Biomedical subjects

M Wilhelm

Publications and source records attributed to M Wilhelm.

At least 19 recordsLinked to original sources

PubMed2001

Quality control of inactivated erysipelas vaccines: results of an international collaborative study to establish a new regulatory test.

According to the specifications of the European Pharmacopoeia (Ph. Eur.) monograph (Swine Erysipelas Vaccine (Inactivated), Monograph no. 64, European Pharmacopoeia, 3rd edn., 1997) on erysipelas vaccines for veterinary use, batch potency is estimated in a multi-dilution assay after immunisation and infection of mice. Recently, we described a serological assay system (ELISA) which has the potential to replace this challenge-based model (Beckmann R, Cussler K. Wirksamkeitsprüfung von Rotlaufimpfstoffen an der Labormaus. ELISA kontra Infektionsversuch. ALTEX 1994;Suppl. 1:39-45; Rosskopf-Streicher U, Johannes S, Hausleithner D, Gyra H, Cussler K. Suitability of an ELISA for the batch potency test in laboratory mice. Pharmeuropa BIO 1998;1:65-70). The humoral immune response is quantified in pooled sera of ten mice three weeks after immunisation. The results are expressed as relative potency (RP) in comparison to a reference serum. After a pre-validation study had been performed with success (Rosskopf-Streicher U, Johannes S, Wilhelm M, Gyra H, Cussler K. Potency testing of swine erysipelas vaccines by serology - results of a pre-validation study. ALTEX 1999;16:123-8), we initiated an international collaborative study with five European manufacturers and seven regulatory authorities to validate the assay and model. All participants were provided with blind-coded erysipelas vaccines of different potencies, the ELISA kit and test instructions. The participants had to immunise mice, to prepare serum samples and to perform the ELISA. Inter-laboratory reproducibility was reported by the pass/fail criteria of the vaccines under test. Intra-laboratory precision was assessed by comparing repeated measurements on three consecutive days. Day-to-day variation within the laboratories was statistically analysed by comparing pairs of RPs using Lin's concordance correlation coefficient. The results show that the ELISA is indeed a suitable alternative to replace the vaccination-challenge test. Furthermore, this new model reduces the number of animals required for the potency test by approximately 80%.

Analysis of Variance↗

PubMed2001

Noncardiac surgery in patients with left ventricular assist devices.

BACKGROUND: Noncardiac surgery, especially abdominal surgical procedures in patients with long-term mechanical circulatory support and strong anticoagulation, is difficult. METHODS: We report on 14 patients (aged 44 +/- 15 years) with a portable Novacor or HeartMate system, who underwent noncardiac surgical procedures while being supported by the device. RESULTS: The patients underwent 20 procedures for noncardiac reasons; most had an intestinal operation or cholecystectomy. Half of the procedures were performed within 30 days after placement of the device (mean interval, 53 +/- 57 days), only 6 interventions were necessary after 100 days of mechanical support. Complications occurred in 8 patients (57%), 5 of whom had undergone cholecystectomy and had unacceptably high sanguineous drainage losses. CONCLUSIONS: An elective surgical procedure can be performed with an acceptable risk if the operation is carefully managed. Postponing resumption of full anticoagulation is advisable as it may reduce bleeding complications without apparently increasing the risk for thromboembolism. Emergency interventions remain a difficult task.

Adult↗

PubMed2001

Comparison of different digestive tract models for estimating bioaccessibility of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) from red slag 'Kieselrot'.

'Kieselrot' (red slag), a highly PCDD/F-contaminated leaching residue from a copper production process, has been used as surface layer for more than 1,000 sports fields, playgrounds and pavements in Germany and neighbouring countries. Children can ingest this material directly by hand-to-mouth activities or soil-pica behaviour. Furthermore secondary contamination of farm land or kitchen gardens by drift of red slag dust may lead to an enrichment of PCDD/F within the food-chain. PCDD/F can be mobilized from contaminated materials by digestive juices and thus become bioaccessible for intestinal absorption. Two different digestive tract models were used to estimate the bioaccessibility of PCDD/F from red slag and to study the influence of food material on the mobilization of the contaminants. The bioaccessibility of PCDD/F from red slag depends on the charge of red slag material used, the bile content of the intestinal juice and on the presence of lipophilic foodstuffs. A low bioaccessibility of less than 5% was found when using a digestive tract model with a low bile content and in absence of food material. The bioaccessibility was estimated to be more than 60% when using a model with a higher bile content and in the presence of whole milk powder. A low bioaccessibility of PCDD/F from red slag in general--as assumed until now and mentioned in legal provision--was not confirmed by our study. Considering observations for the different homologue groups it is obvious that bioaccessibility is the first of several important steps to estimate human health risks arising from contaminated materials. In case red slag contaminated with PCDD/F their absorption rate in the digestive tract and/or metabolism might be at least just like important.

