Biomedical subjects

W C Hubbard

Publications and source records attributed to W C Hubbard.

At least 37 records · Page 2Linked to original sources

PubMed1998

Morphology of single ganglion cells in the glaucomatous primate retina.

PURPOSE: To examine the degenerative effects that prolonged elevation of intraocular pressure (IOP), a risk factor commonly associated with glaucoma, has on the morphology of single ganglion cells in the primate retina. METHODS: The monkey model of glaucoma was combined with intracellular staining techniques using an isolated retina preparation. Midget and parasol cells from normal and glaucomatous eyes were labeled intracellularly, and their axons, somas, and dendritic fields were compared using confocal microscopy. RESULTS: In midget and parasol cells, the earliest signs of pressure-induced degeneration involved structural abnormalities associated with the dendritic arbor. Reductions in axon thickness appeared later, with changes in soma size occurring concomitantly or slightly later. Chronic elevation of IOP resulted in a significant decrease in the mean soma sizes of midget and parasol cells, but only parasol cells showed a significant reduction in dendritic field size and axon diameter. Comparisons of eyes with different levels of optic nerve damage, based on cup- disc ratio, showed that the axons and dendritic fields of parasol cells were significantly smaller at lower cup-disc ratios than were those of midget cells, suggesting a possible differential effect. CONCLUSIONS: In glaucoma, retinal ganglion cells undergo a pattern of degeneration that originates with the dendritic arbor and ends with shrinkage of the cell soma. Although this pattern of degeneration implies early functional deficits and retinal ganglion cell atrophy that occurs earlier than previously thought, based on ganglion cell loss alone, it also suggests a window of opportunity for effective neuroprotection.

Acridine Orange↗

PubMed1997

The Iowa Longitudinal Study of Recent Onset Psychosis: one-year follow-up of first episode patients.

The natural history of schizophrenia remains unclear. One strategy to further inform this area is to prospectively evaluate individuals early in the course of the disorder, both in terms of symptomatic and psychosocial/occupational functioning. Subjects were recruited into the study if they were in the midst of their first psychiatric hospitalization for a non-'organic' psychotic disorder. Subjects were extensively evaluated at index with semi-structured interviews including the Comprehensive Assessment of Symptoms and History (CASH), and followed at 6-month intervals. Data are presented on 35 subjects who were followed through 1 year. There was a significant improvement in overall symptomatology during index hospitalization, but this was accounted for primarily by improvement of positive symptoms, with negative symptoms remaining prominent. No further improvement was noted between discharge and 1-year follow-up in any of the symptom measures. Employment, interpersonal relationships, and sexual activity remained markedly impaired throughout the follow-up period. These data demonstrate that; (1) negative symptoms are prominent and stable early in the course of the disorder; (2) symptom severity at discharge from index hospitalization is predictive of symptom severity at 1 year; and (3) despite substantial overall symptomatic improvement during the first hospitalization, psychosocial and occupational functioning were found to be markedly impaired at 1-year follow-up.

Adult↗

PubMed1997

Preliminary characterization of diacylglycerol generation in human basophils: temporal relationship to histamine release and resolution of degranulation.

Purified human basophils were examined for changes in diacylglycerol levels to determine whether the transient nature of a N-formyl-methionyl-leucyl-phenylalanine (fMLP) -stimulated elevation in membrane protein kinase C (PKC) activity could be explained by the transient production of diacylglycerol (DAG). In preliminary experiments total DAG levels were measured by the DAG kinase assay. Although elevations followed stimulation with 1 microM fMLP (basal levels of 15 pmol/10(6) basophils vs. 45 pmol/10(6) basophils at the 3-min time point), there were no detectable changes in the first 60 s of the reaction. Histamine release is typically complete by 30-45 s. Measurement of inositol trisphosphate indicated a rapid increase by 5 s of 2.5 pmol/10(6) basophils. If DAG were produced at similar levels, the DAG kinase assay would not have detected the elevation. Consequently, fMLP-stimulated basophils were examined for changes in 1-stearoyl, 2-arachidonoyl, 3-sn-glycerol (SA-DAG) and 1-oleoyl, 2-arachidonoyl, 3-sn-glycerol by GC-NICIMS (negative ion chemical ionization mass spectroscopy). A 5-s elevation in these two species averaged 2 pmol/10(6) basophils, consistent with the inositol trisphosphate levels and occurring during the period of histamine release. However, a much more pronounced second phase to the SA-DAG response also occurred, mirroring the total DAG levels. This second phase of the DAG response, either total or SA-DAG, was transient on a time scale temporally coincident with the appearance and resolution of degranulation sacs as measured by fluorescence microscopy. These data suggest that there is selective generation of DAG species in the early reaction and the later appearance of DAG may be related to the formation and resolution of granule structures that follow the secretion of histamine.

