Biomedical subjects

J Huang

Publications and source records attributed to J Huang.

At least 253 records · Page 14Linked to original sources

PubMed2000

Effects of toxaphene on the immune system of cynomolgus (Macaca fascicularis) monkeys. A pilot study.

Toxaphene in glycerol/corn oil was administered at 1mg/kg body weight/day, 7 days/week in gelatin capsules to four healthy young adult cynomolgus (Macaca fascicularis) (two male and two female) monkeys for 52 weeks. Control monkeys ingested glycerol/corn oil only. Testing for immune effects was initiated at 34 weeks of treatment. Results included: reduced anti-sheep red blood cell (SRBC) titres for immunoglobulins (Ig) M and G; increased IgG titres to pneumococcal antigens, but not to the tetanus toxoid antigen; reduced T-helper/inducer mean lymphocyte numbers and the mean T-helper/inducer:T-suppressor/cytotoxic cell ratio and reduced respiratory burst activity in peripheral blood monocytes and granulocytes, albeit no changes on the phagocytic activity of these cells were detected. The above noted effects although not statistically significant (P0.05) suggest that chronic exposure to low levels of toxaphene may be immunosuppressive in cynomolgus monkeys and may pose a hazard to human health. To advance our understanding of the degree of hazard that toxaphene may pose to human health, we have undertaken additional chronic studies with a larger number of animals. Particular attention is focused on determining the potential immunotoxic effects of toxaphene in offspring following in utero exposure.

Animals↗

PubMed2000

Resurfacing deep wound of upper extremities with pedicled groin flaps.

A total of 29 axial pedicled groin skin flaps were applied clinically with satisfactory result excepting for one flap which tailed on transplantation. These cases included severe scar contracture of the dorsum of hands in 20 patients, deeply burned wounds with infection and exposure of deep structure in upper extremities in nine patients, such as electrical burns and hot-crushing injuries. The flap is supplied by two groups of nutrient vessels with abundant vascularization and located in a hidden area. Therefore, the pedicled groin skin flap is still valuable due to its advantages as safe, easy operation and strong antiinfective ability although the free groin flap is more widely used today.

Adult↗

PubMed2000

Hydrolysis kinetics of fenthion and its metabolites in buffered aqueous media.

This study investigates the hydrolysis kinetics of fenthion and its five oxidation metabolites in pH 7 and pH 9 buffered aqueous media at 25, 50, and 65 degrees C. Five metabolites and three hydrolysis products were synthesized and purified. The reactant and the corresponding hydrolysis products were determined by HPLC. Rate constant and half-life studies revealed that fenthion and its metabolites were relatively stable in neutral media, and their stability decreased as pH increased. The half-lives at 25 degrees C ranged from 59.0 days for fenthion to 16.5 days for fenoxon sulfone at pH 7, and from 55.5 days for fenthion to 9.50 days for fenoxon sulfone at pH 9; half-lives were greatly reduced at elevated temperatures. The activation energy (E(a)) was found to range from 16.7 to 22.1 kcal/mol for the compounds investigated. The phenol hydrolysis product of fenthion and fenoxon, 3-methyl-4-methylthiophenol was not stable in pH 7 and pH 9 buffered solutions at 50 degrees C, whereas 3-methyl-4-methylsulfonylphenol and 3-methyl-4-methylsulfinylphenol were relatively stable under the same conditions. At pH 9, the primary hydrolysis mechanisms of fenthion and its oxidation metabolites were combination of hydroxide ion and neutral water molecule attacking on the P atom to form corresponding phenol derivatives. Under neutral conditions, the primary hydrolysis mechanisms of fenthion and its oxidation metabolites were assumed to be the combination of water molecule attacking on the P atom to form phenol derivatives and on the C atom to yield dealkylation products.

Buffers↗

PubMed2000

Effects of social support, regular physician and health-related attitudes on cervical cancer screening in an Asian population.

