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Biomedical subjects

M O Smith

Publications and source records attributed to M O Smith.

At least 37 records · Page 2Linked to original sources
PubMed1996

Fucosidosis in a family of American-bred English Springer Spaniels.

Fucosidosis was detected in a family of English Springer Spaniels in the United States. To our knowledge, these are the first reported cases of this disease in American-bred dogs. Affected and carrier status of dogs were determined by measuring the activity of the enzyme alpha-L-fucosidase in plasma and in leukocytes. Fucosidosis results in neurologic signs, particularly changes in behavior, in adolescent and adult dogs. Late onset of signs may result in misdiagnosis as a primary behavior problem or acquired neurologic disease. Fucosidosis is inherited in an autosomal recessive manner, and carrier dogs are clinically normal. Thus, the abnormal gene can become widespread in a population before homozygous-affected dogs are produced.

Animals↗
PubMed1996

Bisphosphonates induce apoptosis in mouse macrophage-like cells in vitro by a nitric oxide-independent mechanism.

Bisphosphonates (BPs) are an important class of antiresorptive drugs used in the treatment of bone diseases, including osteoporosis. Although their mechanism of action has not been identified at the molecular level, there is substantial evidence that BPs can have a direct effect on osteoclasts by mechanisms that may lead to osteoclast cell death by apoptosis. BPs can also inhibit proliferation and cause cell death in macrophages in vitro. We have now shown that the toxic effect of BPs on macrophages is also due to the induction of apoptotic, rather than necrotic, cell death. Morphological and biochemical features that are definitive of apoptosis (chromatin condensation, nuclear fragmentation, and endonuclease-mediated internucleosomal cleavage of DNA) could be identified in mouse macrophage-like J774 and RAW264 cells, following treatment with 100 microM pamidronate, alendronate, and ibandronate for 24 h or more. Clodronate was much less potent, even at 2000 microM, while 2000 microM etidronate did not cause apoptosis. Apoptosis was not due to increased synthesis of nitric oxide and could not be prevented by inhibitors of nitric oxide synthases. Since macrophages, like osteoclasts, are particularly susceptible to BPs, these observations support the recent suggestion that the mechanism by which BPs inhibit bone resorption may involve osteoclast apoptosis. Furthermore, the macrophage-like cell lines used in this study may be a convenient model with which to identify the molecular mechanisms by which BPs promote apoptosis in osteoclasts. Induction of macrophage apoptosis by BPs in vivo may also account, at least in part, for the anti-inflammatory properties of BPs as well as the ability of BPs to cause an acute phase response.

Alendronate↗
PubMed1996

Identification of peptide epitopes of MAGE-1, -2, -3 that demonstrate HLA-A3-specific binding.

The MAGE gene family of tumour antigens are expressed in a wide variety of human cancers. We have identified 43 nonamer peptide sequences, from MAGE-1, -2 and -3 proteins that contain binding motifs for HLA-A3 MHC class I molecules. The T2 cell line, transfected with the cDNA for the HLA-A3 gene, was used in a MHC class I stabilisation assay performed at 37 degrees C and 26 degrees C. At 37 degrees C, 2 peptides were identified that stabilised HLA-A3 with high affinity (fluorescence ratio, FR > 1.5), 4 peptides with low affinity (FR 1.11-1.49) and 31 peptides that did not stabilise this HLA haplotype (FR < 1.1). At 26 degrees C, 12 peptides were identified that stabilised HLA-A3 with high affinity, 8 peptides with low affinity and 17 peptides that did not stabilise this HLA haplotype. Two peptides stabilised HLA-A3 at both temperatures. Small changes in one to three amino acids at positions distinct from the anchor residues altered peptide affinity. Data were compared to a similar study in which a peptide competition assay was used to investigate MAGE-1 peptide binding to several HLA haplotypes. This study demonstrates that anchor residues do not accurately predict peptide binding to specific HLA haplotypes, changes in one to three amino acids at positions distinct from anchor residues influence peptide binding and alternative methods of determining peptide binding yield different results. We are currently investigating the ability of these peptides to induce antitumour cytotoxic T lymphocyte activity as they may be of potential therapeutic value.

Amino Acid Sequence↗
PubMed1996

Neuroinvasion by simian immunodeficiency virus coincides with increased numbers of perivascular macrophages/microglia and intrathecal immune activation.

