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Biomedical subjects

I Fischer

Publications and source records attributed to I Fischer.

At least 37 records · Page 2Linked to original sources
PubMed2003

Delayed grafting of BDNF and NT-3 producing fibroblasts into the injured spinal cord stimulates sprouting, partially rescues axotomized red nucleus neurons from loss and atrophy, and provides limited regeneration.

Ex vivo gene therapy, utilizing modified fibroblasts that deliver BDNF or NT-3 to the acutely injured spinal cord, has been shown to elicit regeneration and recovery of function in the adult rat. Delayed grafting into the injured spinal cord is of great clinical interest as a model for treatment of chronic injury but may pose additional obstacles that are not present after acute injury, such as the need to remove an established scar, increased retrograde cell loss and/or atrophy, and diminished capacity for regeneration by neurons which may be doubly injured. The purpose of the present study was to determine if delayed grafting of neurotrophin secreting fibroblasts would have anatomical effects similar to those seen in acute grafting models. We grafted a mixture of BDNF and NT-3 producing fibroblasts or control fibroblasts into a complete unilateral cervical hemisection after a 6-week delay. Fourteen weeks after delayed grafting we found that both the neurotrophin secreting fibroblasts and control fibroblasts survived, but that only the neurotrophin secreting grafts provided a permissive environment for host axon growth, as indicated by immunostaining for RT-97, a marker for axonal neurofilaments, GAP-43, a marker for elongating axons, CGRP, a marker for dorsal root axons, and 5-HT, a marker for raphe spinal axons, within the graft. Anterograde tracing of the uninjured vestibulospinal tract showed growth into neurotrophin producing transplants but not into control grafts, while anterograde tracing of the axotomized rubrospinal tract showed a small number of regenerating axons within the genetically modified grafts, but none in control grafts. The neurotrophin expressing grafts, but not the control grafts, significantly reduced retrograde degeneration and atrophy in the injured red nucleus. Grafts of BDNF + NT-3 expressing fibroblasts delayed 6 weeks after injury therefore elicit growth from intact segmental and descending spinal tracts, stimulate modest regenerative growth by rubrospinal axons, and partially rescue axotomized supraspinal neurons and protect them from atrophy. The regeneration of rubrospinal axons into delayed transplants was much less than has been observed when similar transplants were placed acutely into a lateral funiculus or, after a 4-week delay, into a hemisection lesion. This suggests that the regenerative capacity of chronically injured red nucleus neurons was markedly diminished. The increased GAP43 reactivity in the corticospinal tracts ipsilaterally and contralaterally to the combination grafts suggests that these axons remain responsive to the neurotrophins, that the neurotrophins may stimulate both regenerative and sprouting responses, and that the grafted cells continue to secrete the neurotrophins.

Animals↗
PubMed2003

[The importance of bovine neosporosis for abortion in Switzerland].

The protozoan parasite Neospora caninum is one of the most important infectious abortion causes in cattle worldwide. In a Swiss case-control-study we investigated 113 abortion problem farms and 113 control farms. It was possible to detect N. caninum in 21% of 242 investigated aborted fetuses by PCR upon brain samples. Eighty-four % of mothers aborting N. caninum positive fetuses were serologically positive for this parasite. The seroprevalence for N. caninum of all aborting mothers was 44%. Within a period of 3 to 12 months 4,505 cattle from the participating farms were investigated serologically at two different time points. Strong fluctuations of the specific antibody concentration could be observed, resulting in a conversion to seronegativity in the second blood sample in 39% of formerly seropositive animals. Eighteen months after the end of the study, 42 case- and 42 controlfarms were questioned about their present abortion-status. Analysis of the questionnaire revealed that 80% of the former abortion problem farms observed an improvement of the situation. However, in 43% of those farms no preventive measures had been taken and no significant differences in hygiene, forage and animal turnover could be observed between case- and control-farms. Additionally, no significant differences were detected concerning risk factors such as the presence of farm dogs and the disposal procedure for placental and fetal material.

Abortion, Veterinary↗
PubMed2003

Cryofixation of epithelial cells grown on sapphire coverslips by impact freezing.

