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Biomedical subjects

S Fukushima

Publications and source records attributed to S Fukushima.

At least 271 records · Page 15Linked to original sources
PubMed1992

Inorganic alkalizers and acidifiers under conditions of high urinary Na+ or K+ on cell proliferation and two-stage carcinogenesis in the rat bladder.

Effects of alkalizers and acidifiers on bladder cell proliferation and two-stage carcinogenesis were investigated under conditions of high urinary Na+ or K+. Animals were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then received Na3PO4, NaH2PO4, NaCl, NaH2PO4 + NaCl, K3PO4, KH2PO4, KCl, KH2PO4 + KCl or no chemical supplement in the diet from weeks 5 to 8 and from weeks 12 to 20. During weeks 9 to 11, the rats were fed 3% uracil in their diet for acceleration of promotion. Na3PO4 or K3PO4 induced marked natriuresis or kaluresis and alkalinuria associated with strong promoting potential for bladder carcinogenesis. NaH2PO4 induced moderate natriuresis and aciduria and exhibited weak promoting activity. NaH2PO4 + NaCl or KH2PO4 + KCl caused marked increase in the respective cation levels and aciduria with elevation of promotion as compared to NaH2PO4 or KH2PO4 alone. NaCl or KCl induced moderate natriuresis or kaluresis and did not alter urinary pH. NaCl but not KCl also exerted weak promoting activity for bladder carcinogenesis. Increased DNA synthesis after test chemical exposure for 8 weeks and morphological alterations observed by scanning electron microscopy in the bladder epithelium were only quantitatively linked with promoting activity in the Na3PO4 case. With the other treatments no clear correlation between early cell proliferation and promotion potential was apparent. The present results suggest that although elevation in urinary Na+ or K+ level may be an essential factor for promotion of rat bladder carcinogenesis, the action of these cations may depend strongly on urinary alkalinity.

Animals↗
PubMed1992

Synergism of environmental carcinogens and promoters on bladder cancer development initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine in F344 rats.

Synergistic or additive effects of combined treatments with carcinogens or promoters on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated rat bladder carcinogenesis were examined. Male F344 rats were given BBN as an initiator followed by low doses of 3 sodium salts (sodium bicarbonate, sodium L-ascorbate and sodium citrate) and/or 3 antioxidants (butylated hydroxyanisole, butylated hydroxytoluene and tertiary butylhydroxyquinone). Combined treatments with 3 sodium salts or 3 antioxidants, and especially all 6 chemicals together promoted bladder carcinogenesis. In addition, these combined treatments were associated with increased DNA synthesis of the bladder epithelium. Combined administration of the carcinogens, o-anisidine, p-cresidine, and 4-chloro-o-phenylenediamine at low doses also enhanced BBN-initiated bladder carcinogenesis. These results indicate that environmental carcinogens or promoters can exert synergistic or additive actions on bladder cancer induction.

Animals↗
PubMed1992

The modifying effects of indomethacin or ascorbic acid on cell proliferation induced by different types of bladder tumor promoters in rat urinary bladder and forestomach mucosal epithelium.

The effects of indomethacin (IM) or L-ascorbic acid (AsA) on cell proliferation induced by bladder tumor promoters such as butylated hydroxyanisole (BHA), sodium L-ascorbate (Na-AsA), sodium citrate (Na-Cit), and diphenyl (DP) in rat bladder and forestomach epithelium were investigated. Treatment with IM in combination with BHA or Na-AsA diminished DNA synthesis levels of bladder epithelium as compared to the BHA or Na-AsA alone values. On the other hand, AsA further amplified the increase of bladder epithelial DNA synthesis caused by Na-Cit treatment. Histopathologically, administration of Na-AsA in combination with IM reduced the incidence of simple hyperplasia. In contrast, simultaneous treatment with Na-Cit and AsA caused an increase of the hyperplasia development. No apparent combination effects were observed in the DP-treated groups. In forestomach epithelium, AsA enhanced the BHA-induced increase in DNA synthesis and epithelial hyperplasia, characterized by marked basal cell proliferation. The present results thus suggested that IM may exert inhibitory effects on promotion of bladder carcinogenesis by certain tumor promoter types, and AsA may enhance BHA forestomach carcinogenesis.

Animals↗
PubMed1992

Spermidine/spermine N1-acetyltransferase, a new biochemical marker for epithelial proliferation in rat bladder.

We examined the activity of spermidine/spermine N1-acetyltransferase (SAT), a rate-limiting enzyme of the biodegradation of polyamines, in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced transitional cell carcinoma (TCC) and melamine-induced papillomatosis of rat bladder, and compared the activity to that of ornithine decarboxylase (ODC). Both activities were higher in both lesions than in control rats. The difference between SAT and ODC activities in cancerous tissue and papillomatosis was not significant. Cells stained for proliferating cell nuclear antigen (PCNA) were abundant in papillomatosis. TCC had areas with much PCNA. The results indicated that an elevation of SAT activity occurs in both reversible and irreversible proliferation of bladder epithelium and could be important in bladder carcinogenesis.

