Biomedical subjects

C Berney

Publications and source records attributed to C Berney.

At least 19 recordsLinked to original sources

PubMed2006

Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with 'heaves'.

REASON FOR PERFORMING STUDY: Trimetoquinol (TMQ) is a potent beta-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with 'heaves'. OBJECTIVES: To assess the pharmacodynamics of TMQ in horses with 'heaves' to determine potential therapeutic effects. METHODS: Increasing doses of TMQ were administered to horses with 'heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001-0.2 microg/kg bwt i.v. and 0.01-2 microg/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural pressure (deltaPplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 microg/kg bwt) and i.t. (2 microg/kg bwt) TMQ was evaluated over 6 h. RESULTS: Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 microg/kg bwt, and was still increasing after administration of highest dose, 0.2 microg/kg bwt. Airway bronchodilation, measured as a decrease in deltaPplmax, also commenced at 0.01 microg/kg bwt. By the i.t. route, TMQ was 50-100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h. CONCLUSION: When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with 'heaves'. Further studies of TMQ by oral and aerosol routes are necessary. POTENTIAL RELEVANCE: In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of 'heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other beta-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of 'heaves'.

Animals↗

PubMed2004

Multiple intraorbital neurofibromas: a rare cause of proptosis.

BACKGROUND: Orbital neurofibromas are rare, accounting for 0.5 to 2.4 % of all orbital tumors. Generally, they manifest as slowly progressive proptosis, in a young adult or middle-aged person, and are usually solitary lesions. Sometimes, they can be associated with type 1 neurofibromatosis. We present a case of proptosis related to multiple intraorbital neurofibromas in an 82-year-old woman without type 1 neurofibromatosis. HISTORY AND SIGNS: An 82-year-old woman was referred for slowly progressive left proptosis associated with an ocular burning sensation. Neuro-ophthalmic examination revealed 9.5 mm of left exophthalmos, signs of minimal left optic neuropathy but normal extraocular movements. Magnetic resonance imaging revealed the presence of 4 intraorbital lesions. THERAPY AND OUTCOME: The two most anterior tumors were removed. Pathological studies showed these tumors to be neurofibromas. Post-operative evolution was favorable with reduction of left proptosis to 7 mm and disappearance of the burning sensation of the left eye. No other signs of neurofibromatosis were found. CONCLUSIONS: Multiple circumscribed intraorbital tumors are rare. Slowly progressive proptosis with radiological imaging of multiple round lesions should evoke the diagnosis of orbital neurofibromas, even in patients outside the typical age range or without neurofibromatosis.

Aged↗

PubMed2004

Effects of stylopharyngeus muscle dysfunction on the nasopharynx in exercising horses.

REASONS FOR PERFORMING STUDY: Nasopharyngeal collapse has been observed in horses as a potential cause of exercise intolerance and upper respiratory noise. No treatment is currently available and affected horses are often retired from performance. OBJECTIVE: To determine the effect of bilateral glossopharyngeal nerve block and stylopharyngeus muscle dysfunction on nasopharyngeal function and airway pressures in exercising horses. METHODS: Endoscopic examinations were performed on horses at rest and while running on a treadmill at speeds corresponding to HRmax50, HRmax75 and HRmax, with upper airway pressures measured with and without bilateral glossopharyngeal nerve block. RESULTS: Bilateral glossopharyngeal nerve block caused stylopharyngeus muscle dysfunction and dorsal nasopharyngeal collapse in all horses. Peak inspiratory upper airway pressure was significantly (P = 0.0069) more negative at all speeds and respiratory frequency was lower (P = 0.017) in horses with bilateral glossopharyngeal nerve block and stylopharyngeus muscle dysfunction compared to control values. CONCLUSIONS: Bilateral glossopharyngeal nerve anaesthesia produced stylopharyngeus muscle dysfunction, dorsal pharyngeal collapse and airway obstruction in all horses. POTENTIAL RELEVANCE: The stylopharyngeus muscle is probably an important nasopharyngeal dilating muscle in horses and dysfunction of this muscle may be implicated in clinical cases of dorsal nasopharyngeal collapse. Before this information can be clinically useful, further research on the possible aetiology of stylopharyngeus dysfunction and dysfunction of other muscles that dilate the dorsal and lateral walls of the nasopharynx in horses is needed.

