The Royal College of Radiologists Multicentre Guideline Study: implications for clinical practice.
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Humans↗
Biomedical subjects
C J Roberts
Publications and source records attributed to C J Roberts.
Biogenesis of the vacuole in Saccharomyces cerevisiae.
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Endocytosis↗
Membrane protein sorting in the yeast secretory pathway: evidence that the vacuole may be the default compartment.
The targeting signals of two yeast integral membrane dipeptidyl aminopeptidases (DPAPs), DPAP B and DPAP A, which reside in the vacuole and the Golgi apparatus, respectively, were analyzed. No single domain of DPAP B is required for delivery to the vacuolar membrane, because removal or replacement of either the cytoplasmic, transmembrane, or lumenal domain did not affect the protein's transport to the vacuole. DPAP A was localized by indirect immunofluorescence to non-vacuolar, punctate structures characteristic of the yeast Golgi apparatus. The 118-amino acid cytoplasmic domain of DPAP A is sufficient for retention of the protein in these structures, since replacement of the cytoplasmic domain of DPAP B with that of DPAP A resulted in an immunolocalization pattern indistinguishable from that of wild type DPAP A. Overproduction of DPAP A resulted in its mislocalization to the vacuole, because cells expressing high levels of DPAP A exhibited vacuolar as well as Golgi staining. Deletion of 22 residues of the DPAP A cytoplasmic domain resulted in mislocalization of the mutant protein to the vacuole. Thus, the cytoplasmic domain of DPAP A is both necessary and sufficient for Golgi retention, and removal of the retention signal, or saturation of the retention apparatus by overproducing DPAP A, resulted in transport to the vacuole. Like wild type DPAP B, the delivery of mutant membrane proteins to the vacuole was unaffected in the secretory vesicle-blocked sec1 mutant; thus, transport to the vacuole was not via the plasma membrane followed by endocytosis. These data are consistent with a model in which membrane proteins are delivered to the vacuole along a default pathway.
Amino Acid Sequence↗
Comparison of the chromatographic characteristics of metabolites of tacrine hydrochloride in human serum and urine with those of in vitro metabolic products from hepatic microsomes.
There may be as many as five metabolites of THA in man, four corresponding to products in the rat. The study provides some evidence that one of major metabolites is 1-hydroxy-THA but lends no support to the putative oxidative deamination pathway.
Animals↗
Methods for studying the yeast vacuole.
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Alkaline Phosphatase↗
How good are case notes in the audit of radiological investigations?
Audit based on the use of case notes completed in the ordinary course of patient care has not been widely used because of concern about the completeness and adequacy of such records. This paper describes the results of a study carried out to assess whether information contained in case notes was sufficiently reliable to enable clinical effectiveness to be measured. The study examines the extent to which a radiologist and an epidemiologist agree with two experienced clinicians in making retrospective judgements on whether out-of-hours radiological investigations are worthwhile. There was a high measure of agreement; only a relatively small amount of information in the case notes is needed to make valid judgements on clinical performance. The method described here may be applicable to other diagnostic investigations and the results of the study have wide implications for more effective and efficient management of resources within the NHS.
Clinical Competence↗
Gastro-oesophageal reflux during elective laparoscopy.
An oesophageal pH electrode was used to record gastro-oesophageal reflux in 73 women who had elective laparoscopy for various gynaecological procedures. No refluxes were recorded during the 63 procedures from which results could be analysed; the upper 95% confidence limit from this observation is 3 in 63 (4.8%). Two of the excluded women refluxed during episodes of hiccough that occurred shortly after induction of anaesthesia. Tracheal intubation may be required during laparoscopy, although the need to protect against the possibility of aspiration of gastric contents may not be a valid reason unless, with the same logic, it is suggested that all patients who hiccough should be intubated.
Adolescent↗
The effect of propranolol on paracetamol metabolism in man.
Ten healthy volunteers were treated for 4 days with 160 mg propranolol HCl and placebo in random order. At the end of each treatment salivary antipyrine kinetics and the plasma kinetics and urinary excretion of paracetamol and its major metabolites were measured following a 1500 mg oral dose. Propranolol prolonged the half-life of antipyrine by 11 +/- 5% (mean +/- s.e. mean) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol increased the half-life of paracetamol by 25 +/- 12% (P less than 0.05) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol decreased the partial clearance of paracetamol to its cysteine and mercapturate derivatives by 16 +/- 3% (P less than 0.05) and 32 +/- 7% (P less than 0.05), respectively. The partial clearance to the glucuronide conjugate was decreased by 27 +/- 6% (P less than 0.05), whereas that to sulphate was not changed significantly. Propranolol inhibits paracetamol metabolism predominantly through inhibition of the oxidation and glucuronidation pathways.
Acetaminophen↗
Nitrendipine and the humoral control of sodium homeostasis.
