Biomedical subjects

S Köhler

Publications and source records attributed to S Köhler.

At least 19 recordsLinked to original sources

PubMed2006

Widely tunable soliton frequency shifting of few-cycle laser pulses.

Photonic-crystal fibers are employed to demonstrate widely tunable frequency down-conversion of unamplified 6-fs Ti:sapphire laser pulses through the soliton self-frequency shift induced by the Raman effect. Wavelength shifts as large as 500 nm are achieved for input few-cycle pulses with broadband spectra centered at approximately 820 nm. The central wavelength of the redshifted output of a photonic-crystal fiber is smoothly tuned from the low-frequency edge in the spectrum of the 6-fs Ti:sapphire laser pulse up to 1.35 microm by varying the input energy in the fundamental mode of the fiber.

Journal Article↗

PubMed2006

Diffraction-arrested soliton self-frequency shift of few-cycle laser pulses in a photonic-crystal fiber.

The balance between diffraction and index-step guiding in photonic-crystal fibers is controlled by modifying the fiber structure, leading to different wavelength dependences of the effective mode area and providing a mechanism to control nonlinear-optical phenomena. In optical fibers with a steep profile, the guided mode of the light field tends to become much less compact with an increase in radiation wavelength, slowing down the Raman-induced soliton self-frequency shift of an ultrashort laser pulse. A reduction of the soliton self-frequency shift is demonstrated for input laser pulses.

Journal Article↗

PubMed2005

Nonlinear-optical spectral transformation of few-cycle laser pulses in photonic-crystal fibers.

Photonic-crystal fibers with special dispersion profiles are shown to provide a high efficiency of spectral transformation of chirped sub-6-fs Ti:sapphire laser pulses. With the wavelength of zero group-velocity dispersion of the fiber lying within the broad spectrum of the input few-cycle pulse, the output spectra feature well-resolved spectral peaks, indicative of soliton self-frequency shift, four-wave mixing, and Cherenkov emission of dispersive waves. We demonstrate that up to 3% of radiation energy at the output of the fiber can be confined within a spectrally isolated soliton peak centered at , which is ideally suited as a seed for Nd:YAG- and ytterbium-based laser devices.

Journal Article↗

PubMed2005

Retrospective analyses and future predictions of snowmelt-induced acidification: example from a heavily impacted stream in the Czech Republic.

We have combined a long-term hydrochemistry model (MAGIC) with a model that predicts short-term transient changes in hydrochemistry (pBDM) during hydrological events in order to improve the temporal resolution of retrospective analyses and future predictions of streamwater acidification. The model has been applied to a heavily impacted catchment in the Czech Republic. Spring flood acid-neutralizing capacity (ANC), pH, and inorganic monomeric aluminum (Ali(n+)) were simulated for the years of 1860, 1900, 1930, 1950, 1965, and 1985, measured in 1999, and predicted for 2030 using two different emission control scenarios. If the emission reduction according to the current legislation scenario is implemented, the model predicts that the spring flood pH, ANC, and Ali(n+) will recover close to the level of the 1950s by 2030. This will occur despite the annual average chemistry being farfrom having recovered to that level. The results suggest that the recovery of spring flood events is faster then the recovery of annual average chemistry and that much of what is won by further emission reduction will not be fully realized on an annual time scale.

Acid Rain↗

PubMed2005

Fetal lung development in pregnancies of diabetic women assessed by quantitative ultrasonic tissue characterization.

OBJECTIVES: This study was performed to compare quantitative ultrasonic tissue characterization of the fetal lung at different gestational ages in uncontrolled diabetic patients with that in normal uncomplicated pregnancies. METHODS: A total of 44 women at 24-37 weeks' gestation with the diagnosis of diabetes in pregnancy were enrolled. Data were compared to those of the control group, which consisted of 140 women with uncomplicated pregnancies of the same gestational age. Longitudinal and transverse sections of the fetal thorax and upper abdomen were examined. A region of interest of constant size was defined and the tissue-specific gray scale was determined by using interactive software. RESULTS: Compared with normal pregnancies, fetal lungs of diabetic pregnancies have a higher echogenicity between 28 and 37 weeks of gestation. The lung mean gray values (MGV) only differed significantly between 30 and 31 weeks of gestation in the group with diabetes (P = 0.033) compared to the control group. The MGV of the liver in diabetic and normal pregnancies is similar during pregnancy, significant differences being found only at 30-31 weeks of gestation (P = 0.038). The lung-to-liver ratio in the control group showed a significant increase from 24 to 31 weeks and a slight non-significant decrease after 31 weeks. The ratio in the group with diabetes increased slightly up to week 33 and decreased slightly afterwards. CONCLUSION: Fetal lung MGV in uncontrolled diabetic pregnancies compared to that in uncomplicated pregnancies differs significantly only between 30 and 31 weeks of gestation.

