Search PubMed⌕ Search

Biomedical subjects

D G Baker

Publications and source records attributed to D G Baker.

At least 109 records · Page 6Linked to original sources
PubMed1987

The response of a solid tumor to X-irradiation as modified by dose rate, fractionation, and hyperthermia.

The KHT sarcoma in C3H mice was exposed to a total dose of 3000 cGy x-irradiation delivered in three equal fractions at intervals of either 48, 72, or 96 hr. The dose rate was high, 212 cGy/min or low, 19 cGy/min. The effect of hyperthermia, 42.5 degrees C for 30 minutes, was determined by inducing the hyperthermia using either water or ultrasound. For radiation alone at high dose rate, tumor control was maximum at a fraction interval of 96 hr. At low dose rate, local tumor control was not influenced by fractionation interval and was not different from the maximum tumor control achieved at high dose rate. Hyperthermia alone was ineffective for tumor control. When high dose rate irradiation and hyperthermia were combined, thermal enhancement was highest at fractionation intervals of less than 96 hr where the effects or irradiation alone were least. At low dose rate, the thermal enhancement was independent of fractionation interval. Only for irradiation at high dose rate was the ultrasound-induced hyperthermia more effective at potentiating the radiation than water bath-induced hyperthermia. A possible explanation for the interaction of the dose rate effect with fractionation and hyperthermia is proposed.

Animals↗
PubMed1986

The architecture of nerves and ganglia of the ferret trachea as revealed by acetylcholinesterase histochemistry.

The goal of this study was to determine the architecture of the nerves and ganglia of the ferret trachea. Tracheas from four newborn ferrets and three adult ferrets were stained histochemically for acetylcholinesterase activity and analyzed in their entirety as whole mounts. The architecture consisted of one or two longitudinal nerve trunks overlying the posterior surface of the trachealis muscle, a dense plexus of nerves superficial to the trachealis muscle that interconnected these longitudinal nerve trunks, and, on the anterior surface, a plexus superficial to the submucosal glands and located between the cartilaginous rings. In addition, deep neural plexuses were associated with the trachealis muscle and with the submucosal glands. Ganglion cell bodies along the longitudinal nerve trunks were large (mean diameter +/- S.E. = 34.3 +/- 0.3 microns), were usually attached to the nerve trunk by a stalk, and were loosely clustered in groups of as many 38 cell bodies. By contrast, those cell bodies of the superficial muscle and gland plexuses were significantly smaller (mean diameter +/- S.E. = 24.2 +/- 0.3 microns), were never attached by a stalk, and were tightly clustered in ganglia of one to four cell bodies. We conclude that nerves and ganglia of the ferret trachea constitute one or two longitudinal nerve trunks containing ganglia with large cell bodies, two superficial nerve plexuses containing ganglia with small cell bodies overlying the smooth muscle and submucosal glands, respectively, and two deep nerve plexuses providing the terminal innervation to the muscle and glands.

Acetylcholinesterase↗
PubMed1986

Products of polymorphonuclear cell injury inhibit IgG enhancement of monosodium urate-induced superoxide production.

The generation of polymorphonuclear cell (PMN) superoxide ion (O2-) by monosodium urate (MSU) crystals may be important in the pathogenesis of acute gout. Coating MSU crystals with IgG prior to exposure to PMN markedly augmented O2- generation. This augmentation was inhibited by supernates, termed cell lysate, derived from sonicated PMN or PMN exposed to MSU crystals for 5 hours at 37 degrees C. Lysate was effective in inhibiting O2- production when incubated with MSU crystals prior to, during, or after MSU crystals were exposed to IgG. No IgG could be eluted from crystals exposed to both lysate and IgG. Immunoelectron microscopy showed virtually no IgG on crystal surfaces after incubation of crystals with lysate and IgG. These data suggest that products of PMN injury can modulate further PMN responses to MSU crystals. This phenomenon provides a negative feedback loop and is one possible mechanism for the self-limitation of acute gouty attacks.

Animals↗
PubMed1986

Current concepts in the treatment of rheumatoid arthritis.

The treatment of RA is complex and often frustrating. The pathologic process of RA is composed of acute inflammation, chronic immunologic phenomenon, and chronic connective tissue degradation. It is important to understand not only the pathophysiology of RA but also the mechanism of action of our therapeutic drugs so that treatment can be tailored to affect the important aspects of the process leading to end-organ damage. Despite the many drugs available, therapy is still unsatisfactory. Many drugs work in only certain patients. This could be secondary to variability in the disease state or to difference in drug metabolism. A better understanding of both disease and therapeutic agents may lead to better use of our present agents and development of new, more effective treatment modalities.

