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Biomedical subjects

D Ulrich

Publications and source records attributed to D Ulrich.

At least 37 records · Page 2Linked to original sources
PubMed1997

The quality of trabecular bone evaluated with micro-computed tomography, FEA and mechanical testing.

Most standard methods to predict bone quality are merely based on apparent density measurements. However, apparent density alone does neither explain all variation of the mechanical properties nor does it account for the structural anisotropy of trabecular bone. Thus, apparent density alone might not be sufficient to accurately predict the quality of bone. This study investigates if a new approach based on microstructural computer models can provide additional and relevant information on bone quality. 58 human trabecular bone samples from the femoral head were measured with a 3-D micro-Computed Tomography (micro-CT) system providing a voxel representation of the bone microarchitecture with a resolution of 28 microns. Based on such representations, the orthotropic stiffness matrices and the principal directions were computed for 5 mm cubes with microstructural Finite Element Analysis (FEA). For a subset of six samples the moduli were then validated with tri-axial mechanical compression tests. The results show that on average 15% of the variation of the elastic properties are not explained by bone volume fraction. Differences of elastic properties between samples with the same bone volume fraction range up to 53%. The variation of the degree of anisotropy is unrelated to that of the bone volume fraction. Finally, the direction-dependent stiffness of the trabecular bone differs by a factor of four, indicating that one single (isotropic) modulus as predicted from apparent density measurements might not be adequat. It is concluded that micro-CT-based FEA provides new and additional information about anisotropy and mechanical properties in a direct and non-destructive way, and thus will be important in the future for advanced failure risk prediction. An extension to patient examinations using high-resolution CT or MRI techniques is envisaged.

Biomechanical Phenomena↗
PubMed1996

Gamma-aminobutyric acid type B receptor-dependent burst-firing in thalamic neurons: a dynamic clamp study.

Synchronized network responses in thalamus depend on phasic inhibition originating in the thalamic reticular nucleus (nRt) and are mediated by the neurotransmitter gamma-aminobutyric acid (GABA). A suggested role for intra-nRt connectivity in inhibitory phasing remains controversial. Recently, functional GABA type B (GABAB) receptors were demonstrated on nRt cells, and the slow time course of the GABAB synaptic response seems ideally suited to deinactivate low-threshold calcium channels. This promotes burst firing, a characteristic feature of synchronized responses. Here we investigate GABAB-mediated rebound burst firing in thalamic cells. Whole-cell current-clamp recordings were obtained from nRt cells and somatosensory thalamocortical relay cells in rat brain slices. Synthetic GABAB inhibitory postsynaptic potentials, generated by a hybrid computerneuron synapse (dynamic clamp), triggered rebound low-threshold calcium spikes in both cell types when peak inhibitory postsynaptic potential hyperpolarization was greater than -92 mV. The threshold inhibitory postsynaptic potential conductance for rebound burst generation was comparable in nRt (7 nS) and thalamocortical (5 nS) cells. However, burst onset in nRt (1 s) was considerably delayed compared with thalamocortical (0.6 s) cells. Thus, GABAB inhibitory postsynaptic potentials can elicit low-threshold calcium spikes in both relay and nRt neurons, but the resultant oscillation frequency would be faster for thalamocortical-nRt networks (3 Hz) than for nRt-nRt networks (1-2 Hz). We conclude, therefore, that fast (> 2 Hz) GABAB-dependent thalamic oscillations are maintained primarily by reciprocal connections between excitatory and inhibitory cells. These findings further indicate that when oscillatory neural networks contain both recurrent and reciprocal inhibition, then distinct population frequencies may result when one or the other type of inhibition is favored.

Animals↗
PubMed1996

GABAB receptor-mediated responses in GABAergic projection neurones of rat nucleus reticularis thalami in vitro.