1. Nine healthy volunteers received 10 mg nitrendipine or placebo orally in random order. 2. In the subsequent 5 h urinary sodium excretion was 20% higher after nitrendipine, without any significant difference between the volume of urine excreted after nitrendipine or placebo. Mean blood pressure fell by 5 mm Hg (P less than 0.001), and mean heart rate increased by 5 beats min-1 (P less than 0.01) after nitrendipine but did not change after placebo. 3. These changes were accompanied by a significant elevation in plasma renin activity (P less than 0.001). A fall in plasma aldosterone following placebo appeared to be attenuated by nitrendipine. Plasma noradrenaline increased to a peak 3 h after nitrendipine administration (P less than 0.05) but did not change following placebo. A fall in the excretion of 6-keto PGF1 alpha following placebo was attenuated by nitrendipine. The total excretion of 6-keto PGF1 alpha after nitrendipine was significantly greater (P less than 0.05) than after placebo but not difference in the total excretion of PGE2 was detected. Nitrendipine did not affect urinary kallikrein excretion. 4. The natriuretic action of nitrendipine is not mediated by the kallikrein-kinin system, but may be related to changes in renal prostaglandins.
Adult↗
Pharmacokinetics of tacrine hydrochloride in Alzheimer's disease.
The clinical pharmacokinetics of tacrine hydrochloride have been characterized in patients who have Alzheimer's disease. Serum concentrations of the drug and of its probable metabolite were monitored in eight patients after a 25 mg oral dose, in six patients after a 50 mg oral dose, in four patients after repeated administration of 50 mg, and in two patients after a small intravenous dose. Urinary excretion of drug and metabolite for 24 hours was measured in one of the patients who received a small intravenous dose. The serum half-life was 1.59 +/- 0.15 hours (mean +/- SEM) after the 25 mg dose, 2.14 +/- 0.24 hours after the 50 mg dose, and 2.91 +/- 0.39 hours after continuous treatment. After intravenous administration, clearance was above 600 ml/min in both patients, and oral bioavailability was calculated at below 5%. Urine recovery was less than 3% of the dose. The low bioavailability of tacrine hydrochloride is partly explained by presystemic metabolism.
Administration, Oral↗
Structure, biosynthesis, and localization of dipeptidyl aminopeptidase B, an integral membrane glycoprotein of the yeast vacuole.
We have characterized the structure, biogenesis, and localization of dipeptidyl aminopeptidase B (DPAP B), a membrane protein of the yeast vacuole. An antibody specific for DPAP B recognizes a 120-kD glycoprotein in yeast that behaves like an integral membrane protein in that it is not removed from membranes by high pH Na2CO3 treatment. Inspection of the deduced amino acid sequence of DPAP B reveals a hydrophobic domain near the NH2 terminus that could potentially span a lipid bilayer. The in vitro enzymatic activity and apparent molecular weight of DPAP B are unaffected by the allelic state of PEP4, a gene essential for the proteolytic activation of a number of soluble vacuolar hydrolases. DPAP B is synthesized as a glycosylated precursor that is converted to the mature 120-kD species by carbohydrate addition. The precursor form of DPAP B accumulates in sec mutants (Novick, P., C. Field, and R. Schekman. 1980. Cell. 21:205-215) that are blocked at the ER (sec18) or Golgi apparatus (sec7), but not at secretory vesicles (sec1). Immunolocalization of DPAP B in wild-type or sec1 mutant cells shows that the protein resides in the vacuolar membrane. However, it is present in non-vacuolar compartments in sec18 and sec7 cells, confirming that the delivery of DPAP B is blocked in these mutants. Interestingly, DPAP B appears to stain the nuclear envelope in a sec18 mutant, which is consistent with the accumulation of DPAP B in the ER membrane at the restrictive temperature. These results suggest that soluble and membrane-bound vacuolar proteins use the same stages of the secretory pathway for their transport.
Amino Acid Sequence↗
Determination of tacrine hydrochloride in human serum by chloroform extraction, reversed-phase high-performance liquid chromatography and fluorimetric detection.
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Aminoacridines↗
Transforming growth factor beta stimulates the expression of fibronectin and of both subunits of the human fibronectin receptor by cultured human lung fibroblasts.
