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Biomedical subjects

M Sommer

Publications and source records attributed to M Sommer.

At least 37 records · Page 2Linked to original sources

Functional results after anterior cruciate ligament reconstruction using the patellar ligament bone-tendon-bone technique.

This study evaluates the outcome after surgical repair of the cruciate ligament in 129 patients (physical examination plus questionnaire) and another 49 patients (questionnaire only) after a mean interval of 3.2 years. A modified Lysholm score and the OAK score together with KT 1000 arthrometry were used. Ninety-five percent of patients evaluated the overall result as 'excellent' or 'good'. The overall OAK objective score was good or excellent in 81%. Elongation as measured by KT 1000 arthrometry was 1.0 mm (67 N) and 1.2 mm (90 N) on average compared with the contralateral knee.

Anterior Cruciate Ligament Injuries↗

High-dose therapy with ropinirole in patients with Parkinson's disease.

Ropinirole is effective as mono- and combination therapy in PD. Previous studies have used a maximal dose of 24 mg/day; the present study assesses the effect of higher doses (up to 36 mg/day) on patients with motor fluctuations. Outcome measures were changes in the motor function score of the Unified Parkinson's Disease Rating Scale, the duration of dyskinesias and reductions in levodopa dose. 21/22 patients completed the study. The mean daily ropinirole dose at endpoint was 26.2 mg (SD, 4.43 mg, range 20-36 mg). Improvements in motor function (29%) and the duration of dyskinesias (45%) from baseline to endpoint were significant (p < 0.01 and p < 0.05, respectively). The mean levodopa dose fell by 32% during the study (from 599 mg to 409 mg; p = 0.007). Side effects were mild. High-dose ropinirole (20-36 mg/day) was well tolerated and conferred significant clinical benefit on patients with motor fluctuations.

Aged↗

Secretion of cytokines by uroepithelial cells stimulated by Escherichia coli and Citrobacter spp.

Urinary tract epithelial cells (T 24/83) are able to express interleukin (IL)-6, IL-8, platelet-derived growth factor (PDGF) and tumour necrosis factor-alpha, but not IL-1 beta, IL-2, IL-4 and IL-10 in response to an infection with uropathogenic bacteria. The process of cytokine secretion is time dependent, with a significant increase in the cytokine activity after 60 min. The expression of virulence factors of the bacteria does not seem to play a role. The interaction between bacterial products (e.g. lipopolysaccharide) and/or bacterial adhesion mediated by adhesins and specific receptor molecules of cell surfaces may be responsible for the activity of mediator protein expression in the epithelial cells. The release of PDGF and IL-8 was found to be higher when due to Escherichia coli HB 101 (rough form) than that caused by other bacterial strains. Citrobacter CB 3009 provoked the highest level of IL-6. The PDGF level correlated significantly with IL-6 and IL-8 values (P<0.001). There was a significant correlation between the time-dependent release of IL-6 and IL-8 (P<0.05). In epithelial cytokine response to bacterial infection, the reaction of the epithelial cells may modify themselves (e.g. internalization of bacteria) and the immuno-regulatory processes that are caused by infection and responsible for parenchymal injury.

Citrobacter↗

Piracetam affects facilitatory I-wave interaction in the human motor cortex.

OBJECTIVE: To investigate by means of transcranial magnetic stimulation (TMS) the effect of a single oral dose of the GABA derivate piracetam on intracortical facilitatory I-wave interaction. METHODS: The study was performed in 8 healthy volunteers. Before, 1, 3, 6, and 24 h after intake of 4000 mg piracetam, MEPs in the relaxed abductor digiti minimi muscle were elicited by a recently introduced double pulse TMS technique with a suprathreshold first and a subthreshold second stimulus. From interstimulus intervals of 0.5-5.1 ms 3 periods were observed in which MEP facilitation showed maxima - so-called peaks of I-wave interaction - and which were separated by two troughs with no facilitation. We studied the changes in timing and size of the peaks over time. RESULTS: With piracetam, I-wave peaks showed a reduction in size as well as a shortening of the latencies at which the peaks occurred. Both changes were significant at 6 h after drug intake compared to baseline. The effects were partially reversible after 24 h. CONCLUSIONS: The mode of action of piracetam within the nervous system is almost unknown. The peak size reduction was similar to effects that were seen under GABAergic drugs, although GABAergic properties of piracetam have not been observed so far. Shortening of the I-wave peak latencies is a new phenomenon. The results are discussed on the basis of the known therapeutic effects of piracetam in cortical myoclonus and as nootropic agent.

