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Biomedical subjects

J M Davis

Publications and source records attributed to J M Davis.

At least 217 records · Page 12Linked to original sources
PubMed1994

Effect of high- versus moderate-intensity exercise on lymphocyte subpopulations and proliferative response.

The effect of 45 min of high- (80% VO2max) versus moderate- (50% VO2max) intensity treadmill exercise on circulating leukocyte and lymphocyte subpopulations, catecholamine and cortisol concentrations, and the mitogen-stimulated lymphocyte proliferative response was investigated in 10 well-conditioned (mean VO2max 66.0 +/- 1.9 ml/kg/min), young males (mean age 22.1 +/- 1.3 yrs). Blood samples were taken before and immediately after exercise, with three more samples taken during 3.5 h of recovery. Treatment order on the treadmill (graded walking at 7.3 +/- 0.1 km/h, 6.5 +/- 0.6% grade, versus level running at 16.1 +/- 0.3 km/h) was counterbalanced, with subjects acting as their own controls and results analyzed using a 2 x 5 repeated measures ANOVA. The concanavalin A- (Con A) stimulated lymphocyte proliferative response was decreased at 1 h and 2 h post-exercise relative to baseline levels following both exercise-intensity conditions. However, when adjusted on a per-T cell (CD3+) basis to account for the change in number of T cells in the in vivo assay, only the high-intensity exercise condition was associated with a 1-h post-exercise decrease (21%, p = 0.05) in the proliferative response relative to baseline. Exercise at 80% versus 50% VO2max resulted in significantly greater increases in cortisol and epinephrine concentrations, providing a physiological rationale for the immediate-post-exercise lymphocytosis, 1- to 3.5-h lymphocytopenia, and the decrease in Con A-stimulated lymphocyte proliferative response (per CD3+ cell) that occurred in greater measure following high-intensity exercise.

Adolescent↗
PubMed1994

Other diseases in animals.

Experimental inhalation in a number of studies has demonstrated that chrysotile asbestos can cause pulmonary fibrosis and both benign and malignant pulmonary tumours, two lesions which are associated in that the studies reporting high tumour rates also found high levels of asbestosis. One comparison reported that animals with malignant tumours had approximately twice the amount of fibrosis in the lung parenchyma as those of similar age without tumours. Many studies have examined the pathogenicity of asbestos administered by ingestion and most of these included chrysotile asbestos: the results have been universally negative apart from one study with amosite that contained no control animals and is best discarded. Only one inhalation study has reported an examination of the larynxes of animals: this found no pathological changes. In many studies, tumours other than the lung had been listed, but significant numbers of kidney tumours have never been recorded. Injection studies inducing mesothelioma have indicated that fibre geometry is important with long thin fibres (> 8 microns in length and < 0.25 microns in diameter) being the most carcinogenic. This has been difficult to confirm for inhaled fibres although fibres less than 5 microns in length appear to cause neither fibrosis nor pulmonary tumours. Similar results have been found with amosite for fibres up to 10-15 microns although longer fibres do produce these conditions. It is suggested that to produce pulmonary fibrosis and neoplasia fibres may need to be longer than 20 microns. Chrysotile has been shown in many studies to be removed from lung tissue much more rapidly than amphibole fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

Case report: cholangiocarcinoma and hypercalcemia.

Hypercalcemia is a relatively common problem seen in the presence of malignancy, and is the most common life-threatening metabolic disorder in patients with cancer. In the hospitalized patient, malignancy is the most common cause of hypercalcemia. It is estimated that hypercalcemia occurs in 10% to 20% of patients with cancer. Usually, it is a sign of advanced disease. Approximately 85% of patients with cancer and hypercalcemia will have disease metastatic to bone. The remaining 15%, however, will have some other etiology for their hypercalcemia, typically squamous carcinomas of the head and neck, esophagus, and lung. This type of hypercalcemia has been termed humoral hypercalcemia of malignancy and has been associated with the secretion of various cytokines, including parathyroid hormone-related protein. In this case report, the authors document the production of parathyroid hormone-related protein by an adenocarcinoma-cholangiocarcinoma. This is documented both by measurement of the protein in the patient's serum and staining of the protein within the tumor by a monoclonal antibody. A general discussion of hypercalcemia and malignancy also is provided.

Bile Duct Neoplasms↗
PubMed1994

Evidence that asgB encodes a DNA-binding protein essential for growth and development of Myxococcus xanthus.

