Biomedical subjects
Publications and source records attributed to J Knight.
The most serious side effect of ketoconazole is hepatitis, which has proved fatal in seven reported cases. We present a case of fulminant hepatic failure in a 45-year-old Oriental woman that probably would have been fatal except for a successful liver transplant. A review of the literature of fatalities associated with ketoconazole is presented.
OBJECTIVE: To compare the prevalence of antibody to and proviral DNA of the retrovirus HTLV-I in relatives of 11 British patients with tropical spastic paraparesis who had migrated from Jamaica before they developed symptoms, and to examine factors possibly related to transmission of HTLV-I. DESIGN: Migrant, family study. Antibody state was determined by several methods and confirmed by western blotting; the polymerase chain reaction was used to detect proviral DNA. SETTING: Britain and Jamaica. SUBJECTS: All available first degree relatives: those born and still resident in Jamaica (group 1); those born in Jamaica who migrated to Britain (group 2); and index patients' children who were born and resident in Britain (group 3). All had been breast fed and none had had blood transfusions. RESULTS: Of the 66 living relatives, 60 were traced. Seroprevalence among those born in Jamaica (irrespective of current residence) was 22% (10/46; 95% confidence limits 9 to 34%) compared with zero among British born offspring (0/14) and was higher in group 2 at 33% (7/21; 12 to 55%) than in group 1 at 12% (3/25; 0 to 25%). (Patients in group 1 had the greatest mean age.) Proviral DNA was not detected in any subject negative for HTLV-I antibody, making prolonged viral incubation in those negative for the antibody unlikely. CONCLUSION: In this sample factors related to place of birth and early residence were more important in transmission of HTLV-I than maternal or age effects. In areas with a low to moderate prevalence policies of preventing mothers who are carriers of the virus from breast feeding would be premature.
Rabbit antibodies prepared against a v-sea-encoded polypeptide expressed in bacteria were used to characterize the v-sea-encoded proteins in cells transformed by the avian erythroblastosis virus, S13. In addition to the two previously described v-sea-encoded proteins, gp155 and gp70, two additional proteins were identified of molecular weights 38,000 and 36,000 Da. Interestingly, these two proteins were found only in fibroblasts infected with the S13 virus and not in S13-transformed erythroid cells. These two proteins were phosphoproteins, but, unlike the two previously characterized v-sea-encoded proteins, they did not appear to be modified by the addition of N-linked sugars. Possible mechanisms for the biosynthesis of these two new proteins are discussed.
We studied the frequency of antiphospholipid antibodies (aPL) in patients undergoing cardiac valve replacement, and present the results in the context of the pathology of the valve lesions. Forty-eight consecutive patients undergoing valve replacement were studied. Of the whole group, 15 (31%) had antibody levels greater than 2 SD above the mean for a control group of healthy persons and 11 (23%) had a level of greater than 3 SD. There was an increased frequency of elevated antibody levels in patients with valves showing fibrocalcific change and a significant association between aPL and valve thrombus. The possible role of these antibodies in the pathogenesis of the valve lesions is discussed.
The DNA context of nucleotides that a protein recognizes can influence the strength of the protein-DNA interaction. Moreover, in prokaryotes, understanding the quantitative differences in binding affinities that result in part from the DNA context is often important in describing regulatory mechanisms. Nevertheless, these issues have not been a major focus yet for the investigation of protein-DNA interactions in eukaryotes. In this study, we explored the binding specificity and the range of affinities that the BPV-1 E2 transcriptional activator has for DNA. Because E2 binding sites are positioned near several different BPV-1 promoters, such quantitative information may be important to understand transcriptional regulatory mechanisms in BPV-1. Gel retardation assays and DNA footprinting were used to quantitate the affinities of the E2 binding sites in the viral genome. In the process, five sites were discovered, which, on the basis of sequence, had not been predicted previously to interact with the E2 protein. Equilibrium and kinetic studies show that the range of E2 affinities of the 17 sites varied over 300-fold. The sequence elements responsible for E2 recognition of DNA were determined by missing contact analysis of several sites and a point mutation analysis of one site. The results presented show that the affinity of an E2 binding site is to a large extent determined by the availability of specific contacts, but the data also strongly suggest that DNA structure plays an important role.
Recent studies have identified a specific chromosomal translocation, t(X;18)(p11.2;q11.2), in a high proportion of human synovial sarcomas. As a first step towards characterizing the X;18 translocation we have established a synovial sarcoma cell line. Fusion of this cell line to mouse RAG cells gave rise to somatic cell hybrids that contain the derivative (X) marker chromosome in the absence of other genetic material from chromosomes 18 and X. Southern analysis of DNA from these somatic cell hybrids demonstrated that the human X chromosome markers DXS94, DXS14, DXZ1 and DXS62 were retained. In contrast DXS7, GAPDP1, ARAF1, DXS146 were not consistently present in the hybrids indicating that these markers were on the region of the X chromosome replaced by part of the long arm of chromosome 18 during the generation of the X;18 translocation. The predicted position of the translocation relative to X chromosome markers is DXS7-DXS146-X; 18-DXS14-DXZ1-DXS94.
