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Atomic structure of ferredoxin-NADP+ reductase: prototype for a structurally novel flavoenzyme family.

The three-dimensional structure of spinach ferredoxin-NADP+ reductase (NADP+, nicotinamide adenine dinucleotide phosphate) has been determined by x-ray diffraction at 2.6 angstroms (A) resolution and initially refined to an R factor of 0.226 at 2.2 A resolution. The model includes the flavin-adenine dinucleotide (FAD) prosthetic group and the protein chain from residue 19 through the carboxyl terminus at residue 314 and is composed of two domains. The FAD binding domain (residues 19 to 161) has an antiparallel beta barrel core and a single alpha helix for binding the pyrophosphate of FAD. The NADP binding domain (residues 162 to 314) has a central five-strand parallel beta sheet and six surrounding helices. Binding of the competitive inhibitor 2'-phospho-AMP (AMP, adenosine monophosphate) places the NADP binding site at the carboxyl-terminal edge of the sheet in a manner similar to the nucleotide binding of the dehydrogenase family. The structures reveal the key residues that function in cofactor binding and the catalytic center. With these key residues as a guide, conclusive evidence is presented that the ferredoxin reductase structure is a prototype for the nicotinamide dinucleotide and FAD binding domains of the enzymes NADPH-cytochrome P450 reductase, NADPH-sulfite reductase, NADH-cytochrome b5 reductase, and NADH-nitrate reductase. Thus this structure provides a structural framework for the NADH- or NADPH-dependent flavoenzyme parts of five distinct enzymes involved in photosynthesis, in the assimilation of inorganic nitrogen and sulfur, in fatty-acid oxidation, in the reduction of methemoglobin, and in the metabolism of many pesticides, drugs, and carcinogens.

Adenosine Diphosphate↗

[Automatic voice recognition for radiologic reports. Experiment with a prototype in an operational environment].

Large vocabulary speech recognition, its techniques and its software and hardware technology, are being developed, aimed at providing the office user with a tool that could significantly improve both quantity and quality of his work: the dictation machine, which allows memos and documents to be input using voice and a microphone instead of fingers and a keyboard. The IBM Rome Science Center, together with the IBM Research Division, has built a prototype recognizer that accepts sentences in natural language from a 20,000-word Italian vocabulary. The unit runs on a personal computer equipped with a special hardware capable of giving all the necessary computing power. The first laboratory experiments yielded very interesting results and pointed out such system characteristics to make its use possible in operational environments. To this purpose, the dictation of medical reports was considered as a suitable application. In cooperation with the 2nd Radiology Department of S. Maria della Misericordia Hospital (Udine, Italy), a system was experimented by radiology department doctors during their everyday work. The doctors were able to directly dictate their reports to the unit. The text appeared immediately on the screen, and eventual errors could be corrected either by voice or by using the keyboard. At the end of report dictation, the doctors could both print and archive the text. The report could also be forwarded to hospital information system, when the latter was available. Our results have been very encouraging: the system proved to be robust, simple to use, and accurate (over 95% average recognition rate). The experiment was precious for suggestions and comments, and its results are useful for system evolution towards improved system management and efficiency.

Medical Records Systems, Computerized↗

tyk2, prototype of a novel class of non-receptor tyrosine kinase genes.

We previously identified a novel protein tyrosine kinase gene, tyk2, by screening a human lymphoid cDNA library with a tyrosine kinase domain specific c-fms restriction fragment under low stringency hybridization conditions. We have now isolated and sequenced a full length tyk2 cDNA clone; demonstrated that this gene is widely expressed in hematopoietic and non-hematopoietic cell lines; and mapped it to chromosome 19p13.2. The cDNA clone is 4176 nucleotides long and codes for a putative protein with a molecular weight of 134 kilodaltons. Hydrophobicity analysis of our sequence does not identify a transmembrane domain, which is found in all members of the receptor class of protein tyrosine kinases; nor can we detect an SH2 domain, found in all previously identified non-receptor protein kinases. We therefore propose that tyk2 is the prototype of a new class of non-receptor protein tyrosine kinases.

Amino Acid Sequence↗

The CAREPLAN knowledge base. A prototype expert system for postpartum nursing care.