The asg mutants of Myxococcus xanthus are defective in production of extracellular A-signal, which serves as a cell density signal for fruiting-body development. The DNA sequence of asgB, one of the three asg genes, was determined. The deduced amino acid sequence of AsgB contains a DNA-binding helix-turn-helix motif near the C terminus. This putative helix-turn-helix is highly similar to the helix-turn-helix in region 4.2 of major sigma factors, which is the region that recognizes and interacts with -35 sequences of promoters. We propose that AsgB is a transcription factor that binds to DNA sequences similar to the -35 hexamer, TTGACA. Analyses of asgB RNA levels and expression of an asgB-lacZ translational fusion indicate that expression of asgB remains fairly constant during the transition from growth into early development. The mutation within the asgB480 allele was identified as an A-to-G transition that results in a threonine-to-alanine substitution in the predicted protein product. Attempts to replace the wild-type copy of asgB with a null allele failed, indicating that asgB may be essential for growth.

Amino Acid Sequence↗
PubMed1994

Phosphoramidon attenuates big endothelin-1-induced vasoconstriction in canine stomach.

We compared the effects of endothelin-1 and its precursor, big endothelin-1, on vascular resistance of a blood-perfused ex vivo stomach segment of chloralose-anesthetized dogs. In separate groups of dogs, endothelin-1 or big endothelin-1 was infused intra-arterially directly to the gastric segment. Endothelin-1 caused statistically significant dose-related increases in gastric vascular resistance at final blood concentrations of 0.15-10 nM. Although each dose was given for only 5 min, endothelin-1 at concentrations > 0.6 nM caused sustained responses with vascular resistance remaining above control values for approximately 45-90 min. In contrast, however, big endothelin-1 caused a small but statistically significant vasoconstriction only at the highest concentration (10 nM). In other experiments, using 15-min peptide infusions, we found that pretreatment with phosphoramidon, an inhibitor of endothelin-converting enzyme, markedly reduced response to big endothelin-1 but not to endothelin-1. Our results demonstrate that endothelin-1, but not big endothelin-1, is a potent vasoconstrictor of the canine gastric microcirculation. In addition, it appears that big endothelin-1 is degraded to endothelin-1 in the stomach by a phosphoramidon-sensitive metalloproteinase.

Animals↗
PubMed1994

Effects of exercise on macrophage activation for antitumor cytotoxicity.

Recent evidence suggests that exercise affects macrophage functions and that amount of exercise may be important. We determined effects of moderate (MOD) and exhaustive treadmill running (EXH) on 1) ability of macrophages to become activated for antitumor cytotoxicity after injection of heat-inactivated Propionibacterium acnes in vivo, 2) macrophage responsiveness to activating agents lipopolysaccharide and interferon-gamma, and 3) role of glucocorticoids and various macrophage metabolic products in modulating cytotoxicity in exercised animals. Male C3H/HeN mice were randomly assigned to MOD (18 m/min, 5% grade, 30 min/day) or EXH (18-35 m/min, 5%, 2-4 h) on a motor-driven treadmill. Control animals were kept in simulated treadmill lanes located directly over the runners. In general, both MOD and EXH increased cytotoxicity (42 and 22%, respectively, across all experiments; P < 0.05). Enhanced cytotoxicity was not due to altered macrophage adherence, tumor necrosis factor-alpha, interleukin-1 beta, or reactive oxygen species. Reactive nitrogen species were responsible for enhanced toxicity in EXH only. Macrophage cytotoxicity was further increased by lipopolysaccharide and interferon-gamma to a similar maximal level that was the same in all groups. Plasma corticosterone was elevated two- and fourfold in MOD and EXH, respectively, but there was no correlation between plasma corticosterone and macrophage cytotoxicity when compared across all groups even though cells were sensitive to steroid-mediated suppression in vitro. However, consistent with a corticosterone effect, EXH reduced the number of peritoneal macrophages elicited during P. acnes inflammation and abolished the typical exercise-induced increase in cytotoxicity of activated macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Pharmacologic interactions of exogenous lung surfactant and recombinant human Cu/Zn superoxide dismutase.

