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Biomedical subjects

S K Chung

Publications and source records attributed to S K Chung.

At least 55 records · Page 3Linked to original sources

Calcification in chronic maxillary sinusitis: comparison of CT findings with histopathologic results.

BACKGROUND AND PURPOSE: It is important to differentiate fungal from nonfungal sinusitis in order to determine the optimal treatment for chronic sinusitis. The purpose of this study was to describe the CT findings of calcifications in chronic fungal and nonfungal maxillary sinusitis. METHODS: Five hundred ten patients with pathologically proved chronic maxillary sinusitis were studied with unenhanced CT before undergoing sinonasal surgery. In 36 patients, the CT scans were reviewed retrospectively to ascertain the shape and location of intrasinus calcifications. RESULTS: Calcifications were found in 20 (51%) of 39 patients with fungal sinusitis and in 16 (3%) of 471 patients with nonfungal sinusitis. Direct histopathologic correlation was performed in two of 16 patients with nonfungal sinusitis who had intrasinus calcification. The location of intrasinus calcification was central in 95% of the patients with fungal sinusitis and peripheral in 81% of those with nonfungal sinusitis. Although calcifications with a nodular or linear shape were seen in both fungal and nonfungal sinusitis, fine punctate type calcifications were seen only in those with fungal sinusitis (50%) and round or eggshell type calcifications only in those with nonfungal sinusitis (19%). CONCLUSION: Intrasinus calcifications are different in location and shape between fungal and nonfungal maxillary sinusitis. Although intrasinus calcification is uncommon in nonfungal sinusitis, the CT finding of intrasinus calcification may be helpful for differentiating fungal from nonfungal maxillary sinusitis.

Adolescent↗

Effects of sorbitol dehydrogenase deficiency on nerve conduction in experimental diabetic mice.

In this report, we made use of sorbitol dehydrogenase (SDH)-deficient mutant mice (C57BL/LiA) to test whether there is a close correlation between the level of polyol accumulation and the degree of reduction in motor nerve conduction velocity (MNCV) associated with diabetes. The C57BL/LiA mouse has SDH deficiency due to a G-to-A mutation at the +1 position of intron 8, thus producing only aberrant SDH transcripts. These C57BL/LiA mice should have higher levels of polyol accumulation in the peripheral nerve because of the inability to further metabolize sorbitol to fructose. Here, we confirm by Western blot analysis and high-performance liquid chromatography that these mice lack SDH in the sciatic nerve and other various tissues, whereas normal mice possess SDH. These C57BL/LiA mice do not display any obvious phenotype that includes peripheral neuropathy in the normal laboratory environment and breed normally as described previously, although the tissues that normally contain SDH accumulate more sorbitol. This finding suggested that C57BL/LiA mouse strain is a valid model for studying the role in diabetic neuropathy of the polyol pathway, which consists of two enzymes-aldose reductase for converting glucose to sorbitol and SDH for converting sorbitol to fructose. Sorbitol levels in the sciatic nerve of diabetic C57BL/10N, nondiabetic, and diabetic C57BL/LiA mice were increased 4.3-, 16.6-, and 38.1-fold, respectively, above that of nondiabetic C57BL/10N. The fructose level in the sciatic nerve was increased 2.4-fold in diabetic C57BL/10N mice compared with that of nondiabetic and diabetic C57BL/LiA mice. Diabetic SDH-deficient mice showed an MNCV reduction similar in magnitude to that of diabetic C57BL/10N mice, despite greater nerve sorbitol accumulation and the lack of fructose in the former. The present data suggest that the levels of sorbitol and fructose in the sciatic nerve of mice do not correlate with the severity of MNCV deficit associated with diabetes.

Animals↗

Brain tumor in the first year of life: a single institute study.

