Search PubMed⌕ Search

Biomedical subjects

Q Jones

Publications and source records attributed to Q Jones.

At least 19 recordsLinked to original sources

Prostaglandin E2 suppressed IL-15-mediated human NK cell function through down-regulation of common gamma-chain.

NK cell function is regulated by cytokines and certain biochemical mediators in a positive or negative manner. This study was performed to investigate the suppressive effects of PGE(2) on IL-15-activated human NK cell function. Purified NK cells were cultured with 200 ng/ml IL-15 for 2 days in the presence or absence of 10-200 ng/ml PGE(2). PGE(2) significantly suppressed NK cell-mediated cytotoxicity and IFN-gamma production at the secretional and the transcriptional levels. We also evaluated the effect of PGE(2) on the IL-15R complex that consists of IL-2Rbeta, common gamma-chain (gamma(c)-chain), and a specific chain IL-15Ralpha. Percentage of positive cells and number of binding sites for gamma(c)-chain were significantly increased after IL-15 treatment; however, a substantial decrease was observed with PGE(2) cotreatment. In contrast, constitutive expression of IL-2Rbeta was significantly decreased after IL-15 treatment, with no change detected in the presence of PGE(2.) At the transcriptional level, neither IL-15 nor PGE(2) had significant effects on the expression of beta- or gamma(c)-chains. There was a 3-fold increase in the expression of IL-15Ralpha at the transcriptional level that peaked at 8 h after IL-15 treatment; however, PGE(2) had no significant effect. Suppression of NK function by PGE(2) was not due to the endogenous production of IL-4, IL-10, or TGF-beta(1) by NK cells. These results suggest that down-regulation of surface expression of gamma(c)-chain on NK cells may be one mechanism through which PGE(2) mediates suppression of IL-15-activated NK cell function.

Cells, Cultured↗

Trauma patients with positive cultures have higher levels of circulating macrophage migration inhibitory factor (MIF).

Macrophage migration inhibitory factor (MIF) is a pituitary "stress" hormone that plays a critical role in the host immune response. The aims of the study were to determine whether MIF was detectable in the circulation of trauma patients, to assess whether MIF levels were associated with injury severity, days post injury, infection, and to examine concentrations of other pro-inflammatory cytokines in circulation. We collected plasma samples from 35 trauma (multiple injury) patients and 18 healthy controls. Concentrations of MIF, TNF-alpha, IL-1beta, and IL-6 were measured by ELISA. Average MIF concentration in plasma of trauma patients was 14 fold higher than that of healthy controls (19,439+/-2,615 pg/ml in trauma vs 1,337+/-286 pg/ml in control; p=0.0002). There was no correlation between MIF values and injury severity score or days post injury. Average level of IL-6 in trauma patients was 587+/-85 pg/ml but was not correlated with MIF concentration. TNF-alpha and IL-1beta were not detectable in trauma patients or healthy controls. Higher MIF levels were associated with positive cultures (blood, urine, sputum, wound). These data suggest that MIF may be a possible indicator of infection in trauma patients.

Bacterial Infections↗

Mechanism of suppression of natural killer cell activity in trauma patients.

Trauma patients develop a severe immunosuppression that includes suppression of natural killer (NK) cell activity although numbers of NK cells are not reduced. The mechanism of suppression of NK cell activity after major trauma is not known. The aim of the present study was to investigate the in vitro effect of plasma samples from trauma patients (TP) on the cytotoxic activity of normal NK cells. Buffycoat mononuclear cells (5x10(5)/well) were preincubated with either TP or plasma samples from age and sex matched healthy controls (CP) for 0, 16 or 40 h. These effector cells were then cultured with 51Cr labeled K-562 cells (2x10(4)/well) for 4 h at 37 degrees C and % lysis was calculated. No significant differences in % lysis between CP and TP were found with 0 or 16 h preincubation, however 40 h preincubation with TP severely suppressed NK cell function (p=0.003) as compared to preincubation with CP for the same period. Addition of neutralizing anti-IL-4, anti-TGF-beta1, or anti-IL-10 antibodies did not reverse the NK cell suppression. There was a partial reversal of NK cell suppression by catalase but not by SOD or L-NMMA. Removal of monocytes from buffycoat mononuclear cells also significantly reversed the NK cell suppression. These data suggest that suppression of NK cell activity in trauma patients may be an accessory cell dependent phenomenon and may partially depend on production of reactive oxygen metabolites (ROM).

