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Biomedical subjects

W A Phillips

Publications and source records attributed to W A Phillips.

At least 73 records · Page 4Linked to original sources

The effect of fasting, transit plus fasting, and administration of adrenocorticotropic hormone on the source and amount of weight lost by feeder steers of different ages.

Two trials (winter and summer) were conducted to determine effects of fasting and transportation and adrenocorticotropic hormone (ACTH) administration on the amount and source of weight lost by feeder steers. Sixteen steers, in each of two experiments, were adapted to metabolism stalls for 10 d, were fed medium-quality hay at 2.1% of BW for 3 d, and then were subjected to either fasting alone or fasting plus transit for 48 h. In Exp. 1 steers were randomly assigned to treatments. In Exp. 2 steers were blocked by age (OLD or YOUNG) and assigned to treatments. Fecal and urinary excretions accounted for 65 and 38% of the total weight lost in Exp. 1 and 2, respectively. Fasting plus transit did not consistently increase the amount of weight lost compared with fasting alone but increased (P less than .01) plasma glucose concentrations. Injection of ACTH before either fasting alone or fasting plus transit increased (P less than .05) the amount of weight lost as feces. Steers in the OLD group lost more weight during transit and fasting but regained the lost weight faster (P less than .01) during the recovery period than did steers in the YOUNG group. Injecting YOUNG steers with ACTH before fasting alone or fasting plus transit increased plasma fibrinogen (P less than .10) and serum glucose (P less than .05) concentrations more than ACTH injections in OLD steers. Although fasting and transit elicit mobilization of body nutrients and resulted in a loss of BW, these effects were quickly reversed during the poststress period.

Adrenocorticotropic Hormone↗

Effect of pre- and postweaning management system on the performance on Brahman crossbred feeder calves.

During a 3-yr period (1986 through 1988), 117 calves (57 steers and 60 heifers) from the same genetic base and reared under four distinct preweaning management systems were weaned in the fall and transported from Uvalde, TX to El Reno, OK (800 km). Weaning weight and transportation shrink varied more from year to year than among preweaning treatments. Postweaning performance was not affected by preweaning treatment. After a 28- to 32-d receiving period the calves were blocked by sex and previous preweaning treatment, then randomly assigned within block to graze winter wheat forage (WHEAT) or dormant tall-grass native range (GRASS). The WHEAT group gained more (P less than .01) weight than the GRASS group during the winter (November to March), but when both groups were allowed to graze spring wheat pasture (March to June) the GRASS group gained more (P less than .01) weight than the WHEAT calves. During the subsequent finishing phase the GRASS calves were more (P less than .01) efficient than the WHEAT calves in converting DM to gain. Because cattle were slaughtered at the same degree of finish, no differences were noted in carcass characteristics among the pre- or postweaning treatments. Feeder calves exposed to a restrictive period of growth during the postweaning period gained weight more rapidly in a subsequent forage-based stockering system and were more efficient in a grain-based finishing system than nonrestricted calves.

Animal Feed↗

Familial cervical dysplasia.

Nine of twelve family members from three generations were affected by an inherited form of cervical vertebral dysplasia. All of the affected people had an abnormality of the first cervical vertebra. Some also had defects of the axis and caudad to it. The mode of transmission of the disorder is autosomal dominant, with apparently complete penetrance and variable expressivity. Two patients had symptoms. One had a passively correctable tilt of the head, with an associated audible clunk and hypoplasia of the left superior facet of the second cervical vertebra. This patient had no local symptoms, neurological involvement, or muscle spasm. In the other patient, suboccipital pain developed. Radiographs revealed an anterior atlanto-occipital dislocation. The symptoms resolved after reduction and arthrodesis. Because of the apparently complete penetrance of this disorder, physicians caring for patients who have this type of congenital malformation of the cervical spine should consider examination of closely related members of the family. Clinical findings such as tilting of the head, torticollis, or limitation of cervical motion suggest that additional evaluation should be done. The examination should include lateral radiographs of the cervical spine in flexion and extension. Three-dimensional computed-tomography reformatting was helpful in demonstrating the complex cervical anatomy in our patients. Patients who have recognized abnormalities should be followed and should be re-examined whenever local or neurological symptoms develop. A magnetic resonance image of the spine in flexion and extension was valuable for identification of the potentially disastrous situation of impending damage to the cord in patients who had instability and evolving symptoms.

