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PubMed2004

Latest techniques in head and neck CT angiography.

Continuous evolution of multi row CT is increasingly making CT angiography a viable imaging modality for assessment of the supraaortic and intracranial vessels as an anatomically and functionally coherent vascular system. Extended non-invasive examinations with reduced contrast volume have become feasible with the availability of 16 and 64 row MDCT scanners. Prerequisites to obtain high resolution CT angiographies of the head and neck vessels with superior detail include the administration of low contrast volume, high contrast density (400 mg I/ml) contrast media, adequate timing and data acquisition, optimal flow rate (4 ml/s) and saline flushing. Non-invasiveness, delineation of vessel calcification, virtual independence from hemodynamic conditions, and the ability to provide quantification without needing to correct for magnification are all attributes that favour CT angiography over digital subtraction angiography and to some extent even magnetic resonance angiography as an alternative non-invasive technique. CT angiography is established as a modality of choice for the assessment of patients with acute stroke and chronic steno-occlusive disease. CT angiography may indicate the presence of extra- or intracranial acute vessel occlusion and dissection, predisposing atherosclerotic steno-occlusive disease and thus indicate thrombo-embolism or local appositional thrombosis as the principle pathogenic factor. CT angiography is used to assess anatomy, and to depict the presence, location and extent of calcified and non-calcified plaque as a cause of high grade stenosis. Despite relatively limited sensitivity CT angiography is indicated for suspected or confirmed aneurysms that demand further verification of their presence, geometry, or relationship to parent artery branches and osseous anatomic landmarks. Low volume high density contrast media have substantially increased the ability of CT angiography to depict small aneurysms, small branches, and collateral vessels, and to recognize the residual lumen in vessels with high grade stenosis or conditions such as dissection or pseudo-occlusion. Superior detail high resolution CT angiography is thus a viable alternative to DSA, relegating the latter technique to endovascular treatment applications only.

Angiography↗
PubMed1994

Transcatheter arterial embolization with or without cisplatin treatment of hepatocellular carcinoma. A randomized controlled study.

BACKGROUND: This randomized controlled study was objectively designed to evaluate the utility cisplatin (50 mg) in transcatheter arterial embolization (TAE) for treatment of hepatocellular carcinoma (HCC). METHODS: From May 1991 to July 1993, 46 patients were included in the study. All had a pathologic verification of HCC. Clinically, all of the patients were considered inoperable. However, these patients satisfied eligibility criteria for TAE. The patients were divided into two groups by random sampling. In group I, 22 patients received TAE with the regimen of cisplatin (50 mg) mixed with Lipiodol 5-15 ml followed by gelfoam pieces. In group II, 24 patients, as a controlled group, used the regimen of Lipiodol and gelfoam (Spongostan Film, Ferrosan, Denmark) pieces only, without adding any anticancer drug. The two groups were evaluated by a series of imaging studies and various clinical examinations before and after TAE. Subsequently, TAE was performed every 2 or 3 months for all patients until there was no visible tumor, or the patient could not sustain further TAE, or the patient died. RESULTS: In group I, TAE was administered 61 times (average 28 times for each patient), and in group II, 73 times (average 3 times for each patient). The 1-year and 2-year survival rates of group I were 52.5% and 26.2%, and group II were 72.5% and 39.5%. Statistically, there was no significant difference in survival curves and survival rates between these two groups. Tumor response rate of group I was 68% (15/22) and group II was 67% (16/24). There was no significant difference in tumor response between these two groups. The liver and renal function studies after TAE also showed no significant difference between these two groups. CONCLUSIONS: Based on this controlled study, the authors conclude that the addition of cisplatin does not enhance the therapeutic effect of TAE for treatment of HCC.

Adult↗
PubMed1997

Atmospheric leakage and method for measurement of gas exchange rates of a crop stand at reduced pressure.

