PubMed Health⌕ Search

Biomedical subjects

R W Godfrey

Publications and source records attributed to R W Godfrey.

At least 37 records · Page 2Linked to original sources

Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma. A quantitative light and electron microscopic study.

We have obtained airway mucosal biopsies by fiberoptic bronchoscopy for light and electron microscopic analysis of three distinct airway levels of the left lung in three subject groups. Group A: 11 subjects with mild atopic asthma (mean age, 29 yr; %FEV1, 89 to 116%; mean PC20 histamine, 2.42 mg/ml), each biopsied twice, one prior to 4 wk of treatment with either inhaled terbutaline (250 micrograms, two puffs four times daily; n = 5) or inhaled budesonide (200 micrograms, one puff twice daily; n = 6) followed by a second biopsy to allow determination of the effects of treatment. Group B: 10 subjects with severe asthma receiving long-term (average, 3.7 yr) corticosteroid treatment were biopsied once only (mean age, 28 yr; %FEV1, 86 to 129%; mean PC20 histamine, 1.85 mg/ml). Group C: 12 normal healthy control subjects (mean age, 35 yr; %FEV1, 92 to 135%; PC20 histamine greater than 16 mg/ml) biopsied once. By light microscopy of plastic-embedded sections, Group A asthmatics had an increased cellular infiltrate when compared with either the healthy control group or the Group B asthmatics (p less than 0.05). Both asthma groups had a thickening of basement membrane reticular collagen compared with the healthy control group (p less than 0.01). Compared with the control group, there was an increase in the percentage of the total cells that were mast cells (p less than 0.01) and eosinophils (p less than 0.05) in Group A and of eosinophils (p less than 0.01) and histiocytes (p less than 0.01) in Group B. The results of cell counts by electron microscopy largely supported these findings, and, in addition, they demonstrated an increased frequency of foci of free eosinophil granules and decreased numbers of neutrophils (p less than 0.01). By light microscopy, budesonide reduced the percentage of mast cells and eosinophils (p less than 0.05). But for the percentage of lymphocytes, which increased (p less than 0.05), terbutaline was without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Freeze-fracture morphology and quantification of human bronchial epithelial tight junctions.

A comprehensive investigation of the morphology of human airway epithelial tight junctions was carried out by freeze-fracture electron microscopy using quantitative methods designed to analyze a range of junctional characteristics. Extrapulmonary bronchi that appeared grossly normal were taken at sites distant from tumor in lungs resected for pulmonary carcinoma. The absence of cellular atypia in the samples was confirmed by histology. Airway levels I (main bronchus; n = 7 subjects) and II (lobar bronchus; n = 5 subjects) were compared with respect to junctional depth, strand number, and junctional complexity. Junctional complexity was assessed by frequency of strand interconnection and numbers of strands per interconnection. Comparisons between airway levels I and II for these parameters showed that there were no significant differences in strand number or junctional complexity between the two airway levels. However, junctional depth was slightly but significantly reduced at level II compared with level I (P less than 0.01). The arrangement of strands varied considerably from one junction to the next, irrespective of the cell types involved. "Parallel" and "network" patterns of junctions were observed; the existence of gradations between these two patterns indicated that they represent opposite extremes of a single junctional form rather than distinct categories of junction. These results have allowed us to establish a data pool for normal human bronchi from which the structure of epithelial cell junctions in bronchial diseases can be compared.

Bronchi↗

Effect of implanting bull calves with testosterone propionate, dihydrotestosterone propionate or oestradiol-17 beta prepubertally on the pituitary-testicular axis and on postpubertal social and sexual behaviour.

