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Biomedical subjects

C H Hsu

Publications and source records attributed to C H Hsu.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effect of glyoxylate on the function of the calcitriol receptor and vitamin D metabolism.

The biological action of calcitriol is mostly mediated through the interaction of the calcitriol receptor (VDR) with vitamin D response elements (VDREs) of target genes. These interactions produce special proteins that carry out the biological activities of calcitriol. Recently, we showed that the interaction of VDRs with VDREs is inhibited by uremic toxins. We hypothesize that uremic toxins that contain aldehyde or ketone groups potentially could form Schiff bases with lysine residues of the VDR DNA binding domain and inhibit VDR interaction with VDREs. We therefore chose glyoxylate, a compound which has an aldehyde group, to test this hypothesis. In vitro glyoxylate inhibited VDR binding to the osteocalcin and osteopontin VDREs as assessed by electrophoretic mobility shift assay and the inhibition was reversed when glyoxylate was preincubated with lysine. Further, this chemical compound also blocked the induction of chloramphenicol acetyltransferase (CAT) enzyme induced by calcitriol in cells transfected with a calcitriol responsive CAT reporter gene. Since induction of 24-hydroxylase synthesis is a VDR regulated process, we also studied the effect of glyoxylate on the activity of intestinal 24-hydroxylase in rats. This enzyme activity was suppressed in rats infused with glyoxylate. Taken together, our study suggests that glyoxylate could inhibit the interaction of VDR with VDREs and alter the biological action of calcitriol.

Animals↗
PubMed1997

Effect of glucose on the function of the calcitriol receptor and vitamin D metabolism.

The genomic action of calcitriol is mediated through the interaction of the calcitriol receptor (VDR) with vitamin D response elements (VDREs) of the target genes. It has been proposed that chemicals capable of Schiff base formation with the VDR potentially could alter the physiological function of VDR and calcitriol metabolism. Since glucose has been shown to form Schiff bases with proteins, we tested the hypothesis that glucose could influence the function of VDR and thereby alter calcitriol metabolism. Glucose 6-phosphate inhibited VDR binding to the osteocalcin VDRE and chemically modified the DNA binding domain or the dimerization domain of the VDR in vitro. Further, glucose also blocked the production of chloramphenicol acetyltransferase (CAT) enzyme induced by calcitriol in cells transfected with a constructed VDRE attached to a CAT reporter gene. Hyperglycemia induced by glucose infusion or by streptozotocin in normal rats significantly reduced intestinal 1 alpha, 25-dihydroxyvitamin D-24-hydroxylase activity. Taken together, these findings are consistent with the hypothesis that glucose could interact with the VDR to impair its DNA binding and function within cells.

Animals↗
PubMed1996

Ricin depresses cardiac function in the rabbit heart.

Ricin, at toxic glycoprotein from the castor bean, causes myocardial hemorrhage and a decrease in blood pressure. We studied the effects of ricin on myocardial function in the isolated rabbit heart. Rabbits were given 0.22 micrograms/kg of ricin i.v. and 48 hr later, the heart was isolated and retrogradely perfused through the aorta with Tyrode's solution. A latex balloon was inserted into the left ventricle and isovolumic left ventricular function curves were generated. Left ventricular developed pressure (LVDP), heart rate, coronary artery flow, left ventricular end diastolic pressure, myocardial oxygen consumption, oxygen extraction (a - vO2), and contractility (+dp/dt) were measured over a range of left ventricular volumes. Dose-response curves to isoproterenol (10(-9)-10(-8) M) and phenylephrine (10(-9)-10(-6) M) were also obtained. Compared to the control group, ricin pretreatment markedly decreased ventricular compliance (p < 0.01), diminished maximum left ventricular developed pressure (p < 0.05), and reduced maximal +dp/dt (p < 0.05). Myocardial oxygen consumption, heart rate, electrocardiographic PR, QRS, and QT intervals were not different in control and ricin treatment groups. Ricin did not significantly alter the inotropic or chronotropic responses to isoproterenol and phenylephrine. The results from the binding studies showed that ricin neither reduced beta-adrenergic receptor numbers nor altered the dissociation constant. thus, ricin reduced both systolic (LVDP and +dp/dt) and diastolic (compliance) left ventricular functions, perhaps due to increased vascular permeability, without altering responses to the alpha- and beta-adrenoceptor agonists phenylephrine and isoproterenol.

Adrenergic beta-Agonists↗
PubMed1996

Pancreatitis in children--experience with 43 cases.

