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Biomedical subjects

S Fukushima

Publications and source records attributed to S Fukushima.

At least 19 recordsLinked to original sources
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

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

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↗
PubMed1995

Inhibition of intestinal tumor development in rat multi-organ carcinogenesis and aberrant crypt foci in rat colon carcinogenesis by 22-oxa-calcitriol, a synthetic analogue of 1 alpha, 25-dihydroxyvitamin D3.

The modifying effects of 22-oxa-calcitriol (OCT), a synthetic analog of 1 alpha,25-dihydroxyvitamin D3, were assessed in a multi-organ carcinogenesis model using male F344 rats initially treated with five kinds of carcinogens. In experiment 1 the rats were given OCT intraperitoneally at doses of 30 micrograms/kg (25 rats) or 3 micrograms/kg (25 rats), three times a week for 24 weeks after initial carcinogen exposure over 4 weeks and a 2 week non-treatment period. Twenty-two rats received the five carcinogens and were given the vehicle intraperitoneally as a control. A further group of 10 rats was given the 30 micrograms/kg dose of OCT without prior carcinogen application. At the end of the total observation period of 30 weeks the carcinoma incidence in the small intestine of rats given 30 micrograms/kg OCT after carcinogen treatment was 0%. This incidence was significantly smaller when compared with the control group. The incidence of large intestine carcinomas in the 30 micrograms/kg OCT group showed a tendency to decrease. The numbers of small and large intestinal carcinomas per rat were also significantly lower in the group given 30 micrograms/kg OCT than after 3 micrograms/kg OCT or carcinogens alone. Attention was, therefore, focused on colon carcinogenesis and in experiment 2 30 micrograms/kg OCT administered six times a week to rats for 8 weeks after the last injection of N,N'-dimethylhydrazine (DMH) exposure. OCT significantly reduced the formation of DMH-induced aberrant crypt foci, considered to be putative preneoplastic lesions. In experiment 3 30 micrograms/kg OCT was administered six times a week to rats for 4 weeks without prior carcinogen treatment. The proliferating cell nuclear antigen labeling index for the colonic epithelium of rats given 30 micrograms/kg OCT was decreased. Ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities in colonic epithelium, assayed as indicators of cell proliferation, were not significantly decreased as compared with control group values. Furthermore, vitamin D receptors in colonic epithelium were not significantly increased. Thus the present study indicates that OCT can exert inhibitory effects on tumor development in the small and large intestines, although the mechanism is unclear.

Acetyltransferases↗
PubMed1995

Lack of promoting effects of alpha-linolenic, linoleic or palmitic acid on urinary bladder carcinogenesis in rats.

Potential promoting effects of alpha-linolenic, linoleic and palmitic acids were investigated in a two-stage urinary bladder carcinogenesis model. In experiment 1, male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and then basal diet containing 10% alpha-linolenic, 10% linoleic or 10% palmitic acid along with 0.2% butylated hydroxyanisole (BHA) as an antioxidant for 24 weeks. The development of tumors in the urinary bladder was not increased by treatment with any of the fatty acids. In experiment 2, male F344 rats were given 10% alpha-linolenic, 10% linoleic or 10% palmitic acid along with 0.2% BHA in their diet for 8 weeks without prior BBN treatment. The administration of fatty acids was not associated with any increase in the 5-bromo-2'-deoxyuridine labeling index of the urinary bladder epithelium. Serum and/or urine fatty acid levels increased in the cases of alpha-linolenic and linoleic acid treatments, but not with palmitic acid. Under the present experimental conditions neither the two polyunsaturated nor the one saturated fatty acid exerted any promoting effect on urinary bladder carcinogenesis.

Animals↗
PubMed1995

Inhibition of 5'-deoxy-5-fluorouridine phosphorolysis by acyclopyrimidinenucleosides in intestinal tissue homogenates.

This study examined the inhibitory effect of acyclopyrimidinenucleosides on 5'-deoxy-5-fluorouridine (5'-DFUR) phosphorolysis in intestinal tissue derived from rabbit, rat, mouse, and human. 5-Bromoacyclouridine, 5-fluoroacyclouridine, acyclouridine, and 5-nitroacyclouridine showed little or only moderate effect, but acyclothymidine [5-methyl-1-(2'-hydroxyethoxymethyl)uracil] showed strong inhibitory effect on 5'-DFUR phosphorolysis in intestinal tissue homogenates derived from human. In the absence of inhibitor (acyclothymidine), the Vmax of 5'-DFUR phosphorolysis was 2.66 mumol/min and the Km was 0.57 mM in human intestinal homogenates. The Vmax was unaltered by increased inhibitor concentration. The maximal inhibitory effect of acyclothymidine on 5'-DFUR phosphorolysis in rat homogenates was over 90%. The Ki/Km was 0.63 in human, 2.14 in rabbit, 1.09 x 10(-2) in rat, and 1.71 x 10(-2) in mouse. These data show that acyclothymidine is a competitive inhibitor of 5'-DFUR phosphorolysis, and that it can inhibit not only uridine phosphorylase but also thymidine phosphorylase.

