Free flap survival despite severe anemia after fourth degree hand burn.
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Aged↗
Biomedical subjects
E Hofer
Publications and source records attributed to E Hofer.
A new floating sensor array to detect electric near fields of beating heart preparations.
A new flexible sensor for in vitro experiments was developed to measure the surface potential, Phi, and its gradient, E (electric near field), at given sites of the heart. During depolarisation, E describes a vector loop from which direction and magnitude of local conduction velocity theta can be computed. Four recording silver electrodes (14 microm x 14 microm) separated by 50 microm, conducting leads, and solderable pads were patterned on a 50 microm thick polyimide film. The conductive structures, except the electrodes, were isolated with polyimide, and electrodes were chlorided. Spacer pillars mounted on the tip fulfil two functions: they keep the electrodes 70 microm from the tissue allowing non-contact recording of Phi and prevent lateral slipping. The low mass (9.1 mg) and flexibility (6.33 N/m) of the sensor let it easily follow the movement of the beating heart without notable displacement. We examined the electrodes on criteria like rms-noise of Phi, signal-to-noise ratio of Phi and E, maximum peak-slope recording dPhi/dt, and deviation of local activation time (LAT) from a common signal and obtained values of 24-28 microV, 46 and 41 dB, 497-561 V/s and no differences, respectively. With appropriate data acquisition (sampling rate 100 kHz, 24-bit), we were able to record Phi and to monitor E and theta on-line from beat-to-beat even at heart rates of 600 beats/min. Moreover, this technique can discriminate between uncoupled cardiac activations (as occur in fibrotic tissue) separated by less than 1 mm and 1 ms.
Animals↗
Coffee diterpenes prevent the genotoxic effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and N-nitrosodimethylamine in a human derived liver cell line (HepG2).
Aim of the present experiments was to study the genotoxic effects of coffee diterpenoids, namely cafestol palmitate and a mix of cafestol and kahweol (C+K) in human derived hepatoma (HepG2) cells. Furthermore, we investigated the potential protective properties of these substances towards carcinogens contained in the human diet, namely N-nitrosodimethylamine (NDMA) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). C+K and cafestol palmitate were tested over a broad dose range in micronucleus (MN) assays and no indication for genotoxic effects was seen. In combination experiments with PhIP (300 microM), pronounced inhibition (approximately 1.7-fold) of MN formation was observed with C+K and cafestol palmitate at dose levels > or = 0.9 and 1.7 microg/ml, respectively. Enzyme measurements indicate that the protection is due to inhibition of sulfotransferase, an enzyme involved in the activation of the amine, and/or to induction of UDP-glucuronosyltransferase which detoxifies the DNA-reactive metabolites of PhIP. Furthermore, a significant increase of glutathione-S-transferase was seen, whereas the activities of cytochrome P-450 1A1 and N-acetyltransferase 1 were not significantly altered. Also in combination experiments with C+K and NDMA, strong protective effects (50% reduction of genotoxicity) were seen at low dose levels (> or = 0.3 microg/ml). Since inhibition of MN was also observed when C+K were added after incubation with NDMA, it is likely that the chemoprotective effects are due to induction of DNA repair enzymes. Comparison of data on the effects of C+K on the cholesterol metabolism, which was investigated in earlier in vivo studies, with the present findings suggests that DNA-protective effects take place at exposure levels which are substantially lower than those which cause hypercholesterolemia.
Analysis of Variance↗
Evaluation of a RAPD-based typing scheme in a molecular epidemiology study of Vibrio cholerae O1, Brazil.
AIMS: To evaluate the utility of random amplification of polymorphic DNA (RAPD) technique for routine practice in public health laboratories for epidemiological studies of Vibrio cholerae O1 isolates. MATERIALS AND RESULTS: Seventy-nine strains were examined by PCR for the toxin genes (ctx A, zot and ace), virulence-associated genes (tcp A and tox T) and RAPD sequences. Except for one strain (no. 1123) from the Amazonas State, all the strains analysed carried the genes ctx A, zot, ace, tcp A and tox T. RAPD fingerprinting revealed variability but no correlation with serotype, biotype or geographical origin of the isolates was found. CONCLUSION: A standardized RAPD method does not enable the establishment of a pattern data bank for the identification of V. cholerae O1 strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The simplicity and discriminative capacity of this technique make it useful for detecting genetic diversity among micro-organisms from a defined group or for outbreak investigation.
