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Biomedical subjects

A Wu

Publications and source records attributed to A Wu.

At least 55 records · Page 3Linked to original sources
PubMed2000

Deltamethrin induces delayed apoptosis and altered expression of p53 and bax in rat brain.

Our previous work indicates that deltamethrin induces degeneration and apoptosis in rat brain at 24 and 48 h after treatment. To determine whether molecular characteristics of apoptosis is involved in neurodegeneration in rat brain after deltamethrin treatment, we investigated the effects of deltamethrin on the mRNA expression of p53 and bax and their correlation with deltamethrin-induced apoptotic cell death in rat brain. Hematoxylin-eosin and cresyl violet staining revealed numerous degenerative cells in cortex and hippocampus at 5 and 24 h after deltamethrin treatment. Apoptotic cells were detected in cortex and hippocampus of treated rats at 24 h by in situ end labeling, whereas no apoptotic cells were observed in the same brain regions at 5 h after treatment. By using in situ hybridization, it was demonstrated that the increase of p53 and bax mRNA levels appeared at 5 and also at 24 h after treatment. The alterations in mRNA expression of p53 and bax preceded the occurrence of delayed apoptotic cell death in the same brain regions after deltamethrin treatment. These results indicate that (1) deltamethrin induces delayed apoptotic cell death, which may play an important role in deltamethrin-elicited neurodegeneration; (2) deltamethrin leads to the persistent increase of p53 and bax mRNA levels, which may contribute to delayed apoptosis in rat brain following deltamethrin treatment.

Journal Article↗
PubMed2000

Apoptotic cell death in rat brain following deltamethrin treatment.

In the present study we identified the degeneration and apoptotic cell death in rat brain after deltamethrin treatment. By hematoxylin-eosin (H&E) staining, a large number of degenerative cells (pyknosis of nuclei, disruption of eosinophilic cytoplasm) were seen in the hippocampus and cortex at 24 and 48 h after deltamethrin treatment at a dose of 12.5 mg/kg (i.p.) in corn oil. The similar morphological changes of degenerative cells were observed by cresyl violet staining. Numerous apoptotic cells were detected by in situ end labeling (ISEL) and flow cytometric analysis in the hippocampus and cortex at 24 and 48 h following deltamethrin treatment at the same dose, whereas no ISEL-positive cells were seen in the same brain regions of control rats. Moreover, using DNA gel electrophoresis, it was demonstrated that DNA fragmentation was markedly induced in the hippocampus and cortex at 24, 48 and 72 h after treatment. In addition, the protein synthesis inhibitor cycloheximide inhibited the DNA fragmentation elicited by deltamethrin in rat brain. These results indicate that deltamethrin induces degeneration and apoptotic cell death in rat brain, suggesting an important role played by apoptosis in neurotoxicity of deltamethrin.

Animals↗
PubMed2000

Preventive effect of antioxidant on ultraviolet-induced skin cancer in mice.

Reactive oxygen species (ROS) have been shown to be responsible for inducing DNA damage after ultraviolet radiation (UV). Antioxidant, vitamin E and epigallocatechin gallate extracted from green tea, applied topically to the skin, delayed the onset of UV-induced skin cancer in mice. Since olive oil is reported to have a potent antioxidative effect in in vitro system, we asked whether, topical use of olive oil reduces the number and delays the onset of UV-induced skin cancer in mice. We found that super virgin olive oil painted immediately after UVB radiation significantly delayed the onset and reduced the number of skin cancer, but pretreatment of super virgin olive oil and pre- and/or post treatment by regular olive oil neither retarded nor reduced skin cancer formation in UV-irradiated mice. Further, 8-hydroxy-deoxyguanosine (8-OHdG) formation in mice epidermis was apparently reduced by super virgin olive oil painted immediately after UV radiation, although cyclobutane pyrimidine dimers and (6-4) photoproducts were not reduced by olive oil treatment. Our results suggest that daily topical use of super virgin olive oil after sun bathing may delay and reduce UV-induced skin cancer development in human skin, possibly by decreasing ROS-induced 8-OHdG which is responsible for gene mutation.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Point dose variations with time during traditional brachytherapy for cervical carcinoma.

