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Biomedical subjects

A Fujii

Publications and source records attributed to A Fujii.

At least 145 records · Page 8Linked to original sources

Mutagenicity of analgesics, their derivatives, and anti-inflammatory drugs with S-9 mix of several animal species.

An investigation was undertaken to determine whether analgesics and their derivatives (13 compounds), and anti-inflammatory drugs (4 compounds) had mutagenicity. Rec-assay was used to clarify specific DNA-damaging properties, and the Ames test was used to find back-mutations, using S-9 fractions obtained from the liver of 4 animal species pretreated with polychlorobiphenyl. In the Rec-assay, salicylic acid (2 mg), aspirin (5 mg), benzoic acid (4 mg), sulpyrine (0.4 mg), indomethacin (0.1 mg), oxyphenbutazone (0.1 mg) and diclofenac sodium (0.1 mg) showed a DNA-damaging tendency. In the Ames test, mutagenicity of methyl salicylate was demonstrated using the Salmonella typhimurium TA98 strain upon addition of hamster S-9 mixture. Weak mutagenicity was also found using the TA100 strain with rat S-9 mixture for salicylic acid, sulpyrine, indomethacin and oxyphenbutazone, and with hamster S-9 mixture for methyl salicylate, acetaminophen and phenacetine.

Analgesics↗

[Adjuvant chemotherapy with MVP-CAB (methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin and bleomycin) for epithelial tumors of the upper urinary tract].

Surgery plus adjuvant chemotherapy using MVP-CAB (Day 1; methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, and bleomycin 30 mg, Day 2; cisplatinum 50 mg/m2) was conducted in 12 patients with epithelial tumors of the upper urinary tract who had unfavorable prognostic factors (progressive disease which was pT2 or more, or transitional cell carcinoma of grade 2 and 3). The MVP-CAB regimen was as follows: A total of 3 cycles were given either before or after surgery. MVP-CAB was given at 3- to 4-week intervals before surgery, or after surgery if the patient had macroscopic residual lesions. For the patients with micrometastases detected after radical surgery, MVP-CAB was given every 1 to 2 months. The median survival period of the 10 patients who underwent radical surgery was 17 months (5-59 months). The three-year survival rate of these 10 patients (Kaplan-Meier method) was 100% in grade 2 (5 patients), 100% in progressive cancer greater than pT3 (6), and 80% in grade 3 (5). In two patients, residual macroscopic lesions after surgery were confirmed. One of them initially responded to MVP-CAB but died of cancer 21 months later, while the other one did not respond and died of cancer 8 months later. Two renal pelvis cancer patients for whom radical surgery was considered impossible due to distant metastases showed remarkable tumor reduction after MVP-CAB administration (one showed CR for liver metastases and the other showed PR for lymph node metastases).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Kock-rectal bladder. Augmented and valved rectum].

Eight patients with total cysto-urethrectomy underwent an augmented and valved rectum (Kock), a type of continent urinary diversion. A satisfactory outcome was obtained in 6 patients. These 6 patients urinated 6 to 8 times a day (1-2 times during the night). The volume each time was 350-450 ml. Urinary incontinence occurred only 1-2 times a month when deeply asleep, and there were no patients whose daily life was restricted. However, there were 3 patients with urinary tract complications. In 2 of them, urinary diversion was required, and unilateral total ureteral obstruction was observed in the remaining patient. The reason for the complications appeared to be that stapling of the intussusception of the sigmoid colon was performed in 5 placements as described in the original method. Following the 4th patient, we were able to prevent any complication in the urinary tract by stapling of the intussusception in 3 places (at 12, 5 and 7 o'clock), and by suturing mucosa to mucosa of the rectum and intussusception in 6 places with polyglycolic acid suture, and further suturing serosa to serosa of the sigmoid colon and rectum in 4 places with silk suture.

Aged↗

[Adjuvant chemotherapy (MVP-CAB; methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin, and bleomycin) for bladder cancer].