Brain tumors in infants present special diagnostic and therapeutic challenges. To figure out the clinical features, pathological classification of the tumors and the treatment outcome of infantile brain tumors, 458 children (age<16) with brain tumors were reviewed retrospectively. Among them 21 cases (4.6%) were diagnosed during the first 12 months of life. Two tumors were definitely of congenital origin. The majority of infants with brain tumors presented with increased intracranial pressure. Fourteen tumors were located at the supratentorial area. Sixteen cases had neuroepithelial tumors; astrocytoma (optic pathway), supratentorial primitive neuroectodermal tumor (PNET) and medulloblastoma were found in three cases each. There were two treatment-related mortalities. Compared with the outcomes in older children, the treatment outcome was poorer in medulloblastoma and the optic pathway glioma which showed a higher growth potential. Because of the limited application of postoperative adjuvant therapy, radical surgical removal played a more important role in this age group. The prognosis of patients in whom the tumors could not be totally removed, largely depended on the pathological malignancy of the tumors. Though the treatment outcome was not always dismal, immaturity of the brain, higher growth potential, perioperative risks, limitations in adjuvant therapy, and pessimistic attitude on the part of parents made management more challenging.

Adolescent↗

Pinhole SPECT imaging in normal and morbid ankles.

UNLABELLED: Pinhole SPECT can generate sectional nuclear images of a normal and morbid ankle and hindfoot with remarkably enhanced resolution by portraying the topography and pathological alterations in great detail. METHODS: Pinhole SPECT was performed using a commercially available single-head, rotating gamma camera system by replacing the parallel-hole collimator used for planar SPECT with a pinhole collimator. The images were reconstructed in the same way as in planar SPECT by using the filtered back-projection algorithm and a Butterworth filter. First, we compared the scan resolution between the planar and pinhole SPECT images of a thyroid phantom and a normal ankle and hindfoot by working out pinhole SPECT anatomy with CT validation. Second, the clinical usefulness was assessed in one case each of fracture, reflex sympathetic dystrophy syndrome and rheumatoid arthritis of the ankle with radiographic correlation. The resolution of the pinhole SPECT and planar pinhole images was compared for these diseases. RESULTS: The resolution of the pinhole SPECT of a thyroid phantom and of a normal ankle and hindfoot was significantly enhanced compared to the planar SPECT although image distortion was seen in the periphery of the field-of-view. The pinhole SPECT resolution was such that most of the anatomical landmarks were sharply delineated in the ankle and hindfoot and some useful diagnostic signs in the diseased ankle were visible. CONCLUSION: Pinhole SPECT can be performed using a single-head gamma camera system and filtered back-projection algorithm. It generates sectional scan images of both normal and morbid ankle and hindfoot with enhanced resolution portraying many anatomical landmarks and pathological signs in useful detail.

Adult↗

Dual-head pinhole bone scintigraphy.

UNLABELLED: This article describes dual-head pinhole bone scintigraphy (DHPBS), which makes use of two opposing pinhole-collimated detectors to obtain one pair of magnified images of bone and joint at one time. The aims are to reduce scan time and solve the problem of the blind zone that is created in the background in single-head pinhole bone scintigraphy. METHODS: DHPBS was used for normal hip and knee joints and one case each of lumbar spondylosis, vertebral compression fracture and pyoankle. The gamma camera used was a digital dual-head SPECT camera (Sopha Camera DST; Sopha Medical Vision International, Buc Cedex, France) connected to an XT data processor and a printer. Each of two opposing detectors was collimated with either a 3- or 5-mm pinhole collimator. The scan was performed 2-3 hr postinjection of 12-25 mCi 99mTc-oxidronate. Some 1500-2000 Kilocounts were accumulated at 15-40 min per pair. Anterior and posterior views were taken for the spine and hip and medial and lateral views for the knee and ankle. DHPBS images were correlated to radiographs. RESULTS: DHPBS produced a pair of high-resolution bone and joint images at one time, reducing scan time by nearly half for each image. The paired DHPBS images clearly visualized both foreground and background objects, which effectively eliminated the blind zone. CONCLUSION: DHPBS can significantly improve efficiency and diagnostic acumen.

Aged↗

Aberrant mRNA splicing causes sorbitol dehydrogenase deficiency in C57BL/LiA mice.

