Biomedical subjects

G Liu

Publications and source records attributed to G Liu.

At least 19 recordsLinked to original sources

PubMed2007

Development of new RNAi therapeutics.

RNAi-mediated gene inactivation has become a cornerstone of the present day gene function studies that are the foundation of mechanism and target based drug discovery and development, which could potentially shorten the otherwise long process of drug development. In particular, the coming of age of "RNAi drug" could provide new promising therapeutics bypassing traditional approaches. However, there are technological hurdles need to overcome and the biological limitations need to consider for achieving effective therapeutics. Major hurdles include the intrinsic poor pharmacokinetic property of siRNA and major biological restrictions include off-target effects, interferon response and the interference with endogenous miRNA. Recent innovations in nucleic acid chemistry, formulations and delivery methods have gradually rendered it possible to develop effective RNAi-based therapeutics. Careful design based on the newest RNAi/miRNA biology can also help to minimize the potential tissue toxicity. If successful with systemic application, RNAi drug will no doubt revolutionize the whole drug development process. This review attempts to describe the progress in this area, including applications in preclinical models and recent favorable experience in a number of human trials of local diseases, along with the discussion on the potential limitations of RNAi therapeutics.

Animals↗

PubMed2006

Enhancing forest carbon sequestration in China: toward an integration of scientific and socio-economic perspectives.

This article serves as an introduction to this special issue, "China's Forest Carbon Sequestration", representing major results of a project sponsored by the Canadian International Development Agency and the Chinese Academy of Sciences. China occupies a pivotal position globally as a principle emitter of carbon dioxide, as host to some of the world's largest reforestation efforts, and as a key player in international negotiations aimed at reducing global greenhouse gas emission. The goals of this project are to develop remote sensing approaches for quantifying forest carbon balance in China in a transparent manner, and information and tools to support land-use decisions for enhanced carbon sequestration (CS) that are science based and economically and socially viable. The project consists of three components: (i) remote sensing and carbon modeling, (ii) forest and soil assessment, and (iii) integrated assessment of the socio-economic implications of CS via forest management. Articles included in this special issue are highlights of the results of each of these components.

Air Pollution↗

PubMed2006

Determinants of bone mineral density in Chinese-American women.

SUMMARY: Few data are available regarding bone mineral density (BMD) and its determinants among Chinese Americans. We identified determinants of BMD among 359 Chinese-American women in order to identify risk factors for low BMD in this burgeoning population. BMD in Chinese-American women is influenced by a number of factors, including immigration. INTRODUCTION: Osteoporosis and low BMD are common among Chinese women, including Chinese Americans, who are a growing population at risk for osteoporosis in the US. Few data are available regarding BMD and its determinants among Chinese-American women. METHODS: In this study, we examined predictors of BMD in 359 ambulatory Chinese-American women, ages 20-90, using stepwise multiple regression analysis. Variables in the model included age, weight, height, menarche age, years since menopause, immigration age, years in US, percentage of life in US, number of pregnancies, oral contraceptive use, family history of osteoporosis, family history of hip fracture, daily calcium intake, exercise, time outdoors, alcohol consumption and tobacco use. RESULTS: Among premenopausal women, weight was the strongest predictor of BMD, accounting for 10.5% of the variance at the lumbar spine (LS), 15.2% at the total hip (TH) and 16.6% at the femoral neck (FN). Time outdoors was also a positive predictor of BMD (1.4% at LS, 2.8% at TH and 1.6% at FN), while family history of osteoporosis (1.4% at TH) and age (3.7% at FN) were negative predictors. Among postmenopausal women, greater BMD at the LS and TH was associated with greater weight and earlier immigration age. Weight accounted for 16.4% of the variance at the LS and 19.8% at the TH; immigration age accounted for 3.1% of the variance at the LS and 4.1% at the TH. At the FN, years since menopause and weight were predictors of BMD, accounting for 14.4% and 8.7% of the variance, respectively. While older age at immigration had a negative effect on BMD, years in and proportion of life in the United States were not significant predictors of BMD. CONCLUSIONS: Bone mineral density in Chinese-American women is influenced by a number of biological and lifestyle factors, including immigration. The results of this study provide new insights into risk factors for low bone density as they relate to environmental determinants in the growing population of Chinese-American women.

