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At least 163 records · Page 9Linked to original sources
PubMed1994

Induction of an immune network cascade in cancer patients treated with monoclonal antibodies (ab1). II. Is induction of anti-idiotype reactive T cells (T3) of importance for tumor response to mAb therapy?

The antitumor effector functions of unconjugated monoclonal antibodies (mAb) in cancer therapy are not fully understood. Direct cytotoxic mechanisms such as antibody-dependent cellular cytotoxicity, complement-dependent cytolysis and apoptosis have been suggested. Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies as well as the corresponding T cells (T2 and T3) has also been proposed to be of therapeutic significance. In this study induction of an immune network cascade in ten patients with colorectal carcinoma, treated with mAb 17-1A (ab1) was assessed. After treatment, all ten patients had anti-idiotypic antibodies and anti-anti-idiotypic antibodies with ab1-like binding specificity while only five of ten patients had T cells corresponding to ab3 (T3) as assessed by a proliferation assay (DNA synthesis), and an assay of interferon gamma production (ELISPOT) (Enzyme-linked immuno SPOT) in vitro or by a delayed-type hypersensitivity reaction in vivo. Purified T cells from four of the five patients with a positive T3 test responded with DNA synthesis after stimulation using human anti-mAb 17-1A anti-idiotypic monoclonal antibodies. These four patients had a clinical response showing a tumor reduction after therapy, while all six patients lacking a proliferative response failed to show tumor regression. Induction of a cell-mediated immune network cascade might accordingly be an important antitumor effector function of mAb and should be considered in the future design of mAb-based therapy protocols in cancer patients.

Adult↗
PubMed1999

Thermal distribution of radio-frequency inductive hyperthermia using an inductive aperture-type applicator: evaluation of the effect of tumour size and depth.

A new radio-frequency (RF) inductive hyperthermia device using an inductive aperture-type applicator (IATA) is proposed. This paper reports the evaluation of the heating characteristics of the IATA using a computer simulation and clinical thermal parameters obtained during treatment of superficial and subsurface-seated tumours. The configuration of the IATA is a one-turn square column-like coil whose bottom plate is set to face the heating target. The IATA has advantages over RF capacitive-type heating, such as: generating less heat in the subcutaneous fat layer; less convergency of electric line of force at the edge of the applicator; and no physical contact with the target lesion. The induced magnetic fields and electrical currents within the heating substance are simulated using computer-assisted design software for electro-magnetic analysis. A total of 40 superficial and subsurface tumours are treated with the IATA. Invasive thermometry is performed continuously for 110 sessions using multi-sensor probes of an optical thermometer. Thermal parameters (Tmax, Tmin, Tave) are assessed based on the tumour size and depth. The treated tumours are categorised into three groups according to tumour depth: group 1 (< 3 cm, n = 28), group 2 (3-5 cm, n = 35) and group 3 (> 5 cm, n = 47). The computer simulation shows that induced electrical currents run without convergency, parallel to the surface of the heating material. All thermal parameters of group 3 are significantly higher than those of group 1 and 2 (p < 0.05), indicating that the larger lesions tend to abtain a higher temperature distribution. In conclusion, RF inductive hyperthermia using the IATA results in effective temperature distributions in superficial and subsurface tumours, with large tumours being most effectively heated.

Aged↗
PubMed1991

Multiple cytokine interactions regulate Ly-6E antigen expression: cooperative Ly-6E induction by IFNs, TNF, and IL-1 in a T cell lymphoma and in its induction-deficient variants.

The cell surface Ly-6E antigen, known to play a role in T cell activation, is up-regulated by IFNs. In the present study, we investigated the possible interactions between IFNs and other cytokines in this regulation. As a model system, we used the YAC T cell lymphoma, in which Ly-6E is normally absent but can be highly induced both at the mRNA and surface protein levels by IFN-gamma or IFN-alpha/beta. The combination of the two IFNs was found to result in markedly synergistic Ly-6E induction in this cell line. Moreover, mutants of YAC cells were isolated that did not respond to the Ly-6E-inducing action of IFN-gamma or IFN-alpha/beta alone but did respond to their combination. Such a synergistic interaction is consistent with the notion that the two IFN types utilize different intracellular mechanisms to induce Ly-6E expression. Ly-6E induction mediated by IFN-gamma or IFN-alpha/beta was also enhanced by cotreatment with TNF-alpha or IL-1 alpha, which by themselves had no detectable Ly-6E-inducing effect. These two cytokines similarly synergized with IFNs to trigger a response in several Ly-6E-induction-deficient mutants. However, their action could be dissociated in one mutant (B54) where the response to IFN-alpha/beta was enhanced by TNF-alpha, but not by IL-1 alpha. Altogether, these data indicate that Ly-6E antigen expression is regulated by the interaction of several inflammatory cytokines, which may provide a mechanism for the local modulation of T cell activation. The YAC cell mutants described here should facilitate further analysis of the molecular bases of Ly-6E regulation.