Benzofurans↗

PubMed2000

Selective and sensitive assay for the determination of benzodiazepines by high-performance liquid chromatography with simultaneous ultraviolet and reductive electrochemical detection at the hanging mercury drop electrode.

An isocratic chromatographic method for the simultaneous determination of 10 benzodiazepines is presented. The selectivity of the assay was optimized by variation of stationary phase, temperature, as well as ionic strength, composition and pH of the mobile phase and the dependence of the detector response on the applied potential was investigated. The best results with respect to resolution at moderate retention times were obtained with a mixture of 0.02 mol/l phosphate buffer (pH 6) and acetonitrile in a volume ratio of 55:45 (v/v) on a LiChrospher-100 RP-8ec column (150x4.6 mm I.D.). Considerable improvement of selectivity was achieved if the column temperature was kept constant at 12 degrees C. Two detection modes were applied, UV detection at 250 nm, inserted upstream to the electrochemical detector, and reductive electrochemical detection at the hanging mercury drop electrode at -1.4 V (vs. Ag/AgCl), which proved to be especially sensitive in case of nitrophenyl-containing benzodiazepine species. The elaborated assay showed to be linear up to at least 2 mg/l for each compound. Detection limits generally were in the range of 6.5-123 ng/ml (130 pg-2.46 ng on-column, using a 20-microl loop) with relative standard deviations between 1.1 and 8.6% depending on the actual benzodiazepine investigated.

Benzodiazepines↗

PubMed2000

Amacrine cells of the anuran retina: morphology, chemical neuroanatomy, and physiology.

Amacrine cells are third-order retinal interneurons, projecting their processes into the inner plexiform layer. Historically, they were not considered as neurons first. By the middle of the 20th century, their neuronal nature was confirmed, and their enormous diversity established. Amacrine cells have been most successfully subdivided into morphological categories based on two parameters: diameter of the dendritic field and ramification pattern in the inner plexiform layer. Works combining anatomy, physiology, and neurochemistry are scarce and in the case of the anuran retina, the situation is even worse. Correlation between morphology, neurochemistry, and physiology is little studied. Here we try to build up a database and pinpoint some of the missing data. Obtaining those could help to better understand retinal function. Sporadic attempts did not make it possible to develop a comprehensive catalog of morphologically distinct amacrine cell types in the anuran retina. The number of morphologically identified amacrine cells currently stands at 16. The list of neurochemically identified distinct cell types can be given as follows: five types GABA-containing cell types with secondary markers and at least one without; two glycinergic cell types and one interplexiform cell where glycine colocalizes with somatostatin; one dopaminergic amacrine cell and also a variant of this with interplexiform morphology; two types of serotoninergic cells; three NADPHdiaphorase-positive cells, one substance P-positive cell type without identified second marker; one CCK-positive cell type without identified second marker and the calbindin positive cells (at least one but potentially more types). This adds up to 19 cell types, out of which two are interplexiform in character. This is more than that could be identified by purely morphological means. Out of Cajal's original 13 amacrine cell types described in the frog retina, 5 parallel unequivocally with neurons defined by neurochemistry. Three others have one close match each, but their exact identity is uncertain. The remaining amacrine cells have more than one potential matches. At the same time, on one hand the amacrine cell named two-layered by Cajal so far has no match among the neurochemically identified amacrine cells. On the other hand, the interplexiform subtype of the dopaminergic cell, the somatostatin-containing glycinergic interplexiform cell, the starburst cell, and the bistratified neuropeptide Y-immunoreactive cell have no match among Cajal's cells. All in all, the number of known amacrine and interplexiform cells now stands at at least 21 in the anuran retina. Physiological characterization of amacrine cells shows that their general features seem to be rather similar to those described in tiger salamander retina. In Xenopus retina, morphologically and physiologically identified amacrine cells responded to light stimulation most frequently with ON-OFF characteristics. Immunhistochemical identification of the recorded and dye injected cells showed that amacrine cells of the "same physiological type" might have different morphology. In other words, amacrine cells with different morphology can respond similarly to illumination. Even so, small differences between almost identical responses may reflect that the cell they stem from indeed belongs to different cell types.