With the growth of scientific knowledge in the health care disciplines, it has become increasingly difficult for practicing health care professionals to store and manipulate the information required to make clinical decisions. Where the decision making process can be defined and validated, expert systems will be able to assist beginning professionals to learn appropriate patterns of decision making. This article discusses the rationale for utilization of expert systems in a nursing environment. A prototype expert system called CAREPLAN, developed for use in an obstetrical environment, was built using Personal Consultant Plus, a software tool based on the LISP language. The project demonstrates that it is feasible to develop and validate an expert system for a specialized clinical environment in a relatively short period of time in comparison to traditional development methods. Graphics were used to enhance textual information and to increase user appeal. Strategies for future implementation and evaluation are outlined.

Expert Systems↗

Interpreting office radiographs: a research-based curricular prototype for training family practice residents.

Radiographic film interpretation is one area of the family practice residency training curriculum that has been given little focused emphasis. Starting with a series of studies into the office practice of radiology by family physicians to define need, content, and interpretation skill level, and following a systematic curriculum design process, the authors developed a comprehensive curriculum for teaching office X-ray interpretation to family practice residents. The final curricular prototype consists of: 1) a complete set of curriculum objectives; 2) a written monograph; 3) a set of instructional X-rays; and 4) a set of evaluation films. This research-based curriculum development process may serve as a model for developing other educational components for family practice residency training.

Curriculum↗

[Presentation of the prototype of a fully implanted cochlear prosthesis].

Description of the prototype of a fully implanted cochlear implant demonstrating the feasibility of a prosthesis with no external component within the next few years. The battery is reloaded by means of electromagnetic induction, and the sound message is received by a subcutaneous microphone, which already has a satisfactory bandwitch and signal-to-noise ratio. This system can be generally applied to most types of permanent intracorporeal stimulation.

Cochlear Implants↗

Vitamin D-resistant rickets. A prototype of nutritional management of a genetic disorder.

The discovery of the vitamin D endocrine system has opened up many possibilities in our understanding of metabolic bone disease. Of particular importance is the fact that we can now manage certain genetic disorders resulting in vitamin D-resistant rickets or vitamin D-resistant hypocalcemia with the new active hormonal forms of vitamin D and with intelligent dietary management to provide for correction of the mineral difficulty. Thus, in the case of vitamin D dependency, replacement need only be with the missing hormone, 1,25-(OH)2D3. On the other hand, familial hypophosphatemia requires adjustment of the plasma phosphorus by frequent administration of oral phosphate and the adjustment of intestinal calcium absorption by 1,25-(OH)2D3. Renal failure patients require the adjustment of plasma phosphorus concentration and parathyroid hormone status, and the administration of the missing hormone 1,25-(OH)2D3. Hypoparathyroid patients require oral calcium plus 1,25-(OH)2D3, and premature infants require administration of the 1,25-(OH)2D3 because the immature kidneys and immature parathyroid glands fail to produce the required amount of this hormone. Other vitamin D-resistant rachitic conditions cannot be discussed here for lack of space and for lack of information. Undoubtedly, such patients as those having rickets secondary to renal tubular acidosis and rickets secondary to hepatic disorders will eventually come under effecti dietary and hormonal management. In this sense, the vitamin D endocrine system and vitamin D-resistant rickets can serve as a prototype of management of a genetic disorder by dietary means.

Calcium↗

[A proposed prototype for recording and analysis of mandibular movement: the Cinétic].

The investigation of means of recording mandibular movement has aroused the interest of a considerable number of researchers. Their own devices, increasingly ingenious, all display certain advantages and shortcomings. The need for a device more appropriate to the needs of day-to-day odontological use has been felt for some time. By giving a broad explanation of how it works, we have tried to assess the possibilities of the proposed prototype, the Cinetic. It measures movement of the dentalium in all three dimensions simultaneously. Since its reliability, when tested by a study concerning a sample of 40 patients, proved entirely satisfactory, a more sophisticated version was promptly devised. This latest Cinetic allows the ROZENCWEIG dyskinesia index, to be calculated, the FARRAR diagram to be drawn, and the mastication movements to be analysed by giving a visual display of the mandibular opening and closing trajectories, the speed diagram, the duration of the cycle, mandibular velocity and acceleration, and a breakdown of the cycles for each respective side. In order to be fully competitive, the Cinetic lacks the capacity to record and analyse condylar movement. Work on incorporating these features is currently at an experimental stage.