Antigens, Ly↗
PubMed1995

Differential induction of the NF-AT complex during restimulation and the induction of T-cell anergy.

Stimulation of human CD4+ T-cell clones through the T-cell receptor (TcR) by high doses of specific peptide results in the induction of a long-lived state of nonresponsiveness that has been called anergy. During the induction of anergy, T cells are phenotypically similar to cells responding to an immunogenic stimulus. The amount of TcR at the cell surface is downmodulated, whereas the CD2 and CD25 receptors are increased. When restimulated, however, anergic T cells fail to up-regulate transcription of the IL-2 gene and in consequence do not produce IL-2. In this study, we have compared the ability of various transcription factors to bind to their appropriate site on DNA. Factors were isolated from the nuclei of T cells that were in the induction phase of anergy or were undergoing activation. The pattern of binding activity in restimulated T cells is consistent with the pattern that has previously been shown to regulate T-cell-specific expression of the IL-2 and the beta chain of the TcR genes. The measured binding to a TCF-1 site is the same in the nuclei of resting, activated, and anergized cells. The inducible factors NK-kappa B, beta E2, CD28RC, and AP-1 are not expressed in resting cells and are twofold lower in anergized as compared with activated cells. In contrast, anergic T cells express approximately eightfold lower amounts of NF-AT, a member of the class of inducible factors that regulates IL-2 gene transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed2004

Induction versus noninduction therapy in kidney transplantation: considering different PRA levels and different induction therapies.

To evaluate the rate of acute cellular rejection (ACR) and long-term results in different levels of anti-HLA sensitization, using noninduction or different induction therapies, 763 patients who underwent transplantation from January 1995 to December 2001 were evaluated: 213 patients received induction therapy, 71 received Thymoglobulin (Thymo), 66 Simulect, and 44 OKT3. Follow-up time was at least 1 year for all groups. The Simulect group included older recipients and the OKT3 group had more female patients. Simulect and OKT3 groups had more black patients; Thymo and OKT3 groups had more retransplantations. PRA was low in the noninduction group (mean, 7%) and about the same in the Simulect and Thymo groups (mean, 30%). OKT3 was the most sensitized group (mean = 59%). Dialysis during the first posttransplantation week was more frequent among the induction groups (43% vs 65%; P <.005). Fewer patients experienced rejection episodes in the Thymo group (20% vs 50%; P =.02). Patients were classified according to their level of sensitization, and the Thymo group showed the lower rejection rates in all levels (mean, 20%; P =.001). When analyzing PRA >50%, the Thymo group showed lower rejection rates (12% vs 50%; P =.02). At this level of sensitization, there was no significant difference on graft loss and death with a functioning graft. There was a trend to more cytomegalovirus (CMV) disease in the Thymo group (33% vs 23%; P =.08). Two PTLD were diagnosed, both in the noninduction group. Renal function was better in the Thymo group (1.3 mg/dL). In conclusion, Thymo showed lower ACR rates in all PRA groups. No significant differences in CMV infection, tumors, and patient survival were observed.

Adult↗
PubMed1980

Induction of prophage lambda does not require full induction of RecA protein synthesis.

In mitomycin C-treated lambda lysogens, even though the rate of synthesis of RecA protein was greatly reduced by a low concentration of rifampicin (4 microgram/ml), induction of prophage lambda occurred readily as assessed by (i) cell lysis of the lysogens, (ii) production of progeny phage, and (iii) extensive cleavage of lambda repressor. The extent and the rate of cleavage of lambda repressor were not significantly affected by the low rate of synthesis of RecA protein resulting from rifampicin action. However, the yield of phage progeny was reduced and lysis of the cells was slightly delayed. We conclude that in RecA+ bacteria, induction of prophage lambda does not require full induction of RecA protein synthesis.

Autoradiography↗
PubMed2000

Cell death induction by CTL: perforin/granzyme B system dominantly acts for cell death induction in human hepatocellular carcinoma cells.

