Psychosocial issues surrounding the general or restricted use of recombinant factor VIII: hemophilia clinic perspective.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
J R McDonald
Publications and source records attributed to J R McDonald.
Nonionic low-osmolality versus ionic high-osmolality contrast material for intravenous use in patients perceived to be at high risk: randomized trial.
To determine the cost-effectiveness of selective use of nonionic low-osmolality contrast material, the authors randomly assigned 955 patients to receive high-osmolality and 1,158 to receive low-osmolality intravenous contrast material. All patients had one or more of the following perceived risk factors for adverse reactions: prior reaction to contrast material, allergies, asthma, diabetes, cardiac or renal disease, anxiety, severe illness, and age greater than 50 years. The occurrence of any adverse event, need for therapy, or subjective symptoms was assessed in a double-blind fashion. An adverse reaction necessitating the attention of a physician occurred in 3.9% (n = 37) of patients in the high-osmolality and 0.9% (n = 10) of patients in the low-osmolality groups (P less than .000005). Therapy was administered to 1.4% (n = 13) and 0.5% (n = 6), respectively (P = .035). The difference was due to a reduction in urticaria and other mild anaphylactoid reactions. In a multivariate analysis, only prior reactions and allergy were independent risk factors. Selective use of intravenous nonionic contrast material is best justified in those with prior reactions, allergy, or asthma; at least 67% of reactions would be prevented.
Contrast Media↗
Expression and characterization of recombinant human ciliary neurotrophic factor from Escherichia coli.
The gene for ciliary neurotrophic factor (CNTF) was cloned from a human genomic DNA library by screening with a DNA fragment amplified from human genomic DNA using the polymerase chain reaction. A DNA sequence coding for human CNTF was placed under control of an regulatable promoter in the expression vector pJU1003 and transformed into Escherichia coli strain BL21(DE3). Induction of expression in cultures of this transformant led to the accumulation of approx. 25 mg/l per A600 unit of human CNTF. CNTF was purified to homogeneity from cell lysates via anion-exchange, cation-exchange and Zn(2+)-affinity chromatography. Purified CNTF contained less than 0.1% contaminating E. coli proteins, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis and reversed-phase high-pressure liquid chromatography (HPLC). The protein exhibited an ultraviolet absorption maximum at 279 nm with a calculated extinction coefficient of A1%(279) = 9.0. Peptide map and amino acid sequence analyses confirmed that the expressed protein has the amino acid sequence expected for human CNTF, except for the absence of the amino-terminal methionine. High-purified recombinant human CNTF supported the survival of chick embryo parasympathetic, sympathetic and sensory neurons in culture at low picomolar concentrations. These results indicate that the biological activities previously ascribed to impure CNTF preparations indeed reside in one molecule.
Amino Acid Sequence↗
Developing a system for surgical audit.
A system for surgical audit, which has been developed during a 6 year period in an active surgical unit of a teaching hospital, is described. Following a review of the first 3 years of our computerized audit, major modifications to the audit processes and computer program were made. The key lessons for systematic practical surgical audit include the collection of essential data only, establishing audit processes within current department practices, verification of data by consultants, and the provision of incentives for all users. The current system is proving a valuable resource for quality assurance, surgical training and departmental management.
Computer Systems↗
Type II regulatory subunit dimerization determines the subcellular localization of the cAMP-dependent protein kinase.
The type II cAMP-dependent protein kinase (PKA) is localized to specific subcellular environments through binding of dimeric regulatory subunits (RII) to anchoring proteins. Cytoskeletal localization occurs through RII dimer interaction with the PKA substrate molecule microtubule-associated protein 2 (MAP2). RII alpha deletion mutants and RII alpha/endonexin chimeras retained MAP2 binding activity if they contained the first 79 residues of the molecule. Disruption of RII alpha dimerization always prevented MAP2 interaction because 1) RII delta 1-14 (an amino-terminal deletion mutant lacking residues 1-14) was unable to bind MAP2 or form dimers, and 2) a modified RII alpha monomer including residues 1-14 did not bind MAP2. Chimeric proteins containing the first 30 residues of RII alpha fused to endonexin II formed dimers but did not bind MAP2. This suggested other side-chains between residues 30-79 also participate in MAP2 interaction. Peptide studies indicate additional contact with MAP2 may occur through an acidic region (residues 68-82) close to the RII autoinhibitor domain. Therefore, anchored PKA holoenzyme topology may position the catalytic subunit and MAP2 as to allow its preferential phosphorylation upon kinase activation.
Amino Acid Sequence↗
Amino acid sequence and characterization of a protein inhibitor of protein kinase C.