Airway Obstruction↗

PubMed2002

Efficacy of three corticosteroids for the treatment of heaves.

This study used a cross-over design to compare the efficacy of 3 corticosteroids for the relief of airway obstruction and inflammation in 9 heaves-affected horses. The severity of airway obstruction and inflammation was quantified by measurement of lung function and by bronchoalveolar lavage fluid (BALF) cytology, respectively. Airway obstruction was induced by stabling the horses and they remained stabled during the 10 day treatment period. Lung function was measured before treatment (baseline), at Days 3, 7, and 10 of treatment, and after 30 days at pasture. BALF cytology was investigated at baseline, Day 10, and at pasture. All 9 horses received the following 4 treatments in random order: no treatment, daily oral prednisone tablets (1 mg/kg), daily i.v. dexamethasone solution (0.1 mg/kg), and i.m. dexamethasone-21-isonicotinate (0.04 mg/kg) every 3 days. When horses received no treatment, lung function did not change significantly during stabling but improved at pasture. In all horses, daily i.v. administration of dexamethasone solution improved lung function within 3 days to levels as good as or better than those measured at pasture. Dexamethasone-21-isonicotinate was rapidly effective in 8 of 9 horses. The other horse did not respond to this drug. Prednisone tablets were without effect on Days 3 and 7 of treatment, but by Day 10, 5 of 9 horses showed some improvement in lung function. Dexamethasone i.v. solution decreased the percent neutrophils in BALF at Day 10. Other treatments had no effect on BALF cytology. These results demonstrate that dexamethasone rapidly relieved airway obstruction in heaves-affected horses. Oral prednisone had inconsistent effects but may be beneficial in some horses after more than a week of treatment.

Administration, Oral↗

PubMed2001

Effect of topical anesthesia of the laryngeal mucosa on upper airway mechanics in exercising horses.

OBJECTIVE: To determine the effect of desensitization of the laryngeal mucosal mechanoreceptors on upper airway mechanics in exercising horses. ANIMALS: 6 Standardbreds. PROCEDURE: In study 1, videoendoscopic examinations were performed while horses ran on a treadmill with and without topical anesthesia of the laryngeal mucosa. In study 2, peak tracheal and nasopharyngeal pressures and airflows were obtained from horses during incremental treadmill exercise tests, with and without topical anesthesia of the laryngeal mucosa. A nasal occlusion test was performed on each horse while standing during an endoscopic examination for both trials. RESULTS: In study 1, horses had nasopharyngeal collapse while running on the treadmill when the laryngeal mucosa was anesthetized. In study 2, inspiratory upper airway and nasopharyngeal impedance were significantly higher, and peak tracheal inspiratory pressure, respiratory frequency, and minute ventilation were significantly lower in horses when the laryngeal mucosa was anesthetized, compared with values obtained when horses exercised without topical anesthesia. Peak inspiratory and expiratory airflows were lower in horses when the laryngeal mucosa was anesthetized, although differences did not quite reach significance (P = 0.06 and 0.09, respectively). During a nasal occlusion test, horses had episodes of nasopharyngeal collapse and dorsal displacement of the soft palate when the laryngeal mucosa was anesthetized. Upper airway function was normal in these horses without laryngeal mucosal anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Receptors within the laryngeal mucosa may be important in maintaining upper airway patency in exercising horses.

Administration, Topical↗

PubMed2001

Effect of a tongue-tie on upper airway mechanics in horses during exercise.

