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Treatment of neck nodes after induction chemotherapy in patients with primary advanced tumours.

Responsiveness of neck nodes to induction chemotherapy often differs from that of the primary tumour. We have conducted a retrospective study to evaluate the results of treating the neck in a cohort of 350 patients with locally advanced (T3-4) head and neck carcinomas treated with radiation therapy at the primary location of the tumour after induction chemotherapy. One hundred and thirty-nine patients (40%) did not have neck nodes on diagnosis (N0). The treatment of the neck included surgery in 65 patients. Neck dissections were carried out before radiotherapy in 37 patients and after radiotherapy in 28 patients. The frequency of neck treatment failure was 24%. There was a tendency to better neck control when treatment included neck dissection, independently of the neck stage or response to chemotherapy. This tendency was statistically significant in patients with an advanced regional tumour (N2-3) who did not achieve a complete regional response after chemotherapy. In a multivariate analysis the variables that were related to the regional failure were the relapse of the tumour at the primary site, the neck stage (N), the type of treatment used in the neck, and the grade of regional response after induction chemotherapy. Our results lead us to suggest that after induction chemotherapy neck surgery is advisable in all cases with advanced regional disease (N2-3), independently of the grade of response achieved after induction chemotherapy, and is also advisable in N1 patients in whom induction chemotherapy does not achieve a complete response.

Antineoplastic Combined Chemotherapy Protocols↗

Immuno-cytochemical localization of indole-3-acetic acid during induction of somatic embryogenesis in cultured sunflower embryos.

Immature zygotic embryos of sunflower (Helianthus annuus L.) produce somatic embryos when cultured on medium supplemented with a cytokinin as the sole source of exogenous growth regulators. The timing of the induction phase and subsequent morphogenic events have been well characterized in previous work. We address here the question of the role of endogenous indole-3-acetic acid (IAA), since auxins are known to have a crucial role in the induction of somatic embryogenesis in many other culture and regeneration systems. The fact that in the sunflower system no exogenous auxin is required for the induction of somatic embryos makes this system very suitable for the study of the internal dynamics of IAA. We used an immuno-cytochemical approach to visualize IAA distribution within the explants before, during and after the induction phase. IAA accumulated transiently throughout cultured embryos during the induction phase. The detected signal was not uniform but certain tissues, such as the root cap and the root meristem, accumulated IAA in a more pronounced manner. IAA accumulation was not restricted to the reactive zone but the kinetics of endogenous variations strikingly mimic the pulse of IAA that is usually provoked by exogenous IAA application. The direct evidence presented here indicates that an endogenous auxin pulse is indeed among the first signals leading to the induction of somatic embryogenesis.

2,4-Dichlorophenoxyacetic Acid↗

The role of carbohydrates in the induction of flowering in Arabidopsis thaliana: comparison between the wild type and a starchless mutant.

In order to test whether an increased export of carbohydrates by leaves and starch mobilization are critical for floral transition in Arabidopsis thaliana, the Columbia ecotype as well as its starchless mutant pgm and starch-in-excess mutant sex1 were investigated. Induction of flowering was achieved by exposure of plants to either one long day (LD) or one displaced short day (DSD). The following conclusions were drawn: (i) Both the pgm and sex1 mutants have a late-flowering phenotype in days shorter than 16 h. (ii) When inductive treatments cause a large, percentage of induced plants, there is always a large, early and transient increase in carbohydrate export from leaves. By contrast, when an inductive treatment results in only a low percentage of induced plants (pgm plants exposed to one DSD), the export of carbohydrates from leaves is not increased, supporting the idea that phloem carbohydrates have a critical function in floral transition. (iii) Starch mobilization is not required to obtain an increased carbohydrate export when induction is by one LD (extended period of photosynthesis), but is absolutely essential when induction is by one DSD (period of photosynthesis unaffected). (iv) Floral induction apparently increases the capability of the leaf phloem-loading system.

Arabidopsis↗

Usefulness of oral hypnotic premedication for volatile induction of anesthesia in adults.