UNLABELLED: Pancreatitis in children is not common and can be associated with severe morbidity and mortality. We encountered 43 children, ranging in age from 2 to 18 years, with pancreatitis over the past 10 years. The diagnosis of pancreatitis was made in those patients who showed: (1) significant intra-operative pathology or; (2) clinical findings of pancreatic inflammation and laboratory confirmation. More than one third (16 cases) of the cases were due to trauma, other causes included systemic disease (10), structural disease (8), and toxins or drugs (4). Five cases were classified as idiopathic. Most of the patients presented with abdominal pain (95%) and vomiting (56%). Jaundice was found in 7 patients and an abdominal mass in 2. Morbidity included pseudocyst (10), relapse (4), hyperglycaemia (4) and miscellaneous problems. Eight (50%) of the patients with trauma and 6 (86%) of the patients with structural diseases required surgery. Other patients were managed conservatively with bowel rest, gastric decompression, intravenous fluid and total parenteral nutrition. One case had a fatal outcome. All the survivors did well in long term follow up. Relevant literature has been reviewed and the sensitivity of various diagnostic modalities compared and discussed. A lesser known association between pancreatitis and structural anomalies such as choledochal cyst is discussed. To our knowledge, the present review is the first on pancreatitis in Chinese children. CONCLUSION: Pancreatitis can occur from a wide variety of causes and may result in severe complications. Early diagnosis, close monitoring and aggressive intervention are mandatory to reduce morbidity and mortality.

Abdomen, Acute↗
PubMed1996

The integrated design of mechanical bi-leaflet prosthetic heart valves.

A flow model utilizing an irrotational, inviscid algorithm of vortex-ring elements simulating the leaflets and source/sink elements simulating the aortic root coupled with a boundary layer model has been developed to model the internal flow phenomena of bi-leaflet mechanical heart valves implanted in the aortic root. The inviscid representation evaluates the aerodynamic lift, the induced drag, the pitching moment and flow velocity along the leaflet surface thus providing data for evaluating the boundary-layer thickness, the shear stress and flow separation point by the boundary layer theory. Full integration with the geometry enables immediate updates of the flow solution when changes in geometry have been made. It is shown that the effects of the internal flow domain model are necessary in the correct evaluation of lift and drag for subsequent dynamic analysis. The environment presented provides for the ability to produce significant and immediate design changes so that crucial decisions may be made whilst still within the software design loop. New designs are shown along with data for the improved flow model.

Algorithms↗
PubMed1996

Dynamic analysis and geometry models for the design of bi-leaflet prosthetic mechanical heart valves.

This paper provides new geometry definitions for the axi-symmetric stiffening (or sewing) ring, as part of a bi-leaflet prosthetic heart valve, and presents a dynamic behaviour analysis of the leaflet. An optimal stiffening ring geometry may be constructed by considering the point of flow separation on the stiffening ring (measured in the downstream coordinate), the effective orifice area of the stiffening ring and the associated dynamic behaviour of the leaflet. The dynamic model is accomplished by utilizing a second-order rotating system to simulate the opening and closing characteristics of the leaflet. The moments due to the aerodynamic loads are evaluated from an irrotational inviscid flow model, coupled with boundary layer theory, modelling the internal flow phenomena of the bi-leaflet heart valve implanted in the aortic root. It has been shown that this internal flow model provides the correct evaluation of lift and induced drag and the subsequent dynamic characteristics.

Algorithms↗
PubMed1996

Effect of Schiff base formation on the function of the calcitriol receptor.

The genomic action of calcitriol is mediated through the interaction of the calcitriol receptor (VDR) with vitamin D response elements (VDREs) of the target genes. We have shown that the interaction of VDRs with VDREs is inhibited by uremic toxins. We hypothesize that uremic toxins form Schiff bases with the lysine residues of the VDR DNA binding domain and inhibit the VDR interaction with the VDRE. In this study, pyridoxal 5'-phosphate was used as a probe to test Schiff base formation as the inhibitory mechanism, since it forms Schiff bases with steroid receptors. Pyridoxal 5'-phosphate inhibited the VDR binding to the VDREs and chemically modified the DNA binding domain of the VDR in vitro. The inhibition was reversed when pyridoxal 5'-phosphate was preincubated with lysine. Further, this chemical agent also blocked the production of chloramphenicol acetyltransferase (CAT) enzyme induced by calcitriol in cells transfected with a constructed VDRE attached to a CAT reporter gene. This finding is consistent with the hypothesis that pyridoxal 5'-phosphate could interact with the VDR and impair its DNA binding within cells. Since induction of 24-hydroxylase synthesis is a receptor mediated process, we studied the effect of pyridoxal 5'-phosphate on the synthesis of renal 24-hydroxylase in rats. When pyridoxal 5'-phosphate was infused to rats, renal 24-hydroxylase activity was suppressed, consequently, degradation of calcitriol was also reduced in these animals. Thus, chemicals capable of Schiff base formation potentially could alter the physiological function of VDR and calcitriol.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1996