During peak viremia and initial antibody response, rhesus macaques infected with pathogenic and nonpathogenic isolates of SIV show distinct differences in viral load and tissue distribution. Animals infected with pathogenic isolates of SIV invariably have virus in the CSF and brain parenchyma by two weeks postinoculation, whereas animals infected with nonpathogenic isolates do not. Mechanisms underlying neuroinvasion by SIV and HIV are unknown, but recruitment of latently infected mononuclear cells from the peripheral circulation (Trojan horse theory) is frequently proposed. Circulating monocytes, from which perivascular macrophage/microglia are derived, are a likely vehicle for cell-associated transport of virus across the blood-brain barrier. This transport and the kinetics of perivascular macrophage/microglial turnover in the CNS likely depend on endothelial and leukocyte adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), which has previously been shown to be upregulated on cerebrovascular endothelium in SIV encephalitis. To investigate the role of peripheral monocyte recruitment into the perivascular macrophage/microglial cell pool at the time of initial viral neuroinvasion, we examined the temporal relationships among perivascular macrophage/microglia density, endothelial VCAM-1 expression and localization of viral nucleic acid in the CNS of macaques acutely infected with pathogenic and nonpathogenic molecular clones of SIV. The concentration of CSF quinolinic acid, a marker of intrathecal immune and macrophage activation, was examined concurrently. We found that significant increases in the density of perivascular macrophages/microglia coincided with viral neuroinvasion and marked elevations in CSF quinolinic acid. Furthermore, combined in situ hybridization and immunohistochemistry demonstrated that infected perivascular cells were macrophages/microglia. These findings provide evidence suggesting that neuroinvasion occurs through an influx of infected monocytes which take up residence in the CNS as perivascular macrophages/microglia. VCAM-1 expression, however, was not clearly correlated with these events, thus its contribution to initial viral neuroinvasion is unclear.

Animals↗
PubMed1996

Interaction of feeding time and temperature and their relationship to performance of the broiler breeder hen.

Experiments with broiler breeder hens were undertaken to determine effect of feeding time and environmental temperature on various production variables, body weight, and feed consumption. Two temperature treatments were used: low cyclic temperature (10 to 25 C), and high cyclic temperature (21 to 39 C). The three feeding treatments were: fed one daily meal either at 0700 h (Treatment 1) or 1800 h (Treatment 2), or one-half the daily amount at 0700 h and the other half at 1800 h (Treatment 3). In another experiment, hens were assigned to feeding times of either 0700 or 1800 h. Feeding time and temperature did not markedly affect rate of egg production; however, hens at high temperature fed two meals per day produced the fewest eggs. High temperature caused significant reductions in egg weight, specific gravity, and shell thickness. Feeding time and temperature had no effect on time of oviposition, ovulation, or the transit time of the egg through the oviduct. Significant body weight loss occurred in hens at high temperature and fed at 0700 h. Both high temperature and feeding one-half of the daily feed at 0700 and the other half at 1800 h caused a reduction in feed consumption.

Animals↗
PubMed1996

Environmental heat stress does not reduce blood ionized calcium concentration in hens acclimated to elevated temperatures.

Changes in blood concentrations of ionized calcium and total calcium were measured in broiler breeder hens (42 wk old) relative to egg cycle and environmental temperatures. Two environmental temperature treatments were used: 1) temperature cycled daily from a low of 10 C at 0300 h to a high of 25 C at 1600 h; and 2) temperature cycled from a low of 21 C at 0300 h to a high of to a high of 39 C at 1600 h. Serial blood samples were collected from five laying hens per temperature treatment via cutaneous ulnar vein cannula beginning at the time of oviposition and every 4 h thereafter until the next oviposition. Neither blood concentration of ionized calcium nor total plasma calcium was affected by temperature. Results suggest that the supply of calcium available in blood for shell deposition is not diminished in hens acclimated to high environmental temperatures.

Adaptation, Physiological↗
PubMed1995

The use of isolated functional heart to pharmacologically characterize active ingredients in the aqueous extracts of Mareya micrantha.

Aqueous extracts of Mareya micrantha are used as folk medicine in West Africa. However, no systemic investigation directed to the identification of the active ingredients in M. micrantha has been done. Therefore, this study investigated the effects of M. micrantha on the cardiac contractility of the isolated frog heart. Also, two sequential fractions from M. micrantha were separated and their effects on cardiac contractility investigated. M. micrantha concentration-dependently suppressed cardiac contractility. Separation of the cardioactive components in series by column chromatography (Sephadex G-50, Column 2.5 x 30 cm and 1 x 20 cm) produced two fractions which facilitated a leftward shift of the dose-response curve of the cardiodepressant effects suggesting that column chromatograph is effective in the isolation of the cardioactive ingredients in M. micrantha. The data suggest that M. micrantha contains cardioactive components and that contractions of the isolated functional frog heart can be used as a pharmacological activity marker during the process of isolation of cardioactive ingredients in M. micrantha.

