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Biomedical subjects

S Fukushima

Publications and source records attributed to S Fukushima.

At least 181 records · Page 10Linked to original sources
PubMed1996

Initiation-promotion model for assessment of carcinogenicity: medium-term liver bioassay in rats for rapid detection of carcinogenic agents.

To bridge the gap between long-term carcinogenicity tests and short-term screening assays, a medium-term liver bioassay system for rapid detection of carcinogenic agents using male F344 rats has been developed. The system is fundamentally based on the two-stage hypothesis of carcinogenesis: initiation with diethylnitrosamine (200 mg/kg, ip) is followed by test chemical administration during the second stage in combination with 2/3 partial hepatectomy. It requires only 8 weeks for the animal treatment and a further few weeks for quantitative analysis of immunohistochemically-demonstrated glutathione S-transferase placental form positive hepatic foci. A total of 277 chemicals have already been analyzed in this laboratory and the efficacy of the system for hepatocarcinogens has thereby been well established. This bioassay is particularly useful for dose-response and chemical mixture studies usually requiring large-scale experiments and also for evaluation of chemopreventive agents. Furthermore, medium-term multi-organ bioassay system, using 5 different chemical carcinogens (DEN, MNU, BBN, DMH and DHPN) has also been established for rapid detection of not only hepatocarcinogens, but also other carcinogens.

Animals↗
PubMed1996

[Combination therapy with estrogen and UFT in newly diagnosed prostatic cancer (poorly differentiated, stage D2)].

To determine whether long-term oral administration of UFT, a combination of 5-fluorouracil and uracil, in addition to conventional estrogen therapy improved the response and survival of the patients with advanced stage D2 prostate adenocarcinoma, a randomized prospective study was performed with either estrogen alone (Honvan 200 mg/day or presexol 1 mg/day: group A) or estrogen plus UFT (400 mg/day:group B). This study comprises 34 newly diagnosed patients with poorly differentiated prostatic adenocarcinoma (18 patients in group A and 16 in group B). Survival from all causes of death or cancer-specific death were compared using Kaplan-Meier actual methods among the patients separated by histological composition of tumors analyzed WHO histologic patterns, score of extent of disease (EOD), and with or without normalization of serum PSA or PAP levels after treatment. Although combination therapy with UFT against overall survival was effective without statistical significance, better survival in this group than the patients treatment with estrogen alone assessed among the patients whose tumor contained more than 70% of medullary and/or column-cord histological components. The survivals among the patients with EOD score 3 and whose serum PSA or PAP levels did not lead to decrease within normal levels after treatment were also better in group B than in group A. These findings suggest the validity of the combination therapy with UFT in addition to estrogen against highly advanced prostatic cancer patients whose tumor composed of abundant non-hormone-refractor histological components.

Adenocarcinoma↗
PubMed1996

[Perioperative fractionated high dose rate brachytherapy in bone and soft-tissue tumors].

The 13 lesions of 11 patients with bone and soft-tissue tumors (four primary and nine recurrent lesions) were treated with surgery and postoperative fractionated high dose rate (HDR) brachytherapy started on the 6-7th day after surgery. The total dose was 40-50 Gy/7-10 fr/6-7d(bid) at 5 mm from the source. Local control was achieved in eight of 13 lesions (62%). Four of the five uncontrolled lesions had macroscopic residual tumor after the surgery. There was one peripheral nerve damage as a side effect. This study indicates that the use of perioperative fractionated HDR brachytherapy is feasible and well tolerated.

Adolescent↗
PubMed1996

A study of antitumor effects of thymosin on rat and mouse urinary bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine.

N-Butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), which induces bladder carcinoma in female Wistar rats and female C3H/HeJ mice, was given as 0.025% (w/v) solution to rats and 0.05% to mice in the drinking water. Thymosin fraction 5 (TF5) or thymosin alpha 1 (T alpha 1) dissolved in normal saline, and normal saline (control) respectively were injected into the right thigh IM twice a week in the experimental rats. At the 30th week of BBN oral administration, weights of urinary bladder were different among the three groups. Bladder weights and incidence of bladder carcinoma were significantly lower in the TF5-treated group as compared with control group. Natural killer cell activity of splenic lymphoid cells was significantly elevated in the TF5-treated group as compared with the control group. However, these parameters were not significantly different between the T alpha 1-treated group and control saline-treated group. On the other hand, bladder weights and incidence of bladder carcinoma were not significantly different among TF5-, T alpha 1- and saline-treated groups at 10, 15, 20, and 25 weeks of BBN administration in mice according to the same protocol as rats.

