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H Sauer

Publications and source records attributed to H Sauer.

At least 163 records · Page 9Linked to original sources
PubMed1996

[Quantitative magnetic resonance tomography and the severity of deficits in dementia of the Alzheimer type].

The aim of the present study was to investigate the severity of dementia of the Alzheimer type (DAT) with respect to morphological changes revealed by quantitative magnetic resonance imaging (MRI). Seventeen patients with DAT (NINCDS-ADRDA guidelines) and 10 healthy elderly controls were included. The severity of dementia was evaluated on the Mini Mental State Examination (MMSE), the Global Deterioration Scale (GDS) and the Brief Cognitive Rating Scale (BCRS). Three-dimensional MRI sequences were acquired using a 1.5-T Siemens Magnetom. Whole-brain volume and the volume of the amygdala-hippocampus complex (AHC) were assessed using the newly developed software NMRWin. This software provides a semi-automated measure of the whole brain volume, while measurement of substructures requires manual guidance. In addition, the ventricle-brain ratio (VBR) was assessed. All morphometric parameters differed significantly between the two groups. AHC volumes discriminated best between them with only a small overlap. These findings were confirmed when only the data of the mildly demented patients were included in the analysis. The degree of AHC atrophy exceeded that of generalized cerebral atrophy. The severity of dementia as indicated by the MMSE, GDS and BCRS scores was correlated significantly with the volumes of the AHC bilaterally, but not with whole-brain volume or with VBR. These results underline the importance of the mesial temporal substructures in the etiology and progression of DAT and indicate that the volume of the AHC can be monitored by MRI and may be used to follow up the disease process.

Aged↗
PubMed1995

Activation of a Cl(-)-conductive pathway in primary cultures of rat inner medullary collecting duct (IMCD) cells under hypotonic stress.

In intracellular recordings with conventional microelectrodes on rat IMCD cells, we find that hypotonic stress depolarizes membrane voltage and decreases cell input resistance. Ion substitution experiments reveal that these effects are largely due to the activation of a prominent Cl- conductance. After block of this conductance with dideoxyforskolin a smaller concomitant increase in K+ conductance becomes detectable.

Animals↗
PubMed1995

Glial cell line-derived neurotrophic factor but not transforming growth factor beta 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion.

Glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor beta 3 (TGF-beta 3) are members of the TGF-beta superfamily with high neurotrophic activity on cultured nigral dopamine neurons. We investigated the effects of intracerebral administration of GDNF and TGF-beta 3 on the delayed cell death of the dopamine neurons in the rat substantia nigra following 6-hydroxydopamine lesions of dopaminergic terminals in the striatum. Fluorescent retrograde tracer injections and tyrosine hydroxylase immunocytochemistry demonstrated nigral degeneration with an onset 1 week after lesion, leading to extensive death of nigral neurons 4 weeks postlesion. Administration of recombinant human GDNF for 4 weeks over the substantia nigra at a cumulative dose of 140 micrograms, starting on the day of lesion, completely prevented nigral cell death and atrophy, while a single injection of 10 micrograms 1 week postlesion had a partially protective effect. Continuous administration of TGF-beta 3, starting on the day of lesion surgery, did not affect nigral cell death or atrophy. These findings support the notion that GDNF, but not TGF-beta 3, is a potent neurotrophic factor for nigral dopamine neurons in vivo.

Adrenergic Fibers↗
PubMed1995

[Breast carcinoma--revision of follow-up recommendations. 2: Special diagnostic value of bone scintigraphy, thoracic radiography, liver ultrasonic, mammography and laboratory tests].

In the past, recommendations for the follow-up of women who had undergone primary treatment for a local or locoregional breast cancer, were mostly concerned with "programmed" protocols in which the frequency of the follow-up appointments and the examinations to be performed on the respective occasions (e.g. bone scintigraphy, chest X-ray, abdominal ultrasound, mammography and laboratory investigations/tumor markers) were rigidly fixed. The usefulness of these technical procedures is examined critically on the basis of the extensive publications in the literature. With the exception of regular mammography, which is a useful means of detecting malignancies at an early stage, none of the other technical investigations is recommended in women free of symptoms after breast surgery. The reason for this is that they contribute in no way to an improvement in survival or quality of life. By discarding the use of these ineffective diagnostic procedures, considerable savings could be made in the health care sector without any associated loss in the quality of the care afforded the women affected.

