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Biomedical subjects

H Fricke

Publications and source records attributed to H Fricke.

At least 55 records · Page 3Linked to original sources
PubMed1997

Hemodialysis-induced upregulation of granulocyte adhesion molecules CD11b/CD18 is independent from 5-lipoxygenase activity.

Hemodialysis with new cuprophane membranes upregulates expression of granulocyte adhesion molecules and activates 5-lipoxygenase as reflected by the enhanced generation of leukotriene B4 (LTB4). We assessed the role of 5-lipoxygenase activity in hemodialysis-induced upregulation of the granulocyte adhesion molecules, CD11b and CD18, and granulocyte adhesion to human umbilical vein endothelial cells in an ex vivo dialysis model. 5-Lipoxygenase was effectively inhibited by preincubation of human whole blood with the specific inhibitor, BAY X1005. Dialysis with new cuprophane but not with new acrylonitrile membranes significantly upregulated expression of CD11b and CD18 by 6-fold and 4-fold, respectively. Inhibition of 5-lipoxygenase did not affect the expression of CD11b and CD18 during dialysis with either of the two membranes. In contrast to the enhanced expression of CD11b and CD18, adhesion of granulocytes to human umbilical vein endothelial cells did not increase during dialysis, nor was it affected by BAY X1005. These data indicate that ex vivo dialysis with cuprophane membranes upregulates expression of CD11b and CD18 on granulocytes independent of the activation of 5-lipoxygenase.

Adult↗
PubMed1996

T lymphocytes from the normal human peritoneum contain high frequencies of Th2-type CD8+ T cells.

The majority of peritoneal T lymphocytes have been shown to be CD8+ and to co-express CDw60. Expression of CDw60 characterizes CD8 T cells capable of secreting interleukin (IL)-4 and supporting IgG production by B cells. We analyzed at the clonal level the functional cytokine profile of CD8+ T lymphocytes from the normal human peritoneum. While the majority of the clones produced interferon (IFN)-gamma and exhibited high alloantigen-specific cytolytic activity, some clones secreted IL-4 and IL-5 but no detectable IFN-gamma. These Th2-type CD8+ T cell clones provided substantial B cell help for IgG and IgA synthesis and exhibited reduced cytolytic activity. Our results suggest that distinct subsets of CD8+ T cell may occur in different immune compartments.

Antigens, CD↗
PubMed1996

Particulate ANP-sensitive guanylyl cyclase: induction in cultured human peripheral CD3+ mononuclear blood cells.

There have been conflicting reports about the occurrence and/or activity of atrial natriuretic peptide (ANP) sensitive guanylyl cyclase in the immune system. This study reports on ANP-sensitive guanylyl cyclase mRNA expression and guanylyl cyclase activity in human peripheral blood mononuclear cells (PBMC). Reverse transcription polymerase chain reaction (RT-PCR) shows that activated human PBMC of healthy blood donors express functional active ANP-sensitive guanylyl cyclase after vitro culture, whereas freshly isolated PBMC show neither specific mRNA for particulate guanylyl cyclase nor ANP-sensitive activity of this enzyme. To define the subpopulation of PBMC expressing this enzyme, cultivated PBMC were subfractioned and analyzed by RT-PCR and in situ PCR. Only CD3+ PBMC showed mRNA for ANP-sensitive guanylyl cyclase. Induction of the guanylyl cyclase required coincubation with other cells, indicating that a factor or factors secreted from cells other than CD3+ cells induces this expression. In summary, ANP-sensitive guanylyl cyclase is an inducible enzyme in human CD3+ PBMC in contrast to other cells where it is considered to be constitutive.

Animals↗
PubMed1996

Continuous ambulatory peritoneal dialysis impairs T lymphocyte selection in the peritoneum.

