Biomedical subjects

K Y Chen

Publications and source records attributed to K Y Chen.

At least 19 recordsLinked to original sources

PubMed2006

Propagation of the cardiac impulse in the diabetic rat heart: reduced conduction reserve.

Diabetes mellitus is a growing epidemic with severe cardiovascular complications. Although much is known about mechanical and electrical cardiac dysfunction in diabetes, few studies have investigated propagation of the electrical signal in the diabetic heart and the associated changes in intercellular gap junctions. This study was designed to investigate these issues, using hearts from control and diabetic rats. Diabetic conditions were induced by streptozotocin (STZ), given i.v. 7-14 days before experiments. Optical mapping with the voltage-sensitive dye di-4-ANEPPS, using hearts perfused on a Langendorff apparatus, showed little change in baseline conduction velocity in diabetic hearts, reflecting the large reserve of function. However, both the gap junction uncoupler heptanol (0.5-1 mM) and elevated potassium (9 mM, to reduce cell excitability) produced a significantly greater slowing of impulse propagation in diabetic hearts than in controls. The maximal action potential upstroke velocity (an index of the sodium current) and resting potential was similar in single ventricular myocytes from control and diabetic rats, suggesting similar electrical excitability. Immunoblotting of connexin 43 (Cx43), a major gap junction component, showed no change in total expression. However, immunofluorescence labelling of Cx43 showed a significant redistribution, apparent as enhanced Cx43 lateralization. This was quantified and found to be significantly larger than in control myocytes. Labelling of two other gap junction proteins, N-cadherin and beta-catenin, showed a (partial) loss of co-localization with Cx43, indicating that enhancement of lateralized Cx43 is associated with non-functional gap junctions. In conclusion, conduction reserve is smaller in the diabetic heart, priming it for impaired conduction upon further challenges. This can desynchronize contraction and contribute to arrhythmogenesis.

Animals↗

PubMed2006

Energy expenditure of genuine laughter.

OBJECTIVE: To measure energy expenditure (EE) and heart rate (HR) during genuine laughter. DESIGN: Experimental trial of viewing film clips in four cycles either intended to evoke laughter (humorous -10 min) or unlikely to elicit laughter (not humorous -5 min) under strictly controlled conditions of a whole-room indirect calorimeter equipped with audio recording system. PARTICIPANTS: Forty five adult friend dyads in either same-sex male (n=7), same-sex female (n=21) and mix-sex male-female (n=17); age 18-34 years; body mass index 24.7+/-4.9 (range 17.9-41.1). MEASUREMENTS: Energy expenditure in a whole-room indirect calorimeter, HR using Polar HR monitor. Laugh rate, duration and type from digitized audio data using a computerized system and synchronized with HR and EE results. RESULTS: Laughter EE was 0.79+/-1.30 kJ/min (0.19+/-0.31 kcal/min) higher than resting EE (P<0.001, 95% confidence interval=0.75-0.88 kJ/min), ranging from -2.52 to 9.67 kJ/min (-0.60-2.31 kcal/min). Heart rate during laughter segments increased above resting by 2.1+/-3.8 beats/min, ranging from -7.6 to 26.8 beats/min. Laughter EE was correlated with HR (r (s)=0.250, P<0.01). Both laughter EE and HR were positively correlated with laughter duration (r (s)=0.282 and 0.337, both P<0.001) and rate (r(s)=0.256 and 0.298, both P<0.001). CONCLUSION: Genuine voiced laughter causes a 10–20% increase in EE and HR above resting values, which means that 10–15 minutes of laughter per day could increase total EE by 10–40 kJ (2–10 kcal) [corrected].

Adolescent↗

PubMed2006

Pandrug-resistant Pseudomonas aeruginosa among hospitalised patients: clinical features, risk-factors and outcomes.

