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Biomedical subjects

H M Yang

Publications and source records attributed to H M Yang.

At least 37 records · Page 2Linked to original sources

Effects of diesel exhaust particles (DEP), carbon black, and silica on macrophage responses to lipopolysaccharide: evidence of DEP suppression of macrophage activity.

The effects of diesel exhaust particle (DEP) exposure on alveolar macrophage (AM) response to ex vivo and in vivo lipopolysaccharide (LPS) challenge were determined by monitoring LPS-stimulated production of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). The roles of the insoluble particulate and the organic compounds of DEP in altering pulmonary responses were evaluated by comparing the DEP-induced pulmonary responses to those of carbon black (CB), a carbonaceous particle with few adsorbed organic compounds, or to silica, a known pneumotoxic dust. Male Sprague-Dawley rats were exposed to a single intratracheal dose (5 or 35 mg/kg body weight) of DEP, CB, or silica, or to saline vehicle. Rats were sacrificed 1, 3, or 7 d postexposure. To study the responsiveness to the bacterial product LPS, AM isolated from particle-exposed rats were challenged ex vivo with LPS (0.1 microg/10(6) AM) and LPS-stimulated cytokine release was monitored. In addition, rats were exposed intratracheally to a single dose of DEP (5 mg/kg) and 3 d later exposed in vivo to 1 mg/kg LPS for 3 h prior to measurement of cytokine production by AM. DEP exposure resulted in neutrophil infiltration and elevated levels of albumin and lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid; these responses were not substantially different from those elicited by CB or silica exposure. AM from DEP-exposed rats showed increased spontaneous production of IL-1, but not TNF-alpha, while the opposite was true for CB or silica. Upon ex vivo challenge with LPS, AM from DEP-exposed rats showed a significant decrease in the secretion of TNF-alpha and, to a lesser extent, IL-1, compared to the sum of the DEP and LPS effects. In contrast, AM from CB- or silica-exposed rats did not show this decreased responsiveness to subsequent LPS challenge. This inhibitory action of DEP on LPS-stimulated AM production of IL-1 and TNF-alpha was further confirmed by the results obtained from rats exposed to both DEP and LPS in vivo. In summary, these results indicate that while DEP, CB, and silica all induce pulmonary inflammatory responses due to particle stimulation, only DEP suppress AM cytokine release in response to LPS stimulation. The contrasting cellular response with respect to DEP and CB exposures may be due to the presence of adsorbed organic compounds on DEP, which may contribute to the increased susceptibility of hosts to pulmonary infections after DEP exposure.

Albumins↗

Non-linear analysis of the rhythmic activity in rodent brains.

This paper discusses the employment of non-parametric non-linear prediction algorithms to investigate non-linear dynamics in the rhythmic brain activity of rats. Three algorithms (Sugihara-May Simplex, K-neighbour and Casdagli's) were tested yielding similar prediction results which--when subject to a suitable bootstrap based t-tests--revealed that the theta waves recorded in rat brains cannot have their intrinsic non-linearity dismissed at a significance of 0.05.

Algorithms↗

Acquired immunity of a schistosomiasis transmission model--analysis of the stabilizing effects.

A semi-stochastic model for schistosomiasis was developed based on the immune response built up by human host after elapsing a fixed period of time L from the first infection, and on the parasite infection with multiple occurrences. Both acquired immunity and multiple parasite infections reproduced a great endemic stability for the disease and a high value for the basic reproduction ratio.

Animals↗

Liver function in postmenopausal women on estrogen-androgen hormone replacement therapy: a meta-analysis of eight clinical trials.

OBJECTIVE: To compare hepatic biochemical changes of a combined estrogen-androgen preparation with that of estrogen alone in postmenopausal women. DESIGN: Hepatic biochemical values from 511 surgical and 130 nonsurgically menopausal women being treated with hormone replacement therapy were pooled from eight similarly designed studies performed between March 1988 and January 1996 comparing esterified estrogen-methyl-testosterone preparations with esterified estrogen, conjugated equine estrogens, and placebo controls. The eight studies in this meta-analysis were controlled, randomized, multicenter, double-blind with identical or similar treatment arms. For hepatic biochemistry parameters, raw data summaries and mean changes from baseline values with standard error (SE) were evaluated for the dosages and treatment groups at various time periods throughout the studies. RESULTS: Eight controlled trials involving 641 surgically and nonsurgically menopausal women were included. Changes from the pretreatment baseline values of liver function were compared at 1, 3, 6, 12, 18, and 24 months of therapy. No patients demonstrated hepatotoxicity or clinically significant elevation of liver biochemistry values. None of the liver biochemistry changes measured in these studies were of clinical significance, nor were there biochemical differences between estrogen therapy alone compared with combined esterified estrogen-methyltestosterone preparation when administered to postmenopausal women during a period of up to 24 months. CONCLUSIONS: Combined esterified estrogen-methyltestosterone therapy (in doses of 0.625 mg esterified estrogen + 1.25 mg methyltestosterone or 1.25 mg esterified estrogen + 2.5 mg methyltestosterone) was found to be safe regarding hepatic function in postmenopausal women during the course of 24 months in eight controlled clinical trials.