Animals↗
PubMed1996

Transfer of latissimus dorsi for irreparable rotator-cuff tears.

We treated 12 shoulders in ten patients with irreparable rotator-cuff tears by transfer of the latissimus dorsi. There were nine men and one woman. Their average age was 64.0 years and the average follow-up was 35.6 months (26 to 42). The results were excellent in four shoulders, good in four, fair in one, and poor in three. Active forward flexion improved from a preoperative average of 99 degrees to a postoperative average of 135 degrees. Osteoarthritic changes appeared in five shoulders and proximal migration of the humeral head progressed in six. EMG revealed that nine of the 12 transferred muscles showed activity which was synergistic with the supraspinatus on external rotation with abduction. We conclude that latissimus dorsi transfer can be effective in restoring shoulder function after massive irreparable tears of the rotator cuff.

Activities of Daily Living↗
PubMed1995

Induction of CYP isoenzymes in various organs of rats by 3-methylcholanthrene or beta-naphthoflavone.

Induction of cytochrome P450 (CYP) isoenzymes in various organs of rats treated with 3-methylcholanthrene (3-MC) and beta-naphthoflavone (BNF) was immunohistochemically and biochemically investigated. Fifteen male F344 rats were divided into three equal groups. Group 1 was untreated as a control. On days 3, 4, 13 and 14, group 2 animals received 3-MC (20 mg/kg body wt i.p.) dissolved in corn oil while group 3 animals were given BNF (50 mg/kg body wt i.p.) dissolved in corn oil, at days 1, 2, 3, 4, 11, 12, 13 and 14. On days 4 and 14, two or three animals in each group were sacrificed, 15 h after administration of the last test compound. Induction of CYP 1A1, 2C11, 2D1, 2E1, 3A2 and 4A1 in various organs was immunohistochemically examined and the levels of CYP 1A1 protein were measured by Western blotting. 3-MC and BNF induced CYP isoenzymes not only in the liver, but also in the small intestine, large intestine, prostate and seminal vesicles. The results indicate that xenobiotic metabolism can occur in various organs.

Animals↗
PubMed1995

Expression of immunoreactive human hepatocyte growth factor in human esophageal squamous cell carcinomas.

Hepatocyte growth factor (HGF) is a potent mitogen for epithelial cells that promotes cell motility and invasiveness. In this study, we report that the human esophageal squamous cell carcinoma (SCC) shows a significant elevation of HGF concentration (600 +/- 416 ng/100 mg protein), compared to normal mucosa (80 +/- 183 ng/100 mg protein) (P < 0.01). An association could be established between levels of HGF and decreasing differentiation of 37 SCCs. The 2-year crude survival rates were 51.1% and 68.4% at high and low HGF concentrations, respectively. The results indicate that HGF is significantly increased in human esophageal SCCs, especially of poorly differentiated type. HGF might thus be useful as a biological biomarker for characterization of human esophageal SCCs.

Adult↗
PubMed1995

Emergence of adenomatous aberrant crypt foci (ACF) from hyperplastic ACF with concomitant increase in cell proliferation.

