Biomedical subjects

K C Lee

Publications and source records attributed to K C Lee.

At least 19 recordsLinked to original sources

PubMed2006

Errors in ABO labeling of deceased donor kidneys: case reports and approach to ensuring patient safety.

Patient safety in transplantation depends on accurate testing, transcription and transmission of the ABO types of the donor and recipient. Similar to 'near-miss' transfusion labeling errors, three cases of mislabeled ABO types on deceased donor kidney containers were recognized through a pretransplant verification process. Six steps to confirming the organ and ABO identification were developed to ensure safety of the patient and prevent liability for the transplant team and facility. In each case, rapid recognition and documentation of the error source, on site confirmation of the ABO type of the accompanying blood specimen, and full disclosure to the patient and family permitted safe transplantation and avoided the need to pursue a more conservative course that would have required discarding the organs. We advocate following these measures in determining whether to persevere with transplantation of a mislabeled organ.

ABO Blood-Group System↗

PubMed2006

RACK1 inhibits colonic cell growth by regulating Src activity at cell cycle checkpoints.

Previously, we showed that Src tyrosine kinases are activated early in the development of human colon cancer and are suppressed as intestinal cells differentiate. We identified RACK1 as an endogenous substrate, binding partner and inhibitor of Src. Here we show (by overexpressing RACK1, depleting Src or RACK1 and utilizing cell-permeable peptides that perturb RACK1's interaction with Src) that RACK1 regulates growth of colon cells by suppressing Src activity at G(1) and mitotic checkpoints, and consequently delaying cell cycle progression. Activated Src rescues RACK1-inhibited growth of HT-29 cells. Conversely, inhibiting Src abolishes growth promoted by RACK1 depletion in normal cells. Two potential mechanisms whereby RACK1 regulates mitotic exit are identified: suppression of Src-mediated Sam68 phosphorylation and maintenance of the cyclin-dependent kinase (CDK) 1-cyclin B complex in an active state. Our results reveal novel mechanisms of cell cycle control in G(1) and mitosis of colon cells. The significance of this work lies in the discovery of a mechanism by which the growth of colon cancer cells can be slowed, by RACK1 suppression of an oncogenic kinase at critical cell cycle checkpoints. Small molecules that mimic RACK1 function may provide a powerful new approach to the treatment of colon cancer.

Adaptor Proteins, Signal Transducing↗

PubMed2006

PEGylated glucagon-like peptide-1 displays preserved effects on insulin release in isolated pancreatic islets and improved biological activity in db/db mice.

AIMS/HYPOTHESIS: The rapid degradation and clearance of glucagon-like peptide-1 (GLP-1) by the enzymes dipeptidyl peptidase-IV and neutral endopeptidase 24.11 are the main impediments to the development of GLP-1 as a potential glucose-lowering agent. In this study, new enzyme-resistant polyethylene glycol (PEG)-conjugated GLP-1 analogues were designed and examined for metabolic stability and biological potency. MATERIALS AND METHODS: Two mono-PEGylated GLP-1 analogues, N-terminally modified N-PEG/GLP-1 and Lys-modified Lys-PEG/GLP-1, were prepared. Stability was tested in plasma and tissue extracts. In vitro insulin release studies were performed using isolated rat pancreatic islets, while in vivo glycaemic responses were measured in db/db mice. RESULTS: The half-life of Lys-PEG/GLP-1 was 40-, 10- and 28-fold longer than that of GLP-1 in plasma, liver and kidney homogenates, respectively. Lys-PEG/GLP-1 stimulated insulin secretion in the islets in a dose- and glucose-dependent manner, and was as potent as GLP-1. In contrast, N-PEG/GLP-1 showed extended metabolic stability but had significantly lower biological activity. The administration of Lys-PEG/GLP-1 (9 nmol/kg i.p.) to non-fasted db/db mice stabilised glycaemia (p<0.001), whereas GLP-1 (9 nmol/kg) only caused small changes in glucose level. During OGTT in fasted db/db mice, Lys-PEG/GLP-1 administered at 1, 3 and 9 nmol/kg (i.p.) reduced the glucose AUC(0-3h) by 48.7+/-9.4, 55.0+/-2.9 and 63.4+/-2.5%, respectively, compared with placebo (p<0.01), whereas GLP-1 (9 nmol/kg) lowered the glucose level by 39.5+/-12.9% (p<0.01). CONCLUSIONS/INTERPRETATION: This study demonstrates that site-specific PEGylated GLP-1 analogues are resistant to degradation. The enhanced biological potencies of these analogues highlight their potential as new, GLP-1-like glucose-lowering agents.

