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Biomedical subjects

D G Baker

Publications and source records attributed to D G Baker.

At least 91 records · Page 5Linked to original sources
PubMed1990

[Prolonged inflammatory reactions induced by ceramic powders in the rat air pouch model].

The subcutaneous air pouch of the male Sprague-Dawley rat was used to study inflammatory potential of artificial ceramics. Local leukocyte influx, proteinase, prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) levels were measured after injection of hydroxyapatite ceramic (HAP), tricalcium phosphate ceramic (TCP) and apatite-wollastonite glass ceramic (GC) into the pouch. Synthetic monosodium urate crystals (MSU) were used as positive controls and normal saline (NS) as a negative control. The response was monitored over a period of 168 hours by irrigating the pouch with 5 ml of NS and withdrawing 4 ml. MSU produced the greatest response in leukocyte counts, proteinase and PGE2, whereas HAP, TCP and GC often appeared later than with MSU. TNF was significantly detected only after ceramics and not after MSU. The chronic and relatively prolonged reaction to HAP, TCP and GC suggests that an inflammatory reaction may occur after implantation of these ceramics in humans. The increased levels of TNF and production of PGE2, which are substances proposed to contribute to osteolysis associated with loosening, are of special interest for further research.

Animals↗
PubMed1989

A phospholipase A2-activating protein (PLAP) stimulates human neutrophil aggregation and release of lysosomal enzymes, superoxide, and eicosanoids.

We have recently isolated a human phospholipase A2-activating protein (PLAP) that shares antigenic and biochemical similarities with melittin, a well characterized bee venom phospholipase-stimulatory peptide. To explore the potential mechanisms of action of PLAP that extend beyond its effects on eicosanoid synthesis, we examined its effects on the release of human neutrophil lysosomal enzymes and superoxide, and on RBC hemolysis. These results were compared to the effects of melittin, which has been reported to induce enzyme release and hemolysis. We also examined the effects of PLAP on neutrophil aggregation and chemotaxis. PLAP induced neutrophils to release beta-glucuronidase and metalloproteinase enzyme activities as well as produce superoxide ion in both a dose- and time-dependent manner. Eicosanoid synthesis inhibitors did not abrogate these responses. PLAP induced release of arachidonic acid metabolites, but this response could be abrogated by eicosanoid synthesis inhibitors. PLAP also induced neutrophil aggregation and chemokinesis, but not chemotaxis. Concentrations of PLAP that induced these responses did not induce cellular toxicity as determined by light and electron microscopy, lactic dehydrogenase release, trypan blue dye exclusion, and RBC hemolysis. In contrast, prolonged incubation with higher concentrations of PLAP induced cell death that was similar to that observed with melittin. These findings suggest that the mechanisms of action of PLAP extend beyond the eicosanoid synthetic pathway, and that disordered regulation of PLAP may be responsible, at least in part, for chronic immune and inflammatory states.

Animals↗
PubMed1989

Suppression of human synovial cell proliferation by dihomo-gamma-linolenic acid.

Prostaglandin E1 (PGE1) and oils enriched in its precursor fatty acids suppress inflammation and joint tissue injury in several animal models. Since synovial cell proliferation is a hallmark of rheumatoid arthritis, we studied the effect of dihomo-gamma-linolenic acid (DGLA), an immediate precursor of PGE1, on the growth of human adherent synovial cells (ASC) in tissue culture. When stimulated by appropriate concentrations of recombinant interleukin-1 beta (rIL-1 beta), ASC proliferate and produce PGE. DGLA-enriched medium suppressed both baseline and rIL-1 beta-stimulated ASC growth fivefold, compared with medium supplemented with arachidonic acid. Indomethacin reduced the effect of the DGLA. Synovial cells incorporated the DGLA, and rIL-1 beta-stimulated cells that were incubated with DGLA exhibited a 14-fold increase in PGE1 (to 25.2 +/- 6.0 ng/ml, mean +/- SD) and a 70% decrease in PGE2 (to 25.2 +/- 4.2 ng/ml) compared with cells in control medium. At equivalent concentrations (5 x 10(-7) M), PGE1 increased the level of cellular cAMP to a greater extent than did PGE2 (16.8 +/- 2.0 pmoles versus 4.3 +/- 1.9 pmoles, mean +/- SEM). Exogenous PGE1 was also a more effective inhibitor of cell growth. Similarly, cAMP concentrations in cells exposed to DGLA for 6 hours were greater than concentrations in arachidonic acid-enriched cultures (17.8 +/- 3.3 pmoles versus 2.1 +/- 2.0 pmoles). These observations suggest that DGLA can restrain ASC growth, an effect which may be due to its capacity to increase PGE1 production and subsequent cellular cAMP concentration.

