Search PubMed⌕ Search

Biomedical subjects

L J Wallace

Publications and source records attributed to L J Wallace.

At least 91 records · Page 5Linked to original sources

Age-related change in alpha-adrenergic responsiveness of the urinary bladder of the rat is regionally specific.

The effects of age on the responsiveness of the body of the urinary bladder and base of the bladder to alpha-adrenergic agonists were studied. Regions of the bladder were isolated from Fischer 344 rats, ages 7, 16, and 27 months. Maximum isotonic contractions elicited by potassium chloride (KCl) in both regions of the bladder were unaffected by age. In the bladder body there was an age-related increase in the maximum contraction elicited by phenylephrine, norepinephrine and clonidine. No such alteration in responsiveness was observed in the base of the bladder with age. The ED50 values of all three agonists were unchanged with age in both regions of the bladder. The pA2 values of prazosin and yohimbine were approximately 8.5 and 6.0, respectively, in the body of the bladder, and these values were not altered by age. Thus, it is concluded that an age-related increase occurs in the responsiveness of the body of the bladder to alpha-adrenergic activation and that these changes are mediated by alpha 1-adrenoceptors.

Aging↗

Effects of phenothiazines on phosphate incorporation and chloride uptake in isolated intestinal epithelial cells.

Isolated, intact epithelial cells from rat ileum synthesized a variety of radiolabeled compounds when 32Pi was added to the incubation medium. One of these, referred to as P-0.7 because of its Rf value in the thin layer chromatography system used to separate phosphorylated compounds, was found in the extracellular medium but not in extracts of cells. Synthesis of P-0.7 was inhibited by phenothiazines, with an EC50 value of 205 microM for trifluoperazine. Phenothiazines also inhibited uptake into isolated cells, with EC50 values of 288 and 359 microM for trifluoperazine and chlorpromazine, respectively. Effects of the phenothiazines on chloride uptake were not mimicked by the local anesthetic lidocaine (1 mM), the calcium channel blocker verapamil (0.5 mM), SITS or furosemide, or by removal of sodium or calcium from the medium.

Animals↗

Effect of age on cholinergic muscarinic responsiveness and receptors in the rat urinary bladder.

The effects of age on urinary bladder responsiveness to muscarinic agonists and on the Bmax and Kd of the binding of [3H]quinuclidinyl benzilate (QNB) to muscarinic receptors of the bladder were studied. Bladder bodies and bases were isolated from Fischer 344 rats, ages seven, 16 and 27 months. No age-dependent change in maximum KCl-elicited isotonic contractions was observed in either bladder region. The bladder base showed an age-dependent increase in the maximum contractions (Emax) elicited by muscarinic agonists. The Emax values for bladder bases from rats 27 months of age were 44 per cent, 58 per cent and 76 per cent greater than those from rats seven months of age for acetylcholine, bethanechol and oxotremorine, respectively. No such alteration in responsiveness was observed in the bladder body with age. There were no age-related changes in ED50 values for the three agonists in either bladder region. Analysis of [3H]QNB binding in the bladder base demonstrated a modest 18 per cent increase in the Bmax (fmol./mg. tissue) from seven to 16 months and a significant 39 per cent decrease from 16 to 27 months. In the bladder body, the Bmax progressively increased by 25 per cent from seven to 27 months. The Kd values of [3H]QNB did not change with age in either region. The data demonstrate that the age-related increase in the responsiveness of the bladder is regionally specific and cannot be explained by a change in the number or affinity of muscarinic receptors.

Acetylcholine↗

Synovial fluid eosinophilia: a case report in a dog and review of the literature.

The first known report of synovial fluid eosinophilia in a dog is described here. The occurrence of eosinophils in joint fluid is rare. Sporadic cases have been recorded in humans and most can be related to immunemediated reactions, both parasitic and non- parasitic. The dog in this case report had 20-52% eosinophils in multiple joints, as well as hemarthrosis and marked mononuclear cell reactivity. An intense peripheral eosinophilia was demonstrated one week later. The associated lameness resolved with non-steroidal anti-inflammatory therapy. Lack of remarkable history or other clinical symptoms led to a diagnosis of idiopathic, eosinophilic, polyarthritis, likely immune-mediated.

Journal Article↗

Muscarinic receptors on rat ileal villus and crypt cells.

Ileal villus and crypt cells exhibit morphological and biochemical differences which may be responsible for functional differences in relation to ion transport. Cholinergic agonists act directly on epithelial cell muscarinic receptors, but it is not known if these receptors exist on both villus and crypt cells. Using the potent muscarinic antagonist [3H](-)-quinuclidinyl benzilate (QNB) we have determined the distribution of muscarinic receptors in rat ileal villus and crypt cells. Plasma membrane preparations from ileal villus and crypt cells possessed a specific, saturable, and high affinity QNB binding site with apparent dissociation constants of 0.23 +/- 0.05 and 0.21 +/- 0.04 nM (mean +/- s.e., n = 6) and densities of 92.2 +/- 2.8 and 90.1 +/- 16.2 fmol (mg protein)-1, respectively. Both types of cells showed similar potencies for agonist and antagonist competition of QNB binding. The muscarinic receptors in membrane fractions from villus cells were found primarily on the basolateral membrane rather than on the brush border membrane. Secretion induced by cholinergic stimulation of the small intestine might, therefore, be due to an effect on both villus and crypt cells as both types contain muscarinic receptors. Furthermore, such stimulation also may result in mucin secretion, as goblet cells were present in the preparation we studied, and receptors on these cells may have contributed to the amount of binding of [3H]QNB.

