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Biomedical subjects

S Fukushima

Publications and source records attributed to S Fukushima.

At least 199 records · Page 11Linked to original sources
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

Cell proliferation in lung fibrosis-associated hyperplastic lesions.

1. Cell proliferative activity of atypical bronchioalveolar epithelia in lung fibrosis cases treated with bleomycin (BLM) or radiation was investigated by studying the histochemistry of the argyrophil nucleolar organiser regions (AgNORs) and proliferating cell nuclear antigen (PCNA). 2. Five and 14 autopsy cases of individuals who died of pulmonary fibrosis, caused by BLM treatment and irradiation respectively, were compared with (i) six control subjects who proved to have no apparent fibrosis of the lung at autopsy and (ii) four lung squamous cell carcinoma cases. 3. Histopathologically, both the BLM-treated and irradiated cases showed extensive collapse of the lung caused by severe fibrosis, although proliferative epithelial lesions such as atypical bronchioloalveolar hyperplasia and squamous metaplasia were more prominent in the former. 4. The mean AgNOR numbers in both atypical hyperplasias and metaplasias, of either BLM or irradiation cases, were significantly higher than in control bronchioalveolar epithelial areas, whereas they were lower than in the lung cancers. Data for PCNA-labelling indices were in time with those for AgNORs. 5. The results indicate that atypical hyperplastic lesions in the bronchioloalveoli arising during the fibrosing process as induced by BLM, and by irradiation, are highly proliferative.

Adult↗
PubMed1995

Protective effects of some neutral amino acids against hypotonic hemolysis.

The protective effects of some neutral amino acids against hypotonic hemolysis were examined at various pHs. At pH 5.0, 7.0 and 8.0, 50% hemolysis was induced at 200, 160 and 140 mOsM, respectively, suggesting that erythrocyte membranes became more fragile to osmotic shock with decreasing pH. All amino acids tested reduced the hypotonic hemolysis at pH 5.0, but enhanced it at pH 8.0. It is therefore likely that these amino acids controlled the osmotic fragility of the cell membranes. At pH 7.0, glycine (Gly) reduced hypotonic hemolysis with increasing concentration. Phenylalanine (Phe) also reduced hypotonic hemolysis at low concentrations, but had an incrementally opposite effect at high concentrations. It was suggested that Phe interacted with erythrocyte membranes in a similar way to amphipathic drugs. Kinetic studies demonstrated that hypotonic hemolysis occurred immediately, according to osmotic shock, and that Gly and a low concentration of Phe decreased osmotic shock. Phe at a high concentration showed fast hemolysis with a short lag-time. Gly also showed fast hemolysis after the suppression of hypotonic hemolysis. Morphological observations demonstrated that these amino acids induced exvagination, exovesiculation and then invagination. It was suggested that with exvagination, the membrane expansion decreased the osmotic fragility, but the further shape change evoked membrane hole-formation.

Amino Acids↗
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↗
PubMed1995

[Retinopathy and perinatal outcome in diabetic pregnancy].

Sixty patients with diabetes mellitus (DM) antedated pregnancy were enrolled; seven had proliferative retinopathy, 13 had simple retinopathy, and 40 were intact. Diet and/or insulin was prescribed to adjust their glucose control at fasting to < 100 mg/dl, as well as at 2 hours postprandial to < 120 mg/dl. Glycohemoglobin (Hemoglobin A1c) levels ranged between 5.4% and 6.4% in the third trimester in three groups. Incidences of pregnancy complications (toxemia, hydramnios, urinary tract infection and cesarean section) and neonatal complications (low Apgar score, hypoglycemia, jaundice, polycythemia, respiratory distress syndrome and anomaly) did not differ significantly with the grade of retinopathy. Compared with the intact group, the duration of DM was significantly longer in the retinopathy groups and the incidence of fetal distress was significantly higher in the proliferative retinopathy group. In ten of 60 patients (16.7%) the grade of retinopathy progressed during pregnancy. In four patients photocoagulation was performed for neovascularization, and proved to be effective. There was a tendency for those whose retinopathy progressed to the proliferative stage during pregnancy to have larger decreases in glycohemoglobin and for their retinopathy to worsen after delivery. With tight maternal glucose control and intensive fetal surveillance, we obtained good perinatal outcome in pregnancies with diabetic retinopathy, as compared to diabetic pregnancy without diabetic microangiopathy. Careful and frequent monitoring of retinal changes should be required during pregnancy and the postpartum period.

Adult↗
PubMed1995

[Characteristics of early carcinomas and precancerous lesions in the urinary bladder].

Early transitional cell carcinomas of the urinary bladder are morphologically classified into papillary and non-papillary types, carcinoma in situ (CIS). Severe dysplasia is considered as a precancerous lesion for CIS which can be distinguished from the morphological appearance of its AgNORs. The conversion from severe dysplasia to CIS appears to require a longer time than that needed for invasive lesion to develop from CIS. It is postulated that mild or moderate dysplasia results in G1 and 2 grade papillary transitional cell carcinomas. Molecular analysis of different types of dysplasia is therefore clearly warranted to assist in diagnostic classification.

