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Biomedical subjects

M Hinz

Publications and source records attributed to M Hinz.

At least 19 recordsLinked to original sources
PubMed2001

Constitutive NF-kappaB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells.

Constitutively activated nuclear factor (NF)-kappaB is observed in a variety of neoplastic diseases and is a hallmark of the malignant Hodgkin and Reed-Sternberg cells (H/RS) in Hodgkin lymphoma. Given the distinctive role of constitutive NF-kappaB for H/RS cell viability, NF-kappaB-dependent target genes were searched for by using adenoviral expression of the super-repressor IkappaBDeltaN. A surprisingly small but characteristic set of genes, including the cell-cycle regulatory protein cyclin D2, the antiapoptotic proteins Bfl-1/A1, c-IAP2, TRAF1, and Bcl-x(L), and the cell surface receptors CD86 and CD40 were identified. Thus, constitutive NF-kappaB activity maintains expression of a network of genes, which are known for frequent, marker-like expression in primary or cultured H/RS cells. Intriguingly, CD40, which is able to activate CD86 or Bcl-x(L) via NF-kappaB, is itself transcriptionally regulated by NF-kappaB through a promoter proximal binding site. NF-kappaB inhibition resulted in massive spontaneous and p53-independent apoptosis, which could be rescued by ectopic expression of Bcl-x(L), underscoring its dominant role in survival of H/RS cells. Hence, NF-kappaB controls a signaling network in H/RS cells, which promotes tumor cell growth and confers resistance to apoptosis.

Antigens, CD↗
PubMed2001

Fluorescently labeled model DNA sequences for exonucleolytic sequencing.

We describe here the enzyme-catalyzed, low-density labeling of DNAs with fluorescent dyes. Firstly, for "natural" template DNAs, dNTPs were partially substituted in the labeling reactions by the respective fluorophore-bearing analogs. The DNAs were labeled by PCR using Taq DNA polymerase. The covalent incorporation of dye-dNTPs decreased in the following order: rhodamine-green-5-dUTP (Molecular Probes, the Netherlands), tetramethylrhodamine-4-dUTP (FluoroRed, Amersham Pharmacia Biotech), Cy5-dCTP (Amersham Pharmacia Biotech). Exonucleolytic degradation by the 3'-->5' exonuclease activity of T7 DNA polymerase (wild type) in the presence of excess reduced thioredoxin proceeded to complete breakdown of the labeled DNAs. The catalytic cleavage constants determined by fluorescence correlation spectroscopy were between 0.5 and 1.5 s(-1) at 16 degrees C, normalized for the covalently incorporated dye-nucleotides. Secondly, rhodamine-green-X-dUTP (Roche Diagnostics), tetramethylrhodamine-6-dUTP (Roche Diagnostics), and Cy5-dCTP were covalently incorporated into the antisense strand of "synthetic" 218-b DNA template constructs (master sequences) at well defined positions, starting from the primer binding site, by total substitution for the naturally occurring dNTPs. The 218-b DNA constructs were labeled by PCR with a thermostable 3'-->5' exonuclease deficient mutant of the Tgo DNA polymerase which we have selected. The advantage of the special, synthetic DNA constructs as compared to natural DNAs lies in the possibility of obtaining tailor-made nucleic acids, optimized for testing the performance of exonucleolytic sequencing. The number of incorporated fluorescent nucleotides determined by complete exonucleolytic degradation and fluorescence correlation spectroscopy were six out of six possible incorporations for rhodamine-green-X-dUTP and tetramethylrhodamine-6-dUTP, respectively. Their covalent and base-specific incorporations were confirmed by the novel analysis methodology of re-sequencing (i.e. mobility-shift gel electrophoresis, reversion-PCR and re-sequencing) first developed in the paper Földes-Papp et al. (2001) and in this paper. This methodology was then used by other groups within the whole sequencing project.

Base Sequence↗
PubMed2001

Polymer support for exonucleolytic sequencing.

Different kinds of particles were investigated for their potential use as supports for exonucleolytic sequence analysis. Composite beads composed of an unreactive polystyrene "core" and a "shell" of functionalized silica nanoparticles were found to best fulfill the various prerequisites. The biotin/streptavidin system was used for attachment of DNA to composite beads of 6 microm diameter. Applying M13 ssDNA in extremely high dilution (approximately 1 molecule versus 100 beads) with internal fluorescent labels, only a small fraction of beads was found to be associated with fluorescent entities, which likely correspond to a very small number of bound DNA molecules per particle. For better selection and transfer of DNA-containing beads into microstructures for exonuclease degradation the loading experiments were repeated with composite beads of 2.3 microm diameter. In this case a covalent bond was formed between carboxylate-functionalized beads and amino-terminated oligonucleotides, which were detected through external labelling with fluorescent nanoparticles interacting with biotinylated segments of the complementary strand.