In traditional brachytherapy for carcinoma of the cervix, doses are often prescribed to specifically chosen points (A and B) and the normal tissue tolerance calculated at specific reference points in the bladder and rectum. These tolerance doses are often used to modify the brachytherapy treatment plan. It is inherently assumed that the position of the brachytherapy applicator does not change in relation to the relevant anatomical structures over the time-course of an implant. To assess the accuracy of this assumption, 2 sets of localization films were obtained for each implant in 28 patients, 1 prior to loading and another after the removal of the radioactive sources. Significant applicator movement and, consequently, significant dose variations were ob: served. Therefore, isolated one-time dose measurements to normal critical structures should not be used as the sole basis for making therapeutic decisions. The magnitude of dose variations and their clinical significant are discussed.

Brachytherapy↗
PubMed2000

Conformal prostate treatment planning using a low-energy (6-MV) beam.

A 4-field noncoplanar technique for treatment of prostate cancer developed at the University of Michigan was modified for use with low-energy (6 MV) beams. These modifications include the use of wedges on the 2 anterior inferior-superior oblique fields and adjusting the weights of the oblique and lateral fields appropriately. A margin of 1.5 cm around the physician-defined target region was used to define the blocks on each beam's-eye view. Dose distributions produced using this technique with 6-MV and 24-MV beams were compared visually on several dose planes (transverse and sagittal) and quantitatively by dose volume histograms (target, rectum, and bladder). These comparisons showed insignificant differences between the high-energy and low-energy treatment plans. Much larger differences were observed in comparisons of 2 types of coplanar plans with the noncoplanar setup for the 6-MV photon machine. Rectal doses measured in situ were used to help validate the dose distribution predicted by the treatment planning system for the 6-MV noncoplanar technique.

Humans↗
PubMed2000

Helicobacter pylori sero-prevalence in asthma.

Asthma is a very common respiratory disease which is characterized by the presence of cytokine-mediated airway inflammation leading to smooth muscle contraction, oedema and progressive airway damage in some cases. In light of our recent finding of an increased sero-prevalence of Helicobacter pylori in bronchiectasis, we have determined serum levels of H. pylori-specific IgG in asthmatic and control subjects. Altogether 90 consecutive asthmatic [mean age +/- SD 42.6+/-16 years and 52 female (F)] and 97 healthy control subjects (mean age +/- SD 43.2+/-13.3 years and 51 female (F); P = 0.78 and 0.39 respectively) were recruited prospectively. H. pylori sero-prevalence was not significantly different between asthmatic and control subjects (P>0.05). Serum H. pylori IgG levels did not correlate with FEV1 % predicted, FVC % predicted or duration of asthma (P>0.05). Similar to the results of previously published sero-epidemiological studies, there was a weak correlation between serum H. pylori IgG with increasing age (r = 0.43, P = 0.004). Despite the sero-epidemiological association of H. pylori infection with many inflammatory conditions, our data showed no such association for middle age asthmatic patients with mild intermittent asthma in our locality.

Adult↗
PubMed2000

Protective effect of topically applied olive oil against photocarcinogenesis following UVB exposure of mice.

Reactive oxygen species have been shown to play a role in ultraviolet light (UV)-induced skin carcinogenesis. Vitamin E and green tea polyphenols reduce experimental skin cancers in mice mainly because of their antioxidant properties. Since olive oil has also been reported to be a potent antioxidant, we examined its effect on UVB-induced skin carcinogenesis in hairless mice. Extra-virgin olive oil was applied topically before or after repeated exposure of mice to UVB. The onset of UVB-induced skin tumors was delayed in mice painted with olive oil compared with UVB control mice. However, with increasing numbers of UVB exposures, differences in the mean number of tumors between UVB control mice and mice pretreated with olive oil before UVB exposure (pre-UVB group) were lost. In contrast, mice that received olive oil after UVB exposure (post-UVB group) showed significantly lower numbers of tumors per mouse than those in the UVB control group throughout the experimental period. The mean number of tumors per mouse in the UVB control, pre-UVB and post-UVB groups was 7.33, 6.69 and 2.64, respectively, in the first experiment, and 8.53, 9.53 and 3.36 in the second experiment. Camellia oil was also applied, using the same experimental protocol, but did not have a suppressive effect. Immunohistochemical analysis of DNA damage in the form of cyclobutane pyrimidine dimers (CPD), (6-4) photoproducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in samples taken 30 min after a single exposure of UVB showed no significant difference between UVB-irradiated control mice and the pre-UVB group. In the post-UVB group, there were lower levels of 8-OHdG in epidermal nuclei, but the formation of CPD and (6-4) photoproducts did not differ. Exposure of olive oil to UVB before application abrogated the protective effect on 8-OHdG formation. These results indicate that olive oil topically applied after UVB exposure can effectively reduce UVB-induced murine skin tumors, possibly via its antioxidant effects in reducing DNA damage by reactive oxygen species, and that the effective component may be labile to UVB.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Status epilepticus-induced neuronal loss in humans without systemic complications or epilepsy.