Rapid cryofixation of cells cultured on coverslips without the use of chemical fixatives has proved advantageous for the immunolocalization of antigens by electron microscopy. Here, we demonstrate the application of sapphire-attached tissue culture cells (PtK2 epithelial cells and mouse myoblasts) to metal-mirror impact freezing. The potential of the Leica EM-CPC cryoworkstation for routine freezing and for safe transfer of the cryofrozen samples into a sapphire disc magazine for freeze-substitution (SD-FS unit) has been exploited. Subsequently, the SD-FS unit has been tested for its use in methanol freeze-substitution and low temperature embedding for immunoelectron microscopy. The structural preservation of Lowicryl HM20-embedded cells has been assessed as being free of damage by large ice crystals.

Aluminum Oxide↗
PubMed2002

Transplantation of genetically modified cells contributes to repair and recovery from spinal injury.

The effects of transplantation of fibroblasts genetically modified to produce brain derived neurotrophin factor (Fb/BDNF) on rescue of axotomized neurons, axonal growth and recovery of function was tested in a lateral funiculus lesion model in adult rats. Operated control animals included those in which the lesion was filled with gelfoam implant (Hx) and those in which the cavity was filled with unmodified fibroblasts (Fb). Both Fb/BDNF and Fb transplants survived and filled the lesion site. Unoperated control groups showed a marked retrograde death of Red nucleus neurons contralateral to the lesion; Fb/BDNF recipients showed a significant rescue effect. Anterograde and retrograde labeling studies indicated no regeneration of rubrospinal axons into the lesion/transplant in operated control animals, but regeneration into, around, and through the transplant into the host was seen in the Fb/BDNF recipients. All animals showed deficits on the more challenging behavioral tests but the Fb/BDNF recipients showed fewer deficits, particularly in tests of spontaneous vertical exploration, horizontal rope crossing and a sensory test (patch removal). The improved function on these tests in the Fb/BDNF recipients was abolished by a second lateral funiculus lesion rostral to the transport site. These results indicate that delivery of neurotrophic factors by grafting genetically modified cells can improve repair and function after spinal injury.

Animals↗
PubMed2002

A non-randomised pilot study to compare complementary and conventional treatments of acute sinusitis.

BACKGROUND: It is still under discussion whether antibiotics are effective in the treatment of acute sinusitis. Moreover, they are known to have considerable side-effects. In contrast, complementary approaches are reported to have little side-effects and an equivalent efficiency. OBJECTIVES: To assess the success of conventional and complementary treatments of acute sinusitis and to estimate the patient numbers needed to confirm therapeutic equivalence. Treatment success was measured by three different scores, assessed by both patients and physicians. METHODS: Multicentre (2 complementary and 3 conventional ENT centres), non-randomised, controlled clinical trial with 63 patients (complementary group 30, conventional group 33 patients). To control for confounders treatment differences were estimated by propensity score techniques. TREATMENTS: The choice of medication was entirely left to the physician. We recommended to use antibiotics, secretolytics and symptomimetics in the conventional group and a combination of the herbal remedy Sinupret((R)) and the homeopathic remedy Cinnabaris 3X in the complementary group. RESULTS: Treatment differences varied substantially depending on the outcome measure, but they were always not clinically relevant. Conventional treatment was slightly better when the outcome was assessed by the physicians (1.8 score points) but slightly worse when it was assessed by patients (0.2 score points) or in terms of the HCG-5 quality of life score (0.8 score points). p values were always > 0.3. CONCLUSIONS: Both treatments appear to be equally effective (or ineffective). Results might be biased because both treatment groups differed substantially. Randomised trials including at least 400 patients are needed to produce valid results.

Acute Disease↗
PubMed2002

An example on the value of non-randomisation in clinical trials in complementary medicine.

