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Biomedical subjects

P Heinrich

Publications and source records attributed to P Heinrich.

At least 19 recordsLinked to original sources
PubMed1995

Human ciliary neurotrophic factor: a structure-function analysis.

Ciliary neurotrophic factor (CNTF) promotes survival in vitro and in vivo of several neuronal cell types including sensory and motor neurons. The primary structure of CNTF suggests it to be a cytosolic protein with strong similarity to the alpha-helical cytokine family which is characterized by a bundle of four anti-parallel helices. CNTF exerts its activity via complexation with CNTF receptor (CNTF-R). This complex consists of a CNTF-binding protein (CNTF-R) and two proteins important for signal transduction [gp130 and leukaemia inhibitory factor receptor (LIF-R)]. We have shortened the cDNA coding for CNTF at both the 5' and the 3' end and expressed the truncated proteins in bacteria. Biological activities of the protein preparations were determined by their ability to induce proliferation of BAF/3 cells that were stably transfected with CNTF-R, gp130 and LIF-R cDNAs. CNTF proteins with 14 amino acid residues removed from the N-terminus were biologically active whereas the removal of 23 amino acids resulted in an inactive protein. In addition, 18 amino acid residues could be removed from the C-terminus of the CNTF protein without apparent loss of bioactivity, but further truncation at the C-terminus yielded biologically inactive proteins. The introduction of two point mutations into the CNTF protein at a site that presumably interacts with one of the two signal-transducing proteins resulted in a CNTF mutant with no measurable bioactivity. In addition, a model of the three-dimensional structure of human CNTF was constructed using the recently established structural co-ordinates of the related cytokine, granulocyte colony-stimulating factor. CD spectra of CNTF together with our mutational analysis and our three-dimensional model fully support the view that CNTF belongs to the family of alpha-helical cytokines. It is expected that our results will facilitate the rational design of CNTF mutants with agonistic or antagonistic properties.

Amino Acid Sequence↗
PubMed1995

A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6.

The protein tyrosine kinases JAK1, JAK2 and Tyk2 and STATs (signal transducers and activators of transcription) 1 and 3 are activated in response to interleukin-6 (IL-6) in human fibrosarcoma cells. In mutant cells lacking JAK1, JAK2 or Tyk2, the absence of one kinase does not prevent activation of the others; activation does not, therefore, involve a sequential three-kinase cascade. In the absence of JAK1, the phosphorylation of the gp130 subunit of the IL-6 receptor and the activation of STATs 1 and 3 are greatly reduced. JAK1 is also necessary for the induction of IRF1 mRNA, thus establishing a requirement for the JAK/STAT pathway in the IL-6 response. JAK2 and Tyk2 although activated cannot, in the absence of JAK1, efficiently mediate activation of STATs 1 and 3. A kinase-negative mutant of JAK2 can, however, inhibit such activation, and ancillary roles for JAK2 and Tyk2 are not excluded. A major role for JAK1 and the nonequivalence of JAK1 and JAK2 in the IL-6 response pathway are, nevertheless, clearly established for these cells.

Adolescent↗
PubMed1995

Identification of a novel cellulose-binding domain within the multidomain 120 kDa xylanase XynA of the hyperthermophilic bacterium Thermotoga maritima.

A segment of Thermotoga maritima strain MSB8 chromosomal DNA was isolated which encodes an endo-1,4-beta-D-xylanase, and the nucleotide sequence of the xylanase gene, designated xynA, was determined. With a half-life of about 40 min at 90 degrees C at the optimal pH of 6.2, purified recombinant XynA is one of the most thermostable xylanases known. XynA is a 1059-amino-acid (approximately 120 kDa) modular enzyme composed of an N-terminal signal peptide and five domains, in the order A1-A2-B-C1-C2. By comparison with other xylanases of family 10 of glycosyl hydrolases, the central approximately 340-amino-acid part (domain B) of XynA represents the catalytic domain. The N-terminal approximately 150-amino-acid repeated domains (A1-A2) have no significant similarity to the C-terminal approximately 170-amino-acid repeated domains (C1-C2). Cellulose-binding studies with truncated XynA derivatives and hybrid proteins indicated that the C-terminal repeated domains mediate the binding of XynA to microcrystalline cellulose and that C2 alone can also promote cellulose binding. C1 and C2 did not share amino acid sequence similarity with any other known cellulose-binding domain (CBD) and thus are CBDs of a novel type. Structurally related protein segments which are probably also CBDs were found in other multidomain xylanolytic enzymes. Deletion of the N-terminal repeated domains or of all the non-catalytic domains resulted in substantially reduced thermostability while a truncated xylanase derivative lacking the C-terminal tandem repeat was as thermostable as the full-length enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

[Arteriovenous fistulas for hemodialysis--patency rates and complications--a retrospective study].