1. Whole-cell voltage-clamp recordings were obtained from GABAergic neurones of rat nucleus reticularis thalami (NRT) in vitro to assess pre- and postsynaptic GABAB receptor-mediated responses. Presynaptic inhibition of GABA release was studied at terminals on local axon collaterals within NRT as well as on projection fibres in the somatosensory relay nuclei. 2. The GABAB receptor agonist (R)-baclofen (10 microM) reduced monosynaptically evoked GABAA-mediated inhibitory postsynaptic currents (IPSCs) in NRT and somatosensory relay cells to 11 and 12% of control, respectively. 3. Action potential-independent miniature IPSCs (mIPSCs) were observed in both cell types. Mean mIPSC amplitude was 20 pA in both NRT and relay cells at a holding potential of 0 mV. The mean mIPSC frequencies were 0.83 and 2.2 Hz in NRT and relay cells, respectively. Baclofen decreased mIPSP frequency by about half in each cell type without affecting amplitude. 4. Paired-burst inhibition of evoked IPSCs was studied in relay and NRT cells by applying pairs of 100 Hz stimulus bursts separated by 600 ms. The mean ratio of second to first peak IPSC amplitudes was 0.77. 5. In NRT cells baclofen induced a linear postsynaptic conductance increase of 0.82 nS with an associated reversal potential of -121 mV. A small (0.14 nS) GABAB component of the evoked IPSC was detected in only a minority of NRT cells (3 of 18). 6. All pre- and postsynaptic effects of baclofen, as well as PBI, were largely reversed by the specific GABAB receptor antagonist CGP 35348 (0.5 mM). 7. We conclude that activation of GABAB receptors in NRT leads to presynaptic autoinhibition of IPSCs in both NRT and relay cells, and to direct activation of a small linear K+ conductance. In addition our experiments suggest that reciprocal connectivity within NRT can be partially mediated by a small GABAB inhibitory event.

Animals↗
PubMed1996

Activation of Hodgkin cells via the CD30 receptor induces autocrine secretion of interleukin-6 engaging the NF-kappabeta transcription factor.

The CD30 surface molecule is a recently identified member of the tumor necrosis factor/nerve growth factor receptor superfamily. Within the cytoplasmic signal transducing domain, CD30 shares no significant homology to other members of this family. Signaling events engaged via CD30 are still unknown. We here identify the NF-kappabeta transcription factor as a target of the CD30-induced signal pathway in Hodgkin's disease (HD) cells. Exposure of HD cells to CD30 ligand induces release of interleukin-6 (IL-6) that can be duplicated by cross-linking HD-cells to an agonistic anti-CD30 specific monoclonal antibody (alphaCD30), but not by cross-linking to an isotype-identical irrelevant monoclonal antibody. Cross-linking of HD cells to alphaCD30 leads to enhanced accumulation of IL-6 mRNA in a time-dependent fashion resulting from transcriptional activation of the IL-6 promoter. Transient transfection assays using a series of deleted IL-6 promoter constructs linked to the human growth hormone gene as a reporter gene furthermore indicate that transcriptional activation of the IL-6 promoter requires the presence of an intact NF-kappabeta binding site. In addition, introduction of an NF-kappabeta binding site appeared to be sufficient to confer inducibility of an heterologous promoter on activation of CD30 in HD cells. Cross-linking of CD30 promotes rapid and transient binding activity of nuclear proteins to the NF-kappabeta recognition site of the IL-6 promoter. Supershift experiments using a series of monoclonal antibodies recognizing distinct members of the NF-kappaBeta transcription factor family furthermore indicate that in CD30 cross-linked HD cells p50, p65/Rel-A, and Rel-B are present, whereas the c-rel protein is not.

Antibodies, Monoclonal↗
PubMed1996

The extracellular domain of the Epstein-Barr virus BZLF2 protein binds the HLA-DR beta chain and inhibits antigen presentation.

