Effect of subchronic oral treatment with terbium on gastrointestinal uptake of calcium and phosphorus.
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Absorption↗
Biomedical subjects
H Jinno
Publications and source records attributed to H Jinno.
The effect of 1,2,3,4-tetrachlorodibenzo-p-dioxin on drug-metabolizing enzymes in the rat liver.
The effects of 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD) on drug-metabolizing enzymes were studied in male and female rats. 1,2,3,4-TCDD (25, 50, 100 and 200 mumol/kg) was administered by i.p. injection once. Among the cytochrome P-450 (P450)-mediated monooxygenase activities tested, 7-ethoxyresorufin O-deethylase (EROD) activities in both male and female rats, which are associated with CYP1A1, were remarkably induced by all doses of 1,2,3,4-TCDD. The relative induction to each control activity were from 3.0- to 24.5-fold and from 2.2- to 16.5-fold, respectively. Also, 1,2,3,4-TCDD increased other CYP1A-mediated monooxygenase activities such as 7-ethoxycoumarin O-deethylase (ECOD) and 7-methoxyresorufin O-demethylase (MROD) in male and female rats dose-dependently (1.4- to 4.3-fold). Western immunoblotting showed that the levels of CYP1A1 and CYP1A2 proteins in liver microsomes were increased by 1,2,3,4-TCDD. Although the activities of other P450-mediated monooxygenases, namely 7-pentoxyresorufin O-depentylase (PROD), 7-benzyloxyresorufin O-debenzylase (BROD), aminopyrine N-demethylase (APND) and nitrosodimethylamine N-demethylase (NDAND) in both male and female rats were induced at high doses (> or = 50 mumol/kg) of 1,2,3,4-TCDD, the relative level was low compared with those of the CYP1A-mediated monooxygenase such as EROD, ECOD or MROD. In addition to P450-mediated monooxygenase, there was significant induction in the activities of the Phase II drug-metabolizing enzymes, UDP-glucuronyltransferase (UGT) activities towards 4-nitrophenol (4-NP) and 7-hydroxycoumarin (7-HC) and glutathione S-transferase (GST) towards 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB) and DT-diaphorase. These results indicate that 1,2,3,4-TCDD induces both Phase I (CYP1A-mediated monooxygenase) and Phase II drug-metabolizing enzymes (UGT, GST, DT-diaphorase) in the male and female rat liver, and that the alterations of drug-metabolizing enzyme are characteristic of PCDD toxicity.
Animals↗
Effect of 1,2,4-trichlorodibenzo-p-dioxin on drug-metabolizing enzymes in the rat liver.
The effects of 1,2,4-trichlorodibenzo-p-dioxin (1,2,4-TrCDD) on drug-metabolizing-enzymes have been studied in male Wistar rats. 1,2,4-TrCDD (0.1 mmol/kg per day) was administered by i.p. injection for 3 days. Among the cytochrome P-450 (P450)-mediated monooxygenase activities tested, 7-ethoxyresorufin O-deethylase, which is associated with CYP1A1, was remarkably induced by 1,2,4-TrCDD (0.1 mmol/kg). The relative induction to control activity was 32.9-fold. Also, 1,2,4-TrCDD increased other CYP1A-mediated monooxygenase activities such as 7-ethoxycoumarin O-deethylase, 4-nitroanisole O-demethylase, 7-methoxyresorufin O-demethylase and caffeine N-demethylase from 5.7- to 1.9-fold. Western immunoblotting showed that the levels of CYP1A1 and CYP1A2 proteins in liver microsomes were increased by 1,2,4-TrCDD. On the other hand, 7-pentoxyresorufin O-depentylase activity was induced 2.6-fold whereas aniline 4-hydroxylase, nitrosodimethylamine N-demethylase and erythromycin N-demethylase activities were increased slightly (1.3-, 1.6- and 1.3-fold, respectively) by 1,2,4-TrCDD. However, aminopyrine N-demethylase was not significantly induced by 1,2,4-TrCDD. Of the Phase II drug-metabolizing enzymes, DT-diaphorase and glutathione S-transferase (GST) activities towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene, and those of UDP-glucuronyltransferase (UGT) towards 4-nitrophenol and 7-hydroxycoumarin were increased from 2.7 to 1.4-fold by 1,2,4-TrCDD. These results indicate that 1,2,4-TrCDD induces both Phase I and Phase II drug-metabolizing enzymes in the rat liver.
Animals↗
[Giant intrascrotal lipoma: a case report].
