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Sevoflurane versus isoflurane: induction and recovery characteristics with single-breath inhaled inductions of anesthesia.

Because of its nonpungent odor and low blood-gas solubility coefficient, sevoflurane might be an ideal drug for single-breath inhaled induction of anesthesia. Fifty ASA grade I-III ambulatory surgical patients (18-76 yr old) received a single-breath induction with either 5.0% sevoflurane or 5.0% isoflurane (randomized) in a 1:1 N2O/O2 mixture. Anesthesia was maintained with the same anesthetic in 70% N2O until the end of surgery, when anesthetics were abruptly discontinued. Induction times (loss of eyelash reflex) were similar for sevoflurane (75 +/- 3 s, mean +/- se) and isoflurane (67 +/- 4 s, P = not significant). Sevoflurane patients were less likely to have complications during induction (P < 0.005); coughing occurred more frequently with isoflurane (P < 0.001). During induction, heart rate increased with both sevoflurane (from 73 +/- 3 to 90 +/- 4 bpm, P < 0.05) and isoflurane (from 70 +/- 2 to 92 +/- 2 bpm, P < 0.05); the increase with isoflurane was greater than that with sevoflurane. Times to eye opening for sevoflurane (8.1 1 +/- 1.0 min) did not differ significantly from those for isoflurane (10.6 +/- 1.3 min). Patients opened their eyes at lower end-tidal minimum alveolar anesthetic concentration (MAC)-fractions of sevoflurane (0.12 +/- 0.01 MAC) than isoflurane (0.15 +/- 0.01 MAC, P < 0.01). During recovery, patients who received sevoflurane felt less clumsy (P < 0.001) and less confused (P < 0.005) but had higher pain scores (P < 0.005) than those who received isoflurane. Sevoflurane is more suitable than isoflurane for single-breath induction, because it produces a smoother induction with a lower incidence of complications and better patient acceptance.

Adolescent↗

Induction of CO2 and Bicarbonate Transport in the Green Alga Chlorella ellipsoidea (II. Evidence for Induction in Response to External CO2 Concentration).

The critical species and concentrations of dissolved inorganic carbon (DIC) required for the induction of DIC transport during adaptation to low CO2 were determined for the green alga Chlorella ellipsoidea. The concentration of dissolved CO2 needed for the induction of both CO2 and HCO3- transport was independent of pH during adaptation, whereas the total DIC concentration required increased at alkaline pH. At pH 7.5, the minimum equilibrium DIC concentration at which high CO2 characteristics were maintained, i.e. transport was repressed, was 2100 [mu]M, whereas the maximum equilibrium DIC concentration below which DIC transport was fully induced (DICIND) was 500 [mu]M. Intracellular DIC concentration during adaptation to DICIND decreased temporarily after 2 h to 60% of the maximum level but recovered after 3 h of adaptation. After 3 h of adaptation to DICIND, cells exhibited maximum O2 evolution rate at DICIND. When cells partially adapted to DICIND were returned to high CO2, there was an immediate halt to the induction of transport and a gradual decrease in transport capacity over 23 h. The capacity for the induction of transport was unaffected by the absence of light. These results indicate that changes in the internal DIC pool during adaptation to low CO2 do not trigger the induction of DIC transport and that the induction is not light dependent. Induction of DIC transport in C. ellipsoidea appears to occur in response to the continuous exposure of cells to a critical CO2 concentration in the external medium.

Journal Article↗

Propofol for induction of anaesthesia in children. A comparison with thiopentone and halothane inhalational induction.

The induction characteristics, dosage requirements, cardiovascular and respiratory effects of propofol with added lignocaine were compared with those of thiopentone and halothane inhalational induction in two groups of children aged 1-5 years and 5-10 years. Propofol induction produced significantly greater decreases in blood pressure, particularly in the 1-5 year age group. Heart rate was maintained well with all three induction techniques. Pain on injection into a vein on the dorsum of the hand was significantly more common with propofol despite the addition of lignocaine. However, this was mild in the majority of children and did not interfere with the induction of anaesthesia. The incidence of respiratory depression and other adverse effects was low with all three induction methods. The mean induction doses of both intravenous agents were greater in the 1-5-year age group. The ratio of thiopentone to propofol dose was approximately 2.5:1 in both age groups. The high incidence of pain on injection with propofol may prove to be a significant drawback to its otherwise satisfactory use in children.

