Biomedical subjects

R Schmidt

Publications and source records attributed to R Schmidt.

At least 361 records · Page 20Linked to original sources

PubMed1995

Structure-activity relationships of dermorphin analogues containing N-substituted amino acids in the 2-position of the peptide sequence.

A series of dermorphin analogues containing an N-alkylated amino-acid residue Xaa in the 2-position of the peptide sequence was synthesized (Xaa = N-methylalanine, proline, pipecolic acid, N-methylphenylalanine, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid [Tic]). These peptides have the potential of assuming a cis Tyr1-Xaa2 peptide bond. Their in vitro opioid activity profiles were determined in mu- and delta-receptor-representative binding assays and bioassays. Aside from [D-Pro2]dermorphin, all analogues showed high affinity for mu- and/or delta-opioid receptors. Whereas most compounds were found to be full mu-agonists in the guinea pig ileum (GPI) assay, [Tic2]dermorphin (compound 7) was a partial mu-agonist. Replacement of Gly4 in 7 with Phe resulted in an analogue (8) with weak mu-antagonist activity. Furthermore, analogues 7 and 8 both were potent delta-antagonists (Ke = 3-40 nM) against the delta-agonists Leu-enkephalin, DPDPE and deltorphin I in the mouse vas deferens (MVD) assay. Compound 3, containing L-Pro in the 2-position, turned out to be one of the most mu-receptor-selective linear dermorphin analogues reported to date. Low-temperature HPLC experiments using micropellicular octadecyl silica as stationary phase revealed conformational heterogeneity of the dermorphin analogues which was ascribed to cis-trans isomerization around the Tyr1-Xaa2- and Tyr5-Pro6 peptide bonds. In the case of analogue 7 four separate peaks corresponding to the four possible isomers were apparent at -5 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1995

Malignancies of the genito-urinary system following renal transplantation.

OBJECTIVE: To analyse the development of malignancies of the genito-urinary system after renal transplantation. PATIENTS AND METHODS: A total of 868 renal graft recipients were followed up over a mean period of 41.8 +/- 45 months. Fifteen patients received grafts from living related donors and 853 were transplanted with kidneys from cadavers. RESULTS: Twelve patients (1.4%) exhibited cancer of the genito-urinary system: 11 tumours were de novo malignancies. One small renal carcinoma was transplanted from a living related donor. The incidence of tumours of the genito-urinary system was 34 in 100,000 patient years in the patients treated with cyclosporin and 32 in 100,000 patient years in the conventional therapy group. Four patients died within a mean survival time of 14.4 months. Comparison of our results with sex- and age-specific incidence rates in a reference population showed an increase in malignant tumours of the genitourinary system by a factor of 7.3 in males and 11.2 in females. CONCLUSIONS: The frequency of disorders after transplantation necessitates routine examinations in organ transplanted recipients both before and at regular intervals after transplantation, including the patient's native kidneys and cervical smears in females.

Adolescent↗

PubMed1995

Magnetic resonance imaging and spectroscopy findings after focal status epilepticus.

The etiology of cerebral abnormalities after focal status epilepticus (SE) is unknown. Possible causes include hypoxia and the excessive release of excitatory amino acids. Magnetic resonance imaging (MRI) of a 21-year-old patient with "cryptogenic" continuous motor seizures showed swelling and signal hyperintensity of the contralateral parietotemporal cortex, the thalamus, and the ipsilateral cerebellum on T2-weighted images. These regions are connected by glutamatergic pathways. Proton magnetic resonance spectroscopy (MRS) of the cortical lesion yielded a signal peak at the resonance frequency of 2.29 ppm, suggesting a focal increase of glutamate or its degradation product glutamine. At 3-month follow-up, structural alterations had disappeared, but the N-acetyl-aspartate/choline ratio was still reduced in the previously abnormal area. These findings are the first to demonstrate the contribution of MRS to pathophysiologic studies of focal SE in humans and, in combination with the pattern of imaging abnormalities, support a major role of glutamate for seizure-related brain damage.

Adult↗

PubMed1995

Determination of the thermal neutron flux in a fast neutron beam by use of a boron-coated ionization chamber.

