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Biomedical subjects

A M Allen

Publications and source records attributed to A M Allen.

At least 73 records · Page 4Linked to original sources

Angiotensin receptors and the vagal system.

Angiotensin II (Ang II) is known to attenuate the vagal component of the baroreflex at both central and peripheral cardiac sites. Ang II receptor binding sites occur in both the nucleus of the solitary tract (NTS), where they are associated with vagal afferent terminals, and in the dorsal motor nucleus of vagus. In this study we have examined the distribution of Ang II binding sites in the cell bodies of vagal afferents in the nodose ganglion, and investigated whether these receptors are transported in the vagus nerve. Dense Ang II receptor binding was observed over neuronal cell bodies in the nodose ganglion and, in streaks, in the vagus nerve. Vagal ligation distal to the nodose ganglion resulted in a marked accumulation of receptor binding sites, proximal to the ligature, with a moderate increase on the distal side. These results demonstrate that Ang II receptor binding sites occur in the nodose ganglion and are transported centrally in the vagus to be located on presynaptic terminals in the NTS and also peripherally where they may occur on terminals of the vagus.

Animals↗

Comparative neuroanatomy of angiotensin II receptor localization in the mammalian hypothalamus.

1. The distribution of angiotensin II (AII) receptor binding sites in the hypothalamus of rat, rabbit, sheep and human was determined by in vitro autoradiography using 125I-[Sar1,Ile8]-AII as radioligand. 2. High receptor binding levels were observed in the continuum of tissue comprising the anterior wall of the third ventricle, including the subfornical organ, the median pre-optic nucleus and the organum vasculosum of the lamina terminalis. 3. High levels of binding sites were also found in the paraventricular and supra-optic nuclei, the median eminence and the arcuate nucleus. 4. These findings demonstrate sites in the hypothalamus of rat, rabbit, sheep and human where AII could exert its known actions on fluid and electrolyte balance, pituitary hormone release and cardiovascular function.

Aged↗

Angiotensin receptor binding and pressor effects in cat subretrofacial nucleus.

Central administration of angiotensin II (ANG II) increases arterial blood pressure via increased sympathetic activity. We have examined the possibility that one site of action of ANG II is the subretrofacial (SRF) nucleus in the rostral ventrolateral medulla, since this nucleus is known to play a critical role in the tonic and phasic control of arterial pressure. In vitro autoradiography, employing 125I-labeled [Sar1, Ile8]ANG II as radioligand, was used to localize binding sites for ANG II in the cat ventrolateral medulla. A high density of ANG II-receptor binding sites was found confined to the SRF nucleus. In a second group of experiments in anesthetized cats, microinjections of ANG II, in doses ranging from 10 to 50 pmol, were made into histologically identified sites within and outside the SRF nucleus. Microinjections into the nucleus resulted in a dose-dependent increase in arterial pressure, which was abolished by systemic administration of the ganglion-blocking drug hexamethonium bromide. In contrast, microinjections just outside the SRF nucleus had no effect on arterial pressure. It is concluded that activation of ANG II-receptor binding sites within the SRF nucleus leads to an increase in arterial pressure via increased sympathetic efferent activity.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Angiotensin II receptor binding and the baroreflex pathway.

Angiotensin II (Ang II) acts centrally to modulate autonomic activity and cardiovascular function. Using in vitro autoradiography we have determined the distribution of putative receptors for ANG II in brain regions associated with the baroreflex pathway. Ang II receptor binding sites were observed in the nucleus of the solitary tract (NTS), the dorsal motor nucleus of vagus, the rostral and caudal ventrolateral medulla and intermediolateral cell column of the spinal cord. Receptor binding sites were also observed in the nodose ganglion and in association with nerve fibres in the heart. Nodose ganglionectomy and vagal ligation studies revealed that Ang II receptor binding sites are produced in the nodose ganglion and transported in the vagus nerve to terminals of vagal afferent neurones. In the NTS these presynaptic receptors could mediate the known baroreflex inhibitory action of Ang II by inhibition of neurotransmitter release. In the cat, Ang II receptors were sharply localized in the rostral ventrolateral medulla to the subretrofacial nucleus. Microinjection of Ang II (10-50 pmoles) into this region induced a sympathetically-mediated pressor response. Together these results demonstrate several regions within the baroreflex arc which contain Ang II receptors, at which Ang II may modulate cardiovascular control and autonomic function.

Angiotensin II↗

Cecocolitis in immunodeficient mice associated with an enteroinvasive lactose negative E. coli.