Africa, Western↗
PubMed1995

Isolation of cholinergic active ingredients in aqueous extracts of Mareya micrantha using the longitudinal muscle of isolated guinea-pig ileum as a pharmacological activity marker.

In our attempt to isolate the pharmacologically active ingredients in the aqueous extracts of Mareya micrantha, we have selected the contractions of the longitudinal muscle of the isolated guinea-pig ileum preparation as a pharmacological marker to monitor retention of pharmacological activity during the chromatographic separation. The aqueous extracts of Mareya micrantha elicited concentration-dependent contractions of the preparation. The maximum response elicited by the aqueous extracts was 50% of the maximum response elicited by the maximum dose of acetylcholine (ACh), 10(-7) M. Mepenzolate (10(-8)-10(-5) M), a specific muscarinic receptor antagonist, similarly antagonized contractions elicited by the aqueous extracts suggesting that the cholinergic ingredient(s) in the extract are acting at the muscarinic receptors of the preparation. Fraction 2-4, which was separated from the aqueous extracts by Sephadex gel chromatography, dose-dependently elicited contractions of the preparation. The maximum response was 80% of the maximum response elicited by the maximum dose of ACh suggesting that separation has enhanced the cholinergic activity of the content in the extract.

Acetylcholine↗
PubMed1995

Relative biological availability of manganese from manganese proteinate, manganese sulfate, and manganese monoxide in broilers reared at elevated temperatures.

The relative biological availabilities of Mn from Mn proteinate, MnSO4, and MnO were compared under two different environmental conditions. Commercial broilers were reared in brooder batteries between Days 1 and 21 and fed diets containing 0, 1,000, 2,000, or 3,000 mg supplemental Mn/kg diet. On Day 22, birds were transferred to individual cages in two environmental chambers maintaining the same dietary Mn sources and supplemental levels. The temperature in one chamber cycled between 18 and 23.9 C (thermoneutral, TN), and in the other chamber cycled between 23.9 and 35 C (heat distress, HD). Birds in the HD environment were exposed to 8 h of 23.9 C, 4 h of 23.9 to 35 C, 4 h of 35 C, and 8 h of 35 to 23.9 C. Tibia Mn increased linearly (P < .05) with level of supplementation when measured on Days 22 and 47. Based on ratios of slopes from multiple linear regression analysis of bone Mn on Mn intake from various sources, the biological availabilities of Mn proteinate and MnO relative to MnSO4 (100%) were 120 and 91%, respectively, in 21-d-old chicks. In 49-d-old birds, corresponding relative biological availabilities of Mn from proteinate and oxide were 125 and 83%, respectively, in birds reared under TN, and 145 and 82%, respectively, for HD birds.

Animals↗
PubMed1995

Early intrathecal events in rhesus macaques (Macaca mulatta) infected with pathogenic or nonpathogenic molecular clones of simian immunodeficiency virus.

BACKGROUND: Encephalitis is a common and devastating sequela of HIV infection in humans and of simian immunodeficiency virus (SIV) infection in rhesus macaques. We used the SIV-infected rhesus macaque model to study early intrathecal events in the pathogenesis of lentiviral encephalitis. EXPERIMENTAL DESIGN: To examine early events and to compare the neuroinvasiveness and neurovirulence of pathogenic (SIVmac239) and nonpathogenic (SIVmac1A11) molecular clones of SIV and the role of host immunity in the early postinfection period, we inoculated groups of rhesus macaques with each of these clones and compared them with a third group of animals inoculated with pathogenic uncloned SIV (SIVmac). We collected paired cerebrospinal fluid and sera before and at intervals after inoculation and determined albumin and IgG concentrations, SIV-specific humoral immune response, and concentrations of quinolinic acid. Two animals from each group were killed and necropsied at 2, 8, 13, and 23 weeks after inoculation. Routine histopathology and semi-quantitative in situ hybridization were performed on tissue from multiple levels of the central nervous system (CNS). RESULTS: SIVmac and SIVmac-239 invaded both the meninges and the CNS parenchyma simultaneously within 2 weeks of inoculation, whereas nonpathogenic SIVmac-1A11 was not neuroinvasive. Gross disruption of the blood-brain barrier was not detected at any time. However, elevated IgG indices and high levels of cerebrospinal fluid quinolinic acid denoted intrathecal immune activation soon after viral neuroinvasion. Virus load in the CNS declined as the immune response peaked but subsequently increased with waning immunity. One macaque that never developed an SIV-specific immune response died with severe SIV encephalitis. CONCLUSIONS: Our findings support the following hypotheses of early events in SIV neuropathogenesis: (a) Pathogenic virus invades the CNS within days of i.v. inoculation and elicits an intrathecal immune response, including intrathecal synthesis of IgG and macrophage activation; (b) the immune response initially is associated with a decreased virus load in the CNS; (c) as immunodeficiency develops, virus load in the CNS increases once again; and (d) both virus and host factors are important in determining the course of events.

