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Biomedical subjects

C Shaw

Publications and source records attributed to C Shaw.

At least 235 records · Page 13Linked to original sources
PubMed1992

Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise.

The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.

Adult↗
PubMed1992

Low to moderate intensity endurance training in healthy older adults: physiological responses after four months.

OBJECTIVE: To determine the physiological adaptations in previously sedentary healthy older men and women (mean age = 68) to a 16-week low-to-moderate-intensity exercise program. DESIGN: Randomized, controlled trial. SETTING: An exercise facility and testing laboratory in a gerontological research institute. PARTICIPANTS: Two-hundred forty-seven community-dwelling older persons free of significant cardiovascular, pulmonary, or uncontrolled metabolic disease, anemia, electrolyte abnormality, resting BP of 165/90 or greater, or chronic disease affecting the ability to exercise on a bicycle. INTERVENTION: Subjects were randomly assigned to either an exercise (n = 166) or attention control group (n = 81). Exercisers trained thrice weekly for 40 minutes on a cycle ergometer (5-minute warm up, 30 minutes at training heart rate (THR), 5-minute cool down). THR was set at 70% of peak heart rate attained on a maximal exercise test (mean = 115 +/- 15). Control subjects attended weekly group talks. Testing took place before and after the program. RESULTS: Peak attained oxygen uptake (VO2max) increased 8.5% in exercisers and decreased slightly in controls (p less than .001) and oxygen uptake at ventilatory threshold (VeT VO2) increased by 3.5% in exercisers and decreased by 3% in controls (p less than .001). This pattern of a greater increase in VO2max than VeT VO2 is different from that seen in young and middle-aged subjects. CONCLUSION: This study demonstrated that a large scale training program is feasible for healthy older people, that physiologic improvements can be measured after 16 weeks of low-to-moderate-intensity training, and that mechanisms of adaptation to exercise may be different in elderly subjects from those in younger ones.

Adaptation, Physiological↗
PubMed1991

Marsupial possum neurotensin: a unique mammalian regulatory peptide exhibiting structural homology to the avian analogue.

Neurotensin has been isolated from small intestinal extracts of an Australian marsupial, the brush-tailed possum (Trichosurus vulpecula). The primary structure was determined as: pGlu-Leu-His-Val-Asn-Lys-Ala-Arg-Arg-Val-Tyr-Ile-Leu. When compared with bovine neurotensin, marsupial possum neurotensin exhibits four amino acid substitutions. His for Tyr3, Val for Glu4 and Ala for Pro7 are identical with those found in chicken neurotensin. In addition, substitution of Pro10 with Val is unique among all neurotensins sequenced to date. Marsupial possum neurotensin is therefore of unique primary structure, displaying most sequence homology with its avian counterpart. This neurotensin may thus resemble the phylogenetic precursor present at the time of divergence of primitive mammals and birds.

Amino Acid Sequence↗
PubMed1991

Neuropeptides of the primary sensory neurones in rat skin: an ontogenic study.

Cutaneous primary sensory neurones contain a number of biologically-active peptides, including substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP). However, little information is available on ontogenic changes in the tissue concentrations of these neuropeptides. In this study, the concentrations of these neuropeptides have been assessed in dorsal and ventral abdominal rat skin at various stages of development from foetal, early neonatal, late neonatal, weaner to adult, using sensitive and specific radioimmunoassays. In addition, the levels of peptide histidine isoleucine (PHI), a peptide found in non-sensory cutaneous nerves, were assessed to control the study. The levels of PHI and NKA immunoreactivity did not change significantly at any stage of development. However, the levels of SP and CGRP immunoreactivity were significantly elevated in the early neonate with CGRP remaining elevated in the late neonate. The levels of both SP and CGRP were not significantly different between other developmental groups. Significant elevations in cutaneous SP and CGRP concentrations in early neonatal life in the rat, at a time when the pups are blind and naked, may be related to control of cutaneous sensitivity, which during this period of development, has positive survival value for the pups.

Aging↗
PubMed1991

Pancreastatin-like immunoreactivity in human carcinoid disease.