Adult↗

PubMed2006

Bicyclol for chronic hepatitis B.

BACKGROUND: Bicyclol is a novel synthetic 'anti-hepatitis' drug, used in China for chronic hepatitis B. Until now, systematic reviews of bicyclol therapy have not been performed. OBJECTIVES: To study the benefits and harms of bicyclol for patients with chronic hepatitis B. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (July 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to July 2005), EMBASE (1980 to July 2005), Science Citation Index Expanded (1945 to July 2005), The Chinese Biomedical Database (1994 to August 2005), VIP Chinese Science and Technique Journals Database (1994 to August 2005), and China National Infrastructure (CNKI)(1994 to August 2005). We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Randomised clinical trials with bicyclol versus no intervention, placebo, or other interventions were included, irrespective of blinding, publication status, or language. DATA COLLECTION AND ANALYSIS: The primary outcome measures were mortality (total and liver-related) and liver-related morbidity (eg, cirrhosis and carcinoma). Secondary outcome measures were viral response and liver histology. MAIN RESULTS: The search identified one randomised clinical trial comparing bicyclol with bifendate (biphenyldicarboxylate) for patients with hepatitis B. The follow-up was three months. There was no evidence that bicyclol was superior to bifendate for loss of HBeAg (RR 1.38, 95% CI 0.95 to 2.00), seroconversion of HBeAg to HBeAb (RR 1.44, 95% CI 0.90 to 2.29), loss of HBV DNA (RR 1.19, 95%CI 0.93 to 1.53), or number of patients with normalised alanine aminotransferase and aspartate aminotransferase activity (RR 0.88, 95% CI 0.70 to 1.11 and RR 0.97, 95% CI 0.79 to 1.20, respectively). AUTHORS' CONCLUSIONS: Only one randomised clinical trial has examined the potential benefit of bicyclol for patients with chronic hepatitis B. This small, short-term trial found no evidence to support or refute its use. Large, randomised double-blind clinical trials with long-term follow-up are needed to examine the possible benefits and harms associated with bicyclol. Bicyclol can only be recommended for use in randomised trials.

Biphenyl Compounds↗

PubMed2006

Muscle-specific creatine kinase gene polymorphism and running economy responses to an 18-week 5000-m training programme.

OBJECTIVE: To investigate the association between muscle-specific creatine kinase (CKMM) gene polymorphism and the effects of endurance training on running economy. METHODS: 102 biologically unrelated male volunteers from northern China performed a 5000-m running programme, with an intensity of 95-105% ventilatory threshold. The protocol was undertaken three times per week and lasted for 18 weeks. Running economy indexes were determined by making the participants run on a treadmill before and after the protocol, and the A/G polymorphism in the 3' untranslated region of CKMM was detected by polymerase chain reaction-restricted fragment length polymorphism (NcoI restriction enzyme). RESULTS: Three expected genotypes for CKMM-NcoI (AA, AG and GG) were observed in the participants. After training, all running economy indexes declined markedly. Change in steady-state consumption of oxygen, change in steady-state consumption of oxygen by mean body weight, change in steady-state consumption of oxygen by mean lean body weight and change in ventilatory volume in AG groups were larger than those in AA and GG groups. CONCLUSIONS: The findings indicate that the CKMM gene polymorphism may contribute to individual running economy responses to endurance training.

Adolescent↗

PubMed2006

Polymorphisms in the HBB gene relate to individual cardiorespiratory adaptation in response to endurance training.