Animals↗

Intestinal epithelial cells and musculature contain different muscarinic binding sites.

Muscarinic receptors on epithelial cells mediate intestinal secretion, while those in intestinal smooth muscle mediate motility. Experiments were carried out to determine whether the muscarinic receptors mediating each of these two functions in intestinal tissue might be associated with differences in the way agonist and antagonist drugs interact with the receptors. The inhibition constant (Kj) values for atropine, pirenzepine, and oxotremorine competition of specifically bound (3H)QNB were determined using membrane preparations from the muscular coat and from epithelial cells of rat jejunum, ileum, and colon. The Kj values of atropine were similar (1.2-10 nM) when comparing muscle layers and epithelial cells from any intestinal region. In contrast, the Kj values for pirenzepine were significantly higher in membranes from the musculature (400-1,200 nM) than in any of the epithelial cell membranes (20-100 nM). Kj values for pirenzepine in gut muscle were similar to those in heart (300 nM), whereas the Kj values in the cerebral cortex (39 nM) and the epithelial cell membranes closely approximated one another. The Kj values for oxotremorine competition of QNB binding in all intestinal muscular tissues (29-48 nM) and in heart (16 nM) were less than those of the intestinal epithelial cells (100-1,300 nM) or cerebral cortex (71 nM). Thus, pirenzepine and oxotremorine binding studies show that the nature of interactions between these agents and muscarinic sites is different when comparing epithelial cells and musculature of the gut.

Animals↗

Dietary choline affects response to acetylcholine by isolated urinary bladder.

Age-related increases occur in the response of isolated urinary bladders to the parasympathetic neurotransmitter acetylcholine (ACh). Experiments were carried out to determine whether long-term elevation or diminution in the amount of ingested choline can also affect the response of the urinary bladder to ACh. Female C57BL/6J mice were maintained on a choline-deficient chow and on drinking water supplemented with either 0, 1.5, or 4.0 mg/ml choline chloride from 8 to 20 months of age. Isolated bladders from choline deficient animals showed a 46% increase in the maximum response to ACh as compared to those from normal choline animals, while bladders from animals on choline enriched diets showed a 15% decrease in maximum contractile response. Radioligand binding experiments suggested that the functional changes result from alterations in the density of muscarinic receptors in the bladder. The results are consistent with the hypothesis that muscarinic receptors are down-regulated to compensate for increased parasympathetic activity associated with choline-enriched diets and up-regulated to compensate for decreased parasympathetic activity associated with choline-deficient diets.

Acetylcholine↗

Jejunal-ileal differences in dopaminergic but not alpha-adrenergic antisecretory effects.

Clonidine, an alpha-adrenergic agonist, and apomorphine, a dopaminergic agonist, inhibit water secretion in rat intestine induced by dibutyryl cAMP (DBcAMP) in situ. Apomorphine reversed DBcAMP-induced secretion in ileum and jejunum with ED50 values of 90 and 200 nM, respectively. ED50 values for clonidine's antisecretory effect were 32 and 2 microM in ileum and jejunum, respectively. The antisecretory effects of both clonidine and apomorphine were blocked by the alpha-adrenergic antagonist phentolamine and by the dopaminergic antagonists halo-peridol and sulpiride. Phentolamine was about 10-fold more potent against clonidine than against apomorphine in the ileum and the jejunum. Haloperidol and sulpiride were at least 10-fold more potent against apomorphine than against clonidine in the ileum. In contrast, in the jejunum, haloperidol was equally potent in blocking effects of both agonists, while sulpiride did not block the apomorphine effect. The data are consistent with the presence of both alpha 2-adrenergic and DA2-dopaminergic receptors that stimulate absorption in the ileum. In the jejunum, antisecretory effect appears to be mediated by an action on either an alpha 2-adrenergic or a dopaminergic receptor with characteristics different from those of peripheral DA1- or DA2-receptors.

Animals↗

Streptozocin-induced diabetes affects rat urinary bladder response to autonomic agents.

