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At least 1,513 records · Page 84Linked to original sources
PubMed2003

The endothelin system in Morris hepatoma-7777: an endothelin receptor antagonist inhibits growth in vitro and in vivo.

1. Plasma concentrations of endothelin are increased in patients with hepatocellular cancer as well as in patients with liver metastasis. However, the impact of these findings remains uncertain. 2. We thus analyzed the endothelin system in a rat hepatoma model (Morris hepatoma 7777) in vitro and in vivo. 3. Our study revealed that tissue concentrations of endothelin-1 (ET-1) and big-ET-1, the precursor of ET-1, were significantly elevated in Morris hepatoma 7777 as compared to normal liver. The ETA receptor density was significantly elevated, whereas the density of the ETB receptor was decreased in Morris hepatoma 7777. 4. We could also demonstrate that hepatoma cells secrete ET-1. 5. Exogenously added ET-1 enhances hepatoma cell growth in a dose-dependent manner. Endothelin receptor antagonists (ETA and combined ETA/ETB receptor antagonists) inhibit tumor cell growth in vitro. Since the combined ETA/ETB receptor antagonist was more effective in vitro, we used this compound also for in vivo studies and could demonstrate that a combined ETA/ETB receptor antagonist is able to reduce hepatoma growth in vivo. 6. In conclusion, the endothelin system is activated in Morris hepatoma 7777 and contributes to hepatoma growth. Since endothelin receptor antagonists are well-tolerated upcoming clinically used drugs without major side effects, our data might provide a new pharmacological approach to reduce hepatoma growth in vivo.

Animals↗
PubMed2001

Permissible and immunogenic HLA-A mismatches: cytotoxic T-cell precursor frequencies reflect graft survival data.

Analysis of the in vivo immunogenicity of single HLA mismatches, in the context of a patient's own human leukocyte antigen (HLA) phenotype, has been used to define permissible and immunogenic HLA mismatches. Kidney graft survival in the case of permissible mismatches was similar to that of completely HLA matched combinations, whereas immunogenic mismatches lead to a significantly poorer graft survival. The present study tested whether such permissible and immunogenic HLA mismatches are reflected in the in vitro cytotoxic T-lymphocyte (CTL) allorepertoire. Limiting dilution experiments were performed to analyze the number of precursor CTL directed against individual HLA class I antigens. In general, the frequency of CTLp directed against permissible HLA-A antigens (n = 70, mean frequency 27 CTLp per million peripheral blood lymphocytes [PBL]) was found to be significantly lower compared with the CTLp directed against immunogenic HLA-A antigens (n = 73, mean frequency 59 CTLp per million PBL). The difference was found both in healthy individuals and a population of renal transplant candidates. These results were confirmed by a retrospective analysis of CTLp frequencies performed between partly mismatched unrelated bone marrow donors and their potential recipients. In conclusion, on the population level the permissible and immunogenic HLA-A mismatches are indeed reflected in the CTL allorepertoire. However, due to the big overlap of the CTLp frequencies in these populations, the permissible or immunogenic nature of a mismatch for a particular patient should be determined on an individual basis.

Cells, Cultured↗
PubMedDate not supplied

Immunoaffinity purification of the neuropeptide prothoracicotropic hormone from Manduca sexta.

The prothoracicotropic hormones (PTTH) are cerebral peptides that control insect postembryonic development by stimulating the prothoracic glands to synthesize ecdysteroids. Using immunoaffinity chromatography and SDS-PAGE, a 25.5 kDa big PTTH has been purified from Manduca sexta. Based upon SDS-PAGE and Western blot analysis, the native form of big PTTH appears to be a dimer with monomers of 16.5 kDa. Four HPLC-separated fragments of this acidic peptide were sequenced and exhibited no sequence similarity with Bombyx mori PTTH. In agreement with this finding, the basic Bombyx PTTH had no PTTH bioactivity in Manduca. One sequenced fragment of the Manduca PTTH is approximately 70% similar to the vertebrate cellular retinoid binding proteins, suggesting these binding proteins may be present in insects.

Amino Acid Sequence↗
PubMed2006

Molecular diversity of coronaviruses in bats.