The variable pressure growth chamber (VPGC) was used in a 34-day functional test to grow a wheat crop using reduced pressure (70 kPa) episodes totalling 131 hours. Primary goals of the test were to verify facility and subsystem performance at 70 kPa and to determine responses of a wheat stand to reduced pressure and modified partial pressures of carbon dioxide and oxygen. Operation and maintenance of the chamber at 70 kpa involved continuous evacuation of the chamber atmosphere, leading to CO2 influx and efflux. A model for calculating CO2-exchange rates (net photosynthesis and dark respiration) was developed and tested and involved measurements of chamber leakage to determine appropriate corrections. Measurement of chamber leakage was based on the rate of pressure change over a small pressure increment (70.3 to 72.3 kPa) with the pump disabled. Leakage values were used to correct decreases and increases in chamber CO2 concentration resulting from net photosynthesis (Ps) and dark respiration (DR), respectively. Composite leakage corrections (influx and efflux) at day 7 of the test were 9% and 19% of the changes measured for Ps and DR, respectively. On day 33, composite corrections were only 3% for Ps and 4% for DR. During the test, the chamber became progressively tighter; the leak rate at 70.3 kPa decreasing from 2.36 chamber volumes/day pretest, to 1.71 volumes/day at the beginning of the test, and 1.16 volumes/day at the end of the test. Verification of the short-term leakage tests (rate of pressure rise) were made by testing CO2 leakage with the vacuum pump enabled and disabled. Results demonstrate the suitability of the VPGC or conducting gas exhange measurements of a crop stand at reduced pressure.

Air Conditioning↗
PubMed1986

The significance of recurrent childhood respiratory disorders in flight training applicants.

A random sample of 1700 18-year-old applicants for flight training, who had been free from respiratory symptoms for 1 year or more, was screened for respiratory symptoms in the past. Those who denied such a history had a questionnaire sent to their parents for further verification. Altogether 70 subjects with a past history of "wheezing," "asthma," or "spastic bronchitis" were thus identified. Abnormalities in either FEV1/FVC, Vmax50 or Vmax75 were found in 40% of the subjects with a history of childhood "wheezing," "asthma," or "spastic bronchitis," but only in 8% of controls without such a history. A history of wheezing had no effect on the RV/TLC ratio. The age at which the last bout had occurred had no apparent effect on the degree of flow abnormalities. The most sensitive index for a flow abnormality was Vmax50, which was less than 74% of the predicted values in 2/(30%) of the 70 subjects tested. It is concluded that, in subjects with a history of "wheezing," "asthma," or "spastic bronchitis," flow abnormalities may persist even after prolonged remissions.

Adolescent↗
PubMed2003

Dietary fructo-oligosaccharides dose-dependently increase translocation of salmonella in rats.

Prebiotics, such as fructo-oligosaccharides (FOS), stimulate the protective gut microflora, resulting in an increased production of organic acids. This may result in increased luminal killing of acid-sensitive pathogens. However, host defense against invasive pathogens, like salmonella, also depends on the barrier function of the intestinal mucosa. Rapid fermentation of prebiotics leading to high concentrations of organic acids may impair the barrier function. Therefore, we determined the dose-dependent effect of dietary FOS on the resistance of rats to Salmonella enteritidis. Male Wistar rats were fed restricted quantities of a "humanized" purified diet supplemented with 0, 3 or 6 g/100 g of FOS (n = 7 in the 6% FOS group and n = 8 in the other diet groups). After an adaptation period of 2 wk, rats were orally infected with 1.7 x 10(10) colony-forming units of S. enteritidis. Supplement-induced changes in the intestinal microflora and fecal cation excretion were determined before and after infection. Cytotoxicity of fecal water was determined with an in vitro bioassay, and fecal mucins were quantified fluorimetrically. Colonization of S. enteritidis was determined by quantification of salmonella in cecal contents and mucosa. Translocation of S. enteritidis was quantified by analysis of urinary nitric oxide metabolites in time. Before infection, FOS decreased cecal and fecal pH, increased fecal lactic acid concentration and increased bifidobacteria and enterobacteria. FOS also increased cytotoxicity of fecal water and fecal mucin excretion, indicating mucosal irritation. Remarkably, FOS dose-dependently increased salmonella numbers in cecal contents and mucosa and caused a major increase in infection-induced diarrhea. In addition, FOS enhanced translocation of salmonella. Thus, in contrast to most expectations, FOS dose-dependently impairs the resistance to salmonella infection in rats. These results await verification by other controlled animal and human studies.

