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Biomedical subjects

S J Nelson

Publications and source records attributed to S J Nelson.

At least 19 recordsLinked to original sources
PubMed1992

Detection of significant features and statistical analysis of 2D and 3D images of 31P metabolites.

The application of spectroscopy techniques to the study of normal and pathological tissue is currently limited by the difficulties of acquiring precisely localized spectra and analyzing the resulting, relatively low signal-to-noise data. Interpretation of multivoxel spectroscopy data is greatly facilitated by estimating peak parameters and representing their spatial distribution as metabolite images. We present here the new algorithm MIMSTATS, which performs an analysis of these images and determines whether the variations in the images are statistically significant. The algorithm has been developed and tested by application to 31P CSI data from the human forearm and brain. Our results demonstrate that MIMSTATS can detect signal at a very low signal-to-noise ratio in a reliable and reproducible fashion and provides a sound basis for testing hypotheses concerning differences in distribution of metabolites.

Algorithms↗
PubMed1992

Simultaneous detection of ferritin and HIV-1 in reactive microglia.

Using ferritin as a marker of reactive microglia, we demonstrated a close association between proliferation of reactive microglia and expression of human immunodeficiency virus type 1 (HIV-1) in brain tissue from autopsied cases of acquired immunodeficiency syndrome (AIDS). An increased number of ferritin-positive reactive microglia was observed in formalin-fixed paraffin-embedded brain sections from all 13 AIDS cases examined. Similar findings were observed in brain tissue from other neurological diseases (subacute sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis). Multinucleated giant cells were found in 7 of the AIDS cases which were also intensely labeled for ferritin. Dual-label immunohistochemistry using anti-ferritin and cell-specific markers showed that ferritin-positive cells were distinct from astrocytes, neurons and endothelia using anti-glial fibrillary acidic protein (anti-GFAP), anti-neurofilament protein and Ulex europaeus agglutinin 1, respectively. In 5 AIDS brains, only ferritin-positive cells were shown to contain HIV-1 gp41 antigen using dual-label immunohistochemistry. In addition, HIV-1 RNA was localized in ferritin-positive reactive microglia but not in GFAP-positive astrocytes using immunohistochemistry combined with in situ hybridization. Ferritin-positive reactive microglia and multinucleated giant cells were co-labeled with the microglial marker, Ricinus communis agglutinin 1 (RCA-1). However, RCA-1 also extensively stained resting microglia only a few of which were co-labeled for ferritin. The density of ferritin-positive cells was correlated with the presence of HIV-1 RNA-positive cells in AIDS brain. Thus, ferritin immunoreactivity can be used as an activation marker of microglia in archival paraffin sections and reflects the extent of inflammation in HIV-1-infected brain.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Unusual patterns of Histoplasma capsulatum meningitis and progressive multifocal leukoencephalopathy in a patient with the acquired immunodeficiency virus.

Disseminated histoplasmosis (DH) and progressive multifocal leukoencephalopathy occur in acquired immunodeficiency syndrome (AIDS). At autopsy, DH patients with central nervous system involvement almost always show extensive involvement of the lungs and reticuloendothelial system in addition to the brain, and progressive multifocal leukoencephalopathy is manifest as multiple demyelinating lesions in several locations in the brain. We describe an AIDS patient with a long history of aggressively treated DH who died with DH in the brain only; fungus was not found elsewhere at autopsy. In addition, there was a papovavirus infection restricted to the cerebellum with predominant involvement of the internal granular cell layer; again, demyelinating lesions were not found elsewhere in the brain. Each of these patterns of brain involvement is rare. As the incidence of AIDS increases and patients are treated aggressively, the frequency of unusual neuropathologic patterns of opportunistic infections may be expected to increase.

Acquired Immunodeficiency Syndrome↗
PubMed1992

HIV-1 in postmortem brain tissue from patients with AIDS: a comparison of different detection techniques.

OBJECTIVE: The presence of HIV-1 in postmortem brain tissue from 31 patients with AIDS and 12 HIV-1-negative controls was investigated. DESIGN: Most laboratories have access to the methods used. We readily applied in situ hybridization and immunohistochemistry to archival formalin-fixed paraffin-embedded (FFPE) brain specimens. METHODS: The techniques used to detect HIV-1 were explant culture, in situ hybridization with 35S-labeled polymerase (pol) gene riboprobes and immunohistochemistry with monoclonal antibody to gp41. RESULTS: HIV-1 was isolated from explant cultures in 13 out of 20 (65%) patients, whereas HIV-1-infected cells were detected in FFPE brain tissue from nine out of 26 (35%) patients examined by in situ hybridization and in seven out of 26 (27%) patients examined by immunohistochemistry. CONCLUSIONS: Although the isolation technique was the most sensitive of the three techniques tested, infected cells may be identified with in situ hybridization in conjunction with immunohistochemistry.

