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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 847 records · Page 47Linked to original sources

[Combined therapy of polyamine antimetabolite and nitrosourea in human gastric cancer].

Antitumor therapy using the polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), combined with ACNU was studied in human gastric cancer xenotransplanted into nude mice. DFMO 1,000 mg/kg (in two divided doses) and MGBG 50 mg/kg were given i.p. for 6 successive days from the time when the xenotransplanted tumor weighed about 100 mg, and ACNU 20 mg/kg was given i.p. every other day from the same time. Antitumor efficacy was assessed by the time course of tumor weight as well as of DNA biosynthesis and polyamine levels in tumor tissue. Tumor weight was estimated using Battelle's Columbus Institute protocol and DNA biosynthesis was assayed biochemically by 3H-TdR injection at a prescribed interval after termination of therapy. Furthermore, tumoral polyamine levels were assayed by HPLC. This three-drug regimen showed a favorable antitumor effect, compared to those of the other two therapies with DFMO plus MGBG as well as ACNU only. These data suggest that this combined regimen may have a synergistic efficacy judging from the action mechanisms of these three drugs.

Animals↗

[Combined efficacy of polyamine antimetabolites and cis-diamminedichloroplatinum].

The combined antitumor effects of the polyamine antimetabolites, alpha-difluoro methylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), with CDDP were studied using human gastric cancer cells xenotransplanted into nude mice. DFMO (1000 mg/kg in two divided doses) and MGBG (50 mg/kg) were given IP for six consecutive days from the time when the xenotransplanted tumor weighted about 100 mg, and CDDP (3.0 mg/kg) was given IP every other day from the same time. Animals treated with DFMO plus MGBG with or without CDDP as well as with CDDP only displayed suppressed tumor growth, compared to untreated mice. In mice treated with these three drugs, however, tumor growth was rather rapid compared to those treated with CDDP only, although tumoral CDDP levels in animals given DFMO, MGBG and CDDP were higher than those given CDDP only. When DFMO, MGBG and CDDP or DFMO and MGBG were administered, tumoral spermidine and spermine levels decreased markedly. On the other hand, tumor DNA biosynthesis in the CDDP only group dropped markedly 24 hours after the termination of therapy. These results suggest that an alteration in the DNA structure caused by polyamine deficiency may prevent cross-link formation in DNA by CDDP.

Animals↗

[Clinical and laboratory evaluations of ceftazidime in perinatal use. A study of ceftazidime in the perinatal co-research group].

Efficacy and safety of ceftazidime (CAZ) in women during the perinatal period and their neonates were evaluated by a perinatal co-research group, and the results obtained were summarized as follows. Following an intravenous bolus injection or a drip infusion of CAZ from 1 g to 2 g, CAZ was transferred to maternal serum, umbilical cord serum and amniotic fluid rapidly and effectively. In 31 cases of perinatal infections, clinical efficacy was excellent in 10 cases, good in 18 and poor in 3, with an efficacy rate of 90.3%. In 85 cases given CAZ for prophylaxis of infections accompanying premature rupture of the membrane or following cesarean section, prophylactic effects were noted in 81 cases (efficacy rate: 95.3%). Neither adverse effects, nor abnormal laboratory findings were observed in any case. Also, no abnormalities in total serum bilirubin were observed in any neonates. From the above results, CAZ is considered to be a safe and useful drug for infections in women in perinatal period, usually in a unit dose of 1 g twice daily, or if necessary, 2 g twice daily.

Adult↗

[Ceftazidime: placental transfer and pharmacokinetic parameters in the third trimester pregnancy].

Ceftazidime (CAZ), a newly developed cephalosporin with very high stability to beta-lactamase, was evaluated for its transfer into fetus and amniotic fluid in the third trimester pregnancy, following a single bolus intravenous injection at a dose of 1 g. In subjects with various conditions (background factors) standardized, concentrations of CAZ in maternal venous blood, venous and arterial blood in umbilical cord, and amniotic fluid were determined. High concentration of CAZ (10 micrograms/ml or higher) was found to be maintained in fetal blood and amniotic fluid for ca. 4 hours and ca. 8 hours, respectively, after intravenous injection, showing good placental transfer of CAZ. In view of MICs of CAZ, satisfactory clinical efficacy is expected in perinatal infections.

Amniotic Fluid↗

Immunological studies of uveitis. 3. Cell-mediated immunity to interphotoreceptor retinoid-binding protein.

Three patients were seen with the same clinical characteristics which were not described previously: diffuse uveitis with bilateral involvement, onset in the second decade of life, no extraocular signs or symptoms, diffuse retinal capillary leakage on fluorescein angiography but without apparent fundus changes, many vitreous cells but no snowbank-like vitreous opacity, responsiveness to steroid, and good prognosis. The peripheral blood lymphocytes of all three patients responded to bovine and human interphotoreceptor retinoid-binding protein (IRBP), but not to bovine retinal S antigen. It was speculated that these patients were human counterparts of IRBP-induced uveoretinitis that was described in experimental animals.