Twelve non-implanted crossbred bull calves served as controls and 30 crossbred bull calves (10/treatment) were implanted for 82 days, beginning at 34 days of age, to determine the influence of testosterone propionate (TP), dihydrotestosterone propionate (DHTP) and oestradiol-17 beta (E2) on prepubertal and pubertal pituitary-testicular function and on postpubertal social and sexual behaviour. Compared with control bulls, concentrations of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and inhibin concentrations were suppressed (P less than 0.01) in all implanted bulls. Testosterone (T) concentration increased (P less than 0.001) in TP-implanted, but decreased (P less than 0.01) in DHTP and E2 bulls during the implant period. LH response to gonadotrophin-releasing hormone (GnRH) challenge during the implant period (2.5 months of age) was less (P less than 0.01) in TP, E2 and DHTP bulls than in controls. A small but significant T response to GnRH occurred in control bulls at 2.5 months of age. LH and T responses to GnRH challenge at 7 months of age (100 days after implant removal) was similar (P greater than 0.20) in control and implanted bulls. Steroid implants administered prepubertally had no effect (P greater than 0.10) on postpubertal social and sexual behaviours, including number of flehmen responses, abortive mounts, services and competitive order score. Body weight did not differ (P greater than 0.10) between treatment groups, but testis size was reduced (P less than 0.01) during the implant period and up to 10 months of age in treated bulls compared with controls. Testes remained smaller in E2-treated bulls up to the end of the study (23 months of age), but daily sperm production and epididymal weight did not differ (P greater than 0.10) between treatment groups at slaughter. Control bulls reached puberty earlier (P less than 0.01; 270 +/- 11 days of age) than did TP (302 +/- 11 days), DHTP (309 +/- 11 days) or E2 (327 +/- 11 days) bulls. Although puberty was delayed in all implant groups, there was no difference in scrotal circumference at puberty (average 28.4 +/- 0.4 cm) between treatment groups. Our findings indicate that TP, DHTP and E2 implants administered prepubertally result in acute suppression of serum LH, FSH and inhibin during the implant period and in post-implant suppression of testis size and delayed puberty in bulls. The lack of treatment effect on behaviour suggests that steroidal programming of sexual behaviour occurs before 1 month of age in bulls.

Animals↗

Effects of a new compound (Zy 15850A) on cigarette smoke-induced bronchitis in the rat.

The effect of 4H-4 phenylthieno-(3,2-C)-(1)-benzopyran-2-carboxylate (Zy 15850A) on mucous cell hyperplasia was examined in vivo using a well established rat model of cigarette smoke-induced bronchitis. Zy 15850A was given by gavage (25 mg/kg body weight) to male rats before and after sub-acute exposure (i.e. daily for 14 days) to an atmosphere of cigarette smoke (CS). CS significantly increased the thickness of the epithelium at three of the four sites studied in the trachea and in both of the intrapulmonary levels examined. CS increased the number of epithelial mucous cells in all intrapulmonary airways and also increased the mass of submucosal gland present in the larynx and upper trachea. Zy 15850A completely inhibited CS-induced increases in epithelial thickness in the upper trachea and the two intrapulmonary airway levels studied, and tended to inhibit CS-induced epithelial mucous cell hyperplasia in all the six intrapulmonary airway levels examined, with statistically significant inhibition in two. Zy 15850A had no inhibitory effect of the CS-induced enlargement of laryngo-tracheal submucosal glands. We conclude that, in the rat, the predominant inhibitory effect of Zy 15850A is on CS-induced epithelial thickening with weaker inhibitory effects on mucous cell hyperplasia and enlargement of submucosal glands. Zy 15850A is less effective than other mucoregulatory drugs or antiinflammatory agents we have tested in the same bronchitic model.

Animals↗

Physiological responses of newborn Bos indicus and Bos indicus x Bos taurus calves after exposure to cold.

Brahman (n = 9) and 1/2 Simmental x 1/4 Brahman x 1/4 Hereford (n = 11) calves were utilized to determine the influence of exposure to cold on the physiology of the neonate. All calves were removed from their dams within 20 min of birth and prior to suckling. Calves were assigned randomly within breed to either a warm (W; 31 degrees C) or cold (C; 4 degrees C) environmental treatment group. Jugular blood samples were collected via indwelling catheters at 20-min intervals for 180 min. At 100 to 120 min of sampling, all calves were given 1.2 liters of colostrum from their dams via stomach tube. At 120 min, C calves were placed in the W environment. Calf vigor score (CVS) and rectal temperature were determined at each time blood was collected. Serum or plasma was analyzed for glucose (GLU), lactate (LAC), blood urea nitrogen (BUN), hemoglobin (HEM), triglyceride (TRG), triiodothyronine (T3), thyroxine (T4), insulin (INS), cortisol (CORT) and nonesterified fatty acid (NEFA) concentration. Rectal temperature was lower (P less than .01) in C Brahman than in W Brahman and C or W crossbred calves. Crossbred calves had higher (P less than .01) CVS than Brahman calves. Calves in W had lower (P less than .01) GLU than C calves. Brahman calves had higher GLU, LAC, BUN, TRG, T3, T4 and CORT (P less than .05) than crossbred calves. The C Brahman calves had the highest (P less than .05) TRG, CORT, T3 and T4 of all groups. Concentration of NEFA were higher (P less than .01) in C than in W calves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of season and location on semen quality and serum concentrations of luteinizing hormone and testosterone in Brahman and Hereford bulls.

