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Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 505 records · Page 28Linked to original sources
PubMed1993

Antitumor agents. II: Regio- and stereospecific syntheses of 1-beta-alkyl-1-desoxypodophyllotoxin derivatives and biological activity.

1-beta-Alkyl derivatives of 1-desoxypodophyllotoxin were synthesized, and their cytotoxicity and inhibitory effects on DNA topoisomerase II (Topo-II) and tubulin polymerization were examined. The reaction of epipodophyllotoxin derivatives (1a-c) with trimethylallylsilane in the presence of boron trifluoride etherate gave 1-beta-allylated compounds (2a-c). The regiochemistry and the beta-stereochemistry of the 1-allyl group were confirmed by comparison of the 13C-NMR spectra and NOE's (%) of 2c, podophyllotoxin (POD) and epipodophyllotoxin (1b). 1-beta-Alkyl-1-desoxypodophyllotoxin derivatives (3-8) were prepared from 2b. None of the tested compounds (3-8) showed any inhibitory effect on Topo-II. 1-beta-Propyl compound (3) and its 4'-demethyl compound (4) inhibited tubulin polymerization and the cytotoxicities of these compounds were equal to that of VP-16. 1-beta-(2,3-Dihydroxypropyl) compounds (5 and 8) and 1-beta-(2,3-diacetoxypropyl) compounds (6 and 7) showed no inhibitory effect on tubulin polymerization. Although 5 did not inhibit either Topo-II activity or tubulin polymerization, it showed a high cytotoxicity against sarcoma 180.

Animals↗
PubMed1993

Postoperative improvement in blood lactate threshold during exercise in a patient with pulmonary arteriovenous fistula.

A 13-year-old female patient with a pulmonary arteriovenous fistula (PAVF) of 24 percent shunt fraction (SF) underwent resection of segments 8 and 9 of the left lower lobe. Three months after the operation, the shunt became insignificant and PaO2 was normalized. In terms of the maximum work rate, maximum VO2 and the VO2-blood lactate relationship, this patient showed a remarkable postoperative improvement in the exercise capacity.

Adolescent↗
PubMed1993

Histometric changes in connective fibers of the lung following paraquat administration in rats.

Pulmonary fibrosis induction by paraquat was studied histometrically using an image analyzer. Rats were given a subcutaneous injection of paraquat (7 or 25 mg/kg) and autopsied 3, 6 or 9 days later. The percentage of the area of connective fibers per unit area, and lung prolyl hydroxylase activity, as a biochemical parameter, were measured. Rats treated with 25 mg/kg of paraquat showed an increase in the percentage of the area of the connective fibers per unit area and also an increase in lung prolyl hydroxylase activity 6 days later. Thus, pulmonary fibrosis was confirmed both morphologically and biochemically. It is concluded that histometric examination using an image analyzer provides a very accurate method for the evaluation of pulmonary fibrosis.

Animals↗
PubMed1993

The intravenously administered glycerol test.

Three different methods of performing the glycerol dehydration test were evaluated. Method one involved the oral administration of 50 g of 50% glycerol solution; method two was the intravenous administration of 500 ml of 10% glycerol in saline with 5% fructose; and method three involved the administration of 200 ml of the same solution. It was found that intravenous administration was safe and did not give any unpleasant side effects. Both intravenously administered methods appeared to give similar rates of positive diagnosis for Menière's disease.

Administration, Oral↗
PubMed1993

Clinical usefulness of the personal computer for equilibrium examinations.

A personal computer (PC) system and its usefulness for equilibrium examinations is reported. The system was introduced into clinical routine practice for the following purposes: i) Reduction of test result measurement troubles in clinical practice, ii) Clearer observation of eye movements and body sway, iii) Quantitative analysis of nystagmus responses or body sway, iv) Easy introduction into clinical practice of new parameters or new tests, v) Programmable arrangement of stimulating devices, and vi) Effective storage of test data. Our PC system has been successful for these purposes and provided many useful options in equilibrium examinations. Although computer systems for equilibrium examination have not been popular due to high costs, the PC system, which can be obtained at a reasonable price, has become as powerful a device as the conventional small computer, and is expected to become a popular method for both research and routine clinical practice in the near future.

