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Biomedical subjects

W J Chang

Publications and source records attributed to W J Chang.

At least 37 records · Page 2Linked to original sources

Opioid modulation of gonadotropin releasing hormone release from the hypothalamic preoptic area in the pig.

Two experiments (Exp) were conducted to examine in vitro the release of gonadotropin releasing hormone (GnRH) from the hypothalamus after treatment with naloxone (NAL) or morphine (MOR). In Exp 1, hypothalamic-preoptic area (HYP-POA) collected from 3 market weight gilts at sacrifice and sagittally halved were perifused for 90 min prior to a 10 min pulse of morphine (MOR; 4.5 x 10(-6) M) followed by NAL (3.1 x 10(-5) M) during the last 5 min of MOR (MOR + NAL; n = 3). The other half of the explants (n = 3) were exposed to NAL for 5 min. Fragments were exposed to KCl (60 mM) at 175 min to assess residual GnRH releasability. In Exp 2, nine gilts were ovariectomized and received either oil vehicle im (V; n = 3); 10 micrograms estradiol-17 beta/kg BW in 42 hr before sacrifice (E; n = 3); .85 mg progesterone/kg BW in twice daily for 6 d prior to sacrifice (P4; n = 3). Blood was collected to assess pituitary sensitivity to GnRH (.2 microgram/kg BW) on the day prior to sacrifice. On the day of sacrifice HYP-POA explants were collected and treated as described in Exp 1 except tissue received only NAL. In Exp 1, NAL increased (P < .05) GnRH release. This response to NAL was attenuated (P < .05) by coadministration of MOR. Cumulative GnRH release after NAL was greater (P < .05) than after MOR + NAL. All tissues responded similarly to KCl with an increase (P < .05) in GnRH release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Purification and characterization of smooth muscle cell caveolae.

Plasmalemmal caveolae are a membrane specialization that mediates transcytosis across endothelial cells and the uptake of small molecules and ions by both epithelial and connective tissue cells. Recent findings suggest that caveolae may, in addition, be involved in signal transduction. To better understand the molecular composition of this membrane specialization, we have developed a biochemical method for purifying caveolae from chicken smooth muscle cells. Biochemical and morphological markers indicate that we can obtain approximately 1.5 mg of protein in the caveolae fraction from approximately 100 g of chicken gizzard. Gel electrophoresis shows that there are more than 30 proteins enriched in caveolae relative to the plasma membrane. Among these proteins are: caveolin, a structural molecule of the caveolae coat; multiple, glycosylphosphatidylinositol-anchored membrane proteins; both G alpha and G beta subunits of heterotrimeric GTP-binding protein; and the Ras-related GTP-binding protein, Rap1A/B. The method we have developed will facilitate future studies on the structure and function of caveolae.

Animals↗

N-methyl-d,l-aspartate modulation of pituitary hormone secretion in the pig: role of opioid peptides.

Sixteen ovariectomized (OVX) mature gilts, averaging 139.6 +/- 3.1 kg body weight (BW) were assigned randomly to receive either progesterone (P, 0.85 mg/kg BW, n = 8), or corn oil vehicle (OIL, n = 8) injections im twice daily for 10 d. On the day of experiment, all gilts received either the EAA agonist, N-methyl-d,l-aspartate (NMA; 10 mg/kg BW, iv) alone or NMA plus the EOP antagonist, naloxone (NAL, 1 mg/kg BW, iv), resulting in the following groups of 4 gilts each: OIL-NMA, OIL-NMA-NAL, P-NMA and P-NMA-NAL. Blood samples were collected via jugular cannula every 15 min for 6 hr. All pigs received NMA 5 min following pretreatment with either 0.9% saline or NAL 2 hr after blood collection began and a GnRH challenge 3 hr after NMA. Administration of NMA suppressed (P < 0.03) LH secretion in OIL-NMA gilts and treatment with NAL failed to reverse the suppressive effect of NMA on LH secretion in OIL-NMA-NAL gilts. Similar to OIL-NMA gilts, NMA decreased (P < 0.03) mean serum LH concentrations in P-NMA gilts. However, in P-NMA-NAL gilts, serum LH concentrations were not changed following treatment. All gilts responded to GnRH with increased (P < 0.01) LH secretion. Additionally, administration of NMA increased (P < 0.01) growth hormone (GH) and prolactin (PRL) secretion in both OIL-NMA and P-NMA gilts, but this increase in GH and PRL secretion was attenuated (P < 0.01) by pretreatment with NAL in OIL-NMA-NAL and P-NMA-NAL gilts.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Involvement of the central noradrenergic system in opioid modulation of luteinizing hormone and prolactin secretion in the pig.

