Another view of GH neuroregulation: lessons from the sheep.
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Animals↗
Biomedical subjects
C Oliver
Publications and source records attributed to C Oliver.
Species differences between male rat and ram pituitary somatostatin receptors involved in the inhibition of growth hormone secretion.
The sheep is a valuable model in which to study GH neuroregulation as its pattern of GH secretion is very close to that in humans. Furthermore, important differences in somatostatin (SRIH) action between rats and sheep have been found previously. Our goal was to compare in male rat and ram pituitaries the binding characteristics of somatostatin receptors and the effect of SRIH and 17 analogues on GH release. Using radioautography, SRIH binding was seen to be evenly distributed over the anterior pituitary of both species. In the binding assay, binding sites were three times more concentrated in rats than in sheep. Important interspecies differences in the action of SRIH and its analogues were found: they inhibited GH at lower concentrations in rats than in sheep. Seven peptides displayed greater inhibitory ability in sheep than in rats while three were more potent in rats. Agonistic potencies to inhibit GH release in rats were correlated with somatostatin receptors subtype 2 (sst2) affinities. Our data confirm and extend the quantitative differences between rat and sheep in SRIH inhibitory action on GH secretion and confirm that ligand-binding properties of a given receptor subtype cannot be extrapolated across species.
Animals↗
Are low-risk maternity clinics financially viable?
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Birthing Centers↗
Sumatriptan inhibits the release of CGRP and substance P from the rat spinal cord.
The possible presynaptic action of the anti-migraine drug sumatriptan on primary afferent fibres containing substance P and/or calcitonin gene-related peptide was investigated on superfused rat horizontal spinal cord slices with attached dorsal roots. Electrical stimulation of dorsal roots triggered a significant overflow of both peptides; this could be reduced by sumatriptan in a concentration-dependent manner. As expected from the involvement of 5-HT1B/1.D beta receptors, methiothepin, (-)tertatolol and GR 127,935, but not WAY 100,635, prevented the inhibitors effect of sumatriptan. These data support the idea that the anti-migraine action of sumatriptan may involve, at least in part, a presynaptic inhibitory control of nociceptive (trigeminovascular) substance P- and/or calcitonin gene-related peptide-containing sensory fibres.
Animals↗
[Basedow disease following metastatic thyroid cancer].
OBJECTIVES: Metastatic thyroid carcinoma rarely provokes hyperthyroidism. We describe here the main characteristics of this association observed in a 48-year-old woman. CASE REPORT: The patient had presented signs of hyperthyroidism for one year. Clinical examination revealed severe Graves' disease with nodular goiter. Presurgery investigations demonstrated thyroid carcinoma and lung metastasis. Thyroid stimulating immunoglobulins were elevated. After total thyroidectomy, hyperthyroidism persisted, indicating the functional nature of the lung metastases. DISCUSSION: The effect of thyroid stimulating immunoglobulins on the clinical course of thyroid carcinoma and distant metastases remains unknown.
Female↗
Transcytosis of protein through the mammalian cerebral epithelium and endothelium. III. Receptor-mediated transcytosis through the blood-brain barrier of blood-borne transferrin and antibody against the transferrin receptor.
Diferric-transferrin (Tf; 80K mol. wt.) and the OX26 antibody (150K mol. wt.) against the transferrin receptor (TfR) were evaluated in the rat at light and ultrastructural levels as potential vehicles for the blood to brain transcellular transfer (transcytosis) of native horseradish peroxidase (40K mol. wt.), which by itself does not cross the blood-brain barrier (BBB). OX26, the Fab fragment of OX26 (50K mol. wt.), and Tf complexed to two ferric ions were conjugated to HRP irreversibly in a 1:1 molar ratio. The indirect immunoperoxidase technique with OX26 as the monoclonal primary antibody applied to the surface of cryostat sections or delivered intravenously to the live rat revealed TfRs on BBB capillaries, arterioles, and venules; TfRs were absent on non-BBB vessels supplying the circumventricular organs (i.e., median eminence, choroid plexus). OX26-HRP and OX26(Fab)-HRP delivered intravenously and diferric-Tf-HRP administered into the carotid artery labeled BBB vessels throughout the CNS without discernible disruption of the BBB or extravasation of the blood-borne probes into the brain parenchyma. No reaction product for the probes was observed in sites deficient in a BBB. Each of the macromolecular conjugates was endocytosed by BBB endothelia and labeled presumptive endocytic vesicles, endosomes, and dense bodies. OX26-HRP and Tf-HRP, but not OX26(Fab)-HRP, appeared to undergo transcytosis through BBB endothelia for subsequent labeling of perivascular cells. Distinct differences in the intracellular and extracellular distributions between OX26-HRP and Tf-HRP were identified: (1) endocytosis and sequestration of blood-borne OX26-HRP within BBB endothelia were more prominent than those for diferric-Tf-HRP; (2) only OX26-HRP labeled the Golgi complex in BBB endothelia; (3) peroxidase labeling of CNS perivascular clefts and perivascular cells in rats receiving diferric-Tf-HRP was conspicuous at less than 1 h postinjection but not so in rats with blood-borne OX26-HRP at 5 min through 6 h postinjection; and (4) peroxidase-labeled CNS neurons and glial cells were identified readily in rats receiving diferric-Tf-HRP. The results suggest that the receptor-mediated, transendothelial transfer of Tf-HRP from blood to brain is more efficient and direct than that of OX26-HRP. Labeling of the Golgi complex in BBB endothelia with blood-borne OX26-HRP implies that the transendothelial transfer of OX26-HRP follows intraendothelial pathways associated with the process of adsorptive transcytosis. A diagram is provided depicting the possible intracellular and transcellular pathways within BBB endothelia available to blood-borne diferric-Tf and OX26 as vectors for delivery into the CNS of non-lipid-soluble macromolecules that otherwise are denied entry by the blood-brain fluid barriers.
