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PubMed2000

Differential induction of tumor necrosis factor alpha and manganese superoxide dismutase by endotoxin in human monocytes: role of protein tyrosine kinase, mitogen-activated protein kinase, and nuclear factor kappaB.

A mutant Escherichia coli lipopolysaccharide (LPS) lacking myristoyl fatty acid markedly stimulates the activity of manganese superoxide dismutase (MnSOD) without inducing tumor necrosis factor alpha (TNFalpha) production by human monocytes (Tian et al., 1998, Am J Physiol 275:C740.), suggesting that induction of MnSOD and TNFalpha by LPS are regulated through different signal transduction pathways. The protein tyrosine kinase (PTK)/mitogen-activated protein kinase (MAPK) pathway plays an important role in the LPS-induced TNFalpha production. In the current study, we determined the effects of PTK inhibitors, genistein and herbimycin A, on the induction of MnSOD and TNFalpha in human monocytes. Genistein (10 microg/ml) and herbimycin A (1 microg/ml) markedly inhibited LPS-induced protein tyrosine phosphorylation, phosphorylation and nuclear translocation of MAPK (p42 ERK, extracellular signal-regulated kinase), and increases in the steady state level of TNFalpha mRNA as well as TNFalpha production. In contrast, at similar concentrations, genistein and herbimycin A had no effect on the LPS-induced activation of nuclear factor kappaB (NFkappaB) and induction of MnSOD (mRNA and enzyme activity) in human monocytes. In addition, inhibition of NFkappaB activation by gliotoxin and pyrrodiline dithiocarbamate, inhibited LPS induction of TNFalpha and MnSOD mRNAs. These results suggest that (1) while PTK and MAPK are essential for the production of TNFalpha, they are not necessary for the induction of MnSOD by LPS, and (2) while activation of NFkappaB alone is insufficient for the induction of TNFalpha mRNA by LPS, it is necessary for the induction of TNFalpha as well as MnSOD mRNAs.

Benzoquinones↗
PubMedDate not supplied

Labor induction with a prenatal diagnosis of fetal macrosomia.

Since our institution has a low cesarean rate (14%), it was our hypothesis that the rate of cesarean delivery in patients who underwent induction for macrosomia would be similar to the cesarean rate in patients with similar birth weights who entered labor spontaneously. A retrospective analysis of cases seen from December 1993 to July 1995 revealed 53 nondiabetic patients who underwent induction for fetal macrosomia. These study patients were matched to the next nondiabetic patient delivering a child of equal or greater birth weight who entered labor spontaneously. Maternal demographics, labor characteristics, and neonatal outcome data were reviewed. There were no differences between the induction and spontaneous labor groups in maternal age, gestational age, rate of nulliparity, incidence of shoulder dystocia, Apgar scores, or vaginal birth after prior cesarean delivery. The cesarean delivery rate was higher in the induction group when compared to the spontaneous labor group (36% vs. 17%, P < 0.05) despite a lower birth weight in the induction group (4,102 +/- 374 g vs. 349 g, P < 0.05). Regional analgesia was administered more frequently in the induction group (38% vs. 53%, P < 0.05). An increased risk of cesarean delivery was observed in subjects undergoing induction for the indication of fetal macrosomia. These data support a plan of expectant management when fetal macrosomia is suspected.

Analgesia↗
PubMed1989

Lymphokine-activated killer cell induction in tumor-infiltrating leukocytes from colon cancer patients.

Lymphokine-activated killer (LAK) cell induction was evaluated in the peripheral blood mononuclear cells (PBMC) from 28 colon cancer patients and in the tumor-infiltrating leukocytes (TIL) from 20 of the patients' colon cancer specimens. Modulation of LAK cell induction in TIL and PBMC by inhibitors of arachidonic acid metabolism also was examined. LAK cells were induced in vitro in isolated TIL and PBMC by culturing with 500 U/ml of recombinant interleukin-2 (IL-2) for 3 to 5 days, and this was followed by the assessment of cytolytic activity against natural killer (NK)-resistant Chang hepatoma cells. LAK cell induction in the TIL was depressed significantly, compared with LAK cell induction in the PBMC of colon cancer patients (P less than 0.01). In the majority of cases, indomethacin augmented LAK cell induction in the TIL (P = 0.073 for the entire group, compared with cultures not treated with indomethacin) and nordihydroguaiaretic acid (NDGA) depressed LAK cell induction (P less than 0.05 for the entire group, compared with cultures not treated with NDGA). Further characterization of the mechanisms responsible for modulating LAK cell induction in the TIL of cancer patients may identify ways to optimize their use in adoptive cellular immunotherapy.