Cell death induction by cytotoxic T lymphocytes (CTLs) is an important thesis for the understanding of tumor immunotherapy. In the current study we investigated the molecular machinery of CTL-induced cell death in human hepatocellular carcinoma cell lines (HCC lines). CTLs prepared from human peripheral blood induced cell death in all tested HCC lines. As the CTL-induced death system, the effectiveness of Fas ligand/Fas and/or Perforin/Granzyme B systems has been suggested, whereas cell death induction by CTLs was shown independently on Fas expression in the current study. Using various tetrapeptide inhibitors for caspase and its associated factor, we additionally demonstrated that inhibitors for caspase 3 (Ac-DEVD-CHO) and caspase 8/granzyme B (Ac-IETD-CHO) suppressed CTL-induced cell death, but an inhibitor for Fas-activated serine proteinase, which acts for the caspase 3 activator, did not, suggesting that CTL-induced cell death was initiated by the Perforin/Granzyme B system, rather than the Fas ligand/Fas system. On the basis of our current results, we report here that the Perforin/Granzyme B system acts dominantly for the cell death induction of HCC lines.

Animals↗
PubMed1998

Taxane-mediated gene induction is independent of microtubule stabilization: induction of transcription regulators and enzymes that modulate inflammation and apoptosis.

Pharmacological traits of the antineoplastic agent taxol may originate in part from its effects on gene expression and not simply from its effects on microtubule assembly. This prompts three questions. First, how extensive is gene induction by taxol? Second, is gene induction confined to taxol itself, or does it occur with other taxane analogs? Third, do the functions of any induced genes correspond with known attributes of taxol or taxane analogs? We report that taxol induces numerous early-response genes, not just cytokine genes. Previously unidentified taxol-induced genes include genes coding transcription factors with tumor suppressor effects (krox-24) and enzymes that govern proliferation, apoptosis, and inflammation (2'5'-oligoadenylate synthase, cyclooxygenase-2, and an IkappaB kinase termed chuk). Taxotere, a potent analog of taxol, did not induce any of these genes, implying that taxol modulates gene expression by a mechanism that is distinct from microtubule stabilization and cell cycle arrest. Other taxane analogs induce some of the same genes as taxol, indicating that this process is not unique to taxol. Functional changes coincided with changes in gene expression. For instance, induction of tumor necrosis factor alpha (TNFalpha) accentuated apoptosis in cells treated with taxol compared with corresponding cells treated with taxotere. The functions of several induced genes (e.g., krox-24 and cyclooxygenase-2) are self-consistent with beneficial and adverse effects encountered during taxol administration. These results may be relevant to the safe and effective use of taxol or its analogs in oncology and other areas of medicine.

Animals↗
PubMed1997

Induction of VanA vancomycin resistance genes in Enterococcus faecalis: use of a promoter fusion to evaluate glycopeptide and nonglycopeptide induction signals.

To characterize induction of VanA resistance a plasmid was constructed in which the gene for firefly luciferase lucA was placed under the control of the promoter for the VanA resistance genes, the vanH promoter. This system afforded convenient quantitative measurement of induction of the VanA genes. Glycopeptide antibiotics and antibiotics representing 19 different mechanisms of action were evaluated for their ability to induce. Antibiotics that acted as inducers were all inhibitors of late steps of peptidoglycan synthesis. These included moenomycin, bacitracin, tunicamycin, ramoplanin and glycopeptides, but not penicillin or other beta-lactam antibiotics. Glycopeptide antibiotics were the most potent inducers. Both glycopeptides with little or no antimicrobial activity and semisynthetic glycopeptides active against VanA resistant enterococci were inducers. Overall, results suggest that an induction response may involve both an internal signal, such as precursor accumulation, and the glycopeptide molecule itself as a signal. The system may be useful as a screen for new antimicrobial agents.

Anti-Bacterial Agents↗
PubMed1987

Acute ventilatory changes during i.v. induction of anaesthesia with thiopentone or propofol in man. Studies using inductance plethysmography.

We have compared the acute ventilatory changes during induction of anaesthesia with equipotent doses of thiopentone and propofol in 12 premedicated female patients. Using ventilatory inductance plethysmography we have shown that both agents depress respiration to a similar and significant degree (P less than 0.001). However, although the functional residual capacity was reduced in patients receiving propofol, it increased slightly after induction with thiopentone (P less than 0.05).

Adult↗
PubMed1996

Recipient cells expressing single donor MHC locus products can substitute for donor-specific transfusion in the induction of transplantation tolerance when pretreatment is combined with anti-Cd4 monoclonal antibody. Evidence for a vital role of Cd4+ T cells in the induction of tolerance to class I molecules.

