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Biomedical subjects

R Cook

Publications and source records attributed to R Cook.

At least 19 recordsLinked to original sources
PubMed1992

The psychological effects of false-positive results in prenatal screening for fetal abnormality: a prospective study.

The purpose of the study was to describe the impact of false-positive results from initial maternal serum alpha-fetoprotein (MS-AFP) screening. The analyses compared two groups of women, those receiving a negative result (n = 346) and those receiving an initial positive result (n = 26), over four time points--prior to testing, immediately after testing, later in pregnancy, and in the post-partum period. Receiving an abnormal result was associated with high levels of anxiety which were reflected in increased worry about the baby's health and a more negative attitude towards the pregnancy and the baby. Women who had an initial abnormal result were offered a variety of further tests. Those women who went on to have amniocentesis were less worried about their baby's health in the third trimester and also less anxious post-partum than those who did not have amniocentesis. In view of the increasing number of screening tests available, it is necessary to establish whether and how these levels of distress can best be reduced.

Adult↗
PubMed1992

Psychological effects of having amniocentesis: are these due to the procedure, the risk or the behaviour?

The purpose of the study was to examine the impact of amniocentesis on women at risk for having a baby with Down's syndrome because of raised maternal age. Fifty-four of the study participants had amniocentesis and nine did not. At the time of the procedure, those having amniocentesis were significantly more anxious, less certain about the baby's health, and held more negative attitudes towards the baby than women who did not undergo amniocentesis. For women undergoing amniocentesis there was a positive association between perceived risk of having an abnormal baby and anxiety. After the baby's birth, women who had undergone amniocentesis held less positive attitudes to the baby and were significantly more worried about the baby's health. These results suggest that the anxiety surrounding amniocentesis is related both to the procedure and to the perceived likelihood of an abnormal result. The differences between the groups after the birth seem more likely to reflect pre-existing attitudinal differences between the two groups, than the effects of amniocentesis.

Adaptation, Psychological↗
PubMed1992

Transmission studies with simian immunodeficiency virus of macaques; persistent infection of baboons.

The host range of SIVmac was investigated in three monkey species. Blood-borne and cell-adapted virus inocula obtained from a rhesus macaque infected with SIVmac251 were compared. African green monkeys were not susceptible to infection, whereas baboons and rhesus macaques became persistently infected and showed similar patterns of seroconversion. However, in contrast to the macaques, no clinical or histopathological evidence of disease was seen in the baboons 2 years after virus inoculation. Thus baboons could be used as an alternative to macaques in vaccine development studies with this particular isolate of SIVmac. Furthermore, this system may be useful for the investigation of factors responsible for disease progression.

Animals↗
PubMed1991

The impact of selenium supplementation on mood.

The possibility that a subclinical deficiency of the trace element selenium might exist in a sample of the British population was examined by giving a selenium supplement for 5 weeks. Using a double-blind cross-over design, 50 subjects received either a placebo or 100 mcg selenium on a daily basis. On three occasions they filled in the Profile of Moods States. A food frequency questionnaire was used to estimate the intake of selenium in the diet. Intake was associated with a general elevation of mood and in particular, a decrease in anxiety. The change in mood when taking the active tablet was correlated with the level of selenium in the diet, which was estimated from a food frequency questionnaire. The lower the level of selenium in the diet the more reports of anxiety, depression, and tiredness, decreased following 5 weeks of selenium therapy. The results are discussed in terms of the low level of selenium in the food chain in some parts of the world.

Adolescent↗
PubMed1991

Isolation and characterization of a full-length cDNA encoding the 55-kDa rabbit zona pellucida protein.

A full-length cDNA (rc55) encoding the major rabbit zona pellucida (ZP) glycoprotein (55 kDa) has been cloned and sequenced. A lambda gt11 expression library was constructed using poly(A)+ mRNA isolated from sexually immature rabbit ovaries which contain large numbers of developing follicles. The rc55 cDNA was identified using affinity purified polyclonal antibodies specific to ZP antigens which are shared among mammalian species. The deduced amino acid sequence of the full-length rc55 clone was matched to the NH2-terminal 25-amino acid sequence obtained for this protein. The predicted amino acid sequence consists of 540 amino acids including a putative signal peptide of 18-24 residues and six potential N-glycosylation sites. The cDNA hybridizes to a 2000-base species of mRNA from rabbit ovary which is not detected in other rabbit tissues. The message is present early in ovarian follicular development and is approximately 600-fold greater in sexually immature as compared with sexually mature rabbit ovaries. This cDNA was expressed as a cro-beta-galactosidase fusion protein using the pEX expression vector. Antibodies against native rabbit ZP, affinity-purified on the recombinant 55-kDa ZP protein, were found to recognize the native rabbit ZP glycoprotein, indicating partial conservation of native epitopes in the expressed recombinant protein.