8,11,14-Eicosatrienoic Acid↗
PubMed1989

The response of the microvascular system to radiation: a review.

The microvasculature is a ubiquitous organ system having a major role in the pathogenesis of radiation damage to normal tissues. Although the kinetics of radiation damage to endothelial cells is similar to other tissues (as reflected by Do and Dq) the late effect is a manifestation of injury, not only to the endothelial cell population, but also to the basement membrane. Tissue damage is progressive. The initial expression of radiation injury is an increased permeability leading to changes in the extracellular milieu. There is an irregular proliferation of endothelial cells leading to capillaries of irregular diameter and shape. Fibrous proliferation increases the histohematic barrier and is ultimately reflected in a loss of parenchymal cells. Replacement fibrosis progresses until a steady state is reached where the surviving parenchymal cells can be sustained by the microvasculature. The clinical significance depends on the role of the organ system involved. For patients who have medical conditions which adversely effect the stability of the vascular system (hypertension, diabetes, etc.), the expressions of radiation injury may be more severe and increase the morbidity associated with these diseases. Angiogenesis in granulation tissue is less radiosensitive than in steady-state parenchymal tissues. Wound healing is not significantly affected by commonly used therapeutic doses of irradiation, 40-50 Gy delivered 4-6 weeks preoperatively or postoperatively early in the development of the granulation tissue, but may be complicated where a significant degree of fibrosis has developed. The vascular responses leading to telangiectasia were discussed.

Animals↗
PubMed1989

How significant are the risks from occupational exposure to ionizing radiation?

Radiologists and other physicians practicing in specialties where their principal operational procedures involve the use of ionizing radiation have health risks associated with their occupational exposures. Based on two years of film badge records from this institution, it was estimated that the general radiologists received an annual occupational dose equivalent of 350 mrems. The corresponding doses for therapeutic radiologists and those practicing special procedures and cardiac catheterization were 110 mrems and 550 mrems. The estimated excess cancer deaths for general radiologists would be between 0.97 and 1.63 per 1,000 people at risk. The corresponding excess death risk for therapeutic radiologists would be 0.30 to 0.51; for those practicing special procedures and cardiac catheterization, it would be 1.52 to 2.56. The excess risk of cancer deaths to the radiologists could range from 0.3% for the radiotherapist to 1.5% for those practicing special procedures and cardiac catheterizations.

Abnormalities, Radiation-Induced↗
PubMed1989

Immunoglobulin G coating on crystals and ceramics enhances polymorphonuclear cell superoxide production: correlation with immunoglobulin G adsorbed.

Crystals and a group of ceramics used in joint replacement surgery were incubated with polymorphonuclear cells (PMN) with and without adsorbed immunoglobulin G (IgG). All 11 particles tested had the capacity to induce the production of superoxide anion (O2-) to at least some extent. Synthetic calcium pyrophosphate dihydrate crystals (CPPD) and several ceramics adsorbed small amounts of IgG and the increment of superoxide production was also small. Both the augmentation of O2- and the adsorption of IgG to hydroxyapatite type I synthetic crystals and the remaining ceramics were intermediate. Synthetic monosodium urate crystals adsorbed the most IgG and the O2- increments were large. The increase in superoxide production correlated with the amount of IgG bound onto crystals or ceramics. The greater protein binding and phlogistic potential of some ceramics needs to be taken into consideration in their clinical use.

Adsorption↗
PubMed1989

Suppression of acute and chronic inflammation by dietary gamma linolenic acid.