Basophil Degranulation Test↗

PubMed1997

Intraocular pressure and outflow facility are unchanged following acute and chronic intracameral chondroitinase ABC and hyaluronidase in monkeys.

We determined the effect of chronic and acute loss of glycosaminoglycans from the aqueous outflow pathway on intraocular pressure (IOP) and outflow facility in the subhuman primate eye. For the study of the chronic effects of the GAGases, cynomolgus monkeys received intracameral injections of hyaluronidase (Streptomyces, 5 or 50 units, n=2) or chondroitinase ABC (0.05 or 0.25 units, n=2) biweekly for 8 months (4 months for each dose). IOP was measured at 3, 7, 10 and 14 days after each injection. Outflow facility (2-level constant pressure) was determined at 2, 4, 6, and 8 months. Monkeys were killed 6 days after the last injection. The changes in the distribution of hyaluronic acid and sulfated proteoglycans in the outflow pathway were examined using substrate-specific histochemical techniques. The acute effects of these enzymes on outflow facilities (30 min or 2 hr after enzyme) were determined in another group of animals (n=4 for each time enzyme-1). IOP and outflow facility were unchanged compared to controls (heat inactivated enzyme) at any time in the chronically or acutely treated monkeys. Hyaluronic acid staining was absent in the outflow pathways of eyes treated chronically with hyaluronidase compared with control eyes, while collagen-associated sulfated proteoglycans were decreased but not completely removed by the chronic chondroitinase ABC treatment. Chronic loss of these glycosaminoglycans from the trabecular meshwork does not appear to contribute to the IOP elevation and decrease in outflow facility that accompanies open-angle glaucoma. Most importantly, no increase in outflow facility was found with acute hyaluronidase or chondroitinase treatment.

Animals↗

PubMed1996

Quantitation of 1-stearoyl-2-arachidonoyl-sn-3-glycerol in human basophils via gas chromatography-negative ion chemical ionization mass spectrometry.

Investigation of the role of diacylglycerol molecular species in signal transduction in human basophils has been impeded by the lack of an assay method with adequate sensitivity and selectivity. Conversion of 1-stearoyl-2-arachidonoyl-sn-3-glycerol to the pentafluorobenzoyl ester conveys electron-capture properties to the diacylglycerol. The electron-capture derivative of the diacylglycerol is amenable to gas chromatographic analysis and undergoes limited fragmentation under negative ion mass spectrometric conditions with generation of an intense molecular anion at m/z 838. Monitoring m/z 838 for detection of 1-stearoyl-2-arachidonoyl-sn-3-glycerol and m/z 841 for detection of 1-trideuterostearoyl-3-arachidonoyl-sn-2-glycerol employed as the internal standard provides the analytical basis for GC-MS quantitation of the endogenous diacylglycerol in human basophils. The assay displays excellent reproducibility over a wide range of concentrations with variations < or = 10%. The GC-MS assay is highly selective and exquisitely sensitive with a detection limit of < or = 0.20 pg (approximately 30 fmol) for endogenous 1-stearoyl-2-arachidonoyl-sn-3-glycerol per injection. Approximately 400 fmol of the diacylglycerol were extracted from 10(5) stimulated human basophils.

Basophils↗

PubMed1996

Antigen-induced generation of lyso-phospholipids in human airways.

