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Biomedical subjects

C T Lee

Publications and source records attributed to C T Lee.

At least 19 recordsLinked to original sources

Lack of association between COPD and transforming growth factor-beta1 (TGFB1) genetic polymorphisms in Koreans.

OBJECTIVE: Many genetic variations have been suggested as genetic risk factors for the development of chronic obstructive pulmonary disease (COPD), including single nucleotide polymorphisms in the transforming growth factor-beta1 (TGFB1) gene. We attempted to elucidate the association between TGFB1 genetic polymorphisms and COPD among Koreans. DESIGN: The genotypes of 102 male patients with COPD and 159 volunteers with similar distributions of age, sex and smoking intensity, as well as normal pulmonary function, were determined for three previously associated TGFB1 single nucleotide polymorphisms (SNPs), -10807G/A (rs2241712) and -509T/C (rs1800469), located in or near the promoter, and 29T/C (rs1982073), located in exon 1 of the TGFB1 gene. RESULTS: No significant associations between COPD and the three TGFB1 SNPs could be identified. In addition, the haplotypes composed of three TGFB1 SNPs were not associated with the presence of COPD. CONCLUSION: These results differ from previous reports involving Caucasians, and might reflect racial differences in the pathogenesis of COPD.

Chi-Square Distribution↗

Recombinant human erythropoietin independence in chronic hemodialysis patients: clinical features, iron homeostasis and erythropoiesis.

AIMS: Recombinant human erythropoietin (r-HuEPO) is widely used to correct renal anemia in uremic patients. Interestingly, some chronic hemodialysis (HD) patients can maintain high hemoglobin level without the need of r-HuEPO. The aim of this study is to investigate clinical features, iron metabolism and erythropoiesis of these r-HuEPO-independent HD patients. METHODS: r-HuEPO independence was defined in dialysis patients as hemoglobin greater than 12 g/dl and no use of r-HuEPO for at least 6 months. An age- and sex-matched group was selected for comparison. Their underlying diseases, duration of hemodialysis therapy, efficacy of dialysis (Kt/V), normalized protein catabolic rate (nPCR) and body mass index (BMI) were recorded. Laboratory data including: hemoglobin, albumin, high sensitivity C-reactive protein, serum iron, total iron binding capacity, transferrin saturation, ferritin, intact parathyroid hormone, soluble transferrin receptor (sTfR), serum EPO, cortisol, testosterone, aluminum and leptin levels were measured. Renal sonography was also performed in each patient to evaluate renal cyst formation. RESULTS: About 2.3% of all HD patients (21/888; M : F = 18 : 3) were r-HuEPO-independent. These patients had significantly longer HD duration and higher serum EPO and sTfR levels, and lower transferrin saturation rate than dependent groups. Correlation analysis revealed that hemoglobin level strongly correlated with HD duration, serum sTfR and EPO levels. Levels of sTfR were positively related with serum EPO levels and BMI. Multivariate regression analysis showed that level of sTfR was the only independent factor related to r-HuEPO independence. CONCLUSION: R-HuEPO independence is rare among chronic hemodialysis patients. Factors contributing to this dependence are complex and multiple. Level of serum sTfR parallels erythropoiesis and is the most significant factor associated with r-HuEPO independence in chronic HD patients.

Adult↗

Hypercalcaemia and haemophagocytic syndrome: rare concurrent presentations of disseminated tuberculosis in a dialysis patient.

Tuberculosis remains an important cause of infection in chronic haemodialysis patients. Frequent extrapulmonary involvement, non-specific presentation and limited diagnostic tools usually make early diagnosis difficult. Herein, we report on an 83-year-old female patient who had been on regular heamodialysis therapy for 15 years, who presented with asymptomatic hypercalcaemia and pancytopenia. Haemophagocytic syndrome was documented during the admission period. Mycobacterium tuberculosis was cultured from bone marrow 1 month after her demise. This case report highlights the non-specific manifestations of extrapulmonary tuberculosis in dialysis patients and the limited value of conventional diagnostic methods. We would like to recommend aggressive intervention and early tissue aspiration from possible infectious sites when tuberculosis cannot be completely ruled out. Disseminated tuberculosis should be considered as an indication of hypercalcaemia where haemophagocytic syndrome occurs simultaneously.

