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Biomedical subjects

C Bell

Publications and source records attributed to C Bell.

At least 199 records · Page 11Linked to original sources

Evidence that blood vessels in guinea-pig lung are supplied by both noradrenergic and dopaminergic axons.

Assay of catecholamines in guinea-pig lung showed that the amount of dopamine in this tissue is 3-4 times greater than that predicted to be associated only with noradrenergic nerves, and is depleted by animal treatment with 6-hydroxydopamine. Fluorescence microscopy after formaldehyde condensation did not reveal any non-neuronal stores of catecholamines within the lung. The pulmonary and bronchial arterial vessels are accompanied by numerous fine nerve fibres that exhibit immunoreactivity for tyrosine hydroxylase, and are therefore presumed to be catecholaminergic. A small proportion of these fibres are also immunoreactive for DOPA decarboxylase. The results are consistent with innervation of pulmonary and bronchial resistance vessels by dopaminergic as well as noradrenergic sympathetic axons.

Animals↗

Identification of high-risk situations in a behavioral weight loss program: application of the relapse prevention model.

The relapse prevention model has recently been applied to the treatment of obesity in order to explain why people stop practising caloric restriction and hence stop losing weight. This study attempted to identify environmental, affective and physiological variables characterizing 'high risk' situations that lead individuals to either overeat or eat unplanned meals, thereby violating the rules of dietary abstinence. Thirty-five individuals (5 male; 30 female) at least 20 percent above ideal body weight were instructed to keep a continuous record of their eating behavior during a 10-week behavioral weight loss program. Each eating episode was entered into the computer as a separate behavioral observation resulting in 3066 usable observations. Log-linear analysis of multidimensional contingency tables was used to fit Markov chains to the data in order to examine whether dietary slips (overeating; unplanned eating) could be predicted from the following antecedents or pairs of antecedents: meal, people, place, mood, and hunger. Antecedents found to be associated with conditional probabilities 25 percent greater than the unconditional probabilities for unplanned meals and overeating (very much; some) are reported. Three basic categories of high-risk situations emerge: positive social interactions, negative emotions, and physiological craving. Individual differences were observed in the unconditional probabilities of the target behaviors, in exposure to high-risk situations, and in impulsive eating in response to meal, people, place, and hunger.

Adult↗

Safety of long-term large doses of aspartame.

Safety of long-term administration of 75 mg/kg of aspartame per day was evaluated with the use of a randomized, double-blind, placebo-controlled, parallel-group design in 108 male and female volunteers aged 18 to 62 years. Subjects received either aspartame or placebo in capsule form three times daily for 24 weeks. No persistent changes over time were noted in either group in vital signs; body weight; results of standard laboratory tests; fasting blood levels of aspartame's constituent amino acids (aspartic acid and phenylalanine), other amino acids, and methanol; or blood formate levels and 24-hour urinary excretion of formate. There also were no statistically significant differences between groups in the number of subjects experiencing symptoms or in the number of symptoms per subject. These results further document the safety of the long-term consumption of aspartame at doses equivalent to the amount of aspartame in approximately 10 L of beverage per day.

Adolescent↗

Ultrastructural localization and characterization of sensory nerves in the rat kidney.

The ultrastructural localization of sensory nerves in the rat kidney was examined by using the chromaffin reaction to distinguish sympathetic catecholaminergic fibres from sensory fibres. The sensory fibres were further characterized by use of an immunoperoxidase staining method to identify nerves immunoreactive for substance P and for calcitonin-gene-related peptide. Sympathetic fibres were observed in the renal cortex, medulla, and pelvis, but sensory fibres were seen only in the renal pelvis. Immunostaining for substance P labelled 40% of the sensory fibres. Following incubation in calcitonin-gene-related peptide antiserum, 53% of the sensory nerves were positively stained. Simultaneous immunostaining for substance P and calcitonin-gene-related peptide resulted in immunoreactivity in 82% of the sensory fibres, a percentage of axons significantly lower than that expected if the axons containing each peptide had been entirely separate populations. The results indicate that sensory nerves in the rat kidney are located entirely in the renal pelvis. On the basis of their neuropeptide content, there appear to be at least four separate populations of sensory axons present: two large groups containing substance P or calcitonin-gene-related peptide alone and two small groups containing both peptides and containing neither.