Hereford bulls from Montana (MH; n = 15) and Nebraska (NH; n = 15) and Brahman bulls from Texas (BB; n = 18) were relocated to one of three locations (LOC): Montana (MT), Nebraska (NE) or Texas (TX). All bulls were pubertal at the time of relocation in late May 1984. Semen was collected by electroejaculation within 1 wk after relocation and at 90-d intervals beginning in November 1984 through early February 1986. Bulls were given a GnRH challenge (200 micrograms i.m.) during the same week of semen collections. Bulls also were bled for 8 h at 20-min intervals in the fall of 1984 and the spring and fall of 1985 to determine endogenous concentrations of LH and testosterone. Season affected sperm concentration in all breeds (P less than .05) with decreases during the winter in BB and during the summer in NH and MH bulls. Brahman bulls had lower percentage of live cells (LIVE) than NH and MH bulls did (P less than .0001). Brahman bulls decreased in LIVE during the winter (P less than .001). Area under the LH curve after GnRH was lower (P less than .005) in BB than in MH and NH. Brahman bulls in MT had greater (P less than .02) area under the LH curve and lower (P less than .06) area under the testosterone curve than did BB in TX or NE during the winter. There was no seasonal fluctuation in LH or testosterone response to GnRH in NH or MH bulls at any LOC. Area under the endogenous LH curve was lowest (P less than .04) in BB. Basal endogenous testosterone concentration was greater (P less than .03) in NH than in MH or BB. Area under the endogenous testosterone curve was lower (P less than .03) in MH than in NH or BB. These results indicate that BB exhibit seasonal fluctuations in semen quality. This was not so apparent in semen quality traits of Hereford bulls. There also was a seasonal influence in BB on both endogenous testosterone and GnRH-stimulated LH and testosterone concentrations. Compared with Hereford bulls, Brahman bulls had lower endogenous and GnRH-stimulated concentrations of LH.

Animals↗

Influence of dietary energy intake on prepubertal development of Brahman bulls.

Twelve Brahman bulls (paired by sire, weight and age) were assigned randomly and limit fed to gain either .10 to .25 (moderate gain; MG) or .75 to 1.0 (high gain: HG) kg.hd-1.d-1 to examine the effect of dietary energy on onset of puberty. Hip height (HH), scrotal circumference (SC) and serum samples (20 min for 6 h) were obtained at four times (AGE): 0, 56 and 112 d on feed and after appearance of first motile spermatozoa (FS) in the ejaculate of HG bull of the pair. At FS both bulls of a pair were slaughtered, reproductive tissues were collected and in vitro GnRH release from the median eminence (ME) was measured. Increases in BW, HH and SC were greater (P less than .05) in HG bulls. Basal ME GnRH secretion was greater (P less than .05) in HG bulls. Serum LH concentrations were unchanged by energy level (P greater than .10) but increased (P less than .01) with increasing AGE. AGE and energy level increased (P less than .01) basal, mean and total serum testosterone (T) and these two factors acted synergistically (P less than .01). Height and amplitude of T pulses were increased by energy level (P less than .003) and AGE (P less than .002). Testicular T (P less than .08) and development (P less than .05) were increased in HG bulls. Growth hormone peak height and amplitude concentrations following feeding increased with AGE (P less than .06) but were not altered (P greater than .10) by energy level. Serum triglycerides (P less than .03) and BUN (P less than .003) increased with increasing AGE (P greater than .01). These data indicate that dietary energy level influences onset of puberty most directly at the testicular level.

Animals↗

Effect of location and season on body and testicular growth in Brahman and Hereford bulls.

