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Biomedical subjects

B D Perry

Publications and source records attributed to B D Perry.

At least 73 records · Page 4Linked to original sources

Ultrastructural study of ehrlichial organisms in the large colons of ponies infected with Potomac horse fever.

Potomac horse fever is characterized by fever, anorexia, leukopenia, profuse watery diarrhea, dehydration, and high mortality. An ultrastructural investigation was made to search for any unusual microorganisms in the digestive system, lymphatic organs, and blood cells of ponies that had developed clinical signs after transfusion with whole blood from horses naturally infected with Potomac horse fever. A consistent finding was the presence of rickettsial organisms in the wall of the intestinal tract of these ponies. The organisms were found mostly in the wall of the large colon, but fewer organisms were found in the small colon, jejunum, and cecum. The organisms were also detected in cultured blood monocytes. In the intestinal wall, many microorganisms were intracytoplasmic in deep glandular epithelial cells and mast cells. Microorganisms were also found in macrophages migrating between glandular epithelial cells in the lamina propria and submucosa. The microorganisms were round, very pleomorphic, and surrounded by a host membrane. They contained fine strands of DNA and ribosomes and were surrounded by double bileaflet membranes. Their ultrastructure was very similar to that of the genus Ehrlichia, a member of the family Rickettsiaceae. The high frequency of detection of the organism in the wall of the intestinal tract, especially in the large colon, indicates the presence of organotrophism in this organism. Infected blood monocytes may be the vehicle for transmission between organs and between animals. The characteristic severe diarrhea may be induced by the organism directly by impairing epithelial cell functions or indirectly by perturbing infected macrophages and mast cells in the intestinal wall or by both.

Animals

Causative ehrlichial organisms in Potomac horse fever.

An ehrlichia was consistently isolated from the peripheral blood leukocyte fraction of ponies that had been experimentally infected with Potomac horse fever by whole blood transfusion from naturally infected horses. The organism was propagated in a human histiocyte cell line for 3 to 5 weeks and then inoculated intravenously or intradermally into healthy adult ponies. Clinical signs of Potomac horse fever, which varied in the degree of severity, occurred 9 to 14 days post-inoculation in all of the ponies. One pony died 20 days post-inoculation. The ehrlichial organism was reisolated in the human histiocyte cell line from the blood leukocyte fraction of all of the experimental ponies on each day that samples were examined (days 9, 10, 11, 19, and 39). These organisms were identical to those originally detected in the wall of the intestine of ponies with clinically diagnosed Potomac horse fever when compared by light and electron microscopy and an immunofluorescence labeling technique. The immunofluorescent antibody titer became positive in a pony at 20 days postinjection. These results indicate that the ehrlichial organisms is the causative agent of Potomac horse fever.

Animals

Babesia odocoilei Emerson and Wright, 1970 in white-tailed deer, Odocoileus virginianus (Zimmermann), in Virginia.

Pooled blood samples from six white-tailed deer from the Great Dismal Swamp in Virginia were inoculated into two splenectomized deer. A moderately severe clinical reaction ensued, characterized by a hemolytic anemia, and a Babesia found in both recipient animals was presumptively identified as B. odocoilei. This is the first reported identification of this parasite in white-tailed deer in Virginia.

Animals

Acute diarrhea in horses of the Potomac River area: examination for clostridial toxins.

Fecal specimens from horses in Montgomery County, Md, and in Fairfax and Loudoun counties, Va, were examined for Clostridium perfringens type A enterotoxin and for C difficile cytotoxin (92 and 108 specimens, respectively). The toxins were found in feces from horses that had experienced an acute diarrhea syndrome and from clinically normal horses. The toxins did not appear to be primary determinants of the diarrhea syndrome, although they may have contributed to the spectrum of clinical entities observed.

Acute Disease

Brain epinephrine systems: detailed comparison of adrenergic and noradrenergic metabolism, receptor number and in vitro regulation, in two inbred rat strains.

Epinephrine content and PNMT activity in medulla pons and hypothalamus of F344 inbred rats is from 3- to 8-fold higher than that of Buf inbred rats. These strain-dependent differences in brain adrenergic neurons are reciprocally related to altered alpha 1- adn alpha 2-adrenergic receptor density in PNMT-containing brain regions. Radioligand binding indices related to alpha 2-receptor function reveal that receptors may be 'desensitized' as well as 'down-regulated' in the strain with high PNMT activity (F344), and may be 'supersensitive' as well as 'up-regulated' in the strain with low PNMT activity (Buf). The association between epinephrine-containing neurons and alpha-adrenergic receptor regulation appears specific, since alpha-adrenergic receptor density and regulation in brain regions devoid of PNMT and epinephrine is similar in F344 and Buf rats. While noradrenergic metabolism in F344 rats is greater than that in Buf rats, this difference is generalized throughout the brain and, thus, bears no apparent relationship to the localized alterations in alpha-adrenergic receptor density. Moreover, beta-adrenergic receptor density in the 2 strains is similar in all brain regions. These data suggest that a significant proportion of alpha-adrenergic receptors in medulla-pons and hypothalamus are intimately related to and regulated by epinephrine-containing nerve endings.