OBJECTIVE: The crucial role of haemoglobin in endurance performance has been well documented. We examined whether polymorphisms in the HBB gene modified aerobic capacity. METHODS: 102 recruits were trained by running 5000 m three times per week for 18 weeks. Exercise intensity progressively increased from an initial heart rate corresponding to 95% of the individual baseline ventilatory threshold during the first 10 weeks to 105% during the last 8 weeks. The phenotypes measured were running economy and VO(2)max. Running economy was determined by measuring submaximal VO(2) for 5 min at a constant running speed of 12 km.h(-1) and VO(2)max was obtained during an incremental test to exhaustion. Genomic DNA was extracted from white cells of peripheral blood and the -551C/T, intron2,+16C/G and +340 A/T genotypes were examined relative to the TAA site variants by PCR-RFLP. RESULTS: Genotype distributions were in Hardy-Weinberg equilibrium at three loci. None of the running economy and VO(2)max-related traits were associated with the three polymorphisms or haplotypes at baseline, while the training response of running economy was associated with -551C/T and intron2,+16C/G polymorphisms. Subjects homozygous for intron2,+16C/C or -551C/C had decreased oxygen cost of running compared to the other individuals. DISCUSSION: It was concluded that the -551C/C or intron2,+16C/C genotype might explain part of the individual variation in the cardiorespiratory adaptation to endurance training.

Adaptation, Physiological↗

PubMed2006

Expression of aromatase and 17beta-hydroxysteroid dehydrogenase types 1, 7 and 12 in breast cancer. An immunocytochemical study.

It is known that there is a local biosynthesis of estradiol (E2) in breast carcinoma. The steroidogenic enzymes involved in E2 formation are aromatase which transforms testosterone into E2 and androstenedione into estrone (E1) and reductive 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) which convert E1 into E2. Using immunocytochemistry, we have studied the expression of aromatase and the three reductive 17beta-HSDs 17beta-HSD types 1, 7 and 12 in 41 specimens of female human breast carcinoma and adjacent non-malignant tissues. These results were correlated with the estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor, androgen receptor, CDC47 and c-erb B-2 expressions and with the tumor stages. Aromatase was found in 58%, 17beta-HSD type 7 in 47% and 17beta-HSD type 12 in 83% of the breast cancer specimens. The 17beta-HSD type 1 could be detected in only one tumor. A significant correlation was observed between the aromatase, 17beta-HSD type 7 and 17beta-HSD type 12 expression, as well as between each of the two enzymes 17beta-types 7 and 12 and the ERbeta expression. The expression of 17beta-HSD type 12 was significantly higher in breast carcinoma specimens than in normal tissue. There was also a significant association of CDC 47 expression with ERbeta, AR and 17beta-HSD type 12. The results indicate that aromatase, 17beta-HSD type 7 and 17beta-HSD type 12, but not 17beta-HSD type 1, are commonly expressed in human breast cancer. Moreover, the high expression of both 17beta-HSD type 12 and ERbeta in breast carcinoma cells may play a role in the development and/or progression of breast cancer.

17-Hydroxysteroid Dehydrogenases↗

PubMed2006

The role of Ret receptor tyrosine kinase in dopaminergic neuron development.

Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent trophic factors identified for promoting survival and function of dopaminergic (DA) neurons in the midbrain. Ret, a member of the receptor tyrosine kinase (RTK) superfamily transduces GDNF signaling. The role of Ret in the development of DA neurons is not clear however. Here we demonstrate the involvement of Ret in the DA neuron development both in vitro and in vivo. The dopamine transporter (DAT) gene was clearly induced in rat embryonic neural precursors that had been transfected with Ret. Temporary blockade of Ret expression in embryos using Ret antisense oligonucleotides (Ret-AS-ODN) in vivo led to reduced striatal DA content and a decrease of tyrosine hydroxylase (TH) positive fibers in the striatum. Additionally, some DA neurons in the substantia nigra (SN) underwent apoptotic cell death following the Ret-AS-ODN treatment. Taken together, the data suggest that normal function of Ret is required in vivo for the maturation of DA neurons, in particular for cell survival and fiber innervation. We further demonstrated Ret-induced expression of DAT in vitro.