PURPOSE: To determine the regional distribution of neuronal damage caused strictly by status epilepticus (SE) without systemic complications, underlying brain pathology, or a history of preexisting epilepsy. METHODS: The medical records and electroencephalograms (EEGs) of three deceased patients who developed SE in the hospital were reviewed. Their brains were formalin-fixed, and 17 brain regions were selected, embedded in paraffin, and sectioned. Alternate sections were stained with either hematoxylin and eosin and cresyl violet to determine the extent of neuronal loss and gliosis or glial fibrillary astrocytic protein to confirm the extent of astrocytic proliferation. RESULTS: The three patients died 11 to 27 days after the onset of focal motor SE; none had hypotension, hypoxemia, hypoglycemia, or significant hyperthermia. Two patients had no prior seizures and no underlying brain pathology. The third patient, who had leptomeningeal carcinomatosis, had one seizure 2 months before the onset of SE. The duration of SE was 8.8 hours to 3 days. EEGs showed unilateral temporal lobe sharp-wave discharges in one patient and independent temporal lobe sharp-wave discharges bilaterally in the other two patients. In addition to widespread neuronal loss and reactive gliosis in the hippocampus, amygdala, dorsomedial thalamic nucleus, and Purkinje cell layer of the cerebellum, we report for the first time periamygdaloid (piriform) and entorhinal cortical damage occurring acutely after SE in humans. CONCLUSIONS: In the absence of systemic complications or preexisting epilepsy, SE produces neuronal loss in a distribution similar to that from domoic acid-induced SE in humans and from kainic acid- and pilocarpine-induced SE in rats.

Animals↗
PubMed2000

[A comprehensive evaluation on intervention measures for injuries in primary and middle school students].

OBJECTIVE: To explore the intervention measures for prevention and control of injuries and evaluation for their effectiveness in students of middle and primary schools. METHODS: Effectiveness of intervention was evaluated by comparison of incidence of injury before and after intervention in 3,896 students of nine middle and primary schools and comparison with a non-intervention group in 651 students of four primary schools in Jiangmen City, Guangdong Province during January to December, 1999. RESULTS: Incidence of injury dropped to 11.78% after intervention from 50.55% before intervention in the intervention group, with 76.70% of reduction. Proportion of severe injury dropped to 0.65% after intervention from 7.84% before intervention. Incidence of multiple injuries dropped to 3.15% from 19.16%, with 83.56% of reduction. But, in the control group, incidence of injury dropped to 49.00% from 52.67%, with 6.97% of reduction only, with a ratio of reduction of intervention to control of 11.02% and a ratio of cost to benefit of 1:13.9. CONCLUSION: Intervention measures focusing on health promotion can prevent and control the occurrence of injury in students of middle and primary schools cost-effectively.

Accident Prevention↗
PubMed1999

Effects of deltamethrin on nitric oxide synthase and poly(ADP-ribose) polymerase in rat brain.

The effects of deltamethrin on the activities of nitric oxide synthase (NOS) and poly(ADP-ribose) polymerase (PARP) and the protein expression of neuronal NOS (nNOS) and PARP in rat brain were investigated in the present study. The activity of NOS was significantly increased in cortex and hippocampus at 5 h after deltamethrin treatment, and maintained at an increased level at 24 h. The activity of PARP was also elevated at the same time points in the same brain regions of treated rats. By immunohistochemical analysis, it was demonstrated that the nNOS-immunoreactive cells were markedly increased at 24 h after treatment in the cortex and hippocampus, whereas few nNOS-immunoreactive cells were observed in the same brain regions of control and treated rats at 5 h after treatment. The immunoreactivity for PARP was also increased in the same brain regions, showing the similar time course of the induction of nNOS by deltamethrin. These results indicate that deltamethrin increases the activities of NOS and PARP and initiates the protein expression of nNOS and PARP, suggesting that NOS and PARP might play important roles in neurotoxicity of deltamethrin.

Animals↗
PubMed1999

Systemic antitumor immunity in experimental brain tumor therapy using a multimutated, replication-competent herpes simplex virus.