Animals↗
Binding of antibody to the gamma subunit of FCepsilonRI in rat basophilic leukemia cells results in morphological changes without inducing histamine release.
The high affinity IgE receptor on mast cells and basophils is composed of 3 subunits, alpha, beta and gamma. A polyclonal antibody was raised in rabbits to a 13 amino acid synthetic peptide corresponding to the amino terminal portion of the gamma subunit. The antiserum was screened using Western blots of solubilized RBL-2H3 cells and 125I goat anti-rabbit IgG. After purification of the serum on a protein G column, RBL-2H3 cells, mouse mast cells, and human basophils showed a doublet at 20 000 kDa. When 125I labeled, saponin-permeabilized cells were immunoprecipitated with the anti-gamma antibody, all 3 subunits of the IgE receptor complex coprecipitated. Furthermore, binding of the antibody to the cell surface did not induce histamine release. By immunofluorescence of fixed cells, the receptor was evenly distributed in the RBL-2H3 cells. Although no capping was observed when the cells were incubated with the antibody prior to fixation, the antibody did stimulate endocytosis when it was bound to the cells at 25 degrees C or at 37 degrees C, but not at 4 degrees C. Binding of the antibody to the RBL-2H3 cells also induced cell spreading and ruffling of the plasma membrane. The results of this study indicate that the gamma subunit of the high affinity IgE receptor may play a role in signal transduction.
Animals↗
Advantages of an increased dose of MRI contrast agent for enhancing inflammatory synovium.
MRI intravenous contrast enhancement of inflammatory synovium has been studied at two different doses to determine to what extent enhancement is dose dependent. 19 patients with clinically active rheumatoid arthritis involving a knee were scanned twice, one week apart, using 0.1 mmol/kg of gadoteridol (ProHance) on the first occasion and 0.3 mmol/kg on the second. Static pre-and post-contrast images together with dynamic images immediately following injection were obtained on a 1.0T scanner. On subjective assessment, 84% of patients showed improved enhancement. 47% showed more enhancing tissue, a clearer delineation of enhancing tissue or both. Objectively, enhancement was increased significantly at the higher dose, as judged by the percentage increase in mean signal intensity within regions of interest plotted over the suprapatellar pouch (1723% v. 1005% enhancement P < 0.05). In practical terms the better visualization of enhancing tissue achieved with higher doses is likely to reduce margins of error in attempts at quantification from MRI scans, particularly of synovial volume, but emphasizes also the need for care and consistency to be exercised in calculating the exact dose of contrast medium to be administered.
Adult↗
Hormonal response to stress in brittle diabetes.
Acute psychological stress may play a role in the glycaemic instability of some patients with type I diabetes through an increased secretion of insulin-counteracting hormones. To examine the validity of this hypothesis, we subjected to a video-recorded public-speaking stress seven healthy persons, six type I diabetics with stable blood glucose levels and six type I diabetics with unstable or brittle diabetes (with more than 10 hypoglycaemia/month and frequent hyperglycaemia). During the test and on a control day, heart rate, blood pressure, plasma ACTH, cortisol, catecholamines and prolactin were measured. The comparison between the stable and unstable diabetics during the stress session by two-way analysis of variance (group/time) showed a significant difference for heart rate, blood pressure, ACTH and cortisol. Psychological interview showed that most unstable diabetics perceived a link between life stress and their blood glucose control. The unstable patients had much more difficulty in verbalizing their emotions. Our study shows that the two groups of diabetic patients display distinct cardiovascular and neuroendocrine responses to psychological stress, as well as distinct psychological profiles. In conclusion, hormonal response to an acute psychological stress is more pronounced in brittle diabetes and might be one of its pathogenic factors.
