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Biomedical subjects

P Hung

Publications and source records attributed to P Hung.

At least 19 recordsLinked to original sources

Dietary effects of eicosapentaenoic and docosahexaenoic acid esters on lipid metabolism and immune parameters in Sprague-Dawley rats.

Sprague-Dawley rats were fed eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) ethyl esters at the 2% level for 3 weeks to clarify their effects on immune functions. In the rats fed EPA or DHA, serum cholesterol, triglyceride, and phospholipid (PL) levels were significantly lower than those in the rats fed safflower oil. In PL fractions of serum, liver, lung, splenocytes, and peritoneal exudate cells (PEC), increases in linoleic and dihomo-gamma-linolenic acid contents and a decrease in arachidonic acid (AA) content were observed in the rats fed EPA or DHA. In addition, the EPA content increased in the rats fed EPA and DHA. In the rats fed EPA or DHA, a decrease of LTB4 productivity and an increase of LTBs productivity were observed in the PEC, in response to the treatment with 5 microM calcium ionophore A23187 for 20 min. The changes in leukotriene production were more marked in EPA-fed rats than in DHA-fed rats. These results suggest that dietary EPA affects lipid metabolism and leukotriene synthesis more strongly than DHA.

Animals↗

Dietary effect of EPA-rich and DHA-rich fish oils on the immune function of Sprague-Dawley rats.

The dietary effect of fish oils (FOs) rich in eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on the immune function of Sprague-Dawley rats was compared with that of safflower oil. After 3 weeks of feeding at the 10% level of a dietary fat, the IgG and IgM production by splenocytes and IgG production by mesenteric lymph node (MLN) lymphocytes were significantly higher in the FO-fed rats, while no significant difference was found in IgA or IgE productivity by both the spleen and MLN lymphocytes. In the FO-fed rats, peritoneal exudate cells released a lower amount of LTB4, reflecting their lower arachidonic acid level, and a higher amount of LTB5, reflecting their higher EPA level in phospholipids. On these EPA-rich FO exerted a stronger effect than DHA-rich FO immune functions.

Adjuvants, Immunologic↗

Dietary effect of tocopherols and tocotrienols on the immune function of spleen and mesenteric lymph node lymphocytes in Brown Norway rats.

The immunoregulatory effects of dietary alpha-tocopherol (Toc) and tocotrienols (T-3) on humoral and cell-mediated immunity and cytokine productions were examined in Brown Norway rats. We found that the IgA and IgG productivity of spleen and mesenteric lymph node (MLN) lymphocytes was significantly enhanced in the rats fed on Toc or T-3, irrespective of concanavalin A (Con A) stimulation of the lymphocytes. On the contrary, the IgE productivity of lymphocytes from the rats fed on Toc or T-3 was less without Con A stimulation, but was greater in the presence of Con A, especially in the T-3 group. Toc or T-3 feeding significantly decreased the proportion of CD4+ T cells and the ratio of CD4+/CD8+ in both spleen and MLN lymphocytes of the rats fed on Toc or T-3. The interferon-gamma productivity of MLN lymphocytes was higher in the rats fed on Toc or T-3 than in those fed on a control diet in the presence of Con A, while that of spleen lymphocytes was lower in the rats fed on Toc or T-3. In addition, T-3 feeding decreased the productivity of tumor necrosis factor-alpha of spleen lymphocytes, while it enhanced the productivity of MLN lymphocytes. These results suggest that oral administration of Toc and T-3 affects the proliferation and function of spleen and MLN lymphocytes.

Animals↗

Dietary fibers modulate indices of intestinal immune function in rats.