Amino Acid Sequence↗
PubMed1991

Isolation of replication-competent molecular clones of visna virus.

Visna virus is the prototypic member of a subfamily of retroviruses responsible for slow infections of animals and humans. As a part of our investigation of the functions of viral gene products in virus replication, we have isolated three infectious molecular clones and determined the complete nucleotide sequences of two of the clones. We have also characterized the progeny of the biologically cloned viral stocks and of the infectious clones and document considerable heterogeneity in plaque size and antigenic phenotype of the former that is reduced to near homogeneity in the progeny of the infectious clones. It thus should now be possible to trace the emergence of antigenic variants of visna virus as well as ascribe defined functions to structural and regulatory genes of the virus in determining neurovirulence and the slow tempo of infection.

Amino Acid Sequence↗
PubMed1991

Neopterin quantification in acute severe asthma.

To investigate the pathogenic role of cell-mediated immunity (CMI) in acute severe asthma, 10 patients with acute asthma requiring admission to hospital had measurements of serum and urine absolute neopterin and neopterin/creatinine ratios. Serum was collected upon entry to hospital, 24 hr later and at 2 weeks; and urine at 24 hr and at 2 weeks after admission. Comparisons were made with 12 stable asthmatic patients, healthy control subjects, and six renal transplant patients undergoing transplant rejection. In contrast to the renal transplant patients who demonstrated T-lymphocyte-macrophage activation, neopterin concentrations and neopterin/creatinine ratios in both acute and stable asthmatic patients were not elevated. We have not found functional evidence that CMI participates in the pathogenesis of acute severe asthma.

Acute Disease↗
PubMed1991

Perceived risk not actual risk predicts uptake of amniocentesis.

A consecutive cohort of 71 women eligible for amniocentesis because they were over 38 years of age completed questionnaires during the first trimester of pregnancy. Sixty-one women underwent amniocentesis, an uptake rate of 86%. Uptake was associated with a less negative attitude towards termination of an affected baby and a higher perceived risk of the fetus being abnormal. It was not associated with actual age-related risks. There was no significant relation between actual risk and perceived risk. The results of this study suggests that it is important for doctors to understand the basis of women's decisions to have amniocentesis, and the difference between actual and perceived risk if they are to communicate effectively with women about the test and their options.

Abortion, Therapeutic↗
PubMed1991

Res ipsa loquitur in Canadian medical malpractice cases 1975-1988.

There is a perception in some quarters that courts too often, in the interest of compensating victims, find the medical profession at fault for 'failed medical care' which does not amount to negligence. If this were true, judges would likely make liberal use of the evidentiary rules res ipsa loquitur. However, a study of Canadian medical malpractice cases from 1975 to 1988 indicates that this is not the case and that judges on the contrary reject such a liberal use of the rule. Res ipsa loquitur was pleaded in only 37 of 142 cases, it was applied in only 14 of these cases, and the defendant was found liable in only ten of the cases in which it was applied. Furthermore, there is little evidence in these cases that judges are as a matter of policy trying to find legal rules to justify compensating more victims of medical misadventure, regardless of fault. On the contrary, judges not infrequently express sympathy for the plaintiff but nevertheless find for the defendant.

Canada↗
PubMed1990

Chimeric calmodulin-cardiac troponin C proteins differentially activate calmodulin target enzymes.