Between 1 January 2003 and 31 December 2003, 37 patients had positive cultures of pandrug-resistant Pseudomonas aeruginosa (PDRPA) resistant to all commercially available anti-pseudomonal antimicrobial agents in Taiwan, including anti-pseudomonal penicillins, ceftazidime, fourth-generation cephalosporins, aztreonam, carbapenems, aminoglycosides and ciprofloxacin. Nineteen (51.4%) patients had PDRPA infections, including pneumonia (17 patients), catheter-related bacteraemia (one patient) and anal abscess (one patient). Eighteen patients were classified as having PDRPA colonisation, based on absence of clinical signs or symptoms of infection. In total, 92 isolates were recovered from various specimens, with the majority (85.9%) recovered from respiratory tract secretions (sputa, bronchial washings and pleural effusions), followed by urine (4.3%) and catheter tips (3.3%). Twenty-eight (75.7%) patients yielded cultures of non-PDR P. aeruginosa isolates before isolation of PDRPA, with a mean period between the first isolation of non-PDR P. aeruginosa and the isolation of PDRPA of 128.3 days. Most patients had received beta-lactam antibiotics, fluoroquinolones or carbapenems for prolonged periods. Univariate analysis showed that PDRPA infection, male gender and the presence of fever at the time of PDRPA isolation were associated with increased mortality.

Adult↗

PubMed2005

Modulation of potassium currents by angiotensin and oxidative stress in cardiac cells from the diabetic rat.

Diabetes induces oxidative stress and leads to attenuation of cardiac K+ currents. We investigated the role of superoxide ions and angiotensin II (ANG II) in generating and linking oxidative stress to the modulation of K+ currents under diabetic conditions. K+ currents were measured using patch-clamp methods in ventricular myocytes from streptozotocin (STZ)-induced diabetic rats. Superoxide ion levels, indicating oxidative stress, were measured by fluorescent labelling with dihydroethidium (DHE). ANG II content was measured using enzyme-linked immunosorbent asssay (ELISA). The results showed DHE fluorescence to be significantly higher in cells from diabetic males, compared to controls. Relief of stress by the NADPH oxidase inhibitor apocynin or by superoxide dismutase (SOD) but not by catalase reversed the attenuation of K+ currents and reduced DHE fluorescence. In cells from diabetic females, neither apocynin nor SOD augmented K+ currents, ANG II was not elevated and DHE fluorescence was significantly weaker than in cells from males. Reduced glutathione (GSH) also augmented K+ currents in cells from diabetic males but not females. In ovariectomized diabetic females K+ currents were augmented by GSH and apocynin. Current augmentation and the attenuation of DHE fluorescence by apocynin were significantly blunted by excess ANG II (300 nm). Diabetic male rats pretreated with the angiotensin-converting enzyme (ACE) inhibitor quinapril were hyperglycaemic, but their cellular ANG II levels and DHE fluorescence were significantly decreased. In cells from these rats, K+ currents were insensitive to apocynin. In conclusion, diabetes-related oxidative stress attenuates K+ currents through ANG II-generated increased superoxide ion levels. When ANG II levels are lower, as in diabetic females or following ACE inhibition in males, oxidative stress is reduced, with blunted alterations in K+ currents.

Angiotensin II↗

PubMed2005

A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts.

Resveratrol (R-3), a trihydroxy trans-stilbene from grape, inhibits multistage carcinogenesis in animal models. A resveratrol derivative 3,4,5,4'-tetrahydroxystilbene (R-4) exhibits potent growth inhibitory effect against transformed human cells. Here we report that 3,4,5,4'-tetramethoxystilbene (MR-4), converted from R-4, was more potent against cancer cell lines (WI38VA, IMR-90SV, HeLa, LNCaP, HT-29, and HepG2), but had almost no inhibitory effect on the growth of normal cells (WI38, IMR-90, BJ-T) at the concentrations tested. The IC50 value of MR-4 on the growth inhibition of transformed WI38VA human cells was 0.5 microM, as compared to the value of greater than 50 microM for the normal WI38 cells. Resveratrol, however, did not exhibit such clear differential effect and the IC50 value of R-3 for WI38VA cells was about 50 microM. The growth inhibitory effect of MR-4 correlated with the induction of apoptosis in the transformed cells. When normal WI38 cells and transformed WI38VA cells were compared, MR-4 induced increases of the Bax/Bcl-2 mRNA ratio, p53 and Bax protein level, activation of caspases, and DNA fragmentation in transformed, but not in normal cells. Further analysis revealed that MR-4 caused a rapid appearance of perinuclear aggregation of mitochondria in WI38VA but not in WI38 cells, suggesting that the mitochondria could serve as an early target of MR-4. R-3 also induced apoptosis and mitochondrial clustering but only at a much higher concentration, close to 500 microM. Taken together, the specific activation of the mitochondria-mediated apoptotic pathway could be a major reason for the striking differential growth inhibitory effect of MR-4.