Animals↗
PubMed1994

Carnitine prolongs the half-life of ethanol in broilers.

The object was to determine if carnitine attenuated ethanol metabolism in broilers similar to that reported in the rats. Two groups (n = 5) of 5-week-old broilers were given for 10 days the feed with or without 0.5% L-carnitine supplement. A single oral dose of ethanol on day 8 was followed by serial blood samples which were analysed for ethanol. Another dose of ethanol was given on day 10 and 2 hr later, plasma and liver were collected and analysed for ethanol, total lipid, triglycerides and carnitine. The carnitine supplemented diet prolonged the half-life of ethanol due to attenuation of ethanol metabolism which is similar to that reported earlier in rodents. The increases in plasma and hepatic acylcarnitines indicate that supplementary carnitine lessens the load of free acyl groups in the liver by eventual oxidation or excretion.

Animal Feed↗
PubMed1994

Intrathecal synthesis of IgG in simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta).

We examined cerebrospinal fluid (CSF) and serum from 25 simian immunodeficiency (SIV)-infected rhesus macaques for the presence of SIV-specific immunoglobulin G (IgG) and for intrathecal synthesis of IgG. SIV-specific IgG was present in CSF from almost 50% of the macaques. In approximately half of these animals the SIV-specific IgG appeared to be derived from serum by leakage across a disrupted blood-brain barrier, whereas in the remaining animals there was evidence of intrathecal IgG synthesis. There were no significant associations between CSF SIV-specific IgG, intrathecal IgG synthesis and isolation of virus from CSF, clinical status, or neuropathological findings. However, SIV-specific IgG was absent from CSF in all four of the macaques with SIV encephalitis. The presence of SIV-specific IgG in CSF may have a modulating effect on the development of SIV-associated neurological disease.

Animals↗
PubMed1994

Effects of electrolyte and lighting regimen on growth of heat-distressed broilers.

The purpose of this study was to investigate possible interactions between photoschedules [23 h light (L):1 h dark (D); 16L:8D] and electrolytes provided by KCl and NaCl in the drinking water of broilers grown at elevated temperatures. Birds raised on each photoschedule were exposed to 8 h of 23.9 C, 4 h of 23.9 to 35 C, 4 h of 35 C, and 8 h of 35 to 23.9 C. Photoschedule had no effect on body weight gain, feed consumption, or carcass characteristics. Male birds that received NaCl gained 10.5% more (P < .05) weight than those receiving no water additive. Male birds consumed up to 37% more water (P < .05) and gained up to 21% more weight (P < .05) than similarly raised females. There was no effect of electrolytes on carcass characteristics.

Animal Feed↗
PubMed1993

Autoradiographic demonstration of the distribution of diacylglycerol in the gastric muscularis muscle of Bufo marinus: is diacylglycerol one of the second messengers in the muscularis muscle?

The distribution of 1,2-diacylglycerol (DAG) in the muscularis muscle of Bufo marinus has been determined using autoradiographic techniques. Strips of the muscle from the body of the stomach were fixed in 4% paraformaldehyde/2.5% glutaraldehyde, postfixed, washed and longitudinal sections (15 microns) were cut on a cryotome and placed on gelatinized slides. The sections were then incubated in the presence and absence of agonist, acetylcholine (ACh) 10(-5) M or carbachol (CCh) 10(-5) M plus Li+ (10 mM) in the medium which causes a marked potentiation of agonist-stimulated formation of cytidine diphosphate-DAG (CDP-DAG). The sections were processed through an autoradiographic technique using [3H]-cytidine, which binds to 1,2-diacylglycerol within the tissue to form CDP-DAG. Analysis of the developed tissue slides indicated that the dose of ACh (10(-5) M) which had been predetermined to elicit automaticity of the preparation in vitro increased the density of CDP-DAG grains. When the muscle strips were pretreated with ACh (10(-5) M) and CCh (10(-5) M) in the presence of LiCl (10 mM), the density of the CDP-DAG grains were further enhanced. CDP-DAG grains were localized throughout the muscle fibers. The increase in the density of the grains which was induced by the conditions eliciting automaticity suggest that DAG is one of the second messengers in the manifestation of automaticity of the muscularis muscle of Bufo marinus.

