Biomedical subjects
Publications and source records attributed to G Klose.
Videoendoscopy-assisted saphena occlusion (VASO) is an minimally invasive technique for the treatment of varicosis with crossectomy, dissection of perforating veins and occlusion of the saphena by endoscopic control. The advantages are lower level of pain, remobilisation without problems, and fewer complications of wound healing. Early results correspond to stripping.
Mixed aqueous dispersions containing palmitoyloleoylphosphatidylcholine and oligo(ethylene oxide) dodecyl ethers C12EOn with n = 2-8 have been investigated. The aggregates composition has been determined as a function of the aqueous detergent concentration using Laurdan fluorescence spectroscopy. The partition of the detergent between the membranes and the aqueous phase has been analyzed on the basis of the regular solution model. Solubilization has been analyzed in terms of the limiting detergent fraction in the membrane, the minimal detergent fraction in micelles and the critical aqueous detergent concentration using thermodynamical coexistence conditions for the aqueous, bilayer and micellar pseudo-phases. A thermodynamic criterion for solubilization is presented. The standard chemical potential differences of the transfer of the detergents from water to the bilayer have been found to follow the empirical relation delta u o(n = 2-8) = -37.6 + 0.9 n kJ/mol. Thus, a similar conformation and localization of the oxyethylene units within the membrane are suggested.
The dynamic properties of water in phosphatidylcholine lipid/water dispersions have been studied, applying a combination of 2H-NMR techniques (quadrupole splitting and spin-lattice relaxation time) and self-diffusion measurements using pulsed filed gradient (PFG) 1H-NMR. The hydration properties of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine) were compared with those of DOPC (1,2-dioleoyl-sn-glycero-3-phosphatidylcholine) and EYL (egg yolk phosphatidylcholine (lecithin)). A model is presented that assumes an exponentially decaying influence of the bilayer surface on water dynamics as well as on water orientation with increasing hydration. This assumption is based on an exponentially decaying hydration potential which results from direct lipid-water and water-water interactions. The model describes successfully the experimental data for a large water concentration range, especially at low hydration, where other models failed. With the exception of a small fraction of water which is significantly influenced by the surface in slowing down the mobility, the interbilayer water has isotropic, free water characteristics in terms of correlation times and molecular order. Hydration properties of POPC are comparable with those of EYL but differ from DOPC. At very low water content the correlation times of headgroup segmental reorientation and water are similar, indicating a strong coupling of this water to the lipid lattice. The hydration properties of the three lipids studied are explained in terms of slightly different headgroup conformations due to different lateral packing of the molecules by their fatty acid chain composition.
The continuous decrease of the quadrupolar splitting of deuterated water interacting with phosphocholine lipid bilayers with growing water concentration is analyzed as a function of the water activity. From the apparent linear dependence on water activity a measure for hydration forces is obtained. The forces calculated are in the range of published data using sorption isotherms and osmotic stress technique in combination with SAXS. A simple interaction potential which includes orientational order of water adsorbed on surfaces gives a physical base for these findings. Therefore, deuterium NMR may become a powerful tool for hydration force analysis complementing well-known methods.
The reported case of an unsuccessful treatment with acyclovir of herpes simplex virus hepatitis in a young patient, during pregnancy, demonstrates the necessity of an early diagnosis with the consequence of an early therapy. If serum antibodies are not evident, the presumptive diagnosis is based upon the histological demonstration of inclusion bodies in liver biopsy specimens. With the DNA-in-situ hybridisation technique, differentiation of the type of virus infection is possible in a short time. Hence, consideration should be taken that a biopsy of the liver should be done before the coagulation system breaks down due to hepatic necrosis. The risk of the liver biopsy seems to be low compared with the high morbidity and mortality of mother and child in systemic herpes simplex virus hepatitis.
