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PubMed1980

Prophage induction in a permeabilized cell system: induction by deoxyribonucleases and the role of recBC-deoxyribonuclease.

Permeabilized cells able to induce prophage were obtained by plasmolysis and preincubation of the cells in a reaction mixture which allows protein synthesis. These cells became permeable to low-molecular-weight proteins and oligonucleotides. We found that deoxyribonucleases (pancreatic deoxyribonuclease and micrococcal nuclease) triggered prophage (phi 80) induction. This deoxyribonuclease-triggered induction was completely dependent upon the presence of functional recBC genes in the lysogen, regardless of the recombination proficiency determined by recBC and sbcB genes. The possible role of recBC-deoxyribonuclease in prophage induction and recombination is discussed.

Alleles↗

PubMed1997

DNA immunization: ubiquitination of a viral protein enhances cytotoxic T-lymphocyte induction and antiviral protection but abrogates antibody induction.

DNA immunization can induce cytotoxic T lymphocytes (CTL), antibodies, and protection against microbial challenge. The underlying mechanisms remain obscure and must be understood to permit rational manipulation and optimization of the technique. We set out to enhance the intracellular degradation of a viral antigen, with the intent of improving antigen entry into, and presentation by, the class I major histocompatibility complex pathway. We achieved this goal by cotranslational ubiquitination of a plasmid-encoded viral antigen, lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP). We show that native NP is very stable in cell culture, while the ubiquitinated product is so rapidly degraded that it is barely detectable. This rapid degradation leads to more efficient sensitization of target cells in an in vitro cytotoxicity assay, consistent with enhanced antigen presentation, and both degradation and target cell recognition are blocked by a proteasome inhibitor. We have used the plasmid for in vivo studies and find that, remarkably, ubiquitination leads to a complete abrogation of antibody responses, presumably because the encoded protein is so rapidly and completely degraded that insufficient antigen remains to interact appropriately with B cells. In contrast, in vivo CTL induction is improved by ubiquitination of NP. That CTL are induced at all by this rapidly degraded protein may shed light on the mechanism by which CTL are induced by DNA immunization; it has been suggested that CTL induction following intramuscular DNA injection results not from antigen presentation by cells taking up and expressing the DNA but rather from uptake of soluble protein by specialized antigen-presenting cells (APC). It appears to us unlikely that the ubiquitinated protein could function in this manner, since it is so rapidly degraded in vitro and fails to induce antibodies in vivo. Finally, the ubiquitinated protein confers markedly enhanced protection against LCMV challenge. Mice immunized with a plasmid encoding NP show approximately 100-fold reductions in virus titers compared to controls, while mice immunized with a plasmid encoding the ubiquitinated NP show reductions in virus load of at least 5 x 10(4)- to 5 x 10(5)-fold. This is by far the most effective DNA vaccine that we have yet designed. Ubiquitination therefore may improve DNA immunization, but caution is warranted, since immunity to many microbes depends on induction of good humoral immunity, and we show here that this may be prevented by ubiquitination of the encoded protein.

Animals↗

PubMed2004

Mutation of all Runx (AML1/core) sites in the enhancer of T-lymphomagenic SL3-3 murine leukemia virus unmasks a significant potential for myeloid leukemia induction and favors enhancer evolution toward induction of other disease patterns.

SL3-3 murine leukemia virus is a potent inducer of T-lymphomas in mice. Using inbred NMRI mice, it was previously reported that a mutant of SL3-3 with all enhancer Runx (AML1/core) sites disrupted by 3-bp mutations (SL3-3dm) induces predominantly non-T-cell tumors with severely extended latency (S. Ethelberg, J. Lovmand, J. Schmidt, A. Luz, and F. S. Pedersen, J. Virol. 71:7273-7280, 1997). By use of three-color flow cytometry and molecular and histopathological analyses, we have now performed a detailed phenotypic characterization of SL3-3- and SL3-3dm-induced tumors in this mouse strain. All wild-type induced tumors had clonal T-cell receptor beta rearrangements, and the vast majority were CD3(+) CD4(+) CD8(-) T-lymphomas. Such a consistent phenotypic pattern is unusual for murine leukemia virus-induced T-lymphomas. The mutant virus induced malignancies of four distinct hematopoietic lineages: myeloid, T lymphoid, B lymphoid, and erythroid. The most common disease was myeloid leukemia with maturation. Thus, mutation of all Runx motifs in the enhancer of SL3-3 severely impedes viral T-lymphomagenicity and thereby discloses a considerable and formerly unappreciated potential of this virus for myeloid leukemia induction. Proviral enhancers with complex structural alterations (deletions, insertions, and/or duplications) were found in most SL3-3dm-induced T-lymphoid tumors and immature myeloid leukemias but not in any cases of myeloid leukemia with maturation, mature B-lymphoma, or erythroleukemia. Altogether, our results indicate that the SL3-3dm enhancer in itself promotes induction of myeloid leukemia with maturation but that structural changes may arise in vivo and redirect viral disease specificity to induction of T-lymphoid or immature myeloid leukemias, which typically develop with moderately shorter latencies.

