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H Lehmann

Publications and source records attributed to H Lehmann.

At least 19 recordsLinked to original sources
PubMed1992

Comparative study on the thermostability of collagen I of skin and bone: influence of posttranslational hydroxylation of prolyl and lysyl residues.

Pepsin-solubilized collagen I from skin and bone was analyzed with regard to its thermal stability as a triple helical molecule in solution and after in vitro fibril formation. Collagen I from human control bone was compared with samples showing deficiencies or surplus in the degree of hydroxylation of lysine. The helix to coil transitions were studied by circular-dichroism measurements and limited trypsin digestion. Melting of fibrils from standardized in vitro self-assembly was investigated turbidimetrically. Human control bone collagen I has a maximum transition rate (Tm) at 43.3 degrees C in 0.05% acetic acid. This is 1.9 degrees C above control skin (Tm = 41.4 degrees C), most likely, due to a higher degree of prolyl hydroxylation--0.48 in bone vs. 0.41 in skin collagen I. Lysyl overhydroxylation of human and mouse bone collagen I appears to reduce the Tm slightly (approximately 1 degree C). Underhydroxylated bone collagen has a Tm which is 2 degrees C below control. Melting temperatures of in vitro formed fibrils are an indication for higher thermostability in parallel with an increase of lysyl hydroxylation. Accordingly, the melting temperature of such fibrils from human control skin, 49.3 degrees C, exceeds control bone by 1.4 degrees C. The degree of lysyl hydroxylation in these samples is 0.14 and 0.10, respectively. Further underhydroxylation (0.06) reduced it down to 45.4 degrees C, while extensive overhydroxylation did not continue to increase the thermal stability of fibrils.

Adult↗
PubMed1992

On central muscle relaxants, strychnine-insensitive glycine receptors and two old drugs: zoxazolamine and HA-966.

Zoxazolamine is in the centrally-acting muscle relaxant class of drugs, which reportedly act by decreasing CNS interneuronal activity. These drugs, but not anxiolytics, decrease dopaminergic turnover and induce a pacemaker-like discharge pattern in dopaminergic neurons. A mechanism for these effects was not found in previous reports. We observed that (+)-HA-966, an inhibitor of the glycine modulatory site on the NMDA receptor, has a similar effect on dopaminergic impulse flow, which suggested that this may be the possible site of action of classical muscle relaxants. However, a competitive antagonist of NMDA receptors, NPC-12626, had little effect on impulse flow. Binding of 20 nM [3H]-glycine to cortical synaptosomal membranes was inhibited by (+)-HA-966, IC50 = 3.16 microM, but only poorly by zoxazolamine, IC50 V 474 microM, and chlorzoxazone, a related drug, caused no displacement. The drugs were then tested for protection from amphetamine neurotoxicity. Neither 50 mg/kg zoxazolamine nor 30 mg/kg (+)-HA-966 prevented (+)-amphetamine (0.1 mmol/kg plus 10 mg/kg iprindole) depletion of striatal dopamine (DA), but 3.0 mg/kg of MK-801, a non-competitive NMDA receptor antagonist, did protect DA content. Since baclofen induces a regular firing rate in DA neurons, zoxazolamine and (+)-HA-966 were tested for displacement of 10 nM [3H]-1-baclofen from cortical synaptosomal GABAb receptors, but were ineffective. Thus, the effects of these muscle relaxants on DA neurons are mediated by a mechanism other than strychnine-insensitive glycine or GABAb receptors.

Amphetamine↗
PubMed1992

1 alpha-Hydroxycholecalciferol adsorption to peritoneal dialysis bags: influence of time, glucose concentration, temperature, and albumin.