AIDS-Related Opportunistic Infections↗
PubMed1992

Two-dimensional 31P-chemical shift imaging of intramuscular heterogeneity in exercising human forearm muscle.

Two-dimensional phosphorus chemical shift imaging (2D-31P-CSI) was used to investigate macroscopic heterogeneity within the flexor digitorum profundus (FDP) muscle of the human forearm during exercise. Subjects performed low-frequency steady-state finger flexion exercise at submaximal work levels using a bulb ergometer. The number of fingers actively involved in finger flexion exercise was varied in a total of 12 experiments. Active muscles could be determined by the increase of Pi and decrease of phosphocreatine observed in the localized spectra. Within the FDP, regions of active and inactive fibers were significantly different in levels of Pi and phosphocreatine (P less than 0.01) during flexion of individual fingers. Individual flexion of the index finger was found to involve only fibers in the deep region of the FDP. Fibers in the central region were found to be involved in flexion of the middle finger, and fibers in the superficial region were involved in flexion of the ring and little fingers. The results of this study demonstrate the potential of 2D-31P-CSI for in vivo investigation of intramuscular heterogeneity in human skeletal muscle.

Adult↗
PubMed1992

Anthelmintic activity of dioxapyrrolomycin.

Dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 produced by UC 11065 were evaluated as anthelmintics. Assays used to examine these compounds included effects on the free-living nematode Caenorhabditis elegans, ability to clear target nematodes (Haemonchus contortus and Trichostrongylus colubriformis) from jirds, and clearance of Haemonchus contortus from lambs. A crude extract of UC 11065 containing dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 was active against C. elegans and against H. contortus in the jird. Purified and/or synthetic samples of dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 were tested in the jird model; only dioxapyrrolomycin exhibited appreciable activity against H. contortus (greater than or equal to 90.9% clearance at 0.33 mg/jird), while none of the compounds showed appreciable activity against T. colubriformis. Dioxapyrrolomycin cleared 99.9% of H. contortus from lambs at 12.5 mg/kg. An in vitro migration study using susceptible and closantel-resistant H. contortus showed there is cross-resistance between dioxapyrrolomycin and closantel. Dioxapyrrolomycin appears to be a narrow-spectrum anthelmintic which works through a closantel-like mode-of-action.

Actinomycetales↗
PubMed1992

The homogenization of the Metathesaurus schema and distribution format.

The third version of the UMLS Metathesaurus, Meta-1.2, to be released in October 1992, will have a simpler schema and simpler distribution formats than the first two versions, Meta-1.0 and Meta-1.1 released in October 1990 and 1991, respectively. For one thing, it will have only a single kind of entry (Concept), rather than three (Concept, Related, and Synonym). Further, the Relational Format, will consist of four logical relations, or tables, instead of the nearly three score different tables used to represent the same kind of information in Meta-1.1. These four tables will contain, respectively, (1) the names of each concept, (2) the relationships between concepts, (3) attributes of the concepts, and (4) a word-based index into the concept names. We argue that the new schema and formats provide a better conceptual model of the Metathesaurus, and represent the information contained there more uniformly. Even though these changes are incremental and evolutionary, both users and software developers should find the Meta-1.2 significantly easier to understand, and the information contained in it significantly easier to use.

Information Storage and Retrieval↗
PubMed1992

The semantic structure of the UMLS Metathesaurus.

Meta-1.1, the UMLS metathesaurus, represents medical knowledge in the forms of names of concepts and links between those concepts. The representations of the semantic neighborhood of a concept can be thought of as dimensions of the property of semantic locality and include term information (broader, narrower, or otherwise related), the contextual information (parent-child, siblings in a hierarchy), the semantic types, and the co-occurrence data (links discovered empirically from concepts used to index the medical literature.) The degree of redundancy of each of these dimensions was investigated by reviewing the extent of multiple presentations of concepts which appear as related to a given concept. The degree of overlap was surprisingly small. While the co-occurrence data finds some of the links represented by other dimensions, those links are but minute fractions of the vast amount of co-occurrence derived links. Because parent-child relationships are often subsumptive (or categorical) in nature, it might be expected that siblings usually share the same semantic types. While true in the aggregate, the wide variance in percent of types shared may reflect the intended usages of the source vocabularies. Noun phrases were extracted from the definitions of 40 concepts in Meta-1 in order to assess systematically the coverage of important concepts by Meta-1, and to assess whether the links between these definitional concepts, which may have special value, and the concept being defined were indeed present. Out of 161 of these definitional concepts, 29 were not represented in Meta-1, and 37 of those represented in Meta-1 had no direct link to the concept they were defining.(ABSTRACT TRUNCATED AT 250 WORDS)

Semantics↗
PubMed1991

Free magnesium levels in normal human brain and brain tumors: 31P chemical-shift imaging measurements at 1.5 T.

