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Biomedical subjects

A M Allen

Publications and source records attributed to A M Allen.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Alpha 2-adrenoceptor-mediated inhibition of bulbospinal barosensitive cells of rat rostral medulla.

Bulbospinal barosensitive neurons of the rostral ventrolateral medulla (RVLM cells; presumed sympathetic vasomotor premotor neurons) were recorded with iontophoretic electrodes in urethan-anesthetized rats. The majority of these cells were insensitive to intravenous clonidine (Clo; up to 20 micrograms/kg) and insensitive to iontophoretically applied Clo or alpha-methylnorepinephrine (alpha-MNE). These cells (n = 47 of 76) had a spinal conduction velocity of 4.1 +/- 0.2 m/s and a mean firing rate of 20 +/- 1 spikes/s. A second population (n = 29) was powerfully inhibited by intravenous Clo (5-10 micrograms/kg, activity decreased by 83 +/- 11%), iontophoretically applied Clo (decreased by 51 +/- 7%), and iontophoresis of alpha-MNE (decreased by 69 +/- 3%). These cells had a slower conduction velocity (2.0 +/- 0.3 m/s) and a much slower discharge rate (6 +/- 1 spikes/s). Both populations were pulse synchronous at resting arterial pressure. The inhibitory effects produced by iontophoresis of alpha-MNE or Clo were reduced to the same degree (86-98%) by iontophoresis of idazoxan (an alpha 2-adrenergic antagonist with imidazoline structure) and by iontophoresis of piperoxan (65-77%, a nonimidazoline alpha 2-antagonist). The inhibition of RVLM cells by intravenous Clo was reversed by iontophoresis of idazoxan and by intravenous injection of yohimbine (nonimidazoline alpha 2-antagonists). These data suggest that 1) intravenous Clo only inhibits a subpopulation of RVLM sympathetic premotoneurons, possibly the C1 adrenergic cells, 2) this effect of Clo is due to activation of alpha 2-adrenergic receptors rather than nonadrenergic imidazoline binding sites, and 3) these alpha 2-receptors are located on or close to the Clo-sensitive cells and may be continuously activated by endogenously released catecholamines.

Adrenergic alpha-Antagonists

Mapping of angiotensin II receptor subtype heterogeneity in rat brain.

Angiotensin II (Ang II) exerts a number of central actions on fluid and electrolyte homeostasis, autonomic activity, and neuroendocrine regulation. In order to evaluate likely sites where these actions are mediated, Ang II receptor binding was localized in rat brain by in vitro autoradiography with the aid of the antagonist analogue 125I-[Sar1, Ile8]Ang II. Two subtypes of Ang II receptor have been identified using recently developed peptide and nonpeptide antagonists. In the periphery, the receptor subtypes differ in distribution, second messenger coupling, and function. Brain Ang II receptor subtypes were therefore differentiated into AT-1 (type I) and AT-2 (type II) subtypes by using unlabelled nonpeptide antagonists specific for the two Ang II subtypes. AT-1 binding was determined to be that inhibited by Dup 753 (10 microM) and AT-2 binding to be that inhibited by PD 123177 (10 microM). The reducing agent dithiothreitol (DTT) decreased binding to AT-1 receptors and enhanced binding to AT-2 receptors. Many brain structures, such as the vascular organ of the lamina terminalis, subfornical organ, median preoptic nucleus, area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus, which are known to be related to the central actions of Ang II, contain exclusively AT-1 Ang II receptors. By contrast, the locus coeruleus, ventral and dorsal parts of lateral septum, superior colliculus and subthalamic nucleus, many nuclei of the thalamus, and nuclei of the inferior olive contain predominantly AT-2 Ang II receptors. The detailed binding characteristics of each subtype were determined by competition studies with a series of analogues of angiotensin and antagonists. The pharmacological specificity obtained in rat superior colliculus and the nucleus of the solitary tract agreed well with published data on AT-1 and AT-2 receptors, respectively. There was a high degree of correlation between the distribution of Ang II binding sites with published data on Ang II-immunoreactive fields and on the sites of Ang II-responsive neurons. The present study also reveals pharmacological heterogeneity of brain Ang II receptors. The subtype-specific receptor mapping described here is relevant to understanding the role of angiotensin peptides in the central nervous system and newly discovered central actions of nonpeptide Ang II receptor antagonists.

1-Sarcosine-8-Isoleucine Angiotensin II

Angiotensin II receptor binding associated with nigrostriatal dopaminergic neurons in human basal ganglia.

In the human brain, receptor binding sites for angiotensin are found in the striatum and in the substantia nigra pars compacta overlying dopamine-containing cell bodies. In contrast, angiotensin-converting enzyme occurs in the substantia nigra pars reticulata and is enriched in the striosomes of the striatum. In this study, using quantitative in vitro autoradiography, we demonstrate decreased angiotensin receptor binding in the substantia nigra and striatum of postmortem brains from patients with Parkinson's disease. In the same brains the density of binding to angiotensin-converting enzyme shows no consistent change. We propose, from these results, that angiotensin receptors in the striatum are located presynaptically on dopaminergic terminals projecting from the substantia nigra. In contrast, the results support previous studies in rats demonstrating that angiotensin-converting enzyme is associated with striatal neurons projecting to the substantia nigra pars reticulata. These findings raise the possibility that newly emerging drugs that interact with the angiotensin system, particularly converting enzyme inhibitors and new nonpeptide angiotensin receptor blockers, may modulate the brain dopamine system.

Aged

High resolution localization of angiotensin II receptors in rat renal medulla.