Adolescent↗

[An in vitro chemosensitivity test for human breast cancer based on morphological changes in the nucleus].

We have developed a simple in vitro chemosensitivity test for breast cancer. Tumor tissues were chopped finely with razor blade. The cell clumps were pounced into tissue culture medium, which contained a specified level of concentration of anticancer drugs, and incubated at 37 degrees C for four to eight hours. Nine to 10 kinds of drugs were tested on each specimen. After incubation, the clumps were pumped down. The cells were smeared and stained with Giemsa for microscopic examination. The individual tumors showed different sensitivities towards various drugs, and the typical morphological changes observed in their nuclei; were karyorrhexis and karyopyknosis.

Adult↗

[Pharmacokinetic studies on aztreonam in late pregnancy in sheep and humans].

The transplacental passage of single intravenous doses of aztreonam (AZT), 1 g or 2 g, was examined in 7 sheep and 14 women in late pregnancy, respectively and the obtained data were analyzed by a two-compartment model. The obtained results were summarized as follows. After single 2 g intravenous doses were given to pregnant sheep, the mean peak level of AZT in maternal blood was 83.79 micrograms/ml and the half-life of the beta-phase was 1.525 hours. After single 1 g intravenous doses were administered to pregnant women, the mean peak level of AZT in blood was 102.62 micrograms/ml and the half-life of beta-phase was 2.128 hours. The peak levels in umbilical venous blood and amniotic fluid were 14.43 micrograms/ml and 11.86 micrograms/ml, respectively.

Amniotic Fluid↗

[Studies of aztreonam transfer into the fetus and amniotic fluid in early pregnancy].

The materno-fetal transfer of aztreonam by a single intravenous dose of 1 g was examined in 7 volunteer women undergoing induced abortion in early pregnancy and the following results were obtained. After administration of the drug, maternal blood levels at 15, 30, 60 and 120 minutes were 77.24 +/- 6.09 micrograms/ml (Mean +/- S.E.), 37.84 +/- 5.85 micrograms/ml, 25.62 +/- 3.15 micrograms/ml and 18.10 +/- 2.22 micrograms/ml, respectively. Amniotic fluid level of the drug was low in 3 cases, of which amniotic fluid levels were determined; 0.74 microgram/ml after 229 minutes, 0.83 microgram/ml after 280 minutes and 0.74 microgram/ml after 328 minutes. Fetal tissue concentration of the drug was below our detection limit at 120 minutes. Tissue levels of villus and decidua in 6 cases were also too low to be detectable between 89 and 328 minutes after injection.

Adult↗

[Superficial temporal to superior cerebellar artery anastomosis for rostral brain stem infarction].

The authors report a case of superficial temporal to superior cerebellar artery anastomosis (STA-SCA anastomosis) for progressing rostral brain stem infarction with an excellent result. Precise operative techniques were also described. A 47-year-old male was admitted to our hospital on November 9, 1984, because of sudden onset of dysarthria and ataxic gait. CT revealed a low density area in the pons. Left vertebral angiogram showed occlusion of the left vertebral artery just distal to the origin of the posterior inferior cerebellar artery (PICA). Arterial branch of the left cerebellar hemisphere were filled via the left PICA to the left SCA and anterior inferior cerebellar artery anastomosis. Right brachial angiogram showed the hypoplastic right vertebral artery which ended at the PICA. The rostral basilar artery, both posterior cerebral arteries (PCA's) and right SCA were filled through anastomosis from the right PICA. The posterior circulation was not filled by either of the carotid arteries. In spite of antiplatelet agglutination therapy, the patient had two more episodes of dysarthria, dysphagia, right hemiparesis and gait disturbance. Because of progressing stroke, STA-SCA anastomosis was carried out on the right side on February 27, 1985. During operation, the blood pressure was maintained above the level of 130 mmHg, and intravenous mannitol injection and spinal drainage were done to preserve the right temporal lobe from intracerebral hematoma and/or edema caused by retraction. Postoperatively, the patient has been free from new ischemic attack. He has only slight hemiparesis now eight months after operation. Right external carotid angiogram showed a patent STA-SCA bypass and good filling of SCA's and PCA's bilaterally.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Stem↗

[Traumatic anterior cerebral artery aneurysms--experiences in 4 cases and review of the literature].

