Linezolid and reversible myelosuppression.
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Acetamides↗
Biomedical subjects
S L Green
Publications and source records attributed to S L Green.
Device-dependent activity estimation and decay correction of radionuclide mixtures with application to Tc-94m PET studies.
Multi-instrument activity estimation and decay correction techniques were developed for radionuclide mixtures, motivated by the desire for accurate quantitation of Tc-94m positron emission tomography (PET) studies. Tc-94m and byproduct Tc isotopes were produced by proton irradiation of enriched Mo-94 and natural Mo targets. Mixture activities at the end of bombardment were determined with a calibrated high purity germanium detector. The activity fractions of the greatest mixture impurities relative to 100% for Tc-94m averaged 10.0% (Tc-94g) and 3.3% (Tc-93) for enriched targets and 10.1% (Tc-94g), 11.0% (Tc-95), 255.8% (Tc-96m), and 7.2% (Tc-99m) for natural targets. These radioisotopes have different half-lives (e.g., 52.5 min for Tc-94m, 293 min for Tc-94g), positron branching ratios (e.g., 0.72 for Tc-94m, 0.11 for Tc-94g) and gamma ray emissions for themselves and their short-lived, excited Mo daughters. This complicates estimation of injected activity with a dose calibrator, in vivo activity with PET and blood sample activity with a gamma counter. Decay correction using only the Tc-94m half-life overestimates activity and is inadequate. For this reason analytic formulas for activity estimation and decay correction of radionuclide mixtures were developed. Isotope-dependent sensitivity factors for a PET scanner, dose calibrator, and gamma counter were determined using theoretical sensitivity models and fits of experimental decay curves to sums of exponentials with fixed decay rates. For up to 8 h after the end of bombardment with activity from enriched and natural Mo targets, decay-corrected activities were within 3% of the mean for three PET studies of a uniform cylinder, within 3% of the mean for six dose calibrator decay studies, and within 6% of the mean for four gamma counter decay studies. Activity estimation and decay correction for Tc-94m mixtures enable routine use of Tc-94m in quantitative PET, as illustrated by application to a canine Tc-94m sestamibi study.
Animals↗
p21(Cip1) and p27(Kip1) regulate cell cycle reentry after hypoxic stress but are not necessary for hypoxia-induced arrest.
We investigated the role of the cyclin-dependent kinase inhibitors p21(Cip1) and p27(Kip1) in cell cycle regulation during hypoxia and reoxygenation. While moderate hypoxia (1 or 0.1% oxygen) does not significantly impair bromodeoxyuridine incorporation, at very low oxygen tensions (0.01% oxygen) DNA replication is rapidly shut down in immortalized mouse embryo fibroblasts. This S-phase arrest is intact in fibroblasts lacking the cyclin kinase inhibitors p21(Cip1) and p27(Kip1), indicating that these molecules are not essential elements of the arrest pathway. Hypoxia-induced arrest is accompanied by dephosphorylation of pRb and inhibition of cyclin-dependent kinase 2, which results in part from inhibitory phosphorylation. Interestingly, cells lacking the retinoblastoma tumor suppressor protein also display arrest under hypoxia, suggesting that pRb is not an essential mediator of this response. Upon reoxygenation, DNA synthesis resumes by 3.5 h and reaches aerobic levels by 6 h. Cells lacking p21, however, resume DNA synthesis more rapidly upon reoxygenation than wild-type cells, suggesting that this inhibitor may play a role in preventing premature reentry into the cell cycle upon cessation of the hypoxic stress. While p27 null cells did not exhibit rapid reentry into the cell cycle, cells lacking both p21 and p27 entered S phase even more aggressively than those lacking p21 alone, revealing a possible secondary role for p27 in this response. Cdk2 activity is also restored more rapidly in the double-knockout cells when returned to normoxia. These studies reveal that restoration of DNA synthesis after hypoxic stress, but not the S phase arrest itself, is regulated by p21 and p27.
Animals↗
Suspected hypovitaminosis A in a colony of captive green anoles (Anolis carolinensis).
