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Biomedical subjects

T Steiner

Publications and source records attributed to T Steiner.

At least 19 recordsLinked to original sources

Masking of vertebral artery dissection by severe trauma to the cervical spine.

STUDY DESIGN: A prospective case study was performed. OBJECTIVES: To illustrate the association of cervical trauma with vertebral artery dissection, and to propose a diagnostic and therapeutic algorithm for suspected traumatic vertebral artery dissection. SUMMARY OF BACKGROUND DATA: Vertebral artery dissection is a recognized but underdiagnosed complication of trauma to the cervical spine. Symptoms of spinal cord injury, however, may obscure those of vertebral artery dissection, presumably causing gross underdiagnosis of this complication. METHODS: All patients with vertebral artery dissection admitted to the authors' facility between 1992 and 1997 were screened for cervical trauma. RESULTS: This article presents four patients with severe trauma to the cervical spine, defined as luxation, subluxation, or fracture, in whom symptoms of vertebral artery dissection developed after a delay ranging from several hours to weeks. The traumatic vertebral artery dissection typically was located at the site of vertebral injury or cranial to it. One patient with fracture of the odontoid process survived symptom free without ischemic brain infarctions. Another patient survived with traumatic quadriplegia in addition to large cerebellar and posterior cerebral artery infarctions. Two patients died as a result of fulminant vertebrobasilar infarctions, both with only moderate impairment from the primary spinal cord injury. CONCLUSIONS: Early signs of vertebral artery dissection include head and neck pain, often localized to the site of intimal disruption, which may be disguised by the signs of the spinal injury. Early Doppler ultrasound and duplex sonography as a noninvasive screening method should be performed for patients with severe trauma to the cervical spine. In cases of vertebral artery dissection, immediate anticoagulation should be initiated. Traumatologists should be aware of this complication in evaluating patients with severe trauma of the cervical spine, and also for a variety of forensic reasons.

Adult↗

Hydrogen bonds with pi-acceptors in proteins: frequencies and role in stabilizing local 3D structures.

A comprehensive structural analysis of X--H...pi hydrogen bonding in proteins is performed based on 592 published high-resolution crystal structures (< or = 1.6 A). All potential donors and acceptors are considered, including acidic C--H groups. The sample contains 1311 putative X--H...pi hydrogen bonds with N--H, O--H or S--H donors, that is about one per 10.8 aromatic residues. By far the most efficient pi-acceptor is the side-chain of Trp, which accepts one X--H...pi hydrogen bond per 5.7 residues. The focus of the analysis is on recurrent structural patterns involving regular secondary structure elements. Numerous examples are found where peptide X--H...pi interactions are functional in stabilization of helix termini, strand ends, strand edges, beta-bulges and regular turns. Side-chain X--H...pi hydrogen bonds are formed in considerable numbers in alpha-helices and beta-sheets. Geometrical data on various types of X--H...pi hydrogen bonds are given.

Animals↗

Competition of hydrogen-bond acceptors for the strong carboxyl donor.

A database study on the competition of hydrogen-bond acceptors for the strong carboxyl donor in crystals is reported. The relative success in attracting this donor is determined for 34 types of acceptor (O, N, S, halogen and pi acceptors), and a correlation between the success in competition and the average hydrogen-bond distance is established.

Journal Article↗

Interferon-alpha suppresses the antiapoptotic effect of NF-kB and sensitizes renal cell carcinoma cells in vitro to chemotherapeutic drugs.

BACKGROUND: Immunochemotherapy (ICT) with interleukin-2 (IL-2) and interferon-alpha (IFNalpha) with a secondary effector (5-fluorouracil, 5 FU) is the only promising treatment for advanced renal cell carcinoma (RCC). With IFNalpha, besides the activation mechanisms of the immunosystem, a direct antitumor effect on tumor cells is expected. MATERIALS AND METHODS: NF-kB activity in three permanent cell lines (Hep2, HepG2, HT29) and in primary RCC cell lines was measured after incubation with tumor necrosis factor-alpha (TNFalpha), IFNalpha, IFN-gamma, TNFalpha+IFNalpha, and IFNgamma+TNFalpha, respectively. NF-kB activity and induction of apoptosis by chemotherapeutic drugs (5FU and doxorubicin) were determined in cells transfected with a constitutively active NF-kB p65 or a dominant negative IkB. RESULTS: NF-kB signaling induced by TNFalpha is suppressed by IFNalpha and IFNgamma in the permanent cell lines and in the primary RCC tumor cell cultures. In an in vitro ICT model we show that pretreatment of RCC with IL-2 and IFNalpha leads to a diminished NF-kB response to TNFalpha. In certain tumors, this correlates with increased susceptibility to investigated chemotherapeutic drugs as shown by annexin stain and cell elimination. Modulation of the cellular NF-kB state by a constitutively active p65 or a dominant negative IkB mimics this effect. The IkB construct leads to the same effects as IL-2/IFNalpha pretreatment as shown by predominant elimination of the transfected cells from the overall population, while introduction of p65 leads to a partial rescue from the effect of IL-2 and IFNalpha. The described effect, however, applies only to a selection of primary cell cultures. CONCLUSIONS: Besides the immunomodulation effects, treatment of RCC with IL-2/IFNalpha leads to a proapoptotic state in certain tumors. The relevant mediator seems to be IFNalpha by suppression of the antiapoptotic effect of NF-kB. These data can provide an experimental base for correlation with real patient outcome after ICT.