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Mixtures of egg phosphatidylcholine and phosphonic acid diethyl or dibutyl esters of the general type RP(O)(OR')2 with R = hexane or dodecane were studied at room temperature in the fluid lamellar state by X-ray and by neutron diffraction. Generally a molar ratio of lipid and ester of 1:0.5 was used. Additionally an equimolar lipid/ester mixture of hexane phosphonic acid diethyl ester was studied. Depending on the ester used and its concentration a single L alpha-phase was observed above a certain water content which changes to an L alpha + water two phase system at high water concentration. Despite the large amounts of the amphiphilic ester molecules incorporated in the membrane and their high molecular asymmetry, the mixtures qualitatively show the typical hydration and swelling behaviour of non-charged lipid membranes. However, the incorporation of the esters induces a higher hydration capacity, a lateral extension and a decrease in membrane thickness. The position of the ester molecules and their orientation in the membrane were determined by neutron diffraction using partially deuterated esters. The esters were found to be located with their phosphonic moiety near or in the lipid/water interface. The lamellar structure contradicts this location of the cone-shaped ester molecules which should increase the tendency to form hexagonal structures. However, the experimental findings can be understood if one considers a partial interdigitation of the last hydrocarbon groups of the lipid chains accompanied by a larger disorder in the hydrophobic centre of the membrane. In the case of hexane phosphonic acid dibutyl ester, a vertical translocation of the ester takes place below a certain water content where it is distributed between two locations at the lipid water interface and the centre of the membrane.
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The effect of low concentrations of nonionic detergents with different critical micelle concentrations such as Triton X-100, Brij 35 and octylglucoside on rabbit liver microsomes is studied by means of 31P-NMR, 1H-NMR, dynamic light scattering and functional investigations. Hexane phosphonic acid diethyl ester was used as a phosphorus membrane probe molecule to monitor the interaction of detergent molecules with microsomal phospholipids by 31P-NMR. This method is more sensitive than 31P-NMR of phospholipids alone and permitted the estimation of the maximum number of detergent molecules which can be incorporated in microsomes without the formation of mixed micelles outside the membrane. These membrane saturation concentrations were determined to be 0.07 (Brij 35), 0.1 (Triton X-100) and 0.4 (octylglucoside) (molar ratio of detergent/total phospholipids). Above these detergent concentrations, mixed micelles consisting of detergent and membrane constituents are formed, coexisting with the microsomes up to the membrane solubilization concentration. The results indicate a dependence of the membrane saturation concentration on the critical micelle concentration of the detergent and a preferential removal of phosphatidylcholine over phosphatidylethanolamine from the microsomes by all detergents studied.
After a scraping injury to the skin a 47-year-old man developed a generalized Nocardia brasiliensis infection with cutaneous, pulmonary and cerebral dissemination. There was no predisposing underlying illness. High-dosage cotrimoxazol and short-term intrathecal and systemic gentamycin administration achieved extensive healing. This form of treatment would thus seem capable of reversing the otherwise poor prognosis of generalized N. brasiliensis infection.
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Tumor growth in a 72-year-old male patient with malignant haemangiopericytoma in the left hemithorax could be followed radiologically for 4 years before symptoms of recurrent hypoglycaemia appeared. The endogenous insulin level in serum was maximally and serum IGF-1 and IGF-2 markedly reduced. An intravenous arginine load test showed a normal stimulation capacity of the pancreatic glucagon secretion but not that of insulin. After resection of the tumor, blood sugar metabolism was completely normalised. The insulin level, IGF-1 and IGF-2 in serum returned to normal.
By use of 31P-NMR, quasi-elastic light scattering and freeze-fracture electron microscopy it is shown that hexane phosphonic acid diethyl ester (PAE) is incorporated in hepatic microsomes without any alteration of the bilayer structure at two different sites. These findings proved that PAE can be used as molecular 31P-NMR probe in microsomes to get information about lipid-protein interactions. Extensive studies on reconstituted liposomal systems which contained cytochrome P-450 and cytochrome P-450 reductase showed that both proteins influence the localization of incorporated PAE. The results indicate a specific interaction of phosphatidylethanolamine (PE) with cytochrome P-450 in microsomes.