Adult↗
PubMed2001

Extra-amniotic prostaglandin for induction of labour.

BACKGROUND: This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of extra-amniotic prostaglandin for third trimester cervical ripening or induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Date of last search: December 2000. SELECTION CRITERIA: (1) clinical trials comparing extra-amniotic prostaglandin used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: A strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This has involved a two-stage method of data extraction. The initial data were extracted centrally, and incorporated into a series of primary reviews arranged by methods of induction of labour, following a standardised methodology. MAIN RESULTS: Oxytocin was used to initiate or augment labour significantly less frequently with extra-amniotic prostaglandins when compared to placebo (relative risk 0.50, 95% confidence interval 0.38-0.66). No other findings were significant in the comparisons that were made for this review including when extra-amniotic prostaglandins were compared with other methods of cervical ripening or induction of labour. Although this could suggest that extra-amniotic prostaglandins are as effective as other agents, the findings are difficult to interpret because they are based on very small numbers and may lack the power to show a real difference. REVIEWER'S CONCLUSIONS: The studies in this review are limited by their small sample sizes which are in many cases further divided into multiple comparison groups. The analyses resulted in most comparisons showing no significant differences, with wide confidence intervals. Although extra-amniotic prostaglandins may be as effective as other modalities in initiating labour, there is little conclusive information from this review to guide clinical practice. An adequately powered randomised controlled trial would be useful to determine if the use of extra-amniotic prostaglandins would lower the rate of caesarean section. However, in the time since these studies were undertaken the use of extra-amniotic prostaglandins has largely been replaced by other modes of prostaglandin administration.

Cervical Ripening↗
PubMed2001

Hyaluronidase for cervical priming and induction of labour.

BACKGROUND: Dilatation and effacement of the cervix are not only a result of uterine contractions, but are also dependent upon ripening processes within the cervix. The cervix is a fibrous organ composed principally of hyaluronic acid, collagen and proteoglycan. Hyaluronic acid increases as pregnancy progresses, increases markedly after the onset of labour and decreases rapidly after birth of the infant. An increase in the level of hyaluronic acid is associated with an increase in tissue water content. Cervical ripening during labour is characterised by changes of the cervix with softening of the tissue and an increased water content. Cervical injection of hyaluronidase was postulated to increase cervical ripening. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of hyaluronidase for third trimester cervical ripening or induction of labour in comparison with other methods of induction of labour SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Last searched: November 2000. SELECTION CRITERIA: (1) clinical trials comparing hyaluronidase used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: A strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involves a two-stage method of data extraction. MAIN RESULTS: There were no included trials. REVIEWER'S CONCLUSIONS: The role of hyaluronidase as a method of cervical priming or induction of labour is uncertain.

Cervical Ripening↗
PubMed2001

Breast stimulation for cervical ripening and induction of labour.