Anesthesia, Inhalation↗

Enhancement of spontaneous VCA and EA induction in B95-8 cells and EA induction in Raji cells treated with human leukocyte interferon.

The purpose of this study was to determine the antiviral effect of human leukocyte interferon on Epstein-Barr virus (EBV) viral capsid antigen (VCA) and early antigen (EA) induction in B95-8 and Raji cells. Interferon made at the Institute of Virology, Beijing, and that provided by Dr. Cantell gave unexpected results. Both interferon preparations markedly enhanced spontaneous VCA and EA induction in B95-8 cells and EA induction in Raji cells simultaneously treated with croton oil and n-butyrate. Interferon treatment alone had no effect on EA induction in Raji cells. Thus, the effect of interferon on EA and VCA induction was related to the type of EBV infection, i.e., productive or latent. The enhancing activity of interferon could only be partially inhibited by retinoid 7901. It is suggested that the mechanism for enhancement of EA induction by interferon is different from that of EA induction in Raji cells by croton oil and n-butyrate.

Antigens, Viral↗

Follicle-stimulating hormone induction of luteinizing hormone receptor in cultured rat granulosa cells: an examination of the need for steroids in the induction process.

The induction of LH receptors by FSH in cultured rat granulosa cells and the effects of ovarian steroids on this process were examined. Granulosa cells were isolated from the ovaries of untreated immature rats (25 days old) and cultured with highly purified FSH (Sairam; 250 ng/ml). After culture (48-96 h in chemically defined media), both the binding of [125I]hCG and the responsiveness (cAMP and progesterone production) to an acute LH stimulus (100 ng/ml; NIH B8) were measured. The appearance of LH/hCG-binding sites and LH responsiveness indicates the presence of functional LH receptors. The induction of LH receptors by FSH requires a lag period of 24-48 h. After 48 h, the concentration of LH receptors in cultured granulosa cells continues to increase with time in culture with FSH; the continuous presence of FSH is required to maintain the induction process. If granulosa cells are cultured without hormone for 24-48 h before FSH is added, no induction of LH receptors occurs. However, if 17 beta-estradiol (5 X 10(-7) M) is added during this initial period, then the cells are responsive to the later addition of FSH. This maintenance of FSH responsiveness is not observed when dihydrotestosterone or progesterone is substituted for 17 beta-estradiol in the initial culture period. The FSH-dependent induction of LH receptors in cultured rat granulosa cells can be blocked if an inhibitor of steroidogenesis, such as aminoglutethimide phosphate (AGP; 1 mM), is added along with FSH at the initiation of the culture. The inclusion of progesterone, dihydrotestosterone, or 17 beta-estradiol (but not 20 alpha-dihydroprogesterone) in the culture together with FSH and AGP will overcome the inhibition by AGP and restore the induction of LH receptors. The results suggest that steroids produced by the developing follicle can modulate the FSH-dependent induction of LH receptors, and this may play a role in the development of follicular responsiveness to LH.

Animals↗

The effect of antilymphocyte induction therapy on renal allograft survival. A meta-analysis of individual patient-level data. Anti-Lymphocyte Antibody Induction Therapy Study Group.

