Biomedical subjects

S Richter

Publications and source records attributed to S Richter.

At least 37 records · Page 2Linked to original sources

PubMed2004

Search for extraterrestrial point sources of neutrinos with AMANDA-II.

We present the results of a search for point sources of high-energy neutrinos in the northern hemisphere using AMANDA-II data collected in the year 2000. Included are flux limits on several active-galactic-nuclei blazars, microquasars, magnetars, and other candidate neutrino sources. A search for excesses above a random background of cosmic-ray-induced atmospheric neutrinos and misreconstructed downgoing cosmic-ray muons reveals no statistically significant neutrino point sources. We show that AMANDA-II has achieved the sensitivity required to probe known TeV gamma-ray sources such as the blazar Markarian 501 in its 1997 flaring state at a level where neutrino and gamma-ray fluxes are equal.

Journal Article↗

PubMed2004

[Spectral separation in ocular fundus autofluorescence images in patients suffering from age-related macular degeneration].

INTRODUCTION: Alterations in the intrinsic ocular fundus fluorescence are under discussion particularly in connection with age-related macular degeneration. However, further knowledge of the chemical substrate of fluorescence is necessary. METHOD: Ocular fundus autofluorescence was observed using a fundus camera. The fluorescence emission was recorded using a 3-chip CCD camera. For comparison, the fluorescence spectra of lipofuscin, A2-E, FAD, NADH(2) and AGE's were recorded by the Jena ophthalmo-spectrometer. RESULTS: In contrast to the homogeneous intrinsic fluorescence of a normal fundus, the fluorescence images of patients suffering from AMD showed remarkable local differences. The detected fluorescence spectra showed remarkable overlaps. DISCUSSION: We introduced a new technique enabling the detection of spectral differences in images of ocular fundus autofluorescence. Besides the fluorescence of lipofuscin, we found a green one in patients suffering from nonexudative AMD.

Adult↗

PubMed2004

Cerebellar mutism--report of four cases.

The aim of the present study was to investigate the manifestations of mutism after surgery in children with cerebellar tumors. Speech impairment following cerebellar mutism in children was investigated based on standardized acoustic speech parameters and perceptual criteria. Mutistic and non-mutistic children after cerebellar surgery as well as orthopedic controls were tested pre-and postoperatively. Speech impairment was compared with the localization of cerebellar lesions (i. e. affected lobules and nuclei). Whereas both control groups showed no abnormalities in speech and behavior, the mutistic group could be divided into children with dysarthria in post mutistic phase and children with mainly behavioral disturbances. In the mutistic children involvement of dentate and fastigial nuclei tended to be more frequent and extended than in the nonmutistic cerebellar children. Cerebellar mutism is a complex phenomenon of at least two types. Dysarthric symptoms during resolution of mutism support the anarthria hypothesis, while mainly behavioral changes suggest an explanation independent from speech motor control.

Age Factors↗

PubMed2004

Preserved verb generation in patients with cerebellar atrophy.

A role of the right cerebellar hemisphere has been suggested in linguistic functions. Nevertheless, studies of verb generation in cerebellar patients provide inconsistent results. The aim of the present study was to examine verb generation in a larger group of cerebellar patients with well-defined lesions. Ten subjects with degenerative cerebellar disorders and ten healthy matched controls participated. Subjects had to generate verbs to the blocked presentation of photographs of objects (i.e. four blocks of sixteen objects). As control condition, the objects had to be named. Furthermore, dysarthria was quantified by means of a sentence production and syllable repetition task. Volumetric analysis of individual 3D-MR scans was performed to quantify cerebellar atrophy. Cerebellar patients were slower in the sentence production and syllable repetition tasks, and cerebellar volume was decreased compared to controls. Despite cerebellar atrophy and dysarthria, the answers produced did not differ between patients and controls. In addition, both groups revealed the same amount of decrease in verbal reaction time over blocks (i.e. learning). The results suggest that the role of the cerebellum in verb generation is less pronounced than previously suggested.