The complete primary structure has been determined for an inhibitor protein of protein kinase C. The bovine brain-derived inhibitor has a pI of 6 and its N-terminal alanine residue is blocked by acetylation. Fragments obtained by chemical and enzymatic cleavage of the purified inhibitor were analyzed by Edman degradation, fast atom bombardment mass spectrometry, and tandem mass spectrometry. The results establish that the protein has a calculated average molecular mass of 13,690 daltons and contains 125 amino acid residues with the following sequence: (sequence: see text) The inhibitor does not show significant homology with any other known protein. Circular dichroism of the freshly prepared apoprotein indicated a secondary structural content of 23% alpha-helix, 31% beta-sheet, and 11% beta-turn. Immobilization on nitrocellulose followed by exposure to a 65Zn2(+)-containing overlay solution showed that, like protein kinase C itself, the inhibitor is a zinc-binding protein, although the sequence does not reveal a "zinc finger" structure. Competition with 10-fold molar excess Ca2+ or Mg2+ did not reduce the zinc-binding specificity of this inhibitor.
Acetylation↗
Identification of an adipocyte protein that binds to calmodulin in the absence of Ca2+ and is phosphorylated in response to insulin and tumor-promoting phorbol esters.
The present experiments were performed to identify calmodulin-binding proteins phosphorylated in response to insulin. Homogenates were prepared from 32Pi-labeled rat adipocytes. After centrifugation, the supernatants (+/- Ca2+) were applied to calmodulin-Sepharose columns. The bound proteins were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and phosphoproteins were visualized by autoradiography. Several proteins bound to the affinity resin in the presence of Ca2+, two bound +/- Ca2+, but only one protein, Mr = 170,000 (denoted pp170), bound in the absence of Ca2+. Binding of pp170 was inhibited by adding calmodulin (micromolar) or Ca2+ (nanomolar) to extracts prior to affinity chromatography. Physiological concentrations of insulin rapidly and reversibly increased (by as much as 4-fold) 32P-labeled pp170. Phorbol 12-myristate 13-acetate (PMA) increased (up to 3-fold) phosphorylation of pp170; but 4 alpha-phorbol 12,13-didecanoate was without effect. Phosphorylation of pp170 in response to insulin and PMA occurred predominantly on serine residues; no phosphotyrosine was detected. Protein kinase C inhibitors attenuated PMA-stimulated phosphorylation of pp170, but had no effect on insulin-stimulated phosphorylation. Peptide mapping indicated that pp170 was phosphorylated on multiple sites and that insulin stimulated the phosphorylation of at least one site not phosphorylated in response to PMA. The results indicate that insulin and PMA stimulate the phosphorylation of pp170 via different pathways, the latter presumably via protein kinase C.
Adipose Tissue↗
Specific inhibitors of protein kinase C block transmitter-induced modulation of sensory neuron calcium current.
Modulation of neuronal, voltage-dependent calcium current has been described for a number of transmitters and peptides, but the biochemical basis for this phenomenon has not been completely identified. In several cases protein kinase C (PKC) is thought to mediate transmitter inhibition of calcium current; however, a lack of specific PKC inhibitors has hampered a direct physiological test of this idea. We have used the whole-cell, tight-seal configuration of the patch-clamp technique to apply intracellularly two specific PKC inhibitors to the cell bodies of embryonic chick sensory neurons. Both inhibitors, a 17 kd protein purified from bovine brain and a synthetic 13 amino acid "pseudosubstrate" peptide, blocked inhibition of calcium current by either norepinephrine or an exogenously applied PKC activator. These results provide strong evidence that activation of PKC is a prerequisite for the modulation of sensory neuron calcium current by norepinephrine.
Animals↗
Community care needs of people with AIDS--the key informant study: a research method for policy development, service planning, and achieving consensus.
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Acquired Immunodeficiency Syndrome↗
Isolation of two isoforms of a 21,000-dalton Ca2+-binding protein of bovine brain.
Using Ca2+-dependent hydrophobic interaction chromatography we have identified a novel bovine brain Ca2+-binding protein (CaBP) composed of 21 kDa and 23 kDa polypeptides. This calciprotein was further purified by heat-treatment in the presence of Ca2+ and ion-exchange chromatography. The isolated protein exhibits a number of properties in common with proteins belonging to the calmodulin family of CaBPs, including a Ca2+-dependent electrophoretic mobility shift on SDS-polyacrylamide gel electrophoresis, retention of the ability to bind 45Ca2+ after electrophoresis and Western blotting, and a high content of acidic amino acids. We have recently isolated and characterized a 21 kDa CaBP from bovine brain and conclude that the 21 kDa and 21/23 kDa CaBPs are isoforms since they have very similar U.V. absorption spectra and amino acid compositions, and polyclonal antibodies raised in rabbits against the 21 kDa CaBP cross-react to an identical degree with the 21/23 kDa CaBP as determined by the competitive enzyme-linked immunosorbent assay (ELISA). Both proteins contain carbohydrate, but they differ in the degree of glycosylation. Tissue distribution studies indicate the presence of both 21 kDa and 23 kDa Ca2+-binding polypeptides in bovine trachea, aorta, kidney, skeletal muscle and cardiac muscle, and chicken gizzard smooth muscle.
Amino Acids↗
A new software package for private practice.
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Computers↗
Inhibition of the Ca2+- and phospholipid-dependent protein kinase by a novel Mr 17,000 Ca2+-binding protein.