Pancreastatin-like immunoreactivity has been demonstrated in human carcinoid tumors by immunohistochemistry and radioimmunoassay, employing antisera raised to a synthetic C-terminal fragment of porcine pancreastatin. Immunohistochemistry revealed intense immunoreactivity in all tumors. By radioimmunoassay, high concentrations of pancreastatin-like immunoreactivity were measured in carcinoid tumors arising from the fore-gut (mean +/- S.D. and range: 369 +/- 955 and 9.4-3670 pmol g-1, respectively, n = 14), mid-gut (mean +/- S.D. and range: 1354 +/- 1538 and 337-3978 pmol g-1, respectively, n = 5) and in metastases associated with mid-gut tumors (mean +/- S.D. and range: 684 +/- 739 and 31-2255 pmol g-1, respectively, n = 7), compared to corresponding normal tissues (less than 1.4 pmol g-1). Individuals with hepatic metastases and carcinoid syndrome had elevated circulating levels of pancreastatin-like immunoreactivity (mean +/- S.D. and range: 770 +/- 1249 and 42-4120 pmol l-1; n = 12), significantly above the normal, fasting range (mean +/- S.D. and range: 14.9 +/- 7.5 and 4-37.5 pmol l-1, respectively, n = 42). However, patients with non-metastatic carcinoid tumors (n = 4), who had been clinically cured after primary tumor resection, had plasma levels within the normal range. Chromatographic analysis of extracts of primary lung and ileal tumors, hepatic metastases from ileal tumors and plasma from individuals with carcinoid syndrome revealed molecular heterogeneity of pancreastatin-like immunoreactivity.

Adult↗
PubMed1991

Amygdaloid lesions and stimulus-reward associations in the rat.

Rats with amygdaloid lesions were trained on learning set tasks designed to tax stimulus-reward associations. Lesions centred in the medial and ventral half of the amygdala had no effect on the acquisition of two object discriminations but did impair successive reversals of the second discrimination. The same lesions had no effect, however, on the acquisition of a spatial win-stay lose-shift task which taxed one-trial place-reward associations. In a second experiment it was found that lesions in the central and basolateral regions of the amygdala disrupted performance of the same spatial win-stay lose-shift task although, as before, acquisition was unaffected. Taken together these findings support a role for the amygdala in stimulus-reward associations and indicate that it may be particularly important when differing values of reward must be distinguished.

Amygdala↗
PubMed1991

High affinity histamine binding site is the H3 receptor: characterization and autoradiographic localization in rat brain.

The binding of the histamine autoreceptor (H3) agonist [3H]-N alpha-methyl-histamine ([3H]-N-MeHA) was examined in 25 micron thick rat forebrain sections. The specific binding was saturable and of high affinity: Scatchard analysis indicated a Kd of 2 nM and a Bmax of 25 +/- 3 fmol/section. Under similar conditions, [3H]-histamine [( 3H]-HA) bound with a Kd of 8 nM and a Bmax of 20 +/- 2 fmol/section. Competition studies indicated that both ligands bound an identical site which had the pharmacological characteristics of the H3 binding site. The high affinity binding of [3H-N-MeHA was sensitive to the presence of 5'-guanylyl-imidodiphosphate, indicating that the binding site is likely coupled to a G-protein. Autoradiographic studies indicated the [3H]-N-MeHA binding to be greatest in the nucleus accumbens, striatum, substantia nigra pars reticulata, and certain cortical areas. Striatal quinolinic acid lesions greatly reduced binding in both the striatum and ipsilateral substantia nigra, while 6-hydroxydopamine lesions of the nigrostriatal dopamine system were without effect on binding. Therefore, most of the H3 binding sites in the basal ganglia are on striatonigral projection neurons. Cortical quinolinic acid lesions greatly reduced H3 binding in cortex, indicating that the binding in cortex, as in striatum, is largely on intrinsic neurons, rather than on afferents such as histamine nerve terminals.

Animals↗
PubMed1991

The tissue distribution of rat chromogranin A-derived peptides: evidence for differential tissue processing from sequence specific antisera.

The distribution of chromogranin A and related peptides in rat tissues was investigated using sequence specific antisera. N- and C-terminal antisera and a presumptive C-terminal rat pancreastatin antiserum immunostained an extensive neuroendocrine cell population throughout the gastro-entero-pancreatic tract, anterior pituitary, thyroid and all adrenomedullary cells. However, mid- to C-terminal antisera immunostained a subpopulation of chromogranin A positive cells. Most notable of these was with the KELTAE antiserum (R635.1) which immunostained discrete clusters of adrenomedullary cells and antiserum A87A which immunostained a subpopulation of cells in the anterior pituitary and throughout the gastrointestinal tract. The present study has demonstrated the widespread occurrence of chromogranin A and related peptides in rat neuroendocrine tissues and provides evidence of tissue and cell specific processing.

Adrenal Medulla↗
PubMed1991

Hymenolepis diminuta: changes in the levels of certain intestinal regulatory peptides in infected C57 mice.