The cellular localization of angiotensin II (Ang II) receptors in the inner stripe of the outer medulla of the rat kidney was investigated by using high resolution light and electron microscopic autoradiography. Fresh tissue blocks from the inner stripe of the outer medulla were incubated with 125I-[Sar1, Ile8] Ang II and prepared for microscopic autoradiography. At the light microscopic level, 125I-[Sar1, Ile8] Ang II was found to penetrate into the tissue and to bind specifically to sites outlining renal tubules and vasa recta bundles. Electron microscopic autoradiography revealed that silver grains were detected over interstitial cells located between the tubules and components of the vasa recta bundles, but no silver grains were detected overlying the cells of the thin descending or thick ascending limbs of the loop of Henle, the collecting ducts, the vasa recta, or other blood vessels. These interstitial cells contained abundant endoplasmic reticulum, microfilaments, occasional lipid droplets and extensive cytoplasmic processes which closely related to the basement membranes of the vasa recta and loops of Henle. The cells therefore closely resemble type 1 interstitial cells. Since Ang II binding sites are absent in the inner medulla, the cells labelled by this technique must be a subset of type 1 interstitial cells, distinct from the typical lipid-laden interstitial cells most abundant in the inner medulla. These findings demonstrate that type 1 interstitial cells are the primary sites for a high density of Ang II receptors located in the inner stripe of the outer medulla.

Animals

Measuring total plasma amino acid concentrations as a test of exocrine pancreatic function.

Endogenous and exogenous stimulation of the pancreas was studied to determine whether changes in protein output could be linked to decreased total plasma amino acid concentrations. In fasted rats, diversion of pancreatic juice resulted in a transient increase in protein output and a linked fall in total plasma amino acid. In fed animals, however, diversion of juice did not result in any change in protein output or total plasma amino acid concentrations, although protein output was two-fold greater than in fasted animals. Similarly, after atropine treatment, diversion of juice failed to result in any change in protein output or total plasma amino acid in either fed or fasted animals. Stimulation of the gland with increasing doses of cholecystokinin ranging from 1.25 to 10.00 Crick Harper Raper Units, resulted in dose response increases in protein output and corresponding dose response falls in total plasma amino acid concentrations. Maximum decrease in total plasma amino acid concentrations was seen at 50% from the baseline with 5.00 Crick Harper Raper Units of cholecystokinin. These results show that with exogenous and endogenous stimulation in fasted animals, a highly significant, inverse relationship exists between protein output and total plasma amino acid. This relationship is the basis for a reliable, non-invasive test of pancreatic function that allows free mobility, although a period of fasting is required in order to increase the sensitivity of the test.

Amino Acids

Histopathologic observations in weanling B6C3F1 mice and F344/N rats and their adult parental strains.

Weanling Fischer 344/N (F344) rats and the first filial hybrid of C57BL/6 x C3H (B6C3F1) mice and retired breeders from the parental stocks of these strains were monitored over a 5-yr-period by examining the histopathology of selected organs and comparing those results to viral and mycoplasmal serology and the intestinal tract bacterial flora of each animal on an individual basis. Serology gave no evidence of viral infection, but Mycoplasma arthriditis antibodies were detected. Reactivity of serum of adult C57BL/6 female mice with control cells or media (tissue culture, TC) was seen in a significant number of mice. TC reactivity correlated positively with lymphoid perivascular infiltrates, predominantly of the lungs, suggesting an allergic response in development of the lesions. Other lesions of note consisted of Harderian gland inflammation of rats, focal necrotizing lesions of the liver of both species, and thickening of the pleura and adjacent pulmonary interstitium of weanling rats. Embolization of bacteria from the gastrointestinal tract to the liver was considered a possible cause of the liver necrosis in both species. Although lesions of the lung and Harderian gland of the rats are similar to those caused by known viral agents, the cause of the latter could not be determined as these animals were negative for viral antibodies and the former was considered to be related to incomplete pulmonary development in the young rat. Features differentiating the lesions observed in animals of this survey from those caused by viral infection are discussed.

Aging

Localization and characterization of angiotensin II receptor binding sites in the human basal ganglia, thalamus, midbrain pons, and cerebellum.

Angiotensin II (Ang II) binding sites were localized in the thalamus, basal ganglia, midbrain, and pons of the human central nervous system by in vitro autoradiography, employing 125I-[Sar1, Ile8]angiotensin II as the radioligand. High-density binding occurs in the substantia nigra pars compacta, the interpeduncular nucleus and two of the raphe nuclei, the raphe magnus, and median raphe nucleus. Moderate densities occur in the caudate nucleus, putamen, bed nucleus of the stria terminalis, rostral linear nucleus, caudal linear nucleus, dorsal and paramedian raphe nuclei, locus coeruleus, and region of the subcoeruleus, oral dorsal paramedian nucleus, and A5/periolivary region. Low levels occur in the region between the subthalamic nucleus and the zona incerta, the mediodorsal thalamic nucleus, the central gray, the lateral and medial parabrachial nuclei, and the molecular layer of the cerebellum. The high density of Ang II receptor binding in the substantia nigra occurs over pigmented, presumably dopaminergic, neurons. The binding in this site, and in the striatum, is not observed in any of the other species we have studied. It displays similar pharmacological characteristics to the Ang II receptor binding site in other regions of the human brain. Overall we demonstrate a discrete pattern of Ang II receptor binding sites in the human brain, which shows a high correlation with the distribution observed in other mammalian species.

1-Sarcosine-8-Isoleucine Angiotensin II