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Biomedical subjects

J Nelson

Publications and source records attributed to J Nelson.

At least 325 records · Page 18Linked to original sources

Host immune status in uremia. IV. Phagocytosis and inflammatory response in vivo.

Infection is a frequent complication and cause of death in renal failure, but the association between uremia, depressed immune status, and susceptibility to infection is far from proven. In the present studies, the effect of uremia on the inflammatory response and phagocytic ability was investigated in an animal model. The inflammatory response, as measured by the ability of leukocytes to mobilize into subcutaneous implanted sponges, was impaired at 6 hr but was normal 24 hr after implantation. The peripheral blood response of uremic animals to the leukocytosis promoting protein from Bordetella pertussis was similar to that of control animals. Reticuloendothelial clearance of labelled albumin was unimpaired but catabolism of this substance was reduced significantly in uremic animals. The ability of the uremic host to clear an intravenous challenge of virus was also depressed. Phagocytic and bactericidal capability of polymorphonuclear (PMN) leukocytes, measured in vitro by latex ingestion and phagocytosis and killing of Staphylococcus aureus, was normal. PMN phagocytic function in vivo was determined by the clearance of viable Escherichia coli from subcutaneously implanted sponges and no significant difference between control and uremic groups was found. These studies have further defined the effect of uremia on immune mechanisms and support our contention that uremia per se is not a major factor contributing to the compromised immune status in this host.

Animals↗

Depolarization and increased conductance precede superoxide release by concanavalin A-stimulated rat alveolar macrophages.

Rat alveolar macrophages release superoxide into the extracellular medium when stimulated by concanavalin A. This process, the respiratory burst, is characterized by a delay between binding of the stimulus and release of superoxide. It has been proposed that a key event that occurs during this delay period is the alteration of membrane electrical potential. Microelectrode impalement was used to directly measure electrical properties of the plasma membrane. Upon addition of concanavalin A, the membrane potential depolarized 21%, and membrane electrical resistance decreased 16%. Parallel chemical measurement of superoxide release indicated that these changes in electrical properties precede the release of superoxide.

Animals↗

Reactive lymphoid hyperplasia with single class (monoclonal) surface immunoglobulin.

Lymphoid tissues from 12 patients were diagnosed as reactive lymphoid hyperplasia, but surface immunoglobulin studies revealed monoclonal (single class) immunoglobulin staining patterns. Infectious, autoimmune, and immunodeficient conditions were diagnosed on the basis of histology and clinical features. Such surface immunoglobulin restriction has been used as an indicator of a neoplastic lymphoid proliferation, but the cases of these patients, in whom the histologic diagnosis was benign, emphasize the importance of a multiparameter approach to diagnosis. Although at the time of this report none of the patients still available to follow-up study have developed known lymphoid neoplasms, the possibility that monoclonal SIg patterns are a harbinger of neoplastic disease makes continuing follow-up of such patients important.

Adolescent↗

Effect of extracellular calcium on superoxide release by rat alveolar macrophages.

Alveolar macrophages can be stimulated to release superoxide into the extracellular medium. The mechanism of activation of superoxide release has been reported to be mediated by the movement of Ca2+ into the cytosol, but the involvement of extracellular Ca2+ in this process has remained uncertain. Extracellular Ca2+ was not an absolute requirement for activation of superoxide release; however, 1.3 mM extracellular Ca2+ caused an approximate twofold enhancement of superoxide release stimulated by either concanavalin A or formyl-methionyl-leucyl-phenylalanine but had no effect on digitonin-stimulated superoxide release. Concanavalin A-stimulated superoxide was inhibited by the "Ca2+ entry blockers," Mn2+ (1 microM) or methoxyverapamil (D-600) (100 microM). Inhibition by Mn2+ was competitive with extracellular Ca2+, whereas inhibition by D-600 was noncompetitive. Neither inhibitor, however, affected superoxide release after initiation. Thus activation of superoxide release by alveolar macrophages can be accomplished, in part, through the entrance of Ca2+ into the cell.

Animals↗

Fast neutron radiation therapy for glioblastoma multiforme. Results of an RTOG study.

Between January 1977 and September 1980, 166 patients were entered on a RTOG protocol comparing neutron-boost radiotherapy with standard treatment for patients with glioblastomas. Eighty-three patients were randomized to receive a neutron boost and 83 to receive a photon boost after 50 Gy photon, whole-brain irradiation. Of these, six were ineligible and two were cancelled, leaving 158 patients available for analysis. The median survival for the neutron-boost group was 9.8 months, compared to 8.6 months for the photon-boost group. The difference is not statistically significant. Autopsies revealed actively growing persistent tumor in all photon-treated patients compared to no evidence of actively growing tumor in the majority of neutron-treated patients.

Brain Neoplasms↗

Intraoperative irradiation: a pilot study combining external beam photons with "boost" dose intraoperative electrons.

Intraoperative "boost" dose electron beam therapy given in combination with 4500--5000 rad (45--50 Gray) external beam irradiation has been demonstrated as a practical therapeutic modality at the MGH. This procedure has been employed thus far in 58 patients; the results in the initial 36 are analyzed in detail in this paper. Thirty-four of the 36 patients had locally advanced lesions--unresectable, recurrent, or residual disease. Results achieved to date are in full agreement with our expectations: high radiation doses have been delivered to the primary intra-abdominal and pelvic tumors, excluding the sensitive structures from irradiation. This has been accomplished by a truly multidisciplinary effort comprising surgery, anesthesiology, OR nursing, administration, engineers, physicists, therapy technologists, and radiation therapists. Although follow-up is not yet sufficient to judge ultimate efficacy, acute and chronic severe morbidity is low and local control is good. There is justified enthusiasm for continuing the procedure.