PURPOSE: We investigated the effects of oral hypnotic premedication for smooth anesthetic induction and for the patient's comfort under anesthesia, using sevoflurane without nitrous oxide. METHODS: Adult patients were divided into four groups: control ( n= 12), triazolam (0.25 mg; n= 12), zopiclone (7.5 mg; n= 12), and clonidine (0.15 mg; n= 12) groups. Each premedication was given to each patient 1 h before the anesthesia. The patients breathed out to residual volume and then the anesthetic mask was fitted. The repeated vital capacity breathing technique was used, with 5% sevoflurane in 10 l.min(-1) oxygen. Induction time, specific induction side effects, and acceptability of this technique by the patients were recorded by an independent observer. RESULTS: Induction time in the premedicated groups ranged from 66 +/- 12 s (mean +/- SD) to 76 +/- 14 s, and these values were significantly shorter than that in the control group (92 +/- 16 s). The number of patients in whom adverse effects occurred during anesthetic induction was significantly greater in the control group (4 patients; 33%) than in the premedicated groups (1 patient each; 8%). Acceptability of the smell of sevoflurane was significantly higher in the premedicated groups (8-10 patients; 67%-83%) than in the control group (5 patients; 42%). CONCLUSION: Oral hypnotic premedications with either triazolam (0.25 mg), zopiclone (7.5 mg), or clonidine (0.15 mg) are recommended for smoother volatile anesthetic induction and for the patient's comfort in adults.

Journal Article↗

Survival after induction chemotherapy and surgical resection for high-grade soft tissue sarcoma. Is radiation necessary?

BACKGROUND: Induction chemotherapy can produce dramatic necrosis in sarcomas-raising the question of whether or not radiation is necessary. This study reviews the clinical outcome of a subset of patients with high-grade extremity soft tissue sarcomas (STS) who were treated with induction chemotherapy and surgical resection but without radiation. METHODS: Nonmetastatic, large, high-grade STS of the pelvis and extremities were treated with intra-arterial cisplatin, adriamycin, and, after 1995, ifosfamide. After induction, oncologic resection and histologic evaluation were performed. Good responders with good surgical margins were not treated with radiation. RESULTS: Thirty-three patients, with a median follow-up of 5 years, were included. Limb salvage rate was 94%. Median tumor necrosis was 95%. Four patients developed metastatic disease with three subsequent deaths. Two local recurrences occurred; both patients were salvaged with reresection and adjuvant external beam radiotherapy, although one died of metastatic disease 10 years later. Relapse-free and overall survival is 80% and 88% at 5 and 10 years by Kaplan-Meier analysis. CONCLUSIONS: Intensive induction chemotherapy can be extremely effective for high-grade STS, permitting limb-sparing surgery in lieu of amputation. Radiation may not be necessary if a good response to induction chemotherapy and negative wide margins are achieved. All patients with large, deep, high-grade STS of the extremities should be considered candidates for induction chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

MG132 induced apoptosis is associated with p53-independent induction of pro-apoptotic Noxa and transcriptional activity of beta-catenin.

Noxa is a pro-apoptotic BH3-only member of the Bcl-2 family of proteins that is up-regulated at a transcriptional level by the nuclear protein p53 in response to cellular stresses such as DNA damage or growth factor deprivation. Noxa is able to interact with anti-apoptotic members of the Bcl-2 family and causes release of cytochrome c into the cytosol, leading to the activation of caspases and induction of apoptosis. Here we demonstrate that MG132, a proteasomal inhibitor, rapidly induces Noxa mRNA and protein in two human cell lines, T/C28a and Saos2. The induction of Noxa is associated with a significant reduction in the number of metabolically active cells over the first 24 h of exposure to MG132 and progressive activation of caspase-3, a hallmark of caspase-dependent apoptosis. Partial rescue of the phenotype is observed when cells are transfected with Noxa siRNA prior to treatment with MG132, indicating functional significance of the induction of Noxa. p53 has previously been shown to be non-functional in the T/C28a cell line and is absent by Western blotting in Saos2 cells, suggesting that the induction of Noxa is through a p53 independent mechanism. Western blotting and confocal microscopy showed that total beta-catenin protein is increased in both cell lines at the time of Noxa induction, with the bulk of the beta-catenin present in the nucleus. Transfection with the Tcf reporter vector pTOPFLASH confirms that treatment with MG132 leads to early increased transcriptional activity of beta-catenin in both T/C28a and Saos2 cells. However, although over-expression of transcriptionally active beta-catenin in T/C28a cells also induced apoptosis through a p53-independent mechanism, the levels of Noxa protein were unchanged, suggesting that beta-catenin mediated signaling and Noxa may play independent roles in MG132 induced apoptosis. In summary, our results demonstrate that MG132 induces the pro-apoptotic protein Noxa via a p53-independent mechanism that leads to caspase-dependent apoptosis. This is the first report showing that treatment with MG132 induces Noxa. This study also provides further evidence for a link between beta-catenin mediated signaling and the induction of apoptosis.