The effect of exogenous surfactant on the pharmacokinetics of intratracheally administered recombinant human superoxide dismutase (rhSOD) was studied. Five groups of rats received the following intratracheally: 1 mL/kg of saline; 5 or 25 mg/kg of rhSOD; or 4 mL/kg of exogenous surfactant followed in 30 min by 5 or 25 mg/kg of rhSOD. Animals were killed at 24, 48, and 72 h, and serum, bronchoalveolar lavage, and lung tissue were analyzed for rhSOD. rhSOD was not detected in the lungs of saline-treated animals or in serum from any animals. At 24 h, lung-tissue rhSOD was higher in rats treated with surfactant and rhSOD versus rhSOD alone (5 mg/kg: 6.8 +/- 2.5 versus 0 microgram/whole lung, p < 0.05; 25 mg/kg: 29.9 +/- 9.6 versus 0.1 +/- 0.1 microgram/whole lung, p < 0.05). Bronchoalveolar lavage fluid levels correlated well with lung tissue concentrations. By 48 h, lung tissue rhSOD concentrations were insignificant in all groups. rhSOD was still present in lavage fluid from rats treated with surfactant and rhSOD. No rhSOD was detected at 72 h. In separate in vitro experiments, physical and biological drug-drug interaction studies were performed. When radiolabeled rhSOD was combined with exogenous surfactant and centrifuged at 10,000 x g for 30 min, 81.3 +/- 2.5% of rhSOD was found in the supernatant versus 18.7 +/- 2.5% in the surfactant pellet. Serial washing of the surfactant pellet removed virtually all remaining rhSOD. This finding suggests that the rhSOD and surfactant were only weakly associated. Combining rhSOD and exogenous surfactant did not alter the activity of either agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Surfactant therapy and high-frequency jet ventilation in the management of a piglet model of the meconium aspiration syndrome.

In vitro data have shown a concentration-dependent inhibition of surfactant by meconium, while anecdotal reports demonstrate improved oxygenation after surfactant replacement in babies with meconium aspiration syndrome, particularly in conjunction with high-frequency jet ventilation. We randomized 70 newborn piglets to either conventional or high-frequency jet ventilation, followed by insufflation of 3 mL/kg of a 33% meconium solution. Each group was further randomized to one of five surfactant therapies: 1) control, 2) 4 mL/kg Survanta, 3) 8 mL/kg Survanta, 4) 5 mL/kg Exosurf, or 5) 10 mL/kg Exosurf. We followed arterial blood gases and ventilator requirements over 6 h of ventilation. Aspirates of airway fluids were obtained for surface tension measurements, as well as total protein and phospholipid concentrations. Using a previously established scoring system, a pathologist blinded to treatment evaluated four sections of lung per animal for histologic changes of meconium aspiration syndrome. There were no differences noted between groups in any physiologic parameter measured (mean airway pressure, arterial partial pressure of oxygen/alveolar partial pressure of oxygen ratio, etc.) during the 6 h of ventilation. Airway fluid aspirate total protein concentrations increased significantly after meconium instillation (4- to 5-fold, p < 0.007) and remained elevated in spite of surfactant therapy. There was an initial decline in airway phospholipid concentrations after meconium instillation followed by a rise to levels equal to or greater than premeconium levels. Surface tension measurements increased in all groups after meconium insufflation (p < 0.012) and did not decline thereafter, despite standard and twice-standard surfactant doses of both types.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Exercise, monocyte/macrophage function, and cancer.

Epidemiological studies have found a relationship between increased physical activity and lower prevalence and mortality rates for various site-specific cancers. Animal studies are limited and often inconsistent, but also generally support this concept. However, the significance of this research will be questioned until the underlying physiological mechanisms are determined. It now seems likely that components of the innate immune system are involved. One such component includes cells of the monocyte-macrophage (Mo/M phi) lineage that have powerful inhibiting effects on tumor growth and can destroy cancer cells. Recent research suggests that exercise can alter the influx of Mo/M phi into tissues in response to an inflammatory challenge, promote the release of M phi-derived cytokines known to have antitumor properties, increase M phi antitumor cytotoxicity, and increase the number and functional activity of tumor-derived M phi. These effects are likely dependent on the dose of exercise and the functional state of the M phi at the time of the exercise stimulus. However, these responses have yet to be shown to inhibit experimental tumors in vivo. Future research must continue to develop appropriate animal models to study the mechanisms of exercise effects on the initiation, promotion and progression of cancer.

Exercise↗
PubMed1994

The role of clearance and dissolution in determining the durability or biopersistence of mineral fibers.