Catalase↗

Suppression of natural killer cell activity in patients with fracture/soft tissue injury.

BACKGROUND: Natural killer cells (NKCs) participate in "innate" cell-mediated immunity. Fracture/soft tissue injuries are cytokine rich and may influence cell-mediated immunity. OBJECTIVE: To study the effects of fracture cytokines on NKC function. DESIGN: A case-control study. SETTING: A level I trauma center and laboratory in a university medical center. PARTICIPANTS: Patients requiring open fracture fixation and healthy volunteers. INTERVENTIONS: Fracture supernatants and peripheral plasma were collected during open fracture fixation. Volunteer mononuclear cells were used as effector (NKC) sources. Mononuclear cells were preincubated with fracture supernatants, paired peripheral plasma, or normal plasma under various conditions. MAIN OUTCOME MEASURES: Natural killer cell lysis of K562 target cells was assessed by chromium 51 release. RESULTS: Fracture supernatants suppressed NKC function more rapidly than peripheral plasma. Fracture supernatants from 1 to 4 days after injury were most suppressive. Inactivation of complement and reactive oxygen species failed to restore lysis. Neutralizing antibodies to interleukin 4 and interleukin 10 further suppressed lysis. Antibodies to transforming growth factor beta1 failed to restore lysis. The addition of interferon gamma did not restore lysis but the addition of interleukin 12 did. CONCLUSIONS: Fracture supernatants and peripheral plasma from patients with fractures suppress NKCs. The responsible mediators may be concentrated in fracture/soft tissue injuries. Responses to manipulation of the cytokine environment suggest that fracture cytokines may impair cooperation between NKCs and accessory cells.

Adult↗

Incidental depiction of cigarettes and smoking in Australian magazines, 1990-1993.

The study aimed to assess evidence of any increase in apparently incidental photographic depictions of cigarettes or smoking in Australian magazines following the ban on tobacco advertising in the print media introduced in January 1991. We examined 27,704 pages in 20 Australian magazines popular among young people or aimed at low socioeconomic groups during three sample periods in 1990 (before the ban), 1991 and 1993 (after the ban). All photographs showing cigarettes or smoking were counted and a smoking rate per page was calculated. When all 20 magazines were combined, there was a 75 per cent increase in the rate of photographs of smoking per page from 1990 (six months before the ban) to 1991 (six months after the ban). However, there was a reduction of 36 per cent in the rate of smoking photographs per page between 1991 and 1993 (18 months after the ban) and a nonsignificant increase of 12 per cent across the three sample periods. Photographs of smoking are infrequent in Australian magazines (mean: 1:147 pages, range: 1:17 pages to zero). There appears to be a commendable constraint by many Australian magazine editors in limiting the publication of photographs that show smoking or cigarettes. Some magazines never show smoking, indicating that a goal of total absence of photographs of smoking is achievable. Some magazines have room for improvement.

Advertising↗

A model to study the transport function of the intestinal viscera during peritoneal dialysis.

