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Biomedical subjects

S M Gomez

Publications and source records attributed to S M Gomez.

16 recordsLinked to original sources

Birth of scale-free molecular networks and the number of distinct DNA and protein domains per genome.

MOTIVATION: Current growth in the field of genomics has provided a number of exciting approaches to the modeling of evolutionary mechanisms within the genome. Separately, dynamical and statistical analyses of networks such as the World Wide Web and the social interactions existing between humans have shown that these networks can exhibit common fractal properties-including the property of being scale-free. This work attempts to bridge these two fields and demonstrate that the fractal properties of molecular networks are linked to the fractal properties of their underlying genomes. RESULTS: We suggest a stochastic model capable of describing the evolutionary growth of metabolic or signal-transduction networks. This model generates networks that share important statistical properties (so-called scale-free behavior) with real molecular networks. In particular, the frequency of vertices connected to exactly k other vertices follows a power-law distribution. The shape of this distribution remains invariant to changes in network scale: a small subgraph has the same distribution as the complete graph from which it is derived. Furthermore, the model correctly predicts that the frequencies of distinct DNA and protein domains also follow a power-law distribution. Finally, the model leads to a simple equation linking the total number of different DNA and protein domains in a genome with both the total number of genes and the overall network topology. AVAILABILITY: MatLab (MathWorks, Inc.) programs described in this manuscript are available on request from the authors. CONTACT: ar345@columbia.edu.

Biological Evolution↗

Probabilistic prediction of unknown metabolic and signal-transduction networks.

Regulatory networks provide control over complex cell behavior in all kingdoms of life. Here we describe a statistical model, based on representing proteins as collections of domains or motifs, which predicts unknown molecular interactions within these biological networks. Using known protein-protein interactions of Saccharomyces cerevisiae as training data, we were able to predict the links within this network with only 7% false-negative and 10% false-positive error rates. We also use Markov chain Monte Carlo simulation for the prediction of networks with maximum probability under our model. This model can be applied across species, where interaction data from one (or several) species can be used to infer interactions in another. In addition, the model is extensible and can be analogously applied to other molecular data (e.g., DNA sequences).

Amino Acid Motifs↗

A knowledge model for analysis and simulation of regulatory networks.

MOTIVATION: In order to aid in hypothesis-driven experimental gene discovery, we are designing a computer application for the automatic retrieval of signal transduction data from electronic versions of scientific publications using natural language processing (NLP) techniques, as well as for visualizing and editing representations of regulatory systems. These systems describe both signal transduction and biochemical pathways within complex multicellular organisms, yeast, and bacteria. This computer application in turn requires the development of a domain-specific ontology, or knowledge model. RESULTS: We introduce an ontological model for the representation of biological knowledge related to regulatory networks in vertebrates. We outline a taxonomy of the concepts, define their 'whole-to-part' relationships, describe the properties of major concepts, and outline a set of the most important axioms. The ontology is partially realized in a computer system designed to aid researchers in biology and medicine in visualizing and editing a representation of a signal transduction system.

Animals↗

Eosinophilic dermatitis with edema in nine dogs, compared with eosinophilic cellulitis in humans.

A unique eosinophilic dermatitis with edema in dogs is characterized by extremely erythematous coalescing macules and plaques with associated edema, and is similar to eosinophilic cellulitis (Wells' syndrome) in humans. Histopathologic features include a profound eosinophilic dermal infiltrate, focal areas of collagen fiber degeneration surrounded by eosinophils (flame figures), dilated vessels, and dermal edema. Etiopathogenesis is unknown, but a hypersensitivity reaction to medications, arthropod bites, or other foreign antigens is suspected.

Animals↗

Transcranial Doppler in reversible migrainous vasospasm causing cerebellar infarction: report of a case.

A young woman with a history of classic migraine suffered a large cerebellar infarction. Comprehensive evaluation did not disclose any potential causes for the stroke and she had no other risk factors. Transcranial Doppler (TCD) was useful in identifying vasospasm of the vertebral arteries. Following treatment with propranolol, angiography and repeat TCD revealed resolution of the vasospastic disorder. TCD is a useful noninvasive tool in detecting vasospasm associated with ischemic lesions in certain patients with migraine.