Adult↗

Colony stimulating factor-1 is a negative regulator of the macrophage respiratory burst.

Several cytokines have previously been shown to prime macrophages for enhanced release of oxygen radicals in response to subsequent stimulation. We now demonstrate that the presence of the macrophage-specific colony stimulating factor-1 (CSF-1) inhibits the priming of murine macrophages by a variety of agents including tumor necrosis factor alpha, granulocyte/macrophage colony stimulating factor, interferon-gamma, and bacterial lipopolysaccharide. CSF-1 is also able to reduce the respiratory burst in the absence of priming. Our results indicate that CSF-1 is a potent negative regulator of the macrophage respiratory burst which acts to oppose the priming (enhancing) action of macrophage activating agents. We propose that CSF-1 may have a potentially important and previously unrecognized, role as a physiological regulator which restricts or terminates the activation of macrophages in order to prevent an uncontrolled inflammatory reaction.

Animals↗

Priming the macrophage respiratory burst with IL-4: enhancement with TNF-alpha but inhibition by IFN-gamma.

Pre-exposure to bacterial lipopolysaccharide (LPS) or certain cytokines is known to enhance the ability of murine macrophages to generate a respiratory burst in response to subsequent stimulation, a phenomenon referred to as 'priming'. We report here that the cytokine interleukin-4 (IL-4) can prime murine macrophages. Pretreatment of murine bone marrow-derived macrophages (BMM) with 10 U/ml murine IL-4 for 48 hr was found to enhance the respiratory burst following subsequent stimulation with phorbol myristate acetate (PMA) (10(-6) M) or zymosan (1 mg/ml). Human tumour necrosis factor-alpha (TNF-alpha) (10(-9) M) can also prime BMM for an enhanced respiratory burst and the combination of TNF-alpha and IL-4 resulted in an enhanced (greater than additive) priming effect. In contrast, interferon-gamma (IFN-gamma) (100 U/ml), although by itself capable of priming the BMM respiratory burst, was found to antagonize the priming effects of IL-4. These results demonstrate that IL-4 can be added to the growing list of cytokines capable of modulating the respiratory burst response of macrophages, suggesting a possible role for this cytokine in inflammation and in the host response to infection. The opposing effects of TNF-alpha and IFN-gamma when interacting with IL-4 highlight the difficulties in predicting the effect of a given cytokine in vivo, where potential interactions with other cytokines must be considered.

Animals↗

Influence of calcium on the subcellular distribution of protein kinase C in human neutrophils. Extraction conditions determine partitioning of histone-phosphorylating activity and immunoreactivity between cytosol and particulate fractions.

Activation of the neutrophil respiratory burst is thought to involve a translocation and activation of protein kinase C. We report that the presence of Ca2+ during the disruption of unstimulated human neutrophils and cytoplasts resulted in an increase in protein kinase C activity (histone phosphorylation) and immunoreactive protein kinase C species in the particulate (membrane) fraction and a reduction in such activities in the cytosol. This Ca2+-induced translocation of activity was concentration-dependent and occurred at physiologically relevant concentrations of Ca2+ (30-500 nM). The Ca2+-induced membrane association of protein kinase C could be reversed by removal of Ca2+. These findings indicate that the Ca2+ concentration of the extraction buffer can determine the subcellular distribution of protein kinase C in disrupted cells and suggest that the observed location of this enzyme activity in cell fractions may not necessarily reflect the localization in intact cells. These results also raise the possibility that the distribution of protein kinase C between cytosol and membrane is a dynamic equilibrium controlled by levels of free Ca2+. Thus, Ca2+ might regulate distribution as well as activation of protein kinase C.

Biological Transport↗

Phorbol ester-stimulated superoxide production by murine bone marrow-derived macrophages requires preexposure to cytokines.

