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Biomedical subjects

A Burger

Publications and source records attributed to A Burger.

At least 55 records · Page 3Linked to original sources
PubMed1997

Chimeric papillomavirus-like particles.

We have constructed chimeric papillomavirus-like particles (CVLPs) by replacing the 34-carboxy-terminal amino acids of the HPV 16 L1 protein with various parts of the HPV 16 E7 protein. Chimeric proteins were expressed by recombinant baculoviruses and analyzed by electron microscopy for their ability to assemble into virus capsids. We were able to produce CVLPs in high efficiencies with inserts of up to 60 amino acids. CVLPs are able to induce a neutralizing antibody response, assayed by inhibition of hemagglutination of mouse erythrocytes. CVLPs are interacting with the putative receptor for papillomaviruses as they were shown to hemagglutinate mouse red blood cells and bind to and penetrate cells in vitro. As CVLPs follow a similar intracellular pathway as observed earlier for BPV VLPs, we speculate that CVLPs can be used to deliver peptides into mammalian cells in vitro and in vivo, possibly reaching the pathway for MHC class I presentation.

Amino Acid Sequence↗
PubMed1997

The mouse atlas and graphical gene-expression database

The large amounts of gene-expression data on mouse development are now too extensive to be stored in any format other than that of a database. Furthermore, as this data is intrinsically graphical and as, in the early developmental stages at least, its boundaries do not map directly to those of anatomical tissues, the natural way to store it is in graphical format. We are therefore constructing a database able to handle such graphical gene-expression data by mapping it onto 3-D reconstructions of mouse embryos whose tissues have been delineated. This article reviews the progress that has been made in this project and describes its two major components, CD-ROMs of the 3-D reconstructions to be held on the user's computer and a gene-expression database that will be maintained at a host site, the two being linked over the internet by a complex Java-based interface for submitting data and querying the database.Copyright 1997 Academic Press Limited Copyright 1997Academic Press Limited

Journal Article↗
PubMed1997

The polymorphic drug substances of the European pharmacopoeia. Part 9. Physicochemical properties and crystal structure of acetazolamide crystal forms.

The crystal structure of acetazolamide modification I (mod. I) was determined, and its differences compared with the already known crystal structure of the triclinic modification II (mod. II) are discussed. The monoclinic mod. I crystallizes in space group P2(1)/n with four molecules in the unit cell: a = 4.7674, b = 21.956, and c = 8.186 A, beta = 104.23 degrees. In both modifications, the molecules form hydrogen-bonded centrosymmetric dimers. The two modifications differ distinctly in the spatial arrangement of these pairs and in the hydrogen bonds formed between them. The thermodynamic relationship between the two modifications is demonstrated by a semischematic energy/temperature diagram, based on the results of thermal analysis and solubility experiments. Mod. II is the thermodynamically stable modification at 20 degrees C and enantiotropically related to mod. I. The thermodynamic transition point lies between 120 and 148 degrees C. The solid-state properties of acetazolamide are mainly directed by the strong intermolecular hydrogen bond forces. Thus, the metastable mod. I exhibits a higher density than mod. II and a very high kinetic stability at 20 degrees C. Both modifications can be crystallized from water and the solubility differences are very small, so, in addition to mod. II, the metastable but extremely resistant mod. I is suggested to be suitable for use in solid pharmaceutical formulations.

Acetazolamide↗
PubMed1997

Binary system of (R)- and (S)-nitrendipine--polymorphism and structure.

Three monotropically related modifications of (RS)-nitrendipine (RS-NTD) were investigated. With the aid of the optical antipodes of NTD, it was possible to construct a binary phase diagram, from which it is obvious that the thermodynamically stable mod. I of RS-NTD (mp 156-158.5 degrees C, heat of fusion 41.1 +/- 0.2 kJ mol-1) is a racemic compound, while mod. II (mp 130-134 degrees C, heat of fusion 29.4 kJ mol-1) and mod. III (mp 124-126 degrees C, heat of fusion 27.2 kJ mol-1) occur as conglomerates of different modifications of R- and S-NTD. The eutectic points (calculated) are at 150 degrees C and at 19% and 81% molar fraction of an enantiomer, respectively. Two modifications of the enantiomers are characterized (En-mod. I, thermodynamically stable form, mp 156-158 degrees C, heat of fusion 34.5 +/- 1.3 kJ mol-1 and En-mod. III, mp 121 degrees C), whereas a third modification (En-mod. II) must be hypothesized pursuant to the phase diagram (mp ca. 152 degrees C). IR spectra, DSC curves, and X-ray powder diffractograms of the different phases are described. The crystal structure of the enantiomer En-mod. I is reported (monoclinic, P2(1), density 1.346 g cm-3) and compared with the X-ray structure of the racemic compound (monoclinic, P2(1)/c, density 1.356 g cm-3). A comparison with similar studies on nimodipine has been made to emphasize the parallels to a substance of this chemical group.