Adult↗

The stimulus intensity modifies the blink reflex recovery cycle in healthy subjects and in blepharospasm.

OBJECTIVE: The excitability of human brainstem interneurons is measured by the blink reflex recovery cycle and is abnormal in blepharospasm. We wondered whether the results of this paradigm depend on the stimulus intensity. METHODS: We investigated the blink reflex recovery cycle in 13 healthy control subjects and in 13 patients with blepharospasm (7 of them treated with botulinum toxin) using 4 levels of stimulus intensity (5, 12, 19 and 26 mA) and two interstimulus intervals (ISIs, 150 or 250 ms). RESULTS: In all groups the inhibition of the second R2 response was reduced with strong stimulus intensities: In controls, the inhibition of the second R2 decreased significantly (e.g. young controls, ISI 150 ms, from 89.6+/-15.6% at 5 mA to 21.9+/-49.7% at 26 mA, mean+/-standard deviation). In patients the R2 inhibition found at 5 mA was converted in an R2 facilitation at 26 mA, irrespective of the status of treatment. In addition, the patients' results at 5 mA did not differ significantly from the controls' results at 26 mA. CONCLUSIONS: The R2 inhibition and its sensitivity to detect abnormal interneuronal excitability depend on the stimulus intensity, which may act by modifying the excitability of the R2 interneurons.

Adult↗

Differences in the modulating potential of advanced glycation end product (AGE) peptides versus AGE proteins.

Differences in the modulating potential of advanced glycation end product (AGE) peptides versus AGE proteins. Advanced glycation end products (AGEs), identified as irreversible products of a complex reaction of carbonyl groups of reducing sugars with free protein amino groups, are characterized by resistance to proteolytic degradation. The incomplete digestion of AGEs results in low molecular weight AGEs accumulating in the blood of diabetic and uremic patients. We hypothesized that the accumulation of these compounds may contribute to the dysfunction and/or degeneration of tubular epithelial cells. Our study examined whether low-molecular-weight AGE peptides and high-molecular-weight AGE proteins affect the functional cellular properties of two tubular epithelial cell lines: immortalized human kidney tubular epithelial (IHKE) and immortalized rat renal proximal tubular cells (IRPTCs). Parameters of cellular damage and growth behavior were cell counting, analysis of the cellular metabolic activity (MTT assay), as well as cellular proliferation (3[H]-thymidine-incorporation). IHKE treated with bovine serum albumin-AGE (BSA-AGE 50) or BSA-AGE-Pep 50 revealed a decrease in cellular metabolic activity as compared with controls after 48 hours of incubation (73 +/- 9% for BSA-AGE 50 and 62 +/- 11% for BSA-AGE-Pep 50 vs. 89 +/- 8% for BSA Co 50). Low molecular weight BSA-AGE-Pep 50 induced a significantly greater cellular damage in IRPTCs as compared with high molecular weight BSA-AGE 50 after 144 hours of incubation (59 +/- 15% for BSA-AGE 50 vs. 31 +/- 13% for BSA-AGE-Pep 50). The decrease in metabolic activity correlated well with a decrease in cellular proliferation. The results suggest a higher toxic potential of low molecular weight AGE peptides compared with high molecular weight AGE proteins in IRPTC and IHKE. This may provide evidence that low molecular weight degradation products of AGE-modified proteins have an important risk potential.

Animals↗

Temporary warm ischaemia, 5/6 nephrectomy and single uranyl nitrate administration--comparison of three models intended to cause renal fibrosis in rats.