BACKGROUND: Breast stimulation has been suggested as an effective means of inducing labour. It is both an inexpensive and non-medical intervention which allows women greater control over the induction process. It is not clear how breast stimulation increases uterine contractions, however it has been shown to be effective for contraction stress tests and for the augmentation of labour. This is one of a series of reviews of methods of cervical ripening and labour induction using a standardised methodology. OBJECTIVES: To determine the effectiveness of breast stimulation for third trimester cervical ripening or induction of labour in comparison with placebo/no intervention or other methods of induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Last searched: April 2001. SELECTION CRITERIA: (1) randomised controlled trials comparing breast stimulation used for third trimester cervical ripening or labour induction with no intervention or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or the control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaning outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: A generic strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally. MAIN RESULTS: Six randomised controlled trials were included in the analysis involving 719 women. When trials comparing breast stimulation with no intervention were analysed there was a significant reduction in the number of women not in labour at 72 hours (62.7% versus 93.6%, relative risk (RR) 0.67, 95% confidence interval (CI) 0.60 - 0.74). However, this result did not remain significant in women with an unfavourable cervix. There were no instances of uterine hyperstimulation. A reduction in the rate of postpartum haemorrhage was reported (0.7% versus 6%, RR 0.16, 95% CI 0.03 - 0.87). No significant difference was detected in the caesarean section rate (9% versus 10%, relative risk RR 0.90, 95% CI 0.38 - 2.12) or rates of meconium staining. Three perinatal deaths were reported (1.8% versus 0%, RR 8.17, 95% CI 0.45 - 147.77). This finding should be interpreted with caution. The three deaths occurred in the breast stimulation arm of a three-armed trial (breast stimulation versus no intervention versus oxytocin) of questionable quality. The study was very small (n = 57), involved only high risk women, and the method of randomisation was not reported. When comparing breast stimulation with oxytocin alone the analysis found no difference in caesarean section rates (28% versus 47%, RR 0.60, 95% CI 0.31 - 1.18). No difference was detected in the number of women not in labour after 72 hours (58.8% versus 25%, RR 2.35, 95% CI 1.00 - 5.54). There was no significant difference in the rates of meconium staining. There were four perinatal deaths. Three in the breast stimulation arm, and one in the oxytocin arm of the three-armed trial noted above (17.6% versus 5%, RR 3.53, 95% CI 0.40-30.88). REVIEWER'S CONCLUSIONS: Breast stimulation cannot be fully evaluated on efficacy and safety grounds from the included studies. Whilst it would appear beneficial in terms of a reduction in the number of women not in labour after 72 hours, and a reduction in postpartum haemorrhage, until safety issues have been fully evaluated it should not be considered for use in a high risk population.

Breast↗
PubMed2006

Elective repeat caesarean section versus induction of labour for women with a previous caesarean birth.

BACKGROUND: When a woman has had a previous caesarean birth and requires induction of labour in a subsequent pregnancy, there are two options for her care: elective repeat caesarean or planned induction of labour. While there are risks and benefits for both elective repeat caesarean birth and planned induction of labour, current sources of information are limited to non-randomised cohort studies. Studies designed in this way have significant potential for bias and consequently conclusions based on these results are limited in their reliability and should be interpreted with caution. OBJECTIVES: To assess, using the best available evidence, the benefits and harms of elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 1) and PubMed (1966 to January 2006). SELECTION CRITERIA: Randomised controlled trials with reported data that compared outcomes in mothers and babies who planned a repeat elective caesarean section with outcomes in women who planned induction of labour, where a previous birth had been by caesarean. DATA COLLECTION AND ANALYSIS: There was no data extraction performed. MAIN RESULTS: There were no randomised controlled trials identified. AUTHORS' CONCLUSIONS: Planned elective repeat caesarean section and planned induction of labour for women with a prior caesarean birth are both associated with benefits and harms. Evidence for these care practices is drawn from non-randomised studies, associated with potential bias. Any results and conclusions must therefore be interpreted with caution. Randomised controlled trials are required to provide the most reliable evidence regarding the benefits and harms of both planned elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth.

Cesarean Section, Repeat↗
PubMed1993

Differential induction of regulatory genes during mesoderm formation in Xenopus laevis embryos.

Mesoderm development in Xenopus laevis depends on inductive cell interactions mediated by diffusible molecules. The mesoderm inducer activin is capable of redirecting the development of animal explants both morphologically and biochemically. We have studied the induction of four regulatory genes, Mix. 1, goosecoid (gsc), Xlim-1, and Xbra in such explants by activin, and the influence of other factors on this induction. Activin induction of gsc is strongly enhanced by dorsalization of the embryo by LiCl, while expression of the other genes is only slightly enhanced. The protein synthesis inhibitor cycloheximide (CHX) inhibits the activin-dependent induction of Xbra partially, while induction of Mix. 1 and Xlim-1 is essentially unaffected. In contrast, gsc shows strong superinduction in the presence of activin and CHX, and can be induced in animal explants by CHX alone. Induction and superinduction by CHX have previously been observed for immediate early genes in a variety of systems, notably for the activation of c-fos expression by serum stimulation, but have not been reported in early amphibian embryos.

