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Induction of early growth response-1 gene by interleukin-1 beta and tumor necrosis factor-alpha in normal human bone marrow stromal an osteoblastic cells: regulation by a protein kinase C inhibitor.

The early growth response-1 (Egr-1) gene has been identified as a nuclear transcriptional factor and implicated in the regulation of growth and differentiation of osteoblastic cells. In the present study, we investigated whether Egr-1 mRNA is expressed and induced by interleukin-1 beta, (IL-beta) and tumor necrosis factor-alpha (TNF-alpha) in normal human bone marrow stromal (HBMS) and osteoblastic (HOB) cells. Results demonstrate a very low basal expression of Egr-I mRNA which is induced by IL-1 beta, and TNF-alpha in a time- and dose-dependent manner. Egr-1 mRNA induction was detectable within 15 min, reached maximal by 60 min and thereafter declined to basal levels by 120 min. Induction of Egr-1 mRNA by IL-1 beta and TNF-alpha was completely inhibited by H-7 suggesting the mediation of protein kinase C. The induction by IL-1 beta and TNF-alpha of Egr-1 mRNA was independent of de novo protein synthesis since this induction was also observed in the presence of protein synthesis inhibitor cycloheximide. Fetal bovine serum and cycloheximide also independently induced the Egr-1 mRNA. Actinomycin D experiments demonstrated that Egr-1 mRNA is degraded very rapidly with a half-life of 30 min. Our results demonstrate the expression of Egr-1 gene and its induction by IL-1 beta, and TNF-alpha in normal human bone marrow stromal (osteoprogenitor) and osteoblastic cells in primary cultures. Data also reveal that the expression of Egr-1 gene is inhibited by protein kinase C inhibitor H-7 suggesting that the activation of protein kinase C or other protein kinases resulting in the phosphorylation of specific transcription factor(s) is the first immediate early step in the induction of immediate-early Egr-1 gene by IL-1 beta, and TNF-alpha. Results also suggest that Egr-1 is an important mediator of IL-1 beta and TNF-alpha action in normal human osteoblastic cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Darkness induction, retinex and cooperative mechanisms in vision.

We have investigated the darkness induction of surround fields of various composition on a centrally located test field. Darkness induction can be described as a linear subtraction of the luminance of the induction region from the test field luminance, weighted for the size, the length of immediate contact and the distance of the induction field from the test field. Furthermore, closer induction fields exert a shunting effect on the induction effect of fields which are more distally located on the same radius, and neighbouring fields mutually interact. A model is discussed which takes into account these variables. It is compared with older models as well as with the Retinex-model as formulated by Land (1983). Our data and model are closer to the model of Jameson and Hurvich (1964). Neurophysiological correlates and mechanisms are discussed.

Adult↗

Induction of lambdoid prophages by amino acid deprivation: differential inducibility; role of recA.

Lambda prophage in auxotrophic lysogens can be induced by omission of one or combinations of the required amino acids from the culture medium. Such amino acid deprivation can result in nearly as effective induction of lambda as thymine deprivation. Prophage 424 is also induced equally effectively under both conditions although to a lesser extent than lambda. By contrast prophage 21 and lambda i21 are differentially induced effectively by thymine deprivation and virtually not at all during amino acid deprivation. The same differential induction of 21 and equivalent induction of lambda and 424 occur when all three prophages are present in the same lysogen. Increasing the levels of lambda repressor with a cI carrying-plasmid prevented amino acidless induction of lambda as did the lambda ind- mutation. A recA, but not a recB, mutation in the host prevented induction by amino acid deprivation. A recC mutant host showed increased spontaneous induction of lambda and 21 prophages. The findings reported are used as an argument that the recA protease probably is not itself acting as the inducing protease and that a likely source of the observed specificity is an effector molecule. Different effector molecules may be produced in response to different exigent situations, to which the phage repressors may have evolved sensitivity. lambda i80 was inducible both by amino acid and thymine deprivation.

Amino Acids↗

Isolation and physical mapping of temperature-sensitive mutants defective in heat-shock induction of proteins in Escherichia coli.