In a colony of 18 green anoles (Anolis carolinensis), 3 animals experienced focally thickened lips, ulcerative cheilitis, lethargy, depression, and weight loss over a 5-month period. In addition to crickets fed fresh fruit and leafy green vegetables, the diet of the green anoles consisted of a supply of mealworms that had been dusted with a commercial liquid vitamin supplement. The history, clinical findings, and histopathologic lesions were suggestive of hypovitaminosis A, which is known to cause squamous metaplasia of the mucus secreting glands and epithelial surfaces in many species.
Animals↗
p53 checkpoint-defective cells are sensitive to X rays, but not hypoxia.
X-ray-induced damage leads to cell-cycle "checkpoint" arrest by p53-dependent induction of the cyclin-dependent kinase inhibitor p21 (Waf1/Cip1/Sdi1). Human tumor cells that lack this response fail to arrest after exposure to DNA-damaging agents, undergo multiple rounds of endoreduplicative DNA synthesis, and eventually commit to an apoptotic cell death. Since low oxygen tension can also induce p53 protein accumulation, and can lead to cell-cycle arrest or apoptosis, we examined the expression of p21 in tumor cells under normoxic and hypoxic conditions. In a survey of cells, mRNA for the p21 gene was induced two- to threefold in response to hypoxia in a seemingly p53-independent manner. We therefore examined genetically matched cells that differ in their p21 and p53 status for response to ionizing radiation and hypoxia. We found that both p21-deficient and p53-deficient cells exhibit an increase in chromosome instability, an increased level of apoptosis, and a failure to arrest after exposure to ionizing radiation. However, cells that lack either p21 or p53 exhibit no increase in chromosome instability or elevated apoptosis and still arrest in response to hypoxia. Thus, the mechanism responsible for the differential response to either hypoxia or X rays presumably lies in the control of cell-cycle progression in response to stress and its dependence on p21. Since the loss of a DNA-damage-dependent checkpoint does not sensitize cells to killing by stresses that elicit a DNA-damage-independent checkpoint, targeting the function of p21 pharmacologically will not kill tumor cells in situ in the absence of a DNA damage signal.
Apoptosis↗
Dilative cardiomyopathy leading to congestive heart failure in a male squirrel monkey (Saimiri sciureus).
A 17-year-old, 1-kg, colony-housed, male squirrel monkey (Samiri sciureus) developed clinical signs of congestive heart failure. The monkey presented with lethargy, increased heart and respiratory rates, and mild abdominal distention. The clinical history, laboratory analysis, and radiographic findings were consistent with heart failure due to dilative cardiomyopathy. Gross and microscopic examination of the heart confirmed a dilative cardiomyopathy. This is the first report describing congestive heart failure caused by dilative cardiomyopathy in a squirrel monkey. Spontaneous dilative cardiomyopathy may be infrequently observed in the squirrel monkeys because they are not routinely housed in the research environment during their advancing years.
Aging↗
Disease attributed to Mycobacterium chelonae in South African clawed frogs (Xenopus laevis).
The fast-growing nontuberculous mycobacterial species Mycobacterium chelonae was isolated from six captive South African clawed frogs (Xenopus laevis) with chronic weight loss and nonhealing ulcerative skin lesions. Three of the M. chelonae isolates were evaluated to confirm the species identification using polymerase chain reaction restriction analysis. Disease associated with M. chelonae is reported mainly in people and in fish. To our knowledge, this is the first report of disease associated with M. chelonae in a colony of captive Xenopus sp.
Animals↗
Identification and management of an outbreak of Flavobacterium meningosepticum infection in a colony of South African clawed frogs (Xenopus laevis).
During the summer of 1996, an outbreak of Flavobacterium meningosepticum infection developed in a colony of South African clawed frogs (Xenopus laevis). Clinical signs were consistent with septicemia: ascites, anasarca, dyspnea, extreme lethargy, congestion of web vessels, petechial hemorrhages, and sudden death. Mortality rate reached 35%, and all infections were fatal. The organism was resistant to most antibiotics but was susceptible to enrofloxacin, chloramphenicol, and trimethoprim-sulfadiazine. Treatment with trimethoprim-sulfadiazine was unsuccessful. Although the point source of the infection was not determined, several environmental reservoirs were identified, including a communal water barrel and various pieces of equipment. Molecular strain typing by pulsed-field gel electrophoresis and biochemical analyses revealed that frogs were infected with a single strain of F meningosepticum. Sanitation and management procedures were effective in controlling the outbreak.
