Biomedical subjects
Publications and source records attributed to J Nelson.
This report documents sudden, unexpected death in a 5-year-old boy from a ganglioglioma of the medulla. Gangliogliomas are rare, primary brain tumors that are encountered predominantly in childhood. We are unaware of any previous report of a similar case.
Afferents of the large, electrically 'silent' frontal cortex in an egg-laying mammal, the echidna, were studied with the somatopetal axonal transport technique. This cortical area receives thalamic projections only from the anterior part of the anteromediodorsal region. The medial parts of the cortex receive afferents from more medial neurons, whereas the lateral area is innervated from the laterally placed perikarya of this thalamic region. The nonthalamic afferents to the frontal cortex are, with few exceptions, similar to the afferents of the prefrontal cortex in placental mammals. Cortical afferents originate in all layers of the contralateral symmetrical areas and in the ipsilateral paleocortex, especially the cortex in the bottom of the sulcus mu. The claustrum could not be identified, neither cytoarchitecturally nor hodologically. Pending confirmation from studies of the diencephalon, we presently conclude that the large anterior cortical area in this species corresponds to the prefrontal cortex of eutherian mammals. If this conclusion is correct, the echidna is the only species studied to date that has a proportionally larger prefrontal cortex than humans.
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Bsp-1 is an IgM murine monoclonal antibody raised against the human erythroblastic leukemia cell line (HEL) that reacts with basophils but not neutrophils or eosinophils. Western blotting techniques showed that Bsp-1 reacts with a 45-kilodalton surface antigen on HEL cells. The distribution of Bsp-1 antigen on leukemic cells is confined to a basophilic leukemia cell line, KU812, chronic myeloid leukemia with basophilia, and some cases of acute undifferentiated leukemia. Bsp-1 might therefore be a useful reagent for the study of basophil function and differentiation.
In this study, we demonstrated that benzene and its metabolites, phenol and hydroquinone, were toxic to human burst-forming unit-erythroid (BFU-E) growth, hydroquinone being the most toxic. Phenol (10(-4) M) was also found to have a marked toxicity on stromal cell colony formation. BFU-E binding with human-tumor necrosis factor (rHu-TNF) was linear with the number of BFU-E colonies. Recombinant rHu-TNF suppressed BFU-E growth in a dose-dependent manner and this was reversed with anti-TNF antibody. Binding studies of rHu-TNF for human K562 cells indicated that K562 cells have a binding constant of approximately 1075 per cell. The heme pathway enzymes, uroporphyrinogen deaminase, and heme oxygenase activities were measured in BFU-E cultures exposed to iron, interleukins (1 and 2), and various lymphocyte and macrophage-conditioned media with or without hemin. In most instances, hemin was found to stimulate the heme synthetic pathway in the presence of these agents. Iron and adherent (macrophage) cell conditioned media (CM) were found to stimulate heme oxygenase activity. Macrophage CM was found to suppress erythropoiesis in contrast to phytohemagglutinin-stimulated leukocyte (PHAL)-CM, which enhanced erythroid growth. In addition, porphobilinogen deaminase levels were greater in 14-day cultures containing hemin plus PHAL-CM as compared with hemin alone. These results are discussed with respect to the generation of hematopoietic inhibitory-stimulatory factors by the marrow microenvironment and their effects on heme synthesis and degradation.
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Hepatitis delta virus (HDV) is a replication-defective etiological agent of hepatitis that requires hepatitis B virus (HBV) as a helper. A complementary DNA (cDNA) fragment of the RNA genome of HDV was cloned into the plasmid vector pBR322, and the primary nucleotide sequence and predicted protein products of the cDNA fragment were determined. This cloned cDNA fragment has been used as a sensitive radioactive probe for the detection of HDV RNA in the serum of patients with either acute or chronic HDV infections.