We examined the effect of diets enriched in gamma linolenic acid (GLA) on acute inflammation induced by monosodium urate crystals, and on subacute and chronic inflammation induced by complete Freund's adjuvant in the rat subcutaneous air pouch and in rats with adjuvant induced arthritis. Diets were enriched (15% fat) with borage seed oil (23% GLA) or safflower oil (less than 1% GLA). Diets enriched with GLA suppressed inflammation markedly in all models, whereas the safflower oil diet did not influence the inflammatory response. The degree of inflammation was quantified by measuring pouch exudate cell concentration, lysosomal enzyme activity, volume, protein concentration and prostaglandin E2 and leukotriene B4 concentrations. In the chronic air pouch model, the pouch lining was thickened, invaded by mononuclear cells and exhibited proliferation of lining cells 14 days after adjuvant injection. The lesion was far less severe and usual pouch lining architecture was maintained in animals given dietary GLA. Livers of rats fed borage seed oil were enriched in GLA and dihomo gamma linolenic acid (DGLA), and the DGLA/arachidonate ratio was increased 5-fold compared with animals fed safflower oil. Enrichment of diet with plant seed oils rich in GLA may provide a way to alter generation of prostaglandins and leukotrienes and to influence acute and chronic inflammatory responses.

Acute-Phase Reaction↗
PubMed1989

The influence of the surgical wound on local tumor recurrence.

Failure of a primary surgical treatment for cancer is often caused by recurrence of the tumor at the surgical site. The KHT mouse tumor system recapitulates this experience and provides a useful model to test strategies for reducing the incidence of local recurrence after surgical excision. There was an 82% local recurrence of the KHT tumor after surgery. A cell dilution assay indicated that it would require only 39 tumor cells injected into the wound site to result in the same (82%) incidence of tumors. This figure is in contrast to 340 cells required when the cells were injected into an unwounded flank. With the B16 melanoma in C57B1 mice and the Meth A sarcoma in BALB/c mice, the number of cells necessary to induce a tumor (TD/50) was also significantly reduced when the cells were injected into a surgical wound rather than into nonwounded tissue. The difference in cell number was interpreted as the result of the presence of growth factors derived from the traumatized tissue and the inflammatory cells at the wound site. Neither a 5 nor a 15 Gy dose of x-radiation delivered to the wound site immediately after surgical excision of the KHT tumor resulted in a significant reduction in the incidence of local recurrences. When the same doses of x-radiation were given immediately after injecting 36 KHT cells into a wound, no tumors developed. This difference was believed to have resulted from the hypoxic condition in the wound site and the presence of residual clonogenic tumor cells in a nonproliferating (radioresistant) state.

Animals↗
PubMed1988

Suppression of monosodium urate crystal-induced acute inflammation by diets enriched with gamma-linolenic acid and eicosapentaenoic acid.

A subcutaneous air pouch formed in Sprague-Dawley rats was used to study the effect of diets enriched in gamma-linolenic acid (GLA) (in plant seed oil) and eicosapentaenoic acid (EPA) (in fish oil) on acute inflammation induced by monosodium urate crystals. The GLA-enriched diet suppressed significantly the cellular phase of inflammation (polymorphonuclear leukocyte accumulation, crystal phagocytosis, and lysosomal enzyme activity), but it had little effect on the fluid phase (exudate volume and protein concentration). In contrast, the EPA-enriched diet suppressed the fluid phase but not the cellular phase of inflammation. The findings indicate that the fluid and cellular phases of acute inflammation can be controlled independently. A combined diet of fish oil and plant seed oil (EPA-enriched and GLA-enriched) reduced both the cellular and fluid phases of inflammation. Thus, dietary provision of alternative substrates for oxidative metabolism (other than arachidonic acid) modifies monosodium urate crystal-induced acute inflammation.

Animals↗
PubMed1988

Reversal of the relation between respiratory drive and airway tone in cats.