Female↗

The bacterial biogenesis of isobutyraldoxime O-methyl ether, a novel volatile secondary metabolite.

Production of the volatile metabolite, isobutyraldoxime O-methyl ether (IBME) by a Moraxella-like organism NCIB 11650 was investigated under a variety of environmental conditions using gas chromatography. Under aerobic conditions up to 10 micrograms IBME ml-1 was produced on mineral salts media containing 0.5% (w/v) glucose or succinate as sole C source with 0.1% (w/v) NH4Cl as sole N source. Exogenous L-valine further stimulated IBME formation up to 25 micrograms ml-1 but supplementation of the medium with D-isomer or other amino acids had little effect on IBME production and did not lead to the appearance of analogues of IBME. Trapping experiments using [14C]valine confirmed that IBME was derived from this amino acid. Several other bacterial species examined, e.g. Alcaligenes sp. NCIB 11652, another Moraxella-like organism NCIB 11651 and Pseudomonas sp. NCIB 11653 also produced IBME under similar conditions. The Alcaligenes strain synthesized up to 20 micrograms ml-1 in the absence of valine and up to 90 micrograms ml-1 in its presence. The product of IBME exhibited many features characteristic of the formation of a secondary metabolite. Thus biosynthesis was confined to a narrower range of temperature than cell division, was almost completely suppressed by 300 mM-phosphate and was inhibited by high concentrations of readily utilizable C sources. Although IBME synthesis in the Moraxella-like organism NCIB 11650 appeared to be growth-related, its formation by both the Alcaligenes sp. and the Moraxella-like organism NCIB 11651 was delayed until the late-exponential and early-stationary phases of growth. The biological significance of this novel class of secondary metabolite is discussed and a possible biosynthetic route proposed.

Alcaligenes↗

An infant with chronic, relapsing polyneuropathy responsive to steroids.

A seven-week-old infant presented with an acute flaccid paraparesis. Her subsequent course was punctuated by numerous exacerbations, in association with minor intercurrent illness and remissions produced by corticosteroid treatment. Postmortem examination revealed a chronic inflammatory polyradiculopathy. She represents the youngest patient yet described with a chronic, relapsing, steroid-responsive polyneuropathy.

Child, Preschool↗

The evaluation of a Cardiovascular School Health Curriculum: an assessment of long-term cognitive retention and attitudinal correlates.

This study provided evidence that the Cardiovascular School Health Curriculum was successful in increasing the knowledge levels of high school students and maintaining significant portions of that knowledge during a six month period, indicating that with a strong, well developed curriculum, relatively permanent change in knowledge levels can be achieved. This was particularly gratifying to the researchers who believe that the appropriate knowledge of the cardiovascular system, heart diseases and methods of preventing heart and circulatory problems are essential foundations for having positive impact of youths' future behavioral choices. Additional longitudinal studies are planned to augment the findings of this study.

Adolescent↗

Hyperoxia inhibits stimulated superoxide release by rat alveolar macrophages.

Factors responsible for the loss of respiratory burst capacity (stimulated extracellular O2-. release) of alveolar macrophages (AM) exposed to prolonged hyperoxia were assessed. Specific pathogen-free rats were exposed to 1 ATA O2 for 24-72 h, and lungs of survivors lavaged. Release of O2-. by cells after addition of concanavalin A, which stimulated AM but not polymorphonuclear leukocytes (PMN), or digitonin, which stimulated both cell types, was measured using cytochrome c reduction +/- superoxide dismutase. O2-. release by AM declined 47.2% (P less than 0.05) after 24 h of hyperoxia and 100% after 60 h. Percent PMN in the lavage was less than 3% at 0-36 h but increased to 16% at 48 h and to 44% at 72 h. Although addition of PMN to AM in vitro caused inhibition of AM O2-. release, the percent PMN required for inhibition was not reached in vivo until after a significant decline in AM O2-.-releasing capacity had already occurred. Cell-free lavage fluid from either control or hyperoxic rats did not affect AM O2-. release. AM in culture for 24 h in hyperoxia lost 76.7% (P less than 0.005) of O2-.-releasing capacity vs. cells incubated in 20% O2, although dye exclusion was unaffected. The results indicate that the major cause of loss of AM O2-. release by hyperoxia is a direct effect of O2 on the cells.

Animals↗

Further studies with pergolide in Parkinson disease.

Pergolide was administered to 56 patients with advanced Parkinson disease who were no longer satisfactorily responding to levodopa. The group included 45 patients with on-off phenomena. Pergolide, when combined with levodopa, resulted in a 44% decrease in disability as assessed in the on period, a 15% decrease in disability as assessed in the off period, and a 148% increase in the number of hours in which patients were on (from 4.6 +/- 0.3 hours to 11.4 +/- 0.6 hours). All these changes were significant at 1%. Forty-one of the 56 patients (59%) improved when pergolide was added to levodopa. Mean dose of pergolide was 2.5 mg (range, 0.2 to 10.0 mg). Mean duration of the study was 13 months (range, 1 day to 34 months). Maximum improvement occurred within 2 months and began to decline, usually after 6 months. The major adverse effects necessitating discontinuing pergolide were the occurrence of an organic confusional syndrome (six patients), increased dyskinesias (four patients), and cardiovascular abnormalities (three patients). Nine patients discontinued pergolide because of a lack of effect or declining effect.

Adult↗