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Biomedical subjects

A Krause

Publications and source records attributed to A Krause.

At least 109 records · Page 6Linked to original sources
PubMed1998

Selectins as new targets for immunoliposome-mediated drug delivery. A potential way of anti-inflammatory therapy.

Endothelial cell adhesion molecules, which are expressed in response to inflammatory signals to mediate recruitment of leukocytes to sites of inflammation, appear to be excellent targets for drug delivery systems to open new perspectives of antiinflammatory therapies. In this study we describe the preparation and characterization of antibody-coupled liposomes (immunoliposomes) as directed against endothelial (E)-selectins. We have examined the factors affecting the covalent coupling of antibodies to the membrane anchor N-glutaryl-phosphatidylethanolamine via amide bound and have compared them to other coupling procedures. The target sensitivity has been demonstrated in a cell-containing in-vitro model, where liposome binding to selectins under either static, or simulated blood flow conditions was illustrated by using fluorescence microscopical means. It could be shown that even under shear force conditions liposomes selectively accumulate at selectin-containing cells when a specific lipid composition and a certain balance in the lipid/antibody ratio was maintained. Furthermore, the need for polyethylene glycol-derived lipids to sterically stabilize the liposomes for preventing unspecific liposome attachment to cells has been demonstrated.

Animals↗
PubMed1998

A set-theoretic approach to database searching and clustering.

MOTIVATION: In this paper, we introduce an iterative method of database searching and apply it to design a database clustering algorithm applicable to an entire protein database. The clustering procedure relies on the quality of the database searching routine and further improves its results based on a set-theoretic analysis of a highly redundant yet efficient to generate cluster system. RESULTS: Overall, we achieve unambiguous assignment of 80% of SWISS-PROT sequences to non-overlapping sequence clusters in an entirely automatic fashion. Our results are compared to an expert-generated clustering for validation. The database searching method is fast and the clustering technique does not require time-consuming all-against-all comparison. This allows for fast clustering of large amounts of sequences. AVAILABILITY: The resulting clustering for the PIR1 (Release 51) and SWISS-PROT (Release 34) databases is available over the Internet from http://www.dkfz-heidelberg.de/tbi/services/modest/b rowsesysters.pl. CONTACT: a.krause@dkfz-heidelberg.de; m.vingron@dkfz-heidelberg.de

Algorithms↗
PubMed1998

Coiling phagocytosis discriminates between different spirochetes and is enhanced by phorbol myristate acetate and granulocyte-macrophage colony-stimulating factor.

The mechanisms involved in coiling phagocytosis are not yet known, and it is not even clear whether this phenomenon is either an incidental event or a specific response. Therefore, the phagocytic uptake of Borrelia burgdorferi and other spirochetes by human monocytes in vitro was used to investigate the involvement of both sides--microbes and phagocytes--in coiling phagocytosis. As seen with electron microscopy, morphologically similar Borrelia, Leptospira and Treponema strains induced markedly different frequencies of coiling phagocytosis. The monocytes used coiling phagocytosis for both live (motile) and killed (nonmotile) B. burgdorferi, but pseudopod coils were observed neither with fragmented B. burgdorferi nor with cell-free supernatant from B. burgdorferi cultures. Investigation of the relationship of coiling phagocytosis with other pseudopod-based cellular mechanisms revealed that the use of bioreagents that inhibit conventional phagocytosis also inhibited coiling phagocytis but did not affect membrane ruffling. Bioreagents that increase membrane ruffling did not affect phagocytosis of B. burgdorferi, except for granulocyte-macrophage colony-stimulating factor and phorbol myristate acetate, which increased coiling phagocytosis selectively. These results demonstrate that coiling phagocytosis is not induced by microbial motility, viability, or a certain morphology and that it is not a random event. Rather, it is a selective uptake mechanism actively driven by the phagocytes. However, whether coiling phagocytosis represents an independent alternative to conventional phagocytosis or, alternatively, a fault in conventional phagocytosis remains to be determined.

Borrelia burgdorferi Group↗
PubMed1998

Detection of Borrelia burgdorferi by polymerase chain reaction in synovial membrane, but not in synovial fluid from patients with persisting Lyme arthritis after antibiotic therapy.

