Biomedical subjects

B Wang

Publications and source records attributed to B Wang.

At least 163 records · Page 9Linked to original sources

PubMed2001

Generation of dwarf goat (Capra hircus) clones following nuclear transfer with transfected and nontransfected fetal fibroblasts and in vitro-matured oocytes.

The developmental potential of caprine fetal fibroblast nuclei after in vitro transfection and nuclear transfer (NT) into enucleated, in vitro-matured oocytes was evaluated. Fetal fibroblasts were isolated from Day 27 to Day 30 fetuses from a dwarf breed of goat (BELE: breed early lactate early). Cells were transfected with constructs containing the enhanced green fluorescent protein (eGFP) and neomycin resistance genes and were selected with G418. Three eGFP lines and one nontransfected line were used as donor cells in NT. Donor cells were cultured in Dulbecco minimum Eagle medium plus 0.5% fetal calf serum for 4-8 days prior to use in NT. Immature oocytes were recovered by laparoscopic ovum pick-up and matured for 24 h prior to enucleation and NT. Reconstructed embryos were transferred as cleaved embryos into synchronized recipients. A total of 27 embryos derived from transgenic cells and 70 embryos derived from nontransgenic cells were transferred into 13 recipients. Five recipients (38%) were confirmed pregnant at Day 35 by ultrasound. Of these, four recipients delivered five male kids (7.1% of embryos transferred) derived from the nontransfected line. One recipient delivered a female kid derived from an eGFP line (7.7% of embryos transferred for that cell line). Presence of the eGFP transgene was confirmed by polymerase chain reaction, Southern blotting, and fluorescent in situ hybridization analyses. Nuclear transfer derivation from the donor cells was confirmed by single-strand confirmation polymorphism analysis. These results demonstrate that both in vitro-transfected and nontransfected caprine fetal fibroblasts can direct full-term development following NT.

Animals↗

PubMed2001

Cytomorphometric parameters and the metastatic potential of cutaneous and uveal melanoma: a comparison with prognostic factors.

The Mean of the Ten Largest Nuclei (MTLN1) is one of the most important prognostic factors in uveal malignant melanoma. This study was performed to investigate the applicability of nuclear and nucleolar measurements as a prognostic factor for cutaneous melanoma. A routine light microscope (Carl Zeiss: Axiophot EL-Einnsatz; #451888) at 640 times magnification with a Micrometer Eye Piece (Carl Zeiss: #444034) was used to evaluate the correlation of MTLN1 and Mean of Ten Largest Nuclei (MTLN) with the occurrence of metastasis in 58 primary cutaneous melanoma. For uveal melanoma, cytologic classification was used for comparison. Prognostic value was determined by univariate and multivariate linear regression analysis. MTLN1 was the only significant factor for uveal melanoma (p = 0.05). For cutaneous melanoma, all factors were significantly associated with disease progression. MTLN1 was the only one to remain significant (p + 0.027) in multivariate linear regression analysis. Nuclear and nucleolar morphometry are significant prognostic factors for uveal and cutaneous melanoma.

Humans↗

PubMed2001

Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading.