In this study we investigated 213 forearm-fistulas, 233 elbow-fistulas, 21 bridge-fistulas and 3 axillo-axillary vascular accesses. 129 revisions were necessary to preserve the vascular access. The patency rates of the 170 primary forearm fistulas and the 140 primary elbow fistulas were 45 resp. 54%. We preferred the end-to-end-anastomosis for the forearm position and for the elbow the side-to-end-anastomosis. There were no differences between the type of anastomosis, localization and the second constructions as regards the patency rates. The results of the-end-to-end-fistulas were much better in male than female patients. Besides we had better results after thrombectomy in the elbow position compared to the forearm position. We found that a vein diameter less than 2 mm gave worse results. The most frequent complication of the fistulas was the thrombosis. Autologous and alloplastic transplants (grafts) were only taken if it wasn't possible to create an arteriovenous fistula by the orthotopic vessels.

Adolescent↗
PubMed1991

Cloning and chromosomal mapping of nuclear genes encoding chloroplast and cytosolic glyceraldehyde-3-phosphate-dehydrogenase from Arabidopsis thaliana.

Both cDNA and genomic clones for the nuclear genes encoding chloroplast (cp) (gapA and gapB) and cytosolic (gapC) glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Arabidopsis thaliana have been isolated and characterized. Genomic Southern-blot analyses indicate that there is only one copy of each gapA, gapB and gapC gene in A. thaliana. Comparison of the deduced amino acid (aa) sequences shows that the A and B subunits are highly similar (80% positional aa identity), while there is less similarity between the cp and cytosolic subunits (45% aa identity). These relationships are consistent with the idea that the cp and cytosolic GAPDHs evolved from different lineages, as suggested in our previous study of tobacco GAPDHs [Shih et al., Cell 47 (1986) 73-80]. In addition, the chromosomal locations for the three gap genes were determined by restriction fragment length polymorphism mapping; the three gap genes are not closely linked, gapA (55.8 cM) and gapC (0.0 cM) are on chromosome 3, and gapB (51.3 cM) is on chromosome 1.

Amino Acid Sequence↗
PubMed1991

Development of acute pancreatitis in rats after single ethanol administration and induction of a pancreatic juice edema.

The effect of an acute gastral ethanol application and an additional induction of a pancreatic juice edema by an obstruction/hyperstimulation mechanism was studied in rats. Neither ethanol administration nor the combination of ductal obstruction and secretory stimulation resulted in an acute pancreatitis when applied independently. A combination of these factors, however, led to the development of AP in two-thirds of the rats treated in this manner. Its severity was evaluated by the degree of extrapancreatic fat necrosis, the increase in serum amylase and lipase activities, and by histologic investigations. It is assumed that a pancreatic juice edema, provoked by pancreatic secretion at temporary ductal obstruction, could be an important cofactor in formation of ethanol-induced acute pancreatitis.

Acute Disease↗
PubMed1991

Studies on lipid peroxidation in pancreatic tissue. In vitro formation of thiobarbituric-acid-reactive substances (TBRS).

In pathogenic studies on acute pancreatitis the importance of a temporary ischemia on induction of autodigestion was demonstrated. Because of the involvement of oxygen-derived free radicals in the ischemia/reperfusion injury of other tissues we have investigated the influence of artificial oxidants, as FeCl3 and H2O2, on pancreatic tissue and isolated pancreatic acinar cells. Lipid peroxidation was determined as thiobarbituric-acid-reactive substances (TBRS). In these experiments the TBRS concentration was elevated within the first min of incubation with FeCl3. The exposure of pancreas homogenates and intact acinar cells to H2O2 had no remarkable effect on formation of TBRS. Under this condition the survival of cells was strongly reduced, while cells exposed to FeCl3 revealed a remarkably slower rate of cytolysis. The missing correlation between cell lysis and elevation of TBRS suggests that lipid peroxidation might not be essential process in pancreatic acinar cell damage.

Animals↗
PubMed1991

[Regeneration of the sciatic nerve in the rat modified by neurotrophic factors].

In the present study an experimental rat model is presented enabling analysis of nerve regeneration in vivo through preformed tissue holes. The tissue space allows to bridge a gap about 10 mm. The neovascularization could follow the physiological course using the way through the epi- and perineurium in the chamber. The regeneration rate was investigated with and without application of a mixture of gangliosides showing a significant difference between both groups. Gangliosides stimulated the axonal outgrowth and the restoration of well-vascularized nerve fascicles. Further investigations should examine the effects of different neurotrophic substances in the tube.

