Search PubMed⌕ Search

Biomedical subjects

M J Ford

Publications and source records attributed to M J Ford.

At least 37 records · Page 2Linked to original sources

Review article: colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders.

AIM: To review the physiology of colonic motility and sensation in healthy humans and the pathophysiological changes associated with constipation and diarrhoea. SOURCE: Medline Search from 1965 using the index terms: human, colonic motility, sensation, pharmacology, neurohormonal control, gastrointestinal transit, constipation, diarrhoea and combinations of these. RESULTS: In health, the ascending and transverse regions of colon function as reservoirs to accommodate ileal chyme and the descending colon acts as a conduit; the neuromuscular functions and transmitters control colonic motility and sensation and play pivotal roles in disorders associated with constipation and/or diarrhoea. Disorders of proximal colonic transit contribute to symptoms in idiopathic constipation, diarrhoea-predominant irritable bowel syndrome and carcinoid diarrhoea. Colonic function in patients presenting with constipation is best assessed clinically by colonic transit time using radiopaque markers ingested orally. Measurements of colonic contractility are less useful clinically but they can help identify motor abnormalities including colonic inertia; in some patients with irritable bowel syndrome, abdominal pain, urgency and diarrhoea are temporally associated with high amplitude contractions, which originate in the proximal colon and traverse the distal conduit at very high propagation velocities. Visceral hypersensitivity contributes to the urgency and tenesmus in irritable bowel syndrome and inflammatory bowel disease. Colonic motility and sensation can be reduced by anticholinergic agents, somatostatin analogues and 5HT3 antagonists. CONCLUSION: Physiological and pharmacological studies of the human colon have provided new insights into the pathophysiology of colonic disorders, and offer possibilities of novel therapeutic approaches for constipation or diarrhoea associated with colonic motor or sensory dysfunction.

Colon↗

The effect of dietary crude protein on growth, ammonia concentration, and litter composition in broilers.

An experiment was conducted to determine the effect of diets with reduced CP and supplemental amino acids on broiler performance, N excretion, litter characteristics, and equilibrium NH3 gas concentration. Results suggest that reducing CP (and lysine) below 241 g/kg (13.7 g/kg lysine) in the diets fed during the first 3 wk may slightly increase feed:gain and therefore may not be advisable. During the period 22 to 43 d of age there were no significant differences in weight gain and BW at 6 wk of age when reducing CP from 215 g/kg (11.5 g/kg lysine) to 196 g/kg (11.3 g/kg lysine), but feed intake and feed:gain ratio increased. However, reducing CP did cause equilibrium NH3 gas concentration and litter N to decline by 31 and 16.5%, respectively. Both of these advantages will improve air quality within the housing facility and possibly reduce heating costs during winter associated with higher ventilation rates required to reduce elevated NH3 gas concentrations.

Aging↗

The effect of dietary protein and phosphorus on ammonia concentration and litter composition in broilers.

An experiment was conducted to determine whether broiler litter concentration of N and P and equilibrium NH3 gas concentration can be reduced by reducing dietary CP and P levels and supplementing with amino acids and phytase, respectively, without adversely affecting bird performance. Equilibrium NH3 gas concentration above the litter was measured. The experiment was divided into a starter period (1 to 21 d) and grower period (22 to 42 d), each having two different CP and P levels in a 2 x 2 factorial arrangement. The CP treatments consisted of a control with a mean CP of 204 and 202 g/kg for starter and grower periods, respectively, and a low CP diet with means of 188 and 183 g/kg, respectively, but with similar amino acid levels as the control. The P treatments comprised starter and grower control diets containing means of 6.7 and 6.3 g/kg P, respectively, and low P treatment means of 5.8 and 5.4 g/kg P supplemented with 1.0 g/kg phytase. Reducing starter diet CP by 16 g/kg reduced weight gain by 3.5% and, hence, body weight at 21 d of age, but did not affect feed intake or feed efficiency. Reducing P did not affect feed intake and weight gain, but improved feed efficiency by 2.0%. Responses in feed intake and efficiency to CP depended on the level of dietary P. For the grower period there were no significant differences in feed intake, weight gain, and feed efficiency, nor in body weight at 42 d of age, after correcting for 21-d body weight, between CP and P treatments. There were significant (P < 0.001) reductions in litter N and P concentrations, but not equilibrium NH3 gas concentration, moisture content, or pH, for low CP and P diets. Mean equilibrium NH3 gas concentration was 63 ppm. Litter N concentration was reduced 16.3% with the low CP diets, and litter P by 23.2% in low P treatments. The results suggest that dietary manipulation shows merit for reducing litter N and P concentrations while maintaining acceptable production performance from broilers.