A preparation was developed to selectively study the transport properties of the intestinal viscera. A rat was positioned prone on a 100-mL beaker (reservoir) and the viscera were completely immersed and suspended without tension in dialysate solution maintained at 37 degrees C. A volume of 11.6 +/- 0.9 mL was ultrafiltered over a period of 180 minutes with a 5.6% glucose dialysate solution (n = 5) versus 0.5 +/- 0.5 mL for a 1.5% hydrous glucose dialysate solution (n = 4). The suspended viscera were able to absorb glucose from the beaker. The viscera absorbed more glucose when they were suspended in a higher glucose concentration: 922 +/- 46 mg for the 5.6% solution (54% of the initial glucose present) and 151 +/- 13 mg for the 1.5% solution (39% of the initial glucose present). Protein was found to leak from the viscera, and the amount found in dialysate was not related to the concentration of glucose used as dialysate (75 +/- 25 mg for the 5.6% solution and 41 +/- 3 mg for the 1.5% solution; P = NS). Studies also demonstrated transport from blood into the dialysate and that transport into dialysate could be altered by altering visceral blood supply (intravenous infusion of antidiuretic hormone, 800 micrograms/hr). Urea and glucose clearances were greater in the absence of antidiuretic hormone, whereas creatinine and inulin clearances were not different in both groups. This model offers the potential to selectively study the responses of the visceral peritoneum.

Animals↗

An analysis of ultrafiltration during acute peritoneal dialysis in rats.

Transport into and from the peritoneal cavity is effected through separate membranes. Peritoneal function is the sum of the contributions of these membranes. The peritoneal dialysis membranes are defined as intestinal viscera and mesentery, parietal lining membrane, and liver and diaphragm. The present study was undertaken to determine which of these membranes participate in ultrafiltration during peritoneal dialysis. Studies were performed in rats using a hypertonic (1200 mOsm/L) dialysate solution containing 5.6% glucose, 2.8% amino acid, and electrolytes. Both intact and eviscerated rats were studied. The experiments were repeated in animals whose diaphragms were fibrotic and densely adherent to liver. Preparation of the diaphragm did not impact upon ultrafiltration. Ultrafiltration in controls (54 vs. 56 ml with and without a fibrotic diaphragm respectively) and in eviscerated groups (44 vs. 45 ml with and without a fibrotic diaphragm respectively) were not significantly different. However, controls had significantly more ultrafiltration than did eviscerated animals (p less than 0.01). The parietal viscera accounted for 56-59% of the ultrafiltration. This study demonstrates that both the intestinal viscera and parietal walls participate in ultrafiltration.

Animals↗

Enhancement of peritoneal transport in rats by disrupting stagnant fluid films.

Dialysate comes into contact with the active membrane and remains in contact until the fluid is refreshed. This design exaggerates stagnant fluid films. Dialysis rate studies were done to evaluate transport when stagnant fluid films were disrupted. Following anesthesia, 30 mL of commercial 1.5% glucose dialysate containing 100 mg% urea and 25 mg% inulin warmed to 37.5 C were instilled. Dialysate was sampled at 5, 15, 30, 45, and 60 min after instillation. Experimental rats were vibrated at 25 Hz throughout the study. Diffusive mass-transfer coefficients (MTC mL/min 1000 cm2) were calculated, and control and vibrated group means were tested for differences using Student's t-test. The mean MTC values for control (n = 10) and vibrated groups (n = 12), respectively, were: urea 0.8 +/- 0.04, 1.4 +/- 0.2, p less than 0.01; glucose 0.4 +/- 0.03, 0.6 +/- 0.03, p less than 0.01; insulin 0.2 +/- 0.01, 0.2 +/- 0.01, p = NS. Disrupting stagnant fluid films augments peritoneal transport.

Animals↗

Measurements of peritoneal surface area in man and rat.

The peritoneal dialysis system is composed of unique membranes. To better understand the contribution of these membranes to peritoneal transport, the peritoneal surface areas were measured in human subjects and rats.

Animals↗

Systems of membranes involved in peritoneal dialysis.