Aged↗

Differential effects of estrogen-androgen and estrogen-only therapy on vasomotor symptoms, gonadotropin secretion, and endogenous androgen bioavailability in postmenopausal women.

OBJECTIVE: To investigate somatic symptom relief, gonadotropin secretion, and endogenous androgen bioavailability (protein-bound and free) during 3 months of estrogen-androgen therapy or matched estrogen-only replacement therapy. DESIGN: Ninety-three naturally menopausal outpatients with 6 or more months of amenorrhea, who were experiencing mild-to-moderate vasomotor symptoms, were randomized to receive one of five treatments: oral esterified estrogens (0.625 mg or 1.25 mg), oral esterified estrogens combined with methyltestosterone (0.625 mg combined with 1.25 mg methyltestosterone or esterified estrogens 1.25 mg combined with 2.5 mg methyltestosterone), or placebo for 12 weeks. All treatments were preceded by a 4-week placebo lead-in period. RESULTS: Patients receiving the lower dose of estrogen-androgen therapy had fewer somatic menopausal symptoms than patients receiving the lower dose estrogen (0.625 mg), and they experienced somatic symptom relief similar to those patients receiving the higher dose of estrogen (1.25 mg). Significantly greater luteinizing hormone suppression (p < or = 0.03) occurred in estrogen-androgen groups compared to estrogen groups, suggesting that added androgen might mediate a more pronounced negative feedback on the hypothalamic-pituitary axis. Sex hormone-binding globulin increased significantly in both estrogen-treated groups (p < or = 0.01), whereas decreases occurred in both estrogen-androgen groups (p < or = 0.006). The higher dose estrogen-only preparation significantly reduced androstenedione (p < or = 0.01) and dehydroepiandrosterone sulfate (p < or = 0.005). CONCLUSION: The extent of relief with lower dose estrogen-androgen therapy was similar to higher dose estrogen-only treatment. The greater efficacy of combination therapy on somatic symptoms could be mediated by the same mechanism responsible for the suppressive effects of estrogen-androgen therapy on luteinizing hormone secretion. The marked differences in circulating levels of sex hormone building globulin, which were increased by estrogen and decreased by estrogen-androgen, and the resulting impact on bioavailable androgens and estrogens could also explain the differential somatic relief with both treatments. Endogenous adrenal androgens were lower in women treated with esterified estrogens 1.25 mg/day, suggesting that estrogen therapy can produce a significant hypoandrogenic state by inhibiting production or accelerating clearance of adrenal androgens.

Administration, Oral↗

A population model applied to HIV transmission considering protection and treatment.

An epidemiological population model is proposed to assess the impact of protection and/or treatment strategies applied to HIV infection. Sex-education campaigns are the available protection strategy, and drug (or association of drugs) administration is the treatment strategy considered. In this model we assumed recruitment and differential mortality rates for the homosexual population. In addition to the classical threshold contact rate related to the establishment of the disease, we obtained a threshold input rate.

Anti-HIV Agents↗

A two-year, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles.

OBJECTIVE: To compare the effects of two doses of conjugated equine estrogen (CEE) and two of esterified estrogen plus methyltestosterone (E + A) in surgically menopausal women. STUDY DESIGN: A two-year, parallel-group, double-blind study of 311 women who were randomly assigned to one of four regimens: (1) CEE, 0.625 mg/d; (2) CEE, 1.25 mg/d; (3) esterified estrogens, 0.625 mg, + methyltestosterone, 1.25 mg/d; or (4) esterified estrogens, 1.25, + methyltestosterone, 2.5 mg/d. Study parameters were symptoms, lipids, bone mineral density, side effects and safety. RESULTS: All treatments prevented loss of bone in the spine and hip. The higher E + A dose increased spine and hip BMD more than other treatments (P < .002). All treatments improved menopausal symptoms, with non-significantly greater improvements in well-being and sexual interest in the E + A groups. Similar and significant decreases in low-density lipoprotein were observed in all groups, but high-density lipoprotein and triglycerides were increased only in the unopposed estrogen groups (P < .05). Hirsutism was uncommon and similar in all groups at two years. Discontinuation rates and reasons for withdrawal from the study were similar in both groups. No clinically significant side effects or laboratory test abnormalities were seen. CONCLUSION: As compared to estrogen alone, E + A significantly improved BMD and was well tolerated in surgically menopausal women.