Cross-Sectional Studies↗

PubMed2005

[Schizophrenia as a disconnection syndrome. Studies with functional magnetic resonance imaging and structural equation modeling].

Aside from characteristic psychopathological symptoms, cognitive deficits are a core feature of schizophrenia. These deficits can only be addressed within the context of widespread functional interactions among different brain areas. To examine these interactions, structural equation modeling (SEM) was used for the analysis of fMRI datasets. In a series of studies, both in antipsychotic-treated and drug-free schizophrenic patients, a pattern of enhanced thalamocortical functional connectivity could be observed as an indicator for possible disruptions of frontostriatal thalamocortical circuitry. Moreover, drug-free patients and those receiving typical antipsychotic drugs were characterized by reduced interhemispheric corticocortical connectivity. This difference relative to normal controls was less in patients under atypical antipsychotic drugs. The results could be interpreted as a beneficial effect of atypical antipsychotic drugs on information processing in schizophrenic patients. The present findings are consistent with the model of schizophrenia as a disconnection syndrome and earlier concepts of "cognitive dysmetria" in schizophrenia.

Antipsychotic Agents↗

PubMed2005

The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection.

Persistence infection is the keystone of the ruminant and human diseases called brucellosis and Malta fever, respectively, and is linked to the intracellular tropism of Brucella spp. While described as non-motile, Brucella spp. have all the genes except the chemotactic system, necessary to assemble a functional flagellum. We undertook to determine whether these genes are expressed and are playing a role in some step of the disease process. We demonstrated that in the early log phase of a growth curve in 2YT nutrient broth, Brucella melitensis expresses genes corresponding to the basal (MS ring) and the distal (hook and filament) parts of the flagellar apparatus. Under these conditions, a polar and sheathed flagellar structure is visible by transmission electron microscopy (TEM). We evaluated the effect of mutations in flagellar genes of B. melitensis encoding various parts of the structure, MS ring, P ring, motor protein, secretion apparatus, hook and filament. None of these mutants gave a discernible phenotype as compared with the wild-type strain in cellular models of infection. In contrast, all these mutants were unable to establish a chronic infection in mice infected via the intraperitoneal route, raising the question of the biological role(s) of this flagellar appendage.

Animals↗

PubMed2001

Phase II study of combined 5-fluorouracil/ Ginkgo biloba extract (GBE 761 ONC) therapy in 5-fluorouracil pretreated patients with advanced colorectal cancer.

The aim of the study was to evaluate the efficacy, tolerability and quality of life in 5-fluorouracil (5-FU) pretreated colorectal cancer patients after combined 5-FU and Ginkgo biloba extract GBE 761 ONC (i.e. the Ginkgo biloba special extract EGb 761(R)) therapy. Following conventional 5-FU therapy, 44 patients (32 evaluable for response) with advanced progressive colorectal cancer were treated every 3 weeks with courses of 350 mg GBE 761 ONC as a 30 min i.v. infusion on days 1-6 followed by 500 mg/m(2)/d 5-FU as a 30 min i.v. infusion on days 2-6. The response to therapy was evaluated after the second and fourth course of treatment. The data of 32 patients could be evaluated for efficacy. We observed a progression of disease in 22 patients, no change in 8 patients and a partial response in 2 patients (overall response = 6.3%). Seventeen of 22 patients with observed progressive disease showed further progression after two cycles, two after three cycles and three after four cycles. The median survival time was 9.5 months (7.7-11.5 months). GBE 761 ONC was well tolerated. Adverse events that occurred during the study were mainly myelosuppression and gastrointestinal symptoms and were judged to be 5-FU related or consistent with liver toxicity and thus tumour related. Our results suggest a good benefit-risk ratio of the combined 5-FU and GBE 761 ONC therapy as second line treatment in metastatic colorectal cancer. The survival time was similar to that known from second line treatment according to the Ardalan scheme. Since an improvement was observed in some patients despite the failure of the conventional 5-FU pretreatment, it would be interesting to evaluate whether the application of 5-FU plus GBE 761 ONC as a first line treatment is of benefit.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Fast three-dimensional sodium imaging of human brain.

