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Biomedical subjects

C Schwarz

Publications and source records attributed to C Schwarz.

At least 19 recordsLinked to original sources
PubMed2006

Transient change in GABA(A) receptor subunit mRNA expression in Lurcher cerebellar nuclei during Purkinje cell degeneration.

BACKGROUND: Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks. Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Here, we further investigated this phenomenon, using real-time RT-PCR to assess GABAA receptor subunit gene expression during PC degeneration. RESULTS: We observed a specific reduction in gamma2 subunit gene expression, while alpha1-5, beta1-2, gamma1,3 and delta subunits were unaffected. We made two further specific findings. First, the difference in gene expression was shown in tissue from DCN only. Neither the hippocampus nor coronal sections through the forebrain showed such effects. Furthermore, the involvement of different levels of corticosterone, a possible humeral trigger for differences in gene expression, could be excluded. Second, like the known potentiation of GABAergic synapses, the gamma2 down-regulation was present only after the onset of degeneration at p14. The difference in gamma2 mRNA expression, however, appeared transient, since it was no longer detectable in adult Lurcher mice. CONCLUSION: In conclusion, the down-regulation of gamma2 subunits may be related to differences in synaptic efficacy and, as such, may reflect the initial phase of adaptive responses of DCN tissue to massive GABAergic deafferentation. Its transient course, however, does not support the idea that modulations in GABAergic transmission are at the basis of the well-known DCN-based functional benefit of Lurcher mice present throughout their life.

Aging↗
PubMed2006

[Identification of the intercycle FSH signal in urine samples (uFSH)].

OBJECTIVE: The intercycle FSH signal that initiates follicular recruitment and marks the functional onset of the menstrual cycle is of small amplitude and while it commonly occurs on cycle day 3, this often varies. Hence, its identification and measurement in serum (sFSH) requires serial daily samplings. We attempted to determine whether urine measurements of FSH (uFSH) could offer a non-invasive alternative, using a model where the intercycle FSH signal is controlled by timely use of exogenous E2. PATIENTS AND METHODS: Pilot prospective trial in 21 infertile women having received E2, from day 25 of the previous cycle until the 1st Friday after menses. Blood and first void urine samples were collected, starting on the last day of E2 (baseline) for assessing FSH and creatinin. A sonogram was performed for identification of maturing follicles (>12 mm). RESULTS: uFSH and uFSH/Cr showed good correlation with sFSH (R = 0.52 and 0.63, P < 0.0001 and P < 0.0001, respectively). In 15/21 patients who had an intercycle sFSH elevation, this was confirmed by uFSH elevation, both occurring within 2-4 days after stopping E2. In all these women, the sonogram showed evidence of impending ovulation. The amplitude of the uFSH signal was on average 3 times higher than its sFSH counterpart. In 6/21 women, no intercycle FSH elevation was detected and no ovulation occurred. DISCUSSION AND CONCLUSION: Our results show that the intercycle FSH signal can easily be identified and measured in urine. This novel approach permits more precise assessments of ovarian physiology than with blood measurements.

Adult↗
PubMed2006

Diagnosis of renal osteodystrophy.

The idiom renal osteodystrophy (ROD) represents a heterogeneous pattern of bone disturbances caused by chronic renal insufficiency and concomitant diseases. For the clinical decision of therapy it is most important to differentiate between high and low or adynamic turnover ROD because the therapeutically consequences of these two ends of the ROD spectrum are fundamentally different. Bone histology remains the gold standard for the exact classification of ROD. Serological markers of bone metabolism are not suited for the accurate nomenclature of ROD but are useful for the sequential follow up of ROD after a clear diagnosis has been made. Similarly, radiological diagnosis of ROD using dual energy X-ray absorptiometry (DEXA) or quantitative computer tomography scan (q-CT) is inaccurate and thus more suited for the routine follow up of established disease. Besides mineralization, bone strength and the rate of fractures are strongly determined by the architecture of the bone matrix. This information, however, is also only available on bone biopsy sections and cannot be estimated by non-invasive diagnostic methods. In summary, bone biopsy should be used more liberally for correct classification of bone disease. The sequential follow up and guidance of therapy success can be performed by non-invasive procedures such as biochemical bone marker determination in blood. X-ray imaging and densitometry is suitable only for sequential evaluation of osteoporosis.

Acid Phosphatase↗
PubMed2006

Metabolic alkalosis in a hemodialysis patient--successful treatment with a proton pump inhibitor.

Hemodialysis patients develop metabolic acidosis due to their impaired excretion of daily produced protons (H+). The following report will show a rare case of severe metabolic alkalosis (predialysis pH 7.52, base excess (BE) +17) in a hemodialysis woman caused by self-provoked upper gastrointestinal H+ losses based on an eating disorder. Treatment with a proton pump inhibitor resulted in the normalization of acid/base homeostasis (predialysis pH 7.40, BE +1.6).