To explore the immunological roles of dietary fiber, male 4-wk-old Sprague-Dawley rats were fed for 2 wk cellulose (water-insoluble), konjak mannan (water-soluble), pectin (water-soluble) or chitosan (acid-soluble) at 5 g/100 g diet. Serum IgE concentrations in rats fed konjak mannan, pectin and chitosan were significantly lower than in those fed cellulose (mean +/- SEM: 5.0 +/- 1.1, 3.6 +/- 1.3, 3.0 +/- 1.2 and 9.6 +/- 1.9 microg/L, respectively). Rats fed pectin had significantly higher serum IgA and IgG concentrations (358 +/- 38 and 424 +/- 36 mg/L for IgA and IgG, respectively) than those fed cellulose (240 +/- 31 and 337 +/- 25 mg/L) or chitosan (176 +/- 22 and 379 +/- 23 mg/L), while the IgM concentration did not differ among the groups. Concentrations of IgA, IgG and IgM in mesenteric lymph node (MLN) lymphocytes generally were greater, while IgE concentration was lower, in rats fed pectin and chitosan than in those fed cellulose. The proportion of CD4+ T-cells in MLN lymphocytes was also dietary fiber-dependent, and the CD4+/CD8+ ratio was significantly higher in the pectin fed group than in all other groups. Under certain experimental conditions, MLN lymphocytes from rats fed pectin had markedly greater interferon-gamma concentration than cells from other groups, while the effect on tumor necrosis factor-alpha concentration was less marked. Thus, dietary fiber may have an immunoregulatory effect on the intestinal immune system of rats.

Animals↗

Effect of unsaturated fatty acids and antioxidants on immunoglobulin production by mesenteric lymph node lymphocytes of Sprague-Dawley rats.

The effect of UFA on Ig production by rat MLN lymphocytes was examined to clarify their influence on allergic reactions. A 4-h treatment at 1 mM inhibited the production of IgA, IgG, and IgM by the lymphocytes, but stimulated IgE production. The IgE production-stimulating activity became stronger with increasing number of carbon atoms and/or double bonds. However, no saturated fatty acid with carbon numbers from 12 to 18 affected IgE production by the lymphocytes. Hydrogen peroxide exerted Ig production-regulating activity similar to that of UFA, suggesting that the effect of UFA is at least partly due to oxidation products. Thus, the effect of antioxidants on the Ig production-regulating activity of arachidonic acid was examined. alpha-Tocopherol and BHT annulled the stimulation of IgE production by arachidonic acid, but ascorbic acid was not effective. The IgE production-enhancing activity of UFA was closely related to their oxidation rate in culture medium. These results suggest that UFA enhance the allergic reaction through the stimulation of IgE production and the inhibition of IgA production, and that hydrophobic antioxidants are partially effective to annul the adverse effect of UFA.

Animals↗

Effects of n-3 polyunsaturated fatty acids and lectins on immunoglobulin production by spleen lymphocytes of Sprague-Dawley rats.

We examined the effects of n-3 polyunsaturated fatty acid (PUFA), such as alpha-linolenic (alpha-LA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA) on immunoglobulin (Ig) production by spleen lymphocytes of Sprague-Dawley rats. n-3 polyunsaturated fatty acid (PUFA) strongly inhibited the production of IgA and IgM and that of IgG weakly at 100 microM. When the lymphocytes were treated with n-3 PUFA in the presence of other inhibitory biomaterials such as lectins, some PUFA attenuated their inhibitory effect on Ig production. In the presence of concanavalin A (ConA), all n-3 PUFA attenuated the inhibitory effect of ConA on the production of IgM or IgG but increased its inhibition of IgA synthesis. Thus, the interaction of n-3 polyunsaturated fatty acid and lectins in spleen interfere with each other or the expression of Ig production regulating activity.

Animals↗

Free bile acids inhibit IgE production by mouse spleen lymphocytes stimulated by lipopolysaccharide and interleukins.

The interaction of IL-4, IL-5, and free bile acids with the immunoglobulin production by mouse spleen lymphocytes was studied to examine their immunoregulatory activity. In the absence of lipopolysaccharide (LPS), IL-4 enhanced the IgE and IgG production significantly and the IgA production weakly, but not the IgM production. On the other hand, IL-5 had an inhibitory tendency on the IgE and IgA production, though not significantly. In the presence of LPS, both IL-4 and IL-5 significantly enhanced the IgE production by mouse splenic lymphocytes. When the lymphocytes were cultured with the physiological concentration of free bile acids (10 microM) and LPS for 3 days, chenodeoxycholic acid inhibited the IgE production, but cholic and deoxycholic acids did not. In the presence of IL-4 or IL-5, these bile acids cancelled the stimulatory effects of interleukins and rather significantly inhibited the IgE production. These results suggest that these free bile acids act as an anti-allergic agent.