Administration, Oral↗

The loss of immunity in directly transmitted infections modeling: effects on the epidemiological parameters.

When directly transmitted infectious diseases are modeled assuming an everlasting induced immunity (and constant contact rate), there are well-established formulas to deal with, which is not true if we include the loss of induced immunity. In general, the immunity induced by the disease is everlasting. We propose a model considering the loss of immunity and present methods for the estimation of two epidemiological parameters: the force of infection and the basic reproduction ratio. We also analyze the effects of the loss of immunity on these parameters. Based on these results, we concluded that reinfection can play an important role in highly vaccinated populations.

Adolescent↗

MAGE Xp-2: a member of the MAGE gene family isolated from an expression library using systemic lupus erythematosus sera.

Two regions of the genome contain members of the MAGE gene family; Xq27-qter and Xp21.3. We isolated a transcript, MAGE Xp-2, by screening a cDNA library from the human epithelial carcinoma cell line, HEp-2, using autoantibodies from patients with systemic lupus erythematosus (SLE). The open reading frame (ORF) of MAGE Xp-2 is entirely contained in exon 4, a signature feature of the MAGE gene family. While MAGE Xp-2 shares genomic homology with MAGE Xp-1, the predicted proteins are quite divergent. Specific primers were designed to reliably distinguish between MAGE Xp-1 and MAGE Xp-2 expression. MAGE Xp-2 is expressed in testis, but not in other normal tissues. It is also expressed strongly in two of seven melanoma cell lines and one of four breast carcinomas. MAGE gene expression may be important not only for tumor recognition and cancer therapy, but, because it is the apparent target of autoantibodies in SLE sera, it may also play a role in autoimmune diseases.

Amino Acid Sequence↗

Provision of positive and negative selections in retroviral vectors containing the cytosine deaminase gene.

The E. coli cytosine deaminase (CD) provides a negative selection system for suicide gene therapy as CD transfectants are eliminated following 5-fluorocytosine (5FC) treatment. Here we report a positive selection system for the CD gene using 5-fluorouracil (5FU) and cytosine in selection medium to screen for CD-positive transfectants. It is based on the relief of 5FU toxicity by uracil which is converted from cytosine via CD catalysis, as uracil competes with the toxic 5FU in subsequent pyrimidine metabolism. Hence, a retroviral vector containing the CD gene may provide both positive and negative selections after gene transfer. The CD transfectants selected with the positive selection system showed susceptibility to 5FC in subsequent negative selection in vitro and in vivo. Therefore, this dual selection system is useful not only for combination therapy with transgene and CD gene, but can also act to eliminate selectively transduced cells after the transgene has furnished its effects or upon undesired conditions if 5FC is applied for negative selection in vivo.

Animals↗

The stabilizing effects of the acquired immunity on the schistosomiasis transmission modeling--the sensitivity analysis.

A mathematical model is proposed to analyze the effects of acquired immunity on the transmission of schistosomiasis in the human host. From this model the prevalence curve dependent on four parameters can be obtained. These parameters were estimated fitting the data by the maximum likelihood method. The model showed a good retrieving capacity of real data from two endemic areas of schistosomiasis: Touros, Brazil (Schistosoma mansoni) and Misungwi, Tanzania (S. haematobium). Also, the average worm burden per person and the dispersion of parasite per person in the community can be obtained from the model. In this paper, the stabilizing effects of the acquired immunity assumption in the model are assessed in terms of the epidemiological variables as follows. Regarded to the prevalence curve, we calculate the confidence interval, and related to the average worm burden and the worm dispersion in the community, the sensitivity analysis (the range of the variation) of both variables with respect to their parameters is performed.

Animals↗

Dichloroacetic acid pretreatment of male and female rats increases chloroform-induced hepatotoxicity.