Activins↗
PubMed1989

Resistance of fetal PVG rats to induction of allograft tolerance.

Artificially induced immunological tolerance is often envisaged as experimental mimicry of events which occur naturally during the acquisition of self tolerance. Thus, it has been inferred that similar circumstances will facilitate the induction of both types of unresponsiveness. Since tolerance to most self determinants appears to have been established by the time of birth and allograft tolerance can be experimentally induced more readily, if not exclusively, in very young animals, it is commonly assumed that susceptibility to induction of tolerance to foreign antigens will continue to increase as progressively younger animals are tested. The experiments reported in this study extend the range of circumstances under which younger animals may be found to be less susceptible, or even completely resistant, to tolerance induction. While neonatal PVG rats were highly susceptible to the induction of tolerance to (PVG x DA)F1 hybrid determinants, fetal PVG rats were only partially susceptible at 19 days and were completely resistant at 17 and 18 days of gestation. Furthermore, only 39% of neonatal PVG rats that had been inoculated with F1 hybrid bone marrow cells at 18 days of gestation could be rendered tolerant by procedures which were effective in 100% of previously untreated neonates. These observations were interpreted to indicate that a certain stage of maturity must be attained before fetal rats become susceptible to tolerance induction. Asymmetry in susceptibility to tolerance induction in response to the inoculation of F1 hybrid bone marrow cells was observed when PVG and DA fetuses, but not neonates, were compared. This difference in the response of the two strains recalls the divergence in immune reactivity of offspring, previously reported when PVG and DA embryos were transferred to surrogate mothers of the other strain. It is also in agreement with earlier reports of substantial differences in the ease of tolerance induction between different strain combinations. The asymmetry between PVG and DA rats in the present experiments is speculatively attributed to differences in rates of immunological maturation of the two strains.

Animals↗
PubMed1999

Liver-associated lymphocytes expressing NK1.1 are essential for oral immune tolerance induction in a murine model.

Oral tolerance is the induction of immunological hyporesponsiveness towards orally administered antigens. Tolerance initiation involves induction of anti-inflammatory (Th2) lymphocytes, with downregulation of pro-inflammatory (Th1) lymphocytes. The liver was previously shown to play a critical role in oral tolerance induction. The aim of the present study was to test whether liver-associated-lymphocytes expressing the NK1.1 marker (NK1.1+ LAL) are substantial for induction of oral tolerance in an experimental colitis model. Colitis was induced in C57 mice by intracolonic instillation of trinitrobenzensulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Anti-NK1.1 monoclonal antibodies were injected before tolerance induction. Colitis was assessed by standard clinical, macroscopic, and microscopic scores. Serum IFN-gamma, TGF-beta1, and IL4 levels were measured by enzyme-linked immunosorbent assay. To evaluate the role of NK1.1+ LAL in keeping the balance between immunogenic and tolerogenic subsets of cells, we tested whether peripheral lymphocytes harvested from tolerized and NK1.1-depleted nontolerized mice can adoptively transfer the tolerance into naive irradiated rats. Depletion of NK1.1+ LAL prevented immune tolerance induction in the experimental colitis model. NK1.1+ LAL-depleted nontolerized mice, disclosed severe clinical, macroscopic, and microscopic parameters of colitis. These mice had significantly lower TGF-beta1, IL4, and higher IFN-gamma serum levels, and their lymphocytes failed to transfer the tolerance into naive animals. In contrast, the feeding of colitis-extracted proteins, without NK1.1+ LAL depletion, markedly alleviated the disease. Tolerized mice had higher IL4 and TGF-beta1 and lower IFN-gamma serum levels, and adoptive transfer of their suppressor splenocytes markedly alleviated colitis in naive recipients. NK1.1+ LAL plays a critical role in oral tolerance induction. Depletion of this subset of LAL prevents a shift from Th1 to a Th2 type of immune response, hindering the ability to induce immune tolerance.

