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Biomedical subjects

A M Allen

Publications and source records attributed to A M Allen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Angiotensin receptors in the nervous system.

In addition to its traditional role as a circulating hormone, angiotensin is also involved in local functions through the activity of tissue renin-angiotensin systems that occur in many organs, including the brain. In the brain, both systemic and presumptive neurally derived angiotensin and angiotensin metabolites act through specific receptors to modulate many functions. This review examines the distribution of these specific angiotensin receptors and discusses evidence regarding the function of angiotensin peptides in various brain regions. Angiotensin AT1 and AT2 receptors occur in characteristic distributions that are highly correlated with the distribution of angiotensin-like immunoreactivity in nerve terminals. Acting through the AT1 receptor in the brain, angiotensin has effects on fluid and electrolyte homeostasis, neuroendocrine systems, autonomic pathways regulating cardiovascular function and behavior. Angiotensin AT1 receptors are also found in many afferent and efferent components of the peripheral autonomic nervous system. The role of the AT2 receptor in the brain is less well understood, although recent knockout studies point to an involvement with behavioral and cardiovascular functions. In addition to the AT1 and AT2 receptors, receptors for other fragments of angiotensin have been proposed. The AT4 binding site, which binds angiotensin, has a widespread distribution in the brain quite distinct from that of the AT1 and AT2 receptors. It is associated with many cholinergic neuronal groups and also several sensory nuclei, but its function remains to be determined. Our discovery that another brain-derived peptide binds to the AT4 binding site in the brain and may represent the native ligand is discussed. Overall, the distribution of angiotensin receptors in the brain indicate that they play diverse and important physiological roles in the nervous system.

Animals↗
PubMed1998

Angiotensin AT1 receptor-mediated excitation of rat carotid body chemoreceptor afferent activity.

1. A high density of angiotensin II receptors was observed in the rat carotid body by in vitro autoradiography employing 125I-[Sar1, Ile8]-angiotensin II as radioligand. Displacement studies demonstrated that the receptors were of the AT1 subtype. 2. The binding pattern indicated that the AT1 receptors occurred over clumps of glomus cells, the principal chemoreceptor cell of the carotid body. Selective lesions of the sympathetic or afferent innervation of the carotid body had little effect on the density of receptor binding, demonstrating that the majority of AT1 receptors were intrinsic to the glomus cells. 3. To determine the direct effect of angiotensin II on chemoreceptor function, without the confounding effects of the vasoconstrictor action of angiotensin II, carotid sinus nerve activity was recorded from the isolated carotid body in vitro. The carotid body was superfused with Tyrode solution saturated with carbogen (95 % O2, 5 % CO2), maintained at 36 C, and multi-unit nerve activity recorded with a suction electrode. 4. Angiotensin II elicited a dose-dependent excitation of carotid sinus nerve activity (maximum increase of 36 +/- 11 % with 10 nM angiotensin II) with a threshold concentration of 1 nM. The response was blocked by the addition of an AT1 receptor antagonist, losartan (1 microM), but not by the addition of an AT2 receptor antagonist, PD123319 (1 microM). 5. In approximately 50 % of experiments the excitation was preceded by an inhibition of activity (maximum decrease of 24 +/- 8 % with 10 nM angiotensin II). This inhibitory response was markedly attenuated by losartan but not affected by PD123319. 6. These observations demonstrate that angiotensin II, acting through AT1 receptors located on glomus cells in the carotid body, can directly alter carotid chemoreceptor afferent activity. This provides a means whereby humoral information about fluid and electrolyte homeostasis might influence control of cardiorespiratory function.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1998

Bioactive angiotensin peptides.

Angiotensin II is recognised as the principle active peptide of the renin-angiotensin system, exerting effects on fluid and electrolyte homeostasis, and cardiovascular control including neural and long term trophic effects. However, recent studies indicate that other angiotensin peptides such as angiotensin III, angiotensin II (1-7) and angiotensin IV, may have specific actions. Interestingly, recent work involving angiotensin IV demonstrates that this peptide binds to specific receptors and may be involved in memory retention and neuronal development. Furthermore, our demonstration that a globin fragment, LVV-haemorphin-7, binds with high affinity to the angiotensin IV binding site and is abundant in the brain, indicates that this may represent a novel brain neuropeptide system. It now appears, that the renin-angiotensin system is more complex than previously thought and capable of generating multiple, active peptides which elicit numerous diverse actions.

