Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Space Suits”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,063 records · Page 59Linked to original sources
PubMed2003

Nonseparable wavelet-based cone-beam reconstruction in 3-D rotational angiography.

In this paper, we propose a new wavelet-based reconstruction method suited to three-dimensional (3-D) cone-beam (CB) tomography. It is derived from the Feldkamp algorithm and is valid for the same geometrical conditions. The demonstration is done in the framework of nonseparable wavelets and requires ideally radial wavelets. The proposed inversion formula yields to a filtered backprojection algorithm but the filtering step is implemented using quincunx wavelet filters. The proposed algorithm reconstructs slice by slice both the wavelet and approximation coefficients of the 3-D image directly from the CB projection data. The validity of this multiresolution approach is demonstrated on simulations from both mathematical phantoms and 3-D rotational angiography clinical data. The same quality is achieved compared with the standard Feldkamp algorithm, but in addition, the multiresolution decomposition allows to apply directly image processing techniques in the wavelet domain during the inversion process. As an example, a fast low-resolution reconstruction of the 3-D arterial vessels with the progressive addition of details in a region of interest is demonstrated. Other promising applications are the improvement of image quality by denoising techniques and also the reduction of computing time using the space localization of wavelets.

Algorithms↗
PubMed2005

Small-scale temporal variation and the effect of urbanisation on extracellular enzyme activity in streams.

The activity of six extracellular enzymes involved in the degradation of dissolved organic carbon compounds was measured in two highly urbanised and two minimally impacted streams east of Melbourne, Australia, using 4-methylumbelliferyl-substrates. Small-scale temporal variation in enzyme activity was determined by repeatedly sampling the same point in the water column, while the effect of flow was determined by sampling in regions of higher and lower flow in both stream types. Replicate samples showed that enzyme activity was not significantly different over small (minutes) time scales. On five of six sampling occasions the enzyme activity was unaffected by flow. On one sampling occasion in a minimally disturbed stream, the difference between the high- and low-flow regions was statistically significant (ANOSIM, Global R= 0.78, P= 0.03). Enzyme activity profiles (activities of the suite of enzymes) of the streams in urbanised catchments were different to those in minimally disturbed catchments. The measurements made in four different streams showed high reproducibility over short time periods (minutes) which lends greater credibility to analogous spatial studies. Although these results determined that small-scale temporal variability was not significant, and that the effects of flow were generally minimal, it is recommended that spatial and temporal variability in the stream be at least considered before any studies measuring extracellular enzyme activity in stream waters are carried out. Such an approach will lead to conclusions from measurements that are not likely to be confounded by variables such as flow rate or time.

Ecosystem↗
PubMed2002

Lack of cocaine effect on dopamine clearance in the core and shell of the nucleus accumbens of dopamine transporter knock-out mice.

Cocaine produces its reinforcing effects primarily by inhibiting the dopamine transporter (DAT) at the level of presynaptic terminals and increasing extracellular levels of dopamine (DA). Surprisingly, in mice genetically lacking the DAT, cocaine was still able to elevate DA in the nucleus accumbens (NAc). This finding is critically important for explaining the persistence of cocaine reinforcement in DAT knock-out (DAT-KO) mice. However, the mechanism by which cocaine elevates DA is unclear. Here, we tested the recently proposed hypothesis that in the absence of the DAT, the norepinephrine transporter (NET) could provide an alternative uptake site for DA clearance. If true, cocaine could elevate DA levels through its inhibition of the NET. In vitro voltammetry, a technique well suited for evaluating the effects of drugs on DA uptake, was used in the present study. We report that both cocaine and desipramine, a potent NET inhibitor, failed to change DA clearance or evoked release in the NAc of mutant mice. Additionally, fluoxetine, a serotonin transporter (SERT) inhibitor, also had no effect on these parameters. These data rule out the involvement of accumbal NET or SERT in the cocaine-induced increase in extracellular DA in DAT-KO mice. Moreover, the present findings suggest that in the DAT-KO mice, cocaine acts primarily outside the NAc to produce its effects.

Adrenergic Uptake Inhibitors↗
PubMed2001

Minimally invasive subclavian/axillary artery to coronary artery bypass (SAXCAB): review and classification.