Animals↗
PubMed1990

Activation of bone marrow-derived mouse macrophages by bacterial lipopeptide: cytokine production, phagocytosis and Ia expression.

The lipopeptide N-palmitoyl-S-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-(R)-cysteinyl-a lanyl-glycine (Pam3Cys-Ala-Gly), a synthetic analogue of the N-terminal part of bacterial lipoprotein, induces the secretion of interleukin (IL) 1, IL 6 and tumor necrosis factor (TNF)-alpha in bone marrow-derived macrophages that have been cultured in vitro for up to 20 days. IL 6 and TNF-alpha secretion increased from day 6 to day 20 whereas IL 1 secretion increased until day 13 and decreased on day 20. In contrast to the enhancement of cytokine production, phagocytosis of IgG-coated sheep erythrocytes and Ia expression were found to be diminished after treatment with lipopeptide for 24 h. Morphological studies revealed lipopeptide-induced changes of macrophage cultures. The data presented here show the potential of the lipopeptide as a strong activator of bone marrow-derived macrophages.

Animals↗
PubMed1989

[Surgical treatment possibilities in cerebrovascular insufficiency--status and future prospects].

After a short synopsis of the at present ascertained knowledge of the anatomy and pathophysiology of the cerebral blood supply the possibilities of the vascular-surgical treatment are discussed. The desobliteration of extracranial vessels, PTA, vascular resections and appliances of bypass are no concurrent operation techniques, but such ones which are individually to be adapted. The importance of the clinical and non-invasive diagnostics is put before the digital subtraction angiography and the direct angiography. On the basis of the experience of 461 own surgical interventions the stage-conditioned diagnosis is required. Stage II of the transitory ischaemic attack is preferred. In unilocular mediastenoses the extra-intracranial anastomosis now as ever hat its qualification.

Brain Ischemia↗
PubMed1989

[Experiences with percutaneous drainage of abscesses and pseudocysts].

Percutaneous catheterised drainage of abscesses and pseudocysts as well as of circumscribed suppurations in soft-part tissue is considered an established therapeutic approach. Therapeutic puncture or drainage was successfully performed in 19 cases, following CT-targeted fine-needle puncture and subsequent cytological and bacteriological diagnosis. Inflammatory alterations were tackled by antibiotic therapy according to an antibiogram. Complications did not occur.

Abscess↗
PubMed1988

Intron existence predated the divergence of eukaryotes and prokaryotes.

Nucleotide sequences for the nuclear genes encoding chloroplast (GapA and GapB) and cytosolic (GapC) glyceraldehyde-3-phosphate dehydrogenases (GAPDHs) from Arabidopsis thaliana were determined. Comparison of nucleotide sequences indicates that the divergence of chloroplast and cytosolic GAPDH genes preceded the divergence of prokaryotes and eukaryotes. In addition, some intron-exon junctions are conserved among GapB, GapC, and chicken GAPDH genes. These results provide evidence at the molecular level to support the idea that introns existed before the divergence of prokaryotes and eukaryotes.

Animals↗
PubMed1988

[Clinical, immunologic and therapeutic aspects of endangiitis obliterans].

In the period of 1975-1983 twenty-three patients with thromboangiitis obliterans were examined at the Surgical Clinic of the Medical Academy of Magdeburg. The diagnosis was established clinically, angiographically histologically and immunologically. In 7 out of 12 patients histology revealed inflammatory vascular alterations including lymphocyte infiltrates throughout the entire vessel wall and also in the perivascular area. Immunohistology showed in 10 out of 15 patients segmental granular fluorescence identifiable as deposits of IgM and IgG. In 6 cases a complement formation was found. The endangiitis group revealed more frequent and increased immune complexes concentrations. Circulating immune complexes were established by phase-locked radio-immunoassay. The therapy is depended on the localization of the obliteration and can be a lumbar sympathectomy or a vascular reconstruction.

Adult↗
PubMed1988

[Planned reoperation following perforation of peptic ulcer with a simple suture. A differentiated treatment concept].

Even after perforation of chronic peptic ulcer with simple closure, patients continue to be in danger for additional complications of the ulcer ailment. Postoperative conditions of patients with perforated ulcer were analysed for a period of ten years. Classical indications for re-operation were recorded from 60 per cent. A differentiated concept for treatment of ulcer perforation is presented in this paper.

Adult↗