Animals↗

PubMed2000

Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma.

Bisphosphonates are well-known inhibitors of osteoclastic bone resorption, but recent clinical reports support the possibility of direct or indirect antitumor effects by these compounds. Because bisphosphonates share structural homologies with recently identified gamma delta T-cell ligands, we examined the stimulatory capacity of bisphosphonates to gamma delta T cells and determined whether gamma delta T-cell stimulation by bisphosphonates could be exploited to generate antiplasma cell activity in multiple myeloma (MM). All tested aminobisphosphonates (alendronate, ibandronate, and pamidronate) induced significant expansion of gamma delta T cells (V gamma 9V delta 2++ subset) in peripheral blood mononuclear cell cultures of healthy donors at clinically relevant concentrations (half-maximal activity, 0.9-4 mcmol/L). The proliferative response of gamma delta T cells to aminobisphosphonates was IL-2 dependent, whereas activation of gamma delta T cells (up-regulation of CD25 and CD69) occurred in the absence of exogenous cytokines. Pamidronate-activated gamma delta T cells produced cytokines (ie, interferon [IFN]-gamma) and exhibited specific cytotoxicity against lymphoma (Daudi) and myeloma cell lines (RPMI 8226, U266). Pamidronate-treated bone marrow (BM) cultures of 24 patients with MM showed significantly reduced plasma cell survival compared with untreated cultures, especially in cultures in which activation of BM-gamma delta T cells was evident (14 of 24 patients with MM). gamma delta T-cell depletion from BM cultures completely abrogated the cytoreductive effect on myeloma cells in 2 of 3 tested patients with MM. These results show that aminobisphosphonates stimulating gamma delta T cells have pronounced effects on the immune system, which might contribute to the antitumor effects of these drugs. (Blood. 2000;96:384-392)

Alendronate↗

PubMed2000

Expression of an active form of recombinant Ty1 reverse transcriptase in Escherichia coli: a fusion protein containing the C-terminal region of the Ty1 integrase linked to the reverse transcriptase-RNase H domain exhibits polymerase and RNase H activities.

Replication of the Saccharomyces cerevisiae Ty1 retrotransposon requires a reverse transcriptase capable of synthesizing Ty1 DNA. The first description of an active form of a recombinant Ty1 enzyme with polymerase and RNase H activities is reported here. The Ty1 enzyme was expressed as a hexahistidine-tagged fusion protein in Escherichia coli to facilitate purification of the recombinant protein by metal-chelate chromatography. Catalytic activity of the recombinant protein was detected only when amino acid residues encoded by the integrase gene were added to the N-terminus of the reverse transcriptase-RNase H domain. This suggests that the integrase domain could play a role in proper folding of reverse transcriptase. Several biochemical properties of the Ty1 enzyme were analysed, including the effect of MgCl(2), NaCl, temperature and of the chain terminator dideoxy GTP on its polymerase activity. RNase H activity was examined by monitoring the cleavage of a RNA-DNA template-primer. Our results suggest that the distance between the RNase H and polymerase active sites corresponds to the length of a 14-nucleotide RNA-DNA heteroduplex. The recombinant protein produced in E. coli should be useful for further biochemical and structural analyses and for a better understanding of the role of integrase in the activation of reverse transcriptase.

Amino Acid Sequence↗

PubMed2000

Determination of basic nitrogen-containing polynuclear aromatic hydrocarbons formed during thermal degradation of polymers by high-performance liquid chromatography-fluorescence detection.