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Isotopic scaling and the symmetry energy in spectator fragmentation.

Isotopic effects in the fragmentation of excited target residues following collisions of 12C on (112,124)Sn at incident energies of 300 and 600 MeV per nucleon were studied with the INDRA 4pi detector. The measured yield ratios for light particles and fragments with atomic number Z < or = 5 obey the exponential law of isotopic scaling. The deduced scaling parameters decrease strongly with increasing centrality to values smaller than 50% of those obtained for the peripheral event groups. Symmetry-term coefficients, deduced from these data within the statistical description of isotopic scaling, are near gamma = 25 MeV for peripheral and gamma < 15 MeV for central collisions.

Journal Article↗
PubMed2004

Sirolimus-eluting stents for percutaneous coronary intervention in acute myocardial infarction Lesson from a case-controlled comparison of bare metal versus drug-eluting stents in thrombus-laden lesions.

BACKGROUND: Given the encouraging results on early restenosis rate with drug-eluting coronary stents, both safety and 6 months outcomes of PCI with sirolimus-eluting stents (SES) in acute myocardial infarction are scarce. METHODS AND RESULTS: Fifty consecutive patients with acute myocardial infarction were subjected to acute PCI with SES and compared to 50 matched control patients who received a bare metal stent (BMS). All patients were followed over 6 months; in addition repeat angiography was obtained in 88.0% of SES and 92.0% of BMS patients. As a result of matching both groups were similar with regard to demographic, clinical, and infarction characteristics, as well as procedural data and adjunctive medication. SES diameter was 3.0 +/- 0.1 versus 3.3 +/- 0.5 mm with BMS, while the length of stented segment was 24 +/- 11 mm with SES versus 16 +/- 8 mm with BMS (p<0.05). No subacute stent thrombosis occurred in either group. At 6 months, all-cause mortality was 2.0% with SES, and 4.0% with BMS (n. s.); reinfarction rate was 2.0% in both groups, but binary restenosis rate (4.0 versus 18.0%; p<0.05) and target vessel revascularization (TVR) were improved with SES (2.0 versus 16.0%; p<0.05) resulting in lower MACE rate of 6.0 versus 22.0% with BMS (p<0.05). CONCLUSION: Placement of SES with PCI for myocardial infarction is feasible and as safe as BMS; 6-month outcome is superior with SES due to the lower rate of both angiographic restenosis and TVR.

Aged↗
PubMed2004

Restless legs syndrome: an overview of the current understanding and management.

Over the last few years, major progress in research has improved our understanding of the restless legs syndrome (RLS). Although frequently under-diagnosed, several epidemiological studies have estimated its prevalence in western countries at 4-10% of the general population. Its diagnosis is usually made on a clinical basis, according to the criteria established by the International RLS Study Group (Mov Disord 1995; 10:634). Furthermore, major advances have also been achieved regarding our understanding of the pathophysiology of the disorder. Thus, several brain imaging studies, as well as pharmacological challenges, suggest the presence of a dopaminergic dysfunction playing a major role in its causation. In addition, a strong association has been discovered between brain iron deficiency and RLS. Eventually, dopaminergic drugs have shown therapeutic efficacy in various large-scale therapeutic trials, and, today, dopaminergic agonists represent the first line of treatment. In conclusion, these and other recent findings shed light on our understanding and management of one of the most common movement disorders.

Anemia, Iron-Deficiency↗
PubMed2004

Medical thoracoscopy: hormone receptor content in pleural metastases due to breast cancer.

Pleural metastases are common in the course of breast cancer, but, to date, the role of oestrogen receptor (OR) and progesterone receptor (PgR) content in metastatic tissue has been poorly evaluated. A series of 50 consecutive patients with a history of breast cancer (median age 64 yrs, range 40-86 yrs), which presented with pleural effusion and therefore underwent medical thoracoscopy, was analysed. Metastatic pleural involvement was histologically confirmed in all patients. The hormone receptor status of the pleural metastases was investigated using the immunohistochemical method in 49 and the biochemical method in 31 cases. The immunohistochemical test was performed using monoclonal antibodies. Biochemical analysis was performed on specimens quick-frozen in liquid nitrogen. OR and PgR were measured with the dextran-coated charcoal assay and Scatchard analysis. Immunohistochemical analysis yielded 29 OR-positive and 25 PgR-positive cases and biochemical analysis yielded 16 OR-positive and four PgR-positive cases, sometimes discrepant to hormone status of the primary breast cancer. Using a semiquantitative immunoreactive score, there was a significant association between receptor positivity and survival, but only for PgR positivity. Immunohistochemical and biochemical detection of hormone receptors (oestrogen and progesterone) in pleural metastases of breast cancer is feasible based on medical thoracoscopy as the method of choice, by which sufficient specimens may be obtained. The receptor status may enable a decision on antihormonal treatment. Whether a positive receptor status in pleural metastatic tissue is associated with a better prognosis remains to be confirmed.

