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G Schwarz

Publications and source records attributed to G Schwarz.

At least 145 records · Page 8Linked to original sources
PubMed1989

Thermodynamic and kinetic studies on the association of melittin with a phospholipid bilayer.

Association of the amphiphilic peptide melittin with unilamellar vesicles of dioleoylphosphatidylcholine has been experimentally investigated by means of circular dichroism, fluorescence energy transfer and stopped-flow experiments. Circular dichroism changes upon titration of the peptide with vesicles (at low salt concentration) were analyzed to yield thermodynamic association isotherms. These isotherms are quantitatively interpreted in terms of a monomer-monomer partitioning of melittin between the aqueous and bilayer media. The data can be very well fitted by theoretical curves based on a Gouy-Chapman surface potential. Energy transfer involving chemically modified tryptophan confirms a lack of aggregation of the associated peptide. According to the kinetic measurements the association proceeds in practice as a one-step process, which is rather fast but not fully diffusion-controlled. We propose a simple mechanism where the inherent conformational transition determines the overall rate.

Bee Venoms↗
PubMed1989

Persistent reduction of CD4/CD8 lymphocyte ratio and cell activation before the onset of type 1 (insulin-dependent) diabetes.

Over a period of 5 years, lymphocyte subpopulations and their markers of activation were studied prospectively in 56 first degree relatives of Type 1 (insulin-dependent) diabetic probands. Lymphocytes were phenotyped using a panel of monoclonal antibodies which recognise CD3, CD4, CD8 lymphocytes, K/NK cells, HLA Class II products and IL-2 receptors (IL-2r). Twenty-six subjects were negative for islet cell antibody (ICA), 18 had complement fixing ICA (CF-ICA) and 12 only conventional ICA (ICA-IgG). The total number of observations (blood samples collected) was 386. Overall, changes in T cell data were observed in the three groups of first degree relatives compared to 70 normal subjects without a family history of diabetes. Six individuals developed Type 1 diabetes in the course of the study. They all possessed CF-ICA and five out of six showed a persistent reduction (less than 1.5) of the CD4/CD8 lymphocyte ratio before the clinical onset of the disease. Activated lymphocytes were found on two occasions in two of these subjects. We conclude that imbalance of lymphocyte immunoregulatory subsets is present before the onset of Type 1 diabetes in susceptible individuals; the persistence of a reduced CD4/CD8 lymphocyte ratio may reflect the ongoing process leading to B-cell destruction.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

TNF-alpha gene polymorphisms in type 1 (insulin-dependent) diabetes mellitus.

Type 1 (insulin-dependent) diabetes mellitus, like some other autoimmune diseases, is linked to certain alleles coded by genes in the HLA-D region. Sequence analysis of DQ beta chains indicates that aspartic acid at codon 57 confers resistance to the development of Type 1 diabetes. However, a full explanation for the HLA-association of Type 1 diabetes, particularly the increased susceptibility of DR3/4 heterozygotes is still awaited. The localisation of tumour necrosis factor genes on the short arm of chromosome 6 between HLA-B and the complement genes (Class III) prompted us to investigate a possible polymorphism of TNF-alpha at the genomic level in relation to Type 1 diabetes susceptibility. A dialleleic TNF-alpha restriction fragment length polymorphism was found with Ncol and its segregation with HLA-haplotypes analysed in diabetic families. We describe here a strong linkage of TNF-alpha alleles with certain DR haplotypes. For example, the common extended haplotype HLA A1-B8-DR3 was almost exclusively associated with the 5.5 kb TNF-alpha allele whereas Bw62-DR4 with the 10.5 kb allele. Thus both alleles segregate to diabetic patients. DR matched haplotypes of affected family members differed significantly from those of the non-affected at the TNF alpha locus. All affected sibling pairs in 11 multiplex affected families were identical for TNF-alpha alleles, even if they were only haploidentical for HLA-B-DR haplotypes. In addition, heterozygosity for the TNF-alpha alleles was significantly more frequent in the patients. This tight linkage of TNF-alpha alleles with some extended haplotypes could help to explain the HLA-association of Type 1 diabetes as well as some other autoimmune diseases.