Animals↗

PubMed2006

Fusion of the HSV-1 tegument protein vp22 to cytosine deaminase confers enhanced bystander effect and increased therapeutic benefit.

A major limitation in cancer gene therapy, specifically gene-dependent enzyme prodrug therapy (GDEPT), is inefficient gene delivery and expression. The suicide gene cytosine deaminase (CD) and its substrate, 5-fluorocytosine (5-FC), have been extensively explored due to the inherent 'bystander' effect achieved through diffusion of the toxic metabolite 5-fluorouracil (5-FU). In this study, we aimed to enhance this 'bystander' effect by fusing the Saccharomyces cerevisiae CD to the HSV-1 tegument protein vp22, a novel translocating protein. Two constructs were created: one with vp22 fused to CD (vp22CD) and a second wherein a truncated vp22, lacking the necessary residues for trafficking, fused to CD (delvp22CD). The generated 9L stable lines exhibited similar growth rates, enzyme expression, CD activity, and sensitivity to 5-FC and 5-FU. However, mixed population colony formation assays demonstrated greater bystander effect with the vp22CD fusion as compared to delvp22CD. This enhancement was maintained in vivo where 9L tumors expressing 20 or 50% vp22CD exhibited increased growth delay compared to the respective delvp22CD tumors. Moreover, adenoviral transduction of established wild-type 9L tumors showed increased growth delay with vp22CD (Ad-EF_vp22CD) as compared to equivalent CD (Ad-EF_CD) transduced tumors. Finally, confirming the increased efficacy, (19)F magnetic resonance spectroscopy (MRS) of vp22CD-expressing tumors demonstrated increased 5-FU levels as compared to tumors expressing the nontranslocating CD. These results together demonstrated that fusion of vp22 to CD resulted in CD translocation, which in turn amplified conversion of 5-FC to 5-FU in vivo and enhanced the therapeutic benefit of this GDEPT strategy.

Adenoviridae↗

PubMed2006

The placentas of patients with severe acute respiratory syndrome: a pathophysiological evaluation.

AIMS: The pathology of the placentas delivered from pregnant women who had severe acute respiratory syndrome (SARS) in Hong Kong was studied. METHODS: The pathology of the placentas was retrospectively studied in detail and compared with control sets. The clinical data of the women and neonates were also reviewed. RESULTS: A total of seven placentas were studied. The placentas from two women convalescent from SARS in the first trimester were normal. In three placentas delivered in the acute stage of SARS, there were increases in intervillous or subchorionic fibrin which might be related to disturbances in maternal placental blood flow due to the hypoxic respiratory disease. Extensive fetal thrombotic vasculopathy (FTV) with sharply demarcated zones of avascular fibrotic villi was noted in the placentas of two patients convalescent from SARS in the third trimester. Both pregnancies had intrauterine growth retardation, oligohydramnios and newborns small for gestation. The aetiology of the FTV might be related to thrombotic tendency due to SARS or placental hypoxia. CONCLUSIONS: This report highlights placental pathology that was probably the result of pathophysiological alteration of the maternal fetal unit during SARS. Further studies are required to delineate the relationship between severe maternal respiratory disease, placental pathology and pregnancy outcome.

Adult↗

PubMed2006

Glomeruloid haemangioma with cerebriform morphology in a patient with POEMS syndrome.