Sorbitol dehydrogenase (Sord) catalyzes the interconversion of sorbitol and fructose and is functionally important both in the metabolism of dietary sorbitol and as a source of fructose in semen. Together with aldose reductase, Sord forms the polyol pathway, which plays an important role in the etiology of diabetic complications. The Sord-deficient mouse (C57BL/ LiA) is very useful in animal model studies of the involvement of the polyol pathway in both diabetic and congenital cataracts. To understand more about this strain, we characterized the molecular basis underlying this Sord deficiency and found that this was due to a point mutation in the exon 8/intron 8 junction. Substitution of an A for G at the first position of the strictly conserved GT donor completely abolished normal splicing of exon 8. Aberrant splicing of this junction generates at least three types of transcripts: one lacking exon 8, another that has a truncated exon 8, and a third that contains intron sequences. We have devised two convenient PCR-based methods to identify this mutation in C57BL/LiA mice. These methods are useful in animal experiments that involve cross-breeding with these mice because they allow early determination of genotype without the need to sacrifice the animals for enzyme assay.

Alleles↗

Rapid kinetic measurements of 45Ca2+ mobilization reveal that Ins(2,4,5)P3 is a partial agonist at hepatic InsP3 receptors.

Ins(2,4,5)P3, a metabolically stable analogue of Ins(1,4,5)P3, is widely used in analyses of Ca2+ signalling pathways, but its utility depends upon it faithfully mimicking the effects of the natural messenger, Ins(1,4,5)P3, at InsP3 receptors. To compare the kinetics of InsP3-evoked 45Ca2+ mobilization, Ins(1,4,5)P3- and Ins(2,4,5)P3-stimulated 45Ca2+ release from the intracellular stores of permeabilized rat hepatocytes was measured using rapid superfusion. Both Ins(1,4,5)P3 and Ins(2,4,5)P3 caused concentration-dependent increases in the rate of 45Ca2+ efflux, which accelerated towards a peak and then abruptly switched to a bi-exponentially decaying release rate. However, the peak rate of 45Ca2+ mobilization evoked by maximal concentrations of Ins(2,4,5)P3 was only 65+/-3% (n = 3) of that evoked by Ins(1,4,5)P3. Furthermore, Ins(2,4,5)P3 inhibited the peak rate of 45Ca2+ efflux evoked by Ins(1,4,5)P3. These results indicate that Ins(2,4,5)P3 is a partial agonist at hepatic Ins(1,4,5)P3 receptors. Additionally, responses to Ins(2,4,5)P3 were less positively cooperative [Hill coefficient (h) = 1.9+/-0.3] than were those to Ins(1,4,5)P3 (h = 3.0+/-0.2) and the kinetics of termination of 45Ca2+ mobilization were slower. The lesser efficacy of Ins(2,4,5)P3 may account for the lower cooperativity in the responses it evokes, the slower inactivation of InsP3 receptors and the characteristic patterns of Ca2+ spiking it evokes in intact cells.

Animals↗

Pediatric pyeloplasty: outcome analysis based on patient age and surgical technique.

OBJECTIVES: To analyze our experience with open pyeloplasty, with specific emphasis on procedural outcome on the basis of patient age, surgical technique, complication rate, and complication management. METHODS: All patients from 1974 to 1994 who underwent pyeloplasty at our institution were included in our review. Charts were analyzed for age at presentation, presenting signs and symptoms, type of surgical reconstruction, complications and treatment, and final outcome. RESULTS: From 1974 to 1994, 234 pyeloplasties were performed in 227 patients (108 less than 1 year old, 119 more than 1 year old). The percentage of children less than 1 year old increased throughout: 24% for 1975 to 1980, 37% for 1981 to 1990, and 69% for 1991 to 1994. Presenting signs and symptoms varied according to the age of the child at pyeloplasty. For children less than 1 year old, these were prenatal ultrasound in 86 (79%), urinary tract infection (UTI) in 9 (8%), and abdominal mass in 5 (4.6%). For children more than 1 year old, these were pain in 57 (48%), UTI in 29 (24%), hematuria in 12 (10%), and prenatal ultrasound in 3 (2.5%). Reconstruction was a dismembered pyeloplasty in all cases. The majority of patients in both age groups underwent a nonintubated repair (less than 1 year old, 99 of 114; more than 1 year old, 102 of 120). Postoperative results were evaluated by ultrasound or intravenous urography, with improvement or stable results in 95% of children less than 1 year old and in 96% of children more than 1 year old. Complications included UTI in 18 patients (7.7%), recurrent obstruction in 5 (2.1%), and persistent leak in 4 (1.7%). The complication rate was not related to age. CONCLUSIONS: The nonintubated, dismembered pyeloplasty is an excellent technique for all age groups and has a low complication rate.