Apoptosis↗

PubMed2004

Patterns of physical activity in free-living adults in the Southern United States.

OBJECTIVE: To examine the relationship between the amount and patterns of physical activity (PA), body fatness, and age in a heterogeneous adult population in the free living. DESIGN: Cross-sectional study of the amount of PA over a 1-week period. The amount of body movements during PA (PA counts*10(3)) and time spent on various PA intensity categories were calculated from a triaxial accelerometer and compared with subject characteristics, including body fat from hydrodensitometry. PARTICIPANTS: Adult healthy men (n=48) and women (n=72) were recruited from the Nashville, Tennessee area and their PA was monitored in their free-living environment. RESULTS: The average weekday PA counts (176.5+/-60.3, P=0.002, r(2)=0.294), PA counts day-to-day variability (47.3+/-32.7, P=0.002, r(2)=0.286), daily maximum PA counts (241.9+/-89.2, P=0.001, r(2)=0.327), minute-to-minute variability on weekdays (0.281+/-0.091, P=0.001, r(2)=0.362), and the difference between maximum and minimum daily PA counts (130.6+/-78.3, P=0.008, r(2)=0.243) were significantly and negatively correlated with body fatness. During awake time, both men and women spent 10-12 h on low intensity (1.0-2.9 metabolic equivalents (METs)) PA, approximately 1 h on moderate (3.0-5.9 MET), and less than 10 min on vigorous (>6.0 MET) PA each day. On weekends, men and women spent more time at rest (1 MET), less time on low-intensity PA, and men spent more time on moderate PA than on weekdays. CONCLUSIONS: In adults living in the Southern US the amount of free-living PA was negatively correlated with body fatness. Both men and women spent the majority of active time on low and moderate PA. PA patterns on weekends were different than on weekdays and were related to sex and age, but not to body fatness. SPONSORSHIP: National Institutes of Health, US.

Adipose Tissue↗

PubMed2003

A feasibility study on the predictive emission monitoring system applied to the Hsinta power plant of Taiwan Power Company.

The continuous emission monitoring system (CEMS) can monitor flue gas emissions continuously and instantaneously. However, it has the disadvantages of enormous cost, easily producing errors in sampling periods of bad weather, lagging response in variable ambient environments, and missing data in daily zero and span tests and maintenance. The concept of a predictive emission monitoring system (PEMS) is to use the operating parameters of combustion equipment through thermodynamic or statistical methods to construct a mathematic model that can predict emissions by a computer program. The goal of this study is to set up a PEMS in a gas-fired combined cycle power generation unit at the Hsinta station of Taiwan Power Co. The emissions to be monitored include nitrogen oxides (NOx) and oxygen (O2) in flue gas. The major variables of the predictive model were determined based on the combustion theory. The data of these variables then were analyzed to establish a regression model. From the regression results, the influences of these variables are discussed and the predicted values are compared with the CEMS data for accuracy. In addition, according to the cost information, the capital and operation and maintenance costs for a PEMS can be much lower than those for a CEMS.

Automation↗

PubMed2002

Meta-analysis: ribavirin-induced haemolytic anaemia in patients with chronic hepatitis C.

AIM: To use meta-analysis to study the risk of anaemiarelated to ribavirin therapy for chronic hepatitisC. METHODS: The MEDLINE database up to January 2001 was searched for randomized controlled trials of ribavirin (monotherapy or combined with interferon) for chronic hepatitis C. The outcomes evaluated were withdrawal from the study due to anaemia, ribavirin dosage reduction due to a decrease in haemoglobin and haemoglobin levels below 10 g/dL. RESULTS: Based on 17 studies, the overall risk difference (ribavirin vs. no ribavirin) for anaemia was 0.09 [95% confidence interval (CI), 0.04-0.13]. Two Asian studies reported risk differences of 0.29 and 0.22, greater than the pooled risk difference of 0.07 (95% CI, 0.03-0.12) for 15 non-Asian studies. The risk associated with 1 g or more of ribavirin per day was higher (risk difference, 0.09; 95% CI, 0.04-0.14) than that for 0.8 g of ribavirin per day (risk difference, 0.01; 95% CI, - 0.04-0.06). CONCLUSIONS: Chronic hepatitis C patients treated with 1 g or more of ribavirin per day were at a higher risk of developing anaemia. Reported risks were higher among Asian studies, which may be due to differences in study entrance criteria, dosage titration strategy or ethnic vulnerability.

