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Biomedical subjects

A J Miller

Publications and source records attributed to A J Miller.

At least 55 records · Page 3Linked to original sources
PubMed1997

Pharmacologic characteristics of rabbit esophageal muscularis mucosae in vitro.

The aim of this study was to investigate in vitro the pharmacologic properties of rabbit esophageal muscularis mucosae. Stimulation of its motor innervation elicited only atropine-sensitive excitatory responses. This tissue was not refractory to histamine but appeared to be rapidly desensitized to its effects. Responses to adrenoreceptor agonists were produced by excitatory alpha1 and beta1 adrenoreceptors, inhibitory beta3 receptors but not alpha2 receptors. The esophageal muscularis mucosae was only weakly stimulated by neurokinins and bradykinin, and these responses were mediated via NK2, NK3, B1, and B2 receptors, respectively. Adenosine diphosphate and adenosine triphosphate produced approximately 40% maximal contractions through the activation of P2 receptors, whereas adenosine monophosphate and adenosine were without effect. Responses to prostaglandins E2 and F2alpha were < or =10% of the tissues' maximum response to acetylcholine. These data demonstrate that rabbit esophageal muscularis mucosae has a simple excitatory innervation and is only weakly stimulated by a variety of pharmacologic agents. For these reasons it is distinct from muscularis mucosae found elsewhere in the rabbit gastrointestinal tract.

Acetylcholine↗
PubMed1997

Sites of action of IL-1 in the development of fever and cytokine responses to tissue inflammation in the rat.

1. The objective of the present study was to determine the sites of action of the cytokine, interleukin-1 (IL-1), in the febrile response to local inflammation in the rat, by comparing the importance of IL-1 in the local tissues, the circulation and the brain. This was achieved by injecting lipopolysaccharide (LPS, 100 micrograms kg-1) into a subcutaneous air pouch and testing the effects of blocking IL-1 action with the human recombinant interleukin-1 receptor antagonist (IL-1ra) injected either into the air pouch, intraperitoneally (1 mg kg-1, 0 + 1 h, i.p.), or intracerebroventricularly (200 micrograms/rat, 0 + 1 h, i.c.v.). 2. To investigate the effect of IL-1ra on fever and the induction of local and circulating cytokines (IL-1 and IL-6), separate experiments were performed in which groups of animals were killed 1.5, 3 or 5 h after LPS injection. Plasma and pouch fluid samples were collected for bioassay of IL-1 and IL-6. 3. Injection of LPS into the air pouch significantly increased (1.5 degrees C) body temperature, local (air pouch) concentrations of bioactive IL-1 and IL-6, and circulating bioactive IL-6, compared to saline-treated controls. 4. Injection of IL-1ra into the pouch significantly attenuated LPS fever (P < 0.001). This decrease in body temperature was associated with significant inhibition of local IL-1 bioactivity 1.5 (96%), 3 (84%) and 5 h (72%), and in bioactive IL-6 in pouch lavage fluid 1.5 (45%) and 5 h (35%), after LPS injection. The concentration of bioactive IL-6 in the plasma was significantly reduced (39%) at 3 h, when temperature was approaching the maximal value. 5. Both systemic (i.p.) and central (i.c.v.) administration of IL-1ra significantly attentuated LPS fever (P < 0.05). However, it had no effect on either local concentrations of bioactive IL-1 or IL-6, or circulating IL-6, at any of the sample points. 6. These data suggest that IL-1 is released locally, at the site of tissue inflammation and that it is an important mediator of the febrile response to local inflammation. The results also indicate that IL-1 produced locally may contribute to the production of IL-6 which is released into the circulation, and that IL-1 has important actions in the generation of fever at other sites, including the brain.

Animals↗
PubMed1997

Reduced gravitropism in hypocotyls of starch-deficient mutants of Arabidopsis.

Gravitropism was examined in dark- and light-grown hypocotyls of wild-type (WT), two reduced starch mutants (ACG 20 and ACG 27), and a starchless mutant (ACG 21) of Arabidopsis. In addition, the starch content of these four strains was studied with light and electron microscopy. Based on time course of curvature and orientation studies, the graviresponse in hypocotyls is proportional to the amount of starch in a genotype. Furthermore, starch mutations seem to primarily affect gravitropism rather than differential growth since both phototropic curvature and growth rates among the four genotypes are approximately equal. Our results suggest that gravity perception may require a greater plastid mass in hypocotyls compared to roots. The kinetics of gravitropic curvature also was compared following reorientation at 45 degrees, 90 degrees, and 135 degrees. As has been reported for other plant species, the optimal angle of reorientation is 135 degrees for WT Arabidopsis and the two reduced starch mutants, but the magnitude of curvature of the starchless mutant appears to be independent of the initial angle of displacement. Taken together, the results of the present study and our previous experiments with roots of the same four genotypes [Kiss et al. (1996) Physiol. Plant. 97: 237] support a plastid-based hypothesis for gravity perception in plants.