Mutants of Escherichia coli K12 that are partially or totally defective in induction of major heat-shock proteins and cannot grow at high temperature (42 degrees C) were isolated by localized mutagenesis. These mutants carry a single mutation in the gene htp R (formerly hin) located at min 76 on the E. coli genetic map. Some mutants exhibit delayed (partial) induction of heat-shock proteins or require a higher temperature for induction than the wild type, whereas others are not induced under any of these conditions. The maximum temperature that allows growth varies among different mutants and is correlated with the residual induction capacity. Temperature-resistant revertants obtained from each mutant are fully or partially recovered in heat-shock induction. These results indicate that the inability of htp R mutants to grow at high temperature is due to the defect in heat-shock induction. In addition, a couple of mutants was found that produce significantly higher amounts of heat-shock proteins even at 30 degrees C. The htp R gene has been cloned into plasmid pBR322 using the above mutants, and was localized to a DNA segment of 1.6 kilobase pairs. The mutants harboring certain plasmids that carry a part of htp R produce temperature-resistant recombinants at high frequency. This permits further localization of mutations within the htp R gene. Analysis of proteins encoded by each of the recombinant plasmids including the one carrying a previously isolated amber mutation (htp R165) led to the identification of a protein with an apparent molecular weight of about 36,000 daltons as the htp R gene product.

Bacterial Proteins↗

[The influence of role induction on the success of systematic desensitization of socially anxious students (author's transl)].

The so-called nonspecific factors involved in therapy have received little attention up to the present - namely, that of role induction (preparing the clients for treatment by informing them about the rationale of treatment, the treatment process, and their part in therapy). For this reason, we constructed an induction text for systematic desensitization according to the principles of instructional psychology (Ausubel), and proceeded to test it for understandability and therapeutic effectiveness. With control group design which assured the realization of the independent variable of role induction, the effective results of desensitization with role induction were compared both with those of simple desensitization and those of a waiting control group. The resultant differences in the group with role induction indicate the additional advantages of this technique for therapy. Essentially, role induction seems to manifest itself in terms of a contribution to more active, independent role formation on the part of the client.

Adult↗

Capacitive and inductive low frequency impedances of Necturus gallbladder epithelium.

The electrical impedance of Necturus gallbladder epithelium was analysed in the frequency range 0.24 Hz to 6,323 Hz. Under control conditions (NaCl-Ringer's on both sides), the impedance function yields a semicircle with depressed center. When serosal Na+ was replaced by K+, an inductive low frequency (LF) component appeared in the impedance locus. With KCl-Ringer on the mucosal side a second circular arc was observed at frequencies below 1 Hz. The resistive parts of the capacitive and inductive LF components increased after application of TAP+ to the mucosal side. Both LF features were abolished after application of 5 mM TEA+ to the mucosal medium as well as after acidification of the mucosal side. The LF components were depressed by addition of 5 mM Ba2+ to the mucosal solution. As TEA+ blocks apical K+ channels (Van Driessche and Gögelein 1978), it is concluded that the capacitive as well as the inductive LF components are related to transcellular K+ flow. With KCl-Ringer on the mucosal side, mucosa negative potentials increased the equivalent resistance and decreased the equivalent capacitance of the LF impedance. With serosal KCl-Ringer, negative potentials evoked a capacitive component which overlapped with the inductive component observed at open circuit conditions. Positive potentials, however, abolished the capacitive as well as the inductive LF component, elicited by mucosal or serosal KCl-Ringer, respectively. These results demonstrate that serosa to mucosa directed K+ flow causes an inductive LF feature and that mucosa negative potentials elicit a capacitive LF component.

Animals↗

Differential down-regulation and induction responses of testicular steroidogenic cytochromes P-450(cscc) and P-450(C17 alpha) to human choriogonadotropin.

Evidence is presented that the regulation of the cytochrome P-450(C17 alpha) of the steroid-17 alpha-monooxygenase and of the cytochrome P-450(cscc) of the cholesterol-monooxygenase by human choriogonadotropin (hCG) in vivo is mediated by differential mechanisms in the adult rat testis. An initial down-regulation of the cytochrome P-450(C17 alpha) but not of the P-450(cscc) can be demonstrated. Furthermore, induction of the cytochrome P-450(cscc) requires exposure to higher hCG doses (32% of the maximal induction rate of 43.7 pmol/(testis x d) are achieved with 4IU hCG/single dose) than induction of the P-450(C17 alpha) (59% of the maximal induction rate of 48.4 pmol/(testis x d) with 4IU hCG/single dose). Finally, induction of cytochrome P-450(cscc) starts faster after initiation of hCG treatment than induction of P-450(C17 alpha).

Animals↗

Induction of lymphokine-activated killer activity in rat splenocyte cultures: the importance of 2-mercaptoethanol and indomethacin.

