoreactivity in the monkey larynx was studied with light microscopy using the immunofluorescence method. We divided the larynx into the following six regions: epiglottis, arytenoid region, false cords, ventricle, vocal cords and subglottis. The distribution of immunoreactivity in the epithelium and subepithelial layer was determined. CGRP- and SP-like immunoreactive nerve fibers were observed in all regions of the laryngeal epithelium except in the vocal cords. In the epithelium of the epiglottis and arytenoid region, numerous taste buds containing several CGRP- and SP-like immunoreactive nerve fibers were observed. In the subepithelial layer, CRGP- and SP-like immunoreactive nerve fibers were observed in all regions of the larynx. In order of decreasing density, these fibers were found in the arytenoid region (especially the corniculate tubercle), the epiglottis, the false cords, the subglottis, the ventricle, and the vocal cords. In the corniculate tubercle, CGRP- and SP-like immunoreactive nerve fibers formed a network, whereas around the cuneiform tubercle, dense CRPG- and SP-like immunoreactive nerve fibers were noted parallel to the basement membrane. SP-like immunoreactive nerve fibers showed a very similar distribution to the CRPG fibers in the epithelium and the subepithelial layer, but SP-like fibers were sparser in all regions of the larynx. These results, together with previous findings indicate that the arytenoid region and the epiglottis of the monkey larynx play very important roles in airway protection, swallowing, and respiration.

Animals↗

Arterial injuries of the thoracic outlet: a ten-year experience.

Arterial injuries of the thoracic outlet are complex and require a precise plan for adequate management and prompt exposure of injured vessels. Our 10-year experience with 28 such injuries is reviewed. Arteriography was performed whenever possible in stable patients (15) and aided in planning the operative approach. Unstable patients with active bleeding, pulsatile or expanding hematoma, or pulse deficit were taken to the operating room without delay. A thoracic approach was required in 15 patients, and the exposure was extrathoracic in 12 patients. Airway was secured with liberal use of emergency endotracheal intubation (16 patients). Primary repair was possible in 16 patients, with grafting performed in eight and ligation in three. One vertebral artery injury was successfully controlled with embolization. Venous injuries were repaired in six patients and ligation was necessary in eight; there was no significant morbidity. Two patients died in this series from complications of severe hemorrhage. Significant morbidity was encountered from associated neurologic injuries in 15 patients. Stroke was evident in two patients, both of whom were moribund preoperatively. Proximal subclavian artery injuries were particularly more problematic and frequently required an interim anterior thoracotomy for early control of exsanguinating hemorrhage. Our philosophy in the management of these injuries and choices of exposure are discussed in detail.

Adolescent↗