Apoptosis↗

The prognostic value of the changes in the mode of ventricular tachycardia induction noted during therapy with a marked reduction of ventricular ectopic activity.

The prognostic significance of changes in the mode of induction of ventricular tachycardia (VT) noted during therapy was studied in 49 patients with sustained VT or ventricular fibrillation. Before treatment, all patients had inducible sustained VT by programmed stimulation (one to three extrastimuli) and frequent (greater than or equal to 30/hr) ventricular premature complexes (VPCs). On the discharge regimen, VT was no longer inducible by programmed stimulation in 22 patients (group 1). Twenty-seven patients (group 2) with persistent induction of VT despite extensive serial drug testings were discharged on a regimen that resulted in a marked reduction of VPCs on Holter monitoring (greater than or equal to 50% reduction of VPCs, greater than or equal to 90% reduction of couplets, and abolition of nonsustained VT). The modes of induction at baseline and on the discharge regimen were compared in each patient in group 2. Induction of VT was more difficult, requiring more aggressive stimulation protocol in 5 of 27 patients, unchanged in 14 patients, and easier in 8 patients. The duration of follow-up was 20 +/- 13 months (mean +/- SD). Arrhythmia-free survival rates at 6, 12, 18, and 24 months were 95%, 89%, 82%, and 73% in group 1, 92%, 84%, 75%, and 75% in group 2, 93%, 83%, 77%, and 69% in 27 patients with noninducibility or harder induction, and 95%, 90%, 79%, and 79% in 22 patients with the same or easier induction, respectively. The differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Induction of labor with oral prostaglandin E2 in normal and high-risk pregnancies.

There were 153 oral prostaglandin (PG) E2 inductions attempted in 149 patients. For various reasons nine cases were dropped from the study. Of the remaining 144 induction attempts, 96 were judged successful, with a success rate of 67 per cent. Details of these inductions are presented, including summaries of three patients with uterine hypertonus and three with uterine hyperstimulation. As a rule, the labor pattern established with oral PGE2 was effective and indistinguishable from normal spontaneous labor. After review of the data we feel that induction of labor with oral PGE2 is no more hazardous to mother or infant than with other oxytocic agents. In our opinion oral PGE2 offers the obstetrician an additional means for induction of labor in normal and high-risk pregnancies. The need for close observation of the progress of labor during PGE2 inductions is emphasized.

Administration, Oral↗

Effects of induction of general and regional anesthesia for cesarean section on maternal plasma beta-endorphin levels.

Plasma beta-endorphin was measured in 40 healthy pregnant women undergoing cesarean section. Group 1 patients (N = 14) received general anesthesia by rapid-sequence induction and endotracheal intubation with curare, thiopental, and succinylcholine. Anesthesia was maintained with nitrous oxide, oxygen, and muscle relaxant until delivery. Group 2 patients (N = 26) received regional anesthesia (spinal, 14, and epidural, 12). Maternal blood samples were drawn from indwelling venous catheters prior to and after induction of either general or regional anesthesia. Plasma beta-endorphin was determined by radioimmunoassay following silicic acid extraction and gel chromatography. In the 14 patients who underwent general anesthesia, the mean (+/- SEM) plasma beta-endorphin increased significantly (p less than 0.025) from 46 +/- 7.4 to 111.6 +/- 8.9 fmol/ml. There was no significant change in plasma beta-endorphin level of the 26 patients who underwent regional anesthesia; beta-endorphin levels averaged 44.5 +/- 5.1 and 47.6 +/- 4.8 fmol/ml prior to and after induction of anesthesia, respectively. These data demonstrate that plasma beta-endorphin concentrations are elevated following induction of general anesthesia but not with induction of regional anesthesia, which suggests that less stress is associated with regional than with general anesthesia induction in patients undergoing cesarean section.

Anesthesia, Epidural↗

Fetal fibronectin as a selection criterion for induction of term labor.