Animals↗

PubMed1989

Autocrine induction of major histocompatibility complex class I antigen expression results from induction of beta interferon in oncogene-transformed BALB/c-3T3 cells.

By varying growth conditions, we identified a novel mechanism of autocrine regulation of major histocompatibility complex (MHC) class I gene expression by induction of beta interferon gene expression in transformed BALB/c-3T3 cells. Low-serum conditions enhanced MHC class I antigen expression in v-rasKi- and v-mos-transformed BALB/c-3T3 cells but not in untransformed BALB/c-3T3 cells. Transformed and untransformed cells grown under standard serum conditions (10% bovine calf serum) expressed similar cell surface levels of MHC class I antigens. However, low-serum conditions (0.5% bovine calf serum) induced four- to ninefold increases in cell surface levels of MHC class I antigens in both v-rasKi- and v-mos-transformed cells but not in untransformed cells. These increases in MHC class I gene expression were seen at both the mRNA and cell surface protein levels and involved not only the heavy-chain component of the class I antigens but also beta 2 microglobulin. Beta 1 interferon mRNA and beta interferon-inducible 2',5'-oligoadenylate synthetase mRNA were induced by growth under low-serum conditions in transformed BALB/c-3T3 cells, and antibodies to beta interferon blocked the induction of MHC class I antigen expression by serum deprivation in these cells. These results demonstrate that growth under low-serum conditions leads to induction of beta interferon expression in oncogene-transformed cells which then directly mediates autocrine enhancement of MHC class I gene expression.

2',5'-Oligoadenylate Synthetase↗

PubMed1992

Hypnoanalgesia for chronic pain: the response to multiple inductions at one session and to separate single inductions.

Serial hypnotic inductions conveying the same analgesic message produce a progressively longer response in an increasing number of patients. The resulting analgesia appears to be independent of the spacing of inductions--whether given at a single session or on separate occasions--and to depend upon their number. However, multiple inductions at a single session save time. Elimination of pain can be achieved, by either approach, for a year or more in up to 70% of patients.

Adolescent↗

PubMed1993

Induction of anesthesia with sevoflurane, nitrous oxide, and oxygen: a comparison of spontaneous ventilation and vital capacity rapid inhalation induction (VCRII) techniques.

In this study, the vital capacity rapid inhalation induction of anesthesia (VCRII) technique and the conventional spontaneous inhalation induction technique, each using 4.5% sevoflurane in nitrous oxide and oxygen, were compared. The VSRII group (n = 32) and conventional group (n = 32) were each tested on unpremedicated volunteers. VCRII required only half the time of conventional inhalation induction (54 s and 108 s, respectively), and was not associated with cardiovascular instability. Each of the two techniques was found acceptable by most of the volunteers studied (more than 80%). However, sevoflurane is best used with the VCRII technique because VCRII resulted in fewer excitement movements that could lead to severe complications and pronounced excitement.

Adult↗

PubMed1988

Induction of HLA-DR antigen on human squamous carcinoma by recombinant interferon gamma.

The antigen recognition system which plays the major role in immunologic attraction mechanisms, including graft rejection, is the class II major histocompatibility complex containing the HLA-DR locus. Few types of cells constitutively express this antigen, as it is a potent immunological activating signal usually confined to antigen processing cells, activated lymphocytes, and endothelium. Using indirect immunofluorescence, we have observed induction of the HLA-DR glycoprotein in selected head and neck squamous cell carcinoma tissue cultures treated with recombinant interferon gamma. This occurs in concert with growth arrest and morphological changes after rHuIFN-gamma treatment. This report describes the induction of a surface antigen that may have profound prognostic significance. Understanding the kinetics of HLA-DR induction will aid in the design and assessment of adoptive immunotherapy with rHuIFN-gamma.

