Biomedical subjects
K C Lee
Publications and source records attributed to K C Lee.
Chiari-I malformation presenting as vocal cord paralysis in the adult.
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Natural history of moyamoya disease: comparison of activity of daily living in surgery and non surgery groups.
The present study was undertaken to reach a clearer understanding of the natural history of Moyamoya disease. Follow-up studies were performed in 88 patients with Moyamoya disease. They were divided into the ischemia group and the hemorrhage group. The activity of daily living (ADL) of each groups were followed up and compared between those who were surgically treated and conservatively managed. Ischemic manifestations were more common in the younger children and tended to be recurrent, whereas hemorrhagic manifestations were more common in the adults. Follow-up duration of the 36 patients, who were surgically treated, ranged from 6 to 86.4 months (mean: 28.8 months). During the follow-up period, ADL was improved in 17 of 31 ischemic Moyamoya patients (55%); the condition was unchanged in nine (29%); and aggravated in five (16%). Follow-up duration of the 52 patients who were managed without surgery ranged from 12 to 216 months (mean: 67.2 months). In 35 patients of the ischemia group, ADL was aggravated in 49% and improved in only 26% during the follow-up period. However, ADL was aggravated in 12% of 17 hemorrhagic patients, but improved in 53%. Our result suggest that indirect revascularization procedures are effective for prevention of recurrent ischemic attacks which is common in pediatric patients. However, the effectiveness of indirect revascularization for hemorrhagic Moyamoya disease is not clear and requires extended follow-up study.
High altitude training increases reactive carbonyl derivatives but not lipid peroxidation in skeletal muscle of rats.
The oxidative stress related consequences of physical training at high altitude are not known. The hypothesis was tested that physical training and exposure to high altitude have adverse effects on free radical generation and activities of antioxidant enzymes. The present results showed that 4 weeks of exercise at an altitude of 4000 m increased the activity of Mn-SOD in both white and red types of skeletal muscle. The activities of Cu,Zn-SOD, catalase, and glutathione peroxidase, as well as the level of lipid peroxidation measured by TBARS and lipid hydroperoxides, did not change significantly. In contrast, the level of reactive carbonyl derivatives measured by anti-2,4-dinitrophenylhydrazone antibodies and spectrophotometry showed an increase in both types of muscle of altitude trained rats compared with sea level trained and control groups. It was suggested that the oxidative modification of certain amino acids is due to the increasing gap between activity of SOD and peroxide scavenging enzymes, which results in increases in the number of hydrogen peroxide molecules. Thus, since the mechanism of generation and/or the mode of action of radicals resulting in lipid peroxidation and protein oxidation appears to be different in vivo, both processes should be studied during oxidative stress.
Nucleotide(-258) G-to-A transition variant of the liver glucokinase gene is associated with essential hypertension.
Hypertension is a complex disease with strong genetic influences. Essential hypertension has been shown to be associated with insulin resistance. A molecular variant with G-to-A transition at the nucleotide -258 of the liver glucokinase (GCK) promoter was found in diabetic patients. The variant A allele is associated with insulin resistance. We examine the role of this genetic variant in the pathogenesis of hypertension using a population association study. We recruited 205 Taiwanese subjects and they were divided into two groups based on either presence (65 subjects) or absence (140 subjects) of essential hypertension. Genomic DNA was extracted from peripheral leukocytes. Genotypes at this locus were determined by using a polymerase chain reaction restriction fragment length polymorphism. The distribution of genotypic frequency was different between the hypertensive and control groups (P = .009). The frequency of variant A allele was greater in hypertensive subjects than in control (23% v 10%, P = .001). Subjects with at least an A allele had a risk for hypertension by 2.52 times (95% confidence interval 1.29 to 4.91) as compared with those without an A allele. Thus, we first demonstrate the association between the G-to-A variants at the nucleotide -258 of the liver GCK gene and essential hypertension. This may explain the insulin resistance in essential hypertension and the variant A allele as a risk factor for essential hypertension in the Taiwanese population.