Twenty-three patients with bladder cancer (TCC; 18 patients, SCC; 5 patients) were treated with adjuvant chemotherapy (day 1: methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, bleomycin 30 mg, day 2: cisplatinum 50 mg/m2; MVP-CAB). A total of 3 cycles of MVP-CAB were given as preoperative or postoperative therapy. The following results were obtained. Group 1 (purpose to preserve the bladder, preoperative MVP-CAB): Four of 7 patients achieved a partial response. It was possible to perform bladder preservation surgery in 3 of these 4 patients. All 3 patients had pedunculated, solitary tumors, and there was no carcinoma in situ. Group 2 (purpose to improve the prognosis; preoperative MVP-CAB): Hydronephrosis did not resolve in the 4 patients with this complication. They received total cystectomy, and 2 patients died of cancer 23 months later. Group 3 (purpose to improve the prognosis; postoperative MVP-CAB): Ten of 12 patients (total cystectomy; 10 patients, partial cystectomy; 2 patients) survived disease-free for an average of 17 months (5-44 months), 1 patient developed recurrence 12 months later, and 1 patient died of cancer 6 months later. The 1-year survival rate in Group 3 was 86% for TCC, 100% for SCC, 80% for grade 3 TCC, and 89% for pT2 or more advanced cancer.

Antineoplastic Combined Chemotherapy Protocols↗

44-Homooligomycins A and B, new antitumor antibiotics from Streptomyces bottropensis. Producing organism, fermentation, isolation, structure elucidation and biological properties.

Oligomycin antibiotics, 44-homooligomycin A (NK86-0279 II) and B (NK86-0279 I) are newly discovered antitumor antibiotics with the substitution of ethyl for methyl at carbon 26. They were isolated from the culture broth of Streptomyces bottropensis NK86-0279. The structure of these two compounds was deduced by spectroscopic and X-ray crystallographic analyses. These antibiotics showed potent antitumor activities against various tumor cells in vitro, and were active against Colon 26 carcinoma in vivo. Although they showed no activity at 1,000 micrograms/ml against Gram-positive and Gram-negative bacteria and yeast, they have antifungal activity.

Antibiotics, Antineoplastic↗

[Analysis of HLA antigens and immunotherapy for infertile couples who failed to conceive after in vitro fertilization-embryo tubal replacement (IVF-ETR)].

The results of IVF-ETR strongly suggest the existence of implantation failure of unknown etiology. A selected group of 41 couples with long-standing infertility who had one or more failed IVF-ETR cycles were analysed for HLA antigen sharing, and 19 wives were immunized with their husband's purified lymphocytes just before the subsequent trial. Both the number and frequency of shared HLA antigens in these patients were significantly increased, compared with control couples of normal fertility (p < 0.05). After immunization, 7 patients (36.8%) conceived by IVF-ETR, and 5 (71.4%) delivered a healthy baby at term. The pregnant couples shared significantly fewer HLA antigens compared with those who failed to conserve (p < 0.05). Interestingly, the MLR blocking effect was enhanced in the pregnant group after immunization, suggesting the induction of blocking antibodies which are believed essential for the survival of the developing fetus. In contrast, the blocking effect was rather decreased in the nonpregnant group. These results implicate that HLA sharing and inadequate maternal anti-paternal immunity may be related to implantation failure, and immunotherapy can be used to potentiate the maternal immune response, leading to successful implantation in selected patients.

Adult↗

[Endoscopic treatment of early gastric cancer].

We assessed the results of endoscopic resection (ER) of early gastric cancer using electrocoagulation with high frequency current. Resection was performed utilizing endoscopic double-snare polypectomy (EDSP) and electrocoagulation. The initial endoscopic total resection rate was 65.0% (119/183 lesions). There were 32 lesions in which no residual cancer was present at follow-up biopsy or surgery, and when these were included the endoscopic resection cure rate was 82.5%. Extensive tissue necrosis and degeneration occurred in the resected stump as a result of using electrocoagulation. Since an increase in suitable patients and an expansion of the indications for endoscopic resection are anticipated in the future, careful clinical evaluation of endoscopic resection based on the results of pathological assessment of the resected tissue is needed.

Electrocoagulation↗

Therapeutic activity of deoxyspergualin in comparison with cyclosporin A, and its combined use with cyclosporin A and prednisolone in highly allogeneic skin transplantation in the rat.