The Epstein-Barr virus BZLF2 gene encodes a glycoprotein that associates with gH and gL and facilitates the infection of B lymphocytes. In order to determine whether the BZLF2 protein recognizes a B-cell-specific surface antigen, a soluble protein containing the extracellular portion of the BZLF2 protein linked to the Fc portion of human immunoglobulin G1 (BZLF2.Fc) was expressed from mammalian cells. BZLF2.Fc was used in an expression cloning system and found to bind to a beta-chain allele of the HLA-DR locus of the class II major histocompatibility complex (MHC). Analysis of amino- and carboxy-terminal deletion mutants of the BZLF2.Fc protein indicated that the first 90 amino acids of BZLF2.Fc are not required for HLA-DR beta-chain recognition. Site-directed mutagenesis of an HLA-DR beta-chain cDNA and subsequent immunoprecipitation of expressed mutant beta-chain proteins using BZLF2.Fc indicated that the beta1 domain, which participates in the formation of peptide binding pockets, is required for BZLF2.Fc recognition. The addition of BZLF2.Fc to sensitized peripheral blood mononuclear cells in vitro abolished their proliferative response to antigen and inhibited cytokine-dependent cytotoxic T-cell generation in mixed lymphocyte cultures. Flow-cytometric analysis of Akata cells induced to express late Epstein-Barr virus antigens indicated that expression of BZLF2 did not result in reduced surface expression levels of MHC class II. The ability of BZLF2.Fc to bind to the HLA-DR beta chain suggests that the BZLF2 protein may interact with MHC class II on the surfaces of B cells.

Amino Acid Sequence↗
PubMed1995

Human IL-17: a novel cytokine derived from T cells.

A cDNA encoding human IL-17 (hIL-17) was cloned from a CD4+ T cell library. The predicted 155-amino acids sequence contains an N-terminal signal peptide and exhibits 72% amino acid identity with HVS13, an open reading frame from a T-lymphotropic Herpesvirus saimiri, and 63% with murine CTLA8. High levels of hIL-17 were induced from primary peripheral blood CD4+ T cells upon stimulation. When expressed in CV1/EBNA cells, recombinant hIL-17 was secreted in both glycosylated and nonglycosylated forms. A hIL-17.Fc fusion protein and supernatants from cells transfected with hIL-17 induced IL-6 and IL-8 production and enhanced the surface expression of the intracellular adhesion molecule-1 (ICAM-1) in human fibroblasts.

Amino Acid Sequence↗
PubMed1995

Recombinant CD30 ligand and CD40 ligand share common biological activities on Hodgkin and Reed-Sternberg cells.

The CD30 ligand (CD30L) and CD40L are members of the tumor necrosis factor (TNF) protein superfamily, CD30L and CD40L are mainly expressed as membrane-bound proteins by activated T cells. CD30L and CD40L are costimulatory for T cell proliferation and activation. Further, CD40L is a critical signal for T cell-dependent activation of B cells. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the neoplastic component of Hodgkin's disease (HD), express high levels of the counterreceptors CD30 and CD40. We have found that both the recombinant CD30L and CD40L enhanced interleukin (IL)-6, TNF and lymphotoxin (LT)-alpha release from cultured H-RS cells. In addition, CD40L, but not CD30L, induced IL-8 secretion. CD30L and CD40L seem to share some redundant biological activities involved in the deregulated secretion of cytokines known to play a central role in the clinical presentation and pathology of HD. Further, CD30L enhanced surface expression of intercellular adhesion molecule-1 (ICAM-1/CD54) on cultured H-RS cells, which is frequently overexpressed on primary H-RS cells. CD30L- and CD40L-enhanced CD54 surface expression is followed by elevated shedding of CD54, as shown by detection of elevated 82-kDa soluble (s) CD54 levels in culture supernatants after stimulation with both ligands. CD30L and CD40L share common pleiotropic biological activities on CD30+/CD40+ H-RS cells and are elements of the cytokine and cell contact-dependent activation network typical for HD, a tumor of cytokine producing cells.