Syngeneic cells expressing single donor MHC locus products have been shown to induce specific immunological hyporesponsiveness, but not tolerance, to an allograft. In this study we have attempted to potentiate the beneficial effect of pretreatment with single donor MHC locus products by the addition of anti-Cd4(2) monoclonal antibody to the pretreatment protocol. We show that pretreatment with recipient L cells expressing the products of a single donor locus (K, D, or IA) can induce tolerance to a C57BL/10 (H2b) cardiac allograft in C3H/He (H2k) mice, when given in combination with the depleting anti-Cd4 monoclonal antibody YTA 3.1.2. Both the induction and maintenance phases of tolerance were found to be antigen-specific. Cells expressing donor class II antigens, IA(b) were found to be most effective. Interestingly, donor class I molecules were also found to be capable of inducing specific unresponsiveness in combination with anti-Cd4, provided an optimal antigenic load was delivered at the time of pretreatment. Pretreatment with cells expressing donor class I and anti-Cd8 monoclonal antibody had no beneficial effect on graft survival. These data show that single donor MHC locus products can induce immunologic tolerance to fully MHC and minor histocompatibility antigen-mismatched heart grafts when given under the cover of anti-Cd4 mAb. They also show that Cd4+ T cells play an important role in the induction of specific unresponsiveness to class I alloantigen in vivo and suggest that the blockade of T cells capable of recognizing class I alloantigen presented indirectly is important in the induction of tolerance.

Animals↗
PubMed1985

Interferon induction by viruses. XII. Inhibition of protein synthesis renders aged chick embryo cells refractory to interferon induction.

The initial stages of interferon induction in mouse L cells do not require protein synthesis; all steps in the induction process up to and including the transcription of interferon mRNA occurred in the presence of inhibitors of protein synthesis. In contrast, interferon induction in primary chick embryo cells aged in vitro does require a reaction that depends upon protein synthesis, unique in that it is not required for virus replication or the action of interferon.

Animals↗
PubMed1995

Induction of CO2 and Bicarbonate Transport in the Green Alga Chlorella ellipsoidea (I. Time Course of Induction of the Two Systems).

Changes in the physiological properties of the green alga Chlorella ellipsoidea (UTEX 20) were determined during adaptation from high CO2 to air. Cells of C. ellipsoidea, grown in high CO2, had an extremely low affinity for dissolved inorganic carbon (DIC). However, high-affinity DIC transport was induced rapidly after switching to air, which caused a massive decrease in the DIC concentration in the medium. Rates of O2 evolution without added carbonic anhydrase (CA) were compared with calculated rates of uncatalyzed CO2 formation in the medium as a measure of active HCO3-uptake. Cells were found to be able to use HCO3- after 5 h of adaptation and this capacity increased during the next 17 h. The stimulation of O2 evolution upon CA addition was used as a measurement of active CO2 transport: such stimulation occurred 2 h after transfer and increased during the next 5 h. Increases in O2 evolution rates were correlated closely with an increasing capacity to accumulate intracellular pools of acid-labile DIC and with decreases in K1/2(CO2) and CO2-compensation point of the cells. Treatment of cells with cycloheximide (5 [mu]g mL-1) during adaptation completely inhibited DIC transport induction, whereas treatment with chloramphenicol (400 [mu]g mL-1) had no effect, indicating the requirement for cytoplasmic protein synthesis in the induction. These results suggest that both CO2 and HCO3- transport are induced upon transfer of cells from high CO2 to air and that there is a temporal separation between the induction of the two systems.

Journal Article↗
PubMed1988

Anaesthetic induction with isoflurane or halothane. Oxygen saturation during induction with isoflurane or halothane in unpremedicated children.

The authors performed a randomised, prospective trial in which one junior anaesthetist administered gaseous induction of anaesthesia to 50 unpremedicated children with either isoflurane or halothane in nitrous oxide and oxygen. Arterial oxygen saturation and the electrocardiogram were monitored and the incidence of complications noted. Desaturation below 85% occurred in six children, but only with isoflurane. The incidences of complications and desaturation events did not alter throughout the 25 isoflurane inductions. Coughing, movement, laryngospasm and sinus tachycardia occurred more frequently with isoflurane. Isoflurane inductions took longer (7.9 as compared with 5.4 minutes, p less than 0.001) and had 4.25 times the number of complications.

Anesthesia, Inhalation↗
PubMed1989

Rectal induction of anaesthesia in children. A comparison between ketamine-midazolam and halothane for induction and maintenance of anaesthesia.