Biotin↗
PubMed2001

Studies on water transport through the sweet cherry fruit surface: II. Conductance of the cuticle in relation to fruit development.

Water conductance of the cuticular membrane (CM) of sweet cherry (Prunus avium L. cv. Sam) fruit during stages II and III (31-78 days after full bloom, DAFB) was investigated by gravimetrically monitoring water loss through segments of the exocarp. Segments were mounted in stainless-steel diffusion cells, filled with 0.5 ml of deionized water and incubated for 8 h at 25 +/- 2 degrees C over dry silica. Conductance was calculated by dividing the amount of water transpired per unit surface area and time by the difference in water vapor concentration across the segment (23.07 g m(-3) at 25 degrees C). Fruit mass and fruit surface area increased 4.9- and 2.8-fold between 31 and 78 DAFB, respectively. However, CM mass per unit area decreased from 3.9 to 1.5 g m(-2) and percentage of total wax content remained constant at about 31%. Stomatal density decreased from 0.8 to 0.2 mm(-2) (31-78 DAFB). Total conductance of the CM on the fruit cheek (gtot.) remained constant during stage II of development (approx. 1.38 x 10(-4) m s(-1) from 31 to 37 DAFB), increased to 1.73 x 10(-4) m s(-1) during early stage III of fruit growth (43-64 DAFB) then decreased to 0.95 x 10(-4) m s(-1) at maturity (78 DAFB). Partitioning gtot. into cuticular (gcut.) and stomatal conductance (gsto.) revealed that the relative contribution of gcut. to gtot. increased linearly from 30% to 87% of gtot. between 31 and 78 DAFB. respectively. On a whole-fruit basis, g,tot. and gcut. consistently increased up to 64 DAFB, and decreased thereafter. A significant negative linear relationship was obtained between gcut. and CM thickness, but not between the permeability coefficient (p) and CM thickness. Further, p was positively related to strain rate, suggesting that strain associated with expansion of the fruit surface increased p.

Algorithms↗
PubMed2001

Synthesis and localization of the mucin-associated TFF-peptides in the human uterus.

TFF-peptides (formerly P-domain peptides, trefoil factors) are typical secretory products of mucin-producing cells and are thought to influence the rheological properties of mucous gels. Here, the localization of these peptides in the human uterus was investigated. An analysis of TFF-peptides mRNA by the polymerase chain reaction revealed TFF3 mainly in the endocervix and smaller amounts in the endometrium. TFF1 and TFF2 mRNA was detectable occasionally in the endocervix and very rarely in the endometrium. Western blot analysis detected only TFF3 in tissue extracts of the endocervix and as a constituent of human cervical mucus. Immunofluorescence localized TFF3 in the surface epithelium of the endocervix and in gland-like structures of the cervical epithelium.

Blotting, Western↗
PubMed2000

IG-therasorb immunoapheresis in orthotopic xenotransplantation of baboons with landrace pig hearts.