The existence of coronaviruses in bats is unknown until the recent discovery of bat-SARS-CoV in Chinese horseshoe bats and a novel group 1 coronavirus in other bat species. Among 309 bats of 13 species captured from 20 different locations in rural areas of Hong Kong over a 16-month period, coronaviruses were amplified from anal swabs of 37 (12%) bats by RT-PCR. Phylogenetic analysis of RNA-dependent-RNA-polymerase (pol) and helicase genes revealed six novel coronaviruses from six different bat species, in addition to the two previously described coronaviruses. Among the six novel coronaviruses, four were group 1 coronaviruses (bat-CoV HKU2 from Chinese horseshoe bat, bat-CoV HKU6 from rickett's big-footed bat, bat-CoV HKU7 from greater bent-winged bat and bat-CoV HKU8 from lesser bent-winged bat) and two were group 2 coronaviruses (bat-CoV HKU4 from lesser bamboo bats and bat-CoV HKU5 from Japanese pipistrelles). An astonishing diversity of coronaviruses was observed in bats.

Animals↗
PubMed1993

Selenium and the risk of postmenopausal breast cancer in the DOM cohort.

Selenium has been claimed to have chemo-preventive properties. However, data showing that in humans selenium levels are already decreased prior to diagnosis of breast cancer were not available. Such information is mandatory before oral selenium supplementation in the primary prevention of (breast) cancer in humans is acceptable. This question of a 'preventive-potential' of selenium was evaluated in a case-control study nested in a cohort, because this design allows determination of the time-order of preceding selenium levels and subsequent cancer risk. The cohort consisted of 5577 women aged 55-70 years from the DOM project, a population based breast cancer screening program in the Netherlands. Instrumental Neutron Activation Analysis was used to measure the selenium content of toenail clippings. The 69 cases of breast cancer found during follow-up after screening. represent 'recent' tumours since all women had a negative screening mammogram 3-5 years previously. No decreased selenium levels, as measured in nail clippings from the big toes, could be detected in cases-to-be, either when compared to 4 age matched controls per case or when compared with a random control group drawn from the entire cohort. On the contrary, a tendency for slightly higher selenium levels among 'future' cancer cases was observed. As to the sensitivity of detecting differences in selenium by nail clippings, lower selenium could be detected in nails of current smokers. The smoking-related decrease in nail selenium level was of the same order as the differences between breast cancer cases and controls, but was independent of the breast cancer risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2003

Corticofugal modulation of amplitude domain processing in the midbrain of the big brown bat, Eptesicus fuscus.

Recent studies have shown that the corticofugal system systematically modulates and improves subcortical signal processing in the frequency, time and spatial domains. The present study examined corticofugal modulation of amplitude sensitivity of 113 corticofugally inhibited neurons in the central nucleus of the inferior colliculus (IC) of the big brown bat, Eptesicus fuscus. Cortical electrical stimulation decreased the number of impulses and increased the response latency of these neurons. They had an average of 5.9+/-4.4 kHz best frequency (BF) differences between collicular and electrically stimulated cortical neurons. Cortical electrical stimulation synchronized with sound stimulation for 30 min compressed the rate-amplitude functions of half (56, 49.6%) of these collicular neurons and shifted their minimum thresholds (MT) and dynamic ranges (DR) toward that of electrically stimulated cortical neurons for as long as 40 min. These collicular neurons had an average of 1.6+/-1.4 kHz BF differences. The shift in collicular MT and DR significantly increased with differences in MT and DR between collicular and cortical neurons. Cortical electrical stimulation also shifted the BF and best amplitude (BA) of collicular neurons toward that of cortical neurons. The BF shift increased with BF differences and the BA shift increased with BA differences. These data suggest that the corticofugal system modulates collicular responses on the basis of topographic projections between the IC and auditory cortex. However, corticofugal modulation of collicular amplitude sensitivity is primarily dependent upon the difference but not the absolute amplitude sensitivity between collicular and cortical neurons.

Acoustic Stimulation↗
PubMed2000

Telemetry as a new concept in long term monitoring of SIDS-risk infant.