Angiotensin II↗
PubMed1998

Mapping tissue angiotensin-converting enzyme and angiotensin AT1, AT2 and AT4 receptors.

BACKGROUND: The renin-angiotensin system (RAS) functions as both a circulating endocrine system and a tissue paracrine/autocrine system. As a circulating peptide, angiotensin II (Ang II) plays a prominent role in blood-pressure control and body fluid and electrolyte balance by acting on the AT1 receptor in the brain and peripheral tissues. As a paracrine/autocrine peptide, locally formed Ang II also plays additional roles in tissues involving the regulation of regional haemodynamics, cell growth and remodelling, and neurotransmitter release. Evidence is emerging that Ang II is not the only active peptide of the RAS, and other Ang II fragments may also have important biological activities. OBJECTIVES: To provide a morphological basis for understanding novel actions of angiotensin-converting enzyme (ACE), Ang II and related peptides in tissues, this article will review the localization of ACE and AT1, AT2 and AT4 receptors in the central nervous system, blood vessels and kidney. RESULTS AND CONCLUSION: Autoradiographic mapping of the major components of the RAS has proved a valuable strategy to reveal, or suggest, cellular sites of novel actions for Ang II and related peptides in tissues. First, colocalization of ACE and AT1 receptors in the substantia nigra, the caudate nucleus and putamen of human and rat brain, which contain the dopamine-synthesizing neurons, suggests that the central RAS may be important in modulating central dopamine release. Secondly, the distribution of AT4 receptors with a striking association with cholinergic neurons, motor and sensory nuclei in the brain reveals that Ang IV may modulate central motor and sensory activities and memory. Thirdly, the occurrence of high levels of ACE and AT1 and/or AT2 receptors in the adventitia of blood vessels suggests important paracrine roles of the vascular RAS. Finally, the identification of abundant AT1 receptor and elucidation of its roles in the renomedullary interstitial cells of the kidney may provide a new impetus to study further the role of Ang II in the regulation of renal medullary function and blood pressure. Overall, circulating and locally produced Ang II and related peptides may exert a remarkable range of actions in the brain, kidney and cardiovascular system through multiple angiotensin receptors.

Animals↗
PubMed1998

Interaction of circulating hormones with the brain: the roles of the subfornical organ and the organum vasculosum of the lamina terminalis.

1. Most circulating peptide hormones are excluded from much of the brain by the blood-brain barrier. However, they do have access to the circumventricular organs (CVO), which lack the blood-brain barrier. Three of the CVO, the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT) and area postrema, contain neurons responsive to peptides such as angiotensin II (AngII), atrial natriuretic peptide and relaxin. 2. We have studied the patterns of neuronal activation, as shown by Fos expression, in the SFO and OVLT in response to systemically infused AngII, relaxin or hypertonic saline and have found subgroups of neurons activated by the different stimuli. 3. Systemic infusion of relaxin or hypertonic saline activated neurons almost exclusively in the outer regions of the SFO and in the dorsal cap of the OVLT. Many of these neurons send axonal projections to regions of the brain subserving vasopressin secretion and thirst, such as the median preoptic, supraoptic and hypothalamic paraventricular nuclei. 4. At moderate blood concentrations, AngII only stimulates neurons in the inner core of the SFO and lateral regions of the OVLT. Higher levels of AngII in the bloodstream activate additional neurons in the outer parts of the SFO that connect to the supraoptic, paraventricular and median preoptic nuclei and these probably mediate water drinking and vasopressin secretion induced by blood-borne AngII. The efferent connections and the functions mediated by angiotensin-sensitive neurons in the inner core of the SFO and lateral part of the OVLT are unknown.

Angiotensin II↗
PubMed1997

MR diagnosis of traumatic tear of the spring ligament in a pole vaulter.