Dichloroacetic acid (DCA) and chloroform (CHCl3) are both major by-products of drinking water chlorination and DCA increases the hepatotoxicity of CHCl3. In this study, we further characterized this effect and investigated DCA-induced alterations of CHCl3 disposition and metabolism as a possible mechanism for this interaction. Both adult male and female Sprague-Dawley rats were gavaged with three doses (09:00, 16:00 and 09:00 the next morning) of DCA (each 2.45 mmol/kg), then challenged with an i.p. injection of CHCl3 (3.12 or 9.35 mmol/kg). Hepatic damage was assessed 24 h after CHCl3 administration as increased alanine aminotransferase (ALT), ornithine carbomyl transferase (OCT) and bilirubin in plasma. In a separate experiment, rats were pretreated with DCA or were given 14CHCl3 at the same dosages. The disposition of 14C in various tissues and covalent binding of 14CHCl3-derivatives to liver proteins and lipids were determined 1 h later. CHCl3-induced hepatotoxicity was significantly more severe in DCA-pretreated groups. ALT and OCT were more markedly elevated in DCA + CHCl3 (3.12 mmol/kg) groups than NaCl +CHCl3 animals. Plasma bilirubin content was elevated only in DCA + CHCl3 groups and females were more susceptible to this effect. The responses of rats to DCA treatment were somewhat gender-different. DCA treatment increased total cytochrome P450 in females, but not in males. Hepatic glutathione concentration was elevated in males after DCA treatment, but not in females. In the present study we confirmed that DCA pretreatment potentiates the CHCl3-hepatotoxicity of both male and female rats. However, there was little evidence that DCA pretreatment significantly affected CHCl3 disposition or increased CHCl3 binding in vivo.

Animals↗

Dichloroacetic acid pretreatment of male and female rats increases chloroform metabolism in vitro.

The role of metabolism in dichloroacetic acid (DCA) potentiation of CHCl3 hepatotoxicity was investigated. Male and female Sprague-Dawley rats were given three doses (09:00, 16:00 and 09:00 the next morning) of DCA (each 2.45 mmol/kg) by gavage. The rats were euthanized 3 h after the last dose, hepatic microsomes were prepared and 14CHCl3 metabolism was measured in vitro. The binding of 14CHCl3-derivatives to microsomal proteins and lipids was increased 65 and 100%, respectively, in DCA-treated rats compared to their respective NaCl-treated controls. The formation of CO2 (nmol 14CO2/incubation) was significantly elevated in DCA-treated rats compared to controls (10.4 vs 6.3 in males; 10.8 vs 6.1 in females). DCA treatment decreased the apparent Michaelis constant (Km app) for conversion of 14CHCl3 to 14CO2 in rats (0.665 vs 0.415 mM in males, P < 0.05; 0.161 vs 0.081 in females). 14CO2 production and 14C binding were observed under N2 atmosphere, indicating that reactive metabolites of 14CHCl3 were formed by oxidation as well as reduction. Male and female rats metabolized CHCl3 differently. The Km app for CO2 production was up to 5-fold higher in the males than in the females, regardless of DCA treatment. Inhibition by SKF 525-A and piperonyl butoxide was gender dependent in both control and DCA-treated groups. The results showed, that increased bioactivation of CHCl3 by DCA treatment is one element in the DCA-CHCl3 interaction.

Animals↗

Acquired immunity on a schistosomiasis transmission model - fitting the data.

A semi-stochastic model is proposed to analyse the effects of acquired immunity on the transmission of schistosomiasis in the human host. The basic model's assumptions are as follows. The human host is assumed to build up an immune response after elapsing a fixed period of time L from the first infection. This acquired immunity is assumed to be partially effective and it is never lost. The parasite infection event is a Poisson process with multiple occurrences, i.e., in each event one or more cercaria are assumed to invade the host. The model treats deterministically the age distribution of human host. The model shows a good retrieving capacity of real data from two endemic areas of schistosomiasis: Touros, Brazil (Schistosoma mansoni) and Misungwi, Tanzania (Schistosoma haematobium).

Animals↗

[Serological investigation on Yang Xiao-xia's "mysterious disease"].

The famous "mysterious disease" of Yang Xiao-xia, a girl from Shangdong Province, was diagnosed as multi-bacterial synergistic gangrene based on bacteriological, serological and antibiotics sensitivity findings. In order to uncover the initial pathogenic bacteria and to investigate their relationship with environment, a total number of 18 serum samples were collected from volunteers living around patient's home and from patient's relatives. Serological study on 4 bacterial strains isolated from patient, named as Eubacterim lentum, Stereptococcus acidominimus, Y6 and Yp was conducted with Western blot, using whole cell protein preparation was carried out, and data obtained was statistically analysed. Our findings indicated that YP and Y6 strains were interrelated with environment of patient's home and Y6 from the pool where patient visited often and several hours before she intially experienced the disease. The strains of Y6 and YP are virulent to animials, indicating that they serve as potential pathogens. Eubacteriumlentum and Streptococcus acidominimus are irrelevant to environment.

