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Biomedical subjects

H Arnold

Publications and source records attributed to H Arnold.

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

Effects of photodynamic therapy on glioma spheroids.

The present study describes the sensitivity of glioma cells to a haematoporphyrin derivative (Photosan-3) under laser activation (argon-pumped dye laser). The effects of photodynamic therapy (PDT) on cell growth, directional migration and cell invasion were investigated on two human glioma cell lines (GaMg and U-251 Mg). The directional cell migration and spheroid growth was determined for both cell lines exposed to increasing laser energy output (15-35J/cm2) with concentrations of 5 and 7 micrograms/ml of Photosan-3. Both cell lines showed a dose-dependent migratory response to increasing laser irradiation, that was more prominent in the 7 micrograms/ml treatment group. This effect occurred during the first 4 days after drug exposure. Also, spheroids from both cell lines showed a drug and laser output energy dose-dependent inhibition of growth which became apparent after a lag period of 6 days. The lag period was characterized by a decreased growth rate as compared with the control group. During this period the outer cell layers of the spheroids fell apart. The remaining spheroid tissue was not able to migrate and to regrow when exposed to the highest laser energy outputs (30-35J/cm2, 5 and 7 micrograms/ml Photosan-3). These spheroids showed, however, the ability for invasion when confronted with normal brain cell aggregated in vivo. Light microscopic observations of co-cultures between tumour tissue and brain cell aggregates revealed a normal tumour morphology. This indicates that the remaining tumour cells were not dead and could be stimulated to invade the normal tissue when exposed to a normal brain microenvironment.

Adult↗
PubMed1996

Regulation and function of SF/HGF during migration of limb muscle precursor cells in chicken.

Limb muscles of vertebrates are derived from migratory dermomyotomal cells which emanate from a limited number of somites located adjacent to the developing limb buds. We have generated additional limb buds in chicken embryos by implantation of FGF-beads into the interlimb region in order to analyze whether these somites can be programmed to supply ectopic limbs with myogenic precursor cells. We show that migrating myogenic precursor cells are released from somites at the level of the newly formed limb, even when cell migration into the natural limb has been completed. The implantation of FGF beads in the lateral plate mesoderm rapidly induces SF/HGF expression. FGF beads implanted between HH stages 10 and 12 inhibit limb bud formation or shift the normal limb position. When an additional FGF bead was implanted at the original limb position at HH stage 15, SF/HGF expression was transiently induced to low levels without inducing a new limb. This demonstrates that the initial induction of SF/HGF by FGF does not require limb formation. Expression of SF/HGF during early limb bud stages was found in the entire developing bud and the adjacent lateral plate mesoderm with direct contacts to the lateral edge of the dermomyotome. Later, the SF/HGF expression domain retracts to a distal region below the apical ectodermal ridge. To investigate the role of SF/HGF in the migratory process, we implanted beads soaked in SF/HGF-alone or together with FGF into different locations of the developing chick embryo. In the experiments SF/HGF caused delamination of migratory cells from the dermomyotomal epithelium but no chemotactic attraction of migrating cells toward the SF/HGF source.

Animals↗
PubMed1996

Gene targeting the myf-5 locus with nlacZ reveals expression of this myogenic factor in mature skeletal muscle fibres as well as early embryonic muscle.

We have introduced the nlacZ reporter gene into the locus of the myogenic factor gene myf-5 by homologous recombination in embryonic stem (ES) cells. Targeted ES clones were injected into precompaction morula, and the beta-galactosidase expression pattern was monitored. These mice permit the sensitive visualization of myf-5 expression throughout the embryo, and provide a standard for comparing it with that seen with different myf-5/nlacZ transgenes. Thus, in a comparison using ES cells in chimaeric embryos containing the targeted or randomly integrated myf-5/nlacZ construct, we demonstrate that 5.5 kbp of myf-5 upstream flanking sequence including exon1 and most of intron1 directs some skeletal muscle expression, but this is neither qualitatively nor quantitatively equivalent to that of the endogenous gene. Myf-5 is expressed early, before terminal myogenesis takes place in the medial half of the somite, and subsequently it is a major myogenic factor as skeletal muscle forms. All skeletal muscle shows beta-galactosidase activity, even after birth, indicating that myf-5 expression is not confined to primary myotubes, which are derived from embryonic myoblasts, but is also present in muscles containing different adult fibre types. The presence of myf-5 transcripts from the endogenous gene in older muscle was confirmed by in situ hybridization. These results suggest that the myf-5 gene is not activated in only a subset of muscle cells and are consistent with the results on the MyoD knockout mice.