Adult↗

Chimeric immunoglobulin-T cell receptor proteins form functional receptors: implications for T cell receptor complex formation and activation.

We constructed chimeric receptor chains in which an immunoglobulin heavy chain variable region (VH) from a phosphorylcholine-specific antibody is substituted for T cell receptor (Tcr) alpha and beta V regions. We demonstrate that the VH region joined to either the C alpha or the C beta region can form stable chimeric proteins in EL4 T cells. Both chimeric receptor chains associate with CD3 polypeptides in functional receptor complexes and respond to phosphorylcholine coupled to Sepharose beads. The VH-C alpha chimeric chain associates with the EL4 beta chain, while the VH-C beta chimeric protein appears to form either a homodimer or a heterodimer with the native EL4 beta chain. Thus, functional receptor complexes can be formed using two C beta regions, and the C alpha region may not be required for CD3 association and surface expression of Tcr complexes.

Animals↗

Meso-diencephalic infarction: a not so rare form of stroke.

26 patients admitted with clinical pictures consistent with meso-diencephalic infarction were studied using computerized axial tomography, magnetic resonance imaging and angiography. All of the patients presented symptoms in two of three major categories which comprise the "top of the basilar" syndrome. Lesions in the territory of the basilar-communicating artery were demonstrated in 22 of them. The remaining patients died before adequate neuroimaging documentation was obtained. Overall prognosis appeared relatively good since 80% of the patients recovered completely or incompletely from the ictus. Meso-diencephalic infarction is a very important and not uncommon subtype of cerebrovascular disorder.

Adult↗

Transcranial Doppler determination of cerebral perfusion in patients undergoing CPR: methodology and preliminary findings.

STUDY OBJECTIVES: To correlate cerebral arterial blood velocity measurements as determined by transcranial Doppler ultrasound with various resuscitation maneuvers performed in an uncontrolled manner in a series of cardiac arrest patients undergoing standard resuscitation. TYPE OF PARTICIPANTS: Any patient undergoing resuscitation for a nontraumatic cardiac arrest was eligible for the study. INTERVENTIONS: Resuscitation was carried out while flow velocities were monitored in various intracranial arteries by transcranial Doppler ultrasound. Vessel identification was based on the angle and depth of insonation. MEASUREMENTS AND MAIN RESULTS: The internal carotid artery was located more consistently than either middle cerebral or ophthalmic arteries and provided superior waveforms for analysis. Alterations in flow velocity were noted and correlated to various therapeutic interventions. Flow velocities were 70% of normal during the early phase of resuscitation but deteriorated over time until there was no evidence of net forward flow. Even early in CPR, flow was demonstrated only during systole. CONCLUSION: Transcranial Doppler ultrasound appears to be a potentially promising means of determining cerebral flow in patients undergoing CPR.

Brain↗

Transcranial Doppler ultrasonographic assessment of intermittent light stimulation at different frequencies.

Seven normal adult volunteers underwent intermittent photic stimulation at frequencies of 5-60 Hz while their posterior cerebral arteries were monitored using transcranial Doppler ultrasound. Baseline measurements were obtained under conditions of total darkness, and sampling was also done during continuous illumination. Overall variation in mean flow velocity between complete darkness and continuous illumination was 9.8%, but the maximal change (expressed as percentage deviation from baseline) occurred consistently when stimulation was undertaken at frequencies of 10 (21%) and 20 (19%) Hz (p = 0.05). Frequencies higher than 20 Hz resulted in mean flow velocity variations that were not significantly different from that found during continuous illumination. The optimal frequency of intermittent visual stimulation required to induce measurable changes in posterior cerebral artery Doppler characteristics appears to be in the range 10-20 Hz.

Adult↗

Evaluation and follow-up of carotid-cavernous fistulas by transcranial Doppler sonography: illustrative case.

