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Biomedical subjects

G Lassmann

Publications and source records attributed to G Lassmann.

At least 37 records · Page 2Linked to original sources

Intestinal neuronal degeneration in a patient with chronic idiopathic intestinal pseudoobstruction.

Neuropathological examination of the gut in a patient with chronic idiopathic intestinal pseudoobstruction and temporal lobe epilepsy showed a degeneration of Auerbach's and of Meissner's plexus. The extent of generative changes increased in an aboral to oral direction. Neuronal degeneration was characterized by ballooning of the cytoplasm of the ganglial cells, by a hyperargyrophilia, a shortening and dilation of cell processes, and a progressive fragmentation and loss of axons. In rectal biopsies, a PAS-positive granular material was detected in the cytoplasm of ballooned ganglial cells. A severe peripheral neuropathy with fiber degeneration in the posterior columns and axonal lesions within ventral nerve roots and a more recent fiber degeneration in the lateral columns corresponding to the picture of subacute combined degeneration of the spinal cord and a symmetrical Ammon's horn sclerosis was present. This case of progressive intestinal neuronal degeneration of unknown origin is a newly described condition leading to chronic idiopathic intestinal pseudoobstruction.

Adolescent↗

ESR studies of structure and kinetics of radicals from hydroxyurea. An antitumor drug directed against ribonucleotide reductase.

Hydroxyurea (HU) is a clinically applied antineoplastic drug, which quenches tyrosine radicals in the active site of ribonucleotide reductase (RR) and inhibits DNA synthesis in proliferating cells. Under oxidizing conditions (Cu2+ or H2O2) long-lived radicals from HU have been found by ESR. The structure of HU radicals was established to be: (formula; see text). The kinetics of formation and decay of HU radicals after reaction of HU with H2O2 is complex; it exhibits a lag-phase, a maximum, and a decay, all depending on the concentration of HU. Biological consequences of HU radicals for the inhibition of RR as well as their role in cytotoxic events during chemotherapy of cancer are discussed.

Antineoplastic Agents↗

Stability and reactivation of tyrosine radicals from ribonucleotide reductase in tumor cells studied by ESR.

Naturally occurring tyrosine radicals from the M2 subunit of ribonucleotide reductase (RR) have been recorded by ESR in proliferating ordinary Ehrlich-ascites (EA) tumor cells of mice. Tyrosine radicals are stable in EA cells at room temperature for 2 h. Up to 500 mW no microwave saturation occurs. The relatively high stability and non-saturation of tyrosine radicals in EA cells suggests a suitable protein conformation in the M2 subunit enabling a close contact between the tyrosine radical and the antiferromagnetic iron complex. This facilitates an ESR study of functionally essential tyrosine radicals of RR in EA cells at low temperature and recommends this cellular system for studying such processes as inhibition and activation, which change the content of tyrosine radicals of the proliferation-linked RR. Oxygen treatment of non-proliferating (quiescent) EA cells reactivates tyrosine radicals 2-3 fold as found in strongly proliferating cells. We conclude that in quiescent cells, suffering from a lack of oxygen due to their high density in the peritoneal cavity, a reactivation of tyrosine radicals occurs by oxidation of non-radical tyrosine residues of inactive M2 subunits.

Animals↗

Vascular dysplasia of arteries in neurocristopathies: a lesson for neurofibromatosis.

In a 15-year-old girl suffering from congenital constipation, megacolon combined with a 'Ranken neuroma' of the rectum and a short aganglionic segment of distal colon was observed. The specific vascular alterations in the region of the Ranken neuroma (which has previously been described in cases of von Recklinghausen neurofibromatosis) were studied, with an emphasis on immunohistochemical methods. The results suggest that the pericytes are the cells primarily involved in the distinctive alterations of the blood vessels. Respecting the similarities of the location and vascular alterations in the neurocristopathies, von Recklinghausen neurofibromatosis and Hirschsprung's disease, to those seen in vascular fibromuscular hyperplasia, the possible pathogenetic relationships of these kinds of vascular malformations are considered.

Adolescent↗

Megacolon in third-phase malrotation with delayed migration and degeneration of intramural ganglionic cells and nerves.

A woman of 36 was admitted to hospital because of griping abdominal pain which occurred especially during the night when turning in bed. She had a history of constipation and bloating since birth. Irrigoscopy revealed megacolon extending from the middle of the transverse colon to the rectum. A rectal biopsy excluded Hirschsprung's disease. When surgery was performed, megacolon combined with malrotation of the colon was found, only the ascending colon being attached to the abdominal wall. Hemicolectomy was performed. In the megacolon, a cropolith, the size of a foetal head, was found which along with malrotation of the large intestine had caused the woman's symptoms. The nerve supply of the ascending colon was normal but in the megacolon there was evidence of delayed migration of ganglion nerve cells and varying degrees of degeneration of ganglion nerve cells and intraganglionic nerve fibres. Malrotation of the colon associated with megacolon and delayed migration of ganglion nerve cells and degeneration of nerve elements has not been reported previously.