Infection with an atypical (lactose-negative) E. coli was associated with increased mortality rates in a colony of triple immune deficient N:NIH(S) III mice. Affected mice were lethargic and exhibited perianal fecal staining. Slight-to-moderate thickening of the wall of the cecum and colon was found on necropsy examination. Microscopic examination revealed segmental hyperplasia of the cecal and colonic mucosa with clusters of gram negative bacteria on the surface and within the cytoplasm of mucosal epithelial cells. Scattered foci of epithelial invasion and hyperplasia were observed in the colons of C57B1/6N-nunu mice after per os inoculation with the atypical E. coli. Immunocompetant mice housed in the same room as the N:NIH(S) III's remained healthy and exhibited no gross or microscopic lesions in spite of infection.

Animals↗

Angiotensin receptor binding in human hypothalamus: autoradiographic localization.

Binding of 125I-[Sar1,Ile8]angiotensin II in the human hypothalamus was mapped by in vitro autoradiography carried out on frozen sections of hypothalamus from two human brains. Regions showing the greatest specific binding of this radioligand were the organum vasculosum of the lamina terminalis, median preoptic nucleus, subfornical organ, median eminence, arcuate nucleus and paraventricular nucleus. These regions may be sites of angiotensin II receptors involved in the regulation of blood pressure, fluid balance and pituitary hormone secretion.

Aged↗

Reassortment of human rotavirus possessing genome rearrangements with bovine rotavirus: evidence for host cell selection.

Mixed infections of secondary rhesus monkey kidney cells with human rotaviruses carrying rearranged genomes and with bovine rotavirus yielded a high percentage of reassortants. The genotypes of 511 plaque-purified clones raised in either MA104 or BSC-1 cells have been determined and the frequencies of different genotypes have been calculated. It was found that reassortants did not emerge at random; there was non-random association of certain genes; the cell line used to isolate reassortants influenced the result, i.e. host cell factors had a selective effect on a recombinational mixture.

Animals↗

Overlapping distributions of receptors for atrial natriuretic peptide and angiotensin II visualized by in vitro autoradiography: morphological basis of physiological antagonism.

Atrial natriuretic peptides exert actions on many key organs involved in blood pressure and water and electrolyte balance. Many of these actions result in a physiological antagonism of angiotensin. To investigate the morphological basis of this interaction, we have mapped the distribution of receptors for atrial natriuretic peptide and angiotensin II in a number of target organs, using 125I-labelled rat atrial natriuretic peptide (99-126) and 125I-labelled [Sar1,Ile8]angiotensin II. In the kidney both atrial natriuretic peptide and angiotensin II receptors were observed overlying glomeruli, vasa recta bundles (high densities), and the outer cortex (moderate density). In the other tissues studied, atrial natriuretic peptide and angiotensin II receptors were codistributed in the adrenal zona glomerulosa, cerebral circumventricular organs including the subfornical organ, organum vasculosum of the lamina terminalis and area postrema, and the external plexiform layer of the olfactory bulb. The concurrent distribution of specific receptors for both peptides at these sites provides the basis for atrial natriuretic peptide to exert a functional antagonism of the actions of angiotensin II on blood pressure and water and electrolyte homeostasis at multiple sites.

Adrenal Glands↗

Angiotensin II receptors and angiotensin converting enzyme in the medulla oblongata.

Quantitative in vitro autoradiography was used to map angiotensin II (ANG II) receptors and angiotensin converting enzyme (ACE) in sections from rat, rabbit, sheep, and human medulla oblongata and to follow changes in receptor and ACE density after disruption of vagal projections by nodose ganglionectomy in the rat. ANG II receptors and ACE are both concentrated in the nucleus of the solitary tract and dorsal motor nucleus of vagus of the rat, rabbit, sheep, and human. An ANG II receptor-containing band connecting the nucleus of the solitary tract with the dorsolateral medulla was seen in rabbit and human tissue, providing evidence for association of ANG II receptors with vagal afferent fibers. ANG II receptors were found to be concentrated in the rostral and caudal ventrolateral medulla, which corresponded to the region of C1 and A1 catecholamine-containing cell groups in the rabbit. This localization was also evident in rat and human tissue. In all four species, a prominent, ANG II receptor-rich band in the intermediate reticular nucleus was found to connect the ventrolateral medulla and the dorsal vagal complex. In humans and sheep, this band contains puncta that overlie cell bodies. One week after nodose ganglionectomy in the rat, the density of ANG II receptors in the ipsilateral dorsal vagal complex fell markedly. This fall was most prominent in the rostral dorsal motor nucleus of vagus (to 46% of control density) and in the nucleus of the solitary tract (to 56% of control). ACE levels and calcitonin gene-related peptide receptor density were unchanged in both nuclei after ganglionectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry.

