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Biomedical subjects

J Frank

Publications and source records attributed to J Frank.

At least 307 records · Page 17Linked to original sources
PubMed1988

Classification of images of biomolecular assemblies: a study of ribosomes and ribosomal subunits of Escherichia coli.

Images of macromolecules obtained in the electron microscope are subjected to correspondence analysis. The structure inherent in the data in the resulting low-dimensional factor space is characterized by a mixed classification method which combines the dynamic clouds clustering technique with hierarchical ascendant classification (HAC). For our data, the rejection of marginal clusters obtained by dynamic clouds clustering appears as a crucial prerequisite for a stable performance of HAC. The method is applied to two sets of 204 and 177 images that show the 70S ribosome of Escherichia coli, in the range of overlap views as defined by A. Verschoor and co-workers, and to two sets of 480 and 496 images of the 50S subunit of E. coli depleted of L7/L12 proteins in the well-defined crown view. Reproducible classes are obtained, which are characterized by images reconstituted from factorial coordinates. These classes appear to be related to different orientations on the specimen grid (in the case of the 70S particle) and to different conformational states (50S subunit).

Escherichia coli↗
PubMed1988

Spinal cord artifacts from truncation errors during MR imaging.

The significance of linear regions of altered signal intensity that appear in sagittal magnetic resonance (MR) images along the length of the spinal cord was investigated. Examinations were performed on ten healthy volunteers and one patient with spinal cord edema. A 0.5-T or a 1.5-T MR system was used. Sampling-related effects (Gibbs phenomenon) at spinal cord edges and cerebrospinal fluid interfaces can lead to different signal patterns within the spinal cord and canal. These artifacts cause problems in interpretation, especially with the use of small object-to-pixel size ratios, by obscuring anatomy and simulating pathologic conditions such as pseudosyringes. Analysis of these intensity variations and of their dependence on sampling may improve the clinical accuracy of MR imaging.

Humans↗
PubMed1987

Three-dimensional structure of the large ribosomal subunit from Escherichia coli.

The three-dimensional structure of the large (50S) ribosomal subunit from Escherichia coli has been determined from electron micrographs of negatively stained specimens. A new method of three-dimensional reconstruction was used which combines many images of individual subunits recorded at a single high tilt angle. A prominent feature of the reconstruction is a large groove on the side of the subunit that interacts with the small ribosomal subunit. This feature is probably of functional significance as it includes the regions where the peptidyl transferase site and the binding locations of the elongation factors have been mapped previously by immunoelectron microscopy.

Escherichia coli↗
PubMed1987

Hospital treatment of patients with pending criminal charges: an ecological approach.

The treatment of hospitalized patients facing criminal charges is shaped by both their psychopathology and by their involvement with the criminal justice system. Psychopathologic presentation, motivation for hospitalization and/or discharge planning may be influenced by delays and uncertainties generated by the legal system. A review of the often informal nature of the criminal justice process suggests options for clinically oriented intervention in expediting the resolution of patients' psychiatric and legal difficulties.

Antisocial Personality Disorder↗
PubMed1987

Interrelatedness of 5S RNA sequences investigated by correspondence analysis.

Correspondence analysis (a form of multivariate statistics) applied to 74 5S ribosomal RNA sequences indicates that the sequences are interrelated in a systematic, nonrandom fashion. Aligned sequences are represented as vectors in a 5N-dimensional space, where N is the number of base positions in the 5S RNA molecule. Mutually orthogonal directions (called factor axes) along which intersequence variance is greatest are defined in this hyperspace. Projection of the sequences onto planes defined by these factorial directions reveals clustering of species that is suggestive of phylogenetic relationships. For each factorial direction, correspondence analysis points to regions of "importance," i.e., those base positions at which the systematic changes occur that define that particular direction. In effect, the technique provides a rapid determination of group-specific signatures. In several instances, similarities between sequences are indicated that have only recently been inferred from visual base-to-base comparisons. These results suggest that correspondence analysis may provide a valuable starting point from which to uncover the patterns of change underlying the evolution of a macromolecule, such as 5S RNA.

Analysis of Variance↗
PubMed1987

Assessment of protein purity by chromatography and multiwavelength detection.

Commercial protein preparations were analyzed for purity on a size-exclusion column coupled to a photodiode array detector. Two methods that are commonly supplied by the manufacturers of these detectors were used to establish the purity of the eluting peaks. These methods are based on (i) a visual inspection of the superposition of normalized spectra taken upslope, at the apex, and downslope and (ii) the variation of the ratio of the absorbance measured at two different wavelengths. The results obtained were compared with those of a newly developed method, based on a comparison of at least eight peak spectra by means of their correlation coefficients. It was found that the first two methods were not reliable in the case of protein peaks containing a spectrally similar impurity, while with the third method it was possible to detect the presence of only 2% (w/w) of a spectrally closely resembling protein contaminant (r = 0.9997), eluting with a chromatographic resolution of 0.37 sigma. Analysis of the samples with polyacrylamide gel electrophoresis indicated that the new method is at least equally suited to assess protein purity, provided a minimal resolution is achieved by the chromatographic system.