The role of 2-mercaptoethanol and indomethacin in the induction of lymphokine-activated killer (LAK) activity by interleukin-2 (IL-2) in rat splenocyte cultures was investigated. Spleens from 4-month-old male rats of five different strains were tested. Splenocytes were cultured for 3-5 days in the presence of IL-2 (1000 U/ml) and LAK activity was assessed by 4-h 51Cr release assays with P815 and YAC-1 cells as targets. LAK activity could be induced by IL-2 in splenocytes from all rat strains, but only when 2-mercaptoethanol was present in the culture medium. Optimal LAK activity was induced when the 2-mercaptoethanol concentration in splenocyte cultures was at least 5 microM. Different rat strains showed differences in levels of in vitro induction of LAK activity. In the presence of 2-mercaptoethanol the level of LAK activity induced by IL-2 was high in BN and Lewis rats, intermediate in Wistar and Wag rats, and low in DZB rats. In the absence of 2-mercaptoethanol no or minimal LAK activity was induced. Furthermore we observed that addition of 50 microns indomethacin to the culture medium in the presence of 2-mercaptoethanol augmented the induction of LAK activity to some extent. In the absence of 2-mercaptoethanol, addition of indomethacin resulted only in low levels or no induction of LAK activity. We conclude that for optimal induction of LAK activity by IL-2 in rat splenocyte cultures 2-mercaptoethanol is essential, while indomethacin can only marginally further improve this induction.

Animals↗

Metallothionein in isolated pancreatic islets of mice: induction by zinc and streptozotocin, a naturally occurring diabetogen.

Metallothionein (MT) concentrations were determined in the cytosol of isolated pancreatic islets of mice, using both the cadmium (Cd)-heme and the Cd-Chelex assay. Both constitutive MT levels and significant MT induction were detected in islet cells. For MT induction, mice were injected intraperitoneally (i.p.) with either zinc sulfate (Zn) or the diabetogen streptozotocin (STZ). Following an i.p. injection of 15 mg Zn.kg-1 body weight (body wt), the mean index of MT induction found in islets was comparable to that found in liver tissue, which was used as control. After i.p. injection of 30 mg Zn.kg-1 or a single high dose of STZ (100 or 200 mg.kg-1), the indices of MT induction in islets exceeded those in liver by a factor of 1.3, 2.5, or 1.5. After multiple low doses of STZ (3 or 5 x 40 mg.kg-1 given on consecutive days), in contrast, the MT induction indices in islets exceeded those in liver by a factor of 3.5 and 3.9 for 3 x 40 respectively 5 x 40 mg STZ.kg-1. In conclusion, our results demonstrate constitutive MT levels in isolated pancreatic islets and significant MT induction after i.p. injection with Zn or STZ, in particular after repeated low doses of STZ.

Animals↗

I-J-positive cloned macrophages as accessory cells for the induction of suppressor T cells in vitro.

I-A+/I-J+ cloned macrophages, SL-1, played the role of APC in the in vitro induction of Ts against DTH to BCG. By treating SL-1 cells with various antibodies, it was shown that I-J antigens on SL-1 cells are essential for Ts induction, but not for the effector cell induction for DTH. Ia-negative cloned macrophages, SL-4, did not show any APC activity either in suppressor or effector cell induction. The precursors of the Ts were also I-J-positive, and I-J restriction resided between T cells and macrophages in the Ts induction. Thus, it is suggested that the pre-Ts recognizes the antigenic determinants of BCG presented on the APC in association with the I-J antigen and differentiates into the Ts. This pathway seems analogous to that of helper or effector T induction, where the antigenic determinant is recognized by a T cell in association with the I-A antigen on APC.

Animals↗

Induction of labour postdates in primiparae using vaginal prostaglandin tablets.

The management of pregnancy after 40 completed weeks remains controversial because induction of labour has been, in the past, associated with an increase in the incidence of caesarean section. This study examined the use of vaginal prostaglandin tablets for the induction of labour in selected primiparae after forty one weeks of pregnancy. The outcome of prostaglandin induction in 118 consecutive patients was compared with the outcome in 90 consecutive patients who went into labour spontaneously at the same gestation before induction could be undertaken. The active management of labour was applied in both groups and, therefore, the management of labour was strictly standardised. There was no difference between the two groups in the mode of delivery. Nor was prostaglandin induction associated with an increased incidence of prolonged labour. In selected primiparae, the cautious use of vaginal prostaglandin tablets can induce labour successfully postdates without increasing the complications of labour. A larger study is required to examine the effects of the induction of labour at this gestation on the fetal outcome.

Administration, Intravaginal↗

Preoperative parental anxiety predicts behavioural and emotional responses to induction of anaesthesia in children.

