Readability of ENT consent form amendments.
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Comprehension↗
Biomedical subjects
B Bingham
Publications and source records attributed to B Bingham.
The CD4+ T lymphocyte is a site of steroid resistance in asthma.
Phytohaemagglutinin (PHA)-induced T-cell proliferation is suppressed completely in steroid-sensitive asthma (SSA) by fluticasone propionate (FP). By contrast, in patients with steroid-resistant asthma (SRA), this proliferative response is only partially attenuated by steroids, which suggests that the T lymphocyte may harbour a key molecular defect in these patients. Both CD4+ and CD8+ T cells may be involved in orchestrating the inflammation underlying asthma. We examined whether CD4+ or CD8+ T cells isolated from SRA and SSA patients are equally susceptible to steroid suppression of PHA-induced proliferation. Complete suppression of CD4+ T-lymphocyte proliferation was seen in both SSA and control subjects at concentrations of 10(-9) M FP. In contrast, proliferation of CD4+ T cells from SRA patients was only partially inhibited, even at 10(-6) M FP. CD8+ responses from SRA, SSA and controls were all similar, with only a partial suppression of proliferation at 10(-6) M FP. Differential suppression by FP of CD4+ T cells has thus been demonstrated between SRA and SSA patients.
Adult↗
A linear hexapeptide somatostatin antagonist blocks somatostatin activity in vitro and influences growth hormone release in rats.
Somatostatin (SRIF) is the main inhibitory peptide regulating growth hormone (GH) secretion. It has been difficult to establish the role of endogenous SRIF release in the absence of pure SRIF antagonists. Although several SRIF antagonists have recently been described, none have been shown to possess in vivo activity in the absence of added SRIF. Here, an SRIF antagonist with no detectable agonist activity has been identified from a synthetic combinatorial hexapeptide library containing 6.4 x 10(7) unique peptides. Each peptide in the library is amino-terminally acetylated and carboxyl-terminally amidated and consists entirely of D-amino acids. A SRIF-responsive yeast growth assay was used as a primary screening tool, and cAMP accumulation, competitive binding, and microphysiometry also were used to confirm and further characterize SRIF antagonist activity. The hexapeptide library was screened in stepwise iterative fashion to identify AC-178,335, a pure SRIF antagonist of the sequence Ac-hfirwf-NH2. This D-hexapeptide bound SRIF receptor type 2 with an affinity constant (Ki) of 172 +/- 12 nM, blocked SRIF inhibition of adenylate cyclase in vitro (IC50 = 5.1 +/- 1.4 microM), and induced GH release when given alone (50 micrograms intravenously) to anesthetized rats with or without pretreatment with a long-acting SRIF agonist.
Animals↗
Staff comfort/discomfort with problem-based learning. A preliminary study.
Crucial to the implementation and success of any educational program, especially problem-based learning (PBL), is the support and co-operation from staff involved in its use. It is suggested that this support and co-operation is dependent on their understanding of and comfort with the process especially when PBL may require substantial change in teaching practices. This paper reports the results of a pilot survey of staff responses to several aspects of the PBL approach of which the authors became aware. The survey focuses on issues of comfort with the process, knowledge and understanding of PBL, and preparation for the teaching role in PBL. As a preliminary study, it provides some indicators of staff responses to PBL implementation as well as highlighting sources of comfort/discomfort with the process.
Faculty, Nursing↗
A rapid and sensitive binding assay for growth hormone releasing factor.
A binding assay for growth hormone releasing factor (GRF) has been developed using scintillation proximity assay (SPA) technology. Binding conditions were validated by several criteria. Equilibrium binding was attained within three hours at 22 degrees C in crude membrane fractions of HEK293 (293-P2) and GH4C1 (GH4-P1) cells transfected with the porcine GRF receptor. Saturation binding isotherms produced a KD of 296 pM and a Bmax of 4.7 pmols/mg membrane protein in 293-P2 cells. Cells not expressing the GRF receptor displayed no specific binding for the ligand. Competition binding curves produced the following rank order of potency for tested peptides: GRF analogs D-Ala2 = D-Arg2 (IC50 approximately 1 nM) >> PACAP > secretin, VIP (EC50 > 100 nM). Somatostatin (SRIF) binding was also adapted to the SPA format in a GH4C1 cell line transfected with the SRIF receptor subtype 2 (SSTR2) and in HEK293 cells transfected with the SRIF receptor subtype 5 (SSTR5). This assay represents a major improvement for binding measurements of these and potentially many other ligands for G-protein linked receptors, requiring no separation of bound from free hormone, allowing detailed pharmacological evaluations and enabling measurement of equilibrium binding in real time. In the 96-well format, it is suitable for high throughput screening.