We sought to review our experience with salivary mucoepidermoid carcinoma (MEC) over two decades to confirm the validity and reproducibility of histologic grading and to investigate MIB-1 index as a prognosticator. Diagnosis was confirmed on 80 cases, and chart review or patient contact was achieved for 48 patients, with follow-up from 5 to 240 months (median 36 months). Immunohistochemistry with citrate antigen retrieval for MIB-1 was performed on a subset of cases. Kaplan-Meier survival curves were generated for each stage, site, and grade according to our proposed grading system. To address the issue of grading reproducibility, 20 slides were circulated among five observers, without prior discussion; slides were categorized as low-, intermediate-, or high-grade according to one's "own" criteria, and then according to the AFIP criteria proposed by Goode et al.10 Weighted kappa (kappa) estimates were obtained to describe the extent of agreement between pairs of rating. The Wilcoxon signed rank test or the Friedman test as appropriate tested variation across ratings. There was no gender predominance and a wide age range (15-86 years, median 49 years). The two most common sites were parotid and palate. All grade 1 MECs presented as Stage I tumors, and no failures were seen for this category. The local disease failure rates at 75 months for grades 2 and 3 MEC were 30% and 70%, respectively. Tumor grade, stage, and negative margin status all correlated with disease-free survival (DFS) (p = 0.0091, 0.0002, and 0.048, respectively). The MIB index was not found to be predictive of grade. Regarding the reproducibility of grading, the interobserver variation for pathologists using their "own" grading, as expressed by the kappa value, ranged from good agreement (kappa = 0.79) to poor (kappa = 0.27) (average kappa = 0.49). A somewhat better interobserver reproducibility was achieved when the pathologists utilized the standardized AFIP criteria (average kappa = 0.61, range 0.38-0.77). This greater agreement was also reflected in the Friedman test (statistical testing of intraobserver equality), which indicated significant differences in using one's own grading systems (p = 0.0001) but not in applying the AFIP "standardized" grading (p = 0.33). When one's own grading was compared with the AFIP grading, there were 100 pairs of grading "events," with 46 disagreements/100 pairs. For 98% of disagreements, the AFIP grading "downgraded" tumors. This led us to reanalyze a subset of 31 patients for DFS versus grade, for our grading schema compared with the AFIP grading. Although statistical significance was not achieved for this subset, the log rank value revealed a trend for our grading (p = 0.0993) compared with the Goode schema (p = 0.2493). This clinicopathologic analysis confirms the predictive value of tumor staging and three-tiered histologic grading. Our grading exercise confirms that there is significant grading disparity for MEC, even among experienced ENT/oral pathologists. The improved reproducibility obtained when the weighted AFIP criteria were used speaks to the need for an accepted and easily reproducible system. However, these proposed criteria have a tendency to downgrade MEC. Therefore, the addition of other criteria (such as vascular invasion, pattern of tumor infiltration [i.e., small islands and individual cells vs cohesive islands]) is necessary. We propose a modified grading schema, which enhances predictability and provides much needed reproducibility.

Adolescent↗

PubMed2001

Thrombolytic therapy: what is its role in free flap salvage?

Thrombolytic agents have been demonstrated to improve free flap salvage in animal models. However, clinical evidence regarding their efficacy has been scant. The authors reviewed their experience with flap salvage using thrombolytic therapy in 1,733 free flaps from February 1990 to July 1998. Patients with intraoperative pedicle thrombosis were excluded from this review. Forty-one of the 55 free flaps that were reexplored emergently were identified as having pedicle thrombosis. Of these 41 flaps, 28 free flaps were salvaged (flap salvage group, 68%) and 13 free flaps failed (flap failure group, 32%). Thrombolytic therapy (urokinase in 7 patients, tissue plasminogen activator in 1 patient) was used in six flaps in the flap salvage group and two flaps in the flap failure group. Statistical analysis demonstrated no difference between the two groups with regard to thrombolytic therapy. There was also no difference between the two groups with regard to use of systemic heparin (100-500 U per hour) at the time of pedicle thrombosis or with regard to whether Fogarty catheters were used. Smoking, preoperative radiotherapy, and the use of interpositional vein grafts during initial flap reconstruction had no impact on the outcome of flap salvage. The flap salvage group was reexplored at a mean of 1.5 days compared with the flap failure group, which was reexplored at a mean of 4.2 days (p = 0.007). Early detection of pedicle thrombosis remains the most important factor in the salvage of free flaps. Although these numbers are small and definitive statements cannot be made, the role of thrombolytic agents in free flap salvage requires further clinical evaluation.

Fibrinolytic Agents↗

PubMed2001

Synthetic 1,4-anthracenediones, which block nucleoside transport and induce DNA fragmentation, retain their cytotoxic efficacy in daunorubicin-resistant HL-60 cell lines.

