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Biomedical subjects

S Maayani

Publications and source records attributed to S Maayani.

At least 37 records · Page 2Linked to original sources
PubMed1995

B cell differentiation factor-induced B cell maturation: regulation via reduction in cAMP.

We have previously described a novel human B cell differentiation factor (BCDF), 446-BCDF, that is distinct biochemically and functionally from other cytokines. Since signal transduction pathways involved in human B cell differentiation have been incompletely studied and are poorly understood, we assessed the effects of 446-BCDF on various intracellular second messenger systems. After exposure of B cells to 446-BCDF, intracellular cAMP concentration started to decrease at 5 min and was significantly lower at 30 min and reached the lowest level at 4 hr. In most cases, cAMP concentrations returned toward baseline by 24 hr. A cAMP analog (dibutyryl cAMP), a stimulator of adenyl cyclase (forskolin), and phosphodiesterase inhibitors (aminophylline and IBMX) which inhibited the 446-BCDF-induced decrease in intracellular cAMP, inhibited 446-BCDF-induced B cell differentiation, suggesting that the fall in intracellular cAMP was a critical event in this process. To understand the mechanism involved in the reduction of cAMP, B cells were treated with pertussis toxin (PTX), a Gi protein inhibitor. Pertussis toxin blocked 446-BCDF-induced B cell differentiation as well, suggesting that 446-BCDF may function by stimulation of a Gi-linked receptor resulting in the inhibition of adenylate cyclase with a consequent reduction in cAMP. Other cytokines known to promote Ig secretion (IL2 and IL6) also caused a reduction in cAMP, suggesting that this pathway may be generally important in B cell differentiation. Taken together, these data suggest that at least one pathway of terminal maturation in B cells may involve the reduction of intracellular cAMP.

Adenylate Cyclase Toxin↗
PubMed1995

Synthesis of (+)-(R)- and (-)-(S)-trans-8-hydroxy-2-[N-n-propyl-N-(3'-iodo-2'-propenyl)] aminotetralin: new 5-HT1A receptor ligands.

(R,S)-trans-8-Hydroxy-2-[N-n-propyl-N-(3'-iodo-2'- propenyl)amino]tetralin 7, a new radioiodinated ligand based on 8-OH-DPAT, was reported as a potential ligand for 5-HT1A receptors. The optically active (+)-(R)- and (-)-(S)-7 were prepared to investigate the stereoselectivity of (R,S)-7. Racemic intermediate 8-methoxy-2-N-n-propyltetralin was reacted with the acyl chloride of (-)-(R)-O-methylmandelic acid to form a mixture of (S,R)- and (R,R)-diastereoisomers, which were separated by flash column chromatography. After removing the N-acyl group from the diastereoisomers, the desired (+)-(R)- or (-)-(S)-7 was obtained by adding an N-iodopropenyl group. In vitro homogenate binding studies showed the stereoselectivity of this new compound for 5-HT1A receptors. (+)-(R)-7 isomer displayed 100-fold higher affinity than the (-)-(S)-7 isomer. Biochemical study indicated that (+)-(R)-7 potently inhibited forskolin-stimulated adenylyl cyclase activity in hippocampal membranes (Emax and EC50 were 24.5% and 5.4 nM, respectively), while (-)-(S)-7 showed no effect at 1 microM. The radioiodinated (+)-(R)- and (-)-(S)-[125I]7 were confirmed by coelution with the resolved unlabeled compound on HPLC (reverse phase column PRP-1, acetonitrile/pH 7.0 buffer, 80/20). The active isomer, (+)-(R)-[125I]7, displayed high binding affinity to 5-HT1A receptors (Kd = 0.09 +/- 0.02 nM). In contrast, the (-)-(S)-7 isomer displayed a significantly lower affinity to the 5-HT1A receptor (Kd > 10 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗
PubMed1995

Pharmacologic characterization of wool dust extract in isolated guinea pig trachea.