The role of norepinephrine (NE) in the progesterone (P)-dependent endogenous opioid peptide (EOP) suppression of LH and prolactin (PRL) secretion in the pig was studied. Fifteen ovariectomized gilts treated with P (0.85 mg/kg b.w. i.m.) twice daily for 10 days were assigned, 5 gilts each, to the following treatment groups: 1) control, 2) AIMAX (N-methyl-N1[1-methyl-2-propenyl]1,2 hydrazinedicarbothioamide), and 3) anti-GnRH serum. On day 4 of P treatment, AIMAX (125 mg per 1.8 kg feed/day), previously shown to be an NE synthesis inhibitor, was fed daily for 7 days to group 2. On the last day of P treatment, group 3 gilts received an i.v. injection of anti-GnRH serum at 0800 h while Group 1 animals received an i.v. injection of serum collected from hypophysectomized gilts. Jugular blood samples were collected every 15 min for 9 h starting at 1000 h. All gilts received two injections of naloxone (NAL; 1 mg/kg b.w., i.v.) at 1400 h and 1600 h and an injection of a GnRH analogue (D-[Ala6-desGly-NH10]-ethylamide; 5 micrograms/pig, i.v.) at 1800 h. Pretreatment serum LH concentrations were lower (p < 0.05) in AIMAX-treated gilts (0.19 +/- 0.09 ng/ml) than in controls (0.53 +/- 0.09 ng/ml), but were similar to those in GnRH antiserum-treated gilts (0.32 +/- 0.09 ng/ml). NAL increased (p < 0.001) serum LH concentrations in control animals and averaged 1.6 +/- 0.2 ng/ml the first h. AIMAX and anti-GnRH serum blocked the NAL-induced LH secretion. Serum PRL concentrations averaged 6.0 +/- 0.1 ng/ml for all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Toxoplasma gondii peritonitis.

Toxoplasma gondii most often causes encephalitis in HIV-infected patients; infections of other organs are much less often clinically apparent. In particular, peritonitis caused by T. gondii in an Human Immunodeficiency Virus (HIV)-infected patient has been reported only once previously. Herein we report a second case.

Adult↗

N-methyl-d,l-aspartate stimulates growth hormone and prolactin but inhibits luteinizing hormone secretion in the pig.

The effects of n-methyl-d,l-aspartate (NMA), a neuroexcitatory amino acid agonist, on luteinizing hormone (LH), prolactin (PRL) and growth hormone (GH) secretion in gilts treated with ovarian steroids was studied. Mature gilts which had displayed one or more estrous cycles of 18 to 22 d were ovariectomized and assigned to one of three treatments administered i.m.: corn oil vehicle (V; n = 6); 10 micrograms estradiol-17 b/kg BW given 33 hr before NMA (E; n = 6); .85 mg progesterone/kg BW given twice daily for 6 d prior to NMA (P4; n = 6). Blood was collected via jugular cannulae every 15 min for 6 hr. Pigs received 10 mg NMA/kg BW i.v. 2 hr after blood collection began and a combined synthetic [Ala15]-h GH releasing factor (1-29)-NH2 (GRF; 1 micrograms/kg BW) and gonadotropin releasing hormone (GnRH; .2 micrograms/kg BW) challenge given i.v. 3 hr after NMA. NMA did not alter LH secretion in E gilts. However, NMA decreased (P < .02) serum LH concentrations in V and P4 gilts. Serum LH concentrations increased (P < .01) after GnRH in all gilts. NMA did not alter PRL secretion in P4 pigs, but increased (P < .01) serum PRL concentrations in V and E animals. Treatment with NMA increased (P < .01) GH secretion in all animals while the GRF challenge increased (P < .01) serum GH concentrations in all animals except in V treated pigs. NMA increased (P < .05) cortisol secretion in all treatment groups. These results indicate that NMA inhibits LH secretion and is a secretagogue of PRL, GH and cortisol secretion with ovarian steroids modulating the LH and PRL response to NMA.

