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Biomedical subjects

H Wei

Publications and source records attributed to H Wei.

At least 217 records · Page 12Linked to original sources

Relationship of oxidative events and DNA oxidation in SENCAR mice to in vivo promoting activity of phorbol ester-type tumor promoters.

Reactive oxygen species (ROS) have been implicated as being involved in tumor promotion processes. However, the mechanism by which ROS modulate tumor promotion has not as yet been elucidated. In this report, we show that phorbol ester-type tumor promoters (12-O-tetradecanoylphorbol-13-acetate [TPA], mezerein and 12-O-retinoylphorbol-13-acetate [RPA]), which vary in their in vivo potencies, also differ in their effect on formation of hydrogen peroxide (H2O2) and oxidation of normal bases to 5-hydroxymethyl-2'-deoxyuridine [HMdU] and 8-hydroxyl-2'-deoxyguanosine [8-OHdG] in the DNA of SENCAR mouse epidermis, though they are equipotent in causing infiltration of polymorphonuclear leukocytes (PMNs). Treatment of SENCAR mice with the chemopreventive agents (-)-epigallocatechin gallate or tamoxifen (6.5 nmol) prior to application of TPA (6.5 nmol) diminished PMN infiltration, and formation of H2O2, HMdU and 8-OHdG. These results strengthen the evidence that ROS are involved in tumor promotion, and that generation of ROS and the subsequent oxidative DNA modification are related to the tumor-promoting potencies of the different phorbol ester-type promoters.

Animals↗

A flow dialysis cell for on-line measurement of glucose in fermentation broth.

A plate flow dialysis cell, employing an acetate cellulose ultrafiltration membrane, was designed and tested for applicability to on-line sampling in fermentation. The glucose contained in effluents of both sample stream channel (Channel A) and carrier stream channel (Channel B) was determined with an enzyme electrode flow injection analysis system. Glucose penetration rate was defined as Rp, Rp = Gb/(Ga + Gb), here Ga and Gb are glucose concentrations of effluent of channel A and B respectively. A higher penetration rate was obtained when using phosphate buffer (0.01M) as carrier solution instead of using distilled water. Operating pressure differences, temperature and residential time affected glucose penetration. Under the condition of 0.02MPa pressure differences and 0.23 min of residential time (12.8ml/L), Rp was about 12% in the range of 10-70mM with CV < 4%. When sample stream was yeast broth, the glucose penetration rate Rp was stable for at least 48 hr. Good relationship was observed between on-line and off-line sampling for glucose determination in yeast fermentation, the correlation coefficient r was 0.985.

Culture Media↗

A method for the treatment of anisotropic skeletal muscle layer in the electrocardiographic calculation.

This paper presents an effective method for the treatment of anisotropic skeletal muscle layer in the forward calculation of ECG by FEM. The method can be used in principle to find the potential distribution of the torso surface and the current density of the epicardial surface at the same time on a theoretical electrocardiographic model. In this paper we examined theoretically the transformation relationship between the anisotropy in a local coordinate system and that in the global coordinate system, considering that the anisotropic conductivity of the skeletal muscle layer is orthogonal in the local coordinate system, but the components of the conductivity tensor may not be directed along the axes of the global coordinate system. In order to show the calculation accuracy of the method, we introduced an example that has an analytical solution. We found that the analytic solution and the numerical one are very close and agreeable.

Anisotropy↗

Suppression of tumor promoter-induced oxidative events and DNA damage in vivo by sarcophytol A: a possible mechanism of antipromotion.