Aged↗

Response of pulmonary tuberculomas to anti-tuberculous treatment.

Pulmonary tuberculomas are well-circumscribed masses caused by Mycobacterium tuberculosis. However, the response of tuberculomas to anti-tuberculous (TB) treatment has not been well defined as yet. The response of pulmonary tuberculomas to anti-TB treatment was retrospectively reviewed in 45 patients diagnosed between January 1997 and December 2001. The areas of pulmonary tuberculomas were estimated by calculating products of the longest and their perpendicular short diameters on chest radiographs. The response to anti-TB treatment was categorised as "decreased" (> 25% reduction in area versus its initial area), "increased" (> 251% increase) and "no change" (the remainder). The mean of treatment duration was 11.5 +/- 3.6 months. Three months after treatment, 18 patients (40.0%) were categorised as decreased, 25 (55.6%) as no change and two (4.4%) as increased. Twelve months after treatment, out of 42 patients available for chest radiographs, 32 patients (76.2%) were categorised as decreased, nine (21.4%) as no change and one patient (2.4%) as increased. At the last follow-up (mean follow-up 27.0 +/- 10.2 months), 37 patients (82.2%) were categorised as decreased. The majority of pulmonary tuberculomas were decreased by anti-tuberculosis treatment during and even after treatment, although a transient enlargement during the early period of treatment was observed infrequently.

Antitubercular Agents↗

Tuberculous peritonitis in uremic patients.

AIMS: To identify clinical features and treatment response of tuberculous peritonitis (TBP) in a uremic population, a retrospective case-control study was performed. MATERIALS AND METHODS: Thirteen uremic patients with TBP (Group I: 62.7 +/- 6.8 years, male 54%) collected between January 1986 and January 2002 were compared with another two age- and sex-matched controls: 19 non-azotemic patients with TBP (Group II: 62.9 +/- 7.3 years, male 47%) and 30 uremic patients without TBP (Group III: 61.1 +/- 8.7 years, male 47%). Clinical information and data of ascites and blood examinations were evaluated. RESULTS: Significant differences between Groups I and II were found in comorbidity, hypertension, anorexia, percentages of neutrophil and lymphocyte from blood and ascites, and serum calcium (sCa), phosphorus and albumin-adjusted calcium (sAACa). However, no significant differences in duration of symptoms, coexistent pulmonary tuberculosis (p = 0.061), duration or complications of therapy and mortality (p = 0.13) were detected. Significant differences between Groups I and III were found in peripheral white cell counts and percentages of neutrophil and lymphocyte as well as in serum creatinine (sCr), albumin, sCa, sAACa and intact parathyroid hormone (iPTH). CONCLUSIONS: Non-specific symptoms make the diagnosis of TBP in a uremic population difficult. However, neutrophil predominance in blood and ascites, hypoalbuminemia, relatively lower sCr and hypercalcemia with suppressed serum iPTH were found to be characteristic. In TBP uremic patients, therapy complications were not common and there was a tendency for higher mortality, largely due to septic shock.

Aged↗

Isolated fatal renal mucormycosis in a patient with chronic obstructive pulmonary disease and tuberculosis.

Renal mucormyosis is a rare entity and normally diagnosed at postmortem. Isolated cases diagnosed antemortem are even rarer and only a few cases have been reported. The disease is associated with a high mortality rate, especially in patients with underlying disease. Clinical presentation is non-specific and includes flank pain, fever and pyuria with or without haematuria. Identifying fungal hyphae microscopically is essential for diagnosis. We present a rare isolated fatal case of renal mucormycosis in a 77-year-old man with chronic obstructive pulmonary disease (COPD) and old tuberculosis (TB) who had been diagnosed after a right nephrectomy. We believe early diagnosis and appropriate treatment for fungal infection, together with the predisposing underlying disease, is crucial for survival.

Aged↗

Perioperative ulnar neuropathy in orthopaedics: association with tilting the patient.