To evaluate the role of domain I of calmodulin (CaM) in the activation of target enzymes, a series of CaM mutants was constructed in which domain I (49 amino acids) was substantially deleted, or was exchanged with the homologous region (58 amino acids) of cardiac troponin C (cTnC). The proteins are 1) aM, a mutant CaM in which domain I has been deleted; 2) TaM, first domain of cTnC, last three domains of CaM; 3) TaM-BMI, same as TaM, except the nonfunctional first Ca2(+)-binding domain has been restored by mutagenesis; 4) CaT, first domain of CaM, last three domains of cTnC. These proteins were evaluated for Ca2+ binding properties and as activators of three CaM target enzymes, CaM-dependent phosphodiesterase (PDE), smooth muscle myosin light chain kinase (MLCK), and CaM-dependent multifunctional protein kinase (CaM kinase II). The chimeric proteins containing four domains bound Ca2+ in the manner expected from the number and nature of EF hands. In contrast, aM bound only two Ca2+, suggesting that deletion of domain I may have disrupted binding in one of the remaining three domains, and did not activate the three enzymes. The kinetics of activation of PDE by CaM, TaM, and TaM-BMI were identical. Although cTnC and CaT could maximally activate PDE, the Kact for these mutants were greater than 2000 times than for CaM. All mutated proteins except CaT were poor activators of CaM kinase II and this protein activated the kinase to 65% that of CaM, with a nearly identical Kact. CaT and TaM, were poor agonists of MLCK. Activation of Ca2(+)-binding site I in TaM (TaM-BMI), completely prevented activation of MLCK. In addition, TaM-BMI was a potent competitive inhibitor of MLCK activation by CaM (Ki = 66 nM). We conclude 1) a domain I is necessary to activate these target enzymes, and the substitution of the corresponding region of cTnC into CaM leads to differential effects; 2) an active first Ca2(+)-binding site is not essential for activation of PDE and the primary sequence of the first domain of CaM need not be highly conserved; 3) for CaM kinase II, determinants in the first domain are critical whereas more flexibility exists for the remaining three domains; 4) since TaM-BMI acts as a potent competitive inhibitor of MLCK binding of CaM to a target enzyme and activation can be dissociable events.

Amino Acid Sequence↗
PubMed1990

Selenium supplementation improves mood in a double-blind crossover trial.

The possibility that a sub-clinical deficiency of the trace element selenium might exist in a sample of the British population was examined by giving a selenium supplemented for 5 weeks. Using a double-blind crossover design 50 subjects received either a placebo or 100 micrograms selenium on a daily basis. On three occasions they filled in the Profile of Moods state. Mood did not change when taking the placebo, whereas when taking the selenium the subjects reported a substantial improvement after both 2.5 and 5 weeks.

Adolescent↗
PubMed1990

Identification of methionine-containing tryptic peptides of unstable beta-tubulin separated by reverse-phase high-performance liquid chromatography.

Methods for examining altered regions in unstable mutant proteins are described. The strategy is illustrated using assembly defective Chinese hamster beta-tubulin subunits that are rapidly degraded in the cell. These unstable proteins are metabolically labeled to high specific activity and isolated as spots on two-dimensional gels. Conditions for the generation of tryptic peptides from gel pieces containing beta-tubulin and their subsequent resolution by HPLC have been worked out. Through a combination of dual labeling with various tritiated amino acids and [35S]methionine as well as partial sequence analysis, the identification of several HPLC peaks with the known sequence of beta-tubulin has been accomplished. This technique should greatly aid attempts to map the sites of mutational alterations in beta-tubulin polypeptides, and the general strategy should be readily applicable to other mutant proteins.

Amino Acid Sequence↗
PubMed1990

Intravenous fluid load and recovery. A double-blind comparison in gynaecological patients who had day-case laparoscopy.

The effect of intra-operative fluid and dextrose administration upon recovery was tested in a randomised, double-blind trial. Three groups of 25 patients, each undergoing laparoscopic examination as day cases, were studied. The two groups who received fluid (20 ml/kg compound sodium lactate solution) showed significant improvement (p less than 0.05) in the variables that reflected hydration. The fluid group who also received dextrose (1 g/kg) exhibited further significant improvement. Intra-operative fluid and dextrose administration appears to confer some benefit upon recovery in patients who have minor surgery.

Adolescent↗
PubMed1990

Thrombolytic therapy in canine pulmonary embolism. Comparative effects of urokinase and recombinant tissue plasminogen activator.