Animals↗
PubMed2002

Haplotypes of two variants in p16 (CDKN2/MTS-1/INK4a) exon 3 and risk of squamous cell carcinoma of the head and neck: a case-control study.

The frequent loss or promoter methylation of the tumor suppressor gene p16 in head and neck cancer suggests an etiologic role of p16 in this disease. Two adjacent polymorphisms of p16 exon 3, C540G and C580T, were identified recently. C540G is associated with low expression of p53, and both polymorphisms are associated with tumor aggressiveness, suggesting a possible functional relevance. We hypothesized that these two polymorphisms, particularly their haplotypes, are associated with the risk of developing squamous cell carcinoma of the head and neck (SCCHN). To test this hypothesis, we conducted a hospital-based case-control study of 208 patients with SCCHN and 224 cancer-free control subjects to evaluate the association between p16 genotypes/haplotypes and the risk of SCCHN, using a PCR-single strand conformation polymorphism-based genotyping assay. However, our results suggested that no significant differences exist in the distribution of p16 C540G and C580T genotypes between cases and controls. For the C540G polymorphism, the CC, CG, and GG genotype frequencies were 76.9%, 22.1%, and 1.0%, respectively, in the cases, compared with 76.8%, 21.9%, and 1.3%, respectively, for the controls. For the C580T polymorphism, the CC, CT, and TT genotype frequencies were 83.6%, 15.9%, and 0.5%, respectively, in the cases, compared with 82.6%, 16.5%, and 0.9%, respectively, for the controls. The frequencies of three predominant 540C/580C, 540G/580C, and 540C/580T haplotype alleles were distributed similarly in the cases (79.6%, 12.0%, and 8.4%) and in the controls (78.6%, 12.3%, and 9.1%). None of these differences were statistically significant. We conclude that these polymorphic p16 genotypes or haplotypes may not play a major role in the etiology of SCCHN, if any. However, our limited sample size and power call for larger studies for additional verification of our findings.

Aged↗
PubMed2004

Bridging the gap between structural bioinformatics and receptor research: the membrane-embedded, ligand-gated, P2X glycoprotein receptor.

MOTIVATION: No details on P2X receptor architecture had been known at the atomic resolution level. Using comparative homology-based molecular modelling and threading, it was attempted to predict the three-dimensional structure of P2X receptors. This prediction could not be carried out, however, because important properties of the P2X family differ considerably from that of the potential template proteins. This paper reviews an alternative approach consisting of three research fields: bioinformatics, structural modelling, and a variety of the results of biological experiments. MODEL: Starting point is the amino acid sequence. Using the sequential data, the first step is a secondary structure prediction. The resulting secondary structure is converted into a three-dimensional geometry. Then, the secondary and tertiary structures are optimized by using the quantum chemistry RHF/3-21G minimal basic set and the all-atom molecular mechanics AMBER96 force field. The fold of the membrane-embedded protein is simulated by a suitable dielectricum. The structure is refined using a conjugate gradient minimizer (Fletcher-Reeves modification of the Polak-Ribiere method). The results of the geometry optimization were checked by a Ramanchandran plot, rotamer analysis, all-atom contact dots, and the C(beta) deviation. As additional tools for the model building, multiple alignment analysis and comparative sequence-function analysis were used. The approach is exemplified on the membrane-embedded, ligand-gated P2X3 receptor subunit, a monovalent-bivalent cation channel-forming glycoprotein that is activated by extracellular adenosine 5'-triphosphate. From these results, a topology of the pore-forming motif of the P2X3 receptor subunit was proposed. It is believed that a fully functional P2X channel requires a precise coupling between (i) two distinct peptide modules, an extracellularly occurring ATP-binding module and a pore module that includes a long transmembrane and short intracellular part, (ii) an interaction surface with membranes, and (iii) hydrogen bonding forces of the residues and hydrated cations. Furthermore, this paper demonstrates the role of quantitative structure-activity relationships (QSARs) in P2X research (calcium ion permeability of the wild-type and after site-directed mutagenesis of the rat P2X2 receptor protein, KN-62 analogs as competitive antagonists of the human P2X7 receptor). EXPERIMENTAL PROOFS: The predictions are experimentally testable and may provide an additional interpretation of experimental observations published in literature. In particular, there is the good agreement of the geometry optimized P2X3 structure with experimentally proposed P2X receptor models obtained by neurophysiological, biochemical, pharmacological, and mutation experiments. Although the rat P2X3 receptor subunit is more complex (397 amino acids) than the KcsA protein (160 amino acids), the overall folds of the peptide backbone atoms are similar. LIMITATIONS: To avoid semantic confusion, it should be noted that "prediction" is defined in a probabilistic sense. Matches to generic rules do not mean "this is true" but rather "this might be true". Only biological and chemical knowledge can determine whether or not these predictions are meaningful. Thus, the results from the computational tools are probabilistic predictions and subject to further experimental verification. AVAILABILITY: The geometry optimized P2X3 receptor subunit is freely available for academic researchers on e-mail request (PDB format).

