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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 523 records · Page 29Linked to original sources
PubMed1994

[Study for modifying activity of solvents on antitumor activity of paclitaxel].

Paclitaxel, a novel diterpenoid compound, has been used by dissolving in Cremophor EL (polyoxyethylene castor oil) due to its poor aqueous solubility. Cremophor EL was shown to reverse multidrug resistant phenotypes of various cell lines as well as to reverse cross-resistance to paclitaxel of a multidrug resistant cell line in vitro. Thus, a study was carried out to determine the modifying activity of Cremophor EL on the antitumor activity of paclitaxel against P388 leukemia, adriamycin-resistant subline (P388/ADM) and vincristine-resistant subline (P388/VCR) in vivo. Dimethyl sulfoxide (DMSO) was used as a counterpart solvent. The results showed that, although no significant antitumor activity was observed by paclitaxel in both solvents against P388/ADM, a significantly higher antitumor activity was induced by paclitaxel dissolved in Cremophor EL-based solvent compared with DMSO-based solvent against P388/VCR. However, more significant difference in the antitumor activity of paclitaxel against P388 parental line was observed between two solvents and both resistant sublines showed an obvious cross-resistance to paclitaxel. Therefore, it appeared that cross-resistance reversing activity of Cremophor EL is not so high as to be detectable at in vivo level.

Animals↗
PubMed1994

[Schedule dependency of i.v.-paclitaxel against SC-M 109 mouse lung cancer].

Although paclitaxel was shown to have a broad spectrum of antitumor activity against various experimental tumors, the optimal treatment schedule of this drug is not yet determined. In the present study, a trial was carried out to determine the optimal treatment schedule of paclitaxel given i.v. against M 109 mouse lung cancer implanted SC. Schedules examined were: day 1 (d 1) single administration, d 1, 5, 9 intermittent administration, and d 1-5 and d 1-9 daily consecutive administration. As the result, a significant increase of the lifespan was firstly demonstrated by d 1-9 schedule. The optimal dose was as low as 6.5 mg/kg/day (20 mg/m2/day, total 180 mg/m2) and no toxicity was observed with respect to the weight loss. Since the concentration and total amount of Cremophor EL (polyoxyethylene castor oil), which is suspected to be a causative agent for high incidence rate of hypersensitivity reactions by clinical formulation of paclitaxel, inevitably decrease in such a low dose setting, these results should be taken into considerations when exploring the optimal schedule of paclitaxel clinically.

Animals↗
PubMed1994

[Pelvic hyperthermochemotherapy combined with surgery for rectal cancer].

In an attempt to prevent local recurrence, intraoperative pelvic hyperthermochemotherapy (IOPHC) was performed in combination with curative surgery for rectal cancer. One hundred twenty-three patients were divided into four groups: A, 8 patients without nodal involvement (n0) and given IOPHC; B, 22 with nodal involvement (n+) and given IOPHC; C, 47 n0 and no IOPHC; D, 46 n (+) and no IOPHC. Local recurrence developed in one patient in group A (12.5%), 3 in group B (13.6%), 5 in Group C (10.6%), and 16 in Group D (34.8%), respectively. Thus, the rate of local recurrence in group B was low compared to that of Group D, even through there was no statistical difference (p = 0.11). IOPHC may be one option for limiting local recurrence after surgical resection of rectal cancer.

Combined Modality Therapy↗
PubMed1994

Left ventricular diastolic function in patients on maintenance hemodialysis: comparison with hypertensive heart disease and hypertrophic cardiomyopathy.

To elucidate the differences in the left ventricular diastolic function between patients on maintenance hemodialysis with left ventricular hypertrophy and the those with left ventricular hypertrophy from other causes, 20 patients on maintenance hemodialysis (HD group; mean age 44 +/- 12 years), 12 patients with hypertensive heart disease (HHD group; mean age 43 +/- 10 years), and 10 patients with hypertrophic cardiomyopathy (HCM group; mean age 43 +/- 11 years) were examined non-invasively using diastolic time intervals and digitized echocardiograms. Ten age-matched healthy men (N group; mean age 43 +/- 12 years) were also examined. Compared with the HCM group, the HD and HHD groups had a decreased total left ventricular wall thickness and left atrial dimension, an increased ratio between the left ventricular enddiastolic dimension and total left ventricular wall thickness. The isovolumic relaxation and rapid relaxation periods were prolonged in the order of HCM, HHD, HD and N, but the active suction period was prolonged only in the HCM group. The peak rate of change in the left ventricular dimension during the rapid filling period was decreased in the HCM group, compared with the HD and the HHD groups. These results indicate that hemodialysis patients with left ventricular hypertrophy have some impairment in left ventricular diastolic function, but the degree of the disturbance is similar to that observed in those with hypertensive heart disease, but milder than that observed in those with hypertrophic cardiomyopathy.