Adult↗

PubMed2001

Ligands of macrophage scavenger receptor induce cytokine expression via differential modulation of protein kinase signaling pathways.

Our previous works demonstrated that ligands of macrophage scavenger receptor (MSR) induce protein kinases (PKs) including protein-tyrosine kinase (PTK) and up-regulate urokinase-type plasminogen activator expression (Hsu, H. Y., Hajjar, D. P., Khan, K. M., and Falcone, D. J. (1998) J. Biol. Chem. 273, 1240--1246). To continue to investigate MSR ligand-mediated signal transductions, we focus on ligands, oxidized low density lipoprotein (OxLDL), and fucoidan induction of the cytokines tumor necrosis factor-alpha (TNF) and interleukin 1 beta (IL-1). In brief, in murine macrophages J774A.1, OxLDL and fucoidan up-regulate TNF production; additionally, fucoidan but not OxLDL induces IL-1 secretion, prointerleukin 1 (proIL-1, precursor of IL-1) protein, and proIL-1 message. Simultaneously, fucoidan stimulates activity of interleukin 1-converting enzyme. We further investigate the molecular mechanism by which ligand binding-induced PK-mediated mitogen-activated protein kinase (MAPK) in regulation of expression of proIL-1 and IL-1. Specifically, fucoidan stimulates activity of p21-activated kinase (PAK) and of the MAPKs extracellular signal-regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38. Combined with PK inhibitors and genetic mutants of Rac1 and JNK in PK activity assays, Western blotting analyses, and IL-1 enzyme-linked immunosorbent assay, the role of individual PKs in the regulation of proIL-1/IL-1 was extensively dissected. Moreover, tyrosine phosphorylation of pp60Src as well as association between pp60Src and Hsp90 play important roles in fucoidan-induced proIL-1 expression. We are the first to establish two fucoidan-mediated signaling pathways: PTK(Src)/Rac1/PAK/JNK and PTK(Src)/Rac1/PAK/p38, but not PTK/phospholipase C-gamma 1/PKC/MEK1/ERK, playing critical roles in proIL-1/IL-1 regulation. Our current results indicate and suggest a model for MSR ligands differentially modulating specific PK signal transduction pathways, which regulate atherogenesis-related inflammatory cytokines TNF and IL-1.

Androstadienes↗

PubMed2001

Detection of Epstein-Barr virus DNA in the peripheral-blood cells of patients with nasopharyngeal carcinoma: relationship to distant metastasis and survival.

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proved to be an Epstein-Barr virus (EBV)-associated cancer. By use of nested polymerase chain reactions (PCRs), we examined whether the presence of EBV DNA in the peripheral-blood cells (PBC) can serve as a prognostic indicator for NPC. PATIENTS AND METHODS: Peripheral blood from 124 patients with NPC who had no evidence of distant metastasis and 114 healthy volunteers with serologically positive findings for EBV infection was collected prospectively. Plasma and erythrocytes were separated. DNA was extracted from PBCs and analyzed by a nested PCR using primers specific to Epstein-Barr virus nuclear antigen 1 (EBNA-1). All patients were treated by radiotherapy with or without chemotherapy. Clinical parameters and status of EBNA-1 in PBCs were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Positive rates of EBNA-1 DNA in PBCs of NPC patients and healthy volunteers are 71% and 14%, respectively (P =.001). No significant difference was observed with regard to the clinical characteristics of patients who were EBNA-1-positive (n = 88) and those who were EBNA-1-negative (n = 36). After a median follow-up period of 38 months (range, 24 to 56 months), 29 of 88 EBNA-1-positive patients and only one of 36 EBNA-1-negative patients developed distant metastases (P =.00015). Kaplan-Meier estimates of overall survival (P =.0010), metastasis-free survival (P =.0004), and progression-free survival (P =.0004) were significantly lower for the patients in the EBNA-1-positive group than for those in the EBNA-1-negative group. Multivariate Cox analysis confirmed the same results. CONCLUSION: The presence of EBNA-1 DNA in PBCs is a novel, important risk factor for patients with NPC that indicates a significantly higher risk of developing distant metastasis as well as a lower survival rate.