In patients the progression of pathologic renal processes after the treatment of primary disease is a problem of increasing importance and therapeutic strategies are insufficient till now. The aim of this paper was to search for rat models of interstitial fibrosis as a basis for testing therapeutic strategies to prevent end-stage renal failure. Experiments were done on adult female Wistar rats (Han:Wist) to investigate long-term consequences of temporary warm ischaemia, 5/6 nephrectomy (5/6 NX) and single uranyl nitrate (UN) administration (0.3 or 0.5 mg/ 100 g body wt. intraperitoneally). Observation time was 20 weeks after injury in each group. Creatinine clearance, urinary protein excretion and hydroxy-proline (OH-proline) concentration in renal tissue were measured and light microscopic investigations were done to characterise both quality and time course of long-term renal damage in relation to matched control animals. Temporary warm ischaemia and 5/6 NX did not cause any fibrotic changes during the 20 weeks observation period. The higher UN dose led to decreased creatinine clearance, increased urinary protein excretion and enhanced OH-proline concentration in renal tissue. Morphologic investigations showed fibrotic areas containing strongly dilated and atrophic tubules with thickened basal membranes. These effects can be seen from week four after UN administration up to the end of the observation period. In conclusion, administration of one single dose of UN is a simple procedure to induce interstitial renal fibrosis as an experimental model to investigate therapeutic strategies for their prevention.

Animals↗

Granulysin blocks replication of varicella-zoster virus and triggers apoptosis of infected cells.

Granulysin, a lytic protein present in cytolytic granules of human natural killer and cytotoxic T cells, entered cells infected with varicella-zoster virus (VZV). Exposure to granulysin accelerated death of infected cells as assessed by apoptosis markers. The functional domain of granulysin that mediated its antiviral effects was amino acid 23-51; this domain also mediates the additional antitumor cell effects of granulysin. Because granulysin is a product of natural killer cells and T lymphocytes, it is possible that its antiviral activity may act as a mediator of innate and adaptive immune mechanisms.

Amino Acid Chloromethyl Ketones↗

Time course of determination of movement direction in the reaction time task in humans.

The primary motor cortex produces motor commands that include encoding the direction of movement. Excitability of the motor cortex in the reaction time (RT) task can be assessed using transcranial magnetic stimulation (TMS). To elucidate the timing of the increase in cortical excitability and of the determination of movement direction before movement onset, we asked six right-handed, healthy subjects to either abduct or extend their right thumb after a go-signal indicated the appropriate direction. Between the go-signal and movement onset, single TMS pulses were delivered to the contralateral motor cortex. We recorded the direction of the TMS-induced thumb movement and the amplitude of motor-evoked potentials (MEPs) from the abductor pollicis brevis and extensor pollicis brevis muscles. Facilitation of MEPs from the prime mover, as early as 200 ms before the end of the reaction time, preceded facilitation of MEPs from the nonprime mover, and both preceded measurable directional change. Compared with a control condition in which no voluntary movement was required, the direction of the TMS-induced thumb movement started to change in the direction of the intended movement as early as 90 ms before the end of the RT, and maximum changes were seen shortly before the end of reaction time. Movement acceleration also increased with maxima shortly before the end of the RT. We conclude that in concentric movements a change of the movement direction encoded in the primary motor cortex occurs in the 200 ms prior to movement onset, which is as early as increased excitability itself can be detected.

Adult↗

In vitro-prepared advanced glycation end-products and the modulating potential of their low-molecular weight degradation products in IRPTC-A rat proximal-tubular derived kidney epithelial cell line.