Anthracene-1,4-dione and 6,7-dichloro-1,4-anthracenedione (code names AQ1 and AQ4, respectively) are cytostatic (IC50: 53 and 110 nM, respectively) and cytotoxic (IC50: 100 and 175 nM, respectively) in wild-type drug-sensitive HL-60-S tumor cells at day 4 in vitro. Therefore, the antitumor effects of these drugs were assessed and compared to those of daunorubicin (DAU) in HL-60-RV and HL-60-R8 tumor cells, which are, respectively, P-glycoprotein-positive and -negative multidrug-resistant (MDR) sublines. In contrast to DAU, which loses its cytostatic [resistance factors (RFs): 30.3-31.8] and cytotoxic (RFs: 48.8-58.1) activities in MDR sublines, AQ1 inhibits cell proliferation (RFs: 0.9-1.3) and cell viability (RFs: 1.4-1.6) as effectively in HL-60-RV and HL-60-R8 as in HL-60-S cells. Similarly, DAU decreases the rate of DNA synthesis less effectively in MDR sublines (RFs: 8.0-13.3) but AQ1 inhibits the incorporation of [3H]thymidine into DNA to the same degree in HL-60-S as in HL-60-RV and HL-60-R8 cells (RFs: 0.9-1.1). In contrast to DAU, which is ineffective, the advantage of AQ1 is its ability to block the cellular transport of purine and pyrimidine nucleosides in HL-60-S cells, an effect which persists in the MDR sublines (RFs: 1.1). AQ4, which mimics to a lesser degree all the antitumor effects of AQ1, except the inhibition of adenosine transport, also retains its effectiveness in MDR sublines (RFs: 1.1-3.1). The peaks of DNA cleavage caused by DAU and AQ1 in HL-60-S cells shift to lower concentrations with increasing times of drug exposure but DAU loses most of its ability to induce DNA fragmentation in MDR sublines, whereas the levels of AQ1-induced DNA cleavage at 16 and 24 h are nearly equivalent in HL-60-S, HL-60-RV and HL-60-R8 cells. Because they not only mimic the antitumor effects of DAU in the nM range but also block nucleoside transport and remain effective in tumor cells that have developed different mechanisms of MDR, AQ1 and AQ4 analogs might be valuable to develop new means of polychemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Biomechanical evaluation of flexor tendon repair techniques.

Immediate active mobilization of repaired tendons is thought to be the most effective way to restore function of injured flexor tendons. Sixty human flexor digitorum profundus tendons were used to evaluate techniques for active tendon motion. The tendons were divided equally into six groups, and each group was assigned to one of the following techniques: Kessler core suture plus running peripheral suture, Kessler plus cross-stitch suture, Kessler plus Halsted suture, Tang core suture plus running peripheral suture, Tang plus cross-stitch suture, or Tang plus Halsted suture. Immediately after tendon repair, an Instron tensile testing machine was used to measure the 2-mm gap formation force, ultimate strength, elastic modulus, and energy to failure of the tendons repaired by these techniques. Ultimate strength, elastic modulus, and energy to failure were measured in load displacement curve. Results showed that the ultimate strength of the Tang plus Halsted or cross-stitch was, respectively, 116.8 +/- 9.6 N and 94.6 +/- 7.8 N; and 2-mm gap formation force was, respectively, 86.6 +/- 4.9 N and 71.9 +/- 5.1 N. The Tang plus Halsted or cross-stitch methods had a statistically significant increase in ultimate strength and 2-mm gap formation force as compared with the Kessler core suture or Tang plus running peripheral suture method. Elastic modulus and energy to failure of the Tang plus Halsted or cross-stitch suture were statistically higher than those of other techniques. The Tang plus cross-stitch or Tang plus Halsted sutures had the highest strength among the tested methods and are appropriate techniques for tendon repair in which the goal is immediate active tendon motion.

Biomechanical Phenomena↗

PubMed2001

Beneficial effects of growth hormone on bacterial translocation during the course of acute necrotizing pancreatitis in rats.