The thermal neutron distribution in slow and fast neutron beams is usually determined using the foil activation method. In this work a small magnesium walled ionization chamber, in which the inner surface of the wall has been coated with 10B to increase the sensitivity for thermal neutrons, is used to estimate the thermal neutron component of the beam. After calibration and determination of the directional response in a thermal neutron beam a comparison with foil activation at different depths in water was performed to investigate the reliability of the ionization measurements. The chamber was used in a computer controlled water phantom to measure the depth and lateral distribution of the thermal neutron dose. With this arrangement two-dimensional scans of the thermal neutrons could be performed quickly and with high accuracy.

Biophysical Phenomena↗

PubMed1995

Multidrug resistance in Candida albicans: disruption of the BENr gene.

The BENr gene of Candida albicans, which confers resistance on susceptible strains of Saccharomyces cerevisiae to six structurally and functionally unrelated drugs, was described recently (R. Ben-Yaacov, S. Knoller, G. Caldwell, J. M. Becker, and Y. Koltin, Antimicrob. Agents Chemother. 38:648-652, 1994). This gene bears similarity to membrane proteins encoding antibiotic resistance in prokaryotes and eukaryotes. The effect of disruption of this gene on viability and drug susceptibility was determined. The results indicate that the gene is not essential but its inactivation leads to susceptibility to three of the four drugs tested. Inactivation of this gene did not increase the susceptibility of the mutant to benomyl, suggesting that C. albicans has other mechanisms of resistance, some of which may be additional efflux pumps that confer resistance to this tubulin-destabilizing agent.

Benomyl↗

PubMed1995

Venous thrombosis-associated inflammation and attenuation with neutralizing antibodies to cytokines and adhesion molecules.

Thrombosis and inflammation are closely related. However, the response of the vein wall to venous thrombosis has been poorly documented. This study examines the hypothesis that venous thrombosis is associated with an inflammatory response in the vein wall. In a rat model of inferior vena caval thrombosis, vein wall was temporally examined for inflammation by assessment of histopathology, leukocyte morphometrics, and cytokine levels. Animals were killed 1 hour and 1, 3, and 6 days after thrombus induction. Our findings demonstrated an early (day 1) neutrophil infiltration into the vein wall followed by a later (days 3 and 6) monocyte/macrophage and lymphocyte response. Cytokines were elevated only under conditions of venous thrombosis. Levels of epithelial neutrophil activating protein-78 (ENA-78), tumor necrosis factor-alpha (TNF), interleukin-6, and JE/monocyte chemoattractant protein-1 (JE/MCP-1) increased over the 6-day period, while macrophage inflammatory protein-1 alpha (MIP-1 alpha) peaked at day 3 after thrombus induction. Additionally, rats were passively immunized with neutralizing antibodies to TNF, ENA-78, MIP-1 alpha, JE/MCP-1, intercellular adhesion molecule-1 (ICAM-1), and CD18 compared with control antibodies. The most effective antibody early after thrombus induction for attenuating vein wall neutrophil extravasation was anti-TNF (P < .01). The monocyte/macrophage extravasation was inhibited most by anti-ICAM-1 followed by anti-TNF (P < .01). These findings demonstrate that venous thrombosis is associated with significant vein wall inflammation that is partially inhibited by neutralizing antibodies to cytokines and adhesion molecules.

Animals↗

PubMed1995

Anticardiolipin antibodies in normal subjects. Neuropsychological correlates and MRI findings.

BACKGROUND AND PURPOSE: Our aim was to assess the association of elevated anticardiolipin antibody (aCL) titers with silent brain damage and cognitive functioning in middle-aged and elderly normal subjects. METHODS: We determined the IgM and IgG aCL titers from 233 randomly selected clinically normal participants of a population-based stroke prevention study (age range, 44 to 82 years). aCL titers were categorized into negative (0 to 10 U/L), low positive (10 to 20 U/L), and moderately high positive (> 20 U/L). All participants underwent 1.5-T MRI and demanding neuropsychological testing. Semiautomated measurements of the total white matter hyperintensity area and the size of ventricles and cortical sulci were conducted. RESULTS: There were 180 subjects (77.3%) with negative, 35 (15.0%) with low positive, and 18 (7.7%) with moderately high positive aCL titers. The frequency and extent of focal and diffuse brain abnormalities were not related to the aCL status of those examined. However, subjects with positive aCL results performed worse than those with negative findings on almost all tests administered, and this effect was mainly IgG titer related. When an ANCOVA test and partial correlations to correct for slight group differences in age and for the presence of major vascular risk factors were used, values of P < .05 were noted on tests assessing mnemonic and visuopractical abilities. CONCLUSION: Increased aCL titers in normal elderly persons may be associated with subtle neuropsychological dysfunction, but they do not appear to cause any morphological changes as demonstrated by MRI.