Sequence and phylogenetic analysis of the cytoplasmic inclusion protein gene of zucchini yellow mosaic potyvirus: its role in classification of the Potyviridae.
The cytoplasmic inclusion (CI) gene of a Singapore isolate of zucchini yellow mosaic virus (ZYMV-S) was sequenced and compared with CI of 14 other potyviruses. In addition to the consensus sequence GAVGSGKST of nucleotide binding motif (NTBM) which is implicated as a membrane-binding component of the RNA helicase complex, five other conserved motifs were found. Phylogenetic trees were constructed from sequence data for the CI and the coat protein. Similar branching patterns obtained from both CI and coat protein analyses suggests that phylogenetic relationship among potyviruses can be determined using the CI. We propose that phylogenetic analysis of CI gene may be used as an alternative approach for the study of evolution within the family Potyviridae.
Revised cutoff values of serum aminotransferase in detecting viral hepatitis among CAPD patients: experience from Taiwan, an endemic area for hepatitis B.
BACKGROUND: To determine the best cutoff values of aspartate aminotransferase (AST) and alanine amino-transferase (ALT) in detecting viral hepatitis C infection among patients of continuous ambulatory peritoneal dialysis (CAPD). METHODS: 90 (44 male and 46 female) CAPD patients and 526 adult controls (266 male, 260 female) were enrolled. Serum AST and ALT were measured by an auto-analyser monthly. Serum HBsAg was examined using a RIA method and anti-HCV by an second-generation EIA method. The best cutoff values of AST and ALT for detecting viral hepatitis were obtained from the ROC (receiver-operating characteristic) curve. RESULTS: The prevalence of anti-HCV(+) was significantly higher in CAPD patients (16.7%) than in normal controls (4.9%), while that of HBsAg(+) was similar in both groups. CAPD patients had significantly lower levels of serum aminotransferases compared to normal controls. Mean AST were 23.8 IU/l in normal control and 18.8 IU/l in the CAPD patients (P < 0.001). Mean ALT were 21.9 IU/l in normal controls and 15.3 IU/l in the CAPD patients (P < 0.001). CAPD patients with HCV infection had higher serum AST and ALT levels than those without. However, HBV infection did not cause significant serum aminotransferase elevation in patients. The conventional cutoff values of AST (40 IU/l) and ALT (40 IU/l) for detecting viral hepatitis yielded only a sensitivity of 27.3 and 18.2% respectively; on the contrary, our revised cutoff values of AST (24 IU/l) and ALT (17 IU/l) had better sensitivities (AST, 72.7%; ALT, 63.6%). For serial aminotransferase values, the sensitivity of AST and ALT for detecting HCV were 36.4 and 27.3% by conventional criteria, and were both 81.8%, by our newly revised criteria. CONCLUSIONS: Serum aminotransferase cutoff values should be modified for screening viral hepatitis in a CAPD population. Our new cutoff criteria had important clinical implications in providing benefits of earlier detection and possible prevention from chronic hepatic deteriorations.
Effects of repeated short versus single long episodes of focal ischemia on somatosensory evoked potentials and development of cerebral infarction in cats.
The effects of repeated short episodes of focal ischemia at 30-minute intervals or a single equivalent long episode of focal ischemia on neuronal function and development of cerebral infarction were compared using somatosensory evoked potential (SEP) recording and 2,3,5-triphenyltetrazolium chloride staining in a cat model. Seventeen cats underwent transorbital occlusion of the middle cerebral artery (MCA), using one of three procedures: sham-operation; single 1-hour occlusion of the MCA, followed by 3 hours of recirculation; or three 20-minute occlusions of the MCA at 30-minute intervals, followed by 3 hours of recirculation. Two of six cats in the single long-term occlusion group showed recovery of SEP, whereas all six cats in the repeated short-term occlusion group showed recovery of SEP at 3 hours after recirculation. All six cats in the single long-term occlusion group had cerebral infarction of various sizes, but only one cat in the repeated short-term occlusion group developed infarction. Repeated short episodes of focal ischemia are relatively less damaging than a single equivalent long episode of focal ischemia, even if the reperfusion interval is extended to 30 minutes.