PURPOSE: Randomized, controlled trials have not shown that the perioperative use of antilymphocyte antibodies (induction therapy) improves survival of cadaveric kidney allografts. This study combined individual patient-level data from published trials to examine the effect of induction therapy on allograft survival. DATA SOURCES: Randomized, controlled trials identified from MEDLINE. STUDY SELECTION: Published trials that compared adult recipients of cadaveric renal allografts who did and did not receive antilymphocyte antibodies in the perioperative period were selected if individual patient-level data were available. DATA EXTRACTION AND ANALYSIS: Individual patient-level data were collected for each of 628 study patients. Multivariable Cox proportional hazards regression was used to estimate the effect of induction therapy on allograft survival. RESULTS: The adjusted rate ratio for allograft failure with induction therapy compared with conventional therapy was 0.62 (95% CI, 0.43 to 0.90) (P = 0.012) over 2 years and 0.82 (CI, 0.62 to 1.09) (P = 0.17) over 5 years. The effect of induction therapy on allograft survival diminished over time; no benefit overall was seen after 2 years after transplantation (rate ratio, 1.13 [CI, 0.72 to 1.78]) (P > 0.2). Greater HLA-DR mismatch, delayed allograft function, diabetes mellitus in the recipient, African-American ethnicity of the recipient, and presensitization (panel-reactive antibody levels > or = 20%) were significantly associated with allograft failure at 5 years. Among high-risk patients, only those who were presensitized benefited from induction therapy at 2 years (rate ratio, 0.12 [CI, 0.03 to 0.44]) (P = 0.001). Results were similar at 5 years. CONCLUSIONS: Using individual-level data, this study showed a benefit of induction therapy at 2 years, particularly among presensitized patients. Although the benefit of this therapy subsequently waned, presensitized patients continued to have benefit at 5 years.

Adolescent↗

[Effects of midazolam premedication on induction doses of propofol and hemodynamic changes during tumor patient induction].

BACKGROUND AND OBJECTIVE: Midazolam is a useful drug used preoperatively because it can produce anxiolysis and sedation. This study compared the propofol requirements and haemodynamic effects during anaesthetic induction using propofol with premedication of midazolam or luminal. METHODS: Thirty patients (aged 20-65, ASA I-II) undergoing tumor surgery were randomly assigned into 2 groups (group M and group L): group M, receiving 0.5 mg atropine and 0.05 mg/kg midazolam; group L, receiving atropine and 2 mg/kg phenobarbital sodium 30 min before induction as premedication. Anesthesia was induced with propofol at the rate of 30 mg.kg-1.h-1 to achieve enough depth of anesthesia to intubate. Induction time, total propofol dosage, blood pressure, heart rate were recorded before and after induction, and after intubation. Awaken time was also recorded. RESULTS: The time of induction and the propofol dosage in group M (2.8 +/- 0.37 min and 79.9 +/- 15.3 mg) were significantly (P < 0.05) less than that in group L (3.3 +/- 0.54 min and 98.9 +/- 17.4 mg). Blood pressure was unchanged in M group after propofol induction and after the intubation. Heart rate change was much less in group M (P < 0.05). CONCLUSIONS: The results indicate that midazolam compered to phenobarbital sodium as premedication could reduce the usage of propofol, and also provide stable cardiovascular state during propofol induction.

Adjuvants, Anesthesia↗

Induction of microsomal 1-acylglycerophosphocholine acyltransferase by peroxisome proliferators in rat kidney; co-induction with peroxisomal beta-oxidation.

Induction of microsomal 1-acyl-glycerophosphocholine (GPC) acyltransferase in rat tissues by four peroxisome proliferators, clofibric acid, tiadenol, DEHP and PFOA, was examined. Among the nine tissues examined, kidney, liver and intestinal mucosa responded to the challenges by the peroxisome proliferators to induce the enzyme. The treatment of rats with various dose of clofibric acid, tiadenol, DEHP or PFOA resulted in an induction of kidney microsomal 1-acyl-GPC acyltransferase in a dose-dependent manner. Despite the structural dissimilarity of peroxisome proliferators, the induction of microsomal 1-acyl-GPC acyltransferase was highly correlated with the induction of peroxisomal beta-oxidation. The activity of microsomal 1-acyl-GPC acyltransferase was not affected by changes in hormonal (adrenalectomy, diabetes, hyperthyroidism and hypothyroidism) and nutritional (starvation, starvation-refeeding, fat-free-diet feeding and high-fat-diet feeding) states. The induction of renal microsomal 1-acyl-GPC acyltransferase was seen in mice subsequent to the administration of clofibric acid and tiadenol and in guinea pigs subsequent to the administration of tiadenol. These results may indicate that kidney microsomal 1-acyl-GPC acyltransferase is a highly specific parameter responsive to the challenges by peroxisome proliferators and may suggest that the possibility that the inductions by peroxisome proliferators of microsomal 1-acyl-GPC acyltransferase and peroxisomal beta-oxidation in kidney are co-regulated.

