[Comparative study of 5'-DFUR administration in patients with elderly cancer].
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Biomedical subjects
Publications and source records attributed to I Kaneko.
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The circular DNA plasmid, designated pAAT56, has been isolated from strain T88-56 of the Japanese pear pathotype of Alternaria alternata. We determined the complete nucleotide sequence (5354 bp) of pAAT56 and mapped its possible open reading frames (ORFs). Three long ORFs, ORF1 (1290 bp), ORF2 (1653 bp) and ORF3 (690 bp), and four smaller ORFs, ORF4 to ORF7 (> or = 300 bp), were predicted from the sequence. The potential peptides derived from the ORFs other than ORF2 show no homology to other known proteins from a database search. However, ORF2 has significant homology to the pol gene of retrotransposons. The polypeptide derived from ORF2 includes sequences homologous to the reverse transcriptase (RT) and ribonuclease H (RNase H) domains of the retrotransposon Pol peptide. Phylogenetic comparison of RT domains from the retroelements placed pAAT56 in the Ty3/gypsy group of long terminal repeat (LTR) retrotransposons, most closely linked with those of filamentous fungi. The PCR primers were designed on the basis of nucleotide sequences encoding the highly-conserved amino-acid sequences in RT domains among pAAT56 and fungal retrotransposons. The PCR amplified the DNA fragments that possibly encode RT from strains of filamentous fungi that have been reported to carry retrotransposons. These results suggest that pAAT56 has acquired the pol gene from a Ty3/gypsy-group retrotransposon.
We found the presence of plasmid DNA in strain T88-56 of the Japanese pear pathotype of Alternaria alternata, which causes black spot of certain cultivars of Japanese pear by producing host-specific AK-toxin. The plasmid, designated pAAT56, was identified to be an approximately 5.4-kilobase (kb) circular molecule by electron microscopic observation and restriction endonuclease mapping. Southern blot analysis showed that pAAT56 DNA had no homology with either nuclear or mitochondrial DNA. Cultures of strain T88-56 grown at 26 degrees showed markedly reduced plasmid levels relative to those grown at lower temperatures. The strain was completely cured of pAAT56 during growth at 29 degrees. Temperature-dependent curing of pAAT56 was confirmed by using single-protoplast isolates from mycelia grown at 23 degrees, most of which maintained the plasmid, and from mycelia grown at 29 degrees, most of which had lost the plasmid. Northern blot analysis detected the presence of three RNA species (approximately 1.7, 2.7 and 5.4 kb) transcribed from pAAT56. The biological function of pAAT56 was observed using single-protoplast isolates from mycelia that either contained or had been cured of pAAT56. The plasmid-containing isolates tended to be reduced in AK-toxin production and pathogenicity compared with the plasmid-cured isolates.
Mesenteric traction syndrome (MTS) consists of decreased systemic vascular resistance, increased cardiac output, facial flushing and palmar erythema. Local production of PGI2 is thought to be the cause. We experienced a rare case of MTS that occurred during coronary artery bypass graft surgery (CABG). A 64-year-old man was scheduled for CABG for the treatment of angina pectoris. Hemodynamic variables were stable until 50 minutes after surgical incision. Blood pressure fell down suddenly from 110/50 to 70/40 mmHg, accompanied by obvious facial flushing and palmar erythema, when the surgeons were preparing the right gastroepiploic artery. Hemodynamic changes and cutaneous hyperemia returned to the baseline level in about 40 minutes. After this episode, the operation was performed uneventfully. The time sequence between the onset of the surgical procedure and the hemodynamic and cutaneous findings strongly suggest the release of PGI2 and MTS. In patients undergoing CABG with the gastroepiploic artery graft, pretreatment with NSAID might avoid sudden circulatory changes of MTS.