Brazil↗
Use of cardiac electric near-field measurements to determine activation times.
In a recent paper, we described the behavior of the cardiac electric near-field, E, parallel to the tissue surface during continuous conduction. We found that T(E), the time at which the peak near-field, E, occurs, is an accurate marker of local activation time. Examination of experimentally recorded E vector loops revealed a large variety of morphologies. We postulated that propagation around an obstacle could lead to the observed deviations in loop morphology. The purpose of this study was to determine if this was plausible, and if so, whether T(E) remains an accurate time marker of local activation under these conditions. We used a monodomain computer model of a sheet of cardiac tissue with a central conduction obstacle immersed in an unbounded volume conductor. Activation times T(Im), T(phi), and T(E) were derived from the transmembrane current I(m), the extracellular potential phi(e), and E, respectively. The obstacle led to deformations of the vector loops, morphologically similar to those observed experimentally, particularly during the initial and terminal phases, and to a lesser degree near the time of E. Despite these loop deformations, T(E) was an accurate time marker of local activation. We found that T(E) was significantly closer to T(Im) than T(phi). We concluded that isochrone maps computed from T(E) better reflect intracellular activation patterns than those computed from T(phi). For a given electrode spacing of 60 microm, the sensitivity to noise of E was significantly less than that of phi(e). Hence, T(E) was less affected by noise than T(phi).
Animals↗
Cardiac near-field morphology during conduction around a microscopic obstacle--a computer simulation study.
In a recent paper, we described the behavior of the cardiac electric near-field, E, parallel to the tissue surface during continuous conduction. We found that the tip of E describes a vector-loop during depolarization with the peak field, E, pointing opposite to the direction of propagation, phiI(m). Experimentally recorded loop morphologies of E, however, frequently showed significant deviations from the theoretically predicted behavior. We hypothesized that this variety of morphologies might be caused by conduction obstacles at a microscopic size scale. This study examines the influence of obstacles on the morphology of vector loops of E and whether the peak of distorted loops remains a reliable indicator for the direction of propagation. We used a computer model of a sheet of cardiac tissue with a central conduction obstacle immersed in an unbounded volume conductor. We studied the loop morphologies of E and the differences between the intracellularly determined direction of propagation, phiI(m), and the direction of E, phiE. Distortions of the vector loop were morphologically similar to those observed experimentally. Differences between phiI(m) and phiE were less than 18 degrees at all observation sites. The obstacle led to deformations of the loop morphology, particularly during the initial and terminal phases, and to a lesser degree near the instant of E. We concluded that E is a reliable indicator of phiI(m).
Animals↗
The chemistry and biology of ratjadone.
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Antineoplastic Agents, Phytogenic↗
Impaired conditional discrimination learning in schizophrenia.
Learning deficits have repeatedly been found in patients with schizophrenia. Eyelid conditional discrimination learning (ECDL) is a test of discriminative aversive conditioning and places minimal demands on motivation. An ECDL task was used to examine residual and paranoid type individuals with schizophrenia and age- and gender-equivalent healthy controls. In the experiment two differently colored light stimuli were randomly presented. Only one of the stimuli (in reinforced trials) was followed by an aversive airpuff to the cornea, as opposed to unreinforced trials where the stimulus was not followed by an aversive airpuff. Conditioned responses develop to both trial types during the course of the experiment. These conditioned responses consist of reflectory eyelid closures already upon light presentation. The patients showed significantly impaired conditional discrimination learning abilities. There was no significant difference between the results in the two schizophrenia subtypes. Patients failed to increase response frequencies on reinforced trials during the course of the experiment, while controls showed appropriate conditional discrimination ability. Thus the results show an impairment of adequate behavior modification in an aversive conditioning task in individuals with schizophrenia. It is concluded that ECDL might be a trait marker for schizophrenia.