The availability of transcranial Doppler sonography has resulted in an easy, noninvasive, reproducible, and highly reliable method for evaluating the flow characteristics of carotid-cavernous sinus fistulas. It also allows the follow-up of the effect of different interventional measures, specifically, embolization with detachable balloons. An illustrative case is reported, in which the findings of serial transcranial Doppler sonograms are correlated with findings on computed tomographic scans and angiograms. The impact of our findings on future approaches to the hemodynamic classification of these acquired vascular shunts is discussed.

Aged↗

Noninvasive evaluation of ischemic stroke with SPECT.

Technetium Tc 99m DTPA single photon emission computerized tomography (SPECT) brain scans of 20 patients with acute ischemic stroke were reviewed retrospectively and compared with clinical and radiologic (CT) data. Fourteen of the patients had abnormal SPECT studies. The abnormal findings were demonstrated by static views in eight patients, by the flow study in one patient, and by both sets of images in the other five patients. All abnormalities correlated with the clinical syndrome of presentation, and only two of the patients had no corresponding lesions on CT. Of the six patients with normal SPECT scans, two had abnormal CT studies, and in the other four, no lesions were shown at all. The ability of 99mTc DTPA SPECT to display cerebral infarctions appears to be, at best, comparable to that of CT. SPECT also provides qualitative information regarding flow dynamics in the affected hemisphere of some patients (6/20 in our review). This, we believe, represents the objective demonstration of the preexisting insufficient collateral flow in the hemisphere at risk for ischemic stroke.

Adult↗

Acute thalamic esotropia.

Three men developed acute esotropia, stupor, and impaired upward gaze. Vestibulo-ocular stimulation showed that the adducted eye remained immobile while the fellow eye responded normally. The alteration of consciousness, the long-tract neurologic signs, and the esotropia quickly resolved. Upgaze paresis and brief bursts of convergence-retraction nystagmus were the major residual signs. Imaging techniques demonstrated lesions of the contralateral posterior thalamus in each patient. Several mechanisms are proposed to explain the acute esotropia. Impairment of monocular projections in the contralateral posterior thalamus could disinhibit neurons in the oculomotor complex, or ischemia of inputs to neurons involved with vergence control in the midbrain could result in tonic activation of the medial rectus. The clinical and radiographic findings are consistent with infarction in the territory of penetrating branches of the basilar-communicating (mesencephalic) artery. Embolism to the top of the basilar artery is presumed to be the precipitating event.

Acute Disease↗

Cavernous sinus involvement in head and neck cancer.

Spread of tumor to intracranial structures is an infrequent and late manifestation of head and neck cancers. We recently encountered six patients with a distinct clinical syndrome due to involvement of the cavernous sinus, which forms the basis of this report. This syndrome was a source of significant morbidity and mortality, with a mean survival of only 4 months. The diagnosis is often elusive, but is now made more commonly than previously. Whether this reflects increased incidence (due to alterations in the natural history of disease by therapy) or improved diagnosis (due to modern imaging modalities) is unknown. Cavernous sinus involvement may be the first evidence of distant disease in head and neck cancer. Although survival is poor, palliation is worthwhile. Awareness of this syndrome can lead to earlier diagnosis and alteration of treatment.

Aged↗

Capture of rare cells in suspension with antibody-coated polystyrene beads.

A method for the separation of one cell type present in small number from a predominant mixture of cell types using macroscopic polystyrene beads is demonstrated. An antibody specific to murine leukocytes (CD45) was adsorbed to the surface of the beads. Beads and murine hybridoma B cells were placed in test tubes and periodically inverted at fixed time intervals, causing the beads to settle through the suspension under creeping flow conditions. Capture was dependent upon interception: the captured cells must have traveled along streamlines that brought them to within a cell radius of the bead surface. B cells attached to 99-micrometer beads (maximum shear rate 8.1 s-1) were captured with greater efficiency but in lesser quantity than those attached to 170-micrometer beads (maximum shear rate 13.9 s-1). Cell capture unexpectedly reached a plateau in less than 2 h, a phenomenon that appears to involve changes in both the cells and the beads. Capture of cells was effective out to dilutions of 1:10 000 with purity in the captured population of better than 74%. This method allows for the study of physical parameters important for cell attachment and capture as well as for practical separation of rare cells.

Animals↗