OBJECTIVE: Out primary objective was to examine sociodemographic and attitudinal factors that affect uptake of the Pap smear in a multi-ethnic Asian population. METHODS: We conducted a prevalence survey among women aged 50-64 years living in Singapore and ascertained by means of an in-person questionnaire interview their Pap screening history, demographic characteristics, informal social support and attitudes towards early detection. RESULTS: We found that, after adjusting for demographic variables known to be predictors of Pap screening, women who reported ever having a Pap smear were more likely to have close friends with whom they could discuss health (adjusted odds ratio (OR) 2.1, 95% confidence intervals (CI) 1.2-3.6), and have a regular physician (adjusted OR 2.3 (1.3-4.1)). Based on responses to four indices measuring health attitudes, they were significantly less likely to express a fatalistic viewpoint towards health and illness (adjusted OR for highest vs. lowest tertile 0.3 (95% CI 0.1-0.7)), and more likely to believe that early detection could improve the outcome (adjusted OR 3.3 (95% CI 1.4-7.8)). The nature of the test itself was a significant barrier to having a Pap smear, but only among women with fewer years of education. CONCLUSIONS: Our results suggest that, within this Asian population, a multi-pronged approach is required to reach unscreened women. The role of physicians and close friends should be emphasized, and health messages should be formulated to address specific, relevant attitudinal barriers to Pap screening.

Aged↗

PubMed2000

Role of extracellular ionized calcium in the in vitro assessment of GPIIb/IIIa receptor antagonists.

Several preclinical studies have found a poor correlation between the ex vivo platelet inhibitory potency and the in vivo antithrombotic efficacy of GPIIb/IIIa receptor antagonists. The present study was designed to examine the differential in vitro potencies of c7E3, MK-383, DMP-728, and SM-20302 in inhibiting ex vivo platelet aggregation under normocalcemic and hypocalcemic conditions. Human blood was collected in either trisodium citrate (0. 37%) or PPACK (20 microg/mL). Platelet aggregation assays were performed in platelet-rich plasma from citrate-anticoagulated blood (cPRP) and PPACK-anticoagulated blood (pPRP) using ADP (20 microM) and TRAP (10 microM) as agonists in the presence of c7E3, MK-383, DMP-728, or SM-20302. The concentration of ionized calcium in cPRP was 16-19 times lower than that in pPRP. The IC(50) of c7E3 for inhibiting ADP-induced platelet aggregation in cPRP (2.76 +/- 0.11 microg/mL) was 1.6 times lower than that in pPRP (4.46 +/- 0.48 microg/mL; P < 0.05). Similarly, the IC(50) for c7E3 for inhibiting TRAP-induced platelet aggregation in cPRP (4.52 +/- 0.34 microg/mL) was 1.7 times lower than that in pPRP (7.69 +/- 0.43 microg/mL; P < 0.05). MK-383, DMP-728, and SM-20302 also demonstrated 1.96-, 1.15-, and 1.43-fold lower IC(50) values, respectively, in cPRP as compared with pPRP. Chelation of ionized calcium in pPRP led to a progressive increase in platelet inhibition by all the antagonists. These results suggest that the observed in vitro inhibitory potency of a GPIIb/IIIa receptor antagonist is markedly enhanced when trisodium citrate is used as an anticoagulant to collect blood for ex vivo assay. These findings indicate that dosing regimens for GPIIb/IIIa receptor antagonists based on the platelet inhibition profile in citrate may provide misleading information with respect to their true in vivo antithrombotic efficacy.

Adenosine Diphosphate↗

PubMed2000

Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease.

One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid beta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms of the human amyloid precursor protein, show many of the pathological features of Alzheimer disease, including extensive deposition of extracellular amyloid plaques, astrocytosis and neuritic dystrophy. Active immunization of PDAPP mice with human amyloid beta-peptide reduces plaque burden and its associated pathologies. Several hypotheses have been proposed regarding the mechanism of this response. Here we report that peripheral administration of antibodies against amyloid beta-peptide, was sufficient to reduce amyloid burden. Despite their relatively modest serum levels, the passively administered antibodies were able to enter the central nervous system, decorate plaques and induce clearance of preexisting amyloid. When examined in an ex vivo assay with sections of PDAPP or Alzheimer disease brain tissue, antibodies against amyloid beta-peptide triggered microglial cells to clear plaques through Fc receptor-mediated phagocytosis and subsequent peptide degradation. These results indicate that antibodies can cross the blood-brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.

Alzheimer Disease↗

PubMed2000

Vaccinia as a vector for tumor-directed gene therapy: biodistribution of a thymidine kinase-deleted mutant.