Parental presence at induction of anaesthesia is desirable if it makes the child happier and more cooperative. This study evaluated the emotional and behavioural responses of children to being accompanied by a parent at induction of anaesthesia in a paediatric day-care surgical centre. One hundred and thirty-four patients (aged 2-10 yr, ASA physical status I or II) were divided into two groups by day of surgery, to have a parent present at induction of anaesthesia (treatment group), or to be unaccompanied (control group). Before, and at one week after surgery, the child's fears and behaviour were scored by the Hospital Fears Inventory (HFI) and Behavioural Questionnaire (BQ), and parental anxiety by the Parents' Questionnaire (PQ) before and at one week after surgery. The Global Mood Scale (GMS) was used to assess the child's behaviour and the Visual Analogue Scale (VAS) to assess the parent's anxiety on arrival for surgery and at induction of anaesthesia. All patients and parents were disturbed by the experience, but to the same degree in the treatment and control groups. Subgroups of "calm" and "anxious" parents were identified by a median split of their preoperative VAS scores. Children in the "calm-treatment," "calm-control" and "anxious-control" subgroups were similarly upset at induction. Children in the "anxious-treatment" subgroup were the most disturbed at induction, and significantly more than those in the "anxious-control" subgroup. Preoperative parental anxiety levels also correlated with the child's fears and behaviour one week after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Comparison of thiopentone and midazolam for induction of anaesthesia: influence of diazepam premedication.

Forty-eight healthy patients undergoing routine surgery participated in this double-blind parallel study in which thiopentone sodium and midazolam maleate were compared for induction of anaesthesia. Twelve patients in each group received diazepam premedication. The purpose of this study was three fold; first to compare the efficacy of these two drugs as induction agents using fixed criteria, second to find the optimal dose of midazolam for induction and, finally, to evaluate the effects of diazepam premedication on the induction dose of both drugs. The results showed that adequate induction of anaesthesia was achieved using 0.30 milligrams per kilogram of midazolam and 3.99 milligrams per kilogram of thiopentone. These doses were not altered by pre-operative medication with diazepam. The recovery time was significantly prolonged in those patients who had received midazolam. The shortest recovery time was observed in those patients who had received thiopentone with diazepam. There were four cases of phlebitis in the thiopentone group and two in the midazolam group. In conclusion, midazolam maleate, which is a water soluble benzodiazepine, provided satisfactory induction of anaesthesia at a dose of 0.30 milligrams per kilogram. However, recovery time was significantly prolonged in patients who received midazolam.

Adult↗

Anaesthetic induction with alfentanil: comparison with thiopental, midazolam, and etomidate.

The speed, side effects and cardiovascular changes associated with anaesthetic induction and endotracheal intubation following alfentanil (20 micrograms/kg/min, IV), thiopental (84 micrograms/kg/min, IV), etomidate (5 micrograms/kg/min, IV) and midazolam (20 micrograms/kg/min, IV) prior to halothane-nitrous oxide general anaesthesia were evaluated and compared in 80 patients undergoing elective general surgical operations. Anaesthetic induction was fastest with etomidate and thiopental (approximately one minute) and slowest with midazolam (about two minutes). Systolic arterial blood pressure (SBP) was decreased at the moment of unconsciousness with thiopental but unchanged with the other compounds. Heart rate (HR) was increased at unconsciousness with midazolam and thiopental but unchanged with etomidate and alfentanil. After intubation HR was increased in all groups except those induced with alfentanil. Arrhythmias were infrequent (5 per cent or less in all groups). Rigidity during induction only occurred with alfentanil (55 per cent) and pain on injection only with etomidate (35 per cent) and alfentanil (5 per cent). Postoperative vomiting was infrequent in all groups (15 per cent) except etomidate (55 per cent). No patient remembered any aspect of laryngoscopy or the operation and all rapidly regained consciousness at the end of operation. The results of this study demonstrate that with the exception of rigidity (which is easily overcome with succinylcholine) and a slightly slower onset of action, alfentanil compares favourably as an induction agent with thiopental and is better than midazolam and etomidate. Alfentanil is superior to all three other induction agents with respect to cardiovascular stability during induction and intubation.

Adjuvants, Anesthesia↗

Optimal dose of thiamylal in combination with midazolam for induction of anaesthesia.