Because bacterial translocation from the gut is one of the important sources of bacterial infection in acute necrotizing pancreatitis (ANP) and growth hormone (GH) has the ability to promote the intestinal epithelial proliferation, we investigated the effects of GH on bacterial translocation in a rat ANP model. ANP was induced in rats by injection of 5% sodium taurocholate into the biliopancreatic duct. The rats with ANP were treated with either human recombinant GH or placebo. Laparotomized animals without induction of ANP (sham operation [SO]) served as controls. At 24 hours after operation, blood was drawn for bacterial culture and determination of amylase, lipase, and endotoxin. Peritoneal fluid and specimens of mesenteric lymph nodes (MLN), liver, pancreas, and spleen were taken for bacterial culture by standard techniques. Intestinal mucosal permeability was assessed by measuring the movement of 125I-labeled albumin from blood to intestinal lumen. Insulin-like growth factor-1 (IGF-1) mRNA was detected in the liver and ileum by reverse transcriptase-polymerase chain reaction (RT-PCR). Morphologic changes of pancreas and ileum were also analyzed. Administration of GH significantly decreased the serum amylase, lipase activities, plasma endotoxin level, and incidence of bacterial translocation. Moreover, the survival rate of ANP rats was improved. The severity of inflammation in pancreas and ileum was alleviated by GH treatment. Ileal mucosal thickness, villus height, and crypt depth in GH treatment rats were obviously increased compared with those of ANP rats. The intestinal permeability was markedly improved in the GH group versus the ANP group. GH treatment resulted in up-regulation of IGF-1 mRNA expression in ileum, but not in liver. These results suggested that exogenous GH had beneficial effects in maintaining the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation in rats with ANP. One of the mechanisms might be the up-regulation of IGF-1 mRNA in intestine by GH treatment.

Amylases↗

PubMed2001

Diagnostic value of apparent diffusion coefficient hyperintensity in selected patients with acute neurologic deficits.

BACKGROUND AND PURPOSE: A pattern of decreased intensity on apparent diffusion coefficient (ADC) maps is useful in the early detection of ischemic brain injury. Less information exists with regard to patients with acute neurologic deficits in whom there is abnormal conventional magnetic resonance imaging (MRI) and increased ADC intensity. METHODS: The authors identified 13 patients with acute neurologic deficits who underwent diffusion MRI and had calculated ADC maps demonstrating hyper-intensity in regions characterized by computed tomography hypodensity and MRI T2 hyperintensity. The initial and follow-up imaging characteristics and clinical syndromes were recorded. RESULTS: Clinical syndromes included hypertensive encephalopathy, posterior leukoencephalopathy, hyperperfusion following carotid endarterectomy, venous sinus thrombosis, HIV encephalopathy, and brain tumor. Diffusion-weighted imaging (DWI) was hyperintense in 3 of 13 patients, isointense in 4 of 13 patients, heterogeneous in 3 of 13 patients, and hypointense in 3 of 13 patients. The ADC values in these regions were significantly higher than those in control regions (P < .0001). At early follow-up, MRI abnormalities resolved completely in 3 of 13 patients and partially in 9 of 13 patients. MRI abnormalities were unchanged in 1 patient. CONCLUSIONS: In the evaluation of patients with acute neurologic deficits, ADC hyperintensity may identify a subset of patients with vasogenic edema of nonischemic etiology. Frequently, these conditions are potentially reversible if appropriately managed. DWI and conventional images alone are not sufficient to identify these neurologic conditions.

Acute Disease↗

PubMed2001

The contribution of chemoreflex drives to resting breathing in man.