Adult↗

PubMed2004

Deletion of the Gibberella fujikuroi glutamine synthetase gene has significant impact on transcriptional control of primary and secondary metabolism.

In Gibberella fujikuroi, the gibberellin (GA) and bikaverin biosynthesis are under control of nitrogen metabolite repression. However, the signalling components acting upstream of AREA are still unknown. We investigated the role of glutamine synthetase (GS) both as an enzyme and as a possible regulator in the nitrogen regulation system. We cloned and replaced the GS-encoding gene, glnA-Gf. The mutants grow with a phenotype different from the wild type in the presence of glutamine. They were unable to express nitrogen-repressed GA and bikaverin biosynthetic genes even under nitrogen starvation conditions. Complementation with the glnA-Gf wild-type copy fully restored GS activity, the expression of secondary metabolism genes, and the production of GAs and the red pigment, bikaverin. In order to find more target genes of GS, differential cDNA-screening and differential hybridization of macroarrays were performed using cDNA from the wild type and DeltaglnA mutant as probes. Several genes were dramatically up- or downregulated in the mutant. Among them are genes involved in N- and C-catabolism, and in transcriptional and translation control. Some of these genes are also under AREA control. Treatment with the GS inhibitor l-methionine sulphoximine resulted in similar expression patterns as in the glnA mutant with ammonium as nitrogen source, whereas glutamine can overcome the up- or downregulation of most but not all of the target genes. These findings suggest that not only glutamine, but also GS itself might play an important role in nitrogen metabolite repression.

Gene Expression Profiling↗

PubMed2003

Limits on diffuse fluxes of high energy extraterrestrial neutrinos with the AMANDA-B10 detector.

Data from the AMANDA-B10 detector taken during the austral winter of 1997 have been searched for a diffuse flux of high energy extraterrestrial muon neutrinos. This search yielded no excess events above those expected from background atmospheric neutrinos, leading to upper limits on the extraterrestrial neutrino flux measured at the earth. For an assumed E-2 spectrum, a 90% classical confidence level upper limit has been placed at a level E2Phi(E)=8.4 x 10(-7) cm(-2) s(-1) sr(-1) GeV (for a predominant neutrino energy range 6-1000 TeV), which is the most restrictive bound placed by any neutrino detector. Some specific predicted model spectra are excluded. Interpreting these limits in terms of the flux from a cosmological distributions of sources requires the incorporation of neutrino oscillations, typically weakening the limits by a factor of 2.

Journal Article↗

PubMed2003

[Acute headache with meningism and xanthochromic cerebrospinal fluid.An unusual manifestation of cervical epidural abscess].

We report on a 70-year-old female with acute onset of headache, meningism, xanthochromic cerebrospinal fluid, and developing laboratory parameters indicating a systemic infection. Initially, a subarachnoidal hemorrhage was assumed. However, magnetic resonance imaging showed upper cervical osteomyelitis and extending spinal epidural abscess. After application of broad systemic antibiotics, secluded abscess formation was achieved and successful neurosurgical debridement performed. The unusual cranial concentration of the complaints is probably due to the involvement of the craniocervical transition. Cervical epidural spinal abscess represents a potentially dangerous bacterial infection of the upper spine. Inadequate treatment can lead to irreversible neurological deficits. Cervical magnetic resonance imaging is an effective tool for diagnosis, since early diagnosis is important for good prognosis.

Aged↗

PubMed2003

Identification of significant pressures and impacts upon receiving waters.

This study gives a review on the process of identification of significant pressures and impacts, which is an important part of river basin planning and in particular for implementing the EU Water Framework Directive (WFD) (2000/60/EC). The questions: what is a "significant pressure" in terms of the WFD? which sources and driving forces have to be regarded? which data can be used? which pressure on a water body is significant? and which implications and requirements result from the identification process?--should be considered. The European Commission requires reporting from all Member States about the status of the water bodies within a river basin district and about the risk of failing the environmental objectives by the end of 2004. Therefore, a number of prevailing projects across Europe aim to develop a guideline on a common understanding of the most effective approach towards the identification of significant anthropogenic pressures, and the analysis of potential impacts including the identification of appropriate tools and models. In such a guideline suitable and intelligent criteria have to be developed in order to enable a uniform assessment of the anthropogenic pressures within a river basin district.