A 40-year-old Chinese man presented with sensorimotor polyneuropathy, IgAlambda paraprotein, osteosclerotic bone lesions, hypertrichosis, and impotence with decreased testosterone and raised prolactin level. POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome was diagnosed and he was treated with melphalan and prednisolone. After chemotherapy, other manifestations of POEMS syndrome developed, such as multiple haemangiomas over the chest and neck region, splenomegaly and generalized oedema. One haemangioma had a peculiar clinical morphology, similar to the appearance of cerebral gyri. Skin biopsy confirmed the diagnosis of glomeruloid haemangioma. Chemotherapy was then switched to cyclophosphamide and prednisolone, resulting in further improvement in muscle power and hypertrichosis. To our knowledge, this is the first report on a clinically distinctive morphology of glomeruloid haemangioma, and its recognition may increase the index of suspicion for early skin biopsy.

Adult↗

PubMed2006

Metastatic Crohn's disease in a Chinese girl.

Metastatic Crohn's disease, in which non-caseating granulomatous infiltration of the skin occurs at sites separated from the gastro-intestinal tract by normal tissue, is the least common dermatologic manifestation of Crohn's disease. We report a 15-year-old girl with metastatic Crohn's disease presenting as granulomatous vulvar papules and nodules with typical histopathologic features. To the best of our knowledge, this is the first case of metastatic Crohn's disease in Chinese children reported in the English medical literature.

Adolescent↗

PubMed2005

Mutation analysis of hepatitis B virus promoters in chronically infected children.

Hepatitis B viral (HBV) infection in early childhood is one of the leading causes of chronic hepatitis and liver cirrhosis that eventually lead to hepatic carcinoma. Despite the nationwide immunization programs to curtail the vertical transmission of HBV, childhood HBV infection through mothers is still occurring in Korea. As one of the efforts to understand the childhood HBV infection in Korea, four HBV promoter sequences in the sera of the chronically infected children were analyzed. Children harbored diverse viral variants as most of the chronically infected adult patients, but the deletion mutations were rare. The dominant viral sequences in the children were highly similar to the ones in the respective mothers, indicating that the maternal viruses were most likely transmitted to the children. The mutations in X, S1, S2/S promoters did not seem to show any correlation to the severity of the disease nor ages of the children. The mutations that showed some correlation to the severity of the disease were the mutations in C promoter, but the mutations did not seem to be vertically transmitted. Finally, the children with the elevated ALT/AST levels tended to have more child-specific variants suggesting that the accumulation of host-specific mutations might be associated with the development of clinical symptoms.

Adolescent↗

PubMed2005

Successful heart transplantation after 13 hours of donor heart ischemia with the use of HTK solution: a case report.

INTRODUCTION: For heart transplantation (HTx), the recommended ischemic time (IT) for donor heart is not to exceed 6 hours. Though Dr Christiaan Barnard used a donor heart with IT of 16 hours, 50 minutes with a portable hypothermic perfusion system in 1981, the recorded IT of donor hearts reported recently is 8 hours, with no adverse effects. CASE REPORT: The patient, a 14-year-old boy of blood type O, was diagnosed with cardiomyopathy at age 12. In early September 2003, the patient was recommended for HTx. His condition deteriorated 18 days later with low CO, elevated pulmonary vascular resistance, and frequent ventricular tachycardia, further complicated by pneumonia and multiorganism infections, which were contraindications for HTx. On September 22, 2003, a donor heart of blood type O was available 370 km away. Another patient of blood type B with severe heart failure was matched for the HTx. During the intervening time, another donor heart of blood type B became available locally. We matched the type B donor heart to the type B recipient. Since the type O donor heart seemed to be wasted, we performed HTx for the boy. Though preserved for 12 hours in cold cardioplegia, the donor heart was implanted with biatrial anastomosis that took 1 hour. The total IT of this donor heart was 13 hours. The recipient recovered and was discharged 3 months later. CONCLUSIONS: The IT of 13 hours for this donor heart is believed to be a world record. Our experience demonstrates that preservation time of donor heart may exceed 6 hours.

Adolescent↗

PubMed2005

Development of a quantitative assay for SARS coronavirus and correlation of GAPDH mRNA with SARS coronavirus in clinical specimens.

