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Biomedical subjects

Y-T Lee

Publications and source records attributed to Y-T Lee.

9 recordsLinked to original sources

Constitutively active CCK2 receptor splice variant increases Src-dependent HIF-1 alpha expression and tumor growth.

Gastrointestinal (GI) cancers ectopically express multiple splice variants of the cholecystokinin-2 (CCK(2))/gastrin receptor; however, their relative contributions to the cancer phenotype are unknown. The aim of this study was to compare the effects of CCK(2) receptor (CCK(2)R) and CCK(2i4sv)R expression on cell growth both in vitro and in vivo using a human epithelial cell model, HEK239. In vitro, receptor variant expression did not affect cell proliferation either in the absence or presence of agonist. However, in vivo, the expression of CCK(2i4sv)R, but not CCK(2)R, increases HEK293 tumor growth in a constitutive, Src-dependent manner. Enhanced tumorigenicity of CCK(2i4sv)R is associated with an Src-dependent increase in the transcription factor, hypoxia-inducible factor-1alpha, its downstream target, vascular endothelial growth factor and tumor micro-vessel density, suggesting that CCK(2i4sv)R may contribute to the growth and spread of GI cancers through agonist-independent mechanisms that enhance tumor angiogenesis.

Alternative Splicing↗

Pulse pressure, aortic regurgitation and carotid atherosclerosis: a comparison between hypertensives and normotensives.

Pulse pressure (PP) has often been associated with cardiovascular morbidity and mortality. Patients with aortic regurgitation (AR) often have increased PP. The aim of this study is to investigate the associations among PP, AR and extracranial carotid artery (ECCA) carotid atherosclerosis (CA) in hypertensives and age- and sex-matched normotensives. Two hundred and sixty-three hypertensive patients and 270 normotensive subjects from the Chin-Shan Community Cardiovascular Cohort participated in this study in 1996. CA, expressed as maximal common carotid artery intima-media thickness (IMT) > or = 75th percentile and ECCA plaque score > 6, was measured using high-resolution B-mode ultrasonography. The presence of AR was assessed by echocardiography, and their relationships with CA were evaluated. Results showed measurements of CA significantly associated with increased PP. Presence of AR associated with CA, but this relationship was attenuated after controlling for age. Multivariate logistic regression analyses revealed that an ECCA score > 6 significantly increase the risk in conjunction with PP, age and smoking in hypertensives. Correspondingly, CA increased with age, smoking and left ventricular hypertrophy on electrocardiography but not PP in normotensives. In conclusion, higher PP is strongly associated with CA in patients with hypertension. In terms of risk stratification, PP is more important in hypertensives than in normotensives which seem to imply that pulsatile haemodynamic component of BP is crucial in association with atherosclerosis.

Aged↗

Heart transplantation using donors positive for hepatitis.

From May 1994 to September 2003, 177 hearts were procured for heart transplantation (HTx) from donors ranging in age from 1 year 2 months to 66 years 5 months (mean = 30 years). All donors and recipients received serologic tests for hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), and hepatitis C virus antibody (anti-HCV). Thirty-two donors were HBsAg-positive and another four were anti-HCV-positive. Two HBsAg-positive donors were transplanted to patients with no previous evidence of hepatitis. After HTx, one received hepatitis B immunoglobulin prophylaxis and no hepatitis was noted during a 5 years follow-up. The other seroconverted at 4 months after HTx, requiring lamivudine treatment. Another four HBsAg-positive donors were transplanted to HBsAg-positive recipients. All four recipients had hepatitis flare-ups requiring lamivudine treatment. The other 26 HBsAg-positive donors were transplanted to anti-HBs-positive recipients. None suffered from hepatitis. Among the four patients receiving anti-HCV-positive hearts, seroconversion was noted in one recipient at 26 months. This patient never had clinical hepatitis before he died of allograft rejection at 3 years after HTx. The other three recipients remain anti-HCV negative during follow-up of 80, 50, and 46 months. It was concluded the hepatitis B- or C-positive donors could be used as heart donors for status 1 patients. Donors with positive HBsAg may be transplanted to anti-HBs-positive recipients with no HBV infection.

Adolescent↗

Heart transplantation in the patient under ventricular assist complicated with device-related infection.

Ventricular assist devices (VAD) have benefited patients with end-stage heart failure as a bridge to heart transplantation (HTx). We present our experience of HTx in the presence of device-related infection (DRI) including driveline exit site with pocket infections. From May 1996 to April 2003, mechanical circulatory support with the HeartMate VAD was performed in eight patients, and with the Thoratec VAD in seven patients. Although 151 patients underwent HTx during that period, only 8 of the 15 patients had suitable donors and underwent orthotopic HTx. Six of the eight patients developed DRI. Their ages ranged from 18 to 59 years (mean = 36 +/- 14 years). The duration of VAD support ranged from 8 to 287 days (mean = 125 +/- 117 days). The general condition and cardiac function improved gradually under VAD support. At the time of HTx, all six male patients were suffering from DRI. The causative microorganisms were Acinetobacter baumannii (n = 3) methicillin-resistant Staphylococcus aureus (n = 2), and Enterococcus faecium (n = 1). All patients underwent successful HTx, and were discharged in good condition. It is concluded that under the coverage of appropriate antibiotics, HTx can be successfully performed for the patients for VAD support with DRI. It is important to prevent the spread of infection during HTx. Adequate debridement and drainage of the infected materials prevents postoperative wound infections.

Adult↗

Dynamic changes of gene expression profiles during postnatal development of the heart in mice.

OBJECTIVE: To study postnatal cardiac differentiation in the mouse. HYPOTHESIS: There might be mechanisms or factors in cardiac differentiation that could be identified by systematic gene expression analysis during postnatal cardiac development. METHODS: Expression of 6144 genes was examined in mouse heart, from the newborn period (day 0), through day 7 and day 14 day, to adulthood, using the cDNA microarray approach. Northern blotting and immunohistochemical techniques were used to confirm the microarray results. RESULTS: Various cardiac development related genes involving the cell cycle (cyclin B1, proliferating cell nuclear antigen (PCNA), and Ki67), growth factors (IGF-II, pleiotrophin (PTN), and midkine (MK)), and transcriptional regulation, cytoskeleton, and detoxification enzymes were identified by microarray analysis. Some of these genes were also confirmed by Northern blotting and immunohistochemistry of their RNA and protein content. In vivo treatment with PTN (20 ng/g) increased bromodeoxyuridine incorporation (by 2.24-fold) and PCNA expression (by 1.71-fold) during day 7 to day 14, indicating that PTN induces cell proliferation in mouse heart. CONCLUSIONS: Global gene expression analysis in the whole heart may be useful in understanding the orchestrated process of postnatal development or terminal differentiation in the cardiac environment. These data are likely to be helpful in studying developmental anomalies of the heart in neonates.

Animals↗