Wool mill workers develop respiratory symptoms and lung function abnormalities associated with their work in the textile industry. As in other workplaces, which process organic materials, the dust generated in the manufacture of wool has been implicated as a cause of these respiratory problems. Pharmacologic studies of wool dust extract were performed in vitro on guinea pig tracheal (GPT) segments. A wool dust extract (WDE) was prepared from material collected from a mill previously surveyed. When the standardized WDE solution was added to an organ bath in increments of 10, 30, 100, 300, and 1000 microliters it caused a consistent, dose-dependent constriction of GPT. Pretreatment of guinea pig tracheas, prior to WDE challenge, with atropine (10(-6) M), pyrilamine (10(-6) M), indomethacin (10(-6) M), verapamil (10(-6) M), TMBS (10(-6) M), BW755C (10(-6) M) and LY171883 (10(-6) M) was studied in order to evaluate receptor-dependent and -independent characteristics of WDE-induced constriction. WDE-induced bronchoconstriction was partially inhibited by the antihistamine pyrilamine. Atropine and leukotriene inhibitors (LY171883 and BW755C) were not found to have a significant protective effect on WDE-induced constriction. Both TMBS and verapamil (intra- and extracellular calcium blocking agent) suppressed the effect of wool dust extract in the range tested. These findings suggest that in this model, WDE-induced airway constriction is only partly attributable to common mediators of bronchoconstriction (e.g., histamine). The airway effects of WDE may be modulated by calcium channel blocking agents.

Air Pollutants, Occupational↗
PubMed1995

Respiratory function in poultry workers and pharmacologic characterization of poultry dust extract.

A group of 343 workers (252 males and 91 females) employed in four poultry farms in Croatia was studied for the prevalence of acute and chronic respiratory symptoms and lung function changes. There were significantly higher prevalences of chronic cough, chronic phlegm, chronic bronchitis, and chest tightness in poultry workers than in control workers. Male poultry workers who were smokers had significantly higher prevalences of chronic cough, chronic phlegm, and chronic bronchitis than poultry workers who were nonsmokers (P<0.01). Poultry workers exposed for more than 10 years had significantly higher symptoms prevalences than those workers with shorter exposures (except among female smokers). There was also a high prevalence in poultry workers of acute symptoms which developed during the work shift. The measured FVC, FEV1, and FEF25 in poultry workers were significantly lower than predicted normal values. Workers exposed for more than 10 years had lower ventilatory capacity tests (expressed as percentage of predicted) than those workers with shorter exposures. Changes in FEV1, FEF50, and FEF25 were less pronounced than FVC. Additionally we showed that a water-soluble poultry dust extract obtained from this workplace caused a dose-related contraction of nonsensitized guinea pig tracheal smooth muscle when studied in vitro. Pharmacologic studies of this response indicate that it may result from the release of multiple endogenous mediators. Our data suggest that work in poultry farms may, for some workers, cause the development of acute and chronic respiratory symptoms and lung function changes.

Adult↗
PubMed1995

Nerve growth factor amplifies cyclic AMP production in the HT4 neuronal cell line.

There has been considerable interest and controversy in the relationship between nerve growth factor (NGF) and the cyclic AMP (cAMP) second messenger system. We have used a novel, neuronal cell line (HT4) to investigate the effect of NGF on the adenylyl cyclase signaling system. Treatment of cells with NGF (100 ng/ml, 15 min) amplified cAMP accumulation (approximately 75%) in response to activation of adenosine A2 receptors (5 min) with 5'-N-ethylcarboxamidoadenosine or activation of adenylyl cyclase directly with forskolin. Basal cAMP accumulation was not altered by NGF. This amplification appears to be mediated by activation of protein kinase C (PKC) because (1) it was mimicked by activators (phorbol esters and a diacylglycerol analogue) of PKC, (2) the effects of NGF and phorbol ester on cAMP accumulation were not additive, (3) NGF amplification of cAMP accumulation was abolished by down-regulation of PKC, (4) NGF increased cytosolic PKC activity, and (5) inhibitors of PKC blocked the NGF-induced amplification of cAMP accumulation. Although NGF-induced amplification of cAMP accumulation was dependent upon PKC, mechanisms other than the classic activation pathway (i.e., hydrolysis of inositol phospholipids or the production of diacylglycerol) appeared to mediate PKC activation by NGF. The tyrosine kinase inhibitor, lavendustin A, blocked NGF-mediated amplification of cAMP accumulation, suggesting a novel interaction between a tyrosine kinase and protein kinase C.

