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PubMed2000

New prototype NIRS instrument [corrected] to investigate multi-regional cerebral blood and tissue oxygenation and haemodynamics.

Near infra-red spectroscopy (NIRS) is a non-invasive optical technique used to assess blood and tissue oxygenation and haemodynamics in living tissue. It is presently used as a semi-continuous monitoring technique on a research basis. Multi-regional NIRS information could be beneficial for a better understanding of the development of cerebral injuries and the reduction of neurodevelopmental abnormalities in the human newborn. The paper presents the conversion of the continuous wave NIRS single-channel instrument (NIRDCU) into a prototype four-channel instrument which can be used to provide continuous multi-regional information regarding the cerebral blood oxygenation and haemodynamics in the frontal, left parietal, right parietal and occipital region of the neonatal brain. This has been achieved by attaching an optical multiplexing system to the NIRDCU to select different transmitting and receiving fibres, thus addressing different regions in the brain. Preliminary laboratory tests on a phantom and on the adult forearm are presented, illustrating the practicality of regional monitoring.

Adult↗
PubMedDate not supplied

Improved LAboratory Prototype ELectrolarynx (LAPEL): using inverse filtering of the frequency response function of the human throat.

The electrolarynx (EL) provides a valued means of verbal communication for people who have lost their larynx. Existing ELs have some drawbacks such as harsh, raucous, and unpleasant sound and the presence of background noise. This study presents an experimental analysis of two commercial ELs and describes the development and testing of an improved LAboratory Prototype ELectrolarynx (LAPEL) which more accurately simulates the sound of a natural larynx and has lower background noise. This natural sound is obtained by determining the frequency response function (FRF) of the tissue of the human neck and using this information to tailor the input signal to the EL by inverse filtering such that its output spectrum resembles that of the natural larynx. The result was subjectively judged to have a superior and more natural sound than existing electrolarynxes.

Humans↗
PubMedDate not supplied

Evaluation of a prototype steerable angioscopic laser catheter in a canine model: a feasibility study.

To overcome some of the persisting technical problems related to laser angioplasty, a new catheter was designed and investigated in a canine model. This 5F catheter contained a deflectable tip for steerability, an angioscope, and a laser fiber. Catheter steerability, angioscopic function, and the effects of a 480 nm flash lamp pumped pulsed dye laser on normal canine vessel walls were evaluated. Steering, angioscopic guidance, and application of laser energy were easy and fast to perform in a bloodless vessel segment. Maintaining a condition of bloodlessness at the target site, critical to angioscopic guidance, proved to be the most difficult part in this prototype evaluation. It was noted that the 480 nm pulsed dye laser did not cause macroscopic alterations or perforations to the normal vessel wall. We conclude that a relatively simple deflection mechanism of a small-caliber angioscope provides the kind of aiming ability requisite for precise endovascular therapy. Complete bloodlessness of the area is necessary for both viewing and laser ablation at 480 nm.

Angioplasty, Balloon, Laser-Assisted↗
PubMed2002

Beta-thalassaemia prototype of a single gene disorder with multiple phenotypes.

As the defective genes for more and more genetic disorders become unravelled, it is clear that patients with the same genotype can have many different clinical conditions even in monogenic disorders. The remarkable phenotypic diversity of the beta thalassaemias is prototypical of how the wide spectrum in disease severity can be generated. The most reliable and predictive factor of disease phenotype is the nature of the mutation at the beta-globin locus itself. However, relating phenotype to genotype is complicated by the complex interaction of the environment and other genetic factors at the secondary and tertiary levels, some implicated, and others, as yet unidentified. This article reviews the clinical and haematological diversity encountered in beta thalassaemia and their relationship with the underlying genotypes.

Alleles↗
PubMed1989

Digital image display station performance requirements based on physician experience with a prototype system.

The authors report on observations of and interviews with physicians using a prototype digital image display and reporting station. While the users generally agree that image quality is clinically satisfactory, they are unanimous in their opinion that improvements in the man-machine interface are required before case review by this mechanism is clinically acceptable in a production environment. A model image and information user interface is presented. It was developed in answer to the needs of radiologists and referring physicians operating in the imaging department of a community acute-care facility. In such an environment images and related information must be communicated quickly and often simultaneously to different parts of the department and hospital. The user interface with the management system and the management system itself must address the varied functions and the needs of both the medical and clerical staff. Image enhancement processes, for example, must be restricted to those that quickly provide significantly more perceivable diagnostic information. Little-used processes that may occupy significant portions of the display and the console's computing power must be trimmed or eliminated.