Animals↗
PubMed1996

Sublethal effects of prolonged exposure to disulfoton in rainbow trout (Oncorhynchus mykiss): cytological alterations in the liver by a potent acetylcholine esterase inhibitor.

Mature male rainbow trout (Oncorhynchus mykiss) were exposed for 28 days to 0, 1, 5, and 20 micrograms/liter disulfoton, i.e., to concentrations well below any macroscopically visible effect due to the primary acute toxic mechanism of acetylcholine esterase inhibition. In an attempt to reveal sublethal injury of disulfoton in rainbow trout, ultrastructural and stereological parameters were recorded in the liver as the central organ of xenobiotic metabolism in fish. Quantitative methods were definitely not able to replace qualitative techniques because, except for mitochondria, peroxisomes, and hepatocellular lipid inclusions, stereological analysis revealed only insignificant variations of hepatocellular components, whereas hepatocytes displayed a complex pattern of numerous delicate qualitative alterations. Effects were most evident within cisternae of the rough endoplasmic reticulum (RER), thus suggesting modifications of protein metabolism. Structural alterations included degenerative effects such as dilation and vesiculation of RER cisternae, formation of concentric RER arrays and augmentation of smooth endoplasmic reticulum, dilation of Golgi cisternae, and the development of cytoplasmic myelinated bodies as well as stacks of membranous material within mitochondria. Structural integrity and augmentation of peroxisomes and mitochondria as well as increased activity of the Golgi system were indicative of adaptive/compensative reactions following disulfoton treatment. In fact, adaptive effects seemed more pronounced than degenerative phenomena resulting in only minor disturbances in hepatocyte structure following disulfoton exposure. Because most effects had to be classified as unspecific responses to environmental or xenobiotic stressors, no distinct mode of sublethal action can be suggested for disulfoton.

Animals↗
PubMed1996

Modulation of pain perception in man by a vasopressin analogue.

The aim of the present experiment was to test whether vasopressin modulates pain perception in man. Twenty-four male volunteers participated in four sessions, each 2 weeks apart. After an adaptation session the subjects were treated intranasally with either 30 or 60 micrograms desmopressin (DDAVP) or placebo according to a cross-over double-blind design. Pain induction involved mechanical, thermal, and ischemic stimulation DDAVP had no unitary effects on pain perception in the different pain tests. The 30 micrograms dose induced sensitization to thermal stimuli. Neither treatment influenced ischemic pain perception. The mechanical pain threshold of the index finger was increased by the 60 micrograms dose only. After treatment with either dosage of DDAVP the subjects generally tolerated the pressure on their index finger for a longer time than after placebo treatment.

Administration, Intranasal↗
PubMed1996

Cytological and biochemical response of R1 cells and isolated hepatocytes from rainbow trout (Oncorhynchus mykiss) to subacute in vitro exposure to disulfoton.

Ultrastructural, stereological and biochemical alterations in isolated hepatocytes and the permanent fibrocyte-like cell line R1 from rainbow trout (Oncorhynchus mykiss) exposed to 0, 0.2, 2 and 20 mg/l of the phosphorodithioate pesticide disulfoton (Solvirex, O,O-diethyl S-2-ethylthioethyl phosphorodithioate) for up to 5 days were investigated. In both R1 cells and isolated hepatocytes, distinct dose- and time-dependent morphological alterations including diminished amounts of heterochromatin, proliferation of lysosomal elements, dilation and vesiculation of endoplasmic reticulum cisternae, induction of concentric membrane whorls and an increased amount of lipid droplets could be detected at concentrations of > or = 2 mg/l (R1 cells) and > or = 0.2 mg/l disulfoton (hepatocytes). Additional effects in isolated hepatocytes comprised marginalization of heterochromatin, myelin-like structures attached to mitochondrial membranes, formation of ring-shaped mitochondria, proliferation of smooth endoplasmic reticulum, reduction of rough endoplasmic reticulum, induction of ring-shaped Golgi cisternae, glycogen depletion and occurrence of glycogenosomes. Structural changes in isolated hepatocytes could be correlated to suppression of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, alanine aminotransferase, malic enzyme, esterase as well as glutathione S-transferase, but to a stimulation of 7-ethoxycoumarin-O-deethylase and the rate of lipid peroxidation at concentrations > or = 0.01 mg/l disulfoton. Comparison with data from in vivo experiments with rainbow trout indicate the suitability of in vitro techniques for the evaluation of the toxicological potential of a wide range of ecotoxicologically relevant substances.