Adenosine↗
PubMed1994

A potential 5-HT1A receptor antagonist: p-MPPI.

A potential 5-HT1A receptor antagonist, p-MPPI, 4-(2'-methoxy-)phenyl-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido-]ethy l- piperazine, was developed. The [125I]p-MPPI demonstrated high affinity and selectivity toward 5-HT1A receptors; Kd = 0.36 nM and Bmax = 264 fmol/mg of protein in rat hippocampal membrane homogenates. The binding is not sensitive to GTP (300 microM) or Gpp(NH)p (100 microM). In forskolin-stimulated adenylyl cyclase assay using rat hippocampus, p-MPPI (up to 10 microM) showed no agonist activity as compared to that of (+/-)-8-OH-DPAT. At 100 nM it completely antagonized the inhibition of forskolin-stimulated adenylyl cyclase activity produced by 100 nM of (+/-)-8-OH-DPAT. This potential 5-HT1A antagonist may provide a powerful tool for studies of the pharmacology of the 5-HT1A receptor system.

Adenylyl Cyclases↗
PubMed1994

Signal transduction differences between 5-hydroxytryptamine type 2A and type 2C receptor systems.

The cDNAs for human 5-hydroxytryptamine (5-HT)2C and 5-HT2A receptors were stably transfected separately into parent Chinese hamster ovary cells, and cell lines in which levels of transfected receptor protein expression and accumulation of inositol phosphates in response to 5-HT were comparable were chosen for study. The effect of activation of these receptors on 5-HT1B-like receptor-mediated responsiveness (i.e., inhibition of forskolin-stimulated cAMP accumulation) was studied. Activation of 5-HT2C receptors with 5-HT (0.1-100 microM) abolished the 5-HT1B-like response, which returned when 5-HT2C receptors were blocked with mesulergine (1 microM). Furthermore, the maximal response to 5-carboxytryptamine was reduced in a concentration-dependent manner by the 5-HT2A/5-HT2C-selective partial agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. In contrast, activation of 5-HT2A receptors with either 5-HT or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane did not alter the 5-HT1B-like response. The reduction of 5-HT1B-like responsiveness produced by 5-HT2C receptor activation was independent of protein kinase C activation and increases in the intracellular calcium concentration. Although 5-HT2A and 5-HT2C receptors are strikingly similar in structure and pharmacology, and the signal transduction systems coupled to these receptors have been thought to be similar, if not identical, these data provide the first evidence for fundamental differences in the signal transduction systems of these 5-HT2 receptor subtypes.

Amphetamines↗
PubMed1994

5-Hydroxytryptamine type 2A receptors regulate cyclic AMP accumulation in a neuronal cell line by protein kinase C-dependent and calcium/calmodulin-dependent mechanisms.

The effects of 5-hydroxytryptamine (5-HT)2A receptor activation on cAMP formation were studied in a cell line derived from embryonic rat cortex (A1A1). 5-HT (EC50 = 0.87 microM) amplified the amount of cAMP formed in response to 5'-N-ethylcarboxamidoadenosine (an adenosine A2 receptor agonist), cholera toxin, and forskolin after 15 min of coincubation in the presence of the phosphodiesterase inhibitor rolipram. This effect of 5-HT was blocked by 10 nM ketanserin as well as by 10 nM spiperone, indicating a response mediated by the 5-HT2A receptor subtype. Similarly, cAMP accumulation was enhanced by coincubation with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187. After exposure to PMA for 24 hr (PKC-depleted cells), 5-HT and A23187 still enhanced cAMP formed in response to forskolin and 5'-N-ethylcarboxamidoadenosine, whereas the amplifying effects of PMA were abolished. Analysis by Western blots and PKC activity measurements revealed that, of three PKC isoforms detected in A1A1 cells (alpha, delta, and epsilon), only the calcium-independent isoform PKC-epsilon remained in membrane fractions after long term PMA treatment. In PKC-depleted cells, 5-HT-mediated amplification was greatly reduced after treatment with the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (acetoxymethyl)-ester or the calmodulin antagonists calmidazolium and N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide hydrochloride. In addition, 5-HT-mediated amplification of cAMP accumulation was reduced by the PKC inhibitor staurosporine in normal cells but was unaffected in PKC-depleted cells. In conclusion, these data suggest that 5-HT2A receptor activation can amplify cAMP formation in A1A1 cells by two distinct pathways coupled to the hydrolysis of inositol phosphates, i.e., PKC and calcium/calmodulin.