Murine resident peritoneal macrophages (RPM) generate superoxide (O2-) in response to stimulation with PMA or zymosan. Murine bone marrow-derived macrophages (BMM) generate O2- in response to zymosan but not PMA. However, the ability to generate O2- in response to PMA could be induced in BMM by pre-exposing the cells to certain cytokines, including granulocyte-macrophage CSF (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), IFN-gamma, and, to a lesser extent, IL-1 alpha. Bacterial LPS also induced the ability to respond to PMA. These same agents were also shown to prime RPM for enhanced PMA-induced respiratory burst. In contrast to GM-CSF, CSF-1 did not enhance the ability of BMM or RPM to generate O2- in response to PMA. Pretreatment with GM-CSF or TNF-alpha did not significantly affect the zymosan-induced release of O2- by BMM. These results suggest that unprimed BMM have a deficiency in the PMA-dependent signaling pathway that is corrected by exposure to selected cytokines. The results also raise the possibility that the basal ability of tissue macrophages to generate a respiratory burst in response to PMA may be a reflection of in vivo exposure to cytokines.

Animals↗

Activation and proliferation signals in murine macrophages: relationships among c-fos and c-myc expression, phosphoinositide hydrolysis, superoxide formation, and DNA synthesis.

Murine bone marrow-derived macrophages (BMM) undergo DNA synthesis in response to growth factors such as colony stimulating factor-1 (CSF-1) and granulocyte-macrophage CSF (GM-CSF). These macrophages can also be "activated," but without subsequent DNA synthesis, by a number of other agents, including lipopolysaccharide (LPS), concanavalin A, zymosan, formyl-methionyl-leucyl-phenylalanine (FMLP), and the Ca2+ ionophore, A23187. When BMM are treated with a range of stimuli, there is some, although not perfect, correlation between transient elevations in both c-myc mRNA and c-fos mRNA levels and increases in DNA synthesis. However, enhanced DNA synthesis and oncogene expression are readily dissociated from rises in inositol phosphates and, by implication, phospholipase C-mediated hydrolysis of phosphatidyl inositol 4,5-bisphosphate. Superoxide formation in BMM can also be dissociated from the other responses and does not necessarily depend on protein kinase C activation.

Animals↗

Uses and abuses of a biosynthetic dressing for partial skin thickness burns.

The following report reviews 851 applications of Biobrane on partial skin thickness burn wounds awaiting epithelialization. After the patients had been evaluated and resuscitated as needed, the burn wounds were cleansed and debrided. Those evaluated as shallow were treated with Biobrane application. Joint surfaces were splinted for immobilization. The wound was inspected at 24 and 48 h and if any fluid had accumulated it was aspirated and the wound was redressed. When the Biobrane was adherent, the wound was covered with a light dressing and joint immobilization was discontinued. Treatment with Biobrane dressing provided certain advantages over other topical wound care. As the dressing changes were performed less frequently outpatient care was possible, with a resultant decrease in both the length of hospital stay and the ultimate cost of burn care. Wound desiccation is prevented and pain is decreased. Accurate diagnosis of wound depth is crucial if Biobrane is to be used. Very deep wounds will not allow Biobrane adherence, neither will it occur if the wound has a high bacterial count. If joint surfaces are not splinted, the Biobrane will shear and not adhere to the wound. Convex and concave surfaces can be treated with Biobrane, which may need to be meshed.

Adolescent↗

Intracellular platelet-activating factor regulates eicosanoid generation in guinea-pig resident peritoneal macrophages.