A three-dimensional sodium imaging technique with a minimum echo time of 0.9 ms is described in a 2.0 Tesla whole-body system. The relaxation behaviour in vivo of sodium was analysed: a fast T(2)(*) relaxation component between 1.2 and 1.6 ms and a slow T(2)(*) relaxation component between 7.1 ms and 8.4 ms were quantified in brain tissue of three volunteers. Three-dimensional sodium images of the human brain were acquired in 8.5 min with a resolution of 4.7 x 4.7 x 10 mm (0.2 cc voxel size) and a signal-to-noise ratio of 20 in brain tissue and 30 in cerebrospinal fluid.

Biophysics↗

PubMed2001

On the impact of calcified deposits within the rotator cuff tendons in shoulders of patients with shoulder pain and dysfunction.

We wanted to prove the hypothesis that calcified deposits within the rotator cuff tendons are merely an epiphenomenon of complex morphological alterations in the shoulders of patients with shoulder pain and dysfunction. The shoulders of 92 patients with calcified deposits within the rotator cuff tendons as noted on plain radiographs were investigated by means of magnetic resonance imaging (MRI; mean age of patient 51.1 years), as well as the shoulders of 28 age- and sex-matched patients with similar clinical symptoms but without any signs of such calcified deposits on plain radiographs. The MRI protocol comprised a coronal, oblique, T1-weighted, spin-echo sequence, a T2-weighted, turbo spin-echo sequence, a sagittal, oblique, T2-weighted, turbo spin-echo sequence, and an axial, T1-weighted, spin-echo sequence. Furthermore, a coronal, oblique, short tau-inversion recovery sequence and a gradient echo sequence were used. The results were compared with data from healthy, asymptomatic volunteers as reported in the literature. The MRI investigations showed no substantial differences between patients with or without calcified deposits within the rotator cuff tendons, but distinct differences between such patients and healthy, asymptomatic volunteers. For patients with shoulder pain, shoulder dysfunction, and calcified deposits within the rotator cuff tendons, these calcified deposits are most probably not the main cause of the clinical symptoms. Rather, it seems to be useful to consider the results of MRI investigations whenever planning therapeutic procedures for patients with shoulder pain and dysfunction, irrespective of whether or not there are signs of calcified deposits within the rotator cuff tendons on plain radiographs.

Adult↗

PubMed2001

Extracorporeal shock-wave therapy for chronic lateral tennis elbow--prediction of outcome by imaging.

Today the clinical use of extracorporeal shockwave application (ESWA) for the treatment of lateral tennis elbow is hampered by the lack of results from randomized controlled trials and of predictive parameters of clinical outcome. The present prospective study aimed to provide the latter by means of magnetic resonance imaging (MRI). Twenty-three female and 19 male patients with unilateral chronic tennis elbow of the dominant site were clinically examined before and after repetitive low-energy ESWA. MRI was performed before ESWA to evaluate signal intensity changes or contrast enhancement of the common extensor tendon and the lateral epicondyle. After ESWA (mean follow-up period 18.6 months for all patients), clinical evaluation showed a significantly better mean clinical performance after ESWA than before treatment. Interestingly, male patients showed a significantly better mean clinical performance after ESWA than female patients, and male and female patients differed significantly in the signal intensity of the common extension tendon cross-section and tendon thickening on MRI. For female patients, MRI scans could be applied for predicting a positive clinical outcome of ESWA. This study reports the first indication of predictability of positive clinical outcome of the treatment of chronic lateral tennis elbow by ESWA using imaging prior to treatment. This may serve as an important step towards overcoming the therapeutic nihilism with respect to the non-operative management of this condition recently in the literature.

Adult↗

PubMed2001

Screening for people with diabetes mellitus for poor blood glucose control in an ophthalmological laser clinic.

