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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 649 records · Page 36Linked to original sources
PubMed1991

Cadmium toxicity on cultured neonatal rat hepatocytes: biochemical and ultrastructural analyses.

The effects of cadmium exposure on the protein secretory functions of cultured neonatal rat hepatocytes were analyzed by both two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and electron microscopy. [35S]Methionine-labelled protein secretion was significantly depressed by cadmium exposure in a dose-dependent manner (1, 10 and 100 microM). Protein secretory patterns resolved by 2D-PAGE and analyzed by autoradiography showed that besides albumin and transferrin, three polypeptide spots decreased their radiolabelling intensities, whereas four spots appeared due to cadmium exposure. Ultrastructural alterations in cultured neonatal rat hepatocytes induced by cadmium exposure were characterized by condensation of the nuclear chromatin, appearance of intra-nuclear inclusions, decrease in number of microvilli, increase in number of intra-mitochondrial granules and transformation of rough endoplasmic reticulum to cytoplasmic vesicles in a dose-dependent manner. Both biochemical and ultrastructural findings indicate that cadmium adversely affects the protein secretory functions of cultured neonatal rat hepatocytes.

Animals↗
PubMed1991

Renal tubular lesions induced by human Bence Jones protein in the rat: N-acetyl-beta-D-glucosaminidase as a sensitive marker.

The renal tubular lesion induced by human Bence Jones proteins (BJPs) in the rat was investigated to elucidate the initial role of BJPs in the genesis of renal tubular damage in myeloma kidney. Human BJP extracted from the urine collected from a patient with lambda light chain myeloma was given intraperitoneally to Sprague-Dawley rats with a daily dose of 300 mg/day for 5 days (BJP group, n = 16). Daily urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), which may represent the intensity of tubular damage, was measured. On days 10 and 20 after start of the injection, the kidneys were removed and examined by light and electron microscopy. The renal content of NAG was also measured to estimate the lysosomal activity. Both urinary and renal tissue NAG were significantly higher in the BJP group than in control rats injected with bovine serum albumin (n = 16). The most characteristic changes were found in the proximal tubules of the BJP group; the number and size of lysosomes were increased, and some showed enlargement with autophagic vacuolation. However, these were not found in the control group. There were no obvious changes in the distal tubules in either group, and the glomeruli appeared to be intact. These results suggest that BJP directly damages the proximal tubules via the process of catabolism, resulting in injury to these cells, and that the urinary NAG is a sensitive marker to detect early tubular damage by BJP.

Acetylglucosaminidase↗
PubMed1991

[A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers].

A late phase II study of CPT-11, a new derivative of camptothecin, in uterine cervical cancer and ovarian cancer was carried out by a cooperative study group at 26 institutions. Out of 144 patients enrolled, total cases were 110, involving 55 uterine cervical cancers and 55 ovarian cancers. In uterine cervical cancer, 5 cases of complete response (CR) and 8 cases of partial response (PR) were observed, with a response rate of 23.6% and a CR rate of 9.1%. In ovarian cancer, 13 cases of PR were observed, response rate was 23.6%. Both in uterine cervical cancer and ovarian cancer, the 95% confidence interval of response rate was 12.4-34.8%. In cases having undergone previous chemotherapy including platinum, derivatives, the response rate in ovarian cancer was 23.1% (12/52). In cases of uterine cervical cancer having previous radiotherapy, the response rate was 26.8% (11/41). In ovarian cancer of various histological types, a response was observed for not only serous cystadenocarcinoma but also mucinous cystadenocarcinoma, etc. A response was observed in distant metastatic lesions such as lung metastasis as well as primary lesion in uterine cervical cancer and ovarian cancer. Major adverse reactions were leukopenia, nausea and vomiting, diarrhea and anorexia, and these incidences (grade 2 or more) were 87.3, 60.3, 44.0 and 67.2%, respectively. Since some patients experienced severe adverse reactions, caution should be taken in treatment with CPT-11. Besides these reactions, alopecia was observed (33.1%), but severe adverse reactions such as nephropathy were not found. No significant difference in the efficacy and adverse reactions were observed between administration methods; A, 100 mg/m2 once weekly and B, 150 mg/m2 once every 2 weeks. Both were thought to be clinically useful. These results suggest that CPT-11 is clinically effective against uterine cervical cancer and ovarian cancer.

Adult↗
PubMed1991

[Prevention of scald injury due to intraperitoneal hyperthermic perfusion for far-advanced gastric cancer].