Dental Equipment↗

Liver system. III. Prototype to study its unstable equilibrium on human biopsy samples.

Autoisodiasostasis of the liver, i.e., its self-maintenance without change over the course of time, is characterized by a bistable equilibrium between two extreme phases called homopoiesis, during which the liver system repairs its worn structures and replicates its cells, and homeorhesis, during which it satisfies the body's needs. Albumin traffic through the hepatocyte, rendered visible by means of an immunohistological method, has been used as a prototype model to study the dynamics of autoisodiasostasis. An account is given of the oscillation of autoisodiasostasis between homopoiesis and homeorhesis through two intermediate phases. The phase cycle of autoisodiasostasis is illustrated in the form of atemporal bidimensional and tridimensional diagrams. The temporal behavior of the system is represented as a helix trajectory obtained by the projections of homopoiesis-homeorhesis phase cycle on time series.

Adult↗

A prototype articulator for planning orthognathic and craniofacial surgery.

Current techniques and hinge-type articulators do not provide sufficient information and versatility for the planning of orthognathic and craniofacial surgery. Dental articulators either require plaster of paris for mounting or they do not accommodate movement of both casts in all directions of space. A prototype articulator that satisfies movement of both casts in all directions of space is successfully being used as an adjunct in planning orthognathic and craniofacial surgery. There is a need for future development of sophisticated and accurate armamentarium that can be used as an aid in planning and designing surgical procedures.

Dental Articulators↗

ARAMIS (the American Rheumatism Association Medical Information System). A prototypical national chronic-disease data bank.

ARAMIS is a prototype of a national chronic-disease data-bank system consisting of parallel, longitudinal, clinical data sets from 17 diverse locations; the data describe the courses of thousands of patients with rheumatic disease followed over many years. Chronic-disease data-bank systems include the data themselves, protocols to ensure their quality, computer systems for their manipulation, statistical procedures for analysis and an appropriately skilled staff. Such a data resource facilitates analyzing long-term health outcomes and the factors associated with particular outcomes. Such systems are mandated by the overwhelming prevalence of chronic illness; the variability, complexity and uniqueness of a patient's course; the difficulties of traditional randomized approaches in these areas, and the time span required for studying these problems.

Humans↗

Debrisoquine/sparteine-type polymorphism of drug oxidation. Purification and characterization of two functionally different human liver cytochrome P-450 isozymes involved in impaired hydroxylation of the prototype substrate bufuralol.

The debrisoquine/sparteine-type polymorphism of drug oxidation presumably is caused by the absence or deficiency of cytochrome P-450 (P-450) isozyme(s). Using bufuralol 1'-hydroxylation as a prototype reaction of this polymorphism, two functionally distinct forms, P-450 buf I and P-450 buf II, with identical apparent Mr of 50,000 were purified from liver microsomes of three different human livers. P-450 buf I exhibited a marked selectivity for the (+)-enantiomer of bufuralol ((-)/(+) ratio = 0.15), P-450 buf II was nonstereoselective((-)/(+) ratio = 1.03). The Km values for (-)- and (+)-bufuralol were 31 and 54 microM with P-450 buf I and 314 and 245 microM with P-450 buf II. P-450 buf II generated two other metabolites in addition to 1'-OH-bufuralol which were not observed with P-450 buf I. Using the inhibitor quinidine, a Ki of 0.06 microM was observed with P-450 buf I as opposed to 80 microM with P-450 buf II for bufuralol 1'-hydroxylation. A strong immunochemical relatedness of P-450 buf I and P-450 buf II was found since polyclonal antibodies against either form recognized the heterologous antigen to the same extent as the homologous antigen on Western blots and in immunoinhibition and in immunoprecipitation experiments. Cross-reactivity of these antibodies with a microsomal nonheme protein of unknown function (apparent Mr 50,000) also was noted. Western blots of microsomes of in vivo and in vitro phenotyped extensive and poor metabolizer individuals revealed no correlation of in vivo-determined metabolic ratio, microsomal activity, and amount of immunoreactive material. Antibodies against P-450 buf I and P-450 buf II inhibited bufuralol 1'-hydroxylation in microsomes of in vivo and in vitro phenotyped poor metabolizer individuals demonstrating that the residual activities are immunochemically related to the activities in extensive metabolizers.

