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Biomedical subjects

P Canfield

Publications and source records attributed to P Canfield.

At least 19 recordsLinked to original sources

Dominantly inherited beta thalassaemia intermedia caused by a new single nucleotide deletion in exon 2 of the beta globin gene: Hb morgantown (beta91 CTG>CG).

Family members in multiple generations of an Irish-American family were investigated for moderate to severe microcytic anaemia, inherited in an autosomal dominant fashion. A novel frameshift mutation of the beta globin gene was discovered. This study highlights the importance of considering dominantly inherited beta thalassemia in the investigation of anaemia, even in patients with ethnic backgrounds not usually associated with beta thalassaemia.

Adult↗

Magnetic ground state of pure and doped CeFe2.

A combination of neutron elastic and inelastic, resonant x-ray scattering, and 57Fe Mössbauer experiments are used to determine the unusual magnetic ground state of CeFe2. The complementarities between different time-scale techniques may allow one to understand the dynamic features of the ground state in CeFe2 and its pseudobinary compounds, and how the frustration of Fe tetrahedra leads the appearance of antiferromagnetic fluctuations in the presence of ferrimagnetism. The resulting model can be used to rationalize many of the unusual and conflicting experimental results reported for this material in the literature.

Journal Article↗

Immunohistochemical characterization of lymphosarcoma in two alpacas (Lama pacos).

Species cross-reactive anti-peptide antibodies were assessed in formalin-fixed tissue for use in immunophenotyping of lymphosarcoma in two alpacas. Diagnosis of lymphosarcoma was made by routine histopathological examination. Primary antibodies used for immunophenotyping were anti-human CD3 and anti-human CD5 for T cells; and anti-human CD79a and anti-human CD79b for B cells/plasma cells. In one case, most of the neoplastic cells were labelled with both anti-CD3 and anti-CD79b, and smaller numbers were labelled with anti-CD79a. The other case was classified as a B-cell tumour on the basis of labelling of the majority of neoplastic cells with anti-CD79b and anti-CD79a. This is the first recorded attempt at immunophenotyping lymphosarcoma in alpacas and, to our knowledge, the first record of presumptive co-expression of T- and B-cell-associated molecules in lymphosarcoma in the veterinary literature.

Animals↗

Protein microanalysis of animal tears.

Sub-microlitre volumes of normal koala, mouse, dog, rat and cat tears were fractionated using size exclusion-high performance liquid chromatography (SE - HPLC), giving reproducible profiles which were different for each species. Microlitre volumes of tears were also fractionated using sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS - PAGE), resulting in good separation of individual tear proteins with a species specific distribution. Tears from koalas with conjunctivitis and mice with keratitis were similarly examined and showed mostly quantitative changes. These simple, rapid techniques gave reproducible results and, in contrast to conventional separation techniques, used easily obtainable volumes (as little as 0.75 microl) of tears. Their expansion could allow isola tion, identification and quantitation of individual tear components, enabling effective investigation of changes occurring in disease.

Animals↗

Histological and immunohistological study of the developing and involuting superficial cervical thymus in the koala (Phascolarctos cinereus).

The thymuses of 44 koalas, ranging from less than 30 d to more than 14 y of age, were examined histologically and immunohistologically. The thymuses from 17 of these koalas dying acutely through trauma were regarded as not being significantly affected by disease and formed the basis for study of the normal thymus. Most other koalas had chronic illness and, consequently, disease affected (involuted) thymuses. Histologically, thymuses showed obvious corticomedullary differentiation with small Hassall's corpuscles visible in koalas more than 8 mo of age. Most cortical and medullary lymphocytes stained for CD3 and CD5 (T lymphocyte markers) while some cells (predominantly medullary) stained for CD79b (B lymphocytes and plasma cells), IgG (plasma cells) or MHC class II (reticular epithelium, macrophages and possibly lymphocytes). Adults of up to 5-6 y of age which had died through trauma had little evidence of involution and had prominent Hassall's corpuscles and medullary epithelial thymocytes. Thymic eosinopoiesis was an inconsistent finding. In traumatised animals over this age, involution was obvious with fibrous replacement of lobules, loss of Hassall's corpuscles and the development of dilated ducts lined by nonciliated epithelium. However, loss of lymphocytes was gradual and pockets of lymphocytes, centrally located in lobules, were still present in the oldest koala examined. In these involuted thymuses, remaining lymphocytes stained for CD3 and lesser numbers of CD5 and CD79b. Plasma cells were common and often stained both for IgG and MHC class II. Thymuses of chronically diseased koalas showed accelerated involution when age matched with thymuses from traumatised koalas. Chronically ill koalas as young as 18-24 mo showed advanced involution, but the morphological and immunohistological characteristics of involuted thymus from diseased koalas could not be distinguished from those of involuted thymuses derived from traumatised koalas. It was concluded that development of the koala thymus is completed at 8 mo of age and that for normal koalas involution is a gradual process which starts not at but after sexual maturity. Immunohistological characterisation of the thymus was comparable to that reported for a variety of eutherian mammals.

