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Biomedical subjects

K Ohtani

Publications and source records attributed to K Ohtani.

At least 145 records · Page 8Linked to original sources

[Estramustine phosphate, estrogen conjugated with nitrogen mustard inhibits the growth of endometrial cancer cells in vitro].

Estra-1,3,5 (10)-triene-3,17-diol (17 beta)-, 3-[bis(2-chloroethyl) carbamate] (Estramustine EM) was tested for its anticancer effect on human endometrial cancer cell lines: Ishikawa and its estrogen (E) independent sub-clone EIIL (Estrogen Independent Ishikawa Line). The results showed: (1) EM inhibited growth of both cell lines in a dose dependent manner giving ID50 for Ishikawa as 12 microM and for EIIL as 65 microM. (2) The addition of EM to the culture medium caused cell detachment and death associated with a breakdown of DNA to approximately 90 base pair fragments. (3) Reverse transcription-polymerase chain reaction to examine expressions of c-erbB-2, nidogen and fas showed that EM completely abolished fas expression and resulted in a 40% decrease in nidogen expression in Ishikawa but not in EIIL. No change was seen in c-erbB-2 expression. The present data indicate that the E component of EM does not stimulate the growth of Ishikawa or EIIL. Since the growth of both cell lines was inhibited but apparently in an E receptor (ER) dependent manner, EM may be of value in an adjuvant therapy for endometrial cancer, especially an ER positive one.

Adenocarcinoma↗

Increased plasma thrombin-antithrombin III complex levels in non-insulin dependent diabetic patients with albuminuria are reduced by ethyl icosapentatenoate.

Hypercoagulability may increase the risk of cardiovascular disease (CVD) in diabetic patients with albuminuria. Plasma thrombin-anti-thrombin III complex (TAT) levels, representing a functional state of clotting system, were studied in one hundred and fifteen non-insulin-dependent diabetic (NIDDM) patients. The patients were divided into three groups according to the urine albumin index (UAI: mg/g Cr): Group A; UAI < 30, Group B; 30 < UAI < 300, Group C; UAI > 300. The effect of albuminuria on plasma TAT levels was significant (p < 0.02). Ethyl icosapentatenoate (EPA: 1800 mg/day) for 4 weeks significantly (p < 0.0005) decreased plasma TAT levels. These data indicate that the degree of diabetic albuminuria is related to plasma TAT levels in NIDDM patients and that treatment with EPA may reduce TAT levels and possibly therefore the rate of development of CVD in patients with NIDDM.

Albuminuria↗

[Estetrol (E4)].

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Estetrol↗

Effect of sucrose monostearate, an emulsifier, on polyamine metabolism and phosphatidylinositol turnover in Ehrlich ascites tumor cells.

Sucrose esters of fatty acids have antitumor activity. We studied the effect of sucrose monostearate (SS), an emulsifier, on polyamine metabolism and phosphatidylinositol turnover in Ehrlich ascites tumor cells. The activity of ornithine decarboxylase (ODC) was increased in the cells by changing the medium. This increase in the activity was inhibited by adding sucrose stearate, but not sucrose or stearate to the medium. The activity of spermidine/spermine N1-acetyltransferase (SAT), a rate-limiting enzyme of polyamine biodegradation, was enhanced with the addition of SS in a time- and dose-dependent manner. The elevation of SAT activity was completely prevented when cycloheximide was added to the culture simultaneously. In in vitro studies, SS at various concentrations up to 1 mM hardly affected the activities of ODC or SAT. The incorporation of [3H]inositol into both fractions of inositolphospholipid and inositol phosphates was inhibited by SS. These results suggest that the perturbation of polyamine metabolism and phosphatidylinositol turnover is involved in the mechanism of antitumor activity of SS in Ehrlich ascites tumor cells.

Acetyltransferases↗

Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression.

Both positive and negative signals govern the progression of cells from G1 into S phase, and a variety of data implicate the E2F transcription factor as a target for the action of one class of negative regulators, the Rb family of growth suppressors. We now find that the E2F1 gene, which encodes one of the components of E2F activity, is subject to autoregulatory control during progression from G0 to S phase and that this primarily reflects a negative control in G0 and early G1, a time when the majority of E2F activity exits as a complex with Rb family members. In addition, we find that deregulated expression of G1 cyclins in quiescent cells stimulates the E2F1 promoter and that this is augmented by coexpression of cyclin-dependent kinases in an E2F-dependent manner. We conclude that the E2F1 gene is a downstream target for G1 cyclin-dependent kinase activity, most likely as a consequence of phosphorylation of Rb family members, and that the autoregulation of E2F1 transcription may provide a sensitive switch for regulating the accumulation of E2F activity during the transition from G1 to S phase.

Base Sequence↗

Oleanane and ursane glycosides from Schefflera octophylla.