Tumor-directed gene therapy, such as "suicide gene" therapy, requires high levels of gene expression in a high percentage of tumor cells in vivo to be effective. Current vector strategies have been ineffective in achieving these goals. This report introduces the attenuated (thymidine kinase (TK)-negative) replication-competent vaccinia virus (VV) as a potential vector for tumor-directed gene therapy by studying the biodistribution of VV in animal tumor models. A TK-deleted recombinant VV (Western Reserve strain) expressing luciferase on a synthetic promoter was constructed. Luciferase activity was measured in vitro after transduction of a variety of human and murine tumor cell lines and in vivo after intraperitoneal (i.p.) delivery in C57BL/6 mice with 7-day i.p. tumors (10(6) MC-38 cells). Three other in vivo tumor models were examined for tumor-specific gene expression after intravenous delivery of VV (human melanoma in nude mice, adenocarcinoma liver metastasis in immunocompetent mice, and subcutaneous sarcoma in the rat). In addition, a replication-incompetent vaccinia (1 microg of psoralen and ultraviolet light, 365 nm, 4 minutes) was tested in vitro and in vivo and compared with active virus. Luciferase activity in i.p. tumors at 4 days after i.p. injection of VV was >7000-fold higher than lung, >3000-fold higher than liver, and >250-fold higher than ovary. In addition, intravenous injection of VV resulted in markedly higher tumor luciferase activity compared with any other organ in every model tested (up to 188,000-fold higher than liver and 77,000-fold higher than lung). Inactivation of the virus resulted in negligible gene expression in vivo. In summary, VV has a high transduction efficiency in tumor cells with high levels of gene expression. The results suggest a selective in vivo replication of TK-deleted VV in tumor cells. Replication competent, TK-deleted VV appears to be an ideal vector for testing the in vivo delivery of toxic genes to tumor cells.

Animals↗

PubMed2000

Effects of an energy and micronutrient supplement on mental development and behavior under natural conditions in undernourished children in Indonesia.

OBJECTIVES: This paper reports the effects of an energy and micronutrient supplement on mental development and on the social cognitive and emotionally regulatory behaviors of nutritionally at risk infants and toddlers in Pangalengan, Indonesia. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 12 mg iron + 209 kJ; S = 104 kJoule. Supplementation was given for 12 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (N = 53) and an 18-month-old (N = 83) cohort were recruited from day-care-centers. Twenty children who received S belonged to the 12- and 18-month-old cohort. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: Evaluations of intake were made at baseline and every 2 months thereafter. Motor development was assessed with the Bayley Scale and with a custom-made scale to assess gross motor development leading to bipedal locomotion. Four hours of continuous observations were made of the child's interaction with the social and physical environment. RESULTS: In the 12-month-old cohort, as compared with the M and S groups, the children who received the E supplement walked at an earlier age, had higher scores in the Bayley Scale and showed more mature social-cognitive and emotional regulatory behaviors. Similar intergroup differences were observed in the 18-month-old cohort in social cognition and regulation of emotions.

Anemia, Iron-Deficiency↗

PubMed2000

The consistency of the posterior probability of linkage.

When searching for trait loci along the genome, properly incorporating prior genomic information into the analysis will almost certainly increase the chance of success. Recently, we devised a method that utilizes such prior information in the mapping of trait genes for complex disorders (Vieland, 1998; Wang el al. 1999; Vieland et al. 2000). This method uses the posterior probability of linkage (PPL) based on the admixture model as a measure of linkage information. In this paper, we study the consistency of the PPL. It is shown that, as the number of pedigrees increases, the PPL converges in probability to 1 when there is linkage between the marker and a trait locus, and converges to 0 otherwise. This conclusion is shown to be true for general pedigrees and trait models, even, when the likelihood functions are based on misspecified trait models. As part of the effort to prove this conclusion, it is shown that when there is no linkage, the maximum likelihood estimator of the recombination fraction in the admixture model is asymptotically 0.5, even when the admixture model misrepresents the true model.

Computer Simulation↗

PubMed2000

High-affinity anti-ganglioside IgG antibodies raised in complex ganglioside knockout mice: reexamination of GD1a immunolocalization.