The contribution of automatic drives to breathing at rest, relative to behavioural drives such as "wakefulness", has been a subject of debate. We measured the combined central and peripheral chemoreflex contribution to resting ventilation using a modified rebreathing method that included a prior hyperventilation and addition of oxygen to maintain isoxia at a P(ET,O2) (end-tidal partial pressure of oxygen) of 100 mmHg. During rebreathing, ventilation was unrelated to P(ET,CO2) (end-tidal partial pressure of carbon dioxide) in the hypocapnic range, but after a threshold P(ET,CO2) was exceeded, ventilation increased linearly with P(ET,CO2). We considered the sub-threshold ventilation to be an estimate of the behavioural drives to breathe (mean +/- S.E.M. = 3.1 +/- 0.5 l min(-1)), and compared it to ventilation at rest (mean +/- S.E.M. = 9.1 +/- 0.7 l min(-1)). The difference was significant (Student's paired t test, P < 0.001). We also considered the threshold P(CO2) observed during rebreathing to be an estimate of the chemoreflex threshold at rest (mean +/- S.E.M. = 42.0 +/- 0.5 mmHg). However, P(ET,CO2) during rebreathing estimates mixed venous or tissue P(CO2), whereas the resting P(ET,CO2) during resting breathing estimates P(a,CO2) (arterial partial pressure of carbon dioxide). The chemoreflex threshold measured during rebreathing was therefore reduced by the difference in P(ET,CO2) at rest and at the start of rebreathing (the plateau estimates the mixed venous P(CO2) at rest) in order to make comparisons. The corrected chemoreflex thresholds (mean +/- S.E.M. = 26.0 +/- 0.9 mmHg) were significantly less (paired Student's t test, P < 0.001) than the resting P(ET,CO2) values (mean +/- S.E.M. = 34.3 +/- 0.5 mmHg). We conclude that both the behavioural and chemoreflex drives contribute to resting ventilation. Experimental Physiology (2001) 86.1, 109-116.

Adult↗

PubMed2001

SH2 domain-mediated interaction of inhibitory protein tyrosine kinase Csk with protein tyrosine phosphatase-HSCF.

The protein tyrosine kinase (PTK) Csk is a potent negative regulator of several signal transduction processes, as a consequence of its exquisite ability to inactivate Src-related PTKs. This function requires not only the kinase domain of Csk, but also its Src homology 3 (SH3) and SH2 regions. We showed previously that the Csk SH3 domain mediates highly specific associations with two members of the PEP family of nonreceptor protein tyrosine phosphatases (PTPs), PEP and PTP-PEST. In comparison, the Csk SH2 domain interacts with several tyrosine phosphorylated molecules, presumed to allow targetting of Csk to sites of Src family kinase activation. Herein, we attempted to understand better the regulation of Csk by identifying ligands for its SH2 domain. Using a modified yeast two-hybrid screen, we uncovered the fact that Csk associates with PTP-HSCF, the third member of the PEP family of PTPs. This association was documented not only in yeast cells but also in a heterologous mammalian cell system and in cytokine-dependent hemopoietic cells. Surprisingly, the Csk-PTP-HSCF interaction was found to be mediated by the Csk SH2 domain and two putative sites of tyrosine phosphorylation in the noncatalytic portion of PTP-HSCF. Transfection experiments indicated that Csk and PTP-HSCF synergized to inhibit signal transduction by Src family kinases and that this cooperativity was dependent on the domains mediating their association. Finally, we obtained evidence that PTP-HSCF inactivated Src-related PTKs by selectively dephosphorylating the positive regulatory tyrosine in their kinase domain. Taken together, these results demonstrate that part of the function of the Csk SH2 domain is to mediate an inducible association with a PTP, thereby engineering a more efficient inhibitory mechanism for Src-related PTKs. Coupled with previously published observations, these data also establish that Csk forms complexes with all three known members of the PEP family.

Amino Acid Sequence↗

PubMed2001

Asthma, rhinitis, and skin test reactivity to aeroallergens in families of asthmatic subjects in Anqing, China.