To investigate the relationship between aberrant crypt foci (ACF) and colon neoplasia in colorectal carcinogenesis, we evaluated 433 ACF, which were collected from the grossly normal mucosa of surgical specimens from 57 patients with colorectal cancer. The ACF ranged in size from 3 to 412 aberrant crypts/focus. Large ACF (> or = 50 crypts/focus) comprised 25% of the total ACF studied. Histopathologically, 65% (67 of 103) of large ACF were diagnosed as hyperplasia, 10% (10 of 103) as adenoma, and 1% (1 of 103) as within normal colorectal mucosa. The remaining 24% (25 of 103) were diagnosed as "stage I abnormality crypts," which were characterized by their extension of the proliferative compartment to the surface of crypts but with no changes in the major site of proliferation, as designated by E. E. Deschner [Pathol. Annu., 18 (Part 1): 205-219, 1983]. Of the 25 stage I abnormality ACF, 7 ACF coexisted with hyperplasia. Of 10 adenomatous ACF, two coexisted with stage I abnormality crypts. A K-ras codon 12 mutation was identified in 85% (93 of 109) of large ACF. The proliferative activity of stage I crypts was significantly higher than that of hyperplastic crypts in the same ACF. These observations suggest that some hyperplastic ACF may develop into adenomatous ACF by way of stage I abnormality ACF with concomitant acquisition of higher proliferative activity through some genetic and/or epigenetic changes.

Adult↗
PubMed1995

Prognostic significance of the MIB-1 proliferation index for patients with squamous cell carcinoma of the esophagus.

BACKGROUND: A number of studies have indicated that the ki-67 proliferation index is of important prognostic significance for a variety of neoplasias. It was the aim of this study to investigate whether any correlation exits between the MIB-1 proliferation index and various clinicopathologic parameters in squamous cell carcinomas of the esophagus from 72 patients (20 women: median age, 64 years; range, 45-79 years; and 52 men: median age, 61 years; range, 43-77 years). METHODS: Proliferative activity was determined using an immunohistochemical method with monoclonal antibody MIB-1 (ABC method), for tumor samples obtained from individuals who underwent esophagectomy in the period from 1983 to 1991. The percentage proliferation index (PI) was calculated as the number of positive cells divided by the total number of cells examined. Thirty-nine patients (54%) died of recurrence of esophageal cancer, with a median survival span of 15 months (range, 1-58 months). Thirty-three patients (46%) were still alive at the time of this study; their median follow up was 57 months (range, 40-98 months). RESULTS: Significant differences between proliferative index values were recorded for the following parameters: survival rate, P < 0.0001; presence of lymph node metastasis, P < 0.05; size of the primary esophageal lesion, P < 0.01; proliferation pattern of the tumor, P < 0.01; and age of the patients, P < 0.05. No correlation was found regarding histologic differentiation, clinical stage, location of the lesion, intraepithelial cancerous spread, lymphatic and blood vessel invasion, and sex of the patients. CONCLUSION: The MIB-1 proliferation index may be a powerful prognostic marker for patients with squamous cell carcinomas of the esophagus.

Adult↗
PubMed1995

Three-dimensional ultrasound image of the fetal stomach: congenital duodenal obstruction in utero.

To quantitatively characterize the stereographic stomach configuration in utero, 11 fetuses (subject-group) with congenital duodenal obstruction, diagnosed antenatally, between 29 and 37 weeks' gestation were studied. Also included were 879 uncomplicated fetuses between 20 and 40 weeks' gestation as a control-group. Applying the algorithm which we devised: "Modeling a three-dimensional shape from a silhouette by detecting symmetry", we reconstructed the three-dimensional stomach configuration from a two-dimensional ultrasound image for each case. The statistical differences in two parameters, stomach volume and sphericity, between subject- and control-group fetuses, were analyzed using the Grubbs-Smirnoff's test at corresponding gestational ages. From 29 to 37 weeks' gestation, the stomach volume in the subject-group fetuses was found to increase greatly with advancing gestation, having significantly higher values than the control-group fetuses, whereas the stomach sphericity remained unchanged with no significant differences from the control-group fetuses. These findings indicate that the fetal stomach with duodenal obstruction maintains almost the same three-dimensional portrayal in utero as that seen in uncomplicated fetuses, although the stomach becomes extremely enlarged.

Duodenal Diseases↗
PubMed1995

Cancer induction by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carcinogens.

