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Biomedical subjects

H J Chiang

Publications and source records attributed to H J Chiang.

At least 19 recordsLinked to original sources

Structure-function studies of Escherichia coli biotin synthase via a chemical modification and site-directed mutagenesis approach.

In Escherichia coli, biotin synthase (bioB gene product) catalyzes the key step in the biotin biosynthetic pathway, converting dethiobiotin (DTB) to biotin. Previous studies have demonstrated that BioB is a homodimer and that each monomer contains an iron-sulfur cluster. The purified BioB protein, however, does not catalyze the formation of biotin in a conventional fashion. The sulfur atom in the iron-sulfur cluster or from the cysteine residues in BioB have been suggested to act as the sulfur donor to form the biotin molecule, and yet unidentified factors were also proposed to be required to regenerate the active enzyme. In order to understand the catalytic mechanism of BioB, we employed an approach involving chemical modification and site-directed mutagenesis. The properties of the modified and mutated BioB species were examined, including DTB binding capability, biotin converting activity, and Fe(2+) content. From our studies, four cysteine residues (Cys 53, 57, 60, and 97) were assigned as the ligands of the iron-sulfur cluster, and Cys to Ala mutations completely abolished biotin formation activity. Two other cysteine residues (Cys 128 and 188) were found to be involved mainly in DTB binding. The tryptophan and histidine residues were suggested to be involved in DTB binding and dimer formation, respectively. The present study also reveals that the iron-sulfur cluster with its ligands are the key components in the formation of the DTB binding site. Based on the current results, a refined model for the reaction mechanism of biotin synthase is proposed.

Amino Acid Sequence↗

Course and management of renal subcapsular abscess in a 63-year-old diabetic woman.

Renal subcapsular abscess is a very rare disease that is defined by a suppurative process localized to a space between the renal capsule and the renal parenchyma. The course and management of subcapsular abscesses have received less attention than those of renal and perirenal abscesses. We describe a 63-year-old diabetic woman who presented with intermittent fever of 1 month's duration. She was initially treated for suspected acute pyelonephritis then referred to our hospital because of poor clinical response to cefazolin plus gentamicin. Computed tomography of the abdomen revealed a huge subcapsular abscess with displacement and compression of the left renal parenchyma. A percutaneous catheter was inserted and left in place for 8 days; a total of approximately 850 mL of pus was drained. Culture of the pus yielded Klebsiella pneumoniae and Enterobacter cloacae. A 2-week course of moxalactam was administered on the basis of the results of in vitro antibiotic susceptibility testing. The distorted renal parenchyma appeared normal at sonographic follow-up examination 3 weeks after hospitalization. The course and management of this rare entity are presented as a reminder to physicians that renal subcapsular abscess could manifest as fever of unknown origin in a diabetic patient. A high degree of clinical suspicion is required for early diagnosis and treatment in order to achieve a satisfactory outcome.

Abscess↗

TCRV and TCRJ gene usage in MBP responding T cells from (B10.PL x PL/J)F1 mice is biased towards that of B10.PL mice.

We analyzed myelin basic protein (MBP) specific T cell hybridoma clones from (B10.PL x PL/J)F1 mice. MBP-reacting T cell hybridomas from F1 mice preferentially expressed B10.PL TcraV2.3 (53%) and B10.PL TcraV4.2 (13%) with minor expression of TcraV4.4 (13%) gene segments. A dominant expression of TcrbV8.2 (73%) accompanying with TcrbV8.1 (20%) and TcrbV13 (7%) gene segments have been identified in these MBP-reacting T cell hybridomas from F1 mice. There was less restrictive but non-random usage of the TcraJ and TcrbJ gene segments. Overall, the MBP-reacting T cell hybridomas from (B10.PL x PL/J)F1 mice were dominated by the MBP-reacting T cell pattern seen in B10.PL mice.

Amino Acid Sequence↗

Abdominal fluid collection secondary to acute pancreatitis: treated with percutaneous catheter drainage.