1-Acylglycerophosphocholine O-Acyltransferase↗

Induction of 5-aminolaevulinate synthase by two- to five-carbon alcohols in cultured chick-embryo hepatocytes. Relationship to induction of cytochrome P-450.

The induction of 5-aminolaevulinate synthase and of cytochrome P-450 by short-chain aliphatic alcohols was compared in primary cultures of chicken-embryo hepatocytes. Isopropyl alcohol, isobutanol, pentan-1-ol and isopentanol alone caused up to a 4-fold increase in 5-aminolaevulinate synthase, whereas ethanol and propan-1-ol did not. Induction of the synthase by isopentanol was maximal at 8 h, and reached a plateau thereafter, whereas the activity induced by 2-propyl-2-isopropylacetamide continued to increase for 20 h. In the presence of 3,4,3',4'-tetrachlorobiphenyl, an inhibitor of haem synthesis at the uroporphyrinogen decarboxylase step, synergistic induction of 5-aminolaevulinate synthase was observed with all the alcohols except ethanol. Ethanol, but not isopentanol, decreased the extent of induction of 5-aminolaevulinate synthase by 2-propyl-2-isopropylacetamide and 3,4,3',4'-tetrachlorobiphenyl (50% decrease at 112 mM-ethanol). Total protein synthesis was not inhibited by ethanol in these cells. The composition of porphyrins was determined after treatment of cells with ethanol, isopentanol or 2-propyl-2-isopropylacetamide. Untreated cells, when incubated with 5-aminolaevulinate for 6 h, accumulated mainly protoporphyrin. However, when cells were pretreated with ethanol, isopentanol or 2-propyl-2-isopropylacetamide for 20 h, and 5-aminolaevulinate was added, 8- and 7-carboxyporphyrins increased, whereas protoporphyrin decreased. The dose responses for induction of either 5-aminolaevulinate synthase or cytochrome P-450 after a 20 h exposure to 3- to 5-carbon alcohols were identical. The results indicate that: simple alcohols can induce both enzymes; hydrophobicity increases their effectiveness; and induction of both enzymes are probably mediated by a common mechanism.

5-Aminolevulinate Synthetase↗

Selective inhibition by dexamethasone of induction of NO synthase, but not of induction of L-arginine transport, in activated murine macrophage J774 cells.

1. Effects of dexamethasone on induction of nitric oxide (NO) synthase and L-arginine transport by lipopolysaccharide (LPS) were examined in a murine cultured macrophage cell line J774. Metabolism of L-arginine to L-citrulline and subsequent changes in intracellular amino acids pools were correlated with changes in nitrite production. 2. Despite a high intracellular concentration of arginine in activated J774 cells, LPS (1 microgram ml-1, 8 h) induced a 2.4 fold increase in arginine transport. Treatment of cells with cycloheximide (1 microgram ml-1) inhibited the time-dependent (1-8 h) induction of NO synthase and arginine transport mediated by LPS. 3. Induction of NO synthase by LPS (1 microgram ml-1, 24 h) alone was accompanied by a marked increase in arginine utilisation leading to decreased intracellular arginine levels and elevated intracellular and extracellular L-citrulline levels. These changes were further enhanced in the presence of interferon-gamma (IFN-gamma, 100 units ml-1, 24 h). 4. Dexamethasone (1 microM) abolished the increases in both nitrite and citrulline production induced by LPS alone but only partially reversed the combined effects of LPS and IFN-gamma. In contrast, treatment of cells with dexamethasone (10 microM) had no effect on the LPS-mediated induction of arginine transport or the decrease in intracellular arginine concentration. 5. We conclude that induction of arginine transporter activity in LPS-stimulated J774 cells involves de novo synthesis of carrier proteins, which increases transport of exogenous arginine during enhanced NO production. Moreover, the intracellular signalling pathways mediating induction of arginine transport and of NO synthase by LPS in activated macrophages diverge, since only the latter is sensitive to dexamethasone.