Acetyltransferases↗
PubMed1992

Local control of prostate cancer by intraarterial infusion chemotherapy facilitated by the use of angiotensin II.

Intraarterial infusion chemotherapy with angiotensin II was carried out in 8 prostate cancer patients whose ages ranged from 61 to 77 years. They had stage C or D tumor progression and complained of difficult urination, bone pain or lymphedema caused by intrapelvic tumor infiltration. Endocrine therapy had been done before the infusion therapy but the clinical status showed little change with a persistence of local symptoms. Cis-platinum and doxorubicin were infused with an indwelling catheter into both internal iliac arteries. After the completion of 1-5 courses, 6 of 8 patients responded remarkably in local symptoms. It is thought that intraarterial infusion chemotherapy can be used safely and effectively in elderly patients.

Adenocarcinoma↗
PubMed1992

Bellini duct carcinoma of the kidney.

We report a very rare case of Bellini duct carcinoma originating from the collecting tubules of the kidney. A left renal tumor was detected during a health examination and radical nephrectomy was performed. Histological examination showed papillary adenocarcinoma. By means of immunohistochemical methods, we felt that the tumor was a renal carcinoma of Bellini duct origin.

Adenocarcinoma, Papillary↗
PubMed1992

Low susceptibility of nude mice to induction of invasive urinary bladder cancers by N-ethyl-N-(4-hydroxybutyl)nitrosamine.

A time- and dose-dependent study of N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) bladder carcinogenesis was performed in nude mice maintained on tap water containing 0.025% EHBN for 4, 12, and 20 weeks ad libitum. A total of 13 invasive tumors, comprising 11 transitional cell carcinomas (TCCs) (84.6%) and 2 squamous cell carcinomas (SCCs) (15.4%), were found. Compared with previous results for B6C3F1 mice exposed to the same EHBN insult, the numbers of invasive carcinomas induced in nude mice, and especially of SCCs, were low. In order to ascertain whether this difference in cancer incidence between nude and B6C3F1 mice was due to variation in urinary excretion, the metabolism of EHBN was also investigated and compared with that of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Respective total urinary excretions over 48 hr of N-ethyl-N-(3-carboxypropyl)nitrosamine (ECPN) or N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), the ultimate carcinogenic species of EHBN or BBN, were 822.4 +/- 41.4 micrograms and 530.4 +/- 81.0 micrograms, respectively, in nude mice, and 800.6 +/- 83.7 micrograms and 407.8 +/- 69.7 micrograms, respectively, in B6C3F1 mice. In conclusion, although it is apparent that nude mice have a low susceptibility to EHBN induction of urinary bladder cancer, this does not appear to be dependent on reduced metabolism to the active form.

Animals↗
PubMed1992

[Effects of repeated phase shifts in light-dark cycles on lipid metabolism in stroke-prone spontaneously hypertensive rats (SHRSP)].

In the present paper, we employed the stroke-prone spontaneously hypertensive rat (SHRSP) as an animal model and the Kyo: Wistar rat (WKY) as a control, and studied on the effect of repeated phase shifts in light-dark cycles on lipid metabolism. First, we investigated diurnal rhythms of the lipid metabolism in SHRSP and WKY. In both strains, the activities of lipoprotein lipase (LPL) and hepatic microsomal cholesterol 7 alpha-hydroxylase in the dark period were significantly higher than those in the light period. In addition, in SHRSP, the serum apoA-IV level in the dark period was also higher than that in the light period. Next, we repeated the phase shifts in light-dark cycles twice a week with elongation of the light period for 4 weeks. LPL activity in the light period increased in response to the repeated phase shifts in both strains. This might be a defensive reaction to maintain homeostasis in the lipid metabolism in addition to energy production. Moreover, we performed repeated phase shifts in rats fed a high-fat and high-cholesterol diet containing 0.1% propylthiouracil to elucidate the effect on the development of hypercholesterolemia. The repeated phase shifts increased the levels of atherogenic lipoproteins and the atherogenic index (apoB/apoA-I). In particular, the effect was more marked in SHRSP. This deleterious effect could be due to the overproduction of very low density lipoprotein (VLDL, beta-VLDL) in the liver.

Animals↗
PubMed1992

Conversion of dethiobiotin to biotin in cell-free extracts of Escherichia coli.