BACKGROUND AND PURPOSE: Subclavian/axillary artery to coronary artery bypass (SAXCAB) surgery is defined as a minimally (or less) invasive coronary revascularization procedure where one or more grafts are anastomosed to the second or third parts of the subclavian artery or any of the three parts of the axillary artery (inflow source) and attached to one or more coronary arteries, and where there are two separate minimally invasive incisions to expose the target coronary artery and the inflow sources, respectively. The indications and contraindications for SAXCAB surgery are discussed, and the relevant chest wall anatomy and that of the subclavian and axillary arteries are reviewed. The effect of respiration and anatomic variability as they impact the SAXCAB graft are discussed. Three components of the anatomy that are important in SAXCAB surgery are discussed: The relation of the first rib to the clavicle insofar as it affects access to the third part of the subclavian artery, the anatomy of the subclavian and axillary arteries and their branches, and the anatomy of the chest wall and its movement. In addition, the different SAXCAB variations that have been applied clinically are reviewed and classified, and future aspects of SAXCAB research are discussed. SAXCAB surgery is unique among the different types of minimally invasive direct coronary artery bypass (MIDCAB) surgery because of the enormous diversity of the techniques that have been described. Based on these descriptions, a new classification of SAXCAB grafting is proposed depending on whether the graft is inside or outside the rib cage and whether or not the coronary artery is exposed by rib resection or through an intercostal space. The third part of the classification takes into consideration the mode of entry into the chest, whether it is by rib resection or through an intercostal space. METHODS: Inquiries were made by telephone and by mail in the year 2000 to a number of surgeons who had published details of their SAXCAB techniques, and informal information was obtained by a series of personal communications as to the estimated number of operations they had performed and the outcomes. Published data was also used to formulate a rough guide as to the international status of the procedure at this time. RESULTS: The total estimated international experience is about 100 cases and the patency is between 70 and 100 percent in the time frame of about one to two years. CONCLUSIONS: The MIDCAB technique in general has been successful in providing an alternative way to revascularize the coronary arteries, and the SAXCAB has proved to be one of the most interesting classes of MIDCAB surgery. SAXCAB grafts seem to be unique among coronary revascularization procedures and, indeed, probably almost all vascular procedures, in that there is enormous diversity in the route for the graft from the inflow source to the target coronary artery. Being knowledgeable about the different varieties of SAXCAB surgeries will help the surgeon during a rescue operation as the surgery can be tailored to suit a particular patient. The SAXCAB seems to be a very safe operation, and it is striking that so far no one has reported any major complications.

Axillary Artery↗
PubMed1987

Role of cardiopulmonary mechanoreceptors in the postural regulation of renin.

To change the stretch on cardiopulmonary mechanoreceptors, large shifts of blood in the capacity space were elicited by tilting and by exerting positive lower body pressure in the tilted position. Twelve volunteers underwent invasive hemodynamic studies and in 10 other subjects cardiac size was determined by radionuclide cardiography. In all 22 subjects tilting caused the expected increase of renin, which was abolished by lower body compression. Decompression caused renin to increase again. Right atrial pressure in invasive studies and end-systolic and end-diastolic counts in noninvasive studies showed a significant and strong negative correlation with renin and norepinephrine levels. Thus, the degree of stretch of the cardiopulmonary mechanoreceptors is a major determinant of reflex regulation of renin release in humans.

Adolescent↗
PubMed1994

Spatiotemporal response properties of direction-selective neurons in the nucleus of the optic tract and dorsal terminal nucleus of the wallaby, Macropus eugenii.