Animals↗
One class of growth hormone (GH) receptor and binding protein messenger ribonucleic acid in rat liver, GHR1, is sexually dimorphic and regulated by GH.
In the rat, alternatively spliced messenger RNA (mRNA) species encode GH receptor (GHR) and GH-binding protein (GHBP). Additionally, these mRNAs are alternatively spliced in the 5'-untranslated region, resulting in at least two classes of GHR and GHBP mRNA with distinct first exons and identical coding regions. These alternative first exons define two unique classes of GHR and GHBP mRNA (called GHR1 and GHR2). The GHR1 class of RNA is expressed only in the liver, is far more abundant in females than males, and is particularly abundant during pregnancy. GHR1 RNA is induced later in development than is GHR2. Additional classes of GHR and GHBP RNA may also exist. The genomic structure of the GHR1 first exon reveals a putative promotor region with no TATA box, CAAT box, or other sequence elements suggesting specific responses. An in vivo approach was used to investigate the regulation of GHR1 expression. In female rats, gonadectomy was found to reduce the percentage of steady state GHR1 RNA levels in the liver, whereas male castration resulted in an induction of GHR1 RNA. However, short-term treatment with estrogen or testosterone had little effect, suggesting that direct regulation of GHR1 expression may occur through effector(s) other than gonadal steroids. Hypophysectomy abolished GHR1 RNA in females. Treatment of hypophysectomized females and castrated males with GH by single injection did not significantly induce GHR1 RNA, but treatment by continuous infusion of GH did. Little change in non-GHR1 RNA levels was observed for each of these treatments. The results suggest that: 1) the sexual dimorphism observed in total GHR and GHBP RNA in rat liver is attributable to the sexually dimorphic expression of the GHR1 class of RNA; 2) the sexually dimorphic pattern of GH release in rats regulates the GHR1 class of RNA; 3) changes in GHR and GHBP expression observed on gonadectomy, hypophysectomy, GH treatment, and pregnancy are best attributed to GHR1 regulation; and 4) since GHR1 is liver specific, the observed increases in serum GHBP concentration in response to sex steroids, GH pattern, and pregnancy are likely to originate from the liver.
Alternative Splicing↗
Selective uptake of estrogenic compounds by Saccharomyces cerevisiae: a mechanism for antiestrogen resistance in yeast expressing the mammalian estrogen receptor.
Estrogen antagonists such as ICI164,384 do not inhibit 17 beta-estradiol (E2)-dependent gene activity in yeast expressing the mammalian estrogen receptor although these compounds bind to receptors isolated from these cells. Various explanations have been offered for antiestrogen resistance in yeast systems including differences in cell-specific components and lack of permeability of the yeast cell wall to these compounds. We have used a strain of Saccharomyces cerevisiae transformed with the human estrogen receptor gene, and two estrogen response elements linked to a lacZ reporter gene to study the pharmacology of estrogen agonists and antagonists. The rank order of potency of estrogen agonists in this strain (CY525) is similar to that in estrogen-dependent mammalian cells: DES > or = E2 > E1 > E3 = zeranol. Competitive binding with 3H-E2 by these compounds in cell-free extracts of CY525 results in a similar order of potency with a reverse order for E1 and E3. The pure estrogen antagonist ICI164,384 also binds to the receptor from cell-free extracts of CY525 with an IC50 of approximately 14nM. As in mammalian cells ICI164,384 does not induce E2-dependent gene activity. However, unlike mammalian cells, E2-induced gene activity in CY525 is not inhibited by ICI164,384. Intact CY525 cells incubated with 3H-17 beta estradiol were found to specifically bind the labeled ligand since excess unlabeled E2 effectively competed for binding. Unlabeled DES and E1 were also found to compete, however, excess unlabeled ICI164,384, E3 and the second generation antagonist ICI182,720 were unable to displace 3H-E2 binding in intact cells. These results indicate that certain compounds enter the intact yeast cell more readily than others and offer an explanation for antagonist resistance in these organisms.
Base Sequence↗
Regulation of growth hormone receptor and binding protein expression in domestic species.