Adult↗

PubMed1995

ELISA technique for quantification of surfactant protein B (SP-B) in bronchoalveolar lavage fluid.

Surfactant protein B (SP-B) is one of the essential constituents of the alveolar surfactant system, presenting mainly in the form of SP-B dimer. The measurement of this molecule in biologic samples has been hampered by its extreme hydrophobicity and intimate association with surfactant lipids. We developed a solid-phase, adsorption-based enzyme-linked immunosorbent assay (ELISA) technique for the quantification of SP-B in aqueous solutions. The ELISA employs the hydrophobicity of SP-B for direct binding of this compound to polystyrol immunosorbent plates. Samples are mixed with propanol (1:1 vol/vol) to achieve a homogeneous dispersion of their lipophilic constituents prior to adsorption to the wells. After fluid removal by evaporation, trifluoroethanol is added to optimize SP-B-polystyrol binding, and is then removed, again by evaporation. Subsequent washing procedures (diisopropyl-ether/butanol; Tween 20 in phosphate buffered saline [PBS]) selectively remove phospholipids. Solid phase-bound SP-B is detected by a monoclonal mouse antibody against porcine SP-B, cross-reacting with the apoprotein of human origin. For amplification, a biotinylated anti-mouse antibody and the avidin/biotin-peroxidase technique are used. Steep calibration curves with an excellent reproducibility are obtained for SP-B dimer (range: 0.3125 to 40 ng/well), either introduced directly into the immunosorbent-plate wells or previously admixed with synthetic phospholipid mixtures. SP-B monomer is detected with approximately 10% efficiency as compared with the dimer (wt/wt). Cross-reactivities with human SP-A and SP-C or albumin are negligible. Experiments with spiking of human bronchoalveolar lavage fluid (BAL) samples with different quantities of SP-B dimer revealed virtually complete apoprotein recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1995

Hydrolysis of fatty acid esters by Malassezia furfur: different utilization depending on alcohol moiety.

The lipophilic yeast Malassezia furfur belongs to the resident skin flora but has been implicated in various skin diseases. While topical oily preparations may support its growth, their formulation may be altered by yeast-dependent enzymatic degradation. Different synthetic fatty acid (mono-)esters used as refatting agents were mixed with 10(4), 10(5) and 5 x 10(5) yeasts/microliters, respectively, and incubated at 35 degrees C for a maximum of 48 h on selective agar for pathogenic fungi (Merck). The amount and pattern of generated free acids were evaluated by densitometric and gas chromatographic analysis, while yeast density was determined in a Neubauer chamber. Depending on the inoculum, yeast-dependent hydrolysis occurred immediately and was best effected in ethyl esters, followed by isopropyl esters, whereas hydrolysis of decyl oleate was only limited. Of the fatty acids released, unsaturated fatty acids were more stimulative to growth than saturated fatty acids; no toxic effects were observed. In conclusion, yeast-dependent hydrolysis of these synthetic fatty acid (mono-)esters was critically dependent on alcohol moiety, while growth promotion was best effected by unsaturated fatty acids. These results may help to improve the compatibility of topical formulations, especially in seborrheic areas.

Alcohols↗

PubMed1995

[Current status of diagnosis and therapy of chronic collateral ligament instability of the ankle joint: results of a survey of 267 German clinics in 1994].