Carcinoma, Squamous Cell↗

PubMed2005

Induction effects for heterochromatic brightness matching, heterochromatic flicker photometry, and minimally distinct border: implications for the neural mechanisms underlying induction.

Brightness induction refers to the finding that the apparent brightness of a stimulus changes when surrounded by a black versus a white stimulus. In the current study, we investigated the effects of black/white surrounding stimuli on settings made between red and green stimuli on three different tasks: heterochromatic brightness matching (HBM), heterochromatic flicker photometry (HFP), and minimally distinct border (MDB). For HBM, subjects varied the relative luminance between the red and green stimuli so that the brightness of the two colors appeared equal. For the two other tasks, matches were made based on minimizing red/green flicker (HFP) or the saliency of a red/green border (MDB). For all three tasks, the presence of black/white surrounding stimuli significantly altered red/green settings, demonstrating the existence of induction effects. These results are discussed in terms of which underlying color pathways (L+ M versus L-M) may contribute to induction effects for the different tasks.

Adaptation, Ocular↗

PubMed1987

Induction of labor: a prospective, randomized study into amniotomy and oxytocin as induction methods in a total unselected population.

All women (n = 223) scheduled for induction of labor were randomized into start with oxcytocin infusion (O) or amniotomy (A). After 4 h an assessment of the progress and prognosis was made. If the progress was not acceptable O was added to A and A to O. Oxcytocin alone showed the lowest frequency of delivered patients. The "amniotomy only" group showed the shortest duration of delivery. The frequency of complications was low but somewhat higher when the initial step was oxcytocin. Oxcytocin alone is not a good method for induction. Early evaluation of the progress and prognosis of the induction is difficult. The combination of amniotomy and oxcytocin seem to be more essential than the choice of initial step. If, however, an infusion of oxcytocin is the first proceeding, amniotomy should be added on a routine basis and without delay. Bishop score is not a conclusive measure of the readiness of uterus to go into labor. Parity may partly be the explanation but other today unknown factors are probably involved in the inducibility.

Amnion↗

PubMed1999

Pieter Nieuwkoop's contributions to the understanding of meso-endoderm induction and neural induction in chordate development.

Pieter Nieuwkoop, who died September 18, 1996, at age 79 in Utrecht, The Netherlands, is remembered by developmental biologists for his numerous research contributions and integrative hypotheses over the past 50 years, especially in the areas of neural induction, meso-endoderm induction, and germ cell induction in chordates. Most of his experimentation was done on the embryos of amphibia, the preferred vertebrate embryo of the early years of the 20th century. One of his last publications contains a comparison of the experimental advantages and disadvantages of anuran and urodele amphibians (Nieuwkoop, 1996). The significance of his findings and interpretations for developmental biology can be estimated from the fact that researchers of many laboratories worldwide continue to work on the phenomena he first described and to extend the hypotheses he first formulated. The aim of this article is to review Nieuwkoop's main contributions and to cite the recent extensions by others.

Animals↗

PubMed2002

[Expression of Fas and induction of apoptosis by anti-Fas monoclonal antibody in human bile duct carcinoma cells, and enhancement of induction of apoptosis by IFN-gamma].

We investigated the expression of Fas, the induction of apoptosis by anti-Fas monoclonal antibody CH-11, and the effect of IFN-gamma on the induction of apoptosis in human bile duct carcinoma cells HuCCT1 and HuH28. Fas was expressed in 21.7% and 30.9% of HuCCT1 and HuH28 cells, respectively. Pretreatment with IFN-gamma increased the Fas expression by 17.6% in HuCCT1 cells. However, IFN-gamma did not affect the expression of Fas in HuH28 cells. In HuCCT1 and HuH28 cells treated with CH-11, the peak corresponding to that of positive control cells was detected with the TUNEL method by FCM. The condensation and fragmentation of the nucleus, and the apoptotic body were observed as morphological changes specific to apoptosis. CH-11 dose-dependently reduced HuCCT1 and HuH28 cell counts by up to 16.4% and 71.7%, respectively on day 3. Interferon-gamma attenuated the reduction of HuCCT1 cell counts by 12.8% on day 3. However, IFN-gamma had no effect on HuH28 cell counts. These results suggest that Fas was expressed, apoptosis was induced by CH-11 and the induction of apoptosis was enhanced by IFN-gamma in human bile duct carcinoma cells.