Peritoneal lymphocytes (PCL) of 45 healthy individuals, four uremic patients with end-stage renal disease (ESRD) and 25 long-term continuous ambulatory peritoneal dialysis (CAPD) patients were characterized by flow cytometry to investigate whether CAPD alters the phenotype of PCL. B lineage cells constitute a minority of PCL (2.5% of cells). Although the majority of peritoneal T cells expressed alpha beta T cell receptor (TcR), 7% expressed gamma delta TcR, a proportion which was significantly higher than that in peripheral blood (PBMC) (approximately 4%). The majority of PCL T cells exhibited markers of the thymus-dependent lineage (CD2, CD3, TcR alpha beta, CD8 alpha beta or CD4) and surface antigens associated with memory and activation (CD45RO, CD11a, CD18, CD49d, HLA-DR). An average of 75% of both CD4+ and CD8+ PCL T cells of healthy subjects and CAPD patients were CDw60+, thus characterizing the T cell subset containing the helper activity for the mitogen-driven B cell differentiation. CD44s was abundantly expressed on PCL T cells. In contrast to PCL T cells of healthy subjects peritoneal T lymphocytes of CAPD patients exhibited CD44 splice variants containing products of exon-v9 and the proportion of CD44v9+ cells correlated with the frequency of peritonitis episodes the patients had gone through. The majority of PCL T cells of both healthy subjects and CAPD patients were CD8+. A large proportion of CD8+ PCL T cells from healthy subjects expressed the homodimeric CD8 alpha alpha isoform; however, such cells were not found in CAPD patients. In healthy subjects mRNA for the recombination activating gene 1 (RAG-1) was detectable in a PCL population containing CD7-CD34+ and CD7+CD34+ cells. In contrast, neither mRNA transcripts of the RAG-1 gene nor CD34+ cells were detectable in PCL of CAPD patients.

Adult↗
PubMed1996

Modulation of procoagulant and fibrinolytic system components of mesothelial cells by inflammatory mediators.

Human peritoneal mesothelial cells (HMC) play a critical role in maintaining the intraperitoneal balance between fibrinolysis and coagulation by expressing the fibrinolytic enzyme tissue-type plasminogen activator (t-PA) as well as a specific plasminogen activator inhibitor, PAI-1, and the procoagulant protein tissue factor (TF). Of three compounds known to stimulate t-PA synthesis in cultured human endothelial cells, i.e., retinoic acid, the protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate (PMA), and sodium butyrate, only butyrate (1 mM) caused about a threefold increase in t-PA synthesis and mRNA expression in HMC after 24 h of incubation, without markedly affecting PAI-1 synthesis. PMA (10 nM) induced a threefold increase in urokinase-type plasminogen activator (u-PA) mRNA, but u-PA antigen levels in the HMC conditioned media remained below the detection level (0.5 ng/ml), possibly as a result of rapid uptake and degradation by the u-PA receptor. The u-PA receptor mRNA levels were about fivefold enhanced above control levels after PMA treatment of the cells. An increase in intracellular adenosine 3',5'-cyclic monophosphate levels by forskolin (10 microM) diminished t-PA and PAI-1 levels 43 and 17%, respectively. Among the inflammatory mediators tested [tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha, and bacterial lipopolysaccharide], TNF-alpha (10-1,000 U/ml) showed the strongest procoagulant effects. We found that the isoflavone compound genistein (25 micrograms/ml) prevented the TNF-alpha-induced expression of PAI-1 and TF while also slightly counteracting the decrease in t-PA synthesis. The protein kinase C inhibitor R0-318220 (3 microM) only moderately opposed the TNF-alpha-induced changes in t-PA and PAI-1 synthesis but completely prevented the induction of TF mRNA. In summary, our results demonstrate that t-PA synthesis in HMC is relatively insensitive to pharmacological stimulation. To restore the balance between fibrinolysis and coagulation under inflammatory conditions, attempts to interfere with the TNF-alpha-signaling pathway were more successful.

Blood Coagulation↗
PubMed1996

High-flux hemodialysis postpones clinical manifestation of dialysis-related amyloidosis.

