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Biochemistry began as an identifiable, separate discipline at the beginning of the twentieth century. This article traces its early development, focusing on three pioneers--Eduard Buchner, Arthur Croft Hill and Arthur Harden.
Several observations noted by early investigators supported the supposition that in most cases, congenital glaucoma is determined by genetic factors. The genetic heterogeneity of PCG was confirmed by genetic linkage studies conducted in the 1990s when the authors determined that CYP1B1 is the congenital glaucoma gene at the GLC3A locus. The coding sequence of CYP1B1 has been subjected to extensive screening in familial and sporadic cases of glaucoma from numerous countries and from a large number of ethnic groups. These studies have provided evidence for extensive allelic heterogeneity at the GLC3A locus. This article also discusses the molecular evidence for reduced penetrance in congenital glaucoma and the phenotypic heterogeneity of CYP1B1 mutations, mouse models of CYP1B1, and the biochemistry of CYP1B1.
The biochemistry of selenium-containing natural products, including selenoproteins, is reviewed up to May 2002. Particular emphasis is placed on the assimilation of selenium from inorganic and organic selenium sources for selenoprotein synthesis, the catalytic role of selenium in enzymes, and medical implications of an unbalanced selenium supply. The review contains 393 references on key discoveries and recent progress.
The role and historical progress of n.m.r. applications in biochemistry are briefly outlined. Technical advances over the years have made n.m.r., at last, a technique which can give valuable information about a wide range of biochemical topics, from enzyme kinetics in vivo to the structure of protein-DNA complexes. Emphasis here is placed on studies of proteins, especially those made up from mosaics of modules. It is shown that n.m.r. can readily give detailed structural information about individual protein modules and that valuable information about the structure and function of the intact mosaic protein can be inferred.
The work done in the Department of Biochemistry in Oxford during World War II is recounted. Reference is made to the research on burns, nutrition and malaria, but it is mainly concerned with the search for antidotes to mustard gas and lewisite. The discovery of a successful antidote to lewisite is described in some detail.
As technical obstacles yield, en masse protein testing is poised to take one of biochemistry's most exciting techniques into the heart of cellular chemistry. On page 1760 of this issue, researchers report creating arrays of over 10,000 proteins on a piece of glass just half the size of a microscope slide. They then used their arrays to study a variety of protein functions, including identifying members of the array that bind to other free-floating proteins and to small, druglike molecules.
OBJECTIVES: To investigate issues of curriculum in the context of a postgraduate sports medicine training programme, specifically in the field of clinical biochemistry and haematology. METHODS: Following the Delphi methodology, a series of sequential questionnaires was administered to curriculum developers, clinical teachers, examiners, and registrars. RESULTS: Agreement on a core syllabus for this subject with an indication of the core aims and objectives of teaching and learning in this field and the associated required skills and competencies. An indication of current and ideal teaching and learning methods and reasons for these preferences. A consensus of key features of a teaching module for this field and of appropriate methods of examination. CONCLUSIONS: The data derived from this study, as well as the experience of engaging in it, will better inform curriculum developers, teachers, and students of one another's perceptions as to what is important in and appropriate to teaching and learning in this field of sports medicine. Engagement in the exercise and broader consideration of the outcomes by those who develop the curriculum, teach, and formulate the examination process will facilitate attainment of the ideal of well aligned teaching, learning, and examination in this specific field.
A survey was carried out of doctors who used their out-of-hours biochemistry service to find out why requests for investigations were made, how often the results altered patient management, and whether they could define areas where investigations were unproductive. Of 107 questionnaires distributed, 147 (88%) were completed. In 86% the requests were for diagnosis or immediate patient management and in 35% the results actually altered management. Senior clinical staff were more efficient than their juniors in instigating biochemical investigations that proved to be effective. In no instance where the clinical staff predicted that it was unlikely that the results would alter management was management altered. It is suggested that joint reviews of case notes by junior and senior clinical staff would prove to be the most appropriate way to increase the effectiveness and efficiency of clinical investigation.
Two forms--a priority test request form and a telephone results form--provide improved communication between the physician and the emergency laboratory of the Clinical Biochemistry Department. The priority test request form contains a list of available tests and it allows the physician to tell the laboratory exactly when emergency test results are required. The telephone results form ensures that the physician will receive a report, by telephone, of a test result although it may not be an urgent test. This allows a greater control of work flow, both routine and emergency, through the laboratory.
The process of costing clinical biochemistry tests as a component of the commissioning of a unit management budgeting system based on an International Computers Limited (ICL) minicomputer system was examined. Methods of apportioning consumable and labour costs under direct and indirect cost headings and as test and request charges were investigated, and in this currently operational system it was found that 38% of consumable costs and 57% of labour costs were not a direct component of the routine analysis function. Means of assigning test costs to a given request source and the incorporation of such charges into clinical budget statements were looked at. A reduction in laboratory workload did not produce a comparable reduction in laboratory costs. For a theoretical reduction in workload of 20% only a 3.8% laboratory saving in recoverable costs could be expected.