Diabetes Mellitus↗
PubMed1989

Thermodynamics and kinetics of incorporation into a membrane.

Some very recent work on the equilibrium and rate of incorporation of the pore forming peptide alamethicin into phospholipid bilayers is briefly reviewed. The experimental methods and the proceedings to evaluate and interpret the data are generally applicable analogously to other cases of substrates which somehow associate with a membrane. For the special system under consideration, a very high degree of incorporation is observed, reflecting internal aggregation and thermodynamically non-ideal repulsive interactions. These points are included in a basic model which is shown to provide a quantitative fit of the measured results. Stopped-flow experiments have shown that the overall incorporation occurs as a practically one-step process. Its rate is remarkably fast, only slightly slower than the diffusion controlled upper limit. All the kinetic data can be quite satisfactorily interpreted in terms of a reaction scheme with steady-state intermediates comprising the obvious diffusional translocations as well as the accompanying conformational change. In particular, the special findings for the alamethicin system suggest a most simple working hypothesis of the molecular mechanism underlying the voltage-dependent gating effect.

Alamethicin↗
PubMed1989

Multifocal necrotizing fasciitis in varicella.

We describe a two-year-old patient who developed severe necrotizing fasciitis in three nonadjacent sites of his extremities during varicella. The recovery of purulent material by aspiration of deep soft tissues after seven days of fever, leukocytosis, and no response to antimicrobial therapy raised the suspicion of this diagnosis. The patient recovered following surgical drainage, debridement, and subsequent skin grafts. It is emphasized that early diagnosis of this severe complication is important since early surgical intervention decreases morbidity and facilitates recovery.

Chickenpox↗
PubMed1989

TNF-alpha gene polymorphisms: association with type I (insulin-dependent) diabetes mellitus.

The localization of TNF genes on the short arm of chromosome 6 between HLA B and the complement genes focused attention to that genetic region which harbors many immunologically relevant genes and is also thought to hold susceptibility genes for a variety of autoimmune diseases that are linked to specific alleles of particular loci in the HLA D region. Since the recently established HLA-DR-DQ variation accounts only for part of the genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) we searched for genomic variation of the tumour necrosis factor (TNF) alpha. We have identified a TNF-alpha restriction fragment length polymorphism (RFLP) with NcoI and analysed diabetic patients including their families, controls and homozygous typing cell lines (HTC) defined by the 10th International Histocompatibility Workshop. Segregation analysis in families and HTC results show a strong linkage of the TNF-alpha 5.5 kb allele with DR types in particular with A1B8DR3. This tight linkage of TNF-alpha alleles with extended haplotypes and the significant increase of heterozygotes in patients could lead to some explanation of the DR3 association with a variety of autoimmune diseases particularly IDDM.

Diabetes Mellitus, Type 1↗
PubMed1989

Microbial metabolism of quinoline and related compounds. II. Degradation of quinoline by Pseudomonas fluorescens 3, Pseudomonas putida 86 and Rhodococcus spec. B1.

Quinoline catabolism was investigated with different bacterial strains, able to use quinoline as sole source of carbon, nitrogen and energy. Some degradation products of quinoline were isolated from the culture fluids and identified. With Pseudomonas fluorescens and Pseudomonas putida we found 2-oxo-1,2-dihydroquinoline, 8-hydroxy-2-oxo-1,2-dihydroquinoline, 8-hydroxycoumarin and 2,3-dihydroxyphenylpropionic acid as intermediates. With a Rhodococcus strain 2-oxo-1,2-dihydroquinoline, 6-hydroxy-2-oxo-1,2-dihydroquinoline, a red meta-cleavage product and a blue fluorescent compound were isolated. The red compound was identified as 5-hydroxy-6-(3-carboxy-3-oxopropenyl)-1H-2-pyridone. From this the blue fluorescent azacoumarin 2H-pyrano-2-one-[3,2b]-5H-6-pyridone is formed by chemical decomposition. Therefore it can be considered a by-product of quinoline-degradation in Rhodococcus spec. With the present results two different degradation pathways for quinoline in different microorganisms are proposed.