A questionnaire was mailed to the heads of 400 German orthopaedic departments listed by the "Deutsche Gesellschaft für Unfallchirurgie", with the aim of evaluating the diagnostic and therapeutic approaches to chronic ankle instability that were current in 1994. The questionnaire was structured to focus on diagnostic imaging techniques, conservative and surgical management, and postoperative treatment. Evaluable questionnaires were returned from 267 hospitals (66.7%). The number of ligament reconstructions performed per institution ranged from 1 to over 100 (mean 17.5). Radiographic stress investigations and clinical examination were considered by 71.6% of the surgeons to be the most important criteria for surgical therapy. The methods most frequently used for primary reconstruction of the ligaments were: periosteal flaps (45.3%), anatomical repair (23.6%), different tenodeses (20.6%), and free anatomical implants of autologous or exogenous material (10.5%). Half the respondents used reconstruction procedures involving secondary repair of the injured ligament without augmentation or with periosteal flaps. The other half of the German surgeons preferred tenodeses or various other procedures. Conservative management of chronic ankle instability was considered by surgeons to be less appropriate for young active patients. Postoperative treatment includes casting and orthosis. The duration varied from 2 weeks to 8 weeks. The results of the nationwide survey demonstrate that more objective clinical methods of diagnosis are needed to allow preoperative differentiation between functional and mechanical instability. With better knowledge of the function of individual ligaments and more frequent exposure of the ligaments for simple overlap and direct suture, a lower rate of primary non-anatomical reconstructions may be possible in the future.

Adult↗

PubMed1995

[Tuberculosis of the esophagus].

Tuberculosis of the esophagus is a rare disease, occurring in most cases secondary to tuberculous infection of other organs. There are neither characteristic symptoms or diagnostic signs, nor typical X-ray or laboratory findings. Histology, too, often fails to establish a reliable diagnosis, so that esophageal tuberculosis may be mistaken for esophageal carcinoma. Most cases can be successfully treated with antituberculous therapy, although patients with esophageal tuberculosis in the presence of AIDS do not respond as well to anti-tuberculous therapy.

AIDS-Related Opportunistic Infections↗

PubMed1995

[Results of neutron therapy in recurrent malignant salivary gland tumors in the head and neck area].

PURPOSE: The records of 33 patients of recurrent salivary gland tumors of the head and neck regions were analysed. PATIENTS AND METHODS: 33 patients with recurrent salivary gland tumors were treated with fast neutrons of a 14 MeV DT generator. All patients had been operated several times. 10 patients had been irradiated before with photons or electrons. 24 patients had macroscopic tumor. In many cases advanced tumors were treated. RESULTS: The median follow-up of our patients is 33 months. 6 patients are still alive without disease. 5 patients are alive with local recurrence or tumor progression. The calculated survival rate for all patients is 45% at 5 years. The calculated control rate for all patients is 43% at 5 years. Most of the late side effects according to the RTOG/EORTC-score were moderate. Only in one case severe late side effects could be observed. CONCLUSION: According to the literature advanced recurrences of salivary gland tumors should be treated with fast neutrons.

Adult↗

PubMed1995

Esophageal tuberculosis: a differential diagnostic challenge.

Esophageal tuberculosis is a rare clinical picture. It is typically secondary to tuberculous infection of other organs. There are neither diagnostic signs or symptoms nor typical x-ray or laboratory findings. Histology, too, often fails to establish a reliable diagnosis, so that esophageal tuberculosis might be mistaken for esophageal carcinoma. We report the case of a woman with secondary esophageal tuberculosis to illustrate the clinical course and diagnostic problems of this condition.

Aged↗

PubMed1995

Novel classes of responsive and unresponsive C nociceptors in human skin.

One hundred ninety-four cutaneous C-fibers were recorded from the human peroneal nerve; 118 units were found by mechanical stimuli and 76 units were detected by electrical stimulation through a surface electrode. Needle electrodes were then inserted for electrical intradermal stimulation in the innervation territory of the units. Afferent and efferent sympathetic C-fibers were identified by slowing of conduction velocity after activation either by physical or chemical skin stimuli, or by arousal maneuvers eliciting sympathetic reflexes. In addition to mechano-heat-responsive C units (CMH) also found in previous studies, we here report on novel classes of C nociceptors in human skin, namely, units responding only to mechanical stimuli (CM), units responding only to heating (CH), and units that were insensitive to mechanical and heating stimuli and also to sympathetic provocation tests (CMiHi). With the electrical search technique we found 45% CMH, 13% CM, 6% CH, 24% CMiHi, and 12% sympathetic units. Excitation by topically applied mustard oil occurred in 58% of CMH units, and in one-third of CM and CMiHi units, respectively. Some CM, CH, and CMiHi units were sensitized to heating and/or to mechanical stimuli after topical application of mustard oil or capsaicin. These units then acquired responsiveness to a stimulus modality to which they previously were insensitive. Such recruitment of previously silent nociceptors implies spatial summation to the nociceptive barrage at central levels, and may contribute both to primary hyperalgesia to heat and pressure after chemical irritation, and to secondary hyperalgesia as a consequence of central sensitization.