Environmental Monitoring↗

PubMed2001

The topoisomerase II poison clerocidin alkylates non-paired guanines of DNA: implications for irreversible stimulation of DNA cleavage.

Clerocidin, a diterpenoid with antibacterial and antitumor activity, stimulates in vitro DNA cleavage mediated by mammalian and bacterial topoisomerase (topo) II. Different from the classical topoisomerase poisons, clerocidin-stimulated breaks at guanines immediately preceding the sites of DNA cleavage are not resealed upon heat or salt treatment. To understand the mechanism of irreversible trapping of the topo II-cleavable complex, we have investigated the reactivity of clerocidin per se towards DNA. We show here that the drug is able to nick negatively supercoiled plasmids. DNA cleavage by clerocidin in enzyme-free medium is due to the ability of the drug to form covalent adducts with guanines. Indeed, clerocidin was able to specifically react with short oligonucleotides when the guanines were unpaired and exposed as in bulges or in the single-strand form. The clerocidin epoxy group attacks the nitrogen at position 7 of guanines, leading to strand scission at the modified site. Our findings also demonstrate that trapping of topoisomerases by clerocidin is specific for type II enzymes. The guanine-alkylating ability of clerocidin suggests an unprecedented mechanism of topo II poisoning, according to which the enzyme renders the drug reactive toward DNA by distorting the double-helical structure of the nucleic acid at the cleavage site.

Alkylation↗

PubMed2001

Observation of high-energy neutrinos using Cerenkov detectors embedded deep in Antarctic ice.

Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water or ice. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations.

Journal Article↗

PubMed2001

Hepatic arteriolo-portal venular shunting guarantees maintenance of nutritional microvascular supply in hepatic arterial buffer response of rat livers.

To elucidate the hepatic microvascular response upon the hepatic arterial buffer response (HABR), we analysed blood flow (ultrasonic flowprobes) of the hepatic artery (HA) and portal vein (PV), microcirculation (intravital microscopy), and tissue oxygenation (polarography) in anaesthetized Sprague-Dawley rats and re-evaluated the role of adenosine in mediating the HABR by using 8-phenyltheophylline as a competitive antagonist. 2. Upon restriction of PV blood flow to 11 +/- 3 % of baseline values, HA blood flow increased by a factor of 1.77 (P < 0.05), thus confirming HABR. Strikingly, red blood cell velocity and volumetric blood flow in terminal hepatic arterioles (THAs) did not increase but were even found to be slightly decreased, by 8 and 13 %, respectively. In contrast, red blood cell velocity and volumetric blood flow in terminal portal venules (TPVs) decreased to only 66 % (P < 0.05), indicating upstream hepatic arteriolo-portal venular shunting. As a consequence, red blood cell velocity and volumetric blood flow in sinusoids were found to be reduced to only 66-68 % compared with baseline (P < 0.05). Diameters of neither of those microvessels changed, thus excluding THA-, TPV-, and sinusoid-associated mechanisms of vasomotor control in HABR. 3. Tissue PO2 and hepatocellular NADH fluorescence remained unchanged, indicating HABR-mediated maintenance of adequate oxygen delivery, despite the marked reduction of total liver blood flow. Further, hepatic arteriolo-portal venular shunting guaranteed homogeneity of nutritive blood flow upon HABR, as given by an unchanged intra-acinar coefficient of variance of sinusoidal perfusion. 4. Pretreatment of animals with the adenosine antagonist 8-phenyltheophylline completely blocked the hepatic arterial buffer response with the consequence of decreased tissue oxygenation and increased heterogeneity of sinusoidal perfusion. 5. In conclusion, hepatic microhaemodynamics, in particular unchanged diameters of THAs, TPVs and sinusoids, during HABR indicate that reduction in resistance to HA flow is located upstream and functions via hepatic arteriolo-portal venular shunts resulting in equal distribution of microvascular blood flow and oxygen delivery under conditions of restricted PV blood supply.