We constructed the plasmid pTTB151 in which the E. coli bioB gene was expressed under the control of the tac promoter. Conversion of dethiobiotin to biotin was demonstrated in cell-free extracts of E. coli carrying this plasmid. The requirements for this biotin-forming reaction included fructose-1,6-bisphosphate, Fe2+, S-adenosyl-L-methionine, NADPH, and KCl, as well as dethiobiotin as the substrate. The enzymes were partially purified from cell-free extracts by a procedure involving ammonium sulfate fractionation. Our results suggest that an unidentified enzyme(s) besides the bioB gene product is obligatory for the conversion of dethiobiotin to biotin.

Base Sequence↗
PubMed1992

Semiquantitative analysis of the effects of fixation and paraffin embedding on immunoreactivity of renal basement membranes to a monoclonal antibody against type IV collagen.

The effects of formalin fixation and paraffin embedding on the immunoreactivity of human kidney to a monoclonal anti-type IV collagen antibody (JK-199) were examined semiquantitatively by a modified enzyme-linked immunosorbent assay (ELISA). The intensity of immunoreactivity in paraffin sections of the tissue fixed overnight with 10% formalin was approximately 70% of that in frozen sections. Immunoreactivity reduced to this extent did not impair the specific staining of basement membranes. Paraffin sections of tissues fixed 2 days showed 50-60% of the reactivity in the frozen sections of the tissue fixed overnight; the basement membranes in Bowman's capsules were stained positively, but those in other sites were not. The paraffin sections of tissues fixed 7 or 14 days showed no specific immunostaining. The immunoreactivity for type IV collagen in the basement membranes was restored after treatment with pronase E. The immunoreactivity after the enzymatic treatment was about 150% of that in the frozen sections of the overnight fixed specimens.

Antibodies, Monoclonal↗
PubMed1992

[A pathological study of incidental carcinoma of the prostate. Pathological study of age-groups].

We reviewed 66 patients with stage A adenocarcinoma of the prostate who were treated at our 7 affiliated hospitals in Yokohama between 1984 and 1988. Of 1377 patients who underwent subcapsular prostatectomy (SCP) or transurethral resection of the prostate (TUR-P) for benign prostatic hyperplasia, 66 patients (4.8%) were diagnosed as an incidental carcinoma of the prostate. Of these patients, 36 and 30 were in stage A1 and A2, respectively. In the 66 patients, 59 (4.5%) were detected in 1315 TUR-P and 7 (11.3%) in 62 SCP. Elderly patients over 80 years of age had a higher risk of stage A2 disease. In histological grade, well, moderately and poorly differentiated adenocarcinoma were found in 48 patients (72.7%), 13 (19.7%) and 5 (7.6%), respectively. Among the patients with stage A prostate carcinoma the majority of the age-group less than 79 years old had well differentiated adenocarcinoma. In the age-group more than 80 years old, there were 6 (37.5%) moderately and 2 (12.5%) poorly differentiated tumors. In other words, the age-group more than 80 years old tended to have the moderately or poorly differentiated adenocarcinoma more frequently than those other decades. We expect an increase in the number of patients with stage A2 disease in the future with the expansion of the operative indication, especially in elderly patients.

Adenocarcinoma↗
PubMed1992

[Clinical studies on tosufloxacin (TFLX) in urology].

We clinically evaluated the usefulness of a new oral antimicrobial agent, TFLX, in the field of urology. The dose administered was 150 mg t.i.d and the duration of administration was 3 days. The clinical effect was evaluated according to the criteria of the Japanese UTI committee. The clinical response obtained on 164 female patients with acute simple cystitis was excellent in 118, moderate in 44 and poor in 2 patients. The efficacy rate was 98.78%. The clinical response obtained on 4 male patients with acute simple cystitis was excellent in 2 and moderate in 2 patients. The efficacy rate was 100%. The clinical response obtained on 3 female patients with simple pyelonephritis was excellent in 2 and moderate in 1 patient. The efficacy rate was 100%. The clinical response obtained on one patient with non-gonococcal urethritis was excellent by doctor's evaluation. The clinical response obtained on 7 patients with complicated UTI was excellent in 3 and moderate in 4 patients. The efficacy rate was 100%. Three patients complained of stomach distress or malaise and 2 patients developed rash. No abnormal laboratory data were observed. Thus, TFLX appears to be safe and suitable for use in the field of urology.

4-Quinolones↗
PubMed1992

Increased urinary morphine, codeine and tetrahydropapaveroline in parkinsonian patient undergoing L-3,4-dihydroxyphenylalanine therapy: a possible biosynthetic pathway of morphine from L-3,4-dihydroxyphenylalanine in humans.

