Teaching diagnosis by computer.
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Biomedical subjects
Publications and source records attributed to C W Bishop.
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The technique of two-dimensional electrophoresis was used in combination with a highly sensitive silver stain to study vitamin D-dependent calcium-binding protein (CaBP) in rat kidney. Rat renal CaBP was shown to co-migrate almost exactly with CaBP purified from chick intestine suggesting evolutionary conservation of this protein. In some cases rat renal CaBP appeared not as a single polypeptide, but rather as a cluster of 4 polypeptides. Formation of the satellite cluster of CaBP in response to high doses of 1,25-dihydroxyvitamin D3 occurred in young rats which had been maintained on a vitamin D-deficient diet for 2 weeks, as well as in older rats which had been maintained on the same diet for 5 months. The 4 forms of CaBP were not the result of various states of Ca2+ binding, but rather the result of an enzymatic reaction. This was shown by 3 experiments. 1) Adding excess EGTA to samples containing the 4 satellite forms did not change the two-dimensional electrophoretogram. 2) Incubation of purified chick intestinal CaBP with kidney cytosols from D-deficient rats brought about the formation of the satellite CaBP forms from the chick protein. However, purified chick CaBP was unchanged by incubation in buffer alone for up to 2 h at 37 degrees C. 3) Placing rat kidney cytosols in a boiling water bath for 10 min inactivated the factor which generated the satellite forms as would be expected for an enzyme. The physiological significance of these forms of CaBP is as yet unknown.
The time course of calcium-binding protein induction by 1,25-dihydroxyvitamin D3 was examined in embryonic chick duodena by single-label autoradiography. Duodena were excised from 19-day-old embryos, cultured for 24 h in defined medium, and exposed to 1,25-dihydroxyvitamin D3 at 1/2, 1, 1 1/2, 2, 2 1/2, 4, 6, and 20 h before the end of the culture period. Control duodena were identically handled but were not exposed to the hormone. All duodena were pulsed with [14C]leucine during the final 30 min of incubation. Cytosolic proteins, extracted from each radiolabeled tissue, were resolved by two-dimensional electrophoresis and autoradiographs were prepared from the resulting gels. Calcium-binding protein was detectable by autoradiography in duodena cultured with hormone for 1 h or more but not in the control duodena. The autoradiographs were converted to digital images by a scanning densitometer and entered into the Man-computer Interactive Data Access System. The total radioactivity incorporated into calcium-binding protein during the 30-min pulse was determined by computer analysis of the digitized autoradiographs, and the rate of calcium-binding protein biosynthesis was calculated. Duodena cultured with hormone for 1-20 h synthesized calcium-binding protein at rates of 129 +/- 17 to 8800 +/- 110 pg/mg of cytosolic protein/30 min. These rates demonstrate that calcium-binding protein is induced within the first hour of exposure to 1,25-dihydroxyvitamin D3, but in amounts too small to be detected by commonly used immunoassays.
Jelliffe's standards for evaluating measurements of mid-upper arm circumference, triceps skinfold thickness, and mid-upper arm muscle circumference of American adults were compared with percentile distributions developed from the first Health and Nutrition Examination Survey (NHANES I). These comparisons show that the standards poorly represent the adult U.S. population. Replacement of the standards with updated sex-specific values is not recommended, as (a) no single value for each arm parameter can be considered as "normal" for men or women of all ages and (b) the expression of arm measurements as percentages of standards is an inappropriate method of evaluation. Instead, measurements should be evaluated by comparison with age- and sex-specific percentile distributions developed from the NHANES I.
Protein synthesis occurring before the onset of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) stimulation of calcium uptake was examined in embryonic chick duodena by double label autoradiography. Duodena from 19-day-old embryos were cultured for 24 h. Duodena exposed to a saturating concentration of 1,25-(OH)2D3 during the last 2, 4, or 6 h were either cultured with [3H]leucine for the final 2 h or used for calcium uptake assays. Duodena not exposed to the hormone were either cultured with [14C]leucine for the final 2 h or used for calcium uptake assays. Calcium uptake by nonradiolabeled duodena was increased (p less than 0.05) only in tissues exposed to the hormone for 6 h. Tissue uptakes of [3H]leucine and [14C]leucine were identical and linear with time. Soluble proteins were extracted from 3H- and 14C-labeled tissues, mixed, and simultaneously resolved by two-dimensional polyacrylamide gel electrophoresis. Analysis of fluorographs and autoradiographs prepared from the double-labeled gels revealed a protein induced by 1,25-(OH)2D3 within 2 h of exposure to 1,25-(OH)2D3 and at lest 2 h before the calcium uptake response. The induced protein co-migrated with purified chick calcium-binding protein during two-dimensional electrophoresis. These results demonstrate that 1) this protein is the calcium-binding protein and 2) calcium-binding protein is clearly synthesized in the embryonic duodenum before the calcium uptake response to 1,25-(OH)2D3 occurs.
