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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 361 records · Page 20Linked to original sources

The pharmacotherapy of depressive illness in adolescence: II. Effects of lithium augmentation in nonresponders to imipramine.

The antidepressant value of lithium augmentation was assessed in a 3-week open trial involving 24 adolescents who remained highly depressed after 6 weeks of treatment with imipramine hydrochloride. Two patients responded dramatically during the first week, with an additional eight patients showing partial improvement during the 3-week trial. The overall magnitude of improvement in depression ratings was significantly greater than in an historical control group of nonresponders who continued to receive imipramine monotherapy during their hospital treatment. Results suggest the potential use of this adjunctive strategy in some tricyclic resistant adolescent depressives, although it appears less efficacious overall in this age group than in adults.

Adolescent↗

Perception of structured phantom targets in the echolocating bat, Megaderma lyra.

Bats can discriminate among objects with different texture using echolocation. The mechanisms involved in texture discrimination are unknown. In real echoes reflected from three-dimensional objects, the spatial structure of the target creates a specific temporal and spectral pattern. In the experiments described here, simply structured phantom targets mimicking echoes reflected from an object with two parallel planes were generated by adding two differentially delayed copies of the bat's vocalizations. The discrimination performance of Megaderma lyra was studied in a two-alternative, forced-choice experiment using phantom targets with different internal delays and relative amplitudes of the two copies. When the reference target to which the bats were trained was presented, targets differing in internal delay by about 1 microseconds were discriminated. However, discrimination performance was not a globally monotonic function of the internal delay of the unrewarded target. When both targets presented in a trial differed from the reference, the bats still preferred one of them. Changes in overall level of the phantom target echo had little effect on performance; however, performance dropped considerably if only one of the two copies in an echo was attenuated. A model framework is introduced to account for these results. Models based on frequency processing yield better approximations than does a model based on time differences. The model based on spectral correlation gives a unified description of all the data. Although time domain models for texture discrimination cannot be generally refuted, the results presented here show that the discrimination of target surface structure can be explained as a discrimination of echo spectra.

Animals↗

Biodegradation of diphenyl ether and its monohalogenated derivatives by Sphingomonas sp. strain SS3.

The bacterium Sphingomonas sp. strain SS3, which utilizes diphenyl ether and its 4-fluoro, 4-chloro, and (to a considerably lesser extent) 4-bromo derivatives as sole sources of carbon and energy, was enriched from soil samples of an industrial waste deposit. The bacterium showed cometabolic activities toward all other isomeric monohalogenated diphenyl ethers. During diphenyl ether degradation in batch culture experiments, phenol and catechol were produced as intermediates which were then channeled into the 3-oxoadipate pathway. The initial step in the degradation follows the recently discovered mechanism of 1,2-dioxygenation, which yields unstable phenolic hemiacetals from diphenyl ether structures. Oxidation of the structure-related dibenzo-p-dioxin yielded 2-(2-hydroxyphenoxy)-muconate upon ortho cleavage of the intermediate 2,2',3-trihydroxydiphenyl ether. Formation of phenol, catechol, halophenol, and halocatechol from the conversion of monohalogenated diphenyl ethers gives evidence for a nonspecific attack of the dioxygenating enzyme system.

Adipates↗

Mutations in a 19-amino-acid hydrophobic region of the yeast cytochrome c1 presequence prevent sorting to the mitochondrial intermembrane space.

Most mitochondrial proteins destined for the intermembrane space (IMS) carry in their presequence information for localization to the IMS in addition to information for their import. By selecting for mutants in the yeast Saccharomyces cerevisiae that mislocalize an IMS-targeted fusion protein, we identified mutations in the IMS sorting signal of the cytochrome c1 protein. Amino acid substitutions or deletions in a stretch of 19 hydrophobic amino acids of the cytochrome c1 presequence resulted in accumulation of the intermediate form of the cytochrome c1 protein in the matrix. In some cases, the accumulated intermediate appeared to be slowly exported from the matrix, across the inner membrane to the IMS. Our results support the hypothesis that the cytochrome c1 precursor is normally imported completely into the matrix and then exported to the IMS.

