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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 937 records · Page 52Linked to original sources

Antitumor efficacy of seventeen anticancer drugs in human breast cancer xenograft (MX-1) transplanted in nude mice.

To validate the usefulness of a human tumor-nude mice xenograft system as a potential model in the secondary screening of anticancer agents, the antitumor activity of 17 anticancer drugs has been studied in the treatment of a human breast cancer tumor (MX-1) transplanted to nude mice. For evaluation of the antitumor activity of the drugs we employed the LD10 predetermined in BDF1 mice as a standard therapeutic dose. Drugs were administered IV, IP, or PO, and antitumor activity was assessed by drug-induced growth inhibition measured by caliper. Among the 17 anticancer drugs, the most active compounds (maximum inhibition rate of tumor growth: greater than or equal to 90%) are mitomycin C, chromomycin A3, vincristine, vinblastine, vindesine, and hexamethylmelamine. Another group of compounds showed moderate activity (maximum inhibition rate of tumor growth: 89%-50%), these being adriamycin, daunomycin, mitoxantrone, bleomycin, 5-FU, 6-TG, and ftorafur. The remaining four drugs (peplomycin, cytosine arabinoside, 6-MP, and methotrexate) were inactive against the MX-1 tumor. These results suggested that in the nude mouse-human tumor xenograft system of the MX-1 tumor there was a good correlation between the antitumor activity of various anticancer drugs and their clinical efficacy; this system is therefore expected to be a useful model for the secondary screening system.

Animals↗

Reports of two cases of autoimmune thyroiditis while receiving anticonvulsant therapy.

Two cases, one a 15-year-old girl and the other a 12-year-old girl, with goitrous hypothyroidism associated with elevated anti-DNA and antithyroid antibodies are reported. Abnormalities were noticed 1 year and 3 months and 5 years after the start of anticonvulsant therapy in case 1 and case 2, respectively. Alternation of drug (Valproate from ethosuximide) in case 1 resulted in disappearance of the goitre, and the thyroid function tests became normal. The titers of the antithyroglobulin and the antimicrosomal antibodies were reduced (below 1:100) from 1:400 and 1:1600, respectively. Discontinuance of anticonvulsant therapy and replacement therapy with desiccated thyroid in case 2 resulted in clinical improvement, reduction of antithyroglobulin antibody from 1:6400 to 1:400 and of antimicrosomal antibody from 1:409,600 to 1:25,600, and the thyroid function tests becoming normal. The present observations suggest that the anticonvulsants may induce or exacerbate autoimmune mechanisms in certain thyroid diseases.

Adolescent↗

Clinical evaluation of prolonged chemotherapy combined with induction of hepatic drug-metabolizing enzymes as an adjuvant for treating patients with gastric cancer.

A clinical trial of a protracted adjuvant cancer chemotherapy was carried out on 207 patients with operable gastric cancer, from April, 1977, in the First Department of Surgery, Chiba University Hospital and two closely related hospitals. These patients were given intravenously 0.4 mg/kg and 0.2 mg/kg of mitomycin C on the day of operation and the next day, respectively, and then 16 mg/kg intravenously of Futraful (FT-207) daily from the 10th postoperative day until discharge, followed by oral administration of FT-207, 12 mg/kg, for 24 to 36 months after discharge. Two mg/kg of phenobarbital and 30 mg/kg of glutathione were administered randomly to half the number of patients (induction group) to induce hepatic drug-metabolizing enzymes. Significantly higher levels of serum 5-Fluorouracil (5-FU) released from FT-207 were found in the induction group than in the controls. Five-year overall survival rates in the induction and control groups revealed no difference. However, the survival rates in Stage III patients in the induction group were significantly superior in the 3-5 postoperative years, compared to those in the Stage III of the control group, while Stage I, II and IV patients apparently received no benefit from this induction treatment.

Clinical Trials as Topic↗

Purification of small polydisperse circular DNA of eukaryotic cells by use of ATP-dependent deoxyribonuclease.

Small polydisperse circular (spc) DNAs of mouse thymocytes were purified by a procedure involving nitrocellulose column chromatography and the treatment of ATP-dependent DNase, which acts only upon linear DNA molecules. Nitrocellulose column chromatography prior to the enzyme treatment was essential because digestion of linear DNA duplexes by the enzyme was inhibited by the presence of concomitant single-stranded DNAs. Mitochondrial DNAs were eliminated by linearization with XhoI and digestion with ATP-dependent DNase. The size distribution of the purified spc DNA molecules ranged from 0.2 micron to more than 28 micron, with a mean length of 5.4 micron. Circular molecules of more than 0.4 micron long (or 1.2 kb) were free from the contamination of linear DNA fragments and pure enough to be cloned into plasmids.