Adrenal Cortex Hormones↗
PubMed1986

Radiation nephritis. Clinical manifestations and pathophysiologic mechanisms.

Radiation nephritis is both volume and dose related. Clinical experience would indicate that a minimum of one third of the renal volume needs to be excluded from nephrotoxic doses which appears to have a threshold of 2,000 cGy. The site of damage leading to renal failure appears to be the microvasculature ultimately expressed as glomerulosclerosis. How much direct damage to the tubular system contributes to this process is unclear, but undoubtedly the resultant systemic physiologic effects potentiate the expression of damage in the irradiated kidney. The acute syndrome, with all the potential manifestations of renal failure, rarely presents sooner than six months and appears to have no clear prodrome, although it would seem reasonable that a subclinical syndrome consisting of abnormalities detectable by urinalysis may occur. Treatment of radiation-induced nephritis or hypertension is no different from treatment for nephritis from any other cause and should be aggressive with lifelong follow-up. Carcinogenesis is a rare late expression of radiation-induced kidney damage.

Animals↗
PubMed1986

Separation and quantification of prostaglandins E1 and E2 as their panacyl derivatives using reverse phase high pressure liquid chromatography.

Separation and quantification of prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) were achieved using reverse phase high performance liquid chromatography (HPLC). Panacyl bromide (p-(9-anthroyloxy)phenacyl bromide) (PAB) derivatives of PGE2 and PGE1 were prepared. Reverse phase HPLC using a linear gradient of 56% to 80% acetonitrile in water containing 0.10% acetic acid gave baseline resolution of the two derivatives. A 3 um diameter particle, C18 column provided good resolution and reproducible recoveries. Human synovial tissue cells were incubated with the precursor fatty acids for PGE1 or PGE2 and stimulated with a crude Interleukin 1 (IL-1) preparation. Cells grown in the presence of dihomogammalinolenic acid (DGLA), the precursor for PGE1, made significantly more PGE1 than cells grown in control medium or in the presence of arachidonic acid, precursor for PGE2. PGE2 synthesis was reduced when DGLA was added to cells (resting or IL-1-stimulated).

Acetophenones↗
PubMed1986

Interaction of bradykinin and prostaglandin E1 on cardiac pressor reflex and sympathetic afferents.

Bradykinin applied to the epicardium stimulates cardiac sympathetic afferents and evokes a reflex increase in arterial blood pressure. In anesthetized cats we examined the potentiation of these effects by prostaglandin E1 (PGE1) applied to the ventricular epicardium. We recorded cardiac afferent impulses from the second to the fifth left thoracic sympathetic rami. PGE1 (0.1 microgram/ml) alone had little effect on blood pressure, but it significantly increased the pressor response to bradykinin, and it reduced or abolished tachyphylaxis to repeated applications of bradykinin. Both mechanosensitive and chemosensitive sympathetic cardiac afferents were stimulated by bradykinin. Indomethacin (intravenous) caused a small reduction in the afferent response to bradykinin. Epicardial application of PGE1 significantly increased the response (magnitude and duration) of chemosensitive endings to bradykinin but not that of mechanosensitive endings; however, PGE1 abolished the tachyphylaxis of both chemosensitive and mechanosensitive endings to repeated applications of bradykinin. Because both bradykinin and prostaglandins are released in the ischemic myocardium, their interactive effect on cardiac sympathetic afferents could play a part in the sensory and reflex responses to myocardial ischemia.

Action Potentials↗
PubMed1986

Mediator and target cell variability in proliferative response of human adherent synovial cells in culture.

The proliferation of cultures of adherent synovial cells was studied in response to mediators generated from several sources. Monocyte enriched cultures produced factors in the 70-80,000 and 12-16,000 molecular weight range. Both of these areas of activity also stimulate prostaglandin (PGE) from adherent synovial cells and have interleukin 1 (IL-1) activity. The 70-80,000 region appears to be the 12-16,000 molecular weight activity bound to serum components. When stimulated with the same concentration of a single preparation of this monocyte derived factor, cell lines showed great variability, with inhibition of proliferation in 2 cell lines and the remaining exhibiting stimulation. There was no correlation of proliferation with the PGE producing capacity of the cells. The proliferation response showed no correlation to PGE production by particular cell lines. Lymphocyte enriched cultures produced a factor of 36-40,000 daltons that stimulates adherent synovial cell proliferation but does not have PGE stimulating or IL-1 activity.

Arthritis, Rheumatoid↗
PubMed1986

Parasympathetic motor pathways to the trachea: recent morphologic and electrophysiologic studies.