Amino Acid Oxidoreductases↗

SOS-like induction in Bacillus subtilis: induction of the RecA protein analog and a damage-inducible operon by DNA damage in Rec+ and DNA repair-deficient strains.

We quantitated the induction of the Bacillus subtilis Rec protein (the analog of Escherichia coli RecA protein) and the B. subtilis din-22 operon (representative of a set of DNA damage-inducible operons in B. subtilis) following DNA damage in Rec+ and DNA repair-deficient strains. After exposure to mitomycin C or UV irradiation, each of four distinct rec (recA1, recB2, recE4, and recM13) mutations reduced to the same extent the rates of both Rec protein induction (determined by densitometric scanning of immunoblot transfers) and din-22 operon induction (determined by assaying beta-galactosidase activity in din-22::Tn917-lacZ fusion strains). The induction deficiencies in recA1 and recE4 strains were partially complemented by the E. coli RecA protein, which was expressed on a plasmid in B. subtilis; the E. coli RecA protein had no effect on either induction event in Rec+, recB2, or recM13 strains. These results suggest that (i) the expression of both the B. subtilis Rec protein and the din-22 operon share a common regulatory component, (ii) the recA1 and recE4 mutations affect the regulation and/or activity of the B. subtilis Rec protein, and (iii) an SOS regulatory system like the E. coli system is highly conserved in B. subtilis. We also showed that the basal level of B. subtilis Rec protein is about 4,500 molecules per cell and that maximum induction by DNA damage causes an approximately fivefold increase in the rate of Rec protein accumulation.

Bacillus subtilis↗

Steroid induction of delta-aminolevulinic acid synthase and porphyrins in liver. Structure-activity studies and the permissive effects of hormones on the induction process.

Quantitative aspects and structure-activity relationships of the inducing effects of natural steroids on delta-aminolevulinic acid (ALA) synthase and porphyrins have been investigated in monolayer cultures of chick embryo liver cells maintained in a serum-free medium as well as in the chick embryo liver in ovo. Many 5 alpha and 5 beta metabolites of neutral C-19 and C-21 hormones and hormone precursors stimulated porphyrin formation and ALA-synthase induction in the cultured liver cells as we have previously described. In these inducing actions a number of 5 beta epimers (A:B cis) were found to be more potent than their corresponding 5 alpha epimers (A:B trans). The structure-activity relationship between 5 beta and 5 alpha steroid epimers with respect to ALA-synthase induction in culture was also found to prevail with respect to induction of this enzyme in chick embryo liver in ovo. Hemin in concentrations of 2 x 10(-7) M inhibited steroid induction of porphyrin formation, and CaMgEDTA enhanced the responsiveness of the cultured liver cells to steroids by approximately 10 times. The addition of insulin, or insulin plus hydrocortisone or insulin plus hydrocortisone plus triiodothyronine, was important for the maintenance of protein synthesis and essential for maximal expression of the ability of steroids to induce porphyrins and ALA-synthase in the "permissive" effect which insulin, hydrocortisone, and triiodothyronine exert on allylisopropylacetamide induction of porphyrins and ALA-synthase also extends to the induction process which is elicited by natural steroids. These findings also strongly suggest that the regulation of hepatic porphyrin-heme biosynthesis by endogenous as well as exogenous chemicals is significantly influenced by the internal hormonal milieu.

5-Aminolevulinate Synthetase↗

Genetic regulation of UDP-glucuronosyltransferase induction by polycyclic aromatic compounds in mice. Co-segregation with aryl hydrocarbon (benzo(alpha)pyrene) hydroxylase induction.