Aftercare↗
PubMed1995

[Breast carcinoma--revision of after-care recommendations. 1: Results of many large studies from the literature are in agreement].

In the past, recommendations for the follow-up of women who had undergone primary treatment for local or locoregional breast cancer, were mostly concerned with "programmed" protocols in which the frequency of the follow-up appointments, and the examinations to be performed on the respective occasions (e.g. bone scintigraphy, chest X-ray, abdominal ultrasound, mammography and laboratory investigations) were rigidly fixed. Numerous new facts reported in the literature (including prospective randomized studies and meta-analyses) now appear to show that this formalized approach to follow-up brings the patient no advantage in terms of approved chances of being cured, longer survival or better quality of life. For this reason, for breast cancer follow-up, a strategy is proposed that is based on meticulous history-taking and clinical examination, and which also emphasizes psychosocial rehabilitation aspects. Examinations using technical equipment are carried out only when justified by clinical suspicion of recurrent disease.

Aftercare↗
PubMed1995

Brain-derived neurotrophic factor and neurotrophin-4/5 modify neurotransmitter-related gene expression in the 6-hydroxydopamine-lesioned rat striatum.

Disruption of dopaminergic neurotransmission in the striatum by neurotoxic lesions of the substantia nigra leads to increases in glutamic acid decarboxylase and proenkephalin messenger RNA expression, and to decreases in preprotackykinin (the precursor molecule for substance P) messenger RNA expression in the two populations of striatal medium-sized spiny projection neurons. These cells also express TrkB, the neurotrophin receptor for brain-derived neurotrophic factor and neurotrophin 4/5, and TrkC, the receptor for neurotrophin-3. Since there is some indication that exogenous brain-derived neurotrophic factor can exert neuromodulatory effects in the basal ganglia, we studied the effects of repeated intrastriatal injections of the four members of the neurotrophin family of neural growth factors, nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 on the expression of striatal neurotransmitter-related genes in the unilaterally 6-hydroxydopamine-lesioned rat using in situ hybridization histochemistry. We found that 4 micrograms/day of brain-derived neurotrophic factor or neurotrophin-4/5 when injected intrastriatally for eight consecutive days led to a normalization of the denervation-induced decrease of preprotachykinin messenger RNA when compared to animals injected with equivalent doses of nerve growth factor, neurotrophin-3, or vehicle. Neurotrophin-4/5 alone also normalized expression of messenger RNA encoding the 67 x 10(3) mol. wt isoform of glutamate decarboxylase, while none of the neurotrophins had a significant effect on preproenkephalin messenger RNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Hypertonic stress increases the Na+ conductance of rat hepatocytes in primary culture.

We studied the ionic mechanisms underlying the regulatory volume increase of rat hepatocytes in primary culture by use of confocal laser scanning microscopy, conventional and ion-sensitive microelectrodes, cable analysis, microfluorometry, and measurements of 86Rb+ uptake. Increasing osmolarity from 300 to 400 mosm/liter by addition of sucrose decreased cell volumes to 88.6% within 1 min; thereafter, cell volumes increased to 94.1% of control within 10 min, equivalent to a regulatory volume increase (RVI) by 44.5%. This RVI was paralleled by a decrease in cell input resistance and in specific cell membrane resistance to 88 and 60%, respectively. Ion substitution experiments (high K+, low Na+, low Cl-) revealed that these membrane effects are due to an increase in hepatocyte Na+ conductance. During RVI, ouabain-sensitive 86Rb+ uptake was augmented to 141% of control, and cell Na+ and cell K+ increased to 148 and 180%, respectively. The RVI, the increases in Na+ conductance and cell Na+, as well as the activation of Na+/K(+)-ATPase were completely blocked by 10(-5) mol/liter amiloride. At this concentration, amiloride had no effect on osmotically induced cell alkalinization via Na+/H+ exchange. When osmolarity was increased from 220 to 300 mosm/liter (by readdition of sucrose after a preperiod of 15 min in which the cells underwent a regulatory volume decrease, RVD) cell volumes initially decreased to 81.5%; thereafter cell volumes increased to 90.8% of control. This post-RVD-RVI of 55.0% is also mediated by an increase in Na+ conductance. We conclude that rat hepatocytes in confluent primary culture are capable of RVI as well as of post-RVD-RVI. In this system, hypertonic stress leads to a considerable increase in cell membrane Na+ conductance. In concert with conductive Na+ influx, cell K+ is then increased via activation of Na+/K(+)-ATPase. An additional role of Na+/H+ exchange in the volume regulation of rat hepatocytes remains to be defined.