Administration, Oral↗
PubMed1983

Induction of Epstein-Barr virus early antigens by corticosteroids: inhibition by TPA and retinoic acid.

Corticosteroids can induce the synthesis of EBV antigens in the Burkitt lymphoma line Daudi. As early as 12 h after application of the drug, an increase of EA-positive cells can be seen, the maximum induction being reached after 2 days. Nanogram amounts per ml of hormone are sufficient for measurable effects. Early antigen induction by corticosteroids does not require replication of viral DNA. Induction by corticosteroid differs from induction by other systems in two major respects: (1) it does not cooperate with other inducers, and (2) it is specifically inhibited by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Induction by corticosteroids, however, shares at least one retinoic acid-sensitive step with induction by chemicals such as TPA, 5-iodo-2-deoxyuridine (IdUrd), n-butyric acid (n-BA) or inducing serum factor. This study defines three qualitatively different effects of TPA in Daudi cells: an inhibitory effect on EBV induction by corticosteroids and two differential types of synergistic effects with serum factor or n-BA, respectively. In this particular cell line, TPA exhibits no inducing capacity when applied alone.

Adrenal Cortex Hormones↗
PubMed1989

Up-regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of induction of lymphokine (IL-2)-activated killer (LAK) cells by human blood monocytes.

The role of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in monocyte-mediated up-regulation of lymphokine-activated killer (LAK) cell induction by IL-2 was examined. Treatment of blood mononuclear cells (MNC) of healthy donors with GM-CSF for 4 days in the presence of IL-2 resulted in a significant increase in LAK activity against natural killer (NK)-resistant Daudi cells, as assessed by the 4 hr 51Cr-release assay. For determination of the role of GM-CSF in LAK induction, highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated from MNC by counter-flow centrifugal elutriation (CCE). Pre-treatment of monocytes for 4 days with GM-CSF before addition of lymphocytes plus IL-2 resulted in a significant dose-dependent increase in monocyte-mediated up-regulation of LAK induction, but in the absence of monocytes GM-CSF had no effect on LAK cell induction. Similarly, GM-CSF augmented the proliferative response of lymphocytes to IL-2 in the presence of monocytes as assessed by 3H-TdR uptake. Treatment with anti-GM-CSF antibody completely abolished up-regulation of LAK induction by GM-CSF-treated monocytes. When blood monocytes were separated into 5 fractions by CCE, GM-CSF-responding monocytes were found to be responsible for up-regulation of LAK induction. These results suggest that GM-CSF may be important in monocyte-mediated up-regulation of LAK cell induction in vivo.

Colony-Stimulating Factors↗
PubMed1982

Differential reactivation of zinc-mediated metallothionein induction in ultraviolet-irradiated normal and repair-deficient human cells.

The ubiquitous, low-molecular-weight, thiol-rich, metal-binding protein, metallothionein (MT), can be induced in cultured normal human fibroblasts (NF) and xeroderma pigmentosum (XP) cells by exposure to ZnCl2. Both NF and XP cells tolerate up to 200 microM ZnCl2 in the growth medium, upon addition of ZnCl2 (200 microM) to monolayer cultures, both NF and XP cells showed similar kinetics for the induction of MT synthesis: Within 7 hours the MT synthesis rate rose from a low, marginally detectable rate to a maximal rate at least 50-fold greater than the basal rate. The induction of MT synthesis in both cell types was inhibited by actinomycin D (5 microgram/ml), indicating that the induction process is controlled at the level of transcription. Exposure of NF and XP cells to far ultraviolet light (UV) followed by induction with ZnCl2 resulted in a UV dose-dependent decrease in the he maximal rate of MT synthesis measured 8.5 hours postirradiation. The UV sensitivity of the MT induction was greater in XP cells than in NF cells. However, considerations of the differential repair capacities of NF and XP cells superimposed upon the kinetics of MT induction were invoked to explain the apparent differential UV sensitivity of MT induction. Liquid holding recovery experiments showed that NF cells possess the capacity to reactivate this inducible gene function rapidly while XP cells are deficient in the reactivation capacity. These results are discussed in the context of both UV transcriptional mapping of this inducible gene function and development of techniques for measuring repair of transcription-blocking lesions.