Animals↗
PubMed1995

Lesions of the alar ligaments. In vivo and in vitro studies with magnetic resonance imaging.

STUDY DESIGN: This study analyzed anatomic characteristics of the alar ligaments and the possibility of imaging them with magnetic resonance imaging. Also determined was whether artificial ruptures of the alar ligament can be recognized experimentally. OBJECTIVE: To determine the ability of magnetic resonance imaging to visualize normal, torn, resected alar ligaments. SUMMARY OF BACKGROUND DATA: There are no studies about computed tomography or magnetic resonance imaging findings of alar ligaments and after anatomic sections. Direct visualization of the complete ligament is not possible for computed tomography. No precise diagnostic method for showing a ruptured alar ligaments has been described. Magnetic resonance imaging seems to be the method of choice for distinguishing between normal and pathologic soft tissue. METHODS: Fifteen specimens from accident victims underwent anatomic dissection. In addition, ligaments from three groups were examined: 1) eight volunteers, 2) seven patients, and 3) 17 fresh cadaveric specimen before anatomic exploratory dissection. In seven of these specimens, one ligament was cut to simulate an artificial disruption and magnetic resonance imaging was repeated. RESULTS: Lesions of the alar ligaments were found in four of 15 prepared specimens. Using magnetic resonance imaging, the alar ligaments could be identified in all volunteers, patients, and specimen except one. No ruptures were found in the 17 specimens. Of the seven resected specimens, all cuts could be demonstrated by magnetic resonance imaging. CONCLUSION: Magnetic resonance imaging is useful for showing lesions of the alar ligaments because of a high soft tissue contrast, plane independence imaging, possibility of functional scans, and secondary reconstruction from three-dimensional data sets.

Atlanto-Occipital Joint↗
PubMed1995

Acute subdural haematoma from ruptured intracranial aneurysms.

Acute subdural haematoma (SDH) secondary to a ruptured intracranial aneurysm is a rare event. Out of a total of 292 patients with a verified aneurysm (period 1986-1992) in five cases SDH was the diagnosis on CT-evaluation. One patient was in such a bad condition that no treatment was indicated. The remaining four patients were operated on: craniotomy and haematoma evacuation in two cases, craniotomy for haematoma evacuation and aneurysm clipping in the other two cases. Two patients died and two achieved a good outcome.

Acute Disease↗
PubMed1995

Morphology and ultrastructure of the redia and pre-emergent cercaria of Opisthorchis viverrini (Trematoda: Digenea) in the intermediate host Bithynia siamensis goniomphalus (Prosobranchia: Bithyniidae).

The intramolluscan stages of the human liver fluke Opisthorchis viverrini were investigated by light, scanning, and transmission electron microscopy. The morphology of the tegument, and the excretory system of the redia and pre-emergent cercaria as well as glandular cells, tail structure, and the eye spots of the cercarial stage are described. Possible environmental adaptations are discussed. The redia is characterized by a tegument which is folded concentrically and covered with densely arranged microvilli. This tegument is composed of a typical syncytium with submerged tegumental cells. The pre-emergent cercaria is characterized by a long tail with prominent fin folds and obliquely striated muscles. The oral sucker is well developed and protrusible, whereas the ventral sucker is faintly developed. Proteinaceous tegumental spines which are arranged transversally and different kinds of presumed sensory structures cover the cercarial body surface. Two well pigmented eye spots with rhabdomeric photoreceptors are located in the anterior part of the body. An extended protonephridial system is connected to a voluminous excretory bladder. The excretory tube opens at the end of the body and does not lead into the tail. Three types of glandular cells could be differentiated according to their vesicles, which are shed into the syncytial layer.

Animals↗
PubMed1994

Induced hyperthermia in brain tissue in vivo.