Computer Systems↗
PubMed1995

Opinion: a prototype for a computerized national mammography registry and tracking system using telecommunications and the Internet.

In this report, we analyze the feasability and discuss the potential benefits of using currently available technology for the wide-area registration and tracking of mammography patients. In our prototype, three dissimilar computer systems transmitted mammographic data (demographics and the results of mammograms) in a standardized format to a central data repository. Two of the three systems were dedicated computerized mammography systems and one was a general-purpose radiology information system. High-speed modems and the Internet were used to connect with the central repository, which could be queried in real time by remote users. Our results indicated that a busy mammography practice, using the slowest transmission method we tested (14-kilobaud modem), could transmit several days of mammographic data to a central repository in a matter of minutes. To implement systems that provide nation-wide mammographic tracking and follow up, more in-depth planning, development, and testing are necessary.

Computer Communication Networks↗
PubMed1991

A prototype of a high-resolution computerized radiology teaching file.

Computers provide an excellent tool for handling the task of organizing a radiology teaching file. Currently available computerized teaching files are either film-based, slide-based, or use laser-disc video technology for image display. There are obvious advantages to having the management of radiologic images under the control of a computer, and the need for a higher resolution alternative to video laser-disc technology becomes apparent when one tries to computerize a chest radiology teaching file. We describe the prototype of such a system, named MIRTLE, (the Mallinckrodt Institute of Radiology Teaching and Learning Environment) which was designed to integrate text under the control of a custom data base with high-resolution digital images from a Picture Archiving and Communications System. This system with its easy-to-use windows environment should allow a significant increase in the use of the radiology teaching file.

Computer Systems↗
PubMed2002

Gaucher disease: Perspectives on a prototype lysosomal disease.

Gaucher disease is an autosomal recessive trait and the most common lysosomal storage disease. The pathogenesis evolves from the diminished activity of the lysosomal hydrolase, acid beta-glucosidase and the resultant accumulation of glucosylceramide within lysosomes. The pathogenic mechanisms are poorly understood. During the past 2 decades, progress has been made in understanding the biochemical basis and molecular biology of the disease, but more fundamental knowledge is required to relate these advances to the cell and whole body phenotypes. Despite this lack of understanding, enzyme replacement therapy has proved a successful and effective management for Gaucher disease. However, basic details of this therapeutic efficacy require elucidation. Here, we review the current state of the molecular pathogenesis and provide our perspective of some major issues for continued advances in this prototype lysosomal storage disease.

Animals↗
PubMed1999

The fibroblast intermediate conductance K(Ca) channel, FIK, as a prototype for the cell growth regulatory function of the IK channel family.

The fibroblast intermediate conductance, calcium-activated potassium channel (FIK) is proposed here as a functional prototype for other IK channels which to date have undefined physiologic actions. FIK pharmacology in the 10T1/2-MRF4 myogenic fibroblast cell line was determined: to define the relationship of FIK to other IKs; to confirm a physiologic role for FIK; and, thus develop a hypothesis about IK channel family function. Whole cell patch-clamp electrophysiology was used to determine K(0.5) values for FIK block by the structurally related peptides charybdotoxin (ChTX) (7 nm) and iberiotoxin (IbTX) (536 nm), and a new unrelated FIK inhibitor, Stichodactyla toxin (StK) (85 nm). Peptide pharmacology for FIK was consistent with that of recently cloned IKs. ChTX and StK inhibited bFGF stimulated 10T1/2-MRF4 cell proliferation with dose-dependencies consistent with their FIK blocking actions. ChTX, StK, and IbTX also evoked MRF4-dependent transcription as measured by muscle acetylcholine receptor channel functional expression; but they did not evoke subsequent multinucleated fiber formation or myosin heavy chain expression, suggesting a role for FIK in early, rather than late, myogenic events. Thus despite structural differences, ChTX, IbTX, and StK have common effects on cell growth and differentiation reflecting their common FIK blocking action. We suggest that a major function of the IK channel family is to regulate cell growth.