The goal of the current study was to examine the formation of phospholipids, 1-radyl-2-lysosn-glycero-phospholipids (lyso-PL) and 2-acetylated phospholipids (such as PAF) as well as mechanisms responsible for generating these phospholipids in bronchoalveolar lavage fluid (BAI.F) from allergic subjects challenged with antigen. Bronchoalveolar lavage was performed in normal and allergic subjects before, 5-30 min, 6 h, and 20 h after segmental antigen challenge via a wedged bronchoscope. Levels of 1-hexadecyl-2-lyso-phospholipids and 1-hexadecyl-2-acetyl-phospholipids were initially determined by negative ion chemical ionization gas chromatography/mass spectrometry (NICI-GC/MS). Antigen dramatically elevated quantities of 1-hexadecyl-2-lyso-phospholipids in allergic subjects 20 h after challenge when compared to non-allergic controls. In contrast, there was not a significant increase in levels of 1-hexadecyl-2-acetyl-phospholipids after antigen challenge. Closer examination of 1-radyl-2-lyso-sn-glycero-3-phosphocholine (GPC) revealed that 1-palmitoyl-2-lyso-GPC, 1-myristoyl-2-lyso-GPC and 1-hexadecyl-2-lyso-GPC were three major molecular species produced after antigen challenge. 1-palmitoyl-2-lyso-GPC increased sevenfold to levels of 222 +/- 75 ng/ml of BALF 20 h after antigen challenge. The elevated levels of lyso-PL correlated with levels of albumin used to assess plasma exudation induced by allergen challenge. In contrast, the time course of prostaglandin D2 (PGD2) or 9 alpha, 11 beta PGF2 (11 beta PGF2) formation did not correlate with lyso-PL generation. To examine the mechanism leading to lyso-phospholipid formation in antigen-challenged allergic subjects, secretory phospholipase A2 (PI.A2) and acetyl hydrolase activities were measured. There was a significant increase in PLA2 activity found in BALF of allergic subjects challenged with antigen when compared to saline controls. This activity was neutralized by an antibody directed against low molecular mass, (14 kD) human synovial PLA2 and dithiothreitol. Acetyl hydrolase activity also markedly increased in BALF obtained after antigen challenge. This study indicates that high levels of lyso-PLs are present in airways of allergic subjects challenged with antigen and provides evidence for two distinct mechanisms that could induce lyso-PL formation. Future studies will be necessary to determine the ramifications of these high levels of lyso-phospholipids on airway function.

Adult↗

PubMed1996

Mechanisms of prostanoid synthesis in human synovial cells: cytokine-peptide synergism.

Bradykinin (BK)2 and interleukin-1 (IL-1) interact synergistically to stimulate prostaglandin synthesis in human synovial fibroblast-like cells. The effect of BK is rapid and correlates with its capacity to elevate cytosolic levels of calcium ([Ca2+]i), while IL-1's effect is slow and s dependent upon de novo protein synthesis. The mechanism of this synergistic interaction was investigated. In the basal state, high levels of arachidonic acid (AA) were spontaneously released from synovial cells but near absent levels of cyclooxygenase activity prevented metabolism of AA to prostanoid. BK was a potent stimulus for elevating AA, but not prostaglandins, above basal levels. IL-1, in contrast, increased prostaglandins but not AA, above basal levels. IL-1 treatment was not associated with a loss or redistribution of AA among phospholipid classes. These results are consistent with high basal phospholipase activity in synovial cells and demonstrate the ability of BK, presumably via its ability to raise [Ca2+]i, to further elevate this activity(ies). Metabolism of AA to prostanoid is minimal in resting and BK-stimulated synovial cells, however, without the concomitant induction of cyclooxygenase activity by IL-1. These studies clarify the different, but synergistic, mechanisms of action of a peptide and cytokine in stimulating prostanoid synthesis in synovial cells. In addition, these data extend the results of previous investigations in demonstrating that basal phospholipase activity provides sufficient AA substrate for IL-1 induced prostanoid synthesis without invoking the concomitant induction of phospholipase activity by IL-1.

Arachidonic Acid↗

PubMed1996

Aceclidine effects on outflow facility after ciliary muscle disinsertion.

Aceclidine increases outflow facility with little accommodative effect. To determine whether this dissociation resides in the ciliary muscle (CM) or trabecular meshwork (TM), we measured aceclidine effects on perfusion outflow facility in both eyes of 8 rhesus monkeys after unilateral disinsertion of the CM from the TM. Facility in the control eyes increased by approximately 250% following intravenous pilocarpine and by an additional approximately 250% following intracameral pilocarpine, relative to baseline and uncorrected for washout. In CM-disinserted eyes, the facility response to intravenous and intracameral pilocarpine averaged approximately 25% of that in contralateral controls. Cytochalasin B, which acts directly on the TM to increase facility but is not additive to maximal pilocarpine doses in normal eyes, had no additional effect beyond that of pilocarpine in control eyes but induced an additional 100% facility increase relative to baseline in CM-disinserted eyes. The accommodative response to carbachol in CM-disinserted eyes was approximately 80% of that in contralateral controls, consistent with retention of CM contractility and the gonioscopic appearance of shallow CM disinsertion. Intracameral aceclidine HCl doses of 5 and 50 micrograms increased outflow facility by approximately 80 and 250%, respectively, in control eyes, and by approximately 0 and 80% in CM-disinserted eyes. Either the low aceclidine dose affected facility via the CM, while the high dose exerted an additional effect on the TM, or aceclidine acted only via the CM, with the low dose being ineffective and the high dose modestly effective in CM-disinserted eyes because only a few CM-TM attachments remained.