Adenosine↗
PubMed1993

Interactions between responses mediated by activation of adenosine A2 receptors and alpha 1-adrenoceptors in the rabbit isolated aorta.

1. This paper describes aspects of the functional antagonism between the responses mediated by activated alpha 1-adrenoceptors and adenosine A2 receptors in the adventitia- and endothelium-denuded aorta of the rabbit. 2. Adenosine A2 receptor agonists relaxed aortic rings pre-contracted with phenylephrine. The relaxation response was agonist concentration-dependent and saturable. The respective contractile and relaxation responses were stable, reproducible, and reversible. 3. Increasing the phenylephrine concentration caused a progressive attenuation of the action of adenosine A2 receptor agonists, consisting of a decreased maximal response and a dextral shift of the adenosine agonist concentration-response curve. This functional antagonism could be completely reversed upon removal of adenosine by either the addition of adenosine deaminase or by wash-out of the adenosine agonist from the tissue. The relaxation response to the adenosine A2 receptor partial agonists, N6-cyclohexyladenosine and R-(-)-N6-(2-phenylisopropyl)adenosine, was abolished at higher phenylephrine concentrations (e.g. 30 EC50). 4. A 1000 fold increase in the adenosine concentration was required to shift the value of the EC50 of phenylephrine six fold, while a similar increase in the value of the EC50 of adenosine could be elicited by only a 32 fold increase in the phenylephrine concentration. A 30 fold increase in the phenylephrine concentration shifted the value of the EC50 of 5'-N-ethylcarboxamidoadenosine four fold. 5. Analysis of the functional antagonism between the responses mediated by these receptors using the Black & Leff (1983) operational model of agonism allowed for the estimation of the agonist dissociation constant, KA, and the apparent efficacy, tau, for both phenylephrine and adenosine A2 receptor agonists. Increasing the concentration of phenylephrine reduced the value of tau for adenosine agonists in a concentration-dependent and saturable manner. Similarly, increasing the concentration of adenosine reduced the value of tau for phenylephrine in a concentration-dependent and saturable manner. The phenylephrine KA value obtained by the method of functional antagonism (1.9 microM) was similar to that obtained by the receptor inactivation method (2.1 microM). 6. Partial occlusion of the alpha 1-adrenoceptor by the alkylating agent, dibenamine, demonstrated that the magnitude of the adenosine A2 receptor-mediated relaxation was inversely proportional to the number of functional alpha 1-adrenoceptors. 7. It is concluded that the magnitude of functional antagonism is proportional to the stimulus elicited through either receptor. We propose that this tissue preparation and pair of receptors is a good model to study quantitative aspects of functional antagonism between activated receptors.

Adenosine↗
PubMed1992

Kinetics of relaxation responses to vasorelaxants in isolated rabbit aorta.