Management of poor-grade patients with ruptured intracranial aneurysm.
To formulate treatment strategies for poor-grade patients after aneurysmal subarachnoid hemorrhage (SAH), medical records were analyzed for 166 patients who were in Hunt and Hess Grade IV or V among 588 consecutive cases with ruptured intracranial aneurysm admitted during the past 5 years. Causes of unfavorable outcome (poor or dead) in those 166 patients were evaluated to improve the management outcome. Overall management results of the 166 poor-grade patients were favorable (good or fair) in 71 (42.8%), unfavorable in 95 (78 dead, 17 poor). Direct clipping was performed in 90 patients, and the results were favorable in 69 (76.7%) and unfavorable in 21 (23.3%). Surgery was not done in 76 patients because 41 were moribund on arrival, 15 deterioration due to rebleeding, 7 severe brain swelling, 5 serious medical illness, one severe delayed ischemic deficit (DID), and one cerebral infarction following angiography, and 6 refused surgery. Seven patients survived in non-surgery group (2 fair, 5 poor). Direct effects of aneurysm rupture (34.8%) and early rebleeding (34.8%) were the major causes of unfavorable outcome in Grade IV patients, while it was direct effect of aneurysm rupture (91.8%) in Grade V patients. It is suggested that as rebleeding is the only preventable cause of unfavorable outcome, urgent management is necessary to prevent rebleeding, especially for Grade IV patients. Grade IV patients should be treated aggressively with direct clipping for non-complex aneurysms or for patients with hematoma, and coil embolization for complex aneurysms without hematoma.
High incidence of IDDM over 6 years in Edmonton, Alberta, Canada.
OBJECTIVE: To determine the incidence of IDDM among children 0-14 years of age in Edmonton, Alberta, between 1990 and 1995 by means of a population-based registry. RESEARCH DESIGN AND METHODS: Children < 15 years of age diagnosed with IDDM between January 1990 and December 1995 were registered according to criteria of the World Health Organization (WHO) Multinational Project for Childhood Diabetes. The primary source of case ascertainment consisted of office records of pediatricians and endocrinologists. The secondary source consisted of inpatient records from the main city hospitals. RESULTS: Between 1990 and 1995, 211 IDDM patients < 15 years of age were detected by the two sources. All but 15 of them were of European ancestry. The ascertainment-corrected incidence rates of this ethnic group (constituting 77% of the population) for the 6 years were 38.6, 23.5, 23.3, 24.2, 22.0, and 24.3 per 100,000, respectively, with case ascertainment rates of 75-95%. The age-adjusted rate over the 6-year period was 25.7 per 100,000 with a case ascertainment rate of 84.3%. No sex difference was observed. The highest incidence occurred in the 10- to 14-year-old age-group, and more cases were detected between January and March than at other periods in the year. CONCLUSIONS: The incidence of IDDM among the European-derived population in Edmonton between 1990 and 1995 is the highest rate over a 6-year period to be reported in North America, comparable to that in Prince Edward Island, Canada, and to the highest rates in the world.
Stability of Octastatin, a somatostatin analog cyclic octapeptide, in aqueous solution.
In this study, the degradation of Octastatin, a cyclic octapeptide analog of somatostatin, was examined as a function of pH, temperature, buffer, and ionic strength by reversed-phase gradient high-performance liquid chromatography. Degradation of Octastatin followed a first-order kinetics. Various buffer species such as acetate, ammonium acetate, citrate, glutamate, phosphate, and borate showed differing effects on the degradation of the octapeptide. Good stability was found in glutamate and acetate buffer of pH 4.0. Degradation of Octastatin was greater in citrate- or phosphate-containing buffers than in glutamate or acetate buffers. With phosphate buffer, higher buffer concentration caused greater degradation, while in acetate buffer, the effect of buffer concentration and ionic strength was negligible. In addition, the degradation of Octastatin was markedly inhibited by increasing the concentration of glutamate buffer. This study allows the prediction of good stability in acetate buffer (0.01 M, pH 4.0) with a t90% of 84.1 days at 20 degrees C.
