A letter from the Arkansas Foundation for Medical Care, Inc.
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Biomedical subjects
Publications and source records attributed to M C Wilson.
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Borna disease (BD) agent is an infectious pathogen that causes progressive central nervous system (CNS) dysfunction in a wide range of vertebrate hosts. The course of BD in adult rats is biphasic. The acute phase is characterized by aggressive behavior and inflammatory cell infiltrates in brain. With chronic infection animals become listless and inflammation resolves. BD antigens are similarly distributed in neurons in hippocampus, neocortex, cerebellum and brainstem in acutely and chronically infected animals. We have recently examined brain levels of neuronal transcripts in rats with acute and chronic BD. Levels for 3 of these mRNAs, cholecystokinin, glutamic acid decarboxylase and somatostatin, were decreased in acutely infected rats and increased toward control values in chronically infected rats. A fourth transcript, MuBr8, correlated in distribution with BD antigen, was persistently decreased throughout the course of infection. These data may have implications for understanding the pathogenesis of neurologic disturbances in BD and other inflammatory CNS diseases.
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We present a case of massive benign axillary lymph-node hyperplasia in pregnancy and the puerperium in the absence of any breast or axillary pathology, posing a difficult management dilemma.
A case of beta haemolytic Group A streptococcal cervicitis causing disseminated intravascular coagulation, bacteraemic shock, and death in a 57 year old woman is presented.
We have mapped the neuroanatomical distribution of amyloid-beta-protein mRNA within neuronal subpopulations of the hippocampal formation in the cynomolgus monkey (Macaca fascicularis), normal aged human, and patients with Alzheimer disease. Amyloid-beta-protein mRNA appears to be expressed in all hippocampal neurons, but at different levels of abundance. In the central nervous system of monkey and normal aged human, image analysis shows that neurons of the dentate gyrus and cornu Ammonis fields contain a 2.5-times-greater hybridization signal than is present in neurons of the subiculum and entorhinal cortex. In contrast, in the Alzheimer disease hippocampal formation, the levels of amyloid-beta-protein mRNA in the cornu Ammonis field 3 and parasubiculum are equivalent. These findings suggest that within certain neuronal subpopulations cell type-specific regulation of amyloid-beta-protein gene expression may be altered in Alzheimer disease.
Neurofibrillary tangles (NFT) and neuritic plaques (NP), two neuropathological markers of Alzheimer disease, may both contain peptide fragments derived from the human amyloid beta protein. However, the nature of the relationship between NFT and NP and the source of the amyloid beta proteins found in each have remained unclear. We used in situ hybridization techniques to map the anatomical distribution of precursor amyloid-beta-protein mRNA in the neocortex of brains from three subjects with no known neurologic disease and from five patients with Alzheimer disease. In brains from control subjects, positively hybridizing neurons were present in cortical regions and layers that contain a high density of neuropathological markers in Alzheimer disease, as well as in those loci that contain NP but few NFT. Quantitative analyses of in situ hybridization patterns within layers III and V of the superior frontal cortex revealed that the presence of high numbers of NFT in Alzheimer-diseased brains was associated with a decrease in the number of positively hybridizing neurons compared to controls and Alzheimer-diseased brains with few NFT. In contrast, no correlation was found between the densities of NP and neurons containing precursor amyloid-beta-protein mRNA transcripts. These findings suggest that the expression of precursor amyloid-beta-protein mRNA may be a necessary but is clearly not a sufficient prerequisite for NFT formation. In addition, these results may indicate that the amyloid beta protein, present in NP in a given region or layer of cortex, is not derived from the resident neuronal cell bodies that express the mRNA for the precursor protein.
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The distribution of cells containing messenger RNA that encodes amyloid beta protein was determined in hippocampi and in various cortical regions from cynomolgus monkeys, normal humans, and patients with Alzheimer's disease by in situ hybridization. Both 35S-labeled RNA antisense and sense probes to amyloid beta protein messenger RNA were used to ensure specific hybridization. Messenger RNA for amyloid beta protein was expressed in a subset of neurons in the prefrontal cortex from monkeys, normal humans, and patients with Alzheimer's disease. This messenger RNA was also present in the neurons of all the hippocampal fields from monkeys, normal humans and, although to a lesser extent in cornu ammonis 1, patients with Alzheimer's disease. The distribution of amyloid beta protein messenger RNA was similar to that of the neurofibrillary tangles of Alzheimer's disease in some regions, but the messenger RNA was also expressed in other neurons that are not usually involved in the pathology of Alzheimer's disease.