Adult↗

PubMed2001

Rapid reversion of aging phenotypes by nicotinamide through possible modulation of histone acetylation.

Aging appears to be an irreversible process. Here we report that nicotinamide (NAA) can induce rapid and reversible reversion of aging phenotypes in human diploid fibroblasts in terms of cell morphology and senescence-associated beta-galactosidase activity. Although NAA seems to enhance the replicative potential of the cells, it has little effect on their growth rate and life span, suggesting that NAA action is rather separated from the cellular replicative system. The effects are unique to NAA: none ofthe NAA-related compounds examined (an NAD precursor/niacin, NAD analogs, and poly(ADP-ribose) polymerase inhibitors) exerted similar effects. Thus, NAD-related metabolism and poly(ADP-ribosyl)ation are unlikely related to the NAA action. On the other hand, histone acetyltransferase (HAT) activity was elevated in NAA-exposed cells, while in aged cells, HAT activity and histone H4 acetylation were lowered. Taken together, the results suggest that NAA may cause rejuvenation by restoring, at least in part, altered gene expression in aged cells through its activation of HAT.

Acetylation↗

PubMed2001

Resveratrol analog, 3,4,5,4'-tetrahydroxystilbene, differentially induces pro-apoptotic p53/Bax gene expression and inhibits the growth of transformed cells but not their normal counterparts.

Resveratrol, a trihydroxystilbene found in grapes and other plants, has been shown to be active in inhibiting multistage carcinogenesis. Using resveratrol as a prototype, we have synthesized a number of polyhydroxy- and polymethoxy-stilbenes and tested their anti-proliferative effect in normal and transformed human cells. Here we show that one of the resveratrol analogs, 3,4,5,4'-tetrahydroxystilbene (R-4), specifically inhibited the growth of SV40 virally transformed WI38 cells (WI38VA) at 10 microM, but had no effect on normal WI38 cells at even higher concentrations. R-4 also prominently induced apoptosis in WI38VA cells, but not in WI38 cells. RNase protection assay showed that R-4 significantly induced the expression of p53, GADD45 and Bax genes and concomitantly suppressed the expression of bcl-2 gene in WI38VA, but not in WI38 cells. A large increase in p53 DNA binding activity and the presence of p53 in the Bax promoter binding complex suggested that p53 was responsible for the Bax gene expression induced by R-4 in transformed cells. Within 4 h of treatment with R-4, the Bax to bcl-2 protein ratio in WI38 and WI38VA cells was, respectively, 0.1 and 105, a difference of three orders of magnitude. While R-4 prominently induced the p53/Bax pro-apoptotic genes, it also concomitantly suppressed the expression of Cox-2 in WI38VA cells. Taken together, our study suggests that the induction of p53 gene by R-4 in transformed cells may play a key role in the differential growth inhibition and apoptosis of transformed cells.

Apoptosis↗

PubMed2001

Increased bone turnover is associated with protein and energy metabolism in adolescents with sickle cell anemia.

Contribution of bone turnover to the hypercatabolic state observed in sickle cell anemia is unknown. We examined the association between markers of bone turnover and basal rates of whole body protein turnover and energy expenditure in 28 adolescents with homozygous sickle cell anemia (HbSS) and in 26 matched controls with normal phenotype (HbAA). Whole body protein breakdown and synthesis were measured using a stable isotope of [15N]glycine, resting energy expenditure was measured by whole room indirect calorimetry, and the rate of pyridinoline cross-link (PYD) excretion in urine and fasting serum levels of the type I procollagen carboxy-terminal propeptide (PICP) were measured with commercial kits. Urinary PYD and serum PICP were significantly elevated in HbSS patients. The increase in procollagen synthesis, indicated by high levels of PICP, was significantly correlated with increased whole body protein synthesis. The increase in type I collagen degradation, indicated by high PYD excretion, was significantly correlated with increased protein breakdown. We conclude that increased rates of bone turnover contribute to the increased rates of protein turnover and energy expenditure observed in adolescents with homozygous sickle cell anemia.

