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Biomedical subjects

T Hatayama

Publications and source records attributed to T Hatayama.

At least 127 records · Page 7Linked to original sources
PubMed1986

[Phase II study of THP patients with gastrointestinal cancer].

A phase II study on THP((2''R)-4'-0-Tetrahydropyranyladriamycin) was performed in 47 patients with advanced or recurrent gastrointestinal cancer through the cooperation of nine institutions in Hiroshima Prefecture from April 1982 to November 1984. THP was given by means of intravenous infusion and/or intraaortic infusion and the 47 cases were divided into two groups according to the method of administration: (A) 40-60 mg/body every 3 or 4 weeks, or (B) 30 mg/body every week. Among 24 evaluable cases, partial response (PR) was observed in two cases of recurrent metastatic lymph nodes in gastric cancer patients. The (A) method of administration was more effective than (B). Subjective side effects observed were appetite loss, nausea, vomiting and general fatigue, but these were not so severe. Leukocyte nadir occurred at the 1st or 2nd week of THP administration, but thrombocytes were not appreciably decreased.

Antineoplastic Agents↗
PubMed1984

Two species of chromatin-RNA polymerase II complex are commonly present in nuclei of various tissues of rats.

When rat liver nuclei were digested with nuclease, we found that the chromatin-bound RNA polymerase II was liberated as two distinct complexes, peak 1 and peak 2, which seemed to reflect different functional states in cell nuclei. We further examined their occurrence in nuclear digests of various tissues of rats and the following results were obtained. Upon digestion with micrococcal nuclease of nuclei from brain, spleen, testis and kidney, chromatin-bound RNA polymerase II was liberated as two distinct forms which sedimented differently in a sucrose density gradient. The sedimentation rate of peak 1 varied depending on the tissue nuclei examined. After high salt or RNase treatment of the nuclear digests, peak 1 from liver, brain, spleen and testis nuclei showed the same sedimentation rate as did kidney peak 1, the rate for which remained unchanged by these treatments. The results suggested that peak 1 complexes from various tissue nuclei had basically the same structural organization, and we confirmed this by electrophoretic studies on RNase-treated liver and kidney nuclear digests. Peak 2 from various tissue nuclei exhibited identical sedimentation rates. Thus, the chromatin-bound RNA polymerase II seems to exist commonly in two distinct states in cell nuclei of rats.

Animals↗
PubMed1984

Caffeine-induced reorganization of DNA replicating system occurs on or near nuclear matrix in HeLa cells.

Since caffeine reorganizes the DNA replicating system, with several consequences, we studied the effect of caffeine on the DNA replication which normally occurs on or near the nuclear matrix in a variety of eukaryotic cells. When HeLa cells, treated with or without the DNA-damaging agent, neocarzinostatin, were postincubated in the presence or absence of caffeine and then pulse-labeled with [3H]thymidine, the DNA remaining tightly associated with the matrix was enriched in the newly synthesized DNA at the same level as that seen in untreated cells. The nuclear matrix-bound DNA polymerase alpha activity was also the same in these cells. Therefore, in the presence of caffeine, DNA replication, with or without DNA damage, also occurs on or near the nuclear matrix, as is the case in normal DNA replication.

Caffeine↗
PubMed1984

[Ultrasound-guided renal cyst puncture and 95% ethanol instillation. Part 2: Morphological and functional alterations].

Ultrasound-guided renal cyst puncture was performed on 22 cysts which were then 95% ethanol instilled to prevent recurrence of cystic fluid. Cystic lesions disappeared on the ultrasonogram in the follow-up period of 3 to 28 months. On CT, cystic lesions became smaller size but did not disappear. Average CT numbers of the cyst were 8.75 +/- 3.83 before and 12.96 +/- 3.27 after ethanol instillation. The cystic wall became thicker. Caliceal distortion and/or pelvis compression by cystic lesions improved on IVP 2 to 3 days after ethanol instillation. The renal image on Tc-99m-DMSA scintigram showed morphological improvement and DMSA renal uptake rate increased slightly but significantly 2 to 4 weeks after ethanol instillation. There were no major complications with this procedure except for one case in which the tip of the catheter became stuck in the cyst and broke off when the catheter was removed. A slight local irritable pain was noticed in all cases. Half of the patients had hot flushes and/or somewhat drunken sense but these symptoms were only temporary. Antabuse phenomenon appeared in one case with concomitant use of a cephem antibiotics after ethanol instillation. This method of therapy is a safe non-surgical approach to treat renal cysts. 95% ethanol instillation in the cyst seems to prevent recurrence of cystic fluid.