Animals↗
PubMed1994

Dose-dependent inhibition of glutathione S-transferase placental form-positive hepatocellular foci induction in the rat by methyl propyl disulfide and propylene sulfide from garlic and onions.

Two organosulfur compounds, methyl propyl disulfide (MPD) and propylene sulfide (PS) from garlic and onions, were studied for their modifying effects on hepatocarcinogenesis in the F344 rats. Modifying potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form (GST-P)-positive foci in the liver. MPD and PS significantly reduced both these parameters of GST-P-positive foci in a dose-dependent manner. To investigate possible mechanisms of inhibition, ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) activities were measured. In MPD and PS-high dose-treated liver tissue there was a tendency for their decrease, albeit non-significant, which suggested that the inhibitory effect might have been caused by decreased cell proliferation associated with decreased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is thus necessary to consider various effects in assessing possible protective roles of garlic and onions.

Allium↗
PubMed1994

22-Oxa-1,25(OH)2vitamin D3, a synthetic analogue of vitamin D3, has no promoting activity in a rat liver medium-term bioassay.

Modifying effects of 22-oxa-1,25(OH)2vitamin D3(OCT), a synthetic analogue of vitamin D3, were evaluated in a liver medium-term bioassay using glutathione S-transferase placental form (GST-P)-positive foci and 5-bromo-2'-deoxyuridine (BrdU) labeling to give an index of DNA synthesis. F344 rats were given a single intraperitoneal injection of diethylnitrosamine (200 mg/kg body wt.) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, 500 p.p.m. phenobarbital sodium and/or basal diet were fed to the rats for 6 weeks, at the same time as OCT and/or propylene glycol as the vehicle injected intraperitoneally 5 times a week. OCT demonstrated no promoting activity for rat hepatocarcinogenesis, and, in fact, showed a tendency to decrease the area per unit area of (GST-P)-positive foci in the livers of rats fed 500 p.p.m. phenobarbital sodium. However, intergroup differences in areas and numbers per unit area as well as in BrdU labeling indices were not statistically significant.

Animals↗
PubMed1994

Enhancement by organosulfur compounds from garlic and onions of diethylnitrosamine-induced glutathione S-transferase positive foci in the rat liver.

Ten organosulfur compounds from garlic and onions were studied for their modifying effects on diethylnitrosamine-induced neoplasia of liver in male F344 rats using the medium-term bioassay system of Ito based on the two-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form-positive foci in the liver with those of the corresponding control group given diethylnitrosamine alone. In experiments 1 and 2, high doses of diallyl sulfide, diallyl trisulfide, allyl methyl sulfide, allyl methyl trisulfide, and dipropyl sulfide had enhancing effects on focus formation. In contrast, high doses of methyl propyl disulfide and propylene sulfide significantly decreased the number of glutathione S-transferase placental form-positive foci. In the third experiment, combined treatment with the five chemicals that had enhancing activity were fed at low doses and increased the induction of glutathione S-transferase placental form-positive foci. To investigate the mechanism of the modifying effect on hepatocarcinogenesis, ornithine decarboxylase activity was measured in diallyl sulfide-, allyl methyl sulfide-, and dipropyl sulfide-treated liver tissue without prior initiation with diethylnitrosamine, and its activity was increased compared to controls. Spermidine/spermine N1-acetyltransferase activity was not significantly changed. Formation of 8-hydroxydeoxyguanosine, a DNA adduct generated by activated oxygen species, and lipid peroxidation (2-thiobarbituric acid-reacting substance production) were also not changed. These results suggest that the promoting effect could be caused by increased cell proliferation with increased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is appropriate to consider not only the possible protective role of garlic and onions but also their enhancing effects.

Allium↗
PubMed1994

Change in the three-dimensional shape of the stomach in the developing human fetus.

To reveal the developmental characteristics of the fetal stomach in utero, this study was made on 879 subjects from 20 to 40 weeks' gestation. By applying the system of 'Modeling a three-dimensional shape from a silhouette by detecting symmetry' which we devised, we reconstructed the three-dimensional shape, from the outline of the longitudinally transected fetal stomach, obtained from the real-time ultrasound image. Age-related changes in gastric volume and sphericality (parameters produced by the above mentioned method) were analyzed using piecewise linear regression. The fetal stomach volume increased linearly from 20 to 37 weeks' gestation and decreased thereafter to 40 weeks' gestation, with a critical point at 37 weeks' gestation. The sphericality of the fetal stomach shape was also seen to decrease linearly from 20 weeks' to the critical point at 27 weeks' gestation, thereafter remaining constant regardless of the advance in gestation to term. These findings indicate that at 20-27 weeks' gestation, the stomach is of a fusiform-like shape. From 27 weeks' gestation onwards, greater and lesser curvatures become apparent, clearly identifying the cardiac and pyloric regions. The decrease in stomach size after 37 weeks' gestation is also in good accord with the decrease in amniotic fluid volume. The analytical method presented here can help to understand the pathogenesis of gastrointestinal lesions in the developing fetus.

Embryonic and Fetal Development↗