Adolescent↗

PubMed2001

Inhibition of ryanodine binding to sarcoplasmic reticulum vesicles of cardiac muscle by Zn(2+) ions.

Using the assay of [(3)H]ryanodine binding to the sarcoplasmic reticulum, the effect of Zn(2+) on ryanodine receptors (RyRs) of cardiac muscle was investigated. There was no obvious change in the binding at [Zn(2+)](f) of less than 0.2 microM. However, a decrease of the binding became significant with raising [Zn(2+)](f) to 0.5 microM. The inhibitory effect of Zn(2+) was [Zn(2+)](f)-dependent, with IC(50/ZnI) of 2.1+/-0.4 microM (mean+/-S.D.). Scatchard analysis indicates that both an increase of K(d) and a decrease of B(max) were responsible for Zn(2+)-induced decrease of the binding. The Hill coefficient for this inhibitory effect of Zn(2+) was between 0.8 and 1.2. The interactions of the effects of Zn(2+) and various modulators of RyR indicate that the inhibitory effect of Zn(2+) was mostly mediated through inhibiting Ca(2+) activation sites (CaA) on RyR. Since the [Zn(2+)](f) dependence was not clearly changed by [Ca(2+)](f), the inhibitory effect of Zn(2+) may not be due to competition of Zn(2+) with Ca(2+) for CaA and probably is indirect. The inhibitory effect of Zn(2+) could not be antagonized by 2 mM dithiothreitol, a thiol-reducing agent, suggesting that the binding of Zn(2+) ions to RyRs of cardiac muscle is not accompanied by obvious change of redox state of the RyRs. In comparison with that seen in skeletal muscle [3], the effects of Zn(2+) on ryanodine binding to the sarcoplasmic reticulum of cardiac muscle show several distinct differences. It is indicated that the effect of Zn(2+) on RyRs may be isoform-dependent. The physiological significance of the effects of Zn(2+) is discussed.

Animals↗

PubMed2001

Acupuncture for general veterinary practice.

Since the International Society of Veterinary Acupuncture (IVAS) was founded in 1974, acupuncture (AP) has received greater acceptance by veterinary professionals throughout the world. This article introduces some important animal diseases that respond well to AP therapy. These include resuscitation of small animals, treatment of anoestrous gilts and sows, bovine reproductive disease, canine vertebral problems and equine backpain, etc. Conventional medicine considers these to be difficult cases to treat. Veterinarians have become more aware of the benefits of AP especially for those diseases, thanks to the efforts of experienced practitioners and scientists, and the many published reports on veterinary AP that have introduced some good indications for AP therapy in veterinary practice. Possible mechanisms behind the effectiveness of AP are discussed. This article aims to introduce veterinarians to good indications for AP to initiate their interest in the practice of AP. Although this is a rapidly expanding field, a long march must begin with one step. We wish this article to be the shoes for such a march. For more information on veterinary AP, contact IVAS , P.O. Box 1478, Longmont, CO.. 80502, USA (http://www.ivas.org), or your national veterinary acupuncture society (http://www.komvet.at/ ivadkom/vapsocs.htm).

Acupuncture↗

PubMed2001

Pulmonary fungal infection: emphasis on microbiological spectra, patient outcome, and prognostic factors.