Accommodation, Ocular↗

PubMed1996

Indomethacin and epinephrine effects on outflow facility and cyclic adenosine monophosphate formation in monkeys.

PURPOSE: To investigate the effect of indomethacin inhibition of prostanoid production on the epinephrine-stimulated increase in outflow facility and cyclic adenosine monophosphate (cAMP) production in the anterior segment of the monkey eye. METHODS: Topical indomethacin was given 1 hour before the intracameral administration of epinephrine to living cynomolgus monkeys. Outflow facility was measured for 45 to 60 minutes, beginning 3 hours after epinephrine administration, by two-level constant pressure perfusion of the anterior chamber. Cyclic adenosine monophosphate formation was measured in cell membranes isolated from rhesus monkey ciliary muscle, ciliary processes, trabecular meshwork, and iris in the presence of forskolin, indomethacin, epinephrine, or indomethacin and epinephrine combined. RESULTS: Three hours after the intracameral administration of 5.5 micrograms epinephrine, facility increased by approximately 40%, a putatively maximal response, at which time the intracameral epinephrine concentration was approximately 15 microM. Pretreatment with topical indomethacin produced a dose-dependent inhibition of epinephrine's facility-increasing effect; the maximum inhibition of 50% to 70% occurred at an indomethacin dose of 50 to 125 micrograms. Doubling the indomethacin dose (250 micrograms) produced no further inhibition, whereas a fivefold larger epinephrine dose (27.5 micrograms) did not overcome the inhibition. Forskolin and epinephrine both stimulated cAMP production in vitro, whereas [indomethacin] > or = 10(-4) M partially inhibited both basal and epinephrine-stimulated cAMP production in all four tissues. CONCLUSIONS: Approximately half of the epinephrine-induced facility increase is inhibited by indomethacin, but it is unclear whether the indomethacin-inhibitable fraction is mediated by epinephrine-stimulated prostanoid production or release.

Adrenergic Agonists↗

PubMed1996

Unilateral nasal allergen challenge leads to bilateral release of prostaglandin D2.

BACKGROUND: Multiple mediators including prostaglandin D2 and leukotriene B4 have been shown to increase in nasal secretions during the early response to nasal challenge with antigen. OBJECTIVE: Our objective was to investigate the time course of prostanoid and leukotriene B4 release into nasal secretions on both the ipsilateral and contralateral side after a unilateral nasal allergen challenge. METHODS: We performed a controlled, randomized trial. Six volunteers were challenged unilaterally with antigen or diluent in a randomized order and discs were used to collect nasal secretions from both nostrils at 2 min intervals for 20 min after the challenge. Prostanoids and leukotriene B4 (LTB4) in recovered nasal secretions were measured by combined capillary gas chromatography-negative ion chemical ionization mass spectrometry (GC/MS). RESULTS: Nasal allergen challenge resulted in a significant and immediate increase in symptoms and sneezing. PGD2 was significantly elevated above diluent values (0.6 +/- 0.6 pg) 30 s after removal of the allergen disc (P < 0.05), reached its peak (423.2 +/- 182.4 pg) at 2 min and then slowly decreased. PGD2 also increased on the contralateral side after unilateral allergen challenge, reaching peak values about six times lower than on the ipsilateral side (70.8 +/- 21.7 pg at 6 min). Levels of 9a, 11b-PGF2 after antigen provocation became significantly higher than after diluent (0 +/- 0 pg) on the ipsilateral side at 2 min (17.2 +/- 5.9 pg), and reached peak levels at 4 min (25.1 +/- 8.0 pg). LTB4 also increased significantly on the side of challenge. For the other prostanoids measured (PGF2, PGF2 alpha, TxB2, 6kPGF1 alpha), no significant changes in either ipsilateral or contralateral secretions were observed after allergen challenge. CONCLUSIONS: Our study described the kinetics of PGD2 and LTB4 release as well as the contralateral release of PGD2.

