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P C Will

Publications and source records attributed to P C Will.

14 recordsLinked to original sources
PubMed1991

Platelet activating factor as a proinflammatory mediator in acetic-induced colitis in the rat.

Platelet activating factor (PAF) induces neutrophilia and produces a variety of gastrointestinal lesions. The role of PAF as a proinflammatory mediator was examined by measuring the production of PAF and the efficacy of the PAF antagonists WEB 2086 and Ro 24-0238 in acetic acid (HOAc)-induced colitis. PAF levels within the colonic mucosa, as measured by radioimmunoassay, increased from 259 +/- 119 ng/mg in control tissue, to 616 +/- 266 ng/mg in HOAc inflamed tissue. The accumulation of neutrophils within the mucosa was decreased by 53 +/- 10% by pretreatment with 3 mg/kg WEB 2086, and by 43 +/- 11% by 3 mg/kg Ro 24-0238. PAF-induced neutrophilia had no effect on the severity of HOAc-induced colitis, therefore, PAF my be involved in sustaining the chronic inflammation of colitis.

Acetates↗
PubMed1991

Evaluation of an interleukin-1 receptor antagonist in the rat acetic acid-induced colitis model.

The anti-inflammatory activity of the IL-1 receptor antagonist, IL-1ra, was evaluated in the acetic acid (HOAc)-induced model of colitis in rats. Animals treated with 10 mg/kg IL-1ra or vehicle were evaluated for general health, acute phase response, and colonic in flammation 24 hours after the initiation of inflammation. A significant decrease in the accumulation of neutrophils in the colonic mucosa as measured by myeloperoxidase activity was seen in animals with HOAc induced colitis that were treated intraperitoneally with IL-1ra when compared to animals with colitis that had been treated with vehicle. IL-1ra also reduced colonic necrosis measured grossly, although there was no effect on the histology IL-1ra had a modest effect on the HOAc-induced acute phase response, as indicated by changes in the serum iron, albumin and transferrin, but the results were not statistically significant. The number of circulating erythrocytes and neutrophils was significantly increased in animals with HOAc-induced colitis and treated with IL-1ra, suggesting that IL-1ra under these experimental conditions inhibited the migration of neutrophils to the injured colon and also the overall intestinal necrosis in the colon as assessed by gross pathology. IL-1ra may be useful as an intestinal anti-inflammatory agent.

Acetates↗
PubMed1990

Temperature regulation of microtiter plates for enzyme assays.

To facilitate the use of microtiter plates as vessels for enzyme assays, an incubator has been designed to maintain the wells of the microtiter plates at the appropriate temperature. The temperature variation within a single well was +/- 0.02 degrees (standard error of the mean) at 25 degrees C and +/- 0.02 degrees at 37 degrees C. The temperature variation was the same for internal and peripheral wells within the plates, although the internal wells were approximately 0.14 degrees C warmer than the outer wells at 25 degrees C and 0.68 degrees C cooler at 37 degrees C. The overall uncertainty (95% confidence interval) of the well temperature in a typical plate was +/- 0.4 degrees C at 25 degrees C and +/- 0.7 degrees C at 37 degrees C. This uncertainty is realistic for routine enzyme determinations, as opposed to precise studies. The incubator was designed to allow access to the plates from above so that additions could be made during the incubation. To demonstrate the suitability of microtiter plates and the incubator for enzyme determinations, this method was used to measure the activity of myeloperoxidase and alpha-naphthylbutyryl esterase.

Animals↗
PubMed1985

Quantification of ethanol-induced gastric mucosal injury by transmission densitometry.

A method to objectively quantify the extent of ethanol-induced gastric lesions has been developed. The method utilizes a transmission densitometer to measure the optical density of the photographic negative of the stomach mucosa. Tissues from ethanol- and untreated animals are compared with tissues from animals pretreated with prostanoids before ethanol; this method permits a reproducible and objective evaluation of mucosal protection. We demonstrate that the optical density is proportional to subjective score and damage, and that the densitometry method differentiates between the protective effect of different doses of 16,16-dimethyl prostaglandin E2 and natural prostaglandin E2.