BACKGROUND: The major problem of xenotransplantation is, that hyperacute xenograft rejection (HXR) causes graft failure within minutes or a few hours because of natural antibodies and activation of the complement system. As a preclinical model we transplanted pig hearts orthotopically into baboons. To prevent HXR after orthotopic xenotransplantation (oXHTx), the immunoglobulins (Ig) and natural antibodies were adsorbed to reusable Ig-Therasorb immunoadsorption (IA) columns. METHODS: We performed three oXHTx of landrace pig hearts into baboons (19+/-6.8 kg), using extracorporeal circulation (ECC) connected to the IA unit. After separating the recipient's blood into plasma and cellular fraction by a plasma filter, plasma flow was directed to the Ig-Therasorb column coated with polyclonal sheep-antibodies against human IgG, IgM, and IgA. Intraoperative treatment consisted of 4 cycles of IA. For a control, we transplanted one pig heart into a baboon (16.9 kg) without applying IA. Perioperatively, serum concentrations of Ig, anti-pig-antibodies, complement and cardiac enzymes were determined. Tissue samples of myocardium were collected at the end of the study for immunohistochemical examinations, light microscopic examination (LM) and electron microscopic examination (EM). For cardiac monitoring after oXHTx, we used ECG, echocardiography, and invasive measurement of cardiac output. To prevent a mismatch of donor and recipient heart size, the donor pig had a 30-40% lower body weight than the recipient baboon. RESULTS: Four cycles of IA removed >80% of IgG, IgM, and IgA from plasma. The graft of the control animal failed after 29 min. The first oXHTx with IA was intentionally terminated after 100 min, the second oXHTx after 11 hr and the third oXHTx after 21 hr. All xenografts showed no histological signs of HXR. After weaning off ECC, these donor hearts worked in sinus rhythm without electrocardiographic ST-segment elevation. An excellent cardiac output was measured by echocardiography and thermodilution (2 L/min). Serological parameters indicating cardiac damage were significantly lower after IA if compared with the control experiment. Macroscopically, the xenograft of the control animal showed massive hemorrhage in comparison with the almost inconspicuous grafts after IA. The myocardium of the IA group demonstrated fewer deposits of Ig and complement components compared with the control animal. CONCLUSION: Baboons do not hyperacutely reject a porcine xenograft after antibody depletion by the Ig-Therasorb column. In our experiment only 4 cycles of immunoapheresis effectively prevented HXR after oXHTx of baboons. The Ig-Therasorb column is a reusable device, which can be handled easily in combination with the ECC. IA must be tested in oXHTx longterm survival experiments, especially in combination with transgenic pig organs, which could be a reliable preclinical approach for future clinical xenotransplantation.

Animals↗
PubMed2000

Influence of ischemic time on hyperacute xenograft rejection of pig hearts in a working heart perfusion model with human blood.

In xenotransplantation long ischemic time of grafts is supposed to have a marked influence on hyperacute rejection (HXR). We investigated the influence of different cold ischemic times on HXR of ex vivo "working pig hearts" perfused with human blood. Xenoreactive natural antibodies (XNAb) as a trigger of HXR were eliminated by Ig-Therasorb immunoadsorption (IA). Explanted Landrace pig hearts of group G1 and group G3 (with additional IA) underwent 4 h of cold ischemia prior to xenoperfusion. Control groups G2 and G4 (with IA) were kept ischemic for only 46.6 +/- 15.8 and 51.2 +/- 4.2 min, respectively. Ischemic time prolonged the perfusion time in our working heart model (G1: 356 +/- 46.1 min; G2: 125 +/- 31 min; P < 0.05). IA had no additional impact on perfusion time but was effective by itself. The heart weight increased fourfold more in G2 as compared to the other groups. IA without ischemia significantly improved cardiac output in G4 (G3: 198.8 +/- 15.4 mL/min; G4: 338.5 +/- 16.0 mL/min). Coronary flow in G2 was significantly lower than in G1 (G1: 157.9 +/- 9.15 mL/min; G2: 59.4 +/- 20.1 mL/min). Histological signs of HXR (light and electron microscopy) could be found in G2 in contrast to the other groups. Parameters of serological damage showed a minimum in G4 and the maximum in G2. In G1 XNAb were nearly equally eliminated immediately after the start of xenoperfusion as in IA groups G4 and G3. Four hours of ischemic time showed beneficial effects in preventing HXR, possibly caused by changes of the endothelial cell surface (for example, glycosylation or loss of alpha1-3Gal epitopes with a hapten effect).

Acute Disease↗
PubMed2000

Prevention of hyperacute xenograft rejection in orthotopic xenotransplantation of pig hearts into baboons using immunoadsorption of antibodies and complement factors.

To prevent hyperacute xenograft rejection (HXR) caused by preformed natural antibodies (XNAb) after orthotopic heart xenotransplantation (oXHTx) of landrace pig hearts into baboons, we used immunoadsorption of immunoglobulins IgG, IgM and IgA and complement with the reusable Ig-Therasorb column. In addition to functional data, tissue was sampled for histological, immunohistochemical and electron microscopical analysis. We performed three oXHTx of landrace pig hearts to baboons using extracorporeal circulation (ECC) connected to the immunoadsorption unit. Intraoperative treatment consisted of four cycles of immunoabsorption (IA). One oXHTx of a baboon without IA served as a control. A mismatch of donor and recipient heart size was prevented by selecting a 30-40% lower body weight of donor pigs than recipients. Four cycles of IA removed more than 80% of IgG, IgM and IgA, 86% of antipig antibodies and 66% of complement factors C3 and C4 from plasma. The graft of the control animal failed after 29 min. Orthotopic xenotransplantation with IA was selectively terminated after 100 min, 11 h and 21 h, respectively without any histological signs of HXR in light and electron microscopy. After weaning off from ECC these donor xenografts showed sufficient function with normal ECG and excellent cardiac output in echocardiography and invasive measurement (1.93 +/- 0.035 l/min). The myocardium of the control xenograft demonstrated more deposits of Ig and complement components (C3, C4) than in the IA group. Baboons survive HXR after orthotopic pig heart xenotransplantation due to antibody depletion by reusable Ig-Therasorb column treatment. Long-term survival in an orthotopic baboon xenotransplantation model after IA, especially in combination with transgenic pig organs, could be a reliable preclinical trial for future clinical xenotransplantation programs.