The spring ligament is a significant contributor to the stability of the talar head and longitudinal arch of the foot, lending importance to accurate radiologic diagnosis of injury. Using MR, we diagnosed a spring ligament tear with associated navicular dorsal subluxation, confirmed intraoperatively. To our knowledge, there are no previous reports of MR diagnosis of tear of the spring ligament.

Adult↗
PubMed1996

Interactions of angiotensin II with central dopamine.

There is a large body of evidence to support the concept of a relationship between brain Ang II and catecholamine systems. This interaction may participate in some central actions of Ang II such as cardiovascular control, dipsogenesis, and complex behaviours. It also extends to the nigrostriatal dopaminergic system which bear AT1 receptors, both on their cell bodies in the substantia nigra presynaptically, and on their terminals in the striatum, where Ang II can markedly potentiate DA release. This observation suggests that drugs which modulate central Ang II may be useful in regulating central dopaminergic activity.

Angiotensin II↗
PubMed1995

Angiotensin II receptor subtypes in the human central nervous system.

The distribution of the AT1 and AT2 subtypes of angiotensin II receptor was mapped in the adult human central nervous system using quantitative in vitro autoradiography. Binding in all forebrain, midbrain, pontine, medullary and spinal cord sites where angiotensin II receptors have previously been described is of the AT1 subtype, as is binding in the small and large arteries in the adjacent meninges and in choroid plexus. By contrast, both AT1 and AT2 receptors occur in the molecular layer of the cerebellum. Angiotensin II AT1 receptors in the brain show a moderate degree of conservation across mammalian species studied so far, whereas expression of AT2 receptors is more variable, and is more restricted in the human CNS than in many other mammals. These differences between the subtype distributions in humans and other animals indicate the need for care when extrapolating the results of animal studies involving the brain angiotensin system.

Aged↗
PubMed1995

The new nutrition facts label in the print media: a content analysis.

A content analysis was conducted to evaluate the coverage of the new food labels in the print media from December 1, 1992, to August 30, 1993. We used newspaper, magazine, and health newsletter indexes to identify 59 newspaper articles, 16 magazine articles, and 7 health newsletter articles for examination. Articles were evaluated by four trained coders using a pretested coding form addressing 35 aspects of the nutrition label coverage. Twenty percent of articles were double-coded with at least 80% coder reliability. Analysis of the data indicated that health newsletters covered the topic in the most detail, followed by magazines and then newspapers. Ten of 59 (17%) newspaper articles named and defined the term percent daily value, whereas 6 of 7 (86%) health newsletter articles and 9 of 16 (56%) magazine articles provided this information. Analysis of quotes in the articles indicated that more than half of the quotes were from government and industry officials. In contrast, quotes from college and university faculty represented only 5% of total quotes and quotes from dietitians represented less than 8% of total quotes. Coders identified several errors resulting from oversimplification of complex concepts. These findings suggest that dietitians need to increase their exposure with the media and help the media translate complex nutrition labeling information to the public.

Food Labeling↗
PubMed1995

Lumbar spondylolysis: reactive marrow changes seen in adjacent pedicles on MR images.

OBJECTIVE: In a search for ancillary MR findings for the diagnosis of spondylolysis, we performed a retrospective study to characterize changes in MR signal intensity of marrow within lumbar pedicles at the level of a spondylolytic defect. These reactive marrow changes were classified according to the anatomic-pathologic scheme developed for degenerative disk disease by Modic et al. MATERIALS AND METHODS: Two neuroradiologists retrospectively reviewed MR images of 60 patients with lumbar spondylolysis confirmed by conventional radiography or CT. The MR signal of each pedicle at the level of a pars defect was compared on T1- and T2-weighted sagittal images to that at the next higher level. When both observers concurred that the signal of the involved pedicle differed significantly from that of its neighbor, this signal change was classified into one of three types (type I: hypointense on T1-weighted images, hyperintense on T2-weighted images; type II: hyperintense on T1-weighted images, isointense or hyperintense on T2-weighted images; type III: hypointense on both T1- and T2-weighted images). RESULTS: Changes in MR signal intensity of pedicles adjacent to spondylolytic defects were observed in 24 (40%) of the 60 patients. Type I changes were seen in three patients, all less than 24 years old. Type II changes were seen in 17 patients with a median age of 35 years. Type III changes were seen in four patients with a median age of 51 years. The distribution of changes in signal intensity in the pedicle as a function of age was significant (p = .001). CONCLUSION: Categories of changes in MR signal intensity, similar to those described adjacent to degenerating disks, can be seen in lumbar pedicles adjacent to a spondylolytic defect of the pars interarticularis and are distributed as a function of age. Awareness of this finding may aid in establishing the correct diagnosis of spondylolysis on MR imaging and prevent erroneous interpretation of abnormal signal intensity in the pedicles in these patients.