We have studied a series of normal subjects and patients with brain tumors, by using 31P three-dimensional chemical shift imaging to obtain localized 31P spectra of the brain. A significant proportion of brain cytosolic ATP in normal brain is not complexed to Mg2+, as indicated by the chemical shift delta of the beta-P resonance of ATP. The ATP beta-P resonance position in brain thus is sensitive to changes in intracellular free Mg2+ concentration and in the proportion of ATP complexed with Mg because this shift lies on the rising portion of the delta vs. Mg2+ titration curve for ATP. We have measured the ATP beta-P shift and compared intracellular free Mg2+ concentration and fractions of free ATP for normal individuals (n = 6) and a limited series of patients with brain tumors (n = 5). In four of the five spectra obtained from brain tissue containing a substantial proportion of tumor, intracellular free Mg2+ was increased, and the fraction of free ATP was decreased, compared with normal brain.

Adenosine Triphosphate↗
PubMed1991

Detection of herpesvirus DNA in vitreous and aqueous specimens by the polymerase chain reaction.

Members of the herpesvirus family, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV), have been recognized as causal agents of chorioretinal inflammatory diseases. We investigated the use of the polymerase chain reaction for the detection of CMV, HSV, and EBV genomes in aqueous, subretinal fluid, and vitreous specimens in patients with clinically diagnosed CMV retinitis. Cytomegalovirus but not HSV or EBV genomic sequences were detected in all of these clinical specimens. We also investigated 18 normal aqueous and eight normal vitreous specimens obtained from patients undergoing cataract or vitrectomy surgery. Cytomegalovirus, HSV, and EBV DNA were not detected in any of the normal aqueous specimens. There was one weakly positive CMV normal vitreous, but none was HSV or EBV positive by the polymerase chain reaction. These results indicate that the polymerase chain reaction may be useful as a rapid and sensitive diagnostic technique to aid in the confirmation of clinical observations.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Metabolite images of the human arm: changes in spatial and temporal distribution of high energy phosphates during exercise.

Localized variations in metabolites in resting and exercising skeletal muscle have been studied using Chemical Shift Imaging (CSI) techniques to obtain 2-D arrays of 31P NMR spectra from a slice through the human forearm. The excitation profile of the coil resulted in a slice thickness of ca 80 mm and the planar resolution of the CSI data corresponded to either 7, 10 or 14 mm. The metabolite information was represented both as 2-D arrays of spectra and by constructing images of the spatial distribution of different metabolites. Correlation with the anatomy was clearly visualized by overlaying the metabolite images on the appropriate region of the corresponding proton images. At rest, significant variations in the intensity of Pi, phosphocreatine (PCr) and ATP were observed in different regions of the arm. Our planar spatial and temporal (1-9 min) resolution was also sufficient to follow changes in Pi, PCr and pH in response to exercise. These changes were restricted to the exercising muscle and demonstrated heterogeneity both in the kinetics and magnitude of response between different muscles.

Adenosine Triphosphate↗
PubMed1991

Vectorial analysis of the static equilibrium of forces generated in the mandible in centric occlusion, group function, and balanced occlusion relationships.

Mechanical analyses supporting various and prevailing stomatognathic concepts of occlusal function are sparse. This study, using a mechanical model, simulates a system in function and provides a vectorial analysis based on a static equilibrium of forces generated in a mandible at 10 different positions. The positions analyzed were one in centric occlusion and nine in eccentric positions. Four eccentric positions were in a balanced occlusal relationship and five were in group function. Among other conclusions that were drawn, the most relevant seems to be the finding that cusp inclines and condylar path inclination have a profound influence on the forces acting within the joints and dentition.

Bite Force↗
PubMed1991

Refinement of the main chain directed assignment strategy for the analysis of 1H NMR spectra of proteins.

The underlying basis of the main chain directed (MCD) resonance assignment strategy for the analysis of 1H NMR spectra of proteins is reexamined. The criteria used in the construction of the patterns used in the MCD method have been extended to increase the robustness of the approach to the presence of variable protein secondary structure and significant spectral degeneracy. These criteria have led to the development of several dozen patterns exclusively involving the short distance relationships between main chain amide NH-C alpha-H-C beta H (NAB) J-coupled subspin systems of the amino acid residues. The MCD patterns have been examined for fidelity and frequency of occurrence in a database composed of the high resolution crystal structures of 39 proteins. The analysis has identified several extremely robust patterns, suitable for initiating a hierarchical construction of units of secondary structure based upon a systematic analysis of two-dimensional nuclear Overhauser effect spectra. A formal procedure, suitable for the computer assisted application of the MCD strategy, is developed. This procedure, termed MCDPAT, has been applied to the analysis of the crystal structures of human ubiquitin, T4 lysozyme, and ribonuclease A. It has been found that the MCDPAT procedure is conservative producing no significant errors and is globally successful in correctly identifying the appropriate units of secondary structure contained in these three proteins.

