Biomedical subjects

S Minami

Publications and source records attributed to S Minami.

At least 55 records · Page 3Linked to original sources

PubMed2000

Inhibition by neuroprotective drug NS-7 of nicotine-induced 22Na(+) influx, 45Ca(2+) influx and catecholamine secretion in adrenal chromaffin cells.

Adrenal Glands↗

PubMed2000

Vertebral decancellation for severe scoliosis.

STUDY DESIGN: The results of staged surgery including vertebral decancellation were reviewed retrospectively for 21 patients with severe scoliosis. OBJECTIVES: To evaluate the benefits and limitations of vertebral decancellation as new anterior surgical procedure. SUMMARY OF BACKGROUND DATA: The curvatures of severe scoliosis are often very rigid, and surgical correction using the anterior or posterior approach may not achieve the desired correction. Some studies reported neurologic complications might appear due to the aggressive approach or excessive correction force. METHODS: Twenty-one patients (average age, 17.0 years) with severe scoliosis, in whom Cobb angle was over 80 degrees (average angle, 107 degrees), underwent staged anterior and posterior spinal reconstruction. Vertebral decancellation was performed as anterior procedure, and until posterior instrumentation, halo traction was carried out. The transition of curvatures in coronal and sagittal planes was assessed in this series. RESULTS: The average correction rate of lateral curvature at the final follow-up was 46%. The average loss of correction was 2.5 degrees. Kyphosis, measured between T5 and T12, changed from 41 degrees to 36 degrees. Lordosis, measured between L1 and S1, changed from 56 degrees to 45 degrees. Transient neurologic deficit was seen in one case after vertebral decancellation. CONCLUSIONS: Staged surgery including vertebral decancellation is an effective surgical method for patients with severe scoliosis, where an inflexible rigid curve or the risk of occurrence of neurologic complications due to temporary correction may exist.

Adolescent↗

PubMed2000

Age-dependent changes in lipid peroxide levels in peripheral organs, but not in brain, in senescence-accelerated mice.

The tissue concentration of lipid peroxides was determined in the brain, heart, liver, lung and kidney of accelerated senescence-prone (SAMP-8) and -resistant (SAMR-1) mice at 3, 6 and 9 months of age by a method involving chemical derivatization and high performance liquid chromatography. The level of lipid peroxides in the brain did not show an age-dependent change, but at each age the brain level of lipid peroxides was significantly higher in SAMP-8 than in SAMR-1. In contrast, the lipid peroxide levels in the peripheral organs showed increases with aging in both strains, and they were significantly higher in SAMP-8 than in SAMR-1 at both 3 and 6 months of age (except at 3 months of age in the kidney). These results suggest that increased oxidative stress in the brain and peripheral organs is a cause of the senescence-related degeneration and impairments seen in SAMP-8.

Age Factors↗

PubMed2000

Genomic organization and chromosomal mapping of ELKS, a gene rearranged in a papillary thyroid carcinoma.

We recently isolated a novel cDNA, designated ELKS, that was fused to RET cDNA in a papillary thyroid carcinoma. Its encoded polypeptide sequence was rich in glutamic acid (E), leucine (L), lysine (K), and serine (S), and was characterized by the presence of nine alpha-helical coiled-coil domains consisting of periodic heptad repeats. We have now cloned the entire structure of the human ELKS gene from within a 700-kb genomic region represented by overlapping bacteriophage P1-derived artificial chromosome (PAC) and bacterial artificial chromosome (BAC) clones, and localized it to chromosomal band 12p13.3 by fluorescence in situ hybridization. The gene is approximately 500 kb long, with 19 exons and 18 introns; the transcription initiation site within exon 1 is separate from the initiation codon (in exon 2). Analysis of the exon/intron structure revealed that introns interrupt the coding sequence in such a way that many functional segments of the protein are encoded by distinct exons. Exon 1 encodes the 5' non-coding region; exons 2, 3, 6, 7, 8, 9, 11, 14, and 15 encode the nine coiled-coil domains. Exons 17-19 constitute the 3' non-coding region. Analysis of the region immediately upstream of exon 1 showed that it was extremely rich in G/C nucleotides and contained multiple Sp-1 and AP2 binding sequences. The ELKS-RET gene fusion rearrangement we had observed in a papillary thyroid carcinoma occurred between intron 10 of the ELKS gene and intron 11 of RET.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Determination of intracellular and extracellular beta-lactamase activities of Pseudomonas aeruginosa after exposure to beta-lactams in vitro and in vivo.