Animals↗
Hospital blood pressure measurement: staff and device assessment.
Evaluation of the ability of clinical staff to measure blood pressure as well as the functional state of hospital sphygmomanometers has consistently demonstrated marked deficiencies. In this study, the working order of all sphygmomanometers (manual and automated) in a teaching hospital was evaluated. Nursing staff were tested on their knowledge and use of such devices and were also asked to estimate the blood pressure from videotape. The accuracy of a commonly used automated device, Dinamap 8100, was also measured. Of 543 manual sphygmomanometers, 14% were in perfect working order although portable devices were more likely to be functional (47% of 36 units). In contrast, all 135 automated portable devices were in perfect working order although service requirements were seldom met. The mean time since last service was 18 months. There appeared to be an inverse correlation between the availability of automated and manual devices and the maintenance of wall-mounted bedside sphygmomanometers. Staff knowledge about manual devices was adequate as was their ability to accurately measure blood pressure using standardised videotape. Forty-two per cent of 31 nurses who completed the test were correct in 9 of 12 blood pressures. A comparison of this result with a comparable group of nurses tested in 1990 did not detect a significant change in competence. Direct evaluation of the commonly used Dinamap 8100 in 47 hospital patients demonstrated a poor correlation with a mercury sphygmomanometer with a D grade (fail) for systolic and a C grade for diastolic pressure. In summary, maintenance of manual sphygmomanometers was very poor, probably due to their lack of use by clinical staff. This was particularly true for units attached to bedside walls. Nursing staff demonstrated significant deficiencies in manual sphygmomanometer use although their skills were similar to those measured several years earlier. Because of the demonstrated inaccuracy of the Dinamap 8100 automated device, the strong trend towards the use of automated devices instead of manual sphygmomanometers within hospitals cannot be supported.
Adolescent↗
Perception of the horizontal and vertical in tangible displays: minimal gender differences.
A study is reported of gender differences in a haptic version of three Piagetian tests that assess understanding of Euclidian space. A raised-line drawing kit was used both for subject responses and for production of stimuli. To test understanding of the horizontal, subjects felt pictures of a jar at four tilts and were asked to draw the water line. Two methods were used to examine understanding of the vertical. First, subjects drew a hanging electrical cord and light bulb, attached to the ceiling of a bus, parked on hills of four different angles. Subsequently, subjects drew telephone poles (represented by a single line) on hills of four different angles. In the jar task, males and females showed comparable performance, both groups showing large errors. Judgments of the vertical were very similar for males and females in the bus task, but errors diminished considerably for both genders when subjects drew telephone poles on hills. It is suggested that better judgments of the vertical in the pole task probably derive from the use of body-centered spatial reference information.
Analysis of Variance↗
Intersensory conflict between vision and touch: the response modality dominates when precise, attention-riveting judgments are required.
In four experiments, reducing lenses were used to minify vision and generate intersensory size conflicts between vision and touch. Subjects made size judgments, using either visual matching or haptic matching. In visual matching, the subjects chose from a set of visible squares that progressively increased in size. In haptic matching, the subjects selected matches from an array of tangible wooden squares. In Experiment 1, it was found that neither sense dominated when subjects exposed to an intersensory discrepancy made their size estimates by using either visual matching or haptic matching. Size judgments were nearly indentical for conflict subjects making visual or haptic matches. Thus, matching modality did not matter in Experiment 1. In Experiment 2, it was found that subjects were influenced by the sight of their hands, which led to increases in the magnitude of their size judgments. Sight of the hands produced more accurate judgments, with subjects being better able to compensate for the illusory effects of the reducing lens. In two additional experiments, it was found that when more precise judgments were required and subjects had to generate their own size estimates, the response modality dominated. Thus, vision dominated in Experiment 3, where size judgments derived from viewing a metric ruler, whereas touch dominated in Experiment 4, where subjects made size estimates with a pincers posture of their hands. It is suggested that matching procedures are inadequate for assessing intersensory dominance relations. These results qualify the position (Hershberger & Misceo, 1996) that the modality of size estimates influences the resolution of intersensory conflicts. Only when required to self-generate more precise judgments did subjects rely on one sense, either vision or touch. Thus, task and attentional requirements influence dominance relations, and vision does not invariably prevail over touch.