The levels of 10 regulatory peptides in acid-alcohol extracts of three regions of the small intestine (0-20%, 30-60%, and 70-100%, with respect to distance from the pylorus) have been monitored radioimmunometrically in sham-infected male (6-8 week old) C57 mice and mice given a 5-cysticercoid infection of the rat tapeworm Hymenolepis diminuta and autopsied 10 days postprimary infection and 5 days postsecondary infection (administered 28 days postprimary infection). The regulatory peptides examined were gastrin, gastrin-releasing peptide (GRP), glucagon (= enteroglucagon), motilin, neurotensin (NT), pancreatic polypeptide (PP), peptide histidine isoleucine (PHI), somatostatin (SRIF), substance P (SP), and vasoactive intestinal peptide (VIP). Statistical analyses revealed significant deviations from control values of five of the peptides (enteroglucagon and SP, both elevated; NT, PHI and VIP, all lowered) in intestinal tissue from infected mice; measurement of the same peptides in colonic extracts revealed no significant differences between infected and sham-infected mice. Parallel changes in peptide levels between normal infected and immunosuppressed infected mice were not evident, although elevations in the tissue levels of enteroglucagon and SP were found in infected Wistar rats (normal host). Results are discussed with respect to a peptidergic involvement in the pathology and host immune response to an intestinal tapeworm.

Animals↗
PubMed1991

Cytochemical demonstration of cholinergic, serotoninergic and peptidergic nerve elements in Gorgoderina vitelliloba (Trematoda: Digenea).

Standard enzyme cytochemical and indirect immunocytochemical techniques have been used in conjunction with light and confocal scanning laser microscopy (CSLM) to visualize cholinergic, serotoninergic and peptidergic nerve elements in whole-mount preparations of the amphibian urinary-bladder fluke, Gorgoderina vitelliloba. Cholinesterase (ChE) activity was localized in paired anterior ganglia, a connecting dorsal commissure and in the origins of the ventral nerve cords. Cholinergic ganglia were also evident in shelled embryos in the uterus. Serotonin-immunoreactivity (IR) was more extensive than ChE activity and was identified in both the central and peripheral nervous systems. Serotoninergic nerve fibres were associated with the somatic musculature and female reproductive ducts. Antisera to nine mammalian peptides and one invertebrate (FMRFamide) peptide have been used to investigate the peptidergic nervous system in the parasite. Immunoreactivity was obtained to five peptides, namely pancreatic polypeptide (PP), peptide YY (PYY), neuropeptide Y (NPY), substance P (SP) and FMRFamide. Peptidergic nerve fibres were found to be more abundant than demonstrable cholinergic or serotoninergic nerve fibres. NPY-IR was identified only in the main components of the central nervous system. However, PP- and PYY-IR occurred in the anterior ganglia, dorsal commissure, main nerve cords and in numerous small varicose fibres that ramified throughout the worm. Additionally, PP-immunoreactive nerve fibres were found to innervate the musculature of the female reproductive tracts. Six sites of IR were found in the acetabulum, using antisera directed towards the C-terminal end of PP and PYY, and these matched with the distribution of six non-ciliated rosette-like papillae observed by scanning electron microscopy. SP- and FMRFamide-IR were identified in the CNS, and FMRFamide-immunopositive nerve fibres were also evident in association with the gonopore cirrus region and with the terminal excretory pore. Results are discussed with respect to possible roles for each of the neurochemical types.

Animals↗
PubMed1991

Characterization and differential regulation of GABAA and benzodiazepine receptors in rat neocortex.

We have characterized the gamma-aminobutyric acid-A (GABAA) and benzodiazepine (BZ) receptors in in vitro living slices of adult rat neocortex using [3H]SR95531, a GABAA antagonist, and [3H]flunitrazepam (FNZ), a BZ ligand. [3H]SR95531 labelled a single population of GABAA receptors with a Bmax of 1030.7 fmol/mg protein and a Kd of 43.5 nM. [3H]FNZ also labelled a single binding site with a Bmax of 4239 fmol/mg protein and a Kd of 22 nM. The GABAA receptor labelled using [3H]SR95531 could be down-regulated by 2 h preincubations in GABA and the GABAA agonist muscimol (8% and 11%, respectively). Increases in cellular electrical activity induced by a combination of veratridine and glutamate led to an average increase in GABAA receptor number of 58%. The BZ binding site labelled with [3H]FNZ was down-regulated by clonazepam (-55%), increased by GABA (+17%), but not altered by changes in electrical activity. The present results demonstrate the rapid differential regulation of a ligand-gated receptor by agonist stimulation or increases in bioelectric activity. Such regulation may provide clues to the nature of the modifications which occur following changes in cellular activity in the cortex.