Chemical Phenomena↗
PubMed1988

Voltage-dependent pore activity of the peptide alamethicin correlated with incorporation in the membrane: salt and cholesterol effects.

Strong aggregation of incorporated alamethicin in the bilayer of lipid vesicles has been observed spectroscopically at aqueous peptide concentrations above a critical value c*. On the other hand, in conventional gating studies with planar lipid films, the onset of conducting pore formation can be characterized by a threshold voltage V.. We present experimental evidence of a direct correspondence between the effects on c* and V. when these parameters are modulated by adding NaCl (to the aqueous medium) or cholesterol (to the lipid moiety). A quantitative analysis supports the idea that the measured aggregation actually results in pore formation, the voltage-dependence being due to an electric field effect on the partition equilibrium of the peptide between the aqueous and the lipid phases.

Alamethicin↗
PubMed1988

Predicting insulin-dependent diabetes.

719 first-degree relatives of diabetic children were followed up to assess the value of HLA haplotype sharing and of islet-cell antibodies (ICA) for prediction of insulin-dependent diabetes (IDDM). Within a maximum of 8 years' follow-up (3384 patient-years of observation) 16 unaffected relatives (5 parents and 11 siblings) became insulin dependent. The cumulative risk of becoming insulin dependent by age 25 was 16% for siblings sharing two HLA haplotypes with the proband, 9% for those sharing one haplotype, and zero for those sharing none. 13 of 24 (54%) subjects positive for complement-fixing ICA on three or more occasions became insulin dependent, as against 1 of 30 (3%) with noncomplement-fixing ICA alone and 2 of 665 (0.3%) ICA-negative subjects; by life-table analysis the risks after 8 years of known ICA status are 76%, 3%, and 0.6%, respectively. In terms of total time at risk ICA-positive family members had a relative risk of 75.2 compared with ICA-negative individuals. With positivity for complement-fixing ICA the relative risk was 188.5.

Actuarial Analysis↗
PubMed1988

Electric field effects on the virus M13, detected by electro-optical measurements.

We have carried out transient electric birefringence experiments with M13 in aqueous solution. A normal effect with a negative sign is superimposed by anomalous positive effects. These prevail more and more upon raising the field strength. They apparently reflect electrically induced structural transitions. The threshold field strength decreases when buffer and/or electrolyte is removed.

Birefringence↗
PubMed1988

Acute midbrain syndrome as an adverse reaction to tetanus immunization.

An acute midbrain syndrome III/IV developed twice after tetanus immunization. The occurrence of nearly identical episodes was remarkable, as well as the relatively rapid return to normal consciousness and neurological status after deep coma. Special emphasis is placed upon the chronological relationship of the coma to the immunization and upon immunological tests (tetanus antibody titres) performed to confirm the diagnosis.

Adult↗
PubMed1988

[Increase in intracranial pressure in monitoring brain stem auditory evoked potentials using headphones].

Ten measurements of intracranial pressure (ICP) (ventricular n = 5, epidural n = 3) in 8 patients (3 after aneurysm surgery, 5 with head trauma) were performed before and after application of conventional headphones for stimulating brainstem auditory evoked potentials (BAEP). The effects of miniature earphones and sound tubes on ICP were also studied. In 7 of 10 measurements after application of headphones a reversible increase of ICP (mean 26 +/- 19% in patients with ICP greater than 10 mmHg was recorded; in 3 patients (ICP less than or equal to 10 mgHg) no changes of ICP were seen. Using miniature earphones and sound tubes no increase of ICP was noted in any patient, and hence these can be recommended for stimulating BAEP in case of increased ICP.

Acoustic Stimulation↗
PubMed1988

Visual contrast enhancement with a patterned overlay.