OBJECTIVES: To identify possible sites of bacterial persistence in patients with treatment resistant Lyme arthritis. It was determined whether Borrelia burgdorferi DNA may be detectable by polymerase chain reaction (PCR) in synovial membrane (SM) when PCR results from synovial fluid (SF) had become negative after antibiotic therapy. METHODS: Paired SF and SM specimens and urine samples from four patients with ongoing or recurring Lyme arthritis despite previous antibiotic therapy were investigated. A PCR for the detection of B burgdorferi DNA was carried out using primer sets specific for the ospA gene and a p66 gene of B burgdorferi. RESULTS: In all four cases, PCR with either primer set was negative in SF and urine, but was positive with at least one primer pair in the SM specimens. In all patients arthritis completely resolved after additional antibiotic treatment. CONCLUSIONS: These data suggest that in patients with treatment resistant Lyme arthritis negative PCR results in SF after antibiotic therapy do not rule out the intraarticular persistence of B burgdorferi DNA. Therefore, in these patients both SF and SM should be analysed for borrelial DNA by PCR as positive results in SM are strongly suggestive of ongoing infection.

Adult↗
PubMed1998

Medical and interventional therapy of coronary artery disease in women.

Coronary artery disease is the leading cause of death in women, and the importance of this condition is not generally appreciated. Few studies are available that investigate the response of women to the various therapeutic agents that are used in this disease. Those that are available suggest that risk factor reduction and estrogen replacement therapy are important, and that aspirin and vitamin E may be helpful in primary prevention in women. After myocardial infarction, thrombolytics and percutaneous transluminal coronary angioplasty reduce mortality and beta-adrenergic blocking agents and ACE inhibitors are valuable. Elective percutaneous transluminal coronary angioplasty appears to have similar success rates in men and women. In order to most effectively treat women with coronary artery disease, studies on their response to therapy are needed.

Adrenergic beta-Antagonists↗
PubMed1997

A liposome-based model system for the simulation of lectin-induced cell adhesion.

A parallel plate flow chamber with defined wall shear rates was developed in order to study and simulate cellular adhesion to biological membranes as mediated by lectin/carbohydrate interactions. Planar bilayers containing clustered areas of various long-chain alkyl mannosides as carbohydrate ligands and supported on transparent materials were used as model membranes. Their interaction with liposomes bearing Concanavalin A as model cells was observed fluorimetrically by confocal laser scanning microscopy. The use of supported membranes made it possible to study the dependence of adhesion upon different physicochemical parameters of membranes. The liposomes of this model were able to simulate the lectin-mediated adhesion of cells in a shear flow. Once specific receptor-mediated adhesion had taken place, liposomes tended to attach irreversibly to the membrane. This could be avoided by employing lipid compositions which represent a special balance between charged and polyethylene glycol-coupled lipids. This is discussed in term of the interplay between the various attractive and repulsive forces at membrane surfaces. The dependence of liposome adhesion upon the shear rate could be detected. These results were used to evaluate binding forces between lectin-bearing liposomes and ligand-containing planar bilayers.

Cell Adhesion↗
PubMed1997

T cell cytokine pattern in the joints of patients with Lyme arthritis and its regulation by cytokines and anticytokines.

OBJECTIVE: To investigate whether type 1 helper (Th1) or Th2 cytokines are found in the joints of patients with Lyme arthritis, and whether the cytokine pattern can be modulated by cytokines or anticytokines. METHODS: The cytokine pattern in the joints of 10 patients with Lyme arthritis was investigated. Expression of interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), interleukin-4 (IL-4), and IL-10 was measured by enzyme-linked immunosorbent assay (ELISA), after stimulation of synovial fluid mononuclear cells (SFMC) with Borrelia burgdorferi (Bb) in the supernatant. Expression of cytokine messenger RNA and protein in synovial membrane (SM) and nonstimulated SFMC was studied using semiquantitative reverse transcriptase-polymerase chain reaction and immunohistologic techniques. The effects of recombinant cytokines or neutralizing anticytokine antibodies on cytokine production in Bb-stimulated SFMC were investigated by ELISA. RESULTS: SFMC produced high amounts of IFN gamma and TNF alpha, but little or no IL-4, upon stimulation with Bb antigen, indicating a Th1-type cytokine pattern. In SM, IFN gamma was detectable in all patients, while the other cytokines were less frequently found. Serial sections of SM revealed that all cytokines were located in the same area. The Th1 response, especially the production of TNF alpha, could be down-regulated in vitro by both endogenous and exogenous IL-10, but not by IL-4 or anti-IL-12. CONCLUSION: A Th1-type cytokine pattern was found in the joints of patients with Lyme arthritis. This Th1 response could be down-regulated by IL-10, suggesting insufficient IL-10 production in vivo.