BACKGROUND: Randomised clinical trials may in principle show a small external validity. Non-randomised clinical trials therefore are sometimes regarded as an appropriate alternative when complementary and conventional treatments are compared. OBJECTIVES: To assess the value of advanced statistical methods in the process of estimating differences between a complementary and a conventional treatment of acute sinusitis in a non-randomised clinical trial. METHODS: Multicentre, non-randomised, controlled clinical trial comparing 2 complementary and 3 conventional ENT centres. Patients were free to choose the physician (and hence the therapy). Treatment differences were estimated by controlling for confounders in analyses of covariance or by propensity score techniques. RESULTS: Most potential confounders (sex, age, life-style parameters) did not have significant effects on the choice of therapy. Disease severity and previous ENT surgery were the main confounding factors. At study onset they almost cause a defined separation of both treatment groups. As a result estimated treatment differences vary substantially depending on the chosen statistical model. CONCLUSIONS: When comparing complementary and conventional treatments, non-randomised clinical trials may be misleading. Results may be strongly biased even when advanced statistical methods are used. Trials of complex statistical designs are needed to give valid results.

Acute Disease↗
PubMed2001

A Swiss case-control study to assess Neospora caninum-associated bovine abortions by PCR, histopathology and serology.

Neospora caninum is one of the most frequent infectious organisms causing abortion in cattle worldwide. The present case-control study was designed to assess the importance of bovine neosporosis for causing abortion in Swiss cattle and to identify selected risk factors. Infection was primarily diagnosed by a N. caninum-specific PCR and serology, complemented with histopathology and immunohistochemistry. A total of 113 case and 113 corresponding control-farms were studied for 1.5 year. During this time period, 242 abortions were reported and referred for bacteriological, virological, parasitological and pathohistological examinations. N. caninum was detected by PCR in the brains of 21% of all aborted fetuses. Microscopic lesions indicative for cerebral protozoa infection were detected in 84% of PCR-positive fetal brains. Bovine viral diarrhea virus (BVDV) was demonstrated in 7% of the cases, and bacterial infections were detected in 4% of the abortions. One or more N. caninum-abortions occurred in 20% of the herds (41 case-farms and 3 control-farms). Serological examination of aborting mother cows revealed a significantly higher percentage of N. caninum-seropositive animals (44%) in comparison to the prevalence in a randomly selected population (12%). However, in eight cases (4% of all investigated abortions) seronegative cows aborted N. caninum PCR-positive fetuses, and in 50 cases the fetus remained negative although the respective mother cow was N. caninum-seropositive. Repetitive serological investigations (at a 3-12 months interval) of 3551 cows from case- and control-farms showed a decrease of the overall N. caninum-seroprevalence from 17 to 12%. Ninety out of 3008 seronegative animals were converted to N. caninum-seropositivity. Conversely, 212 out of 543 initially seropositive animals became seronegative for their second serum sample. The obtained data underlined the importance of N. caninum as a causative agent for abortion in Swiss cattle. Furthermore, PCR was confirmed to be a valuable diagnostic tool for the primary diagnosis of N. caninum in aborted fetuses. On the other hand, the value of serology appears to be hampered by the temporal instability of N. caninum antibody concentrations in adult cattle, including especially seronegativity of some individual animals. Thus, seronegativity in a mother cow or heifer does not exclude N. caninum-associated abortions.

Abortion, Veterinary↗
PubMed2001

Dynamics of semiconductor lasers subject to delayed optical feedback: the short cavity regime.

We give experimental and numerical evidence for a new dynamical regime in the operation of semiconductor lasers subject to delayed optical feedback occurring for short delay times. This short cavity regime is dominated by a striking dynamical phenomenon: regular pulse packages forming a robust low-frequency state with underlying fast, regular intensity pulsations. We demonstrate that these regular pulse packages correspond to trajectories moving on global orbits comprising several destabilized fixed points within the complicated phase space structure of this delay system.

Journal Article↗
PubMed2001

Transplants of cells genetically modified to express neurotrophin-3 rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats.