Replication-competent, attenuated herpes simplex virus (HSV) vectors have been developed for viral oncolytic therapy of primary and metastatic malignant brain tumors. However, the role of the host immune responses in the brain has not been elucidated. N18 neuroblastoma cells were used as a tumor model in syngeneic A/J mice to test the therapeutic efficacy of G207, a conditionally replicating HSV vector, in an immunocompetent condition. G207 inoculated intraneoplastically exhibited a prominent oncolytic antitumor effect in mice harboring N18 tumors in the brain or subcutaneously, and, in addition, elicited a systemic antitumor immune response. Subcutaneous tumor therapy with G207 caused regression of a remote, established tumor in the brain or in the periphery, which was potentially mediated by the systemic antitumor immune response, and provided persistent tumor-specific protection against N18 tumor rechallenge in the brain as well as in the periphery. Antitumor immunity was associated with an elevation of specific CTL activity against N18 tumor cells that persisted for at least 13 months. The results suggest that the oncolytic antitumor action of replication-competent HSV may be augmented by induction of specific and systemic antitumor immunity effective both in the periphery and in the brain.

Animals↗
PubMed1999

Correlation of the expression of human telomerase subunits with telomerase activity in normal skin and skin tumors.

BACKGROUND: Telomerase activation is thought to be crucial for the continued growth or progression of cancer cells. Three major subunits of human telomerase, human telomerase RNA (hTR), telomerase-associated protein (TP1), and human telomerase catalytic subunit (hTERT) have been identified recently. In the current study, the expression of these telomerase subunits was examined in various human skin tumors and in normal skin samples, and the correlation of their expression with telomerase activity was evaluated. METHODS: Forty-five skin tumors, including benign, premalignant, and malignant tumors, and 19 samples of normal skin were analyzed by reverse transcriptase-polymerase chain reaction for the expression of telomerase subunits and by telomeric repeat amplification protocol assay for telomerase activity. RESULTS: TP1 expression was found in 43 of 45 skin tumors (95.6%) and in all normal skin samples analyzed. hTR expression was found in 42 of 45 skin tumors (93.3%) and in 18 of 19 normal skin samples (94.7%). In contrast, hTERT expression was detected in 33 of 45 skin tumors (73.3%) and in only 3 of 19 normal skin samples (15.8%). Telomerase activity was positive in 33 of 45 skin tumors (73.3%) and in 3 of 19 normal skin samples (15.8%). All together, 53 of 64 cases (82.8%) were concordant for both results (P < 0.001), i.e., telomerase activity positive and hTERT positive, or telomerase activity negative and hTERT negative. CONCLUSIONS: Activation of telomerase activity in skin tumors is strongly correlated with hTERT expression.

Catalytic Domain↗
PubMed1999

Thymic transplantation across an MHC class I barrier in swine.

Thymic tissue transplantation has been performed previously in adult mice to induce donor-specific tolerance across allogeneic and xenogeneic barriers. We have now attempted to extend this technique to a large animal preclinical model and describe here our initial studies of allogeneic thymic transplantation in miniature swine. Two miniature swine were thymectomized before thymic tissue transplantation, and two remained euthymic. Donor thymic tissue was harvested from SLA class I-mismatched juvenile pigs and placed into recipient sternocephalicus muscle, kidney capsule, and omentum. A 12-day course of cyclosporin A was started on the day of transplantation. Allogeneic thymic engraftment could only be achieved in euthymic and not in thymectomized miniature swine using this treatment regimen. Both nonthymectomized animals showed good graft development, with evidence of thymopoiesis, as indicated by positive CD1 and host-type SLA class I immunoperoxidase staining of immature graft-infiltrating cells. Both animals also demonstrated donor-specific T cell hyporesponsiveness, as measured by MLR and cell-mediated lympholysis. The thymic grafts continued to develop despite the appearance of high levels of anti-donor specific cytotoxic IgG Abs. Thus, thymic tissue transplanted across an SLA class I barrier can engraft and support host thymopoiesis in euthymic miniature swine. The presence of the host thymus was required for engraftment. These data support the potential of thymic transplantation as part of a regimen to induce donor-specific tolerance to xenogeneic organ grafts.

Animals↗
PubMed1999

Opposing effects of reactive oxygen species and cholesterol on endothelial nitric oxide synthase and endothelial cell caveolae.