A cloned cDNA (1.65 kb) containing the complete glycoprotein gene of the Josiah strain of Lassa virus was inserted into the thymidine kinase (TK) gene of the New York Board of Health (WYETH) strain of vaccinia virus. The Lassa virus glycoprotein precursor, GPC, and the posttranslational cleavage products, G1 and G2, were shown by Western blot analysis to be properly expressed in cells infected with the recombinant virus. Northern blot hybridization of total cytoplasmic RNA extracted from recombinant virus infected cells demonstrated the presence of RNA transcripts of appropriate size considering the site of transcription initiation from the vaccinia P7.5 promoter, the size of the Lassa glycoprotein gene, and the presumed location of the transcription terminator in the vaccinia thymidine kinase gene. All guinea pigs vaccinated with the recombinant virus survived a lethal challenge infection with Lassa virus, whereas 80% of control animals died. The vaccinated guinea pigs did, however, develop transient, low-grade, fevers and detectable viremias following infection with Lassa virus, indicating that protection was not complete.
The isolation and characterization of a temperature-sensitive mutant (ts1 S13) of the avian erythroblastosis virus, S13, is described. The temperature-sensitive lesion in ts1 S13 was identified as affecting the tyrosine kinase activity but not the plasma membrane localization of the ts1 S13 v-sea gene product. Erythroblasts transformed by ts1 S13 can be induced to synchronously differentiate into erythrocytes in an erythropoietin (EPO)-dependent fashion. Analysis of erythrocyte-specific gene expression in ts1 S13 erythroblasts reveals that the transformed, self-renewing erythroblasts obtained at permissive temperature already express all erythrocyte genes tested for, although at a low level. Upon differentiation induction, expression of erythrocyte-specific genes is not coordinately regulated but rather involves complex regulatory mechanisms that appear to be specific for the individual genes.
The measurement of clinical skills performance continues to pose a challenge for nurse educators. This paper will report on the use of the objective structured clinical examination (OSCE) to measure the psychomotor learning outcomes of a programme designed to assist students to learn to conduct a nursing neurological examination. The OSCE has a tradition in medicine, having been developed by Ronald Harden in Scotland and first reported in the British Medical Journal in 1975. The University of Ottawa has the longest North American experience with this type of evaluation procedure and there is an increasingly rich medical literature referring to the OSCE. Although the OSCE appears to be a promising method for evaluating competence in the performance of clinical skills, there are no studies in the nursing literature examining the use of the OSCE as a method for evaluating the performance of clinical skills by nurses. Our experience suggests that the OSCE may be a powerful tool in the evaluation of clinical competence in nursing and that it may also be an effective facilitator for learning to perform clinical skills in nursing.
Cells transformed by the avian erythroblastosis virus S13 contain three proteins derived from the v-sea oncogene, gp155, gp70 (a cleavage product of gp155), and p38. It is not clear whether only one or all three of these proteins are required for transformation by S13. S13 transformed erythroblasts and fibroblasts revert to a normal morphology in the presence of the alpha glucosidase-1 inhibitor castanospermine, whereas cells transformed by the v-src or v-erbB oncogenes are unaffected by this drug. Treatment with castanospermine does not alter the tyrosine kinase autophosphorylation activity of any of the v-sea products, and the synthesis and processing of p38 is unaffected. Castanospermine modifies the structure of the carbohydrate chains of gp155 such that the glucose residues are retained, thereby inhibiting complex chain formation. Analysis of revertant S13 transformed cells shows that the proteolytic cleavage of the modified form of gp155 is inhibited, resulting in a very low yield of a modified form of gp70. There is no detectable effect of castanospermine on the transport of v-sea gene products to the cell surface. However, due to the inhibition of proteolytic cleavage, the modified form of gp155 is now the major v-sea encoded protein expressed on the cell surface. Thus it appears that the cell surface expression of a v-sea encoded protein with tyrosine kinase autophosphorylating activity is insufficient for cell transformation.
Pholasin is the protein-bound luciferin from the bivalve mollusc Pholas dactylus which reacts with its luciferase and molecular oxygen to produce light. Pholasin was purified 226-fold with a yield of 58% from P. dactylus to give a preparation free from luciferase contamination. The ratio (k) of endogenous pholasin chemiluminescence to that when maximally stimulated by luciferase was 8.12 X 10(-6) +/- 0.87 X 10(-6) (mean +/- SD, n = 6), equivalent to a t 1/2 of 23.7 h at pH 9. Pholasin could detect reactive oxygen metabolite production from neutrophils stimulated by the chemotactic peptide N-formyl-Met-Leu-Phe, in the presence and absence of 2-chloroadenosine or cytochalasin B, and by latex beads in the presence and absence of cytochalasin B. Pholasin was also able to detect a longer-lived oxidative activity distinct from myeloperoxidase, and released from neutrophils activated by latex beads or chemotactic peptide; luminol could not. Under optimal conditions pholasin produced a signal some 50-100 times that of luminol in the presence of activated neutrophils. This enabled activation of a single neutrophil by chemotactic peptide (1 microM) to be detected, giving a signal of 194 +/- 21 chemiluminescent counts per second, some six times that of the background signal (mean +/- SD, n = 2). Pholasin thus provides an indicator sufficiently sensitive to establish whether neutrophil activation occurs through thresholds in individual cells.