The incidence and causes of perioperative ulnar neuropathy in a prospective series of 203 consecutive patients were examined. Three percent of patients had ulnar neuropathy develop in the entire prospective series. The incidence was 6% in patients having total hip arthroplasty. There was a highly significant association between a tilted body position on the operating table and development of ulnar neuropathy on the contralateral side. This position rotates the arm internally and places the ulnar nerve at risk for direct compression.

Adolescent↗

Outcome of pregnancy in Asian women with systemic lupus erythematosus: experience of a single perinatal centre in Singapore.

OBJECTIVE: To study maternal and fetal outcomes in women with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Retrospective study of 27 pregnancies in 18 women with SLE in a single centre. RESULTS: The mean age was 30 years and most patients were nulliparous. Twenty-six of 27 pregnancies were in disease remission at the time of booking. Renal impairment was present in 7 pregnancies (6 women), of whom 2 were in end-stage renal disease on dialysis. Gestational diabetes developed in 4 pregnancies. There were 6 cases of pre-existing hypertension and 5 with superimposed pre-eclampsia. One woman developed intrapartum eclampsia. Two women had secondary antiphospholipid syndrome (APS) and suffered late fetal losses; in addition, they also developed SLE flares in the form of autoimmune haemolytic anaemia in the postpartum period. There was no maternal mortality. There was one termination of pregnancy for severe renal disease. The median gestational age at delivery was 38 weeks (range, 24 to 40 weeks) and the mean birth weight was 3047 g; the median Apgar scores were 8 and 9 at 1 and 5 minutes of life, respectively. There were 5 cases of intrauterine growth restriction (IUGR), 4 of which occurred in women with renal impairment. There were no cases of congenital heart block or neonatal lupus. There was a late fetal loss at 24 weeks in a woman with secondary APS. There were 2 preterm deliveries (7.4%) due to intervention for IUGR. CONCLUSION: Good pregnancy outcomes can be expected in women with SLE in remission. Pre-pregnancy counselling is crucial to achieve this. All pregnancies should still be considered high risk and be managed jointly between the obstetricians, the perinatologists and the physicians. In particular, those with renal impairment are at increased risk of IUGR, superimposed pre-eclampsia and preterm births. Co-existing APS augurs a poorer prognosis for pregnancy outcome, and may present atypically as autoimmune haemolytic anaemia in the postpartum period.

Abortion, Spontaneous↗

An adenovirus expressing mutant p27 showed more potent antitumor effects than adenovirus-p27 wild type.

The main inhibitory action of p27, a cyclin-dependent kinase inhibitor (CDKI), arises from its binding with the cyclin E/cyclin-dependent kinase 2 (Cdk2) complex that results in G(1)-S arrest. Degradation of p27 is mediated by phosphorylation of Thr-187 of p27, which follows ubiquitination. In this study, we generated two adenoviruses expressing wild-type p27 (ad-p27wt) and mutant p27 (ad-p27mt), with mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC), which was produced with the belief that mutant p27 would bind cyclin E/CDK2 more stably and show more potent antitumor effects. Ad-p27wt and ad-p27mt expressed p27 proteins that were indistinguishable by anti-p27 antibody. A pulse chase experiment showed that p27mt was more resistant to degradation than p27wt. In human lung cancer cell lines, ad-p27mt showed stronger growth inhibition than ad-p27wt. Both types of ad-p27 induced G(1)-S arrest and apoptosis; however, ad-p27mt induced stronger G(1)-S arrest and apoptosis. Intratumoral injection of ad-p27mt induced partial regression of established tumors and inhibited the growth of human lung cancer xenografts more strongly than ad-p27wt. From these results, we conclude that ad-p27mt has the potential to become a novel and powerful gene therapy tool.

Adenoviridae↗

Non-local concepts and models in biology.

In this paper, we consider local and non-local spatially explicit mathematical models for biological phenomena. We show that, when rate differences between fast and slow local dynamics are great enough, non-local models are adequate simplifications of local models. Non-local models thus avoid describing fast processes in mechanistic detail, instead describing the effects of fast processes on slower ones. As a consequence, non-local models are helpful to biologists because they describe biological systems on scales that are convenient to observation, data collection, and insight. We illustrate these arguments by comparing local and non-local models for the aggregation of hypothetical organisms, and we support theoretical ideas with concrete examples from cell biology and animal behavior.