It is generally accepted that to cause pulmonary disease, mineral fibers must be relatively long and thin but also able to remain in the lung for long periods. This "biopersistence" of fibers is limited by two main mechanisms of fiber clearance: removal by macrophages after phagocytosis and, for some fibers, by actual dissolution. The relative importance of these mechanisms has not been properly evaluated for any type of fiber and will certainly vary with mineral type. The efficiency of macrophage clearance is greatest with short fibers (< 5 microns long) and is reduced as fibers get longer. Fibers > 50 microns long cannot be cleared by macrophages and for some mineral types they may remain in the lung permanently. Others may fracture into shorter lengths, perhaps aided by chemical dissolution, and thus become susceptible to macrophage clearance. However, for a number of areas relating to fiber removal from the lung parenchyma detailed information is still needed: Do dusts differ in their ability to attract macrophages and stimulate these cells to phagocytosis? Following dust uptake what controls the movement of macrophages? Some may penetrate to the interstitium, some phagocytosing fibers in interstitial sites may migrate back to the alveolar space. Some move to the mucociliary escalator and some to the lymphatics. Some, most importantly, move to the pleura. Fibers are found and phagocytosed in the interstitium during the early stages of disease development, but with time many fibers appear isolated in areas of fibrous tissue. Are such fibers subsequently ignored or can they reenter the disease process after years of isolation? Finally, can phagocytosis by macrophages effect dissolution of fibers?(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Use of the short-term inflammatory response in the mouse peritoneal cavity to assess the biological activity of leached vitreous fibers.

We used a special-purpose glass microfiber sample, Johns-Manville Code 100/475, to study the effects of various acid and alkali treatments on biological activity as assessed by inflammation in the mouse peritoneal cavity, the leaching of Si, and the phase contrast optical microscopy (PCOM) fiber number. We used mild and medium treatments with oxalic acid and Tris buffer and harsh treatment with concentrated HCl and NaOH. Mild oxalic acid and Tris treatment for 2 weeks had no effect on any of the end-points, but prolonging the mild oxalic acid treatment time to 2 months reduced the biological activity and the fiber number. Medium oxalic acid treatment reduced the biological activity and the fiber number and caused a loss of Si. Medium Tris alkali treatment reduced the PCOM-countable fibers and the biological activity but did not cause a substantial loss of Si. Harsh treatment with strong HCl did not affect the fiber number or cause leaching but the biological activity was reduced; strong NaOH reduced the fiber number and biological activity, and caused marked leaching of Si. The medium oxalic acid conditions (pH 1.4) were more acid than those found in lung cells but produced the same effects (reduction in fiber number and biological activity) as the more physiological mild treatment (pH 4.0), when prolonged. This study suggests that medium oxalic acid treatment can be used as a short-term assay to compare loss of Si, reduction in fiber number, and change in biological activity of vitreous fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Depot antipsychotic drugs. Place in therapy.

The pharmacokinetics of depot antipsychotic medications are such that an intramuscular injection given at intervals of from 1 to 4 weeks will produce adequate plasma concentrations that are sufficient to prevent relapse over the dosage interval. Such medication is useful in patients who do not reliably take their oral medication. The pharmacokinetics and clinical actions of various depot formulations of antipsychotic drugs have been extensively studied. Unfortunately, patients who do not reliably take their oral medications are unlikely to volunteer for controlled studies. This is because the same factors that influence a patient to not cooperate with the physician in taking the medication as prescribed will also interfere with their willingness to volunteer for research protocols. Thus, evidence from blinded controlled trials may not necessarily reflect the actual patient population at risk. We feel that particularly important evidence of efficacy of depot vs oral medication comes from mirror-image studies. In these trials, the number of hospitalisations after initiation of depot medication is compared with that observed when the patient was solely taking oral medication. Studies of this type show that depot medication substantially reduces the rate of relapse. There is considerable evidence about how long depot medications should be used. For many patients, depot medication to prevent relapse in schizophrenia should be used for the life of the patient. As the conventional antipsychotic agents are replaced by a new generation of agents, the need for depot formulations will continue, and the knowledge gained about the current formulations should transfer to future generations of drugs.

Antipsychotic Agents↗
PubMed1994

Comparison of DonJoy ankle ligament protector and subtalar sling ankle taping in restricting foot and ankle motion before and after exercise.

Clinicians often must select an appropriate prophylactic ankle support system for their patients from a variety of ankle orthoses and ankle taping configurations. The purpose of this study was to compare the effectiveness of the DonJoy Ankle Ligament Protector and a newly developed ankle taping procedure in restricting foot and ankle motion before and after exercise. Subjects were eight males and eight females who reported no history of ankle injury during the 6 months prior to testing, neurological condition, lower extremity arthritis, lower extremity fracture, or cardiac or balance problems. A Biodex dynamometer and computer were used to impose passive moments and to measure eversion and inversion prior to application of the ankle support systems, following application, and following 10 minutes of figure-of-eight running and 20 unilateral toe raises. Both ankles of each subject were assessed for each ankle support system. Subjects also compared the support systems for comfort, stability, and cosmetic acceptability. Both ankle support systems significantly reduced eversion and inversion following application and following exercise compared with preapplication measurements. Eversion measurements increased significantly following exercise for both ankle support systems compared with postapplication measurements. Inversion displacement following application was greater for the Ankle Ligament Protector than the ankle taping system. The two ankle support systems did not differ significantly following exercise for eversion or inversion measurements. The results may assist clinicians in selecting either of these ankle support systems for use in protection against ankle sprain injury.