Fifty-six cases of cataract removal in dogs by phacofragmentation and aspiration were reviewed. Improvement of vision was detected in the immediate postoperative period in 53 (94.6%) of 56 dogs. Vision was present in 25 (85.2%) of 29 dogs evaluated at 2 years after surgery, and in 5 (71.4%) of 7 dogs evaluated 4 years after surgery. Reasons for failure of visual improvement and complications in visual eyes were related primarily to development of postoperative anterior uveitis. Age of the dog at surgery was not a significant factor in the restoration of vision.
Blue cone monochromacy (BCM) is an infrequent X-linked retinal disorder typified by poor central visual acuity and color discrimination, early onset of nystagmus, variable degrees of myopia and astigmatism, and a nearly normal retinal appearance. The physiologic functions of rods and blue cones are preserved. The regional location of the genetic mutation causing BCM has been unknown. We have applied the modern molecular techniques of analysis of restriction fragment length polymorphisms to three multigenerational kindreds in which BCM is segregating. Significant linkage is established to two DNA markers, DXS15 and DXS52, each of which maps to the vicinity of Xq28. Regional localization of the locus for BCM has the potential to improve carrier detection and to provide antenatal diagnosis in families at risk for the disease.
Forty gonadally intact male Wistar rats, 200-225 g, were utilized to study the behavioral and physiological effects of testosterone (T) pellet administration. T was administered via pellets (10, 25, 50, and 100 mg) implanted subcutaneously in the dorsal region of the neck. Fifty mg lactate pellets were utilized as the control. T plasma levels were determined using RIA procedures on days 30, 60, and 90 after pellet implantation. T (50 and 100 mg) resulted in plasma concentrations significantly greater than controls. T (100 mg) and lactate control groups were subjected to a competition situation utilizing an estrogen-primed female as the goal object. Subjects were exposed to the test procedure prior to the implantation of the pellets. T resulted in previously defined losers becoming winners in the competition situation on days 30, 60, and 90 post-implantation. T implantation did not significantly affect muricidal behavior as compared to lactate controls. On day 90, the subjects were sacrificed, and the organ/body-weight ratios determined for the heart, liver, testes, and skeletal muscles of the left shoulder girdle. T (100 mg) resulted in a decrease in the testes/body-weight ratio as compared to controls, while the liver/body-weight ratio was increased in this group T (100 mg) also resulted in an increase in the activity of serum enzyme glutamic-oxaloacetic transaminase (SGOT) on day 90 post-implantation. Food intake and body weight were monitored throughout the course of the study. However, no significant differences from controls were noted.
Male Wistar rats were tested in 3 competitive situations to determine the effects of d-amphetamine (AMP) on competitive behavior. Subjects were initially tested in a fixed-pair food competition paradigm. Based on the percentage of pellets obtained, a winner and loser were defined for each pair. AMP (2.0 and 4.0 mg/kg) was then administered to one or both members of pair, and the effects of the drug on the defined winners and losers were determined. AMP did not significantly alter the percentage of pellets obtained by losers except when only the winners were administered AMP (4.0 mg/kg). Subjects were then tested in a round-robin competition paradigm in which each subject was paired with every other subject. The animals were ranked according to the percentage of pellets obtained out of a possible 450 pellets. AMP (2.0 mg/kg) decreased pellet acquisition in higher ranking subjects, whereas pellet acquisition was increased in lower ranking subjects. The effects of AMP were also evaluated in a "worker-parasite" paradigm. Subjects were individually conditioned to press a lever using an FI schedule for presentation of a food pellet. When the lever was located on the wall opposite the food hopper, a worker and parasite were defined for each pair. The worker was the subject that made the most responses on the lever while obtaining fewer reinforcements. Subjects that were defined as winners in the fixed pair food competition emerged as the workers in this situation. AMP (0.8 mg/kg) given concurrently to both subjects resulted in a reversal of roles; the parasites now emitted the majority of responses and obtained less pellets. The data indicate that AMP has a differential effect on participants in competitive situations when all subjects in the situation are treated.
The motility of bovine and ovine spermatozoa has been studied under aerobic and anaerobic conditions, using a dual beam laser velocimeter. Cells swimming under aerobic conditions were found to be characterized by a translational swimming speed and a rotation rate that were approximately double those of cells swimming in an anaerobic environment. Both types of spermatozoa have been found to exhibit a sudden coordinated transition between fast and slow swimming states when the available oxygen is exhausted. This transition from aerobic to anaerobic swimming states has also been shown to be reversible. Studies of the duration of aerobic motility using the same apparatus have shown that the cells have a constant motile efficiency over the temperature range 32 degrees-42 degrees C.