Adult↗
PubMed1984

Undermethylation of DNA in mononucleosomes solubilized by micrococcal nuclease digestion of HeLa cell nuclei.

To examine the distribution of 5-methylcytosine in chromatin DNA, DNA of HeLa cells was labeled with [3H-methyl]methionine and [14C] thymidine and analyzed after extensive digestion of the nuclei with micrococcal nuclease. When the chromatin solubilized with the nuclease was fractionated on a sucrose density gradient, DNA in mononucleosomes was considerably depleted in 5-methylcytosine, as compared with polynucleosomes. Electrophoretic separation of DNA from the chromatin also revealed the depletion of 5-methylcytosine in the mononucleosomal size of DNA. This was confirmed by the chromatographic analysis of 5-methyldeoxycytidine after enzymatic digestion of the DNA to nucleosides. Thus the DNA in mononucleosomes solubilized by extensive micrococcal nuclease digestion is depleted in 5-methylcytosine, suggesting that 5-methylcytosine is preferentially missing from the DNA in the nucleosome core particles.

Cell Nucleus↗
PubMed1983

Mode of inhibition of DNA replication in neocarzinostatin-treated HeLa cells.

The effect of antitumor antibiotic neocarzinostatin on DNA replication in HeLa cells was studied by pulse-labeling of DNA with [3H]thymidine and sedimentation analysis of the DNA with alkaline sucrose gradients. The drug, which produced DNA damage, primarily inhibited the replicon initiation in the cells at low doses (less than or equal to 0.1 microgram/ml), and at high doses (greater than or equal to 0.5 microgram/ml) inhibited the DNA chain elongation. An analysis of the number of single-strand breaks of parental DNA, induced by neocarzinostatin, indicated that inhibition of the initiation occurred with introduction of single-strand breaks of less than 1.5 . 10(4)/cell, while inhibition of the elongation occurred with introduction of single-strand breaks of more than 7.5 . 10(4)/cell. Assuming that the relative molecular mass of DNA/HeLa cell was about 10(13) Da, the target size of DNA for inhibition of replicon initiation was calculated to be about 10(9) Da, such being close to an average size of loop DNA in the cell and for inhibition of chain elongation, 1-2 . 10(8) Da which was of the same order of magnitude as the size of replicons. Recovery of inhibited DNA replication by neocarzinostatin occurred during post-incubation of the cells and seemed to correlate with the degree of rejoining of the single-strand breaks of parental DNA. Caffeine and theophylline enhanced the recovery of the inhibited replicon initiation, but did not aid in the repair of the breaks in parental DNA.

Antibiotics, Antineoplastic↗
PubMed1983

Transcribing chromatin is not preferentially enriched with acetylated histones.

Chromatin fragments of the RNA polymerase II-transcriptional complex were purified from the micrococcal nuclease digest of rat liver nuclei in the presence of n-butyrate, a potent histone deacetylase inhibitor. Polyacrylamide gel electrophoretic analysis in Triton acid-urea revealed that the extent of histone acetylation of the complex did not differ markedly from that of the total chromatin.

Acetylation↗
PubMed1983

[Clinical significance of measurement of immunosuppressive acidic protein (IAP) in lung cancer].

Immunosuppressive acidic protein (IAP) was investigated in 37 patients with lung cancer. A positive rate of IAP in patients was 62.2% and it was higher than that in pulmonary benign diseases except infectious cases. Serum IAP levels increased in accordance with the progress of disease, but no relationship with histological findings was observed. No significant correlation was found between serum IAP levels and in vivo PPD skin test. However, in patients with more than 1000 micrograms/ml of serum IAP levels, higher proportion of patients with negative PPD skin test was observed, indicating the depressed immunity of these patients. From these results, it was suggested that the effects of treatment and prognosis could be predicted by pre-and post-operative IAP levels.

Adult↗
PubMed1982

Characteristic distribution of two forms of chromatin-bound RNA polymerase II in rat liver nuclei.

We have shown that, in rat liver nuclei, the chromatin-bound RNA polymerase II is released as two different forms on digestion with micrococcal nuclease or DNase I (peak 1 and peak 2). To elucidate the origin of the two forms of the enzyme, we examined their distribution in fractionated chromatins obtained by mild micrococcal nuclease digestion of the nuclei. About half of the total peak 2 activity was recovered in a nuclease-sensitive chromatin fraction which contained DNA enriched in the sequences appearing in the polysomal polyadenylated mRNA. On the other hand, four-fifths of the total peak 1 activity was recovered in a nuclease-resistant chromatin fraction which contained DNA comprising only two thirds of the transcribed sequences. Furthermore, during the nuclease digestion, peak 2 activity was rapidly released from the chromatin, whereas peak 1 activity was gradually released. These results indicate that the two forms of RNA polymerase II are distributed differently in the cell nuclei.