Adenosine↗

PubMed2001

The phylogenetic relationships of "predatory water-fleas" (Cladocera: Onychopoda, Haplopoda) inferred from 12S rDNA.

Within the Cladocera, the water-fleas, four major taxa can be distinguished: Anomopoda, Ctenopoda, Haplopoda, and Onychopoda. Haplopoda and Onychopoda are called "predatory water-fleas." The Haplopoda is monotypic; its only representative, Leptodora kindtii, is common in palearctic and nearctic freshwater bodies. The Onychopoda show a remarkable geographic distribution. Most of the described species are restricted to the Caspian Sea, the Aral Sea, and peripheral areas of the Black Sea, including the Sea of Azov--all remnants of the Eastern Paratethys. The remaining onychopods are either freshwater inhabitants or marine animals, widespread in the world oceans. We present molecular evidence for a sister group relationship between Haplopoda and Onychopoda within the Cladocera. The Onychopoda and its three families are monophyletic. We suggest an independent invasion into the Ponto-Caspian basin at least three times, twice originating in the palearctic freshwater bodies and once starting from the world oceans.

Animals↗

PubMed2001

Clinical controlled study on plaque and gingivitis reduction under long-term use of low-dose chlorhexidine solutions in a population exhibiting good oral hygiene.

The aim of this randomized, parallel-group, placebo-controlled, blind clinical study was to examine the dental plaque and the gingivitis inhibitory effects of two low-dose 0.06% chlorhexidine (CHX) preparations in comparison to a commercially available 0.1% CHX solution, an amine fluoride/stannous fluoride (ASF) solution and a water control as an adjunct to the daily mechanical oral-hygiene measures. After prophylaxis, 81 medical students performed their tooth cleaning and were asked to rinse for 30 s, according to the instructions given by the manufacturers with the assigned amount of the following solutions: once daily 10 ml ASF 250 ppm or twice daily each 10 ml CHX 0.06% with fluoride, 10 ml CHX 0.06% without fluoride, 15 ml CHX 0.1% or 100 ml tap water. The plaque index (PlI), the gingival index (GI) and the discoloration index (DI) were taken at day -14 and months (M) 0, 1, 2, 3 and 6. In this study group with good oral hygiene, all test products led to a reduction of the PlI scores when used as supplements to the usual mechanical hygiene measures. At M3 subjects using both the 0.1% as well as the 0.06% CHX showed significantly less plaque accumulation than those using ASF. In the GI a significant difference between the control and 0.1 % CHX was found at M3 and at M6. If a further decrease in the GI is wanted, a minimum concentration of 0.1% CHX for long-term use in association with habitual cleaning is needed, which, however, should be limited to special patients. If maintaining clinical health is the goal, the other solutions are a good alternative to 0.1% CHX because they exhibit less staining.

Adolescent↗

PubMed2001

Preparation and investigation of tumor affinity, uptake kinetic and transport mechanism of iodine-123-labelled amino acid derivatives in human pancreatic carcinoma and glioblastoma cells.

In developing radioiodinated agents for pancreatic and brain tumor imaging by single photon emission tomography (SPET), we prepared p-amino-3-[123I]iodo-l-phenylalanine (IAPA), p-[123I]iodo-l-phenylalanine (IPA), L-8-[123I]iodo-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (ITIC) and L-3-[123I]iodo-alpha-methyl-tyrosine (IMT) in radiochemical yields up to 95%, and we investigated their uptake in human pancreatic carcinoma and glioblastoma cells as well as the mechanisms promoting the tumor uptake. The radiopharmaceutical uptake into tumor cells was rapid (t(1/2) < or = 5 min) and temperature- and pH-dependent. The radioactivity concentration in tumor cells varied from 10 to 33% of the total activity (105-310 cpm/1000 cells) following a 30-min incubation at 37 degrees C (pH 7.4). In comparison, accumulation of the radiopharmaceuticals into normal brain and pancreatic tissue remained relatively low. Depolarizing the plasma membrane potential in high K+ buffer significantly altered the radioactivity concentration in the tumor cells, suggesting that membrane potential plays a certain role in the cellular uptake. Competitive inhibition experiments with specific amino acid transport inhibitors indicated that the uptake of IAPA, IPA and IMT into human pancreatic carcinoma and glioblastoma cells is predominantly mediated by the L and ASC transport systems, while no substantial involvement of the transport system A in their tumor uptake could be demonstrated. In contrast, results of the present investigation indicated that ITIC is not taken up into tumor cells via the common neutral amino acid carrier systems, including the A, L and ASC system. Furthermore, preloading with naturally occurring L-amino acids failed to stimulate the cellular uptake of the radiopharmaceuticals. These data indicate that the investigated radiopharmaceuticals exhibit interesting characteristics with promise for in vivo tumor investigations to ascertain their potential as radioligands for glioma and pancreatic carcinoma imaging by SPET.