Adult↗
An inhibitory role of the phosphatidylinositol 3-kinase-signaling pathway in vascular endothelial growth factor-induced tissue factor expression.
Vascular endothelial growth factor (VEGF) is not only essential for vasculogenesis and angiogenesis but is also capable of inducing tissue factor, the prime initiator of coagulation, in endothelial cells. In this study we have analyzed the VEGF-elicited pathways involved in the induction of tissue factor in human umbilical cord vein endothelial cells. Using specific low molecular weight inhibitors we could demonstrate a crucial role of the p38 and Erk-1/2 mitogen-activated protein (MAP) kinases. In contrast, treatment with wortmannin or LY294002, inhibitors of phosphatidylinositol 3 (PI3)-kinase, resulted in a strong enhancement of the VEGF-induced tissue factor production, indicating a negative regulatory role of the PI3-kinase on tissue factor-inducing pathways. Accordingly, transduction with constitutively active Akt led to a reduction of VEGF-induced tissue factor production. Western blot analyses using antibodies specific for phosphorylated p38 showed an enhanced activation of this MAP kinase in human umbilical cord vein endothelial cells when stimulated with VEGF in the presence of wortmannin in comparison to either agent alone. Thus, the negative regulation of the PI3-kinase pathway on endothelial tissue factor activity can be explained at least in part by a suppression of this MAP kinase-signaling pathway. This is the first demonstration of a reciprocal relationship between procoagulant activity and the PI3-kinase-Akt signaling pathway, and it reveals a novel mechanism by which tissue factor expression can be controlled in endothelial cells.
Adenoviridae↗
Characterization and evaluation of some virulence markers of Listeria monocytogenes strains isolated from Brazilian cheeses using molecular, biochemical and serotyping techniques.
A total of 207 L. monocytogenes strains isolated from different types of cheeses commercialized in the city of Rio de Janeiro, Brazil, were serotyped and evaluated for their ability to produce beta-haemolysin and lecithinase and to adsorb Congo red dye. Of the 207 strains, 59.9, 27.5 and 12.6% belonged to serotypes 1/2a, 1/2b and 4b, respectively. In addition, 175 strains of L. monocytogenes produced lecithinase while strains of the other species did not. Some of the non-L. monocytogenes strains adsorbed the dye Congo red, while some L. monocytogenes did not. Statistical analysis of the results showed significant differences (P < 0.05) amongst the virulence tests and the three serotypes found. In the present study, 32 L. monocytogenes strains were also analyzed by RAPD (randomly amplified polymorphic DNA). RAPD analysis allowed the discrimination among strains of different serotypes, as well as among strains of the same serotype. It is important to emphasize that the use of more than one primer is needed for characterization of L. monocytogenes strains. With RAPD the strains were grouped into six different profiles, some of them common for strains belonging to different serotypes. The results also indicated a close genetic relationship among strains of different serotypes.
Bacteriological Techniques↗
A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex.
The NK gene complex is a region on human chromosome 12 containing several families of lectin-like genes including the CD94 and NKG2 NK receptor genes. We report here that the region telomeric of CD94 contains in addition to the LOX-1 gene the novel human DECTIN-1 and the CLEC-1 and CLEC-2 genes within about 100 kb. Sequence similarities and chromosomal arrangement suggest that these genes form a separate subfamily of lectin-like genes within the NK gene complex. DECTIN-1 is selectively expressed in dendritic cells and to a lower extent in monocytes and macrophages. mRNA forms with and without a stalk exon are observed. During functional maturation of dendritic cells the level of DECTIN-1 mRNA is down-regulated several-fold. CLEC-1 is found to be not only expressed in dendritic cells, but also in endothelial cells and in the latter aspect resembles the LOX-1 gene. Whereas recombinant full-length DECTIN-1 and LOX-1 are transported to the cell surface, CLEC-1 proteins accumulate in perinuclear compartments. We propose that this family of lectin-like genes encodes receptors with important immune and/or scavenger functions in monocytic, dendritic and endothelial cells.
Amino Acid Sequence↗
The centromeric part of the human natural killer (NK) receptor complex: lectin-like receptor genes expressed in NK, dendritic and endothelial cells.