Caloric Tests↗
PubMed1993

Both beta-1 and beta-2 adrenoceptors are coupled to the cyclic AMP system in connecting tubules of rabbit nephron.

The connecting tubule (CNT), a segment interposed between distal convoluted tubules and collecting ducts, is a well defined segment in the rabbit nephron and have been shown to contain adenylate cyclase activity which is responsive to the beta agonist isoproterenol (ISO) and the nonselective beta blocker propranolol. We examined whether ISO also increased cAMP levels in the intact microdissected CNT in the presence of 1-methyl-3-isobutyl-xanthine and, in particular, which subtype of beta adrenoceptors was stimulated. ISO increased cAMP contents in a dose-dependent way (ED50 approximately equal to 10(-7) M) and the maximal stimulation was achieved at 1 microM ISO. Norepinephrine also elevated cAMP content in the CNT to the same extent as ISO. The increase in cAMP stimulated by ISO and norepinephrine was inhibited by 1 microM propranolol but not by 1 microM phenoxybenzamine. ISO-induced cAMP increased was blocked by the beta-1 antagonist metoprolol and also by the beta-2 antagonist ICI-118551 independently in a dose-dependent manner, and maximal inhibition was observed at 1 microM of both antagonists. These results indicate that both beta-1 and beta-2adrenoceptors appear to be located in the rabbit CNT and both can be positively coupled to adenylate cyclase to generate cAMP accumulation.

Adrenergic alpha-Antagonists↗
PubMed1993

[Neuropathology required from "brain death"].

We have pathoanatomically investigated Japanese 84 autopsied patients who had been clinically judged to be in a state of "brain death". 1) The finding observed in all the cases was that the brains revealed a severe state of increased intracranial pressure (IICP) with secondary hemorrhages involving the brain stem tegmentum. 2) Autolysis was observed in all the brains, especially in their brain stems, and the degree was always severer than in the visceral organs (VOs). 3) We considered that in all the cases cessation of cerebral blood flow occurred at least in the brain stem tegmentum by the time of the judgements. 4) We pointed out that like the VOs, the spinal cord under a certain level of the cervical segments continued to live until the cardiac stop. 5) We also considered that in nearly half the cases the neurons of the hypothalamus, especially of its supraoptic nucleus, tended to live long, for 3 to 4 days, even after the judgements.

Autolysis↗
PubMed1993

The presequence of a precursor to the delta-subunit of sweet potato mitochondrial F1ATPase is not sufficient for the transport of beta-glucuronidase (GUS) into mitochondria of tobacco, rice and yeast cells.

A precursor to the delta-subunit of sweet potato mitochondrial F1ATPase (pre-F1 delta) has an amino-terminal (N-terminal) presequence of 45 amino acid residues and its N-terminal 18 residues may form an amphiphilic alpha-helix, which is typical of mitochondrial targeting signals [Kimura et al. (1990) J. Biol. Chem. 265: 6079]. Fusion genes consisting of sequences that encoded the 25 (DG25), 46 (DG46) and 73 (DG73) N-terminal amino acids from pre-F1 delta fused to the N-terminus of the coding sequence of bacterial beta-glucuronidase (GUS) were placed downstream of the 35S promoter of cauliflower mosaic virus and used to transform suspension-cultured tobacco cells, rice calli and tobacco plants. Fusion genes were also placed downstream of the yeast GAL10 promoter and introduced into Saccharomyces cerevisiae cells. In these transformed cells, only the DG73 GUS-fusion protein was transported into mitochondria and subjected to proteolytic cleavage of the presequence. Neither transport to mitochondria nor processing of the presequence of the DG46 GUS-fusion protein, which contained the entire presequence and the processing site, occurred in either plant or yeast cells. These results indicate that the presequence of pre-F1 delta is not sufficient for the transport of the GUS protein into mitochondria in tobacco, rice and yeast cells. The requirement for the longer polypeptide from pre-F1 delta in the transport of the GUS protein into mitochondria could be due either to the lack of sufficient information for mitochondrial targeting within the presequence or to the nature of the passenger protein, GUS, used in this study.