Animals↗

Lowering the cholesterol content of MA104 cells inhibits receptor-mediated transport of folate.

The folate receptor is clustered on the surface of MA104 cells in association with caveolae. This relationship is thought to be essential for the proper internalization and recycling of the receptor during the delivery of 5-methyltetrahydrofolate to the cytoplasm of folate-depleted cells. Both the clustered organization of the receptor and the integrity of caveolae are disrupted when cells are deprived of cholesterol. We now show that cholesterol depletion of MA104 cells markedly reduces the rate of 5-methyltetrahydrofolate internalization and causes a 70% decline in the number of receptors present in the internal, recycling compartment. This effect is consistent with morphologic data showing that cholesterol-depleted MA104 cells have a reduced number of caveolae as well as fewer receptors per caveolae.

Animals↗

Growth hormone secretion, serum, and cerebral spinal fluid insulin and insulin-like growth factor-I concentrations in pigs with streptozotocin-induced diabetes mellitus.

Diabetes mellitus was induced using streptozotocin in five gilts between 8 and 12 weeks of age. Gilts were maintained with exogenous insulin (INS) except during experimental periods. Four litter-mate gilts served as controls. At 9 months of age, all gilts were ovariectomized, and 30 days after ovariectomy, Experiment (Exp) 1 was conducted. Jugular vein catheters were inserted and blood samples were collected every 10 min for 8 hr. Experiment 2 was conducted when gilts were 11 months of age. Venous blood and cerebrospinal fluid (CSF) samples were collected in the absence (Phase I) or presence (Phase II) of INS therapy. In Experiment 1, plasma glucose concentrations were greater (P < 0.05) in diabetic (465 +/- 17 mg/100 ml) than in control (82 mg +/- 17 mg/100 ml) gilts, whereas serum INS was lower (P < 0.0001) in diabetic gilts (0.3 +/- 0.02 vs 0.9 +/- 0.05 ng/ml) and insulin-like growth factor-I was similar in diabetic and control gilts (32 +/- 3 vs 43 +/- 4 ng/ml, respectively). Mean serum GH concentration was 2-fold greater (P < 0.02) in diabetics (2.8 +/- 0.4 ng/ml) than in control gilts (1.2 +/- 0.2 ng/ml). Diabetic gilts exhibited a greater (P < 0.05) number of GH pulses than control gilts (3.2 +/- 0.4 vs 1.5 +/- 0.3/8 hr, respectively). In addition, GH pulse magnitude was markedly elevated (P < 0.02) in diabetic (5.8 +/- 0.4 ng/ml) compared with control gilts (3.3 +/- 0.6 ng/ml). Mean basal serum GH concentrations were greater (P < 0.07) in diabetic (2.2 +/- 0.5 ng/ml) compared with control gilts (1.0 +/- .1 ng/ml). In Experiment 2, CSF concentrations of insulin-like growth factor-I, INS, GH, and protein were similar for diabetic and control gilts in both phases. Serum GH levels were similar for diabetics and controls in Phase I, but were greater (P < 0.05) in diabetics than in controls in Phase II. CSF glucose levels were greater in diabetic than in control gilts in both the presence (P < 0.003) and absence (P < 0.0002) of INS therapy, whereas plasma glucose was greater (P < 0.003) in diabetic than in control gilts in the absence of INS, but returned to control concentrations in the presence of INS. However, serum GH levels were unchanged after INS therapy in the diabetic gilts. In conclusion, altered GH secretion in the diabetic gilt may, in part, be due to elevated CSF glucose concentrations, which may alter GH-releasing hormone and/or somatostatin secretion from the hypothalamus.

Animals↗

Cucurbitacin contents in Hemsleya dolichocarpa.

Hemsleya dolichocarpa was studied for its cucurbitacin contents during growing period. A colorimetric method was used to determine the total cucurbitacin levels, and a TLC densitometric assay was employed for estimating dihydrocucurbitacin F and its acetate, two active principles in Hemsleya plants. Cucurbitacin contents rise progressively from May to November; the month of November is thus the most desirable time for harvesting plant materials for medicinal uses. It was noticed that the spoiled plant samples gave an intense color reaction while dihydrocucurbitacin F and its acetate levels were not significantly altered. The accuracy of the assays is discussed.