To evaluate whether the viscera contribute to the system of membranes used in peritoneal dialysis, dialysis rate studies were performed comparing control rats (n = 9, mean peritoneal area 509 +/- 38 cm2) with eviscerated rats (n = 12, mean peritoneal area 200 +/- 123 cm2). The mass transfer coefficient (MTC) and absorption from the peritoneal cavity were calculated for urea, creatinine, and inulin, which had been added to commercially available 1.5% hydrous dextrose dialysate. Rates of peritoneal blood flow to the peritoneal membranes remaining after evisceration were similar for both groups. Urea, creatinine, glucose, and inulin were used as markers to compare control and eviscerated animals. The MTC results were (in milliliters per minute, mean +/- SEM): urea 3.0 +/- 0.3, 4.1 +/- 0.5 (P less than 0.01); creatinine 1.4 +/- 0.2, 2.0 +/- 0.2 (P less than 0.05); glucose 1.2 +/- 0.3, 1.7 +/- 0.2 (P less than 0.09); inulin 0.3 +/- 0.02, 0.6 +/- 0.1 (P less than 0.01); and MTC inulin/MTC urea 0.16 +/- 0.01, 0.14 +/- 0.01. Absorption of urea, creatinine, glucose, and inulin from the peritoneal cavity was only 10% to 23% greater among control animals. Whether the results were caused by nonparticipation of the intestinal viscera or other mechanisms, such as improved contact between dialysate and membrane, awaits further study.

Animals↗

The importance of the abdominal viscera to peritoneal transport during peritoneal dialysis in the dog.

The authors sought to evaluate the dialyzing surfaces important for peritoneal dialysis. They reasoned that the most definitive way to evaluate whether any of the gut and associated membranes contributed to transport was to see if transport changed when they were removed. Paired studies measuring rates of peritoneal uptake of glucose, urea, and inulin were carried out in dogs. In the morning, the animals were tested with all peritoneal membranes intact. In the afternoon, the studies were repeated after evisceration. The mass transfer coefficients (MTC ml/min)--glucose (viscera 4.4 +/- 0.7, no viscera 4.9 +/- 0.3)--urea (viscera 16.8 +/- 2.4, no viscera 13.8 +/- 1.0);--inulin (viscera 1.6 +/- 0.6, no viscera 2.2 +/- 0.7) were not changed nor was the amount of mass absorbed significantly different. MTC and peritoneal absorption were unaffected by omentectomy, mesenterectomy, or evisceration. Whether these results were due to nonparticipation of these structures in peritoneal transport or other mechanisms await further studies.

Absorption↗

Evaluation of a peritoneal dialysis solution containing polymer.

Glucose is used in peritoneal dialysate to produce the gradient for ultrafiltration. The peritoneal membrane's low reflection coefficient for glucose imposes a demand for high transmembrane concentrations, perhaps adding unwanted body burden of glucose. A polymer with a lower permeation rate used as an osmotic agent would circumvent this. We evaluated the mass transfer coefficient (mtc), T1/2 disappearance from the peritoneal cavity and ultrafiltration capabilities of a 900 dalton (Mn) starch derived polymer. We compared an 8% (455 mOsm/L) and a 10% (484 mOsm/L) polymer (Pol) solution to available dialysate solutions containing 2.5% (399 mOsm/L) and 4.25% (491 mOsm/L) X glucose (Glc). The dialysate compositions were otherwise similar. Using a randomized complete block design, 5 anephric dogs maintained on chronic peritoneal dialysis were studied. The mtc (ml/min) was greater for the glucose than the polymer solutions (p less than 0.05): 2.5%-13 and 4.25%-14 vs 8%-5 and 10%-6. The T1/2 disappearance (min) was also greater (p less than 0.05): 2.5% Glc-112 and 4.25% Glc-111 vs 8% Pol-281 and 10% Pol-252. Over a 180 min. period the 2.5% glucose solution generated the least volume of ultrafiltrate (ml, p less than 0.05): 2.5% Glc-113 and 4.25% Glc-589 vs 8% Pol-640; 10% Pol-912. We conclude that the lower permeation rate of the polymer yields ultrafiltration at a lower dialysate osmolality. A polymer solution may be a feasible alternative to glucose.