Animals↗

PubMed2006

Cadmium removal from aqueous solution by gene-modified Escherichia coli JM109.

The article extended the study on the bioaccumulation of cadmium by genetically engineered bacterium Escherichia coli (namely M4) simultaneously expressing a cadmium transport system and metallothionein (MT). The growth of M4 showed resistance to the presence of cadmium. Compared with Cd2+ uptake capacity by original host bacterial cells, The Cd2+ accumulation of M4 was enhanced more than one-fold. M4 could effectively bind Cd2+ over a range of pH from 4 to 8. The presence of Ni2+ and Mn2+ did not influence Cd2+ uptake remarkably, but Cu2+, Pb2+ and Zn2+ posed serious adverse effects. EDTA could drastically decrease Cd2+ bioaccumulation by M4, whereas the effect of citrate was relatively slight.

Biological Transport↗

PubMed2006

Thrombolytic therapy for pulmonary embolism.

BACKGROUND: Thrombolytic therapy is usually reserved for patients with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clot more rapidly than heparin and might reduce the death rate associated with PE. However, there are still concerns about the possible risk of adverse effects of thrombolytic therapy, such as major or minor haemorrhages. OBJECTIVES: To assess the effectiveness and safety of thrombolytic therapy in patients with acute PE. SEARCH STRATEGY: We sought trials through the Cochrane Peripheral Vascular Diseases Group's Specialised Register (January 18, 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (January 1966 to December 2004), EMBASE, CINAHL, LILACS and SCISEARCH (all November 2004). We also searched individual trial collections and private databases, along with bibliographies of relevant articles. Relevant medical journals were handsearched. The most recent search was on February 6, 2006. SELECTION CRITERIA: Randomised controlled trials that compared thrombolytic therapy with placebo or heparin or surgical intervention in patients with acute PE. We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug. DATA COLLECTION AND ANALYSIS: Two authors (DB and WQ) assessed the eligibility and quality of trials and extracted data. MAIN RESULTS: Results were similar between thrombolytics compared with heparin alone or placebo and heparin in terms of:a) death rate: odds ratio (OR) 0.89; 95% confidence interval (CI) 0.45 to 1.78; b) recurrence of pulmonary embolism: OR 0.63; 95% CI 0.33 to 1.20;c) major haemorrhagic events: OR 1.61; 95% CI 0.91 to 2.86;d) minor haemorrhagic events: OR 1.98; 95% CI 0.68 to 5.75. We found no trials comparing thrombolytic therapy to surgical intervention. Using recombinant tissue-type plasminogen activator (rt-PA) and heparin together compared to heparin alone appeared to reduce the need for further treatment for in-hospital events (OR 0.35; 95% CI 0.17 to 0.71). Thrombolytics improved haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment and echocardiograms to a greater extent than heparin alone. AUTHORS' CONCLUSIONS: We cannot conclude whether thrombolytic therapy is better than heparin for pulmonary embolism based on the limited evidence found. More double-blind RCTs, with subgroup analysis of patients presenting with haemodynamically stable acute pulmonary embolism compared to those patients with a haemodynamic unstable condition, are required.

Fibrinolytic Agents↗

PubMed2006

A referent bone mineral density database for Chinese American women.