Peripheral lymphocyte cells from patients suffering from Crohn's disease were analyzed for the expression of the "activation" antigens T9 and HLA-DR on their cell surface. It was found that high numbers of "activated" lymphocytes, the majority of which have proven to be T cells, could be detected in patients with active Crohn's disease, whereas in healthy controls and inactive disease only a small subfraction of lymphocytes was positive for these antigens. This difference was highly significant (p = 0.0001). Within the subpopulation of T9-positive cells the ratio between T4- and T8-positive cells is about 1.8 (compared with 2.0 in the total T-cell subset). All HLA-DR-positive, non-B and non-glass-adherent cells could be detected in the T9-positive cell fraction. The presence of T9 antigens was found to correlate with the grade of severity of the disease as assessed by a Crohn's disease activity index. The presence of high amounts of T cells exhibiting this antigen is not restricted to Crohn's disease but is thought to be of importance as a marker for the involvement of the immune system in other maladies as well. Nevertheless, the determination of T9 antigen is expected to provide objective data reflecting the severity of Crohn's disease.
Elevated numbers of peripheral T cells expressing the activation associated antigen T9 are found in patients with active Crohn's disease. Expression of T9 is found to be correlated to the activity of the disease. However the presence of activated peripheral T cells is not restricted to Crohn's disease, but could also be found in other maladies with a supposed involvement of the immune system, e.g. ulcerative colitis, sarcoidosis, connective tissue disease and after organ transplantation. Significant elevation of the number of activated T cells could not be detected in cases of viral or bacterial enteritis and coeliac disease. Analysing the subset of T9 positive T cells with regard to the expression of Fc alpha receptors, a significantly increased number of Fc alpha receptor positive cells, within the subset of T9 positive cells in the peripheral blood of patients with Crohn's disease and ulcerative colitis was found, which could not be demonstrated in the case of other diseases analysed in this study. Thus the T9+ Fc alpha receptor +T cell subset may be considered to be pathognomonic for inflammatory bowel diseases. Analysis of the regulatory properties of T9 positive cells, with regard to the immunoglobulin isotype secretion in a pokeweed mitogen stimulated autologeous B cell assay, suggests that peripheral T9 positive T cells are involved in the suppression of IgA synthesis or secretion.
The 81 MHz 31P-NMR spectra of isolated rabbit liver microsomes before and after trypsin treatment and of the total microsomal lipid extract were recorded in the 4-40 degrees C temperature range. In both treated and untreated microsomes at 4 degrees C most of the phospholipids gave rise to typical bilayer spectra whereas the lineshape of the latter in the 25-37 degrees C temperature range becomes narrower and more symmetrical. Quasi-elastic light scattering (QELS) measurements revealed that the microsomes maintain their size in the temperature region of the measurements. We interpret the lineshape changes for untreated microsomes above 25 degrees C as being determined by lateral diffusion. This is supported by lineshape calculations as a function of the lateral diffusion coefficient. The different spectral behavior of enzymatically active (untreated) and inactive (treated) microsomes suggests that the membrane proteins influence the lateral diffusion of the phospholipids.
A portacaval shunt was closed in a 30 year old female patient. Angiography showed a distinct decrease in diameter of the hepatic arteries during the first 6 months after surgery, and a lesser further decrease in the following time.
A 72-year-old man had had recurrent fever of undetermined cause, for which he had repeated periods in hospital. There were no specific organ-related symptoms. Conventional radiology of the vertebrae, tomography, CT scan and CT-guided needle biopsy finally revealed the presence of staphylococcal spondylitis of thoracic vertebrae 11 and 12 with bilateral paravertebral abscesses. Particularly valuable diagnostically was the CT scan with demonstration of bony destruction in the axial plane and of the paravertebral soft-tissue changes, as well as the use of CT-assisted puncture of the abscess. Asymptomatic spondylitis should be thought of as a possible cause of pyrexia of unknown origin.