In an attempt to prevent scald injury on the peritoneo-serosal surface due to intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer patients, a histamine H2-receptor antagonist, cimetidine, was prescribed for 9 patients. The IPHP treatment was carried out with a closed circuit using a heated perfusate, and intra-abdominal temperature was kept over 44 degrees C throughout IPHP, for 120 minutes. Of 18 patients given IPHP, 9 were administered intravenously cimetidine at a dose of 50 mg/kg just before IPHP (cimetidine group) and the remaining 9 were prescribed IPHP and not given cimetidine (control group). Amounts of exudate and protein from peritoneal cavity and serum histamine were compared between the two groups. The amount of intra-abdominal exudate was 768 +/- 95 ml for 24 hours in the control group, against 408 +/- 75 ml in the cimetidine group. The protein amounts in exudate throughout IPHP were 62.5 +/- 23.5 g in the control group, against 15.9 +/- 5.4 g in teh cimetidine group. Both the exudate and protein amounts were significantly decreased in the cimetidine group, compared with the controls (p = 1.416 x 10(-7), p = 5.358 x 10(-5)). Serum histamine levels in the cimetidine group increased 2.5 to 6.5 fold for over 12 hours after IPHP, compared to those in the control group. These findings suggest that cimetidine suppresses scald injury on the peritoneo-serosal surface by competitive inhibition with histamine. Consequently, histamine originated from the scald region was released into the circulating blood. Thus, cimetidine helped to prevent thermal injury due to the IPHP.

Body Temperature↗
PubMed1991

[Placental transfer and pharmacokinetic parameters of flomoxef during the perinatal period].

Flomoxef (FMOX), a new oxacephem with low MIC values against not only Gram-negative bacilli (GNB) but also against Gram-positive cocci (GPC), was evaluated for its transfer into fetus, amniotic fluid, maternal milk, spinal fluid and urine during the perinatal period following a single intravenous drip infusion at a dose of 1 g for 30 minutes. The results obtained are summarized below. 1. High concentrations of FMOX were demonstrated in maternal serum, umbilical arterial serum and amniotic fluid with Cmax values of 48.0, 10.99 and 10.20 micrograms/ml, respectively. 2. Maternal urinary excretion rate was 65.4% in the first 6 hours after administration. 3. In contrast, maternal milk and spinal fluid levels were lower than 3 and 0.20 micrograms/ml, respectively. These results showed a good placental transfer of FMOX, which is very useful for various perinatal infections. No adverse effects were observed in mothers and neonates during the course of this study.

Adult↗
PubMed1991

[Clinical studies on flomoxef in pregnant women with infections during the perinatal period].

Clinical efficacies of flomoxef (FMOX), which is a newly developed oxacephem antibiotic, were evaluated in 14 cases of obstetric and gynecologic infections during the perinatal period. The results were excellent in 6 cases (42.9%) and good in 8 cases (57.1%). No side effects nor abnormal clinical laboratory test results were observed in mothers or neonates. Thus, FMOX appears to be a useful antibiotic for perinatal infections.

Adult↗
PubMed1991

[Cross-resistance of HO-221 and various antitumor agents in sublines of mouse leukemia].

HO-221, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2- nitrobenzoyl) urea is a new benzoylphenylurea derivative. The compound exhibits significant antitumor effects against various animal tumors, and was especially effective against the solid tumors implanted subcutaneously. HO-221 inhibits DNA polymerase alpha activity strongly in vitro. In this study, we examined the cross-resistance of HO-221 to various antitumor agents using sublines of mouse leukemia. HO-221 showed antitumor effects in mice bearing L 1210 or P 388 leukemia resistant to 10 antitumor agents, DM (daunomycin), MMC (mitomycin C), CDDP (cisplatin), 5-FU (5-fluorouracil), Ara-C (cytosine arabinoside), MTX (methotrexate), CPA (cyclophosphamide), CQ (carboquone), ADM (adriamycin) and VCR (vincristine), respectively. These antitumor agents were also effective in P 388 leukemia resistant to HO-221 (P 388/HO-221). Furthermore, CDDP- and MMC-resistant sublines showed a collateral sensitivity to HO-221 in vivo. The grow the inhibitory effects were also noted in vitro in ADM-, CDDP- and MMC-resistant cells by HO-221. However, the in vitro experiments didn't show such collateral sensitivity on the resistant sublines. These results suggest that there is no cross-resistance between HO-221 and other known antitumor agents, and that HO-221 seemed to be worth for evaluating clinical usefulness.