Low-molecular advanced glycation end-products (AGEs)-degradation products resulting from a proteolysis of tissue or circulating AGEs represent up to 80% of AGE plasma immunoreactivity. These AGE peptides contribute to the dramatic increase in AGE levels in end-stage renal disease even in the absence of diabetes. Because glomerular filtered AGE-degradation products may accumulate within intracellular compartments of proximal tubular epithelial cells, we investigated whether there is a pathway potentially mediating damaging effects of AGE-degradation products by perturbation of the function of the tubuloepithelium. Proximal tubular-derived rat kidney cells (IRPTC) were incubated with high-molecular AGEs highly modified by incubation of bovine serum albumin (BSA) with glucose for 50 days in vitro, and with low-molecular AGE-degradation products derived from proteolytic cleavage and isolated in the molecular range between 1 and 30 kDa. The proliferation of IRPTC (3H-thymidine incorporation) was reduced to 89+/-1% and 69+/-2% after 24 hr of incubation with BSA-AGE and BSA-AGE-degradation products, respectively. The cell viability of IRPTC was reduced significantly to 59+/-15% and 31+/-13% after 144 hr of incubation with BSA-AGE and BSA-AGE-degradation products, respectively. Conditioned media obtained from IRPTC incubated for 72 hr with BSA-AGE and its degradation products increased the proliferation rate of renal fibroblasts (RFb) to 222+/-24% and 449+/-40%, respectively. Incubation of IRPTC with BSA-AGE-degradation products increased the expression of endothelin-1 (ET-1) mRNA to 210% after 1 hr; the expression of platelet-derived growth factor-B (PDGF-B) mRNA reached 184% after 2 hr. Regarding the toxicity of AGEs to the kidney, low-molecular weight AGE-degradation products possibly form an individual fraction with a comparatively higher toxic potential.

Animals↗

Active site modulation in the N-acetylneuraminate lyase sub-family as revealed by the structure of the inhibitor-complexed Haemophilus influenzae enzyme.

The N-acetylneuraminate lyase (NAL) sub-family of (beta/alpha)(8) enzymes share a common catalytic step but catalyse reactions in different biological pathways. Known examples include NAL, dihydrodipicolinate synthetase (DHDPS), d-5-keto-4-deoxyglucarate dehydratase, 2-keto-3-deoxygluconate aldolase, trans-o-hydroxybenzylidenepyruvate hydrolase-aldolase and trans-2'-carboxybenzalpyruvate hydratase-aldolase. Little is known about the way in which the three-dimensional structure of the respective active sites are modulated across the sub-family to achieve cognate substrate recognition. We present here the structure of Haemophilus influenzae NAL determined by X-ray crystallography to a maximum resolution of 1.60 A, in native form and in complex with three substrate analogues (sialic acid alditol, 4-deoxy-sialic acid and 4-oxo-sialic acid). These structures reveal for the first time the mode of binding of the complete substrate in the NAL active site. On the basis of the above structures, that of substrate-complexed DHDPS and sequence comparison across the sub-family we are able to propose a unified model for active site modulation. The model is one of economy, allowing wherever appropriate the retention or relocation of residues associated with binding common substrate substituent groups. Our structures also suggest a role for the strictly conserved tyrosine residue found in all active sites of the sub-family, namely that it mediates proton abstraction by the alpha-keto acid carboxylate in a substrate-assisted catalytic reaction pathway.

Amino Acid Sequence↗

Lasting influence of repetitive transcranial magnetic stimulation on intracortical excitability in human subjects.

We studied the effects of a train of 30 pulses of repetitive transcranial magnetic stimulation (rTMS) at frequencies of 5 and 15 Hz and at an intensity of 120% of resting motor threshold on human motor cortex excitability. Intracortical inhibition (ICI) and intracortical facilitation (ICF) after rTMS were tested by a conditioning-test designed paired-pulse paradigm. After 15 Hz rTMS, ICI was significantly reduced for 3.2 min, ICF was enhanced for 1.5 min, muscle evoked potentials from single TMS were increased in the first 30 s only. After 5 Hz rTMS ICI was significantly reduced in the first 32 s. We conclude that high-frequency suprathreshold rTMS transiently suppresses the activity of the intracortical inhibitory circuitry and, with a different time course, increases the excitability of the excitatory circuitry.

Adult↗

Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: a (31)P chemical shift spectroscopic-imaging study.