Animal Communication↗

Preservation of ancient and fertile lithospheric mantle beneath the southwestern United States.

Stable continental regions, free from tectonic activity, are generally found only within ancient cratons-the centres of continents which formed in the Archaean era, 4.0-2.5 Gyr ago. But in the Cordilleran mountain belt of western North America some younger (middle Proterozoic) regions have remained stable, whereas some older (late Archaean) regions have been tectonically disturbed, suggesting that age alone does not determine lithospheric strength and crustal stability. Here we report rhenium-osmium isotope and mineral compositions of peridotite xenoliths from two regions of the Cordilleran mountain belt. We found that the younger, undeformed Colorado plateau is underlain by lithospheric mantle that is 'depleted' (deficient in minerals extracted by partial melting of the rock), whereas the older (Archaean), yet deformed, southern Basin and Range province is underlain by 'fertile' lithospheric mantle (not depleted by melt extraction). We suggest that the apparent relationship between composition and lithospheric strength, inferred from different degrees of crustal deformation, occurs because depleted mantle is intrinsically less dense than fertile mantle (due to iron having been lost when melt was extracted from the rock). This allows the depleted mantle to form a thicker thermal boundary layer between the deep convecting mantle and the crust, thus reducing tectonic activity at the surface. The inference that not all Archaean crust developed a strong and thick thermal boundary layer leads to the possibility that such ancient crust may have been overlooked because of its intensive reworking or lost from the geological record owing to preferential recycling.

Journal Article↗

In vivo antitumor effect of herpes simplex virus thymidine kinase gene therapy in rat hepatocellular carcinoma: feasibility of adenovirus-mediated intra-arterial gene delivery.

Transfer of the herpes simplex virus-thymidine kinase gene, followed by the administration of ganciclovir (HSV-tk/GCV), has been a major approach for cancer gene therapy. We investigated the antitumor effect of the HSV-tk/GCV strategy with the rat orthotopic hepatocellular carcinoma (HCC) model and the tumor-selective gene delivery by an adenovirus-mediated gene transfer through the hepatic artery. The complete antitumor effect was demonstrated, after the treatment with GCV in rat HCC established by the implantation of HSV-tk transferred rat HCC cells. The in vivo bystander effect was also observed. The marked infiltration of CD4+ and CD8+ T lymphocytes, macrophages and NK cells were found in the tumor area. After the injection of adenovirus carrying the LacZ gene into the hepatic artery, the selective expression of transgene in the tumor cell was achieved. These findings indicate that the HSV-tk/GCV strategy, using an adenoviral vector, could be a promising avenue for the treatment of hepatocellular carcinoma.

Adenoviridae↗

Growth-inhibitory effect of adenovirus-mediated p53 gene transfer on medulloblastoma cell line, Daoy, harboring mutant p53.

To improve the survival rate, gene therapy, such as the replacement of inactivated tumor suppressor genes, has become a new investigational adjuvant treatment modality for human malignancies. We investigated the effect of adenovirus(Ad)-mediated transfer of wildtype p53 tumor suppressor gene on the medulloblastoma cell line, Daoy, which harbors mutant-type p53 gene. At 50 multiplicity of infection (moi), immunohistochemical staining with p53 monoclonal antibody showed positive staining in all cells 2 days after Ad-CMV-p53 infection. The high expression of wild-type p53 protein was detected in Ad-CMV-p53-infected cells, and expression of wild-type p53 protein peaked on day 2 after the infection. The growth of Ad-CMV-p53-infected cells was greatly suppressed in vitro, and the Ad-CMV-p53 treatment significantly reduced the tumor mass in vivo. The mean weight of Ad-CMV- infected tumors was only 16% of those which were mock infected, and 25% of those which were Ad-CMV-beta-gal infected. On microscopic examination, Ad-CMV-p53-infected tumors showed numerous apoptotic bodies. This Ad-CMV-p53 gene transfer showed high transduction efficacy and expression, resulting in significant growth inhibition of Daoy harboring mutant type p53.