To determine the effects of location and season on growth of bulls, Hereford bulls from Montana (MH; n = 15) and Nebraska (NH; n = 15) and Brahman bulls from Texas and Louisiana (BB; n = 18) were moved to three locations: Montana (MT), Nebraska (NE) or Texas (TX). Each location received 5 NH, 5 MH and 6 BB. Control bulls (not relocated) were maintained at each location. All bulls were pubertal at the time of relocation in May 1984. At 28-d intervals, body weight, hip height, testis length and scrotal circumference were recorded for each bull for 22 mo after relocation. Paired testes volume (PTV) was calculated. Among Hereford bulls, body weights were similar (P greater than .10) in all control and relocated bulls by the end of the study, except that MH bulls moved to TX had lower body weights (P less than .01). Brahman bulls moved to northern locations had dramatically reduced body weights, compared to control Brahmans kept in TX; body weight of Brahman bulls in MT remained lower (P less than .01) at the end of the study. Brahman bulls in NE and MT had smaller scrotal circumference and PTV (P less than .01) than did control Brahmans in TX during the 1st yr after relocation. Relocated BB exhibited marked seasonal fluctuations in testis size, with increases during the summer and decreases during the winter (P less than .01); seasonal changes were not apparent in control Brahmans in TX. These results indicate that moving Brahman bulls to northern environments reduced body weight gain and caused dramatic seasonal changes in testis size; these effects were more pronounced in Brahman bulls moved to the most northern location.

Animals↗

Influence of single or multiple sires and serving capacity on mating behavior of beef bulls.

A study was conducted to determine the effect of serving capacity (SC) on sexual behavior of yearling bulls during single- and double-sire pasture matings. Approximately 60 crossbred virgin bulls were subjected to 3 SC tests, and 20 bulls were selected that were similar in age, BW, testes size and semen quality. Ten bulls were high SC (greater than or equal to 3 services/test) and 10 bulls were low SC (less than or equal to 2 services/test). Competitive order among the 20 bulls also was determined. Single-sire tests were conducted with 15 intact estrual heifers and 1 bull in a pasture for 6 h. Double-sire tests were conducted with 30 estrus-induced, ovariectomized heifers and 1 high SC and 1 low SC bull of approximately equal competitive order for 6 h. Bulls in double-sire tests had more (P less than .007) mounts than those in single-sire tests. High SC bulls in double-sire tests served more heifers (P less than .04) and had more services (P less than .04) than any other SC group and test type. There was no difference (P greater than .10) in the number of mounts or services between high and low SC bulls in single-sire tests. High SC bulls had a greater (P less than .002) percentage of mounts that culminated in a service that did low SC bulls. Conception rate was not different (P greater than .10) between SC groups in single-sire tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of zeranol on sexual development of crossbred bulls.

Three groups of 1/2 Simmental X 1/4 Brahman X 1/4 Hereford bull calves were used during two different years to study effects of zeranol on sexual development. At 154 d of age, half the calves were implanted with 36 mg zeranol and half, not implanted, served as controls. Implanted calves were reimplanted at 90-d intervals throughout the trial (9 mo) each year. Trial 1 was conducted with 24 calves and Trial 2 was conducted the following year with 10 bulls. Twenty-four days after weaning (200 d of age) and at 28-d intervals thereafter, bulls in drylot in Trial 1 were weighted, scrotal circumference (SC) was measured and an ejaculate of semen was collected by electroejaculation to determine puberty. At these times, bulls were given 200 micrograms of GnRH i.m. and blood was collected at 0, 1, 2, 3, 4 and 5 h after GnRH. Serum concentrations of LH and testosterone (TEST) were determined. At slaughter, testis weight, length and circumference and pubertal status were recorded. Bulls implanted with zeranol had smaller SC than control bulls during the entire 9-mo period (P less than .0001). More control bulls reached puberty than did implanted bulls (82.4 vs 23.5%, respectively; P less than .001). Control bulls had larger testis measurements at slaughter (P less than .0001). Implants did not alter total weight gain or ADG (P greater than .10).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of luteolysis and estrous synchronization by a prostaglandin analog (Luprostiol) in Brahman cows and heifers.

A trial was conducted to evaluate the ability of a prostaglandin analog, Luprostiol (LP), to synchronize estrus in Brahman cows and heifers. Animals were injected with either 0, 3.75, 7.5, 15 or 30 mg LP or 500 micrograms cloprostenol (CLP) on d 8 or 9 after estrus (d 0). All concentrations of LP (greater than 0 mg) and CLP caused luteolysis in cows and heifers, as indicated by a decline (P less than .01) in serum progesterone concentration after injection. Animals receiving 0 or 3.75 mg LP had a longer (P less than .04) interval to estrus after injection than did animals in other treatment groups. The proportion of animals exhibiting estrus by 120 h after injection was influenced by dose of LP (P less than .0001; 0, 3.75 mg less than 7.5, 15 and 30 mg and CLP) but not by age. Cows had a lower (P less than .01) progesterone concentration than heifers on d 10, 11 and 12 after LP-induced estrus. Progesterone concentration was lowest (P less than .01) on d 10, 11 and 12 after LP-induced estrus in cows given 15 mg LP or CLP. First-service conception rate was similar between cows and heifers, but it was lower (P less than .01) in animals given 15 or 30 mg LP. Both estrogen and LH concentrations were decreased (P less than .01) at the time of estrus by the 15 and 30 mg of LP. Luprostiol can cause luteolysis and estrous synchrony in Brahman cattle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vasopressin induces V1 receptors to activate phosphatidylinositol- and phosphatidylcholine-specific phospholipase C and stimulates the release of arachidonic acid by at least two pathways in the smooth muscle cell line, A-10.