Transforming growth factors of the beta-class (TGFs-beta) stimulate extracellular matrix synthesis and have been implicated in embryogenesis, wound healing, and fibroproliferative responses to tissue injury. Because cells communicate with several extracellular matrix components via specific cell membrane receptors, we hypothesized that TGFs-beta may also regulate the expression of such receptors. We confirmed that TGF-beta 1 increases the expression of fibronectin, an adhesive glycoprotein expressed during embryogenesis and tissue remodeling. Based upon the 48-72-h period required for a maximal fibroproliferative response to dermal injections of TGF-beta 1, we exposed human fetal lung fibroblasts (IMR-90) to TGF-beta 1 for periods up to 48 h in vitro. We observed as much as 6-fold increases in fibronectin synthesis by 24 h as previously reported for fibroblastic cells (Ignotz, R. A., and Massagué, J. (1986) J. Biol. Chem. 261, 4337-4345; Ignotz, R. A., Endo, T., and Massagué, J. (1987) J. Biol. Chem. 262, 6443-6446; Raghow, R., Postlethwaithe, A. E., Keski-Oja, J., Moses, H. L., and Kang, A. H. (1987) J. Clin. Invest. 79, 1285-1288), but up to 30-fold increases by 48 h. These increases are accompanied by similar increases in fibronectin mRNA levels which are prevented by actinomycin D treatment. Using a monospecific antibody raised to the human placental fibronectin receptor complex, we found that TGF-beta 1 stimulated fibronectin receptor synthesis up to 20-40-fold and increases mRNA levels encoding both the alpha- and beta-subunits up to 3-fold, compared to control IMR-90 in serum-free medium. Actinomycin D blocks TGF-beta 1-mediated increases in receptor mRNA levels. The earliest detectable TGF-beta 1-mediated increases in fibronectin receptor complex protein synthesis and mRNA levels occur at 8 h, whereas the earliest increases in fibronectin protein synthesis and mRNA levels occur at 12 h. These results demonstrate that TGF-beta 1 stimulates fibronectin receptor synthesis, extending the diverse stimulatory activities of this polypeptide to matrix receptors. In addition, because fibronectin matrix assembly may involve the fibronectin cell adhesive receptor complex, increased receptor expression may help drive fibronectin deposition into matrix.
Cell Line↗
Do nizatidine and cimetidine interact with ibuprofen?
The potential for interaction between ibuprofen and two histamine H2-receptor blocking drugs--nizatidine and cimetidine--was investigated in six healthy male volunteers aged 20 to 25 years. Each subject received placebo, nizatidine 300 mg and cimetidine 800 mg orally at 9.00 p.m. daily for six doses in three randomised treatment periods separated by eight days. On the third day of each treatment period ibuprofen 400 mg was administered at the same time and venous blood samples were taken at intervals throughout the night and subsequently up to 84 h after administration. There was no difference in the area under the plasma concentration-time curve, rate of absorption or half-life of elimination of ibuprofen between the three treatments. The elimination half-life of ibuprofen on placebo was 2.04 h. The elimination half-life of nizatidine on ibuprofen was 1.72 h and that of cimetidine was 3.54 h. The latter is higher than previously reported in normal subjects. It is concluded that neither H2-blocker affects the kinetics of ibuprofen in man.
Adult↗
Rare earth screens: prevention of radiogenic cancers versus local budgets.
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Costs and Cost Analysis↗
Effects of cimetidine and carbenoxolone on gastric mucus.
The effect of cimetidine on normal human gastric mucus has been compared with that of carbenoxolone, a drug believed to enhance mucus production. Each drug was given for two weeks, the gastric contents aspirated over a timed period and the results assessed in unstimulated and pentagastrin stimulated secretions. The volume, dry weight and the carbohydrate contents of non-diffusable glycoconjugates, high molecular mass glycoproteins and glycopolypeptides were investigated. Both drugs reduced the volumes of stimulated secretions. This was statistically significant after cimetidine. More importantly neither drug affected the amount of non-diffusable glycoconjugates, so that the concentration remained the same or increased. Both drugs reduced the monosaccharide content of the high molecular mass fractions. This reached significance for the stimulated secretion after cimetidine. As the carbohydrate content of the glycopolypeptides was unchanged this indicated the presence of a non-mucin glycoprotein or protein. Overall there was no fundamental difference between the results for cimetidine and carbenoxolone.
Adolescent↗
The radiobiology of 24 keV neutrons. Measurement of the relative biological effect free-in-air, survival and cytogenetic analysis of the biological effect at various depths in a polyethylene phantom and modification of the depth-dose profile by boron 10 for V79 Chinese hamster and HeLa cells.
HeLa human carcinoma cells and V79 Chinese hamster fibroblasts have been irradiated in vitro with a beam of neutrons with a nearly pure 24 keV spectrum. The relative biological effectiveness (RBE) of the filtered neutron beam relative to 60Co gamma radiation was determined by irradiation of cell cultures "free-in-air". The values obtained for the RBE at 37% survival were 5.8 +/- 0.8, at a dose of 0.69 +/- 0.06 Gy for the HeLa cells and 3.14 +/- 1.1 at a dose of 1.09 +/- 0.091 Gy for the V79 cells. Cytogenetic analysis of the damage in irradiated V79 cells gave an RBE of 6.7 +/- 1.4. Irradiation in a polyethylene phantom markedly attenuated the beam's biological effect. For both cell lines 2 cm of polyethylene virtually eliminated cell killing. Addition of boron 10 to the medium led to increased cell killing and a value of 4 was obtained for the RBE of the 10B(n, alpha)7Li reaction in HeLa cells.
Animals↗
Plasma lipoproteins and fatty liver in dairy cows.
Dairy cows were classified on the basis of a histological study after a hepatic biopsy conducted in the second week post partum (mild fatty liver, moderate fatty liver, severe fatty liver). Plasma lipoproteins were separated into various density classes by repeated ultracentrifugation. The results indicate that the beginning of lactation is associated with a low concentration of the 1.006 to 1.063 g ml-1 lipoprotein fraction. The lowest concentrations occurred in cows with severe steatosis or during the evolution of moderate steatosis.
Animals↗