Adult↗
PubMed1994

Effects of exercise on the immune response to cancer.

This study examined the effects of two doses of exercise on tumor incidence and progression, and the number and activity of intratumoral phagocytic cells (80% macrophages [M phi's]). Male mice were randomly assigned to control (CON), moderate (MOD) or exhaustive (EXH) treadmill running. Mice were inoculated subcutaneously with 2.5 x 10(5) mammary adenocarcinoma cells after 3 d of running (3 h after the last run at a point when enhancement in M phi cytotoxicity is observed). This tumor was chosen due to its susceptibility to M phi inhibition in vitro and in vivo. Mice continued daily running for 14 d. Food intakes were higher during the last 3 d in MOD and EXH, but body weights were no different. Flow cytometer analysis of tumor masses revealed that MOD had greater numbers of phagocytic cells (vs EXH) with slightly higher phagocytic activities (vs CON and EXH) (P < 0.05). However, no group differences in tumor appearance were seen except on day 7 when CON had less observable tumors than MOD and EXH (P < 0.05). Tumor size was also not different between groups at any point. These results indicate that moderate exercise can increase the phagocytic capacity of intratumoral phagocytic cells, but these changes had no apparent effect on tumor incidence or progression in this study.

Adenocarcinoma↗
PubMed1994

Neutrophil leukotriene generation increases after cardiopulmonary bypass.

BACKGROUND: Leukotriene B4 has been shown to play a role in the systemic inflammatory response after cardiopulmonary bypass in experimental animal models; however, the importance of this mediator in human beings undergoing cardiac operations has not been established. METHODS: The neutrophils of ten patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were studied for their ability to generate leukotrienes at the time of the induction of anesthesia, the institution of cardiopulmonary bypass, the removal of the aortic crossclamp, at the end of the operation, on admission to the intensive care unit, and on postoperative days 1 and 2 RESULTS: After cardiopulmonary bypass, the generation of chemotactic leukotrienes rose significantly and remained elevated on the first postoperative day compared with prebypass values (prebypass 133.8 +/- 10.7 versus postbypass 192.7 +/- 19.2 [p < 0.05] and first postoperative day 196.6 +/- 13.8 [p < 0.05]). The increases in plasma complement and lactoferrin levels, although significant, were not sustained. In addition to the neutrophil count, the potential leukotriene and oxygen radical produced was significantly increased, and this increase was correlated with postoperative length of stay. CONCLUSION: These observations support the laboratory data documenting that the rise in leukotriene generation after cardiopulmonary bypass includes human patients.

Aged↗
PubMed1994

Neutrophil leukotriene generation and pulmonary dysfunction after abdominal aortic aneurysm repair.

BACKGROUND: The purpose of this study was to assess the role of polymorphonuclear neutrophil (PMN)-generated leukotriene B4 (LTB4) as an etiologic agent in the pulmonary dysfunction seen after operation in patients undergoing abdominal aortic aneurysm repair. METHODS: Blood was analyzed in 10 consecutive patients undergoing elective infrarenal abdominal aortic aneurysm repair for plasma thromboxane B2, lactoferrin, C3a, and PMN-generated LTB4. RESULTS: There was a close linear correlation (r = 0.88; p < 0.001) between aortic clamp time and PMN LTB4 production. Conversely, aortic clamp time and the ratio of arterial oxygen pressure to fraction of inspired oxygen, a measure of pulmonary function, were inversely related (r = -0.80; p < 0.008). PMNs from patients with long aortic cross-clamp times generated three times more LTB4 than those patients with short cross-clamp times (194 +/- 29.6 vs 64.9 +/- 9.7 ng per 5 x 10(6) PMN; p < 0.05). Similarly, the pressure/inspired oxygen ratio was significantly lower on admission to the intensive care unit in patients with long cross-clamp times as compared with patients with short cross-clamp times (237 +/- 14 vs 342 +/- 5; p < 0.005). In addition, patients with long cross-clamp times remained intubated longer than patients with short times (1.6 +/- 0.2 vs 0.6 +/- 0.4 days; p < 0.05). CONCLUSIONS: These data suggest a causal role for LTB4 in the generation of pulmonary dysfunction in patients undergoing abdominal aortic aneurysm repair, similar to what has been shown in animal models.

Aged↗