INTRODUCTION: While osteoporosis is common among women of Chinese descent, a readily available bone mineral density (BMD) referent database for Chinese American women does not exist. Fracture risk among this population is currently assessed using a Caucasian reference as well as diagnostic criteria for osteoporosis developed for postmenopausal Caucasian women. Many studies indicate that there are important racial differences in skeletal health and fracture risk, an observation that makes the application of Caucasian data to all groups problematical. This study was undertaken to establish a BMD referent database in Chinese American women and to compare it with a Caucasian female database. It is expected that a race-specific database will be useful in the assessment of bone health for Chinese American women. METHODS: Healthy Chinese American women (n=359), ages 20-90, were recruited. Along with dual-energy X-ray absorptiometry (DXA) of the total hip and lumbar spine, demographic, medical, familial, nutritional, and behavioral data were obtained. The mean and standard deviation for BMD at each site was calculated for each 10-year age group and compared to mean BMD values for Caucasian women supplied as found in the Hologic DXA instrument. Osteoporosis diagnosis rates for this cohort, calculated with the Caucasian and newly established Chinese American BMD referent values, were compared with each other. RESULTS: Compared with Caucasian women, Chinese American women have significantly lower BMD at the lumbar spine, total hip, and femoral neck across a wide spectrum of age groups. As a consequence, more than one-half of Chinese American women>or=50 years of age, who would be characterized as osteoporotic using a Caucasian referent, would not be diagnosed as such if a Chinese American referent were utilized. CONCLUSION: Chinese American reference BMD values are significantly lower than those for Caucasian women. Future studies relating Chinese American BMD values to fracture risk are necessary in order to determine if ethnic database-derived T-scores would be more predictive of fracture risk and to develop meaningful diagnostic criteria for this population.

Absorptiometry, Photon↗

PubMed2006

A quantitative evaluation of peroxidase inhibitors for tyramide signal amplification mediated cytochemistry and histochemistry.

Many peroxidase inhibitors have been used in horseradish peroxidase (HRP) mediated immunostaining and in situ hybridization to quench background peroxidase activity. However, the efficacy of these inhibitors has been controversial, partially due to the lack of a quantitative study. Tyramide signal amplification (TSA) is much more sensitive than other HRP-mediated methods but its super-sensitivity also demands effective inhibition of background peroxidase activity. In searching for an effective peroxidase inhibitor, we have systematically evaluated the efficacy of several peroxidase inhibitors by quantifying the fluorescence intensity in cultured fibroblasts and tissue sections treated with the inhibitors. For cultured cells, 0.05 mM of phenylhydrazine and 1 unit/ml of glucose oxidase gave only moderate inhibition of HRP activity while 1 mM of sodium azide (NaN(3)), 3% of hydrogen peroxide (H(2)O(2)), NaN(3)/H(2)O(2) combined and 0.02 N hydrochloric acid (HCl) provided more complete inhibition. However, the inhibitory effect of NaN(3)/H(2)O(2) is reversible upon removal of the inhibitors and followed by incubation and wash to mimic antibody interactions. Similar results were obtained from rat skin wound tissues that have strong endogenous peroxidase activity. Our results recommend the use of HCl and caution the use of phenylhydrazine, glucose oxidase, NaN(3) and H(2)O(2) as potent peroxidase inhibitors.

Animals↗

PubMed2006

Association of haemoglobin level with morbidity and mortality of patients with locally advanced oesophageal carcinoma undergoing radiotherapy--a secondary analysis of three consecutive clinical phase III trials.