Twelve triterpene glycosides were isolated from the bark of Schefflera octophylla of Vietnamese origin. Three of them were identified as asiaticoside, cauloside D and 3 alpha-hydroxyurs-12-ene-23,28-dioic acid 28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside. The structures of nine new glycosides were elucidated by chemical and spectroscopic evidence. Including the known compounds, the 12 glycosides consisted of six pairs of corresponding ursene and oleanene glycosides and all of them had the same triose moiety at the C-28 position. The names scheffurosides A-F and scheffoleosides B-F were proposed for corresponding pairs of ursene and oleanene glycosides, respectively.

Carbohydrate Sequence↗

Diterpenoid glycosyl esters from Phlomis younghusbandii and P. medicinalis roots.

From the roots of Phlomis younghusbandii collected in Tibet, new furanolabdane-type diterpenoid glycosides named phlomisosides III and IV were isolated together with a known sweet furanolabdane-type diterpenoid glycoside, phlomisoside I. The structure of the common aglycone of phlomisosides III and IV, which we have named phlomisoic acid, was established as 15,16-epoxy-8,13(16),14-labdatrien-19-oic acid by MS and NMR spectroscopy. Phlomisosides III and IV are tasteless and the structures of these were determined to be the beta-D-xylopyranosyl(1-->2)-beta-D-glucopyranosyl and the alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester of phlomisoic acid by chemical and spectroscopic methods, respectively. The diterpenoid glycoside constituents of the roots of P. medicinalis collected in Tibet were also elucidated, and baiyunoside and phlomisosides II and III were isolated and identified.

Carbohydrate Sequence↗

Induction of manganese superoxide dismutase by cytokines and lipopolysaccharide in cultured mouse astrocytes.

To determine whether cytokines or lipopolysaccharide (LPS) are involved in the induction of superoxide dismutase (SOD) in the nervous system, we examined the effects of these substances on the levels of SOD in cultured mouse astrocytes. Treatment of astrocytes with 10(2) to 10(4) U/ml tumor necrosis factor-alpha for 3 days increased the levels of Mn SOD in a dose- and time-dependent manner to as much as six times the level under nontreated conditions. Treatment with 1.0 microgram/ml LPS for 3 days elicited a fourfold increase in levels of Mn SOD, and the effect of LPS was also dose dependent. Furthermore, Mn SOD in astrocytes was induced by a 3-day exposure to interleukin-1 alpha at concentrations of 10(2) or 10(3) U/ml. However, these stimuli had no effect on levels of copper-zinc SOD (Cu/Zn SOD) in astrocytes. By contrast, interferon-gamma did not change the levels of either Mn or Cu/Zn SOD in the cells. The results indicate that the selective induction of Mn SOD by cytokines and LPS, which has been observed in nonnervous tissues, may also occur in nervous tissues. The induction of Mn SOD may represent a mechanism for protection of cells from oxidative stress.

Animals↗

Functional properties of a Drosophila homolog of the E2F1 gene.

A variety of studies have now implicated the cellular transcription factor E2F as a key participant in transcription control during the cell growth cycle. Although the recent isolation of molecular clones encoding proteins that are components of the E2F activity (E2F1 and DP-1) provides an approach to defining the specific involvement of E2F in these events, definitive experiments remain difficult in the absence of appropriate genetic systems. We have now identified a Drosophila equivalent of E2F1 that we hope will allow an eventual genetic approach to the role of E2F in cellular regulatory events. A cDNA clone was isolated from a Drosophila cDNA library by using a probe containing sequence from the E2F1 DNA binding domain. The sequence of the clone, which we term drosE2F1, demonstrates considerable homology to the human E2F1 sequence, with over 65% identity in the DNA binding region and 50% identity in the region of E2F1 known to interact with the retinoblastoma gene product. A glutathione S-transferase-drosE2F1 fusion protein was capable of binding specifically to an E2F recognition site, and transfection assays demonstrated that the drosE2F1 product was capable of transcription activation, dependent on functional E2F sites as well as sequences within the C terminus of the protein. Finally, we have also identified E2F recognition sequences within the promoter of the Drosophila DNA polymerase alpha gene, and we demonstrate that the drosE2F1 product activates transcription of a test gene under the control of this promoter. We conclude that the drosE2F1 cDNA encodes an activity with extensive structural and functional similarity to the human E2F1 protein.

Amino Acid Sequence↗

Saponins from Vietnamese Ginseng, Panax vietnamensis HA et Grushv. Collected in central Vietnam. II.

Further investigation on the saponin composition of rhizomes and roots of Panax vietnamensis HA et GRUSHV. has resulted in the isolation and structural elucidation of seven new dammarane saponins named vina-ginsenosides-R3 (12), -R4 (11), -R5 (16), -R6 (17), -R7 (6), -R8 (20), -R9 (22), together with the identification of six known saponins including 20-gluco-ginsenoside-Rf (10), ginsenoside-Rc (4), notoginsenoside-R6 (9), quinquenoside-R1 (5), gypenoside XVII (2) and majoroside F1 (21). The structures of the novel saponins were established on the basis of chemical and spectral evidence. Vina-ginsenoside-R3 is the first naturally occurring glycoside of dammarenediol II, while vina-ginsenosides-R5 and -R6, two ocotillol-type saponins, are two other examples of saponins having the rare alpha-glucosyl linkage.