1. The spatial and temporal response characteristics of direction-selective neurons in the nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN) of the wallaby were established using moving sinusoidal gratings. This is the first comprehensive investigation of the spatiotemporal response characteristics of NOT-DTN neurons in any species. 2. The analysis revealed two main classes of cells. The first class, referred to as slow neurons, are maximally sensitive to motion at low temporal frequencies (< 1 Hz) and high spatial frequencies (0.5-1.0 cpd). The second class, referred to as fast neurons, are most sensitive to motion at high temporal frequencies (> 10 Hz) and moderate to low spatial frequencies (0.1-0.5 cpd). The fast neurons also have a domain of high sensitivity at low temporal frequencies and high spatial frequencies. As the neurons are tuned to specific temporal frequencies of motion, rather than image velocities, it is suggested that the motion detectors are of the delay-and-compare type and code local motion-related changes in contrast or luminance. 3. Both classes of neuron are highly direction-selective in the midranges of their spatiotemporal tuning curves, i.e., the firing rates increase during motion in the preferred direction (temporonasal movement through the visual field of the contralateral eye) and decrease during motion in the opposite direction. At high temporal and low spatial frequencies, however, the slow neurons are inhibited by motion in both directions along their preferred axis. It is argued that this bidirectional inhibition at high speeds may act to inhibit ocular following during saccades and may act as a gain control mechanism preventing excessive overshoot in eye velocity at motion onset, when retinal-slip velocities are high. 4. The fast neurons probably have two functions. First, they are suited to initiating ocular following responses when image motion is quite fast. Second, their spatiotemporal tuning makes them candidates for supplying a velocity error signal into the velocity storage mechanism, which is most prominent at high stimulus speeds. 5. Fourier analysis of the peristimulus time histograms derived from the response of both the slow and fast neurons revealed that the main frequency components of the responses occurred at the fundamental and second harmonic frequencies of the input signal at low stimulus temporal frequencies (< 3.04 Hz). At higher stimulus frequencies, the responses contained significant frequency components at higher odd-harmonics of the input signal.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2004

Electrostatic influence on rotational mobilities of sol-gel-encapsulated solutes by NMR and EPR spectroscopies.

The rotational mobilities of small solute molecules encapsulated in tetramethyl orthosilicate (TMOS) sol-gels have been investigated by EPR spectroscopy of encapsulated nitroxide probes and by high-resolution NMR spectroscopic measurements of transferred NOE's (trNOE's), of T(1)'s, and of T(1)'s in the rotating frame (T(1)rho). The two spectroscopic methods are sensitive to motions on different time scales and hence, are nicely complementary. Suites of neutral, positively, and negatively charged nitroxide probes (EPR) and of simple diamagnetic small molecules (NMR) were selected to disclose influences of electrostatic interactions with the sol-gel walls and to probe the presence of multiple populations of molecules in distinct regions of the sol-gel pores. For neutral and negatively charged solute probes, both techniques disclose a single population with a significantly increased average rotational correlation time, which we interpret at least in part as resulting from exchange between free-volume and transiently immobilized surface populations. The electrostatic attraction between cationic probes and the negatively charged sol-gel walls causes the positively charged probes to be more effectively immobilized and/or causes a greater percentage of probes to undergo this transient immobilization. The EPR spectra directly disclose a population of cationic probes which are immobilized on the X-band EPR time scale: tau(c) greater than or approximately equal 10(-7) s. However, NMR measurements of trNOE's and of T(1)rho demonstrate that this population does exchange with the free-volume probes on the slower time scale of NMR. This approach is equally applicable to the study of solutes within other types of confined spaces, as well.

Cyclic N-Oxides↗
PubMed2005

Investigation of fatalities due to acute gasoline poisoning.

This paper presents a simple, rapid, reliable, and validated method suited for forensic examination of gasoline in biological samples. The proposed methodology has been applied to the investigation of four fatal cases due to gasoline poisoning that occurred in Spain in 2003 and 2004. Case histories and pathological and toxicological findings are described in order to illustrate the danger of gasoline exposure under several circumstances. Gasoline's tissular distribution, its quantitative toxicological significance, and the possible mechanisms leading to death are also discussed. The toxicological screening and quantitation of gasoline was performed by means of gas chromatography (GC) with flame-ionization detection, and confirmation was performed using GC-mass spectrometry in total ion chromatogram mode. m,p-Xylene peak was selected to estimate gasoline in all biological samples. Gasoline analytical methodology was validated at five concentration levels from 1 to 100 mg/L. The method provided extraction recoveries between 77.6% and 98.3%. The limit of detection was 0.3 mg/L, and the limit of quantitation was 1.0 mg/L. The linearity of the blood calibration curves was excellent with r2 values of > 0.997. Intraday and interday precisions had a coefficient of variation < or = 5.4% in all cases. Cases 1 and 2 consist of the accidental inhalation of gasoline vapor inside a small enclosed space. Case 3 is a death by recreational gasoline inhalation in a male adolescent. Heart blood concentrations were 28.4, 18.0, and 38.3 mg/L, respectively; liver concentrations were 41.4, 52.9, and 124.2 mg/kg, respectively; and lung concentrations were 5.6, 8.4, and 39.3 mg/kg, respectively. Case 4 was an accidental death due to gasoline ingestion of a woman with senile dementia. Peripheral blood concentration was 122.4 mg/L, the highest in our experience. Because pathological findings were consistent with other reports of gasoline intoxication and constituents of gasoline were found in the body, cause of death was attributed to acute gasoline intoxication. As a rule, this kind of poisoning offers little difficulty in diagnosis because there is a history of exposure, and the odor usually clings to the clothes, skin, or gastric contents. However, anatomic autopsy findings will be nonspecific and therefore toxicological analysis is necessary. There is a paucity of recent references regarding analytical and toxicological data, and this article provides evidence about toxic concentrations and is a useful adjunct to the postmortem toxicological interpretation of fatalities if the decedent has been involved in gasoline use.

