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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

Stereochemical properties of the binding site of liver microsomal cytochrome P-450 as studied by substrate analogous spin labels.

For the characterization of the substrate binding site optical and EPR measurements with spin labelled substrates on solubilized and pure cytochrome P-450 were performed. Analogously to the unlabelled derivatives spin labelled n-alkylamines and isocyanides with different chain lengths are type II substrates. The Ks-values evaluated from optical (P-450 = 1.98 . 10(-6) M) and ESR (P-450 = 1.98 . 10(-4) M) measurements are very similar indicating no concentration dependences. Contrary to the unlabelled n-alkylamines the spin labelled compounds show an affinity almost independent of the chain lengths. The SL-substrates with a short distance between the functional group and the NO-group bound to P-450 induce pronounced changes of the ligand field of the heme iron and a large broadening of the signal of the immobilized nitroxide indicating intensive interactions between the unpaired electron of the nitroxide group and the paramagnetic heme iron. Elongation of the alkyl chains results in spectra of the Fe3+ complexes with only slight modification and a remained unbroadened signal of the immobilized nitroxide. The binding of the substrate through their functional groups together with a 1:1 stoichiometry of the P-450 SL-IC-complex give evidence for the same binding site in the near vicinity of the heme iron.

Animals

[The neural periphery in lichen planus lesions (author's transl)].

In 12 patients suffering from generalized Lichen planus (L.p.) the neural periphery of lesions was studied by modern histochemical and electron microscopical methods. In contrast to the investigations published until now on this subject no signs of neural hyperplasia in L.p. could be found. Only some nerves localized in the Lichen planus infiltrate exhibited morphological changes indicating increased neural de- and regeneration in this region. According to the results obtained the nerve changes in L.p. are caused by the typical inflammatory reaction found in this dermatosis. Therefore the neural theory of L.p. cannot be sustained on a histological basis.

Adolescent

Different types of benign nerve sheath tumors. Light microscopy, electron microscopy and autoradiography.

In a light-, electronmicroscopic and autoradiographic study different types of nerve sheath tumors were classified. Their cellular population was quantitatively evaluated in the electron microscope. In the neurinoma the predominant cell was found to be the Schwann cell, but in the different types of neurofibromata a variable content of connective tissue cells was noted. T-HE DIFFUSE NEUROFIBROMATA SHOWED A QUANTITATIVE CELLULAR COMPOSITION SIMILAR TO NORMAL PERIPHERAL NERVES. In the plexiform neurofibroma a large number of fibroblasts were present and in the argyrophilic neurofibroma high content of perineurial cells was found. In autoradiographic sections the tumors showed in general a low proliferation rate (L.i. 1-3.6%). In the argyrophilic neurofibrom a higher labelling index (9.5%) was found.

Adolescent

[Clinical, histological and electron microscopic findings in neurofibromatosis (Recklinghausen's disease) occurring in childhood (author's transl)].

A follow-up study was carried out of the clinical symptoms and the radiological and histological alterations in five cases of neurofibromatosis (Recklinghausen's disease) with onset during early childhood. The clinical manifestation of the disease was predominantly restricted to the face. In the histological ultrastructural investigation different types of neurofibroma were detected (plexiform neurofibroma, argyrophilic neurofibroma and diffuse neurofibrma). Preliminary results are presented on the basis of a correlation between the clinical findings and the histological types of neurofibroma with special reference to the demarcation of the tumours, recurrence following surgical removal and the prognosis as to the clinical course of the disease. Nevertheless, definite conclusions will be possible only by continuous observation of a larger number of patients by means of standardized clinical, radiological and histological methods of investigation.

Adolescent

Diminished content of enterochromaffin cells in the rectal mucosa of an infant.

This report deals with an extremely small number of enterochromaffin cells in the rectum of a newborn male. This finding occurred only in 200 biopsies. The correlations to connatal disturbances of the motility of the intestine in the newborn are discussed. The frequency of this alterations seems to be comparable with other disturbances of cells of the neural crest, as for example pigment anomalies. Although further biochemical investigations could not be carried out because of technical difficulties, the case seems to be worth publishing for theoretical and practical reasons and in view of the possibility of special treatment.

Chromaffin System

Morton's metatarsalgia. Light and electron microscopic observations and their relation to entrapment neuropathies.

The dissected plantar nerves of 105 patients with clinical symptoms of Morton's disease were examined under light and electron microscopy. Of the 105 cases, 75 showed characteristic neuronal lesions; in the others different pathologic substrates responsible for the clinical symptoms could be demonstrated. The nervous lesions are characterized by: 1. Thickening of the walls of the endoneurial vessels produced by multiple layers of basement membranes. 2. Edema and sclerosis of the endoneurium. In the electron microscope the endoneurium was filled by deposits of fibrils with a tubular substructure and a diameter of 100-110 A. 3. Thickening of the perineurium. 4. Degeneration of the nerve fibers without signs of wallerian degeneration or obvious reactive Schwann's cell hyperplasia. The possible pathogenetic mechanisms of Morton's disease and some clinical problems are discussed.

Adult

[Spectroscopic investigatons on the structural thermal stability of leucine aminopeptidase. ESR, CD and fluorescence studies].