OBJECTIVE: We examined whether the presence of fetal fibronectin in cervicovaginal secretions can be used as a selection criterion for induction of labor at term. STUDY DESIGN: Cervicovaginal secretions of 64 women who were scheduled for induction of labor were examined for fetal fibronectin and divided into group A (positive for fibronectin) and group B (negative for fibronectin). Both groups were examined for Bishop score, the number of prostaglandin tablets administered, and the interval between induction of labor and delivery. RESULTS: In group A the interval between induction of labor and delivery was significantly shorter (p < 0.0001) than in group B. The number of prostaglandin tablets administered to group A was likewise significantly lower (p < 0.0001). Unsuccessful induction of labor only occurred in women with fibronectin-negative cervicovaginal secretions. CONCLUSION: The assessment of the fibronectin content of cervicovaginal secretions constitutes a viable instrument in the decision-making process preceding induction of labor.

Biomarkers↗

Cervical ripening before medical induction of labor: a comparison of prostaglandin E2, estradiol, and oxytocin.

OBJECTIVE: Our purpose was to evaluate the effectiveness of oxytocin, prostaglandin E2 intracervical gel, and estradiol cream for ripening the very unfavorable cervix in patients requiring induction of labor at term. STUDY DESIGN: This prospective, randomized study was conducted in a population of women with a very unfavorable cervix (Bishop score < 4) requiring induction of labor. The patients received prostaglandin E2 gel (0.5 mg) intracervically (three doses 6 hours apart), 4 mg estradiol cream in the anterior fornix of the vagina (three doses 6 hours apart), or oxytocin at induction per protocol with an infusion pump. RESULTS: Ninety-nine women were recruited into this trial and evenly distributed among the three groups. The demographics of maternal age, race, parity, gestational age, initial Bishop score, and indication for induction were similar among the groups. The incidence of cesarean deliveries was similar in the three groups with approximately 59% of pregnancies delivered abdominally. For patients undergoing abdominal delivery the maximum cervical dilatation among the oxytocin, estradiol, and prostaglandin E2 groups was similar (3.90 +/- 3.02 cm, 3.63 +/- 2.79 cm, and 4.65 +/- 2.78 cm, respectively; p > 0.05). For all patients birth weight and Apgar scores at 1 and 5 minutes were comparable across all regimens (p > 0.05). In the subset of patients delivered vaginally patients receiving oxytocin for cervical ripening had the greatest improvement in Bishop score over baseline (p = 0.023) with an improvement of 7.08 +/- 2.42. CONCLUSION: No differences were detected among prostaglandin E2 gel, estrogen, and oxytocin in relation to cervical ripening in patients with an unfavorable cervix at term who require an induction of labor. Patients with a very unfavorable cervix at term who require delivery may benefit from serial ripening and inductions.

Adult↗

Temporal profile of the induction of heat shock protein 70 and heat shock cognate protein 70 mRNAs after transient ischemia in gerbil brain.

Distributions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after 2, 5 and 15 min of transient global ischemia in gerbil forebrain were investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. Morphological studies were also performed at the dorsal hippocampal level of coronal sections from the identical brains until 7 days after the reperfusion. Following 2 min of ischemia, HSP70 and HSC70 mRNAs were induced together in hippocampal dentate granule cells at 1 and 3 h of the reperfusion. No histological change was observed in brain cells. Following 5 min of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. The induction of HSP70 mRNA in hippocampal CA1 cells sustained until 2 days, while that of HSC70 mRNA declined gradually. Only CA1 cells were lost at 7 days of the reperfusion. Following 15 min of ischemia, the mRNAs were induced in more extensive brain regions including neocortex and thalamic nuclei. In hippocampal CA1 cells, inductions of HSP70 and HSC70 mRNAs diminished by 2 days corresponding with the neuronal damage. HSC70 mRNA induction was not so much as HSP70 mRNA induction especially in hippocampal CA1 and thalamic cells. Our results showed that HSP70 and HSC70 mRNAs were generally induced together after transient ischemia, but that the inductions were spatially and chronologically different after different periods of ischemia. The dissociation of the induction was also found in cells severely injured after 5 and 15 min of ischemia.

Animals↗

Is alpha-chloralose plus halothane induction a suitable anesthetic regimen for cerebrovascular research?