Accidents, Occupational↗
PubMed1990

[Tube-free translaryngeal superposed jet ventilation].

Microsurgical operations on the larynx require sufficient space for the surgeon in order to achieve the best surgical result. After preliminary experimental studies we integrated two jets of a specific size into the Kleinsasser tube. Simultaneously, we developed a "superimposed jet-ventilation system", which consists of a low-frequency jet ventilation and superimposed high-frequency jet ventilation. Respiration was maintained with a mixture of oxygen and air, whereby an additional increase in air and volume via the Kleinsasser tube, which is open on the outside, can be sustained on account of the Venturi effect. We tested this tubeless translaryngeal superimposed jet-ventilation system in 48 patients. Anesthesia was carried out by continuous intravenous administration of Propofol and intermittent doses of Sufentanil and Vecuronium as required. The clinical results showed optimal ventilation without hypercapnia. The arterial pC0(2) levels were below 42 mmHg. The arterial p0(2) levels were above 120 mmHg with a FIO2 of 40%. No complications were observed with regard to respiration during any of the operations. The surgeon had optimal conditions to carry out the operation. Because of the absence of a plastic tube, inhalation anesthetics and nitrous oxide, laryngeal laser surgery is another field of application for which this form of tubeless jet ventilation is excellently suited. We tested it with 12 patients, and no complications due to laser anesthesia were observed. We consider this form of a tubeless superimposed translaryngeal jet ventilation to be a great improvement in microlaryngeal surgery.

Adult↗
PubMed2003

Modulation and rehabilitation of spatial neglect by sensory stimulation.

After unilateral cortical or subcortical, often parieto-temporal lesions, patients exhibit a marked neglect of their contralateral space and/or body side. These patients are severely disabled in all daily activities, have a poor rehabilitation outcome and therefore require professional treatment. Unfortunately, effective treatments for neglect are just in the process of development. The present chapter reviews three aspects related to the rehabilitation of neglect. The first part summarizes findings about spontaneous recovery in patients and experimental animals with neglect. The second part deals with techniques and studies evaluating short-term sensory modulation effects in neglect. In contrast to many other neurological syndromes spatial neglect may be modulated transiently but dramatically in its severity by sensory (optokinetic, neck proprioceptive, vestibular, attentional, somatosensory-magnetic) stimulation. In part three, current treatment approaches are summarized, with a focus on three novel techniques: repetitive optokinetic stimulation, neck vibration training and peripheral somatosensory-magnetic stimulation. Recent studies of repetitive optokinetic as well as neck vibratory treatment both indicate significantly greater as well as multimodal improvements in neglect symptomatology as compared to the standard treatment of neglect. This clear superiority might result from the partial (re)activation of a distributed, multisensory vestibular network in the lesioned hemisphere. Somatosensory-magnetic stimulation of the neglected or extinguishing hand provides another feasible, non-invasive stimulation technique. It may be particularly suited for the rehabilitation of somatosensory extinction and unawareness of the contralesional body side. Finally, pharmacological approaches for the treatment of neglect are shortly addressed. Isolated drug treatment of neglect is currently no successful rehabilitation strategy due to inconsistent results as well as possible side effects. However, combined behavioural and drug treatments might yield better results. This has to be tested empirically in patient studies. In conclusion, the findings obtained in short-term sensory stimulation studies led to the development of effective techniques for the long-term rehabilitation of neglect. Future rehabilitation studies should evaluate effective treatment combinations considering all possible techniques and devices (behavioural, pharmacological, prosthetic or physiological).