Sarcophytol A (Sarp A), a nontoxic compound isolated from marine soft coral, inhibits the in vivo effects of tumor promoters. However, the mechanism of its action is unknown. Our studies show that Sarp A suppresses oxidant formation and DNA oxidation in the epidermis of SENCAR mice exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA). In the short-term experiments, mice were topically pretreated with different doses of Sarp A before 6.5 nmol TPA, and the same treatment was repeated 20 h later. Sarp A significantly decreased the TPA-induced infiltration of neutrophils, the levels of myeloperoxidase in the dermis, and the formation of H2O2, cis-thymidine glycol, 8-hydroxyl-2'-deoxyguanosine, and 5-hydroxymethyl-2'-deoxyuridine in the epidermis. In the long-term studies, repeated TPA applications (3.2 nmol twice a week for 16 weeks) increased cis-thymidine glycol 2.7-fold, 5-hydroxymethyl-2'-deoxyuridine 3.4-fold, and 8-hydroxyl-2'-deoxyguanosine 3.3-fold in epidermal DNA over the basal levels. Application of 350 nmol Sarp A before each TPA treatment significantly decreased the formation of oxidized DNA bases even below those present in the control mouse skin. Histological examination showed that Sarp A also alleviated the TPA-induced inflammatory response and infiltration of phagocytes. Thus, it is possible that suppression of tumor promotion by Sarp A is due (at least in part) to its inhibitory effects on tumor promoter-mediated migration and activation of phagocytes, oxidant formation, and DNA base oxidation.

Animals↗

The screening diagnosis of tetrahydrobiopterin deficient phenylketonuria.

Since 1990, 20 diagnostically confirmed phenylketonuria (PKU) patients have been screened with a tetrahydrobiopterin (BH4) loading test, in which plasma phenylalanine and urinary pterin metabolites were investigated, ind activity of dihydropteridine reductase (DHPR) was determined as well. The results showed that there was no statistical difference between the concentrations of plasma phenylalanine before and after BH4 (20mg/kg) administration in all patients, and values of urinary neopterin and biopterin were within the range of classic PKU. All patients but one had normal activity of DHPR in red cells. This suggests that incidence of BH4 deficiency in PKU patients amounts to five percent (1/20) which is almost the same as reported abroad.

Biopterins↗

Hypothalamic-pituitary function assessment in children by a combined stimulation test.

We utilized a combined stimulation test using insulin, thyrotropin-releasing hormone, gonadotropin-releasing hormone and levodopa to assess multiple pituitary hormones including growth hormone, thyrotropin, prolactin and gonadotropins in 32 children of short stature and 18 girls with early appearance of puberty. It was found that this combined stimulation test can assess multiple hormone responses with satisfactory results in a single 90-min test. Compared with any of those laborious classic stimulation tests alone, it is easier to be carried out and willingly accepted by children.

Child↗

Activation of oncogenes and/or inactivation of anti-oncogenes by reactive oxygen species.

Abundant evidence indicates that reactive oxygen species (ROS) are involved in mutagenesis and carcinogenesis. These chemical-generated or phagocyte-released ROS are known to cause a variety of genetic alterations which lie at the heart of the carcinogenic process. ROS have also been shown to cause malignant transformation of normal cells, and to increase expression of certain proto-oncogenes such as c-fos and c-jun. It is known that certain proto-oncogenes and anti-oncogenes may serve as the targets of carcinogens of various sorts. I hypothesize that ROS-mediated DNA damage may cause mutations and/or deletions in certain specific coding regions of tumor-related genes, and could be responsible for subsequent activation of oncogenes and/or inactivation of anti-oncogenes.

Animals↗

Experimental study of high-frequency two-way jet ventilation.