Beta-lactamase production in Pseudomonas aeruginosa was determined in in-vitro models and in rat pouch infection models after exposure to ceftazidime, imipenem, and piperacillin. Exposure of 28 P. aeruginosa strains to 1/4 minimum inhibitory concentration (MIC) of ceftazidime, imipenem, and piperacillin for 24 h enhanced intracellular beta-lactamase activities in 14, 22, and 6 strains, respectively, of the 28 clinical strains tested, and enhanced extracellular beta-lactamase activities which were not detected without exposure to antibiotics, in 7, 23, and 1 of the 28 strains, respectively. Extracellular beta-lactamase activity from P. aeruginosa S-1278, producing an inducible beta-lactamase, scarcely increased after exposure to ceftazidime and piperacillin 24 h after incubation, while the activity increased after exposure to imipenem over the range of 1/8 to 8 MIC. In the rat granuloma pouch models infected with P. aeruginosa S-1278, ceftazidime and piperacillin, after single administration (20 mg/kg) and serial administration (20 mg/kg per day x 3 days), did not enhance extracellular beta-lactamase activities. However, the activities were enhanced with single and serial administrations of imipenem, and levels over 10 mU/ml were detected until the third day. The beta-lactamase activity, similar to the activity found in rat pouches after serial administration of imipenem, inactivated various cephalosporins. In conclusion, extracellular beta-lactamase activity was detected both in vitro and in vivo after exposure to a good inducer, and extracellular beta-lactamase remained at infection site at levels that could inactivate cephalosporins.

Animals↗

PubMed2000

A new model of pulmonary superinfection with Aspergillus fumigatus and Pseudomonas aeruginosa in mice.

We have produced a new model of pulmonary super-infection with Aspergillus fumigatus and Pseudomonas aeruginosa in immunosuppressed mice. Male ICR mice were given an intratracheal inoculation of 4 x 10(5) conidia of A. fumigatus in agar beads, and were immunosuppressed with 100 mg/kg subcutaneous injections of cortisone acetate on days 7, 9, 12, 14, and 16 after inoculation. Twelve days after inoculation, with the agar beads, the mice were challenged with the intranasal instillation of 2 x 10(6) CFU of P. aeruginosa. The survival rates of superinfected, A. fumigatus-alone, P. aeruginosa-alone, and non-infected mice were 50%, 30%, 90%, and 100% 14 days after pseudomonal infection (26 days after inoculation of A. fumigatus), respectively. In the superinfected mice, both A. fumigatus and P. aeruginosa were detected more than 10 days after pseudomonal infection (22 days after inoculation of A. fumigatus). Histopathological examination revealed peribronchial necrosis around A. fumigatus hyphae and inflammation by P. aeruginosa. This infection model in mice would be useful for studying the pathogenesis of superinfection.

Animals↗

PubMed2000

Poor clinical significance of p53 gene polymorphism in acute myeloid leukemia.

The cancer susceptibility according to the p53 polymorphism at codon 72 has been in controversy. In this study, the clinical significance of p53 polymorphism in de novo acute myeloid leukemia (AML) was examined. Although the allelic frequency of Arg in 200 patients with AML (64.3%) tended to be greater than that in normal controls (56. 6%), these frequencies were within the normal range according to the previous data in Japan (from 59.9 to 65.3%). p53 mutations, found in nine (4.5%) of the 200 patients, were not related to the polymorphism. Six of 93 patients showing heterozygosity at codon 72 had allelic imbalance according to the polymerase chain reaction assay, which occurred in either allele and was associated with p53 mutation and poor prognosis (P=0.01). However, the p53 polymorphism was not associated with clinical features, complete remission rates or prognosis of AML. These results indicate that the p53 genotype at codon 72 is useful to detect loss of heterozygosity but not associated with risk, pathophysiology or therapeutic response of AML.