Sudden Infant Death Syndrome (SIDS) is the most frequent cause of infant death within the period of 2 to 12 months in western countries. It has been found that a suit similar to that worn by the astronauts during the execution of experiments on the Spacelab Mission D-2 is a very simple and useful means to carry the sensors required to monitor vital signs of babies at risk. A small baby-suit has been developed with the same technology used for the Spacelab Mission. The baby s suit is equipped with similar sensors to record thoracic and abdominal respiratory movements as its big -space travel brother-. This is a typical example of a successful technology transfer from medical aerospace activities into fields of daily clinical routine. In addition to the above described sensors, ECG-electrodes were integrated, as well as sensors to record vascular oxygen saturation and the corresponding pulse curve, and the baby s movements. All these vital signs are registered by a medical monitor, and permanently stored and automatically analysed online. In case of a life-threatening situation the system alerts simultaneously the personal at hospital and the parents at home. The requisite software algorithms have been developed by DLR in Cooperation with the pediatricians of the Pediatric Hospital in Köln-Porz, Cologne. When the system registers an alteration of the parameters above described -as a signal of a change in the baby s health condition- all vital signs are transfered in real-time to the supervising hospital via radio data transmission devices, mobile phone or a fixed network phone. The parents are also alerted by the device, and they can carry out the necessary reanimation procedures in case of an emergency. Parents will be trained in such actions when newborns must to be monitored. But nevertheless, they are guided and tele-assisted by an expert via telephone during the action. A clinical field trial, that will start in December 1999 at the Pediatric Hospital in Köln-Porz, Cologne, will evaluate the benefits of teleprotection by home monitoring of SIDS risk-babies.

Humans↗
PubMed2001

Observations as to male fertility in the Flemish environment and health studies.

We report the observations made on 101 healthy non-smoking men aged 21-40 (50 from two industrial suburbs of the big city of Antwerp and 51 from Peer, a predominantly rural municipality with 14,622 inhabitants, 70 km east of Antwerp, chosen as the "control" area in spite of its intensive agriculture). Persons with known occupational exposures, persons working in a region with characteristics clearly different from the area of residence, and people commuting over long distances were excluded from the study. Sperm morphology was significantly worse in Peer than in Antwerp. Serum testosterone levels were significantly lower in Peer than in Antwerp. The proportions of men with very low and low serum testosterone levels, of men with very low and low spermatozoa concentrations and of men with very low and low percentages of spermatozoa with normal morphology, were all higher in Peer than in Antwerp. We speculate that both the lower testosterone concentrations and the poorer sperm quality are due to disturbance of the hypothalamic-pituitary-testicular function by hormone disrupters. Our data suggest that exposure to levels of environmental pollution which are widespread in developed nations, can have unfavourable effects on endocrine equilibrium and may disturb male fertiline disrupters.

Adult↗
PubMed2005

Molecular analysis of coat protein coding region of tobacco stunt virus shows that it is a strain of Lettuce big-vein virus in the genus Varicosavirus.

To evaluate the relationship between tobacco stunt virus (TStV) and Lettuce big-vein virus (LBVV), we determined nucleotide sequences of the coat protein (CP) coding region of five TStV and three LBVV isolates and compared them with those of one Japanese and four Spanish isolates of LBVV. CP coding regions were identical in size and the nucleotide and amino acid sequence identities between TStV and LBVV were 95.6-96.5% and 97.2-98.7%, respectively. Phylogenetic analysis of nucleotide sequences indicated that TStV was very closely related to LBVV and a strain of LBVV rather than a distinct species.

Amino Acid Sequence↗
PubMed2006

Membrane leakage induced by dynorphins.

Dynorphins, endogeneous opioid peptides, function as ligands to the opioid kappa receptors and induce non-opioid excitotoxic effects. Here we show that big dynorphin and dynorphin A, but not dynorphin B, cause leakage effects in large unilamellar phospholipid vesicles (LUVs). The effects parallel the previously studied potency of dynorphins to translocate through biological membranes. Calcein leakage caused by dynorphin A from LUVs with varying POPG/POPC molar ratios was promoted by higher phospholipid headgroup charges, suggesting that electrostatic interactions are important for the effects. A possibility that dynorphins generate non-opioid excitatory effects by inducing perturbations in the lipid bilayer of the plasma membrane is discussed.