Acoustic Stimulation↗
PubMed2001

Structure and sequence conservation of a putative hypoxia response element in the lactate dehydrogenase-B gene of Fundulus.

Many aquatic habitats are characterized by periodic or sustained episodes of low oxygen concentration, or hypoxia, and organisms that survive in these habitats do so by utilizing a suite of behavioral, physiological and biochemical adjustments to low oxygen (1-3). In the killifish Fundulus heteroclitus, one response to prolonged exposure to hypoxia is an increase in the activity of lactate dehydrogenase-B (LDH-B), the terminal enzyme of anaerobic glycolysis, in liver tissue (4). An increase in glycolytic enzyme activity also occurs in mammalian cells during hypoxia, a process due, in part, to increased rates of gene transcription mediated by the hypoxia-inducible transcription factor, HIF-1 (5). Given that a homolog of HIF-1 has been identified in fish (6), we hypothesized that HIF might be involved in the observed up-regulation of LDH-B in F. heteroclitus. Herein, we describe the presence of DNA elements in intron 2 of the Ldh-B gene from F. heteroclitus that resemble hypoxia response elements (HRE) describedfor mammalian genes (7-10). Specifically, over a region of approximately 50 base pairs we identified two consensus HIF-1 binding sites, as well as DNA elements that may bind other transcription factors (e.g., cyclic AMP response elements; CRE). We found that these sites were perfectly conserved among geographically diverse populations of F. heteroclitus, as well as being highly conserved among multiple species in the genus Fundulus. The spacing, orientation, and sequence conservation of these putative regulatory elements suggest that they may be functionally involved in the hypoxic regulation of Ldh-B in these fish.

Animals↗
PubMed2003

MLC dosimetric characteristics for small field and IMRT applications.

The objective of this work was to measure the performance characteristics of a double-focus multileaf collimator (MLC) for intensity modulated radiation therapy (IMRT), specifically the variation in penumbra and leakage for narrow fields as a function of field position over a 20x27 cm space available for segmented MLC IMRT. Measurements were made with 6 MV x rays through a MLC containing 29 leaf pairs (27 pairs of 1 cm width), and EDR2 film at 10 cm depth in solid water at 100 cm SAD. Films were digitized with 0.17 mm resolution and converted to dose. Interleaf and intraleaf transmission were measured along 11 vertical profile locations. Leaf-end transmission was measured along horizontal profiles for each of 9 different leaf abutments, traveling over a 20 cm range. In-plane penumbra measurements were made through a single leaf retracted, for 7 different leaves. Cross-plane penumbra (leaf-end) measurements were made for all 27 leaf pairs, where the 1 cm field width was placed in 11 different off-axis positions (20 cm range). Interleaf leakage (range 1.0%-1.5%), intraleaf transmission (range 0.6%-0.8%), and leaf-end transmission (range 0.8%-2.7%) were consistent for all leaf pairs at a given abutment position. The penumbra for these 1-cm-wide fields was measured to be 0.36 cm+/-0.03 cm for 99% of the measurements. In conclusion, the penumbra and leakage of the double-focus MLC were remarkably consistent for the range of leaf positions studied, producing dosimetric characteristics that are well suited for IMRT segments where opposing leaf pairs are often separated by 10 mm or less.

Equipment Failure Analysis↗
PubMed2000

Hitting moving objects. The dependency of hand velocity on the speed of the target.

In previous studies, subjects did not hit slowly moving objects as quickly as fast ones, despite being instructed to hit them all as quickly as possible. In those studies the targets moved at constant but unpredictable velocities, and it has been suggested that subjects were unable to adjust the hand's path to suit the velocity of the target. To compensate for this, they adjusted the speed of their hand to that of the target (speed coupling). According to this hypothesis, speed coupling is necessary only when subjects are unable to correctly predict the next target velocity and only if they have to be accurate. We show here that decreasing the uncertainty about the upcoming target's velocity or enlarging the tip of the hitting weapon does not make speed coupling disappear. Moreover, there is a negative correlation between hand velocity and strength of speed coupling, whereas the hypothesis predicts a positive correlation. The hypothesis is therefore rejected. We propose that speed coupling is a result of different speed-accuracy tradeoffs applying to different target velocities.