Adenoviruses, Human↗

Characterization of action potential waveform-evoked L-type calcium currents in pituitary GH3 cells.

The response of the L-type Ca2+ current (ICa,L) in pituitary GH3 cells to variations in the action potential (AP) waveform was examined using the whole-cell configuration of the patch-clamp technique. ICa,L evoked during an AP waveform exhibited an early and a late component. The early component occurred on the rising phase of the AP; the late component coincided with the falling phase. Prolonging the falling phase of the AP increased the Ca2+ charge carried by ICa,L, although the amplitude of the late ICa,L was reduced. Prolonging the peak voltage of the AP waveform, however, increased the amplitude of the late component. ICa,L inactivated during a train of AP waveforms. When Ba2+ was used as the charge carrier, current inactivation during a train of APs decreased. Likewise, ICa,L evoked by the AP templates with irregular bursting pattern was inactivated. When the repetitive firing of APs with depolarizing potentials was replayed to cells, Ca2+ entry was not only spread over the entire AP, but also occurred during the interspike voltage trajectory. After application of thyrotropin releasing hormone (TRH; 10 microM), ICa,L in response to rectangular pulses was increased and the current/voltage relation shifted slightly to more negative values. TRH (10 microM), thapsigargin (10 microM) or cyclopiazonic acid (30 microM) enhanced the late component of the AP-evoked ICa,L. TRH also attenuated the inactivation of ICa,L during a train of APs. These results indicate that in pituitary GH3 cells, the time course and kinetics of ICa,L during the AP waveforms is distinct from that evoked by rectangular voltage clamp. Changes in the shape and firing pattern of APs in GH3 cells can modulate Ca2+ influx through L-type Ca2+ channels. Ca2+ release from internal stores may affect the magnitude of AP-evoked ICa,L in these cells.

Action Potentials↗

Serotyping and antimicrobial susceptibility of group B Streptococcus over an eight-year period in southern Taiwan.

The increase in penicillin resistance among pneumococci and viridans streptococci and the development of serotype-specific conjugate vaccine have increased the need for knowledge of the antimicrobial susceptibility and the capsular serotypes of group B streptococci. Over an 8-year period, 351 group B streptococcal isolates from southern Taiwan were tested for antimicrobial susceptibility and serotype determination. Eighty-seven percent of the isolates were typeable. Types III (28.5%) and V (27.1%) were the most common serotypes. The occurrence of type V isolates increased with age, while that of type III isolates decreased with age, showing a predominance in children less than 1 year of age. Of 118 isolates from cases of invasive infection, types Ia, Ib, II, III, IV, and V accounted for 12.7, 11.9, 0.8, 33, 1.7, and 26.3%, respectively. Using the agar dilution method, all isolates were found to be susceptible to penicillin, cefotaxime, and vancomycin, 99.4% to ofloxacin, 78.1% to chloramphenicol, 63.2% to azithromycin, 62.6% to erythromycin, 57.3% to clindamycin, and 2.8% to tetracycline. Chloramphenicol resistance was associated with type III isolates (59 of 100, 59%) and erythromycin and azithromycin resistance with type Ib isolates (25 of 33 176%], and 21 of 33 [64%], respectively). Thus, 72% of the isolates from invasive infections were serotype III, V, or Ia, and penicillin remains the drug of choice for treatment or prophylaxis of group B streptococcal infections in southern Taiwan, despite the high prevalence of penicillin resistance among Streptococcus pneumoniae and viridans streptococci.

Adolescent↗

Renal mass within a horseshoe kidney: preoperative evaluation with three-dimensional helical computed tomography.

Tumors arising within a horseshoe kidney are uncommon and may be difficult to characterize. We report a case of transitional cell carcinoma in a horseshoe kidney. Although several conventional imaging techniques were used to define the mass, each provided limited information. Recent advances in computer technology permit radiologic imaging to provide detailed examination of the horseshoe kidney with a single study. We describe the use of three-dimensional multislice helical computed tomography as the preferred modality to clarify the suspected neoplasm, vasculature, and collecting system of a horseshoe kidney. High-quality anatomic characterization will certainly enhance the opportunity for nephron-sparing surgery within this population.

Carcinoma, Papillary↗