Amino Acid Sequence↗
PubMed1990

Mode of cleavage of pig big endothelin-1 by chymotrypsin. Production and degradation of mature endothelin-1.

Pig endothelin-1 [ET-1-(1-21)] seems to be produced via proteolytic processing between Trp-21 and Val-22 of an intermediate form consisting of 39 amino acid residues, termed big ET-1-(1-39), by a chymotrypsin-like proteinase. We examined the chymotryptic-cleavage sites of big ET-1-(1-39) by reverse-phase h.p.l.c. and sequence analysis, and found that chymotrypsin cleaved initially the Tyr-31-Gly-32 bond of big ET-1-(1-39), followed by cleavage between Trp-21 and Val-22. Furthermore, chymotrypsin hydrolysed the generated ET-1-(1-21), producing a single major product that had the same amino acid sequence as ET-1-(1-21) with a cleavage between Tyr-13 and Phe-14. The disulphide bridge between Cys-1 and Cys-15 remained intact. These results indicate that the conversion of big ET-1-(1-39) into ET-1-(1-21) catalysed by chymotrypsin requires hydrolysis of the Tyr-31-Gly-32 bond before that of the Trp-21-Val-22 bond, an event followed by cleavage between Tyr-13 and Phe-14 within the loop of ET-1-(1-21). Thus a chymotrypsin-like proteinase might be involved not only in the production but also in the degradation of ET-1-(1-21) in vivo.

Amino Acid Sequence↗
PubMed1976

Stimulation of DNA synthesis by big and little gastrin (G-34 and G-17).

Fasted rats were injected six times over a 48-hr period with G-17 I, G-17 II, G-34 II in doses doubling from 3.38 nmoles per kg to 54 nmoles per kg. Twelve rats were studied at each dose. NaCl-injected animals were used as controls. The rats were killed and the in vitro incorporation of [3H]thymidine into DNA as well as the total DNA content of the mucosa of the duodenum and oxyntic gland area of the stomach were determined. All gastrins, as well as pentagastrin, stimulated DNA synthesis. Peak stimulation occurred at 13.5 nmoles per kg for G-17 I and G-17 II and at 6.75 nmoles per kg for G-34 II. Pentagastrin's peak trophic effect was produced by 325 nmoles per kg. In order to compare the efficacies of the various types of gastrins, 60 rats were divided into groups of 12. One group received saline and the other four groups received the maximally effective dose of one of the four types of gastrins. The responses to each of the gastrins were not significantly different, and DNA synthesis was doubled in each tissue. Total DNA content increased slightly, but significantly, in response to each gastrin. Several conclusions can be drawn from these data: (1) G-17 and G-34 possess trophic activity; (2) the efficacies of pentagastrin, G-17 I, G-17 II, and G-34 II for the stimulation of DNA synthesis are not significantly different; (3) sulfation of G-17 has no significant effect on its trophic activity; (4) based on the effects of exogenous molar doses and their respective half-lives, both G-17 and G-34 would be expected to contribute to the trophic effect of endogenous gastrin; and (5) G-17 and G-34 are at least as effective in stimulating DNA synthesis as they are in stimulating gastric acid secretion.

Animals↗
PubMed2005

Genomic peculiarity of coding sequences and metabolic potential of probiotic Escherichia coli strain Nissle 1917 inferred from raw genome data.

Probiotic Escherichia coli strain Nissle 1917 (O6:K5:H1) is a commensal E. coli isolate that has a long tradition in medicine for the treatment of various intestinal disorders in humans. To elucidate the molecular basis of its probiotic nature, we started sequencing the genome of this organism with a whole-genome shotgun approach. A 7.8-fold coverage of the genomic sequence has been generated and is now in the finishing stage. To exploit the genome data as early as possible and to generate hypotheses for functional studies, the unfinished sequencing data were analyzed in this work using a new method [Sun, J., Zeng, A.P., 2004. IdentiCS--identification of coding sequence and in silico reconstruction of the metabolic network directly from unannotated low-coverage bacterial genome sequence. BMC Bioinformatics 5, 112] which is particularly suitable for the prediction of coding sequences (CDSs) from unannotated genome sequence. The CDSs predicted for E. coli Nissle 1917 were compared with those of all five other sequenced E. coli strains (E. coli K-12 MG1655, E. coli K-12 W3110, E. coli CFT073, EHEC O157:H7 EDL933 and EHEC O157:H7 Sakai) published to date. Five thousand one hundred and ninety-two CDSs were predicted for E. coli Nissle 1917, of which 1065 were assigned with enzyme EC numbers. The comparison of all predicted CDSs of E. coli Nissle 1917 to the other E. coli strains revealed 108 CDSs specific for this isolate. They are organized as four big genome islands and many other smaller gene clusters. Based on CDSs with EC numbers for enzymes, the potential metabolic network of Nissle 1917 was reconstructed and compared to those of the other five E. coli strains. Overall, the comparative genomic analysis sheds light on the genomic peculiarity of the probiotic E. coli strain Nissle 1917 and is helpful for designing further functional studies long before the sequencing project is completely finished.