Animals↗

The innervation of the renal cortex in the dog. An ultrastructural study.

Two cytochemical techniques were used at the ultrastructural level to study the distribution of specific axon types to different intrarenal structures in the dog. Using the chromaffin reaction to distinguish catecholaminergic fibres from other axon populations, it was found that the renal cortex of the dog is supplied only by catecholaminergic nerves. Immunostaining for tyrosine hydroxylase (TH) labelled all of the intracortical nerves, and 20% to 25% of these profiles also contained dopa decarboxylase (DDC)-immunoreactivity, indicating they were dopaminergic rather than noradrenergic. Both DDC-positive and DDC-negative axons were seen in close association (approximately 80 nm) with blood vessels and juxtaglomerular cells as well as tubular epithelial cells. The distribution of TH- and DDC-immunoreactive nerves in the renal cortex is compatible with existing functional evidence indicating that both dopaminergic and noradrenergic nerves are involved in the regulation of renal blood flow, tubular reabsorption and renin release.

Animals↗

Comparison of resting and stimulus-evoked catecholamine release from the femoral and renal vascular beds of the dog.

Plasma levels of dopamine (DA) and noradrenaline (NA) were measured in arterial and in femoral and renal venous blood of chloralose-anaesthetised dogs at rest, and during electrical stimulation of the femoral and renal sympathetic nerve supplies. In the femoral bed, sympathetic nerve stimulation elevated venous efflux of NA, but did not reproducibly elevate DA efflux: when this was increased, it comprised less than 1% of the stimulus-evoked catecholamine efflux. By contrast, renal nerve stimulation liberated both NA and DA from the kidney, and DA comprised about 8% of the total stimulus-evoked efflux. Comparison of efflux from intact and denervated kidneys indicated substantial neurogenic release of both NA and DA at rest, with DA comprising 20% of this efflux. The results extend previous evidence for dopaminergic sympathetic innervation of the dog kidney, and suggest that both dopaminergic and noradrenergic renal nerves are tonically active in anaesthetised animals.

Animals↗

A flow injection system with in-series ultraviolet and electrochemical detection for the simultaneous determination of lovastatin and butylated hydroxyanisole in a tablet.

A flow injection (FI) method has been developed to determine simultaneously a drug with an ultraviolet chromophore, lovastatin, and butylated hydroxyanisole (BHA) in a tablet. The system involves ultraviolet (UV) absorbance detection for the drug and oxidative amperometric electrochemical detection for BHA. The method has been shown to be reproducible for routine determinations with an accuracy of +/-1% for lovastatin and +/-4% for BHA. Precision for both analytes was approximately +/-1% (RSD). The use of FI compared with HPLC for these determinations has led to a dramatic decrease in the time required per assay. The method with UV detection has been shown to be specific for the drug in the presence of potential autoxidation products as well as BHA and its oxidation products. The use of electrochemical detection in series allows the method to be simultaneously specific for low levels of BHA (40 microg/tablet) in the presence of its oxidation products as well as the drug and its potential autoxidation products.

Journal Article↗

Neurochemistry of the sympathetic innervation to the uterus.

1. The uterus is supplied by numerous noradrenergic sympathetic nerve fibres, which supply the intramural vasculature and also, in some species at least, the myometrium. 2. Pregnancy is associated with progressive loss of catecholamine from these nerves. Although some direct mechanical damage due to stretching of the uterine wall contributes to this effect, it is primarily due to hormonal influences. 3. In animal experiments, the changes in uterine catecholamine occurring during pregnancy are mimicked by intra-uterine administration of progesterone. 4. The action of progesterone appears not to be selective for pelvic sympathetic neurons, or those in which transmitter turnover rate is particularly slow. The mechanism of depletion is probably through inhibition of tyrosine hydroxylase activity. 5. The functional role of this phenomenon during pregnancy, if one exists, seems likely to be related to protection of the fetoplacental blood supply against sympathetically mediated vasospasm. It is also possible that circulating progesterone may have a general inhibitory action on the female sympathetic nervous system.