A method for the simultaneous determination of 22 nitrogen-containing polynuclear aromatic hydrocarbons (PAHs) (15 azaarenes and seven amino-PAHs) in the gaseous products of the thermal degradation of polymers is described. After desorption and clean-up using cation-exchange chromatography (PRS cartridge) the samples were analyzed by HPLC-FD. The validation was carried out with real nylon 6 combustion samples. The recoveries of the compounds are in the range of 89-99% for the extraction and 91-100% for the clean up procedure. The detection limits ranged from 7 to 160 pg. The high recovery values, due to the quick and efficient clean-up procedure, resulted in low relative standard deviations (with the exception of acridine and 2-aminoanthracene <5%). The applicability of the method is also investigated for the determination of the N-PAHs in a pyrolysis sample.

Chromatography, High Pressure Liquid↗

PubMed2000

Mast cells migrate from blood to brain.

It is well established that mast cells (MCs) occur within the CNS of many species. Furthermore, their numbers can increase rapidly in adults in response to altered physiological conditions. In this study we found that early postpartum rats had significantly more mast cells in the thalamus than virgin controls. Evidence from semithin sections from these females suggested that mast cells were transiting across the medium-sized blood vessels. We hypothesized that the increases in mast cell number were caused by their migration into the neural parenchyma. To this end, we purified rat peritoneal mast cells, labeled them with the vital dyes PKH26 or CellTracker Green, and injected them into host animals. One hour after injection, dye-filled cells, containing either histamine or serotonin (mediators stored in mast cells), were located close to thalamic blood vessels. Injected cells represented approximately 2-20% of the total mast cell population in this brain region. Scanning confocal microscopy confirmed that the biogenic amine and the vital dye occurred in the same cell. To determine whether the donor mast cells were within the blood-brain barrier, we studied the localization of dye-marked donor cells and either Factor VIII, a component of endothelial basal laminae, or glial fibrillary acidic protein, the intermediate filament found in astrocytes. Serial section reconstructions of confocal images demonstrated that the mast cells were deep to the basal lamina, in nests of glial processes. This is the first demonstration that mast cells can rapidly penetrate brain blood vessels, and this may account for the rapid increases in mast cell populations after physiological manipulations.

Age Factors↗

PubMed2000

Decrease of PCDD/F levels in human blood--trend analysis for the German population, 1991-1996.

More than 500 whole blood samples of normal subjects from Germany collected in 1991-1996 have been analyzed for polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) by capillary gas chromatography/high-resolution mass spectrometry. Over the examined time period a continuous decrease of the PCDD/F concentrations in human blood was observed. The mean levels found were about 42.7 pg I-TEq/g (lipid basis) in 1991 and 20.7 pg I-TEq/g (liquid basis) in 1996 [median: 40.8 and 19.2]. A reduction to about half was found for most congeners. Each 1-year subset of the entire collective shows a positive correlation of the PCDD/F blood levels with age for most of the congeners, the sum values, and the calculated toxicity equivalents. For statistical evaluation a multiplicative model was used: Concentration in blood = A x ageB. The correlation is mostly pronounced for lower chlorinated PCDD and for 2,3,4,7,8-PentaCDF.

Adolescent↗

PubMed2000

Primary gastric non-Hodgkin's lymphoma: requirements for diagnosis and staging.

Tumor stage and histological grading (low grade vs. high grade) determine the prognostic outcome of primary gastric mucosa-associated lymphoid tissue (MALT)-type non-Hodgkin's lymphoma (NHL). Any diagnostic uncertainty of clinical staging may have potentially important therapeutic implications, especially if a non-surgical approach is favored. Diagnostic procedures for evaluation of gastric lymphoma include gastrointestinal endoscopy, endoscopic ultrasound of the upper gastrointestinal tract, conventional abdominal and cervical ultrasound, thoracic and abdominal computed tomography (CT) scans and bone marrow biopsy. In the present overview, the value of clinical diagnostic procedures is discussed with respect to clinical and endoscopic criteria which may be helpful for evaluation of gastric NHL. Furthermore, clinical staging methods such as endoscopic ultrasound are assessed which may allow pre-operative determination of tumor and lymph-node stage. These novel approaches are compared with the gold standard of pathohistological analysis. In conclusion, the diagnostic procedures presented appear to be helpful for establishing an early diagnosis, however, innovative methods such as endoscopic-bioptic mapping of the stomach and ultrasound-guided fine-needle biopsy techniques may improve pre-therapeutical work-up.

Gastroscopy↗

PubMed2000

Persistent polyclonal B-cell lymphocytosis--an important differential diagnosis of B-cell chronic lymphocytic leukemia.