A dot-screen pattern was devised and superimposed on computed tomography images to improve contrast at a viewbox. The phenomenon is believed to be probably related to lateral inhibition. To evaluate its usefulness, the device was used on 12 images (eight showed metastatic liver lesions, and four were normal); each image was viewed without the device by ten observers. Three control images were viewed a second time without the device. The remaining nine images were viewed a second time with the device. The overlay improved diagnostic performance in nine observers. Sensitivity improved by 12%, and confidence in true-positive findings increased by 41.6%. Forty-five percent of false-negative findings were converted to true positive with the use of the overlay.

Humans↗
PubMed1988

[Multimodal evoked potentials and heart rate variability in comatose patients. 2. Visual evoked potentials and computed tomographic findings].

Visual evoked potentials (VEPs) were examined as an integrated parameter in a multimodal EP study of brain bioelectrical activity in 33 comatose patients (Glasgow Coma Score 3-6) after craniocerebral trauma. Recordings were performed not only from the occipital (01-02) but also from the central (Cz-C3, Cz-A1, Cz-C4) and frontal (F3-F4) areas. The results show an attenuation of the vertex VEP (SNR 3.2 +/- 1.7) and an increase in the occipital VEP (SNR 4.8 +/- 2.3) as compared to the control group (SNR vertex 7.0 +/- 3.0/SNR occipital 3.9 +/- 2.0). In addition, 16 of the comatose patients showed a very considerable loss of the normally polyphasic character of the occipital VEP in favour of a potential that looked almost monophasic; this was either left or right dominant, and was recorded as a negative or positive potential, respectively, in bipolar recording (01-02). Comparison of the electrophysiological and computer tomography findings showed a laterally correlated change in the occipital VEP: contralateral to the injured hemisphere, the VEP was dominant, ipsilateral it was reduced or extinguished.

Adolescent↗
PubMed1988

[Assessing the function of patients with consciousness disorders using evoked potentials].

Multimodal evoked potentials (long latency somatosensory and visual evoked potentials, brainstem auditory evoked potentials) were performed in comatose patients. For the long-latency EP-components a signal-to-noise ratio (SNR) was calculated (SNR is defined as ratio of the largest EP-peak-to-peak amplitude and the mean amplitude of a period prior to the stimulation). An unmeasurable or questionable EP was defined when SNR less than 2.6. The highest correlation (r = 0.72) was found between the clinical state, represented by Glasgow Coma Score, and the SEP. The long latency SEPs appeared as a sensitive parameter in postacute states of brain disorders. The vertex VEP had a similar correlation (r = 0.66) to the clinical state; the occipital VEP showed no correlation. Emergency from coma and recovery was accompanied by an increasing spread of the VEP over the whole scalp. The use of auditory brainstem evoked potentials in coma and brain death ist demonstrated; applications and problems are discussed.

Brain↗
PubMed1987

Alamethicin incorporation in lipid bilayers: a thermodynamic study.

Interaction of the peptide antibiotic alamethicin with phospholipid vesicles has been monitored by changes in its circular dichroic and fluorescent properties. The data are consistent with an incorporation of the peptide in the lipid bilayer. Aggregation of alamethicin in the membrane phase is evident from a characteristic concentration dependence of the incorporation, reflecting the existence of a critical concentration. The data can be fully understood in terms of a theoretical approach that includes aggregation and thermodynamic nonideality. Thermodynamic parameters of the peptide-lipid interaction have been evaluated under a variety of conditions of temperature, ionic strength, and lipid type (saturated and unsaturated fatty acid chains). From the results obtained in this study, one can extrapolate to the incorporation behavior of alamethicin at low concentrations, as they are typical for measurements of conductance across planar lipid films. This leads to a simple explanation of the voltage-gating mechanism of alamethicin in a straightforward way.

Alamethicin↗
PubMed1987

Basic kinetics of binding and incorporation with supramolecular aggregates.

Supramolecular particles of spherical shape (such as micelles, vesicles, etc.) are imagined to interact with small (bio)molecules so that either binding or incorporation occurs. This is generally described as an association process whose rate is determined by appropriate diffusion and actual transformation steps. Along these lines pertinent expressions for the phenomenological rate constants are given. In addition, an upper bound for the rate of incorporation has been derived. The results are discussed with respect to their usefulness in practice.

Kinetics↗