Thirty children were randomly allocated to one of three anaesthetic techniques. Rectal anaesthesia induction with a mixture of ketamine 10 mg.kg-1 BW and midazolam 0.2 mg.kg-1 BW and maintenance of anaesthesia with either intravenous ketamine or halothane were compared to induction and maintenance with halothane. Rectal induction was found reliable and useful. The frequency of side effects, the recovery time, and the time until the child could be discharged were similar in the groups maintained with halothane, whereas recovery was prolonged when intravenous ketamine was used for maintenance.

Anesthesia, Inhalation↗
PubMed2006

Long-lasting synaptic loss after repeated induction of LTD: independence to the means of LTD induction.

Short- and long-lasting synaptic plasticity is assumed to be the cellular basis of short- and long-lasting memory, respectively. However, the cellular consequences leading to the long-lasting synaptic plasticity, assumed to include the processes of synapse formation and elimination, remain unknown. Using hippocampal slices maintained stably in culture, we found previously that the repeated induction of long-term potentiation (LTP) triggered a slowly developing long-lasting enhancement in synaptic transmission strength accompanied by synapse formation, which was separate from LTP itself. We recently reported a phenomenon apparently of a mirror-image effect. The repeated activations of metabotropic glutamate receptor (mGluR), which induces long-term depression (LTD), triggered a long-lasting reduction in synaptic strength accompanied by synapse elimination. To clarify whether the reported long-lasting effect was specific to the drugs used previously and whether the effect was specific to mGluR-mediated LTD, we exposed the cultured slices repeatedly to another Group I metabotropic glutamate receptor (mGluR) agonist, an N-methyl-d-aspartate receptor agonist, and a Na+/K+-pump inhibitor. All these treatments resulted in an equivalent long-lasting synaptic reduction/elimination when repeated three times, indicating that the repeated LTD induction leads to synapse elimination. The independence of synapse elimination to the means of LTD induction suggests that the signals leading to short-term plasticity and long-term plasticity are independent. Detailed inspections in the representative case of mGluR activation revealed that the reduction in synaptic strength developed with a approximately 1-week delay from the decrease in the number of synaptic structures. This synapse elimination should be unique as it is activity-dependent rather than inactivity-dependent.

Animals↗
PubMed1995

Feline inductive odontogenic tumor (inductive fibroameloblastoma)--a tumor unique to cats.

The inductive fibroameloblastoma is a rare odontogenic tumor that occurs in young cats of either sex, predominantly in the anterior maxilla. This article critically reviews the previously published examples with emphasis on microscopic features, relationship to ameloblastic fibroma, and biologic behavior; an additional example is described. This tumor differs microscopically from human ameloblastic fibromas in that it is not well-circumscribed but rather originates multifocally within the supporting connective tissue as characteristic, spherical condensations of fibroblastic connective tissue (ectomesenchyme) associated with islands of odontogenic epithelium. Its biologic behavior requires further study but the tumor apparently is unique to cats and is distinct from human ameloblastic fibroma. Consequently, feline inductive odontogenic tumor is suggested as being a more appropriate designation than inductive fibroameloblastoma.

Ameloblastoma↗
PubMed2005

Functional induction and de-induction of P-glycoprotein by St. John's wort and its ingredients in a human colon adenocarcinoma cell line.

Continuous use of St. John's wort decreases the bioavailabilities of a variety of drugs. This interaction is attributed to the induction of cytochrome P450 3A4 and/or P-glycoprotein. In this study, we aimed to examine the chronic effects of St. John's wort and its constituents, hyperforin and hypericin, on the expression and function of P-glycoprotein in an intestinal cell line, LS 180. We also examined the acute inhibitory effect of St. John's wort on P-glycoprotein by using LLC-GA5-COL150 cells, which overexpress P-glycoprotein. St. John's wort and hyperforin but not hypericin increased the expression of P-glycoprotein in LS 180 cells. Removal of St. John's wort resulted in a restoration of P-glycoprotein level within 48 h. The content of hyperforin in St. John's wort extract was high enough to induce P-glycoprotein, suggesting that the induction of P-glycoprotein by St. John's wort can be almost attributable to hyperforin. The LS 180 cells chronically exposed to St. John's wort or hyperforin exhibited the increase in the function of P-glycoprotein assessed by the efflux of digoxin, and the activities correlated well with P-glycoprotein level. On the other hand, St. John's wort and its two constituents did not show any acute effect on P-glycoprotein-mediated transport of digoxin. St. John's wort induced P-glycoprotein in vitro that functions as a drug efflux pump. Hyperforin is considered to be a primary cause of the inductive effect of St. John's wort. Long-term administration of St. John's wort may cause clinically significant decrease in the plasma concentrations of P-glycoprotein substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