Five cases of traumatic anterior cerebral artery aneurysms are reported with special emphasis on the initial CT findings of these cases. One case was already reported by Endo (1974). The cases are three in children and two in adults, male four cases and female one case. Four cases had closed head injury, one open. Consciousness level on admission were diversely from clear to semicomatose. Three cases experienced rupture of aneurysms. Time of diagnosis from trauma was from two days to 34 days. Location of aneurysms were near the junction of callosomarginal artery three cases, frontopolar artery one case, and A1-A2 junction one case. Operation was performed in four cases. Results were good in three cases and fair in a case. A case of no operation had fracture of anterior skull base and died from massive nasal and oral bleeding. Autopsy showed an aneurysm of A1-A2 junction, extending to sphenoid sinus. Histological findings of aneurysmal walls were pseudoaneurysm in all cases. There were 48 cases of traumatic anterior cerebral artery aneurysms in the literature. Most of cases are near the junction of callosomarginal artery. As the etiology of the aneurysm it is said that falx cerebri damages the arterial wall. We consider tear of junction of callosomarginal artery is a important factor, since the brain can easily move at the anterior portion of falx. It is very difficult to diagnosis traumatic aneurysms before rupture. But in our three cases of traumatic anterior cerebral artery aneurysms, computed tomographies of very early stage of trauma showed interhemispherical high density area, hematoma and hemorrhage of corpus callosum.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Injuries↗

Reconstruction of chronic massive rotator cuff tears with synthetic materials.

Synthetic materials for repairing experimental massive rotator cuff tears were investigated in 60 rats. The same materials were investigated for massive rotator cuff ruptures in 25 patients. The materials were well tolerated when used for repair of torn segments of the musculotendinous cuff. Of 25 patients with massive rotator cuff tears, 23 had satisfactory functional results. The muscle strength tests on tendons repaired with Teflon felt (which was thicker than the other materials) were superior to results of repairs with other materials; 3-5 mm proved to be the optimum thickness of Teflon felt used for repair of the musculotendinous cuff.

Aged↗

Immunocytochemical localization of factor VIII-related antigen in the human umbilical vein.

The immunocytochemical localization of factor VIII-related antigen in the human umbilical vein was investigated with the light microscopic immunoperoxidase and immunoelectron microscopical protein A-gold techniques. The light microscopic observation showed that peroxidase reactions were found exclusively in the endothelia of the vessel. By the protein A-gold method, immunoreactive gold particles were located in endothelial specific granules (Weibel-Palade bodies). These data suggest that endothelial specific granules are storage sites of factor VIII-related antigen.

Antigens↗

Biodegradable mitomycin C microspheres given intra-arterially for inoperable hepatic cancer. With particular reference to a comparison with continuous infusion of mitomycin C and 5-fluorouracil.

Thirty-two patients with inoperable hepatic cancer underwent intra-arterial hepatic infusion using mitomycin C (MMC) and 5-fluorouracil (5-FU) or intra-arterial hepatic chemoembolization using heated albumin microspheres containing MMC with an average diameter 45 +/- 8 micron. Nineteen of the 32 patients received the MMC microsphere treatment and another 13 received the conventional infusion treatment, lasting for 3.4 months. The administered doses of MMC microspheres were 11.7 +/- 11.1 mg as MMC in the 12 with metastatic cancer and 6.9 +/- 2.1 mg as MMC in the 7 with hepatocellular cancer (HCC). On the contrary, the 13 patients who underwent conventional infusion had average doses of MMC 34.5 +/- 17.3 mg and of 5-FU 13.4 +/- 7.7 g, over 3.4 months. An objective tumor response was obtained in 13/19 (68.4%) under MMC microsphere chemoembolization, compared to 6/13 (46.2%) under the conventional infusion. The average level of CEA in the 12 with metastatic cancer, who underwent MMC microsphere therapy, dropped from 57.7 ng/ml to 16.5 ng/ml, while that in the 10 patients on conventional infusion dropped from 24.0 ng/ml to 17.4 ng/ml; that of alpha-fetoprotein dropped in all 7 with HCC on MMC microsphere chemoembolization, compared to a fall in 1/3 on conventional infusion. With the MMC microsphere treatment, 5 patients from colorectal cancer lived for 15.6 +/- 7.6 months, 2 are alive with a long life expectancy; and 7 patients from gastric or pancreatic cancer lived for only 9.3 +/- 3.3 months. In case of conventional infusion, 6 patients from colorectal cancer survived for 8.6 +/- 3.2 months; and 4 patients from gastric or gallbladder cancer survived for 6.0 +/- 1.0 months. The MMC microsphere treatment is superior at P = 0.059 in survival duration to the conventional infusion treatment. However, much the same survival occurred in 7 on MMC microsphere chemoembolization and 3 on continuous infusion.

Adult↗

The generation of interleukin-2-dependent suppressor T-cells from patients with systemic metastasis of gastric carcinoma and the phenotypic characterization of the cells defined by monoclonal antibodies.