Amino Acid Sequence↗
PubMed1993

Effect of the angiotensin converting enzyme inhibitor, captopril, on proteinuria in chronic glomerular disease.

The antiproteinuric effect of the angiotensin-I-converting enzyme inhibitor, captopril, was studied in 14 patients (10 men and 4 women, age range of 24 to 60 years) with chronic glomerulonephritis in whom IgA nephritis had been confirmed by renal biopsy. Eight of the 14 patients had received antihypertensive drugs such as calcium channel blockers, diuretics or beta-blockers. Captopril was added to these regimens at 25 mg twice daily in 3 patients, and 37.5 mg in 11 patients. Proteinuria decreased from 2.55 +/- 0.48 g/day to 1.58 +/- 0.35 g/day within three months after the start of administration. In 4 patients (28.6%), the extent of reduction was over 50%, and in 8 patients (57.1%), over 25%. Blood pressure, creatinine clearance and serum creatinine were not changed significantly. There was a positive linear correlation between the extent of reduction of proteinuria and the increase in plasma renin activity (r = 0.93, p < 0.001). We conclude that captopril reduces proteinuria in some patients with IgA nephritis whose plasma renin activity responds to the drug.

Adult↗
PubMed1993

[Comparison of gastrointestinal toxicity of 5-FU derivatives].

Gastrointestinal toxicities of tegafur (FT) and doxifluridine (DFUR) were compared using mouse intestinal enzymes as the marker. Enzyme activities were decreased during repeated administration of these 5-FU derivatives. When the drugs were administrated once a day, the decrease of enzyme activities were almost equal, but when administrated twice a day. DFUR showed greater decrease. Pharmacokinetical analysis revealed faster catabolism of DFUR than FT. In vitro 5-FU formation by GI extract was much higher from DFUR than FT. These data show a good agreement with the fact that the incidence of diarrhea is much higher in DFUR than FT.

Administration, Oral↗
PubMed1993

[Elevation of serum apo E-rich HDL concentration in a patient with cholestatic liver disease].

A remarkable elevation of serum HDL cholesterol concentration (165mg/dl) was found in a 42-year-old Japanese male with chronic pancreatitis who had been cholestatic for several years. An abnormal slow alpha-migrating lipoprotein, larger in particle size and more enriched with cholesteryl ester and apo E than normal HDL, was found in the patient's plasma. Quantitative determination of apo E-rich HDL revealed a striking increase of this lipoprotein in plasma. After choledocho-jejunostomy, a prompt and remarkable decrease of plasma apo E-rich HDL was observed, indicating a direct contribution of cholestasis to the accumulation of apo E-rich HDL in plasma in this patient.

Adult↗
PubMed1993

Detailed analysis of genetic alterations in colorectal tumors from patients with and without familial adenomatous polyposis (FAP).

To examine early genetic events during colorectal carcinogenesis, we searched for genetic alterations in 75 adenomas from seven patients with familial polyposis coli (FAP) and in 64 sporadic colorectal tumors (63 carcinomas and one adenoma). We investigated germ-line and somatic mutations in the APC gene, somatic mutations in the K-ras and p53 genes, and loss of heterozygosity (LOH) on chromosome 8p21-22. Thirty-two FAP adenomas carried detectable somatic mutations in the APC gene. The frequency of somatic APC mutations among adenomas was the same regardless of differences in size or histopathological classification. On the other hand, K-ras mutation was very rare in small adenomas where dysplasia was mild or moderate but frequent in large adenomas with severe dysplasia. Mutation of the p53 gene was observed in only two adenomas and LOH on 8p22 was detected in none. These results imply that a second 'hit' in the APC gene, but not necessarily mutation in K-ras or p53, is an important and critical event for formation of a colorectal adenoma.