Amino Acid Sequence↗
PubMed1994

The effects of intrahippocampal raphe and/or septal grafts in rats with fimbria-fornix lesions depend on the origin of the grafted tissue and the behavioural task used.

Long-Evans female rats sustained electrolytic lesions of the fimbria and the dorsal fornix and, two weeks later, received intrahippocampal suspension grafts of fetal tissue. The grafts were prepared from regions including either the medial septum and the diagonal band of Broca (septal grafts), or the mesencephalic raphe (raphe grafts), or from both these regions together (co-grafts). All rats were submitted to a series of behavioural tests (home cage and open-field locomotion, spontaneous alternation, radial-arm maze and Morris water maze performance) run over two periods after grafting (one to nine weeks and 20-35 weeks). Two weeks after completion of behavioural testing, histological (acetylcholinesterase and Cresyl Violet staining) and/or neurochemical (choline acetyltransferase activity, high-affinity synaptosomal uptake of choline and serotonin, noradrenaline, serotonin and 5-hydroxyindolacetic acid concentrations) verifications were performed on the hippocampus. Compared to sham-operated rats, lesion-only rats exhibited hyperactivity which was transient in a familiar environment (home cage) and lasting in an unfamiliar one (open field), decreased rates of spontaneous T-maze alternation, and impaired memory performance in both the radial-arm maze and the Morris water maze. These rats also showed decreased cholinergic and serotonergic markers with a maximal depletion in the septal two-thirds of the hippocampus. Noradrenaline concentration tended to be increased in the dorsal third of the hippocampus, but was not modified in the other two-thirds. While septal grafts specifically increased the cholinergic markers and raphe grafts the serotonergic ones, neither of these grafts produced a lasting effect on any behavioural variable. Conversely, the co-grafts, which increased both the cholinergic and serotonergic markers in the septal two-thirds of the hippocampus, completely normalized the Morris water maze probe trial performance, but failed to affect any of the other behavioural variables. Our present results confirm that grafts of fetal neurons injected into the denervated hippocampus may induce a neurochemical recovery that depends on the anatomical origin of the grafted cells, and that co-grafting two fetal brain regions allows the combination of their individual neurochemical properties. Furthermore, our results show that these neurochemical effects of the co-grafts may be involved in the recovery of behavioural function observed in the water maze. However, somewhat paradoxically, those effects appear inefficient for inducing any recovery in other behavioural tasks, even in the radial-arm maze; which is assumed to measure similar spatial functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

A C-terminal peptide of bovine rhodopsin binds to the transducin alpha-subunit and facilitates its activation.