The distinctive features of the parasympathetic motor pathway to the trachea include: preganglionic fibers, many with an inspiratory rhythm, that converge onto ganglion cells and excite them through nicotinic receptors; an elaborate plexus of nerves and ganglia that covers the posterior surface of the trachea and extends anteriorly between each cartilaginous ring; ganglion cell bodies with heterogeneous morphologic and electrical properties--some large, others small, some with an inspiratory rhythm, and others with an expiratory rhythm; the trachealis muscle, which contracts with an inspiratory rhythm and closely parallels activity in the phrenic nerve.

Animals↗
PubMed1985

Cyclic adenosine 3'5' monophosphate stimulates prostaglandin E production by human adherent synovial cells.

Production of prostaglandin E (PGE) by rheumatoid synovium appears important to regulation of the pathologic process in rheumatoid arthritis. Cells derived from human synovium by proteolytic digestion produce large amounts of PGE which in turn can elevate synovial cell cAMP levels and inhibit cell proliferation. Data presented here indicate that cAMP can further increase production of PGE from adherent synovial cells (ASC). PGE production occurs over 12-72 hr and is not due to the ability of cAMP to inhibit cell proliferation. Exposure of cells to cAMP results in increased release of 3H arachidonic acid from precursors but not in activation of the cyclooxygenase enzyme. This phenomenon suggests the presence in adherent synovial cells of a mechanism for amplifying PGE production.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Inspiratory rhythm in airway smooth muscle tone.

In anesthetized paralyzed open-chested cats ventilated with low tidal volumes at high frequency, we recorded phrenic nerve activity, transpulmonary pressure (TPP), and either the tension in an upper tracheal segment or the impulse activity in a pulmonary branch of the vagus nerve. The TPP and upper tracheal segment tension fluctuated with respiration, with peak pressure and tension paralleling phrenic nerve activity. Increased end-tidal CO2 or stimulation of the carotid chemoreceptors with sodium cyanide increased both TPP and tracheal segment tension during the increased activity of the phrenic nerve. Lowering end-tidal CO2 or hyperinflating the lungs to achieve neural apnea (lack of phrenic activity) caused a decrease in TPP and tracheal segment tension and abolished the inspiratory fluctuations. During neural apnea produced by lowering end-tidal CO2, lung inflation caused no further decrease in tracheal segment tension and TPP. Likewise, stimulation of the cervical sympathetics, which caused a reduction in TPP and tracheal segment tension during normal breathing, caused no further reduction in these parameters when the stimulation occurred during neural apnea. During neural apnea the tracheal segment tension and TPP were the same as those following the transection of the vagi or the administration of atropine (0.5 mg/kg). Numerous fibers in the pulmonary branch of the vagus nerve fired in synchrony with the phrenic nerve. Only these fibers had activity which paralleled changes in TPP and tracheal tension. We propose that the major excitatory input to airway smooth muscle arises from cholinergic nerves that fire during inspiration, which have preganglionic cell bodies in the ventral respiratory group in the region of the nucleus ambiguus and are driven by the same pattern generators that drive the phrenic and inspiratory intercostal motoneurons.

Airway Resistance↗
PubMed1985

Nuclear magnetic resonance evaluation of synovial fluid and articular tissues.

In vitro studies were performed on joint tissues and fluid to evaluate the potential for nuclear magnetic resonance (NMR) in the study of joint disease. Values for spin lattice relaxation times, spin-spin relaxation times and mobile proton content were obtained on 51 consecutive whole synovial fluids (SF). Correlations were sought between NMR values and white blood counts, protein content, calcium, phosphorus, and diagnosis. Only a very weak correlation (0.444) was noted with total SF protein. Albumin added in vitro did produce good correlation (0.975). NMR values were not altered by the addition of monosodium urate, of calcium pyrophosphate, or hydroxyapatite crystals. In vitro measurements of dissected canine articular tissue showed differences in NMR between the different joint components and between inflamed and noninflamed tissues. Our findings suggest that estimation of the amount of inflammation by NMR values is not possible at this time, but with refinements of techniques, magnetic resonance imaging may provide superb images of articular soft tissue structures.

Animals↗
PubMed1984

Effect of hyperthermia on murine myeloid precursors.