A 33 year-old parturient with triplet pregnancy underwent emergency cesarean section at 35 week of gestation under general anesthesia. The patient had received magnesium sulfate to prevent uterine contraction immediately before the cesarean section. Although serum magnesium value was not beyond therapeutic levels (3.3 mEq.l-1), the neuromuscular blocking effects with vecronium were strengthened. It was not likely that volatile anesthetic enhanced neuromuscular blockade produced by vecuronium because the onset time of vecuronium had already been faster than that in pregnant patients untreated with magnesium before she was exposed to isoflurane. In addition, it is possible that magnesium could interfere with postpartum uterine contractions because of its tocolytic properties. Magnesium sulfate therapy has several implications to anesthetic agents. We, anesthesiologists, should know about the biophysiological effects of magnesium and control the interaction between anesthetic agents and this electrolyte.
The purpose of this study was to assess the utility of dynamic MR hepatocholangiography with the Gd-EOB-DTPA enhanced SIP Fast GRE sequence in the hepatobiliary system. The SIP Fast GRE sequence was used for sequential imaging of the hepatobiliary system with a frame rate of 3 sec in a 256 x 192 matrix. Dynamic sequential acquisition was performed for 51 min before and after the injection of 30 mu mol/kg of Gd-EOB-DTPA in a rabbit. Dynamic images of the hepatobiliary system were obtained in the rabbit study. Dynamic MR hepatocholangiography provides better functional information than conventional MR cholangiography.
We studied 12 cases of right aortic arch (RAA) with MRI, and the anatomical relationship between right aortic arch and the esophagus and trachea were analysed. Three of 12 cases showed RAA with mirror-image branching. Nine cases were RAA with aberrant left subclavian artery. The proximal portion of the aberrant left subclavian artery in the retrotracheoesophageal space was expanded just like a pouch. The pouch was the 8th segment dorsal aortic root and the so-called aortic diverticulum. This was one of the causes of symptoms such as wheezing and dysphagia. We divided the configuration of aortic diverticulum into two types, bulging type and saccular type, on the basis of coronal images. Two cases were bulging type, seven saccular type. The axial images in two cases showed compressed esophagus, and in three cases showed displacement of the trachea, narrowing of the space like a triangle surrounded by the aortic arch, aortic diverticulum and aberrant left subclavian artery. We drew lines and measured the angle of the aortic arch with the aberrant left subclavian artery on the axial images of these cases. We found that cases with an angle of less than 60 degrees showed a high correlation with the causes of compression of the esophagus or displacement of the trachea. It was necessary to follow such patients with MRI.
beta-Amyloid cores contain considerable amounts of D-Ser and D-Asp residues in Alzheimer's disease. We investigated the cytotoxic effects of various synthetic beta-amyloids, including D-Ser-substituted derivatives, on primary cultured neurons and nonneuronal HeLa cells. beta 25-35, its D-Ser26-substituted derivative, and beta 1-40 in 10-100 nM specifically suppressed mitochondrial succinate dehydrogenase activity [MTT [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] reduction] in HeLa cells, which are dependent on ATP production mainly from glycolysis, but did not exert detectable cytotoxicity, assessed by dye exclusion test, NADH levels, and uptake of [3H]Leu and [3H]Tdr. The beta-amyloids, on the other hand, did exert neurodegenerative effects on rat hippocampal cultured neurons in which ATP is mostly synthesized by the mitochondrion. The activities of beta 25-35 and [D-Ser26] beta 25-35 are dependent on their having beta-structures and not random forms. Although beta 25-35 was degraded rapidly by proteinase(s) in brain extract or leucine aminopeptidase, [D-Ser26] beta 25-35 is fairly resistant. These results indicate that one of the primary targets of beta-amyloids is suppression of mitochondrial succinate dehydrogenase, and the vulnerability of the brain of beta-amyloids can be explained by its large dependence on mitochondrial energy production. Moreover, racemization of serine residues of beta-amyloids may be involved in neurodegeneration and formation of senile plaques through escaping from the degradation process by brain proteinases.