Carbohydrate Sequence↗

Saponins from Vietnamese ginseng, Panax vietnamensis Ha et Grushv. collected in central Vietnam. III.

Five new dammarane saponins derived from four new aglycones were isolated from the rhizomes and roots of Panax vietnamensis Ha et Grushv. On the basis of physicochemical and spectral evidence, the structures of these compounds were established as 6-O-beta-D-glucopyranosyl 20(S),25-epoxydammarane-3 beta,6 alpha,12 beta,24 alpha-tetrol (1), 6-O-beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl 20(S),25-epoxydammarane-3 beta,6 alpha,12 beta,24 alpha-tetrol (2), 6-O-beta-D-glucopyranosyl dammarane-3 beta,6 alpha,12 beta,20(S),24 xi,25-hexol (5), 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D- glucopyranosyl dammarane-3 beta,12 beta,20(S),24 xi,25-pentol (8) and 6-O-beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl 20(S),24(S)-epoxydammarane-3 beta,6 alpha,12 beta,25 xi,26-pentol (10). The trivial names, vina-ginsenoside-R10, -R11, -R12, -R13 and -R14, respectively, were assigned to the new saponins.

Carbohydrate Sequence↗

A novel human tyrosine kinase gene inducible in T cells by interleukin 2.

We have cloned a novel human protein tyrosine kinase gene specific to T cells by the polymerase chain reaction method. This gene encodes a 620 amino-acid polypeptide including a catalytic domain for tyrosine kinase, an SH2 domain and an SH3 domain, seemingly belonging to the src family. However, characteristics of a long unique N-terminal stretch and lack of a myristylation site at the N-terminus and of a kinase regulatory tyrosine residue in the C-terminus classify this molecule into a new subfamily comprising recently cloned mouse tec, itk/tsk and human atk/bpk genes. This gene was transcriptionally induced in normal T cells by interleukin 2 stimulation. These results suggest the crucial roles of this gene in T cell proliferation and differentiation.

Amino Acid Sequence↗

Autopsy case of hepatocellular carcinoma associated with lupoid hepatitis and complicated by malignant lymphoma.

An 81-year-old woman in whom liver dysfunction had been pointed out 3 years previously was diagnosed as having liver cirrhosis due to lupoid hepatitis. Considering the poor prognosis of cirrhosis and her age, immunosuppressive therapy was not adopted. Nine months later, a small liver tumor was found by ultrasonography and was diagnosed as hepatocellular carcinoma (HCC). The tumor was treated with transcatheter arterial embolization, but grew continuously. She also developed gingival lymphoma that was successfully treated. Three years after initial diagnosis of lupoid hepatitis, she died of hepatic failure. An autopsy was performed and confirmed the clinical diagnosis, liver cirrhosis with HCC. HCC is regarded as a rare complication of lupoid hepatitis, but cases of HCC complicating lupoid hepatitis may increase with progress in treatment methods and elongation of survival. The present case suggests that any malignancy can be developed in long-term surviving patients with lupoid hepatitis.

Aged↗

A rapid molecular diagnosis of posttransfusion graft-versus-host disease by polymerase chain reaction.

A woman with recurrent Paget's disease of the vulva developed acute graft-versus-host disease (GVHD) 12 days after radical surgery and massive blood transfusion. Molecular diagnosis of lymphocyte chimerism in the peripheral blood was made by polymerase chain reaction (PCR) directed against a Y chromosome-specific sex-determining region Y (SRY) gene. PCR with skin biopsy after onset of GVHD also revealed infiltration of SRY-positive donor lymphocytes. The diagnosis was confirmed by HLA-DNA typing with PCR-sequence-specific oligonucleotide that revealed the presence of complex HLA-DR chimerism in the peripheral lymphocytes collected after onset of GVHD. The use of SRY-directed PCR is a rapid technique for the early diagnosis of acute posttransfusion GVHD in female patients.

Base Sequence↗

Screening of plant constituents for effect on glucose transport activity in Ehrlich ascites tumour cells.

The effect of plant extracts on D-glucose uptake by Ehrlich ascites tumour cells was examined. Among the 23 extracts of medicinal plants, five samples inhibited, and six samples activated, the uptake significantly. From one of the active plants, Lagerstroemia speciosa, two triterpenoids, colosolic acid and maslinic acid were isolated. Colosolic acid was shown to be a glucose transport activator. Since this compound was known to have hypoglycemic activity, our simple in vitro bioassay method can at least be used as a first screening for anti-diabetic activity.

Animals↗