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Biomedical subjects

I Burger

Publications and source records attributed to I Burger.

13 recordsLinked to original sources

Confirmation of communication between deep venous drainage and the vein of galen after treatment of a vein of Galen aneurysmal malformation in an infant presenting with severe pulmonary hypertension.

Vein of Galen aneurysmal malformations (VGAM) are characterized by multiple arteriovenous connections draining into a markedly enlarged median draining vein. This ectatic vein is not the vein of Galen, but its embryonic precursor, the median prosencephalic vein of Markowski. During normal development, the posterior portion of the median prosencephalic vein persists as the vein of Galen, while its anterior portion regresses in parallel with the formation of the internal cerebral veins (ICV). It has been traditionally thought that, in children with a VGAM, the deep venous system does not connect to and, a fortiori, does not drain into the ectatic median prosencephalic vein/vein of Galen. This report describes a case of successfully treated VGAM in which the drainage of an ICV into the vein of Galen was only demonstrated by follow-up MR imaging and venography. The potential implications of this finding for the management of VGAMs are discussed.

Cerebral Angiography↗

Urban cause-specific socioeconomic mortality differences. Which causes of death contribute most?

BACKGROUND: Cause-specific information on socioeconomic differences in health is necessary for a rational public health policy. At the local level, the Municipal Health Service studies these differences in order to support the authorities in policy making. METHODS: Mortality data of the under 65 age group in The Hague were analysed (1982-1991) at residential area level. RESULTS: Causes of death with a high socioeconomic gradient among males were: homicide, chronic liver disease, 'other' external causes of injury, diabetes, bronchitis, emphysema and asthma, and motor vehicle accidents; and among females: diabetes, ischaemic heart disease, 'other' diseases of the circulatory system, signs, symptoms and ill-defined conditions, malignant neoplasm of cervix, and 'other' diseases. Main contributors to the mortality differences between the highest and lowest socioeconomic quartiles among males were: ischaemic heart disease (17.3%), 'other' diseases of the circulatory system (10.2%), signs, symptoms and ill-defined conditions (9.0%), 'other' external causes of injury (8.6%), and chronic liver disease (7.2%); and among females: ischaemic heart disease (25.5%), 'other' diseases (20.1%), signs, symptoms and ill-defined conditions (18.6%), 'other' diseases of the circulatory system (11.0%), and diabetes (9.1%). Among females the contributions of malignant neoplasms of breast (-16.3%) and colon (-5.5%) and suicide (-4.3%) were negative. CONCLUSIONS: The diseases that are the main contributors to urban socioeconomic mortality differences can be influenced by public health policy.

Adolescent↗

Metabolism of activated complement component C3 is mediated by the low density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor.

Complement component 3 (C3) and alpha(2)-macroglobulin evolved from a common, evolutionarily old, ancestor gene. Low density lipoprotein-receptor-related protein/alpha(2)-macroglobulin receptor (LRP/alpha(2)MR), a member of the low density lipoprotein receptor family, is responsible for the clearance of alpha(2)-macroglobulin-protease complexes. In this study, we examined whether C3 has conserved affinity for LRP/alpha(2)MR. Ligand blot experiments with human (125)I-C3 on endosomal proteins show binding to a 600-kDa protein, indistinguishable from LRP/alpha(2)MR by the following criteria: it is competed by receptor-associated protein (the 39-kDa receptor-associated protein that impairs binding of all ligands to LRP/alpha(2)MR) and by lactoferrin and Pseudomonas exotoxin, other well known ligands of the multifunctional receptor. Binding of C3 is sensitive to reduction of the receptor and is Ca(2+)-dependent. All these features are typical for cysteine-rich binding repeats of the low density lipoprotein receptor family. In LRP/alpha(2)MR, they are found in four cassettes (2, 8, 10, and 11 repeats). Ligand blotting to chicken LR8 demonstrates that a single 8-fold repeat is sufficient for binding. Confocal microscopy visualizes initial surface labeling of human fibroblasts incubated with fluorescent labeled C3, which changes after 5 min to an intracellular vesicular staining pattern that is abolished in the presence of receptor-associated protein. Cell uptake is abolished in mouse fibroblasts deficient in LRP/alpha(2)MR. Native plasma C3 is not internalized. We demonstrate that the capacity to internalize C3 is saturable and exhibits a K(D) value of 17 nM. After intravenous injection, rat hepatocytes accumulate C3 in sedimentable vesicles with a density typical for endosomes. In conclusion, our ligand blot and uptake studies demonstrate the competence of the LRP/alpha(2)MR to bind and endocytose C3 and provide evidence for an LRP/alpha(2)MR-mediated system participating in C3 metabolism.

Animals↗

Glial cells in the developing and adult olfactory lobe of the moth Manduca sexta.