PURPOSE: The study was performed to test the effect of a structured intervention in diabetic patients with poor glycaemic control in an ophthalmological department. PATIENTS AND METHODS: All the patients attending the ophthalmological out-patient department with the need for laser therapy due to diabetic retinopathy were investigated from January to March 1998 (Type 1: n=20, Type 2: n=144). If an HbA(1c)-level higher than 9.0% was found the patient was informed within 1 week and a standardised letter was sent to the primary care physician and the local ophthalmologist. Over the first 3 months of 1999 the effect was evaluated. RESULTS: HbA(1c) values higher than 9.0% were found in eight/20 of the patients (40%) with Type 1 diabetes and in 61/144 of the patients (54%) with Type 2 diabetes. In 55% this new information in the context of the need for laser therapy resulted in the acceptance of a structured intervention by the patient. This led to an improvement of the HbA(1c) in the people with Type 1 diabetes. CONCLUSION: Patients with poor blood glucose control can be identified in an ophthalmological department. The need for laser therapy can be used to motivate the patients for a significant improvement of the quality of blood glucose control.

Blood Glucose↗

PubMed2001

Secretion of listeriolysin by Brucella suis inhibits its intramacrophagic replication.

The introduction into Brucella suis 1330 of a plasmid allowing the heterologous expression of a hybrid cytolysin containing listeriolysin from Listeria monocytogenes, and its export via the Escherichia coli hemolysin secretion pathway, resulted in secretion of active listeriolysin monitored by erythrocyte lysis. In contrast to observations with the nonhemolytic control strain, the phagosomes of infected human monocytes containing the hemolytic B. suis were partially disrupted, and this strain failed to multiply in human macrophage-like cells. These results added strong evidence supporting the proposal that the phagosome of the macrophage was the predominant niche of brucellae in their mammalian hosts.

Animals↗

PubMed2001

Major outer membrane protein Omp25 of Brucella suis is involved in inhibition of tumor necrosis factor alpha production during infection of human macrophages.

Brucella spp. can establish themselves and cause disease in humans and animals. The mechanisms by which Brucella spp. evade the antibacterial defenses of their host, however, remain largely unknown. We have previously reported that live brucellae failed to induce tumor necrosis factor alpha (TNF-alpha) production upon human macrophage infection. This inhibition is associated with a nonidentified protein that is released into culture medium. Outer membrane proteins (OMPs) of gram-negative bacteria have been shown to modulate macrophage functions, including cytokine production. Thus, we have analyzed the effects of two major OMPs (Omp25 and Omp31) of Brucella suis 1330 (wild-type [WT] B. suis) on TNF-alpha production. For this purpose, omp25 and omp31 null mutants of B. suis (Deltaomp25 B. suis and Deltaomp31 B. suis, respectively) were constructed and analyzed for the ability to activate human macrophages to secrete TNF-alpha. We showed that, in contrast to WT B. suis or Deltaomp31 B. suis, Deltaomp25 B. suis induced TNF-alpha production when phagocytosed by human macrophages. The complementation of Deltaomp25 B. suis with WT omp25 (Deltaomp25-omp25 B. suis mutant) significantly reversed this effect: Deltaomp25-omp25 B. suis-infected macrophages secreted significantly less TNF-alpha than did macrophages infected with the Deltaomp25 B. suis mutant. Furthermore, pretreatment of WT B. suis with an anti-Omp25 monoclonal antibody directed against an epitope exposed at the surface of the bacteria resulted in substancial TNF-alpha production during macrophage infection. These observations demonstrated that Omp25 of B. suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages.

Antibodies, Bacterial↗

PubMed2001

Identification of the nik gene cluster of Brucella suis: regulation and contribution to urease activity.

Analysis of a Brucella suis 1330 gene fused to a gfp reporter, and identified as being induced in J774 murine macrophage-like cells, allowed the isolation of a gene homologous to nikA, the first gene of the Escherichia coli operon encoding the specific transport system for nickel. DNA sequence analysis of the corresponding B. suis nik locus showed that it was highly similar to that of E. coli except for localization of the nikR regulatory gene, which lies upstream from the structural nikABCDE genes and in the opposite orientation. Protein sequence comparisons suggested that the deduced nikABCDE gene products belong to a periplasmic binding protein-dependent transport system. The nikA promoter-gfp fusion was activated in vitro by low oxygen tension and metal ion deficiency and was repressed by NiCl(2) excess. Insertional inactivation of nikA strongly reduced the activity of the nickel metalloenzyme urease, which was restored by addition of a nickel excess. Moreover, the nikA mutant of B. suis was functionally complemented with the E. coli nik gene cluster, leading to the recovery of urease activity. Reciprocally, an E. coli strain harboring a deleted nik operon recovered hydrogenase activity by heterologous complementation with the B. suis nik locus. Taking into account these results, we propose that the nik locus of B. suis encodes a nickel transport system. The results further suggest that nickel could enter B. suis via other transport systems. Intracellular growth rates of the B. suis wild-type and nikA mutant strains in human monocytes were similar, indicating that nikA was not essential for this step of infection. We discuss a possible role of nickel transport in maintaining enzymatic activities which could be crucial for survival of the bacteria under the environmental conditions encountered within the host.