The present study examines the adsorptive phenomenon of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) to peritoneal dialysis bags. One minute after injection of 1 alpha-OHD3 into the dialysis bags, a significant adsorption to the bags was observed in experiments where albumin was not added. A higher temperature (37 degrees versus 23 degrees C) in bags containing 13.6 mg glucose/ml resulted in less adsorption (P < 0.05). Adding albumin to bags at 37 degrees C with a glucose concentration of 13.6 mg/ml, reduced the adsorptive phenomenon significantly (P < 0.01). Bags tested at 37 degrees C with a glucose concentration of 38.6 mg/ml resulted in a significantly higher 1 alpha-OHD3 adsorption than bags containing 13.6 mg glucose/ml (P < 0.01). It is concluded that adsorption of 1 alpha-OHD3 to dialysis bags is affected by time, albumin, temperature and glucose concentrations. Substantial amounts of 1 alpha-OHD3 is retained by the peritoneal dialysis system when albumin is not added.

Adsorption↗
PubMed1992

(+-)-1-hydroxy-3-aminopyrrolidone-2 (HA-966) inhibits the activity of substantia nigra dopamine neurons through a non-N-methyl-D-aspartate receptor-mediated mechanism.

(+-)-1-hydroxy-3-aminopyrrolidone-2 [(+/-)-HA-966] is known to cause a rapid and selective increase in striatal dopamine (DA) levels--an effect that has been attributed to the compound's presumed ability to block the spontaneous electrical activity of nigrostriatal DA neurons. In the present series of experiments, extracellular single unit recording techniques were used to explore this premise in the chloral hydrate-anesthetized rat and to compare the pharmacological effects of the racemic form of HA-966 with its resolved enantiomers. Systemic administration of (+/-)-HA-966 produced a dose-dependent inhibition in the firing rate of DA neurons in the zona compacta of the substantia nigra. The highest dose tested (40 mg/kg i.v.) completely inhibited the spontaneous activity of all cells tested. Pretreatment with naloxone (5 or 10 mg/kg i.v.) reduced the initial rate of decline in firing rate and the duration of inhibition but did not prevent a single dose of 40 mg/kg of (+/-)-HA-966 from totally inhibiting DA cell impulse flow. Systemic administration of the (-)-enantiomer of HA-966 (30 mg/kg i.v.) inhibited neuronal activity in a manner analogous to a single injection of 40 mg/kg of (+/-)-HA-966. Comparable doses of the (+)-enantiomer failed to affect significantly the firing rate of substantia nigra DA neurons but suppressed bursting activity and "normalized" neuronal discharge pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

In vitro production of anti-neutrophilocyte-cytoplasm-antibodies (ANCA) by Epstein-Barr virus-transformed B-cell lines in Wegener's granulomatosis.

The frequent detection of anti-neutrophilocyte-cytoplasm-antibodies (ANCA) in patients with Wegener's granulomatosis (WG) led to the supposition that this disease might be of autoimmune nature. For some authors assume that Epstein-Barr virus (EBV) infection of human B-lymphocytes besides polyclonal activation could reveal the cryptic immune status against different autoantigens in patients with autoimmune diseases we investigated EBV-transformed B-lymphocytes from patients with Sjögren's syndrome, mixed connective tissue disease, WG and healthy blood donors. Two stable B-cell lines (Ho3, We1) could be established. Inhibition experiments showed that antibodies produced by transformed B-lymphocytes and serum ANCA (C-ANCA type) of 10 WG patients recognized the identical antigen. Stimulation of one clone (Ho3) with interleukin 6 (IL-6) led to a switch from IgM to IgG production. Antibodies produced by this clone also stained glomeruli of human frozen kidney sections. Western blot analysis using immunoaffinity purified antigen prepared from human granulocytes revealed a reaction with a protein of approx. 29 kD MW. Our data underscore some new aspects concerning the direct pathogenicity of C-ANCA confirming the hypothesis that the autoimmune B-cell repertoire in WG not only reflects a polyclonal B-cell activation but is shaped by antigen driven responses.

Aged↗
PubMed1991

[Technical indications and results of totally implantable catheter systems].