Congenital aglossia with situs inversus totalis--a case report.
Hypoglassia or aglossia is an uncommon anomaly, either of which may occur as an isolated finding or in association with other deformations, especially limb anomalies. Their genetic background is uncertain, and drug induced teratogen has not been clearly identified. We experienced a case of congenital aglossia with situs inversus in a female infant aged twelve days. Her initial complaints at admission were feeding difficulty and weight loss. In a review of literature, the association with situs inversus is very rare and only three cases have been reported until now.
Adrenal carcinosarcoma--a case report.
Carcinosarcoma of the adrenal gland is an extremely rare variant of adrenocortical carcinoma, characterized by a biphasic pattern of carcinoma and sarcoma-like components. We report a case of adrenal carcinosarcoma occurring in a 61-year-old Korean man who presented with right flank pain of one month duration radiating to the back and right iliac crest. The tumor measured 12 x 12 x 7 cm and adhered to the liver and right upper pole of the kidney. The carcinomatous component of the tumor showed polygonal cells in a broad anastomosing trabecular pattern with delicate slit-like vascular channels; the sarcomatous component showed uniform spindled cells in a fascicular pattern. Both the carcinomatous and sarcomatous portions of the tumor were positive for pan-cytokeratin, and vimentin stained only the sarcomatous areas.
Morphological characteristics of the developing human brain during the embryonic period.
Many features of the developing nervous system are visible from external observations of intact human embryos. In this study, a photographic atlas from the 4th to the 7th week after ovulation (Carnegie stages 10-18) is provided. The neural folds began to fuse at stage 10, and the rostral and caudal neuropore were closed during stages 11 and 12, respectively. The three primary divisions of the brain were distinguishable before closing of the neural tube. The five secondary brain vesicles were formed during stages 14-15. The development of the cerebellum and cerebrum were first observed at stages 14 and 15, respectively. The mesencephalic flexure was seen at stage 12, and the cervical flexure and pontine flexure at stage 14. After stages 18-19, it became increasingly difficult to identify detailed features of the brain from the surface. Results from this study will help to correlate the characteristic findings of the developing central nervous system of human embryos from stereomicroscopical and light microscopical observations and to locate the exact parts of the developing human brain for other purposes.
Magnetic resonance cholangiography in hepatolithiasis.
OBJECTIVES: Our objective was to examine the usefulness of magnetic resonance cholangiography in hepatolithiasis. METHODS: Ten patients with hepatolithiasis were studied by ultrasonography, computed tomography, direct cholangiography, and magnetic resonance cholangiography to detect stones and to determine the morphological features of the bile ducts. In nine patients who underwent surgery, dilation and stenosis of the bile ducts were confirmed by intraoperative cholangioscopy, pathology, or both. RESULTS: Stones were demonstrated in seven patients by ultrasonography, in eight by computed tomography, in seven by direct cholangiography, and in all by magnetic resonance cholangiography. The locations of stones were identified in four patients by ultrasonography, in seven by computed tomography, in six by direct cholangiography, and in nine by magnetic resonance cholangiography. Among nine patients with dilation of the bile ducts, the dilation was shown by ultrasonography in seven, by computed tomography in eight, by direct cholangiography in six, and by magnetic resonance cholangiography in eight. Among seven patients with stenosis of the bile ducts, this stenosis was shown by direct cholangiography in four and by magnetic resonance cholangiography in six. Ultrasonography and computed tomography did not show the stenosis. Sensitivity for detection of biliary stenosis was significantly higher in magnetic resonance cholangiography. CONCLUSIONS: This study shows that magnetic resonance cholangiography not only detects stones, but can also delineate detailed information on the bile ducts, which is useful in the planning of treatment for hepatolithiasis.
The outcome of terminal liver cirrhosis patients requiring mechanical ventilation.