Concerning hypothermia treatment, knowledge of time-temperature and of temperature distributions within tumor volumes is essential in order to obtain the maximal therapeutic effect. New techniques are being developed to overcome these difficulties. Two different heat sources, a contact Nd:YAG laser system and an automatically controlled high-frequency current system were investigated on 15 rabbits. Changes of the intracerebral temperature were registered at 4 different distances from the energy source. The intracerebral temperature was increased to 42.5 degrees C at a distance of 5 mm to the heat source and maintained at this level for a period of 60 min. The contact Nd:YAG laser system reached 42.5 degrees C at 3 W of output power. Using higher laser output power, brain tissue herniation (brain edema) through the burrhole was observed. The automatically controlled high-frequency current system reached 42.5 degrees C at 18.75 W of output current. A very small herniation of brain tissue could be observed using higher output current. Both heat sources presented an exponential decrease of the temperature profile depending on the distance. The tissue heat clearance was compensated for by intermittent laser or high-frequency current application. Both systems proved efficient for inducing hyperthermia as needed for antitumoral therapy.

Animals↗
PubMed1994

Gain and loss of the ability to compete. Some aspects of German neurosurgery up to 1939.

Sketchy biographies of 4 German neurosurgeons (Krause, Foerster, Stieda, Tönnis) demonstrate how neurosurgery in Germany rapidly developed and flourished from the end of the 19th century to the middle of the thirties. However, the dictatorship of Hitler, racial persecution, and the Second World War disturbed this promising development markedly and the aftermath was prolonged. It took many years to restore disrupted international relations and to regain the ability to compete in the scientific field.

Germany↗
PubMed1994

Interaction between human medulloblastomas and foetal rat brain aggregates in vitro.

The invasiveness of three medulloblastoma permanent cell lines (D-283, D-341, and DAOY), a human medulloblastoma biopsy, and in addition, a human rhabdomyosarcoma permanent cell line (TE-671), which previously had been regarded as a human medulloblastoma, was studied in an organ co-culture assay. All the four cell lines and the biopsy were co-cultured with normal rat brain cell aggregates for up to six days in vitro. The medulloblastoma biopsy, the D-283 and the D-341 cells invaded the brain tissue by diffuse single cell infiltration. The medulloblastoma cell line (DAOY) showed an invasive pattern similar to that observed earlier for most glioblastoma cell lines. This was characterized by massive cell replacement and destruction of normal brain tissue. The rhabdomyosarcoma cell line (TE-671) presented a solid invasive pattern with a fairly well defined border between normal brain and tumour tissue. Thus, the organ co-culture assay system in vitro seems to mimic several aspects of the in situ invasive behaviour of medulloblastomas. It may, therefore, provide new perspectives for pretreatment investigations with chemotherapy and radiotherapy of these malignancies.

Animals↗
PubMed1994

Early management in poor grade aneurysm patients.

Aneurysm surgery began in Lübeck only in 1986 when the department was completely reorganized. Early operation in the good grade patients (I-III, according to Hunt and Hess) was performed. In every case we also discussed the feasibility of operating on the poor grade patients (Hunt and Hess IV and V). During a five-year period (1986-1991) a total of 277 SAH patients were admitted to the department. 109 (39%) patients arrived in a poor grade (Hunt and Hess IV or V), 12 of these patients died within hours of admission. 25 patients, who presented with a large intracerebral and/or subdural haematoma, were urgently operated upon by haematoma evacuation and aneurysm clipping. An external ventricular drainage was performed on 72 patients. Of the ventriculostomy group 33 patients improved and 27 were operated upon. In 17 of the 39 patients without improvement after CSF-drainage we decided to operate. Overall 69 patients were surgically treated (craniotomy, aneurysm clipping) and 40 were not. The mortality rate in the surgical cases was 16 (23%) compared with 30 (75%) without operation. It is concluded that poor grade aneurysm patients can achieve a better outcome with active treatment based on immediate ventriculostomy and optimal haemodynamic parameters after haematoma evacuation and early occlusion of the aneurysm.

Aneurysm, Ruptured↗
PubMed1994

Aneurysm surgery in poor grade patients. Results, and value of external ventricular drainage.