Bacterial Infections↗

Dichloroacetic acid treatment increases hepatic CYP2E1 in male and female rats.

Previously, we showed that the pretreatment of dichloroacetic acid (DCA) increased CHCl3-induced hepatotoxicity in vivo and CHCl3 metabolism in vitro in both male and female rats. The effects of DCA on hepatic cytochrome P450-dependent monooxygenases were studied in this experiment. Male and female Sprague-Dawley rats were treated with DCA (each 2.45 mmol/kg) three times (9 AM, 4 PM, and 9 AM) and hepatic microsomes were prepared 3 hr after the last treatment (the same procedure as previous studies). After DCA treatment, the total content of cytochrome P450 (0.67 nmol/mg protein vs 0.79) and the activity of NADPH-dependent cytochrome P450 reductase (227 nmol/mg protein/min vs 332) were significantly increased in female rats, but they were unchanged in males (0.99 vs 0.98 for P450; 315 vs 311 for reductase). Induction of CYP2E1 was observed in both sexes, evidenced as increased activities of aniline and p-nitrophenol hydroxylases and increased CYP2E1 protein amount determined by immunoblot assay. In contrast, the CYP2B-related activity (dealkylation of pentoxyresorufin) and immunoreactive protein did not increase after DCA treatment in either males or females. The activity of ethoxyresorufin dealkylase was decreased in DCA-treated males compared to their controls (310 pmol/mg protein/min vs 229, p < 0.05), but it was not significantly affected in females. These data demonstrate that DCA treatment of both male and female rats altered the population of hepatic cytochrome P450. The results support the hypothesis that DCA increases CHCl3 metabolism, and therefore hepatotoxicity, by inducing CYP2E1.

Animals↗

Anterior chamber fluid cultures following phacoemulsification and posterior chamber lens implantation.

BACKGROUND AND OBJECTIVE: A randomized, prospective study was undertaken to evaluate the incidence of positive cultures in the anterior chamber following cataract surgery when using intracameral gentamicin compared with no antibiotic. PATIENTS AND METHODS: A total of 97 patients were enrolled-- 48 receiving gentamicin in the irrigating solution and 49 receiving no intracameral antibiotics (control group). Each cataract extraction was accomplished by phacoemulsification followed by intraocular lens implantation. At the end of surgery, o.1 ml of anterior chamber fluid from each case was collected and cultured. RESULTS: All cultures were negative in the group receiving gentamicin. However, one positive culture occurred in the control group. There was no significant difference in the positive culture rate between the two groups (P = .52). CONCLUSION: This study suggests that cataract extraction with phacoemulsification and intraocular lens implantation has greatly reduced the incidence of bacterial contamination of anterior chamber fluid, with or without the use of intracameral antibiotic.

Anterior Chamber↗

An attempt to explain interindividual variability in 24-h urinary excretion of inorganic arsenic metabolites by C57 BL/6J mice.

Forty C57 BL/6J mice, injected subcutaneously with 0.5 mg/kg arsenic as sodium arsenite, were examined for 24-h urinary excretion of total arsenic metabolites, creatinine and S-adenosylmethionine (SAM) and for 24-h faecal excretion of arsenic and levels of arsenic in the blood, liver, kidneys, lung, skin, spleen and bone at 24-h post-dose. Total urinary arsenic metabolites were calculated by summing up the inorganic (Asi), monomethylated (MMA) and dimethylated (DMA) derivatives directly measured by selective arsine generation-atomic absorption spectrometry (AG-AAS) or were measured by AG-AAS following complete mineralization. Both sets of results showed interindividual differences varying by as much as 7-fold and correlated with the 24-h urinary excretion of both SAM (r = 0.84 and r = 0.86, respectively) and creatinine (r = 0.82 and r = 0.87, respectively). There was interindividual variability of about a 30-fold range in 24-h faecal excretion of arsenic which correlated inversely with 24-h urinary excretion of arsenic metabolites (r = -0.69) and 24-h urinary excretion of both creatinine (r = -0.70) and SAM (r = -0.67). Body tissue levels of arsenic were low and not related to 24-h urinary excretion of arsenic metabolites, SAM and creatinine. Taken together, the results indicate that differences in the profile of urinary arsenic excretion and in the retention of arsenic in a particular organ do not contribute to interindividual variability in 24-h urinary excretion of arsenic metabolites by C57 BL/6J mice, but that variability in faecal excretion does, at least in part. It is speculated that there is most likely a predominant contribution from a diffuse tissue retention of arsenic or from a third route of arsenic elimination, i.e. respiratory, to this phenomenon in view of the small faecal contribution.

Animals↗