Hand↗
PubMed1997

Persistent patterns of brain activity: an EEG coherence study of the positive effect of music on spatial-temporal reasoning.

Motivated by predictions from the structured trion model of the cortex, behavioral experiments have demonstrated a causal short-term enhancement of spatial-temporal reasoning in college students following exposure to a Mozart sonata, but not in control conditions. The coherence analysis of electroencephalogram (EEG) recordings is well suited to the neurophysiological investigation of this behavioral enhancement. Here we report the presence of right frontal and left temporo-parietal coherent activity induced by listening to Mozart which carried over into the spatial-temporal tasks in three of our seven subjects. This carry-over effect was compared to EEG coherence analysis of spatial-temporal-tasks after listening to text. We suggest that these EEG coherence results provide the beginnings of understanding of the neurophysiological basis of the causal enhancement of spatial-temporal reasoning by listening to specific music. The observed long-lasting coherent EEG pattern might be evidence for structured sequences in cortical dynamics which extend over minutes.

Adult↗
PubMed2003

An in silico assessment of gene function and organization of the phenylpropanoid pathway metabolic networks in Arabidopsis thaliana and limitations thereof.

The Arabidopsis genome sequencing in 2000 gave to science the first blueprint of a vascular plant. Its successful completion also prompted the US National Science Foundation to launch the Arabidopsis 2010 initiative, the goal of which is to identify the function of each gene by 2010. In this study, an exhaustive analysis of The Institute for Genomic Research (TIGR) and The Arabidopsis Information Resource (TAIR) databases, together with all currently compiled EST sequence data, was carried out in order to determine to what extent the various metabolic networks from phenylalanine ammonia lyase (PAL) to the monolignols were organized and/or could be predicted. In these databases, there are some 65 genes which have been annotated as encoding putative enzymatic steps in monolignol biosynthesis, although many of them have only very low homology to monolignol pathway genes of known function in other plant systems. Our detailed analysis revealed that presently only 13 genes (two PALs, a cinnamate-4-hydroxylase, a p-coumarate-3-hydroxylase, a ferulate-5-hydroxylase, three 4-coumarate-CoA ligases, a cinnamic acid O-methyl transferase, two cinnamoyl-CoA reductases) and two cinnamyl alcohol dehydrogenases can be classified as having a bona fide (definitive) function; the remaining 52 genes currently have undetermined physiological roles. The EST database entries for this particular set of genes also provided little new insight into how the monolignol pathway was organized in the different tissues and organs, this being perhaps a consequence of both limitations in how tissue samples were collected and in the incomplete nature of the EST collections. This analysis thus underscores the fact that even with genomic sequencing, presumed to provide the entire suite of putative genes in the monolignol-forming pathway, a very large effort needs to be conducted to establish actual catalytic roles (including enzyme versatility), as well as the physiological function(s) for each member of the (multi)gene families present and the metabolic networks that are operative. Additionally, one key to identifying physiological functions for many of these (and other) unknown genes, and their corresponding metabolic networks, awaits the development of technologies to comprehensively study molecular processes at the single cell level in particular tissues and organs, in order to establish the actual metabolic context.

Arabidopsis↗
PubMed1983

Classification and identification of Mycobacterium africanum by pyrolysis mass spectrometry.

Pyrolysis mass spectrometry was used to classify and identify strains of Mycobacterium africanum and of M. tuberculosis, M. bovis and M. bovis BCG. The multicharacter mass pyrograms were evaluated by computerized data handling procedures that were suited for classification and identification. The results revealed considerable heterogeneity among the African strains, which was shown to be linked to the geographic distribution of the strains. On the basis of a routine mass spectrometric identification key the African strains were identified without exception as belonging to, what is referred to as the 'Tuberculosis complex' (i.e. the clinically relevant group formed by strains of M. Tuberculosis, M. bovis and M. bovis BCG). Classification of the strains by means of discriminant analysis indicated an intermediate clustering for the majority of the African strains and overlap for some African strains with in particular M. bovis. It was concluded that from the mass spectrometric data a species status for the group of African strains was not justifiable.