Amino Acid Sequence↗

Carbamazepine-induced systemic lupus erythematosus.

A 21-year-old woman suffering from bipolar affective disorder developed systemic lupus erythematosus (SLE) with characteristic laboratory findings, 18 months after starting carbamazepine maintenance treatment. SLE receded after withdrawal of carbamazepine and treatment with anti-inflammatory drugs. Although both the spontaneous occurrence of SLE and the psychosis as a sign of CNS involvement of SLE cannot be excluded, SLE could be considered as an adverse effect of carbamazepine.

Adult↗

Fast quantitative assay of sequence-specific endonuclease activity based on DNA sequencer technology.

A quantitative assay of the sequence-specific endonuclease activity of Vsr DNA mismatch endonuclease is described. The procedure rests on fluorescently labelled oligonucleotide substrates and an automated DNA sequencer to determine amounts of both educt and product of the reaction; thus each individual measurement is internally standardized. The assay achieves high sample throughput by parallel measurement of multiple samples. Because of its capacity to produce and process large sets of experimental data, the system is particularly well suited for the determination of reaction kinetics. The procedure lends itself to further simplification by implementing software additions for direct peak integration. Obviously, the principle of the assay can be extended to the study of other enzymes, such as restriction endonucleases or sequence-specific proteases.

Base Sequence↗

Immunological and beta-cell-specific characteristics of diabetes-prone BB/OK rats and their congenic derivatives--a comparative study.

In a comparative study congenic rat strains bearing either the genetic background of diabetic BB/OK rats and the MHC (RTla) of diabetes-resistant LEW.1A rats (BB.1A/OK) or vice versa carrying the genetic background of LEW.1A rats in combination with the MHC (RTlu) of diabetic BB/OK rats (LEW.1BB/OK) and their parental rat strains BB/OK and LEW.1A were checked for insulin secretion of pancreatic islets, for the number of splenic and peripheral blood mononuclear cells (MNC) as well as for the mitogenic response of splenic MNC. Glucose stimulated insulin secretion of isolated islets of Langerhans was not different in 50, 70 and 100 day-old congenic rats and the progenitor rat strains excluding an impact of the genotype on this beta-cell-specific function. The number of splenic and peripheral blood MNC was reduced in BB/OK and BB.1A/OK rats compared to LEW.1A and LEW.1BB/OK rats. Splenic MNC from BB/OK and BB.1A/OK rats displayed a strongly decreased total [3H]thymidine incorporation under basal conditions as well as upon mitogenic stimulation by ConA in comparison with MNC from LEW.1A and LEW.1BB/OK rats. Thus, the occurrence of lymphopenia and the impairment of mononuclear cell proliferation in BB/OK rats is not related to the RTlu haplotype of the MHC but is linked to non-MHC genes as indicated by the phenotypic expression of these traits in congenic BB.1A/OK rats.

Animals↗

[Is there an unusual incidence of the manifestation of intracranial angiomas in pregnancy? Risk assessment based on 17,733 patients over 10 years].

From 1979-1988, 134 inpatients (m:f = 80:54) were treated because of an intracranial angioma (AVM). The male/female ratio was 3/2 in general as well as during the "reproductive age" (15-45 yrs). In 6 patients (20-27 yrs; grav 2/para 1: n = 3; grav 1/para 0: n = 3) the AVM became symptomatic during pregnancy (n = 4: 23-33 gestational week) or at birth (n = 2). In the group of the presently non-pregnant women (n = 40) 47 uncomplicated deliveries had occurred years before. We conclude that the available data neither allow us to reject nor to confirm the hypothesis that pregnancy and/or delivery influence the manifestation of cerebral AVMs. The reasons for this dilemma of epidemiology are discussed.

Adolescent↗

[Clinical use of photodynamic therapy in gynecologic tumor patients--antibody-targeted photodynamic laser therapy as a new oncologic treatment procedure].

