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Biomedical subjects

A Engel

Publications and source records attributed to A Engel.

At least 163 records · Page 9Linked to original sources
PubMed1996

Brain abscesses: the lung connection.

Pulmonary arteriovenous fistulas are uncommon abnormalities of capillary development which cause right to left shunting and, if not treated, may lead to severe neurological complications, including meningitis and brain abscess. Pulmonary arteriovenous fistulas are commonly a result of hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease) and both conditions may be readily diagnosed by careful history taking and physical examination. Two cases of brain abscess associated with hereditary haemorrhagic telangiectasia, which remained unrecognized for many years, are reported. These cases emphasize the importance of early diagnosis and treatment of pulmonary arteriovenous fistula in preventing central nervous system infections.

Adult↗
PubMed1996

Levels of cytokines and cytokine inhibitors in the neutropenic patient with alpha-hemolytic streptococcus shock syndrome.

The pathogenesis of alpha-hemolytic streptococcus shock syndrome (SS), a life-threatening complication in neutropenic patients following aggressive chemotherapy that is caused by viridans streptococci, is unknown. We measured serum concentrations of proinflammatory and antiinflammatory cytokines and T cell activation markers in two patients with lethal alpha-hemolytic streptococcus SS. The results were compared with those for controls, two neutropenic patients with uncomplicated bacteremia due to gram-positive organisms and four patients with neutropenia and bacteremia due to gram-negative organisms (two of whom had lethal septic shock). In patients with alpha-hemolytic streptococcus SS, levels of interleukin (IL) 1 were undetectable, levels of tumor necrosis factor (TNF) alpha were only slightly elevated, and IL-6 was the only proinflammatory cytokine that was found in high concentrations and had a late peak level at the time of clinical deterioration. IL-6 levels were much higher in patients with alpha-hemolytic streptococcus SS than in controls with uncomplicated bacteremia due to gram-positive organisms but were comparable with those in controls with bacteremia due to gram-negative organisms. Soluble TNF receptor fragments and IL-1 receptor antagonist apparently were not protective despite high serum concentrations.

Adult↗
PubMed1996

Conformational change of the hexagonally packed intermediate layer of Deinococcus radiodurans monitored by atomic force microscopy.

Both surfaces of the hexagonally packed intermediate (HPI) layer of Deinococcus radiodurans were imaged in buffer solution by atomic force microscopy. When adsorbed to freshly cleaved mica, the hydrophilic outer surface of the HPI layer was attached to the substrate and the hydrophobic inner surface was exposed to the stylus. The height of a single HPI layer was 7.0 nm, while overlapping edges of adjacent single layers adsorbed to mica had a height of 14.7 nm. However, double-layered stacks with inner surfaces facing each other exhibited a height of 17.4 nm. These stacks exposed the outer surface to the stylus. The different heights of overlapping layers and stacks are attributed to differences in the interaction between inner and outer surfaces. At high resolution, the inner surface revealed a protruding core with a central pore connected by six emanating arms. The pores exhibited two conformations, one with and the other without a central plug. Individual pores were observed to switch from one state to the other.

Bacterial Proteins↗
PubMed1996

Lesions of the acetabular labrum: accuracy of MR imaging and MR arthrography in detection and staging.

PURPOSE: To determine the accuracy of magnetic resonance (MR) imaging and MR arthrography in the detection and staging of lesions of the acetabular labrum. MATERIALS AND METHODS: Fifty-seven hips of 56 patients with chronic hip pain and a strong clinical suspicion of labral lesions were examined with a three-dimensional gradient-echo sequence in the coronal oblique and sagittal oblique projections before and after the intraarticular injection of gadopentetate dimeglumine. The labra were evaluated on the basis of morphology, signal intensity, the presence or absence of a tear, and their attachment to the acetabulum. Twenty-two of the hips underwent surgical intervention, and 35 hips were treated conservatively. RESULTS: Twenty of the 22 labra with surgical proof were staged accurately with MR arthrography. On the conventional MR images, only eight of the 22 labra were staged correctly. Whereas the sensitivity of MR arthrography was 90% and its accuracy was 91%, the sensitivity of MR imaging was 30% and its accuracy was 36%, compared with surgical findings. CONCLUSION: MR arthrography enables accurate detection and staging of lesions of the acetabular labrum and appears to be indicated in the assessment of chronic hip pain in patients with a strong suspicion of labral lesions.