Aging↗

Stimulation of bicarbonate secretion by alpha- and beta-adrenoceptor agonists in rat caecum in vitro.

This study examines the effects of adrenergic drugs on bicarbonate secretion by the rat caecum in vitro. Noradrenaline, phenylephrine but not clonidine, stimulated secretion in a concentration-related manner. Noradrenaline responses were antagonised by alprenolol (20 microM) but not phentolamine (10 microM) whilst phenylephrine was antagonised by phentolamine (10 microM), prazosin (5 microM) but not yohimbine (5 microM), alprenolol or tetrodotoxin (1 microM). Replacement of mucosal Cl- abolished the phenylephrine response. Combined stimulation with maximum concentrations of phenylephrine and isoprenaline gave a response which was not greater than that to either agonist alone but it did involve both alpha- and beta-adrenoceptors as judged from the effects of alprenolol and phentolamine either alone or combined. Submaximum concentrations of the two agonists did show additive responses. The results show that alpha 1- but not alpha 2-adrenoceptor agonists stimulate bicarbonate secretion and may act on the same transport mechanism as beta-adrenoceptor agonists. Noradrenaline stimulates via beta-adrenoceptors.

Adrenergic alpha-Agonists↗

Traumatic injuries occurring in possums and gliders in the Blue Mountains, New South Wales.

Twenty common brushtail possums (Trichosurus vulpecula), 23 ringtail possums (Pseudocheirus peregrinus) and five sugar gliders (Petaurus breviceps) from the Blue Mountains, New South Wales, Australia were evaluated for traumatic injuries between 1989 and 1990. Ten brushtail possums and five ringtail possums were hit by motor vehicles with injuries primarily to the anterior of the body. Fifteen ringtail possums and all sugar gliders were attacked by cats. Four brushtail possums were attacked by dogs. The remaining nine possums had evidence of intraspecific fighting (n = 2) or other types of trauma. Brushtail and ringtail possums were presented primarily during their main breeding seasons. There was no sex predilection. More ringtail than brushtail possums were subadults and these were injured primarily at the time of dispersal.

Accidents, Traffic↗

Stimulation of bicarbonate secretion by atypical beta-receptor agonists in rat cecum in vitro.

This study examined the effects of beta-adrenoceptor agonists on bicarbonate secretion by the rat cecum in vitro. Isoprenaline, the beta 2-selective agonist salbutamol and the 'atypical' beta-agonist SR58611A stimulated bicarbonate secretion in a concentration related manner. Another atypical agonist, BRL 37344, also stimulated. Responses to isoprenaline were antagonised by alprenolol and propranolol (both 20 microM) but not the selective antagonists practolol (10 microM) or ICI 1185511 (1 microM). Responses to SR 58611A were only antagonised by alprenolol. Replacement of Cl- by NO3- on the mucosal surface reduced basal secretion and abolished the response to isoprenaline. Exposure to a single concentration of atypical agonist resulted in desensitisation to a second application and to isoprenaline. There was no evidence of desensitisation with isoprenaline or salbutamol. The results show that beta-adrenoceptor agonists stimulated bicarbonate secretion in contrast to the previously described inhibitory effect of cholinergic drugs in this tissue. Stimulation was mediated by beta-adrenoreceptors, which had properties consistent with the atypical receptors described in gut smooth muscle and in adipose tissue. Both adrenergic and cholinergic drugs may act on the same mechanism of secretion which may involve an exchange of HCO3- for mucosal Cl-.

Adrenergic beta-Agonists↗

Beta-adrenoceptor agonist stimulation of acid secretion by rat stomach in vitro is mediated by 'atypical' beta-adrenoceptors.