Adolescent↗
PubMed1997

[Acute Borrelia infection. Unilateral papillitis as isolated clinical manifestation].

BACKGROUND: Borrelia burgdorferi is the cause of erythema chronicum migrans and Lyme disease. Ticks like Ixodes ricinus are responsible for transmission. Frequently, the tick bite is not noticed by the patient. Eye manifestations, such as keratoconjunctivitis, scleritis, chronic uveitis, vitritis, chorioretinitis, optic nerve disease, orbital myositis and paresis of the eye muscles, often occur after a long period of time and vary greatly. PATIENTS AND METHODS: We present below the case reports of a man 38 years old and a woman of 31, each with manifestation of an ocular Borrelia infection (papillitis and panuveitis, respectively). RESULTS: By antibody-screening with the ELISA technique and Western Blot analysis we were able to prove the serological infection. After specific antibiotic therapy, ocular inflammation improved rapidly, as did visual acuity. The papillitis only healed partially. CONCLUSIONS: In case of therapy-resistant inflammation of the eye we have to exclude general infections because cortisone therapy alone may result in worsening the condition. VECP can be used effectively in the differential diagnosis of papilloedemas. Early diagnosis and therapy of an acute Borrelia infection restrict the extent of the lesions and prevent ocular and general late manifestations. Seronegative values in subjects strongly suspected of having Lyme disease do not necessarily exclude the diagnosis of Lyme disease.

Borrelia burgdorferi Group↗
PubMed1997

[Open foramen ovale in patients with arterial vascular occlusions of the retina and optic nerve].

BACKGROUND: We examined the frequency and significance of persistent foramen ovale (PFO) in patients with ocular circulatory disturbance. PATIENTS AND METHODS: Forty patients with acute arterial occlusions of the posterior bulb segment were investigated by means of transthoracic and transesophageal echocardiography (TEE). The parallel presence of cerebral ischemia was clarified on the basis of existing CCT findings and by additional HMPAO-SPECT investigation. RESULTS: PFO was identified in nine of the patients investigated. The probability of paradoxical embolism arises from further findings: eight of those with PFO (89%) showed echocardiographic signs of right heart strain, indicating previous pulmonary embolism, compared with only three of those without PFO (10%). Five of those with PFO showed a potential source of embolism, two of them with phlebothromboses in their clinical history and three with additional atrial septal aneurysm. Cardiovascular risk factors were prevalent in the group without PFO. Both groups had a mean age of approximately 60 years. Signs of cerebral ischemia were present in the SPECT or CT findings for four of the patients with PFO and nine of those without. CONCLUSIONS: From our findings, it appears highly probable that ocular arterial occlusion is caused by paradoxical embolism. PFO should be taken into account in establishing a diagnosis, including diagnosis in elderly patients.

Adult↗
PubMed1997

Simple ovarian cysts in premenopausal patients.

OBJECTIVE: To compare clinical, ultrasonographical, and cytological findings with the histopathological diagnosis of unilocular, anechoic smooth-walled cystic ovarian tumors ('simple ovarian cysts'). METHOD: In 140 premenopausal women simple ovarian cysts were removed by laparoscopy following ultrasound evaluation. In this retrospective study the histopathological diagnosis was correlated with clinical data, sonographic characteristics, macroscopic impression and with cytological findings. RESULTS: Histopathology revealed 21 (15.0%) functional cysts, 31 (22.1%) retention cysts, 9 (6.4%) endometriomas, 3 (2.1%) cystic teratomas, 12 (8.6%) undifferentiated cysts and 64 (45.7%) cystadenomas. No mentionable differences were correlated with the patient's age or the size of the cyst as determined by ultrasound. Classically, 'chocolate-like' cystic fluid characterizes endometriomas. However, in the present study cysts with different histopathological classifications exhibited similar fluid characteristics. The cytological diagnosis was correct in only 53 (37.9%) of all 140 cases. CONCLUSION: In premenopausal women differential diagnosis of ovarian cysts is not possible by clinical characterization, either by ultrasound or cytological evaluation. Simple ovarian cysts should be observed for at least 8 weeks or 2 menstrual cycles, respectively. If persisting over that period, the ovarian cyst should be removed by laparoscopy, but not by cyst aspiration.