Acetabulum↗
PubMed1996

Does benzene cause multiple myeloma? An analysis of the published case-control literature.

Two case series and two epidemiological studies in the 1970s and 1980s suggested that benzene exposure might be a risk factor for multiple myeloma. An analysis has now been conducted of the published population-based and hospital-based case-control studies published through mid-1995 that permit examination of the relationship between multiple myeloma and benzene exposure or surrogates for benzene exposure. No increased association was found between multiple myeloma and benzene exposure or exposure to chemical groups that included benzene. The odds ratios from these analyses approximated 1.0. Exposures to petroleum products and employment in petroleum-related occupations did not appear to be risk factors for multiple myeloma. Cigarette smoking, as a surrogate of benzene exposure, was not found to be associated with myeloma, while some studies of products of combustion described as "engine exhaust" did show a significant association with multiple myeloma. In toto, the population-based and hospital-based case-control literature indicated that benzene exposure was not a likely causal factor for multiple myeloma.

Benzene↗
PubMed1995

Functional significance of symmetrical versus asymmetrical GroEL-GroES chaperonin complexes.

The Escherichia coli chaperonin GroEL and its regulator GroES are thought to mediate adenosine triphosphate-dependent protein folding as an asymmetrical complex, with substrate protein bound within the GroEL cylinder. In contrast, a symmetrical complex formed between one GroEL and two GroES oligomers, with substrate protein binding to the outer surface of GroEL, was recently proposed to be the functional chaperonin unit. Electron microscopic and biochemical analyses have now shown that unphysiologically high magnesium concentrations and increased pH are required to assemble symmetrical complexes, the formation of which precludes the association of unfolded polypeptide. Thus, the functional significance of GroEL:(GroES)2 particles remains to be demonstrated.

Adenosine Triphosphate↗
PubMed1995

Ocular lens gap junctions: protein expression, assembly, and structure-function analysis.

Recent advances in understanding lens fiber gap junction formation are reviewed. These include studies of junctional protein expression in the embryonic lens, and of age related changes affecting gap junction structure and composition in the adult lens. An in vitro assembly system based on detergent solubilized pore complexes and endogenous lipids has been developed to provide information on the molecular interactions involved in gap junction formation and to provide material for structure analysis. Important information on the electrical properties of lens gap junction channels is obtained using electrophysiological techniques including planar lipid bilayer analysis and patch clamping.

Animals↗
PubMed1995

Isolation and structural characterization of trimeric cyanobacterial photosystem I complex with the help of recombinant antibody fragments.

A monoclonal antibody was derived from mice immunized with the native trimeric, photosystem I (PSI) complex from the cyanobacterium Synechococcus PCC 7002 which reacts with a conformational epitope of the PSI complex. As seen by immunoelectron microscopy, the mAb bound to the stromal side of the thylakoid membranes. The DNA sequence encoding variable regions of the mAb was cloned into recombinant plasmids, sequenced and expressed in Escherichia coli. ELISA, Western blots and immunoelectron microscopy provided evidence that the expressed paired variable domain (Fv) fragments bind to the antigen in the same way as the parent mAb. A one-step purification was applied to purify the trimeric PSI complex using an affinity tag attached to the Fv fragment. Analysis by gel electrophoresis and N-terminal sequencing revealed the presence of the psaA, psaB, psaC, psaD, psaE, psaF and psaL gene products. The antenna size of the isolated PSI/Fv was 139 +/- 9 chlorophyll a/primary electron donor. Flash-induced absorption-change measurements showed that the complex exhibited electron transfer from the primary electron donor, P700, to the Fe-S center, FA/FB. The position of the bound Fv fragment on the trimeric PSI surface was determined by high-resolution electron microscopy and digital image processing.

Amino Acid Sequence↗
PubMed1995

Force-induced conformational change of bacteriorhodopsin.