BACKGROUND: Complicated pancreatic inflammatory diseases are often life-threatening, multifocal, and multibacterial disorders. Untreated, these lesions often prove fatal. The purpose of the study is to describe interventional radiologic techniques for diagnosis and treatment of complicated peripancreatic fluid collections. METHODS: Between January 1994 and December 1995, 17 patients with abdominal fluid collection from complicated acute pancreatitis underwent percutaneous drainage following initial diagnosis with computed tomography (CT). These patients required multiple CT examinations, multiple catheter insertions, multiple catheter manipulations, and long-term catheter drainage. RESULTS: Twenty-five infected fluid collections among these 17 patients were percutaneously drained. Sixteen (94%) patients were successfully treated with catheter drainage alone. Surgical treatment was necessary in one patient because of segmental stricture of transverse colon caused by inflammation and adhesion of transverse mesocolon. Catheter drainage duration averaged 31 days. Patients required an average of three catheter manipulations and four abdominal CT scans. Mean hospital stay was 42 days (range, 11-95 days), and mean ICU stay was 25 days (range, 1-70 days). CONCLUSIONS: The study confirms that complicated peripancreatic fluid collections can be safely and effectively treated in most patients with percutaneous catheter technique.

Abscess↗

Epitope specificity and T cell receptor usage in type II collagen induced autoimmune ear disease.

An immune response directed against type II collagen (CII) has been reported in several autoimmune diseases including the animal models of collagen-induced arthritis (CIA) and collagen-induced autoimmune ear disease (CIAED). In this communication, we have found that T cells from type II collagen-immunized DBA/1-lac could transfer auricular chondritis to naive mice. The T cells from type II collagen-immunized H-2r and H-2q mice recognize different epitopes from the CB11 peptide of CII. The CII-specific T cells from H-2q background mice recognize peptide residues p121-147 (P1) but do not respond to residues p211-247 (P2). The T cells of H-2r mice immunized with CII respond better to P2 rather than P1. By altering certain amino acids within these epitopes, the response of CII-specific TCR to antigen has been increased or abolished. Our results suggest that the lysine residues at positions 129, 141, and 147 in P1, the arginine residue at position 227, and glutamic acid at position 230 in P2 might play an important role in the trimolecular interaction. Ten clonally distinct T cell hybridomas specific for CII have been established from H-2r B10.RIII mice and the beta chains of their TCR have been analyzed. Three subfamilies, V beta 1, V beta 6, and V beta 8, were utilized with dominant expression of V beta 8 (60%). This is quite similar to the pattern found in type II collagen-induced arthritis in H-2q mice. This preferential use of V beta 8 in CIAED implies that an immunotherapy may make it possible to control this autoimmune disease, even in a MHC-diverse situation.

Amino Acid Sequence↗

Non-surgical retrieval of intravascular foreign body: experience of 12 cases.

An intravascular foreign body is an iatrogenic complication that occurs during arterial or venous catheterization or interventional procedures. The foreign body could either be a catheter fragment, a dislodged coil, or a steel guide wire. From January 1987 to December 1992, 12 cases of intravascular foreign-body removals were performed by a percutaneous method at Mackay Memorial Hospital. Of the 12 cases, five were dislodged steel guide wires, four were broken CVP catheters, two were dislodged coils, and one was Port-A fragment. The techniques we used were the loop-snare technique (two cases) and stone basket retriever (10 cases). Eleven cases of intravascular foreign bodies were removed by non-surgical percutaneous retrieval but one case was a failure due to improper extraction of a dislodged steel guide wire. The patient received surgical extraction by regional venotomy finally. No major complications were noted during or after these procedures.

Adolescent↗

A single Ser-180 mutation desensitizes feedback inhibition of the phenylalanine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthetase in Escherichia coli.

The Escherichia coli phenylalanine-sensitive DAHP (3-deoxy-D-arabino-heptulosonate 7-phosphate) synthetase (aroG product) is one of the DAHP synthetase isozymes that catalyze the first committed step in the biosynthesis of aromatic amino acids and vitamins. Through target-directed mutagenesis of the cloned aroG on a plasmid vector, followed by screening of phenylalanine-resistant colonies, we isolated a clone (pG908) showing feedback-insensitive mutation of DAHP synthetase. The mutations were identified as a T-->A mutation at nucleotide 22, and a C-->T mutation at nucleotide 539, causing a Leu-8 to Ile-8 mutation and a Ser-180 to Phe-180 substitution, respectively. The resulting enzyme exhibited comparable enzymatic activity to the wild type, but the degree of feedback inhibition had declined from approximately 60% to less than 10% in the presence of 20 mM phenylalanine in the assay medium. Replacement of Ile-8 by Leu, and substitution of Phe-180 with Ser, Asn and Cys, using site-directed mutagenesis, demonstrated that Ser-180 is a critical residue in the feedback inhibition of AroG. The result suggests that the major role played by Ser-180 may not involve a simple charge-size effect in the Phe-binding site of the enzyme molecule, but rather may involve more complicated molecular interactions occurring in the feedback inhibition mechanisms.