The clinical report addresses the first application of a antibody-targeted photodynamic laser therapy with Phthalocyanines. Photodynamic therapy (PDT) has been proposed as a further treatment modality in oncology. The concept of PDT is based on the interaction between a dye which is accumulated in the target and laserlight. The phototoxic effect is achieved by the augmentation of oxygen radicals. The improvement of the selectivity and the reduction of side-effects is achieved by our concept of using an antibody-targeted phthalocyane induced PDT. The clinical application of the antibody-targeted Phthalocyanine was performed in 3 patients suffering from an advanced ovarian carcinoma (FIGO III). By means of an ultramicroscopical analysis a selective devitalisation of tumor cells was demonstrated. The perspective of PDT reaches far beyond the application for the ovarian carcinomas and relates to all tumor types, where the presence of tumor-associated antigens implicates a treatment in a similar way.

Combined Modality Therapy↗

Photodynamic laser therapy of carcinomas--effects of five different photosensitizers in the colony-forming assay.

Photodynamic therapy (PDT) with laser radiation opens a new field in the treatment of malignancies. We evaluated the phototoxic effects of five different substances for photodynamic therapy in concentrations showing no systemic toxicity. We used gynecologic tumor cells and evaluated the photodynamic effects for cell growth in a colony-forming assay. For Indigocarmin we found a reduction in the colony-forming assay compared to the control group from 87% to 66% after irradiation at 50 mumol/l and 608 nm wavelength. "IR 132" showed a reduction in the colony-forming assay from 73% to 72% 50 mumol/l (590 nm). For the incubation of the HeLa cells with 50 mumol/l of "Sulfo-Phthalocyanin" we found a reduction of the colony-forming potential from 81% to 67% (595 nm). The most strikingly differences were found for the incubation and irradiation of Methylene Blue, showing a reduction from 77% to 16% caused by a toxic effect of the substance itself (5 mumol/l, 660 nm) and "Sulfo-Aluminium-Phthalocyanin" stained cells, which shows a reduction from 86% to 17% (50 mumol/l, 675 nm). We see the possibility of a photoactivation and cell devitalisation by "Sulfo-Aluminium-Phthalocyanin" and laser radiation. A future clinical trial would seem justified.

Cell Survival↗

Diastolic tension and contraction amplitude in calcium-loaded rat ventricular myocardium are differently affected by drugs.

1. To obtain a measure of drug effects on myocardial function during diastole, the following experimental protocol was designed: rapid electrical stimulation (5 Hz) at high Ca02+ caused an elevated diastolic tension, which could be subjected to drug-induced alterations. 2. Antiarrhythmic drugs (quinidine, propafenone, procainamide, mexiletine) were able to lower diastolic force without appreciably decreasing contraction amplitude. Calcium antagonists (nifedipine, verapamil) lowered both parameters in parallel. 3. Veratridine and Bay K 8644 both enhanced diastolic tension, but only Bay K 8644 concomitantly elevated contraction amplitude. 4. These findings may be explained when taking into account differential actions of sodium- and calcium channel modulating drugs, respectively, on cellular Ca2+ movements. In quantitative terms, the non-linear dependence of myocardial force on Cai2+ also had to be considered.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

The effect of masker spectral asymmetry on overshoot in simultaneous masking.

"Overshoot" is a simultaneous masking phenomenon: Thresholds for short high-frequency tone bursts presented shortly after the onset of a broadband masker are raised compared to thresholds in the presence of a continuous masker. Overshoot for 2-ms bursts of a 5000-Hz test tone is described for four subjects as a function of the spectral composition and level of the masker. First, it was verified that overshoot is largely independent of masker duration. Second, overshoot was determined for a variety of 10-ms masker bursts composed of differently filtered uniform masking noise with an overall level of 60 dB SPL: unfiltered, high-pass (cutoff at 3700 Hz), low-pass (cutoff at 5700 Hz), and third-octave-band-(centered at 5000 Hz) filtered uniform masking noises presented separately or combined with different bandpass maskers (5700-16000 Hz, 5700-9500 Hz, 8400-16000 Hz) were used. Third, masked thresholds were measured for maskers composed of an upper or lower octave band adjacent to the third-octave-band masker as a function of the level of the octave band. All maskers containing components above the critical band of the test tone led to overshoot; no additional overshoot was produced by masker components below it. Typical values of overshoot were on the order of 12 dB. Overshoot saturated when masker levels were above 60 dB SPL for the upper octave-band masker. The standard neurophysiological explanation of overshoot accounts only partially for these data. Details that must be accommodated by any full explanation of overshoot are discussed.