A novel Mr 17,000 Ca2+-binding protein isolated from bovine brain was found to be a potent inhibitor of the Ca2+- and phospholipid-dependent protein kinase (protein kinase C), also isolated from bovine brain. Half-maximal inhibition by this calciprotein of the initial rate of phosphorylation of histone III-S by protein kinase C occurred at a calciprotein concentration of 2.2 microM under standard conditions. Comparison of the effects of a number of Ca2+-binding proteins on protein kinase C activity indicated that the Mr 17,000 Ca2+-binding protein was the most potent inhibitor, followed by the intestinal Ca2+-binding protein and calcineurin. Calmodulin, troponin C, S-100 protein and a Mr 21,000 Ca2+-binding protein of bovine brain were relatively weak inhibitors of protein kinase C. The inhibitory effect of the Mr 17,000 Ca2+-binding protein was apparently not due to its interaction with phospholipid or the basic protein substrate and therefore appears to be due to a direct effect on the protein kinase C. These observations suggest that the novel Mr 17,000 Ca2+-binding protein, and possibly other Ca2+-binding proteins, may play a physiological role in regulating the activity of protein kinase C.
Animals↗
Symptoms at one year following concussion from minor head injuries.
Of 131 patients with mild concussion, 19 (14.5%) still had symptoms after 1 year. Of these 19 patients, 10 had some symptoms of which they had not complained at 6 weeks. Symptoms at 1 year were more common among women and among patients who had had positive neurological findings at 24 h. Of the 19 patients who had symptoms at 1 year, 8 were involved in law suits and 6 had been suspected of malingering 6 weeks after their accident. Five of these patients were both involved in law suits and suspected of malingering.
Adolescent↗
A prospective study of liver enzyme and other changes following repeat administration of halothane and enflurane.
A prospective study of liver enzymes and other measurements following repeat administrations of halothane or enflurane was carried out in patients undergoing minor urological operations. The patient populations were similar with respect to frequency of factors which might influence liver function, social habits, drug therapy and time intervals between administrations. Sixty-three received two or more administrations of halothane and 66 received two or more administrations of enflurane, both drugs given with nitrous oxide in oxygen. There was a greater frequency of increased enzymatic activity following repeat administrations of halothane than following enflurane and the average alanine aminotransferase and gamma glutamyl transpeptidase concentrations were increased to a greater degree following halothane than enflurane. There was no change in the eosinophil count and no significant postoperative morbidity. Change in alanine aminotransferase, lactate dehydrogenase and gamma glutamyl transpeptidase occured more frequently in obese patients receiving halothane.
Aged↗
Frequency of atopy and allergy in an anaesthetic patient population.
Ten thousand patients presenting for anaesthesia in the British Isles were questioned about a possible history of atopic or allergic disorders. The overall percentage frequency of atopy was 8.5, comprising eczema 2.4, hay fever 3.8 and asthma 3.5. The frequency of allergies was 13.5, of which penicillin was the most common (6.2). Females had a significantly greater frequency of atopy or allergy than males. Patients with a history of atopic disorders had a higher frequency of allergies than the non-atopic group (36.2% compared with 11.4%) and vice versa.
Adolescent↗
Frequency of previous anaesthesia in an anaesthetic patient population.
Ten thousand patients presenting for anaesthesia were questioned about their anaesthetic history; 6672 had received an anaesthetic previously, 19.2% in the preceding 4 weeks. Of 2780 in whom the agents were known, 80.4% had received thiopentone, 18.1% Althesin and 57.4% halothane. Thirty-seven per cent of the total survey population had received two or more anaesthetics.
Adolescent↗
A comparison of neural tube defects identified by two independent routine recording systems for congenital malformations in Northern Ireland.
The efficiency of two systems for recording congenital malformations has been compared; one system, the Registrar General's Congenital Malformation Notification, is based on registering all malformed infants, and the other, the Child Health System, records all births. In Northern Ireland for three years [1974--1976], using multiple sources of ascertainment, a total of 686 infants with neural tube defects was identified among 79 783 live and stillbirths. The incidence for all neural tube defects in 8 60 per 1 000 births. The Registrar General's Congenital Malformation Notification System identified 83.6% whereas the Child Health System identified only 63.3% of all neural tube defects. Both systems together identified 86.2% of all neural tube defects. The two systems are suitable for monitoring of malformations and the addition of information from the Genetic Counselling Clinics would enhance the data for epidemiological studies.
Humans↗
Anticholinergic drugs in anaesthesia. A survey of their present position.
A survey was carried out amongst anaesthetists in the United Kingdom and Ireland regarding the use of anticholinergic drugs. Sixty-two per cent of these anaesthetists use these drugs routinely in premedication. The drugs are nearly always atropine or hyoscine and are used mainly for reducing secretions and protection against vagal stimulation. A longer-acting drug was desired by 22% and 60% would like to use an orally effective anticholinergic drug. Though quite a number of minor side effects are high-lighted, the majority do not consider these serious enough to stop routine use. There is now a tendency amongst many anaesthetists either not to use these drugs routinely or use them less often, more rationally and in reduced dosage.
Atropine↗