The present paper demonstrates the efficacy of a novel immunosuppressive agent, deoxyspergualin (DSG), in rat skin transplantation despite major histocompatible antigen differences, both by itself and in combination with cyclosporin A (CyA) and prednisolone (PD). DSG significantly prolonged the median survival time (MST) of WKAH skin on F344 rats, when given at daily doses of 1.5-12 mg/kg i.p. for 10 days starting from day one after grafting. A significant increase of the MST has been observed also in the rats orally receiving CyA at daily doses of 12.5-50 mg/kg according to the same dosing protocol. DSG was as effective as CyA in prolonging the MST. In contrast, when treatment started 4 days after grafting (at the time of the rejection crisis), DSG (6 mg/kg) was able to reverse the rejection, whereas CyA (50 mg/kg) was not. When DSG (1.5 mg/kg) and CyA (6.25 or 12.5 mg/kg) were given together from day one after grafting, the combined therapy was superior to each monotherapy. Similarly, when DSG (1.5 mg/kg) and PD (10 mg/kg) were given simultaneously from the rejection crisis, the combined therapy was demonstrated to have stronger activity than any of the monotherapies. Moreover, the skin-allografted rats could be switched successfully either from CyA to DSG treatment or from DSG to CyA treatment.

Animals↗

[A clinical study of xanthogranulomatous pyelonephritis (XGP) with special emphasis on the magnetic resonance imaging].

Xanthogranulomatous pyelonephritis (XGP) is an uncommon form of granulomatous inflammation characterized by destruction and replacement of the renal parenchyma by masses of lipid-laden macrophages. We report the first case of the pyonephrotic type of XGP in which Magnetic resonance imaging (MRI) was used in Japan, and summarize the clinical characteristics of 163 cases with XGP in the Japanese literature for age, sex, laboratory data, preoperative diagnosis and operation. A 56-year-old female was admitted with left flank pain. Left nephrectomy was performed following diagnosis of XGP by computed tomography (CT) and MRI. Histopathological findings confirmed the diagnosis of XGP. Furthermore, we evaluated the MR images in XGP. MR images correlated well with the CT images showing an enlarged multiloculated kidney. The internal portion of the loculated areas were of intermediate intensity on T1-weighted images, and became very intense on the T2-weighted sequences, indicating a long T2. MRI appears to be of value in the investigation of renal mass lesions.

Female↗

Antitumor activity of 2'-deoxy-2'-methylidenecytidine, a new 2'-deoxycytidine derivative.

The antitumor activity of 2'-deoxy-2'-methylidenecytidine (DMDC), an inhibitor of DNA synthesis, was examined and compared with that of 1-beta-D-arabinofuranosylcytosine (ara-C) against various murine tumors and human tumor xenografts. Against P388 murine leukemia, repeated treatments of DMDC were more effective than its single administration. Interestingly, DMDC was effective against colon 26 murine carcinoma, M5076 murine reticulum cell sarcoma, LX-1 human lung cancer xenograft, and SK-Mel-28 human melanoma xenograft, which are less sensitive or refractory to ara-C, while DMDC was not more potent against murine leukemias P388 and L1210 than ara-C. The in vitro cytotoxic effects of DMDC and ara-C against L1210 leukemia cells were prevented dose dependently by deoxycytidine, suggesting that DMDC, like ara-C, may require phosphorylation by deoxycytidine kinase for antitumor activity. DMDC was effective against human and murine experimental tumor models, especially nonleukemic tumors refractory to ara-C, suggesting that DMDC will be a promising agent for the treatment of cancer.

Animals↗

Ampicillin concentrations in human oral tissues following a single oral administration of lenampicillin.

1. Ampicillin concentrations in serum (n = 20), gingiva (n = 12), jawbone (n = 13), dental follicle (n = 12), radicular granuloma (n = 2) and radicular cyst (n = 2) were measured in specimens obtained during 0.5-2.5 hr after a single oral administration of lenampicillin (equivalent to 500 mg of ampicillin). 2. Measurable ampicillin concentrations were found in all serum and tissues. 3. Ampicillin concentrations in serum and tissues except for some gingiva and jawbone exceeded MIC for 90% of clinically isolated strains of alpha-hemolytic Streptococci. 4. Ampicillin concentrations in gingiva and jawbone were below the MIC for 90% in 2 out of 12 and 4 out of 13 specimens, respectively.

Adult↗

Deoxyspergualin in lethal murine graft-versus-host disease.