Immunoprophylaxis of allergen-induced immunoglobulin E synthesis and airway hyperresponsiveness in vivo by genetic immunization.

The efficacy of an "allergen-gene immunization" protocol in altering allergic response was examined. Intramuscular injection of rats with a plasmid DNA encoding a house dust mite allergen into the muscle results in its long-term expression and the induction of specific immune responses. Significantly, this approach prevents the induction of immunoglobulin E synthesis, histamine release in bronchoalveolar fluids, and airway hyperresponsiveness in rats challenged with aerosolized allergen. Furthermore, this suppression is persistent and can be transferred into naive rats by CD8+ T cells from gene-immunized rats. These findings suggest that allergen-gene immunization is effective in modulating allergic responses, and may provide a novel therapeutic approach for allergic diseases.

Animals↗
PubMed1996

Inhibition of specific IgE response in vivo by allergen-gene transfer.

DNA immunization has been an attractive approach in altering the host immune response to antigen. To examine the utility of DNA immunization in allergic response, we examined the in vivo efficacy of an 'allergen-gene immunization' approach in the modulation of allergen-specific IgE responses in mice. Our results showed first that I.m. injection of a gene construct (pCMVD) containing an important house dust mite allergen gene (Dermatophagoides pteronyssinus group 5 allergen; Der p 5) results in the induction of Der p 5-specific IgG antibodies, but not IgE antibody. We next examined the effect of transduced allergen gene on the expression of specific IgE response in mice after i.p. challenge with recombinant Der p 5 (rDer p 5). Both vector (mock) control- and pCMVD-treated mice were i.p. sensitized with rDer p 5 at 3 weeks after injection of gene construct. Results showed that there is a 90% reduction in the level of specific IgE in pCMVD-treated mice when compared with mock-treated mice. Furthermore, the suppression of specific IgE response can be adoptively transferred with CD8+ T cells from pCMVD-treated mice and such inhibition is in an antigen-specific manner, since the level of specific IgE to an irrelevant allergen, Der p 1, remained unchanged in comparison to that of the mock-treated group. In addition, Der p 5-specific CD8+ T cells could produce high levels of IFN-gamma which probably inhibit allergen-specific IgE responses. Taken together, our results suggest that allergen-gene transfer is effective in the modulation of allergen-specific IgE responses and may provide a novel therapeutic approach.

Adoptive Transfer↗
PubMed1996

Acute health hazards of firefighters after fighting a department store fire.

The purpose of this study was to evaluate the health hazards of firefighters after fighting a department store fire which lasted for 40 hours. Respiratory symptoms of 168 firefighters were collected and the pulmonary functions of 149 firefighters were measured by spirometer two days after fighting the fire and compared to 32 controls. The principal symptoms manifested by firefighters were burning eyes and mucous membrane irritation. Cross-sectional study of the pulmonary functions showed that FEV1.0, FEV1.0/FVC and the flow rates (MMF, FEF25%, and FEF75%) in smoking exposed firefighters were significantly lower than those in smoking controls. However, only FEV1.0 (%) was significantly lower in nonsmoking exposed firefighters than in nonsmoking controls. Both FVC and FEV1.0 showed a declining trend with the duration of fire fighting. This study provides further evidence that firefighters are exposed to irritants during fighting a fire. Exposure to the combustion products could lead to pulmonary function defects, especially in smoking firefighters.

Case-Control Studies↗
PubMed1996

Glutathione-S-transferase induces murine dermatitis that resembles human atopic dermatitis.