Murine bone marrow was exposed to hyperthermia temperatures of 41.5 to 45.5 degrees C. The proliferation capacity of myeloid progenitor and committed precursors was assayed in vivo utilizing spleen colony formation and diffusion chamber (DC) techniques. The survival of both pluripotential (CFU-S) and committed myeloid (CFU-DG) stem cells decreased exponentially with an increase in the heating period. Progression from CFU-S to CFU-DG significantly altered thermal sensitivity in the temperature range examined. Proliferation of mature granulocyte-monocytes (G-M) in DC is more thermostable than their stem cell precursors. Heat inactivation energies (enthalpies) of CFU-S and CFU-DG were derived from the slope of the heating time survival curves. Enthalpy of CFU-S is 300 kcal/mole below 43 degrees and 105 kcal/mole above 43 degrees. The enthalpy of CFU-DG is 250 and 145 kcal/mole below and above 43 degrees, respectively.

Animals↗
PubMed1984

Chloroquine inhibits the production of a mononuclear cell factor by inhibition of lectin binding.

The effect of chloroquine (CQ) on the ability of normal human peripheral blood monocytes to produce a soluble mononuclear cell factor (MCF) capable of stimulating prostaglandins from adherent rheumatoid synovial cells was studied. CQ inhibited concanavalin A (Con A)- and bacterial peptidoglycan-induced MCF activity, but not colchicine-induced activity, in a dose-dependent manner. After incubation with CQ for 20 minutes, 3H Con A binding was reduced by 50%, and metabolism of pre-bound 3H Con A was inhibited. These data suggest that CQ can inhibit MCF production by inhibition of lectin binding, perhaps by inhibition of receptor recycling.

Cell Survival↗
PubMed1984

Lithium stimulation of murine hematopoiesis in liquid culture: an effect mediated by marrow stromal cells.

Lithium has previously been observed to stimulate in vitro Dexter culture hemopoiesis with increases in granulocytes, megakaryocytes, and pluripotent stem cells (CFU-S). In the present study, a two-phase murine Dexter culture system was established to study the mechanism of lithium-mediated stem cell stimulation. Different lots of horse sera or fetal calf sera were found to have markedly different effects on Dexter culture growth; given the appropriate sera supplementation, supernatant cells from Dexter cultures established from C57BL/6J mice 3 wk previously were free of stromal-forming capacity, but had stem cells and could grow on 900-950 R irradiated stroma. Conversely, in vitro irradiation (900-950 R) of 3-wk cultures resulted in a stem-cell-free adherent monolayer that could support growth for up to 9 wk in culture. The stroma from Dexter cultures preexposed to lithium chloride (1.0 mmole/liter) for 3 wk, irradiated (900 R), and then refed with 3-wk Dexter supernatant cells has an enhanced capacity to support cell production, CFU-S, and probably granulocyte-macrophage colony-forming cell (GM-CFU-C) production, as compared to stroma not preexposed to lithium. Lithium carryover was ruled out in these experiments. These data indicate that lithium stimulates CFU-S and in vitro granulopoiesis by an indirect effect on a radioresistant adherent stromal cell.

Animals↗
PubMed1984

Hematopoietic regulatory factors produced in long-term murine bone marrow cultures and the effect of in vitro irradiation.

The nature of hematopoietic regulatory factors elaborated by the adherent (stromal) cells of long-term murine bone marrow cultures and the effect of in vitro stromal irradiation (XRT) on the production of these factors was investigated. Using an in situ stromal assay employing a double layer of semisolid agar, it was possible to demonstrate stromal elaboration of at least two colony-stimulating activities, ie, granulocyte/macrophage colony-stimulating activity (G/M-CSA) and megakaryocyte colony-stimulating activity (Meg-CSA). Exposure of the stroma to XRT resulted in dose-dependent elevations of both activities that correlated inversely with total myeloid cell mass as determined by concurrent reductions in total supernatant cell recoveries from irradiated cultures. Mixture experiments that combined control and irradiated stroma revealed that the hematopoietically active control stroma could block detection of XRT-related G/M-CSA elevations. These data implicate a local negative feedback mechanism in the regulation of hematopoiesis. Antiserum directed against purified L cell colony-stimulating factor (CSF) reduced granulocyte/macrophage colony formation in the target layer but did not effect the increased Meg-CSA. While a radioimmunoassay for L-cell type CSF was unable to detect significant differences in concentrated media from control and irradiated cultures, bioassays of these media revealed XRT-related G/M-CSA elevations. These results indicate that the G/M-CSA elaborated in these cultures is immunologically distinct from the Meg-CSA produced, and although distinct from L cell CSF, the G/M-CSA is crossreactive with the L cell CSF antiserum. Morphologic, histochemical, and factor VII antigen immunofluorescent studies were performed on the stromal cell population responsible for production of these stimulatory activities. In addition to "fat" cells, the stromal cells remaining after XRT were composed of two predominant cell populations. These included a major population of acid phosphatase and nonspecific esterase-positive macrophage-like cells and a minor population of factor VII antigen negative epithelioid cells.

Animals↗