Animals↗
PubMed2003

Prediction of the prototype of the human Toll-like receptor gene family from the pufferfish, Fugu rubripes, genome.

The insect Toll family of proteins and their mammalian counterparts seemingly shared one common ancestor and evolved independently. Here we demonstrated that the prototype of the mammalian-type (M-type) Toll family is shared by the fish and humans. According to the draft of the pufferfish Fugu genome project, the signature Toll-IL-1 receptor homology domain (TIR domain) has been conserved during evolution. FuguTLR2, 3, 5, 7, 8 and 9 members correspond structurally to respective mammalian TLRs. One Fugu TLR showed equally high amino acid identity to human TLR1, 6 and 10, and we named it FuguTLR1. Fugu rubripes has genes for TLR21 and 22, which are unique to fish. One possible interpretation of these findings is that TLR1, 2, 3, 4, 5, 7, 8, 9, 21 and 22 existed in the ancestral genome common to fish and mammals, and that TLR4 was lost in the fish lineage, while TLR21 and 22 were lost in the mammalian lineage. Strikingly, a solitary ascidian, Halocynthia roretzi, has only a few Toll-like proteins, which, like Caenorhabditis elegans Toll, represent primitive ones before the expansion of the Toll family. Therefore, the expansion of TLR genes should have occurred earlier than fish, but not C. intestinalis, separated evolutionarily from mammals. These results infer that the appearance of the M-type innate system was completed before or concomitant with the appearance of acquired immunity. We interpret the present data to mean that the differences of TLRs identified in this study between fishes and humans may be rather peripheral, partially due to selection pressure exerted by pathogens in distinct environments.

Amino Acid Sequence↗
PubMed1999

A new goat adenovirus isolate proposed as the prototype strain for goat adenovirus serotype 1.

A virus isolated from the brain of a 3-year-old goat with encephalitis was identified as an adenovirus based on morphological and physicochemical characteristics. Neutralization tests and restriction endonuclease analysis comparing the caprine adenovirus with the prototype ovine and bovine adenovirus serotypes indicated that the caprine isolate was antigenically different and produced a unique restriction pattern and may represent a new adenovirus species. A limited seroepidemiologic study using adult goat and sheep sera collected from around the Unites States indicated that approximately 60 and 80 percent, respectively, had specific antibody for this isolate.

Adenoviridae↗
PubMed2003

Experimental autoimmune encephalomyelitis: cytokines, effector T cells, and antigen-presenting cells in a prototypical Th1-mediated autoimmune disease.

Experimental autoimmune encephalomyelitis (EAE) is widely depicted as the prototypical CD4+ Th1-mediated autoimmune disease. Microglia and perivascular macrophages are believed to act as antigen-presenting cells during the effector phase of EAE. In this article, recent data that challenge these conceptions are reviewed. Several recent studies have shown that myelin-reactive CD8+ T cells can mediate inflammatory demyelination. Furthermore, dendritic-like cells have been detected in EAE lesions and implicated in encephalitogenic T-cell activation. Although Th1 polarizing monokines, such as interleukin-12 (IL-12) and possibly IL-23, are critical for the manifestation of EAE, individual Th1 effector cytokines were found to be dispensible.

Animals↗
PubMed1980

Evaluation of ischemic heart disease with a prototype volume imaging computed tomographic (CT) scanner: preliminary experiments.

A prototype synchronous volumetric computed tomographic X-ray scanner was used to demonstrate, in individual experiments, the possibility of estimating percent coronary arterial stenosis, regional myocardial blood supply and regional myocardial wall dynamics. Scans were obtained during angiography in intact anesthetized dogs or in an isolated metabolically supported working left ventricular preparation. Percent arterial stenosis was quantitated using the percent change in brightness area product of successive cross-sectional images of contrast agent-filled Tygon tubing sutured to the epicardium. Myocardial blood supply was evaluated by the transmural and circumferential extent and th time rate of change of myocardial opacification during coronary angiography. The regional time rate of change of left ventricular wall thickening during the systolic phase of the cardiac cycle was demonstrated in the isolated ventricle preparation. The recently installed Dynamic Spatial Reconstructor high speed volumetric scanning system will be used to make these measurements from scan data obtained during a single angiogram in man.

