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Biomedical subjects

S Chung

Publications and source records attributed to S Chung.

At least 91 records · Page 5Linked to original sources

Ipsilateral island fibula transfer for segmental tibial defects: antegrade and retrograde fashion.

Five patients with segmental tibial defects whose contralateral fibula could not be used as a donor were treated with ipsilateral island fibular transfer in an antegrade or retrograde fashion. Antegrade-flow pedicled flaps based on the peroneal vessel as in the conventional free flap were used for the proximal or middle one-third tibial defects, whereas retrograde-flow pedicled flaps based on the communicating branch between the peroneal and posterior tibial vessels were used for the middle or distal one-third of the tibia. All patients had one of the following problems: a previously failed free flap, below-knee amputation of the opposite leg because of open tibia fracture, refusal to use the contralateral sound leg, or poor general condition to endure a lengthy operation. Four of the patients also had an associated fibular fracture on the same leg, which was ultimately used as one of the osteotomy sites. The follow-up period was from 31 to 48 months. Time to bony union ranged from 4 to 7 months. Time to full weight bearing was from 5 to 9 months after operation. All of the transferred fibulas showed hypertrophy after weight bearing. Nonunion occurred in two cases, which were treated with a long leg cast and cancellous bone graft, respectively. The limb was shorter by an average of 0.5 cm in three cases, longer by 1.1 cm in one case, and in the last case, it was uncheckable because the opposite limb was previously amputated. Limited arc of rotation was not a problem. Other disabling complications were not seen. We believe that these methods can be a valuable alternative to the contralateral free fibula flap in certain cases.

Adult↗

A single-stage two-flap method for reconstruction of partial auricular defect.

Two flaps, consisting of a postauricular skin flap and a mastoid fascial flap, were used for coverage of both sides of a grafted framework in one stage for repair of one-fourth to half auricular composite defect after trauma or inflammation. The method was safe, and the postauricular donor scar was minimal. Additionally, it was beneficial in restoring similar ear shape and size with a natural cartilage convolution.

Adult↗

Endoscopic management of advanced oesophageal cancer.

Effective palliation of dysphagia is the goal in the majority of patients with oesophageal cancer. A number of methods have been developed to achieve this objective. The choice of method is determined mainly by the physical characteristics of the tumour causing the dysphagia. The low complication rate, ease of insertion as a result of small delivery systems, and the large stent diameters which are achieved with self-expanding metal stents, have made these an increasingly popular alternative compared to other methods.

Deglutition Disorders↗

Veno-veno bypass of the inferior vena cava in trauma, tumor, and transplantation.

Interrupting the venous return from below the diaphragm is usually associated with sudden hypotension, hypovolemic cardiac failure, and increased bleeding secondary to acute venous hypertension and hepatic congestion. Shaw, Starzl, and Griffith developed a veno-veno bypass technique to shunt the somatic and splanchnic venous return around the retrohepatic vena cava to the superior vena cava. This permitted continuation of venous return and simultaneous blood warming, allowing surgeons to perform complex procedures in a dry operative field. These bypass techniques have evolved since their introduction in the 1980s and are now being applied for the removal of otherwise nonresectable tumors of the liver, adrenal gland, and kidney. Further, traumatic injuries to the hepatic veins and the retrohepatic cava associated with a high mortality rate can be repaired safely using vascular isolation techniques and bypass.

Journal Article↗

Expression of Kv1.5 K+ channels in activated microglia in vivo.

We examined the expression of outward rectifier K+ channels in activated microglia in vivo. For this purpose, lipopolysaccharide (LPS, 2 microg) was injected into the cortex near the hippocampal region of rat brains, and K+ channel expression was examined using antibodies against shaker-type K+ channels, Kv1.5 and Kv1.3. OX-42-positive microglia were found around the injection sites from 8 h after the LPS injection and remained there for 3 days. The OX-42-positive microglia expressed Kv1.5 immunoreactivity, and the time course of Kv1.5 expression was closely correlated with that of OX-42. In saline-injected brains, OX-42-positive cells also expressed Kv1.5 immunoreactivity even though far fewer OX-42-positive cells were found. Increase of Kv1.5 expression after LPS injection was also demonstrated by immunoblot analysis. On the other hand, Kv1.3 immunoreactivity was barely detected in OX-42-positive cells over the entire experimental period. The expression of Kv1.5 preceded that of inducible nitric oxide synthase (iNOS), which is a prominent indication of microglial activation. iNOS was not detectable until 12 h, and thereafter it was maintained for 3 days together with Kv1.5 and OX-42. These results suggest that in vivo as well as in vitro activated microglia expressed outward K+ channels and that some of the channels at least are Kv1.5.

Animals↗

In situ gene transfer into rat auxiliary liver transplant.