We compared thrombolytic and pulmonary hemodynamic effects of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) in canine micropulmonary thromboembolism. Dogs were embolized with radioactive autologous blood clot to increase mean pulmonary artery pressure (from 13 to 34 mm Hg, p less than 0.005) and decrease cardiac output (2.5 to 1.6 L min, p less than 0.005). Four groups of six dogs were treated. We employed two doses of UK, 30,000 U/kg (UK30) and 60,000 U/kg (UK60), and two doses of rtPA, 1 mg/kg (rtPA1) and 2 mg/kg (rtPA2). Drugs were infused over 15 min. Rate and extent of pulmonary thrombolysis were assessed by continuously counting over both lung fields with a gamma camera. Compared with treatment with UK, both rtPA regimes significantly increased thrombolysis. Mean total pulmonary thrombolysis was 14 and 23% with UK30 and UK60, respectively, and 35 and 43% with rtPA1 and rtPA2. Corresponding to the increased thrombolysis, pulmonary hemodynamics improved most with rtPA. From 90 min to 3 h, pulmonary artery pressure was significantly lower with both rtPA regimes than with either UK regime. These results indicate, at least in the model employed, that compared with treatment with UK, pulmonary thrombolysis and corresponding hemodynamic improvement are greatest with rtPA.

Animals↗
PubMed1990

Torulopsis glabrata vaginitis: clinical aspects and susceptibility to antifungal agents.

Torulopsis glabrata is second only to Candida albicans in frequency of isolation from the vagina in both asymptomatic women and patients with yeast vaginitis. We retrospectively studied 33 patients from whom vaginal isolates of T glabrata were obtained. Torulopsis glabrata caused symptomatic vaginitis in 42% of the patients but was unassociated with symptoms in 30%; in 27% of patients, its importance was uncertain because of concomitant pathology. Antifungal susceptibility testing was performed on 39 T glabrata strains isolated from 39 patients. The minimal inhibitory concentrations (MICs) of the majority of T glabrata isolates fell within the sensitive range of the antimycotic drugs tested; however, no correlation was found between in vitro antifungal MICs and the response to azole drug therapy. Clinical success was achieved in 67% of the patients although mycologic cure occurred in only 33%. A small number of patients developed recurrent and often chronic Torulopsis vaginitis unresponsive to conventional therapy. Limited experience suggests that vaginal boric acid therapy may be of value in these recalcitrant cases.

Adult↗
PubMed1989

Subunit composition of the purified dihydropyridine binding protein from skeletal muscle.

The dihydropyridine (DHP) receptor from rabbit skeletal muscle has been characterized by affinity labeling and purification. Two procedures were used for purification: one that was a procedure modified from that of Curtis and Catterall (1984) and one that employed an anti alpha 1 monoclonal antibody (Mab) affinity column. In addition, both digitonin and CHAPS solubilizations were utilized with each purification technique. The major findings are as follows: (1) In contrast to the behavior in digitonin, neither the 52K (beta) nor the 140K (alpha 2) polypeptide quantitatively copurifies with the 170K (alpha 1) polypeptide when the purification is carried out in CHAPS. This has been shown by use of both wheat germ and monoclonal antibody columns. The digitonin-extracted receptor complex bound to the Mab affinity column loses alpha 2 and beta when the digitonin is replaced by CHAPS, and when the complex is bound to a WGA column, a CHAPS wash causes dissociation of alpha 1, beta, and gamma from alpha 2. Loss of binding of dihydropyridines occurs with the CHAPS wash but can be partially restored by the addition of the CHAPS wash to the material eluted from the column with N-acetylglucosamine. (2) Although both detergents solubilized greater than 80% of the polypeptides associated with the DHP binding site, the ability of these proteins to bind dihydropyridines is reduced more by CHAPS treatment than by digitonin treatment, raising the possibility that subunit interactions contribute to high-affinity binding. Alternatively, CHAPS may remove tightly bound lipids necessary for binding or cause irreversible denaturation of the binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗
PubMed1989

Interaction of tetrahydropteroylpolyglutamates with two enzymes from mitochondria.

The dissociation constants of tetrahydropteroylpolyglutamates, having from one to six glutamate residues, have been determined for the two mitochondrial enzymes serine hydroxymethyltransferase and dimethylglycine dehydrogenase. The ratios of the dissociation constants for the mono- and hexaglutamate forms of the coenzyme were 200 and less than 10 for serine hydroxymethyltransferase and dimethylglycine dehydrogenase, respectively. Km and kcat values were determined for the reversible interconversion of serine and glycine as a function of the number of glutamyl residues on the coenzyme. The values in the serine to glycine direction did not significantly change with the number of glutamyl residues, but in the glycine to serine direction, there was a 9-fold increase in the kcat/Km when the longer chain polyglutamates were used as the coenzyme substrate. A sensitive and rapid method for determining the dissociation constants of proteins which bind either tetrahydropteroylpolyglutamates or their 5-methyl and 5-formyl conjugates is described.

Animals↗