Friends and influence: the history of the '42 Club'.
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Biomedical subjects
Publications and source records attributed to C Booth.
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The identification of a common mutation, delta F508, in the CFTR gene allowed, for the first time, the detection of cystic fibrosis (CF) carriers in the general population. Further genetic studies revealed > 100 additional disease-causing mutations in this gene, few of which occur on > 1% of CF chromosomes in any ethnic group. Prior to establishing counseling guidelines and carrier risk assessments, we sought to establish the frequencies of the CFTR mutations that are present in CF families living in the Chicago area, a region notable for its ethnic heterogeneity. Our sample included 283 unrelated CF carriers, with the following ethnic composition: 78% non-Ashkenazi Caucasians, 5% Ashkenazi, 9% African-American, 3% Mexican, 0.3% Native American, and 5% mixed ancestry. When a panel of 10 mutations (delta F508, delta I507, G542X, G551D, R553X, S549N, R1162X, W1282X, N1303K, and 1717-1G-->A) was used, detection rates ranged from 75% in non-Ashkenazi Caucasians to 40% in African-Americans. These data suggest that the goal of screening for 90%-95% of CF mutations may be unrealistic in this and other, similar U.S. populations.
The adaptability of Escherichia coli dihydrofolate reductase (DHFR) is being explored by identifying second-site mutations that can partially suppress the deleterious effect associated with removal of the active-site proton donor aspartic acid-27. The Asp27----serine mutant DHFR (D27S) was previously characterized and the catalytic activity found to be greatly decreased at pH 7.0 [Howell et al. (1986) Science 231, 1123-1128]. Using resistance to trimethoprim (a DHFR inhibitor) in a genetic selection procedure, we have isolated a double-mutant DHFR gene containing Asp27----Ser and Phe137----Ser mutations (D27S+F137S). The presence of the F137S mutation increases kcat approximately 3-fold and decreases Km(DHF) approximately 2-fold over D27S DHFR values. The overall effect on kcat/Km(DHF) is a 7-fold increase. The D27S+F137S double-mutant DHFR is still 500-fold less active than wild-type DHFR at pH 7. Surprisingly, Phe137 is approximately 15 A from residue 27 in the active site and is part of a beta-bulge. We propose the F137S mutation likely causes its catalytic effect by slightly altering the conformation of D27S DHFR. This supposition is supported by the observation that the F137S mutation does not have the same kinetic effect when introduced into the wild-type and D27S DHFRs, by the altered distribution of two conformers of free enzyme [see Dunn et al. (1990)] and by a preliminary difference Fourier map comparing the D27S and D27S+F137S DHFR crystal structures.
OBJECTIVE: To assess the effectiveness of decontamination procedures in general practice. DESIGN: Anonymous postal questionnaire survey of 600 general practitioners randomly selected from the national register. SETTING: General practices throughout the United Kingdom. SUBJECTS: 382 General practitioners, a response rate of 65%. RESULTS: 186 General practitioners had autoclaves but 125 used hot water disinfectors or chemical disinfectants to reprocess instruments. 22% (474/2132) Of high risk instruments were inadequately decontaminated. Decontamination was performed by the practice nurse or receptionist in 306 practices. Knowledge of treatment of spillages of blood fluids was uncertain, and only 114 general practitioners used effective methods for dealing with spillages. CONCLUSIONS: A comprehensive central code of practice for control of infection is needed for primary health care staff.
The endoplasmic reticulum (ER) contains a family of luminal proteins (reticuloplasmins) that are normally excluded from the secretory pathway. However, reticuloplasmins are efficiently secreted when murine fibroblasts are treated with calcium ionophores. The secreted and cellular forms of endoplasmin are clearly distinguishable on the basis of gel mobility and endoglycosidase H sensitivity. Reticuloplasmin secretion leads to the depletion of the proteins from the ER and their accumulation in the Golgi apparatus. The stress response to calcium ionophore induces reaccumulation of reticuloplasmins in the ER and suppresses their secretion. Secretion is also associated with changes in the structure and distribution of the ER. These observations show that perturbation of cellular calcium levels leads to the breakdown of the mechanism for ER retention of reticuloplasmins and suggest a role for calcium ions in their sorting from secretory proteins.
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The endoplasmic reticulum (ER) of a typical interphase 3T3 fibroblast consists of a compact perinuclear arrangement of cisternae and lamellae which can be observed by immunofluorescence with anti-endoplasmin. During mitosis the reticulum dissociates into small fragments from which it appears to re-assemble in the daughter cells. When interphase 3T3 cells are exposed to calcium ionophores, but not other ionophores, there is a similar dissociation of the ER into small uniform fragments, which are dispersed throughout the cytoplasm. Electron microscopy shows that the fragments consist of small vesicular structures and that essentially all of the rough ER except the nuclear envelope is dissociated. The dissociation of the ER by calcium ionophore is a relatively specific process since other organelles and supramolecular assemblies remain unaffected. When cells with dissociated ER are returned to normal medium, there is a rapid reassembly of the fragments into the continuous reticulum. In a proportion of the cells it is possible to observe linear arrays of the fragments, which probably represent intermediates in the re-assembly process. These observations demonstrate that the ER in interphase 3T3 cells can be dissociated into, and re-assembled from, small fragments. Re-assembly of the ER from the fragments is dependent on the presence of millimolar levels of calcium in the external medium. In the presence of calcium, re-assembly is inhibited by the calcium channel blocker, verapamil. Thus calcium ions appear to play an important role in ER structure and assembly.
The authors believe that literature and music as an adjunct in teaching psychiatric-mental health nursing are enriching for students and faculty. Although a systematic evaluation process has not yet been completed, anecdotal evidence suggests that more interesting classes and greater learning results from a variety of teaching methods (Bloom, 1976; Shipman & Shipman, 1985). The students learn from the life experiences of others portrayed by the characters in literary and musical form. Insights into the psychodynamics of human behavior are gleaned through the study of the reality of the total person rather than a focus on mental disorders. Moreover, students take a more active role in learning since they problem-solve in class rather than the more passive role that usually accompanies the lecture format. Through the increased use of reflection, analysis, and self-discovery, students hopefully will continue to utilize these processes, thereby increasing their awareness of the psychological aspects of everyday media, valuing human behavior, and perceiving the world in a more integral whole.
Blood samples were collected on a random basis from two canine populations. The haemoglobin concentration, erythrocyte count, haematocrit, leucocyte count and differential leukocyte count were investigated in a population of kennelled dogs and a population of dogs of a rural township in a developing country. The means of five of the nine haematological parameters evaluated were found to be statistically significantly different between the two groups. It is postulated that these differences were due to the difference in diet, type and severity of disease, parasites present in the population, and to a lesser extent to breed and age differences.
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Pharmaceutical products which are to be given by injection are required by law to be sterile and pyrogen-free. This paper outlines some of the advantages and disadvantages of the rabbit pyrogen test. It then covers briefly the history of the development of the Limulus Amoebocyte Lysate assay, followed by the advantages and disadvantages this assay has for use in the pharmaceutical industry.