Adult↗

PubMed1995

Neurological soft signs in neuroleptic-naive and neuroleptic-treated schizophrenic patients and in normal comparison subjects.

OBJECTIVE: The goal of this study was to assess neurological soft signs and developmental reflexes in schizophrenic patients who had never received neuroleptic medication and those who were receiving neuroleptic medication. METHOD: Neurological soft signs and developmental reflexes were examined in 26 schizophrenic patients who had never received a neuroleptic, 126 schizophrenic patients who were currently receiving neuroleptics, and 117 normal subjects. RESULTS: Soft signs were present in 23% of the neuroleptic-naive and 46% of the medicated schizophrenic patients. Developmental reflexes were present in 19% of the neuroleptic-naive and 12% of the medicated patients. Both soft signs and developmental reflexes were absent in the normal subjects. There were significant differences between patients and normal subjects in neurological soft signs and developmental reflexes. The possibly confounding variables of age, age at onset, duration of illness, number of hospitalizations, Abnormal Involuntary Movement Scale (AIMS) scores, and Simpson-Angus Scale extrapyramidal symptom scores were assessed by using logistic regression in the patients who were receiving neuroleptics. AIMS scores and Simpson-Angus Scale scores correlated with soft signs in these patients. CONCLUSIONS: The presence of neurological soft signs in schizophrenic patients who had never received neuroleptics indicates that these signs are present independent of medication effects, but it is possible that neuroleptics contribute to the prevalence of these abnormalities, as demonstrated by the patients who were receiving neuroleptics.

Adult↗

PubMed1994

Simultaneous quantitation of endogenous levels of cortisone and cortisol in human nasal and bronchoalveolar lavage fluids and plasma via gas chromatography-negative ion chemical ionization mass spectrometry.

Investigation of the influence of pulmonary disease upon local catabolism of cortisol in vivo is limited by the lack of availability of a selective and sensitive assay for simultaneous quantitation of cortisol and cortisone in lung and nasal lavage fluids as well as in plasma. Synthesis of bispentafluorobenzylcarboxymethoxime derivatives of cortisone and cortisol followed by trimethylsilylation yields compounds with almost ideal gas chromatographic properties. The derivatized steroids generate intense M(-.)-181 fragment ions in negative ion chemical ionization mass spectrometry. Monitoring of ions at m/z 829 and m/z 903, respectively, for cortisone and cortisol and corresponding fragment ions generated from multideuterated internal standards provides the analytical basis for assessment of local in vivo conversion of cortisol to cortisone in the respiratory system of human subjects. The assay method displays excellent reproducibility with variations < or = 10%. Detection limits are < or = 1 pg of steroid analyte per injection (S/N > 3). Endogenous levels of cortisone and cortisol, respectively, measured in human samples were as follows: nasal lavage fluid, 47 and 25 pg/ml; bronchoalveolar lavage fluid, 380 and 153 pg/ml; plasma 12.8 and 61.6 ng/ml.

Bronchoalveolar Lavage Fluid↗

PubMed1994

Apraclonidine and brimonidine effects on anterior ocular and cardiovascular physiology in normal and sympathectomized monkeys.

Apraclonidine and brimonidine administered topically to one eye of ketamine-anesthetized normal cynomolgus monkeys each produced a dose-related bilateral reduction in intraocular pressure which was not dependent on intact sympathetic innervation. Brimonidine was more potent and efficacious (10-12 mmHg maximum intraocular pressure reduction 2 hr after 200 micrograms) but produced a shorter-lasting effect than apraclonidine (4 mmHg maximum intraocular pressure reduction 1-6 hr after 600-1000 micrograms). Apraclonidine had little effect on pupil diameter, but brimonidine produced a dose-related bilateral miosis which was dependent on intact sympathetic innervation. Neither drug significantly affected refractive error. Topical brimonidine, but not apraclonidine, produced a dose-dependent reduction in mean arterial blood pressure, while both drugs lowered heart rate. A dose-dependent bilateral reduction in aqueous humor flow rate calculated over a 6-hr period following drug administration was produced by both topical apraclonidine (maximum 30-35% reduction with 600 micrograms) and brimonidine (maximum 30-45% reduction with 50-250 micrograms), which was not dependent on intact sympathetic innervation. Maintenance of blood pressure by intravenous infusion of angiotensin II had no effect on the aqueous humor flow suppression produced by 100 micrograms of topical brimonidine, but pentobarbital anesthesia abolished it. Intracameral injection of 10 micrograms brimonidine in rhesus monkeys produced an ipsilateral approximately 15% reduction in aqueous humor flow calculated for the 1-3 hr post-injection period. The cardiovascular and contralateral ocular effects observed with both drugs are presumably related to the monkeys' small body weight, and the magnitude of IOP reduction for a given degree of flow suppression would be greater in hypertensive than in normotensive eyes. Caution must therefore be exercised in extrapolating from our data in ocular normotensive monkeys to the glaucomatous human.