Adult↗
PubMed2003

L-DOPA-induced excessive daytime sleepiness in PD: a placebo-controlled case with MSLT assessment.

A 74-year-old patient with idiopathic Parkinson's disease was evaluated for unintended sleep episodes that occurred after long-term treatment with 400 mg/day of L-dopa. Overnight sleep studies and multiple sleep latency testing were carried out under double-blind administration of either L-dopa or placebo. Mean sleep latency with L-dopa was 7 minutes, in contrast to a normal value of 19 minutes, 25 seconds with placebo. The authors' results suggest that L-dopa may cause daytime somnolence in some patients with Parkinson's disease.

Aged↗
PubMed2003

Lurcher mice exhibit potentiation of GABA(A)-receptor-mediated conductance in cerebellar nuclei neurons in close temporal relationship to Purkinje cell death.

In heterozygous Lurcher mice (Lc/+), the Purkinje cells (PCs) degenerate almost totally during postnatal development. On the other hand, their projection target, the deep cerebellar nuclei (DCN), shows few signs of degeneration and seems to play an important role in maintaining a residual cerebellar function in Lc/+. We asked whether the DCN in Lc/+ develop cellular adaptations allowing them to cope with the loss of GABAergic PC input. Using whole-cell patch-clamp recordings, we measured inhibitory postsynaptic currents from DCN of Lc/+ and wild-type mice (WT). In experiments on phenotypically striking Lc/+ studied well after the onset of the PC degeneration, we found enlarged average synaptic conductances (g(syn)) compared with WT. We next investigated postnatal mice before and after the onset of PC death. In younger animals </= postnatal day (p) 13, no difference was found in g(syn) between the two groups. At p14, g(syn) in Lc/+ showed an increase, while those in WT stayed on the level found in younger animals. A peak-scaled nonstationary fluctuation analysis suggests that an increase in the average number of channels open at peak is the basis for the change in g(syn). The changes in g(syn), suitable to increase the efficacy of GABAergic transmission, occur in close temporal relationship to PC death and, thus, may reflect a functional adaptation to the loss of the DCN's main GABAergic afferents.

Animals↗
PubMed2002

MEA-Tools: an open source toolbox for the analysis of multi-electrode data with MATLAB.

Recent advances in electrophysiological techniques have created new tools for the acquisition and storage of neuronal activity recorded simultaneously with numerous electrodes. These techniques support the analysis of the function as well as the structure of individual electrogenic cells in the context of surrounding neuronal or cardiac network. Commercially available tools for the analysis of such data, however, cannot be easily adapted to newly emerging requirements for data analysis and visualization, and cross compatibility between them is limited. In this report we introduce a free open source toolbox called microelectrode array tools (MEA-Tools) for the analysis of multi-electrode data based on the common data analysis environment MATLAB (version 5.3-6.1, The Mathworks, Natick, MA). The toolbox itself is platform independent. The file interface currently supports files recorded with MCRack (Multi Channel Systems, Reutlingen, Germany) under Microsoft Windows 95, 98, NT, and 2000, but can be adapted to other data acquisition systems. Functions are controlled via command line input and graphical user interfaces, and support common requirements for the analysis of local field potentials, extracellular spike activity, and continuous recordings, in addition to supplementary data acquired by additional instruments, e.g. intracellular amplifiers. Data may be processed as continuous recordings or time windows triggered to some event.

Action Potentials↗
PubMed2002

Tight junction proteins: a novel class of integral membrane proteins. Expression in human epidermis and in HaCaT keratinocytes.

Tight junction proteins comprise a novel group of integral membrane proteins necessary for cell-to-cell contacts and responsible for the barrier function in epithelial and endothelial cells in various tissues. The tight junction membrane domain contains at least three distinct proteins, named occludin, claudin and junctional adhesion molecule. Claudins are products of a gene family consisting of more than 20 members. We investigated mRNA expression of occludin and 13 different claudins in neonatal foreskin, adult skin and cultivated HaCaT keratinocytes by the Northern blot technique, and performed immunohistochemical staining of adult skin for occludin, claudin 1 and claudin 2. Occludin, claudin 1 and claudin 3 mRNAs were expressed in human neonatal and adult keratinocytes as well as in HaCaT keratinocytes. All other tested claudins were negative. Immunohistochemical staining of adult skin was positive for occludin in the intercellular space of the granular layer, and for claudin 1 in the inter-cellular space of the spinosum layer and basal layer, but negative for claudin 2 in all skin layers. Claudin 1 was also positive in the outer root sheath of hair follicles. Our results indicate that occludin, claudin 1 and claudin 3 are involved in cell-to-cell contacts between keratinocytes in human epidermis, although their functional importance remains unknown.