Gangliosides, sialic acid-bearing glycosphingolipids, are highly enriched in the vertebrate nervous system. Anti-ganglioside antibodies are associated with various human neuropathies, although the pathogenicity of these antibodies remains unproven. Testing the pathogenic role of anti-ganglioside antibodies will be facilitated by developing high-affinity IgG-class complement-fixing monoclonal anti-bodies against major brain gangliosides, a goal that has been difficult to achieve. In this study, mice lacking complex gangliosides were used as immune-naive hosts to raise anti-ganglioside antibodies. Wild-type mice and knockout mice with a disrupted gene for GM2/GD2 synthase (UDP-N-acetyl-D-galactosamine : GM3/GD3 N-acetyl-D-glactosaminyltransferase) were immunized with GD1a conjugated to keyhole limpet hemocyanin. The knockout mice produced a vigorous anti-GD1a IgG response, whereas wildtype littermates failed to do so. Fusion of spleen cells from an immunized knockout mouse with myeloma cells yielded numerous IgG anti-GD1a antibody-producing colonies. Ganglioside binding studies revealed two specificity classes; one colony representing each class was cloned and characterized. High-affinity monoclonal antibody was produced by each hybridoma : an IgG1 that bound nearly exclusively to GD1a and an IgG2b that bound GD1a, GT1b, and GT1aalpha. Both antibodies readily readily detected gangliosides via ELISA, TLC immune overlay, immunohistochemistry, and immunocytochemistry. In contrast to prior reports using anti-GD1a and anti-GT1b IgM class monoclonal antibodies, the new antibodies bound avidly to granule neurons in brain tissue sections and cell cultures. Mice lacking complex gangliosides are improved hosts for raising high-affinity, high-titer anti-ganglioside IgG antibodies for probing for the distribution and physiology of gangliosides and the pathophysiology of anti-ganglioside antibodies.

Animals↗

PubMed2000

Fibrillation is more complex in the left ventricle than in the right ventricle.

INTRODUCTION: The mechanisms that maintain ventricular fibrillation (VF) are not completely understood. It has been proposed that increased ventricular wall thickness destabilizes VF wavefronts and therefore is an important determinant of VF activation patterns. We hypothesized that if this is the case, then VF patterns on the thin-walled right ventricle (RV) should be simpler than those on the thick-walled left ventricle (LV). METHODS AND RESULTS: In seven open chest pigs, we mapped VF simultaneously from two epicardial recording arrays, one on the RV and one on the LV. Each array contained 504 unipolar electrodes (in a 21 x 24 grid) spaced by 2 mm. We used specialized pattern analysis methods to compute quantitative descriptors of RV and LV activation patterns. Our data show that VF is more organized in the RV than the LV, containing fewer, larger wavefronts that follow fewer distinct pathways and are less likely to fragment or collide with other wavefronts. The incidence, size, and cycle length of reentrant circuits were similar in the two ventricles, but RV reentry persisted for more cycles. These results are not predicted by the differences in electrophysiologic properties between LV and RV that have been reported in mammalian hearts. CONCLUSION: The geometry of the ventricular wall, particularly wall thickness, is an important determinant of VF activation patterns.

Action Potentials↗

PubMed2000

Suppression of primary tumor growth in a mouse model of human neuroblastoma.

BACKGROUND/PURPOSE: Neuroblastoma is the most common tumor of the abdomen in children. Consistently effective treatments are lacking for aggressive disease. The authors previously reported that therapy with anti-vascular endothelial growth factor (VEGF) antibodies suppresses both growth and metastasis in an experimental model of Wilms' tumor. The authors hypothesized that, in a parallel model of neuroblastoma, anti-VEGF treatment would inhibit (1) growth and (2) metastasis. METHODS: Primary tumors were established in the kidneys of nude mice. In cohort 1 (n = 42), mice were killed at 3 time-points, and tissues were evaluated histologically. Tumors were assayed for VEGF. In cohort 2 (n = 28), anti-VEGF antibody or vehicle was administered. Tumor weights and the incidence of metastases in the 2 groups were compared. VEGF deposition was evaluated by immunohistochemistry. RESULTS: Mice displayed large tumors with liver and lung metastases. VEGF levels in tumors increased over time. Antibody-treated animals displayed significantly smaller tumors, but incidence and size of metastases were unaffected. VEGF was localized to tumor stroma immunohistochemically, with no difference in pattern observed in control and antibody-treated tumors. CONCLUSIONS: Anti-VEGF antibodies inhibit primary tumor growth in experimental neuroblastoma, but not metastasis. This may contrast with the effect of the same antibody in a parallel model of Wilms' tumor.