Acute Disease↗
PubMed2000

Studies on water transport through the sweet cherry fruit surface: characterizing conductance of the cuticular membrane using pericarp segments.

Water conductance of the cuticular membrane (CM) of mature sweet cherry fruit (Prunus avium L. cv. Sam) was investigated by monitoring water loss from segments of the outer pericarp excised from the cheek of the fruit. Segments consisted of epidermis, hypodermis and several cell layers of the mesocarp. Segments were mounted in stainless-steel diffusion cells with the mesocarp surface in contact with water, while the outer cuticular surface was exposed to dry silica (22 +/- 1 degrees C). Conductance was calculated by dividing the amount of water transpired per unit area and time by the difference in water vapour concentration across the segment. Conductance values had a log normal distribution with a median of 1.15 x 10(-4) m s(-1) (n=357). Transpiration increased linearly with time. Conductance remained constant and was not affected by metabolic inhibitors (1 mM NaN3 or 0.1 mM carbonylcyanide m-chlorophenylhydrazone) or thickness of segments (range 0.8-2.8 mm). Storing fruit (up to 42 d, 1 degrees C) used as a source of segments had no consistent effect on conductance. Conductance of the CM increased from cheek (1.16 +/- 0.10 x 10(-4) m s(-1)) to ventral suture (1.32 +/- 0.07 x 10(-4) m s(-1)) and to stylar end (2.53 +/- 0.17 x 10(-4) m s(-1)). There was a positive relationship (r2=0.066**; n=108) between conductance and stomatal density. From this relationship the cuticular conductance of a hypothetical astomatous CM was estimated to be 0.97 +/- 0.09 x 10(-4) m s(-1). Removal of epicuticular wax by stripping with cellulose acetate or extracting epicuticular plus cuticular wax by dipping in CHCl3/methanol increased conductance 3.6- and 48.6-fold, respectively. Water fluxes increased with increasing temperature (range 10-39 degrees C) and energies of activation, calculated for the temperature range from 10 to 30 degrees C, were 64.8 +/- 5.8 and 22.2 +/- 5.0 kJ mol(-1) for flux and vapour-concentration-based conductance, respectively.

Biological Transport↗
PubMed2000

Clinical performance and periodontal outcome of temporary crowns and fixed partial dentures: A randomized clinical trial.

STATEMENT OF PROBLEM: Different materials (autopolymerizing, dual curing, and light initiated) are used for fabricating provisional restorations during prosthetic treatment. Randomized clinical trials that have evaluated these provisional materials have not been published. PURPOSE: This clinical trial compared the handling, fitting, plaque adherence, gingivitis, color stability, and the subjective assessment of the provisional materials by the patient and the dentist for 2 autopolymerizing (Protemp, Luxatemp), 1 dual-curing (Provipont), and 1 light-initiated (Triad-VLC) material for the manufacturing of temporary crowns and fixed partial dentures. MATERIAL AND METHODS: Thirty subjects in need of 2 similar fixed prosthetic restorations (single crowns ¿20, three-quarter crowns ¿2, connected crowns ¿9, or fixed partial dentures ¿30) were treated with 1 temporary restoration of Protemp II (control) and one randomly selected from Luxatemp, Provipont, or Triad-VLC materials. The mean time of treatment was 37.5 days (minimum 2 days, maximum 156 days). All restorations were manufactured intraorally with a vacuum-formed template. RESULTS: Mechanical and retentive characteristics revealed a high level of clinical reliability. Plaque adherence of the teeth with temporary restorations was significantly increased (P =.0039) compared with the untreated mesial reference teeth. CONCLUSION: The advantageous mechanical properties of the light-curing and dual-curing materials reviewed in dental literature were clinically offset by disadvantages in handling.

Chi-Square Distribution↗
PubMed1999

Structure of the Xenopus laevis TFF-gene xP4.1, differentially expressed to its duplicated homolog xP4.2.