Adult↗

PubMed1995

Cine phase contrast angiography of normal and diseased peripheral arteries. Preliminary results.

Cine phase contrast angiography (PCA) is a modified MR phase contrast sequence that acquires up to 22 coronal phase images per mean cardiac cycle. The ability of the sequence to visualise local haemodynamics was investigated in 7 normal volunteers and 9 patients with flow disturbances of the peripheral arteries using a 1.5 T imager. Functional flow information provided by coronal cine PCA was correlated with quantitative data obtained by MR flow measurements and vessel morphology confirmed by conventional angiograms. Due to the yet suboptimal image quality, an aortic dissection and 1 of 4 aneurysms could not be depicted morphologically. The temporal pattern of arterial perfusion in cine PCA corresponded with flow velocity versus time data provided by quantitative MR flow measurements. Accuracy and time resolution of cine PCA was thus sufficient to provide functional information on the severity of occlusive vascular disease.

Adult↗

PubMed1995

Adaptation and abstraction as steps towards case-based reasoning in the real medical world: case-based selection strategies for antibiotics therapy.

In this paper we describe an approach to making suitable case-based reasoning methods for real medical world problems. As an example: for the class of therapeutic problems, we choose therapy advice as antibiotics for patients in an intensive care unit, who have an infectious disease as an additional complication. As rapid advice is needed and the agent is unknown, we use an expected agent spectrum based on medical background knowledge and known resistances, which will both be adapted with the results of the laboratory. Case-based reasoning retrieval methods provide the advice for similar former patients. The old solutions are adapted to be applicable to the new medical situation of the current patient. Because of the large and incrementally increasing number of cases, we use prototypes as a structural aid. We present some experimental results of studies about the performance of our prototype design.

Anti-Bacterial Agents↗

PubMed1994

Sensitization of insensitive branches of C nociceptors in human skin.

1. Eighteen cutaneous mechanosensitive C nociceptors were recorded from the peroneal nerves of healthy human subjects. Their identity was continuously monitored by intracutaneous electrical stimulation, and their activation by mechanical or transcutaneous electrical stimulation was detected by slowing of conduction velocity during the relative refractory period. 2. Mechanoreceptive fields (mRFs) mapped with suprathreshold von Frey hair stimuli covered an area of 99 +/- 21 mm2 (mean +/- S.E.M.). Two of the units had separate mRFs, with borders about 0.5-1.5 cm apart from each other and the largest of these units had a maximal diameter of 4.5 cm. 3. Successive topical application of mustard oil and capsaicin induced expansions of mRFs by 57 +/- 14 mm2 in eight of fifteen units. 4. In twelve units transcutaneous electrical stimulation delivered through a pointed electrode was used for mapping the electroreceptive fields (eRFs). The borders of the eRFs and the mRFs were identical for two of twelve units only. In the other ten units additional mechano-insensitive areas (55 +/- 22 mm2) were detected from which transcutaneous electrical stimuli could activate the respective unit. 5. Application of mustard oil and capsaicin to these mechano-insensitive areas sensitized five of eight units to mechanical stimuli. In these cases the mRF after sensitization exactly corresponded to the eRF. 6. It is concluded that there are insensitive branches in human mechanosensitive cutaneous C nociceptors that can be detected by transcutaneous electrical stimulation and sensitized by topical application of chemical irritants. Activation of those branches in the course of inflammatory processes may contribute to spatial summation at central synapses and hence to hyperalgesia.

Adult↗

PubMed1994

RPS2 of Arabidopsis thaliana: a leucine-rich repeat class of plant disease resistance genes.

Plant disease resistance genes function is highly specific pathogen recognition pathways. PRS2 is a resistance gene of Arabidopsis thaliana that confers resistance against Pseudomonas syringae bacteria that express avirulence gene avrRpt2. RPS2 was isolated by the use of a positional cloning strategy. The derived amino acid sequence of RPS2 contains leucine-rich repeat, membrane-spanning, leucine zipper, and P loop domains. The function of the RPS2 gene product in defense signal transduction is postulated to involve nucleotide triphosphate binding and protein-protein interactions and may also involve the reception of an elicitor produced by the avirulent pathogen.

Amino Acid Sequence↗