Adult↗
PubMed1995

Imaging of the total hip arthroplasty.

More than 75,000 total hip arthroplasties are done yearly in the United States. Although modern cementing techniques have improved the longevity of cemented implants, uncemented prostheses have become popular, especially in younger, more active patients. There is also a trend toward modular components. These mechanical devices will all ultimately fail if subjected to sufficient use and stresses over time, though the specific causes and modes of failure vary widely. Loosening remains the primary cause of implant failure. There is a growing awareness of the role of wear particles in periprosthetic bone resorption with or without loosening. Stress shielding, dislocation, periprosthetic and prosthetic fractures, infection, heterotopic ossification, and stress concentration are also frequently encountered clinical problems. Conventional radiographs are the mainstay in evaluating total hip arthroplasty, with computed tomography and nuclear medicine imaging playing smaller roles.

Follow-Up Studies↗
PubMed1995

Imaging of the total knee arthroplasty.

We have reviewed the essentials of TKA imaging. Because the purpose of a knee arthroplasty is to relieve pain and improve function, radiographs should be viewed in the context of these goals.

Humans↗
PubMed1994

Distribution of angiotensin II receptor binding in the spinal cord of the sheep.

The distribution of angiotensin II binding sites has been mapped at segmental levels throughout the spinal cord of the sheep using in vitro autoradiographic methods. Binding of 125I-[Sar1.Ile8] Ang II is most prominent in the lateral horns of the thoracolumbar and sacral regions containing the sympathetic and parasympathetic preganglionic neurons respectively. Binding is also present in the dorsal horns of the grey matter, in the central canal region, dorsal root ganglia and associated with non-neuronal elements such as the ependyma surrounding the central canal, and blood vessels. Displacement with receptor antagonists specific for AT1 and AT2 subtypes, indicates that angiotensin II receptors in the spinal cord are of the AT1 type. These data help to interpret the physiological actions of angiotensin II in the spinal cord, particularly with respect to its autonomic components.

Animals↗
PubMed1993

Role of the spinal cord in generating the 2- to 6-Hz rhythm in rat sympathetic outflow.

In baroreceptor-denervated animals, sympathetic nerve discharge (SND) displays a 2- to 6-Hz rhythm. Current theories suggest that this rhythm is generated by a neural oscillator in the medulla. In urethan-anesthetized rats, we have examined the effect on the 2- to 6-Hz rhythm of lumbar SND produced by 1) altering the firing pattern of a major output of this medullary network [the rostral ventrolateral medulla (RVLM)] and 2) disrupting the interactions between medulla and spinal cord (SC). Microinjection of muscimol [gamma-aminobutyric acid (GABA) agonist] unilaterally or a mixture of kynurenic acid (KYN; broad spectrum, excitatory amino acid antagonist) and bicuculline (GABAA antagonist) bilaterally into RVLM produced little effect on the 2- to 6-Hz rhythm. Intrathecal injection of KYN or transection of the cervical SC also had little effect once SND had been restored by intrathecal injection of kainic acid (excitatory amino acid agonist). Thus, whereas an excitatory input to the spinal cord is required for the generation of basal SND, patterning of this input is not critical for production of the 2- to 6-Hz SND rhythm that, in this species, may be essentially of spinal origin.

Animals↗