BACKGROUND: Liver cirrhosis is a common problem in Taiwan. Without liver transplantation, patients with end-stage liver cirrhosis frequently die of various complications and often require mechanical ventilatory support prior to their death. The purpose of this study was to investigate the in-hospital and short-term outcome of such patients. METHODS: A retrospective review of 47 medical records of mechanically ventilated patients with primary diagnosis of liver cirrhosis, admitted from November 1990 to September 1993, allowed analysis of disease course and outcome for these patients. RESULTS: Among the 47 patients, a Child-Pugh's class A patient receiving temporary mechanical ventilation (MV) after elective devascularization surgery was excluded from analysis. Among the remaining medically treated 46 patients, there were 33 Child-Pugh's class C patients, 9 class B patients and 4 unclassified patients. Primary reasons for endotracheal intubation and MV included airway protection, acute respiratory distress and shock. Of these patients, shock was present in 39 cases, upper gastrointestinal bleeding in 34, systemic inflammatory response syndrome in 32, renal insufficiency with creatinine greater than 1.3 mg/dl in 32, bacteremia in 14, parenchymal lung disease in 16, spontaneous bacterial peritonitis in 10, and intracerebral hemorrhage in 1 during their hospital courses. Thirty-eight patients (83%) died within 72 hours after being placed on mechanical ventilation. Patients requiring MV with complications of bacteremia, parenchymal lung disease or renal insufficiency during hospitalization were found to have a 100% mortality rate. Successful weaning occurred in only 3 of 46 patients (8.7%). Of these three, two (4.3%) went home alive and had survived over six months after discharge. CONCLUSIONS: It was concluded that cirrhotic patients requiring MV have an extremely poor prognosis. Patients and their families should be fully informed of the prognosis, and routine use of MV should not be encouraged in patients with terminal stage liver disease.
Monovalent cation transport: lack of structural deformation upon cation binding.
Cations often deform the structure of regulatory proteins to affect a functional response, but for other protein functions a more passive effect is desired. For instance, it is shown here that in the conductance of Na+ by the gramicidin channel there appears to be no significant structural deformation of either the side chains or backbone upon Na+ binding in the channel. This is based on 15N and 13C chemical shifts, 2H quadrupolar interactions, and 15N-2H dipolar interactions obtained by solid-state NMR spectroscopy of uniformly aligned lipid bilayer preparations of the gramicidin channel in the presence and absence of Na+. This conclusion is despite some significant changes in the 15N alpha and 13C1 chemical shift values which are argued here to be the result of indirect polarization effects upon cation binding rather than reflections of structural and dynamic changes. The lack of structural deformation implies that Na+ moves to the carbonyl oxygens lining the pore of this channel for solvation rather than the carbonyl groups moving in toward the channel axis. This forces the cations onto a helical path following the positions of the carbonyl oxygens around the channel pore. Furthermore, an ideal binding site geometry for Na+ in the channel is avoided. Instead, adequate binding energy is provided by the channel to compensate for the loss of hydration energy when the cations enter the channel. The avoidance of strong binding ensures that efficient transport of the cations through the channel can be realized.
Ligand-dependent conformational plasticity of the periplasmic histidine-binding protein HisJ. Involvement in transport specificity.
The periplasmic histidine permease of Salmonella typhimurium is composed of a membrane-bound complex and a soluble histidine-binding protein (the periplasmic receptor), HisJ. Liganded receptor interacts with the membrane-bound complex, inducing ATP hydrolysis and substrate translocation. Preliminary evidence had shown a lack of direct correlation between the affinity of HisJ for a ligand and translocation efficiency, suggesting that the precise form of the receptor is important in determining its interaction with the membrane-bound complex. We have investigated the nature of the conformations assumed by HisJ upon binding a variety of ligands by tryptophan fluorescence enhancement, reaction with a closed form-specific monoclonal antibody, and changes in UV absorption spectra. It is demonstrated that although HisJ binds all the ligands and undergoes a conformational change, it assumes measurably different conformations. We also show that the interaction between HisJ and the membrane-bound complex depends on the nature of the ligand. Transport specificity appears to be defined, at least in part, by the conformation of the bound receptor, manifested either by the effect of a given ligand on the closed structure per se, or by the effect of ligand association on the equilibrium constant relating the open and the closed liganded forms.