Induction of hepatic 4-methylumbelliferone UDP-glucuronosyltransferase (EC 2.4.1.17) by polycyclic aromatic compounds, such as 3-methylcholanthrene or beta-naphthoflavone, occurs in C57BL/6N, A/J, PL/J, C3HeB/FeJ, and BALB/cJ but not in DBA/2N, AU/SsJ, AKR/J, or RF/J inbred strains of mice. This pattern of five responsive and five nonresponsive mouse strains parallels that of the Ah locus, which controls the induction of aryl hydrocarbon (benzo[alpha]pyrene) hydroxylase (EC 1.14.14.2). Induction of the transferase is maximal in C57BL/6N mice with 200 mg of 3-methylcholanthrene/kg body weight; no induction occurs in nonresponsive DBA/2N mice even at a dose of 400 mg/kg. The rise of inducible transferase activity lags 1 or more days behind the rise of inducible hydroxylase activity and peaks 5 days after a single dose of 3-methylcholanthrene. In offspring from the appropriate backcrosses and intercross between C57BL/6N and DBA/2N parent strains, the genetic expression of 3-methylcholanthrene-inducible transferase activity is inherited as an additive (co-dominant) trait. This expression differs distinctly from that of the inducible hydroxylase activity, which is inherited almost exclusively as a single autosomal dominant trait in these same animals. The more potent inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin induces the transferase more than 3-fold in C57BL/6N mice and less than 2-fold in DBA/2N mice, whereas the hydroxylase is induced equally (about 8-fold) in both strains. A dose of 3-methylcholanthrene given 3 days after 2,3,7,8-tetrachlorodibenzo-p-dioxin, at a time when hydroxylase induction in both strains is very high, does not enhance the rise in inducible transferase activity seen in C57BL/6N or DBA/2N mice which have received 2,3,7,8-tetrachlorodibenzo-p-dioxin alone. These data indicate that (a) the inducibility of two metabolically coordinated membrane-bound enzyme activities may be regulated by a single genetic locus, and (b) although the hydroxylase can be fully induced in the nonresponsive DBA/2N strain by 2,3,7,8-tetrachlorodibenzo-p-dioxin prior to 3-methylcholanthrene treatment, metabolites of the 3-methylcholanthrene treatment, metabolites of the 3-methylcholanthrene treatment, metabolites of the 3-methylcholanthrene, presumably present in the liver, are incapable of inducing further the transferase activity. The difference in sensitivity between 3-methylcholanthrene and the more potent inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin for both the hydroxylase and the transferase activities suggests the possibility of a common receptor in regulating both enzyme induction processes.

Age Factors↗

Hepatic induction in the avian embryo: specificity of reactive endoderm and inductive mesoderm.

Mesoderm of precardiac and cardiac region ('cardiac' mesoderm) of chick, quail and mouse embryos could induce hepatic epithelium in the endoderm of the anterior half of young quail or chick embryos (anterior endoderm) in vitro as well as in vivo. No species specificity in the induction of hepatic epithelium by the 'cardiac' mesoderm could be observed. The hepatic induction, was controlled strictly by tissue specificity of both endoderm and mesoderm. Replacement of the 'cardiac' mesoderm or the anterior endoderm by non-cardiac mesoderms or endoderms other than the anterior endoderm resulted in failure of hepatic induction. Only the anterior endoderm was found to have competence for hepatic induction, indicating that it was committed, in unknown ways, to react with 'cardiac' mesoderm, and can properly be called pre-hepatic endoderm. Comparison between the development of hepatic endoderm and the hepatic induction potency of 'cardiac' mesoderm, which was most intense during 1- to 1.5- incubation days and decreased gradually with the increase of the stage, suggests that in normal development the 'cardiac' mesoderm actually induces hepatic epithelium in the competent endoderm. Hepatic-induction potency remained up to 6 days, and was found in truncus arteriosus, ventricle and auricle areas and in endocardial and myocardial layers of the heart.