OBJECTIVE: To determine the effect of a tongue-tie on upper airway mechanics in exercising horses. ANIMALS: 5 Standardbreds. PROCEDURE: Peak inspiratory and expiratory tracheal and pharyngeal pressures and airflow were measured while horses exercised on a treadmill with and without a tongue-tie. Respiratory rate was also measured. Horses ran at speeds that corresponded to 50 (HR50), 75, 90 (HR90), and 100% of maximal heart rate. The tongue-tie was applied by pulling the tongue forward out of the mouth as far as possible and tying it at the level of the base of the frenulum to the mandible with an elastic gauze bandage. Peak inspiratory and expiratory tracheal, pharyngeal, and translaryngeal resistance, minute ventilation, and tidal volume were calculated. Data were analyzed by use of 2-way repeated-measures ANOVA. For post hoc comparison of significant data, the Student-Newman-Keuls test was used. RESULTS: We were unable to detect significant differences between groups for peak inspiratory or expiratory tracheal or pharyngeal resistance, peak pressure, peak expiratory flow, tidal volume, respiratory rate, or minute ventilation. Horses that ran with a tongue-tie had significantly higher peak inspiratory flows, compared with horses that ran without a tongue-tie. In the post hoc comparison, this effect was significant at 4 m/s, HR50, and HR90. CONCLUSION AND CLINICAL RELEVANCE: Application of a tongue-tie did not alter upper respiratory mechanics in exercising horses and may be beneficial in exercising horses with certain types of obstructive dysfunction of the upper airways. However, application of a tongue-tie does not improve upper airway mechanics in clinically normal horses.

Animals↗

PubMed2001

Stabling is associated with airway inflammation in young Arabian horses.

We examined the effect of stabling on upper and lower airway inflammation in 14 yearling Arabian horses that had been at pasture since birth. Horses were divided into 2 groups of 7. One group was stabled for 3 months and the other remained at pasture. The groups were then switched over for another 3 months. The nasopharynx, guttural pouches and trachea were examined endoscopically and bronchoalveolar lavage performed every month. An upper airway inflammation score was devised based on the magnitude of pharyngeal lymphoid hyperplasia and guttural pouch inflammation. During stabling this score remained constant, whereas it decreased during the 3 months at pasture. Stabling was also associated with a higher number and percentage of neutrophils in bronchoalveolar lavage fluid and with a smaller percentage of lymphocytes. There was no correlation between upper airway inflammation score and bronchoalveolar lavage cytology. During a nasal occlusion test, dorsal displacement of the soft palate occurred more times in stabled than in pastured horses, but this was heavily biased by the results from one animal. We conclude that stabling is associated with inflammation of both the upper and lower airway of young horses.

Animals↗

PubMed2000

Evolution of Antp-class genes and differential expression of Hydra Hox/paraHox genes in anterior patterning.

The conservation of developmental functions exerted by Antp-class homeoproteins in protostomes and deuterostomes suggested that homologs with related functions are present in diploblastic animals. Our phylogenetic analyses showed that Antp-class homeodomains belong either to non-Hox or to Hox/paraHox families. Among the 13 non-Hox families, 9 have diploblastic homologs, Msx, Emx, Barx, Evx, Tlx, NK-2, and Prh/Hex, Not, and Dlx, reported here. Among the Hox/paraHox, poriferan sequences were not found, and the cnidarian sequences formed at least five distinct cnox families. Two are significantly related to the paraHox Gsx (cnox-2) and the mox (cnox-5) sequences, whereas three display some relatedness to the Hox paralog groups 1 (cnox-1), 9/10 (cnox-3) and the paraHox cdx (cnox-4). Intermediate Hox/paraHox genes (PG 3 to 8 and lox) did not have clear cnidarian counterparts. In Hydra, cnox-1, cnox-2, and cnox-3 were not found chromosomally linked within a 150-kb range and displayed specific expression patterns in the adult head. During regeneration, cnox-1 was expressed as an early gene whatever the polarity, whereas cnox-2 was up-regulated later during head but not foot regeneration. Finally, cnox-3 expression was reestablished in the adult head once it was fully formed. These results suggest that the Hydra genes related to anterior Hox/paraHox genes are involved at different stages of apical differentiation. However, the positional information defining the oral/aboral axis in Hydra cannot be correlated strictly to that characterizing the anterior-posterior axis in vertebrates or arthropods.

Amino Acid Sequence↗

PubMed2000

A novel monoclonal antibody, C41, reveals IL-13Ralpha1 expression by murine germinal center B cells and follicular dendritic cells.