In industrialized countries with a Western lifestyle, sensitization to perennial aeroallergens is strongly associated with asthma, whereas sensitization to seasonal aeroallergens is closely related to allergic rhinitis. Little is known, however, about the relation between skin test reactivity to aeroallergens and either asthma or rhinitis in mainland China. We studied 10,009 members of 2,544 families in Anqing (China) that were selected on the basis of physician-diagnosed asthma in at least two siblings. Generalized estimating equations were employed to study the association between skin test reactivity to aeroallergens and either asthma or rhinitis. After adjustment for age, sex, intensity of smoking, skin test reactivity to other aeroallergens, and household correlations, sensitization to dust mite was an independent predictor of both asthma (OR = 1.3, 95% CI = 1.1 to 1.5, p = 0.008) and rhinitis (OR = 1.3, 95% CI = 1.0 to 1.8, p = 0.04). Sensitization to mold was significantly associated with asthma (OR = 1.6, 95% CI = 1.1 to 2.3, p = 0.008), and sensitization to silk was an independent predictor of rhinitis (OR = 1.5, 95% CI = 1.1 to 2.2, p = 0.02). Although 46.9% of the study participants were sensitized to at least one allergen, only 3.5% of study subjects reported nasal symptoms consistent with rhinitis. Among asthmatic subjects, 6.2% reported nasal symptoms. Whereas sensitization to perennial aeroallergens was associated with asthma among families of asthmatic subjects in rural China, sensitization to silk was the strongest predictor of rhinitis in this population. Our findings also suggest that allergic rhinitis is far less common among asthmatic subjects in rural China than in asthmatic subjects in industrialized countries with a Western lifestyle.

Adolescent↗

PubMed2001

Association of asthma with beta(2)-adrenergic receptor gene polymorphism and cigarette smoking.

Recent studies have suggested that two polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) gene at codons 16 (arginine to glycine) and 27 (glutamine to glutamate) affect an individual's airway responsiveness, or response to acute or chronic beta(2)-agonist therapy but are not risk factors for asthma. We hypothesize that there is an interaction effect on asthma between the beta(2)AR gene polymorphisms and cigarette smoking. A case-control study was conducted in 128 asthma cases and 136 control individuals identified from 10,014 studied subjects in rural Anqing, China. Allele-specific polymerase chain reaction (PCR) was used to genotype beta(2)AR gene polymorphisms. Multiple logistic regression was used to adjust for potential confounding factors. We found a marginally significant interaction between cigarette smoking and beta(2)AR-16 genotype after adjusting for important confounding factors (p = 0.06). Specifically, we found that compared with never-smoking Gly-16 homozygotes, those ever-smokers who are Arg-16 homozygotes had a significantly increased risk of asthma (odds ratio [OR] = 7.81; 95% confidence interval [CI]: 2.07 to 29.5). This association showed a clear dose-response relationship with the number of cigarettes smoked. However, there was no significant association of asthma with polymorphisms of the beta(2)AR at position 27 (OR = 1.38; 95% CI: 0.69 to 2.73). Our study suggests a gene-environment interaction between the Arg-16 genotype and ever cigarette smoking with respect to the susceptibility of an individual to asthma.

Adult↗

PubMed2001

BR22, a novel protein, interacts with thyroid transcription factor-1 and activates the human surfactant protein B promoter.

Surfactant protein (SP)-B expression is restricted to type II pneumocytes and Clara cells in the lung. Previously, a promoter region of human SP-B gene from -64 to -118 has been identified as critical for the tissue-specific expression of this gene. Two cis-elements for thyroid transcription factor (TTF)-1 and hepatocyte nuclear factor (HNF)-3alpha binding were found within this area. Using an oligonucleotide fragment, we incorporated this region sequence into the promoter of a HIS3 reporter gene in yeast. With this modified yeast a human lung complementary DNA (cDNA) library was screened for DNA-binding proteins, other than TTF-1 and HNF-3alpha, that interacted with this promoter segment. A cDNA clone encoding a novel polypeptide, BR22, was identified that activated the reporter gene expression in yeast. This gene is expressed in many tissues and encodes a protein with bipartite nuclear localization signals. Studies using in vivo yeast two-hybrid analysis, in vitro protein-protein interactions, and coimmunoprecipitation analyses demonstrated that BR22 formed a protein complex with TTF-1. In vivo cotransfection studies further indicated that BR22 could act with TTF-1 to synergistically activate the SP-B promoter in mammalian cells. Our data suggest that BR22 is a TTF-1-associated protein. Through a protein-protein interaction with TTF-1, BR22 can form a complex and activate the human SP-B promoter in vivo.