Animals↗

PubMed2000

Nuclear morphology in breast cancer: is pleomorphism an illusion?

Nuclear pleomorphism is an underlying theme of cancer histology. Any medical practitioner, not just the pathologist, would have at one time or another in a Pathology practical class, looked at histopathology slides and convinced himself or herself that cancer cells indeed looked more variable in size and shape than nontumorigenic cells. However, data from our nuclear morphometric analysis of cells in breast cancer and adjacent benign tissues appears to suggest that the larger size of the cancer cell nuclei could make any change in nuclear shape and size more noticeable and apparent than their benign counterparts. We hypothesize that the phenomenon of nuclear pleomorphism is due partly to observational subjectivity.

Breast Neoplasms↗

PubMed2000

High frequency allelic loss on chromosome 17p13.3-p11.1 in esophageal squamous cell carcinomas from a high incidence area in northern China.

Allelic loss on chromosome 17p has been reported frequently in esophageal squamous cell carcinoma (ESCC) and generally encompasses the p53 locus at 17p13.1. However, a good correlation between allelic loss on 17p and mutation of p53 has not been found. This suggests the possibility that unknown tumor suppressor genes near p53 may be involved in the development of ESCC. To evaluate this possibility, we analyzed 30 microsatellite markers covering the entire short arm of chromosome 17 in 56 ESCC patients from a high risk population in northern China, including 34 with a family history of upper gastrointestinal (UGI) cancer and 22 without a family history of any cancer. Cancer lifestyle risk factors and clinical/pathological characteristics were also collected. We found frequent allelic loss (>/=65%) at 28 of the 30 markers evaluated in these ESCC patients. The highest frequencies of allelic loss (> or =80%) were found in three smaller regions: deletion region I located at 17p13.3-p13.2 (between D17S849 and D17S1828); deletion region II located at 17p13.2-p13.1 (between D13S938 and TP53); deletion region III located at 17p13.1-p12 (between D17S804 and D17S799). A number of genes have already been identified in these deleted regions, including: OVCA1, OVCA2 and HIC-1 in deletion region I; p53 in deletion region II; ZNF18, ZNF29, ALDH3 and ALDH10 in deletion region III. These results will help us direct future testing of candidate genes and narrow the search region for major new tumor suppressor genes that may play a role in the pathogenesis of ESCC.

Adult↗

PubMed2000

Vitamin D receptor gene polymorphisms and osteoarthritis of the hand, hip, and knee: acase-control study in Japan.

OBJECTIVE: To investigate the association between vitamin D receptor (VDR) gene polymorphisms andJapanese female patients with osteoarthritis (OA) of the hand, hip, and knee. METHODS: BsmI,ApaI, andTaqI restriction fragment length polymorphisms (RFLPs) of the VDR gene were analysed in 270Japanese female patients with radiographic OA of the hand, hip, tibiofemoral (TF) joint, andpatellofemoral (PF) joint, as well as in female controls. RESULTS: There was no significant association between the VDR gene RFLPs and OA of the hand, hip, TFjoint, PF joint, or polyarticular involvement. The previously detected preventive genotype of the VDRgene was uncommon in our test population. CONCLUSION: The relative importance of VDR gene polymorphism in the development of OA may vary betweenethnic groups.

Adult↗

PubMed2000

A 1-year follow-up study of dynamic magnetic resonance imaging in early rheumatoid arthritis reveals synovitis to be increased in shared epitope-positive patients and predictive of erosions at 1 year.