Cytochrome P-450 Enzyme System↗

Idiopathic adolescent scoliosis--a prototype of degenerative joint disease. The relation of biomechanic factors to osteophyte formation.

A study was performed to evaluate the presence of degenerative joint disease (DJD) in idiopathic adolescent scoliosis (IAS) and correlate DJD with biomechanic factors. The average age of the subjects was 19 years (range, 12-30). Osteophytes reflecting the presence of degenerative joint disease occurred in apophyseal and/or intervertebral joints of 74% of 100 subjects. Osteophytes were correlated with curve angle and apical rotation. Compression forces are of pathogenic significance in the localization of osteophytes in IAS. IAS can serve as a naturally occurring prototype for the study of the influence of biomechanic factors on the pathogenesis of DJD.

Adolescent↗

Asymmetric transfer of prototype information between vision and audition.

Specific and nonspecific transfer of pattern class concept information between vision and audition was examined. In Experiment 1, subjects learned visually or auditorily to distinguish between two pattern classes that were either the same as or different from the test classes. All subjects were then tested on the auditory classification of 50 patterns. Specific intramodal and cross-modal transfer was noted; subjects trained visually and auditorily on the test classes were equivalent in performance and more accurate than untrained controls. In Experiment 2, the training of Experiment 1 was repeated, but subjects were tested visually. There was no evidence of auditory-to-visual transfer but some suggestion of nonspecific transfer within the visual modality. The asymmetry of transfer is discussed in terms of the modality into which patterns are most likely translated for the cross-modal tasks and in terms of the quality of prototype formation with visual versus a,ditory patterns.

Auditory Perception↗

Evaluation of prototype equipment for digital subtraction angiography in diagnosing intracranial lesions.

Two prototype units for digital subtraction angiography have been developed by Japanese manufacturers. Their performance in demonstrating various intracranial lesions in 121 patients was evaluated. Comparison with conventional selective catheter angiography was possible in 77 patients. Digital subtraction angiography proved useful in preoperative evaluation of pituitary tumors when transsphenoidal surgery was being considered; demonstration of faint tumor stains which might be missed on conventional angiography; demonstration of larger aneurysms, arteriovenous malformations, and tumors as a screening technique; demonstration of abnormalities involving the dural sinuses; and follow-up of patients after surgery or embolization.

Brain Diseases↗

A prototype 'fifth pathway' program for Americans studying abroad.

A problem of American citizens studying medicine abroad is reviewed along with that of foreign medical graduates who are foreign nationals, and a prototype "fifth pathway" program is briefly described. The objective of the program is the return of qualified American students who study medicine abroad to the mainstream of contemporary American medical education and the preparation of these students for further graduate education and the fulfillment of responsible roles in the delivery of health care.

Clinical Competence↗

MR imaging of pituitary adenomas using a prototype resistive magnet: preliminary assessment.

Magnetic resonance (MR) images were obtained with a prototype resistive magnet system in 10 patients, all of whom had been shown to have pituitary tumors by enhanced high-resolution computed tomography (CT). Histologic verification was obtained in eight cases. Inversion-recovery (IR) T1-weighted images revealed the tumor in six of nine cases; saturation-recovery (SR) images with less T1 weighting identified seven of nine tumors; Carr-Purcell-Meiboom-Gill (CPMG) spin-echo T2-weighted images revealed two of four tumors. MR images failed to demonstrate three microadenomas: 5 X 5 X 8 mm, 6 X 6 X 6 mm, and one less than 5 mm in estimated size. In the last pretreatment study, CT had demonstrated a 13 mm maximum diameter adenoma. Repeat CT at the time of MR imaging also showed a partially empty sella and did not resolve the residual adenoma. The larger adenomas were identified readily by MR imaging, which, unlike CT, suggested old tumor hemorrhage in two cases, which was confirmed at surgery and histologic examination. MR and CT images were also compared for relative effectiveness in identifying important perisellar structures.

Adenoma↗