3-Deoxy-7-Phosphoheptulonate Synthase↗

Percutaneous biliary stone removal under fluoroscopy.

BACKGROUND: Bile duct stone is a common biliary tract disease in Taiwan. Surgery and choledochoscopy are the current methods of treatment. This is a retrospective review of 65 cases who were admitted with postoperative biliary residual stones, or cholangitis secondary to the biliary stones. Percutaneous biliary stone removals under fluoroscopy were attempted. METHODS: Either a T-tube tract or percutaneous transhepatic cholangial drainage tract or both were used for stone removal. Angiographic superselective catheterization technique was applied for superselective cholangiography to identify the location of stones and to deliver basket and electrohydraulic lithotripsy probe to the site of the stones. Balloon dilation was applied for biliary stricture. RESULTS: Most of the cases needed multiple sessions (four, on an average) to remove all stones. There were 52% of the cases who needed balloon dilation for associated biliary strictures, and 7.7% of the cases had residual stones at the end of the procedure, because of technical difficulties. Chills and fever, pancreatitis, hepatic arterial injury and perforation of the common bile duct were procedure-related complications. In follow-up studies, 15% of the cases had recurrent biliary stones and 4.6% of the patients expired from malignant biliary tumors. CONCLUSIONS: Percutaneous biliary stone removal under fluoroscopy is beneficial for direct visualization of the location and number of the stones, and the architectural changes of the bile ducts. Superselective catheterization and balloon dilation were responsible for the high success rate (92.5%) here.

Adolescent↗

Bile duct stents in the management of hepatolithiasis with long-segment intrahepatic biliary strictures.

Biliary stricture represents a challenging problem in the treatment of hepatolithiasis because of its association with treatment failure and stone recurrence. The long-segment type of stricture is difficult to manage and is likely to recur. To investigate the necessity for biliary stenting after balloon dilatation therapy, 20 consecutive patients with long-segment strictures who had 22 stents (group 1) were compared with ten patients who refused stenting (group 2). The long-segment strictures in group 1 were located on the right side in 80 per cent of patients, on the left side in 10 per cent, and were bilateral in 10 per cent. The stents, varying from 8 to 12 Fr, were retained for at least 6 months. They were inserted through the routes of a matured T tube track (five cases), percutaneous transhepatic track (14 cases), a jejunal limb (two cases) and a fistula (one case). Complications of stenting consisted of dislodgement (one case), haemobilia (two cases), cholangitis (two cases) and intrahepatic abscess (one case). The cumulative probability of stricture recurrence in group 1 was 10 per cent, 15 per cent and 21 per cent at 2, 3 and 4 years, respectively, whereas in group 2 it was 80 per cent at 2 years (P less than 0.003). The results suggest that intrahepatic biliary stenting after balloon dilatation appears necessary and helpful in the management of hepatolithiasis with long-segment biliary strictures.

Adult↗

The value and role of computed tomography in blunt injury of the abdomen.

The use of computed tomography (CT) has had a tremendous impact on the evaluation and management of blunt abdominal trauma. The ability of CT to confirm the absence of intraperitoneal injury and/or significant hemoperitoneum, in correlation to the patient's physiological status, provides extremely valuable information so that unnecessary abdominal surgery is avoided. CT not only demonstrates the presence of injury and delineates it's extent, including the size of the hemoperitoneum, but may also provide information concerning the hemodynamic status of the patient. We reviewed the abdominal CT examination of 38 patients with blunt abdominal trauma at our institution from April 1989 to May 1990. There were no false negative cases and only one false positive case. Thus, we concluded that CT is not only a highly sensitive and accurate modality, but also an invaluable radiological diagnostic tool in the evaluation of blunt abdominal injury.

Abdominal Injuries↗

Secondary biliary cirrhosis. A limiting factor in the treatment of hepatolithiasis.