To evaluate the antisecretory activity of berberine sulfate (BS), we studied 165 adult patients with acute diarrhea due to enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae in randomized controlled trials. In patients with ETEC diarrhea who received 400 mg of BS in a single oral dose, the mean stool volumes were significantly less than those of the controls during three consecutive 8-hr periods after treatment (P less than .05). At 24 hr after treatment, significantly more patients who were treated with BS and had ETEC diarrhea stopped having diarrhea as compared with the controls (42% vs 20%, P less than .05). In patients with cholera who received 400 mg of BS, the mean 8-hr stool volume during the second 8-hr period after treatment declined to 2.22 liters, which was significantly less than the 2.79 liters found in the controls (P less than .05). However, patients with cholera who received 1200 mg of BS plus tetracycline did not have significant reduction in stool output compared with patients who received tetracycline alone. No side effects of BS were noted. These results indicated that BS is an effective and safe antisecretory drug for ETEC diarrhea, whereas the activity against cholera is slight and not additive with tetracycline.
This article examines the question of whether or not nursing is or should be a profession. The conclusion is based primarily on an analysis of what constitutes a profession and an empirical study of some nursing practices and attitudes. The analysis of professions recognizes three prominent models in sociology: trait, functional, and power or control. It bypasses these in favor of a "cluster concept," which asserts that the public has a number of expectations of an occupation before it will bestow the status of profession upon it. We then give an analysis of some of the results of the survey of a sample of Missouri registered nurses. The gist of the data is said to reflect the facts that these nurses think nursing is or should be a profession, but that other factors tend to show that nursing lacks the requisite cluster to substantiate the claim to be a profession. We conclude that nursing should perhaps not be a profession since it has been a bastion of the "ethics of compassion" in a world that is increasingly beset by an "ethics of competence."
Admissions to the Medical Paediatric Unit at Derby Regional Hospital in 1984 were reviewed. There were 536 admissions (289 males and 247 females). The average number of inpatients per day was 11.7, average duration of stay was 8.0 days, and there was one hospital death. Aboriginal children represented 90% of admissions and 59% of these were under two years of age. Several major problems were often encountered in individual children; these included respiratory, gastrointestinal and renal disease, failure to thrive and anaemia. Plasma electrolyte levels were measured in 82 children with gastroenteritis. Of these children 45 (55%) had a serum potassium level of less than 3.0 mmol/L and eight (10%) had a serum potassium level of less than 2 mmol/L. One hundred and four children were diagnosed as having pneumonia; 74 (71%) of them responded to penicillin. In 19 (21%) of 92 children who failed to thrive, no definite medical cause was found. The remainder had a combination of diarrhoeal disease, and chest and urinary tract infections. Anaemia, renal calculi and rheumatic fever are also common medical problems in the Kimberley region.
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Purified human erythrocyte acetylcholinesterase was labeled by reductive radiomethylation with saturating amounts of [14C]formaldehyde and sodium cyanoborohydride. Acid hydrolysis and automated amino acid analysis permitted both identification of radiomethylated components by their coelution with radiomethylated standards and quantitation of these components. The methylated N-terminal amino acids glutamate and arginine were observed at levels of 0.66 and 0.34 residues, respectively, per 70-kilodalton subunit, and lysine residues were methylated on their epsilon-amino groups to a level of 7.40 residues per subunit [Haas, R., & Rosenberry, T.L. (1985) Anal. Biochem. 148, 154-162]. In addition, each subunit contained 1.35 residues of methylated ethanolamine and 0.98 residue of methylated glucosamine. Papain digestion cleaved the intact enzyme into two fragments, an enzymatically active hydrophilic fragment and a small hydrophobic fragment that represented the membrane-binding domain. The radiomethylated amino acids were quantitatively retained in the hydrophilic fragment, while the methylated ethanolamine and glucosamine were confined exclusively to the hydrophobic domain fragment. This fragment included the C-terminal dipeptide of the subunit. Peptide sequencing by manual Edman methods was combined with radiomethylation to demonstrate the sequence His-Gly-ethanolamine-Z for the hydrophobic domain fragment. The ethanolamine residue in this sequence is in amide linkage to the C-terminal Gly and is clearly distinct from the ethanolamine residues in Z which are susceptible to radiomethylation in the intact enzyme. Since Z also includes glucosamine and 2 mol of fatty acids [Roberts, W.L. & Rosenberry, T.L. (1985) Biochem. Biophys. Res. Commun. 133, 621-627], we conclude that the membrane-binding domain of human erythrocyte acetylcholinesterase is a covalently linked glycolipid at the C-termini of the subunits.(ABSTRACT TRUNCATED AT 250 WORDS)