In order to investigate the possible roles of the intracellular domains of rhodopsin in the functional coupling of the photoreceptor to transducin, different peptides that correspond to parts of the known sequence of rhodopsin were synthesized. Since we have found tht the binding of rhodopsin to the alpha subunit of transducin (alpha T) increases the susceptibility of alpha T to phosphorylation by protein kinase C-beta 1, we used this phosphorylation reaction as an initial screen for peptides that mimic the actions of rhodopsin. The results of this screen indicated that a peptide from the C-terminal tail of rhodopsin (amino acids 325-338; KNPLGDDEASTTVS-amide; designated as peptide 3) was capable of interacting with the alpha T subunit. Evidence that peptide 3 binds to alpha T at a site that overlaps the rhodopsin-binding domain was obtained from experiments showing that peptide 3 inhibited the rhodopsin-stimulated GTPase activity of alpha T and that this inhibition was overcome at high levels of rhodopsin. A potentially important outcome of the peptide 3/alpha T interaction is the facilitation of the activation of the alpha T subunit. This was first demonstrated in fluorescence experiments where the binding of peptide 3 was shown to strongly promote the enhancement of the tryptophane emission of alpha T that is elicited by the addition of NaF. Specifically, the EC50 for NaF was shifted from approximately 4 mM in the absence of peptide 3 to below 0.5 mM in the presence of peptide 3. Further verification that peptide 3 facilitated the ability of NaF to activate the alpha T subunit was obtained from experiments measuring the alpha T GDP/NaF-stimulated hydrolysis of cyclic GMP by the cyclic GMP phosphodiesterase.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

[The use of neuroendoscopy in the treatment of intraventricular and paraventricular brain tumors].

BACKGROUND AND PURPOSE: Because of their deep location, intra- and para- ventricular brain tumors pose an important therapeutic issue. Technical difficulties during the operation often result from the alteration of anatomy produced by the tumor, which brings about the risk of injury to functionally important structures. The authors assess clinical usefulness of neuroendoscopy in the treatment of discussed tumors. MATERIAL AND METHODS: Medical records of 16 adult patients treated between 2000 and 2003 were analyzed. The diagnosis was based on CT with 3D reconstruction and MRI. In 7 cases the tumor was located in the third ventricle, in 4--in lateral ventricles, in 5--paraventricularly. Surgery was performed using a rigid neuroendoscope and/or neurofiberscope equipped with the basic set of endoscopic instruments. The efficacy of the procedure was evaluated by clinical, CT and MRI follow-up examinations. The intended and achieved aim of the operation as well as the remote outcome were analyzed. RESULTS: The planned aim of the procedure was achieved in 12 (75%) patients. In 3 cases the tumor was removed totally, in 5--tumor mass was reduced restoring the cerebro-spinal fluid passage, in 4--tumor biopsy was performed. In 4 patients different obstacles made it impossible to achieve the intended aim of the procedure. 1 patient died in the direct postoperative course. In the long-term postoperative follow-up ranging from 8 to 44 months (median: 23 months), the clinical condition improved or was stable in 10 patients, 2 patients were reoperated, 2 became dependent and 1 was lost for follow-up. CONCLUSIONS: Neuroendoscopy offers new options in the treatment of intraventricular and paraventricular brain tumors allowing for their removal, reduction, histopathological verification and restoration of the cerebrospinal fluid passage. The outcome is good with a low complication rate.

Adult↗
PubMed1983

The regulation of acetylcholine receptor expression in mammalian muscle.

The synthesis of functional AChRs can be described as a pathway leading from the translation of subunit mRNAs to the plasma membrane forms of extrajunctional and junctional receptors (Fig. 9). We have not included in this scheme pretranslational steps for the synthesis and processing of RNA coding for receptor subunits because very little is known about such processes. Several aspects of Figure 9 are worthy of note: It is now well established that polypeptide synthesis is initiated on free cytoplasmic polysomes and that once sufficient nascent subunits bearing signal peptides at the amino terminus is formed, polysomes assemble with the membranes of the rough endoplasmic reticulum via a mechanism that employs the signal recognition particle (Anderson et al. 1982). Nascent subunits undergo cotranslational insertion through the rough endoplasmic reticulum membrane, signal peptide removal, and core glycosylation (Anderson and Blobel 1981; Merlie et al. 1981; Anderson et al. 1982; Sebbane et al. 1983). Anderson and Blobel (this volume) have demonstrated that subunits synthesized in vitro and inserted into membrane vesicles do not undergo heterologous subunit-subunit associations. We have shown that alpha- and beta-subunits newly synthesized in vivo are not associated with each other. Our data indicate that the alpha-subunit is initially present in vivo in a conformation that is radically different from its native conformation in the mature receptor complex. We assume that beta-, gamma-, and delta-subunits also are synthesized as conformationally "immature" forms, but verification of this point must await the availability of new monoclonal antibody specificities. Our data indicate that only a fraction of the newly synthesized alpha-subunit undergoes conformational maturation to the 5S species which binds both alpha-bungarotoxin and anti-main immunogenic region monoclonal antibodies. alpha-Subunits synthesized during a 5-minute pulse labeling require 30 minutes for completion of this process. alpha-Subunits that do not undergo conformational maturation are degraded rapidly (t1/2 = 0.5 hr) ( Merlie et al. 1982). Assembly of alpha- and beta-subunits synthesized during a 5-minute pulse labeling lags for approximately 30 minutes and is not complete until 90 minutes. Finally, assembled receptors are transported to the surface and appear in the plasma membrane. These processes occur during expression of AChRs in differentiated myoblasts. We do not know how undifferentiated myogenic cells, in vivo or in tissue culture, differ with regard to any of these steps.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