The aim of this study was to determine whether alpha-chloralose, when associated with an initial period of halothane, is a suitable anesthetic regimen for cerebrovascular studies. For this purpose, rats anesthetized with alpha-chloralose plus halothane induction were first subjected to noxious stimuli, and the behavior, EEG and systemic variables were recorded. During a second step, cortical blood flow was measured with laser-Doppler flowmetry and the time-course of the cerebrovascular reactivity to hypercapnia were measured in artificially ventilated rats anesthetized with either alpha-chloralose (40 mg.kg-1, s.c.) plus halothane induction (1.5% given during the first 45-60 min) or halothane alone (1.5%). Finally, an experimental paradigm was developed that allowed the comparison of the hypercapnic reactivity, both in awake and anesthetized conditions in the same animal. Our results show that the association of alpha-chloralose with halothane leads to stable cardiovascular parameters and immobility of ventilated rats, placed in ear bars without curare, for 3 h without any sign of discomfort. Based on EEG criteria, we found that halothane induction lengthens the duration of alpha-chloralose anesthesia (253 +/- 19 vs. 200 +/- 15 min, P < 0.01). Under alpha-chloralose alone or in association with halothane induction, the vascular reactivity to hypercapnia was considerably impaired (-85% compared to the awake state, P < 0.01), but this impairment was transient, since a control reactivity was restored 150-190 min after induction of anesthesia. Under halothane alone, the vascular reactivity remained reduced throughout the experiment. These results provide evidence that alpha-chloralose plus halothane induction is a suitable anesthetic regimen which displays a temporal window of normal cerebrovascular reactivity.

Anesthesia↗

Inductive interactions in the spatial and temporal restriction of lens-forming potential in embryonic ectoderm of Xenopus laevis.

The process of lens cell determination in amphibians is currently viewed as one involving a series of inductive interactions. On the basis of previous investigations, these interactions are thought to begin during gastrulation when the presumptive foregut endoderm and then the heart mesoderm come into contact with the presumptive lens ectoderm. This earlier period of induction is followed by the later interaction of the optic vesicle with the lens-forming ectoderm. Transplantation experiments were performed to determine the relative significance of the early and later periods of induction in the process of lens cell determination in the anuran Xenopus laevis. Various ectodermal tissues were transplanted either into the lens-forming region of open neural plate stage host embryos or over the newly formed optic vesicle of later neurula stage embryos. All transplanted tissues were labeled with the intracellular marker horseradish peroxidase to assess the exact origins of any induced lens structures. The results indicate that all nonneural ectodermal tissues have some lens-forming potential early during gastrulation; however, this potential is restricted to the lens-forming region, and perhaps nearby regions, later in development during the time of neurulation. Furthermore, the results show that the optic vesicle is not a substantial inductor of the lens in tissues that have not been previously exposed to the earlier series of inductive interactions that take place during gastrulation and neurulation. Since the optic vesicle does not appear to be a sufficient inductor of the lens, these earlier inductive interactions are, therefore, essential in the process of lens cell determination in Xenopus. These earlier inductive interactions lead to a steady increase in what may be called a lens-forming bias in the presumptive lens ectoderm during this period of development. The eventual loss in the ability of nonlens ventral ectoderm to respond to these lens inductors is presumably the result of other determinative processes that occur in this tissue.

Animals↗

The induction of a neural-specific gene, SCG10, by nerve growth factor in PC12 cells is transcriptional, protein synthesis dependent, and glucocorticoid inhibitable.

We describe features of the regulation of a neural-specific gene, SCG10, which is induced by nerve growth factor (NGF) during the neuronal differentiation of the rat pheochromocytoma cell line PC12. Induction of SCG10 mRNA occurs within 12-24 hr of exposure to NGF, is sustained in the continued presence of the neurotrophic factor, and involves a mechanism that is, at least in part, transcriptional. Unlike the rapid, transient transcriptional activations of genes such as c-fos, SCG10 induction requires ongoing protein synthesis, suggesting the participation of a de novo synthesized regulatory protein in mediating the effects of NGF on this gene. Although c-fos itself may play this role, its induction is clearly insufficient to cause an induction of SCG10. NGF, FGF, and, to a lesser extent, phorbol esters induced SCG10, whereas EGF and dibutyryl cAMP did not. In these characteristics, SCG10 induction appears to constitute a reliable molecular index of the transcription-dependent neuronal differentiation induced by NGF. Glucocorticoids, which inhibit NGF-induced neurite outgrowth from normal primary chromaffin cells, partially blocked SCG10 induction in PC12 cells. A reciprocal pattern of regulation by NGF and glucocorticoids was observed for tyrosine hydroxylase mRNA. These data suggest that environmental signals such as NGF may act on specific genes, both positively and negatively, to control the choice of alternative fates by developing neural crest cells.

Animals↗

Reversible induction of actin rods in mouse C3H-2K cells by incubation in salt buffers and by treatment with non-ionic detergents.