Antineoplastic Agents, Phytogenic↗

[Effect of combinations of anticancer drugs with interferons on human lung cancer cell lines evaluated by human tumor clonogenic assay].

Using the double agar layer method of human tumor clonogenic assay, the anticancer effect of different combinations of anticancer drugs and interferons was tested on 3 lung cancer cell lines, PC-13, PC-14, and Calu-1. The anticancer drugs and the concentrations used in this study were cisplatin (1.0 microgram/mL), adriamycin (1.0 microgram/mL), mitomycin C (0.2 microgram/mL), VP-16 (5.0 micrograms/mL) and 5-FU (5.0 micrograms/mL). Three kinds of interferon, alpha, beta and gamma in 5,000 units/mL, were tested in combination or in sequence with other anticancer drugs on lung cancer cell lines. The results demonstrate an enhanced anticancer effect on PC-14 only with sequential or simultaneous combination of VP-16 with alpha, beta and gamma interferons; and on Calu-1, only with sequential use of adriamycin and beta-interferon. Our results indicate that there is no unique way of combining anticancer drugs and interferons which can obtain an enhanced anticancer effect on all lung cancer cell lines. The best combination of interferon and anticancer drugs seems to be influenced by the biological characteristics of the cancer cells.

Antineoplastic Combined Chemotherapy Protocols↗

Pharmacokinetics of sufentanil in the elderly surgical patient.

The effect of age on the distribution and elimination of sufentanil was studied in seven elderly (77 +/- 5 yr, mean +/- SD) and seven younger (41 +/- 15 yr) neurosurgical patients. Following a single IV bolus of sufentanil 2 micrograms.kg-1 multiple arterial samples were obtained at timed intervals and plasma concentrations of sufentanil were measured by radioimmunoassay. Pharmacokinetic variables were calculated from the derived compartmental models. The initial volume of distribution was significantly smaller in the elderly patients (310 +/- 109 ml.kg-1 vs 491 +/- 112 ml.kg-1 mean +/- SD). Elimination half-lives, plasma clearances, and total volumes of distribution were similar for elderly and younger subjects. Six of seven elderly patients required administration of naloxone at the termination of surgery to achieve an adequate rate of ventilation (greater than eight breaths.min-1) while only one younger patient required antagonism of ventilatory depression. The authors believe that age-related differences in the action of sufentanil cannot be accounted for by the observed differences in the initial volume of distribution. It is concluded that alterations in pharmacodynamics appear to be of greater importance in the prolonged opioid effect seen in the elderly.

Adult↗

Serum prolactin and growth hormone responses to naloxone and intracerebral ventricle morphine administration in heifers.

These studies examined responses of serum prolactin (PRL) and growth hormone (GH) to opioid agonist and antagonist administration in heifers. To minimize nonspecific and behavioral effects and to facilitate future studies with specific opioid receptor agonists, a cannula was placed within the third cerebral ventricle of the brain of 4- to 10-mo-old heifers to directly access hypothalamic regions involved in the regulation of PRL and GH secretion. Increasing doses of morphine (M) from 2 to 1,500 micrograms injected into the third cerebral ventricle increased (P less than .001) serum PRL concentrations in a dose-related manner. Growth hormone responses were variable, resulting in elevated (P less than .05) serum concentrations following morphine, but no dose-related effects were apparent. Both PRL and GH responses to 700 micrograms M were absent when an intracerebral ventricle injection of an equimolar dose of naloxone, an opioid receptor antagonist, was administered prior to M. In a replicated 4 x 4 latin square, the effects of intravenous naloxone on PRL and GH responses was tested in young (86 +/- 11 d) and older (234 +/- 6 d) heifers. Naloxone at doses of 1, 2 and 4 mg/kg reduced (P less than .05) serum concentrations of PRL for 45 to 60 min. Mean concentrations of GH tended to be higher (P less than .07) in older heifers All doses of naloxone decreased (P less than .05) serum GH concentrations in older heifers but proved ineffective in younger heifers. There were no differences between doses of naloxone on either PRL or GH. These data suggest that endogenous opioids are involved in the regulation of PRL and GH secretion in heifers.

Animals↗

Elevation of glutathione levels and glutathione S-transferase activity in arsenic-resistant Chinese hamster ovary cells.