Amino Acid Sequence↗

PubMed2001

Involvement of p53-dependent apoptosis in radiation teratogenesis and in the radioadaptive response in the late organogenesis of mice.

The irradiation of fetuses at the late period of organogenesis has been known to induce a dramatic increase in malformations. The mechanisms involved, however, have remained unclear for a long time. Using the mouse limb bud system, we first found that radiation-induced apoptosis is involved in the malformation, namely, radiation-induced apoptosis in the predigital regions of embryonic limb buds is responsible for digital defects in mice. An examination of embryonic C57BL/6J mice with different p53 (trp53) status enabled us to further find that susceptibility to radiation-induced apoptosis in the predigital regions and digital defects depend on both the p53 status and the radiation dose; p53 wild-type mice appeared to be the most sensitive, while p53 knockout mice were the most resistant. These results indicate that p53-dependent apoptosis mediates radiation-induced digital defects in the later organogenesis period. The existence of a radioadaptive response in embryonic mice, which has not been reported so far, was found by irradiating embryos with either 5 cGy or 30 cGy on embryonic day 11 prior to a challenging irradiation at 3 Gy on embryonic day 12. p53-heterozygous embryos did not show the radioadaptive response, indicating the involvement of p53 in the radioadaptive response in embryogenesis.

Adaptation, Physiological↗

PubMed2001

Fas-independent apoptosis induced by UVC in p53-mutated human epithelial tumor A431 cells through activation of caspase-8 and JNK/SAPK.

A431 cells/UVC-induced apoptosis/Caspase 8/Fas/JNK/PAPK. We previously observed that p53-mutated human epithelial tumor A431 cells underwent apoptosis after ultraviolet C (UVC) irradiation through the caspases-8 and -3 pathway. Fas/FasL is known to initiate apoptosis in several cell lines via caspase-8 activation. Then, to determine if Fas/FasL mediates apoptosis in A431. we investigated Fas expression and modulation in UVC-irradiated A431 cells. A431 constitutively expressed Fas, which gradually decreased after UVC-irradiation. Pretreatment with a neutralizing anti-Fas antibody, ZB4, did not abrogate the UVC-induced apoptosis. An agonistic anti-Fas antibody, CH11, very slowly induced apoptosis in A431. suggesting that the constitutively expressed Fas had a low functional potential. Hence, UVC-induced apoptosis in A431 seems to occur independent of the Fas signal. Interestingly, however, a pretreatment with CH11 remarkably potentiated UVC-induced apoptosis. An inhibitor of caspase-8, Ac-IETD-CHO, partially inhibited UVC-induced apoptosis. JNK was phosphorylated immediately after exposure to UVC. prior to apoptotic chromatin condensation. Our data suggest that the activation of caspase-8 occurs independent of Fas upregulation, and that JNK/ SAPK contributes to UVC-induced apoptosis in human epithelial A431 cells.

Apoptosis↗

PubMed2001

Genetic variation in the promoter region of the beta2 bradykinin receptor gene is associated with essential hypertension in a Chinese Han population.

The present study examined whether a genetic variant (-58T/C) in the promoter region of the human beta2 bradykinin receptor gene was genetically involved in essential hypertension. Chinese hypertensive subjects (n = 120) and normotensive controls (n = 98; sex- and age-matched with hypertensives) were recruited from the outpatients of Fu Wai hospital. Distribution of the -58T/C polymorphism was determined in patients and controls by means of PCR, SSCP, cloning and sequencing. The allelic frequencies were 0.56 for the C allele and 0.44 for the T allele in hypertensive subjects, and 0.46 for the C allele and 0.54 for the T allele in normotensive subjects. The allelic frequencies were in Hardy-Weinberg equilibrium. Significant differences between hypertensive and normotensive subjects were seen in the genotypes distribution (p = 0.045) and allelic frequencies (p = 0.033). These results suggested that -58C allele of the human beta2 bradykinin receptor gene may be an independent risk factor for essential hypertension in the Chinese Han population.