TFF-peptides (formerly P-domain peptides, trefoil factors) represent major secretory products of mucous epithelia in mammals and amphibia. The nucleotide sequence of a large portion of a gene encoding the TFF-peptide xP4.1 from Xenopus laevis and its genomic organization were determined in the present study. The peptide xP4.1 containing four TFF-domains is thought to represent the functional frog homolog of human TFF2 (formerly hSP). The xP4.1 gene analyzed spans a region of about 7 kb and consists of six exons. Each TFF-domain is encoded by a single exon flanked by type 1 introns typical of shuffled modules. The 5'-upstream region contains a TATA-box, and potential binding sites for hepatocyte nuclear factor 3 and AP-1. Furthermore, the cDNA sequence of a transcript named xP4.2 with 91% similarity to xP4.1 is presented. RT-PCR analysis revealed that xP4.1 and xP4.2 genes are differentially expressed. xP4.1 transcripts are detectable only in the stomach, but not in the esophagus, whereas xP4.2 transcripts are found both in the esophagus and in the stomach with a descending gradient from fundus to antrum.

Amino Acid Sequence↗
PubMed1999

Secretion of TFF-peptides by human salivary glands.

TFF-peptides (formerly P-domain peptides, trefoil factors) are typical secretory products of mucin-producing cells and seem to influence the rheological properties of mucous gels. Here, localization studies of TFF-peptides in human salivary glands are presented. Expression studies (polymerase chain reaction) revealed mainly TFF3 transcripts in submandibular and sublingual glands and trace amounts in parotid glands. Only low levels of expression of TFF1 could be monitored in submandibular and sublingual glands, and TFF2 transcripts were hardly detectable in all three major salivary glands. This result was partly confirmed by Western blot analysis, which only detected TFF3 in submandibular glands, but not in sublingual and parotid glands. TFF3 was also shown to be a constituent of human saliva. Immunofluorescence localized TFF3 solely in the secretory granules of serous cells of submandibular glands but not in mucous cells. This localization is remarkably similar to that of the unique low-molecular-weight mucin MUC7, which interacts with a number of oral microorganisms.

Blotting, Western↗
PubMed1999

The influence of antibody and complement removal with a Ig-Therasorb column in a xenogeneic working heart model.

OBJECTIVE: Organ transplantation is limited by the number of brain-dead human donors. Xenotransplantation could be an alternative to guarantee a constant supply of organs. A major problem of xenotransplantation are xenogeneic natural antibodies (XNAb) directed against species-specific antigens of a discordant donor species (e.g. pig). They trigger the hyperacute xenograft rejection (HXR). Re-usable immunoapheresis (LA)-columns Ig-Therasorb (Therasorb, Baxter) were used to adsorb these XNAb. The effect of immunoapheresis of the perfusing human blood was investigated in ex vivo working pig hearts. METHODS: Hearts of 12 landrace pigs (body weight 14-31 kg) were explanted after inducing cardiac arrest with 4 degrees C Celsior solution. Human blood (500 ml, heparinized) was obtained from healthy volunteers. In group 1 (G1, n = 6), blood as perfusate remained untreated. In group 2 (G2, n = 6), native blood was separated by plasmapheresis into cellular components and plasma. The latter passed through the Ig-Therasorb column for removal of immunoglobulins (so-called immunoadsorption or immunoapheresis). After back-table preparation the hearts were mounted to the working heart model. After 20 min of reperfusion in Langendorff mode, the working heart mode was established. Blood samples were taken isochronously for measurement of: CK(-MB), LDH, ASAT, troponin, immunoglobulins, complement activity, anti-pig antibodies and others. After cessation of the heart, atrial and ventricular tissue samples were taken for histological examinations (light/electron microscopy and immunohistochemistry). RESULTS: Two cycles of immunoapheresis reduced the levels of IgG by 84%, IgM by 83.3% and IgA by 76%. In G2, the antibody immunoadsorption of blood prolonged the duration of the working heart mode significantly to 335+/-37.5 min. In contrast, hearts of group 1 (control) failed after 125+/-31.3 min. Heart rate was significantly different between both groups (G1, 77.3+/-6.1 beats/min; G2, 86.5+/-5.5 beats/min). In G2 cardiac output was 118% and mean coronary flow was 154.6% higher than in G1. CK, LDH and ASAT showed no differences in the two groups. Heart weight increased significantly more in group 1 than in G2. Histological examination indicated specific signs of HXR in G1 after 1.5 h, whereas in G2 only slight unspecific damages were found after 6 h. CONCLUSION: Antibody removal by means of immunoapheresis results in a significantly improved xenogeneic cardiac function. Immunoapheresis may, therefore, become an important adjunct in future pig-to-man clinical xenotransplantation.