Animals↗

Phentolamine lacks alpha 2-adrenoceptor agonist activity in anaesthetized dogs.

1. This study was performed in order to determine whether the blockade of sympathetic vasoconstriction in anaesthetized dogs by phentolamine is due to the antagonist action of the drug at postjunctional adrenoceptors, or is due to depression of neurotransmitter release by an agonist action at prejunctional adrenoceptors. 2. In dogs made areflexic by ganglion blockade with hexamethonium, phentolamine (0.5 mg i.a. or 0.5 mg kg-1 i.v.) elevated or did not affect femoral blood flow. By contrast, clonidine (0.5-2.5 nmol, i.a.) produced femoral vasoconstriction, which was attenuated by prior administration of phentolamine. 3. Prior blockade of prejunctional alpha 2-adrenoceptors with yohimbine (30 micrograms kg-1, i.v.) did not reduce the blocking effect of phentolamine (0.5 mg kg-1, i.v.) on neurogenic vasoconstriction. 4. The results indicate that, in anaesthetized dogs, phentolamine lacks appreciable agonist activity at either prejunctional or postjunctional alpha 2-adrenoceptors. The blockade of neurogenic responses by phentolamine is therefore likely to be due to postjunctional adrenoceptor blockade.

Adrenergic alpha-Agonists↗

Renal tubular cells are potential targets for epidermal growth factor.

Epidermal growth factor (EGF) is a potent polypeptide mitogen with various receptor-mediated growth effects on cells from the skin, breast, and gastrointestinal tract. Recent studies indicate that EGF is produced in the kidney and is excreted in the urine, but the biological significance of renal EGF is uncertain. We demonstrate in vitro mitogenicity of EGF for LLC-PK1 cells, a tubular epithelial cell line derived from pig kidney cortex. Furthermore, when subconfluent monolayers of LLC-PK1 cells are exposed to EGF for 24 h, sodium-dependent phosphate transport is stimulated (209-410% of control). These cells possess EGF-specific high-affinity binding sites at their surface (Kd 300-700 pM) but cannot synthesize the growth factor. EGF binding sites are not a peculiarity of the LLC-PK1 cell line, since similar sites are present on MDCK cells (derived from dog kidney distal tubule or collecting duct), primary cultures of mouse proximal tubular cells, and freshly prepared membrane fractions from mouse kidney. Cortical basolateral membranes are highly enriched in EGF binding sites, whereas EGF binding by brush-border membrane fractions is minimal and is compatible with contamination.

Animals↗

Ganglioside composition in human cataractous nuclei.

Gangliosides were isolated from human cataractous nuclei by solvent extraction, dialysis, and thin-layer chromatography and compared to gangliosides present in human whole normal and cataractous lenses. Three predominant gangliosides were tentatively identified as GM1, GM3, and GD1a, and several other resorcinol-positive components were observed in each of the sets of lens tissue. Thin-layer chromatographic patterns were similar, although some minor and possibly significant differences in band intensities were observed when chromatograms of gangliosides from cataractous nuclei and cataractous whole lenses were visually compared with those of whole normal lenses. Total ganglioside extracts were methanolyzed and the fatty acid methyl esters extracted with hexane and resolved by gas chromatography. Nervonic acid (C-24:1) content was increased in cataractous nuclei as compared to normal and cataractous whole lenses.

Cataract↗

Prostatic carcinogenesis evoked by cellular interaction.

Inoculation of tumorigenic prostatic stroma and nontumorigenic prostatic epithelia into the subcutaneous space of syngeneic rats induced the development of carcinosarcoma. The induced tumors, which were composed of a mixture of adenocarcinoma and fibrosarcoma, were androgen responsive. This model offers a novel mechanism for prostatic carcinogenesis in which prostatic fibroblasts determine epithelial growth, androgen responsiveness, and tumorigenicity. Our results emphasize the potential importance of an epigenetic pathway in prostatic carcinogenesis.

Androgens↗