Arsenic (As) is environmentally ubiquitous and an epidemiologically significant chemical related to certain human cancers. Dimethylarsinic acid (cacodylic acid; DMA) is one of the major methylated metabolites of ingested arsenicals in most mammals. To evaluate the effects of DMA on chemical carcinogenesis, we conducted a multiorgan bioassay in rats given various doses of DMA. One-hundred twenty-four male F344/DuCrj rats were divided randomly into 7 groups (20 rats each for groups 1-5; 12 rats each for groups 6 and 7). To initiate multiple organs and tissues, animals in groups 1-5 were treated sequentially with diethylnitrosamine (100 mg/kg body weight, i.p., single dose at the commencement) and N-methyl-N-nitrosourea (20 mg/kg body weight, i.p., 4 times, on days 5, 8, 11, and 14). Thereafter, rats received 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times, on days 18, 22, 26, and 30). During the same period, the animals were sequentially administered N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water, during weeks 1 and 2) and N-bis(2-hydroxypropyl)nitrosamine (0.1% in the drinking water, during weeks 3 and 4; DMBDD treatment). After a 2-week interval, groups 2-5 were given 50, 100, 200, or 400 ppm DMA, respectively, in the drinking water. Groups 6 and 7, which were not given DMBDD treatment, received 100 and 400 ppm DMA during weeks 6-30. All rats were killed at the end of week 30. In the initiated groups (groups 1-5), DMA significantly enhanced the tumor induction in the urinary bladder, kidney, liver, and thyroid gland, with respective incidences in group 5 (400 ppm DMA) being 80, 65, 65, and 45%. Induction of preneoplastic lesions (glutathione S-transferase placental form-positive foci in the liver and atypical tubules in the kidney) was also significantly increased in DMA-treated groups. Ornithine decarboxylase activity in the kidneys of rats treated with 100 ppm DMA was significantly increased compared with control values (P < 0.001). In conclusion, DMA is acting as a promoter of urinary bladder, kidney, liver, and thyroid gland carcinogenesis in rats, and we speculate that this may be related to cancer induction by As in humans.

Acetyltransferases↗
PubMed1995

Absence of promoting potential of bracken fern (Pteridium aquilinum) in rat urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine and uracil.

Conventional studies on bracken fern (Pteridium aquilinum; PA) carcinogenicity have used high dietary concentrations (around 30%) and long-term exposure (up to 52-70 weeks) without consideration of the multistep character of the chemical carcinogenesis process. The present study evaluated specifically the promoting potential of 3-5% dietary crude PA in the rat urinary bladder mucosa in a 32-week-long initiation-promotion assay for chemical carcinogenesis. Initiation of urothelial carcinogenesis was accomplished with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Uracil (U) was provided through the diet in order to expand the population of initiated cells. Seven groups (G) of male Wistar rats were submitted to the following treatments: G1 = BBN (n = 8); G2 = U (n = 10); G3 = BBN-U (n = 9); G4 = BBN-PA-U-PA (n = 16); G5 = PA (n = 8); G6 = BBN-PA (n = 10); G7 = PA-U-PA (n = 12). At the end of the experiment rats presenting epithelial papillary or nodular hyperplasia (PNH), papillomas (PAP), or simultaneous PNH plus PAP numbered, respectively G1: 2-0-1; G2: 0-0-0; G3: 3-0-2; G4: 4-3-2; G5: 1-0-1; G6: 8-0-0; and G7: 0-0-0, with no significant differences in the incidence of lesions among the groups. More frequent and more severe lesions occurred in BBN-initiated animals, predominantly in those also exposed to uracil (G3 and G4). Low-dose crude bracken fern in the diet does not promote rat urinary bladder carcinogenesis after a 32-week period of exposure, even when the initiated urothelial cell population has been expanded through a mechanical stimulus.

Animals↗
PubMed1995

Validation of silver-stained nucleolar organizer regions for evaluation of invasive character of urinary bladder carcinoma in rats and mice.