The antennal lobe of the moth contains several classes of glial cells that are likely to play functional roles in both the developing and mature lobe. In this study, confocal and electron microscopy were used to examine in detail the morphology of two classes of glial cells, those associated with olfactory receptor axons as they course to their targets in the lobe and those that form borders around the synaptic neuropil of the olfactory glomeruli. The former, the nerve-layer glia, have long processes with multiple expansions that enwrap axon fascicles; the latter, the neuropil glia, constitute two subgroups: complex glia with large cell bodies and branching, vellate arbors; and simple glia, with multiple, mostly unbranched processes with many lamellate expansions along their lengths. The processes of complex glia appear to be closely associated with axon fascicles as they enter the glomeruli, while those of the simple glia surround the glomeruli as part of a multi-lamellar glial envelope, their processes rarely invading the synaptic neuropil of the body of the glomerulus. The full morphological development of antennal-lobe glial cells requires more than two-thirds of metamorphic development. During this period, cells that began as cuboidal or spindle-shaped cells that were extensively dye-coupled to one another gradually assume their adult form and, at least under nonstimulated conditions, greatly reduce their coupling. These changes are only weakly dependent on the presence of olfactory receptor axons. Glial processes are somewhat shorter and less branched in the absence of these axons, but basic structure and degree of dye-coupling are unchanged.

Animals↗

Triterpenoid saponins from Becium grandiflorum var. obovatum.

Two new triterpenoid saponins, beciumecine 1 and 2, were isolated from the root bark of Becium grandiflorum var. obovatum and their structures established as 3-O-(beta-D-glucopyranosyl) terminolic acid 28-O-beta-D-apiofuranosyl(1-3)-[alpha-L-rhamnopyranosyl (1-3)-beta-D-xylopyranosyl(1-4)]-alpha-L-rhamnopyranosyl (1-2)-alpha-L-arabinopyranoside and 3-O-(beta-D-glucopyranosyl) 24-hydroxyterminolic acid 28-O-alpha-L-rhamnopyranosyl(1-3)-beta-D-xylopyranosyl(1-4)-alpha-L- rhamnopyranosyl(1-2)-alpha-L-arabinopyranoside, respectively.

Antineoplastic Agents, Phytogenic↗

Vaccination against tick-borne encephalitis virus, a flavivirus, prevents disease but not infection, although viremia is undetectable.

By adoptive transfer of sera or immunoglobulin preparations, vaccine-induced protection against TBEV has been demonstrated to be mediated by antibodies to the surface protein of TBEV, glycoprotein E. Nevertheless, the mechanism of vaccine-induced protection against TBEV remains unclear. Protection by E antibodies without in vitro neutralization was shown by one group, whereas others found a correlation between protection in vivo and neutralization in vitro. Here, the authors confirm in a mouse model of tick-borne encephalitis (TBE) that immunization with the whole-killed virus vaccine protects mice against a subsequent challenge with a highly lethal dose of virus, i.e. 250 LD50 doses. Vaccine-induced immunity, however, is not completely neutralizing as demonstrated by the development of immune responses to a non-structural virus protein absent from the vaccine, yet expressed in the course of virus replication. Antibodies specific for the non-structural protein 1 (NS1) and cytotoxic T-cells could be detected after, but not prior to, virus challenge of vaccinated animals, establishing that protection by this highly effective vaccine is not equivalent with complete neutralization of the challenge virus.

Adoptive Transfer↗

Detection of tick-borne encephalitis virus by sample transfer, plaque assay and strand-specific reverse transcriptase polymerase chain reaction: what do we detect?

Experimental inoculation of mice provides a well characterized model for studying infection with tick-borne encephalitis virus (TBEV), a flavivirus pathogenic for humans. Conflicting data on the kinetics of viremia and the development of virus titers in the brain, however, were only recently shown to have resulted from the use of assay systems with different levels of sensitivity in the titration of TBEV, i.e. plaque assay or sample transfer into naive recipient mice. Theoretically, RT-PCR could extend further the detectability to antibody-neutralized virus and when undertaken strand-specifically discriminate active replication from the mere presence of TBEV. We have compared the conventional methods for detection of TBEV with a newly devised RT-PCR method. As expected, RT-PCR, in contrast to the infectivity assays, detected antibody-neutralized virus. Furthermore, the mere presence or active replication of the virus could be differentiated by strand-specific RT-PCR. Plaque assay and sample transfer, in contrast, both detected only infectious virus. However, whereas sample transfer provides higher sensitivity for detection of TBEV from solid organs, the plaque assay is less costly and considering animals welfare more convenient. Thus, the newly devised method may allow the resolution of unanswered questions, while both the traditional infectivity assays retain their benefits in certain situations.

Animals↗

Antibodies protect mice against challenge with tick-borne encephalitis virus (TBEV)-infected macrophages.