The human natural killer (NK) receptor complex encompasses a region of about 2 Mb on the short arm of chromosome 12. It contains at least 18 lectin-like receptor genes, of which some are expressed in NK and NK/T cells and function as NK receptors. Close to the CD94 and NKG2 NK receptor genes in the centromeric part, a novel family of genes, expressed in myeloid, dendritic and/or endothelial cells, recently became evident. These genes encode a receptor for oxidized low density lipoprotein in endothelial cells and three other receptors potentially serving regulatory functions in dendritic cells. Although the overall structure of the human NK receptor complex is similar to the syntenic rodent regions, the centromeric part lacks the cluster of Ly49 genes. This supports the notion that recognition of MHC class Ia molecules has evolved separately in rodents and humans in the lectin-like Ly49 and the killer immunoglobulin-like receptors, respectively. In the telomeric part, other lectin-like genes expressed in different hematopoietic lineages are found. The receptors of the NK receptor complex apparently serve important functions in several leukocytes and in endothelial cells, and the exact role of these receptors, their ligands, and their distinct and co-ordinate regulation in different cell lineages warrants further investigation.
Animals↗
["I am a Misunderstood Being on Earth" - Concept of illness of patients suffering from schizophrenic psychosis before and after psychoeducational treatment].
OBJECTIVE: To determine the effects of a psychoeducational intervention on the individual concepts of illness of patients suffering from schizophrenia. METHOD: 27 patients with a diagnosis of schizophrenia according to ICD-10 were interviewed with open ended questions about their concept of illness at admission to a day hospital and after 10 weeks of attending a psychoeducational program. Questions concerned terminology, diagnosis, prognosis, interventions and aetiology. A qualitative analysis of these data is presented. RESULTS: The terms used to describe the illness were mostly colloquial. Highly individualized and heterogeneous concepts of illness, aetiology and helpful interventions and a positive view regarding prognosis prevailed. Changes over time were limited and arbitrary. CONCLUSIONS: The concepts offered by professionals were adopted in a very limited way, which can be understood in the context of highly individualized ways of coping with diagnosis and illness.
Adolescent↗
Specificity, diversity, and convergence in VEGF and TNF-alpha signaling events leading to tissue factor up-regulation via EGR-1 in endothelial cells.
Tissue factor (TF) has been shown to be up-regulated in endothelial cells by the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) as well as by the main angiogenic factor VEGF. Since both stimuli induce the transcription factor EGR-1, which is critically involved in TF gene regulation, we used EGR-1-dependent TF induction as a model to identify potential cross-talks between the various signal transduction cascades initiated by VEGF and TNF-alpha. The data show that at the MAP kinase level, VEGF mainly activates ERK1/2 and p38 MAP kinases in human endothelial cells. TNF-alpha is able to activate all three MAP kinase cascades as well as the classical inflammatory IkappaB/NFkappaB pathway. Furthermore, the MEK/ERK module of MAP kinases appears to act as the convergence point of VEGF- and TNF-alpha-initiated signaling cascades, which lead to the activation of EGR-1 and subsequent TF expression, whereas the upstream signals are distinct. We found that induction of TF by VEGF via EGR-1 is strongly PKC dependent. The TNF-alpha-initiated MEK/ERK cascade connected to EGR-1 and TF expression is clearly less sensitive to PKC inhibition. TNF-alpha-mediated activation of MEK/ERK and EGR-1 can be blocked by adenoviral expression of a dominant negative mutant of IKK2, whereas the VEGF signaling pathway is unaffected. Thus, our data demonstrate a new link between the classical inflammatory IKK/IkappaB and the MEK/ERK cascades triggered by TNF-alpha. The additional finding that EGF induces ERK and EGR-1 in a PKC-independent manner and that this signal is not sufficient to up-regulate TF emphasizes the importance of a VEGF-specific signaling pattern for the induction of TF.
Cells, Cultured↗
Bone marrow fibroblasts in patients with advanced lung cancer.