Animals↗
PubMed1991

[Clinical evaluation of intra-peritoneal hyperthermic perfusion under hypothermic general anesthesia for advanced gastric cancer].

Right after surgery, intra-peritoneal hyperthermic perfusion (IPHP) was performed under hypothermic general anesthesia for 41 gastric cancer patients with peritoneal dissemination or serosal invasion. The control group consisted of 40 patients given surgery alone. With respect to the direct antitumor efficacy of IPHP, there were no cancer cells in the peritoneal lavage from Douglas' pouch and, ascitic effusion disappeared in all patients with peritoneal dissemination. The 1- and 3-year survival rates for the IPHP group were 68% and 39%, whereas those of the control group were 30% and 0%, respectively. The survival rates for the IPHP group were better than those for the control group, with a statistically significant difference of p = 8.1 x 10(-7). As to prevention of recurrence, the incidence of peritoneal dissemination for the IPHP group was lower at p = 0.002 than the control group.

Anesthesia, General↗
PubMed1991

[Clinical evaluation of intra-operative pelvic hyperthermochemotherapy combined with operation for rectal cancer].

In order to prevent local recurrence, intra-operative pelvic hyperthermochemotherapy (IOPHC) combined with surgery for rectal cancer has been performed. In this study, we evaluated the clinical effect of IOPHC in 20 patients who were given IOPHC, compared with 13 patients who underwent curative surgery without IOPHC (control group). The IOPHC procedure was as follows: After rectal amputation, the pelvic cavity was filled with a physiological saline containing 40 micrograms/ml of MMC. Then, the physiological saline was warmed and maintained by the apparatus (heater) we devised at 45 degrees C for 90 minutes. Local recurrence occurred in 2 cases of IOPHC group (2/20:10.0%), and in 3 cases in the control group (3/13:23.1%). On the other hand, distant metastases developed approximately at the same rate in the IOPHC group (4/20:20.0%) and control group (2/13:15.4%). Thus, IOPHC is a feasible approach to reduce local recurrence of rectal cancer.

Combined Modality Therapy↗
PubMed1991

Aberrant accumulation of phospholipase C-delta in Alzheimer brains.

Since phosphoinositide-specific phospholipase C (PLC) is one of the key molecules in signal transduction, the authors assessed its involvement in Alzheimer's disease (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. 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 is a crucial event that ultimately may contribute to the formation of PHF.

Aged↗
PubMed1991

[Antitumor spectra of ranimustine against various human tumors].

Ranimustine (MCNU) has been shown to exhibit high antitumor activity and broad antitumor spectra against various experimental tumors. These effects were comparable to those of nimustine (ACNU). However, clinical applications of ACNU are indicated to various types of malignancies including solid tumors, while those of MCNU are almost limited to hematological ones. Therefore, the antitumor activity of MCNU was examined against 55 specimens from 15 types of solid tumors and compared with those of ACNU and 8 other drugs. Drug sensitivity was examined by a morphological method measuring the proportion of degenerative changes in the nucleus of drug-treated and untreated tumor cells. MCNU showed antitumor activities (measured by karyorrhexis) against adenocarcinoma of the lung, squamous cell carcinoma of the lung, renal cell carcinoma, bladder tumor, ovarian cancer and brain tumor. In addition, MCNU and ACNU showed a similar positive rate (15-16%) in this experiment and this was the highest among all drugs examined. Although MCNU and ACNU showed similar antitumor spectra, a clear difference was observed when the antitumor activities of both drugs were compared in each identical specimen. These results clearly suggest that MCNU is worthy of clinical study to examine the antitumor activity against various solid tumors.

Antineoplastic Agents↗
PubMed1991

[Clinicopathologic study of adult-onset membranoproliferative glomerulonephritis].

We analyzed clinicopathologic characteristics of adult-onset membranoproliferative glomerulonephritis (MPGN) by comparing two tentatively-classified subgroups. Group A consisted of 9 patients in whom more than 50% of glomeruli showed mixed segmental and global duplication of glomerular basement membrane (GBM), and Group B 9 patients with global duplication of GBM. Group A showed a tendency for more favorable clinical course and outcome than Group B. Nephrotic syndrome was present in 33% of Group A and 100% in Group B, hypertension in 22% and 44%, hypocomplementemia in 44% and 67% at the time of renal biopsy. Deterioration of renal function, at comparable durations of follow-up of 62 +/- 12 (M +/- SE) and 53 +/- 13 months, was observed in 22% of Group A and 56% in Group B, respectively. Histologically, mesangial proliferation and tubulointerstitial change were more pronounced and frequency of sclerosing glomeruli was greater in Group B. There was also a negative correlation between the extent of global double contour and renal function as assessed by creatinine clearance at the time of renal biopsy (r = -0.55, P less than 0.05). These results indicate that the high incidence of global double contour, in addition to the presence of marked tubulointerstitial change and sclerosing glomeruli, may relate to progressive deterioration of renal function in MPGN. That outcomes for Group A and Group B may be different when clinical parameters, including the durations from onset of symptoms to the time of biopsy and length of follow-up periods, are comparable also indicates that these two groups should be considered separate entities, at least on the basis of clinical results.