Antibodies, Monoclonal↗

PubMed2003

[Occupational exposure of operating room staff to anesthetic gases during inhaled induction--a comparison with intravenous anesthesia induction].

BACKGROUND: The risk of occupational exposure to waste anesthetic gases still remains during inhaled induction. In this study we investigated how much we were occupationally exposed to anesthetic gases during induction period. METHODS: Twenty-six adult patients were induced with sevoflurane 5% using a face mask for three minutes and maintained with sevoflurane 1% after end-tracheal intubations (IH-Group). Twenty-two adult patients were induced with intravenous anesthetics and maintained with sevoflurane 1% after end-tracheal intubations(IV-Group). The concentration of sevoflurane was measured by Multi-gas Monitor 1302 (Bruel & Kjaer: Denmark) every 70 seconds. Sample gas was suctioned from breathing zone of anesthesiologists. All of our operating rooms are equipped with waste gas scavenging system. RESULTS: The peak concentration of sevoflurane is significantly higher in IH-Group (15.91 +/- 22.64 ppm) compared with IV-group (0.36 +/- 0.25 ppm). The period when sevoflurane concentration exceeded 0.5 ppm is significantly longer IH-Group (18.55 +/- 10.51 min.) compared to IV-Group (1.92 +/- 4.56 min.). CONCLUSION: The induction with intravenous anesthetics is a better method in order to reduce occupational exposure of anesthesiologists to anesthetic gases.

Adult↗

PubMed1992

Role of fos-AP-1 binding sequence (FAP) in the induction of c-fos expression by purified C-kinase and in c-fos down-regulation following serum induction.

Microinjection of purified calcium phospholipid-dependent protein kinase (C-kinase) resulted in the rapid and transient induction of c-fos in quiescent rat embryo fibroblats. This C-kinase-induced expression of c-fos was prevented by in vivo competition using co-injection of oligonucleotides corresponding to the sequence of either the serum response element (SRE) or the fos AP-1 binding sequence (FAP) adjacent to SRE. This indicates that both these sequences must be involved in the binding/activation of protein factors required for the induction of c-fos by C-kinase. In contrast, the induction of c-fos by serum or by casein kinase II microinjection, which is also inhibited by injection of SRE oligonucleotides, is only delayed and then markedly prolonged by injecting TRE/FAP sequence, demonstrating that the FAP site plays a prominent role in vivo in the down-regulation of the endogenous c-fos gene expression.

Animals↗

PubMed1989

[Artificial induction of labor at term for medical reasons. Comparison of 2 technics for labor induction, oxytocin + early artificial rupture of the membranes versus prostaglandin E2 vaginal gel. Open randomized controlled study].

Labor induction for medical reasons is a situation rather well-controlled by the combination: "oxytocin-amniotomy" when the cervix is favorably open. However, new induction techniques are currently under study, especially vaginal administration of PGE2 which presents the advantage of being simple to administer and better accepted by the patients. This study compared the classical technique, oxytocin perfusion and early artificial rupture of the membranes, with the vaginal administration of PGE2 gel (first dose: 1 mg, second dose 1 or 2 mg, six hours later). The success rate of both techniques is comparable, approximately 70 p. cent. Also, the times between amniotomy and delivery are identical, approximately 5 hours. On the contrary, the lapses of time between the onset of the induction and the delivery, vary significantly, being always longer in the PGE2 group. However, the dose of vaginal PGE2 gel as well as the time of artificial membrane rupture could be modified in order to decrease the delay of the effect.

Administration, Intravaginal↗

PubMed1986

Prostaglandin E counteracts the gamma interferon induction of major histocompatibility complex class-II antigens on U937 cells and induction of responsiveness of U937 colony-forming cells to suppression by lactoferrin, transferrin, acidic isoferritins, and prostaglandin E.