AIMS: To develop a quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) for severe acute respiratory syndrome coronavirus (SARS-CoV) detection and explore the potential of using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as an internal control to exclude false negative results. METHODS: SARS-CoV and GAPDH mRNA were both measured in 26 specimens from 16 patients with SARS, 40 follow up specimens from the same batch of patients, and appropriate control subjects. The relation between SARS positivity and GAPDH mRNA concentration was investigated using the chi2 test. Increasing the sensitivity for SARS-CoV and GAPDH mRNA detection was investigated in follow up specimens in which SARS-CoV and GAPDH mRNA were not detected initially. RESULTS: Varying amounts of SARS-CoV were found in the 26 SARS-CoV positive specimens and SARS-CoV was not detected in the 40 follow up specimens and controls. In addition, concentrations of GAPDH mRNA were significantly different between the patients with SARS, follow up specimens, and healthy controls (Kruskal-Wallis test, p<0.05). Moreover, GAPDH mRNA concentrations were highly correlated with SARS-CoV positivity (chi2 = 5.43; p<0.05). Finally, SARS-CoV and GAPDH mRNA were both detected in three follow up urine specimens that were initially negative when the amount of cDNA used was increased from 5 microl to 10 and 15 microl. CONCLUSIONS: This Q-RT-PCR assay can be used to detect SARS-CoV. Moreover, GAPDH mRNA may be useful to rule out false negative results in SARS-CoV detection, and the current extraction method for urine may not be sensitive enough to detect low titres of SARS-CoV.

Actins↗

PubMed2005

Use of intrathecal neostigmine as an adjunct to other spinal medications in perioperative and peripartum analgesia: a meta-analysis.

Intrathecal neostigmine has been used as an adjunct to intrathecal local anaesthetic or opioid to prolong regional analgesia and improve haemodynamic stability, with variable results. This meta-analysis aims to evaluate the effectiveness and side-effects of intrathecal neostigmine in the perioperative and peripartum settings. The literature search was based on Cochrane Controlled Trials Register, EMBASE and MEDLINE (from 1966 to 14 November 2003) databases. Volunteer and animal studies were excluded. We identified 26 studies and 19 were considered suitable for detailed data extraction. Intrathecal neostigmine increased the incidence of nausea and vomiting (OR 5.0, 95% CI: 3.4 to 7.3; P<0.00001), bradycardia requiring intravenous atropine (OR 2.7, 95% CI: 1.4 to 5.4; P=0.005), and anxiety, agitation, or restlessness (OR 10.3, 95% CI: 3.7 to 28.9; P=0.00001). It improved the overall 24 hour VAS score (-1.4 VAS pain score, 95% CI: -1.7 to -1.2, P<0.00001), delayed the time of first request for rescue analgesia (168 min, 95% CI: 125 to 211; P<0.00001), and reduced the total number of rescue injections of nonsteroidal anti-inflammatory drug within the first 24 hours (-0.8, 95% CI: -1.1 to -0.4; P=0. 00001). It did not affect the duration of motor blockade (3.5 min, 95% CI: -1.5 to 8.6; P=0.17) or the total amount of ephedrine required (-0.4 mg, 95% CI: -1.5 to 0.7; P=0.5). Adding intrathecal neostigmine to other spinal medications improves perioperative and peripartum analgesia marginally when compared with placebo. It is associated with significant side-effects and the disadvantages outweigh the minor improvement in analgesia achieved.

Adjuvants, Anesthesia↗

PubMed2005

Parallel, solution phase synthesis of dihydropyridine miticides via a versatile multicomponent reaction.

A novel class of highly active dihydropyridine miticides was prepared using a multicomponent reaction process. The initial lead was rapidly optimized using solution phase parallel synthesis techniques and a positional scanning approach. Detailed structure-activity relationships were developed for the amino and carbonyl components of the molecule and used to select the best candidates for broad field testing. The chemistry, biology and toxicology of these compounds will be presented along with numerous structural variants of the reaction products.

Agrochemicals↗

PubMed2004

Specific heat and Lindemann-like parameter of metallic clusters: mono- and polyvalent metals.