Adult↗
PubMed2001

Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis.

OBJECTIVE: The apolipoprotein E (APOE) polymorphism is known to impact on various neurologic disorders and has differential effects on the immune system and on CNS repair. Previous findings concerning a possible modulation of the clinical course of MS have been inconsistent, however. METHODS: In a cross-sectional study, the authors investigated 374 patients with clinically definite MS and a disease duration of at least 3 years and related their clinical and demographic findings to the allelic polymorphism of the APOE gene. The genotype distribution of patients with MS was compared with a cohort of 389 asymptomatic, randomly selected elderly volunteers. RESULTS: The authors found no significant differences in the distribution of genotypes between patients with MS and controls. However, patients with MS with the epsilon4 allele (n = 85) had a significantly higher progression index of disability (0.46 +/- 0.4 versus 0.33 +/- 0.26; p < 0.004) and a worse ranked MS severity score (5.1 +/- 1.9 versus 5.7 +/- 1.7; p = 0.05) than their non-epsilon4 counterparts, despite significantly more frequent long-term immunotherapy in epsilon4 carriers (74% versus 58%; p < 0.007). The annual relapse rate in epsilon4 carriers (0.87 +/- 0.56) was significantly higher than in patients with MS without an epsilon4 allele (0.71 +/- 0.47; p = 0.03). CONCLUSIONS: These results suggest no effect of the APOE genotype on susceptibility to MS, but indicate an association of the APOE epsilon4 allele with a more severe course of the disease.

Adult↗
PubMed2001

Spatial arrangement of cerebro-pontine terminals.

Understanding the interaction of the cerebral cortex and cerebellum requires knowledge of the highly complex spatial characteristics of cerebro-cerebellar signal transfer. Cerebro-pontine fibers from one neocortical site terminate in several sharply demarcated patches across large parts of the pontine nuclei (PN), and fibers from different neocortical areas terminate in the same pontine region. To determine whether projections from segregated neocortical sites overlap in the PN, we studied double anterograde tracing of cerebro-pontine terminals from large parts of rat neocortex. In none of these experiments, including double injection into two functionally related areas, were we able to demonstrate overlapping patches, although close spatial relationships were always detected. This non-overlapping distribution is consistent with a compartmentalized organization of the cerebro-pontine projection and may be the basis of the fractured type of maps found in the cerebellar granular layer. The critical distance between two sites on the neocortical surface that project to non-overlapping patches in the PN was found to be 600 microm, by using double injection within the whisker representation of the primary somatosensory area. This matches the diameter of dendritic trees of layer 5 projection neurons, indicating that non-overlapping populations of neocortical projection neurons possess non-overlapping patches of pontine terminals. Estimations based on this critical distance and the pontine volume anterogradely labeled by one injection site indicate that the size of the PN may be well suited to accommodate a complete set of non-overlapping pontine patches from all possible neocortical sites.

Animals↗
PubMed2001

The contribution of adhesion molecule expression in donor kidney biopsies to early allograft dysfunction.

BACKGROUND: Renal allograft rejection is associated with the expression of adhesion molecules on vascular endothelial and tubular epithelial cells. METHODS: To assess whether the number of cell adhesion molecules expressed in donor kidneys can predict early rejection or delayed graft function, kidney biopsies from 20 living and 53 cadaveric kidney donors were obtained before engraftment into the recipients and the expression of the cell adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule (E-selectin) were determined by immunohistochemistry. RESULTS: All biopsies from living donors showed significantly lower expression of ICAM-1 and VCAM-1 compared to biopsies from cadaveric donors. There was no difference in the expression of adhesion molecules on tubular cells between transplants with primary function compared to allografts with early rejection in living donated kidneys (ICAM-1: 2+/-8 vs. 3+/-8%; VCAM-1: 9+/-7 vs. 1+/-1%), as well as in cadaveric kidneys (ICAM-1: 38+/-29 vs. 39+/-38%; VCAM-1: 55+/-27 vs. 48+/-29%). The expression of ICAM-1 molecules on tubular cells was determined to be a predictor for the occurrence of delayed graft function in cadaveric kidneys (ICAM-1: 65+/-24* vs. 38+/-29% delayed graft versus primary graft function). No delayed graft function occurred in recipients of living donated kidneys. CONCLUSIONS: These data suggest that adhesion molecule expression in donor biopsies is not a predictor for early allograft rejection, but can be used as a marker for the development of postischemic acute renal allograft failure.

Adult↗