Adolescent↗
Vasopressin levels in Cushing's disease: inferior petrosal sinus assay, response to corticotrophin-releasing hormone and comparison with patients without Cushing's disease.
BACKGROUND: Higher vasopressin (AVP) levels have been found in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the contralateral one, suggesting a potential pathogenetic role of AVP in Cushing's disease. DESIGN: In order to investigate AVP release, plasma ACTH and AVP concentrations were assayed in the inferior petrosal sinuses and in the peripheral blood before and after CRH stimulation. PATIENTS: Twenty patients with Cushing's disease and 12 with other pituitary diseases were subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Ten healthy sex and age-matched subjects served as control for peripheral AVP values. MEASUREMENTS: Plasma ACTH concentrations were measured by RIA using commercial kits. Plasma AVP concentrations were assayed by RIA in acetone extracts of 1-2 ml plasma. RESULTS: Plasma AVP levels in the inferior petrosal sinuses were significantly higher in Cushing's disease than in patients with other pituitary diseases (P < 0.05) and in both groups AVP levels were higher in the inferior petrosal sinuses than in the peripheral blood (P < 0.01). In Cushing's disease, ACTH, but not AVP levels, were higher in the inferior petrosal sinus ipsilateral to the adenoma than in the contralateral one (P < 0.01). Seven patients showed a significant ACTH and AVP increase (greater than 50% of baseline) after CRH stimulation in the inferior petrosal sinus ipsilateral to the adenoma. Conversely, no change was found in AVP levels in the remaining 13 patients. When AVP values were analyzed in relation to surgical cure, higher inferior petrosal sinus levels (P < 0.05) were found in 6 patients with poor outcome: 4 of these patients had significantly decreased plasma AVP concentrations (by 32-43% of baseline) after CRH bolus. Peripheral AVP levels were similar in healthy subjects and patients with Cushing's disease whereas they were significantly reduced in patients with other pituitary diseases (P < 0.002). CONCLUSIONS: The results of this study show that patients with Cushing's disease and poor surgical outcome had the highest AVP levels in our series. CRH administration caused different effects on AVP levels: it increased them in 35% of patients whereas there was no response in the remaining patients. On the basis of these findings, it is hypothesized that AVP might be involved in the persistence of ACTH hypersecretion in a subset of patients poorly responsive to surgery.
Adenoma↗
Intravenous MRI contrast enhancement of inflammatory synovium: a dose study.
A dose study was performed of MRI intravenous contrast medium enhancement of rheumatoid synovium in the knee, comparing the enhancement with gadoteridol at doses of 0.1 and 0.3 mmol/kg. A measurable and significant difference was demonstrated which has particular relevance to the accuracy of dose calculations needed when performing quantitative studies.
Adult↗
Corticotropin-releasing hormone administration increases alpha-melanocyte-stimulating hormone levels in the inferior petrosal sinuses in a subset of patients with Cushing's disease.
The effect of corticotropin (ACTH)-releasing hormone (CRH) administration on alpha-melanocyte-stimulating hormone (alpha-MSH), ACTH and beta-endorphin (beta-EPH) was evaluated in the inferior petrosal sinuses and in the periphery of 30 patients affected with Cushing's disease subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Baseline PRL levels, sensitivity to dexamethasone and surgery outcome were compared to alpha-MSH response. CRH bolus did not modify alpha-MSH concentrations either in the inferior petrosal sinuses or in the periphery in the 30 patients considered as a whole. In 7 of 30 patients, however, a greater than 50% increase over baseline alpha-MSH levels (from 50 to 115.5%) was recorded in the inferior petrosal sinus ipsilateral to the adenoma (from 42.9 +/- 1.7 to 76.4 +/- 4.6 ng/l; p < 0.001), whereas no change was found in the contralateral inferior petrosal sinus or in the periphery. Conversely, as expected, ACTH and beta-ELI significantly increased in all the patients after CRH both in the inferior petrosal sinuses and in the periphery (particularly in the inferior petrosal sinus ipsilateral to the adenoma). No difference in sensitivity to dexamethasone (urinary cortisol percent decrease: 66.4 +/- 4.9 vs. 67.8 +/- 3.4) and surgery outcome (chi 2 test: p = 0.7) was found between patients with alpha-MSH response to CRH and patients without such a response. By contrast, baseline PRL levels, although being normal in both groups, were significantly higher in patients with alpha-MSH response to CRH (18.1 +/- 1.6 vs. 10.1 +/- 0.7 micrograms/l; p < 0.001). In conclusion, the results of the present study suggest that in a subset of patients with Cushing's disease (23.3% of our series) alpha-MSH may be released after the administration of CRH together with ACTH and beta-EPH by adenomatous corticotrophs. In this subset of patients, PRL levels may be in the upper normal range.