Transient responses of isolated tissues to drugs are best studied by application of non-steady-state protocols in which the data collected are analyzed using kinetic models. The time dependence of the relaxation response of the adventitia- and endothelium-denuded rabbit aorta to four vasorelaxants (nitroglycerin, sodium nitroprusside, 5'-N-ethylcarboxamidoadenosine and isoproterenol) was analyzed by an exploratory kinetic model. A rapid relaxation (t1/2 = 1-3 min) was elicited by all vasorelaxants. An apparent desensitization or fade of the relaxation response to nitroglycerin or isoproterenol was visualized as the partial regaining of tissue tone (t1/2 = 2-3 min). The relaxation responses to sodium nitroprusside or 5'-N-ethylcarboxamidoadenosine were stable for at least 60 min and did not exhibit an apparent regaining of tension. Tissues rendered desensitized by either isoproterenol or nitroglycerin responded fully to sodium nitroprusside or 5'-N-ethylcarboxamidoadenosine. The rate constant for relaxation was vasorelaxant concentration-dependent and saturable for all vasorelaxants. For isoproterenol, nitroglycerin, and 5'-N-ethylcarboxamidoadenosine the rate constant for relaxation was inversely proportional to the contractile stimulus, as was the magnitude of relaxation for all vasorelaxants. Although the magnitude and rate constant of the fade was not concentration-dependent for isoproterenol, it was inversely proportional to the nitroglycerin concentration. The rate constant of the fade was proportional to the contractile stimulus for isoproterenol and nitroglycerin, and the magnitude of the fade was proportional to the contractile stimulus for nitroglycerin. We propose that kinetic studies of responses in isolated vasculature supersede studies performed under steady-state conditions, for they extend our knowledge of the manner by which the steady-state is achieved and allow for a quantitative analysis of the time-dependent changes which should assist in elucidating the biochemical basis of the observed physiological response.

Adenosine↗
PubMed1992

Immunological and respiratory changes in animal food processing workers.

A group of 35 men employed in the processing of animal food was studied to assess the relation between respiratory findings and immunological status. The most frequent positive skin prick reactions to occupational allergens were to fish flour (82.9%), followed by carotene (77.1%), corn (65.7%), four-leaf clover (62.9%), sunflower (54.3%), chicken meat (31.4%), soy (28.6%), and yeast (22.7%). Increased total IgE serum levels were found in 14/35 (40.0%) animal food workers compared to 1/39 (2.6%) in a healthy population (p less than 0.01). A significantly higher prevalence of chronic respiratory symptoms was found among the exposed workers compared to control workers. There was however, no significant difference in the prevalence of chronic respiratory symptoms between animal food workers with positive and negative skin tests to house dust or to fish flour or among those with increased or normal IgE (except for dyspnea). The frequency of acute symptoms associated with the work shift was high among the animal food workers but similar by immunological status. There were significant mean across-shift reductions for all ventilatory capacity tests, being particularly pronounced for FEF25. Workers with positive skin tests to fish flour antigen had significantly larger across-shift reductions in FEF25 than workers with negative skin reactions. An aqueous extract of animal food dust caused a dose-related contractile response of isolated guinea pig tracheal muscle in vitro. Our data suggest that, in addition to any immunological response animal food dust may produce in vivo, it probably also causes direct irritant or pharmacological reactions on the airways as suggested by our in vitro data.

Adult↗
PubMed1992

Immunological findings and respiratory function in cotton textile workers.

Immunological parameters were studied in a group of 24 cotton textile workers. These were volunteers from a cohort of 106 (83 women and 23 men) previously studied textile workers. A group of 30 employees from a bottle packing plant served as a control for the immunologic studies. The subgroup of volunteers undergoing immunologic testing did not differ from the original cohort of textile workers in age, sex, smoking history, or prevalence of most chronic respiratory symptoms, nor were there any significant differences in baseline lung function or across-shift changes. The 24 cotton worker volunteers underwent skin testing with extracts of cotton dust and cotton seed. Eight of these 24 (33.3%) had positive tests, and 5 of the 8 had elevated serum immunoglobulin E (IgE) levels. Only one of the 8 skin-test-positive workers had symptoms of byssinosis. Only 1 of 30 control workers' skin tested with cotton extract reacted, and none had an increased serum IgE level (P less than 0.01). Both baseline lung function and across-shift changes did not differ between workers with positive and negative skin test reactions or between workers with normal and elevated IgE levels. Additionally, we studied the response in vitro of nonsensitized guinea pig trachea to cotton bract extract and demonstrated a dose-dependent contractile response. These data suggest that while immunological findings are frequent in textile workers, they correlate poorly with respiratory symptoms and function and may not be the basis for the airway obstruction seen in this disease.