Antineoplastic Agents↗

Differential expression of cytokines and cytokine receptors in renal cell carcinoma.

Modulation of immunomechanisms by tumor cells can be caused by secretion of cytokines. In vitro data are usually gained in culture systems. It is debatable whether these systems are representative of the conditions inside the respective tumor tissues. Immunohistochemical studies of tumor tissue cryostats were compared with those in matched primary renal cell carcinoma tumor cell cultures. Results were correlated with histopathological characteristics and the in vitro cytotoxic effect of autologous tumor infiltrating lymphocytes (TILs). Expression of all studied cytokines and cytokine receptors could be shown in cryostats and cell cultures, but the detection pattern varied individually. The immunohistochemical results in cryostats were in good accordance with those in cell cultures. Expression of TGFbeta1 both in cryostats and cell cultures significantly correlated with the lack of cytotoxic activity of autologous TILs. Representative data can be obtained in tumor culture systems of primary renal cell carcinoma. TGFbeta1 secretion could play an important role in the interactions between tumor and cytotoxic cells.

Carcinoma, Renal Cell↗

Stroke magnetic resonance imaging within 6 hours after onset of hyperacute cerebral ischemia.

We studied the diagnostic and prognostic value of diffusion- and perfusion-weighted magnetic resonancce imaging (DWI and PWI) for the initial evaluation and follow-up monitoring of patients with stroke that had ensued less than 6 hours previously. Further, we examined the role of vessel patency or occlusion and subsequent recanalization or persistent occlusion for further clinical and morphological stroke progression so as to define categories of patients and facilitate treatment decisions. Fifty-one patients underwent stroke magnetic resonance imaging (DWI, PWI, magnetic resonance angiography, and T2-weighted imaging) within 3.3 +/- 1.29 hours, and, of those, 41 underwent follow-up magnetic resonance imaging on day 2 and 28 on day 5. In addition, we assessed clinical scores (on the National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, Barthel Index, and Modified Rankin Scale) on days 1, 2, 5, 30, and 90 and performed volumetric analysis of lesion volumes. In all, 25 patients had a proximal, 18 a distal, and 8 no vessel occlusion. Furthermore, 15 of 43 patients exhibited recanalization on day 2. Vessel occlusion was associated with a PWI-DWI mismatch on the initial magnetic resonance imaging, vessel patency with a PWI-DWI match (p < 0.0001). Outcome scores and lesion volumes differed significantly between patients experiencing recanalization and those who did not (all p < 0.0001). Acute DWI and PWI lesion volumes correlated poorly with acute clinical scores and only modestly with outcome scores. We have concluded on the basis of this study that early recanalization saves tissue at risk of ischemic infarction and results in significantly smaller infarcts and a significantly better clinical outcome. Patients with proximal vessel occlusions have a larger amount of tissue at risk, a lower recanalization rate, and a worse outcome. Urgent recanalization seems to be of utmost importance for these patients.

Aged↗

Active-site gorge and buried water molecules in crystal structures of acetylcholinesterase from Torpedo californica.

Buried water molecules and the water molecules in the active-site gorge are analyzed for five crystal structures of acetylcholinesterase from Torpedo californica in the resolution range 2.2-2.5 A (native enzyme, and four inhibitor complexes). A total of 45 buried hydration sites are identified, which are populated with between 36 and 41 water molecules. About half of the buried water is located in a distinct region neighboring the active-site gorge. Most of the buried water molecules are very well conserved among the five structures, and have low displacement parameters, B, of magnitudes similar to those of the main-chain atoms of the central beta-sheet structure. The active-site gorge of the native enzyme is filled with over 20 water molecules, which have poor hydrogen-bond coordination with an average of 2.9 polar contacts per water molecule. Upon ligand binding, distinct groups of these water molecules are displaced, whereas the others remain in positions similar to those that they occupy in the native enzyme. Possible roles of the buried water molecules are discussed, including their possible action as a lubricant to allow large-amplitude fluctuations of the loop structures forming the gorge wall. Such fluctuations are required to facilitate traffic of substrate, products and water molecules to and from the active-site. Because of their poor coordination, the gorge water molecules can be considered as "activated" as compared to bulk water. This should allow their easy displacement by incoming substrate. The relatively loose packing of the gorge water molecules leaves numerous small voids, and more efficient space-filling by substrates and inhibitors may be a major driving force of ligand binding.

Acetylcholinesterase↗

Elevated plasma TGF-beta1 in renal diseases: cause or consequence?