AIM: To examine a model for the evaluation of appropriateness of testing in an emergency biochemistry laboratory. METHODS: A model was devised in which incoming emergency test requests were categorised as appropriate or inappropriate. Explicit criteria were used to define eight minor categories, which were chosen to reflect accurately current working practice within the hospital and laboratory. Five junior medical staff each undertook a prospective 24 hour assessment, during which time all incoming requests were monitored and categorised according to these criteria. Concordance between monitors was evaluated before and during assessments. RESULTS: Of 509 requests, 384 (75%) were appropriate and 125 (25%) were inappropriate according to the criteria used to define categories. Inappropriate requests fell into three main groups: preoperative samples (43.2% (54/125) of all inappropriate requests), missed routine samples (33.6% (42/125)) and accelerated (priority) analyses (16% (20/125)). Various other reasons accounted for the remaining 7.2% (9/125). CONCLUSION: This model may be used to obtain valid information about current clinical and laboratory practice. Strategies to reduce the number of inappropriate requests have been identified in order to reserve the emergency service for situations of true need.
This lecture consists of a short appraisal of some of the main features that have characterized the growth of biochemistry during the course of the 20th century. It dwells on the early impacts of vitalism, the emergence and elucidation of the vitamins, the discovery of coenzymes, the concept of active centres of enzymes, the development of experimental techniques (including the use of isotopes), the genetic code, and on the development of molecular biology and closely allied fields of investigation. It concludes with a consideration of the influence of the study of membranes and of neurochemistry on current biochemical thought.
Mechanical processes are involved in nearly every facet of the cell cycle. Mechanical forces are generated in the cell during processes as diverse as chromosomal segregation, replication, transcription, translation, translocation of proteins across membranes, cell locomotion, and catalyzed protein and nucleic acid folding and unfolding, among others. Because force is a product of all these reactions, biochemists are beginning to directly apply external forces to these processes to alter the extent or even the fate of these reactions hoping to reveal their underlying molecular mechanisms. This review provides the conceptual framework to understand the role of mechanical force in biochemistry.
Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in basrelief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (> or = 50 microns), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.
This review covers biosensors based on piezoelectric crystals, optical systems, field effect transistors and thermistors. Piezoelectric crystal or microgravimetric biosensors have been used for immunoassay. Optical biosensors are described in which waveguides are used to transmit changes in optical characteristics or, in an innovative mode, the evanescent wave component of a completely internally-reflected light beam is used to study optical changes. Optical biosensors have been used in immuno and in enzyme-based assays. Field effect transistors detect changes in ion concentrations and have been applied to the detection of biochemical reactions which involve a change in concentration of a specific ion. Thermistors are used to monitor the heat produced as the result of an exothermic enzymatic reaction and this has been applied to the assay of compounds or enzymes of interest. Biosensors may find a role in clinical biochemistry in low volume testing, patient self-testing and in vivo monitoring.
A questionnaire was sent to 35 doctors who were believed to have trained in clinical biochemistry in Scotland between 1 January 1985 and 31 December 1989. Thirty replies were received from 23 individuals who were still employed in the specialty (including seven consultants and nine senior registrars) and from seven individuals who had left. Twenty considered that training within the laboratories in which they were employed had not been satisfactory. The main emphasis of training was directed towards reporting duties, clinical liaison, research, teaching and outpatient clinics. Little training was provided for the development of analytical experience, personnel selection and laboratory management. Those surveyed identified poor training in laboratory management as the main aspect of training which required improvement.
Highly effective separation and highly sensitive detection reagents for clinical chemistry and biochemistry were developed and their applications were investigated. The sensitive detection of carboxylic acids was accomplished using 9-anthryldiazomethane (ADAM) which gave intensely fluorescent derivatives from carboxylic acids without catalysts or heating. 1-Pyrenyldiazomethane was then synthesized and proved to react also readily with carboxylic acid and more sensitive than ADAM. The optical resolution of amino acid enantiomers was achieved using 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC). GITC derivatized enantiomeric amino acids under mild conditions to give highly hydrophobic diastereomers which could be resolved on conventional reversed phase columns and easily detected by the absorption based on the thiourea structure. Then we devised an o-phthalaldehyde-N-acetylcystein reagent (OPA/NAcCys) giving diastereomers which were also resolved on a reversed phase column and detected fluorometrically with excellent sensitivity. OPA/NAcCys was useful for the assay of D-amino acids in the blood of uremic patients. The hypochlorite-thiamine method for the assay of proteins and peptides was established providing sensitive fluorometry, which well reflected the number of peptide groups in the molecule. This principle was applied to the assay using N-chlorodansylamide, designed for the fluorometry of peptides. The alkaline ninhydrin method was applied to the detection of guanidino compounds in the blood of uremic patients. Several fluorometric methods for the simultaneous detection of reducing and non-reducing carbohydrates, and guanidines were found to be useful reagents for this purpose because these compounds were resistant to the oxidation with periodate. Then protamine-bound columns were prepared for the separation of carbohydrates on HPLC, which showed excellent recovery of reducing carbohydrates in comparison with conventional alkylamino columns.
Medline is the US National Library of Medicine database that is used for searching the medical biochemistry literature. The database is structured using medical subject subheadings (MeSH terms) to classify the content of references; indexing is done manually using MeSH terms as key words. Searching the database effectively means finding the maximum number of relevant references together with the minimum number of irrelevant ones. This article is aimed at explaining the limitations of Medline and suggesting some solutions to key problems. The goal is that users can improve their literature search technique by employing a structured approach. As usual, asking relevant questions before starting a search is essential.