Adult↗
PubMed1992

Immunological findings in hemp workers.

Immunological status and its relation to respiratory findings were studied in 42 female textile workers occupationally exposed to hemp dust and in 49 female control workers. Skin prick tests with hemp or flax dust extracts from different parts of the mill in hemp workers demonstrated the following frequencies of positive tests to antigens: a mixture of hemp and flax extracts (64%), followed by flax extracts (48%), hemp from combing machines (41%), hemp from carding machines (38%), hemp from spinning and weaving machines (33%), and hemp from softening machines (20%). The prevalence of positive skin tests to hemp or flax allergens in control workers was consistently lower, ranging from 21 to 5%. Increased total serum IgE was recorded in 35.7% of hemp workers compared to only 5.0% of control workers (P < 0.05). Hemp workers with positive skin tests had significantly higher prevalences of chronic respiratory symptoms than those with negative skin tests. There were, however, no differences for acute symptoms between workers with positive and negative skin tests. Across-shift changes and baseline lung function were not different when compared by immunologic status. We showed additionally that a water-soluble extract of hemp dust causes a dose-related contraction of nonsensitized guinea pig tracheal smooth muscle when studied in vitro. Our results suggest that frequent immunologic abnormalities can be documented in hemp workers but, with the exception of chronic respiratory symptoms, in general, these do not correlate with respiratory findings.

Adult↗
PubMed1992

Allosteric interactions between the binding sites of receptor agonists and guanine nucleotides: a comparative study of the 5-hydroxytryptamine1A and adenosine A1 receptor systems in rat hippocampal membranes.

The ternary complex formed between agonist, receptor and guanine nucleotide binding protein and its destabilization by guanine nucleotides (GN) was utilized to study early events in signal transduction, by characterizing the allosteric interactions between agonist and GN binding to the receptor/guanine nucleotide binding protein, G complex for adenosine A1 and 5-hydroxytryptamine1A receptors. The functional interaction between the ternary complex and GTP was examined by assaying adenylyl cyclase activity. Binding of a full adenosine A1 agonist ([3H]-R-(-)-N6-(2-phenylisopropyl)adenosine), and a full [(+-)-[3H]-8-hydroxydipropylaminotetralin] and partial ([3H]-8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8- azaspirol[4.5]-decane-7,9-dione) 5-hydroxytryptamine1A agonist was examined in relation to the binding of GN. The amount of ternary complex formed depended upon receptor type and drug relative efficacy. The ratio between the drug's EC50 value (adenylyl cyclase) and dissociation constant (binding) was also receptor and drug relative efficacy dependent. 5'-Guanylylimidodiphosphate (100 microM) caused an approximately 50% decrease in the Bmax for all drugs without affecting Kd values. 5'-Guanylylimidodiphosphate and guanosine 5'-O-(3-thiotriphosphate) attenuated [3H]-agonist binding in a concentration-dependent and saturable manner, with IC50 values increased 2- to 6-fold with increasing receptor occupancy. IC50 values were approximately one-tenth lower at the 5-hydroxytryptamine1A receptor than adenosine A1 receptor; similar values were obtained for inhibition of (+-)-[3H]-8-hydroxydipropylaminotetralin and [3H]-8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8- azaspirol[4.5]-decane-7,9-dione binding, suggesting an independence of agonist efficacy. We propose that the stabilization of the ternary complex by hormone binding, measured by Bmax values, is related to drug-relative efficacy, thus the amount of ternary complex available for destabilization by GN is greater for the more efficacious agonist. This is translated into greater relative efficacy observed in the maximal inhibition of adenylyl cyclase.

Allosteric Regulation↗
PubMed1991

Immunological and respiratory changes in soy bean workers.