ATP-Binding Cassette Transporters↗

PubMed2001

Characterization of Brucella suis clpB and clpAB mutants and participation of the genes in stress responses.

Pathogens often encounter stressful conditions inside their hosts. In the attempt to characterize the stress response in Brucella suis, a gene highly homologous to Escherichia coli clpB was isolated from Brucella suis, and the deduced amino acid sequence showed features typical of the ClpB ATPase family of stress response proteins. Under high-temperature stress conditions, ClpB of B. suis was induced, and an isogenic B. suis clpB mutant showed increased sensitivity to high temperature, but also to ethanol stress and acid pH. The effects were reversible by complementation. Simultaneous inactivation of clpA and clpB resulted in a mutant that was sensitive to oxidative stress. In B. suis expressing gfp, ClpA but not ClpB participated in degradation of the green fluorescent protein at 42 degrees C. We concluded that ClpB was responsible for tolerance to several stresses and that the lethality caused by harsh environmental conditions may have similar molecular origins.

Adenosine Triphosphatases↗

PubMed2001

Episodic memory for object location versus episodic memory for object identity: do they rely on distinct encoding processes?

Three experiments were conducted to determine whether encoding processes that support episodic memory for object location are distinct from those that support memory for object identity. Guided by transfer-appropriate processing notions, we examined with an incidental learning paradigm whether an attentional focus on object location at encoding promotes subsequent recovery of object location, whereas a focus on object identity promotes recovery of object identity. We found that judging spatial relationships at encoding selectively supports recovery of object location, provided the test assesses memory for these relationships (rather than absolute location); our results also showed that judging physical and semantic object attributes promotes recovery of object identity preferentially. Contrasting with these domain-specific effects was evidence that identification processes involved in object naming boost memory for object identity as well as for absolute object location. Object identification at encoding may support memory performance in both domains by triggering the binding of identity and location information through a mechanism of object-based attentional selection.

Adult↗

PubMed2001

Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. See The biology behind: K. A. Foon and M. Bhattacharya-Chatterjee, Are solid tumor anti-idiotype vaccines ready for prime time? Clin. Cancer Res., 7:1112-1115, 2001.

The aim of the present study was to assess whether the induction of specific immune responses by vaccination with the murine monoclonal anti-idiotypic antibody ACA125, which imitates the tumor-associated antigen CA125, has a positive influence on the survival of patients with recurrent ovarian carcinoma. Forty-two patients with platinum-pretreated recurrences were included in a clinical Phase I/II trial of consolidation in third-line therapy. Patients initially received four immunizations with 2 mg of alum-precipitated anti-idiotype ACA125 every 2 weeks and then monthly applications. No serious allergic reactions could be detected within a maximal control period of 56 months. Hyperimmune sera of 27 of 42 patients (64.2%) showed increased concentrations of human antimouse antibodies. Specific anti-anti-idiotypic antibodies as a marker for induced immunity were detected in 28 of 42 patients (66.7%). The survival of the whole ACA125-treated collective of patients after a mean of 12.6 antibody applications was 14.9 +/- 12.9 months. The survival of patients with a positive immune response was 19.9 +/- 13.1 months in contrast with 5.3 +/- 4.3 months in those patients without detectable anti-CA125 immunity (P < 0.0001). According to these results, vaccination with a suitable anti-idiotypic antibody offers an effective way to induce specific immunity against a primarily nonimmunogenic tumor antigen such as CA125 and is associated with a positive impact on the survival of patients with recurrent ovarian cancer with few side effects, which warrants a Phase III trial for ovarian cancer patients after primary therapy.

Antibodies, Anti-Idiotypic↗