The Brownian-type molecular dynamics simulation is revisited and applied to study the thermal and geometric properties of four mono- and two polyvalent metallic clusters. For the thermal property, we report the specific heat at constant volume CV and study the solid-liquid-like transition by scrutinizing its characteristic. For the geometric property, we calculate the root mean square relative bond-length fluctuation delta as a function of increasing temperature. The thermal change in delta reflects the movement of atoms and hence is a relevant parameter in understanding the phase transition in clusters. The simulated results for the CV of alkali and aluminum clusters whose ground state structures exhibit icosahedral symmetry generally show one phase transition. In contrast, the tetravalent lead is quite often seen to exhibit two phase transitions, a premelting process followed by a progressive melting. In connection with the premelting scenario, it is found here that those (magic number) clusters identified to be of lesser stability (among other stable ones) according to the second energy difference are clusters showing a greater possibility of undergoing premelting process. This energy criterion applies to aluminum clusters nAl=28 and 38. To delve further into the thermal behavior of clusters, we have analyzed also the thermal variation of deltaT and attempted to correlate it with CV(T). It turns out that the premelting (if exist) and melting temperatures of the smaller size clusters (n less, similar 50) extracted from CV do not always agree quantitatively with that deduced from delta.

Journal Article↗

PubMed2004

Enhancement of the resolution of surface plasmon resonance biosensors by control of the size and distribution of nanoparticles.

A new resolution-enhanced surface plasmon resonance (SPR) biosensor offers a tenfold improvement in resolution compared with conventional SPR biosensors in the detection of the surface coverage of biomaterials. The proposed optical biosensor, based on the attenuated total-reflection method, excites both the surface plasmons and particle plasmons to enhance the local electromagnetic field by control of the size and volume fraction of embedded Au nanoparticles to increase the resolution of the device. The SPR biosensor design is based on the Maxwell-Garnett model and the Fresnel equations, and the device is fabricated with a cosputtering deposition system.

Biocompatible Materials↗

PubMed2004

Radiographic contrast study of the upper gastrointestinal tract of eight dogs using carboxymethylcellulose mixed with a low concentration of barium sulphate.

To evaluate the efficacy of a mixture of barium and carboxymethylcellulose (CMC) suspension in upper gastrointestinal contrast studies, and to determine its optimal concentration and method for use, eight healthy beagle dogs underwent conventional upper gastrointestinal contrast imaging and a modified procedure using a mixture of barium sulphate and CMC. Four different procedures were carried out on the dogs at weekly intervals. In the first, the dogs were administered 10 ml/kg of 60 per cent barium suspension for conventional study of the upper gastrointestinal tract. The second, third and fourth procedures involved modified methods in which the dogs were given 10 ml/kg of a mixture of 25 per cent barium and 0.5 per cent CMC prepared to a low, moderate or high viscosity, respectively. All four procedures were evaluated by four criteria: the quality of the images obtained, the translucency and distensibility of the bowel, and the transit time. The method of imaging which used a moderately viscious CMC formulation provided excellent image quality, high translucency, a rapid transit time and suitable bowel distension to enable more precise diagnosis of disorders of the gastrointestinal tract.

Administration, Oral↗

PubMed2004

Heart transplant coronary artery disease in Chinese recipients.

BACKGROUND: Transplant coronary artery disease is the principle limiting factor for long-term survival of heart transplantation (HTx) recipients. We reviewed our data to assess the incidence of this disorder among Chinese HTx recipients and to compare it with the results of Western studies. MATERIAL AND METHODS: From July 1988 to May 2002, 182 patients received 184 orthotopic HTx. One hundred sixty-three recipients survived for at least 1 year with available SPECT scans or coronary angiogram studies. The data set included donor characteristics, recipient characteristics, active cytomegalovirus (CMV) infection rate, rejection episodes, immunosuppressants, and human leukocyte antigen (HLA) mismatches. RESULTS: Surgical mortality in our program was 4.3% and the actuarial freedom from coronary artery disease at 1, 3, and 5 years was 99%, 95%, and 92%, respectively. Angiogram results were stratified into coronary artery disease (n = 15) or absence of the disorder (n = 148) groups. Only older donor age showed statistical significance between the groups. Compared with the Western series, the present data show higher actuarial survival rates and freedom from coronary artery disease. There were statistically significant differences in regard to graft ischemia time, proportion of male recipients, ischemic heart disease, rejection episodes during the first year, and incidence of CMV infection. CONCLUSIONS: SPECT scan can detect coronary artery disease before there is significant stenosis of the coronary artery with acceptable survival rates. Chinese HTx recipients show a lower incidence of the disorder, lower rates of ischemia heart disease, lower proportion of male gender, lower incidence of CMV infection, fewer rejection episodes during the first year, and less ischemic time than Western recipients, which maybe the contributing factors to their better survival.