Animals↗

Lens induction in axolotls: comparison with inductive signaling mechanisms in Xenopus laevis.

Amphibian lens induction is an embryonic process whose broad outlines are conserved between anurans and urodeles; however, it has been argued that some aspects of this process differ significantly between even closely related species. Classical embryologists concluded that in some species direct contact between the optic vesicle and ectoderm was both necessary and sufficient to induce the ectoderm to form a lens, while in other species tissues other than the optic vesicle induce lens formation. Recent studies of lens induction in Xenopus have argued that lens induction may be more conserved evolutionarily than was previously thought and that the different conclusions reached in the classical literature may be due more to experimental methodology than to actual differences in the process of lens induction. We have tested this hypothesis by examining the timing of lens induction in the axolotl and the ability of various tissues to induce lenses in explant cultures. We find that, despite the evolutionary divergence between Xenopus and Ambystoma, the mechanism of lens specification is substantially similar in the two species. These results support the hypothesis that the mechanism of lens induction is evolutionarily conserved among amphibians.

Ambystoma↗

Induction chemotherapy with idarubicin plus N4-behenoyl-1-beta-D-arabinofuranosylcytosine in acute myelogenous leukemia: a newly designed induction regimen--a prospective, cooperative multicenter study.

This report describes the results of induction chemotherapy with idarubicin (IDA) plus N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), a newly designed induction regimen, in cases of previously untreated acute myelogenous leukemia (AML). The study was conducted by the Multicenter Clinical Study Group of the Korean Biologic Response Modifier Society (KBRMS). From March 1994 through January 1995, 40 patients were treated. The median age was 30 years (range, 15 months to 65 years), with a distribution according to the French-American-British (FAB) classification of one MO, nine MI, 15 M2, six M3, four M4, and five M5 patients. Remission induction therapy consisted of IDA 12 mg/m2 intravenously (i.v.) over 30 minutes daily on days 1 to 3, in combination with BH-AC 300 mg/m2 over 4 hours daily on days 1 to 7 (in patients aged 41 to 65 years, BH-AC dosage was decreased to 200 mg/m2/d). Complete remission (CR) was achieved in 30 patients (75%), 22 by the first induction therapy and eight by the second induction therapy. Ten patients (25%) failed to respond to therapy, six due to resistant disease and four due to death caused by aplasia. The time to CR was 30 days, the median granulocytopenic period was 19 days, and the thrombocytopenic period was 24 days. All nonhematologic side effects such as nausea, vomiting, mucositis, skin eruption, liver and cardiac dysfunction, and neurotoxicity, were transient and tolerable. These data indicate an efficacy comparable to that of other combinations of IDA (or other anthracyclines) with cytosine arabinoside (Ara-C) for remission induction in AML.

Adolescent↗

Suppressor cell induction in vitro. II. Cellular requirements of suppressor cell induction.

The cellular requirements for the induction of antigen-specific suppressor cells (SC) in vitro were studied. Macrophage depletion, by either nylon wool or polystyrene columns or iron (and magnet) treatment or a combination of methods, did not diminish SC induction, in contrast to its effect on helper cell induction. The requirement for T-T interaction in SC induction using splenic T cells was studied by the use of adult thymectomy and anti-lymphocyte serum, which selectively deplete short-lived and recirculating T cells respectively. Since suppressor cell induction was markedly diminished, or abolished by either procedure, but reconstituted by mixing these 2 populations, it was concluded that there was T-T interaction in the development of SC, just as there is in the induction of other T cell reactions, such as the graft-versus-host response, the T killer cell response, the helper cell response and, tentatively, delayed hypersensitivity. By the use of double-chamber tissue culture flasks, with the 2 cell populations separated by a cell impermeable membrane, it was found that T-T interaction does not require cell contact and is thus mediated by factor(s). The direct precursor of antigen-specific suppressor cells is resistant to adult thymectomy but sensitive to anti-lymphocyte serum.

Animals↗