Chromosome Mapping↗
PubMed2004

Characterization of the MEK5-ERK5 module in human neutrophils and its relationship to ERK1/ERK2 in the chemotactic response.

The role of the extracellular signal-regulated kinase (ERK) 1 and ERK2 in the neutrophil chemotactic response remains to be identified since a previously used specific inhibitor of MEK1 and MEK2, PD98059, that was used to provide evidence for a role of ERK1 and ERK2 in regulating chemotaxis, has recently been reported to also inhibit MEK5. This issue is made more critical by our present finding that human neutrophils express mitogen-activated protein (MAP) kinase/ERK kinase (MEK)5 and ERK5 (Big MAP kinase), and that their activities were stimulated by the bacterial tripeptide, formyl methionyl-leucyl-phenylalanine (fMLP). Dose response studies demonstrated a bell-shaped profile of fMLP-stimulated MEK5 and ERK5 activation, but this was left-shifted when compared with the profile of fMLP-stimulated chemotaxis. Kinetics studies demonstrated increases in kinase activity within 2 min, peaking at 3-5 min, and MEK5 activation was more persistent than that of ERK5. There were some similarities as well as differences in the pattern of activation between fMLP-stimulated ERK1 and ERK2, and MEK5-ERK5 activation. The up-regulation of MEK5-ERK5 activities was dependent on phosphatidylinositol 3-kinase. Studies with the recently described specific MEK inhibitor, PD184352, at concentrations that inhibited ERK1 and ERK2 but not ERK5 activity demonstrate that the ERK1 and ERK2 modules were involved in regulating fMLP-stimulated chemotaxis and chemokinesis. Our data suggest that the MEK5-ERK5 module is likely to regulate neutrophil responses at very low chemoattractant concentrations whereas at higher concentrations, a shift to the ERK1/ERK2 and p38 modules is apparent.

Chemotaxis↗
PubMed1993

Metabolism of endothelin-1 and big endothelin-1 by recombinant neutral endopeptidase EC.3.4.24.11.

1. Inhibitors of neutral endopeptidase EC.3.4.24.11 (NEP) have been shown to attenuate the hypertensive effect of big-endothelin-1 (BET-1) in rats. To determine whether NEP converts BET-1 to endothelin-1 (ET-1), the effect of a recombinant NEP (rNEP) on BET-1 and on ET-1 was assessed in vitro. 2. Incubation of [125I]-ET-1 with 1 microgram ml-1 of rNEP resulted in degradation of the peptide within minutes. Increase in the amount of rNEP to 10 micrograms ml-1 led to total cleavage of [125I]-ET-1 within seconds. 3. Phosphoramidon (10 microM) or SQ-28,603 (100 microM) totally suppressed the degradation of [125I]-ET-1 by rNEP. 4. The degradation of [125I]-BET-1 by either 1 or 10 micrograms ml-1 of rNEP was much slower than that of [125I]-ET-1. Again, both phosphoramidon and SQ 28,603 protected the peptide from degradation. 5. Intact [125I]-ET-1 was not observed when [125I]-BET-1 was incubated with rNEP. 6. These data show that neutral endopeptidase EC.3.4.24.11 is not an endothelin converting enzyme.

Alanine↗
PubMed1998

Fibrocartilages in the extensor tendons of the interphalangeal joints of human toes.