CD30 Ligand↗
PubMed1995

Purinergic inhibition of GABA and glutamate release in the thalamus: implications for thalamic network activity.

Adenosine is a CNS depressant with both pre- and postsynaptic actions. Presynaptically, adenosine decreases neurotransmitter release in the hippocampus but only at excitatory terminals. In the thalamus, however, we show that, in addition to its actions at excitatory synapses, adenosine strongly suppresses monosynaptic inhibitory currents both in relay cells of the thalamic ventrobasal complex (VB) and in inhibitory neurons of the nucleus reticularis thalami (nRt). A concomitant increase in transmission failures and results coefficient of variation analysis are both consistent with a presynaptic mechanism. Pharmacological manipulations support an A1 receptor-mediated process. Slow thalamic oscillations induced in vitro by extracellular stimulation and recorded with extracellular multiunit electrodes in VB and nRt are dampened by adenosine without affecting their periodicity. We conclude that adenosine can presynaptically down-regulate inhibitory postsynaptic responses in thalamus and exert robust antioscillatory effects, likely by synergistic depression of both excitatory and inhibitory neurotransmitter release.

Adenosine↗
PubMed1995

HP-228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro.

alpha-Melanocyte stimulating hormone has been shown to prevent endotoxin shock. A heptapeptide analog (HP-228) has recently been synthesized and shown to be an even more potent protective agent. Because the hypotensive and toxic actions of lipopolysaccharide (LPS) appear to involve the induction of type II nitric oxide synthase (iNOS), we have examined the actions of HP-228 on nitric oxide production using an endotoxemia model in conscious rats given E. coli LPS (5 mg/kg i.v.) and monitored for 6 h. A group of rats received HP-228 (30 micrograms/kg) 30 min before LPS. Using nitro L-arginine methyl ester-sensitive cGMP production as an estimate of nitric oxide synthase activity in aortic segments, ex vivo, we determined that LPS increases iNOS activity and that HP-228 pretreatment markedly reduces this response. Additionally, the rate of conversion of 3[H]-arginine to 3[H]-citrulline was significantly reduced in lung homogenates from HP-228-treated rats. HP-228 did not alter the activity of the constitutive nitric oxide synthase in aortic rings or in cerebella. In isolated rat aortic smooth muscle cells, LPS or interleukin-1 beta caused prominent rises in nitric oxide generated by iNOS. HP-228 did not antagonize the effect of these inducing agents. However, in these cells, plasma obtained from rats 1 h after administration of HP-228 prevented the induction of iNOS by both LPS and interleukin-1 beta. In conclusion, HP-228 prevents the in vivo induction of nitric oxide synthase by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease.

CD40 was originally described as a B-cell-restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD); were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H-RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD.

Adult↗
PubMed1994

Electronic structure of motoneurons in spinal cord slice cultures: a comparison of compartmental and equivalent cylinder models.