A PCR-SSP method to specifically select HLA-A*0201 individuals for immunotherapeutic studies.

HLA-A*0201 is an important restriction element for peptide presentation to T cells in disease and cancer. Mutation studies and analyses using cytotoxic T lymphocytes have shown the functional relevance of subtype-specific differences in HLA-A2 molecules for peptide binding and T-cell receptor recognition. Therefore, many immunotherapeutic studies need to accurately select HLA-A*0201-positive individuals. We designed an easy, robust approach based on the polymerase chain reaction using sequence-specific primers (PCR-SSP) to specifically distinguish A*0201-positive individuals from other HLA-A2 subtypes described to date. The first step includes reactions that give information whether the sample donor is HLA-A2 and, if so, whether the individual is homozygous or heterozygous for HLA-A2. Further, it is determined whether the sample has an HLA-A*0209 or an HLA-A*0201 sequence at the corresponding position in exon 4. Samples that may contain an HLA-A*0201 allele according to the results of this first step are subtyped in a second step nested PCR. Here the strategy is focussed on the discrimination of HLA-A*0201 from the other subtypes by considering divergent nucleotide positions in two ways. One SSP combination amplifies the HLA-A*0201 sequence while a corresponding SSP combination specifically amplifies the subtype or group of subtypes differing from HLA-A*0201 at this position. Thus, at relevant polymorphic nucleotide positions the HLA-A*0201 sequence is both directly and indirectly confirmed. This strategy strongly enhances the reliability of the subtyping and allows better verification of HLA-A*0201-positive patient selection for clinical studies.

Alleles↗
PubMed2001

Effects of pH on protein association: modification of the proton-linkage model and experimental verification of the modified model in the case of cytochrome c and plastocyanin.

Effects of pH on protein association are not well understood. To understand them better, we combine kinetic experiments, calculations of electrostatic properties, and a new theoretical treatment of pH effects. The familiar proton-linkage model, when used to analyze the dependence of the association constant K on pH, reveals little about the individual proteins. We modified this model to allow determination not only of the numbers of the H+ ions involved in the association but also of the pK(a) values, in both the separate and the associated proteins, of the side chains that are responsible for the dependence of K on pH. Some of these side chains have very similar pK(a) values, and we treat them as a group having a composite pK(a) value. Use of these composite pK(a) values greatly reduces the number of parameters and allows meaningful interpretation of the experimental results. We experimentally determined the variation of K in the interval 5.4 < or = pH < or = 9.0 for four diprotein complexes, those that the wild-type cytochrome c forms with the wild-type plastocyanin and its mutants Asp42Asn, Glu59Gln, and Glu60Gln. The excellent fittings of the experimental results to the modified model verified this model and revealed some unexpected and important properties of these prototypical redox metalloproteins. Protein association causes a decrease in the pK(a) values of the acidic side chains and an increase in the pK(a) values of the basic side chains. Upon association, three carboxylic side chains in wild-type plastocyanin each release a H+ ion. These side chains in free plastocyanin have an anomalously high composite pK(a) value, approximately 6.3. Upon association, five or six side chains in cytochrome c, likely those of lysine, each take up a H+ ion. Some of these side chains have anomalously low pK(a) values, less than 7.0. The unusual pK(a) values of the residues in the recognition patches of plastocyanin and cytochrome c may be significant for the biological functions of these proteins. Although each mutation in plastocyanin markedly, and differently, changed the dependence of K on pH, the model consistently gave excellent fittings. They showed decreased numbers of H+ ions released or taken up upon protein association and altered composite pK(a) values of the relevant side chains. Comparisons of the fitted composite pK(a) values with the theoretically calculated pK(a) values for plastocyanin indicated that Glu59 and Asp61 in the wild-type plastocyanin each release a H+ ion upon association with cytochrome c. Information of this kind cannot readily be obtained by spectroscopic methods. Our modification of the proton-linkage model is a general one, applicable also to ligands other than H+ ion and to processes other than association.