The cytoplasmic surface topography of purple membranes imaged by the atomic force microscope depends mainly on the force applied to the stylus. Imaged at forces of 300 pN, individual bacteriorhodopsin molecules reveal two domains. The resulting donut-shaped trimers reversibly transform into structures exhibiting three prominent protrusions when scanned at 100 pN. In parallel, the height of the protein moiety above the lipid layer increases from 4 A to 6 A. From the known structure of bacteriorhodopsin it appears that this change may be related to a bending of the most prominent cytoplasmic loop.

Bacteriorhodopsins↗
PubMed1995

Towards the molecular architecture of the asymmetric unit membrane of the mammalian urinary bladder epithelium: a closed "twisted ribbon" structure.

The asymmetric unit membrane (AUM) forms numerous plaques covering the apical surface of mammalian urinary bladder epithelium. These plaques contain four major integral membrane proteins called uroplakins Ia, Ib, II and III, which form particles arranged in a well-ordered hexagonal lattice with p6 symmetry and a lattice constant of 16.5 nm. Bovine AUM plaques negatively stained with anionic sodium silicotungstate revealed structural detail to 3.1 nm resolution. Correlation averaging resolved each particle into 12 stain-excluding domains arranged in two concentric rings (inner ring radius (rm) = 3.7 nm, outer ring radius (rout) = 6.6 nm), each with six domains which were rotated by roughly 30 degrees relative to each other. Negative staining with cationic uranyl formate increased the resolution to 2.2 nm and unveiled distinct connections between adjacent AUM particles. These connections may provide a molecular basis for the observed insolubility of the plaques in many detergents. Examination of the luminal face of freeze-dried/unidirectionally metal-shadowed AUM plaques established a left-handed vorticity of the 16 nm protein particles, whereas the cytoplasmic face exhibited no significant surface corrugations. Three-dimensional reconstruction from sodium silicotungstate-stained specimens revealed the AUM particles to be built of six "V-shaped" subunits anchored upright in the membrane. The mass density distribution within uranyl formate-stained AUM particles was similar except that the inner tip of each V was bridged to the outer tip of an adjacent V, so that the 16 nm AUM particle appeared as a continuous, "twisted ribbon" embracing a central cavity. Finally, mass measurements of unstained/freeze-dried plaques by scanning transmission electron microscopy yielded a total mass of 1,120 kDa per membrane-bound AUM particle. By imposing constraints on the possible uroplakin stoichiometries within AUM plaques, these data provide a first glimpse of the molecular architecture of the 16 nm particles constituting the plaques.

Animals↗
PubMed1995

Model structure of the Omp alpha rod, a parallel four-stranded coiled coil from the hyperthermophilic eubacterium Thermotoga maritima.

Omp alpha is an outer-membrane protein that spans the periplasmic space of the hyperthermophilic eubacterium Thermotoga maritima. The molecule contains a globular head with an apparent diameter of 8 nm and a rod-shaped tail of 40 nm length. The sequence of the globular domain is homologous to a conserved region of cell wall-bound proteins and probably attaches Omp alpha to the peptidoglycan. The sequence of the rod domain resembles that of coiled coil proteins and ends in a transmembrane segment that anchors Omp alpha to the outer membrane. We have analysed Omp alpha by scanning transmission electron microscopy (STEM) and by statistical sequence analysis methods. The Omp alpha rod is a tetramer with an unusual periodicity of hydrophobic residues close to 3.6 that differs from the 3.5 periodicity of canonical coiled coils. This is due to periodic omissions of three residues in the heptad repeat pattern ("stutters") whose effect is to locally distort the packing of hydrophobic layers in the core of the coiled coil. Residues in position alpha are shifted to occupy a position halfway between positions alpha and d (x layers) and residues in positions d and e are shifted so that both participate in core packing interactions (da layers). Such distorted layers are frequently found in helical bundles and are characteristic of helices that do not undergo supercoiling. The only homo-oligomeric coiled coil of known structure which contains x and da layers is the three-stranded coiled coil of influenza haemagglutinin. Using geometric constraints derived from this structure, we have built a model for the Omp alpha rod in which the helices have a crossing angle of less than 15 degrees and maintain a residual degree of supercoiling with a pitch of approximately 40 nm. Our analysis of distorted layers in the hydrophobic core of coiled coils and helical bundles shows that stutters must not be viewed as discontinuities but rather as a departure from the canonical "knobs-into-holes" packing that allows helices to interact at a low angle without supercoiling. Although stutters have been considered to weaken helical interactions, their occurrence in a rigid, highly thermostable coiled coil indicates that this may not be generally true. Our analysis also indicates that skips and stutters are two different conventions for describing the same underlying structural feature.