Chromatography, High Pressure Liquid↗
PubMed1987

Cytochrome c binds to lipid domains in arrays of mitochondrial outer membrane channels.

Computer-averaged electron microscopic images of negatively stained crystalline arrays of fungal mitochondrial outer-membrane channels in the presence and absence of cytochrome c were compared. Neither the apo- nor the holo- forms of cytochrome c significantly changed the stain distribution in the protein regions of the channel arrays. However, both forms of cytochrome c caused significant stain exclusion from the lipid domains in the arrays, suggesting binding of the polypeptides at these loci. The implications of binding of apocytochrome c to clusters of exposed phospholipids on the mitochondrial outer membrane are discussed with respect to the mechanism of uptake of this polypeptide by mitochondria.

Computer Simulation↗
PubMed1987

Three-dimensional reconstruction from a single-exposure, random conical tilt series applied to the 50S ribosomal subunit of Escherichia coli.

We present a new reconstruction method that takes advantage of the fact that many biological macromolecular assemblies show a preferred orientation with respect to the plane of the specimen grid in the electron microscopic preparation. From one micrograph taken of such a specimen tilted by a large angle, a conical tilt series with random azimuthal angles can be extracted and used for a three-dimensional reconstruction. Our technique allows the determination of the molecular structure under low-dose conditions, which are not achievable with reconstruction methods that use conventional tilt series. The reconstruction method combines a number of existing image processing techniques with a newly developed weighted back-projection algorithm designed for three-dimensional reconstruction from projections taken with arbitrary projecting directions. The method is described as it was applied to the three-dimensional reconstruction of the structure of the 50S ribosomal subunit of Escherichia coli (E. coli).

Escherichia coli↗
PubMed1987

Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial. A phase III, Southwest Oncology Group Study (7613).

The term soft tissue sarcoma refers to a large variety of malignant tumors arising in extraskeletal connective tissues that connect, support, and surround discrete anatomic structures. All visceral organs also contain a connective stroma that can undergo malignant transformation. Because of the histological similarities of this group of tumors and their relative rarity, treatment prescriptions for patients that have disseminated disease are most often uniform. In this study, we asked the question whether adding a third drug (cyclophosphamide or actinomycin D) to Adriamycin (Adr [Adria Laboratories, Columbus, OH])-(3,3-dimethyl-1-triazeno)- imidazole-4-carboxamide (DTIC) would improve the response rate and/or survival. A unique feature of this cooperative group clinical trial was the mandatory pathology review of the histological material. All patients of the Southwest Oncology Group between June 1, 1976, and November 17, 1979, who had a biopsy-confirmed diagnosis of a soft tissue sarcoma with convincing clinical or biopsy-documented evidence of metastatic disease were eligible for the study. Patients were randomized to receive (1) Adr, 60 mg/m2 intravenously, day 1, and DTIC, 250 mg/m2 every 3 weeks (104 patients); (2) Adr and DTIC as in (1) and cyclophosphamide, 500 mg/m2, day 1 (112 patients); or (3) Adr and DTIC as in (1) and actinomycin D, 1.2 mg/m2, day 1, (119 patients). There was no statistically significant difference in response rates (33%, 34%, and 24%) (P = .25). Median durations of response were 31 weeks in the Adr-DTIC arm, 26 weeks in the cyclophosphamide-DTIC-Adr arm, and 23 weeks in the Adr-DTIC-Actinomycin D arm (P = .78). Median durations of survival were 37, 42, and 50 weeks, respectively. Again, no statistically significant differences were observed (P = .59). Toxicities from each of these treatment arms were formidable and were equivalent. Prognostic factor analysis showed a prognosis based on bone marrow reserve, sex, and pathology subtype favorable to patients.

Adolescent↗
PubMed1987

Evaluation of the demented patient.

An adequate history from the patient and a family member, an examination for signs and symptoms suggestive of contributing organic disease, plus an individualized diagnostic battery of laboratory tests are sufficient workup for most patients presenting with the dementia syndrome. Electroencephalography, computerized axial tomographic scanning, or psychometric testing are not usually required. The results of eight studies investigating demented individuals are reviewed. Across these studies, 56 percent of cases were attributable to primary dementia, 15 percent were secondary to reversible causes, 13 percent were secondary to irreversible conditions, and 15 percent of individuals had been wrongly labeled demented. Of reversible dementias including depression, 56 percent of patients improved with therapy. Metabolic disorders were associated with about 25 percent of reversible dementias and accounted for less than 5 percent of all patients investigated for the dementia syndrome.