BACKGROUND: A replication-defective retrovirus BAG vector was tested for in situ delivery of the beta-galactosidase gene to auxiliary liver transplant in a rat model. METHODS: The BAG vector, which was shown to be effective in genetic transduction of cultured NIH/3T3 cells, was produced in a psi2 packaging cell and later amplified in a selected PA317 clone. Hepatocyte replication was induced by one-third hepatectomy of the donor liver, and the procedure was followed by auxiliary partial liver transplantation. Twenty-four hours after hepatic induction or transplantation, viral supernatant at 37 degrees C was perfused into the liver graft via the portal vein during a temporary occlusion of the graft portal vein. RESULTS: All animals survived the transplantation procedures and were killed at specified time intervals. Histochemical staining of the liver graft specimens indicated the expression of beta-galactosidase in the gene transferred group but not in the control animals. As demonstrated by polymerase chain reaction assay, the proviral beta-galactosidase sequence was present in the graft specimens, but absent from all other tissues tested. CONCLUSIONS: In short, the retrovirus BAG vector can be useful for in situ delivery of foreign genes to liver graft in transplantation and other clinical settings, providing a simple, consistent, and reliable alternative in hepatic gene therapy experiments.

3T3 Cells↗

Expression and function of outward K+ channels induced by lipopolysaccharide in microglia.

Cultured microglia exposed to lipopolysaccharide (LPS) express outward K+ currents. These currents are due to the expression of new K+ channels detected by antibodies against Kv1.5, a shaker type delayed rectifier. We examined whether the K+ currents are involved in microglial activation. The amount of nitrite, converted from nitric oxide (NO), was measured as an indication of microglial activation [Chao, C. C., Hu, S., Molitor, T. W., Shaskan, E. G., and Peterson, P. K. (1992) J. Immunol. 149, 2730-2741]. Nitrite was detected starting from 24 h after LPS treatment and continuously increased over 4 days. Contrary to this, in the presence of 4-aminopyridine (4-AP, 2 mM), a blocker of outward K+ currents, nitrite production was reduced to less than 50%. However, the treatment of 4-AP 24 h after LPS did not reduce nitrite production. Other K+ channel blockers having a less blocking effect on outward K+ currents, such as 5 mM tetraethylammonium (TEA) and 1 mM Cs+, had little effect. The present study shows that the outward K+ channels induced by LPS are immunologically related to Kv1.5 and also suggests that these channels are required for microglial activation, particularly for the initiation of the activation process.

Animals↗

Nitric oxide directly activates calcium-activated potassium channels from rat brain reconstituted into planar lipid bilayer.

Using the planar lipid bilayer technique, we tested whether NO directly activates calcium-activated potassium (Maxi-K) channels isolated from rat brain. We used streptozotocin (STZ) as NO donor, and the NO release was controlled with light. In the presence of 100-800 microM STZ, the Maxi-K channel activity increased up to 3-fold within several tens of seconds after the light was on, and reversed to the control level several minutes after shutting off the light. Similar activation was observed with other NO donors such as S-nitroso-N-acetylpenicillamine and sodium nitroprusside. The degree of activity increase was dependent upon the initial open probability (P[init]). When the P(init) was lower, the activity increase was greater. These results demonstrate that NO can directly affect the Maxi-K channel activity, and suggest that the Maxi-K channel might be one of the physiological targets of NO in brain.

Action Potentials↗

The Elav-like proteins bind to AU-rich elements and to the poly(A) tail of mRNA.

The Elav-like proteins are specific mRNA binding proteins which are required for cellular differentiation. They contain three characteristic RNP2/RNP1-type RNA binding motifs. Previously we have shown that the first and second RNA binding domains bind to AU-rich elements in the 3'-UTR of mRNA. In this paper we show that the Elav-like proteins exhibit poly(A) binding activity. This activity is distinct from poly(A) binding activities that have been previously described. The Elav-like proteins specifically bind to long chain poly(A) tails. We have shown that the third RNA binding domain encompasses this poly(A) binding activity. Using poly(A)-Sepharose beads in a 'sandwich' assay we have shown that the Elav-like proteins can bind simultaneously to the AU-rich element and to the poly(A) tail.

Base Sequence↗

The Elav-like proteins bind to a conserved regulatory element in the 3'-untranslated region of GAP-43 mRNA.

Previous studies have identified three brain proteins (40, 65 and 95 kDa, respectively) that specifically bind to the 3'-untranslated region of GAP-43 mRNA. In this study, using a specific monoclonal antibody, we now show that the 40-kDa proteins are members of the Elav-like protein family. This family of specific RNA-binding proteins comprise three neural specific members called HuD, HuC, and Hel-N1. We have shown that purified recombinant HuD can bind with high affinity to GAP-43 mRNA. In addition, we have mapped the binding site to a highly conserved 26-nucleotide sequence within the regulatory element. The binding of HuD to this site is readily displaced by RNA oligonucleotides encoding other HuD binding sites. We also show that only the first and second RNA binding domains of HuD are required for selective binding to GAP-43 mRNA.