Acoustics↗

Relative changes in oxyhemoglobin, deoxyhemoglobin and intracranial blood volume during surfactant replacement therapy in infants with respiratory distress syndrome.

Oxy-, deoxyhemoglobin and total blood volume were studied by near-infrared spectroscopy (NIRS) during surfactant replacement therapy. These parameters were compared with parameters watched during conventional noninvasive monitoring (pulseoximetry, transcutaneous pO2 and pCO2, heart rate). Seven premature infants (28 +/- 3 weeks of gestation, 940 g birth weight) were given surfactant intratracheally. Immediately after surfactant administration, oxyhemoglobin decreased, deoxyhemoglobin and total blood volume increased. The prior status was re-established after 60-220 s and then oxyhemoglobin increased to a very stable maximum. NIRS allows continuous bedside noninvasive monitoring of all parameters.

Blood Gas Monitoring, Transcutaneous↗

Animal experiments for the evaluation of laserspectroscopy in the fetus during labor.

Laserspectroscopy with near-infrared light is newly available for clinical application. The equipment consists of a near-infrared data collection unit (NIRDCU) and a personal computer. Emission of laser light at wavelengths of 775, 805, 845 and 904 nm is provided by the four laser diodes of the NIRDCU. By analyzing changes of optical density during laser radiation, information is obtained regarding the intracellular redox state and relative changes of blood volume. During measurement with the system on the fetal scalp during delivery we were able to get a first impression of the method's potential. While the application of the laser sensors is still cumbersome, signals providing information of the relative changes of hemoglobin concentration, relative changes of blood volume and cytochrome aa3 seems achievable. Laserspectrophotometric monitors may become safe, low cost and portable instruments for the non-invasive assessment of the biochemical and biophysical status in the fetus.

Animals↗

Continuous intrapartum transcutaneous carbon dioxide measurements during fetal arrhythmia.

In nine cases of fetal arrhythmias without cardiac anomalies or congestive heart failure a vaginal delivery was attempted. Due to these arrhythmias adequate fetal heart rate monitoring during labor was not possible. All cases were continuously monitored during labor with the transcutaneous measurement of fetal carbon dioxide tension (tcpCO2). Seven patients could be delivered spontaneously. In one of these cases the newborn was acidotic at birth (pH less than 7.20 in the umbilical artery) which was correctly identified (tcpCO2 greater than 60 mmHg). All newborns were vigorous (Apgar score after 1 minute greater than 7). In cases with uninterpretable fetal heart rate patterns tcpCO2 monitoring of the fetus during labor is an alternative method of fetal surveillance, which identifies fetal distress and can prevent unnecessary operative deliveries.

Acid-Base Equilibrium↗

[The central nervous system of infants born to HIV-positive mothers-- neuropathology, immunohistochemistry in in situ hybridization].

The central nervous system (CNS) of 12 fetuses from human-immunodefiency-virus-seropositive mothers was investigated. Postconceptional ages ranged between 15 and 21 weeks. 3 preterm infants born to HIV positive mothers whose survival ranged from 6 hours to 6 months were included in the study. In all cases, the development of the CNS was macroscopically normal. The microscopic examination showed many ectopic neurons indicating disturbances of normal neuronal migration. As a regular finding there was a significant increase in microglia in all areas of the CNS but no microglial nodules were found. In all cases haematogenous monocytes were scattered in the perivascular space of the cerebral parenchyma as well as in the chorioid pexus. The virus-antigen p24 could neither be detected immunohistochemically in the paraffin sections nor in the frozen material of the brain or by in-situ-hybridization. In contrast, in five of the cases investigated the placenta showed macrophages, socalled Hofbauer cells with p24-associated antigen.

Antigens, Viral↗