Adult↗
PubMed1994

Comparative clinicopathologic features of early gastric cancer in young and older patients.

BACKGROUND: The clinicopathologic features of advanced gastric cancer have been analyzed in young or older patients; however, with regard to early gastric cancer, it remains unknown whether the features differ between young and older patients. Reported here is an analysis of clinicopathologic characteristics in young and in older patients. METHODS: This study is based on a retrospective review of 25 patients less than 40 years of age with early gastric cancer and of 64 patients more than 70 years of age with early gastric cancer. These patients were treated from 1977 through 1991. RESULTS: Because in the older group there were early double cancers in three patients and quadruple cancers in one, 70 early cancers were present in these 64 patients. Although the young group included a larger percentage of women, the ratio of mucosal cancer to submucosal and the incidence of nodal metastasis did not differ between the groups. Poorly differentiated adenocarcinoma was detected in 13 (52%) of the 25 younger patients, whereas in the older group it was present in 6 cancers (8.6%) alone. The number of metastatic nodes and extent of nodal metastasis were more severe in the young group, but survival rates did not differ between the groups. The depressed type of lesion was present in all patients in the young group, whereas it was only 41 of 70 cancers in the older group. CONCLUSIONS: These findings suggest that early gastric cancer in young adults has aggressive features as based on the histologic pattern, in particular with cancer invasion into the submucosal layer. For these patients nodal extirpation and postoperative adjuvant chemotherapy should be performed in an attempt to prevent lymphatic or hematogenic metastases.

Adult↗
PubMed1994

[Studies on clinical usefulness of new tumor markers of ovarian cancer, CA54/61 and CA602--III. Measurement of serum samples from patients with various benign or malignant diseases].

Serum samples from patients with benign or malignant diseases were measured for the newly developed tumor markers CA54/61 and CA602 with the respective EIA kits for assessment of their utility as tumor markers. A total of 5236 patients were entered into the study, consisting of ovarian cancer patients, those with other cancers, pregnant women, and healthy volunteers. The CA54/61-positive rate with a cut-off value of 12 U/ml was 61.2% for ovarian cancers (50.4% with a cut-off value of 20 U/ml). A positive rate of 75.0% (64.4%) was achieved for mucinous cystadenocarcinoma, which was high, compared with that for CA125. On the other hand, the false-positive rate was 12.2%(5.9%) for benign ovarian tumors, and as low as 18.5%(8.7%) for endometriosis. The CA602-positive rate with a cut-off value of 63 U/ml was as high as 76.0% for ovarian cancers (69.8% with a cut-off value of 90 U/ml). On the other hand, the false-positive rate was relatively high at 21.9% (12.6%) for benign ovarian tumors, and 56.7% (40.0%) for endometriosis. These positive rates were therefore similar to those for CA 125. The levels of both CA54/61 and CA602 antigens well reflected the postoperative prognosis. These results suggest the utility of CA54/61 and CA 602 as tumor markers of ovarian cancers.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

Pre- and postnatal development of rabbit foliate papillae with special reference to foliate gutter formation and taste bud and serous gland differentiation.

The epithelial downgrowth arises in the presumptive foliate papilla region of the tongue approximately at prenatal day 22, and the distal portion of the primary epithelial cell cords transforms to the bifurcated serous gland and excretory duct between prenatal day 30 and postnatal day 2. The excretory ducts extend upward through the primary epithelial cell cords at rather random intervals and are open to the tongue surface between postnatal days 1 and 2. In this process, successive connections between the adjacent ascending excretory ducts occur mainly due to desquamation of the keratinized lining cells of the ducts, resulting in the formation of the foliate gutter. Taste bud primordia appear in the primary epithelial cell cords by nerve penetration through the basal lamina from prenatal day 30 and nearly fully formed taste buds facing the ascending excretory ducts have been already observed before the foliate gutter formation is completed. In the differentiation process of chemoreceptor (type III) cells from less-differentiated basal (type IV) cells, subsurface cisterns of endoplasmic reticulum are occasionally present where nerve endings make contact. Since subsurface cisterns have been considered to be involved in reciprocal or efferent synaptic transmission, it is reasonable to consider that these morphological specializations may take a role in neurotrophic signals for differentiation of the chemoreceptor cells.

Animals↗
PubMed1993

Aberrant phosphoinositide metabolism in Alzheimer's disease.