Calcium Channel Blockers↗
PubMed1997

[A model of integrated partial inpatient rehabilitation].

This article deals with a new form of rehabilitation in Germany: the partly inpatient rehabilitation. This kind of rehabilitation comprises an offer for regular inpatient rehabilitation excluding overnight stay, breakfast and evening meal. In total the quasi inpatient rehabilitation is qualitatively equal to regular inpatient rehabilitation in respect of rehabilitative outcome. This new kind of rehabilitation contributes to a flexible and requirements-oriented health service in the German rehabilitation system. In this respect, "quasi inpatient rehabilitation" seems to be a valuable complement to traditional inpatient and out-patient rehabilitation, though quasi inpatient rehabilitation cannot generally replace traditional rehabilitation.

Adult↗
PubMed1996

Structural and functional characterisation of the voltage sensor in the ion channel human annexin V.

The ion channel properties of human annexin V, a calcium- and phospholipid-binding protein of the annexin family, have been structurally and functionally investigated by analysing the mutant Glu112 -->Gly. Glu112 forms a salt bridge with Arg271 located in the interior of the hydrophilic pore of the molecule which is conserved within the annexin family. The crystal structures of the mutant and wild-type proteins are very similar and show only marginal conformational changes around the mutation site. Electron microscopic images show a conserved four-domain structure upon membrane binding as in the wild-type annexin V. The channel properties of the mutant are drastically changed, as the mutant has lost the voltage-dependent channel gating and the selectivity for calcium ions over monovalent cations. These results strongly support the hypothesis that the central, hydrophilic pore is the ion-conducting pathway.

Annexin A5↗
PubMed1996

The crystal structure and ion channel activity of human annexin II, a peripheral membrane protein.

Annexin II binds in a calcium-dependent manner to acidic phospholipids and is a substrate of some protein kinases. An N-terminally shortened form of human annexin II was crystallized and its molecular structure determined. It is very similar to two previously described members of this protein family, annexin I and annexin V. The protein structure is nearly completely alpha-helical organized as four compact domains which consist of five alpha-helices each. The domains surround a hydrophilic pore. The calcium binding sites are located at the convex side of the structure as in annexin V. Recombinant and natural porcine annexin II are active as ion channel with characteristics similar to annexin V, while N-terminally shortened annexin II and the heterotetramer (annexin II-p11)2 are inactive. Two cysteine residues, Cys133 and Cys262, form a disulphide bridge connecting domains II and III, adding further weight to the notion that ion channel activity does not require major structural rearrangements.

Amino Acid Sequence↗
PubMed1996

Gastrointestinal bleeding of obscure origin: role of enteroclysis.

The purpose of this work was to assess retrospectively the yield of enteroclysis in 124 unselected patients presenting with obscure gastrointestinal bleeding. Of 1000 consecutive patients who were examined by enteroclysis 124 presented with occult gastrointestinal bleeding. A total of 61 patients with an unknown source of bleeding at the time of discharge, but with established gastrointestinal bleeding, were followed up by questionnaire to correlate the initial degree of bleeding with the incidence of recurrence of bleeding. Enteroclysis was normal in 109 cases. An abnormality was found subsequently be the cause of bleeding in the small intestine in 16 patients. Enteroclysis was positive in 14 cases, negative in 2 and false positive in 1. There was positive correlation between the initial degree of haemorrhage and the rate of recurrence. Enteroclysis detected the cause in 11% of patients who presented with bleeding of unknown origin. In patients with minor haemorrhage there was no recurrence of bleeding in most cases.

Adolescent↗
PubMed1996

The underlying cellular mechanism of fibrosis.