Animals↗

Studies on aspirin derivatives with very little side effect. IV. Inhibitory effect of aspirin-isopropylantipyrine (AIA) on several experimental thromboses.

The effect of a new aspirin derivative, aspirin-isopropylantipyrine (AIA), with potent platelet anti-aggregant activity, on several experimental thromboses was evaluated and compared with that of aspirin. AIA (50 mg/kg, s.c.) as well as aspirin (50 mg/kg, s.c.) significantly inhibited thrombus formation in extracorporeal shunt model of rats. AIA (50 mg/kg, s.c.) significantly shortened the duration of apnea and respiratory distress induced by a rapid injection of adenosine 5'-diphosphate in rats, while aspirin (50 mg/kg, s.c.) did not. Inhibitory effect of AIA (50 mg/kg, s.c.) on arachidonic acid-induced mortality in mice was less than that of aspirin (50 mg/kg, s.c.). AIA and aspirin (10 mg/kg/d X 10, s.c.) had no effect on laurate-induced arterial occlusive disease in rats. AIA (200 microM) showed weak and reversible inhibition of prostaglandin I2 generation in isolated rat aorta strip, while aspirin (200 microM) showed irreversible inhibition. AIA (50 and 200 microM inhibited Ca2+-, K+- or norepinephrine-induced contraction on isolated rat aorta strip. AIA (200 microM) had no effect on malondialdehyde formation, cyclic AMP level and adenylate cyclase activity in rat platelets. AIA (100 microM) inhibited arachidonic acid-induced contraction on rat fundus strip by about 50%, while aspirin (100 microM) did not. These results strongly suggest that anti-thrombotic activity of AIA was originated at least from its anti-aggregant effect on platelets, differing from aspirin.

Adenosine Diphosphate↗

Cellular kinetics of gastrointestinal mucosa, with special reference to gut endocrine cells.

After 3H-thymidine autoradiography was introduced to the study of cellular kinetics, the epithelial cells of the gastrointestinal mucosa have been examined extensively with regard to their kinetic behavior. After reviewing the knowledge on the kinetics of different epithelial cells in the stomach and small and large intestine, this article concentrates on the origin, differentiation and turnover of gut endocrine cells which have been under much controversy. Autoradiographic and other investigations of EC cells support the view that these cells are not neuroectodermal in origin, but differentiate from an immature type of gut epithelial cells. We investigated the kinetics of the antral G cells in the hamster, G cells and S cells in the rat duodenum by the combined utilization of 3H-thymidine autoradiography with immunohistochemistry, and confirmed that these cells are derived from the same precursor cells as the other mucosal cells of the gastrointestinal tract. The half-life of the antral G cells was estimated at 10-15 days, while the turnover time of the G cells and S cells in the duodenum were calculated at 3-4 days and 2 days, respectively. These data also support the belief that gut endocrine cells originate from the endoderm. Histopathological alterations such as antral gastritis and intestinal metaplasia, as well as vagal denervation, were shown to influence the population of the antral G cells in man and the hamster. This supports the view that intrinsic and extrinsic stimuli might alter the kinetics of gut endocrine cells.

Animals↗

Anomalous branch of the internal carotid artery supplying circulation of the anterior cerebral artery. Case report.

Angiographic and operative investigations revealed an anomalous branch of the internal carotid artery (ICA) in a patient with an anterior communicating artery (ACoA) aneurysm. The anomalous vessel originated from the right ICA at the level of the ophthalmic artery, and pursued an infraoptic and prechiasmatic path to supply both pericallosal arteries. The clinical features and possible genesis of this anomaly are discussed. This irregularity is frequently associated with intracranial aneurysms, especially those of the ACoA, and with other anomalies.

Arachnoid↗

Anterior inferior cerebellar artery aneurysm. Report of three cases.

Three cases of aneurysms of the anterior inferior cerebellar artery are reported. Two of the aneurysms were located in the cerebellopontine angle and one in the ventral portion of the pons. Through a suboccipital craniectomy, beck clipping was performed on one aneurysm, neck ligation on another, and coating on the third. A discussion of the surgical procedures and complications includes a review of previous reports.

Adult↗

Early detection of multiple gestations following hMG-hCG therapy by ultrasonography and midluteal phase progesterone determinations.