Over the last 17 years, 83 cases of polyclonal B-cell lymphocytosis (PPBL) have been published. This rare hematological disorder of unknown etiology is characterized by morphologically atypical lymphocytes, polyclonal immunoglobulin M production in association with smoking, female gender, and HLA-DR7 phenotype. We studied another male patient with PPBL. In contrast to normal B-cells, PPBL cells showed no response to interleukin-4 with regard to CD23 and human leukocyte antigen-DR expression. F2mu antibodies failed to co-stimulate interleukin-4-mediated CD23 expression. Crosslinking membrane immunoglobulin M receptors by F2mu resulted in elevated human leukocyte antigen-DR expression but did not induce in vitro proliferation of PPBL cells. This indicates a different activation and differentiation status than normal B-cells.

Adult↗

PubMed2000

Effect of high dose platelet inhibitor treatment on thromboembolism in Novacor patients.

BACKGROUND: Thromboembolism and bleeding are among the most hazardous complications following implantation of long-term left ventricular support systems. This report focuses on the effect of high dose platelet inhibitor treatment in patients with the Novacor system to prevent thromboembolic events. METHODS: Thirty-eight (out of 58) Novacor patients (43+/-11 years old) were studied in a non-randomized manner. Postimplantation: 20 patients were treated with heparin only (control group), whereas in the other 18 patients aspirin (3x330 mg/day) and dipyridamol (3x75 mg/day) were added to the treatment protocol (aspirin group). RESULTS: Age, body size, underlying heart disease and support interval were comparable among both groups, however, patients in the aspirin group were much sicker with regard to urgency status, postoperative right heart failure and hematologic disorders. Cerebral thromboembolic complications were lower in the aspirin group (33% of patients, 0.4+/-0.7 events) as compared to the control group (55% (P=0.18), 1.4+/-2.3 events (P=0. 048)). Non-cerebral thromboembolism of surgical relevance was rare. The incidence of bleeding complications was mildly increased in the aspirin group. CONCLUSION: The addition of high dose platelet inhibitors seems to lower the incidence of thromboembolism in Novacor patients.

Adult↗

PubMed2000

Chromosomal rearrangements affecting biofilm production and antibiotic resistance in a Staphylococcus epidermidis strain causing shunt-associated ventriculitis.

During two clinical courses of shunt-associated meningitis in a 3-month-old child, five multiresistant S. epidermidis isolates were obtained and analyzed with regard to biofilm production and antibiotic susceptibility. Three S. epidermidis strains, which were initially isolated from the cerebrospinal fluid, produced biofilms on polystyrene tissue culture plates. Following antibiotic treatment and subsequent exchange of the shunt system, sterilization of the CSF was achieved. However, after three weeks a relapse of the infection occurred. The two S. epidermidis isolates obtained now were biofilm negative, but showed an identical resistance pattern as those from the previous infection, except that resistance to rifampicin and increased mininal inhibitory concentrations of aminoglycoside antibiotics had emerged. DNA fingerprinting by PFGE indicated the clonal origin of all isolates. However, some DNA rearrangements and differences in the IS256-specific hybridization patterns could be identified in the isolates from the second infection period that led to altered biofilm formation and increased expression of aminoglycoside resistance traits. The data evidence that variation of biofilm expression occurs in vivo during an infection and highlight the extraordinary genome flexibility of pathogenic S. epidermidis.

Anti-Bacterial Agents↗

PubMed2000

Dietary intake of lead, cadmium, copper and zinc by children from the German North Sea island Amrum.