Hypertonic treatment (0.5 M NaCl in phosphate-buffered saline, pH 7.2) at 37 degrees C for 20 min slightly delayed the mitotic frequency for non-irradiated cells in G1 and G2 phases. The mitotic frequency for irradiated cells in G2 was delayed by hypertonic treatment, and that in G1 was slightly delayed by hypertonic treatment. Hypertonic treatment in non-irradiated cells did not induce any chromosomal or chromatid aberrations in either G1 or G2. Chromosomal aberrations caused by gamma-irradiation were slightly enhanced by hypertonic treatment, and chromatid aberrations were markedly enhanced by hypertonic treatment. The enhancement ratio of gamma-irradiation-induced chromatid breaks and exchanges was 1.4 and 3.0, respectively. This cell cycle dependency of chromosome aberrations induced by postirradiation hypertonic treatment was the same as that of cell survival. These findings suggested that hypertonic treatment modifies the rejoining of DNA strand breaks in G2, but slightly modifies that in G1.
The anti-fungal antibiotic, radicicol, produced in the culture broth of Neocosmospora tenuicristata, was found to induce differentiation of HL-60 cells into macrophages from the following evidence: (1) it caused morphological changes into macrophage-like cells, (2) induced NBT (Nitrobluetetrazolium) reduction activity, (3) induced phagocytosis, and (4) induced alpha-naphthyl acetate esterase activity. The concentration of radicicol required to differentiate HL-60 cells is 50-100 ng/ml, and the incubation time required for commitment of differentiation is 16 hours. Flow cytometry analysis indicated that radicicol blocks the cell cycle of HL-60 cells at the G1 and G2 sites. In addition, radicicol induced reversal of the transformed phenotype of ras-transformed NIH3T3 cells (DT cells) at 25 ng/ml.
Mesenteric traction syndrome consists of cutaneous hyperemia with hypotension and tachycardia. NSAIDs could inhibit the phenomenon, but there are few reports about when to administer these drugs. In this study, we evaluated the effect of indomethacin on preventing mesenteric traction syndrome when administered preoperatively and just after induction of anesthesia. Thirty-six patients scheduled for abdominal hysterectomy were studied. Patients were randomized into three groups. Group C (n = 12); control, group T (n = 12); indomethacin 50 mg suppository just after induction of anesthesia, group P (n = 12); indomethacin 50 mg suppository about 90 min before incision. The effect of indomethacin was evaluated from the extent of cutaneous hyperemia. MTS was suppressed in group P, but not in group T (P < 0.05). We concluded that indomethacin suppository just after induction could not prevent mesenteric traction syndrome.
Using a polymerase chain reaction (PCR) method, we tested for the hepatic mitochondrial DNA (mtDNA) deletion in 40 hepatic tumors (28 hepatocellular carcinomas [HCCs], 9 other malignant tumors, and 3 benign tumors) and in the livers of 71 patients, including 16 pediatric patients with end-stage liver disease who underwent living related donor liver transplantation and 16 liver donors. A 4977 base pair (bp) deletion of mtDNA was detected in 36 of 55 specimens of non-tumor portions of adult liver (65.5%). However, none of the specimens obtained from cirrhotic livers of the 16 pediatric patients younger than 13 years of age had the 4977 bp deletion. The frequency of mtDNA deletion was significantly decreased compared with normal liver in HCCs (7 of 28) and other malignant liver tumors (2 of 9). The frequency of this deletion was unrelated to the presence of liver cirrhosis, patient's gender, hepatitis B virus surface antigen status, and hepatitis C virus antibody status.
A 70-yr-old man who was diagnosed as early gastric cancer showed leukocytopenia after total gastrectomy. Osteosclerotic findings on radiography were not remarkable. 99mTc-HMDP bone scintigraphy showed diffusely increased uptake in the axial skeleton, but visualization of the kidney and urinary bladder was apparent. However, whole body 201Tl-chloride scintigraphy showed diffuse abnormal visualization of axial skeleton. Physical and ultrasonographic examination indicated no abnormality in prostate. Afterward, further investigation, including bone marrow biopsy and immunohistochemical study, confirmed the diagnosis of bone metastasis from prostatic cancer. Microscopically, metastatic tumor cells were located in the intertrabecular space. Furthermore, no osteoclastic bone resorption or new trabecular bone formation was seen in this biopsy specimen. These findings suggest that whole body 201Tl-chloride scintigraphy can be a useful non-invasive diagnostic tool to investigate patients with suspicious malignancy in the bone marrow.