We previously reported elevated levels of TGF-beta1 in patients with renal carcinoma. Certain aspects led us to ask whether they might be caused by chronic damage to the kidney(s). Here we report on an extended set of patients with various renal diseases, lung cancer, humoral immunodeficiency and controls. For latent TGF-beta1 in plasma, we find that the control, immunodeficiency, lung cancer and kidney transplant groups do not differ significantly (means, 7.0-8.8 ng/ml). Also, acute short-term renal stress (extracorporal lithotrypsy) does not lead to an increase of TGF-beta1. However, the pyelonephritis patients present with levels of 19.0 ng/ml, chronic extracorporal dialysis patients with 15.5 ng/ml, and renal cell carcinoma patients with 22.8 ng/ml. For active TGF-beta1 these findings are exactly recovered. For serum levels, only the renal carcinoma group presents with significantly elevated levels of TGF-beta1. Kidney transplantation seems to normalize TGF-beta1 levels, while in the kidney cancer patients surgery has an effect only in part of the group. We conclude that elevated plasma TGF-beta1 levels are common in at least two chronic renal disease conditions, and that it normalizes with restoration of renal function. It is tempting to speculate that chronic elevation of TGF-beta1 in these patients may be critically involved in these conditions predisposing to renal cancer.

Carcinoma, Renal Cell↗

[Treatment of acute clinical stroke].

Stroke is an emergency. Treatment must begin as soon as possible because significant sustained neurological improvement has been demonstrated when thrombolytic treatment, mainly with recombined tissue plasminogen activator (rtPA) is initiated within the first hours of stroke onset. On the other hand in the acute phase of stroke it is critical that patients get adequate management for the prevention of early complications. Management of the acute phase of stroke is the target of this article. Preclinically started treatment must be continued in the neurological emergency unit. Clinical examination is followed by technical investigations: cerebral computer tomography (CCT) is the most useful radiological investigation in the acute phase. It allows to distinguish between ischemia and hemorrhagic lesions and also to rule out nonstroke brain conditions. Multimodal magnetic resonance imaging (mMRI) may provide data on viable versus irreversibly damaged tissue. Sufficient stroke treatment is based on well managed in-hospital infrastructure. Thrombolysis is the only causative treatment of stroke in selected patients. Complications of acute stroke comprise changes of blood pressure with hemodynamically relevant effects on cerebral perfusion pressure, acute post- ischemic brain edema, and intracerebral bleedings.

Brain↗

Diffusion of water molecules in crystalline beta-cyclodextrin hydrates.

To understand the rapid diffusion mechanism of water molecules in the crystal lattice of hydrated beta-cyclodextrin (beta-CD), molecular dynamics (MD) simulations of crystalline beta-CD were performed at five different relative humidities corresponding to hydration states ranging from beta-CD-9.4H2O to beta-CD-12.3H2O, and in aqueous solution. The trajectories for the crystalline beta-CD hydrates had lengths of 4 ns each, whereas the simulation in aqueous solution extended to 2 ns. Transport of water molecules in the crystal was characterized in terms of a spatially varying diffusion constant and the main direction of diffusion, which were evaluated using newly developed algorithms. The main diffusion pathway winds through the cavities of adjacent doughnut shaped beta-CD molecules and is slightly slanted with respect to the crystallographic b-axis. Water molecules outside the beta-CD cavities have access to the main diffusion pathway. The diffusion constant for transport of water molecules along the main pathway calculated from the MD simulation data adopts 1/30 of the value in bulk water at room temperature. This is in agreement with estimates that can be made from experimental data on the adjustment of a beta-CD crystal to changes in relative humidity.

Algorithms↗

Triphenylmethanol-triphenylphosphine oxide (1/1)

In the crystalline 1:1 molecular complex of triphenylmethanol (TPMeOH) and triphenylphosphine oxide (TPPO), C(19)H(16)O. C(18)H(15)OP, molecular dimers are formed which are linked by O-H. O=P hydrogen bonds. The dimers are aligned by sixfold phenyl embraces to form columns. The structure is disordered with half a dimer per asymmetric crystal unit, i.e. with only one molecular site which is half-occupied by both TPMeOH and TPPO.

Journal Article↗

Hydrogen bonding in two salts of 3-methylthio-4-(propargylthio)quinoline

In 3-methylthio-4-(propargylthio)quinolinium chloride monohydrate, C(13)H(12)NS(2)(+).Cl(-).H(2)O, and 3-methylthio-4-(propargylthio)quinolinium trichloroacetate, C(13)H(12)NS(2)(+).C(2)Cl(3)O(2)(-), the terminal alkyne group forms C[triple-bond]C-H.O hydrogen bonds of favourable geometry. The conformation of the flexible propargylthio group is different in the two structures.

Journal Article↗

Bis(4-propargyloxy-3-quinolylthio)methane.

The molecular structure of the title compound, C(25)H(18)N(2)O(2)S(2), in the crystal is characterized by almost parallel quinoline and propargyl groups that point in opposite directions out of the quinoline planes. Intermolecular C[triple-bond]C-H...N hydrogen bonding is observed, but the hydrogen-bond geometry is poor.

Analgesics↗

C

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Journal Article↗