Amyloidosis due to the retention of beta 2-microglobulin (beta 2-MG) is a frequent complication of hemodialysis (HD). Significant amounts of beta 2-MG can be removed from the body by highly permeable HD membranes, whereas conventional low-flux membranes are impermeable for the molecule. In a prospective and controlled study we investigated whether high-flux HD could delay the onset of dialysis-related amyloidosis (DRA). Twenty patients treated with cuprophane low-flux HD membranes were matched for age and previous time on HD either to continue their HD regimen or to receive HD treatment with high-flux polysulfone membranes. For 6 years each patient was examined for manifestations of DRA once a year or upon individual needs, additionally, serum beta 2-MG levels were monitored. After 6 years of follow-up no clinical signs of DRA were found in any of the patients dialyzed with high-flux polysulfone membranes, whereas 8/10 of the conventionally dialyzed patients had CTS and/or osteoarticular lesions. Serum levels of beta 2-MG were significantly reduced in patients treated with high-flux polysulfone membranes.

Adult↗
PubMed1995

T lymphocytes from normal human peritoneum are phenotypically different from their counterparts in peripheral blood and CD3- lymphocyte subsets contain mRNA for the recombination activating gene RAG-1.

The surface antigens of peritoneal lymphocytes of healthy human individuals were studied. B lineage cells comprised 2.3% of the total peritoneal lymphocyte population. Although the majority of peritoneal cavity lymphocyte (PCL) T cells expressed alpha beta T cell receptor (TcR), up to 17% expressed gamma delta TcR. The majority of PCL exhibited markers of the thymus-dependent lineage (CD2+ CD3+ TcR alpha beta + CD4+ or CD8 alpha + beta +) and surface antigens associated with memory and activation (CD45RO+ CD11a+ CD18+ CD49d+ HLA-DR). Up to 92% of both CD4+ and CD8+ T cells bore CDw60, thus characterizing the T cell subset containing helper activity for mitogen-driven B cell differentiation. The majority of PCL T cells were CD8+ and, in addition, up to 60% of this population expressed the homodimeric CD8 alpha + beta -. Messenger RNA for the recombination activating gene RAG-1 was examined in CD3- PCL depleted of CD19+ lineage cells. The PCL population which comprised cells containing RAG-1 mRNA transcripts was CD19-, surface IgM-, cytoplasmic IgM- and CD2- CD3- CD4- CD8- CD56-. However, this population was CD7+ (approx. 75%), and contained both CD7- CD34+ (up to 3%) and CD7- CD34+ (up to 3%) cells. These findings are compatible with the hypothesis that the adult human peritoneum provides a microenvironment capable of supporting a thymus-indenpendent differentiation of T lymphocytes.

Adult↗
PubMed1995

Biocompatible intermittent hemodialysis.

Since intermittent hemodialysis was first used systemically during the Korean war, the mortality of acute renal failure (ARF) in critically ill patients has remained high ( > or 50%). The lack of improvement may be a result of better resuscitation techniques and intensive care management that allow more severely ill patients to survive long enough to develop ARF. The concept that those patients with ARF die with, but not of, renal failure was challenged recently by the results of three prospective randomized trials. Each tested the hypothesis that the course of ARF and the fate of critically ill patients may be affected adversely by bioincompatibility reactions due to the dialysis membrane used (activation of complement and neutrophils). Schiffl and colleagues were the first to publish a full report on the results of their investigation comparing bioincompatible cuprophane (CUP) and biocompatible acrylonitrile AN 69 (Hospal, Lyon, France) membranes in 52 patients with ARF following cardiovascular surgery. The AN 69 group had a lower death rate (38% vs. 65%, p = 0.052), a lower proportion of patients dying from Gram-negative sepsis (40% vs. 71%, p = 0.0162), and an improved recovery of renal function. A similar trial comparing the use of CUP with biocompatible polymethyl-methacrylate (PMMA) was performed in 72 patients with medical categories of ARF. Again, the use of a biocompatible membrane resulted in an improved survival rate (57% vs. 37%, p = 0.11) and better recovery of renal function (62% vs. 37%, p = 0.04). Of the 20 patients in each group who initially had nonoliguric ARF, the survival rates were 80% with PMMA and 40% with CUP (p = 0.01). The preliminary results of another multicenter study including 121 patients dialyzed with either bioincompatible cellulosic membranes or PMMA or polysulfone membranes seem to confirm these findings. The management of critically ill patients is sophisticated and expensive. The use of biocompatible membranes adds little to the overall costs and appears to be justified.