STUDY OBJECTIVES: To investigate the microbiological spectra, patient outcome, and prognostic factors of pulmonary fungal infection. DESIGN: The medical and microbiological records of patients with pulmonary fungal infection were retrospectively analyzed. SETTING: A university-affiliated tertiary medical center. PATIENTS AND METHODS: From January 1988 to December 1997, all cases of pulmonary fungal infection were reviewed. The criteria for inclusion were obvious lung lesion shown on chest radiographs and one of the following: (1) the presence of fungi in or isolation of fungi from the biopsy specimen of open thoracotomy, thoracoscopy, transbronchial lung biopsy, or ultrasound-guided percutaneous needle aspiration/biopsy; or (2) isolation of fungi from pleural effusion or blood, with no evidence of extrapulmonary infection. RESULTS: A total of 140 patients were included. Ninety-four cases of pulmonary fungal infection (67%) were community acquired. The most frequently encountered fungi were Aspergillus species (57%), followed by Cryptococcus species (21%) and Candida species (14%). There were 72 patients with acute invasive fungal infection, with a mortality rate of 67%. Multivariate logistic regression analysis showed that nosocomial infection (p = 0.014) and respiratory failure (p = 0.001) were significantly and independently associated with death of acute invasive fungal infection. CONCLUSIONS: Pulmonary fungal infection of community-acquired origins is becoming a serious problem. It should be taken into consideration for differential diagnosis of community-acquired pneumonia. Furthermore, acute invasive fungal infection is associated with a much higher mortality rate for patients with nosocomial infection or complicating respiratory failure. Early diagnosis with prompt antifungal therapy, or even with surgical intervention, might be warranted to save patients' lives.

Adult↗

PubMed2000

Protein-tyrosine phosphatase D1, a potential regulator and effector for Tec family kinases.

Etk, also named Bmx, is a member of the Tec tyrosine kinase family, which is characterized by a multimodular structure including a pleckstrin homology (PH) domain, an SH3 domain, an SH2 domain, and a catalytic domain. The signaling mechanisms regulating Etk kinase activity remain largely unknown. To identify factor(s) regulating Etk activity, we used the PH domain and a linker region of Etk as a bait for a yeast two-hybrid screen. Three independent clones encoding protein-tyrosine phosphatase D1 (PTPD1) fragments were isolated. The binding of PTPD1 to Etk is specific since PTPD1 cannot associate with either the Akt PH domain or lamin. In vitro and in vivo binding studies demonstrated that PTPD1 can interact with Etk and that residues 726-848 of PTPD1 are essential for this interaction. Deletion analysis of Etk indicated that the PH domain is essential for PTPD1 interaction. Furthermore, the Etk-PTPD1 interaction stimulated the kinase activity of Etk, resulting in an increased phosphotyrosine content in both factors. The Etk-PTPD1 interaction also increased Stat3 activation. The effect of PTPD1 on Etk activation is specific since PTPD1 cannot potentiate Jak2 activity upon Stat3 activation. In addition, Tec (but not Btk) kinase can also be activated by PTPD1. Taken together, these findings indicate that PTPD1 can selectively associate with and stimulate Tec family kinases and modulate Stat3 activation.

Animals↗

PubMed2000

Differential effects of theaflavin monogallates on cell growth, apoptosis, and Cox-2 gene expression in cancerous versus normal cells.

Theaflavin (TF-1), theaflavin-3-monogallate and theaflavin-3'-monogallate mixture (TF-2), and theaflavin-3,3'-digallate (TF-3) are the major black tea polyphenols. Here we compared the effects of these polyphenols on cell growth, apoptosis, and gene expression in normal and cancerous cells. We showed that TF-2 (10-50 microM) inhibited the growth of SV40 transformed WI38 human cells (WI38VA) and Caco-2 colon cancer cells but had little effect on the growth of their normal counterparts. The IC50s of TF-2 for the growth inhibition of WI38 and WI38VA cells were, respectively, 300 and 3 microM. The other two black tea polyphenols, TF-1 and TF-3, did not exhibit such differential growth-inhibitory effect. TF-2, but not TF-1 or TF-3, induced apoptosis in transformed WI38VA cells but not in normal WI38 cells, suggesting that apoptosis was responsible, at least in part, for the differential growth-inhibitory effect of TF-2. Cox-2 has been implicated in intestinal carcinogenesis. Among the tea polyphenols tested, TF-2 and, to a lesser degree, (-)-epigallocatechin gallate inhibited cyclooxygenase (Cox)-2 gene expression. TF-2 at 50 microM completely blocked the serum-induced Cox-2 gene expression at both mRNA and protein level. Other genes, including c-fos, c-myc, thymidine kinase, proliferating cell nuclear antigen, BRCA1, BRCA2, and Cox-1, were not significantly affected by TF-2. These findings suggest that TF-2 may be responsible, at least in part, for the chemopreventive activity in black tea extracts.

Antioxidants↗