Female↗

PubMed2000

Prognostic value of p53 gene mutations and the product expression in de novo acute myeloid leukemia.

In acute myeloid leukemia (AML), p53 mutations are reportedly infrequent but associated with a poor prognosis. The majority of mutations are missense mutations, which generally lead to accumulation of nuclear p53 protein. However, the prognostic significance of the accumulation remains unknown in AML. In this study, we compared the prognostic value of p53 mutations versus accumulation of the product. p53 mutations were found in 9 (4.5%) of 200 patients with de novo AML. The p53 mutation detectable (mutation+) group had a worse prognosis (p = 0.0009) than the mutation not detectable (mutation-) group. Multivariate analysis showed that the p53 mutation was an independent factor (p = 0.005) for short overall survival as well as 60 yr or older (p = 0.001) and unfavorable karyotypes (p = 0.001). In 79 of the 200 patients, the expression of p53 was studied by immunocytochemistry (ICC) using anti-p53 monoclonal antibody (DO-7). All samples carrying missense mutations (N = 6) were positive for ICC in over 15% of nuclei of each sample, chosen as the optimized cutoff value of p53 accumulation. Accumulation was thus found in 14 of the 79 patients. However, there was no prognostic difference according to the accumulation, because the mutation-/accumulation+ group (N = 8) tended to have a good prognosis. These findings indicate that molecular detection of p53 mutations yields better prognostic information than ICC. In a subset of AML, p53 protein might be accumulated without mutation presumably due to upstream signals of p53.

Acute Disease↗

PubMed2000

Short- and long-term differential effects of neuroprotective drug NS-7 on voltage-dependent sodium channels in adrenal chromaffin cells.

In cultured bovine adrenal chromaffin cells, NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride], a newly-synthesized neuroprotective drug, inhibited veratridine-induced (22)Na(+) influx via voltage-dependent Na(+) channels (IC(50)=11.4 microM). The inhibition by NS-7 occurred in the presence of ouabain, an inhibitor of Na(+),K(+) ATPase, but disappeared at higher concentration of veratridine, and upon the washout of NS-7. NS-7 attenuated veratridine-induced (45)Ca(2+) influx via voltage-dependent Ca(2+) channels (IC(50)=20.0 microM) and catecholamine secretion (IC(50)=25.8 microM). Chronic (>/=12 h) treatment of cells with NS-7 increased cell surface [(3)H]-STX binding by 86% (EC(50)=10.5 microM; t(1/2)=27 h), but did not alter the K(D) value; it was prevented by cycloheximide, an inhibitor of protein synthesis, or brefeldin A, an inhibitor of vesicular transport from the trans-Golgi network, but was not associated with increased levels of Na(+) channel alpha- and beta(1)-subunit mRNAs. In cells subjected to chronic NS-7 treatment, (22)Na(+) influx caused by veratridine (site 2 toxin), alpha-scorpion venom (site 3 toxin) or beta-scorpion venom (site 4 toxin) was suppressed even after the extensive washout of NS-7, and veratridine-induced (22)Na(+) influx remained depressed even at higher concentration of veratridine; however, either alpha- or beta-scorpion venom, or Ptychodiscus brevis toxin-3 (site 5 toxin) enhanced veratridine-induced (22)Na(+) influx as in nontreated cells. These results suggest that in the acute treatment, NS-7 binds to the site 2 and reversibly inhibits Na(+) channels, thereby reducing Ca(2+) channel gating and catecholamine secretion. Chronic treatment with NS-7 up-regulates cell surface Na(+) channels via translational and externalization events, but persistently inhibits Na(+) channel gating without impairing the cooperative interaction between the functional domains of Na(+) channels.