Acute Kidney Injury↗
PubMed1993

Hypertension secondary to early-stage kidney disease: the pathogenetic role of altered cytosolic calcium (Ca2+) homeostasis of vascular smooth muscle cells.

We have examined cardiovascular pressor responsiveness to infused norepinephrine (NE) as related to endogenous plasma NE and plasma renin and to platelet free cytosolic (Ca2+) in 36 patients with early-stage kidney disease and 27 matched normal subjects. The 27 hypertensive patients and the normal subjects did not differ in blood volume, plasma renin, and NE; however, the hypertensive patients had a higher exchangeable body sodium content. Basal plasma NE levels, the relationship between plasma NE measured during NE infusion and the corresponding NE infusion rate, as well as the total plasma clearance for NE did also not differ significantly between the two study groups. In contrast, the threshold or pressor doses of infused NE significantly decreased in the patients with kidney disease. Antihypertensive pharmacotherapy with (Ca2+) channel blockers and/or loop diuretics normalized blood pressure and cardiovascular NE hyperresponsiveness and reduced blood volume, exchangeable body sodium, and platelet free cytosolic (Ca2+). In contrast, experimental digitalisation as a model for in vivo sodium/potassium adenosine triphosphatase inhibition augmented NE responsiveness and raised platelet free cytosolic (Ca2+). Incubation of platelets from normal subjects with plasma ultrafiltrate from hypertensive patients gave evidence for an endogenous factor capable to raise free cytosolic (Ca2+) and to act synergistically with digoxin. Hypertension secondary to early-stage kidney disease is related to an impairment of sodium excretion leading to an expansion of blood volume and exchangeable body sodium. This may result in increased secretion of endogenous factors, leading to alterations of cytosolic (Ca2+) homeostasis of vascular smooth muscle cells followed by elevated peripheral resistance and thus blood pressure.

Adult↗
PubMed1991

Close tetrapod relationships of the coelacanth Latimeria indicated by haemoglobin sequences.

The origin of tetrapods has been debated for many years. In traditional systematics, the extinct lobe-finned bony fish (Rhipidistia) are regarded as the closest relatives of tetrapods. Among living fish, the coelacanth Latimeria chalumnae (Actinistia), which is the only recent representative of the Crossopterygii (Actinistia and Rhipidistia), the lungfish (Dipnoi) and ray-finned fish (Actinopterygii), have each been considered as sister-groups of the tetrapods. We have now determined the sequence of the alpha- and beta-globin chains of coelacanth haemoglobin and compared them with all known haemoglobins of bony and cartilaginous fish as well as those of tadpoles and adult amphibians. Haemoglobins of bony fish match more closely those of larval than adult amphibians. The beta chains of Latimeria match those of tadpoles more closely (54%) than do those of any other fish, whereas the alpha chains of Latimeria (45.4%), and especially of teleosts (49.2%), are closer to those of larval amphibians than are those of lungfish (39.8%). If only synapomorphous sequence matches (those at derived positions shared by one bony fish and tadpoles but not by any other bony fish) are considered, both Latimeria globin chains have distinctly more identities with phase of tadpoles than do those of any bony fish. Thus the primary structure of Latimeria haemoglobin indicates that the coelacanth is the closest living relative of tetrapods.

Amino Acid Sequence↗
PubMed1991

Idiotype specific T-cell lines inducing experimental systemic lupus erythematosus in mice.

Immunization of mice with either antibodies bearing the 16/6 idiotype (16/6 Id) or anti-idiotypic antibodies against the 16/6 Id induces experimental systemic lupus erythematosus (SLE). We report here the establishment and characterization of 16/6 Id-specific T-cell lines from C3H.SW (H-2b) and BALB/c (H-2d) mice. Both lines proliferate specifically in response to the 16/6 Id in an H-2-restricted manner. The injection of 16/6 Id-specific T cells into syngeneic mice led to the development of experimental SLE. Furthermore, inoculation of the 16/6 Id-specific T-cell line derived from C3H.SW mice into the H-2 compatible C57BL/6 mice, which are non-responders to the 16/6 Id, induced experimental SLE. This report provides direct evidence for the role of idiotype-specific T cells in the induction of experimental SLE.

Animals↗