Adrenergic alpha-Agonists↗

PubMed1994

Blood and bronchoalveolar eosinophils in allergic subjects after segmental antigen challenge: surface phenotype, density heterogeneity, and prostanoid production.

Eosinophil infiltration into the airways has been implicated in the pathophysiology of asthma. To improve our understanding of the function of eosinophils in asthma, we have compared the phenotype and function of eosinophils obtained simultaneously from blood and bronchoalveolar lavage (BAL) of allergic subjects 19 hours after segmental lung allergen challenge. Eosinophils were purified by discontinuous density gradient centrifugation, and their distribution at various layers was quantitated. Eosinophils at the 1.080 to 1.085 gm/ml interfaces from blood and BAL (purity > 70%) were analyzed by immunofluorescence and flow cytometry for several surface markers including adhesion-activation antigens. Eosinophils in BAL from antigen-challenged sites were markedly increased compared with control diluent-challenged BAL sites (0.3% +/- 1% vs 28.1% +/- 9.7%, n = 12, p < 0.002), and a greater percentage were hypodense (specific gravity < 1.080 gm/ml) than in peripheral blood (51.3 +/- 5.3 vs 19.0 +/- 4.4, n = 15, p < 0.01). In vitro, resting and activated BAL eosinophils biosynthesized less thromboxane B2 than blood eosinophils. Although both BAL and blood eosinophils expressed similar levels of Fc gamma RII (CD32), CD11a, and CD45, resting levels of Mo-1 (CD11b) were upregulated on BAL eosinophils (mean fluorescence intensity, 316% +/- 48% of blood eosinophils, n = 5, p < 0.05). Blood eosinophils stimulated in vitro with 1 mumol/L platelet activating factor or N-formyl-methionyl-leucyl-phenylalanine achieved levels of CD11b expression similar to those of BAL eosinophils. In contrast, CD11b expression on BAL eosinophils could not be further increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Obstruction of aqueous humor outflow by cross-linked polyacrylamide microgels in bovine, monkey, and human eyes.

PURPOSE: Orcolon, a synthetic viscoelastic, may have contributed to refractory intraocular pressure (IOP) elevation after intracameral injection in some patients. Cross-linked polyacrylamide (microgels), an altered form of the polymer, was investigated as an etiologic candidate. METHODS: Four adult rhesus monkeys underwent anterior chamber exchange with mock aqueous humor containing microgels in one eye and a vehicle in the other. Outflow facility (perfusion) and IOP (applanation) were determined before and at various times thereafter. Facility also was determined before and after microgel or vehicle infusion into organ-cultured individual human (n = 9) and paired calf (n = 6) anterior segments. Representative monkey and human eyes were examined by light and electron microscopy. RESULTS: In the microgel-infused monkey eyes, IOP was consistently higher, by approximately 5 mmHg for approximately 1 month. In all three species, microgel infusion acutely decreased facility by approximately 50% to 80%. In the living monkeys where longer-term observation and retesting were possible, a facility reduction of approximately 40% to 50% persisted for at least 1 to 2 months, and rechallenge again produced an acute 80% facility decrease and subsequent 10-mmHg IOP rise. Results of electron microscopic examination in human and monkey eyes showed accumulation of microgels in the cribriform meshwork and beneath the inner wall of Schlemm's canal, with no cellular alterations or inflammatory infiltrate. CONCLUSIONS: Cross-linked polyacrylamide microgels can produce an acute and longstanding obstruction of trabecular drainage experimentally, and might therefore do so clinically.