Animals↗

PubMed2000

Masculinizing effect of dihydrotestosterone on growth hormone secretion is inhibited in ovariectomized rats with anterolateral deafferentation of the medial basal hypothalamus or in intact female rats.

There is a striking sex difference in the pattern of growth hormone (GH) secretion in rats. Our previous studies showed that short-term administration of pharmacological doses of testosterone or dihydrotestosterone (DHT) masculinized the GH secretory pattern in ovariectomized (OVX) rats. The locus where testosterone or DHT interacts with the somatotropic axis is believed to be the hypothalamus. To obtain insights into this phenomenon, we administered a single dose of DHT s.c. to adult OVX rats at 0.01, 0. 1 or 1 mg/rat. Blood GH concentrations were measured in unanaesthetized rats. Six to 12 h after the s.c. administration of all three doses of DHT, the GH secretory pattern revealed a male-like secretory pattern as shown by episodic bursts occurring at 2-3-h intervals with low or undetectable trough levels. When anterolateral deafferentation of the medial basal hypothalamus (ALC) was performed, the blood concentrations revealed irregularly occurring small fluctuations, instead of the usual high bursts, but the basal GH concentration was significantly higher than that of OVX-sham-operated rats. DHT treatment did not elicit pulsatile GH secretion or alter GH concentrations in OVX rats with ALC. When intact adult female rats received DHT at a dose of 1 mg/rat, the male-like GH secretory pattern was not induced. These results suggest that neural inputs from the anterolateral direction to the medial basal hypothalamus are necessary for the masculinizing effect of DHT on the GH secretory pattern in OVX rats, and that oestrogen in intact female rats prevents the masculinizing effect of DHT.

Afferent Pathways↗

PubMed2000

Distribution of c-fos mRNA in the brain following intracerebroventricular injection of nitric oxide (NO)-releasing compounds: possible role of NO in central cardiovascular regulation.

We injected nitric oxide (NO)-releasing compounds and NO synthase (NOS) inhibitors into the brains of conscious, freely moving rats and measured the effects on mean arterial blood pressure (MAP) and heart rate, as well as on the expression of c-fos mRNA, neuronal NOS (nNOS) mRNA and NADPH-diaphorase, an indicator of NOS activity. When administered i.c.v., the NO donor, NOC-18, caused a significant fall in MAP and heart rate, whereas the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), induced a significant rise in MAP. The same dose of NOC-18 or L-NAME when administered i.v. did not affect MAP and heart rate. Centrally administered NOC-18 induced c-fos mRNA expression in several regions of the brain involved in the baroreceptor response, including the nucleus of the solitary tract, the area postrema and the rostral ventrolateral medulla, as well as areas involved in the integration of autonomic, neuroendocrine and behavioural responses, including the medial preoptic area, the organum vasculosum lamina terminalis, the bed nucleus of stria terminalis, the paraventricular nucleus (PVN), the supraoptic nucleus (SON), the central nucleus of amygdala (CeA) and the locus coeruleus. Most of the areas that expressed c-fos also contained nNOS mRNA and/or NADPH-d-positive neurones and fibres. i.c.v. injection of L-NAME induced c-fos mRNA expression in PVN, SON, locus coeruleus and NTS, suggesting a tonic inhibition of neuronal activity by NO or stimulation of neuronal activity by endogenous NO. i.v. injection of NOC-18 or L-NAME did not induce any significant c-fos mRNA expression in rat brain. These results demonstrate that NO acts directly in the brain to reduce the systemic blood pressure, and that the endogenous NO pathway may play a role in cardiovascular and autonomic regulation by modulating neuronal activities in discrete regions of the brain.

Amygdala↗

PubMed2000

Protein kinase C-alpha and -epsilon down-regulate cell surface sodium channels via differential mechanisms in adrenal chromaffin cells.