Adult↗

EPR spectroscopic analysis of binding sites of a cancerostatic agent on erythrocyte membranes.

A biologically highly active antitumor agent, chloroethyl-nitrosourea-piperidine-N-oxyl, was found to bind covalently to sulfhydryl groups of membrane proteins of erythrocytes. The agent penetrates the erythrocyte membrane very easily within three minutes. Mainly two different binding sites are distinguishable with rather high rotational mobility of the NO-moiety and high polarity of their environment. The lowered broadening of bound label suggests pocket-like binding sites with a limited accessibility for paramagnetic ions. Besides common concepts that antitumor agents often bind to DNA and inhibit cell proliferation, further targets on plasma membranes are taken into consideration for antitumor agents.

Alkylating Agents↗

Conformational alterations within the glycocalyx of erythrocyte membranes studied by spin labelling.

The structure of the glycocalyx of the membrane of human erythrocytes and spectrin-depleted vesicles was studied under various conditions by two spin-labelling approaches: covalently labelling sialic acid residues of the glycocalyx and incorporation of a charged hydrophobic spin probe, CAT 16, being sensitive to alterations on the membrane surface into the lipid phase. Although cell electrophoretic measurements which were performed, additionally, indicated an erection of the glycocalyx upon decreasing the ionic strength of the suspension medium a more restricted mobility of spin-labelled sialic acid residues was found, in this case probably due to electrostatic interactions. The enhanced mobility of the spin probe CAT 16 at low ionic strength as well as in the case of neuraminidase-treated cells could be caused by reduced steric and electrostatic interaction with glycoproteins and glycolipids. La3+ adsorption and virus attachment on the human erythrocyte membrane were accompanied with a reduced mobility of sugar headgroups of the surface coat. No indication of cluster formation or lateral segregation of glycophorin molecules was found upon virus binding. After denaturation of the spectrin cytoskeleton of intact erythrocytes, increased mobility of spin-labelled sialic acid residues was observed.

Electron Spin Resonance Spectroscopy↗

Structural alterations of the human erythrocyte membrane upon influenza virus attachment.

Molecular events on the human erythrocyte membrane subsequent to influence virus binding were investigated by electron spin resonance (ESR) measurements after spin labeling of the cell membrane at different positions. Virus binding affected the glycocalyx structure as well as the physical state of the cytoskeleton at the inner leaflet, but not the lipid phase. A lateral reorganization of spin-labeled glycophorin was not indicated after virus attachment.

Absorption↗

Ribonucleotide reductase in ascites tumour cells detected by electron paramagnetic resonance spectroscopy.

Tyrosine radicals localized in the M2 subunits of ribonucleotide reductase have been detected by electron paramagnetic resonance (EPR) in ordinary ascites tumour cells. The intensity of its doublet EPR spectrum is higher in rapidly proliferating cells. Hydroxyurea, a specific inhibitor of this enzyme, decreases the concentration of the tyrosine radical. Whereas in different ascites tumours the doublet EPR spectrum dominates at g = 2.004, in solid tumours another more intense EPR spectrum from nitrosyl-hemoproteins appears. In conclusion, EPR spectroscopy can be used to monitor the content and variations of active M2 subunits of ribonucleotide reductase in intact ascites tumour cells.

Animals↗

Spectroscopic characterization of vesicle formation on heated human erythrocytes and the influence of the antiviral agent amantadine.

EPR investigations on the vesiculation process of heated human erythrocytes were performed, using different fatty acid spin labels. Spectrin denaturation and vesiculation do not influence the fluidity of the lipid phase of the remaining membrane of human erythrocytes: Vesicles released differ in chemical composition as well as in the lipid fluidity of their membrane from the intact human erythrocyte membrane. A reduced cholesterol-to-phospholipid ratio and a depletion of spectrin was found. By changing the ionic concentration of the suspension medium an effect on membrane spectra and on vesicle release was established. The adamantane derivative amantadine causes fluidization of the human erythrocyte membrane and inhibits vesicle release. Based on these results, a model for the mechanism by which adamantane-like molecules could interact with membranes is proposed.

Amantadine↗

[Muscle spindles and sensory nerve endings in the urethral sphincter].

Neurohistological investigations of the external urethral sphincter in a 2-day-old female baby proved the up till now not verified existence of muscle spindles. These are rare in number, in the majority containing only one intrafusal fiber. Beside of the spindles encapsulated nerve endings, situated in the interstitial tissue and marginal parts of the muscle fascicles, were detected.