Multiple gestations after human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG) therapy were detected within 7 gestational weeks (GW) by ultrasound examinations and also by "midluteal phase" (MLP) progesterone (P) concentrations. The mean MLP-P level in nonconception cycles following hMG-hCG therapy was 25.1 +/- 2.1 ng/ml. In the pregnancies following hMG-hCG therapy, MLP-P levels were 32 ng/ml, 37 ng/ml, and 56 ng/ml. These values were associated with a singleton, twin, and triplet pregnancies, respectively. Ultrasonography revealed the number of gestational sacs within 7 GW in each instance. We suggest that assay of MLP-P is useful in women receiving regimens for induction of ovulation. Efforts may as well be made to ascertain multiple conceptions by ultrasound examinations in patients whose MLP-P levels are far above the mean MLP-P level in hMG-hCG-induced cycles.

Chorionic Gonadotropin↗

Idiotype-specific T lymphocytes. I. Regulation of antibody production by idiotype-specific H-2-restricted T lymphocytes.

Cytotoxic T lymphocytes (CTL) specific for MOPC-104E myeloma cells of BALB/c origin could be induced in BALB/c, (BALB/c X BALB.B)F1, and (BALB/c X BALB.K)F1 mice. (BALB/c X BALB.B)F1 CTL activity specific for MOPC-104E was effectively inhibited by anti-H-2d but not by anti-H-2b alloantiserum. However, the activity was hardly blocked by specific anti-idiotypic antibodies to MOPC-104E. For further analysis of the recognition of idiotype on target cells by CTL, the effect of those lymphocytes on anti-dextran B1355S antibody-producing B lymphocytes, which have a cross-reactive idiotype to MOPC-104E, was investigated. Lymphocytes from the CTL population did inhibit antibody production by dextran-immune spleen cells, but those from the CTL population specific for irrelevant myeloma cells (MOPC-167) did not. The (BALB/c X BALB.K)F1 CTL population suppressed the antibody production of BALB/c but not of BALB.K. This indicates that F1 cells can preferentially see H-2 antigens of immunizing myeloma cells on target B lymphocytes. The inhibition of antibody production was antigen specific and was only restricted to the PFC that were inhibitable by anti-idiotypic antibodies. The surface phenotypes of the cells that inhibited the antibody production were Thy-1+, Lyt-1-, Lyt-2+, and I-J-. These results strongly suggest that CTL specific for MOPC-104E recognize self H-2 antigens simultaneously with idiotypic determinants on B lymphocytes. Possible immunoregulatory roles of idiotype-specific CTL on antibody production systems are also suggested.

Animals↗

[Clinical evaluation of SPG (schizophyllan) as a therapeutic adjuvant after surgery of gastric cancer--controlled study by an envelope method].

SPG, a beta-1, 3 glucan extracted from cultured Schizophyllum commune Fries, was clinically evaluated for its efficacy in adjuvant immunochemotherapy for postoperative gastric cancer by the SPG cooperative study group comprising 43 hospitals. On the day of operation and the next day, patients were given intravenously 0.4 mg and 0.2 mg/kg of mitomycin C, respectively. Subsequently, they were randomly allocated to either the SPG group or control group. From the 10th to 20th postoperative days, the SPG group was intramuscularly given SPG at a dose of 20 mg twice a week or 40 mg once a week in combination with tegafur, while the control group was given only tegafur. Significant prolongation of life span of the SPG group was confirmed in Stage III. Minor side effects due to SPG were noted in 2.6% (5/190).

Adjuvants, Immunologic↗

[Clinical evaluation of schizophyllan (SPG) in advanced gastric cancer--a randomized comparative study by an envelope method].

To clarify the clinical efficacy of SPG, a beta-1, 3 glucan extracted from cultured Schizophyllum commune Fries, a randomized comparative study was performed in combination with mitomycin C+5-fluorouracil (MF protocol) or tegafur (F protocol). A total of 514 cases with inoperable or recurrent gastric cancer were randomly allocated to either the SPG group or the control group, 367 of which were finally assessed for clinical efficacy. SPG was intramuscularly given at a dose of 20 mg twice a week or 40 mg once a week. Significant prolongation of life span was confirmed in the SPG group (MF protocol: p less than 0.01, F protocol: p less than 0.05), although the combination of SPG did not demonstrate a remarkable antitumor effect in both MF and F protocols. Among immune response parameters tested, the positive reactions in the PHA skin test were maintained in the SPG group and decreases in lymphocyte counts were inhibited by SPG in the MF protocol. Side effects associated with SPG therapy were noted in 6 of 258 cases treated with SPG. From these results, it is indicated that the combination of SPG and the chemotherapeutic agents may be useful in treating patients with inoperable or recurrent gastric cancer.

Adjuvants, Immunologic↗