Adult↗

PubMed2004

Effect of TCDD on corpus cavernosum histology and smooth muscle physiology.

A polyhalogenated aromatic hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is one of the most potent toxic environmental pollutants. Decreases in spermatogenesis and the ability to conceive and carry a pregnancy to term are the most sensitive signs of reproductive toxicity by TCDD in the mammal, but no report of its effect on the erectile function exists. We performed this study to investigate the effect of TCDD on the erectile function. New Zealand white rabbits were treated intraperitoneally with 1 microg/kg of TCDD. At 4 (Gr I) and 8 (Gr II) weeks after the administration of TCDD, cavernosal tissues were harvested for strip study in the organ bath and testes were prepared for histologic examination. Compared to the maximal amplitude of 17.1+/-4.12 mN in normal control (Gr III), the contractions to cumulative concentrations of NE (10(-8)-10(-4) M) were significantly decreased to 6.57+/-1.34 and 5.45+/-1.01 mN in Groups I and II, respectively. Compared to 51.12+/-7.38% in Gr III, relaxation to cumulative concentration (10(-8)-10(-4) M) of acetylcholine was significantly decreased to 17.25+/-2.17% (Gr I) and 9.73+/-2.17% (Gr II) at a concentration of 10(-4) M, respectively. Compared to 75.12+/-13.18% in Gr III, relaxation to cumulative concentration (10(-8)-10(-4) M) of SNP was significantly decreased to 31.49+/-7.89% (Gr I) and 18.54+/-6.12% (Gr II) at a concentration of 10(-4) M, respectively. Histologically, intracavernosal fibrosis, abnormal subtunical deposition of fat and decreased sinusoidal space with consequent increase of trabecular smooth muscle contents were identified in TCDD-treated groups. In TCDD-treated animals, seminiferous tubules showed a decrease of germ cells with vacuolar degeneration and apoptotic cells. Spermatids were hardly seen. These results suggest that TCDD inhibits spermatogenesis and has a potential harmful effect on erectile function via changes of corpus cavernosum histology and smooth muscle physiology.

Acetylcholine↗

PubMed2004

Performance of large-size superconducting coil in 0.21T MRI system.

A high-temperature superconductor (HTS) was used on magnetic resonance imaging (MRI) receiver coils to improve image quality because of its intrinsic low electrical resistivity. Typical HTS coils are surface coils made of HTS thin-film wafers. Their applications are severely limited by the field of view (FOV) of the surface coil configuration, and the improvement in image quality by HTS coil is also reduced as the ratio of sample noise to coil noise increases. Therefore, previous HTS coils are usually used to image small in vitro samples, small animals, or peripheral human anatomies. We used large-size HTS coils (2.5-, 3.5-, and 5.5-in mean diameter) to enhance the FOV and we evaluated their performance through phantom and human MR images. Comparisons were made among HTS surface coils, copper surface coils, and cool copper surface coils in terms of the signal-to-noise ratio (SNR) and sensitivity profile of the images. A theoretical model prediction was also used to compare against the experimental result. We then selected several human body parts, including the wrist, feet, and head, to illustrate the advantage of HTS coil over copper coil when used in human imaging. The results show an SNR gain of 200% for 5.5-in HTS coil versus same size copper coils, while for 2.5- and 3.5-in coils it is 250%. We also address the various factors that affect the performance of large size HTS coils, including the coil-to-sample spacing due to cryogenic probe and the coil-loading effect.

Electric Conductivity↗