Afferent Pathways↗

[Afferent innervation of musculus sphincter ani externus of men].

Investigations of the existence and distribution of muscle spindles and tendon organs in the human voluntary anal sphincter muscle in 53 cases of autopsy material from both female and male persons (age: 27th week of gestation to 81 years) brought forward the following results: Similar to animals, muscle spindles are formed in the last trimenon of gestation. They are more numerous as has been expected hitherto and there are different types with a different content of intrafusal fibers. Lamellar corpuscular organs are situated around the ending of the muscle fibers in the anal skin. In our opinion they are to substitute muscle tendon organs which could not be detected.

Adolescent↗

The nerve response after autotransplantation of the rabbit ear.

Neurohistologic investigations on 16 autotransplants of the rabbit ear ranging from 3 weeks to 18 months after replantation are described. This study investigated degeneration and regeneration of the adrenergic nerves of the vascular system and the afferent endings in hairy skin. Histochemical techniques, including hematoxylin-eosin staining by cholinesterase and glyoxylic acid fluorescence, and impregnation techniques with silver and osmium-zinc iodide were used. Central nerve reinnervation was started as early as 3 weeks after autotransplantation and usually was completed after 8 weeks. Spotty small areas of incomplete reinnervation could be found in the skin adnexa (hairs) even after 18 months. After transplantation the regeneration nerves were not attached to the vascular wall and were not incorporated in the Schwann cells of the distal parts of the transected and repaired vessels. The newly formed adrenergic nerve plexus was less dense than the normal one. Areas of patchy reinnervation and denervation were observed in peripheral vessels after 18 months. The defects in the restoration of the adrenergic vascular plexus similar to insufficient afferent reinnervation of skin and vessels may be responsible for the cold intolerance seen clinically and experimentally.

Animals↗

[Functional and morphologic studies on the reinnervation of the replanted rabbit external ear].

Disturbances observed int he thermoregulation of replanted extremities were the stimulus for this experimental study. We chose the auricular conchae of rabbits as an experimental model, as these show--as do the fingers--innervation with the sympathic nervous system and fulfil thermoregulatoric functions. Twenty-five of thirty auricular conchae of rabbits took completely after amputation and replantation. Blood flow measurements with 133 Xenon, thermographic and histologic examinations were performed. Thermography showed dysfunction with temperature provocation even one year after replantation. Histological examinations revealed partly deficient reinnervation in vessels and also in cutaneous appendages.

Animals↗

Effect of poly(ethylene glycol) on the polarity of aqueous solutions and on the structure of vesicle membranes.

The partitioning of TEMPO into phosphatidylcholine vesicle membranes is reduced upon addition of poly(ethylene glycol). This is caused by reduced polarity of the aqueous phase as well as decreased membrane fluidity in the presence of poly(ethylene glycol). The isotropic hyperfine splitting of TEMPO in aqueous poly(ethylene glycol) solutions was used as a measure of solvent polarity. The alterations of the membrane fluidity were detected by means of two different fatty acid spin labels. The influences of physicochemical properties of an aqueous poly(ethylene glycol) phase on the membrane structure of cells and vesicles are discussed in the light of membrane fusion.

Cyclic N-Oxides↗

Influence of polyethylene glycol on the structure of the erythrocyte membrane: an ESR study.

Using a fatty acid spin label (I (10, 3)) it was found that the membrane fluidity of intact human erythrocytes is not influenced by polyethylene glycol (PEG) up to a concentration of 10 wt%. On the contrary a drastic effect of PEG on the spectrum of maleimide spin labeled membrane proteins of erythrocyte ghosts were detected. It is suggested that aggregation and/or conformational changes of membrane proteins were induced by PEG.

Blood Proteins↗

Analysis of paramagnetic intermediates at the reaction of hemoglobin with nitrite using EPR.

The autocatalytic oxidation of hemoglobin by nitrite was analysed. It was shown that the obtained paramagnetic species have a strong temperature dependence. The time of annihilation of these species decreases about 4 times in the temperature region between 10 degrees C and 30 degrees C, whereas the time of formation decreases only 1.7 times. These data explain the strange temperature dependence of the formation of methemoglobin by nitrite and support the assumption that the short-lived radical is localized on the hemoglobin molecule.

Adult↗

Structural transitions of the erythrocyte membrane: an ESR approach.

The effect of temperature and ionic strength on the ESR spectrum of the fatty acid spin label I (10,3) in membranes of freshly drawn human red blood cells has been investigated. The results suggest that the microviscosity of the membrane is not strongly influenced by the ionic strength. Discontinuities at various temperatures could be observed, which disappear after cholesterol treatment. The possible role of membrane lipids and proteins on the thermotropic membrane behaviour observed is discussed. It is assumed that the spectra are averaged signals from different regions of the membrane.

Blood Sedimentation↗