Animals↗
PubMed1985

Regulation of amiloride-sensitive electrogenic sodium transport in the rat colon by steroid hormones.

The role of steroids in the regulation of colonic sodium transport was examined by infusing steroids into adrenalectomized (ADX) rats and evaluating the short-circuit current (ISC) in vitro. Amiloride-sensitive ISC was induced by aldosterone and corticosterone with half-maximal doses (ED50) of 2 and 260 micrograms X kg-1 X h-1), respectively. Synthetic glucocorticoids such as methylprednisolone (33 mg/kg) and dexamethasone (ED50 = 30 micrograms X kg-1 X h-1) were also effective. Supramaximal doses of aldosterone (7.5 times ED50) for 24 h increased the total ISC (7-fold), the amiloride-sensitive ISC (366-fold), and the conductance (2-fold), as well as the potassium-stimulated phosphatase activity (2-fold) (reported previously). Compared with aldosterone, supramaximal doses of dexamethasone (4 times ED50) produced greater increases in the total ISC (15-fold) and the amiloride-sensitive ISC (674-fold). In contrast to aldosterone, dexamethasone also increased the amiloride-insensitive ISC (3-fold). Glucocorticoid action was not mediated by insulin since the ISC from diabetic ADX rats was increased by dexamethasone to a similar extent (11-fold) as in nondiabetic rats. Estradiol, progesterone, and testosterone did not stimulate the colonic ISC of ADX rats. The ED50 values of corticosterone and aldosterone, measured in terms of amiloride-sensitive sodium transport, produced serum levels that were slightly above those of unstressed, adrenal-intact animals and thus must be considered physiological. It is concluded that at physiological levels both steroids may mediate amiloride-sensitive sodium transport in the rat colon. However, as judged from changes in serum steroid levels, aldosterone is the physiological regulator of elevated sodium absorption in sodium deficiency.

Adrenalectomy↗
PubMed1985

Amiloride-sensitive salt and fluid absorption in small intestine of sodium-depleted rats.

Secondary hyperaldosteronism produced by Na+ depletion was associated with increases in salt and fluid absorption in both the small intestine and the distal colon but not in the cecum and the proximal colon. Because these changes had not been documented for the small intestine, this study focused on the regulation of this tissue. Increased NaCl and water absorption was expressed in vitro by increases in short-circuit current and transepithelial potential and in vivo by increased fluid absorption and a decreased luminal content of Na+ and water. For example, the short-circuit current in the ileum of Na+-depleted rats was 2-fold that of adrenalectomized and 1.3-fold that of adrenal-intact control animals. The short-circuit current was inhibitable 24 +/- 14% by micromolar concentrations of amiloride in Na+-deficient animals compared with 1 +/- 3% in control animals. Similarly, ileal fluid absorption in vivo was 2.3-fold higher in Na+-deficient relative to control animals. The additional fluid absorption was sensitive to 50 microM amiloride, whereas amiloride had no effect in control animals. Furthermore, the Na+ content of the chyme from the ileum of Na+-deficient animals was about half that of controls. These results suggest that mineralocorticoids can induce the amiloride-sensitive Na+ transporter in the small intestine and that this type of epithelial salt transport can become a major pathway for salt retention by the small intestine.

Adrenalectomy↗
PubMed1979

Evidence against a specific effect of serum from patients with cystic fibrosis on sodium-dependent glucose transport in the rat jejunum.