The development of the total implantable catheters has produced a lot of benefits, specially in oncological patients, who save venose punctions for blood controls and for administration of cytostatics. Important conditions for the success of the catheters are to avoid unnecessary manuvres during the surgical act and the postoperative care. In the University Hospital of Münster 68 children have been treated between 1984 and 1988 with this system. The implantation was mostly performed in oncological patients but also in patients who needed a total parenteral nutrition. With optical and electronic microscope studies has been observed that in the inside part of the Port and the catheter, deposits with different characteristics have been found. These deposits could be divided in four groups depending on the structure.

Catheters, Indwelling↗
PubMed1990

A critical crosslink region in human-bone-derived collagen type I. Specific cleavage site at residue Leu95.

Collagen was extracted from human adult bone by limited pepsin digestion and collagen types were purified by consecutive salt precipitation first under neutral and then under acid conditions. In SDS/PAGE, all collagen type I preparations showed a protein band [alpha 1s(I)] migrating between alpha 1(I) and alpha 2(I) as well as a band [alpha 2s(I)] migrating in front of alpha 2(I). The collagenous nature of the pepsin-stable alpha 1s(I) protein was clearly demonstrated by digestion with human-leucocyte-derived collagenase, immunoblotting with antibodies against collagen type I and amino acid analysis. Partial amino acid sequencing of alpha 1(I) and alpha 1s(I) identified alpha 1s(I) as a shortened alpha 1(I) chain due to a specific cleavage site between residues Leu95 and Asp96 which is in close vicinity to the hydroxylysine-derived crosslink at position 87. In circular dichroism, the proportion of thermally labile collagen molecules was proportional to the amount of shortened alpha 1(I) and alpha 2(I) chains, respectively. The melting temperature was found to be 36 +/- 0.5 degrees C as judged from circular dichroism and susceptibility to proteolysis. Our data provide clear evidence that a shortened alpha 1-derived collagen chain can be extracted from human adult bone whereas it is hardly found in human skin. The unique cleavage site might provide important information about the collagen I molecule embedded in the calcified matrix of human bone.

Adult↗
PubMed1989

Herpesvirus in harbour seals (Phoca vitulina): isolation, partial characterization and distribution.

From post-mortem material (liver and lung) and leucocytes of four (3.6%) out of 112 examined harbour seals during the seal epizootic in 1988 six cytopathogenic viral isolates were obtained which were provisionally classified as herpes-like viruses. Results of physico-chemical and electron microscopic investigations suggested their relationship to the herpesvirus family. Serological examinations were carried out with sera from wildlife as well as captive animals using herpesvirus isolates from four different seals. The neutralization tests revealed as only moderate distribution of seropositive reagents up to 53% of the wildlife seal population. Amongst the seals in the orphanage of Norddeich a very small number of seropositive animals was found. The results obtained indicated a minor role of herpesviruses as primary cause of seal mortality in the North Sea during the 1988 season.

Animals↗
PubMed1985

A critical comparison of the freehand razor-blade dissection method according to Wilson with an in situ sectioning method for rat fetuses.

Two methods of dissecting rat fetuses are compared: the generally well-known freehand razor-blade dissection method according to Wilson and an in situ sectioning method (ISM). For this purpose the substance EGYT 1978 was used, which induces--inter alia--cardiovascular anomalies. Thirty-nine gravid rats were given either the test drug (EGYT 1978, 400 mg/kg body weight) or the vehicle orally from the 6th to the 15th day of gestation. The fetuses were assigned randomly to either dissection group. Both methods of examination revealed approximately the same number of anomalies per organ system. A comparison of the types of anomaly found showed, however, relevant differences in the nature of the changes revealed by the two methods. The in situ sectioning method was clearly superior to the freehand razor-blade dissection method for the detection of discrete anomalies of the cardiovascular system. We therefore recommend the in situ sectioning method as the method of choice for examining small fetuses from teratological experiments.

Animals↗