Adolescent↗
Mechanical ventilation increases substance P concentration in the vagus, sympathetic, and phrenic nerves.
Substance P (SP), a neurotransmitter localized to primary sensory neurons, is found in the vagus nerve, nodose ganglion, sympathetic chain, and phrenic nerve in various animal species. However, the changes in endogeneous SP concentration under various circumstances that involve the participation of cardiorespiratory afferent nerves are still unexplored. In the present study, attention was focused on the variations in SP content measured by radioimmunoassay (RIA) in respiratory afferent nerves (vagus nerve, cervical sympathetic chain, phrenic nerve) and respiratory muscles (diaphragm, intercostal muscles) during positive inspiratory pressure (PIP) breathing alone or PIP with an expiratory threshold load (ETL) in rabbits. SP was found in all sampled structures in spontaneously breathing control animals, prevailing in the nodose ganglion. Left-versus right-sided differences were noticed in nerves. As compared with that in control animals, the SP concentration was markedly higher in vagal and sympathetic nervous structures during PIP or PIP with ETL, and also in the phrenic nerve during ETL breathing. The SP content did not vary in respiratory muscles. These observations suggest that two very common circumstances of mechanical ventilation are associated with an increased SP concentration in nervous structures participating in the control of breathing.
Animals↗
Effect of thyroid hormones on peptidylglycine alpha-amidating monooxygenase gene expression in anterior pituitary gland: transcriptional studies and messenger ribonucleic acid stability.
Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is a multifunctional protein containing two enzymes that act sequentially to catalyze the alpha-amidation of neuroendocrine peptides. The regulatory mechanism(s) involved in the tissue-specific induction of PAM messenger RNA (mRNA) by thyroid status have been investigated in rat anterior pituitary gland. In this tissue, cellular PAM mRNA increases in response to hypothyroidism (4- to 7-fold above basal levels). To gain further insight into this pretranslational control, nuclear in vitro run-on transcription assays were performed. Using PAM complementary DNAs and intronic probe, we showed that the transcriptional rate of rat pituitary PAM gene in isolated nuclei was not altered by thyroid status. Primary rat pituitary cells cultures from hypo- and euthyroid rats in the presence of actinomycin D showed that hypothyroidism increased the half-life of PAM mRNA from 9-10 h to 15-17 h. Taken together, these data suggest that hypothyroidism induces PAM mRNA levels by increasing its stability in the cytoplasm.
Animals↗
The tragedy of violence.
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Domestic Violence↗
Virus removal studies using nanofiltration membranes.
Nanofiltration of immunoglobulin products was investigated as a virus removal step using Planova-controlled pore size membranes. For these studies, purified preparations of an IgG and an IgM were tested with 15 nm and 35 nm Planovace nanofiltration membranes, respectively. The results of spiking studies with four model viruses indicated that both the Planova 15 and 35 membranes removed 6-7 log10 plaque or focus forming units of murine xenotropic retrovirus, simian virus 40 and pseudorabies virus. Although two tandem Planova 35 membranes were tested for clearance of poliovirus, only the Planova 15 membrane removed this virus. Nanofiltration experiments were carried out with protein concentrations up to 12 mg/ml for the IgG and 1-2 mg/ml for the IgM, and protein recovery was excellent.
Animals↗
Molecular aspects of the regulation of the hypothalamo-pituitary-adrenal axis during development in the rat.
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Animals↗
A mutation in glyceraldehyde 3-phosphate dehydrogenase alters endocytosis in CHO cells.
The CHO cell mutant FD 1.3.25 exhibits both increased accumulation and altered distribution of endocytosed fluid phase tracers. Neither the rate of tracer internalization nor the kinetics of recycling from early endosomes was affected, but exocytosis from late endocytic compartments appeared to be decreased in the mutant. Endocytosed tracer moved more rapidly to the cell poles in FD1.3.25 than in wild type cells. An abundant 36-kD polypeptide was found associated with taxol-polymerized microtubules in preparations from wild type and mutant; in the former but not the latter this polypeptide could be dissociated by incubation of the microtubules in ATP or high salt. The 36-kD polypeptide co-electrophoresed in two dimensions with the monomer of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Analysis of cDNA clones showed that the mutant is heterozygous for this enzyme, with approximately 25% of the GAPDH RNA containing a single nucleotide change resulting in substitution of Ser for Pro234, a residue that is conserved throughout evolution. Stable transfectants of wild type cells expressing the mutant monomer at approximately 15% of the total enzyme exhibited the various changes in endocytosis observed in FD1.3.25.
Animals↗