Arsenic-resistant Chinese hamster ovary (CHO) cells were established by progressively increasing the concentration of sodium arsenite in culture medium. One of the resistant clones, SA7, was also cross-resistant to As(V), Zn, Fe(II), Co, and Hg. The susceptibilities to sodium arsenite in parental CHO cells, revertant SA7N cells, and resistant SA7 cells were correlated with their intracellular glutathione (GSH) levels and glutathione S-transferase (GST) activity. The resistance in SA7 cells was diminished by depletion of GSH in cells after treatment with buthionine sulfoximine. Furthermore, after reexposure of revertant SA7N cells to sodium arsenite, the intracellular GSH levels, GST activity, and resistance to sodium arsenite were raised to the same levels as SA7 cells. These data indicate that the elevation of intracellular GSH levels and GST activity in SA7 cells may be responsible for the resistance to arsenite. A p25 protein, which could be a monomer subunit of GST, accumulated in SA7 cells. In addition, an outward transport inhibitor, verapamil, indiscriminately increased the arsenite toxicity in resistant and parental cells.

Animals↗

Rapid multielement analysis of oyster and cockle tissue using X-ray fluorescence spectrometry, with application to reconnaissance marine pollution investigations.

Forty-two elements in four standard reference materials and oyster and cockle tissue were analysed by the X-ray fluorescence spectrometry (XRF) method. Comparisons between certified values for standard reference materials and those of the authors indicate that XRF is suitable for determining Ba, Br, Cu, Fe, Mn, Pb, Rb, Sr, and Zn in organic matrix. Results for As, Cd, Cr, and Ni indicate that XRF is not reliable when analysing within approximately 2 mg kg-1 of the detection limits for these elements. XRF has been used to show that cockles accumulate Fe, Hg, I, Pb, Sr, Ti and Zn and oysters accumulate Cr, Cu, Fe, La, Ni, Ti, Yb, and Zn in moderately polluted areas. Values for As, Cu, Fe, Hg, Ni, Pb, Ti and Zn have been verified using atomic absorption spectroscopy. Whilst Hg was successfully determined, its limit of detection using XRF (9 mg kg-1) is too high if results are to be compared with the commonly used health standard for Hg in edible marine biota (0.5 mg kg-1 wet wt.). XRF has the capacity however to give an accurate linear response to a broad range of elements in approximately the 0-500 mg kg-1 range and is sensitive to much higher values without further sample manipulation. Hence, XRF has potential to be employed more extensively than is presently the case for elemental monitoring in broad-ranging reconnaissance marine pollution studies.

Animals↗

Marine-acquired infections. Hazards of the ocean environment.

Numerous pathogenic bacteria are found in seawater. They can cause several environmental infections, such as conjunctivitis, otitis externa, wound infections, pneumonia, and gastrointestinal illness. The incidence of some of these infections could be lowered if people took care to avoid eating undercooked seafood, swimming in brackish water, or sustaining lacerations in a marine environment. However, such infections will probably increase in frequency as more people visit ocean resorts. Prompt elimination of the infective agent, adequate wound care, and avoidance of reexposure can minimize the severity of the condition.

Bacterial Infections↗

Post-treatments with sodium arsenite during G2 enhance the frequency of chromosomal aberrations induced by S-dependent clastogens.

Treatment with sodium arsenite during the G2 phase potentiated the chromatid breaks and chromatid exchanges induced by ultraviolet light or 4-nitroquinoline 1-oxide but not those induced by methyl methanesulfonate, ethyl methanesulfonate, mitomycin C or cisplatin in Chinese hamster ovary cells. A comparison was made between the effects of treatment during G2 with sodium arsenite, cytosine-beta-D-arabinofuranoside, aphidicolin, hydroxyurea, caffeine, 3-aminobenzamide and novobiocin on the frequency of chromosomal aberrations induced by the above-mentioned S-dependent clastogens. It was found that the effects varied considerably, both quantitatively and qualitatively. However, potentiation was more often observed in the chromosomal aberrations induced by ultraviolet light and 4-nitroquinoline 1-oxide than by other S-dependent clastogens, and the frequency of chromatid exchanges was potentiated only in cells pretreated with ultraviolet light or 4-nitroquinoline 1-oxide. Furthermore, for all of the S-dependent clastogens studied, treatment with cytosine-beta-D-arabinofuranoside during the G2 phase potentiated the frequency of chromatid breaks but not the frequency of chromatid exchanges.

Animals↗