We have identified morphine and codeine in human urine by means of gas chromatography/mass spectrometry. Gas chromatography/mass spectrometry was also used to quantitate the two alkaloids and tetrahydropapaveroline (THP) in urine of both normal subjects and parkinsonian subjects receiving L-dopa therapy. The morphine, codeine and THP levels in healthy nondrinker controls were 2.93 +/- 0.23, 2.01 +/- 0.53 and 6.70 +/- 1.13 pmol/ml (mean +/- S.E.M.), respectively. In contrast, the urinary levels of codeine and THP in L-dopa-treated parkinsonian patients were significantly elevated to 62.20 +/- 17.54 and 31.04 +/- 15.69 pmol/ml, respectively. Some of the parkinsonian patients showed high urinary morphine levels. Morphine excretion was also enhanced in patients complaining of severe pain due to herpes zoster (24.60 +/- 9.51 pmol/ml) but not in patients with severe pain due to cerebral embolus. These alkaloid levels in the urine of abstinent alcoholics were very low. There were significant correlations among these three alkaloid levels in the urine. The results indicate that morphine and codeine are synthesized in the body from L-dopa and/or dopamine, via the THP-related pathway.

Adult↗
PubMed1991

A new approach to chemoembolization for unresectable hepatocellular carcinoma using aclarubicin microspheres in combination with cisplatin suspended in iodized oil.

Sixty-six consecutive patients with unresectable hepatocellular carcinoma (HCC) were treated with transcatheter arterial chemoembolization (TACE) using aclarubicin microspheres (ACRms) in combination with cisplatin suspended in iodized oil (Lipiodol, Laboratoire Guerbert, Paris, France) (CSL). The stages of the disease were as follows: Stage I (n = 1), Stage II (n = 10), Stage III (n = 26), and Stage IV (n = 29). The effectiveness of TACE was assessed by comparing ACRms with CSL with ACRms without CSL. Of 66 patients treated with ACRms and CSL, 62 (93.9%) could be examined for response. According to response criteria, there were 31 (50.0%) partial responses and 17 (27.4%) minor responses. In 13 cases (21.0%) there was no change and in 1 case (1.6%) there was progressive disease. The cumulative survival rate was 80.7% at 1 year, 64.2% at 2 years, and 50.6% at 3 years. The rates were significantly higher than those of the group treated with ACRms. Eleven patients in the ACRms and CSL group experienced clinical complications: cholecystitis (4.5%), pancreatitis (3.0%), liver abscess (3.0%), hepatic failure (3.0%), gastrointestinal bleeding (1.5%), and renal failure (1.5%). No lethal side effects related to the therapy were observed. TACE using ACRms in combination with CSL prolongs the survival of patients with unresectable HCC.

Aclarubicin↗
PubMed1991

YM175, a new bisphosphonate, increases serum 1,25-dihydroxyvitamin D in rats via stimulating renal 1-hydroxylase activity.

Effect of YM175, a new bisphosphonate, on vitamin D metabolism was studied in rats. When animals were treated with the compound, serum 1,25-dihydroxyvitamin D increased in a dose dependent manner. The effect was also detected in thyroparathyroidectomized animals. The effect appears to be due to the stimulation of renal production of the hormone, since renal 1-hydroxylase was also elevated in these animals. However, when kidneys were incubated with YM175 and then renal 1-hydroxylase activity was examined, the enzyme activity was not different from that of non-treated control kidney. We conclude therefore that YM175 indirectly stimulates renal 25-hydroxyvitamin D-1-hydroxylase by increasing circulating parathyroid hormone via an unknown mechanism independent of parathyroid hormone. This is the first direct demonstration of increase in the renal production of 1,25-dihydroxyvitamin D resulting from bisphosphonate treatment.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1991

A rapid in vivo bioassay for the carcinogenicity of pesticides.

Eight pesticides were tested in a bioassay based on the induction of preneoplastic lesions in the liver. Rats were given diethylnitrosamine intraperitoneally at 200 mg/kg bw and two weeks later were treated with pesticides for six weeks and then killed; all rats had a partial hepatectomy at week 3. Hepatocarcinogenic potential was assessed by comparing the number and area of glutathione s-transferase (placental form) -positive foci in the liver with those of controls given diethylnitrosamine alone. Positive results were seen with Chinomethionat, Phosmet and Propiconazole; the results obtained with Captan and Prochloraz were borderline; Benomyl, Daminozide and Folpet gave negative results. Our findings provide enough experimental evidence to indicate that great care should be exercised in the use of these compounds.

Animals↗
PubMed1991

Lack of synergism in rat urinary tract carcinogenesis between prior uracil treatment and N-butyl-N-(4-hydroxybutyl)-nitrosamine administration.

Combination effects of sequential treatment with uracil prior to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) with regard to carcinogenesis in the urinary bladder and renal pelvis were investigated in male F344 rats. Uracil was administered for 15, 10 or 5 weeks followed by BBN for 23 weeks, the total observation time being 40 weeks. Carcinoma(s) and papilloma(s) were induced in the urinary tract by the 15-week uracil treatment independent of subsequent BBN administration. It was concluded that uracil administration prior to BBN treatment is not associated with any synergistic effects, although both uracil and BBN alone exerted carcinogenicity.

Animals↗