Immunological and respiratory findings were studied in a group of 19 male soybean workers. Twenty control workers also participated in the immunological studies. All soybean workers had positive immediate skin reactions to soybean extract, as did 19/20 control workers. Similarly, 18/19 soy workers reacted to soy antigen prepared after separation from oil, but only 3/19 to soy lecithin antigen and 1 to soy oil antigen. A majority of soy workers (13/19) reacted to house dust. Only 3/19 soy workers had increased levels of soy-specific IgE. The prevalence of chronic respiratory symptoms was higher in exposed than in control workers, being significantly different for dyspnea (P less than 0.01). Workers with increased specific serum IgE or positive skin tests to house dust did not have any more symptoms than workers with negative tests. Ventilatory function was significantly worse in soybean workers than expected. Nevertheless, workers with positive skin or serological tests to house dust had across-shift changes similar to those with negative tests. These data suggest that skin and airway responses to soybean components (particularly the non-lipid ones) are very frequent among soybean workers. In the current study specific (soy) and non-specific (house dust) skin tests and immunoglobulins did not allow us to identify the workers at risk of developing symptoms or lung function abnormalities. This suggests that in addition to any atopic mechanisms, the irritant effect of soy dust may play a role in this occupational airway disease.

Adult↗
PubMed1991

Immunological and respiratory findings in swine farmers.

The prevalence of respiratory symptoms and ventilatory capacity abnormalities in relation to immunological status was studied in 32 swine farmers and in 39 controls. A large number of swine farmers reacted to swine confinement building antigens (swine hair, 34%, swine confinement agents, 28%) but also to other extracts such as animal food (78%) and corn flour (37%). Control workers also reacted to these antigens in similar frequencies. Increased serum IgE levels were found in 3 swine farmers (9.4%) and all 3 had positive skin tests to at least one of the swine antigens. Among control workers one (2.6%) had an increased serum IgE level; this worker exhibited a positive skin reaction to swine food antigen. Swine farmers with positive skin reactions had across-shift reductions of FEF50 and FEF25 significantly larger than those with negative skin tests (P less than 0.01). Preshift measured ventilatory capacity data (FEV1, FEF50, FEF25) in swine farmers with positive skin tests were significantly lower (compared to predicted) than in those with negative skin tests. Additionally, we showed that a water-soluble swine confinement building antigen causes a dose-related contraction of nonsensitized guinea pig trachea smooth muscle studied in vitro. Our data indicate significant differences in lung function between swine workers with positive and negative skin tests. We suggest that skin testing may be helpful in identifying workers at risk for developing lung disease.

Adult↗
PubMed1991

Functional antagonism between hormone receptor systems: modulation of glycoprotein secretion in secretory epithelial cells.

A physiologic response such as mucin secretion from epithelial cells in vivo may be under the control of several endogenous substances such as acetylcholine, norepinephrine, and vasoactive intestinal peptide (VIP). These substances may simultaneously activate distinct membrane receptors that exist on the same epithelial cells, and this activation may result in reciprocal physiologic responses or functional antagonism. To test whether simultaneous activation of the VIP and muscarinic receptors or of beta-adrenoreceptors and muscarinic receptors affect mucin secretion in a reciprocal manner, we studied some characteristics of the resultant physiologic response in human epithelial cells secreting radiolabeled mucin-like glycoprotein (MLGP). Both basal and methacholine (M.chol)-induced MLGP secretion could be blocked by VIP (1 pM to 1 microM) and by isoproterenol (ISO) (0.1 nM to 10 nM) in a concentration-dependent and reversible manner. In a membrane preparation from the same cells, VIP (1 to 1,000 nM) and ISO (0.1 to 10 microM) stimulated adenylyl cyclase activity in a concentration-dependent and nonadditive manner. In the same membrane preparation, no effect of M.chol was observed on this response to VIP or to ISO. It is proposed that functional antagonism at the cellular level between basal or cholinergic-stimulated mucin secretion and either activated beta-adrenergic or VIP receptors may play a crucial role in modulation of mucin secretion from epithelial cells.

Adenylyl Cyclases↗