Animals↗

Role of antiribosomal P protein antibodies in the diagnosis of lupus isolated to the central nervous system.

BACKGROUND: When lupus presents with isolated central nervous system findings, the usual serologic markers are often absent and diagnostic difficulty with a delay in treatment is common. OBJECTIVE: To report the usefulness of antiribosomal P protein antibodies in the diagnosis of lupus isolated to the central nervous system when results of tests for anti-double-stranded DNA antibodies are negative. DESIGN: Case report. SETTING: University medical center. PATIENT: The patient was evaluated and treated on referral and follow up for 1 year. RESULTS: We describe a patient with acute onset of psychosis followed by coma and focal clonic movements with undetectable DNA antibodies. Serum antiribosomal P protein antibody levels were elevated. Steroid therapy was followed by marked clinical improvement and a decrease in antibody titer. CONCLUSION: Antiribosomal P protein antibodies provide an important confirmatory test for the diagnosis of lupus isolated to the central nervous system when results of tests for anti-double-stranded DNA antibodies are negative.

Adult↗

Modulation of large conductance Ca2+-activated K+ channel by Galphah (transglutaminase II) in the vascular smooth muscle cell.

Among G-proteins, Gh is unique in structural differences in the GTP-binding domain and possessing transglutaminase activity. We have studied the role of G protein in modulation of large conductance Ca2+-activated K+ (Maxi-K+) channel by the inside-out mode of patch clamp in smooth muscle cells from superior mesenteric artery of the rabbit. When the non-hydrolyzable GTP analogue, GTPgammaS, was applied, the channel activity was increased about 2.5-fold. Addition of GDPbetaS resulted in reversal of the GTPgammaS effect. When the Galphah7 antibody was applied, the GTPgammaS-stimulated channel activity was significantly inhibited to control level, suggesting that Galphah is involved in activation of the Maxi-K+ channel in smooth muscle cells.

Animals↗

Differential expression of multiple cathepsin mRNAs in the rat testis during maturation and following lonidamine induced tissue restructuring.

In the seminiferous epithelium, germ cell development behind the blood-testis barrier involves continual degradation and renewal of inter-testicular cell junctions. This allows: (i) the translocation of developing germ cells from the basal lamina to the adluminal compartment during spermatogenesis, and (ii) the eventual release of mature spermatids into the tubular lumen during spermiation. Throughout spermatogenesis, cellular debris must also be removed from the epithelium Thus, it is conceivable that proteases, protease inhibitors, and cell junctional components are involved in these events. The present study sought to examine whether testicular cells can express multiple cathepsin mRNAs given that these proteases are involved in the degradation and processing of proteins as well as in tissue regeneration. By using total RNA isolated from primary cultures of Sertoli, Leydig, and germ cells for reverse-transcription and polymerase chain reaction (RT-PCR), the mRNAs of cathepsin B, C, D, H, L, and S were shown to be expressed by Sertoli and Leydig cells, whereas germ cells isolated from adult rats expressed all of the above cathepsin mRNAs except cathepsin D. Throughout postnatal development and maturation, the testicular steady-state mRNA levels of cathepsin B, C, D, L, and S remain relatively unchanged with the exception of cathepsin H whose mRNA level increased during maturation and peaked at 45-60 days of age. Using lonidamine, an anti-spermatogenic drug which is known to induce premature release of germ cells without affecting Leydig cell function by disrupting the inter-Sertoli-germ cell junctions, we have examined the differential expression of these cathepsin mRNAs in the testis at the time of extensive tissue restructuring. It was noted that the expression of cathepsin L and S in the testis increased significantly concomitant with the disappearance of elongate spermatids whereas the expression of cathepsin B, C, D, and H increased significantly when most of the round spermatids and spermatocytes were depleted. These results illustrate the intricate inter-relationship between these proteases in the testis during maturation and tissue restructuring.

Age Factors↗

A deficiency screen for zygotic loci required for establishment and patterning of the epidermis in Caenorhabditis elegans.