Cells, Cultured↗
PubMed1985

Retinoids antagonize the induction of ornithine decarboxylase activity by phorbol esters and phospholipase C in rat tracheal epithelial cells.

In this study we examined the action of phorbol esters, several phospholipases and retinoids on the induction of ornithine decarboxylase (ODC) activity in rat tracheal epithelial cells. 12-O-Tetradecanoylphorbol-13-acetate (TPA) induces ODC activity in these cells in a dose-and time-dependent manner. This induction is inhibited by cycloheximide indicating a requirement for protein synthesis. Tracheal epithelial 2C5 cells contain two binding sites for phorbol esters, one with a high affinity KD,1 = 4.58 nM and one with a low affinity KD,2 = 344.8 nM. The ability of several phorbol esters to induce ODC correlates well with the described efficacy with which they bind to the receptor and is in agreement with the concept that phorbol ester receptors are involved in the induction of ODC. There is strong evidence that the phorbol ester receptor is the protein kinase C for which diacylglycerol is the physiological ligand. Treatment of cells with phospholipase C generates diacylglycerol and induces ODC activity in a dose- and time-dependent manner. Treatment with phospholipase A2 or D has no effect on ODC activity. These results support the concept that activation of protein kinase C is related to the induction of ODC activity. The induction of ODC by TPA as well as by phospholipase C is inhibited by retinoids. Specific cytosolic binding proteins for retinoids might be involved in at least some of the responses to these compounds. To examine whether the binding proteins are involved in the inhibition of ODC we determined the presence of these binding proteins and the structure-activity relationship of retinoids. Both retinol and retinoic acid-binding proteins can be detected in 2C5 cells, their levels are 1.06 and 3.36 pmoles/mg protein, respectively. The ability of several retinoids to inhibit ODC induction correlates well with their binding activity and support a role for these binding proteins in the action of retinoids on ODC induction.

Animals↗
PubMed1990

Improved coupling between proliferation-arrest and differentiation-induction in ML-1 human myeloblastic leukemia cells.

Proliferation and differentiation are coupled in normal cells and are aberrant in leukemia cells. The studies reported here were aimed at more effectively coupling proliferation-arrest and differentiation-induction in a human myeloblastic leukemia cell line (ML-1). This was accomplished by using reduced serum conditions in conjunction with a differentiation-inducing agent: cells were first incubated in reduced serum [0.3% fetal bovine serum (FBS)] instead of standard conditions (7.5% FBS) and, second, exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA). The effects of this protocol were as follows: first, cell proliferation was slowed and cells accumulated in G0/G1 phase of the cell cycle; this occurred with only a minimal decrease in viability [to approximately 88-92% (0.3% FBS) from greater than or equal to 96% (7.5% FBS)]. Second, the induction of differentiation was accelerated; this allowed the time of exposure to TPA to be decreased. Acceleration of induction was very pronounced when cells were maintained in 0.3% FBS both before and during exposure to TPA, with TPA at concentrations above the minimum sufficient for induction but below those causing significant cytotoxicity; as little as 1 hour of TPA exposure resulted in near-maximal induction (approximately 80%) with this protocol, compared to the greater than or equal to 1 day required with previous standard protocols. In sum, conditions that slow ML-1 cell proliferation (0.3% FBS) enhance TPA-induced differentiation, substantially narrowing the time frame of induction; these conditions should be useful for studying the molecular mechanisms that underlie the induction process.

Cell Cycle↗
PubMed1990

Induction of heat shock (stress) genes in the mammalian brain by hyperthermia and other traumatic events: a current perspective.