To test the idea that genetically engineered cells can rescue axotomized neurons, we transplanted fibroblasts and immortalized neural stem cells (NSCs) modified to express neurotrophic factors into the injured spinal cord. The neurotrophin-3 (NT-3) or nerve growth factor (NGF) transgene was introduced into these cells using recombinant retroviral vectors containing an internal ribosome entry site (IRES) sequence and the beta-galactosidase or alkaline phosphatase reporter gene. Bioassay confirmed biological activity of the secreted neurotrophic factors. Clarke's nucleus (CN) axons, which project to the rostral spinal cord and cerebellum, were cut unilaterally in adult rats by T8 hemisection. Rats received transplants of fibroblasts or NSCs genetically modified to express NT-3 or NGF and a reporter gene, only a reporter gene, or no transplant. Two months postoperatively, grafted cells survived at the hemisection site. Grafted fibroblasts and NSCs expressed a reporter gene and immunoreactivity for the NGF or NT-3 transgene. Rats receiving no transplant or a transplant expressing only a reporter gene showed a 30% loss of CN neurons in the L1 segment on the lesioned side. NGF-expressing transplants produced partial rescue compared with hemisection alone. There was no significant neuron loss in rats receiving grafts of either fibroblasts or NSCs engineered to express NT-3. We postulate that NT-3 mediates survival of CN neurons through interaction with trkC receptors, which are expressed on CN neurons. These results support the idea that NT-3 contributes to long-term survival of axotomized CN neurons and show that genetically modified cells rescue axotomized neurons as efficiently as fetal CNS transplants.

Animals↗
PubMed2001

In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP.

Human marrow stromal cells (hMSCs) are multipotential stem cells that can be differentiated into bone, cartilage, fat, and muscle. In the experiments here, we found that undifferentiated cultures of hMSCs express some markers characteristic of neural cells such as microtubule-associated protein 1B (MAP1B), neuron-specific tubulin (TuJ-1), neuron-specific enolase (NSE), and vimentin. By treating hMSCs with 0.5 mM isobutylmethylxanthine (IBMX)/1 mM dibutyryl cyclic AMP (dbcAMP) for 6 days, about 25% of the hMSCs differentiated into cells with a typical neural cell morphology and with increased levels of both NSE and vimentin. The data suggested that the hMSCs may have been differentiated into early progenitors of neural cells in vitro under conditions that increase the intracellular level of cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Chaos synchronization and spontaneous symmetry-breaking in symmetrically delay-coupled semiconductor lasers.

We present experimental and numerical investigations of the dynamics of two device-identical, optically coupled semiconductor lasers exhibiting a delay in the coupling. Our results give evidence for subnanosecond coupling-induced synchronized chaotic dynamics in conjunction with a spontaneous symmetry-breaking: we find a well-defined time lag between the dynamics of the two lasers, and an asymmetric physical role of the subsystems. We demonstrate that the leading laser synchronizes its lagging counterpart, whereas the synchronized lagging laser drives the coupling-induced instabilities.

Journal Article↗
PubMed2001

Radial glial cell line C6-R integrates preferentially in adult white matter and facilitates migration of coimplanted neurons in vivo.

C6-R is a cell line derived from C6 glioma cells that exhibits key properties of radial glia including the ability to support neuronal migration in culture. To explore its potential use in promoting neuronal migration in vivo, we analyzed the behavior of C6-R cells in the intact and injured adult rat CNS. At 6-11 days postimplantation at the splenium of the corpus callosum, green fluorescent protein-labeled C6-R cells were observed primarily in either the corpus callosum or the hippocampus in the brain, and in the spinal cord they migrated more extensively in the white matter than in the grey matter. To determine whether C6-R cells retain their ability to promote neuronal migration in vivo, they were coinjected with labeled neurons into adult brain. When rat embryonic neurons were coimplanted with C6-R cells, the neurons and C6-R cells comigrated through a much larger volume than neurons alone or neurons coimplanted with fibroblasts. In brains preinjured with ibotenic acid, C6-R cells as well as coimplanted neurons distributed widely within the lesion site and migrated into adjacent brain tissue, while transplants with neurons alone were restricted primarily to the lesion site. The results suggest that radial glial cell lines can serve as a scaffold for neuronal migration that may facilitate development of experimental models for neural transplantation and regeneration.

Animals↗
PubMed2001

[Antibiotic resistance of Staphylococcus aureus in urban experience: 6 month study in Aquitaine].