Arabidopsis↗
PubMed1997

Local cytokine induction by LPS in the rat air pouch and its relationship to the febrile response.

Peripheral induction of cytokines is a critical event in the induction of febrile responses. The sequence of induction and site of action of these cytokines, however, remain unclear. The objective of the present study was to investigate the kinetics of local and systemic production of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF), with the aim of identifying the relationship between these cytokines and the febrile response induced by injection of lipopolysaccharide (LPS) into a subcutaneous air pouch in the rat. Intrapouch injection of LPS induced dose-dependent fevers and increases in the concentration of bioactive IL-6 in the plasma. Further studies using 100 microg/kg LPS demonstrated significant increases in local (air pouch) concentrations of bioactive IL-1, TNF and IL-6, and circulating IL-6. No significant increases in TNF or IL-1 were detected in the plasma of the same animals. Local TNF was induced rapidly and peaked 1 h after LPS injection. The kinetics of local IL-1 and IL-6 induction were similar and both peaked after 3 h. The rise in local IL-6 preceded that of plasma IL-6 and reached a peak concentration that was 25-fold higher than that observed in the plasma. The data indicate that IL-1 and TNF act locally at the site of inflammation and that locally induced IL-6 is the important systemic mediator of the response.

Animals↗
PubMed1997

A randomized crossover study comparing the efficacy and tolerability of a novel once-daily morphine preparation (MXL capsules) with MST Continus tablets in cancer patients with severe pain.

The efficacy, tolerability and 24-h duration of action of MXL capsules, a novel once-daily morphine preparation, were compared with twice-daily morphine tablets (MST Continus tablets) in patients with severe cancer pain. Eighty-five patients were recruited to this randomized, double-blind, double-dummy, crossover study. There was no significant difference between the two treatment groups in the number of occasions that escape medication was required, the pain scores at each of three time points throughout the day, and the number of nights woken due to pain. Both preparations were well tolerated with no significant difference in the number or severity of reported symptoms and side-effects. Sixteen patients withdrew from the study, of whom 13 withdrew for nontreatment-related reasons. There was no difference between the preparations in terms of expressed treatment preference. MXL capsules were shown to provide effective analgesia over the 24-h dosing interval which was comparable to that of MST Continus tablets administered twice daily.

Analgesics, Opioid↗
PubMed1997

Functional anatomy of the paranasal sinuses.

Paranasal sinus anatomy possesses great complexity and is rather variable from person to person. Significant differences in structure may also exist between the two sides of the same person. Therefore, a detailed knowledge of the anatomy of the sinuses is critical in performing procedures such as functional endoscopic sinus surgery.

Ethmoid Sinus↗
PubMed1997

Comparison of conventional and deep plane facelift.

Revitalization of the aging face is a complex process that must include several components all working together in harmony to create a natural, youthful appearance. As more details of the facial anatomy have been described, the facelift operation has expanded tremendously to include deeper layers of the face with a goal of achieving both a longer lasting effect from surgery and a more complete recontouring effect of the melolabial fold. A comprehensive understanding of the anatomy of the face and the different procedures available is necessary in order to perform facelift surgery effectively and safely.

Aged↗
PubMed1996

Potassium homeostasis in vacuolate plant cells.

Plant cells contain two major pools of K+, one in the vacuole and one in the cytosol. The behavior of K+ concentrations in these pools is fundamental to understanding the way this nutrient affects plant growth. Triple-barreled microelectrodes have been used to obtain the first fully quantitative measurements of the changes in K+ activity (aK) in the vacuole and cytosol of barley (Hordeum vulgare L.) root cells grown in different K+ concentrations. The electrodes incorporate a pH-selective barrel allowing each measurement to be assigned to either the cytosol or vacuole. The measurements revealed that vacuolar aK declined linearly with decreases in tissue K+ concentration, whereas cytosolic aK initially remained constant in both epidermal and cortical cells but then declined at different rates in each cell type. An unexpected finding was that cytoplasmic pH declined in parallel with cytosolic aK, but acidification of the cytosol with butyrate did not reveal any short-term link between these two parameters. These measurements show the very different responses of the vacuolar and cytosolic K+ pools to changes in K+ availability and also show that cytosolic K+ homeostasis differs quantitatively in different cell types. The data have been used in thermodynamic calculations to predict the need for, and likely mechanisms of, active K+ transport into the vacuole and cytosol. The direction of active K+ transport at the vacuolar membrane changes with tissue K+ status.

Journal Article↗
PubMed1996

Interleukin-1 receptor antagonist inhibits endotoxin fever and systemic interleukin-6 induction in the rat.