In order to identify likely sites of action in insulin in rat brain we have used the technique of in vitro autoradiography and computerized densitometry to map, characterize, and quantify its receptors in coronal and sagittal sections. A discrete and characteristic distribution of insulin receptor binding was demonstrated, with specific binding representing 92% of total binding. Displacement and specificity competition curves in olfactory bulb are typical for authentic insulin receptors, and computer analysis indicates a single class of binding site with a dissociation constant (Kd) 0.48 nM for choroid plexus and 0.44 nM for olfactory bulb external plexiform layer. Insulin receptor density is maximum in the choroid plexus, and high in the external plexiform layer of olfactory bulb. Structures of the limbic system and hypothalamus reveal moderate to high insulin receptor density, particularly the lateral septum, amygdala, subiculum, hippocampal CA1 region, mammillary body, and arcuate nucleus. Moderate insulin receptor density occurs in regions of cerebral cortex and cerebellum, and moderate to low binding occurs in discrete brainstem and midbrain structures. Insulin binding in the pituitary gland is greatest in the anterior lobe, with clear distinction from intermediate and posterior lobes. The circumventricular organs and the thalamus show low insulin binding. We conclude that insulin receptors are widespread throughout rat brain, with concentration in regions concerned with olfaction, appetite, and autonomic functions. The distribution is distinct from other neuropeptides and not related to either vascularity or cell density. A common feature of regions rich in insulin receptors is that they contain dendritic fields receiving rich synaptic input. Whether insulin plays a specific neurotransmitter or metabolic role in these sites remains unclear, but these studies have provided detailed information on potential sites of action of insulin in the brain, and will allow further studies to examine insulin receptor function in specific brain regions.

Animals↗

In vitro autoradiographic localization of ANP receptors in rat kidney and adrenal gland.

The radioligand 125I-ANP-(99-126) was used to map receptors for atrial natriuretic peptide (ANP) in the rat kidney and adrenal gland using in vitro autoradiography and computerized densitometry. In the kidney a very high density of receptors was found overlying glomeruli; these sites had a binding affinity constant of 0.48 +/- 0.06 X 10(-9) M-1 and a site concentration 818 +/- 108 fmol X mg protein-1. A moderate density of receptors was seen in the inner renal medulla; these sites had a binding constant of 0.9 +/- 0.2 X 10(9) M-1 and a receptor concentration of 204 +/- 44 fmol X mg protein-1, and moderate receptor density was also seen in the inner stripe of the outer medulla overlying vasa recta bundles. Diffuse low-density binding was also detected in the outer cortex. In all cases these patterns were abolished by 1 micron ANP-(101-126) or 1 microM atriopeptin III but not by a range of unrelated peptides. In the adrenal, a high density of binding was found overlying the zona glomerulosa, whereas a moderate density occurred in the zona fasciculata. Binding was not detected in the adrenal medulla. These results provide evidence for several classes of ANP receptor distribution in kidney and adrenal and suggest multiple roles of the peptide in fluid and electrolyte homeostasis.

Adrenal Glands↗

Local actions of angiotensin II: quantitative in vitro autoradiographic localization of angiotensin II receptor binding and angiotensin converting enzyme in target tissues.

In order to gain insight into the local actions of angiotensin II (ANG II) we have determined the distribution of a component of the effector system for the peptide, the ANG II receptor, and that of an enzyme-catalysing ANG II formation, angiotensin converting enzyme (ACE), by in vitro autoradiography in several target tissues. The superagonist ANG II analog, 125I[Sar1]ANG II, or the antagonist analog, 125I[Sar1,Ile8]ANG II, were used as specific radioligands for ANG II receptors. A derivative of the specific ACE inhibitor, lysinopril, called 125I-351A, was used to label ACE in tissues. In the adrenal, a high density of ANG II receptors occurs in the glomerulosa zone of the cortex and in the medulla. ACE is also localized in these two zones, indicating that local production of ANG II may occur close to its sites of action in the zona glomerulosa and adrenal medulla. In the kidney, a high density of ANG II receptors is associated with glomeruli in the cortex and also with vasa recta bundles in the inner stripe of the outer medulla. ACE is found in very high concentration in deep proximal convoluted tubules of the cortex, while much lower concentrations of the enzyme occur in the vascular endothelium throughout the kidney. In the central nervous system three classes of relationships between ANG II receptors and ACE are observed: In the circumventricular organs, including the subfornical organ and organum vasculosum of the lamina terminalis, a high concentration of both components occurs. Since these structures have a deficient blood-brain barrier, local conversion of circulating angiotensin I (ANG I) to ANG II may contribute to the action of ANG II at these sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

Reassortment of human rotaviruses carrying rearranged genomes with bovine rotavirus.