Antibiotic resistance of Staphylococcus aureus has been surveyed by eight city laboratories of the Aquitaine area, during a six month-period (january to june 1998). Antibiotic susceptibility testing has been performed by the disk diffusion method, and the results have been collected and analysed using the SIRscan system. After elimination of the redundant strains, a total of 747 isolates has been retained. They were mainly isolated from pus (64%) collected from patients of the community (40%) or hospitalized in 30 private clinics or nursing homes. The percentages of resistant strains (community/institutions) were: benzylpenicillin: 90% (87/92%), oxacillin: 39% (23/50%), kanamycin: 37% (22/47%); gentamicin: 13% (8/16%), tobramycin: 37% (21/47%), amikacin: 21% (13/27%); netilmicin: 6% (5/7%), erythromycin: 33% (30/35%), spiramycin: 72% (77/69%), lincomycin: 24% (17/29%), pristinamycin: 2% (1/2%), tetracycline: 17% (14/19%); pefloxacin: 40% (25/50%), fosfomycin: 9% (6/12%), rifampicin: 10% (7/13%), fusidic acid: 14% (11/15%), cotrimoxazole and vancomycin: 0%. Meticillin-susceptible strains of S. aureus were mostly sensitive to other antibiotics (< or = 6% resistant strains, except for erythromycin: 22%). Among meticillin-resistant S. aureus, heterogeneous strains with a KT phenotype, and various resistance patterns to the remaining antibiotics were predominant (61%), compared to the homogeneous strains with a KTG phenotype and multiresistant to the other antibiotics (32%). The frequencies of resistant strains were highly variable depending on the specimen, the laboratory and the health care institution, except for cotrimoxazole and vancomycin which were always active.

Anti-Bacterial Agents↗
PubMed2001

Grafting of encapsulated BDNF-producing fibroblasts into the injured spinal cord without immune suppression in adult rats.

Grafting of genetically modified cells that express therapeutic products is a promising strategy in spinal cord repair. We have previously grafted BDNF-producing fibroblasts (FB/BDNF) into injured spinal cord of adult rats, but survival of these cells requires a strict protocol of immune suppression with cyclosporin A (CsA). To develop a transplantation strategy without the detrimental effects of CsA, we studied the properties of FB/BDNF that were encapsulated in alginate-poly-L-ornithine, which possesses a semipermeable membrane that allows production and diffusion of a therapeutic product while protecting the cells from the host immune system. Our results show that encapsulated FB/BDNF, placed in culture, can survive, secrete bioactive BDNF and continue to grow for at least one month. Furthermore, encapsulated cells that have been stored in liquid nitrogen retain the ability to grow and express the transgene. Encapsulated FB/BDNF survive for at least one month after grafting into an adult rat cervical spinal cord injury site in the absence of immune suppression. Transgene expression decreased within two weeks after grafting but resumed when the cells were harvested and re-cultured, suggesting that soluble factors originating from the host immune response may contribute to the downregulation. In the presence of capsules that contained FB/BDNF, but not cell-free control capsules, there were many axons and dendrites at the grafting site. We conclude that alginate encapsulation of genetically modified cells may be an effective strategy for delivery of therapeutic products to the injured spinal cord and may provide a permissive environment for host axon growth in the absence of immune suppression.

Alginates↗
PubMed2001

Transplantation and gene therapy: combined approaches for repair of spinal cord injury.

Motor and sensory functions are lost after spinal cord injury because neurons die or atrophy and axons fail to regenerate. Until fairly recently, it was believed that damaged neurons could not be replaced and injured axons could not regenerate, and, therefore, functions dependent on injured neurons could not be recovered. We now know that damaged neurons can be rescued by providing therapeutic factors or replaced by grafting. In addition, the adult CNS contains a population of precursor cells with a potential to generate new neural cells, whose numbers and composition can be modified by extrinsic factors. The pioneering studies of Aguayo demonstrated that CNS axons could regenerate in the right environment. Subsequent studies have revealed the identity of some of the inhibitory molecules in myelin and scar tissue, and we now have a better understanding of how the CNS environment can be modified to become more permissive to regeneration. Axons that regenerate must find an appropriate target, but it may not be essential to reestablish the precise topography for some functions to be restored. There are now new and promising strategies for delivery of therapeutic genes to protect neurons and to stimulate regeneration. The ability to engineer cells by gene therapy combines the therapeutic values of cell transplantation and gene delivery. These remarkable developments from many disciplines have generated a new level of optimism in the search for a cure for CNS injury and in particular spinal cord injury. In this review, the authors summarize recent progress in these strategies and some of the challenges that remain in elucidating the most efficacious protocols for rescuing injured neurons, encouraging regeneration of their axons, and promoting recovery of function.