Although a number of studies indicate that the pyrogenic activity of lipopolysaccharide (LPS) and/or interleukin (IL)-1 is mediated via induction of IL-6, this has been questioned by recent evidence demonstrating a dissociation between fever and circulating IL-6. The present study reexamines this relationship by use of human recombinant interleukin-1 receptor antagonist (IL-1ra). Injection of LPS (100 micrograms/kg ip) into rats induced fever (2.0 degrees C) that was significantly inhibited (P < 0.05) when IL-1ra (16 mg/kg ip) was given 1 and 2 h after LPS. The rise in plasma IL-6 preceded the febrile response by 1-1.5 h and, although the concentrations of bioactive IL-6 in plasma and cerebrospinal fluid (CSF) were not reduced at 4 h, at 2 h plasma and CSF IL-6 bioactivity was inhibited by 80 and 70%, respectively, after a single injection of IL-1ra (16 mg/kg ip). Intracerebroventricular injection of IL-1ra (200 micrograms/rat) inhibited LPS fever but did not affect the plasma IL-6 bioactivity measured 2 or 4 h after intraperitoneal LPS. These data show that peripheral IL-1 plays a part in the induction of both fever and the rise in plasma IL-6 that precedes it, and that IL-1 within the brain is also important in the induction of fever by LPS.

Animals↗
PubMed1996

Eustachian tube dysfunction.

The eustachian tube has several functions that are important in maintaining the normal state of the middle ear. The ability of the eustachian tube to carry out these functions changes with age. Certain pathophysiologic mechanisms may affect the normal state of the eustachian tube and predispose people, especially children, to otitis media.

Aging↗
PubMed1996

Visualization of the lymphatics of the heart and the mediastinal drainage pathways in the living cynomolgous (Macaca mulatta) monkey.

Our interest in the effects of impaired cardiac lymph drainage on coronary atherosclerosis led us to study the cardiac lymphatic anatomy in the monkey, generally considered the ideal experimental animal for examining coronary artery disorders. Short-term and long-term studies to visualize the cardiac lymphatic system and its mediastinal drainage pathways in 14 living monkeys confirmed that the epicardial collecting lymphatic anatomy is comparable to that of man, dog, and pig. These lymphatics, and particular lymphatic drainage to the cardiac lymph node in the right mediastinum, are difficult to visualize, in good part, because lymph uptake of such tracers as India Ink and T1824 blue dye is extremely slow. By modifying our techniques and taking cognizance of the slow lymphatic uptake of the tracers, we have been more successful in visualizing the mediastinal cardiac lymph node. Though our studies confirm that the lymphatic drainage of the monkey heart is similar to that in other mammals, we conclude that the "monkey model" has several drawbacks to study the effects of impaired cardiac lymph flow because of the laborious requirements to visualize successfully the cardiac lymph node. Perhaps the development of new markers would make this lymphatic system more approachable for experimental investigation.

Animals↗
PubMed1995

Xenopus oocytes as a heterologous expression system for plant proteins.

The Xenopus oocyte is a robust and convenient system for the transient expression of many different animal proteins and it has recently been demonstrated that oocytes can also translate, process, and target plant proteins. This expression system can also be used to clone genes, characterize function, and study posttranslational processing of proteins. Here we describe the methodology for the expression of plant proteins, in particular membrane proteins, in Xenopus oocytes.

Animals↗
PubMed1995

Plasticity of craniomandibular muscle function: 31P magnetic resonance spectroscopy of the rabbit masseter muscle.

The masseter muscle was studied during postnatal development of the rabbit from the juvenile to adult stage in which the oral function was altered during maturation by modifying the diet to soft food. The muscle was assessed using phosphate magnetic resonance (31P NMR) spectroscopy with a single-turn copper surface coil to study potential changes in phosphate metabolism. The 31P NMR spectra consisted of five peaks related to unbound forms of inorganic phosphate (Pi), creatine phosphate (PCr), and three peaks related to the adenosine triphosphate (ATP). The masseter was assessed in one group of five rabbits at 8 weeks postnatally (juvenile) and after 4 months of this experimental group masticating on soft food. They were compared with a control group of five rabbits raised on a normal hard diet. The Pi/PCr ratio increased in the adult masseter much higher during twitching, tetany, and periodic contraction than in the juvenile regardless as to whether the adult animal had been raised from the juvenile period on soft or hard diet. There were relatively few differences between the experimental adult animals raised on a soft diet and the normal adult animals despite the soft diet animals demonstrating a significantly lower weight and smaller muscle mass. These findings suggest that chronic underuse of the masseter muscle by decreasing the masticatory loads has a minimal effect on the phosphate metabolism of the maturing masseter.

Adaptation, Physiological↗