BACKGROUND AND METHODS: A new mode of jet ventilation, high-frequency two-way jet ventilation, was devised and introduced to increase CO2 elimination. High-frequency two-way jet ventilation was achieved by adding reverse jet pulses inside the trachea through an intratracheal reverse jet system to the expiratory phase of common high-frequency jet ventilation. The ventilatory efficiency and features of high-frequency two-way jet ventilation were investigated and compared with those features of high-frequency jet ventilation in ten dogs in the same experimental condition. Random sample selection and randomized crossover trial were used for comparison between high-frequency two-way jet ventilation and high-frequency jet ventilation. Peak inspiratory pressure, end-expiratory pressure, and the arterial blood gas variables (PaO2, PaCO2, and pH) were measured during the study. RESULTS: PaCO2 with high-frequency two-way jet ventilation was about 35% lower than that with high-frequency jet ventilation (from 45 to 29 torr [6.0 to 3.9 kPa], p less than .01). Simultaneously, peak inspiratory pressure and end-expiratory pressure during high-frequency two-way jet ventilation were significantly lower than those same variables measured during high-frequency jet ventilation. End-expiratory pressure of high-frequency two-way jet ventilation was a negative pressure (-2.45 +/- 0.45 cm H2O). The pH of high-frequency two-way jet ventilation was significantly higher than that of high-frequency jet ventilation. CONCLUSIONS: Compared with high-frequency jet ventilation, high-frequency two-way jet ventilation demonstrated a ventilatory feature of increasing CO2 elimination and simultaneously decreasing airway pressure.

Animals↗

In vivo formation of oxidized DNA bases in tumor promoter-treated mouse skin.

There has been a paucity of evidence showing that 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a potent tumor promoter, causes DNA damage in vivo. We show that oxidized DNA bases are formed in the epidermis of TPA-treated SENCAR mice in a dose- and time-dependent manner. As measured by high-performance liquid chromatography and acetylation of nucleosides with [3H]acetic anhydride, these oxidized DNA derivatives include cis-thymidine glycol, 5-hydroxymethyl-2'-deoxyuridine, and 8-hydroxyl-2'-deoxyguanosine. Their maximal formation induced by a single TPA dose occurred within 6-8 h (a 2-5-fold increase). The level of 8-hydroxyl-2'-deoxyguanosine was the lowest (3.2/10(5) bases) and remained almost unchanged for 18 h; thymidine glycol (29.1/10(4) bases) and 5-hydroxymethyl-2'-deoxyuridine (17.3/10(4) bases) declined gradually but were still above controls at 24 h. Reapplication of TPA 20 h after the first dose (time of the maximal polymorphonuclear leukocyte infiltration) enhanced the net formation of 8-hydroxyl-2'-deoxyguanosine by 3.8-fold (P less than 0.05), of cis-thymidine glycol by 1.9-fold (P less than 0.001), and of 5-hydroxymethyl-2'-deoxyuridine by 2.0-fold (P less than 0.01), as compared to those maximally produced by a single TPA dose. Thus, the infiltration of polymorphonuclear leukocytes into TPA-treated mouse skin, which was corroborated by histological examination and the presence of polymorphonuclear leukocyte-specific myeloperoxidase, might play an important role in TPA-induced DNA oxidation in vivo. Our findings provide proof that tumor promoters can induce genetic modification in vivo that is oxidative in nature. Hence, formation of oxidized DNA bases may be responsible for the genetic effects of tumor promoters in carcinogenesis.

Animals↗

Skeletal muscle amino acid and myofibrillar protein mRNA response to thermal injury and infection.

Skeletal muscle changes associated with severe injury were investigated in male Wistar rats subjected to 30% full thickness scald injury (burn) and thermal injury followed by immediate colonization with 10(8) colony-forming units of Pseudomonas aeruginosa (BI). Freely fed animals (FF) and animals pair fed to the BI animals (PF) served as controls. Thermal injury in conjunction with infection produced a rapid and sustained muscle cellular membrane depolarization (transmembrane potential difference at 12 h after injury: FF 92.1 +/- 0.3 and BI 85.2 +/- 2.3 mV; P less than 0.05). This was followed by body weight loss and skeletal muscle protein wasting (gastrocnemius protein at 7 days: FF 0.35 +/- 0.01 and BI 0.16 +/- 0.03 g; P less than 0.05) and intracellular high-energy phosphate depletion (ATP at 10 days: FF 6.6 +/- 0.4 and BI 4.5 +/- 0.4 mumol/g tissue; P less than 0.05). These body and cellular changes were not accounted for by the anorexia alone. Marked alterations in intracellular free amino acids were also noted in the BI group characterized by increases in levels of all amino acids (total intracellular free amino acids at 7 days: FF 51 +/- 7 and BI 91 +/- 12 mM; P less than 0.05) except intracellular glutamine (at 7 days: FF 6.0 +/- 0.2 and BI 2.4 +/- 0.6 mM; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Preparation and certification of lyophilized human urine for trace metals reference material in China.