Synthesis of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) is critical for normal vascular homeostasis. eNOS function is rapidly regulated by agonists and blood flow and chronically by factors that regulate mRNA stability and gene transcription. Recently, localization of eNOS to specialized plasma membrane invaginations termed caveolae has been proposed to be required for maximal eNOS activity. Because caveolae are highly enriched in cholesterol, and hypercholesterolemia is associated with increased NO production, we first studied the effects of cholesterol loading on eNOS localization and NO production in cultured bovine aortic endothelial cells (BAECs). Caveolae-enriched fractions were prepared by OptiPrep gradient density centrifugation. Treatment of BAECs with 30 microgram/mL cholesterol for 24 hours stimulated significant increases in total eNOS protein expression (1.50-fold), eNOS associated with caveolae-enriched membranes (2.23-fold), and calcium ionophore-stimulated NO production (1.56-fold). Because reactive oxygen species (ROS) contribute to endothelial dysfunction in hypercholesterolemia, we next studied the effects of ROS on eNOS localization and caveolae number. Treatment of BAECs for 24 hours with 1 micromol/L LY83583, a superoxide-generating napthoquinolinedione, decreased caveolae number measured by electron microscopy and prevented the cholesterol-mediated increases in eNOS expression. In vitro exposure of caveolae-enriched membranes to ROS (xanthine plus xanthine oxidase) dissociated caveolin more readily than eNOS from the membranes. These results show that cholesterol treatment increases eNOS expression, whereas ROS treatment decreases eNOS expression and the association of eNOS with caveolin in caveolae-enriched membranes. Our data suggest that oxidative stress modulates endothelial function by regulating caveolae formation, eNOS expression, and eNOS-caveolin interactions.

Animals↗
PubMed1999

Prostaglandin E2 enhancement of interferon-gamma production by antigen-stimulated type 1 helper T cells.

Prostaglandin E2 (PGE2) is a potent mediator generated in immune tissues by cyclooxygenation of arachidonic acid. PGE2 affects T cell functions through four homologous G protein-coupled receptors termed EP1R, EP2R, EP3R, and EP4R that differ in tissue distribution and signaling. Antigen-evoked secretion of interferon-gamma (IFN-gamma) by sperm whale myoglobin-specific Th1 cells of DBA/2 mouse I-Ed-restricted clones, that express EP3Rs and EP4Rs, was enhanced a maximum of 3-fold by 10(-10) to 10(-8) M PGE2 and 2.5-fold each for the EP1R/EP3R-directed agonist sulprostone (10(-8) and 10(-7) M) and for the EP4R/EP3R/EP2R agonist misoprostol (10(-9) M). Neither PGE2 nor the synthetic analogs affected secretion of IFN-gamma by PMA plus ionomycin-stimulated clones of Th1 cells. Antigen-evoked secretion of IFN-gamma by influenza hemagglutinin-specific mouse lymph node Th1 cells, that also express EP3Rs and EP4Rs, was increased a maximum of 12-fold by 10(-9) to 10(-8) M PGE2, 14-fold by 10(-9) M sulprostone, and 10-fold by 10(-9) M misoprostol. Production of IFN-gamma by either type of Th1 cell was not affected significantly by 10(-6) M PGE2 alone. The generation of IFN-gamma by antigen-stimulated Th1 cells thus is significantly enhanced by physiologically relevant concentrations of PGE2.

Animals↗
PubMed1999

Deletion of chromosome 1 predicts prognosis in pancreatic endocrine tumors.

Endocrine tumors, such as parathyroid adenomas and pheochromocytomas, frequently have deletions of chromosome 1, suggesting that inactivation of a tumor suppressor gene from chromosome 1 is important in their tumorigenesis. We hypothesized that deletion of chromosome 1 may contribute to pancreatic endocrine tumor formation. Twenty-nine sporadic and MEN1 pancreatic endocrine tumors were studied for loss of heterozygosity (LOH) with 12 chromosome 1 microsatellite markers. LOH on chromosome 1 was identified in 10 of 29 (34%) tumors studied. Allele loss occurred more frequently in tumors with hepatic metastases (7 of 8) than tumors without metastases (3 of 21) (P = 0.004). Tumors in patients with lymph node involvement and patients with multiple endocrine neoplasia type 1 did not demonstrate LOH for chromosome 1 markers. These data suggest that loss of chromosome 1 is associated specifically with the development of hepatic metastases in patients with sporadic pancreatic endocrine tumors.

Chromosomes, Human, Pair 1↗