Age Factors↗

Binding and activity of the nine possible regioisomers of myo-inositol tetrakisphosphate at the inositol 1,4,5-trisphosphate receptor.

All 9 racemic regioisomers (15 enantiomerically) of myo-inositol tetrakisphosphates (IP4s): DL-Ins(1,2,4,5)P4 [A], DL-Ins(1,2,4,6)P4 [B], Ins(1,2,3,5)P4 [C], Ins(1,3,4,6)P4 [D], Ins(2,4,5,6)P4 [E], DL-Ins(1,3,4,5)P4 [F], DL-Ins(1,2,5,6)P4 [G], DL-Ins(1,2,3,4)P4 [H] and DL-Ins(1,4,5,6)P4 [I] [Chung S-K., Chang Y-T. Synthesis of all possible regioisomers of myo-inositol tetrakisphosphate. J Chem Soc Chem Commun 1995; 11-13] were investigated for their ability to bind to the D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptor in bovine adrenal cortical membranes, and for their ability to mobilize 45Ca2+ from Ins(1,4,5)P3-sensitive Ca2+ stores in permeabilized Chinese hamster ovary (CHO) cells. DL-Ins(1,2,4,5)P4 (Ki = 11 nM) bound to Ins(1,4,5)P3 receptors with an affinity only 2-fold lower than Ins(1,4,5)P3 (Ki = 6 nM). Ins(1,2,3,5)P4, Ins(1,3,4,6)P4, Ins(2,4,5,6)P4, DL-Ins(1,3,4,5)P4, DL-Ins(1,2,3,4)P4 and DL-Ins(1,4,5,6)P4 bound with affinities of between 0.4-0.7 microM. DL-Ins(1,2,4,6)P4 and DL-Ins(1,2,5,6)P4 bound to the Ins(1,4,5)P3 receptor with low affinity (approximately 2-3 microM). All but one of the IP4s mediated release of 45Ca2+ from stores of permeabilized CHO cells with a similar rank order of potency as that for Ins(1,4,5)P3 receptor binding, being between 16-fold and 50-fold less potent at releasing 45Ca2+ compared with their apparent binding affinities to the Ins(1,4,5)P3 receptor. The notable exception was Ins(1,2,3,5)P4, which showed an approximately 200-fold lower potency compared with its affinity for the Ins(1,4,5)P3 receptor. Ins(1,2,3,5)P4 may be a useful lead compound for the rational design of novel synthetic Ins(1,4,5)P3 analogues possessing structure-activity profiles with relatively high binding affinity, but low intrinsic efficacy, and hence partial agonists and antagonists at the Ins(1,4,5)P3 receptor.

Animals↗

Mouse models for human diseases.

Mice are increasingly being used as models for the study of various human diseases. This is primarily because among mammalian modals, they are most amenable to genetic manipulations. As we attempt to understand the molecular mechanism of diseases, it is imperative that the genes involved in the disease process be identified. One approach is to study mouse mutants with symptoms analogous to human diseases, and try to identify the genes responsible. Another approach is to manipulate the expression of genes suspected to be involved and see how they affect the disease development. This review briefly discusses the concept of manipulating gene expression by transgenic and gene knockout technology and illustrates this with how these technique are used to study the mechanism of diabetic complications.

Journal Article↗

Prestenotic bronchial radioaerosol deposition: a new ventilation scan sign of bronchial obstruction.

UNLABELLED: This study was performed to assess the diagnostic usefulness of aerosol ventilation scanning in bronchial obstruction and bronchial stenosis. METHODS: Seven patients of bronchial obstruction and one patient with stenosis were studied. In each patient, obstruction was confirmed by bronchography, bronchoscopy and/or CT scan. Ventilation scanning was performed using the 99mTc-phytate aerosol generated by a BARC jet nebulizer. Scan manifestations were assessed in correlation with those of plain chest radiography, bronchography, CT scan and/or bronchoscopy. RESULTS: In every patient, the ventilation scan showed characteristic intense aerosol deposition in a short, slightly dilated, clubbed, bronchial segment immediately proximal to obstruction or stenosis. Typically, it was accompanied by a distal airspace deposition defect. CONCLUSION: Intense, segmental, bronchial aerosol deposition with distal lung defect was a specific finding of bronchial obstruction and stenosis. The sign was especially useful when obstruction was obscured by the associated, bizarre lung disease and in a small bronchus.