To investigate whether the coexistence of secondary biliary cirrhosis plays a limiting role in the treatment of hepatolithiasis, we retrospectively compared the clinical course and results of stone treatment in 30 patients with secondary biliary cirrhosis (8 in Child's class A and 22 in Child's class B) (group 1) and 240 patients with noncirrhotic biliary calculi (group 2). The hospital mortality, morbidity of treatment, mortality of treatment, and the percentage of treatment failure in group 1 were 20%, 40%, 6.7%, and 16.7%, respectively. Those in group 2 were 8%, 10%, 3.8%, and 10%, respectively. The modes of treatment for stone removal included surgery with postoperative cholangioscopy and percutaneous transhepatic cholangioscopy. There was a statistically significant difference between these two groups in the hospital mortality and the morbidity of treatment. We conclude that hepatolithiasis and biliary stricture should be treated early, before the development of secondary biliary cirrhosis. However, even after cirrhosis occurs, aggressive treatment does not increase the mortality of treatment or the treatment failure rate.

Adult↗

Delayed formation of gallstone after transcatheter arterial embolization for hepatocellular carcinoma. Is elective cholecystectomy advisable during hepatectomy?

Two hundred twenty-five transcatheter hepatic arterial embolizations (TAEs) were performed on 137 patients with hepatocellular carcinoma (HCC) during a three-year period. The postembolization changes of the gallbladder were studied by regular follow-up with ultrasonography. Twenty-four patients (10.7%) were found to have an acute infarction of the gallbladder within two weeks immediately following chemoembolization. Gallbladder infarction was related to inadequate superselectivity, regurgitation of chemoembolus, or unavoidable anatomic limitations. Four of the 24 patients were found to have delayed formation of gallstones, with the time lapses after TAEs being 2, 2, 3, and 5 months, respectively. One patient underwent surgical reexploration for cholecystectomy 14 months after resection of her HCC because of intractable symptoms and signs of chronic cholecystitis. There are four possible mechanisms of development of gallstones. Cholecystectomy should be performed during the elective hepatectomy for resectable HCC in patients who have received preoperative TAEs.

Acute Disease↗

Aneurysmal dilatation of the portal vein.

In the following study, a case involving an aneurysmal dilatation of the portal vein is reported. The 5-year-old boy had a 2 month history of intermittent abdominal pain. A segmental dilatation of the portal vein was noted in the sonographic examination. The portal vein aneurysm diagnosis was later confirmed by superior mesenteric angiography and computed tomography. In our review of the literature, less than 30 cases of portal venous aneurysm have been reported. To our knowledge, this is the youngest case with such an anomaly.

Arteriovenous Fistula↗

Effects of quinidine and cimetidine on the methamphetamine level in the rat brain.

The drug interaction between methamphetamine and quinidine/cimetidine was investigated in terms of distribution of methamphetamine to the brain. The concentrations of methamphetamine and amphetamine in the brain after an s.c. injection of methamphetamine were determined in rats pretreated with a single oral dose of quinidine or cimetidine. Both drugs markedly enhanced the increase in the concentrations of methamphetamine and its metabolite, amphetamine. These results suggest that the recent finding of the enhancements of the behavioral effect of methamphetamine by quinidine and cimetidine is due to the increase in levels of methamphetamine and amphetamine in the brain by these pretreatment drugs.

Amphetamine↗

Studies on the mechanism of interaction between methamphetamine and quinine in rats.

Interactions between methamphetamine and quinine were studied using two different tests. The duration and intensity of methamphetamine-induced stereotyped behavior was enhanced by pretreatment of rats with quinine. Pretreatment of rats with SKF-525A and CCl4 also resulted in the enhancement of methamphetamine-induced stereotyped behavior. Pretreatment with phenobarbital shortened the stereotypy evoked by methamphetamine. Furthermore, urinary excretion patterns of methamphetamine and its metabolites were determined following the administration of the drug to rats which had been pretreated with certain drugs. Quinine, SKF-525A and CCl4 inhibited the urinary excretion of p-hydroxylated metabolites and increased the excretion of the unchanged methamphetamine and amphetamine. These results strongly suggest that the enhancement of methamphetamine-induced stereotyped behavior in the rats pretreated with quinine, SKF-525A and CCl4 could be ascribed to the inhibition of the p-hydroxylation reaction of methamphetamine and thus may lead to the increased concentration and pharmacological effect of the drug.

Animals↗