Fibrosis is a common sequela of various exogenous insults to a variety of parenchymal tissues. The underlying mechanisms of the induction and progression of fibrosis both at the molecular and cellular level have not been clarified so far. In the present study the cellular processes that ultimately may lead to interstitial fibrosis are described using the model of radiation-induced terminal differentiation in the fibroblast/fibrocyte cell system. The data reported herein will provide evidence that exogenously induced changes in the proliferation and differentiation pattern of the fibroblast/fibrocyte cell system based on either autocrine and/or paracrine mediators represent the underlying cellular mechanism of fibrosis. Using co-culture systems of parenchymal cells (fibroblasts and type II pneumocytes), the intercellular communication via cytokines, which may lead to fibrosis have been studied. TGF beta 1 could be described as one key modulator of these cellular processes.

Animals↗
PubMed1995

Identification of novel genes from stomach cancer cell lines by differential display.

Gastric cancer is a leading cause of cancer death in many parts of the world. None of the tumor markers available to date provide for a reliable screening/diagnostic test. By using differential display technology on gastric cancer nonmetastatic (RF1) and metastatic (RF48) cell lines, we have isolated six novel cDNA clones. Five of them have not been previously identified. However, one of them appears to be the human homolog of the bovine oligomycin sensitivity conferral protein (oscp). Northern blot analysis showed that this clone is expressed at a much higher level in the metastatic (RF48) than the nonmetastatic (RF1) cancer cell line from the same patient. High level expression of the same gene is also observed in the breast cancer cell lines BT20 and T47D. The other five novel clones isolated showed either low or no expression in the RF1 and RF48 gastric cell lines, but variable levels of expression were detectable in breast cancers cell lines and normal tissues.

Adenosine Triphosphatases↗
PubMed1994

[Primary quality control in Israel Air Force clinics].

The practice of primary medicine within a military framework differs from that in the civilian environment in: accessibility, its consumers, obligations of the providers, involvement of the funder (the commanders), and ability to define and enforce professional guide lines. These differences influence the scope of medical service, as well as affect the methods and results of quality control. A system of quality control evaluation and feedback of military primary care in 16 Israel Air Force clinics was carried out by a team of experienced physicians using peer group review and according to a specially prepared protocol. Emphasis was placed on medical record assessment using obligatory markers of adequate medical evaluation and treatment. Identification of the population at risk, further medical training, and medical administration with a direct effect on the quality of medical treatment were also evaluated. 2 quality control surveys with feedback were carried out 6 months apart. The overall mean score was 81.66 +/- 7.16% at the first evaluation, increasing to 88.60 +/- 7.46% at the second (p < 0.01). The greatest improvements were in follow-up of population at risk (increasing from 68.4% to 86.4%, p < 0.025), training of medical teams, (from 75.7% to 87.5%, p < 0.05) and patient case management (from 79.4% to 85.1%, N.S.). Categories in which there was no improvement were medical records, recovery of old medical files and patient education. The categories in which there was improvement had a common denominator: "recognition of importance" and "provision of patterns" by headquarters. The quality control system was designed for routine use, and not as a research project.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerospace Medicine↗
PubMed1994

Three-dimensional structure of membrane-bound annexin V. A correlative electron microscopy-X-ray crystallography study.

We have used electron microscopy to analyse the structure of wild-type human annexin V (recombinant and placental) and of several mutants (single and double point mutants) bound to monolayers composed of DOPS, DOPE, or brain extract (Folch fraction III). On these phospholipids and on DOPS/DOPC (3:1, w/w) protein trimers, as also found in 3-D crystals, assemble to form a hexagonal lattice with a unit vector length of about 18 nm. The resolution obtained in projection is 1.7 to 2.2 nm for wild-type and mutants. There are no significant differences between the annexin V mutants and the wild-type protein at this resolution. All proteins bind as trimers with their convex side harbouring the Ca(2+)-binding sites facing the membrane. A comparison of the 3-D reconstruction of annexin V wild-type with the high resolution crystal structure shows that the domain structure is preserved but the relative orientation of the modules (II/III) and (I/IV) is slightly changed so that the Ca(2+)-binding sites in all four domains (including the recently observed binding site in domain III) become coplanar to the membrane. The thickness of the molecule obtained in the 3-D reconstruction corresponds well with the thickness of the high resolution crystal structure indicative of peripheral binding of annexin V without substantial penetration of the membrane.

Annexin A5↗
PubMed1994

Structural and electrophysiological analysis of annexin V mutants. Mutagenesis of human annexin V, an in vitro voltage-gated calcium channel, provides information about the structural features of the ion pathway, the voltage sensor and the ion selectivity filter.