Responsiveness to IL-13 involves at least two chains, IL-4Ralpha and IL-13Ralpha1. Although mouse B cells express IL-4Ralpha, little is known about their expression of IL-13Ralpha chains. To investigate this topic further, we have generated a monoclonal antibody (C41) specific for murine IL-13Ralpha1. Using C41, IL-13Ralpha1 expression was detected on germinal center (GC) B cells by flow cytometry and immunohistochemistry. In addition, IL-13Ralpha1 was observed on follicular dendritic cells, but not interdigitating dendritic cells in the T cell areas. Furthermore, resting B cells also expressed IL-13Ralpha1, and in the presence of IL-13 produced increased amounts of IgM in response to in vitro CD40 stimulation. However, C41 was unable to neutralize this bioactivity. The distribution of IL-13Ralpha1 on murine B cells and during GC reactions suggests a role for IL-13 during B cell differentiation.

Animals↗

PubMed2000

[Mydriasis induced by splinter from belladonna bush].

AIM: Pupillary dilatation with alcaloids from the Atropa belladonna plant have been used since antiquity. It is less known that the wood of the plant contains an even higher concentration of alkaloids than the ripe fruit. METHODS: Clinical case. RESULTS: A 32-year-old patient presented with a foreign body sensation after a splinter got in his eye while chopping wood of an Atropa belladonna bush in the underbrush. Ophthalmic examination showed a visual acuity of 0.9 s.c. (1.0 with pinhole) and a pupil in a fixed mydriasis without any visible rupture of the sphincter muscle. After a 3-day follow-up the pupil returned to normal size and visual acuity recovered to 1.25 s.c. CONCLUSION: The wood of the Atropa belladonna plant contains a very high concentration of alkaloids. A well-directed history may help to discover this less well-known cause of an accidental mydriasis.

Adult↗

PubMed2000

Elongation factor 1-alpha sequences do not support an early divergence of the Acoela.

The phylogenetic position of the Acoela is a key problem in the understanding of metazoan evolution. Recent studies based on 18S ribosomal DNA (rDNA) sequences have placed the Acoela in an extremely basal position as the sister group to all other extant triploblastic animals, suggesting that the phylum Platyhelminthes is polyphyletic. In order to test the results obtained with 18S rDNA, we sequenced elongation factor 1-alpha (EF1a) for the acoel Convoluta roscoffensis and five species of Turbellaria (two polyclads, Leptoplana tremellaris, and Prostheceraeus vittatus, and three triclads, Crenobia alpina, Schmidtea polychroa, and Girardia tigrina). Phylogenetic analyses of EF1a sequences show that the acoel sequences branch within the Platyhelminthes, in opposition to the 18S rDNA data. Moreover, comparison of the central variable region of EF1a shows similar sequence signatures between C. roscoffensis and the three triclad species. Although EF1a sequences fail to prove the monophyly of the phylum Platyhelminthes, they do not confirm the early divergence of the Acoela.

Amino Acid Sequence↗

PubMed2000

Relationship between clinical signs and lung function in horses with recurrent airway obstruction (heaves) during a bronchodilator trial.

During a trial to determine the dose response to the beta2-adrenergic agonist pirbuterol, we judged the severity of airway obstruction by use of a clinical scoring system and compared this to objective data obtained by quantitative measures of lung function. Six horses affected by recurrent airway obstruction were used in this trial. Four hundred and sixty-eight measurements of lung function and clinical scores were obtained from 13 measurement periods when horses received each of 6 doses of pirbuterol. Scores of 1-4 were assigned to degree of nasal flaring and abdominal effort and summed for a total score. The veterinarian scoring the signs did not know the dose of pirbuterol received by the horse and was unaware of the lung function data. Nasal, abdominal and total scores were significantly related to changes in lung function and changes in breathing pattern. There were significant differences between total scores greater than 5 in indices that reflected changes in breathing strategy (peak inspiratory and expiratory flow), peripheral airway obstruction (dynamic elastance), and effort of breathing (maximal change in pleural pressure). Below a total score of 5, there were fewer significant differences in lung function even though measurements of pulmonary resistance and dynamic elastance indicated considerable airway obstruction. Failure of clinical score to reflect this low-grade airway obstruction suggests that airway disease is underdiagnosed and its detection would be helped by the availability of a convenient lung function test.

Airway Obstruction↗

PubMed2000

Environment and prednisone interactions in the treatment of recurrent airway obstruction (heaves).