Homogenisation and fractionation of cells in the presence of Mg2+ or EDTA resulted in unoccupied oestrogen receptor being recovered in the particulate fraction. Nuclei were partially purified by pelleting at 100,000 g through 41% and 44% (w/w) sucrose (in buffer containing Mg2+ or EDTA), plasma membranes being collected from the top of the 41% barrier. In Mg2+-prepared fractions, both 5'-nucleotidase and unoccupied receptor were distributed between plasma membrane, partially-pure nuclei and mitochondrial/microsomal pellets. Lactate dehydrogenase was not a significant contaminant of particulate fractions. In EDTA fractions, the majority of binding activity was in the partially-pure nuclei (which were extensively disrupted) and mitochondrial/microsomal pellets. Little or no binding was found in the EDTA-prepared plasma membranes which were amorphous in appearance. Mg2+-prepared nuclei, freed of membranous contamination by pelleting through 1.8 M sucrose, were intact by electron microscopy but had no 5'-nucleotidase or unoccupied receptor. These data suggest that recovery of receptor in partially-pure nuclei during fractionation is not caused by trapping of cytosolic protein but rather by redistributed nuclear receptor having become bound to adhering plasma membrane fragments during homogenisation. Implications for the study of cell-free systems are discussed.
Eighty male undergraduates were administered either glucose or 5, 10, 20, or 40 mg of hydrocortisone in a double-blind procedure. After 60 min they were asked to listen to eight 12 word lists and then asked to recall the words. In addition to the expected effects of rate of presentation, serial position, and practice there was a significant interaction between dose of hydrocortisone and practice. Early recall was facilitated by all doses used whereas later recall was facilitated by treatment with 40 mg and impaired by treatment with 5 mg. These findings are discussed in the context of the effects of pituitary adrenocortical hormones and memory function.
Patients on long-term home parenteral nutrition (HPN) are known to frequently develop hepatic steatosis or steatohepatitis. The etiology of this steatosis or steatohepatitis is unknown, but carnitine deficiency has been one of the postulated mechanisms. The importance of L-carnitine in hepatic fatty acid oxidation and the steatosis observed in primary and acquired carnitine deficiencies prompted us to determine plasma carnitine levels in 37 patients receiving long-term HPN. Thirteen patients (35%) had low total and free plasma carnitine levels. Fifteen of the 37 HPN patients were matched for age and sex with 15 patients with Crohn's disease who did not require HPN. Mean total and free plasma carnitine values were significantly lower (p less than 0.001) in these 15 HPN patients (32.2 +/- 11.9 and 28.4 +/- 10.8) when compared to Crohn's patients not requiring HPN (49.1 +/- 10.9 and 46.4 +/- 11.5). Associations were not detected between plasma carnitine and clinical or biochemical parameters that might have explained the low values.
The effect of hyperoxia on the Ca2+ dependence of stimulated superoxide anion radical (O2-.) production (the respiratory burst) of rat alveolar macrophages was investigated. Enhancement of the concanavalin A (con A)-stimulated respiratory burst by extracellular Ca2+ was suppressed by O2 exposure. Similarly, the inhibitory effect of verapamil on the con A-stimulated respiratory burst was reduced by O2 exposure. O2 exposure also inhibited con A stimulation that was independent of Ca2+ entry. Exposure to O2 also caused a decline in O2-. production stimulated by either A23187 or phorbol myristate acetate (PMA). With A23187 stimulation, extracellular Ca2+ was essential for either air-exposed (control) or O2-exposed cells. With PMA, stimulation was independent of extracellular Ca2+ for either air or O2-exposed macrophages and verapamil did not inhibit. Free intracellular Ca2+ concentration ([Ca2+]i) was measured in control and O2-exposed alveolar macrophages. Hyperoxic exposure did not alter [Ca2+]i in unstimulated cells. In controls, con A stimulated an immediate increase in [Ca2+]i followed by a rapid decrease and a second rise and fall. The second elevation was suppressed by verapamil or ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetraacetic acid or O2 exposure. The results of both the respiratory burst assays and measurement of con A-stimulated changes in [Ca2+]i suggest that Ca2+ entry involved in stimulus-response coupling is suppressed in cellular O2 toxicity.
We describe morphologically documented necrotizing cerebral vasculitis in a young man with ulcerative colitis. This case supports the evolving concept that ulcerative colitis may be accompanied by systemic vasculitis. The cerebral vasculitis was treated successfully with immunosuppressive therapy.