The dietary intake of metals was studied in seven male and seven female children at the age of 1.5 to 5.3 years living in a remote area of Germany, the North Sea island Amrum. The dietary intake of lead and cadmium was measured by a seven-day-duplicate study using atomic absorption spectrometry. The dietary intake of copper and zinc were calculated from food diaries. The median lead and cadmium intakes were 2.1 micrograms/(kgbw x week) [range: 0.63-5.1 micrograms/(kgbw x week)] and 2.7 micrograms/(kgbw x week) [range: 1.7-4.4 micrograms/(kgbw x week)]. The median daily intake of copper and zinc were 1.1 mg/d (range: 0.54-2.5 mg/d) and 5.7 mg/d (range: 2.7-14 mg/d). Compared to the provisional tolerable weekly intake (PTWI) of 25 micrograms/(kgbw x week) proposed by the WHO the dietary intake of lead was low. The median amounted to 8.5% and the maximum to 20% of the PTWI. The cadmium intake was comparatively high. The median amounted to 39% and the maximum to 63% of the PTWI [7 micrograms/(kgbw x week)]. The median intake of copper was in the range of the values recommended by the German Society of Nutrition (0.7-1.0 mg/d and 1.0-1.5 mg/d for children at the age of 1-< 4 years and 4-< 7 years). Twenty-three percent of the calculated intakes were below these values. The median intake of zinc however did not reach the recommended dietary intake of 7 and 10 mg/d for children at the age of 1-< 4 years and 4-< 7 years.

Cadmium↗

PubMed2000

Impact of silver and copper on the survival of amoebae and ciliated protozoa in vitro.

The efficacy of 1:10 silver/copper combinations for inactivation of Hartmannella vermiformis amoebas and the ciliated protozoan Tetrahymena pyriformis in vitro was studied. Tetrahymena and Hartmannella/isolate 19 were inactivated for 2 log steps by 100 + 1000 micrograms/l Ag + Cu. Hartmannella/isolate 21 was more resistant. 500 + 5000 micrograms/l produced only a 0.6 log reduction. The investigations clearly showed that levels within the limit of the German drinking water regulation (10 + 100 micrograms/l Ag + Cu) could not inactivate these protozoas in vitro.

Amebiasis↗

PubMed2000

Scanning electron microscopical investigations of broncho-alveolar casts after intratracheal asbestos fibre instillation.

The evaluation of the toxicity of mineral fibres has been tried to achieve in experimental animal models. However, the appearance of fibres in the pleural space could not be explained satisfactorily. Histomorphological examinations showed that intratracheal instillation of asbestos fibres leads to parabronchial and intraalveolar granulomatous tissue reactions and bronchial epithelial regenerations. For further elucidation of the pathogenesis of lung cancer and of mesothelioma the localisation and transport of inhaled fibres is of high interest. Thus, a three dimensional visualization of the structure of rat lungs before and after intratracheal instillation of UICC crocidolite fibres was performed by plastic casts to follow the way of asbestos fibres in the lung tissues and the pleura. The casts allowed to demonstrate airway structures with imprints of epithelial cells and blood vessels of normal and treated animals by scanning electron microscopy. Instilled asbestos fibres transformed bronchial structures and resulted in cystic deformations of the pleural surface. The penetration of single fibres through bronchial trunks and the visceral pleura could be shown for the first time in a three-dimensional topography of the affected tissue. Now, there is support for similar results of histomorphological examinations indicating the possibility that asbestos fibres could penetrate the pleura and migrate into the pleural space. The question if the migration of fibres is a mechanical movement or an active transport is still under discussion.

Animals↗

PubMed2000

Gonadal steroids regulate the number and activational state of mast cells in the medial habenula.

While mast cells in connective tissues have long been associated with allergic reactions, it is now clear that they are also present within the central nervous system under normal physiological conditions. The mast cell population increases 10-fold in the medial habenular region of the brain within 2 h after pairing in doves. The first study explored whether this increase was due to exposure to gonadal steroids. Light microscopic immunocytochemistry indicates an increased number of brain MC following exposure to either testosterone (T) or dihydrotestosterone (DHT) in the male, or 17beta estradiol (E) in the female, but not in cholesterol-treated controls. Thus, the increased habenular MC population is produced by gonadal hormones in the absence of sexual behavior, is not sexually dimorphic, and does not require aromatization of androgen. In the next study, MC activational state was determined using electron microscopy. Cells were categorized into five states: (I) resting; (II) initiation of degranulation; (III) fully degranulated; (IV) piecemeal secretion; and (V) resynthesizing. Hormone treatment (T, DHT, or E) resulted in a significant increase in the percent of cells in activated states. MC granules contain a wide range of biologically active molecules. The release of these granule contents into the neuropil of the central nervous system is likely to have wide ranging effects at multiple levels including vascular permeability and neuronal excitability. In that steroid treatment is known to result in such effects, the present demonstration of a hormonally induced shift in MC secretory state is one avenue by which these effects are mediated.

Animals↗