To examine the relationship between respiratory drive and airway tone in the exercise pressor reflex in the cat, we recorded tension in a tracheal segment and activity in the phrenic nerve, before and after injecting capsaicin in various doses (0.3-20 micrograms/kg) into the femoral artery. Injection of all doses of capsaicin relaxed the tracheal segment. However, high doses of capsaicin evoked neural apnea followed by increased phrenic nerve activity whereas low doses evoked only increased phrenic nerve activity. All responses were abolished by cutting hindleg nerves. We were certain that relaxation was due to decreases of parasympathetic bronchoconstrictor activity and not to increases in activity of other inhibitory pathways, because we found no change in capsaicin-evoked relaxation after beta-adrenergic blockade with propranolol and no capsaicin-evoked relaxation after muscarinic blockade with atropine and restoration of tone with 5-hydroxytryptamine. These results provide good evidence that injecting capsaicin into the femoral artery reverses the direct relation between respiratory drive and airway tone and does so by decreasing parasympathetic bronchoconstrictor activity.

Animals↗
PubMed1988

Radiology, is there an occupational hazard?

The practicing radiologist in the United States receives an annual average x-ray dose of 3.2 mSv. This dose of radiation results in between 17 and 28 cancer deaths among the 19,000 radiologists at risk, or an excess cancer risk of between 0.53% and 0.87%. The sub-population of cardiologists and radiologists who perform special procedures is expected to be at a higher risk of death from cancer than the general or therapeutic radiologist. The genetic risk to the children of the radiologist corresponds to a 0.09 to 1.26 excess of cases of genetically-determined disease among the 4047 children in the first generation, or between a 0.02% to 0.31% increase above the expected incidence. The progeny of radiologists who have received larger doses in the course of performing cardiac catheterizations or other special procedures are expected to be at a higher risk of expressing a genetically-determined disease than the progeny of the general radiologist. The small size of the population at risk combined with the small magnitude of the risk makes it unlikely that epidemiological studies will be able to demonstrate a statistically significant increased risk of death from cancer or of genetic sequelae in the near future.

Cardiac Catheterization↗
PubMed1988

Absence of nonadrenergic noncholinergic relaxation in the cat cervical trachea.

Published in vivo experiments have not supported in vitro reports of the presence of nonadrenergic noncholinergic (NANC) inhibitory pathways in the cat trachea. We therefore examined these pathways, measuring tension in an innervated tracheal segment, flow resistance in more distal airways, and dynamic compliance, in 10 anesthetized mechanically ventilated cats. Initially, cervical vagal stimulation evoked contraction followed by relaxation of smooth muscle of trachea and lower airways; sympathetic stimulation evoked relaxation only. After muscarinic blockade and restoration of smooth muscle tone with 5-hydroxytryptamine (5-HT) applied topically to the tracheal mucosa, vagal stimulation did not affect tracheal segment tension, whereas sympathetic-evoked relaxation was preserved. Similar results were found when tone was restored with intravenous 5-HT, with vagal stimulation also decreasing resistance and increasing compliance. We conclude that NANC pathways are present in lower airways but not in the cervical trachea of the cat. We hypothesize that parasympathetic constriction of cat airway smooth muscle can occur without simultaneous NANC activation, whereas NANC activity occurs only in tandem with parasympathetic stimulation.

Airway Resistance↗
PubMed1988

Prolonged inflammatory reactions induced by artificial ceramics in the rat air pouch model.

The male Sprague-Dawley rat subcutaneous air pouch was used to study the inflammatory potential of artificial ceramics that are used in joint replacement surgery. Local leukocyte influx, proteinase, prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) levels were measured after injection of hydroxyapatite type I ceramic (HAP), tricalcium phosphate ceramic (TCP) and apatite-wollastonite glass ceramic (GC) into the pouch. Synthetic monosodium urate crystals (MSU) were used as positive controls and normal saline (NS) was a negative control. The response was monitored over 168 h by irrigating the pouch with 5 ml of NS and withdrawing 4 ml. MSU produced the greatest response in leukocyte counts, proteinase and PGE2, whereas HAP, TCP and GC elicited less response. The peak response with HAP, TCP and GC often appeared later than with MSU. TNF activity was significantly detected only after ceramics and not after MSU. The chronic and relatively prolonged reaction to some ceramics suggests that an inflammatory reaction may be seen after human implantation of these ceramics. The increased levels of TNF and production of PGE2, which is one substance proposed to contribute to bone lysis associated with loosening, are of special interest.

Air↗
PubMed1988

The effect of hyperthermia on radiation-induced carcinogenesis.