Growth hormone receptor (GHR) expression has been analyzed at the RNA level. In the rat, relative expression of the RNA species encoding the GHR and the GH-binding protein (GHBP) appears to be sensitive to endocrine status. Full-length GHR cDNA clones from ovine, porcine, and chicken were used as probes to investigate the existence of unique RNAs for GHBPs in these species. In the sheep and pig, only a single, approximately 4.5-kb RNA is apparent. Although quite high levels of GH binding activity are found in pig serum, a variety of methods failed to isolate a separate GHBP message, suggesting that porcine GHBP is produced via a mechanism different from that which is known for rat. One class of chicken GHR cDNA, resulting from alternative use of a splice acceptor 17 bases upstream of the intron 6/Exon 7 junction, is also presented.
Animals↗
Pre-admission assessment clinics: an answer to non-attendance for ENT operations.
Non-attendance by patients for elective surgery with insufficient time to find replacement leads to wasted theatre time and wasted resources. The introduction of pre-admission clinics at the North Riding Infirmary, Middlesbrough has alleviated this problem and has led to considerable financial savings. A 12 month prospective study has shown an increase in operations performed from 3738 to 3944. Financial savings have not been taken into consideration in this publication.
Elective Surgical Procedures↗
Tissue distribution and ontogeny of growth hormone receptor messenger ribonucleic acid and ligand binding to hepatic tissue in the midgestation sheep fetus.
While circulating GH concentrations are high in fetal life, skeletal growth is only slightly reduced by GH deficiency in utero. This has been explained by the relatively low binding of GH to fetal hepatic tissue, suggesting a lack of GH receptors (GHR). The GHR also recognizes ovine placental lactogen (oPL), which may have a specific role either as a fetal growth-promoting hormone or in regulating fetal metabolism. We investigated GHR expression and membrane binding of ovine (o) GH and oPL in various ovine fetal tissues and in maternal liver at different gestational stages. Singleton-bearing ewes at 51, 95, and 120 days gestation were killed. Liver, muscle, kidney, and brain samples were taken from the fetuses as well as placentas and livers from the ewes (n = 3/gestational age). GHR mRNA measured by Northern blot analysis was expressed at high levels in maternal liver at all gestational stages. A major band was observed at 4.4 kilobases (kb), and three minor bands were observed at 2.5, 1.7, and 8.1 kb. In fetal and placental tissue, only the 4.4-kb band was detected. This was present as early as day 51 of gestation in liver, kidney, lung, heart, and placenta and increased slightly with advancing gestation. On day 51, the expression of GHR mRNA in muscle was negligible, but by day 95, muscle expressed higher concentrations than fetal liver. Placental samples showed only a slight signal, with no change over the gestational range studied. In situ hybridization revealed the placental mRNA to be primarily associated with the decidua. Hepatic tissue showed specific binding to [125I]oGH and [125I]oPL from 51 days gestation. [125I]oPL showed a higher [51 days, 17.9 +/- 1.9% (mean +/- SEM); 95 days, 11.5 +/- 1.6%; 120 days, 16.3 +/- 0.9%] specific binding to the liver membranes than [125I]oGH (51 days, 2.1 +/- 0.7%; 95 days, 2.6 +/- 0.3%; 120 days, 3.5 +/- 0.4%). We conclude that oGHR are present as early as day 51 of gestation in various tissues, including liver. The message appears later in skeletal muscle than in liver. As the GH receptor binds oPL with higher potency than oGH, the parallel ontogenic changes in [125]oGH and [125]oPL binding in the liver do not support the presence of a PL receptor under independent developmental regulation.
Animals↗
A functional polyadenylation signal is embedded in the coding region of chicken growth hormone receptor RNA.
A study of chicken GH receptor (cGHR) expression has revealed that the two major liver and skeletal muscle transcripts of the cGHR are developmentally expressed. Expression of the larger (4.7 kilobases) transcript increases with age. The smaller transcript (0.7 kilobases) is a truncation product, resulting from alternative usage of a functional polyadenylation [poly(A)] signal embedded in the coding sequence. The extent to which alternative cleavage and polyadenylation occur displays some tissue and sex specificity. Cleavage and polyadenylation occur down-stream of the AATAAA portion of the poly(A) signal (cGHR positions 304-309) and up-stream of a GT-rich sequence. The truncated transcript appears to be translated, based on its association in vivo with polyribosomes, although the physiological role of the putative protein product of this truncated transcript is as yet unknown. Three other avian species (quail, turkey, and duck) also show a polyadenylated truncation of the GHR message due to a poly(A) signal at the same location in the coding sequence. In cell culture expression, mutation of AATAAA to AACAAG prevents production of the truncated transcript. In a chimeric construct, the signal and neighboring sequence from the cGHR are sufficient to confer cleavage and polyadenylation upon the rat GHR, a gene that otherwise lacks the internal poly(A) signal. Alternative polyadenylation within the coding region of a structural gene is discussed as a heretofore unknown means of post-transcriptional regulation of a gene product.