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An enzyme in the cytoplasmic membrane, nitrate reductase, can be solubilized by heating membranes to 60 degrees C for 10 min at alkaline pH. A protease in the cell envelope has been shown to be responsible for this solubilization. The localization of this protease in the outer membrane was demonstrated by separating the outer membrane from the cytoplasmic membrane, adding back various forms of outer membrane protein to the cytoplasmic membrane, and following the increase in nitrate reductase solubilization with increasing amounts of outer membrane proteins. This solubilization is accompanied by the cleavage of one of the subunits of nitrate reductase and is inhibited by the protease inhibitor p-aminobenzamidine. Analysis of membrane proteins synthesized by cells grown in the presence of various amounts of p-aminobenzamidine revealed that p-aminobenzamidine affects the synthesis of the major outer membrane proteins but has little effect on the synthesis of cytoplasmic membrane proteins. When outer membrane is reacted with the protease inhibitor [3H]diisopropylfluorophosphate, a single protein in the outer membrane is labeled. Since the interaction with diisopropylfluorophosphate is inhibited by p-aminobenzamidine, it is suggested that this single outer membrane protein is responsible for the in vitro solubilization of nitrate reductase and the in vivo processing of the major outer membrane proteins.
The observation that oxygen represses nitrate reductase biosynthesis in a hemA mutant grown aerobically with or without delta-aminolevulinic acid indicates that cytochromes are not responsible for nitrate reductase repression in aerobically grown cells.
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Reference values for the mid-upper arm muscle area, mid-upper arm fat area, subscapular skinfold thickness, and sum of triceps and subscapular skinfold thicknesses of American adults were developed from data collected by the National Center for Health Statistics during the first National Health and Nutrition Examination Survey, 1971 to 1974. The reference values were compared to other reference values derived from a similarly conducted cross-sectional survey of the American population, the Health Examination Survey of 1960 to 1962. These comparisons revealed that arm muscle area and subscapular skinfold thickness of men and arm muscle area of women continuously increase with aging from 18 to 74 yr; arm fat area and sum of skinfold thicknesses of men increase with aging from 18 to 34 yr but stabilize or decrease with further aging; and arm fat area, subscapular skinfold thickness, and sum of skinfold thicknesses of women increase with aging from 18 to 64 yr but decrease thereafter. As these parameters frequently change more than 20% over the period of a single decade, it is important that age be considered in nutritional evaluations based on anthropometric measurements. Changes in these four parameters with successive generations are also frequently large. Consequently, it is imperative that the reference values used in nutritional assessment protocols be updated at regular intervals.
Modern technology has sparked the creation of computing systems that perform many medically related tasks, but communication between these systems is limited, in part by differences in the terminology used for various purposes and in part by the changing nature of medical concepts. The Unified Medical Language System represents an attempt to find a means of translation between diverse knowledge systems. An alternative, which we propose, is to agree on a knowledge base for the future and make use of present accomplishments in moving toward that goal.
A scheme for the continuing development of Meta-1, a taxonomy of medical subjects based; on MeSH and other systems, is described. The objective is a single, structured classification for medical knowledge.
Over the centuries, the medical record has become stereotyped. Reconsidering the purpose and organization of this document leads me to propose a four-part format consisting of administrative data, a patient synopsis, a chronological medical record, and a detailed medical record. The patient would be identified only in the administrative data section, leaving the rest of the record available for management, outcome, and cost studies, and protecting the patient's privacy. Adoption of this four-part format would make it easier to locate information in the medical record and would facilitate computerization. If the phraseology could be standardized, the new format would also allow easier data flow from one medical record to another and permit the construction of standardized disease profiles. Data on individual patients could then be compared with standardized profiles to identify deficiencies and redundancies in patient care.
Codes are used in every aspect of our daily lives, and many of the coding schemes in use are inappropriate, poorly implemented, or too fragmented in their coverage. This paper describes various approaches to coding, pointing out their strengths, weaknesses, and most appropriate applications. Those attempting to set up a coding scheme are strongly advised to analyze their needs, select the approach that is best for the application at hand, and carefully monitor the implementation of the coding system they choose. Only by understanding and monitoring our coding schemes can we minimize the amount of inappropriate and exasperating codes in our daily lives.
The body of medical knowledge is so vast, and finding a fact within it is often so difficult and frustrating, that various systems have been proposed to help. reviewing the various approaches reveals some of the difficulties of the retrieval task and why it has not been easy to devise a general approach. The imprecision of medical terminology is a major stumbling block. The development of specialized systems to serve particular medical interests has hampered the wider applicability of many such systems. This article offers eight characteristics for an ideal medical knowledge system. The key is for each medical term to be coded and independently defined, with synonymous terms to be equated through term codes. Any coded term could become the nucleus of a cluster of related, coded terms. The knowledge system would encompass all of medicine, would be in the public domain, and would be independent of hardware and software. While such a system is utopian, consideration of its characteristics can further the development of better interim systems.
Carefully structured medical knowledge can be used for a variety of purposes, including medical records, drug and test ordering, and differential diagnosis. The Framemed system divides medical information into 26 domains and arranges the items in a hierarchical sequence. The knowledge in the system resides in descriptive, relational, and conditional records created by experts in the various domains, who must sign and date each record as it is developed and are entirely responsible for its contents. Formation of the hierarchies requires careful attention to concepts and yields a logical framework for a standardized terminology that is in the public domain.