Animals

Inheritance of adrenal phenylethanolamine N-methyltransferase activity in the rat.

Phenylethanolamine N-methyltransferase (PNMT) is the enzyme that catalyzes the S-adenosyl-L-methionine-dependent methylation of (-)norepinephrine to (-)epinephrine in the adrenal medulla. Adrenal PNMT activity is markedly different in two highly inbred rat strains; enzyme activity in the F344 strain is more than fivefold greater than that in the Buf strain. Initial characterization of the enzyme in the two inbred strains reveals evidence for catalytic and structural differences, as reflected in dissimilar Km values for the cosubstrate (S-adenosyl-L-methionine) and prominent differences in thermal inactivation curves. To assess adrenal PNMT activity in an F344 X Buf pedigree, we employed a statistical procedure to test for one- and two-locus hypotheses in the presence of within-class correlations due to cage or litter effects. The PNMT data in the pedigree are best accounted for by segregation at a simple major locus superimposed upon a polygenic background; data obtained from the biochemical studies suggest that the major locus is a structural gene locus.

Adrenal Medulla

Assessment of the functional role of brain adrenergic neurons: chronic effects of phenylethanolamine N-methyltransferase inhibitors and alpha adrenergic receptor antagonists on brain norepinephrine metabolism.

The potential role of brain adrenergic neurons in regulating noradrenergic neuronal metabolism was assessed using inhibitors of phenylethanolamine N-methyltransferase (PNMT), the enzyme responsible for epinephrine production. Two centrally active PNMT inhibitors (SK&F 64139 and LY134046) were administered over a 6-day treatment period to cause prolonged reductions in epinephrine formation. In brain regions containing endogenous epinephrine (medulla-pons and hypothalamus), chronic treatment with PNMT inhibitors produced: 1) reductions of epinephrine content, 2) elevation of tyrosine hydroxylase activity and 3) elevation of alpha-1 and particularly alpha-2 adrenergic receptor radioligand binding sites; neither norepinephrine turnover nor beta adrenergic receptor binding was affected. In brain regions devoid of endogenous epinephrine (cerebellum, frontal cortex and hippocampus), chronic treatment with PNMT inhibitors produced 1) a variable increase in tyrosine hydroxylase activity (cerebellum only) and 2) a reduction in norepinephrine turnover; neither alpha or beta adrenergic receptor binding was altered. A PNMT inhibitor failing to cross the blood-brain barrier, SK&F 29661, and an alpha-1 adrenoceptor antagonist, prazosin, had no effect on brain catecholamine metabolism. High doses of an alpha-2 adrenoceptor antagonist, yohimbine, increased medulla-pons tyrosine hydroxylase activity but also resulted in prominent reductions in norepinephrine content in all brain regions. The results suggest that prolonged reductions in endogenous brain epinephrine formation produce unique effects on brain norepinephrine function; these effects are regionally distinctive and are qualitatively different from the effects seen with chronic alpha-1 or alpha-2 adrenergic receptor blockade. These data are consistent with regulation of brainstem norepinephrine-containing cell bodies by endogenous adrenergic systems, probably via medullary-pontine alpha-2 adrenergic receptors.

Adrenergic alpha-Antagonists

Interactions of neuroleptic compounds at alpha 2-adrenergic receptor affinity states in bovine caudate nucleus.

Several recent studies have suggested a connection between neuroleptics and/or dopamine systems, and alpha 2-adrenergic receptors. Competition of a variety of neuroleptics at specific alpha 2-adrenergic binding sites (labeled with [3H]rauwolscine or [3H]p-aminoclonidine) in bovine caudate and cortex was examined. Few of the compounds were potent competitors, with (+)-butaclamol, alpha-flupenthixol, clozapine and pimozide the most potent (IC50 range 100-600 nM), while triflupromazine, mesoridazine, and haloperidol were the least potent (IC50 range 5 000-10 000 nM). These findings indicate that few, if any, of the examined neuroleptics have specific, high-affinity interactions with the multiple affinity states of the alpha 2-adrenergic receptor.

Animals

Strain differences in rat brain epinephrine synthesis: regulation of alpha-adrenergic receptor number by epinephrine.