Cytochrome c Group↗
PubMed1996

Verification of cardiac doppler tissue images using grey-scale M-mode images.

Doppler tissue imaging (DTI) is a new ultrasonic technique that can be used to give quantified information about the motion of the myocardium. DTI M-mode recordings can be generated that display cardiac wall motion in great detail. In order to verify the motion as displayed in these images comparisons were made with simultaneously obtained grey-scale M-mode recordings. After capturing 135 simultaneous DTI and grey-scale M-mode recordings, those were selected in which wall motion could be accurately assessed from the grey-scale recording. Comparison with the DTI images shows: (1) that DTI accurately displays the direction of wall motion; and (2) that DTI displays whether the wall is thickening or thinning as a velocity distribution across the heart wall. This information is more reliably displayed and easier to interpret in the DTI M-mode recordings than in the grey-scale M-mode recordings.

Animals↗
PubMed1984

Latent abnormalities of sinus node function in patients with organic heart disease and normal sinus node on clinical basis.

Sinus node (SN) function was analyzed in 22 patients (mean age: 46.2 +/- 12.9 years) with organic heart disease and normal SN on clinical basis (group I) and in 20 normal subjects (mean age: 43.9 +/- 15.6 years), (control group). Sinus cycle length (SCL), corrected sinus node recovery time (CSRT) and sinoatrial conduction time (SACT) were analyzed. After the control study, autonomic blockade (AB) was induced by i.v. propranolol (0.2 mg/Kg) and atropine (0.04 mg/Kg). Measurements of SCL, CSRT and SACT were then repeated. The mean SCL values were very similar in the two groups during the control state and after AB. There were no significant differences in SACTs between the two groups during the control state or after AB. On the contrary, the CSRT of group I was significantly longer than that of control group during the control state (344.8 +/- 78.9 versus 262.2 +/- 46.3 msec, P less than 0.001) and after AB (238.9 +/- 72.8 versus 166.8 +/- 39.3 msec, P less than 0.001). The analysis of real depression of SN automaticity (CSRT minus SACT) in the two groups shows that prolongation of CSRT in group I during the control study and after AB is related to an intrinsic abnormality of SN automaticity; on the contrary, no dysfunctions of the autonomic nervous system appear. These data indicate that the intrinsic abnormality of SN automaticity represents the earliest involvement of the SN in subjects with organic heart disease and normal SN on clinical basis, although this conclusion is speculative and requires experimental verification.

Adolescent↗
PubMed1991

Bionic organs.

When a lizard loses its tail, a new caudal appendage soon grows to replace the one that is missing. But when a human loses a kidney, severs a peripheral nerve or worse, the spinal cord, that organ is lost forever. Such at least is conventional thinking. But imagine that the victim of an industrial accident with a paralyzed hand could achieve new levels of function by inducing axonal regrowth through a synthetic nerve guidance channel; or that a Parkinsonian patient's symptoms could be relieved by implanting in his brain neural tissue encased in a selectively permeable polymer envelope; or that the inexorable progression of the vascular complications of juvenile diabetes could be stopped, even reversed, by a membrane-protected xenograft of insulin-producing tissue. This is the dream of bionic organ science. It is predicated on two lines of technological achievement: the availability of ultra-thin, biocompatible, selectively permeable polymer membranes which can protect a transplant against immune rejection while allowing solute exchange between the graft and its environment; and the synthesis of novel materials, some biostable, some bioresorbable, which can serve as scaffolding or anchor for tissue regrowth in the geometrically and chemically controlled environment of an implant. The fabrication, growth and survival of composites of living tissues with synthetic polymers, often enhanced by the incorporation of specific cell growth factors or inhibitors, has been demonstrated at the tissue culture level, and extended in vivo to experimental models of human endocrine deficiency or neurological defects. The key to progress with bioartificial organs is the confluence of knowledge ranging from materials science to cell and molecular biology to experimental surgery. Obstacles to clinical implementation of this new therapeutic concept include: large scale procurement of specific tissue structures or isolated postmitotic cells from animal sources; demonstration of safety and efficacy of spontaneously occurring, bioactive tumor cell lines; verification of long-term stability and bio-acceptance of polymer implants; and industrialization of the fabrication process to meet quality control, shelf-life and commercial distribution requirements.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Visualization by a matrix of light-emitting diodes of interference effects from a radiative four-applicator hyperthermia system.