Recurrent airway obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional benefit. Twelve RAO-susceptible horses were stabled, fed hay, and bedded on straw until they developed airway obstruction. At this point, bedding was changed to wood shavings and they were fed a pelleted diet for 2 weeks. Lung function was measured and bronchoalveolar lavage was performed before and 3, 7, and 14 days after environmental modification. In a crossover design, horses were treated for the 14 days with prednisone tablets (2.2 mg/kg bwt, q. 24 h). Horses then returned to pasture for 30 days. Airway obstruction was greatest before environmental modification. Significant improvement in lung function occurred within 3 days of the change in environment and continued to Day 7. Airway function was best after 30 days at pasture. The clinical response achieved by environmental modification was not significantly improved by addition of oral prednisone. The total number of cells, total neutrophils, and percent neutrophils was greatest before environmental modification. In the absence of prednisone, total and percent neutrophils did not decrease until Day 14 and total cell number until 30 days at pasture. In the presence of prednisone, total cells and total and percent neutrophils decreased by Day 3 and again at pasture. The fact that lung function can be improved within 3 days by environmental management alone emphasises the need for allergen reduction as the cornerstone of treatment of RAO. Although prednisone induced a more rapid reduction in airway inflammation, this was not associated with a more rapid improvement in airway function.

Airway Obstruction↗

PubMed1999

A member of the dendritic cell family that enters B cell follicles and stimulates primary antibody responses identified by a mannose receptor fusion protein.

Dendritic cells (DCs) are known to activate naive T cells to become effective helper cells. In addition, recent evidence suggests that DCs may influence naive B cells during the initial priming of antibody responses. In this study, using three-color confocal microscopy and three-dimensional immunohistograms, we have observed that in the first few days after a primary immunization, cells with dendritic morphology progressively localize within primary B cell follicles. These cells were identified by their ability to bind a fusion protein consisting of the terminal cysteine-rich portion of the mouse mannose receptor and the Fc portion of human immunoglobulin (Ig)G1 (CR-Fc). In situ, these CR-Fc binding cells express major histocompatibility complex class II, sialoadhesin, and CD11c and are negative for other markers identifying the myeloid DC lineage, such as (CD11b), macrophages (F4/80), follicular DCs (FDC-M2), B cells (B220), and T cells (CD4). Using CR-Fc binding capacity and flow cytometry, the cells were purified from the draining lymph nodes of mice 24 h after immunization. When injected into naive mice, these cells were able to prime T cells as well as induce production of antigen-specific IgM and IgG1. Furthermore, they produced significantly more of the lymphocyte chemoattractant, macrophage inflammatory protein (MIP)-1alpha, than isolated interdigitating cells. Taken together, these results provide evidence that a subset of DCs enters primary follicles, armed with the capacity to attract and provide antigenic stimulation for T and B lymphocytes.

Animals↗

PubMed1999

A soluble form of IL-13 receptor alpha 1 promotes IgG2a and IgG2b production by murine germinal center B cells.

A functional IL-13R involves at least two cell surface proteins, the IL-13R alpha 1 and IL-4R alpha. Using a soluble form of the murine IL-13R alpha 1 (sIL-13R), we reveal several novel features of this system. The sIL-13R promotes proliferation and augmentation of Ag-specific IgM, IgG2a, and IgG2b production by murine germinal center (GC) B cells in vitro. These effects were enhanced by CD40 signaling and were not inhibited by an anti-IL4R alpha mAb, a result suggesting other ligands. In GC cell cultures, sIL-13R also promoted IL-6 production, and interestingly, sIL-13R-induced IgG2a and IgG2b augmentation was absent in GC cells isolated from IL-6-deficient mice. Furthermore, the effects of the sIL-13R molecule were inhibited in the presence of an anti-IL-13 mAb, and preincubation of GC cells with IL-13 enhanced the sIL-13R-mediated effects. When sIL-13R was injected into mice, it served as an adjuvant-promoting production to varying degrees of IgM and IgG isotypes. We thus propose that IL-13R alpha 1 is a molecule involved in B cell differentiation, using a mechanism that may involve regulation of IL-6-responsive elements. Taken together, our data reveal previously unknown activities as well as suggest that the ligand for the sIL-13R might be a component of the IL-13R complex or a counterstructure yet to be defined.