The beneficial effect of deoxyspergualin (DSG, NKT-01) on lethal graft-versus-host disease in mice has been studied in a major histoincompatible donor-recipient combination. Suppression of the effector mechanisms responsible for the lethal outcome in this GVHD model is also noted. This study reveals: (1) DSG has a marked potential for treatment of lethal GVHD; (2) DSG and methotrexate in combination yield longer survival times than DSG or MTX alone; (3) long-term survivors, following DSG treatment, become stable chimeras as evidenced by cell-surface analysis of spleen cells; and (4) high activity of H-2-reactive cytotoxic T lymphocytes is detected in spleens of the mice with lethal GVHD, whereas natural killer activity is only slightly increased. DSG inhibits CTL activity not only in the induction stage but also in the advanced stage of the disease. These findings indicate that DSG might be beneficial in clinical bone marrow transplantation either alone or in combination with MTX.

Animals↗

Conformational studies of cyclo(L-Phe-L-Pro-Gly-L-Pro)2 by 13C nuclear magnetic resonance.

The 13C-NMR spectrum (Fig. 2,1) of cyclooctapeptide cyclo(L-phe-L-Pro-Gly-L-Pro)2 (A) in CDC13 suggested that its conformation involved the coexistence of two kinds of C2-symmetric conformation with trans-trans-trans-trans and cis-trans-trans-trans forms. Adding 0.5 equivalent of CsSCN or one equivalent of DL-Phe-OMe.HCl to the solution of cyclopeptide (A) in CDC13 yielded 13C-NMR spectra (Fig. 2,2 and Table I) which suggested a single C2-symmetric conformation with trans-trans-trans-trans form, resulting from the formation of complexes with CsSCN or DL-Phe-OMe.HCl. The 13C-NMR spectrum of complexes of A with DL-Phe-OMe.HCl displayed separate resonances for C(gamma), C(o), C(m), C(alpha), and C(beta) of D-Phe-OMe.HCl and L-Phe-OMe.HCl (Table I).

Amino Acid Sequence↗

Gingival hyperplasia induced by nifedipine.

We describe 4 cases of gingival hyperplasia induced by nifedipine, together with clinical and histological findings. Hyperplasia of the interdental papillae was observed in all cases. Histologic examination showed multilayered epithelial parakeratosis with variations in the width, proliferation, reticulation and elongation of the rete pegs. Substitution of another drug and improvement of oral hygiene led to reduction of the gingival overgrowth without gingivectomy. These treatments are essential for gingival hyperplasia induced by nifedipine.

Aged↗

[Treatment of newly diagnosed stage D2 prostatic carcinoma with hormonal therapy alone, or chemotherapy agents in combination with hormones].

From June 1984 to March 1988, patients with newly diagnosed stage D2 prostate cancer were treated with protocol 1. This comprised oral hormonal agents either diethylstilbestrol diphosphate (Honvan: 300 mg/day) or estramustine phosphate (Estracyt: 560 mg/day), or chlormadinone acetate (Prostal: 100 mg/day), plus intravenous cyclophosphamide (CPM, 0.5-1 g/m2) every 3-4 weeks. From May 1988, protocol 2 was used in a randomized study of castration alone versus castration plus intravenous methotrexate (MTX, 20 mg/m2) every 2 weeks. Forty-nine of 53 patients who underwent the two protocols were evaluable for the response. The response rates according to the NPCP criteria were 92% (11/12) for Honvan, 100% (9/9) for Estracyt, 78% (7/9) for Prostal and castration plus MTX, and 80% (8/10) for castration alone. There were no significant differences among these treatments. The median response duration and survival time (months) were 16 and 44, respectively, for Honvan, 19 and 37 for Estracyt, 12 and 43 for Prostal, 11 and 15 for castration plus MTX, and 13 and 13 for castration alone. The short survival times of the castration alone and castration plus MTX groups were due to a short follow-up period. There were no statistical differences among the oral hormonal agent plus CPM groups. However, the 2-year survival rate (Kaplan-Meier method) was higher in the CPM and MTX groups than in the castration alone group. Survival was longer in the good performance status (P.S.) group than the poor P.S. group (p less than 0.05 by Wilcoxon test) and in the responders than the non-responders (p less than 0.01). Side effects were not excessive in the chemotherapy groups and patient compliance was good.