BACKGROUND: The molecular and functional basis of allergen-induced inflammation seen in atopic dermatitis (AD) remains undefined. OBJECTIVE: The objective of this study is to establish a murine model to dissect the pathological mechanisms of inflammatory reactions leading to the development of AD. METHODS: An inbred strain of mice, BALB/c, when injected peritoneally with 30 micrograms of recombinant Sj26 protein (rSj26), a glutathione-S-transferase of Schistosoma japonicum worm, developed systematic dermatitis 21 days after immunization. The pathology of the dermatitis was examined by histological evaluation and immunostaining. The immediate skin hypersensitivity was demonstrated by serum transfer and skin test. Epicutaneous patch test was used to demonstrate the antigen-specific late phase response. RESULTS: Significant responses of rSj26-specific IgE were detected 2 weeks after immunization, and such changes paralleled formation of skin lesions. The diseased skin pathology showed inflammatory changes such as infiltration of mononuclear cells and eosinophils in the dermis and mild spongiosis in the epidermis. Numerous IgE bearing cells were also detected in the dermis. Peripheral blood showed eosinophilia at the same time. In addition, rSj26-specific positive skin test and epicutaneous patch test could be demonstrated in rSj26-sensitized mice. CONCLUSIONS: These results suggest that rSj26 is capable of eliciting atopic dermatitis-like lesions in BALB/c mice. This can be a useful animal model for elucidating allergen-induced immune responses and the development of various therapeutic interventions of atopic dermatitis in humans.

Animals↗
PubMed1995

Ricin disturbs calcium homeostasis in the rabbit heart.

Ricin, a toxic lectin from the castor bean, affects the cardiovascular system. Because calcium is very important in cardiotoxicity and cell intoxication, we studied the effects of ricin pretreatment to rabbits on basal intracellular calcium levels and calcium uptake and release from isolated papillary muscle, microsomes, and mitochondria. An increase in basal intracellular calcium levels was observed. Ricin pretreatment nearly doubled the intracellular-free Ca2+ concentration as measured by fura-2 fluorescence microscopy in isolated myocytes (p = 0.002). Ricin did not alter basal calcium efflux in isolated papillary muscles. However, ricin inhibited the NE-induced calcium efflux (expressed as fractional efflux ratios) in papillary muscles from rabbits receiving the minimum lethal dose of ricin at 25-35 minutes (p = 0.002 and 0.003, respectively). Ricin depressed basal calcium uptake into isolated papillary muscles at 5 minutes (mean +/- SEM, mumol/g wet weight) (control: 3.68 +/- 0.57; ricin: 2.31 +/- 0.28, p = 0.045, n = 6). Ricin pretreatment significantly depressed calcium uptake into microsomes (mean +/- SEM, mumol/g protein) (control: 9.9 +/- 1.9; ricin: 3.1 +/- 1.9, p = 0.025, n = 6). Calcium uptake into mitochondria was increased at the beginning (2 minutes, p = 0.048), but not thereafter. Thus, administration of ricin disturbed calcium homeostasis in the rabbit heart, which may be at least partially responsible for altering cardiac function and myocardial cell death.

Animals↗
PubMed1995

Interindividual differences in the concentration of 1-hydroxypyrene-glucuronide in urine and polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells after charbroiled beef consumption.

Biological markers of internal dose and macromolecular dose from PAHs provide a potential means of assessing environmental exposure to PAHs through inhalation, ingestion and percutaneous absorption. In this study we examined the time course and interindividual variation of 1-hydroxypyrene-glucuronide (1-OHP-gluc) excretion in urine and PAH-DNA adduct formation in peripheral white blood cells (WBCs) after charbroiled (CB) beef consumption. As a marker of internal dose, 1-OHP-gluc was measured in human urine using immunoaffinity chromatography and synchronous fluorescence spectroscopy. PAH-DNA adducts were measured in WBCs by enzyme-linked immunosorbent assay (ELISA) in order to assess macromolecular dose. Ten healthy non-smoking males consumed identical amounts of CB beef on five consecutive days. Multiple blood and urine samples were collected before, during, and after the feeding period. The morning after the first day of CB beef consumption, individual urinary concentrations of 1-OHP-gluc increased 10- to 80-fold (range: 2.0-16.6 pmol/ml urine) above pre-feed baseline concentrations (0.23 +/- 0.11 pmol/ml) in the 10 subjects. 1-OHP-gluc concentration decreased to near baseline levels by 24-72 h after CB beef consumption ended. In contrast, PAH-DNA adducts in WBCs increased markedly in only four of 10 subjects during or after CB beef consumption. Significant interindividual variation was observed for both urinary 1-OHP-gluc concentration (P < 0.001 by Kruskal-Wallis) and PAH-DNA adduct levels (P < 0.005) during the feeding period. The mean urinary 1-OHP-gluc concentration for each subject during and immediately after (days 2-8) the feeding period was significantly correlated with their mean PAH-DNA adduct level in WBCs during the same time period (Spearman r = 0.79, P < 0.01). Evidence of segregation of the subjects into separate response groups based on level of urinary 1-OHP-gluc was observed, suggesting that discrete determinants may regulate the absorption, metabolism and/or excretion of ingested pyrene.