1. The role of intracellular platelet-activating factor (Paf) in arachidonic acid (AA) mobilization from guinea-pig peritoneal macrophages has been investigated by use of the potent and selective Paf receptor antagonists, WEB 2086 and CV 6209. 2. Adherent macrophages contained cell-associated Paf which was increased by exposure to formyl-methionyl-leucyl-phenylalanine (fMLP), endotoxin and the ionophore, A23187. However, only endotoxin and A23187 caused release of detectable amounts of Paf into the extracellular medium. 3. Exogenous Paf and each of the above stimuli mobilized previously incorporated [14C]-AA and increased the generation of prostacyclin (PGI2) in resident macrophages. 4. WEB 2086 (10-100 microM) and CV 6209 (0.1-10 microM) reduced both basal and stimulated PGI2 generation and WEB 2086 inhibited the mobilization of [14C]-AA. In addition, WEB 2086 (10 microM) inhibited fMLP-and Paf-induced superoxide anion generation. Responses to A23187 were not inhibited by either antagonist. 5. Activation of macrophages by fMLP caused a short burst of intracellular Paf generation but none was detected in the supernatants. The time-course of PGI2 synthesis followed closely that of Paf. 6. These data suggest that intracellular Paf generation is important for subsequent AA mobilization and may have a wider role in signal transduction processes.

6-Ketoprostaglandin F1 alpha↗

Lipopolysaccharide priming of human neutrophils for an enhanced respiratory burst. Role of intracellular free calcium.

Lipopolysaccharide (LPS) pretreatment "primes" neutrophils to release increased amounts of superoxide anion (O2-) when stimulated. We investigated the molecular basis of this enhanced activity. Comparison of kinetic parameters of the respiratory burst NADPH oxidase in unstimulated LPS-primed and control neutrophils disclosed a similar Km for NADPH and no difference was seen in the content of cytochrome b. Pertussis toxin, which inhibits some G proteins, did not prevent priming. Change in membrane potential (delta psi) was five-fold greater in LPS-primed cells and paralleled the increased O2- release. Cytofluorographic analysis indicated that the increased change in delta psi was due to the creation of a new population of active cells. Changes in the concentration of intracellular free Ca2+ ([Ca2+]i) are believed to antecede changes in delta psi. There was a consistent increment (67 +/- 8%, n = 12) in resting [Ca2+]i in cells preincubated with LPS compared with control. When stimulated, the peak [Ca2+]i was significantly higher in LPS-primed cells. Ca2+-dependent protein kinase C activity was unaltered in resting and FMLP-stimulated neutrophils preexposed to LPS. Addition to cells of the intracellular Ca2+ chelator MAPTAM before preincubation with LPS blocked the changes in [Ca2+]i and the enhanced respiratory burst that characterize LPS priming. The increased resting [Ca2+]i in LPS-primed cells may enhance stimulus-induced cellular activity by modifying a Ca2+-dependent step in signal transduction.

Calcium↗

Effects of supplemental silage on forage intake and utilization by steers grazing wheat pasture or bermudagrass.

Seven trials were conducted to determine the effects of increasing amounts of silage (corn, wheat or sorghum) on forage intake, gastrointestinal tract fill, fecal output and ruminal flow and degradation of forage by cattle grazing wheat pasture or bermudagrass. In each of 3 yr, 24 steers grazed a common wheat or bermudagrass pasture and were randomly allocated to four treatments (0, .35, .70 or 1.05 kg silage DM.100 kg body weight-1.d-1). Intake and ruminal flow of forage were measured by feeding a single pulse dose of Yb-labeled forage followed by collection of fecal samples for 4 to 5 d and fitting Yb concentrations to a one-compartment, age-dependent model. Ruminal digestion kinetics of wheat forage were estimated in situ using eight ruminally cannulated steers fed 0 or .55 kg sorghum silage DM.100 kg body weight-1.d-1. Supplemental silage decreased wheat forage (P less than .10) and bermudagrass (P less than .01) intake linearly. However, total forage intake of bermudagrass plus silage increased linearly (P less than .05). Each kilogram of added silage DM decreased DM intake of wheat forage by .66 +/- .25 and of bermudagrass by .63 +/- .17 kg. Flow and turnover of wheat forage or bermudagrass were not altered (P greater than .15) by supplemental silage. Silage consumption increased extent of ruminal degradation of wheat forage DM (P less than .05; 63.1 vs 52.5%), indicating a positive associative effect of silage on wheat forage utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

The management of rotatory atlanto-axial subluxation in children.