Is the heat shock response physiologically relevant? For example, following hyperthermia or ischemia, what neural cell types show induction of heat shock genes and what is the time course of the effect? Initial experiments in this area demonstrated the prominent induction of a 70 kDa heat shock protein (hsp70) when labeled brain proteins isolated from hyperthermic animals were analyzed. Recently, in situ hybridization and immunocytochemistry have been utilized to map out the pattern of expression of both constitutively expressed and stress-inducible members of the hsp70 multigene family. Different types of neural trauma have been found to induce characteristic cellular responses in the mammalian brain with regard to the type of brain cell that responds by inducing hsp70 and the timing of the induction response. Fever-like temperature causes a dramatic induction of hsp70 mRNA within 1 hr in fiber tracts of the forebrain and cerebellum, a pattern consistent with a strong glial response to heat shock. Tissue injury, namely, a small surgical cut in the cerebral cortex, induces a rapid and highly localized induction of hsp70 mRNA in cells proximal to the injury site. Using an immunocytochemical approach, a neuronal pattern of induction of hsp70 has been demonstrated following ischemia or kainic acid-induced seizures. It is apparent that the pattern of induction of hsp70 may be a useful early marker of cellular injury and may identify previously unrecognized areas of vulnerability in the nervous system.

Animals↗
PubMed2006

Incorporation of photodynamic therapy as an induction modality in non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: Incorporation of photodynamic therapy (PDT) into the induction therapy regimen utilized for treatment of locally advanced primary non-small cell bronchogenic carcinoma (NSCLC) is explored. STUDY DESIGN/MATERIALS AND METHODS: We present a retrospective review of 41 patients diagnosed with non-metastatic NSCLC who underwent induction PDT with chemotherapy and/or radiation. RESULTS: Fifty percent of patients initially deemed unresectable, were able to undergo definitive surgical resection after trimodality induction therapy. Twenty-seven percent of patients considered to require pneumonectomy were able to have a lobectomy. The pathological stage was less than the preinduction clinical stage in 14 of 22 cases; of which four patients had no residual tumor. There was no 30/90-day postoperative mortality. Mean survival was 35.9 months (lobectomy), 25.5 months (pneumonectomy) and 14.7 months (no surgery). Median survival was 78% (12 months) and 46% (36 months). The main postoperative complication following pneumonectomy was bronchopleural fistula formation. All patients who developed this complication had undergone trimodality induction therapy. Incorporation of PDT into the induction arsenal for patients with loco-regionally advanced NSCLC may be safely performed. CONCLUSIONS: PDT may define an alternative induction strategy for patients requiring pneumonectomy; further studies exploring the true efficacy of PDT as an induction modality are encouraged.

Adult↗
PubMed2003

Pre-induction sonographic measurement of cervical length in prolonged pregnancy: the effect of parity in the prediction of the need for Cesarean section.

OBJECTIVE: To examine the effect of parity on the relationship between pre-induction cervical length and the risk of Cesarean section in women undergoing induction of labor for prolonged pregnancy. METHODS: In 382 singleton pregnancies, induction of labor was carried out at 41 + 3 to 42 + 1 weeks of gestation. The cervical length was measured by transvaginal sonography before induction. In 71 of these cases a Cesarean section was required for either fetal distress or failure to progress and 311 women delivered vaginally. The effect of parity and pre-induction cervical length on the risk of Cesarean section was examined. RESULTS: In nulliparous women the incidence of Cesarean section was significantly higher than in multiparous women (28.1% vs. 8.9%). In both nulliparae and multiparae there was a significant association between pre-induction cervical length and the rate of Cesarean section. Logistic regression analysis demonstrated that cervical length and parity provided significant independent prediction of all Cesarean sections and Cesarean sections for failure to progress. The odds of Cesarean section increased by about 10% with each increase of 1 mm in cervical length, over the mean cervical length of 20 mm for nulliparae and 18 mm for multiparae, and the odds was about 75% lower in multiparae, compared to nulliparae with the same cervical length. Receiver-operating characteristics curves (ROC) demonstrated that cervical length was better than the Bishop score in the prediction of all Cesarean sections (area under ROC = 0.72 vs. 0.68) and Cesarean sections for failure to progress (area under ROC = 0.76 vs. 0.69). CONCLUSION: In women undergoing induction of labor for prolonged pregnancy, cervical length and parity provide significant independent prediction of the likelihood of Cesarean section.

Abortion, Induced↗