Incubating conditions which induced actin paracrystal-like intracellular structures (actin rods) were investigated by using several cell lines. We have found that an incubation of cells of a mouse fibroblastic cell line, C3H-2K, in an isotonic solution of NaCl containing 1 mM MgCl2, 1 mM CaCl2 and 10 mM MES, pH 6.5, induced disintegration of stress fibers and formation of actin rods in the cytoplasm. Actin rods were induced also by incubating in salt buffers in which Na+ of the above solution was substituted by most cations except K+ or Rb+. When the actin rod-forming cells were transferred back to DMEM containing 10% FBS, actin rods disappeared and stress fibers subsequently re-formed within 1 h at 37 degrees C. Although the induction was observed in NaCl buffer at a wide range of pH values (5.5-10), the optimal pH was 6.5. Formation of actin rods is dependent upon cellular metabolism, as it was inhibited at 4 degrees C, or by metabolic inhibitors. Incubation in NaCl buffer induced actin rods in HeLa, L, NRK, BALB/c 3T3 and Swiss 3T3 cells, but not in CEF or MEF cells. A decrease in cell volume was observed parallel with the induction of actin rods, except for CEF and MEF cells. Alterations in intracellular concentrations of Na, K or Ca were not correlated with the induction, however. Actin rods were also induced in C3H-2K cells by a brief treatment with non-ionic detergents. Tween 80 at concentrations as low as 0.003% was effective for the induction, but did not increase the passive membrane transport of p-nitrophenylphosphate. In contrast to the induction by NaCl buffer, treatment with Tween 80 induced numerous tiny actin rods at 4 degrees C, which became larger when further incubated at 37 degrees C. Double immunofluorescence staining with anti-actin antibody and anti-vinculin antibody showed that vinculin plaques remained at least in an early stage of the actin rod formation. We discuss the mechanism for the induction of actin rods based upon the present findings.

Actins↗

Glucose deprivation results in the induction of glucose-regulated proteins and domes in MDCK monolayers in hormonally defined serum-free medium.

Madin-Darby canine kidney (MDCK) cells spontaneously form dome-like structures in vitro, a phenomenon which has been proposed to be indicative of cellular differentiation. This study indicates the existence of a correlation between the induction of domes and of glucose-regulated proteins during glucose starvation. When MDCK monolayers were glucose deprived, domes appeared very rapidly. After only 3 h of glucose deprivation domes appeared in 69% of the microscope fields. The level of expression of glucose-regulated proteins (grps) as well as domes was examined over a 6-h time interval of glucose deprivation. Both grp 76 and 97 were induced over this time interval, with grp 76 being the more readily detectable. The level of induction of grp 76 as a function of time was quantitated by means of densitometry measurements. The induction of domes was examined in parallel with the induction of grp 76. The results indicated that the induction of grp 76 and domes occurs with a similar time course. The effect of glucose deprivation on the initial rate of ouabain-sensitive Rb+ uptake was also examined. Within the first 4 h of glucose deprivation, the initial rate of ouabain-sensitive Rb+ uptake did not differ significantly in glucose-deprived and control MDCK monolayers. These observations indicate that unlike the case with other methods of dome induction (e.g., treatment with either prostaglandin E1 (PGE1) or hexamethylene bis-acetamide (HMBA] glucose deprivation does not affect the Na+K+ ATPase activity of MDCK monolayers. These observations suggest that PGE1, HMBA, and glucose deprivation affect dome formation in MDCK monolayers by means of distinct mechanisms.

Acetamides↗

Induction of c-fos mRNA and protein in neurons and glia after traumatic brain injury: pharmacological characterization.

Focal brain injury in mice induced c-fos mRNA and protein in neurons throughout the damaged neocortex, including the piriform and the entorhinal cortices, as well as in nonneural brain cells (e.g., glia, pia, ependyma). The pattern of c-fos induction after injury suggested that injury led to spreading depression which then led to c-fos induction in neurons. Human neurons in the temporal cortex and hippocampus also showed c-fos protein induction after neurosurgical trauma. The c-fos mRNA and protein induction in mouse neurons was prevented by the noncompetitive NMDA antagonist ketamine but only partially inhibited by the voltage-dependent calcium channel antagonist nifedipine and the calmodulin antagonist trifluoperazine. The c-fos protein induction in nonneural brain cells after injury was not affected by these drugs. Thus, induction of c-fos in neocortical neurons after focal brain injury is partly NMDA receptor mediated.

Animals↗