Aged↗

PubMed2001

Association of airway responsiveness with asthma and persistent wheeze in a Chinese population.

STUDY OBJECTIVES: Data from a cross-sectional study were analyzed to examine the association of increased airway responsiveness with physician-diagnosed asthma and persistent wheeze. DESIGN: Two methods for calculating the provocative dose that decreases the airflow rate by 20% (PD(20)) were used as indexes for increased airway responsiveness: (1) a 20% drop in FEV(1) calculated from baseline FEV(1) (PD(20)b), and (2) a 20% drop in FEV(1) from FEV(1) measurements after inhalation of saline solution (PD(20)s). Both PD(20)b and PD(20)s were measured through induction by varying doses of methacholine. SETTING: Anqing, Anhui Province, China. PARTICIPANTS: Study subjects were 8 to 74 years of age and were classified into four groups: children (< 15 years old), young adults (15 to 29 years old), adults (30 to 44 years old), and older adults (> or 5 years old). INTERVENTIONS: The differences in estimated odds ratios of airway hyperresponsiveness with asthma and wheeze, sensitivity and specificity, and coefficients of variation were compared between PD(20)b and PD(20)s. The sample for analysis consisted of 10,284 subjects from 2,663 nuclear families with complete data on wheeze, asthma, and major potential confounding factors. MEASUREMENTS AND RESULTS: The prevalence of asthma in this sample was lowest in subjects with no demonstrable PD(20) and had a reverse dose-response relationship with PD(20) across all age groups. Using the receiver operating characteristic, the sensitivity and specificity of the PD(20)s or PD(20)b were found to be almost identical. A similar trend was found for persistent wheeze, although the estimated odds ratios for persistent wheeze appeared slightly smaller than those for physician-diagnosed asthma. CONCLUSIONS: This study demonstrates a dose-response relationship between increased airway responsiveness and asthma and wheeze in this Chinese population. PD(20)s or PD(20)b yielded virtually indistinguishable results, which indicated that either of the two tests could serve as an index of airway hyperresponsiveness.

Adolescent↗

PubMed2001

Dioxin exposure is an environmental risk factor for ischemic heart disease.

Epidemiologic studies have linked dioxin exposure to increased mortality caused by ischemic heart disease. To test the hypothesis that dioxin exposure may constitute an environmental risk factor for atherosclerosis, we exposed C57BL/6J mice to 5 microg/kg of dioxin daily for 3 d, and measured various molecular and physiological markers of heart disease. Dioxin treatment led to an increase in the urinary excretion of vasoactive eicosanoids and an elevation in the mean tail-cuff blood pressure. In addition, dioxin exposure led to an increase in triglycerides, but not in high-density lipoproteins, in both Apoe(+/+) mice and in hyperlipidemic Apoe(-/- mice. Dioxin exposure also led to an increase in low-density lipoproteins in Apoe(-/-) mice. After treatment, dioxin was associated with low-density lipoprotein particles, which might serve as a vehicle to deliver the compound to atherosclerotic plaques. Dioxin treatment of vascular smooth-muscle cells taken from C57Bl/6J mice resulted in the deregulation of several genes involved in cell proliferation and apoptosis. Subchronic treatment of Apoe(-/-) mice with dioxin (150 ng/kg, three times weekly) for 7 or 26 wk caused a trend toward earlier onset and greater severity of atherosclerotic lesions compared to those of vehicle treated mice. These results suggest that dioxin may increase the incidence of ischemic heart disease by exacerbating its severity.

Animals↗