Adult↗
PubMed1997

Feasibility of prenatal diagnosis and carrier detection in South African haemophilia A patients.

The feasibility of DNA diagnosis for haemophilia A was tested in South African patients and families by screening for the common inversion mutation in the factor VIII gene and for the intragenic microsatellite markers in introns 13 and 22. The allele frequencies at the two microsatellite loci were significantly different, with informativity being higher in the Negroid (100%) than the Caucasoid group (67%). In severely affected haemophiliacs the inversion was found in 43% (6/14) of Negroids but in only 32% (13/41) of Caucasoids. Presence of a second common unidentified mutation may account for the low frequency in the latter. Haplotype analysis shows a disproportionately high frequency of an (AC)20 intron 13-(AC)26 intron 22 inversion negative Caucasoid haemophilia chromosome, supporting a founder effect.

Black People↗
PubMed1997

[Protracted course of polychondritis as the etiology of progressive nose deformity, subglottic tracheal stenosis and inner ear hearing loss].

BACKGROUND: Relapsing polychondritis is a rare recurring inflammatory disorder with variable clinical course. Its etiopathogenesis is unknown, but autoimmune mechanisms are likely to be involved. PATIENT: We present a case report of a 42-year-old woman with polychondritis manifested in very slowly progressing destruction of the nasal cartilage, additional subglottic tracheal stenosis, and increasing cochlear dysfunction. RESULT: We describe and document by a series of photographs the very protracted course of the disease in this patient from early youth until now. Clinical signs and differential diagnosis in polychondritis are discussed. CONCLUSION: An early diagnosis in slowly progressing cases like this has to be established in order to permit adequate use of glucocorticoids and/or immunosuppressive drugs, to check the progress of the disease and prevent potentially lethal complications.

Adult↗
PubMed1997

Impaired sympathetic influence on the immune response in patients with rheumatoid arthritis due to lymphocyte subset-specific modulation of beta 2-adrenergic receptors.

Previous studies have demonstrated that an alteration of the interaction between the immune system and the autonomic nervous system may contribute to the pathogenesis of inflammatory arthritides. To address this issue further in patients with rheumatoid arthritis (RA), this study aimed at determining the modulation of beta-adrenergic receptors (beta 2R) on lymphocyte subsets and its impact on cell reactivity. beta 2R were determined on CD4+ and CD8+ peripheral blood lymphocytes (PBL) and synovial fluid lymphocytes (SFL) from RA patients and normal donors. In parallel, the influence of catecholamines on OKT3-induced T-cell activation was studied. In patients with RA, beta 2R on SFL were significantly decreased compared to beta 2R on PBL. Furthermore, a disease activity-correlated significant decrease of beta 2R on CD8+ PBL was observed. This decrease of beta 2R was paralleled by a reduced suppressive effect of catecholamines on OKT3-induced lymphocyte proliferation. Our data give further evidence for an impaired sympathetic influence on the immune response in RA.

Adult↗
PubMed1997

Rhizobia modulate root-hair-specific expression of extensin genes.

Three cDNAs (ext3, ext127, and ext26), originally isolated by differential screening from a root-hair cDNA library of Vigna unguiculata, were found to encode extensin-like cell wall proteins. Transcripts homologous to these cDNAs were only detected in root hairs where mRNA levels decreased 1 day after inoculation with rhizobia. This coincided with the onset of root-hair deformation, the first morphological step in the Rhizobium-legume interaction. Decreases in transcript levels following inoculation with wild-type Rhizobium sp. NGR234 were more pronounced than with NGR delta nodABC, a mutant deficient in Nod-factor production. Inoculation with a rhizobial strain carrying a mutation in a gene encoding a transcriptional activator for nod genes (NGR delta nodD1) did not repress mRNA levels, indicating that a second nodulation signal may be present that is nodD dependent. Application of purified NodNGR factors only affected transcript levels of ext3. The genomic locus of the gene homologous to ext26 (Ext26G) was cloned. In the 5' flanking region, several potential TATA boxes and CAP signals were identified. Part of the promoter region shares homology with the Pisum sativum seed lectin promoter and the Nicotiana tabacum nitrate reductase promoter region. Nonetheless, the function of these homologous regions in gene regulation is unknown.

Amino Acid Sequence↗