Amino Acids↗

PubMed2001

Intracavernous injections: still the gold standard for treatment of erectile dysfunction in elderly men.

The objective of this work was to determine the effectiveness of intracavernous injections (ICI) of vasoactive drugs in elderly men with erectile dysfunction and to compare the results obtained with the injection of two different drug combinations. It was a case control study. The sample consisted of 300 men, 63-85 y of age (mean 67.1) with erectile dysfunction of organic origin. Among the patients 180 underwent first trial with injection of prostaglandin E1 (PE). Further on these 180 patients and another 120 (in total 300 patients) were treated with a triple combination of papaverine hydrochlorate, phentolamine messylate and prostaglandin E1 (PPR). The number of responders to the injection of either PE alone or the drug combination was recorded. The quality of the erections was evaluated in the outpatient clinic by the medical staff and through patient's report after home trial. The average volume of either PE or PPR necessary to obtain a functional erection was measured. We observed a statistically significant association between the results obtained after the injection of PPR as compared to PE (chi2 with 2 d.f.: 34.666; P= < 0.001). A functional erection was obtained in 224/300 (74.7%) after the injection of PPR as compared to 87/180 men (48.3%) treated with PE. The average volume of PPR necessary to obtain a functional erection was 0.35+/-0.14 ml whereas that of PE was 1.3+/-0.3 ml. intracavernous injection of vasoactive drugs is still one of the most successful therapies for patients suffering from organic impotence. It is less effective in the older age group as compared to younger. However, if this form of therapy is chosen for aged men the triple combination therapy (PPR) yields a higher response rate than that obtained with prostaglandin alone.

Aged↗

PubMed2001

Loss of physiologic hepatic blood flow control ("hepatic arterial buffer response") during CO2-pneumoperitoneum in the rat.

UNLABELLED: We analyzed whether a compensatory increase of hepatic arterial (HA) flow, known as the "hepatic arterial buffer response" (HABR), may serve for maintenance of liver blood supply during laparoscopy-associated portal venous (PV) flow reduction. We assessed HA and PV flow, as well as hepatic tissue oxygenation (PO2) during CO2-pneumoperitoneum in anesthetized and mechanically ventilated Sprague-Dawley rats (n = 7). Control animals (n = 7) without pneumoperitoneum, but tourniquet-induced PV flow reduction served to demonstrate physiologic HABR. Although stepwise tourniquet-induced reduction of PV flow to 20% of baseline values led to a significant (P < 0.05) increase of HA flow from 4.3 +/- 0.7 mL/min to 9.9 +/- 1.7 mL/min, stepwise intraabdominal pressure-induced decrease of PV flow was paralleled by a linear reduction of HA flow from 2.4 +/- 0.3 mL/min to 1.2 +/- 0.5 mL/min at 18 mm Hg intraabdominal pressure. This loss of HABR was sustained during a subsequent 2 h-period of CO2-pneumoperitoneum contrasting the 2 h of maintenance of HABR in controls. Hepatic tissue PO2 decreased during the 2 h-period of pressure- and tourniquet-induced PV flow reduction by 35% to 51%, respectively. On tourniquet release, all variables regained baseline values, whereas evacuation of the pneumoperitoneum allowed all variables except hepatic PO2 to return to baseline, indicating prolonged tissue hypoxia despite restored total liver blood flow in the Laparoscopic group. Concomitantly, increased liver enzyme activities reflected moderate tissue damage after 2 h of pneumoperitoneum. In conclusion, intraabdominal CO2-insufflation-induced hemodynamic alterations may impair tissue oxygenation and enzyme release, indicating the potential risk for hepatic tissue damage after prolonged periods of laparoscopic interventions. IMPLICATIONS: We investigated the effect of CO2-pneumoperitoneum on liver blood flow, hepatic tissue oxygenation (PO2) and liver enzyme release. CO2-insufflation reduces portal venous flow without a compensatory increase of hepatic arterial flow ("hepatic arterial buffer response"), resulting in reduced hepatic PO2 and increased ratios of serum alanine aminotransferase to serum aspartate aminotransferase.