Age Factors↗
Recurrent simple nasal polyps associated with Sheehan's syndrome.
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Female↗
Surgical anatomy of the lateral nasal wall.
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Humans↗
The embryonic development of the lateral nasal wall from 8 to 24 weeks.
This histological study of 20 fetal heads aged between 8 and 24 weeks of gestation demonstrates and describes the embryonic development of the lateral wall of the nose. The three turbinates (inferior, middle, and superior) arise as soft-tissue swellings (preturbinates) by 8 weeks' gestation. A cartilage capsule surrounds the nose at 8 weeks and by 9 weeks, medially directed flanges of cartilage have invaded all three preturbinates. The uncinate process arises from the medial surface of the lateral cartilaginous capsule and is first identifiable by 10 weeks. An "air space" progressively develops from 11 to 12 weeks lateral to the cartilaginous uncinate process and from this space, the embryonic channel to the maxillary sinus develops. The embryonic woven bone of the maxilla can be identified from 9 to 10 weeks and enlarges both absolutely and relatively to the nasal cavity, so that by 13 to 14 weeks, this expanding bone forms the lateral wall of the inferior meatus as the cartilaginous nasal capsule regresses.
Embryonic and Fetal Development↗
Diagnosis of rhinoliths with rigid endoscopy.
Three cases of rhinolithiasis are presented in which the diagnosis was facilitated by rigid endoscopic nasal examination. Coronal CT scans were used to delineate accurately the size and site of the rhinoliths. Neutron activation analysis was used in their elemental analysis.
Adult↗
The secondary middle turbinate.
During functional endoscopic sinus surgery, the ethmoidal infundibulum and bulla are accessed through the middle meatus. This paper describes a secondary middle turbinate which arises from the lateral wall of the middle meatus, posterosuperior to the infundibulum and points superiorly within the meatus. A secondary middle turbinate was identified bilaterally in 6 out of 400 coronal CT scans of the nasal cavity and paranasal sinuses. The secondary middle turbinate did not obstruct the osteomeatal complex in any of our patients.
Congenital Abnormalities↗
Pitfalls in computed tomography of the paranasal sinuses.
The advent of functional endoscopic sinus surgery has created the need for high-quality radiographic images to assess the paranasal sinuses, document the detailed anatomy of the lateral nasal wall and provide an anatomical map allowing safe functional endoscopic sinus surgery. This paper will discuss our experience of 410 paranasal sinus coronal CT scans performed by the technique described by Zinreich prior to consideration of functional endoscopic sinus surgery. The main indications for the scans were acute recurrent sinusitis, abnormal diagnostic nasal endoscopic examination and persistent facial pain. We will consider both the radiological and surgical difficulties that have arisen from the use of this technique and highlight some of the methods to avoid these difficulties. Claustrophobia and limitation of neck movements, particularly in patients over the age of 60, were the most common factors leading to suboptimal scans. Ensuring that the patient was in a symptom-free interval, the differential diagnosis of the opacified paranasal sinus and patients with gross polypoid disease created the most difficulty in interpretation. The anatomical assessment of the frontal recess and the identification of the optic nerve posterolateral to the posterior ethmoidal cell have created the greatest anatomical difficulty.
Artifacts↗
Ethmomaxillary sinus and hypoplasia of maxillary sinus.
In a series of 410 coronal CT scans performed to assess paranasal sinus disease, we have identified eight cases in which an ethmomaxillary sinus was present. The ethmomaxillary sinus was unilateral in five cases and bilaterally present in three. The sex incidence was equal. Four patients had generalized mucosal disease of their paranasal sinuses which included the ethmomaxillary sinus whereas four patients had osteomeatal complex disease and sparing of their ethmomaxillary sinus. The characteristic radiological features of an ethmomaxillary sinus were drainage into an enlarged superior meatus, reduction in the size of the maxillary sinus and a normal bony orbital cavity. The differential diagnosis of an apparently hypoplastic maxillary sinus is briefly discussed.
Congenital Abnormalities↗