To identify genomic regions required for establishment and patterning of the epidermis, we screened 58 deficiencies that collectively delete at least approximately 67% of the Caenorhabditis elegans genome. The epidermal pattern of deficiency homozygous embryos was analyzed by examining expression of a marker specific for one of the three major epidermal cell types, the seam cells. The organization of the epidermis and internal organs was also analyzed using a monoclonal antibody specific for epithelial adherens junctions. While seven deficiencies had no apparent effect on seam cell production, 21 were found to result in subnormal, and five in excess numbers of these cells. An additional 23 deficiencies blocked expression of the seam cell marker, in some cases without preventing cell proliferation. Two deficiencies result in multinucleate seam cells. Deficiencies were also identified that result in subnormal numbers of epidermal cells, hyperfusion of epidermal cells into a large syncytium, or aberrant epidermal differentiation. Finally, analysis of internal epithelia revealed deficiencies that cause defects in formation of internal organs, including circularization of the intestine and bifurcation of the pharynx lumen. This study reveals that many regions of the C. elegans genome are required zygotically for patterning of the epidermis and other epithelia.

Animals↗

Alterations in the carnitine metabolism in epileptic children treated with valproic acid.

Serum concentrations of total carnitine, free carnitine and acylcarnitine were measured in forty-one epileptic patients treated with valproic acid (VPA). Among them, 14 patients were on VPA monotherapy and 27 were on VPA polytherapy. Forty-one age and sex matched healthy normal controls were also evaluated for carnitine metabolism. The mean total and free carnitine were significantly lower in both the VPA monotherapy and polytherapy groups compared with the controls. However, there were no significant differences in concentrations of carnitine between the VPA polytherapy and VPA monotherapy groups. Patients treated with VPA polytherapy had lower carnitine than those treated with VPA monotherapy. An inverse correlation was found between serum concentrations of carnitine and duration of treatment in patients treated with VPA. However, there was no significant correlations between serum concentrations of carnitine and those of VPA. Also, correlation between serum concentrations of carnitine and the activities of serum GOT and GPT was not significant. After L-carnitine supplementation in eleven patients with hypocarnitinemia, the concentrations of carnitine were significantly increased.

Administration, Oral↗

Comparison of the bonding power of various autologous fibrin tissue adhesives.

OBJECTIVE: Three known autologous fibrin tissue adhesives were evaluated for bonding power on Silastic and animal and human tissues. These adhesives were also injected into living tissue to determine if any of these fibrin glues cause inflammatory or deleterious reactions when kept in living tissue for a sustained period. METHODS: In Part I of our study, blood was drawn from 59 healthy volunteers, and autologous fibrin tissue adhesives were manufactured using the cryoprecipitation (AFTA-C), ammonium sulfate (AFTA-A), and ethanol/freezing (AFTA-E) methods. Blocks were then prepared using Silastic, porcine dermis, and human dura mater and bonded together for 10 or 30 minutes using the three adhesives. The blocks were then separated while bonding power was measured. In Part II of our study, 0.01 mL AFTA-C, AFTA-A, or AFTA-E was injected subcutaneously into the auricles of 60 rats. The rats were then killed 3, 7, 14, or 21 days later, and the auricles were examined histologically for signs of toxicity. RESULTS: The bonding powers of AFTA-E and AFTA-C were found to be statistically similar, and both were statistically stronger than AFTA-A. The injection of AFTA-A, AFTA-E, and AFTA-C into rat auricles did not cause any adverse effects. CONCLUSIONS: All three methods for manufacturing AFTA are effective in producing a reliable, stable fibrin glue. However, AFTA-E and AFTA-C demonstrate stronger bonding power than AFTA-A. In addition, all three forms of AFTA produce no undesirable tissue changes when injected into rat auricles.

Animals↗

Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25.

The interferon regulatory factor (IRF) genes encode a family of transcription factors involved in the transcriptional regulation of interferon and the interferon stimulated genes through recognition of the interferon stimulated response element. We previously reported the cloning of a murine lymphocyte-specific IRF (mLSIRF), which was rapidly induced following B- or T-cell receptor crosslinking. To study the role of LSIRF in human lymphocyte development, we have cloned the complete 5.3-kb cDNA for the human homolog (hLSIRF). hLSIRF is a protein of 450 amino acids with a predicted molecular weight of 51.6 kDa and possesses 92% identity at the amino acid level to mLSIRF, including near identity in the DNA-binding domain. In Northern blot analysis, a single transcript of approximately 5 kb was highly expressed in spleen and peripheral blood lymphocyte. hLSIRF mRNA was rapidly induced in peripheral T cells after crosslinking the T-cell receptor. Analysis of tumor cell lines showed that hLSIRF mRNA was basally expressed in most B- but not T-cell lines. Surprisingly hLSIRF mRNA was also found in the melanoma line G361 and is expressed in normal melanocytes as well. Sequence from a genomic clone for hLSIRF was compared to that from mouse and revealed an identical exon-intron structure and a conserved PU-1-binding motif in the promoter. By FISH analysis, hLSIRF was mapped to 6p23-p25.

Amino Acid Sequence↗