Animals↗
PubMed1999

Effects of prolonged cold storage time in xenotransplantation.

BACKGROUND: Ischemia and reperfusion injury after prolonged ischemic time (IT) has a marked influence on hyperacute xenograft rejection (HXR). The aim of the study was to investigate the impact of different cold ischemic times on the HXR of ex vivo "working pig hearts" perfused with human blood. Xenoreactive natural antibodies (XNAb) as the trigger of HXR were reduced by immunoadsorption (IA) using an Ig-Therasorb column. METHODS: Hearts of 24 Landrace pigs (13-31 kg) were harvested after cardioplegia with Celsior-solution and split into 4 groups. In Group C1 (n = 6) the short ischemic time (IT) lasted 48.9+/-10 minutes on the average prior to start of xenoperfusion, in Group I1 IT lasted 4 hours instead. Groups C2 and 12 experienced the same IT as C1 and I1, respectively, but underwent 2 cycles of IA in addition. IA removed immunoglobulins IgG, IgM and IgA from the perfusate. In the working heart mode hemodynamic parameters were measured in defined intervals. Blood samples were collected at the same time to determine myocardial enzymes, immunoglobulins, complement and anti-pig-antibodies. At the end of the study (cardiac arrest) tissue was sampled for histologic examination (light/electron microscopy (LM/EM) and immunohistochemistry). RESULTS: Survival time of the control Group C1 was 125 minutes. IA resulted in an extension of perfusion time to 6.5 hours in C2. Four hours of IT (I1) prolonged the working time of hearts when compared with C1. IA had no additional impact (I2). Heart weight increased significantly in C1 without IA. Cardiac output and coronary flow in C1 were significantly lower when compared with the other 3 groups. IA improved cardiac output (CO) in C2 (vs C1, p < 0.001). Histologic signs of HXR (LM/EM) could be found in C1 in contrast to the other groups. Serologic parameters for myocardial damage were higher in groups with prolonged IT than in groups with short IT. CONCLUSION: Prolonged ischemia and reperfusion injury showed controversial effects in this specific xenogeneic heart transplant model. In contrast to observations in allogeneic transplantation 4 hours of IT showed a beneficial behaviour of the xenografts. Reasons could be either a protective effect of the Celsior solution or changes of the endothelial cell surface (in terms of glycosylation or loss of alpha1-3Gal-epitopes). Tolerance of prolonged IT would allow transportation of xenografts over long distances.

Animals↗
PubMed1999

NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition.

Nuclear factor kappa B (NF-kappaB) has been implicated in the regulation of cell proliferation, transformation, and tumor development. We provide evidence for a direct link between NF-kappaB activity and cell cycle regulation. NF-kappaB was found to stimulate transcription of cyclin D1, a key regulator of G1 checkpoint control. Two NF-kappaB binding sites in the human cyclin D1 promoter conferred activation by NF-kappaB as well as by growth factors. Both levels and kinetics of cyclin D1 expression during G1 phase were controlled by NF-kappaB. Moreover, inhibition of NF-kappaB caused a pronounced reduction of serum-induced cyclin D1-associated kinase activity and resulted in delayed phosphorylation of the retinoblastoma protein. Furthermore, NF-kappaB promotes G1-to-S-phase transition in mouse embryonal fibroblasts and in T47D mammary carcinoma cells. Impaired cell cycle progression of T47D cells expressing an NF-kappaB superrepressor (IkappaBalphaDeltaN) could be rescued by ectopic expression of cyclin D1. Thus, NF-kappaB contributes to cell cycle progression, and one of its targets might be cyclin D1.

3T3 Cells↗
PubMed1997

[Long-term results and costs of elective bypass operation of infrarenal aortic aneurysm].

During a 10-years-period from 1978-1987 n = 545 patients were operated upon for infrarenal aortic aneurysm. Hospital mortality was 6.4%. In 95.6% of the patients information concerning state and cause of death were achieved. Cumulative survival was 64.6% at 5 years and 41.0% at 10 years, the mean survival being 95.1 month. Preoperative risk factors like age, coronary artery disease and hypertension had a negative impact on the long-term results. The costs were calculated according to the "Gesundheitsstrukturgesetz" and on the mean in-hospital-stay of 16.4 days.

Aged↗