Africa↗
PubMedDate not supplied

Relationships between Molecular Complexity, Biological Activity, and Structural Diversity.

Following the theoretical model by Hann et al. moderately complex structures are preferable lead compounds since they lead to specific binding events involving the complete ligand molecule. To make this concept usable in practice for library design, we studied several complexity measures on the biological activity of ligand molecules. We applied the historical IC50/EC50 summary data of 160 assays run at Novartis covering a diverse range of targets, among them kinases, proteases, GPCRs, and protein-protein interactions, and compared this to the background of "inactive" compounds which have been screened for 2 years but have never shown any activity in any primary screen. As complexity measures we used the number of structural features present in various molecular fingerprints and descriptors. We found generally that with increasing activity of the ligands, their average complexity also increased, and we could therefore establish a minimum number of structural features in each descriptor needed for biological activity. Especially well suited in this context were the Similog keys and circular substructure fingerprints. These are those descriptors, which also perform especially well in the identification of bioactive compounds by similarity search, suggesting that structural features encoded in these descriptors have a high relevance for bioactivity. Since the number of features correlates with the number of atoms present in the molecule, also the number of atoms serves as a reasonable complexity measure and larger molecules have, in general, higher activities. Due to the relationship between feature counts and densities on one hand and biological activity on the other, the size bias present in almost all similarity coefficients becomes especially important. Diversity selections using these coefficients can influence the overall complexity of the resulting set of molecules, which has an impact on the biological activity that they exhibit. Using sphere-exclusion based diversity selection methods, such as OptiSim together with the Tanimoto dissimilarity, the average feature count distribution of the resulting selections is shifted toward lower complexity than that of the original set, particularly when applying tight diversity constraints. This size bias reduces the fraction of molecules in the subsets having the complexity required for a high, submicromolar activity. None of the diversity selection methods studied, namely OptiSim, divisive K-means clustering, and self-organizing maps, yielded subsets covering the activity space of the IC50 summary data set better than subsets selected randomly.

Drug Design↗
PubMed2000

[Pleomorphic adenoma: a case treated by laryngotracheal resection and reconstruction].

Benign Pleomorphic Adenoma (PA) is a tumor rarely found in tracheal and laryngotracheal sites. A review of the literature published since 1922 has revealed only 30 certain cases of which 3 presented simultaneous involvement of both larynx and trachea. The present work describes the thirty-first case (the fourth with a laryngotracheal localization), diagnosed in a white, 40-year-old male who had been complaining of acute dyspnea for the last three years. Initially these symptoms had been interpreted as asthmatic crises. During one of these episodes, the patient underwent emergency tracheotomy and a laryngotracheoscopy revealed a rounded cricotracheal lesion with smooth surface and approximately 4 cm in cranio-caudal diameter. The mass occupied 90% of the air space and originated from the posterolateral right portion of the cricoid, and from the first 3 tracheal rings. CT and esophagoscopy ruled out its transmural invasion into the esophagus. Under rigid bronchoscopy, assisted NdYAG laser debulking was performed for biopsy purposes. The histological diagnosis was benign AP. For this reason a Grillo cricotracheal resection was performed with exeresis of the cricoid arch, mucosa of the cricoid plate and the first 4 tracheal rings. Reconstruction of the respiratory tract was achieved through termino-terminal cricothyrotracheal anastomosis. The initial diagnosis was confirmed and the resection edges were without evidence of neoplasm. Post-operative recovery proceeded without complications and the patient was discharged 7 days after surgery. Endoscopic and radiological follow-up after 30 months is still negative for any neoplastic recurrences. The laryngo-tracheal lumen is within the norm and cord motility has been preserved. The authors then describe the clinical, anatomopathological and radiological elements which prove useful in evaluating tracheal neoplasms and they underline the problems of differential diagnosis between benign AP and adenoid-cystic carcinoma. In addition, the various therapeutic options are discussed with special attention being focused on surgery through external approaches. Given the location of the AP described, the Grillo procedure-most commonly used in cases of inflammatory cricotracheal stenoses-proved well suited to the loco-regional control of the neoplasm. Stringent respect for some parts of this surgical technique make it possible to reduce post-operative complications to a minimum.

Adenoma, Pleomorphic↗