The preparation of lyophilized human urine certified reference material (CRM) was established on the basis of literature in other countries and domestic conditions. The homogeneity and stability of the CRM accord with the stipulations. The certified values were determined by 14 high level laboratories in China using nine methods with different principles and have been examined by the National Institute for Occupational Safety and Health (NIOSH) using Inductively Coupled Plasma--Mass Spectrometry (ICP-MS). This CRM has been approved as first grade national reference material. It can be used in quality control of routine analysis, test of new methods, and as standard material for calibration of analytical instruments and as certified reference material for quantity transmission and analysis arbitration.

China↗

Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice.

This investigation studied the effect of topical application of apigenin on skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA) in SENCAR mice. Apigenin was a potent inhibitor of epidermal ornithine decarboxylase induction by TPA in a dose-dependent manner from 1 to 20 mumol. Two tumorigenesis studies were conducted. In the first study, 20 mumol of apigenin was applied topically and no effect on body weight was observed. By week 33 after DMBA initiation, 48% of DMBA/TPA-treated mice developed carcinomas, while none occurred in DMBA/apigenin/TPA-treated groups. In the second study, doses of 5 and 20 mumol of apigenin were used. The papilloma incidence for 0, 5, and 20 mumol apigenin at 26 weeks after DMBA was 93.3, 58, and 39.3%, and papilloma numbers per mouse were 7.5, 2.5, and 1.8, respectively. Apigenin prolonged by 3 weeks the latency period of tumor appearance. In addition, apigenin significantly inhibited the incidence of carcinoma and the numbers of carcinomas. The incidence of carcinomas per tumor-bearing animal and the ratio of carcinomas/papillomas in two apigenin-treated groups decreased although there were no significant differences between the three groups. These data indicate that apigenin inhibited skin papillomas and showed the tendency to decrease conversion of papillomas to carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗

The acute splanchnic and peripheral tissue metabolic response to endotoxin in humans.

The in vivo alterations in organ-specific substrate processing and endogenous mediator production induced by endotoxin were investigated in healthy volunteers. An endotoxin bolus (20 U/kg) produced increased energy expenditure, hyperglycemia, hypoaminoacidemia, and an increase in circulating free fatty acids. These changes included increased peripheral lactate and free fatty acid output, along with increased peripheral uptake of glucose. Coordinately, there were increased splanchnic uptake of oxygen, lactate, amino acids, and free fatty acids, and increased splanchnic glucose output. There were no changes in circulating glucagon, or insulin and transient changes in epinephrine and cortisol were insufficient to explain the metabolic changes. Plasma cachectin levels peaked 90 min after the endotoxin infusion, and hepatic venous (HV) cachectin levels (peak 250 +/- 50 pg/ml) were consistently higher than arterial levels (peak 130 +/- 30 pg/ml, P less than 0.05 vs. HV). No interleukin 1 alpha or 1 beta was detected in the circulation. Circulating interleukin 6, measured by B.9 hybridoma proliferation, peaked 2 h after the endotoxin challenge (arterial, 16 +/- 2 U/ml; HV, 21 +/- 3 U/ml). The net cachectin efflux (approximately 7 micrograms) from the splanchnic organs demonstrates that these tissues are a major site for production of this cytokine. Hence, splanchnic tissues are likely influenced in a paracrine fashion by regional cachectin production and may also serve as a significant source for systemic appearance of this cytokine.