In cultured bovine adrenal chromaffin cells, our [3H]saxitoxin ([3H]STX) binding, immunoblot, and northern blot analyses specified protein kinase C (PKC) isoform-specific posttranscriptional and posttranslational mechanisms that direct down-regulation of cell surface Na channels. Immunoblot analysis showed that among 11 PKC isoforms, adrenal chromaffin cells contained only conventional (c)PKC-alpha, novel (n)PKC-epsilon, and atypical (a)PKC-zeta. Treatment of adrenal chromaffin cells with 100 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) or 100 nM phorbol 12,13-dibutyrate (PDBu) caused a rapid (<15 min) and sustained (>15 h) translocation of PKC-alpha and -epsilon (but not -zeta) from cytosol to membranes, whereas a biologically inactive 4alpha-TPA had no effect. Thymeleatoxin (TMX), an activator of cPKC, produced similar membrane association of only PKC-alpha at 100 nM, with the potency of TMX being comparable with those of TPA and PDBu. Treatment with either 100 nM TPA or 100 nM TMX reduced cell surface [3H]STX binding to a comparable extent at 3, 6, and 12 h, whereas TPA lowered the binding to a greater extent than TMX at 15, 18, and 24 h; at 15 h, Gö6976, a specific inhibitor of cPKC, completely blocked TMX-induced decrease of [3H]STX binding while preventing by merely 57% TPA-induced decrease of [3H]STX binding. Treatment with 100 nM TPA lowered the Na channel alpha-subunit mRNA level between 3 and 12 h, with its maximum 52% fall at 6 h, and it was accompanied by a subsequent 61 % rise of the beta1-subunit mRNA level at 24 h. Gö6976 failed to prevent TPA-induced reduction of the alpha-subunit mRNA level; TMX did not change the alpha- and beta1-subunit mRNA levels throughout the 24-h treatment. Brefeldin A, an inhibitor of vesicular exit from the trans-Golgi network, augmented TPA- and TMX-induced decrease of [3H]STX binding at 1 and 3 h. Our previous and present studies suggest that PKC down-regulates cell surface Na channels without altering the allosteric gating of Na channels via PKC isoform-specific mechanisms; cPKC-alpha promotes Na channel internalization, whereas nPKC-epsilon decreases the alpha-subunit mRNA level by shortening the half-life of alpha-subunit mRNA without changing its gene transcription.

Adrenal Glands↗

PubMed2000

Up-regulation of cell surface insulin receptor by protein kinase C-alpha in adrenal chromaffin cells: involvement of transcriptional and translational events.

Our previous study showed that treatment of cultured bovine adrenal chromaffin cells with phorbol 12, 13-dibutyrate (PDBu) or 12-O-tetradecanoylphorbol 13-acetate (TPA) caused a rapid (<15 min) and persistent (>15 h) translocation of both conventional (c) protein kinase C-alpha (PKC-alpha) and novel PKC-epsilon (but not atypical PKC-zeta) from cytosol to membranes, whereas thymeleatoxin (TMX) increased the similar but selective membrane association of only cPKC-alpha. In the present study, chronic (>/=12 h) treatment of chromaffin cells with PDBu raised cell surface (125)I-insulin binding without altering the K(D) value; it developed in a concentration (EC(50) = 1.9 nM)-and time (t(1/2) = 14.6 h)-dependent manner, reaching its maximum 115% increase at 48 h. Either TPA (30 nM) or TMX (EC(50) = 6.4 nM) also increased (125)I-insulin binding by 97 or 88%, whereas the biologically inactive 4alpha-TPA had no effect. The increasing effect of PDBu (30 nM for 24 h) on (125)I-insulin binding was significantly blocked, even when H7, an inhibitor of PKC, was added at 8 h after the initiation of PDBu treatment. Concurrent treatment with brefeldin A, an inhibitor of vesicular transport from the trans-Golgi network, cycloheximide, an inhibitor of protein synthesis, or 5,6-dichlorobenzimidazole riboside, an inhibitor of RNA synthesis, abolished the PDBu-induced increment of (125)I-insulin binding. Western blot analysis, using antibody against the beta-subunit of the insulin receptor, showed that treatment with PDBu (30 nM) or TMX (EC(50) = 2.3 nM) increased levels of insulin receptor precursor (approximately 190 kDa; t(1/2) = 7.1 h) and insulin receptor beta-subunit (t(1/2) = 15.4 h), causing their almost maximum 52 and 59% rises, respectively, at 24 h. Northern blot analysis revealed that PDBu or TMX increased levels of insulin receptor mRNAs by approximately 35% as soon as 3 h, producing its monophasic peak approximately 76% increases at 24 h. All of these increasing effects of PDBu and TMX on (125)I-insulin binding and insulin receptor beta-subunit and insulin receptor mRNA levels were entirely prevented by simultaneous treatment with Gö6976, a selective inhibitor of cPKC. These results suggest that long-term activation of cPKC-alpha up-regulates the density of the cell surface insulin receptor via transcriptional/translational events.