PURPOSE: The optimal dose range of thiamylal, combined with midazolam, in the induction of anaesthesia was evaluated using haemodynamic variables. METHODS: The 200 patients, aged 30 to 70 yr, were randomly divided into five groups by midazolam dosage. Anaesthesia was induced with midazolam 0.05, 0.075, 0.10, 0.15, or 0.20 mg.kg-1. Two minutes later, 50 mg thiamylal was administered followed by 25 mg increments until verbal response and eyelash reflex disappeared and blood pressure decreased to a level less than that of preinduction. Tracheal intubation was performed with 0.15 mg.kg-1 vecuronium. Blood pressure and heart rate were monitored during induction. Optimal induction was defined as a systolic blood pressure one minute after intubation within +/- 20% of that before induction. RESULTS: There were 164 patients whose systolic blood pressure were within these criteria. Blood pressure decreased two minutes after induction and 3 to 15 min after intubation in all groups. Heart rate increased one minute after intubation in 0.05 mg.kg-1, 0.075 mg.kg-1 and 0.10 mg.kg-1 midazolam groups. The optimal range of thiamylal was 4.0 +/- 1.1 (mean + SD), 3.1 +/- 1.2, 2.8 +/- 1.1, 2.3 +/- 1.2, and 1.7 +/- 1.0 mg.kg-1 in combination with midazolam 0.05, 0.075, 0.10, 0.15, and 0.20 mg.kg-1, respectively. CONCLUSION: The optimal dose range, to maintain haemodynamic stability, for thiamylal induction of anaesthesia in combination with midazolam, 0.05-0.2 mg.kg-1 was found to range from 4.0 to 1.7 mg.kg-1.

Adult↗

A comparison of propofol and thiopentone as induction agents in outpatient surgery.

We studied 90 healthy ASA physical status I or II female patients scheduled for outpatient therapeutic abortions. Sixty patients received induction doses of propofol (2.5 mg X kg-1) and 30 patients received thiopentone (4 mg X kg-1). Anaesthesia was maintained with nitrous oxide plus additional doses of the agent used for induction. Comparisons were made regarding the efficacy of induction and maintenance, rapidity of recovery, haemodynamic and respiratory variables and side effects. The number of "excellent" inductions was significantly different (p = 0.02), with 97 per cent of the patients induced with propofol and 80 per cent of the patients induced with thiopentone receiving this rating. A larger number of patients receiving propofol exhibited minor extraneous muscular movement during induction (p = 0.01). Recovery for the propofol group was significantly more rapid than with the thiopentone group (p = 0.001). The respiratory effect of the two drugs was not significantly different. Propofol caused a decrease in pulse rate and a decrease in systolic, diastolic and mean pressure which were significantly greater than with thiopentone. From the observations made we conclude that propofol has the potential to be an excellent induction and maintenance agent for outpatient surgery in combination with nitrous oxide alone.

Abortion, Therapeutic↗

Premedication with intramuscular midazolam: effect on induction time with intravenous midazolam compared to intravenous thiopentone or ketamine.

Our study sought to determine whether premedication with intramuscular midazolam would decrease the time to induction of anaesthesia with intravenous midazolam, and if so whether induction of anaesthesia would be as rapid as with thiopentone or ketamine, intravenously. Eight-nine patients, ASA physical status I or II, received midazolam 0.2 mg X kg-1, thiopentone 3.0 mg X kg-1, or ketamine 2.0 mg X kg-1 intravenously 60-90 min after intramuscular injection of either midazolam 0.07 mg X kg-1 or matching placebo. Time to induction of anaesthesia or the dose required to induce anaesthesia with intravenous midazolam was not decreased by midazolam premedication. Both with or without premedication, midazolam induction time was longer than with thiopentone or ketamine. Midazolam induction was associated with a lower incidence of blood pressure increase than with ketamine induction, and a lower incidence of apnea than that with either thiopentone or ketamine.

Adolescent↗

Promotion of bacteriophage induction and recombination by the cloned Bordetella pertussis recA gene is copy-number dependent.

Favre and coworkers (Favre et al., Biochimie 73:235-244, 1991) previously reported that the Bordetella pertussis recA gene present at high copy number could promote a low frequency of recombination, but not bacteriophage induction in Escherichia coli RecA- mutants. Reexamination of these phenotypes demonstrated that, in contrast to the previous study, when this gene is present at high copy number, it can stimulate a 2- to 4-log frequency of bacteriophage induction in the presence of mitomycin C, but no appreciable spontaneous induction. The cloned gene, whether it was present in high or low copy number, also promoted a low frequency of intrachromosomal recombination of two duplicated genes in Escherichia coli. These results suggest that a high concentration of the B. pertussis RecA protein is required to promote high-frequency mitomycin C-stimulated bacteriophage induction, but it facilitates intrachromosomal recombination at a very low frequency in E. coli RecA- mutants. The ability of the B. pertussis RecA protein to promote mitomycin C induction and its inability to appreciably stimulate spontaneous induction of bacteriophage suggest that this protein possesses a unique phenotype compared with other RecA proteins.

Bacteriophage lambda↗