The thermal behaviour of leucine aminopeptidase (LAP, EC: 3.4.11.1) from bovine eye lens has been investigated in the temperature region 20--70 degrees C by spin-labelling of SH-groups (ESR), by CD and by fluorescence of tryptophane residues. Enzymatic activity of LAP was compared with spectroscopic data in this temperature region. From 20-60 degrees C the structural parts (alpha, beta, random coil) estimated from CD spectra remain unchanged. Within 20-55 degrees C no irreversible exposure of tryptophane residues takes place. In both types of spin-labelled LAP the strong immobilizing environment of the label retains its highly ordered structure up to 55 degrees C. Reversible changes of mobility and polarity of the environment of the label induced by temperature within 20-50 degrees C do not reduce the enzymatic activity and are regarded as local loosening of ordered structure. At 65 degrees C strong precipitation occurs. From 55 degrees C to 65 degrees C tryptophane residues are irreversibly exposed. The highly ordered environment of the label is destroyed about 55 degrees C, and a considerable amount of spin label molecules is reduced at the NO group by exposed SH groups. The above mentioned local loosening of structure becomes irreversible at 60 degrees C. The environment of both labels dominating above 60 degrees C is highly mobile and strongly polar and represents an extensively unfolded conformation. Until 60 degrees C no essential disordering of protein structure leading to a decrease of enzymatic activity occurs. Above 60 degrees C a sharp breakdown of ordered structures takes place, which is accompanied by a strong diminution of enzymatic activity.

Animals

Adsorption of small molecules to bovine serum albumin studied by the spin-probe method.

A spin-probe technique is used for quantitative EPR studies of adsorption of small molecules on globular proteins, of the rigidity of their binding to the protein and of the polarity of the environment. In the case of bovine serum albumin it is shown that nitroxyl radical (2, 2, 6, 6-tetramethyl-4-oxy-1-oxyl-piperidine)-stearate (I) has an adsorption behaviour similar to that of the fatty acids, nitroxyl radical (2, 2,4, 4-tetramethyl-1, 2, 3, 4-tetrahydro-5, 6-benzo-gamma-carboline-3-oxyl) (II) to that of the tryptophan molecule. Radical I rotates relative to the protein molecule, while Radical II is rigidly bound to the protein.

Adsorption

[Finding of ganglion cells in the mucosa of the colon, sigmoid flexure, and rectum (author's transl)].

The ectopic position of the ganglion cells of Meissner's plexus in the basal and central portions of the mucosa in the colon descendens and sigmoid flexure, as they were found by Stöhr in humans, by Ohkubo in monkeys, and by Meier-Ruge in neuronal colon dysplasia, can be considered a relatively frequent finding. The present authors also observed the cells in human biopsy material. The same position in the rectal mucosa, frequently seen in Morbus Down, seems to be a rare occurrence. The clinical relevance of an ectopic position of ganglion cells is not yet known.

Adolescent

Spin-labeling studies of urea-treated leucine aminopeptidase.

1. Leucine aminopeptidase (EC 3-4-11-1) from bovine eye lens was spin-labeled at the most reactive thiol groups with 2,2,6,6-tetramethyl-4-[2-iodoacetamido]-piperidine-1-oxyl. 2. Electron spin resonance spectra show two spectral parts corresponding to two local conformational states in the environment of bound label. One state (A) exhibits a strong immobilizing effect on the mobility of the bound label whereas the other one (B) immobilizes weakly. Independently on the degree of labeling a ratio of A:B approximately 4:1 was estimated. In B a hydrophobic environment of label was observed. 3. Treatment of leucine aminopeptidase by 6.2 M urea leads to the following structural changes. a) An additional weakly immobilizing conformational state (B') with reduced hydrophobic interactions and increased mobility representing an unfolded conformational state appears. B' shows a time-dependent increase of its extent at the expense of B and A' (half conversion time about 0.5 h). The extent of this conformational change is larger, if the enzyme is additionally complexed with Mn2+. b) Mn2+ complexed with the protein is partly released producting hydrated Mn2+. c) After withdrawal of urea the observed conformational changes in leucine aminopeptidase are fully reversible, giving the initial ratio of A:B approximately 4:1 even after long incubation. 4. 6.2 M urea is not able to destroy the strongly immobilizing conformational state A completely.

Animals

[Catabolic processes in the rectal mucosa. Light and electron microscopic studies].

The phagocytosing activity of macrophages and fibrocytes of the lamina propria was examined by means of light and electron microscopy; the material had been obtained through 121 biopsies performed on patients ranging in age from 3 weeks to 43 years (113 taken from the rectum, 8 from the small intestine). The phagocytosing activity of the stroma has been known since the studies of v. Möllendorf, Clara, Patzelt, Maximov, Malatzkaya carried out on guinea pigs, rats, birds and a few human embryos. In recent years this problem has been raised again by some American authors. Our studies close the gap existing for the age group ranging from birth to the 16th year. It was demonstrated that the rate of this activity is much higher than hitherto assumed by Askar, Ekuan and Hill, Azzopardi and Evans. The authors discuss the reasons for these discrepancies in the finding, and the origin and composition of the substances ingested.

Adolescent