Animals↗

The transcription factor Sp1 is required for induction of the murine GM-CSF promoter in T cells.

The cis-acting region, GM-kappa B/GC-box (positions -95 and -73), within the murine GM-CSF gene promoter is required for maximal induction by stimulation with phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) in T cells. GM-kappa B defines a binding site for NF-kappa B, and GC-box defines a binding site for three (A1, A2, B) constitutive proteins. We report here that three copies of the GC-box can functionally compensate for the GM-kappa B/GC-box region, suggesting that the GC-motif can function independently of the GM-kappa B motif. The major GC-box binding activity A1 was purified and identified as the transcription factor Sp1. We show that depletion of Sp1 (A1) from nuclear extracts specifically decreases in vitro transcription activity on GM-CSF templates. Since the human GM-CSF promoter has a base difference within the GC-box, we speculate that this may explain why the human promoter is weak and that an upstream enhancer is required for the induction of the human GM-CSF gene.

Animals↗

Evaluation of the safety of inguinal hernia repair in the elderly using lignocaine infiltration anaesthesia.

Repair of inguinal hernia using local anaesthesia is becoming increasingly popular as it avoids many of the systemic side effects associated with general or spinal/epidural anaesthesia and provides excellent early postoperative pain relief. Dosages of local anaesthetic approaching the recommended maximum are frequently required for adequate anaesthesia of the inguinal region. The present study describes the disposition and safety of lignocaine with adrenaline in 14 elderly patients to ascertain its safety with a view to more widespread application of the technique in more complicated hernia repairs. Serial plasma lignocaine concentrations were determined for up to 24 h following doses approaching the recommended maximum for infiltration (7 mg/kg). Peak lignocaine concentrations (normalized to 7 mg/kg) ranged from 0.23 to 0.90 mg/L (mean of 0.54 mg/L); that is, the maximum recorded concentration was less than one-fifth the toxicity threshold for lignocaine of 5 mg/L. The study suggested that the majority of patients tolerated the local anaesthetic approach very well and that the wide safety margin allowed ample scope to develop the local anaesthetic approach for the repair of more complex hernia repairs (e.g. large, bilateral or strangulated herniae, or those in obese patients) without risk of exposing patients to lignocaine concentrations which may cause toxic side effects.

Age Factors↗

The granulocyte-macrophage colony-stimulating factor promoter cis-acting element CLE0 mediates induction signals in T cells and is recognized by factors related to AP1 and NFAT.

Expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in T cells is activated by the combination of phorbol ester (phorbol myristate acetate) and calcium ionophore (A23187), which mimic antigen stimulation through the T-cell receptor. We have previously shown that a fragment containing bp -95 to +27 of the mouse GM-CSF promoter can confer inducibility to reporter genes in the human Jurkat T-cell line. Here we use an in vitro transcription system to demonstrate that a cis-acting element (positions -54 to -40), referred to as CLE0, is a target for the induction signals. We observed induction with templates containing intact CLE0 but not with templates with deleted or mutated CLE0. We also observed that two distinct signals were required for the stimulation through CLE0, since only extracts from cells treated with both phorbol myristate acetate and A23187 supported optimal induction. Stimulation probably was mediated by CLE0-binding proteins because depletion of these proteins specifically reduced GM-CSF transcription. One of the binding factors possessed biochemical and immunological features identical to those of the transcription factor AP1. Another factor resembled the T-cell-specific factor NFAT. The characteristics of these two factors are consistent with their involvement in GM-CSF induction. The presence of CLE0-like elements in the promoters of interleukin-3 (IL-3), IL-4, IL-5, GM-CSF, and NFAT sites in the IL-2 promoter suggests that the factors we detected, or related factors that recognize these sites, may account for the coordinate induction of these genes during T-cell activation.

Animals↗

Initial safety and immunogenicity studies of an oral recombinant adenohepatitis B vaccine.