Adenomatous Polyposis Coli↗
PubMed1993

[Experimental study on the combined treatment of UFT with etoposide against mouse Lewis lung carcinoma].

Synergistic cytotoxicity between FUra and etoposide was determined in Lewis lung carcinoma (3LL) cells by clonogenic assay. With the same exposure condition, chasing the time course of DNA strand breaks and repair by DNA unwinding assay. DNA repair in the exposure sequence of etoposide prior to FUra was remarkably delayed more than that by etoposide alone. There was a little overlap in normal tissue toxicity of UFT and etoposide since 65% of the full dosages of the two agents can be used in combination and main toxicities (suppression of body weight, decrease in WBC and damage of intestinal mucosa) were dispersed with dependence on the schedule of administration. Moreover, this combined treatment with the most tolerated dose resulted in the highest survival effect on 3LL-bearing mice than each agent alone. These data suggest that combination chemotherapy of UFT with etoposide show high antitumor activity and low host toxicity, and will be clinically useful.

Animals↗
PubMed1992

Hepatitis C virus infection in hepatocellular carcinoma. Detection of plus-strand and minus-strand viral RNA.

BACKGROUND: Although serum antibody to hepatitis C virus (anti-HCV) is found in many patients with hepatocellular carcinoma, the actual roles of HCV in carcinogenesis are unknown. METHODS: With reverse transcription followed by the polymerase chain reaction (RT-PCR), HCV RNA was examined in the sera and liver tissues of 16 patients with hepatocellular carcinoma who did not have hepatitis B virus markers, 13 of whom had anti-HCV. RESULTS: In the 13 patients with anti-HCV, the HCV genomic plus-strand RNA was detected more frequently in noncancerous tissues (8 patients, 61.5%) and in sera (6 patients, 46.2%) than in cancerous tissues (3 patients, 23.1%). No viral RNA was found in either sera or tissues in the three patients without anti-HCV. By using a sense primer for the RT in the RT-PCR assay, amplification was attempted of a putative complementary minus-strand RNA that is believed to reflect viral replication in the eight patients with the plus-strand RNA. The minus-strand RNA was found in the noncancerous tissues of six patients; it was not detected in the cancerous tissues. CONCLUSIONS: These results suggest that HCV can infect and replicate predominantly in noncancerous cells but rarely in tumor cells.

Aged↗
PubMed1992

Camptothecin analog (CPT-11)-sensitive human pancreatic tumor cell line QGP-1N shows resistance to SN-38, an active metabolite of CPT-11.

In the course of our study to determine the cross-sensitivity between CPT-11 and its active metabolite, SN-38, we found a SN-38-resistant human pancreatic tumor cell line, QGP-1N, which shows sensitivity to CPT-11. The IC50 of SN-38 was 152 times greater for QGP-1N than for SUIT-2, also a human pancreatic tumor cell line, whose IC50 of CPT-11 was similar to that for QGP-1N. The uptakes of CPT-11 and SN-38 and the intracellular conversion of CPT-11 to SN-38 could not explain the difference in sensitivity. DNA synthesis of QGP-1N cells was inhibited by CPT-11 which did not affect that of SUIT-2, while SN-38 inhibited the DNA synthesis of SUIT-2 at lower concentrations than that of QGP-1N. The inhibition test of topoisomerase I catalytic activity by CPT-11 or SN-38 revealed no difference in the biochemical properties of the topoisomerase I enzymes to the compounds between these two cell lines. These results indicate that CPT-11 should have its own inhibitory effect on DNA synthesis through a yet unknown mechanism in QGP-1N cells, although SN-38 plays an essential role in the antitumor activity of CPT-11 in SUIT-2 cells. In some cases, the antitumor effect of CPT-11 might be consequent not only on SN-38 but also on CPT-11 itself.

Antineoplastic Agents, Phytogenic↗