Adult↗
Animal models for motor neuron disease.
Motor neuron disease is a general term applied to a broad class of neurodegenerative diseases that are characterized by fatally progressive muscular weakness, atrophy, and paralysis attributable to loss of motor neurons. At present, there is no cure for most motor neuron diseases, including amyotrophic lateral sclerosis (ALS), the most common human motor neuron disease--the cause of which remains largely unknown. Animal models of motor neuron disease (MND) have significantly contributed to the remarkable recent progress in understanding the cause, genetic factors, and pathologic mechanisms proposed for this class of human neurodegenerative disorders. Largely driven by ALS research, animal models of MND have proven their usefulness in elucidating potential causes and specific pathogenic mechanisms, and have helped to advance promising new treatments from "benchside to bedside." This review summarizes important features of selected established animal models of MND: genetically engineered mice and inherited or spontaneously occurring MND in the murine, canine, and equine species.
Amyotrophic Lateral Sclerosis↗
Alterations in cyclin-dependent protein kinase 5 (CDK5) protein levels, activity and immunocytochemistry in canine motor neuron disease.
Hereditary canine spinal muscular atrophy (HCSMA) is a dominantly inherited motor neuron disease in Brittany spaniels that is clinically characterized by progressive muscle weakness leading to paralysis. Histopathologically, degeneration is confined to motor neurons with accumulation of phosphorylated neurofilaments in axonal internodes. Cyclin-dependent kinase 5 (CDK5), a kinase related to the cell cycle kinase cdc2, phosphorylates neurofilaments and regulates neurofilament dynamics. We examined CDK5 activity, protein levels, and cellular immunoreactivity in nervous tissue from dogs with HCSMA, from closely age-matched controls and from dogs with other neurological diseases. On immunoblot analysis, CDK5 protein levels were increased in the HCSMA dogs (by approximately 1.5-fold in both the cytosolic and the particulate fractions). CDK5 activity was significantly increased (by approximately 3-fold) in the particulate fractions in the HCSMA dogs compared to all controls. The finding that CDK5 activity was increased in the young HCSMA homozygotes with the accelerated form of the disease, who do not show axonal swellings histologically, suggests that alterations in CDK5 occurs early in the pathogenesis, prior to the development of significant neurofilament pathology. Immunocytochemically, there was strong CDK5 staining of the nuclei, cytoplasm and axonal processes of the motor neurons in both control dogs and dogs with HCSMA. Further immunocytochemical studies demonstrated CDK5 staining where neurofilaments accumulated, in axonal swellings in the dogs with HCSMA. Our observations suggest phosphorylation-dependent events mediated by CDK5 occur in canine motor neuron disease.
Animals↗
Variants of alpha 1-proteinase inhibitor in black and white South African patients with focal glomerulosclerosis and minimal change nephrotic syndrome.