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Aspergillus terreus produces a unique enzyme, blasticidin S deaminase, which catalyzes the deamination of blasticidin S (BS), and in consequence confers high resistance to the antibiotic. A cDNA clone derived from the structural gene for BS deaminase (BSD) was isolated by transforming Escherichia coli with an Aspergillus cDNA expression library and directly selecting for the ability to grow in the presence of the antibiotic. The complete nucleotide sequence of BSD was determined and proved to contain an open reading frame of 393 bp, encoding a polypeptide of 130 amino acids. Comparison of its nucleotide sequence with that of bsr, the BS deaminase gene isolated from Bacillus cereus, indicated no homology and a large difference in codon usage. The activity of BSD expressed in E. coli was easily quantified by an assay based on spectrophotometric recording. The BSD gene was placed in a shuttle vector for Schizosaccharomyces pombe, downstream of the SV40 early region promoter, and this allowed direct selection with BS at high frequency, following transformation into the yeast. The BSD gene was also employed as a selectable marker for Pyricularia oryzae, which could not be transformed to BS resistance by bsr. These result promise that the BSD gene will be useful as a new dominant selectable marker for eukaryotes.
The purpose of this study was to evaluate repeated use of Drug Infusion Balloon catheter (DIBC) experimentally and clinically. 1. Experimental study: The changes in flow rate by repeated use of DIBC (40 ml.12 h-1 type) were measured under room temperature (21 degrees C). 2. Clinical study: Ten patients scheduled for upper abdominal surgery were studied. DIBC (40 ml.12 h-1 type) was filled with midazolam, buprenorphine, and lidocaine. Twelve hours later, the same DIBC was filled with buprenorphine and lidocaine. The mean flow rates were, on first use; 2.91 +/- 0.51, on the second use; 2.88 +/- 0.45, on the third use; 2.75 +/- 0.44, and on the fourth use; 2.69 +/- 0.38 (ml.h-1, mean +/- SD, n = 6, P < 0.05). In the clinical study, pain scores, rates of supplemental analgesic infusion during 0-12 h period were not different from those during 12-24 h period. No complications were observed in this study. Repeated use of DIBC up to four times yielded reproducible results (+/- 8%). Repeated use of DIBC for postoperative pain relief, changing the contents according to the severity of pain, might be a useful and cost saving method.
A new screening method for inducers of colony-stimulating factors (CSFs) was established using KM-102, a human bone marrow stromal cell line as the producer. In this method, the assay system which uses CSF dependent cell lines is combined with the CSF production system. Interleukin-1 (IL-1), which is known to upregulate CSF production in many cell populations, was used as a positive control for production of granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF). Induction in the positive controls was clearly detected within 24 hours. Activators of protein kinase C (PKC), protein phosphatase inhibitors and lipopolysaccharide (LPS) were positive in this assay system, but muramyl dipeptide (MDP) and Bestatin which are known macrophage activators, were negative. Inducers of CSFs were successfully detected using this assay method. Among 1,600 microbial strains tested, 2 actinomycete strains were found to produce active substances. One strain produces teleocidin-A, a strong activator of PKC, and the other strain produces a mixture of active compounds including three novel compounds. These three compounds do not induce terminal differentiation of HL-60 cells, suggesting that they are not teleocidin-like substances and form a new class of CSF inducers.
Three metabolites were isolated from the culture broth of an actinomycete strain identified as Streptomyces platensis SANK 60191, that induce the production of colony-stimulating factors (CSFs) by stromal cell line KM-102 at ED50 concentrations from 40 to 200 ng/ml. The compounds induced quantities of granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) comparable to those induced by interleukin-1, a strong CSF inducer. These metabolites were called leustroducsins (A, B and C) and were later found to be structurally related to phoslactomycins. This is the first report of CSF inducing activity by members of the phoslactomycin class.