Adult↗
PubMed1995

Altered vitamin D metabolism and receptor interaction with the target genes in renal failure: calcitriol receptor interaction with its target gene in renal failure.

The genomic action of calcitriol is mediated through the interaction of the calcitriol receptor (VDR) with the vitamin D response elements of the target genes. Although decreased VDR concentration in renal failure could diminish the biological action of calcitriol, recent study indicates that uremic toxins could modify the VDR DNA-binding domain and inhibit the binding of the VDR to the vitamin D response elements. The latter reaction could also account for end-organ resistance in renal failure. The inhibitory action of uremic toxins has been tested in vivo by a method using gene transcription. It was demonstrated that uremic ultrafiltrate blocks calcitriol-induced chloramphenical acetyltransferase reporter constructs containing a synthetic vitamin D response element in JEG-3 cells. Taken together, the findings indicate that uremia could underlie the calcitriol resistance in renal failure. The modification of the VDR may involve Schiff base formation between lysine residues of the VDR DNA-binding domain and reactive aldehydes accumulated in uremia. This suggestion is on the basis of the finding that the VDR and other steroid receptors form Schiff bases with pyridoxal 5'-phosphate and weaken the binding of these receptors to the DNA cellulose.

Animals↗
PubMed1995

Inhibition of calcitriol receptor binding to vitamin D response elements by uremic toxins.

The genomic action of calcitriol (1,25-dihydroxy-vitamin D3) is mediated through the interaction of the calcitriol receptor (VDR) with vitamin D response elements (VDREs). Although renal failure is associated with resistance to the action of calcitriol, the mechanism of this resistance is not well understood. Therefore, we used the electrophoretic mobility shift assay to compare the ability of VDRs from normal and renal failure rats to bind to the osteocalcin gene VDRE. The results indicate that VDRs from renal failure rats have only half the DNA binding capacity as VDRs from control rats, despite identical calcitriol binding. Furthermore, incubation of normal VDRs with a uremic plasma ultrafiltrate resulted in a loss of > 50% of the binding sites for the osteocalcin VDRE. When VDRs bound to DNA as heterodimers with retinoid X receptors, the inhibitory effect of the uremic ultrafiltrate was due to a specific interaction with the VDR, not retinoid X receptors. In addition, uremic ultrafiltrate blocked calcitriol-induced reporter gene activity in transfected JEG-3 cells. Taken together, the results indicate that an inhibitory effect of a uremic toxin(s) on VDR-VDRE binding could underlie the calcitriol resistance of renal failure.

Animals↗
PubMed1995

Presacral tumor: a review of forty-five cases.

Forty-five patients with primary presacral tumors underwent their treatment at Division of Colon Rectal Surgery, Chang Gung Memorial Hospital, from 1978 to 1992. These 45 patients, 20 male and 25 female, ranged from 15 to 76 years of age (mean, 41.1 years). Congenital tumors (47 per cent) were the most frequent histologic type, followed by miscellaneous tumors (36 per cent). Forty-eight per cent of patients had malignant tumors. All benign congenital cysts were in females. These tumors presented a variety of symptoms and signs. Diagnosis could be made by digital examination in 43 (96 per cent) of the patients. Computed tomographic scan was the most important diagnostic tool in determining the extent and degree of tumor invasion. The positive rate was 100 per cent in 21 patients. As for operative methods, abdominal approach was selected in 24 patients, transacral in 13 patients, abdominal/sacral combined in 6 patients, and biopsy only in two patients. Postoperative complications occurred in 16 patients (36 per cent), but there were no operative deaths. Of the tumors that underwent resection, 23 had total resection (18 benign and 5 malignant) and 22 incomplete (5 benign and 17 malignant). Benign tumors had a good chance with resection of the lesion (P < 0.05). For patients with malignant tumors, the 5-year survival rate was 40.7 per cent. Whenever possible, total resection could offer better results for presacral tumor, whether the lesions were benign or malignant.

Adolescent↗