1. A previous study showed beta-adrenoceptor agonists stimulated acid secretion by rat stomach in vitro. The receptors could not be classed as either the beta 1- or beta 2-subtype. This study examines the effect of 2 'atypical' beta-agonists on acid secretion. 2. Basal and isoprenaline-stimulated acid secretion were compared in tissues bathed either in HEPES/O2- or HCO3-/CO2-buffer. Basal secretion was underestimated in HCO3- by an amount equal to the rate of base section. Tissues responded well in HEPES buffer and there was no base secretion following acid inhibition with SCH 28080. HEPES was used for the study. 3. SR 58611A stimulated acid in a concentration-related way (0.1-5 microM). Maximum response at 1 microM was equal to the response to a maximal concentration of isoprenaline. BRL 37344 (1 microM) also stimulated to the same extent. 4. Responses to isoprenaline (5 microM) and SR 58611A (1 microM) were reduced by propranolol (10 microM) but not by alprenolol (10 microM) or by practolol (12.5 microM) plus ICI 118551 (1 microM). 5. Exposure to SR 58611A (1 microM) led to desensitization to isoprenaline but not to bethanechol (1 microM) or histamine (50 microM). 6. We conclude that a HEPES/O2-buffer is advantageous when measuring gastric acid secretion in vitro and the stimulatory effect of beta-adrenoceptor agonists is mediated by 'atypical' receptors.

Adrenergic beta-Agonists↗

The effect of drugs acting on cholinoceptors and mucosal chloride on luminal bicarbonate transport by rat caecum under in vitro conditions.

1. The transport of HCO3- (Jsm) from a HCO3(-)-buffered serosal to an unbuffered mucosal saline solution has been studied in rat caecum in vitro. 2. Carbachol, bethanechol and acetylcholine (ACh) caused a concentration-dependent fall in Jsm with similar maximum effects. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP) also inhibited Jsm but the effect was less than with the other drugs. Maximum cholinoceptor inhibition was less than that obtained with anoxia. 3. Responses were blocked by atropine (10(-5) M) but hexamethonium (2 x 10(-4) M) significantly altered the response only to DMPP. 4. Physostigmine (10(-5) M) shifted the ACh response curve to the left but physostigmine itself caused inhibition of Jsm which was blocked by atropine. 5. Substitution of mucosal Cl- by NO3- reduced Jsm to a similar extent to maximum cholinoceptor effect and abolished responses to bethanecol. Anoxia further reduced Jsm in the presence of NO3-. 6. Mucosal SITS and DIDS (1 mM) reduced Jsm but this was less than the maximum inhibition seen with drugs acting on cholinoceptors or mucosal Cl- removal. Serosal DIDS caused a similar inhibition. 7. We conclude that cholinoceptor agonists inhibit but do not abolish luminal bicarbonate transport by an action on muscarinic receptors.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Characteristics of luminal bicarbonate secretion by rat cecum in vitro.

Under in vitro conditions the rat cecum transported HCO3- from the serosal to an unbuffered solution in contact with the mucosal side [Js----m = 7.12 +/- 0.18 mumol.cm-2.h-1 (n = 149)]. With reversed tissues, a significantly lower flux was obtained [Jm----s = 2.47 +/- 0.11 mumol.cm-2.h-1 (n = 42)]. Both fluxes were stable for several hours. Increasing the H+ gradient across the tissue for 60 min did not change either flux. Anoxia for 45 min reversibly reduced Js----m by 65 +/- 3% (n = 20) but had no effect on Jm----s. Both fluxes were linearly related to HCO3- concentration on the buffered side, but the slope for Js----m was 3.5 times that for Jm----s. When tissues were initially set up in HEPES buffer rather than HCO3-, Js----m was 0.12 +/- 0.05 mumol.cm-2.h-1 (n = 6), which is not significantly different from zero. Replacement of Na+ by choline reduced Js----m by 40 +/- 3% (n = 11) and ouabain (1 mM) by 24 +/- 3% (n = 5). Replacement of Cl- with isethionate or K+ with Na+ for 60 min did not alter Js----m. Serosal application of DIDS (0.5 mM) reduced Js----m by 24 +/- 6% (n = 6), but SITS (0.5 mM), furosemide (1 mM), acetazolamide (0.1 mM), amiloride (1 mM), and a proton pump inhibitor (Sch 28080, 50 microM) had no effect. Mucosal application of DIDS, furosemide, and amiloride had no effect on Js----m. Serosal tetrodotoxin (1 microM) and indomethacin (28 microM) were also without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