In a previous study we demonstrated that the incidence of fibroblast colony-forming units (CFU-F) was very low in bone marrow primary cultures from the majority of untreated advanced non-small lung cancer patients (LCP) compared to normal controls (NC). For this reason, we studied the ability of bone marrow stromal cells to achieve confluence in primary cultures and their proliferative capacity following four continuous subcultures in consecutive untreated LCP and NC. We also evaluated the production of interleukin-1beta (IL-1beta) and prostaglandin E2 (PGE2) by pure fibroblasts. Bone marrow was obtained from 20 LCP and 20 NC. A CFU-F assay was used to investigate the proliferative and confluence capacity. Levels of IL-1beta and PGE2 in conditioned medium (CM) of pure fibroblast cultures were measured with an ELISA kit and RIA kit, respectively. Only fibroblasts from 6/13 (46%) LCP confluent primary cultures had the capacity to proliferate following four subcultures (NC = 100%). Levels of spontaneously released IL-1beta were below 10 pg/ml in the CM of LCP, while NC had a mean value of 1,217 +/- 74 pg/ml. In contrast, levels of PGE2 in these CM of LCP were higher (77.5 +/- 23.6 pg/ml) compared to NC (18.5 +/- 0.9 pg/ml). In conclusion, bone marrow fibroblasts from LCP presented a defective proliferative and confluence capacity, and this deficiency may be associated with the alteration of IL-1beta and PGE2 production.
Adult↗
Vibrio cholerae resistant to 2,4-diamino-6,7-diisopropylpteridine (O/129) isolated from patients with enteritis in Ceará, Brazil.
This paper reports the characterization of clinical Vibrio cholerae resistant to vibriostatic agent O/129, using classical and plasmid analysis. In a study conducted during December 1991-September 1993, two of 7,058 V. cholerae strains, obtained from patients suspected to have cholera in the State of Ceará, northeast Brazil, were resistant to 150 micrograms of the vibriostatic agent O/129 (2,4-diamino-6,7-diisopropylpteridine). One strain was identified as V. cholerae O1 El Tor Inaba and the other one as serogroup O22. Only one O1 strain harboured a plasmid of 147 kb transferable to Escherichia coli K12, and five strains of V. cholerae O1 and non-O1 were sensitive to O/129 and plasmid-negative at a frequency between 8 x 10(-2) and 3.6 x 10(-5). Additionally, O/129-resistant strains of V. cholerae O1 and O22 were resistant to trimethoprim/sulphamethoxazole.
Anti-Bacterial Agents↗
The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region.
The natural killer (NK) gene complex is a genomic region containing lectin-type receptor genes. We have established a contig of PAC and BAC clones comprising about 1 Mb of the centromeric part of the NK gene complex. This region extends from the LOX-1 gene, which encodes a receptor for oxidized LDL and was found within 100 kb telomeric of the STS marker D12S77, contains the CD94 and NKG2 NK receptor genes and reaches beyond D12S852 on the proximal side. In this part we have mapped the human LY49L gene, a homologue of the rodent Ly49 genes, which encode important MHC class I receptors for the regulation of NK cell activity in rodents. The LY49L gene is localized 100 to 200 kb centromeric of the NKG2 gene cluster and 300 to 400 kb telomeric of the STS marker D12S841. Genomic sequencing of the complete gene including promoter and intron sequences confirmed that the structure is similar to the mouse Ly49 genes. Screening of several cDNA libraries did not detect any transcripts of putative additional human LY49 genes. In addition, in the course of these studies several EST sequences were localized in the region, one immediately upstream of the LY49L gene.
Antigens, CD↗
The NKG2 natural killer cell receptor family: comparative analysis of promoter sequences.
The NKG2 receptor family is crucially involved in target cell recognition by natural killer cells and comprises several activating as well as inhibitory family members. We have established approximately 3 kilobases of upstream promoter sequences of the human NKG2-C, -E and -F genes and have carried out a comparative analysis with available NKG2-A sequences. We found extended regions of homology which contain numerous putative transcription factor binding sites conserved in the NKG2 genes. However, variation in Alu insertion among family members has led to promoter structures unique to the respective family members, which could contribute to differences in transcriptional initiation as well as gene-specific regulation.
Base Sequence↗