Adult↗

Serum cachectin/tumor necrosis factor in critically ill patients with burns correlates with infection and mortality.

Serum cachectin/tumor necrosis factor (TNF), a cytokine implicated in the pathogenesis of septic shock, may appear in the circulation during serious infection, but the frequency of detection of elevated serum levels during protracted critical burn injury is unknown. Serial serum samples taken from 43 critically ill patients with burns with and without sepsis were analyzed for TNF using an enzyme-linked immunosorbent assay (ELISA). TNF was detectable (greater than 34 picograms per milliliter) at one or more time points in 69 per cent of the patients with sepsis versus 33 per cent of those without sepsis, in 71 per cent of the patients who died versus only 31 per cent of the survivors and in only one healthy normal control patient (n = 21). The frequency of the appearance of TNF correlated with both infection and mortality rate. Moreover, all three patients with TNF levels greater than 540 picograms per milliliter died. Neither the size of the burn nor injury from inhalation correlated with detection of TNF. A subset of 16 patients was studied longitudinally from admission until resolution of injury and these data demonstrate that TNF appears transiently and repetitively in the circulation of patients during infection and protracted critical burn injury. Also, serum cortisol levels were significantly higher during sepsis and death in the absence of serum TNF, compared with sepsis and death with detectable cachectin, suggesting that cortisol may interact with the production or detection of this cytokine during ongoing infection and lethal injury. In this study, we have demonstrated that serum TNF is detectable with greater frequency and in higher concentration in patients with sepsis and in those who ultimately succumb to the burn injury, that serum TNF appears transiently and repetitively in the circulation during injury and that higher serum cortisol levels are correlated with the absence of serum TNF during sepsis and lethal injury.

Burns↗

Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man.

beta 2-IFN/hepatocyte stimulating factor/IL-6 is a cytokine secreted by monocytes, fibroblasts, and endothelial cells in cell culture that possesses diverse biologic activity including the stimulation of acute phase plasma protein synthesis and immunomodulation. The circulating levels of this cytokine in man in response to bacterial LPS (endotoxin) were studied. A single i.v. bolus of endotoxin (20 U/kg) produced a monophasic rise in circulating immunoreactive IFN-beta 2/IL-6 and IFN-beta 2/IL-6 bioactivity (hepatocyte stimulation and B cell differentiation assays) peaking 2 to 4 h after the endotoxin challenge. Peak IFN-beta 2/IL-6 levels ranged from 4.1 to 27.5 ng/ml. Associated with this was a rise in circulating C-reactive protein levels detected 20 h after the endotoxin bolus. Thus, IFN-beta 2/IL-6 is likely one of the endogenous mediators which is triggered in man during bacterial infection and likely participates in the metabolic and immune responses of the infected host.

Adult↗

Starvation leads to decreased levels of mRNA for myofibrillar proteins.

Malnutrition is a common complicating factor in surgical illness. To investigate the cellular changes and mechanisms responsible for the protein wasting associated with nutritional deprivation, Sprague-Dawley rats were subjected to total protein-calorie starvation for 3 (n = 12) or 5 days (n = 12) and compared to freely fed animals monitored for 3 (n = 8) or 5 (n = 8) days. Gastrocnemius protein and RNA content and levels of mRNA coding for the myofibrillar proteins myosin heavy chain, myosin light chain, and alpha-actin were measured. Starvation resulted in a significant decrease in gastrocnemius mass and protein content, and was associated with decreases in mRNA levels for the three myofibrillar proteins assayed. We conclude that changes in mRNA levels for these proteins likely contribute to the loss of peripheral protein which occurs during total nutritional deprivation. In addition, the changes in mRNA levels for these three structural proteins appear to be coordinate, suggesting that transcription of no single myofibrillar protein is rate-limiting in the regulation of skeletal muscle protein content.

Actins↗