The rat thoracic aortic smooth muscle cell line, A-10, expresses vasopressin receptors of the V1 subtype. Vasopressin treatment of these cells stimulated the release of arachidonic acid and the formation of diacylglycerol and phosphocholine. These responses to vasopressin were inhibited by the V1-specific antagonist SK&F 100273, indicating that these were receptor-mediated phenomena. The mechanisms by which V1 receptors mediate arachidonic acid release appeared to be unaffected by cycloheximide or actinomycin D, suggesting that the release is independent of protein and RNA synthesis. The V1 receptors also appeared to be coupled to a phospholipase C which can hydrolyze phosphatidylcholine, a possible source of the released arachidonic acid. Phosphocholine and diacylglycerol were also generated. The release of arachidonic acid, phosphocholine, or diacylglycerol was not affected by prior treatment of the cells with pertussis toxin (islet-activating protein). Thus, the release of these second messengers is not mediated by the guanine nucleotide-binding protein Gi or other pertussis toxin-sensitive substrates. We conclude that V1 receptors induce the release of arachidonic acid and the formation of diacylglycerol and phosphocholine via the activation of both a phosphatidylinositol- and phosphatidylcholine-specific phospholipase C.

Animals↗

Interleukin-1 stimulation of phospholipase activity in rat synovial fibroblasts. Possible regulation by cyclooxygenase products.

Tritiated arachidonic acid (3H-AA)-labeled rat synovial fibroblasts stimulated with human recombinant interleukin-1 beta (rIL-1 beta) released incorporated radiolabel in a time-dependent and dose-dependent manner, with labeled prostaglandins representing 29% of the released radiolabel. Treatment of the cells with dibutyryl cAMP or prostaglandin E2 enhanced both spontaneous and rIL-1 beta-induced 3H-AA release; treatment with indomethacin or naproxen inhibited the response. The effects of these cyclooxygenase inhibitors on 3H-AA release were not reversed by the addition of prostaglandin E2. The activities of phospholipase A, phospholipase C, and diglyceride lipase were detected in the homogenates of rat synovial fibroblasts. Pretreatment of synovial cells with rIL-1 beta resulted in a threefold stimulation of phospholipase A activity and a slight increase in phospholipase C activity in cell homogenates. These data show that rIL-1 beta stimulates phospholipase activities in rat synovial fibroblasts and that at least one of these activities may be regulated by either prostaglandins or cAMP.

Animals↗

FMLP-induced arachidonic acid release, phospholipid metabolism, and calcium mobilization in human monocytes. Regulation by cyclic AMP.

Radiolabeled human peripheral blood monocytes released [3H]arachidonic acid upon challenge with the calcium ionophore A23187 (10 microM), or f-Met-Leu-Phe (FMLP, 1 microM). Chromatographic analysis of [3H]arachidonic acid labeled phospholipids showed that stimulation by FMLP reduced the amount of labeled phosphatidylcholine exclusively. Treatment of the monocytes with 10(-3) M dibutyryl cyclic AMP (d-cAMP) or 5 X 10(-4) M isobutylmethylxanthine (IBMX) substantially inhibited [3H]arachidonic acid release (30%) and depletion from labeled phosphatidylcholine (PC) in FMLP--but not calcium ionophore--stimulated cells. Using the fluorescent probe Indo-1, the FMLP-induced cytosolic calcium increase was unaffected by 10(-3) M dibutyryl cyclic AMP. The results suggest that FMLP-stimulated phospholipase activity is regulated by cyclic AMP, but not by depressing receptor-medicated increases in cytoplasmic free calcium.

1-Methyl-3-isobutylxanthine↗

Interleukin-1 and tumor necrosis factor are not synergistic for human synovial fibroblast PLA2 activation and PGE2 production.