TBEV is a flavivirus highly pathogenic for humans. By transfer of antibodies directed to the TBEV surface glycoprotein E into mice, immune protection against subsequent inoculation with free TBEV particles could be achieved. After natural TBEV infection via the skin, however, cells of the monocyte/macrophage lineage were recently demonstrated to represent an important source of local virus replication before viraemia occurs. Whether antibodies can protect against virus challenge when contracted in the form of infected cells, however, is still unclear. In the current study, TBEV antibodies protected mice against challenge with either free virus or TBEV-infected macrophages equally well. This observation may be of more general significance.

Animals↗

Reactivity of European and American isolates of Borrelia burgdorferi with different monoclonal antibodies by means of a microimmunoblot technique.

Ten European and 3 North American isolates of Borrelia burgdorferi were compared as to their reactivity with 9 mouse monoclonal antibodies (MMA) to the type strain B. burgdorferi B31, and 1 MMA directed against B. hermsii. A Treponema pallidum strain was used for a genus-specific control. Differences in the protein patterns of the European and the North American strains were mostly based on the absence of distinct OspA and OspB bands. The OspA MMAs H 5332 and H 3TS were reactive with 3 European and the 3 North American strains. H 5332 alone reacted with another 3 strains from Europe, the remaining 4 were not recognized by one of the OspA MMAs. OspB MMAs showed reactivity with 3 European and the 3 North American strains. Of the flagella antibodies MMA H 9724 and H 604 reacted with all strains, whereas H 6TS reacted just with 2 each of the European and North American strains. There was no reactivity at all with the B. hermsii monoclonal H 9E11. No MMA reacted with the T. pallidum strain. According to a proposal for a serotyping system based upon major surface proteins of B. burgdorferi by A. G. Barbour, 6 of the strains investigated belong to serotype I, 3 to serotype II, and 4 to serotype III. Reactivity with 4 MMAs to OspB allowed to establish 5 subtypes. The geographical origin of the strains seems to be in relation with respective subtypes, an observation which needs to be substantiated for a larger group of strains. The microimmunoblot technique proved to be a useful tool which saves material and time and yields reproducible results.

Animals↗

Borrelia transfer by ticks during their life cycle. Studies on laboratory animals.

Ticks of the species Ixodes ricinus were cultured in the laboratory. Yellow silver rabbits, gerbils and white mice served as blood hosts. Borrelia burgdorferi could be detected by means of an IFA test in homogenates of female ticks, their eggs as well as the respective larval and nymphal ticks. Blood infection of splenectomized gerbils and ordinary white mice or of ordinary white mice alone has been demonstrated after feeding of larval or nymphal ticks on them, respectively. Spirochetemia started 5 to 8 days after feeding and lasted for ca 3 weeks. Two distinct peaks in the cell count of spirochetal organisms per ml blood plasma could be observed on days 11-13 (5 X 10(5) to 2 X 10(6) cells/ml) and 17-19 (10(5) cells/ml), regardless whether splenectomized gerbils or white mice were used. The results display that B. burgdorferi is vertically from the female ticks to their eggs and transstadially transmitted. The transmission-rate from larval to nymphal ticks is 100%. These findings show the tick itself as a main reservoir of B. burgdorferi. The established mouse-model appears to be a useful tool to detect Borrelia carrying ticks.

Animals↗

Optimization of isolated hyperthermic limb perfusion.

During isolated limb perfusion, we studied the impact of limb temperature on the concentration of cytostatic drugs in the tissue to identify a possible selective absorption of cytostatic agents by the various tissues. Ten consecutive patients with malignant melanoma were randomly divided into two different groups and perfused with 1 mg cisplatin per kg body weight. In one group the cytostatic agents were injected under hyperthermic conditions (39.5 degrees C) and in the other group under normothermic conditions (37 degrees C). The platinum concentration in the melanoma was twice as high in the hyperthermic group as in the group under normothermic conditions. In the tumor-free tissue the platinum concentration decreased with temperature while it remained constant in the musculature. This selective concentration of cisplatin in the tumor under hyperthermic conditions is accompanied by fewer side effects. Follow-up will show whether the oncological results will be improved in the hyperthermic conditions as one might expect.

Chemotherapy, Cancer, Regional Perfusion↗

Passive immunization reduces immunity that results from simultaneous active immunization against tick-borne encephalitis virus in a mouse model.

Concomitant administration of an antigen and antibodies of the respective specificity has been shown to result in reduced levels of actively produced antibodies. This has also recently been observed in a clinical trial on simultaneous passive and active immunization against tick-borne encephalitis virus (TBEV). In the current study the influence of simultaneous passive and active immunization on vaccine induced protective immunity against TBEV has been evaluated in a mouse model. Two immunizations with licensed whole-killed TBEV vaccines gave close to complete protection. Administration of human or mouse TBEV antibodies together with the first vaccine dose resulted in a significant reduction of vaccine induced protection against TBEV challenge. This effect was even more pronounced than that observed earlier on the levels of vaccine induced antibody.

Animals↗