A series of 8 rat and 16 mouse invasive bladder carcinomas were investigated for the presence of silver-stained nucleolar organizer regions (AgNORs) to clarify whether this parameter is applicable to the estimation of their invasive character. With regard to number of AgNORs per cell, neither rat nor mouse carcinomas showed any difference between invasive and noninvasive sites within the same tumor. However, the frequency of cancer cells bearing bizarre dots, irregular in size and shape, was significantly higher at sites of actual invasion. Quantitative data generated using an image analyzer revealed significantly lower values for NOR roundness and significantly larger NOR size in invasive sites than in noninvasive sites in all groups. Double staining for the proliferation marker proliferating cell nuclear antigen (PCNA) and AgNORs was performed on eight rat carcinomas and a close correlation between the two was confirmed. Thus the number of AgNORs in PCNA-positive cells was significantly greater than in PCNA-negative cells. Furthermore, a particularly strong correlation was observed for incidences of PCNA-positive cells and bizarre dots (P < 0.01). The quantitative data also demonstrated significant differences in size and shape of dots. It is concluded that AgNORs have diagnostic value for the invasive character of bladder carcinomas.

Animals↗
PubMed1995

Adjuvant-induced persistent photosensitivity models in guinea pigs. I. Induction of persistent photosensitivity.

Induction of persistent photosensitivity in guinea pigs was carried out in an attempt to induce a model suitable to clarify the mechanism of human persistent light reactors. Guinea pigs were treated with intradermal injection of adjuvant which consisted of desiccated Mycobacteria followed by topical application of hapten solution and irradiation with UVA. Unequivocal skin reactions were subsequently elicited with UVA exposure in the absence of hapten application. This enhanced UVA reactivity persisted and could be elicited for more than 2 years. In these guinea pigs, remarkably increased sensitivity to UVB was also observed. These animals appear quite similar to persistent light reactors among humans. Muramyl dipeptide used in place of Mycobacteria was also found to be effective in inducing photosensitivity to UVA. There were great differences of reactivity noted among different strains of guinea pig, suggesting that persistent photosensitivity is influenced by genetic background. Enhanced UV sensitivity was induced without hapten application, only with injections of adjuvant and UVA irradiation in the immunization procedure. These results suggest that this model will be useful to study chronic actinic dermatitis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Adjuvant-induced persistent photosensitivity models in guinea pigs. II. Characterization of immunological mechanisms.

The immunological characteristics of our adjuvant-induced persistent photosensitivity (AIPP) guinea pig model were examined. The sensitivity to long-wavelength ultraviolet light (UVA) was transferred with peritoneal exudate cells. Proliferative response was observed in peritoneal exudate cells and lymph node cells concomitantly cultured in the presence of sera that had previously been irradiated with UVA. Cervical lymph nodes of AIPP animals were found to be hypertrophic, and the ratio of major histocompatibility complex (MHC) class II positive cells was increased as compared to that of intact guinea pigs. These results suggest that persistent photosensitivity elicited with UVA is based on cellular autoimmunity. Thus, the AIPP guinea pig model should be useful to study the mechanism of persistent photosensitivity disease in humans.

Adjuvants, Immunologic↗
PubMed1995

Frequent mutations of the p53 gene and infrequent H- and K-ras mutations in urinary bladder carcinomas of NON/Shi mice treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

To elucidate whether common genetic events in human urinary bladder carcinogenesis also occur in rodent models, we investigated the presence of p53, H- and K-ras mutations in 18 urinary bladder carcinomas induced by various concentrations of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male NON/Shi mice. Histopathologically, all were invasive, 11 being squamous cell carcinomas (SCCs) and the remaining seven being transitional cell carcinomas (TCCs). Using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis followed by DNA sequencing, p53, H- and K-ras mutations were observed in 14 (78%; exons 5-7), two (11%; one each on exons 1 and 2) and one (5.6%; exon 1) animals respectively. The frequencies of mutations in p53 exons 5, 6 and 7 were 7 (39%), 4 (22%), and 9 (50%) respectively, and no mutation was found in exon 8. All mutations involved one base-pair substitution with or without amino acid changes and the types of base-pair substitution were random. No evident association was observed between mutation sites and the histological phenotypes. In conclusion, p53 mutations are frequent in BBN-induced mouse invasive urinary bladder tumors, at similar levels to those observed for human high-grade invasive carcinomas, and this plus their distribution suggests their possible participation in this model of urinary bladder carcinogenesis.

Amino Acid Sequence↗