Acetylcholine↗
PubMed1993

Effects of sex, age, puncture site, and blood contamination on the clinical chemistry of cerebrospinal fluid in rhesus macaques (Macaca mulatta).

Paired CSF and serum samples were obtained from 109 rhesus macaques aged 1 to 18 years. The CSF and serum IgG and albumin concentrations were determined, using radial immunodiffusion; CSF total protein and glucose were determined, using colorimetric methods; and Na, K, and Cl concentrations were determined, using ion-specific electrodes. The CSF protein values were lower than those reported for non-human primates, and this finding was confirmed by results of agar gel electrophoresis. Animal age and sex had no significant effects on CSF composition, but serum IgG concentration increased with age. Concentrations of total protein, albumin, and IgG were greater, and concentrations of glucose and potassium were lower in CSF obtained from the lumbar rather than the cisternal site. Composition of CSF was not significantly altered by contamination with blood at values up to 10,000 RBC/microliters. The CSF albumin quotient, IgG quotient, and IgG index were determined and differed markedly from values reported for human beings, indicating that the properties and specificity of the blood-brain barrier may be species-specific.

Age Factors↗
PubMed1992

Research note: broiler acclimation to heat distress and feed intake effects on body temperature in birds exposed to thermoneutral and high ambient temperatures.

Relationships between ambient temperature, bird acclimation to cycling temperature, heat distress, and feed consumption were evaluated in two experiments. In the first experiment, birds previously acclimated to cycling temperature heat distress (24 to 35 C) for two 24-h cycles were observed to have 24% lower (P less than .01) feed consumption than birds previously housed at 24 C and experiencing their first heat distress exposure. A significant (P less than .01) acclimation history by ambient temperature interaction was detected, with acclimated birds having a higher rectal temperature (42.3 versus 41.2 C) when housed at 24 C and a lower rectal temperature (44.2 versus 44.6 C) when exposed to 35 C than did the unacclimated controls. In the second experiment, feed intake and acclimation effects were separated by precision-feeding birds 0, 5, and 10% of body weight. Rectal temperature in the 24 C and 35 C environments increased linearly (P less than .01) as feeding level increased for both acclimated and unacclimated birds. Similar to the first experiment, an ambient temperature by acclimation history interaction was detected (P less than .01), with acclimated birds exhibiting increased body temperature when housed in thermoneutral environments and lower body temperature when exposed to high ambient temperature distress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1992

Elevated vascular cell adhesion molecule-1 in AIDS encephalitis induced by simian immunodeficiency virus.

AIDS encephalitis is a common sequela to HIV-1 infection in humans and simian immunodeficiency virus (SIVmac) infection in macaques. Although lentiviral-infected macrophages comprise parenchymal inflammatory infiltrates in affected brain tissue, the mechanisms responsible for leukocyte trafficking to the central nervous system in AIDS are unknown. In this study, we investigated the expression of various endothelial-derived leukocyte adhesion proteins in SIVmac-induced AIDS encephalitis. Encephalitic brains from SIVmac-infected macaques, but not uninflamed brains from other SIVmac-infected animals, were found to express abundant vascular cell adhesion molecule-1 (VCAM-1) protein on the majority of arteriolar, venular, and capillary endothelial cells. Soluble VCAM-1 concentrations in cerebrospinal fluid (CSF) from encephalitic animals were increased approximately 20-fold above those from animals without AIDS encephalitis. Expression of other endothelial-related adhesion molecules, including E-selectin, P-selectin, and intercellular adhesion molecule-1 (ICAM-1), was not uniformly associated with AIDS encephalitis. Thus, the presence of VCAM-1 in both brain and CSF was uniformly associated with SIVmac-induced disease of the central nervous system, and this expression may, at least in part, influence monocyte and lymphocyte recruitment to the central nervous system during the development of AIDS encephalitis. Moreover, measurement of soluble VCAM-1 in CSF may assist in the clinical assessment of animals or people with AIDS.

AIDS Dementia Complex↗