AIMS: To investigate the strength of association between anaemia and overall survival, locoregional control, and late radiation complications in patients with locally advanced oesophageal carcinoma undergoing radiotherapy with or without chemotherapy and hyperthermia. MATERIALS AND METHODS: Between March 1996 and December 2002, 303 patients with locally advanced squamous cell carcinoma of oesophagus enrolled in three consecutive prospective phase III trials conducted in our department were included in this study. These patients received one of the following four irradiation schedules: late course accelerated hyperfractionated (LCAF) radiotherapy alone, LCAF combined with concurrent chemotherapy, LCAF combined with hyperthermia, and continuous accelerated hyperfractionated (CAHF) radiotherapy according to each protocol. According to the haemoglobin levels measured before radiotherapy, patients were stratified to normal haemoglobin group (> or = 12.0 g/dl for men, or > or = 11.0 g/dl for women) or anaemic group (< 12.0 g/dl for men, or < 11.0 g/dl for women). Overall survival, locoregional control rate and late irradiation toxicity were estimated by Kaplan-Meier method. RESULTS: Of 303 eligible patients, 243 patients (80.2%) had normal haemoglobin level and 60 patients (19.8%) were anaemic. The 5-year overall survival was 39% in patients with normal haemoglobin level, whereas, 22%, with anaemia patients (P = 0.001). The 5-year locoregional control rate at 5 years was 68% in patients with normal haemoglobin, versus 62%, with anaemia patients (P = 0.050). The 5-year rate of radiation toxicity of grade 3 or greater was 29% in patients with normal haemoglobin level, but it was 8%, with anaemic patients (P = 0.033). From multivariate analyses, T stage, location of tumour and haemoglobin level were found to be independent predictors for survival. T stage, gender and haemoglobin level were independent predictors for locoregional control. It was also detected that age and haemoglobin level played as independent predictors for development of radiation toxicity. CONCLUSIONS: For patients with locally advanced oesophageal carcinoma undergone irradiation, anaemia associated a statistically significant reduction in survival and locoregional control rates, but also decreased radiation toxicity rates. Therefore, haemoglobin level should be considered as a stratification variable in prospective clinical trials.

Adult↗

PubMed2006

Effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia in Chinese population.

Therapy with losartan compared to irbesartan was performed in a Chinese sample of hypertensive patients with elevated serum uric acid (SUA) levels. After 1 week of screening and a 2 week single-blinded placebo baseline period, patients were treated for 4 weeks with losartan 50 mg or irbesartan 150 mg. After 4 weeks, patients with SiDBP <90 mmHg and SiSBP <140 mmHg continued the same dose regimen for another 4 weeks. If blood pressure was not controlled after 4 weeks of treatment, the dose of either regimen was doubled to losartan 100 mg and irbesartan 300 mg. There were 351 patients randomized (176 to losartan and 175 to irbesartan), and of these, 325 patients completed the study (162 in the losartan group and 163 in the irbesartan group). At baseline, the median SUA level in the losartan group was 422 and 420 micromol/l in the irbesartan group. At 8 weeks of therapy, SUA decreased by 63 mumol/l in the losartan group compared to 12 mumol/l in the irbesartan group (P < 0.0001). Blood pressure declined comparably in both groups from 151/92 mmHg at baseline to 137/83 and 135/83 (losartan and irbesartan, respectively, NS). No severe AEs were found for either treatment group. Therapy with losartan decreased SUA levels significantly more than irbesartan in Chinese patients with hypertension and elevated SUA levels, demonstrating the unique uricosuric effect of this ARB in this ethnic group.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

Phagocytosis of apoptotic cells and immune regulation.

The termination of the apoptotic programme occurs in most cases via recognition and clearance by phagocytes, especially the professional phagocytes, such as macrophages and immature dendritic cells. Engulfed cells do not simply disappear from the midst of living tissues. The fine-defined presentation of yielded self-antigens to T cells is a central event in the induction or the maintenance of the peripheral immune tolerance to self. Conversely, abnormality in this pathway may contribute to the pathogenesis of systemic and organ-specific autoimmune diseases. We herein reviewed the relationship between phagocytosis of apoptotic cells and immune regulation, especially the effects of engulfed apoptotic cells on immune tolerance and autoimmune diseases.

Animals↗

PubMed2006

Combined multicolor-FISH and immunostaining.

The combination of multicolor-FISH and immunostaining produces a powerful visual method to analyze in situ DNA-protein interactions and dynamics. Representing one of the major technical improvements of FISH technology, this method has been used extensively in the field of chromosome and genome research, as well as in clinical studies, and serves as an important tool to bridge molecular analysis and cytological description. In this short review, the development and significance of this method will be briefly summarized using a limited number of examples to illustrate the large body of literature. In addition to descriptions of technical considerations, future applications and perspectives have also been discussed focusing specifically on the areas of genome organization, gene expression and medical research. We anticipate that this versatile method will play an important role in the study of the structure and function of the dynamic genome and for the development of potential applications for medical research.