Suppressor cells, which might be activated in patients with gastric carcinoma, were successfully enriched by the use of interleukin-2 (IL-2) prepared from human tonsils and spleens. That is, peripheral blood lymphocytes cultured for 3 or 4 weeks with IL-2 strongly inhibited the patient's own lymphocyte-proliferative responses to alloantigen or phytohemagglutinin (PHA). Quantitative fluorescence measurement for immunologic analysis of phenotypic characterization of the cells was made on FACS-IV with monoclonal antibodies anti-Leu-1 anti-Leu-2a, anti-Leu-3a, anti-Leu-4, anti Leu-5, anti-Leu-7, and anti-HLA-DR and goat anti-human immunoglobulin (Ig). Functional suppressor T-cells expanded with IL-2 showed the following phenotype: Leu-1+ Leu-2a+, Leu-3a-, Leu-4+, Leu-5+, Leu-7-, HLA-DR+, human Ig-. The IL-2-dependent suppressor T-cells could be obtained only when the cells were derived from patients with systemic metastasis of gastric carcinoma. These findings suggest that generation of IL-2-dependent suppressor T-cells is the result of large tumor burdens; this may exert negative cellular control in the immune responses, thus inducing the status of the lower cell-mediated antitumor immunity, and may promote cancer progression in gastric cancer patients.

Adult↗

Increased beta-aminoisobutyric acid in rat liver with 6-azauracil and its enantiomer.

When 6-azauracil was subcutaneously injected, beta-aminoisobutyric acid and beta-alanine contents were increased 22 and 61-fold, respectively, in rat liver. Incorporation of [methyl-14C]thymine into beta-aminoisobutyric acid was increased to 42-fold by 6-azauracil treatment. The absolute configuration of this amino acid was proved to be the (R)-form by means of a gas-chromatographic technique. 6-Azauracil inhibited beta-alanine-pyruvate aminotransferase activity with an I50 of approx. 2.5 mM.

Aminoisobutyric Acids↗

Antitumor effects of two polyamine antimetabolites combined with mitomycin C on human stomach cancer cells xenotransplanted into nude mice.

The antitumor effects of alpha-difluoromethylornithine (DFMO), methylglyoxal-bis-guanylhydrazone (MGBG) and mitomycin C (MMC), administered separately or in various combinations, on human stomach cancer cells xenotransplanted into BALB/c nude mice were studied using the protocol of Battelle's Columbus Laboratories (Ovejera et al., 1978). DFMO (1,000 mg/kg in 2 divided doses) and MGBG (50 mg/kg) were given intraperitoneally (i.p.) for 7 consecutive days from the time when the tumor weighed about 100 mg. MMC (2 mg/kg) was given i.p. every other day from the same time. Animals treated with either DFMO or MGBG alone displayed tumor growth comparable to that seen in untreated controls. In mice treated with DFMO plus MGBG with or without MMC, or in mice treated only with MMC, tumor growth was significantly lower than in untreated mice. In the group which received only combined DFMO/MGBG there was a rapid regrowth of the tumor after termination of therapy. Tumor putrescine levels decreased within 4 days following the administration of DFMO; however, spermidine levels did not decline with either DFMO or MGBG treatment even after 7 days. When combined DFMO/MGBG was given, there was a significant decline in spermidine levels 7 days after the initiation of treatment. In contrast, when MMC alone was administered, putrescine and spermidine levels in the tumor did not differ from those in control mice. Spermine decreased markedly in tumor with the combined administration of DFMO/MGBG as well as with combined DFMO/MGBG/MMC, but decreased only slightly when MMC alone or MMC plus either DFMO or MGBG was administered. By the 7th treatment day, DNA biosynthesis in the tumor had dropped markedly in all groups except those receiving DFMO or MGBG alone.

Adenocarcinoma, Papillary↗

Antigenic determinant and interspecies cross-reactivity of a monoclonal antibody to poly(ADP-ribose) synthetase.

A monoclonal antibody (1F4) was prepared against calf thymus poly(ADP-ribose) synthetase. It was classified as IgG1/kappa and its antigenic determinant was localized on the 46 kDa portion of the enzyme molecule which contains the site for the binding of DNA. When calf thymus DNA-binding proteins were subjected to immunostaining after electrophoresis and transblotting to a nitrocellulose filter, the native enzyme (120 kDa) and its endogenous degradation products (80, 64 and 32 kDa) were detected. When the interspecies cross-reactivity was examined using DNA-binding proteins from 6 different sources, 1F4 reacted with the 120- and 32-kDa protein bands in HeLa cells, mouse testis and chicken liver as in the case of calf thymus. These results indicate that the antigenic structures of poly(ADP-ribose) synthetase and its degradation products are highly conserved in various animal cells.

Animals↗