Since phosphoinositide-specific phospholipase C (PLC) is one of the key molecules in signal transduction, its involvement was assessed in Alzheimer's disease (AD). The phosphatidyl-inositol (PI)-specific PLC activity in the Alzheimer cytosolic and particulate fractions was not significantly different from that in the control fractions. The PI-specific PLC activity as a function of the free Ca2+ concentration was also similar between control and Alzheimer brains. These results suggest that the PI-specific PLC activity is not altered in AD. Immunostaining of a specific antibody against the PLC isozyme, PLC-delta, demonstrated that this enzyme was abnormally accumulated in neurofibrillary tangles (NFT), the neurites surrounding senile plaque (SP) cores, and neuropil threads in AD brains. Western blot analysis confirmed that PLC-delta was concentrated in the paired helical filament (PHF)-rich fraction of AD brains. PLC-delta marked the same neurons containing tau immunoreactivity and yet tau and PLC-delta often marked different structures within the same neuron, with tau more clearly on NFT and PLC-delta covering it superficially. The double stain with PLC-delta and basic fibroblast growth factor (bFGF) binding suggest that PLC-delta is an intracellular marker, showing little overlap with bFGF binding, an extracellular marker. All of this was consistent with the electron microscopy, with PLC-delta being NFT associated. Antibodies to other PLC isozymes did not produce positive immunostaining of these pathologic structures. Moreover, diffuse and amorphous deposits of PLC-delta were found to precede the accumulation of fibrillary deposits. These results suggest that PLC-delta accumulation plays a possible role in the formation of intraneuronal inclusions in AD.

Alzheimer Disease↗
PubMed1993

Hereditary nodular heterotopia accompanied by mega cisterna magna.

This is the first report of hereditary nodular heterotopia accompanied by mega cisterna magna. Magnetic resonance imaging documented multiple bilateral subependymal nodules, which were isointense to gray matter. This disease entity is considered a dominant trait, since the mother and two daughters, half-sisters, were affected.

Adult↗
PubMed1993

Identity of D-3-aminoisobutyrate-pyruvate aminotransferase with alanine-glyoxylate aminotransferase 2.

D-3-Aminoisobutyrate-pyruvate aminotransferase (EC 2.6.1.40) and alanine-glyoxylate aminotransferase 2 (EC 2.6.1.44) were co-purified from rat liver as a single protein. The ratio of the two activities remained constant after Sephacryl S-200 chromatography and chromatofocussing. The Km value for beta-alanine as a substrate with 1 mM glyloxylate as amino group acceptor was 1.4 mM. The activity was inhibited by (S)-alanine with Ki = 2.2 mM. The Km for (S)-alanine as substrate with 1 mM glyoxylate as amino group was 6 mM. This activity was inhibited competitively by beta-alanine with Ki = 0.7 mM. (R)-3-aminoisobutyric acid, 5-aminolevulinic acid, NG,NG'-dimethyl-(S)-arginine, and (S)-2-aminobutyric acid were active competitively with respect to beta-alanine with Km of 0.12 mM, 2.1 mM, 6.4 mM and 11.3 mM, respectively. Antiserum to rat liver D-3-aminoisobutyrate-pyruvate aminotransferase inhibited alanine-glyoxylate aminotransferase activity in rat liver in the same way as that of D-3-aminoisobutyrate-pyruvate aminotransferase. Alanine-glyoxylate aminotransferase activity and D-3-aminoisobutyrate-pyruvate aminotransferase activities were inactivated competitively with respect to beta-alanine by 5-fluorouracil and 6-azauracil, which are chemotherapeutic reagents used to cancer. These experiments indicate that D-3-aminoisobutyrate-pyruvate aminotransferase is identical with alanine-glyoxylate aminotransferase 2, aminolevulinate aminotransferase, 2-aminobutyrate aminotransferase and dimetylarginine-pyruvate aminotransferase.

Alanine↗
PubMed1993

Reduction of low-molecular-weight acid phosphatase activity in Alzheimer brains.

Recent studies in Alzheimer brains have shown aberrant protein phosphorylation, suggesting an alteration in protein kinases and/or phosphoprotein phosphatases. In the present study, the activity of acid phosphatase was investigated in samples prepared from postmortem normal human and Alzheimer brains. p-Nitrophenyl phosphate, a nonprotein phosphoester, was used as a substrate for acid phosphatase. The separation profile on Sephadex G-100 gel filtration chromatography revealed that two major forms of high-molecular-weight and low-molecular-weight acid phosphatase were present in the crude extracts of both rat and human brains. Another class of zinc ion (Zn2+)-dependent acid p-nitrophenyl phosphatase was also detected in rat and human brains. In Alzheimer brains, the low-molecular-weight acid phosphatase activity was significantly decreased compared to that in control brains; however, the high-molecular-weight and Zn(2+)-dependent acid phosphatase activity in control and Alzheimer brains was not different. These results suggest that reduced activity of the low-molecular-weight acid phosphatase, which possesses phosphotyrosine protein phosphatase activity, might be linked to aberrant protein tyrosine phosphorylation found in Alzheimer brains.

Acid Phosphatase↗