Animals↗

Substitution of a starch polymer for glucose in peritoneal dialysis.

We compared a starch-derived polymer (molecular weight = 900) as the osmotically active agent in peritoneal dialysate (3 and 6% solutions) to results obtained with commercially available glucose dialysate (1.5 and 4.25%). 12 dogs were dialyzed with glucose for 7 days, and 9 received the polymer for 5 days. For dialysate exchanges with an intraperitoneal residence of 240 min the 1.5 and 3% solutions generated similar volumes of ultrafiltrate as did the 4.25 and 6% solutions. However, for exchanges of 960 min the 1.5% dialysate was significantly reabsorbed when compared to the other dialysate concentrations. The serum polymer concentration increased with continued dialysis. The rate of transfer from dialysate to serum in man must still be determined. The lower diffusivity of the polymer will certainly be evidenced. For certain clinical applications where diminished ultrafiltration occurs, the polymer may be of benefit to man.

Animals↗

A model of long-term peritoneal dialysis in the dog.

We describe two preparations for chronic peritoneal dialysis in the dog. In one group uremia was induced by nephrectomy and in the other by ureteral ligation. Peritoneal access was obtained using the Ash disc column catheter. Survival of the animals ranged from 27 to 83 days. Using a dialysis schedule similar in concept to continuous ambulatory peritoneal dialysis in man we found that dialysate-induced ultrafiltration, equilibration of solute between serum and dialysate, as well as protein losses into dialysate approximated values found in patients undergoing continuous ambulatory peritoneal dialysis. Careful attention to detail is required in order to maintain these animals. The advantages of these models are their technical simplicity and prolonged survival making intermediate range studies feasible. Disadvantages include anemia, seen in the anephric animals, technical problems with the disc column catheter, the need for maintenance of strict aseptic technique when performing dialysis exchanges, and difficulties maintaining adequate nutrition.

Animals↗

Chronic hemodialysis in the anephric goat.

The Spanish brush goat (Capra hiricus) was studied as an animal model for the anephric state. This rugged animal has a hardy appetite and offers ready blood access for dialysis and sampling. BUN, plasma creatinine and potassium could be brought to normal values by daily hemodialysis. Continual weight loss, severe anemia and some tendency for the development of hypertension were observed despite dialysis. Maintenance of a healthy rumen proved a continual challenge but was possible by hyperalimentation and vigorous dialysis immediately postnephrectomy.

Animals↗

Intraperitoneal feeding.

This study evaluated the peritoneal cavity as the sole route for alimentation in 300 g growing rats. Initial studies demonstrated that a solution of high osmolality was required to provide sufficient calories. A nutrient solution was formulated by mixing 20% glucose with electrolytes (10 ml) and 8.5% amino acids with electrolytes (20 ml). Instilling 30 ml of nutrient solution induced an IP volume of 60 ml, which was absorbed in 24 hours. Rats were studied in four groups for 7 days. One group received nutrient solution IP (n = 10); a second group received the same amount PO (n = 10); the third group received electrolytes IP (n = 10); and a fourth group was fed rat chow PO (n = 10). Rats fed this nutrient solution (IP and PO) were acclimatized by administering one third of their required nutrient the first 4 days. On the next 3 days they received two thirds of their required nutrient. Both groups fed nutrient solution (IP and PO) lost 23% body weight. Electrolyte and rat chow fed groups lost 26% and gained 8% of body weight, respectively. Due to the high osmolality (1200 mOsm/L) of this nutrient solution, sufficient food could not be delivered via the peritoneal cavity to adequately feed growing rats. Studies were then initiated to formulate another nutrient solution that contained lipids. This solution (678 mOms/L) contained 20% glucose with electrolytes (10 mls), 8.5% amino acids with electrolytes (20 ml), and 10% lipids without electrolytes (30 ml). Glucose and amino acids contained the same electrolyte concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