Animals↗

PubMed1999

Determinants of the maximal change in pleural pressure during tidal breathing in COPD-affected horses.

In six COPD-affected horses, we analysed the factors responsible for the changes in pleural pressure (delta Pplmax) that occur during tidal breathing. Four-hundred-and-sixty-eight measurements of each parameter: pulmonary resistance (RL), dynamic elastance (Edyn), air flow rates, and the timing of breathing, were gathered during a trial of the bronchodilator pirbuterol. Data were placed into seven ranks, based on the magnitude of delta Pplmax; rank 1: 5-15; rank 2: 15-25; rank 3: 25-35; rank 4: 35-45; rank 5: 45-55; rank 6: 55-65; and rank 7 > 65 cm H2O. Up to rank 4 (45 cm H2O), the increase in delta Pplmax was due to increases in RL, Edyn, and inspiratory and expiratory air flow rates. Further increases in delta Pplmax were due to continuing increases in Edyn and flow rates with little change in resistance. The increase in inspiratory flow rates was the result of a decrease in inspiratory time. The large increase in peak expiratory flow could not be explained by the small decrease in expiratory time and must therefore be due to a change in breathing strategy as delta Pplmax increased. Changes in air flow rates as well as changes in RL and Edyn must be considered as reasons for a change in delta Pplmax when evaluating horses with COPD.

Airway Resistance↗

PubMed1999

Aerosolized albuterol sulfate used as a bronchodilator in horses with recurrent airway obstruction.

OBJECTIVE: To determine the dose of aerosolized albuterol sulfate required to cause bronchodilation in horses with recurrent airway obstruction (RAO) and duration of this effect. ANIMALS: 19 horses with RAO (10 in experiment 1; 9 in experiment 2). PROCEDURE: Horses were moved from pasture to stables, and airway obstruction was induced. Pulmonary function was measured in 10 horses before and 5, 10, and 30 minutes after administration of vehicle or 120, 240, 360, or 720 microg of the drug. Nine horses received vehicle or 360 or 720 microg of albuterol, and pulmonary function was measured at baseline and 5 minutes and 1, 2, 3, 4, 5, 6, and 7 hours later. Horses were evaluated for adverse drug effects. RESULTS: 360 microg of albuterol was required to cause significant bronchodilatation; 720 microg did not enhance bronchodilatation or increase duration of action. Depending on which pulmonary function parameter was evaluated, bronchodilatation achieved by use of albuterol lasted between 30 minutes and 1 hour. Because there was a significant vehicle effect, the combined effect of vehicle and drug lasted up to 3 hours. Adverse effects were not observed. CONCLUSIONS: Aerosolized albuterol, 360 or 720 microg, is a safe and effective bronchodilator in horses with RAO. Onset of action is rapid (5 minutes), and effects last from 30 minutes to 3 hours. CLINICAL RELEVANCE: Aerosolized albuterol is useful for treatment of bronchospasm in horses with RAO.

Administration, Inhalation↗

PubMed1998

The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas.

We have generated a mouse bearing a null allele of the gene encoding basic helix-loop-helix (bHLH) protein p48, the cell-specific DNA-binding subunit of hetero-oligomeric transcription factor PTF1 that directs the expression of genes in the exocrine pancreas. The null mutation, which establishes a lethal condition shortly after birth, leads to a complete absence of exocrine pancreatic tissue and its specific products, indicating that p48 is required for differentiation and/or proliferation of the exocrine cell lineage. p48 is so far the only developmental regulator known to be required exclusively for committing cells to an exocrine fate. The hormone secreting cells of all four endocrine lineages are present in the mesentery that normally harbors the pancreatic organ until day 16 of gestation. Toward the end of embryonic life, cells expressing endocrine functions are no longer detected at their original location but are now found to colonize the spleen, where they persist in a functional state until postnatal death of the organism occurs. These findings suggest that the presence of the exocrine pancreas is required for the correct spatial assembly of the endocrine pancreas and that, in its absence, endocrine cells are directed by default to the spleen, a site that, in some reptiles, harbors part of this particular cellular compartment.

Animals↗