Aged↗
PubMed1986

Purification and characterization of quinoprotein glucose dehydrogenase from Acinetobacter calcoaceticus L.M.D. 79.41.

Quinoprotein glucose dehydrogenase (EC 1.1.99.17) from Acinetobacter calcoaceticus L.M.D. 79.41 was purified to homogeneity. It is a basic protein with an isoelectric point of 9.5 and an Mr of 94,000. Denaturation yields two molecules of PQQ/molecule and a protein with an Mr of 48000, indicating that the enzyme consists of two subunits, which are probably identical because even numbers of aromatic amino acids were found. The oxidized enzyme form has an absorption maximum at 350 nm, and the reduced form, obtained after the addition of glucose, at 338 nm. Since double-reciprocal plots of initial reaction rates with various concentrations of glucose or electron acceptor show parallel lines, and substrate inhibition is observed for glucose as well as for electron acceptor at high concentrations, a ping-pong kinetic behaviour with the two reactants exists. From the plots, Km values for glucose and Wurster's Blue of 22 mM and 0.78 mM respectively, and a Vmax. of 7.730 mumol of glucose oxidized/min per mg of protein were derived. The enzyme shows a broad substrate specificity for aldose sugars. Cationic electron acceptors are active in the assay, anionic acceptors are not. A pH optimum of 9.0 was found with Wurster's Blue and 6.0 with 2,6-dichlorophenol-indophenol. Two types of quinoprotein glucose dehydrogenases seem to exist: type I enzymes are acidic proteins from which PQQ can be removed by dialysis against EDTA-containing buffers (examples are found in Escherichia coli, Klebsiella aerogenes and Pseudomonas sp.); type II enzymes are basic proteins from which PQQ is not removed by dialysis against EDTA-containing buffers (examples are found in A. calcoaceticus and Gluconobacter oxydans).

Acinetobacter↗
PubMed1986

Hydrazone formation of 2,4-dinitrophenylhydrazine with pyrroloquinoline quinone in porcine kidney diamine oxidase.

Homogeneous diamine oxidase (EC 1.4.3.6) from porcine kidney was treated with the inhibitor 2,4-dinitrophenylhydrazine (DNPH). The coloured compounds formed were detached with pronase and purified to homogeneity. When the reaction with DNPH was conducted under an O2 atmosphere, the product (obtained in a yield of 55%) was the C(5)-hydrazone of pyrroloquinoline quinone (PQQ) and DNPH, as revealed by its chromatographic behaviour, absorption spectrum and 1H-NMR spectrum. Only 6% of this hydrazone was formed under air, the main product isolated being an unidentified reaction product of DNPH with the enzyme. Porcine kidney diamine oxidase is the second mammalian enzyme shown to have PQQ as its prosthetic group. In view of the requirements for hydrazone formation with DNPH, it is incorrect to assume that inhibition of this type of enzymes with common hydrazines is simply due to blocking of the carbonyl group of its cofactor.

Amine Oxidase (Copper-Containing)↗
PubMed1986

Computer-averaged views of the 70 S monosome from Escherichia coli.

The prokaryotic (70 S) monosome, composed of a roughly hemispherical 50 S large subunit and an elongate 30 S small subunit, appears in the electron micrograph in only a few common views representing the small number of preferred orientations assumed by the particle. Two of these, termed O and L views, have previously been characterized as the overlap and non-overlap projections; a third view, which we term the R view, represents the other endpoint of a rotational continuum with the overlap or O view. Tilt studies enabled us to calibrate this range as spanning approximately 50 degrees. The disjunct set of L views was averaged, and the reproducible resolution was determined to be 1/3.5 nm-1. The combined sets of O and R views were analyzed by correspondence analysis, and a continuous "rotation series" of subaverages was obtained. Interpretation of the views in the light of what is known about the morphologies of the individual subunits allows a general picture of the mutual fit of the subunits in the monosome to be conceived.

Computers↗
PubMed1986

Purification, crystallization and preliminary X-ray investigation of quinoprotein methylamine dehydrogenase from Thiobacillus versutus.

The enzyme methylamine dehydrogenase or primary-amine:(acceptor) oxidoreductase (deaminating) (EC 1.4.99.3) was purified from the bacterium Thiobacillus versutus to homogeneity, as judged by polyacrylamide gel electrophoresis. The native enzyme has a Mr of 123 500 and contains four subunits arranged in a alpha 2 beta 2 configuration, the light and heavy subunits having a Mr of 12900 and 47500 respectively. The isoelectric point is 3.9. The purified enzyme was crystallized from 37--42% saturated ammonium sulphate in 0.1 M sodium acetate buffer, pH 5.0. The space group is P3(1)21 or P3(2)21, with one alpha 2 beta 2 molecule in the asymmetric unit. The cell dimensions are: a = b = 13.01 nm; c = 10.40 nm. The X-ray diffraction pattern extends to at least 0.25-nm resolution.

Crystallization↗