Ammonia↗

Variation in ATP requirement during influenza virus transcription.

The ATP requirement of influenza A virus RNA-dependent RNA polymerase was studied during in vitro transcription reactions. In complete transcription reactions, the Km for ATP was 10-fold higher than the Km values for the other NTPs. However, during transcription elongation the Km for ATP was as low as the Km values for the other NTPs, suggesting a special requirement for ATP during transcription initiation. Gel analysis of RNA products of transcription initiation reactions showed that the incorporation of AMP into nascent RNA was more efficient at positions 4, 6 and 7 relative to the template RNA than at position 5. The polymerase produced short, abortive transcripts with lengths corresponding to positions 3 and 4 relative to the template but never to position 5 or longer. These results suggest that incorporation of AMP at position 5 induces the influenza A virus polymerase to go through a transition from a transcription initiation to an elongation complex. This functional change of the polymerase complex rather than a requirement for ATP beta-gamma bond hydrolysis is the most likely reason for the particularly high Km for ATP during the early phase of transcription. This conclusion is supported by the fact that the ATP analogue ATPgammaS [adenosine 5'-O-(3-thiotriphosphate)] can efficiently replace ATP in in vitro transcription reactions and shows a comparable drop of Km between transcription initiation and elongation.

Adenosine Monophosphate↗

Congenital cutaneous candidiasis associated with respiratory distress and elevation of liver function tests: a case report and review of the literature.

We describe congenital cutaneous candidiasis (CCC) in a term newborn. The mother had candidal vaginitis 1 week before delivery. At birth, the infant had a generalized, intensely erythematous, papulovesicular eruption, respiratory distress and elevation of liver function tests. The child responded well to intravenous amphotericin B plus topical and oral nystatin. There have been 13 previously reported cases of CCC in infants weighing more than 1500 gm who had evidence of systemic infection. Two deaths were attributed to candidal pneumonia and sepsis. The majority of infants with CCC have infection localized to the skin, but if there is any evidence of respiratory distress or signs of sepsis the possibility of systemic candidiasis and the need for parenteral antifungal therapy must be considered.

Amphotericin B↗

Inferences about the origin of a field cricket hybrid zone from a mitochondrial DNA phylogeny.

Two closely related eastern North American field crickets, Gryllus firmus and G. pennsylvanicus, hybridize along a zone that extends from Connecticut and the Hudson River Valley, south along the eastern front of the Appalachian Mountains to at least Virginia. Here we use mitochondrial DNA (mtDNA) sequences to construct a population phylogeny for this pair of hybridizing cricket species. Using a phylogenetic approach, we attempt to discriminate between alternative population histories (secondary contact vs. primary intergradation) leading to formation of the hybrid zone. A strict consensus tree, based on > 1600 bp of the COI-COII region of the mtDNA genome, reveals four exclusive groups, which correspond to regional grouping of conspecific crickets. Surprisingly, the mtDNA sequence data do not reveal any synapomorphies for either G. pennsylvanicus or G. firmus. However, the mtDNA data do reveal a clear north-south split within each of the cricket species, a pattern not seen for morphological or other molecular characters. The biogeographical history of the north-south divergence events remains a puzzle. Observed gene genealogies support a model of secondary contact for the southern part of the hybrid zone. Sequence divergence data argue that lineages currently found in New York and New England were already distinct when this region became habitable following the most recent glaciation.

Animals↗

Pearl millet in layer diets enhances egg yolk n-3 fatty acids.

A study was conducted to determine whether substitution of pearl millet for corn in layer diets could enrich egg yolks with n-3 fatty acids. Seventy-two Single Comb White Leghorn hens of a commercial strain in their second cycle of production were fed isocaloric, isonitrogeneous diets (2,860 kcal AMEn/kg and 16% CP) formulated with corn, equal amounts of corn and pearl millet, or pearl millet as the grain source. Each of the three diets was fed to eight replicate groups of three hens for 6 wk. Dietary treatments had no effect on feed intake, BW, egg production, egg weight, and yolk weight. Feeding millet in place of corn significantly decreased yolk pigmentation. The ratio of n-6 fatty acids to n-3 fatty acids in eggs was 13.1, 10.1, and 8.3 for hens fed corn, corn+pearl millet, and pearl millet, respectively. Feeding pearl millet produces eggs significantly (P < 0.05) enriched in n-3 fatty acids.

Analysis of Variance↗

A null mutation in the Bacillus subtilis aconitase gene causes a block in Spo0A-phosphate-dependent gene expression.