Animals↗
PubMed1984

Polymyositis and interstitial lung disease in a patient with anti-Jo1 prototype.

The most common marker autoantibody among patients with polymyositis is anti-Jo1. The patient (John P.) providing the prototype serum for this specificity had both interstitial lung disease and polymyositis. A preliminary survey by Ouchterlony analysis and counter immunoelectrophoresis of serum from 15 patients with idiopathic interstitial lung disease revealed no anti-Jo1 or other precipitating autoantibodies. This provides no evidence to suggest that anti-Jo1 has specificity for interstitial lung disease per se. However, this autoantibody may serve as a possible marker for some patients with overlap of polymyositis and interstitial lung disease. The several interesting features about this patient's diseases and course are discussed.

Antibody Specificity↗
PubMed1989

Stopped-flow front-face fluorometer: a prototype design to measure hemoglobin R----T transition kinetics.

Stopped-flow techniques are successfully used to study the kinetics of the R----T transition of hemoglobin (Hb). We have previously used front-face fluorometry to demonstrate that (i) the intrinsic fluorescence of Hb primarily originates from beta 37 Trp; (ii) the intrinsic fluorescence is sensitive to the R----T transition; and (iii) the emission of the fluorescent probes bound to specific sites on the Hb molecule (beta 93 Cys) is sensitive to the R----T transition. These findings suggested that a stopped-flow front-face fluorometer could probe R----T transitions at specific sites, such as the aromatic amino acids and sites selectively binding extrinsic fluorophores. We have developed a prototype instrument using as the core a Gibson-Durrum stopped-flow apparatus on line with a digital data analysis system using a modified Marquardt algorithm. Excitation (470 nm) and emission light (520 nm) were selected by narrow band pass filters. To study the R----T transition, a solution of purified oxy Hb A covalently bound to the fluorescent probe 5-iodoacetamidofluorescein (Hb A-AF) (1.0 g%) was mixed rapidly with deoxygenated buffer (pH 7.35, 0.05 M potassium phosphate) containing 2 mg/ml of sodium dithionite. The hemoglobin, at a final concentration of 0.5 g% after mixing, is essentially completely tetrameric. A first-order reaction was observed with a rate constant near 8 s-1, similar to the oxygen dissociation rate reported for oxy Hb A.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMedDate not supplied

Comparative chemical and biological studies of four prototype phosphoraziridine antineoplastic agents.

The chemical alkylating activities of four prototype phosphoraziridine antineoplastic agents were compared with their biological effects on V-79 Chinese hamster lung fibroblasts. It was found that the chemical reactivity patterns correlate well with all of the biological parameters examined in this study, i.e. cytotoxicity, DNA synthesis, and production of alkali labile strand breaks. Specifically, the 2,2-dimethylaziridine derivatives (AB-132 and AB-163) showed higher initial activities reaching a plateau after a short reaction time in all of the systems used in this study while the unsubstituted aziridine derivatives (AB-100 and D-63) reacted more slowly but continued to exert their action in a linear fashion to produce greater overall effects. These findings are consistent with the conclusion that the difference between the time-dependent biological activities of these drugs closely follows the different chemical mechanisms of their alkylating reactions (SN1 vs SN2). The more rapid action and subsequent hydrolytic inactivation of the 2,2-dimethylphosphoraziridines as effective alkylators could be the basis of their lower hemopoietic toxicity compared to conventional alkylating agents including their own C-unsubstituted aziridine analogs. The much more rapid action of the 2,2-dimethylphosphoraziridines on DNA inside the cell may have some bearing on their radiation potentiating activity, but this aspect and the cholinesterase inhibitory activity of these agents (which may depend on phosphorylation) were not investigated in the present study.

Alkylating Agents↗
PubMed1975

A prototype segmental model for blood flow and heat transfer in the limb.

A general modeling technique for characterizing the blood flow and heat tranfer properties in the human limb is reported in this paper. The basic idea is to take the segmental approach so that a lumped model for each segment can be constructed. Consequently, a prototype segmental computer model is proposed which describes, in general terms, the interrelationships between the circulatory system and the thermal system of the limb. Simulation study of digital response to hand cooling is made and the results agree very well with the experimental data.

Body Temperature Regulation↗