Animals↗
PubMed1982

[Basic and clinical evaluations of cefmetazole in postoperative wound infections].

The time course of the concentration of cefmetazole (CMZ) in the serum and in skin and intestinal tissues was determined after a single intravenous injection of 2 g of the drug. CMZ moved into them well. Furthermore, 41 patients with postoperative wound infection (superficial in 29 and deep in 12) were treated with CMZ 2-4 g daily. Bacteriological examination of the lesions with simultaneously carried out. As a result, 101 strains of bacteria were isolated and identified. Mixed infection was found in 27 cases (65.9%). Fifteen strains (14.9%) of E. coli, 15 (14.9%) of B. fragilis, 7 (6.9%) of Klebsiella sp. and 7 (6.9%) of Proteus sp., were the main bacteria isolated. Eight cases (19.5%) had mixed infection of E. coli and B. fragilis. The committee (3 members) evaluated CMZ to be effective in 75.6% (31 of 41 cases) and bacteria disappeared in 60.5% (23 of 38 cases). The side effects observed were pyrosis and feeling of gastric malaise in 1 case. The results suggest that CMZ is useful, which exerts an excellent effect on postoperative wound infections.

Adolescent↗
PubMed1981

Partial characterization of RNA polymerase II complex released by micrococcal nuclease digestion of rat liver nuclei.

Two forms of RNA polymerase II were released from rat liver chromatin by micrococcal nuclease digestion of the nuclei. One from behaved like a free RNA polymerase II and the other like a complex with other nuclear components. Both forms of RNA polymerase II activity were recovered in the 0.16 M NaCl-soluble fraction of the nuclear digest, and the complexed from the RNA polymerase II could transcribe its endogenous template under conditions permitting only of elongation of the RNA synthesis. The RNA polymerase II complex was further purified by gel filtration chromatography and column electrophoresis. Analysis of protein and DNA of the partially purified complex suggested that the RNA polymerase II was bound to mono- or dinucleosomes carrying some characteristic nonhistone proteins. Furthermore, in experiments on tissues from starved rats, the two forms of RNA polymerase II were found to originate from different functional states of the chromatin-bound enzyme in vivo.

Animals↗
PubMed1979

DNA damage and repair in relation to cell killing in neocarzinostatin-treated HeLa cells.

To elucidate the mechanism of the cell killing activity of neocarzinostatin on mammalian cells, the drug-induced damage of DNA and its repair were examined. Very low doses of neocarzinostatin, at which high survival of cells was observed, clearly produced single-strand breaks of DNA and decomposition of the 'DNA complex', but these damages appeared to be repaired almost completely. At higher doses of neocarzinostatin, single-strand breaks were repaired to a considerable extent while double-strand breaks seemed not to be repaired. The number of non-repairable single-strand breaks was about twice that of double-strand breaks. This implies that single-strand breaks are repaired except for those constituting double-strand breaks. Although at low levels of neocarzinostatin repair of double-strand breaks may occur, the correlation existing between the colony-forming ability of cells treated with neocarzinostatin and non-repairable DNA breakage suggests that production of a small number of critical non-repairable double-strand breaks per cell may be responsible for the cell killing activity of the drug.

Antibiotics, Antineoplastic↗
PubMed1978

Nucleotide specificity in DNA scission by neocarzinostatin.

Using the DNA sequencing technique of Maxam and Gilbert, we show that the protein antibiotic neocarzinostatin, cleaves double-stranded phiX174 DNA restriction fragments almost exclusively at deoxythymidylic and deoxyadenylic acid residues in a reaction requiring 2-mercaptoethanol. Overall, deoxythymidylic acid residues are attacked much more frequently than are deoxyadenylic acid residues, although there is variability in the attack rate for both nucleotides at different locations in the DNA molecule. While all deoxythymidylic acid residues are sites of scission by neocarzinostatin, not all deoxyadenylic acid residues are cleavage sites. There appears to be no clear-cut nucleotide sequence specificity in determining cleavage frequency. Single-stranded DNA is a very poor substrate for neocarzinostatin-induced scission; with one single-stranded DNA fragment, cleavage occurs at a position that is not attacked in double-stranded DNA. The possible significance for its biological activity of a drug that can attack both members of a DNA base pair is discussed.

1-Propanol↗