Enzymes↗
PubMed1991

Implementation of the main chain directed assignment strategy. Computer assisted approach.

A computer-assisted procedure has been developed to apply the main chain directed (MCD) assignment strategy to the analysis of 1H NMR spectra of proteins. The underlying mathematical foundation of this procedure, termed MCDPAT, is presented. MCDPAT is based upon the expanded library of MCD patterns defined previously (A.J. Wand and S.J. Nelson. 1991. Biophys. J. 59:1101-1112), and has been evaluated with both simulated and experimental data from the protein ubiquitin. The influence of the precision, spectral variation, and inherent degeneracy upon the design of the procedure is explored. Several approaches have been taken to overcome the uncertainty introduced by these variables. These include a hierarchical approach to both primary pattern recognition and subsequent construction of MCD-defined units of secondary structure. It is shown that the MCDPAT procedure, in conjunction with automated statistically based spectral analysis, leads to the successful MCD assignment of the protein ubiquitin. The implications and limitations of this approach are discussed.

Hydrogen↗
PubMed1991

Dynamic stereotactic radiosurgery using a linear accelerator.

We describe a system for stereotactic radiosurgery with a linear accelerator. This technique allows treatment of small (less than 40 mm diameter) intracranial lesions, including vascular malformations, and primary and metastatic tumors that are deep within the brain or in areas not amenable to open surgery. A beam of ionizing radiation (1800 to 2500 cGy) is focused on the center of the lesion, which is determined by stereotactic localization. "Dynamic rotation" of the linac gantry and table continuously about this predetermined point ensures that only the lesion receives the full radiation dose, while the normal structures in the head receive minimal amounts of radiation. The system combines, for the first time in one place, elements of radiosurgical technique developed at various centers. Testing for accuracy compares favorably with results at other centers using linac-based systems as well as comparing favorably with the gamma knife.

Brain Neoplasms↗
PubMed1991

Biomedical database inter-connectivity: an experiment linking MIM, GENBANK, and META-1 via MEDLINE.

The linkage of disparate biomedical databases is an important goal of the Unified Medical Language (UMLS) Project. We conducted an experiment to investigate the feasibility of using UMLS resources to link databases in clinical genetics and molecular biology. References from MIM ("Mendelian Inheritance in Man") were lexically mapped to the equivalent citations in MEDLINE. The MeSH major subject headings by which the citations in a particular MIM entry had been indexed were used to develop a "genetic-disorder-centered view of the world" in Meta-1 (the first official version of the UMLS Metathesaurus). Our hypothesis was that these MeSH subject headings could provide access to a "semantic neighborhood" in Meta-1 that would be relevant to a particular genetic disorder. By browsing in this "semantic neighborhood," a user could select various combinations of terms with which to search MEDLINE through an interface between Meta-1 and Grateful Med. Such searches might retrieve citations that were more recent than those in MIM or that provided useful supplementary information. Since some MEDLINE records contain pointers to entries in GENBANK, information about genetic sequences related to a particular clinical genetic disorder could also be retrieved. This scenario was implemented for a small number of MIM entries, providing a concrete demonstration that linking disparate electronic databases in an important subdomain of biomedicine is relatively straightforward.

Databases, Factual↗
PubMed1991

From meaning to term: semantic locality in the UMLS Metathesaurus.

The Unified Medical Language System Metathesaurus represents the results of a synthesis of existing biomedical naming systems (thesauri). The naming and other information about the meanings in the Metathesaurus can be used to find the preferred naming of that meaning in the source chosen by the user, by exploiting the property of semantic locality. The aspects of semantic locality in the Metathesaurus which can be thus exploited are the terms, the semantic types, the use of that term in a source context, and the co-occurrence of terms in MEDLINE. To find how a meaning is named in the source of choice, a user must exploit one of these aspects of semantic locality, entering a term somehow related to the term being sought, and navigating to the preferred term. While the first three of these aspects of semantic locality are normative, the last is empirical. Testing of the utility of the aspects of semantic locality in information retrieval would require a uniform interface with 1, no Metathesaurus, 2, the Metathesaurus without the aspects in question, and 3, the Metathesaurus including all the aspects. Other potential uses of empirically derived semantic locality include defining or suggesting potentially relevant concepts in a given situation.

Semantics↗