Patterns of arachidonic acid release and metabolism were altered in human synovial fibroblasts following exposure to cytokines. Recombinant interleukin-1 induced an approximate 3-fold increase in [3H]-AA release, a 7-fold increase in PGE2 production and a 2-fold increase in PLA2 activity in human synovial fibroblasts. Recombinant tumor necrosis factor induced similar responses, however, the magnitude was less than that mediated by interleukin-1. A combination of the two cytokines had an additive effect on [3H]-AA release and PLA2 activity while PGE2 production was similar to that detected using interleukin-1 alone. [3H]-AA, was released in substantial amounts when sodium fluoride was used as a stimulus but PGE2 was not. These data show that tumor necrosis factor and interleukin-1 can both activate synovial cell PLA2 and induce generation of PGE2, but act in an additive rather than a synergistic fashion. Furthermore, the data show that PGE2 production is not always concordant with [3H]-AA release, suggesting that appropriate enzyme(s) must be activated.

Arachidonic Acid↗

The effect of using the Breeding Soundness Evaluation as a selection criterion for Santa Gertrudis bulls on bulls in subsequent generations.

Results of Breeding Soundness Evaluations (BSE) used to select Santa Gertrudis bulls over a 10-yr period were analyzed in retrospect to determine the effect on bulls in subsequent generations. Bulls were tested at three ages: 16 mo (n = 1,936), 20 mo (n = 3,111) and at maturity (> or = 24 mo, n = 3,814). Scrotal circumference (SC) and sperm motility and morphology were evaluated. Sixteen-mo-old bulls were required to have an SC > or = 30 cm to be tested. During 1977 to 1980, 20-mo-old bulls with an SC < 30 cm were culled, and the minimum SC was increased to 32 cm during 1981 to 1986. Mature bulls during this period were required to have an SC > or = 35 cm to be tested. A BSE < 60 was considered a failing score, and bulls were culled at this level. There was a positive correlation between SC and sperm motility and SC and sperm morphology in 16-mo-old and 20-mo-old but not in mature bulls (P < 0.0001). The percentage of bulls passing the BSE was positively correlated with SC at all ages (P < 0.0001), and the passing rate increased over the years (P < 0.0001). Scrotal circumference increased over the years in bulls that passed the BSE (P < 0.0001). This increase with years was not as apparent in the semen quality traits measured. By using the BSE and a minimum SC to select prospective herd sires, the proportion of bulls passing the BSE is expected to increase in subsequent generations. Santa Gertrudis bulls can be reliably selected for use as herd sires at 16 mo of age.

Journal Article↗

Oral N-acetylcysteine speeds reversal of cigarette smoke-induced mucous cell hyperplasia in the rat.

We set out to determine whether or not the "mucolytic" drug N-acetylcysteine would speed the reversal of cigarette smoke-induced secretory-cell hyperplasia to normal, similar to that found previously for two nonsteroidal antiinflammatory drugs. Cigarette smoke alone significantly (p less than 0.01) increased the number of secretory cells in seven out of eight airway levels studied and maintained a significant increase in five of the levels at least 3 weeks after cessation of exposure. Treatment of rats with N-acetylcysteine, as 1% of their drinking water during the recovery period, reduced the time taken for secretory cell number to return to normal to between 4 days and 3 weeks, depending on airway level.

Acetylcysteine↗

Recombinant tumor necrosis factor and interleukin-1 both stimulate human synovial cell arachidonic acid release and phospholipid metabolism.

Stimulation of [3H]-arachidonic acid labeled human synovial cells with 3.0 X 10(-10)M recombinant interleukin-1 or tumor necrosis factor resulted in the release of incorporated radiolabel (41.1% and 27.7% respectively). Analysis of [3H]-arachidonic acid labeled phospholipids showed that interleukin-1 and tumor necrosis factor diminished [3H]-arachidonic acid in phosphatidyl-choline phosphatidylserine and phosphatidylinositol. Treatment of [3H]-arachidonic acid labeled cells with 10(-3)M dibutyryl cyclic AMP or 10(-6)M PGE2 did not affect spontaneous or stimulated [3H] arachidonic acid release significantly. These data show that recombinant interleukin-1 and tumor necrosis factor stimulate human synovial cell phospholipase activity in a similar manner and that this activity is not affected significantly by agents that elevate cyclic AMP.

Arachidonic Acid↗