A simple, unique tool has been constructed at a very low cost for visualization of the electric field distribution in a phantom exposed to radiofrequency fields from a four-applicator hyperthermia system. The tool consists of a thin Perspex plate to which light-emitting diodes (LEDs) have been attached in a regular pattern. The leads of these LEDs have been bent in the form of dipoles. Electric field distributions can be made visible, because the light intensity from an individual LED dipole in a RF field is a function of the local electric field strength. The LED dipoles were arranged in a 11 x 15 matrix with a mutual distance of 2 cm. Experiments have been performed in a cylinder with a length of 100 cm and with an elliptical cross-section of 24 cm x 36 cm. The cylinder was filled with saline to simulate the electric properties of biological tissue. The matrix plate was shaped like the cross-section inside the phantom, and could be moved to any position under the externally applied antennae. In our department the applicators installed form a system of four coherent waveguide radiators operating at a frequency of 70 MHz. Photographs have been taken from the distribution of the light intensity through transparent windows at the outer ends of the phantom. The advantage of the LED matrix is the fact that the effect of changing phase relations, amplitudes or position of any applicator on the electric field distribution can be seen instantaneously. The interference effects of multiple fields, i.e. extinction and reinforcement, become easily visible. Typical examples demonstrate the necessity to obtain the field distribution not only along some previously chosen lines, but in the whole transversal midplane. The attenuation of field strength due to the presence of the matrix varies only slightly from the edge to the centre of the matrix, so the pattern of light intensity is in good qualitative agreement with the pattern of field strength. The LED matrix has been very useful in the verification of pretreatment planning calculations, and is already used for intercomparison and evaluation studies of similar hyperthermia equipment.

Biophysical Phenomena↗
PubMed1995

Comparison of low-pressure versus standard-pressure fixation Carpentier-Edwards bioprosthesis.

Intermediate-phase clinical results of 51 low-pressure (LP) and 234 standard-pressure (SP) fixation porcine Carpentier-Edwards (CE) valves implanted between 1977 and 1991 were compared for valve-related events. Group similarities included New York Heart Association functional class, ejection fraction, and sex. Patients with SP valves were younger (mean age, 58 versus 68 years; p = 0.0001). There were 20 in-hospital deaths (8.6%) in the SP valve group and 5 (9.8%) in the LP valve group (p = 0.79). Follow-up was 99%, with a mean of 104 months in the SP valve group versus 55 months in the SP valve group (p = 0.0001). The actuarial survival rate was 48.2% and 22.3% at 10 and 15 years, respectively, in the SP valve group and 34.1% at 10 years in the LP valve group (p = 0.42). Freedom from events at 5, 10, and 15 years in the SP valve group and at 5 years in the LP valve group was as follows: for late valve-related events, 86.3%, 51.4% and 20.2%, respectively, in the SP valve group versus 85% in the LP valve group (p = 0.44); for valve-related death, 96.4%, 93.6%, and 87.3% in the SP valve group versus 100% in the LP valve group (p = 0.20); for structural valve failure, 96%, 68%, and 35% in the SP valve group versus 100% in the LP valve group (p = 0.09); and for reoperation, 95%, 61%, and 30% in the SP valve group versus 92% in the LP valve group (p = 0.82). In conclusion, this study revealed no significant statistical difference between LP and SP valves. In the LP valve group, structural valve failure/valve-related death was not observed, perhaps indicating a more favorable result. Absolute verification of this trend awaits long-term follow-up.

Actuarial Analysis↗