The response of the urinary bladder body and base to autonomic agents was studied in streptozocin (STZ)-diabetic rats. The bladder body region from 6-wk diabetic rats showed no changes in response to acetylcholine, phenylephrine, or isoproterenol. In contrast, the bladder base region showed a 39% increase in contractile response to acetylcholine and a 37% increased response to phenylephrine. In tissues from 47-wk diabetic animals, the bladder body showed a 51% increased contractile response to acetylcholine and a 37% increased relaxation response to isoproterenol. The bladder base showed a 66% increased contraction to acetylcholine. Thus, in the bladder base, enhanced responses to acetylcholine are detected soon after induction of diabetes and continue to increase as the diabetic state progresses. Moreover, in the same bladder region, an increase in responsiveness to alpha-adrenergic stimuli occurs. In the bladder body, enhanced responses to cholinergic and to beta-adrenergic stimuli occur, but are only observed in a more chronic diabetic state. The data suggest that an effect associated with autonomic diabetic neuropathy of the urinary bladder is an increased postsynaptic responsiveness to cholinergic stimuli in both regions.

Acetylcholine↗

Evaluation of autogeneic and allogeneic cortical chip grafting in a feline tibial nonunion model.

A feline tibial nonunion model was used to evaluate the efficacy of fresh autogeneic and deep-frozen allogeneic cortical chip grafts for bone repair. Rigidly fixated tibial ostectomies with a segmental defect length of 1 cm were grafted with 3 mm X 2 mm chips of cortical bone in 12 skeletally mature cats. Six cats were given fresh autogeneic bone (group A) and 6 were given deep-frozen allogeneic bone (group B). Bone healing was evaluated radiographically and histologically over a 12-week period. Consolidating bony callus and palpable stability of the tibia after bone plate removal were evident in all group A cats and 4 of the 6 group B cats by 12 weeks after surgery. Bone remodeling had progressed to intermediate restoration of diaphyseal structure in 2 cats of each group. Fibrous replacement of graft chips, absence of bony callus, and instability of the tibia after bone plate removal were evident in 1 group B cat at 12 weeks. The remaining group B cat was withdrawn from the study at 6 weeks due to loosening of the bone plate and screws.

Animals↗

Evaluation of Key's hypothesis in the feline tibia: an experimental model for augmented bone healing studies.

Key's hypothesis states that a segmental long bone defect 1.5 times the diaphyseal diameter exceeds the regenerative capacity of bone in skeletally mature dogs and results in nonunion. This hypothesis was evaluated in 5 adult cats with rigidly fixated segmental tibial ostectomies ranging from 1.25 to 1.52 times the diaphyseal diameter. Clinical, radiographic, and histologic data were obtained over a 12-week period. Healing was classified as mature bony union, clinical union, delayed union, or nonunion. Absence of a consolidating callus and instability after removal of fixation devices was found for all cats at 12 weeks. Scant formation of new bone within the gap was histologically evident for only 1 cat. In the remaining 4 cats, fibrous tissue and striated muscle predominated within the gap, and independent healing of the proximal and distal cut ends of the bone were observed. The occurrence of 4 nonunions and 1 equivocally delayed union indicated that Key's hypothesis overestimates the regenerative capacity of bone in the cat. Failure of this experimental model to produce clinical union within 12 weeks demonstrated that this model is a valid method of investigating augmented bone healing techniques that promote union within this period in the cat.

Animals↗

Angles of inclination and anteversion in hip dysplasia in the dog.

The angles of inclination and anteversion of the femoral head and neck were measured on 150 limbs of 75 dogs. These hip angles were compared with pathoanatomic and radiographic scores of hip dysplasia. There was a minimal difference between dysplastic and healthy dogs in the angles of inclination and anteversion. It was concluded that in this series of dogs, hip angles did not have a part in the development of hip dysplasia.

Animals↗

Age-related changes in sensitivity of rat urinary bladder to autonomic agents.

Experiments were done to determine if age-related changes occur in autonomic regulation of rat urinary bladder. The maximum contractile responses to acetylcholine were 63% and 15% greater in isolated bladders from 29-month and 17-month animals, respectively, as compared to 7-month animals. The amounts of [3H]quinuclidinyl benzilate bound to membrane preparations were 46% and 7% greater. In contrast, no age-related changes were observed in phenylephrine-induced contraction or in isoproterenol-induced relaxation of bladder. Thus, the urinary bladder of aged rats appears to develop increased sensitivity to cholinergic stimuli because of an increase in the number of muscarinic cholinergic receptors.

Acetylcholine↗

Canine hip dysplasia in German Shepherd Dog-Greyhound crossbreeds.

Nineteen German Shepherd Dog-Greyhound crossbreeds in 7 litters were evaluated by pathoanatomic and/or radiographic examination of their pelves when 12 to 24 months old (mean, 19 months). The prevalence of hip dysplasia in the crossbreeds was 42% (8/19). The prevalence of hip dysplasia in purebred German Shepherd Dog half-siblings in 16 litters produced by parents of the crossbreeds when mated to other German Shepherd Dogs was 35% (16/46). When numerical values were assigned to the pathoanatootmic and radiographic evaluations of the pelves, it was found that the severity of dysplastic changes in the crossbreeds were not significantly different from those changes in their purebred German Shepherd Dog half-siblings. It was concluded that selection for normal hips through mating German Shepherd Dogs with Greyhounds would be no more effective in lowering the prevalence of hip dysplasia than would selection within the German Shepherd Dog breed, which would be more desirable with regard to maintaining the standard of the breed.

Animals↗