OBJECTIVE: To determine the prevalence and biochemical characteristics of certain alleles of alpha 1-proteinase inhibitor in black and white South African patients with two common types of pathology causing the nephrotic syndrome. DESIGN: A cross sectional study of black and white patients with focal glomerulosclerosis (FGS) or minimal change disease (MCNS) and black and white controls. SETTING: The patients were drawn from the Paediatric Nephrology Units at the Johannesburg and Baragwanath Hospitals and the controls were drawn from the South African Blood Transfusion Service and the Paediatric Nephrology Clinic in Johannesburg. RESULTS: There was a significant increase in the prevalence of the V allele in black patients with FGS (12%) as compared to black controls (1%) (p = 0.01). None of the white patients with FGS had the V allele but two out the five coloured (mixed race) patients had the V allele (20%). An increase in the prevalence of the S allele of alpha 1PI was found in white patients with FGS and MCNS (10%) as compared to white controls (2%). The plasma elastase inhibitory capacity (EIC) associated with the phenotypes (PI) M1 (Ala213)S, M1 (Ala213) V, and M1 (Ala213) M1 (Ala213) was significantly decreased as compared to the EIC associated with PI M1 (Val213) M1 (Val213) (p = 0.006, p = 0.004, and p = 0.025, respectively). Twelve of 13 patients with FGS and infected with tuberculosis had either the M1 (Ala213) V or F alleles and required transplantation owing to the severity of the disease. All of these patients were either black or coloured. However, eight of 12 patients with FGS who had the M1 (Ala213) V or S alleles but were PPD negative did not require transplantation. CONCLUSION: It is possible that the combination of functionally less efficient alpha 1PI and an inflammatory challenge associated with an infection such as tuberculosis could predispose black and coloured nephrotic patients to more aggressive scarring in FGS.
Adolescent↗
Polymorphisms of the beta chain of the high-affinity immunoglobulin E receptor (Fcepsilon RI-beta) in South African black and white asthmatic and nonasthmatic individuals.
We used amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) to document the prevalence of three mutations in the beta chain of the high-affinity IgE receptor (Fcepsilon RI-beta): I181L, V183L, and E237G in a sample of black and white asthmatic and control subjects in South Africa to determine whether these variants contribute to the enhanced IgE responses in these groups and also to determine whether the discrepancy in the prevalence of atopy in these groups could be attributed to these variants, as whites tend to be more atopic than blacks. There was a significant difference in the frequency of I181L between white asthmatics (28%) and white control subjects (3%) (p = 0.00001), and between black control subjects (16%) and white control subjects (p = 0.002); no difference in the frequency of I181L was observed between black asthmatics (22%) and black control subjects (16%). V183L was found in one black asthmatic who was also positive for I181L and E237G. There was a significant difference in the frequency of E237G between black asthmatics (20%) and white asthmatics (12%) (p = 0.05), and between control subjects (20%) and white control subjects (5%) (p = 0.003). E237G was more prevalent in blacks (20%) than in whites (8.5%) (p = 0.001). I181L might predispose to atopy in the white population, but not in the black population. The significantly higher prevalence of E237G in blacks than in whites might explain why blacks tend to have more severe asthma than whites and might offer more insight into the higher asthma mortality rate in the black population as compared with the white population.
Adolescent↗
Hereditary canine spinal muscular atrophy: genetics, neurophysiology, and pathology.
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Animals↗
Cyclin-dependent protein kinase 5 activity increases in rat brain following ischemia.
Cyclin-dependent kinase 5 (CDK5) is the 34 kDa catalytic subunit of a recently characterized neuronal cdc2-like protein kinase which appears to be involved in regulation of the neurocytoskeleton. Using the rat postdecapitative model, the effect of brain ischemia on histone H1 and tau protein CDK5 phosphorylating activity was examined. Histone H1 kinase activity increased in both cytosolic and particulate fractions of the hippocampus and neocortex after 5 min and 15 min of ischemia, then declined to control levels. CDK5 tau protein phosphorylating activity increased after 15 min ischemia; however, no electrophoretic shifts or changes in radiodensity of the tau bands were observed autoradiographically. On Western blot analysis, the CDK5 protein band did not change after 25 min ischemia, despite the increase and subsequent decline in enzyme activity. These data demonstrate a postischemic increase in CDK5 activity, an associated increase in CDK5 tau phosphorylating activity and a decline in activity in the absence of massive proteolysis. CDK5 appears to play a role in the events associated with neuronal response to ischemic injury.
Animals↗
Rabies.
Equine rabies is a sporadic but highly fatal zoonotic disease. The disease persists in wildlife populations throughout the United States, Canada, Mexico, and other parts of the world. It remains a threat to all domestic species, including the horse. This article reports recent advances in the molecular virology of the rabies virus and its pathogenesis, and it also reviews the history, clinical signs, diagnostic tests, vaccination protocols, and postexposure management recommendations for the equine species.
Animals↗