OBJECTIVES: Dynamic magnetic resonance imaging (MRI) allows visualization of the synovial membrane and measurement of synovitis within the joint. A cohort of patients with early rheumatoid arthritis (RA) were studied using MRI of the dominant wrist and clinical assessments. Associations between synovitis and the shared epitope genotype (SE) were looked for and synovitis as a predictor of joint erosion was examined. METHODS: Gadolinium-enhanced MRI scans of the dominant wrist were performed in 42 early RA patients at baseline (median disease duration = 4 months) and after 1 yr. Images were obtained at 42-s intervals over the first 6 min after gadolinium-diethylenetriamine pentaacetic acid injection using six cuts in the coronal plane, 2 mm apart. The site of maximal synovial enhancement was selected as the region of interest (ROI). The rate of enhancement (E-rate) was calculated and compared with synovitis scores from static MRI scans, clinical disease activity scores and HLA-DRB1*04/01 genotyping [sequence-specific primer polymerase chain reaction (SSP-PCR) and DNA sequencing]. RESULTS: Reproducibility of the E-rate measurement was assessed by re-evaluating 10 randomly selected scans in a blinded fashion. Intra-observer reliability was high with an intraclass correlation coefficient of 0.91, 95% confidence interval (CI) 0.65-0.97. The E-rate correlated strongly at baseline with the maximum level of synovial enhancement (E-max) (r = 0.88, P < 0.0001) and the static MRI synovitis score (r = 0.52, P = 0.0004). There was also a weaker but significant correlation between E-rate and the pain score (r = 0.29, P = 0.04). The E-rate fell from baseline to 1 yr (P = 0.02) concordant with clinical improvement after treatment with standard therapies. E-rate scores were higher in SE+ than SE - patients (F(1,25) = 5.19, P = 0.03) and were predictive of MRI erosions at 1 yr [chi-square = 5.0 (1 d.f.), P = 0.03]. The baseline C-reactive protein (CRP) was also predictive of MRI erosions at 1 yr to a similar degree [chi-square = 4.7 (1 d.f. ), P = 0.03] but the mean static synovitis score at baseline was the strongest predictor [chi-square = 9.2 (1 d.f.), P = 0.003]. CONCLUSIONS: These results show that dynamic MRI can be used to score synovitis objectively in early RA patients. Synovitis was greater in SE+ patients, suggesting an early genetic influence on joint inflammation, and was predictive for the development of erosions at 1 yr.

Adult↗

PubMed2000

Prevalence of hip osteoarthritis and acetabular dysplasia in french and japanese adults.

OBJECTIVE: : To determine ethnic variations of acetabular morphology, and to delineate their relationship with hip osteoarthritis (OA). METHODS: : Radiographs of 283 French men, 118 French women, 414 Japanese men and 368 Japanese women, aged 20-79 yr, who underwent intravenous urography were assessed by a single observer for morphometric measurement and hip OA scoring. RESULTS: : The standardized morbidity ratio (SMR) for hip OA was highest in French men and lowest in Japanese men, whereas the SMR for acetabular dysplasia was highest in Japanese women and lowest in French men. French men and women had the highest centre-edge angle, followed by Japanese men then Japanese women. CONCLUSION: : In a large number of subjects assessed by a single observer, this study confirms other previous reports that the relationship between acetabular dysplasia and risk of hip OA is negative.

Acetabulum↗

PubMed2000

Rac1 inhibits TNF-alpha-induced endothelial cell apoptosis: dual regulation by reactive oxygen species.

Reactive oxygen species (ROS) have been implicated as mediators of tumor necrosis factor-alpha (TNF) -induced apoptosis. In addition to leading to cell death, ROS can also promote cell growth and/or survival. We investigated these two roles of ROS in TNF-induced endothelial cell apoptosis. Human umbilical vein endothelial cells (HUVECs) stimulated with TNF produced an intracellular burst of ROS. Adenoviral-mediated gene transfer of a dominant negative form of the small GTPase Rac1 (Rac1N17) partially suppressed the TNF-induced oxidative burst without affecting TNF-induced mitochondrial ROS production. HUVECs were protected from TNF-induced apoptosis. Expression of Rac1N17 blocked TNF-induced activation of nuclear factor-kappa B (NF-kappaB), increased activity of caspase-3, and markedly augmented endothelial cell susceptibility to TNF-induced apoptosis. Direct inhibition of NF-kappaB through adenoviral expression of the super repressor form of inhibitor of kappaBalpha (I-kappaB S32/36A) also increased susceptibility of HUVECs to TNF-induced apoptosis. Rotenone, a mitochondrial electron transport chain inhibitor, suppressed TNF-induced mitochondrial ROS production, proteolytic cleavage of procaspase-3, and apoptosis. These findings show that Rac1 is an important regulator of TNF-induced ROS production in endothelial cells. Moreover, they suggest that Rac1-dependent ROS, directly or indirectly, lead to protection against TNF-induced death, whereas mitochondrial-derived ROS promote TNF-induced apoptosis.

Adenoviridae↗