Aerosols↗

Induction of axon-like processes from axotomized retinal ganglion cells of adult hamsters after intravitreal injection of sciatic nerve exudate.

We have shown previously that intravitreous transplantation of a peripheral nerve (PN) graft stimulates a subpopulation of retinal ganglion cells (RGCs) to sprout axon-like processes. The present study examined whether the effect of PN graft was due to diffusible factors released from the graft. Injection of sciatic nerve exudate into vitreous of the eye induced the formation of axon-like processes. Significantly more RGCs with axon-like processes were stained after injection of exudate from the distal stump than the proximal stump of the transected sciatic nerve. Thus, our results showed that trophic factors released from the intravitreous PN can induce the formation of axon-like processes and that more trophic factors are secreted from the distal than the proximal stump of the transected sciatic nerve.

Animals↗

Determination of specificity of a high-affinity inositol 1,3,4,5-tetrakisphosphate binding site at a 42 kDa receptor protein, p42IP4: comparison of affinities of all inositoltris-,-tetrakis-, and -pentakisphosphate regioisomers.

The specificity of the binding site of p42IP4, a high-affinity 42 kDa Ins (1,3,4,5)P4 receptor protein identified by photoaffinity labelling (Reiser et al., Biochem. J. 280, 533, 1991) was analyzed by determining the affinities for all possible inositoltris-, -tetrakis-, and -pentakisphosphate regioisomers. We tested the purified receptor protein displaying a Kd of 2.2 nM for Ins (1,3,4,5)P4 which was unequalled by any of the other inositoltetrakis- and -trisphosphate regioisomers. The affinities of inositoltetrakisphosphates were 25 to 150 times lower, with a substitution at C-2 having the largest effect in reducing the affinity. The inositoltrisphosphate isomers were three orders of magnitude less potent than Ins (1,3,4,5)P4, apart from D/L-Ins (3,4,5)P3. The pentakisphosphate Ins(1,3,4,5,6)P5 had an affinity for the solubilized and purified receptor comparable to that of D-Ins (1,3,4,5)P4. This lack of discrimination was unique for the solubilized receptor, since it was not observed with the membrane-associated receptor protein. Most importantly, D-Ins (1,3,4,5)P4 and D-Gro PtdIns (3,4,5)P3 had identical affinities with the 42 kDa protein. Thus, this protein p42IP4 selectively recognizes two potential second messengers.

Animals↗

Synthesis and iron binding studies of myo-inositol 1,2,3-trisphosphate and (+/-)-myo-inositol 1,2-bisphosphate, and iron binding studies of all myo-inositol tetrakisphosphates.

The first syntheses of the natural products myo-inositol 1,2,3-trisphosphate and (+/-)-myo-inositol 1,2-bisphosphate are described. The protected key intermediates 4,5,6-tri-O-benzoyl-myo-inositol and (+/-)-3,4,5,6-tetra-O-benzyl-myo-inositol were phosphorylated with dibenzyl N,N-di-isopropylphosphoramidite in the presence of 1H-tetrazole and subsequent oxidation of the phosphite. The crystal structures of the synthetic intermediates (+/-)-1-O-(tert-butyldiphenylsilyl)-2,3,O-cyclohexylidene-myo-inos itol and (+/-)-4,5,6-tri-O-benzoyl-1-O-(tert-butyldiphenylsilyl)-2,3-O-cycl ohexylidene- myo-inositol are reported. myo-Inositol 1,2,3-trisphosphate, (+/-)-myo-inositol 1,2-bisphosphate, and all isomeric myo-inositol tetrakisphosphates were evaluated for their ability to alter HO. production in the iron-catalysed Haber-Weiss reaction. The results demonstrated that a 1,2,3-grouping of phosphates in myo-inositol was necessary for inhibition, also that (+/-)-myo-inositol 1,2-bisphosphate potentiated HO. production. myo-Inositol 1,2,3-trisphosphate resembled myo-inositol hexakisphosphate (phytic acid) in its ability to act as a siderophore by promoting iron-uptake into Pseudomonas aeruginosa.

Binding Sites↗