Alanine Transaminase↗

PubMed2001

DNA-interactive anticancer aza-anthrapyrazoles: biophysical and biochemical studies relevant to the mechanism of action.

The physicochemical and DNA-binding properties of anticancer 9-aza-anthrapyrazoles (9-aza-APs) were investigated and compared with the carbocyclic analogs losoxantrone (LX) and mitoxantrone (MX). Unlike their carbocyclic counterparts, the tested 9-aza-APs do not undergo self-aggregation phenomena. The pyridine nitrogen at position 9, missing in the carbocyclic derivatives, is involved in protonation equilibria at physiological pH. In addition, 9-aza-APs are electrochemically reduced at a potential intermediate between LX and MX. These data fully agree with quantum mechanical calculations. Binding to nucleic acids was examined by spectroscopic, chiroptical, and DNase I footprinting techniques as a function of ionic strength and base composition. The 9-aza-APs exhibit prominent affinity for DNA, with an important electrostatic contribution to the binding free energy. A very remarkable sequence preference pattern dramatically favors GC steps in double-helical DNA, whereas the carbocyclic reference compounds show a substantially lower selectivity for GC. A common DNA complexation geometry, considerably differing from that of MX, characterizes all anthrapyrazoles. Hence, bioisosteric substitution and ring-hydroxy deletion play an important role in defining the physicochemical properties and in modulating the affinity of anthrapyrazoles for the nucleic acid, the geometry of the intercalation complex, and the sequence specific contacts along the DNA chain. Drug stimulation of topoisomerase II-mediated DNA cleavage is remarkably attenuated in the aza-bioisosteric derivatives, suggesting that other non-enzyme-mediated cytotoxic mechanism(s), possibly connected with free radical production, are responsible for efficient cell killing. The biophysical and biochemical properties exhibited by 9-aza-APs contribute to clarifying the peculiar pharmacological profile of this family of compounds.

Animals↗

PubMed2001

Low incidence of reactive arthritis in children following a salmonella outbreak.

OBJECTIVES: To assess the incidence of reactive arthritis (ReA) in an outbreak of salmonella infection in a large cohort of children in Germany. METHODS: A few days after the salmonella outbreak all parents of affected children and all paediatricians and general practitioners in the region were provided with detailed information about the possibility of ReA. Six weeks after the outbreak a telephone call was made to all general practitioners and paediatricians to identify patients with ReA. Ten weeks after the outbreak a questionnaire assessing symptoms of ReA was mailed to all parents, and after a period of 4 months paediatricians and general practitioners were contacted again to search for additional unreported cases of ReA. RESULTS: Of the 286 children (age range 11 months to 9 years) with diarrhoea and stool cultures positive for Salmonella enteritidis lysotype 8/7, not a single case of arthritis was reported over the 4 month period. However, six children (2%) had arthralgia of various duration (1 day to 6 weeks) with a single recurrence in one child. The joint pattern was oligoarticular and lower limb joints (knee/ankle) were affected exclusively. CONCLUSION: The incidence of ReA after salmonella infection in children appears to be very low which may be related to differences in the immune response between children and adults.

Arthritis, Reactive↗