Adrenal Medulla↗

PubMed2000

Therapeutic effects of parenteral beta-lactam antibiotics on experimental otitis media caused by penicillin-resistant Streptococcus pneumoniae in guinea-pigs.

The therapeutic effects of parenteral beta-lactam antibiotics were evaluated in experimental acute otitis media caused by penicillin-resistant Streptococcus pneumoniae (PRSP) in guinea-pigs. Cefotaxime, ceftriaxone and piperacillin significantly reduced viable cell counts of PRSP in the middle ear at a dose of 50 mg/kg bd for 3 days (P < 0.01 compared with control). The therapeutic effects of cefotaxime, ceftriaxone and piperacillin were superior to those of cefotiam and ceftazidime. These therapeutic effects reflected both in vitro activity and pharmacokinetic properties of the drugs.

Animals↗

PubMed2000

Clinical significance of major and minor bcr/abl chimeric transcripts in essential thrombocythemia.

BACKGROUND: Contradictory results have been reported in terms of detecting bcr/abl transcripts in patients with essential thrombocythemia. The aim of this study was to investigate whether the bcr/abl transcript could be found in patients with essential thrombocythemia (ET). METHODS: The bcr/abl transcript was amplified by the RT-nested PCR method using RNA extract from leukocytes taken from 14 essential thrombocythemia patients. The amplified DNAs were electrophoresed in 1% agarose and visualized with ethidium bromide. The DNA bands associated with the bcr/abl transcript were then extracted and followed by DNA sequence analysis. RESULTS: Major bcr/abl transcripts of the b3a2 type and minor ones of the e1a2 type were found in one and two ET patients, respectively. The incidence of bcr/abl transcripts was 21.4% (three of 14 patients). CONCLUSION: Our experiments confirmed that bcr/abl transcripts are present in some patients with essential thrombocythemia.

Adult↗

PubMed2000

Amino acid substitutions in a variant of IMP-1 metallo-beta-lactamase.

In the course of surveying for the carbapenem-hydrolyzing metallo-beta-lactamase gene bla(IMP) in pathogenic bacteria by the PCR method, we detected a gene encoding a variant metallo-beta-lactamase, designated IMP-3, which differed from IMP-1 by having low hydrolyzing activity for penicillins and carbapenems. PCR product direct sequencing of a 2.2-kb segment revealed that the gene bla(IMP-3) was located on a cassette inserted within a class I integron in the pMS390 plasmid. The 741-bp nucleotide sequence of bla(IMP-3) was identical to that of bla(IMP-1), except for seven base substitutions. Among these were two, at nucleotide positions 314 and 640, which caused amino acid alterations. Hybrid bla genes were constructed from bla(IMP-3) and bla(IMP-1) by recombinant DNA techniques, and beta-lactamases encoded by these genes were compared with those of the parents IMP-3 and IMP-1 under the same experimental conditions. The kinetic parameters indicated that the inefficient hydrolysis of benzylpenicillin, ampicillin, imipenem, and ceftazidime by IMP-3 was due to the substitution of glycine for serine at amino acid residue 196 in the mature enzyme. This alteration corresponded to the presence of guanine instead of an adenine at nucleotide position 640 of the bla(IMP-3) gene. This indicated that extension of the substrate profile in the metallo-beta-lactamase IMP-1 compared to IMP-3 is the result of a one-step single-base mutation, suggesting that the gene bla(IMP-3) is an ancestor of bla(IMP-1).