Sera from patients with cystic fibrosis of the pancreas (CF) and normal human sera were assayed for the ability to inhibit sodium-dependent glucose transport in rat brush-border membrane vesicles. Fresh CF and age- and sex-matched control sera were both inhibitory when compared to physiologic saline. The inhibition by CF serum was 44 +/- 13% (mean +/- SD) at a final serum concentration of 6.7%, 67 +/- 34% at 10% serum, and 68 +/- 28% at 20% serum. The ratio of the inhibition of CF sera compared to that of control sera was 1.00, 0.78, and 0.93 at 6.7, 10, and 20% serum concentrations, respectively. Although a slightly greater inhibition by CF serum was observed at a concentration of 10%, this is probably not significant because no difference could be detected at a concentration of 20% serum. Glucose transport in the presence of serum was sensitive to phlorizin indicating that the residual glucose transport was proceeding by the sodium-dependent glucose transport system. These findings suggest that CF serum does not specifically inhibit the sodium-dependent glucose transport system. The intravesicular space accessible to glucose was reduced in the presence of CF or control serum. Fresh CF serum was 1.4 times more effective than fresh control serum (P less than 0.01). The presence of substantial vesicle-shrinking activity in control serum indicates that this activity cannot be considered specific for CF.

Animals↗
PubMed1978

The metabolism of methadone by cultured mammalian cells.

Rat hepatoma tissue culture cells and mouse leukemic cells were found to metabolize [1-3H] methadone to at least 2 unidentified radioactive compounds. These results suggest that cultured cells may be useful models for studying methadone metabolism by specific cell types.

Animals↗
PubMed1978

Characterization of HeLa 5'-nucleotidase: a stable plasma membrane marker.

5'-Nucleotidase, assayed as 5'-AMPase, has been extensively characterized and established as a stable, quantitative plasma membrane marker in HeLa S3 cells. The membrane 5'-AMPase has a Km of 7.0 microM. Relative affinities of the other 5'-mononucleotides for the enzyme are 5'-GMP > 5'-TMP > 5'-UMP > 5'-CMP. There are activity optima at pH7 and 10; the latter is Mg(2+)-dependent. The membrane preparations have a small amount of acid phosphatase activity that is distinct from 5'-AMPase activity but no alkaline phosphatase. AOPCP, ADP, and ATP are strongly inhibitory. Mg2+, Ca2+, or Co2+ additions do not affect the pH 7.0 activity; Mn2+ activates slightly, whereas Zn2+, Cu2+, and Ni2+ are inhibitory. EDTA slowly inactivates, but removal of the EDTA without the addition of divalent cations restores activity. The inactivation is also substantially reversed by Co2+ or Mn2+, but reactivability by divalent cations decreases with time in EDTA. ConA strongly inhibits, and alpha-methyl-D-mannoside or glucose (the latter much less efficiently) relieves the inhibition, indicating that the 5'-AMPase is a glycoprotein. Histidine is also inhibitory. Ouabain, phloretin, cytochalasin B, cysteine, phenyl-alanine, MalNEt, and IAA are without effect. 5'-AMPase activity codistributes with pulse-bound [3H]ouabain when either of two cell fractionation procedures are used. The 5'-AMPase activity per cell is constant at different cell densities in exponentially growing cells, and activity per unit cell volume remains constant throughout the cell cycle. These properties, together with its absence in other organelles, its stability to storage, its insensitivity to certain experimental manipulations, and its general insensitivity to inhibitors of specific transport systems, make 5'-AMPase a useful quantitative marker in studies on the regulation of HeLa membrane transport systems. Key Words: HeLa, 5'-nucleotidase, plasma membrane marker, non-specific phosphatases, divalent ions, ConA, AOPCP, cell cycle, mitochondria, transport inhibitors.

5'-Nucleotidase↗
PubMed1978

Methadone induced lysis of mammalian cells.

Methadone induced lysis of human erythrocytes and mouse leukemic cells was studied. The cells lyse without prior swelling that is a necessary step of colloid osmotic lysis. Methadone is accumulated by both cell types, and is widely distributed intracellurly in mouse leukemic cells. The maximum lytic rate is roughly proportional to the amount of methadone uptake and the Q10 for lysis is equal to the Q10 for methadone partitioning between octanol and water. It is concluded that the cells lyse as a result of a non-specific disruption of the plasma membrane.

Animals↗
PubMed1977

Digoxin binding.

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Blood Proteins↗