Administration, Oral↗

[Combination chemotherapy with methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin, and bleomycin (MVP-CAB) for metastatic urothelial cancer].

We studied 31 patients with bidimensionally measurable metastases of urothelial cancer who were treated with a planned regimen (20 mg/m2 methotrexate, 0.6 mg/m2 vincristine, 500 mg/m2 cyclophosphamide, 20 mg/m2 adriamycin, and 30 mg bleomycin on day 1, and 50 mg/m2 cisplatinum on day 2) in cycles given every 3 weeks. CR was achieved in 4 patients (13%) and PR in 17 patients (55%). The response rates according to the disease characteristics were 71% for TCC, 33% for SCC, 67% for renal pelvis tumors, 67% for bladder tumors, 73% for lung metastases, 67% for liver metastases, and 67% for lymph node metastases. The median response duration and the number of cycles of therapy were 32 months/3 cycles for patients with a CR and 6 months/6 cycles for those with a PR. The median duration of survival was 32 months (range: 3-46) in CR, 11 months (range: 1-37) in PR, and 6 months (range: 2-10) in non responders (NC + PD). A significant prolongation of survival was noted in patients with either CR (p less than 0.01) or PR (p less than 0.05). Then main toxic effects were pulmonary fibrosis and myelosuppression. Two patients aged 73 and 81 died of pulmonary fibrosis. However, it was possible to prevent pulmonary fibrosis by not administering bleomycin to patients over 70 years of age, or to patients with pulmonary dysfunction. WBC count nadirs of less than 2,000/m3 were noted in 22 patients (71%). Platelet count nadirs of greater than 5 x 10(4)/mm3 were noted in 7 patients (23%). However, there were no deaths due to myelosuppression.

Antineoplastic Combined Chemotherapy Protocols↗

Structural analysis of the human HOX4A homeobox gene.

The HOX4A gene, one of a cluster of homeobox-containing genes on human chromosome 2, has been isolated by screening a genomic cosmid library with the HOX4B cDNA probe. The amino acid sequence was predicted according to the conceptual translation of 13 homology groups of human HOX genes (1). The HOX4A gene consists of at least two exons separated by a long intron of 1860 bp. The HOX4A protein predicted from the nucleotide sequence of the HOX4A gene is comprised of 416 amino acid residues. Comparison of the predicted HOX4A protein with the HOX2G protein revealed three regions of sequence similarity: an N-terminal octapeptide, a hexapeptide (pre-box) upstream of the homeodomain, and the homeodomain at the C-terminus.

Animals↗

Application of immunocytochemistry to the cytologic study of peritoneal fluids in patients with ovarian cancer.

Immunocytochemical methods were evaluated for their usefulness in the identification of malignant cells in cytologic preparations of peritoneal fluids of ovarian cancer. The antibodies used for this study were anti-cancer antigen-125 (CA-125) antibody, anti-carbohydrate antigen 19-9 (CA 19-9) antibody, anti-carcinoembryonic antigen (CEA) antibody and anti-epithelial membrane antigen (EMA) antibody. The immunohistochemical and cytochemical results using 4 antibodies for both the histologic specimens and the imprinted smears from tumor tissues of the same patients were compatible in 91.8% (both positive or both negative) of the cases. Reactivities of ascitic specimens taken from benign gynecological lesions were 39.4% with anti-CA-125, 12.1% with anti-CA 19-9, 6.1% with anti-EMA, while none of the 33 cases reacted with anti-CEA antibodies. Comparison of the immunoreactivity with the 4 antibodies in histologic specimens and peritoneal smears with Pap-positive cytology taken from the same patients showed 82.9% compatibility. However, 40% incompatibility was found in the anti-CA-125 staining. Some of the mesothelial cells contained in the peritoneal fluids reacted with the anti-CA-125 antibody. Except for the anti-CA-125 staining, compatibility was 90.3%. These results indicate that the anti-CA-125 antibody can not be used to distinguish benign from malignant cells, while anti-CEA antibody has high specificity for malignant cells. CA19-9, CEA and EMA stainings may be valuable criteria in the cytologic diagnosis of effusions. However, it is possible that individual use of these antibodies may lead to a false negative diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