Although actively transcribed and present as multiple genomic copies, a distinct class of endogenous murine leukemia virus-related sequence does not give rise to infectious virus. Since the long terminal repeat at the 3' terminus provides the transcriptional start site after reintegration, we determined the structure and potential promoter activity of that sequence obtained from cDNA of endogenous retroviral transcripts. These studies demonstrate that the distinctive 3' long terminal repeat sequence of these transcripts could serve as an effective promoter of transcription and, therefore, may not be the primary defect in the infectious cycle of retroviral replication but may result in the propagation of these endogenous retroviral sequences in the genome as retrotransposons.
Between 1982 and 1985, 1015 mares were evaluated using the following parameters: age, mare status (maiden, barren, lactating), Caslick index, Caslick operation, ovarian cycle, ovarian and follicular size, treatments (hCG and intrauterine infusions), number of ovulations after mating (184 mares), number of conceptuses present, dimensions of embryonic vesicles, and pregnancy status 45 days after mating. Mares were examined ultrasonographically between Days 12 and 25 to detect the presence of embryonic vesicles and measure the dimensions of each vesicle. The data were analysed by a stepwise logistic regression method. Mare and follicular status were significant (P less than 0.005) predictors of pregnancy outcome. Results from 2949 mare cycles (268 maiden; 1047 lactating; 618 barren) for twin conceptus rates were 15.3%, 8.8% and 14.0% respectively. Based on follicle status, twin-conceptus rates with a single palpable follicle greater than 25 mm in diameter were 11% in maiden, 11% in barren and 5.3% in lactating mares. In 23.7% of cycles (22.4%, 28.8% and 20.7%) 2 palpable follicles greater than 25 mm were recorded, resulting in twin conception rates of 30%, 23.3% and 22% in maiden, barren and lactating mares, respectively. Twin conceptus rate for all mares with a single follicle greater than 25 mm was 7.6% and with 2 follicles greater than 25 mm 23.6%. Mares with 2 large follicles (greater than 40 mm) at mating had a 38.2% (29/76) twin conception rate. Mares with known synchronous double ovulations had a 40% (22/55) twin conception rate. An analysis of co-variance was used to calculate the daily embryonic growth rate between Days 10 and 16 of gestation for 11 Standardbred mares.(ABSTRACT TRUNCATED AT 250 WORDS)
The late asthmatic response is defined as airway obstruction that occurs hours after antigen exposure in some atopic asthmatics. The importance of this reaction is that the airway obstruction may be severe, prolonged, and difficult to control unless corticosteroids are employed. In addition, this response may lead to an increase in airway reactivity. To investigate the immunopathogenesis of this disorder, an animal model in rabbits was developed. In this model, antigen-specific IgE was associated with the late asthmatic response and antigen-specific IgG was associated with blunting of the reaction. Antigen challenge of immune rabbits led to edema within the large airways shortly after antigen exposure, with infiltration of inflammatory cells (neutrophils and eosinophils) into the large and small airways during the late response. The infiltrates became more mononuclear with time and resolved over 10 days. As in humans, the late response was associated with an increase in airway reactivity and correlated temporally with infiltration of the airways with neutrophils and eosinophils. The contribution of granulocytic cells to the airway responses to antigen was studied by granulocyte depletion, which prevented both the late response and the heightened airway reactivity. In addition, transfusion of a neutrophil-rich population of white cells into granulocytopenic immune rabbits restored both responses. Thus, in this animal model, the antigen-induced late asthmatic response and subsequent increase in airway reactivity were dependent on the presence of granulocytes at the time of exposure to antigen.
A recently developed direct-smear fluorescent antibody (DFA) cytology method of detecting chlamydial infection was evaluated in an area where trachoma is endemic. Four hundred seventy-five children aged 2 to 10 years were examined, and adequate conjunctival cytology specimens were collected from 457 (96%). Trachomatous inflammatory changes were observed in 114 (25%) of the children. The DFA cytologic technique has a high specificity (100%) but a low sensitivity (8%). It offers a number of advantages over existing laboratory methods for diagnosing trachoma in the field. It is a rapid, simple, and easily transferred test that has a high specificity. Although DFA cytology shares the low sensitivity of other laboratory methods of diagnosing trachoma, we believe its logistical advantages make it the laboratory test of choice.