Adolescent↗
PubMed1991

[An analysis of prognostic significance of new FIGO staging (1989) of endometrial cancer].

Histopathologic factors were investigated in the data for ninety-one patients with endometrial carcinoma who were treated surgically. Each of these subjects was reclassified according to the new FIGO surgical criteria (1989) for stages and the relationship between the new classifications and the prognosis of patients was analyzed. One third of the patients (24/72) with clinical FIGO stage I (1983) had extracorporeal spread of the disease and these cases were reclassified as surgical stages II and III. Among clinical stage Ib patients there were many more with extracorporeal spread than among those in clinical stage Ia (p less than 0.005) although there was no difference between the histopathological characteristics (histologic grade, myometrial invasion, cervical involvement, adnexal involvement and pelvic lymph node metastasis) of the stage Ia and Ib groups. Univariate survival analysis revealed that the histologic grade (p less than 0.05), myometrial invasion (p less than 0.05), cervical involvement (p less than 0.005) and pelvic lymph node metastasis (p less than 0.005) correlated with the patient's prognosis. Multivariate survival analysis with the proportional hazard regression model showed that cervical involvement (p = 0.05) and the new stage classification (p = 0.03) correlated significantly with the prognosis. The cumulative 5-year survival rate by clinical stage (1983) was 87% for stage I (Ia: 96%, Ib: 80%) and 72% for stage II, between which no significant difference was determined. The survival rate for stage III was not calculated because there was only one case with stage III disease in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1990

Irreversible inhibition of D-3-aminoisobutyrate-pyruvate aminotransferase by gabaculine.

Gabaculine, 5-amino-1,3-cyclohexadienylcarboxylate, is an analogue of GABA and a potent irreversible inhibitor of GABA aminotransferase. However, D-3-aminoisobutyrate-pyruvate aminotransferase for which GABA was neither a substrate nor an inhibitor was also inactivated by gabaculine. The Ki for D-3-aminoisobutyrate-pyruvate aminotransferase was 8.3 x 10(-6) M, and the Kcat for its turnover was 0.31 min-1 at 25 degrees C. beta-Alanine protected the enzyme from inactivation by gabaculine, but GABA did so to much a lesser extent.

4-Aminobutyrate Transaminase↗
PubMed1990

Effects of bepridil compared to those of its quaternary analogue on femoral arteries from spontaneously hypertensive rats.

The effects of bepridil and its quaternary analogue, methylated bepridil, were studied on femoral arterial strips from spontaneously hypertensive rats (SHR). Methylated bepridil relaxed precontracted strips more rapidly than did bepridil, but bepridil was a more potent vasorelaxant. Both drugs non-competitively inhibited arterial contraction evoked by voltage-dependent or alpha-adrenoceptor-operated Ca2+ influx with bepridil being more potent than methylated bepridil. In the absence of extracellular Ca2+, the contractile responses of Wistar-Kyoto rats (WKY) and SHR arteries to norepinephrine and caffeine were reduced similarly by methylated bepridil and bepridil. It is suggested that the effects of bepridil involve both extracellular and intracellular actions. The altered sensitivity of the contraction mechanism with norepinephrine-releasable Ca2+ to the Ca2+ antagonist may be due to an abnormality in the intracellular vasocontraction process distal to Ca2+ release from storage sites of the SHR blood vessels.

Animals↗
PubMed1990

Evaluation of interconversion between (R)- and (S)-enantiomers of beta-aminoisobutyrate.

The conversion of (R)- to (S)-beta-aminoisobutyrate was observed in the presence of D-3-aminoisobutyrate-pyruvate aminotransferase, aminobutyrate aminotransferase, pyruvate and L-glutamate. The reverse reaction was also found in the presence of 2-oxoglutarate and L-alanine. Neither D-3-aminoisobutyrate-pyruvate aminotransferase nor aminobutyrate aminotransferase revealed a racemase activity of the enantiomorphs.

4-Aminobutyrate Transaminase↗