1. Voltage-clamp, current-clamp, and morphological data were obtained from visually identified motoneurons in organotypic cocultures of rat embryonic spinal cord, dorsal root ganglia, and skeletal muscle. The cells were injected with Biocytin during whole-cell patch-clamp recordings and stained with horseradish peroxidase. 2. The somata and dendritic trees of the cells were reconstructed with a semiautomatic reconstruction system. The motoneurons had a common multipolar shape. An elliptic soma gave rise to 3-9 stem dendrites with a mean diameter of 2.5 +/- 0.9 (SD) micron terminating in 24 +/- 7 dendritic endings. The mean total dendritic path length was 3,306 +/- 1,075 microns. The mean total membrane surface area was 15,594 +/- 10,404 microns 2 with a dendritic to somatic membrane surface area ratio of 3.4 +/- 1.4 (n = 7 cells). 3. The ratio between the sum of the diameters of the two daughter branches and the diameter of the parental branch each raised to the 3/2 power at all branch points was 1.3 +/- 0.28 (n = 8 cells). The dendritic trees of the cells tapered continuously from the soma to the distal ends. The mean normalized dendritic trunk parameter of all cells was 0.62 +/- 0.22. 4. The motoneurons had a mean input resistance RN of 498 +/- 374 M delta, a mean membrane time constant (tau m) of 22 +/- 4.6 ms, and a mean dendritic dominance (rho) of 2.7 +/- 0.86 (n = 5 cells). The mean electronic length (L) calculated from tau m and the slowest voltage-clamp time constant (tau VC1) was 0.7 +/- 0.04 (n = 7 cells). 5. The specific membrane capacitance (Cm) estimated from the charge of the capacitive current during a voltage step and the total membrane surface area was 1.08 +/- 0.3 microF/cm2 (n = 6 cells). 6. Compartmental computer models were constructed of individual cells. Experimental and simulated voltage transients were matched with Cm = 1 microF/cm2, a uniform membrane resistivity (Rm) = tau m/Cm and a cytosolic resistivity (Ri) of 308 +/- 39 omega.cm (n = 3 cells). 7. The mean electrotonic length of the dendritic paths was 0.83 +/- 0.2 (n = 5 cells). The mean input resistance at the dendritic terminals (RT) was 1,413 +/- 260 M omega. Synaptic conductances were applied at all distal dendritic compartments of the model cells. The resulting synaptic currents were calculated at the input site and at the soma. The mean transient current attenuation ratio was 4.7 +/- 1.7 under idealized voltage-clamp conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Miniature excitatory synaptic currents corrected for dendritic cable properties reveal quantal size and variance.

1. Non-NMDA (N-Methyl-D-aspartate) receptor mediated miniature excitatory synaptic currents (mEPSCs) were recorded from motoneurons in organotypic cultures of embryonic rat spinal cord. 2. Amplitude histograms of mEPSCs were unimodal and skewed toward larger events. The mean of the modes of the amplitude histograms was -18 pA with a maximal amplitude range of -4 to -160 pA for individual mEPSCs. 3. Current transients to a short voltage pulse were used to estimate the passive cable parameters of the motoneurons. The mean membrane time constant (tau) and the mean electrotonic length (L) were 20 and 0.96 ms, respectively. 4. The amplitudes of the mEPSCs were corrected for imperfect space and voltage clamp. The resulting amplitude histograms could be fitted by the sum of two Gaussian curves, revealing a mean quantal size of -48 pA with a coefficient of variation (cv) of 0.28. 5. Our data suggest that quantal size and its variance are masked by the cable properties of the neurons and that simultaneous release of elementary quanta occurs occasionally.

Animals↗
PubMed1990

No measurable increase in thymidine glycol or 8-hydroxydeoxyguanosine in liver DNA of rats treated with nafenopin or choline-devoid low-methionine diet.

Male rats were treated for 2 months with 1000 ppm nafenopin in the diet or for 4 or 7 days with a choline-devoid low-methionine diet. DNA was isolated from the livers and analyzed for the presence of cis-thymidine glycol-3'-phosphate (cis-dTGp) by 32P-postlabeling and for the level of 8-hydroxy-deoxyguanosine (8-OH-dG) by electrochemical detection (ECD). In no DNA sample was the level of cis-dTGp above the limit of detection of 1 modified thymidine per 10(6) nucleotides. With 8-OH-dG, a background level of this modification of 20 8-OH-dG per 10(6) nucleosides was found in liver DNA of control rats, which was not affected by either treatment. It is postulated for thymidine glycol that a potential increase was below the limit of detection or was rapidly repaired in vivo and that the steady-state level of endogenous 8-hydroxydeoxyguanosine appears not to be influenced by the treatments chosen.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1990

[Functional diagnosis in follow-up of temporal arteritis treatment].