Animals↗

PubMed2006

Adenoviral vectors encoding tumor necrosis factor-alpha and FasL induce apoptosis of normal and tumoral anterior pituitary cells.

Our previous work showed that tumor necrosis factor (TNF)-alpha and FasL induce apoptosis of anterior pituitary cells. To further analyze the effect of these proapoptotic factors, we infected primary cultures from rat anterior pituitary, GH3 and AtT20 cells with first-generation adenoviral vectors encoding TNF-alpha, FasL or, as a control, beta-galactosidase (beta-Gal), under the control of the human cytomegalovirus promoter. Successful expression of the encoded transgenes was determined by immunocytochemistry. Although we observed basal expression of TNF-alpha and FasL in control cultures of anterior pituitary cells, fluorescence-activated cell sorting (FACS) cell cycle analysis showed that the overexpression of TNF-alpha or FasL increases the percentage of hypodiploid lactotropes and somatotropes. Nuclear morphology and TUNEL staining revealed that the cells undergo an apoptotic death process. We detected strong immunoreactivity for TNFR1 and Fas in the somatolactotrope cell line GH3. TNF-alpha, but not FasL, was expressed in control cultures of GH3 cells. The infection of GH3 cells with adenovirus encoding TNF-alpha or FasL increased the percentages of hypodiploid and TUNEL-positive cells. TNF-alpha or FasL immunoreactivity was not observed in the corticotrope cell line AtT20. However, adenovirus encoding TNF-alpha or FasL efficiently transduced these cells and increased the percentages of hypodiploid and TUNEL-positive cells. The expression of beta-Gal was detected in all these cultures but did not affect cell viability. In conclusion, these results suggest that death signaling cascades triggered by TNF receptor 1 (TNFR1) and Fas are present in both normal and tumoral pituitary cells. Therefore, overexpression of proapoptotic factors could be a useful tool in the therapy of pituitary adenomas.

Adenoviridae↗

PubMed2006

FK506 in the treatment of children with nephrotic syndrome of different pathological types.

OBJECTIVE: To evaluate the efficacy of FK506 in the treatment of children with nephrotic syndrome of different underlying pathology. METHODS: 12 patients were treated with FK506 with a dosage of 0.1 - 0.15 mg/kg/d while corticosteroid dose was tapered stepwise. This therapeutic course lasted 3 - 6 months during which the plasma concentration ofFK506 was monitored. RESULTS: 12 children with different pathological types nephrotic syndrome were treated with FK506, including 4 cases of MCN, 6 cases of MsPGN, and 1 case of MPGN and 1 case of FSGS. After 2-month duration, 8 patients got complete remission including 4 cases of MCN and 4 cases of MsPGN and 3 children including 1 case of MsPGN, 1 case of MPGN, and 1 case of FSGS got partial remission. Only 1 child with MsPGN was considered to be a treatment failure. The overall response rate was 91.67% with the plasma concentration of FK506 maintained at 5 approximately 12 ng/ml, and the response time was 10 - 38 days. After 1-month duration, all patients except one experienced a reduction in proteinuria to normal levels or a partial response (50% reduction in protein excretion), significant increase in serum albumin, decrease in serum cholesterol and triglyceride and disappearance of edema. 2 months later, in 11 patients, blood biochemical values had returned to normal levels. The drug was generally well-tolerated. 3 patients had anorexia, nausea, vomiting. 2 patients experienced transient elevated serum creatinine which was reversible after the adjustment of dosage. 3 patients had minor changes in urine NAG. Only 2 of all patients relapsed. CONCLUSION: FK506 is one of the effective immunosuppressants. In this study, FK506 in combination with a small doses of steroid while decreasing FK506 dosage plays a role in consolidating the curative effect and preventing relapse. In conclusion, FK506 may be effective in the treatment of nephrotic syndrome.

Adolescent↗