The established human monoblast or early monocyte cell line, U937, was evaluated for modulating influences of prostaglandin E2 (PGE2) on human gamma interferon (HuIFN gamma) induction of MHC class-II (Ia) antigens on U937 cells and the HuIFN gamma induction of responsiveness of U937 colony-forming cells (CFC) to inhibition by lactoferrin (LF), transferrin (TF), acidic isoferritins (AIF), and prostaglandin E (PGE). U937 CFC were induced to a state of responsiveness to the suppressive influences of PGE by HuIFN gamma. When MHC class-II antigens were induced on U937 cells and the cells sorted on the fluorescence activated cell sorter (FACS) IV into positive and negative cells, colony formation by the MHC class-II antigen+ population of cells was suppressed by LF, TF, AIF, and PGE2. Colony formation by the sorted population of MHC class-II antigen- cells was not influenced significantly by LF, TF, AIF, or PGE2. When PGE was present in the suspension culture for 72 h with U937 cells exposed to HuIFN gamma plus indomethacin, it blocked the induction of MHC class-II antigens as well as the associated inhibition of U937 CFC by LF, TF, AIF, and PGE2.

Cell Line↗

PubMed1987

Induction of general anesthesia in children with midazolam--is there an induction dose?

The pharmacodynamics of midazolam was studied in 27 children undergoing elective surgery at five different dose levels (0.075-0.6 mg/kg) in attempting to find a suitable induction dose for general anesthesia. A comparison of the highest dose was made to thiopentone 5 mg/kg. Even an induction dose of 0.6 mg/kg of midazolam was found to be unreliable in children, but effective enough to cause significant fall in systolic blood pressure after induction (p less than 0.05). In the children premedicated with atropine and pethidine thiopentone resulted in a more rapid closure of the eyes (p less than 0.01) and disappearance of the eye-lid reflex (p less than 0.01) than the high dose of 0.6 mg/kg of midazolam. Moreover, midazolam failed to induce sleep in a considerable fraction of the children even at the highest dose employed. The thiopentone group was more alert in the recovery room at 30 min after wake-up. The amnestic effect of thiopentone and midazolam were equal.

Anesthesia, General↗

PubMed1992

Whether cytochrome P450 induction accompanies glucuronosyl and glutathione transferase induction by isomers of dipyridyl appears unrelated to dose and iron chelation properties.

Administration of 4,4'dipyridyl to rats induces the activities of xenobiotic transferases (phase II drug metabolizing enzymes), UDP-glucuronosyl-transferase and glutathione-S-transferase, and also the concentration and activity of cytochrome P450 (a phase I drug metabolizing enzyme). 2,2'Dipyridyl, an isomer possessing iron chelation properties, only induces the phase II enzymes. Although the magnitude of the phase II induction by 2,2'dipyridyl increases with increasing dosages, the selective induction of only phase II activities remains inviolate. Co-administration of 2,2'dipyridyl does not prevent 4,4'dipyridyl from inducing cytochrome P450, suggesting that the iron chelation property is not the factor that precludes 2,2'dipyridyl from coordinately inducing cytochrome P450 with the transferases.

2,2'-Dipyridyl↗

PubMed1998

Mechanism of the synergistic induction of CYP2H by isopentanol plus ethanol: comparison to glutethimide and relation to induction of 5-aminolevulinate synthase.

We had previously found that combined treatment with isopentanol and ethanol synergistically induced CYP2H protein and activity in cultured chick nepatoytes. Here we investigated the mechanism of induction of CYP2H by the alcohols and whether they caused a coordinate induction of 5-aminolevulinate synthase (ALAS) mRNA. Treatment with isopentanol alone or in combination with ethanol resulted in coordinate increases in CYP2H1 and ALAS mRNAs. With isopentanol alone, the amounts of CYP2H1 and ALAS mRNAs at 4 to 6 h were similar to those observed after treatment with the alcohol combination, but declined by 11 h. Readdition of isopentanol at 11 h again increased the expression of both mRNAs, indicating that the decreases at 11 h were due to limiting amounts of inducer. Similar results were observed in cells exposed to low concentrations of glutethimide. In the combined alcohol treatment, increases in CYP2H1 and ALAS mRNAs were sustained from 4 h to 11 h after addition of the alcohols, but decreased to control levels by 24 h. Using pulse labeling to measure de novo synthesis of CYP2H1/2 protein, we found that the increases in CYP2H1/2 protein reflected the increases in CYP2H1 mRNA. The half-life of CYP2H1/2 protein, measured from pulse-chase experiments, was approximately twofold greater than the half-life of CYP2H1 mRNA. Our results indicate that the alcohols and glutethimide coordinately increase ALAS and CYP2H1 mRNA, and that increases in CYP2H1/2 protein arise from increases in its mRNA.

5-Aminolevulinate Synthetase↗