Fourteen patients (28 eyes) suffering from histologically confirmed temporal arteritis were examined with oculo-oscillodynamography (OODG) according to Ulrich and Ulrich as well as with orbital dynamography (ODG) according to Hager. These examinations were performed before and during prednisolone treatment. When ocular and orbital vessels are involved, temporal arteritis will result in a strong reduction of the ocular and orbital pulse blood volumes. Ocular perfusion pressures may also be reduced. In all 28 eyes of the 14 patients, OODG showed the ocular pulse blood volumes to be significantly reduced, while with ODG the ocular pulse blood volumes appeared to be within the normal range in 50% of the cases. Therefore, OODG is more reliable than ODG in the diagnosis of temporal arteritis. When performed during prednisolone treatment, OODG is a very sensitive indicator of successful or unsuccessful therapy. OODG permits an early detection of relapses and helps to avoid their sequelae. Since OODG can be repeated as often as desired and can be performed within a short time, it is very suitable for controlling the management of temporal arteritis.

Aged↗
PubMed1988

[Temporal arteritis--diagnosis and therapeutic control].

33 patients suffering from temporal arteriitis (Morbus Horton) were investigated noninvasively by Oculo-Oscillo-Dynamography (OODG), Orbita-Dynamography (ODG) and Temporalis-Dynamography (TDG). The ocular, orbital and temporal oscillograms and oscillodynamograms revealed characteristic and unmistakable alterations; i.e., striking reduction of the pulse volumes and a decrease of the blood pressures in the respective circulatory regions as a result of a stenosing and occluding vascular process. The 3 methods yielded typical patterns of the occluding process, which led to the conclusion that in untreated persons the stenosing process of the arteritis cranialis tends to start in the vascular branches of the external carotid artery and subsequently includes branches of the internal carotid system, such as the ophthalmic artery. High doses of prednisolone resulted in reopening of the vessels that had been stenosed and occluded by arteritis, and in most cases restored normal circulation in the regions examined within several weeks or months. From the investigations made on 66 eyes of the 33 patients, the authors conclude that combined use of OODG, ODG, and TDG makes it possible to diagnose temporal arteritis with a high degree of certainty. In all 33 cases the disease was diagnosed with OODG, ODG and TDG and confirmed histologically. Since the OODG, ODG, TDG examinations are well tolerated by the patient and can be repeated at any time, it is suggested to employ them for the supervision of therapy as well to detect any possible relapse of the inflammatory occluding vascular process.

Dose-Response Relationship, Drug↗
PubMed1985

Effects of N-nitrosomorpholine and phenobarbital on UDP-glucuronyltransferase in putative preneoplastic foci of rat liver.

Effects of initiators and promoters of hepatocarcinogenesis on UDP-glucuronyltransferase and arylhydrocarbon hydroxylase were investigated in foci of altered hepatocytes. A single administration of N-nitrosomorpholine (75 mg/kg, 24 h after partial hepatectomy) was used for initiation and chronic administration of phenobarbital (0.1% in tap water) for promotion. Histological evidence indicated that ATPase-negative, gamma-glutamyltranspeptidase-positive, and UDP-glucuronyltransferase-positive foci were highly correlated. Based on this evidence ATPase-negative foci were used as a guide to monitor early lesions and to microdissect lyophilized foci and extra-focal tissue. It was found that treatment with N-nitrosomorpholine led to a permanent increase of UDP-glucuronyltransferase activity in foci tissue (3- to 5-fold, detected 180 and 330 days after initiation). In contrast, arylhydrocarbon hydroxylase activity was decreased by 50%. Administration of phenobarbital further increased UDP-glucuronyltransferase activity in focal tissue (up to 9-fold, compared with control liver). However, this further increase of enzyme activity by phenobarbital was reversible. The results suggest that (i) initiation by chemical carcinogens leads to permanent alterations of drug metabolizing enzymes, consistent with increased toxin-resistance of initiated hepatocytes, and (ii) chronic administration of phenobarbital markedly enhances gene expression of UDP-glucuronyltransferase in initiated hepatocytes.

Adenosine Triphosphatases↗