Rotaviruses isolated from chronically infected immunodeficient children were previously shown to contain RNA yielding abnormal migration profiles on gels: normal RNA segments were lost or decreased in concentration, and additional bands of dsRNA were found which were derived (rearranged) from genome segments of lower molecular weight by concatemer formation. These viruses grew very slowly during passage in secondary rhesus monkey kidney cells. Upon superinfection with the tissue culture-adapted UK Compton strain of bovine rotavirus (BRV) extensive genome reassortment occurred. Clones with the following reassorted genome patterns were isolated: (i) RNA segments 5 or 6 of BRV were replaced by the corresponding RNA segments of human rotavirus; (ii) RNA segments 9 or 11 of BRV were replaced by different rearranged bands of RNA of human rotavirus; (iii) reassortants were observed containing more than one segment/rearranged band of human rotavirus RNA in different combinations. The reassortant viruses possessed functional proteins coded for by the genome segments and/or by rearranged bands of RNA of the human rotaviruses. Rearrangement of parts of the rotavirus genome may be a mechanism of evolution of these viruses.

Animals↗

Isolation, propagation, and characterization of a newly recognized pathogen, cilia-associated respiratory bacillus of rats, an etiological agent of chronic respiratory disease.

A Gram-negative, filamentous, rod-shaped bacillus which failed to grow in cell-free media was isolated in apparently pure culture from the bronchial scraping and washing of a laboratory rat suffering from chronic respiratory disease by inoculating embryonated chicken eggs via the allantoic route. None of the embryos died during 20 serial passages at weekly intervals. The bacillus was reisolated in embryonated eggs from cesarean-derived barrier-maintained N:SD(SD) rats 8 and 12 weeks after intranasal inoculation with 10th-passage allantoic fluid. The inoculated rats were housed in Horsfall-type units and remained free from other known respiratory pathogens, including mycoplasmas and murine viruses, throughout the study. The bacillus colonized the ciliated epithelial cells of the respiratory tract and caused a marked peribronchial infiltration and hyperplasia of mononuclear cells which progressed with time. The bacillus, ca. 0.2 micron wide by 4 to 6 micron long, stained very poorly with basic aniline dyes but was readily demonstrated with the Warthin-Starry silver technique. It was heat labile (56 degrees C for 30 min); spore forms were not observed. It withstood freeze-thawing and was successfully stored at -70 degrees C. Although no visible means of locomotion was observed with the electron microscope, a slow gliding motility, sometimes with bending and flexing of bacilli apparently adherent to the glass surface, was observed with phase microscopy. As an etiological agent of chronic respiratory disease of rats, this cilia-associated respiratory bacillus (tentatively designated the CAR bacillus) may be the first recognized gliding bacterium known to cause disease in a warm-blooded vertebrate.

Animals↗

Clinical manifestations of mousepox in an experimental animal holding room.

A study of the clinical aspects of mousepox was conducted during the 1979-80 outbreak at the National Institutes of Health. The disease was detected serologically in a room located adjacent to the index room. The index room received animals prior to this outbreak from a noncommercial colony which later was found to be infected with mousepox. The infection was present in the room for at least 6 weeks prior to the completion of the study. The paucity of clinical signs and low mortality were striking when compared to previous descriptions of mousepox in the United States. Only 27 of the 939 mice in the room were infected, and only one of these had typical skin lesions. A few of the mice had non-specific signs such as ruffled hair coat and hunched appearance. Minimal spread of the disease was evidenced by clustering of infected cages on one of five animal racks in the room.

Animals↗

Pathology and diagnosis of mousepox.

The pathologic changes of mousepox were studied during an outbreak at the National Institutes of Health in 1979. The most consistent lesions were necrosis of lymphatic tissues, especially the spleen, lymph nodes, and Peyer's patches. Hepatic necrosis and jejunal hemorrhage also were found. In two transmission studies, the disease was experimentally induced in BALB/cAnN and C3H/HeN-nu mice. Athymic mice were found to be highly susceptible, and they developed fulminant disease. The diagnosis was confirmed by demonstration of pox virions in infected tissues by electron microscopy, staining of viral antigen by immunoperoxidase methods, and by isolation of the virus in chorioallantoic membranes of hen's eggs and in cultures of chick embryonic cells.

Animals↗