Adult↗
PubMed2000

Bilateral growth-related protein expression suggests a transient increase in regenerative potential following brain trauma.

The potential of mature central nervous system (CNS) neurons to regenerate after injury represents a fundamental issue in neurobiology. The regional expression of proteins associated with axonal elongation, such as microtubule-associated protein 1B (MAP1B), its phosphorylated isoform (MAP1B-P), growth-associated protein 43 (GAP-43), and polysialylated neural cell-adhesion molecule (PSA-NCAM), was examined using immunohistochemistry from 24 hours to 2 months following lateral fluid percussion brain injury of moderate severity (2.4-2.6 atmospheres) in anesthetized rats. Uninjured (control) rats were subjected to anesthesia and surgery without injury or were subjected to anesthesia alone. Within the site of maximal injury, only increases in MAP1B and MAP1B-P were observed. Increased immunoreactivity was observed bilaterally for all growth-related proteins that were evaluated. By 24 hours postinjury, MAP1B and MAP1B-P increased within the cortex (P < 0.01) and the hippocampus (P < 0.001), whereas MAP1B-P also was elevated in the thalamus (P < 0.05). Within the dentate gyrus, increased immunoreactivity was observed for all proteins examined. By 48 hours postinjury, GAP-43 was elevated bilaterally within the inner molecular layers of the dentate gyrus (P < 0.005) and within the stratum lacunosum moleculare (P < 0.01), the stratum radiatum (P < 0. 005), and the stratum oriens (P < 0.05) of the hippocampus. Increased numbers of PSA-NCAM-labeled neurons were observed in the granule cell layers of the dentate gyrus from 48 hours through 2 weeks postinjury (P < 0.0005). The bilateral nature of increased expression of growth-related proteins differs from unilateral patterns of neuronal degeneration previously characterized for the lateral fluid-percussion model of brain injury. Taken together, these results suggest the existence of a temporary posttraumatic state in which the CNS may have increased regenerative potential. Enhancement of such a response may be one therapeutic strategy in treating CNS injury.

Animals↗
PubMed2000

Characterization and intraspinal grafting of EGF/bFGF-dependent neurospheres derived from embryonic rat spinal cord.

Recent advances in the isolation and characterization of neural precursor cells suggest that they have properties that would make them useful transplants for the treatment of central nervous system disorders. We demonstrate here that spinal cord cells isolated from embryonic day 14 Sprague-Dawley and Fischer 344 rats possess characteristics of precursor cells. They proliferate as undifferentiated neurospheres in the presence of EGF and bFGF and can be maintained in vitro or frozen, expanded and induced to differentiate into both neurons and glia. Exposure of these cells to serum in the absence of EGF and bFGF promotes differentiation into astrocytes; treatment with retinoic acid promotes differentiation into neurons. Spinal cord cells labeled with a nuclear dye or a recombinant adenovirus vector carrying the lacZ gene survive grafting into the injured spinal cord of immunosuppressed Sprague-Dawley rats and non-immunosuppressed Fischer 344 rats for up to 4 months following transplantation. In the presence of exogenously supplied BDNF, the grafted cells differentiate into both neurons and glia. These spinal cord cell grafts are permissive for growth by several populations of host axons, especially when combined with exogenous BDNF administration, as demonstrated by penetration into the graft of axons immunopositive for 5-HT and CGRP. Thus, precursor cells isolated from the embryonic spinal cord of rats, expanded in culture and genetically modified, are a promising type of transplant for repair of the injured spinal cord.

Animals↗