Annexin V binds to phospholipids in a calcium-dependent manner and exhibits calcium channel activity in vitro. We prepared a variety of mutants yielding information about the structure-function relationship of the ion channel activity. All mutants were characterized by X-ray crystallography, electron microscopy and electrophysiological measurements. Their structures are insignificantly changed whereas their electrophysiological properties are drastically different. Glu95, located in the central hydrophilic pore of the molecule, is crucial for the ion selectivity filter as its exchange leads to reduced calcium and increased sodium conductance. The removal of Glu17, located on the protein surface and far from the ion conduction pathway, leads to the appearance of a second conductance level of 9 pS in addition to the conductance level of about 30 pS in the wild-type molecule. This was also the case for Glu78, which is part of a weak calcium binding site. The exchange of Glu17 and Glu78 produced a mutant retaining only the smaller conductance level. We conclude that these two residues influence the angle between the two halves of the molecule, which determines the diameter of the ion conduction pathway, thereby leading to the occurrence of a second conductance level.

Amino Acid Sequence↗
PubMed1994

Annexin V: the key to understanding ion selectivity and voltage regulation?

Annexin V is a Ca(2+)-dependent membrane-binding protein that forms voltage-dependent Ca2+ channels in phospholipid bilayers and is the first ion channel to be structurally and functionally characterized. Data outlined here indicate that key amino acid residues act as selectivity filters and voltage sensors, thereby regulating the permeability of the channel pore to ions.

Annexin A5↗
PubMed1994

Immunohistochemical studies on regeneration in cultured epidermal autografts used to treat full-thickness burn wounds.

The normal pattern of healing following culture grafting is not well-established. The present study describes the immunohistochemical expression of differentiation markers during various stages of wound healing after resurfacing full-thickness burn wounds with cultured epidermal autografts. For this purpose, biopsy specimens were obtained from six patients 6 days to 4.5 years after transplantation. A panel of monoclonal antibodies was used against various differentiation-specific protein markers, including cytokeratins, involucrin, transglutaminase and filaggrin. Findings from early and late biopsies were compared with site-matched normal skin and cultured epidermal sheets. The persistence of cytokeratins 6 and 16, and to a lesser extent, the abnormal distribution of involucrin up to 4.5 years after resurfacing burns with cultured autografts was observed. These findings confirm previous studies--that the newly formed epidermis after culture grafting remains in a hyperproliferative state for a long time, which may be caused by the absence of a modulating dermal factor. Our results suggest that keratinocyte maturation following culture autografting does not return to normal for at least 4.5 years after healing of full-thickness burn wounds.

Adolescent↗
PubMed1994

The role of lecithin: cholesterol acyltransferase for lipoprotein (a) assembly. Structural integrity of low density lipoproteins is a prerequisite for Lp(a) formation in human plasma.

The composition of lipoproteins in the plasma of patients with LCAT deficiency (LCAT-D) is grossly altered due to the lack of cholesteryl esters which form the core of normal lipoproteins. When plasma from LCAT-D patients and their relatives was examined we found that nine heterozygotes had plasma Lp(a) levels of 2-13 mg/dl whereas none of 11 affected homozygous individuals from different families contained detectable amounts of Lp(a) in their plasma. Therefore, the binding of apo(a) to LDL density particles was studied in vitro using LDL density fractions prepared from patients, and recombinant apo(a) [r-apo(a)], which was expressed and secreted by transfected COS-7 cells. The LDL from heterozygotes were chemically indistinguishable from normal LDL and homogeneous with regard to morphology, whereas the crude LDL floating fraction from homozygotes consisted of a heterogeneous mixture of large vesicles, and small spheres resembling normal LDL. The LDL density fraction from the LCAT-D patient lacked almost completely cholesteryl esters. Incubation of LCAT-D plasma with active LCAT caused a substantial augmentation of the original subfraction which morphologically resembled normal LDL. Using r-apo(a) and normal LDL or LDL of heterozygous individuals, apoB:r-apo(a) complexes were formed when incubated at 37 degrees C in vitro for 20 h. In contrast, the total LDL floating fraction from a homozygous LCAT-D patient failed to form apoB:r-apo(a) complexes. After treatment with active LCAT, a significant apoB:r-apo(a) association was observed with LCAT-D LDL-density particles. Our data emphasize the importance of the integrity of LDL structure and composition for the formation of Lp(a). In addition, we demonstrate that the absence of LCAT activity has a fundamental impact on the regulation of plasma Lp(a) levels.

Apolipoproteins A↗