Amino Acid Substitution↗

PubMed2000

[In vitro interaction of piperacillin and imipenem/cilastatin combined with aminoglycosides against Pseudomonas aeruginosa].

The in vitro interactions of piperacillin (PIPC) and imipenem/cilastatin (IPM/CS) combined with 5 kinds of aminoglycosides (gentamicin, tobramycin, amikacin (AMK), isepamicin and netilmicin) were investigated against IPM/CS-susceptible (MIC of IPM/CS was < or = 3.13 micrograms/ml) and IPM/CS-resistant (MIC of IPM/CS was > or = 12.5 micrograms/ml) Pseudomonas aeruginosa. The following results were obtained. 1. In the checkerboard dilution studies, the combinations of PIPC with aminoglycosides showed synergistic effect for more than 50% of the each 54 strains of IPM/CS-susceptible and IPM/CS-resistant P. aeruginosa. The synergistic/additive effects of PIPC with aminoglycosides were demonstrated for all tested strains. 2. In the checkerboard dilution studies, the combinations of IPM/CS with aminoglycosides showed no antagonism against any strains. The synergistic effects of IPM/CS with aminoglycosides were demonstrated for 0 to 14.8%, and these values were smaller than the combinations of PIPC with aminoglycosides. 3. Corresponding to the results of checkerboard dilution studies, the combination of PIPC with AMK was more effective than the combination of IPM/CS with AMK on the killing curve for IPM-resistant P. aeruginosa. In conclusion, PIPC showed the synergistic effects in combinations with aminoglycosides against IPM/CS-resistant P. aeruginosa. These results suggest that the combination therapies of PIPC with aminoglycosides are useful for the clinical treatment of serious infections due to P. aeruginosa.

Amikacin↗

PubMed2000

[Effect of etoposide added to individualized induction therapy of adult acute myeloid leukemia--the JALSG-AML-92 Study. Japan Adult Leukemia Study Group].

A multicenter prospective randomized study was undertaken to assess the efficacy of etoposide added to the standard remission induction therapy for acute myeloid leukemia (AML). Consecutively registered newly diagnosed adult AML patients were randomized to receive either daunorubicin (40 mg/m2/day x 4 or more), behenoyl cytarabine (200 mg/m2/day x 10 or more) and 6-mercaptopurine (70 mg/m2/day x 10 or more) (BH-AC-DM), or the same three drugs plus etoposide (100 mg/m2/day x 5) (BH-AC-EDM) for response-oriented individualized induction therapy. The patients achieving complete remission (CR) received the same 3 courses of consolidation therapy followed by 6 courses of maintenance/intensification therapy. M3 was excluded and M0 was included. Of 667 patients registered, 655 were evaluable. The median age was 49 years (range, 15 to 85). CR rates were 77% in the BH-AC-DM group and 75% in the BH-AC-EDM group. In M4 patients, CR rates were 86% and 69% (p = 0.009), and, in M5, 80% and 77% (p = 0.810) in the BH-AC-DM and BH-AC-EDM groups, respectively. The predicted 6-year overall survival rates were 30% and 38% for BH-AC-DM and BH-AC-EDM groups, and the disease-free survival (DFS) rates of CR patients were 25% and 35% (p = 0.925), respectively. In conclusion, the present study failed to show any advantage of the addition of etoposide to the standard individualized induction therapy in adult AML, even among M4 and M5. These above data have already been published in the Int J Hematol (70: 87-104, 1999).

Adolescent↗