We have examined the effects of a 24-h exposure to clinically achievable concentrations of adriamycin, melphalan, 5-fluorouracil, and vincristine on the estrogen binding capacity of MCF-7 human breast cancer cells using a whole cell binding assay. Adriamycin (0.018 to 1.8 microM), melphalan (0.1 to 5 microM), 5-fluorouracil (0.077 to 15.4 microM), and vincristine (0.01 to 1 nM) reduce the estrogen binding capacity in a dose dependent manner. The rate of protein synthesis is reduced following exposure to 5-fluorouracil but not following exposure to adriamycin, melphalan, or vincristine. The rate of cell proliferation, influx of the ligand, and the Kd of remaining estrogen receptor are unaltered following drug exposure. These drugs may, therefore, be inducing a nonspecific reduction in the rate of receptor recycling and/or synthesis. Vincristine (1 nM) abolished estrogen receptor expression but following removal of the drug receptor levels did not reach that expressed in untreated cells for at least 48 h. Prior exposure to vincristine (1 nM) reduced the antiproliferative effects of tamoxifen (2 microM) toward MCF-7 cells.
To determine the extent of agreement on underlying cause of death between death certificates and autopsy reports, we analyzed 272 randomly selected autopsy reports and corresponding death certificates from among all such data on autopsies performed in Connecticut in 1980. In 29 per cent of the deaths, a major disagreement on the underlying cause of death led to reclassification of the death in a different International Classification of Diseases major disease category. In an additional 26 per cent, the death certificate and autopsy report agreed on the major disease category but attributed the death to a different specific disease. Deaths due to neoplasms were most accurately diagnosed, with a sensitivity of 87 per cent and a positive predictive value of 85 per cent. Deaths resulting from diseases of the respiratory or digestive system were associated with the highest rates of disagreement. Diseases most commonly overdiagnosed were circulatory disorders, ill-defined conditions, and respiratory diseases. Diseases most commonly underdiagnosed as the cause of death on the death certificate were specific traumatic conditions and gastrointestinal disorders. The autopsy remains an important method for ensuring the quality of mortality statistics.
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Cardiac output was measured by two-dimensional echocardiographic Doppler technique in 55 adult patients in the intensive care unit. Doppler cardiac output determinations were measured from four sites (suprasternal long axis of the ascending aorta, suprasternal long axis of the descending aortic, apical left ventricular outflow tract, and parasternal long axis of the main pulmonary artery) and were compared to cardiac output determined by thermodilution for a total of 101 observations (r = 0.84). Mean cardiac output was 5.3 L/min (range 1.8 to 9.5 L/min) by Doppler technique and 5.1 L/min (range 1.6 to 8.9 L/min) as measured by thermodilution. Correlation of Doppler cardiac output with thermodilution cardiac output gave r values of 0.85, 0.83, 0.90, and 0.81 from the ascending aorta, descending aorta, left ventricular outflow tract, and pulmonary artery, respectively. Averaging of data in patients in whom more than one determination was possible resulted in improved correlation (r = 0.94). Thus, cardiac output can be measured with reasonable accuracy by Doppler from a variety of sampling sites and averaging of data from more than one site may improve these results.
The effects of t-butyl hydroperoxide on glutathione and NADPH and the respiratory burst (an NADPH-dependent function) in rat alveolar macrophages was investigated. Alveolar macrophages were exposed for 15 min to t-butyl hydroperoxide in the presence or absence of added glucose. Cells were then assayed for concanavalin A-stimulated O2 production or for NADPH, NADP, reduced glutathione, glutathione disulfide, glutathione released into the medium and glutathione mixed disulfides. Exposure of rat alveolar macrophages to 1 X 10(-5) M t-butyl hydroperoxide causes a loss of concanavalin A-stimulated superoxide production (the respiratory burst) that can be prevented or reversed by added glucose. Cells incubated without glucose had a higher oxidation state of the NADPH/NADP couple than cells incubated with glucose. With t-butyl hydroperoxide, NADP rose to almost 100% of the NADP + NADPH pool; however, addition of glucose prevented this alteration of the NADPH oxidation state. Cells exposed to 1 X 10(-5) M t-butyl hydroperoxide in the absence of glucose showed a significant increase in the percentage GSSG in the GSH + GSSG pool and increased glutathione mixed disulfides. These changes in glutathione distribution could also be prevented or reversed by glucose. With 1 X 10(-4) M t-butyl hydroperoxide, changes in glutathione oxidation were not prevented by glucose and cells were irreversibly damaged. We conclude that drastic alteration of the NADPH/NADP ratio does not itself reflect toxicity and that significant alteration of glutathione distribution can also be tolerated; however, when oxidative stress exceeds the ability of glucose to prevent alterations in oxidation state, irreversible damage to cell function and structure may occur.