Twenty-three children who were treated for rotatory atlanto-axial subluxation between 1975 and 1986 were retrospectively studied. The success of closed reduction with traction and the length of hospitalization were related to the duration of symptoms before admission. In sixteen of the children, who were seen less than a month after the onset of symptoms, the subluxation reduced either spontaneously or after a short period of traction. Of the seven remaining children, who were seen more than one month after the onset of symptoms, three eventually needed a posterior atlanto-axial arthrodesis. Dynamic computed-tomography scans, with the head rotated maximally to each side, were made for five children, and proved to be an excellent method of documenting the presence of rotatory atlanto-axial subluxation.

Adolescent↗

Extracorporeal hemolysis in orthopedic patients. Report of two cases.

Two patients who had extracorporeal hemolysis of their blood transfusions are reported. In both cases, accidental overheating and hemolysis of the transfused blood caused a gross hemoglobinuria. Because the etiology of the hemolysis was not readily apparent at the time, both patients were managed as though they had had an acute hemolytic transfusion reaction. Because there was no activation of the complement cascade by antigen-antibody complexes, both patients suffered no ill effects. Differentiation of extracorporeal hemolysis from hemolytic transfusion reactions requires a careful inspection of all blood administration equipment, as well as an analysis of the untransfused blood in both bag and tubing. Patients undergoing orthopedic procedures account for 15% of all blood transfused in the United States. Awareness of adverse effects of transfusion is therefore important to orthopedic surgeons.

Adult↗

Emergency transport and positioning of young children who have an injury of the cervical spine. The standard backboard may be hazardous.

In ten children who were less than seven years old, an unstable injury of the cervical spine was found to have anterior angulation or translation, or both, on initial lateral radiographs that were made with the child supine on a standard flat backboard. In all ten patients, extension was the proper position for reduction of the injury of the cervical spine. Young children have a large head in comparison with the rest of the body. When a young child is positioned on a standard backboard, the neck may be forced into relative kyphosis. Supine and upright lateral radiographs that were made of seventy-two children who did not have a fracture also demonstrated more relative cervical kyphosis in younger children when they were in the supine position. Calculations from anthropometric data documented disproportionate rates of growth of the head and the chest. The circumference of the head grows logarithmically, but the circumference of the chest grows linearly. This disproportionate growth causes young children to have a relatively large head. When they lie supine, the neck is flexed. To prevent undesirable cervical flexion in young children during emergency transport and radiography, a standard backboard can be modified to provide safer alignment of the cervical spine. This can be accomplished by the use of a recess for the occiput to lower the head or of a double mattress pad to raise the chest.

Age Factors↗

Activation of the respiratory burst in macrophages. Phosphorylation specifically associated with Fc receptor-mediated stimulation.

Inflammatory macrophages elicited from the peritoneal cavity of mice injected with endotoxin can avidly ingest E opsonized with IgG antibody (EIgG) or with IgM antibody and C (EIgMC). However, only ingestion of EIgG is associated with activation of the respiratory burst and release of superoxide anion. We compared the endogenous phosphorylation of proteins from macrophages stimulated by interaction with EIgG or EIgMC on the premise that proteins phosphorylated after stimulation by EIgG but not EIgMC could play a role in activating the enzyme (oxidase) responsible for the respiratory burst. Proteins were separated by one-dimensional and two-dimensional electrophoresis in polyacrylamide gels. We found that proteins with approximate Mr of 20 kDa, 23 kDa, 46 kDa, 48 kDa (three proteins), 67 kDa, and 130 kDa were more heavily phosphorylated after EIgG stimulation than after EIgMC stimulation. Exposure to PMA, which activates the respiratory burst oxidase, induced phosphorylation of the 23-kDa, 48-kDa group, and 130-kDa proteins that were phosphorylated after stimulation by EIgG. Activity of protein kinase C was found to be significantly increased in the particulate fraction of macrophages stimulated by EIgG but not in the particulate fraction of EIgMC-stimulated cells. These data are compatible with the hypotheses that phosphorylation of specific cellular proteins, especially with a Mr of approximately 48 kDa, is involved in activation of the respiratory burst oxidase, and that function of protein kinase C also plays a part in this activation process.

Animals↗