The citB gene of Bacillus subtilis encodes aconitase, the enzyme of the Krebs citric acid cycle, which is responsible for the interconversion of citrate and isocitrate. A B. subtilis strain with an insertion mutation in the citB gene was devoid of aconitase activity and aconitase protein, required glutamate for growth in minimal medium, and was unable to sporulate efficiently in nutrient broth sporulation medium. Mutant cells failed to form the asymmetric septum characteristic of sporulating cells and were defective in transcription of the earliest-expressed spo genes, that is, the genes dependent on the Spo0A phosphorelay. However, this early block in sporulation was partially overcome when cells of the citB mutant were induced to sporulate by resuspension in a poor medium. Accumulation of citrate in the mutant cells or in their culture fluid may be responsible for the early block, possibly because citrate can chelate divalent cations needed for the activity of the phosphorelay.

Aconitate Hydratase↗

Gene gun-mediated skin transfection with interleukin 12 gene results in regression of established primary and metastatic murine tumors.

Particle-mediated (gene gun) in vivo delivery of the murine interleukin 12 (IL-12) gene in an expression plasmid was evaluated for antitumor activity. Transfer of IL-12 cDNA into epidermal cells overlying an implanted intradermal tumor resulted in detectable levels (266.0 +/- 27.8 pg) of the transgenic protein at the skin tissue treatment site. Despite these low levels of transgenic IL-12, complete regression of established tumors (0.4-0.8 cm in diameter) was achieved in mice bearing Renca, MethA, SA-1, or L5178Y syngeneic tumors. Only one to four treatments with IL-12 cDNA-coated particles, starting on day 7 after tumor cell implantation, were required to achieve complete tumor regression. This antitumor effect was CD8+ T cell-dependent and led to the generation of tumor-specific immunological memory. By using a metastatic P815 tumor model, we further showed that a delivery of IL-12 cDNA into the skin overlying an advanced intradermal tumor, followed by tumor excision and three additional IL-12 gene transfections, could significantly inhibit systemic metastases, resulting in extended survival of test mice. These results suggest that gene gun-mediated in vivo delivery of IL-12 cDNA should be further developed for potential clinical testing as an approach for human cancer gene therapy.

Animals↗

Hyperventilation alters colonic motor and sensory function: effects and mechanisms in humans.

UNLABELLED: BACKGROUND & AIMS. Hyperventilation-induced hypocapnia affects hemodynamic function and enhances colonic motility. The aims of this study were to determine the effects of hypocapnic hyperventilation on colonic motility and sensation in health and to explore the putative neurohumoral mechanisms. METHODS: In experiment 1, colonic tone, sensation, plasma levels of cortisol, beta-endorphin, selected gut neuropeptides, norepinephrine, epinephrine, and splanchnic blood volume were measured during two sequences of hypocapnic hyperventilation. In experiment 2, colonic tone and sensation were assessed during eucapnic hyperventilation and abdominal compression. RESULTS: Hypocapnic hyperventilation, but not eucapnic hyperventilation or abdominal compression, significantly increased colonic tone and sensitivity to balloon distention (P = 0.017) without altering humoral mediators or splanchnic blood volume. Plasma norepinephrine level increased (P = 0.017) and splanchnic blood volume decreased (P = 0.028) during 5 minutes after hyperventilation, consistent with homeostatic responses. CONCLUSIONS: Increased colonic tone and sensation during hypocapnic hyperventilation are not caused by colonic compression. These effects of hyperventilation are not mediated humorally but may result from direct metabolic effects of hypocapnia on colonic muscle or from changes in central autonomic control of colonic smooth muscle.

Adult↗

Selection on X-linked genes during speciation in the Drosophila athabasca complex.

We present the results of a restriction site survey of variation at five loci in Drosophila athabasca, complimenting a previous study of the period locus. There is considerably greater differentiation between the three semispecies of D. athabasca at the period locus and two other X-linked genes (no-on-transient-A and E74A) than at three autosomal genes (Xdh, Adh and RC98). Using a modification of the HKA test, which uses fixed differences between the semispecies and a test based on differences in Fst among loci, we show that the greater differentiation of the X-linked loci compared with the autosomal loci is inconsistent with a neutral model of molecular evolution. We explore several evolutionary scenarios by computer simulation, including differential migration of X and autosomal genes, very low levels of migration among the semispecies, selective-sweeps, and background selection, and conclude that X-linked selective sweeps in at least two of the semispecies are the best explanation for the data. This evidence that natural selection acted on the X-chromosome suggests that another X-linked trait, mating song differences among the semispecies, may have been the target of selection.

Alcohol Dehydrogenase↗

Cutaneous lymphangiectases associated with severe photoaging and topical corticosteroid application.