Inbred tht strains Fischer 344 (F344) and Buffalo (BUF) differ in serveral physiological and behavioral measures. It was found that the activity of adrenomedullary and regional brain phenylethanolamine N-methyltransferase is at least four times higher in F344 rats than in BUF rats; these strain-dependent differences corresponded directly with the epinephrine content of the medulla-pons and hypothalamus. Conversely, alpha-adrenergic receptor density in brain regions containing phenylethanolamine N-methyltransferase is two to three times lower in F344 rats than in BUF rats; alpha-receptors in frontal cortex (a brain region lacking phenylethanolamine N-methyltransferase activity and epinephrine) are similar in both strains. These findings suggest that strain-dependent differences in alpha-receptors are regulated by inherited differences in presynaptic adrenergic neuronal function in different brain regions.

Adrenal Medulla

Effects of calcium and strontium in the process of acetylcholine release from motor nerve endings.

1. The effects of Ca and Sr ions on synchronous acetyleholine (ACh) secretion (the impulsive, physiologically functional form of secretion which produces an end-plate potential in response to a single nerve impulse) and on asynchronous ACh secretion (the delayed, residual increase in miniature end-plate potential frequency evoked by repetitive nerve impulses or by accumulation of intracellular divalent cations) were studied at frog neuromuscular junctions.2. In a comparison of their extracellular effects, Ca was far more effective than Sr in supporting synchronous ACh secretion but less effective than Sr in mediating asynchronous release evoked by repetitive nerve impulses.3. In studies of their intracellular effects, Sr and Ca were delivered to the nerve terminal cytoplasm using liposomes as a vehicle. Ca-containing liposomes, although producing effects on asynchronous ACh secretion that were indistinguishable from those of equimolar Sr-containing liposomes, were more effective than Sr-containing liposomes in increasing synchronous release.4. Extracellular Ca behaved as a potent competitve inhibitor of asynchronous, neurally evoked release mediated by Sr. In contrast, intracellular Ca (i.e. liposomal Ca), whilst increasing synchronous ACh release, failed to antagonize evoked asynchronous release.5. The results demonstrate that synchronous and asynchronous secretion have different sensitivities to alterations in intracellular divalent cation concentrations. It is suggested that selectivity for Ca over Sr may occur at intraterminal sites responsible for synchronous ACh secretion but not at sites responsible for asynchronous ACh release. Furthermore, Ca appears to bind with high affinity as an antagonist at the external surface of the nerve ending. These results are discussed in conjunction with current theories of depolarization-secretion coupling.

Acetylcholine

[3H]rauwolscine (alpha-yohimbine): a specific antagonist radioligand for brain alpha 2-adrenergic receptors.

[3H]Rauwolscine, a specific and potent alpha 2-antagonist radioligand, was used to characterize alpha 2-receptor binding in bovine cerebral cortex. [3H]Rauwolscine binding was reversible, stereospecific, and saturable. Association, dissociation, and saturation studies revealed one site interactions (k -1/k+1 = 1.2 nM, KD = 2.5 nM, Bmax = 160 fmol/mg protein) and competition studies indicated that [3H]rauwolscine labeled the alpha 2-receptor. Agonists inhibited [3H]rauwolscine binding in a shallow, GTP-sensitive manner. These results suggest that [3H]rauwolscine specifically labels both the high and low affinity states of the alpha 2-receptor in brain membranes.

Animals

Ecology and epidemiology of raccoon rabies.

Two areas of the United States presently are experiencing epizootics of raccoon rabies, which have been followed by the development of an enzootic state. These include four southeastern and five mid-Atlantic states. Information was obtained from 1,610 raccoons submitted for rabies testing in four of the affected mid-Atlantic states during 1982 and 1983 and from 798 raccoons from Virginia during 1984 and 1985. Analysis of the two sets of data provided an opportunity to characterize certain aspects of the epizootic. Raccoons collected during the day or at dusk and those that behaved abnormally were more likely to be rabid. Many human exposures to raccoons were preventable or may not have necessitated treatment. Eight (3%) of 291 serum samples from raccoons in an epizootic area had titers of antibody to rabies virus (complete neutralization) of greater than or equal to 1:25. Field trials of baiting systems incorporating an oral raccoon rabies vaccine are being conducted in Virginia, Washington, D.C., and Pennsylvania.

Animals

Serological study of ovine toxoplasmosis in Colombia: prevalence of haemagglutinating antibodies to toxoplasma in sheep.

A total of 1655 ovine sera from the six principal sheep rearing areas of Colombia were examined for toxoplasma antibodies using the indirect haemagglutination test. It was shown that 58 per cent of these samples had titres of 1/16 or greater. Seropositive animals were distributed throughout all the areas studied. The possible factors affecting the distribution of seropositive sheep in one of the areas are discussed.

Animals