Animals↗
PubMed1995

[Adjuvant chemotherapy in soft-tissue sarcomas?].

PURPOSE: Patients with high-grade soft-tissue sarcomas have a bad prognosis because of frequent generalisation especially with lung metastases. The question is if there is a chance to modify the prognosis of these high risk patients by any form of adjuvant chemotherapy. PATIENTS AND METHODS: Published randomised studies with a no-chemotherapy control arm are reviewed. The most important criteria are disease-free survival and especially overall survival. RESULTS AND CONCLUSIONS: Postoperative adjuvant chemotherapy for high-grade soft-tissue sarcomas is still investigational. This holds true for all localisations: e. g. extremities, head and neck, trunk. More clinical studies are needed to establish any indication for routine application of cytostatic drugs in this setting. Other experimental procedures are also not yet prepared for widespread use outside of clinical trials: pre-operative ("neoadjuvant") induction chemotherapy, regional perfusion with cytostatics (+/- hyperthermia) or externally applied deep regional tumor hyperthermia with systemic chemotherapy. From the actual knowledge it should be concluded that the uncontrolled adjuvant treatment of soft-tissue sarcomas with cytostatic drugs might provoke more risks of side effects than gain in survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Cell adhesion to the apical pole of epithelium: a function of cell polarity.

Human uterine epithelium displays a distinct polarized organization with apical, lateral, and basal plasma membrane domains. Although non-adhesive throughout most of the menstrual cycle, epithelial cells allow attachment of trophoblast cells to their apical pole during embryo implantation. A recent hypothesis postulates that epithelial cells turn off genes for apical-basal polarity and turn on genes for a more mesenchyme-like phenotype allowing cell-cell interaction with trophoblast. Using an in vitro assay human uterine cell lines (RL95-2, HEC-1-A, AN3-CA) were selected on the basis of adhesiveness for trophoblast-type cells (JAR). Subsequently, uterine cells were examined for epithelium-specific ultrastructure using transmission electron microscopy, and for the expression of E-cadherin, alpha 6-, beta 1-, beta 4-integrin subunits and cytokeratin using immunocytochemistry, confocal laser scanning microscopy, and surface replication technique. HEC-1-A monolayers are non-adhesive for JAR cells and appear highly polarized expressing E-cadherin, alpha 6-, beta 1-, beta 4-integrin subunits, and cytokeratin. Both, integrins and E-cadherin, are present at the lateral membrane. RL95-2 monolayers which are adhesive for JAR cells appear non-polarized. Like HEC-1-A cells, RL95-2 cells express E-cadherin, alpha 6-, beta 1-, and beta 4-integrin subunits, and cytokeratin. In contrast to HEC-1-A cells, integrins and E-cadherin are distributed at the entire cell surface. AN3-CA monolayers are non-adhesive for JAR cells and appear non-polarized. Cells lack epithelial-specific markers such as keratin and E-cadherin. They show only low expression of alpha 6-, beta 1-integrin subunits and lack beta 4-integrin subunit. Conversely, they express vimentin. Thus, modulation of the epithelial phenotype of uterine cells, i.e. loss of apical-basal polarity, might prepare the apical cell pole for cell-cell interaction with trophoblast. However, loss of cell polarity would not lead to enhancement of adhesiveness for trophoblast if accompanied by a loss of epithelium-specific adhesion molecules.

Cadherins↗
PubMed1994

Human embryonic dopamine neurons xenografted to the rat: effects of cryopreservation and varying regional source of donor cells on transplant survival, morphology and function.