Animals↗
PubMed1995

Behavior of propylene glycol (PG) in dermis after treatment of rat intact skin surface with fatty acids, fatty amines or azone dissolved in PG.

Rat abdominal intact skin was treated with fatty acids, fatty amines, or Azone which were dissolved in propylene glycol (PG) and PG appearing in the rat dermis was studied. Analysis was done by Fourier transform infrared/attenuated total reflection (FT-IR/ATR) spectroscopy. The appearance of PG with time seemed to be in three phases when the skin sample was treated with a skin penetration enhancer such as oleic acid: (1) in the first stage, PG penetrated the skin barrier which was not substantially altered, and gradually appeared in the dermis; (2) in the second stage, it rapidly distributed in/throughout the dermis, and this rapid distribution was probably due to the alteration of the dermal structure: the penetration enhancing effect of the enhancer was thought to reach maximal; and (3) in the third stage, PG was saturated in the dermis. The value of T(max alteration), at which the alteration of the dermal structures is completed, showed that the action of both oleic acid and oleylamine were more rapid than other enhancers. Both the value of PG peak area(max) at the third stage which reflects the distribution volume of PG in the dermis and the value of T(sat) at which PG is saturated in the dermis were calculated, and the results suggested that both the distribution volume of PG in the dermis and the time of the saturation varied depending on the enhancer. In conclusion, our present work indicated the importance and necessity of evaluating the rate and extent of appearance of a drug in the dermis to characterize an enhancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Amines↗
PubMed1995

[Planning for brachytherapy using a 3D-simulation model].

A 3D-simulation model made with a milling system was applied to HDR-brachytherapy. The 3D-simulation model is used to simulate the 3D-structure of the lesion and the surrounding organs before the actual catheterization for brachytherapy. The first case was recurrent prostatic cancer in a 61-year-old man. The other case was lymph node recurrence of a 71-year-old woman's upper gum cancer. In both cases, the 3D-simulation model was very useful to simulate the 3D-conformation, to plan the treatment process and to avoid the risk accompanying treatment.

Aged↗
PubMed1995

A case report of inflammatory pseudotumor of the urinary bladder.

A case of an inflammatory pseudotumor of the urinary bladder in a 46-yr-old man is presented. This rare, benign, and presumed non-neoplastic, reactive lesion must be differentiated from sarcomas of the urinary bladder. In the present case, we could demonstrate an inflammatory and reactive nature for the pseudotumor. Histologically, the presence of many Brunn's nests with infiltration of inflammatory cells and proliferation of capillaries in the myxoid stroma indicated a chronic inflammatory background for this lesion. It is apparent from morphology and immunohistochemistry findings that the proliferating spindle-shaped cell is of mesenchymal origin and not malignant in nature. These findings suggest that chronic inflammation can induce an overreaction of the bladder wall resembling tumor formation.

Granuloma, Plasma Cell↗
PubMed1995

The frequency of 4977 base pair deletion of mitochondrial DNA in various types of liver disease and in normal liver.

Using a polymerase chain reaction (PCR) method, we tested for the hepatic mitochondrial DNA (mtDNA) deletion in 40 hepatic tumors (28 hepatocellular carcinomas [HCCs], 9 other malignant tumors, and 3 benign tumors) and in the livers of 71 patients, including 16 pediatric patients with end-stage liver disease who underwent living related donor liver transplantation and 16 liver donors. A 4977 base pair (bp) deletion of mtDNA was detected in 36 of 55 specimens of non-tumor portions of adult liver (65.5%). However, none of the specimens obtained from cirrhotic livers of the 16 pediatric patients younger than 13 years of age had the 4977 bp deletion. The frequency of mtDNA deletion was significantly decreased compared with normal liver in HCCs (7 of 28) and other malignant liver tumors (2 of 9). The frequency of this deletion was unrelated to the presence of liver cirrhosis, patient's gender, hepatitis B virus surface antigen status, and hepatitis C virus antibody status.

Adolescent↗