We report an elderly patient with lymphangiectases arising within skin affected by photoaging, steroid atrophy, and inflammation. Bullous lesions appeared in several sites following a year of topical corticosteroid applications for neurodermatitis. Light and electron microscopy showed that the bullae consisted of dilated lymphatic vessels within the dermis. There was also marked nodular elastosis and attenuation of dermal collagen. We suggest that this patient's lymphangiectases resulted from abnormal structure and function of the dermis due to photoaging and steroid atrophy.

Administration, Topical↗

Autonomic control of colonic tone and the cold pressore test.

BACKGROUND: Cardiovascular responses to cold stimulation are well characterised. It is unclear, however, whether cold pain stimulates responses in colonic tone in the transverse and sigmoid regions. AIMS: To assess the effects of cold stimulation on tone nd motility in the transverse and sigmoid colon and on cardiovascular autonomic activity. METHODS: Phasic and tonic motility of the transverse and sigmoid colon, pulse rate, and beat to beat pulse variability (which are measures of centrally mediated changes in autonomic function) were measured before, during, and after a standard cold pressor test in 22 healthy volunteers. RESULTS: Cold pain induced a significant increase in colonic tone but not phasic contractility in the transverse and sigmoid regions. Simultaneously, cold pain increased pulse interval variability. CONCLUSION: The findings are consistent with the hypotheses that cold pain produces coactivation of both the sympathetic and parasympathetic limbs of the autonomic nervous system and that cold induced changes in colonic tone are temporally associated with alterations in central autonomic nervous activity.

Adult↗

Psychosensory modulation of colonic sensation in the human transverse and sigmoid colon.

BACKGROUND & AIMS: Psychosensory stimulation increases the perception of stimuli in different regions of the human colon. The aim of this study was to determine the perception of pain and gas during distention of two colonic regions in healthy volunteers during stress and relaxation. METHODS: In 22 healthy subjects, phasic distentions of transverse and sigmoid colon were performed using infinitely compliant balloons, and symptoms were measured before and during one of three randomized treatments: sham or active relaxation or mental stress. Anxiety ratings and somatic cold-pain sensitivity were included in a multivariate regression model. RESULTS: Mental stress increased levels of anxiety (P < 0.05) and the sensation of gas (P < 0.01), but not pain (P = NS), during transverse colon distentions and the sensations of gas and pain during sigmoid distentions (P < 0.05). Active relaxation reduced only sensation of gas in the sigmoid colon. Somatic pain sensitivity and pretreatment colonic sensory scores were significantly associated with the sensory scores during treatments. CONCLUSIONS: Psychosensory stimulation increases colonic sensation during short-term distention in two regions of the human colon; relaxation alone exerts a smaller influence on sensations arising in the sigmoid colon.

Adult↗

Taking training seriously: a policy statement on public health training by the Joint Council of Governmental Public Health Agencies.

Continuing education and on-the-job training in public health has suffered serious neglect over the past years. As a result, many state and local public health entities have failed to keep step with emerging challenges facing the public's health--challenges that require new and innovative approaches to prevention and treatment. In this article, the Joint Council of Governmental Public Health Agencies seeks to affirm the importance of public health training by examining barriers to training; identifying areas in which training should be emphasized; providing examples of successful training programs; and recommending ways in which public health leaders can revitalize training programs.

Education, Continuing↗

Differences in colonic tone and phasic response to a meal in the transverse and sigmoid human colon.

It is not yet clear whether the regional differences in the physical properties of the colon influence its motor responses. Tonic and phasic colonic motility and compliance of the transverse and sigmoid colon were therefore assessed using a combined barostat-manometry assembly in 22 healthy subjects. Measured colonic compliance was corrected by subtraction of the compliance of the closed barostat system. The mean (SEM) preprandial colonic volumes in the transverse and sigmoid colon were similar (150 (12) and 128 (13) ml, p = NS), corresponding to calculated mean (SEM) colonic diameters of 4.3 cm and 4.0 cm respectively. The mean increase in colonic tone postprandially was significantly greater in the transverse (24.1% (3.5)) than in the sigmoid colon (13.1% (3.0), p < 0.01). The mean increase in phasic contractility was significantly greater, however, in the sigmoid than in the transverse colon (1270 (210) and 425 (60) mm Hg/90 min respectively, p < 0.01). Compliance was greater in the transverse than sigmoid colon (7.6 (0.44) and 4.1 (0.15) ml/mm Hg, p < 0.001). The fasting volume of the colon was significantly correlated with the magnitude of the tonic response to the meal in the transverse and sigmoid colon (p < 0.001 for both). In conclusion, there are quantitatively different but qualitatively similar phasic and tonic responses to the meal in the two colonic regions. Differences in the viscoelastic and luminal dimensions may partly account for these differences in tonic responses.

Adult↗