Amino Acid Sequence↗
PubMed1995

Native Escherichia coli OmpF porin surfaces probed by atomic force microscopy.

Topographs of two-dimensional porin OmpF crystals reconstituted in the presence of lipids were recorded in solution by atomic force microscopy (AFM) to a lateral resolution of 10 angstroms and a vertical resolution of 1 angstrom. Protein-protein interactions were demonstrated on the basis of the AFM results and earlier crystallographic findings. To assess protein-lipid interactions, the bilayer was modeled with kinked lipids by fitting the head groups to contours determined with AFM. Finally, two conformations of the extracellular porin surface were detected at forces of 0.1 nanonewton, demonstrating the potential of AFM to monitor conformational changes with high resolution.

Crystallography, X-Ray↗
PubMed1995

The thermosome of Thermoplasma acidophilum and its relationship to the eukaryotic chaperonin TRiC.

A high molecular-mass protein complex from the archaebacterium Thermoplasma acidophilum, referred to here as the 'thermosome', is built from two subunits (M(r) 58 and 60). The thermosome has been purified to homogeneity. The molecular mass of the native complex was determined to be 1061 +/- 30 Da by scanning transmission electron microscopy. It shows a weak ATPase activity and is able to bind denatured polypeptides. Averages obtained from electron micrographs of negatively stained molecules in the end-on and side-on orientations, respectively, were compared with those of the t-complex polypeptide 1 ring complex (TRiC), isolated from bovine testes. Both molecules consist of two stacked pseudo eightfold symmetric rings which build up a cylindrical particle with a large cavity in the center. Sequence alignments of peptides generated from both subunits of the thermosome and different subunits of TRiC reveal a high partial similarity to each other and to the archaebacterial chaperonin thermophilic factor 55 from Sulfolobus shibatae as well as to eukaryotic TCP1 proteins. These striking structural similarities confirm the proposition that all these molecules belong to a single protein family which is structurally and functionally related to the GroEL class of molecular chaperones.

Adenosine Triphosphatases↗
PubMed1995

Human breast sarcoma and human breast implantation: a time trend analysis based on SEER data (1973-1990).

Since the demonstration in the 1940s of foreign body induction of sarcomas in rodents, the safety of artificial implants in humans has been a matter of concern. In this study, we assess the risk for the development of breast sarcomas in women with silicone breast implants. Our analysis is based on the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database for the years 1973-1990 and on estimates of breast implantation rates from about 1960 onward. We have divided the SEER data into two equal time periods, 1972-1981 and 1982-1990. For each time period, we estimated the average annual number of women in the United States who had received breast implants 10 or more years earlier. This analysis allows for a 10 year latency period for the induction of breast sarcoma. We calculated that the average number of women in the U.S. 10 or more years post breast implantation was 55,000 for the 1973-1981 period and 509,000 for the 1982-1990 period. We then examined the SEER data to observe whether there was a concomitant rise in the female breast sarcoma incidence rates between these two time periods. We found the mean age-adjusted incidence rate of breast sarcomas was 0.13 per 100,000 women for the initial 9-year period, 1973-1981, and 0.12 per 100,000 women for the latter 9-year period, 1981-1990.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Imaging purple membranes in aqueous solutions at sub-nanometer resolution by atomic force microscopy.

Purple membranes adsorbed to mica were imaged in buffer solution using the atomic force microscope. The hexagonal diffraction patterns of topographs from the cytoplasmic and the extracellular surface showed a resolution of 0.7 and 1.2 nm, respectively. On the cytoplasmic surface, individual bacteriorhodopsin molecules consistently exhibited a distinct substructure. Depending on the pH value of the buffer solution, the height of the purple membranes decreased from 5.6 nm (pH 10.5) to 5.1 nm (pH 4). The results are discussed with respect to the structure determined by cryo-electron microscopy.

Adsorption↗