Ten groups of mice were exposed to either a single (30 Gy) or multiple (six fractions of 6 Gy) X-ray doses to the leg. Eight of these groups had the irradiated leg made hyperthermic for 45 min immediately following the X irradiation to temperatures of 37 to 43 degrees C. Eight control groups had their legs made hyperthermic with a single exposure or six exposures to heat as the only treatment. In mice exposed to radiation only, the postexposure subcutaneous temperature was 36.0 +/- 1.1 degrees C. Hyperthermia alone was not carcinogenic. At none of the hyperthermic temperatures was the incidence of tumors in the treated leg different from that induced by X rays alone. The incidence of tumors developing in anatomic sites other than the treated leg was decreased in mice where the leg was exposed to hyperthermia compared to mice where the leg was irradiated. A systemic effect of local hyperthermia is suggested to account for this observation. In mice given single X-ray doses and hyperthermia, temperatures of 37, 39, or 41 degrees C did not influence radiation damage as measured by the acute skin reactions. A hyperthermic temperature of 43 degrees C potentiated the acute radiation reaction (thermal enhancement factor 1.1). In the group subjected to hyperthermic temperatures of 37 or 39 degrees C and X rays given in six fractions, the skin reaction was no different from that of the group receiving X rays alone. Hyperthermic temperatures of 41 and 43 degrees C resulted in a thermal enhancement of 1.16 and 1.36 for the acute skin reactions. From Day 50 to Day 600 after treatment, the skin reactions showed regular fluctuations with a 150-day periodicity. Following a fractionated schedule of combined hyperthermia and X rays, late damage to the leg was less than that following X irradiation alone. Mice subjected to X rays and hyperthermic temperatures of 41 and 43 degrees C had a lower median survival time than the mice treated with hyperthermia alone. This effect was not associated with tumor incidence.

Animals↗
PubMed1987

In vivo activity of tracheal parasympathetic ganglion cells innervating tracheal smooth muscle.

In vivo intracellular recording and intrasomal injection of Lucifer yellow revealed two populations of postganglionic parasympathetic neurons in the tracheal ganglia of cats. One consisted of large cells that had an inspiratory rhythm, had a significant post-spike afterhyperpolarization, and projected to the tracheal smooth muscle. The second consisted of small cells that fired with an expiratory rhythm, had no significant afterhyperpolarization, and projected to the intercartilaginous spaces.

Animals↗
PubMed1987

Laboratory diagnosis of Giardia duodenalis infection in dogs.

Results of trichrome staining of fecal samples and intestinal contents preserved in polyvinyl alcohol fixative, fecal flotation utilizing unpreserved feces, and enzyme-linked immunosorbent assay of serum specimens were compared for the diagnosis of Giardia duodenalis infections in dogs. Trichrome staining of preserved fecal samples resulted in the identification of 44 (92%) of the 48 infected dogs from a group of 200 dogs. Trichrome staining of preserved intestinal contents resulted in the identification of 26 (54%) of the infected dogs, and fecal flotation resulted in the identification of 23 (48%) of the infected dogs. Giardia duodenalis antibodies were not detected consistently in the sera of infected dogs.

Animals↗
PubMed1987

Catecholamines abolish vagal but not acetylcholine tone in the intact cat trachea.

To obtain evidence in the airways that catecholamines inhibit cholinergic neurotransmission, we recorded transverse tension in the posterior wall of an upper tracheal segment in anesthetized cats and compared the inhibitory effect of stimulating cervical sympathetic nerves when segment contraction was evoked by endogenous acetylcholine (vagal tone) with the effect when contraction was evoked by exogenous acetylcholine applied directly to the mucosal surface of the tracheal segment (ACh tone). We found that sympathetic stimulation abolished all contraction evoked by vagal tone but reduced ACh tone by only one-half. In a second group of cats we compared the inhibitory effects of sympathetic stimulation and intravenous isoproterenol during vagal and ACh tone and also during tone evoked by exogenous 5-hydroxytryptamine (5-HT tone). Sympathetic stimulation or isoproterenol injection abolished all vagal and 5-HT tone but again reduced ACh tone by only one-half. Our results suggest that catecholamines released from sympathetic nerves or injected into the circulation completely inhibit vagal tone. This inhibition may be partially responsible for inducing relaxation in airway smooth muscle.

Acetylcholine↗