The extensor tendons of the fingers and toes form part of the capsule of the interphalangeal joint and press against the proximal phalanx during flexion. Previous work on the fingers has shown that there is a "sesamoid" fibrocartilage on the deep surface of each tendon that labels immunohistochemically for a variety of glycosaminoglycans and collagens. However, we know little about the molecular composition of the tendon in the toes. This question is of special interest, because the mechanics of the interphalangeal joints differ in the upper and lower limbs-the toes balance the forefoot, distribute load during the gait cycle, and transmit the pull of larger muscles. This means that their extensor tendons are more often under higher tension than those in the fingers. Here, we report the presence of an equivalent fibrocartilage and compare its immunolabelling characteristics in all the toes. Six forefeet were removed from elderly cadavers, and the interphalangeal (IP) joints were fixed in 90% methanol. The extensor tendon and its enthesis were dissected out from the IP joint of the big toe and from the proximal interphalangeal (PIP) joint of all lesser toes, decalcified, cryosectioned, and immunolabelled with a panel of monoclonal and polyclonal antibodies for type I, II, III, and VI collagens; chondroitin 4 and 6 sulphates; and dermatan and keratan sulphate. Antibody binding was detected with the Vectastain ABC Elite avidin-biotin-peroxidase kit (Vector Laboratories, Burlingame, CA). The extensor tendon in all the toes had a metachromatic, sesamoid fibrocartilage on its deep surface that immunolabelled for all glycosaminoglycans and for type I, III, and VI collagens. Labelling for type II collagen was seen in the sesamoid fibrocartilage of all toes but was particularly characteristic of the 2nd through 5th toes. The immunolabelling patterns of the enthesis fibrocartilage were similar in all toes and to results reported previously for fingers. The normal occurrence of type II collagen in the sesamoid fibrocartilage of the 2nd through 5th toes is in contrast to our published data on the fingers. The finding can be related to the more constant loading of the tendon in the toes. The greater prominence of type II collagen in the sesamoid fibrocartilage of the 2nd through 5th toes could be related to a difference in joint position during walking between the 1st toe and the 2nd through 5th toes--the PIP joints of the latter are usually more flexed than the IP joint of the former.

Adult↗
PubMed1991

Endothelin-1 is expressed and released by a human endothelial hybrid cell line (EA.hy 926).

A permanent vascular endothelial cell line, EA.hy 926, was shown to express endothelin-1 (ET-1) mRNA and to secrete big ET-1 and ET-1 into culture medium. The concentration of both big ET-1 and ET-1 was significantly increased in EA.hy 926 culture medium by phosphoramidon, a metalloproteinase inhibitor, suggesting that phosphoramidon sensitive protease(s) may be responsible for the degradation of ET-1 and big ET-1. EA.hy 926 cells responded to various regulators of ET-1 similarly as primary human vascular endothelial cells. The production of ET-1 was increased by thrombin and decreased by vasodilators such as atrial natriuretic peptide, brain natriuretic peptide and nitroprusside, and by 8-bromo cyclic GMP and papaverine. This continuous human endothelial hybrid cell line could facilitate studies of regulation of ET-1 production in human endothelial cells, which in primary cultures have limited replication potential.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Pulse repetition rate increases the minimum threshold and latency of auditory neurons.

The effect of pulse repetition rate on auditory sensitivity of the big brown bat, Eptesicus fuscus, was studied by determining the minimum threshold, response latency and recovery cycle of inferior collicular neurons at different repetition rates under free field stimulation conditions. In general, collicular neurons shortened the response latency and increased the number of impulses monotonically or non-monotonically with stimulus intensity. They recovered at least 50% when the interpulse interval was 10-57 ms. In addition, they increased the minimum threshold, lengthened the response latency, and reduced the number of impulses discharged to each pulse with increasing repetition rate. The increase in minimum threshold with repetition rate is partly because the neuron can not recover from previous stimulation when the interpulse interval is shortened. This increase reduces a neuron's response sensitivity and thus diminishes its number of impulses to each presented pulse. This increase also reduces the effectiveness of a given stimulus intensity which contributes to the lengthening of the neuron's response latency. Data obtained from single neuron recordings are used to highlight these observations. Implications of present findings regarding the bat's echolocation are also discussed.

Acoustic Stimulation↗