The attitude concerning early clipping of aneurysms or generally aneurysm surgery in poor grade patients is controversial. There is no discussion about the space-occupying haematomas that must be removed urgently even in grade V patients if they have been admitted immediately after the acute event. Several patients in grade IV or V following a pure subarachnoid haemorrhage, can be improved by external ventricular drainage and thereafter their aneurysm operated upon with a better chance. Intelligible, the frequency of shunts needed is higher in poor than in good grade patients. Nevertheless, it can be reduced if the pressure, against what CSF is drained off, is kept on a higher level (about 20 cm H20) once the patient has stabilised. It also appears recommendable to operate upon aneurysms in patients who persist for several days in a condition no better than grade IV, rather than to assume an expectative attitude, for aneurysm rerupture mostly terminates the life of the patient, whereas clipping gives a change of recovery.

Aged↗
PubMed1994

Interactions between fetal rat brain cells and mature brain tissue in vivo and in vitro.

Fetal as well as mature neural cells were homografted into the right cerebral hemisphere of adult BD-IX rats. The animals were sacrificed 7 d after implantation, and the localization of implanted cells was visualized by fluorescence and light microscopy. The cell implants were prestained with the fluorescent vital dye 1,1'-Dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI) to discriminate between implanted cells and host brain tissue. At the implantation site, the fetal brain cells as well as the cells from immature brain cell aggregates showed diffuse infiltration into the surrounding host brain tissue of up to 0.5 mm. Extensive cell migration along the corpus callosum for up to 5 mm in the coronal and to a lesser extent in the sagittal plane was also observed. In addition, fetal cells were distributed in the subarachnoid space of both cerebral hemispheres and showed a distinct association with larger blood vessels. Cells from mature brain aggregates did not migrate as far as fetal cells and showed only a local infiltration into the host neuropil. Fluorescent microspheres as well as fixed fetal brain cells were implanted, either alone or in combination with vital cells to distinguish between active cell migration and passive cell displacement. The microspheres and the fixed cells were found either localized to the implantation pathway or distributed in the corpus callosum for up to 2 mm in the coronal plane without any dispersion in the sagittal plane. The microspheres also showed an extensive displacement in the subarachnoid space. In vitro co-culture experiments between two immature aggregates showed a complete fusion of the two aggregates during a 96 h culture period. In co-cultures between two mature aggregates complete fusion was not prominent, although the confrontation zone appeared diffuse. Confrontations between a mature and an immature aggregate showed the same pattern of interaction as seen for the two mature aggregates. It is concluded that carbocyanine dyes may be used as a tracer for transplanted cells. Cells from fetal rat brain cell aggregates, opposed to those from mature aggregates, showed extensive migration along well defined anatomical structures in the mature along well defined anatomical structures in the mature brain. Some of the spread of cells following implantation is probably due to passive movement since inert microspheres will spread into certain areas of the CNS.

Animals↗
PubMed1993

Proliferation, migration and invasion of human glioma cells exposed to antifolate drugs.

The present study describes the effects of 2 folate antagonists, methotrexate (MTX) and the lipophilic antifolate trimetrexate (TMX) on 2 permanent human glioma cell lines (GaMg and D-54Mg) grown as monolayers and as multicellular tumor spheroids. In addition, the effects of drug exposure on tumor cell invasion was studied using a three-dimensional organ co-culture system. In monolayer cultures, TMX was a more potent inhibitor of cell growth than MTX, especially towards the GaMg cell line. The 2 drugs, however, showed similar cytotoxicity as assessed by the plating efficiency assay. Reduced ability of directional migration of cells on a plastic surface was seen by either antifolate usually at concentrations to 10-fold higher than those exerting a cytotoxic effect in the plating efficiency assay. TMX was somewhat more potent than MTX as an inhibitor of spheroid growth. When tumor spheroids were exposed to MTX or TMX at concentrations that caused 65 to 70% inhibition of cell migration, there was a latent period of 4 to 5 days before inhibition of spheroid growth ensued. Invasion was investigated in a co-culture system, where tumor spheroids were confronted with fetal rat brain cell aggregates. Neither drug reduced tumor cell invasion, although histological examination revealed toxic effects both in GaMg and in D-54Mg spheroids. We conclude that spheroids from human glioma cells were less sensitive to the antifolates than monolayers. For both drugs a latency period was observed before inhibition of spheroid growth. The spheroids retained their ability to invade normal brain tissue when exposed to levels of folate antagonists inhibiting spheroid growth.

Animals↗