When grafting human mesencephalic tissue to patients suffering from Parkinson's disease, the number of surviving dopamine (DA) neurons in the graft is probably crucial. It may be possible to increase the number of DA neurons available for grafting to a patient by pooling tissue from many human embryos collected over several days or by obtaining more DA neurons from each embryo. We have addressed these issues by cryopreserving human mesencephalic DA neurons prior to transplantation and also by grafting human embryonic diencephalic DA neurons. The effects of cryopreservation were assessed 4-15 weeks after xenografting ventral mesencephalic tissue into the DA-depleted striatum of immunosuppressed rats with unilateral 6-hydroxydopamine lesions of the mesostriatal pathway. Control rats grafted with fresh mesencephalic tissue displayed robust reductions in amphetamine-induced turning following transplantation. Functional effects of the cryopreserved mesencephalic grafts were only observed in the one rat out of nine which contained the largest graft in this group. The number of tyrosine hydroxylase immunoreactive neurons in animals transplanted with cryopreserved tissue was significantly reduced to 9% of fresh tissue control grafts. Morphological analysis showed that cryopreserved DA neurons were approximately 22% and 28% smaller regarding the length of the long and short axis, respectively, when compared to the neurons found in fresh grafts. In the second part of the study, the survival and function of human embryonic diencephalic DA neurons were examined following xenografting into the DA-depleted rat striatum. A reduction of motor asymmetry was observed in two out of seven diencephalon-grafted rats. This finding was consistent with a good graft survival in these particular rats, which both contained large grafts rich in tyrosine hydroxylase immunoreactive neurons. Moreover, there was immunopositive staining for graft-derived fibers in the rat striatum containing tyrosine hydroxylase and human neurofilament, both in rats grafted with mesencephalic and diencephalic DA neurons. These findings suggest that cryopreservation, using the current technique, is not a suitable storage method for use in clinical trials of DA neuron grafting in Parkinson's disease. On the other hand, the application of alternative sources of DA neurons may in the future develop into a strategy which can increase the number of neurons obtainable from each human embryo.

Amphetamine↗
PubMed1994

Brain-derived neurotrophic factor enhances striatal neuropeptide expression in both the intact and the dopamine-depleted rat striatum.

In order to elucidate the importance of the striatal GABAergic neurones in mediating functional effects of exogenously applied brain-derived neurotrophic factor (BDNF) in the basal ganglia, we performed daily injections of BDNF or vehicle into the dopamine-depleted striatum of unilaterally 6-hydroxydopamine-lesioned rats for 1 week. In situ hybridization revealed that BDNF exacerbated the lesion-induced up-regulation of preproenkephalin (PPE) mRNA, and completely reversed the lesion-induced decrease of preprotachykinin (PPT) mRNA. In contrast, striatal levels of trkB mRNA were not significantly affected by BDNF administration. Up-regulation of PPE and PPT mRNA was also observed in unlesioned BDNF-injected animals. We conclude that exogenously applied BDNF increases neuropeptide mRNA expression in striatal neurones independently of the presence of a dopaminergic innervation.

Animals↗
PubMed1994

Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat.

In order to develop a rodent model displaying a progressive degeneration of the dopamine neurons of the substantia nigra, we bilaterally injected the tracer substance FluoroGold into the terminal field of the nigrostriatal projection, i.e. the striatum. One week later, rats received unilateral injections of 20 micrograms 6-hydroxydopamine into one of the two striatal tracer deposits. Groups of animals were killed one, two, four, eight and 16 weeks later. Ipsilateral to the lesion there was a progressive loss of FluoroGold-labelled nigral cells, with cell counts dropping from 96% of the contralateral side at one week to 59% at two weeks, 35% at four weeks, 23% at eight weeks and down to 15% at 16 weeks. Labelled nigral neurons ipsilateral to the lesion showed a moderate to marked atrophy at all investigated time points. The number of tyrosine hydroxylase-immunoreactive cells was decreased to 83% of contralateral at one week, 39% at two weeks, 44% at four weeks, 34% at eight weeks and 52% at 16 weeks postlesion. Rhodamine fluorescence immunocytochemistry showed that the proportion of surviving ipsilateral fluorogold-labelled cells displaying immunoreactivity for tyrosine hydroxylase was 69% at one week postlesion, 51% at two weeks, 63% at four weeks, 69% at eight weeks and 76% at 16 weeks. We conclude that injection of 6-hydroxydopamine into the terminal field of nigral dopaminergic neurons causes a progressive degeneration of these cells, starting between one and two weeks after lesion and continuing over eight to 16 weeks. This degeneration is preceded, and accompanied by, cellular atrophy and a partial loss of marker enzyme expression, thus yielding an animal model which mimics the degenerative processes in Parkinson's disease more closely than the animal models available so far. The present model may be helpful in investigating the in vivo effects of putative neuroprotective agents and neurotrophic factors.

Animals↗