Animals↗
PubMed1991

Isolation and partial sequencing of a pancreatic polypeptide-like neuropeptide from the liver fluke, Fasciola hepatica.

1. A pancreatic polypeptide (PP)-immunoreactive neuropeptide has been isolated and partially sequenced from the liver fluke, Fasciola hepatica. 2. Gel permeation chromatography of an acid ethanol extract of cattle flukes showed that the peptide is similar in size to mammalian (bovine) PP. 3. The Fasciola peptide was purified to homogeneity by means of reverse-phase HPLC, employing different column chemistries. 4. The purified peptide was sequenced using automated gas-phase Edman degradation and the first 24 amino acid residues determined.

Amino Acid Sequence↗
PubMed1991

The distribution of neuropeptides in the ocular tissues of several mammals: a comparative study.

1. The distribution of several neuropeptides (vasoactive intestinal peptide, substance P, somatostatin and neurotensin) was assessed in ocular tissues from the cow, sheep, rabbit and rat. 2. Vasoactive intestinal peptide was most abundant in the choroid and sclera in all species except the rat. Substance P was most abundant in the retina of cow and rat and in the iris/ciliary body of sheep and rabbit. Somatostatin and neurotensin were most abundant in the retina of all species examined. 3. Regulatory peptides thus display distinct regional distributions within the ocular tissues of a single species of mammal and, in addition, exhibit interspecific variation.

Animals↗
PubMed1991

Quantification and partial characterisation of regulatory peptides in the liver fluke, Fasciola hepatica, from different mammalian hosts.

1. Extracts of the liver fluke, Fasciola hepatica from three different hosts (cow, sheep, rat) have been subjected to radioimmunoassay using antisera to 6 mammalian regulatory peptides. 2. Immunoreactivity was measured to pancreatic polypeptide, substance P, peptide histidine isoleucine and gastrin-releasing peptide. Levels of each peptide varied considerably in flukes from different hosts. 3. Reverse-phase HPLC of rat and sheep fluke extracts revealed three molecular forms of tachykinin immunoreactivity and single peaks of pancreatic polypeptide and peptide histidine isoleucine immunoreactivity. No GRP-immunoreactivity was detected by RIA of HPLC fractions.

Animals↗
PubMed1991

Immunocytochemical and radioimmunometrical demonstration of serotonin- and neuropeptide-immunoreactivities in the adult rat tapeworm, Hymenolepis diminuta (Cestoda, Cyclophyllidea).

Standard indirect immunocytochemical techniques have been interfaced with confocal scanning laser microscopy (for whole-mount preparations) and epifluorescence microscopy (for cryosections) to investigate the occurrence and distribution of serotoninergic and peptidergic nerve elements in adult H. diminuta. Serotonin (5-HT)-immunoreactivity (IR) was widespread throughout the worm, occurring in the paired cerebral ganglia, transverse commissure, the 10 longitudinal nerve cords and in a plethora of small nerve fibres of the peripheral nervous system. An abundance of serotoninergic nerve cell bodies was found in association with the lateral nerve cords. The genital atrium and accessory reproductive ducts were richly innervated with serotoninergic nerve fibres. Thirty-five antisera to 20 vertebrate regulatory peptides and 1 invertebrate peptide (FMRFamide) were used to screen the worm for neuropeptide IR. Immunostaining was obtained with antisera raised to pancreatic polypeptide (PP), peptide YY (PYY), neuropeptide Y (NPY), substance P (SP), peptide histidine isoleucine (PHI), xenopsin (XP) and FMRFamide. The most extensive pattern of IR occurred with antisera to PP and PYY, IR being evident in the cerebral ganglia, transverse commissure, longitudinal nerve cords and in small nerve fibres that ramified throughout the parenchyma. A series of bipolar nerve cell bodies between the median nerve cords displayed PP/PYY-IR. The distribution of FMRFamide-IR was reminiscent of the PP/PYY pattern but was less extensive. Comparison of the serotoninergic and peptidergic nervous systems has revealed general similarities and some distinct differences, especially with regard to the distribution of immunoreactive nerve cell bodies. Quantitative data are presented on the levels of PP-, SP-, PHI-, and gastrin-releasing peptide (GRP)-immunoreactivities demonstrable in acid-alcohol extracts of whole worms. The highest level of peptide IR determined was recorded for PP.

Animals↗