Orally administered adenovirus may be a useful vaccine carrier of cloned antigens of other pathogens. A recombinant adenohepatitis vaccine Wy-Ad7HZ6-1, which expressed hepatitis B surface antigen and contained a large deletion in early region 3 (E3), was constructed and studied in humans. Volunteers received Wy-Ad7HZ6-1 (n = 3), adenovirus type 7 vaccine (n = 3) or placebo (n = 3). Recipients of Wy-Ad7HZ6-1 shed less vaccine virus in the stool for a shorter period and had a lower titre of anti-adenovirus type 7 antibodies than recipients of the adenovirus 7 vaccine. None of the three Wy-Ad7HZ6-1 vaccinees developed antibody to hepatitis B surface antigen after this one dose primary immunization regimen. The E3 region may be required for optimal enteric growth of adenovirus-vectored vaccines.

Adenoviruses, Human↗

AIC2A is a component of the purified high affinity mouse IL-3 receptor: temperature-dependent modulation of AIC2A structure.

IL-3, a potent hemopoietic growth factor, interacts with distinct classes of receptor, one of high affinity and the other of low affinity. The gene for a 115 kDa, low affinity IL-3 binding protein (AIC2A) was recently cloned. Ligand affinity purification was used to show that the AIC2A gene product participates in the formation of a high affinity IL-3 receptor (IL-3R). Cells were incubated with biotin-IL-3 at 4 degrees C and IL-3 bound to the low affinity site was removed by washing, cells were detergent extracted, and then streptavidin - agarose was used to purify proteins bound to biotin-IL-3. A 115 kDa phosphotyrosine (Ptyr)-containing protein was specifically purified and its identity as AIC2A was shown in Western assays using polyclonal anti-AIC2A antibodies. A brief temperature shift of the intact, biotin-IL-3-treated cells from 4 to 37 degrees C, prior to receptor purification, results in structural and compositional changes in the IL-3R, including: (i) a 10-20 kDa increase in the apparent Mr of both the AIC2A and the Ptyr antigens, and (ii) the association of a serine/threonine kinase. These observations indicate that in its native environment, the low affinity IL-3 binding protein, AIC2A, participates to form the high affinity IL-3R and is a substrate for a tyrosine kinase. Moreover, a ligand-induced, temperature-regulatable structural change in the IL-3R may be of importance in the transduction of information through the receptor, as suggested by the enhanced association of the IL-3R with a serine/threonine kinase.

Amino Acid Sequence↗

Clinical and serologic responses to acellular pertussis vaccine in infants and young children.

We administered diphtheria, tetanus, and pertussis (DTP) vaccine containing acellular (lymphocytosis promoting factor and filamentous hemagglutinin) pertussis vaccine to three groups of 20 children each (4 to 6 years, 17 to 21 months, and 5 to 9 months of age). All the children tolerated the vaccine well; no reactions occurred that contraindicated further immunization. Older children had significantly more local (redness or swelling) and systemic (fever or fretfulness) reactions than younger children. Eighty percent to 90% of the children in the two older age groups had fourfold or greater increases in antibody titers to DTP antigens one month after vaccination. The postvaccine concentrations of antibody to tetanus and diphtheria were greater than 0.01 IU/mL in all children. Serologic responses to lymphocytosis promoting factor and filamentous hemagglutinin varied with age; significantly more older children than younger children had four-fold or greater increases. Acellular pertussis DTP vaccine was antigenic in young children and was less reactogenic than standard whole cell DTP vaccine according to rates reported in previous studies.

Antibodies↗

The effects of homogeneous human prealbumin on in vitro and in vivo immune responses in the mouse.

A highly purified preparation of human prealbumin was shown to potentiate the sensitivity of rosette spleen forming cells of adult thymectomized mice to azathioprine in vitro and in vivo and to induce the appearance of the Thy 1, 2 antigen in vitro on spleen cells of adult thymectomized mice. Prealbumin also enhanced IgM antibody synthesis to sheep red blood cells (SRBC) in vitro in 12 week old mice and in vivo in aged (45 - 58 week old) and nude (nu/nu) mice. In vivo administration, to mice that had been pre-treated with hydrocortisone, resulted in a decrease in the specific activity of thymocyte terminal deoxynucleotidyl transferase. The data indicate that the prealbumin molecule possesses immunopotentiating properties in a number of in vitro and in vivo immunocompromised murine models and that the immuno-enhancing properties of the partially purified preparation previously described were in fact due to the prealbumin component and not to other contaminating proteins.

Adjuvants, Immunologic↗