BACKGROUND: (31)Phosphorous magnetic resonance spectroscopy has been widely used to evaluate schizophrenic patients in comparison to control subjects, because it allows the investigation of both phospholipid and energy metabolism in vivo; however, the results achieved so far are inconsistent. Chemical shift imaging (CSI) has the advantage that instead of only one or a few preselected voxels the tissue of a whole brain slice can be examined. The aim of the present investigation was to determine whether the results of previous studies of our group, showing that phosphodiesters (PDE) are decreased in the frontal lobe of schizophrenic patients as compared to control subjects, might be confirmed in an independent unmedicated patient sample using the CSI technique. METHODS: A carefully selected new cohort including 11 neuroleptic-free schizophrenic patients and 11 age- and gender-matched healthy control subjects was recruited. CSI was applied and an innovative analysis method for CSI data based on a general linear model was used. RESULTS: PDE, phosphocreatine, and adenosine triphosphate (ATP) were found to be significantly decreased in the frontal lobe of patients with schizophrenia. CONCLUSIONS: Because PDE was decreased in schizophrenic patients, the membrane phospholipid hypothesis of schizophrenia could not be corroborated. Further results indicate decreased ATP production in the frontal lobe of patients with schizophrenia.

Adenosine Triphosphate↗

Varicella-zoster virus infection of a human CD4-positive T-cell line.

Varicella-zoster virus (VZV) is a human alpha-herpesvirus that causes varicella (chickenpox) at primary infection and may reactivate as herpes zoster. VZV is a T-lymphotropic virus in vivo. To investigate the T-cell tropism of VZV, we constructed a recombinant virus expressing green fluorescent protein (VZV-GFP) under the CMV IE promoter. Coculture of VZV-GFP-infected fibroblasts with II-23 cells, a CD4-positive human T-cell hybridoma, resulted in transfer of virus to II-23 cells. II-23 cells are susceptible to VZV-GFP infection as demonstrated by expression of immediate/early (IE62), early (ORF4), and late (gE) genes. Recovery of infectious virus was limited, with only 1 to 3 in 10(6) cells releasing infectious virus by plaque assay, indicating that transfer of virus results in a limited productive infection. In vitro infection of II-23 cells will be useful for further analysis of VZV tropism for T-lymphocytes.

CD4-Positive T-Lymphocytes↗

Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis.

The penultimate step in carnitine biosynthesis is mediated by gamma-trimethylaminobutyraldehyde dehydrogenase (EC 1.2.1.47), a cytosolic NAD(+)-dependent aldehyde dehydrogenase that converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine. This enzyme was purified from rat liver, and two internal peptide fragments were sequenced by Edman degradation. The peptide sequences were used to search the Expressed Sequence Tag data base, which led to the identification of a rat cDNA containing an open reading frame of 1485 base pairs encoding a polypeptide of 494 amino acids with a calculated molecular mass of 55 kDa. Expression of the coding sequence in Escherichia coli confirmed that the cDNA encodes gamma-trimethylaminobutyraldehyde dehydrogenase. The previously identified human aldehyde dehydrogenase 9 (EC 1.2.1.19) has 92% identity with rat trimethylaminobutyraldehyde dehydrogenase and has been reported to convert substrates that resemble gamma-trimethylaminobutyraldehyde. When aldehyde dehydrogenase 9 was expressed in E. coli, it exhibited high trimethylaminobutyraldehyde dehydrogenase activity. Furthermore, comparison of the enzymatic characteristics of the heterologously expressed human and rat dehydrogenases with those of purified rat liver trimethylaminobutyraldehyde dehydrogenase revealed that the three enzymes have highly similar substrate specificities. In addition, the highest V(max)/K(m) values were obtained with gamma-trimethylaminobutyraldehyde as substrate. This indicates that human aldehyde dehydrogenase 9 is the gamma-trimethylaminobutyraldehyde dehydrogenase, which functions in carnitine biosynthesis.

ATP-Binding Cassette Transporters↗