Acrylic Resins↗

PubMed1994

Nasal allergen challenge generates 1-0-hexadecyl-2-lyso-sn-glycero-3-phosphocholine.

We studied antigen-induced platelet activating factor and the 1-0-hexadecyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF) in nasal lavage fluids (NLF) by combined gas chromatography/mass spectrometric analysis (GC/MS). During the early allergic reaction, there was a dramatic increase in the levels of lyso-PAF that peaked at 15 min (2.6 +/- 5.2 ng/ml, mean +/- SEM, n = 6). Increasing doses of antigen produced a dose-dependent increase in the levels of lyso-PAF that peaked at the highest dose. Levels of lyso-PAF correlated strongly with those of N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity (rs = 0.82, p = 0.0001) and histamine (rs = 0.57, p = 0.002). There was a no significant increase in the quantity of lyso-PAF found in NLF from allergic individuals challenged with diluent or nonallergic individuals challenged with antigen. In subjects showing a late phase reaction, as indicated by symptoms and histamine release, we detected lyso-PAF along with TAME-esterase activity and histamine during the late phase reaction. In contrast to lyso-PAF, PAF levels were near or below the detection limit of the assay in NLF and remained unchanged after antigen challenge. We also investigated the potential pathways for lyso-PAF generation from 2-acetylated phospholipids. We found that the time required for deacetylation of 50% of [3H]PAF (t1/2) to lyso-PAF was 50 min in baseline secretions and 10 and 22 min in NLF obtained 10 min and 24 h after antigen challenge, respectively. These data suggested that catabolic pathways were present in NLF.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗

PubMed1994

Ragweed antigen E and anti-IgE in human central versus peripheral isolated bronchi.

The ability of antigen to contract passively sensitized tissues was examined in human central (5 to 12 mm) and peripheral (0.5 to 2 mm) bronchi. Both central and peripheral bronchi contracted to ragweed antigen E (RW AgE), and these contractions were virtually abolished by a combination of indomethacin, cysteinyl-leukotriene, and histamine antagonists. There were, however, quantitative differences in contractile responses and in mediator release to RW AgE between central and peripheral bronchi. RW AgE was approximately 20-fold more potent in contracting peripheral bronchi compared with central bronchi. On a per weight of tissue basis, RW AgE released six-fold more histamine, 15- to 20-fold more immunoreactive leukotriene D4 (i-LTD4) and two- to 10-fold more prostanoids in the peripheral bronchi compared with central bronchi. Anti-IgE mimicked the effect of RW AgE with respect to inflammatory mediator release and with respect to the magnitude of the contractile response in peripheral and central bronchi. Anti-IgE, however, was more potent in contracting central than peripheral bronchi. Moreover, in peripheral bronchi, contractile responses to anti-IgE were only partially inhibited by a combination of indomethacin, cysteinyl-leukotriene, and histamine antagonists. These results indicate that the qualitative characteristics of antigen-induced mediator release and muscle contraction are similar in central versus peripheral bronchi. However, RW AgE is much more potent in causing smooth muscle constriction, and is capable of releasing a greater quantity of inflammatory mediators in peripheral bronchi/bronchioles than in the more central bronchi.

Adult↗

PubMed1994

Recombinant stem cell factor-induced mast cell activation and smooth muscle contraction in human bronchi.

The effect of human recombinant stem cell factor (SCF) on inflammatory mediator release and smooth muscle contraction was evaluated in human isolated intralobar bronchi. Bronchi from 21 of 26 donors contracted in response to SCF. The threshold concentration was approximately 0.01 micrograms/ml. At 1 micrograms/ml, the tissues contracted to about 60% of the carbamylcholine-induced maximum contraction. The responses to SCF mimicked those obtained with anti-IgE. Thus, the contractions to SCF and anti-IgE were inhibited to a similar extent by a combination of a cysteinyl-leukotriene receptor antagonist and a histamine H1 receptor antagonist. SCF also mimicked the effect of anti-IgE in releasing histamine, i-LTD4, and PGD2 from the bronchi. At a threshold concentration for contraction (0.01 micrograms/ml), SCF had no effect on subsequent responses to anti-IgE in the bronchi. The data suggest that human recombinant SCF contracts airway smooth muscle by stimulating the release of contractile mediators from bronchial mast cells. The data fail to support the hypothesis that SCF primes bronchial mast cells to subsequent immunologic stimuli.

Antibodies, Anti-Idiotypic↗