A case of giant intrascrotal lipoma is presented. The patient was a 72-year-old man with the chief complaint of painless swelling in the scrotum which had been noticed about 10 years previously. In the right scrotum, an elastic soft mass with negative transillumination was palpated. Ultrasonography and X-ray film demonstrated that it was solid mass. Under the diagnosis of intrascrotal tumor, an operation was performed. As the testis, epididymis, and spermatic cord was intact, the tumor was removed. The pathological diagnosis of the tumor was a well-capsulated benign lipoma. Including the present case, 29 Japanese cases of intrascrotal lipoma are reviewed.
Aged↗
[Targeting therapy using monoclonal antibody directed against growth factor receptors].
Targeting therapy is expected to be a new effective anti-cancer treatment in near future. Major advances are achieved by considerable effort in this area. Monoclonal antibodies that recognize tumour-associated antigens were conjugated to chemotherapeutic drugs, toxins and radionuclides with various procedures. To apply this new therapy for clinical use, many problems still remain to be clarified. These problems consist of human anti-mouse antibody, antigenic heterogeneity and low tumour uptake. By our experiment, growth factor receptor was an ideal target for targeting therapy and immunoconjugate directed against growth factor receptor showed selective cytotoxicity to cancer cells with expression of growth factor receptor. Moreover, cytotoxic effect was positively correlated with expression level of growth factor receptor.
Animals↗
Urinary excretion of cyclic AMP in cadmium-intoxicated rats.
To obtain further information on the negative calcium balance caused by Cd, the factors associated with serum calcium and phosphorus homeostasis other than inhibition of intestinal calcium absorption were studied by using urinary cyclic 3',4'-adenosine monophosphate (cAMP). In rats exposed to Cd for 30 d, the levels of urinary excretion of cAMP after treatment with parathyroid hormone (PTH), parathyroidectomy (PTX), or 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3) showed almost the same patterns as those of control rats: the response of urinary cAMP to treatment with PTH was not influenced by continuous oral administration of Cd. On the other hand, in rats exposed to Cd for 90 d without the other three treatments, the amount of urinary excretion of cAMP was markedly higher than in control rats. In PTX rats exposed to 90 d of Cd, urinary cAMP was unchanged, but it was markedly increased when the parathyroid was intact, with or without treatment with PTX. This phenomenon indicated hyperparathyroidemia in response to continuous oral administration of Cd for 90 d. The negative calcium balance with hyperparathyroidemia occurred after continuous oral administration of Cd and developed via increased urinary excretion of calcium. Urinary excretion of cAMP in Cd-exposed rats was unaffected by the administration of 1 alpha-OH-D3.
Administration, Oral↗
Generation of hypophosphatemia in rats by continuous oral administration of cadmium.
To obtain further information on the negative calcium balance caused by cadmium (Cd), the factors associated with serum calcium and phosphorus homeostasis other than inhibition of intestinal calcium absorption were studied by using parathyroid hormone (PTH) and 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3). In rats exposed to Cd for 30 or 90 days, the concentrations of serum calcium after treatment with PTH, parathyroidectomy (PTX) or 1 alpha-OH-D3 showed almost the same patterns as those of control animals. It was considered that the mechanism of regulation of calcium in Cd-exposed rats was normal. The continuous oral administration of Cd generated hypophosphatemia in rats. On the other hand, in 30- and 90-day-treated rats, the low concentration of serum phosphorus caused by Cd was further decreased by administration of PTH, whereas it was increased by PTX. The hypophosphatemia found in rats exposed to Cd for 30 days, but not for 90 days, was reversed by treatment with 1 alpha-OH-D3. From these results, it was concluded that the hypophosphatemia caused by long term oral administration of Cd resulted from secondary hyperparathyroidism, due to inhibited calcium absorption from the intestine, as was demonstrated previously.
Administration, Oral↗
Prostate growth factor in the extracts of benign prostatic hypertrophy. Partial purification and physicochemical characterization.
The biochemical and physicochemical properties of prostate growth factor (PGF) in the extracts of benign prostatic hypertrophy (BPH) were investigated. The PGF activity stimulating the proliferations of fibroblasts (mouse 3T3 and human BUD-8 cells) was detected predominantly in BPH prostate, and also in normal human prostates and well-differentiated adenocarcinoma prostates. No significant correlation between PGF contents and BPH tissue weight or histological differences (fibromuscular or glandular type) was detected. Gel filtration and isoelectric focusing indicated that partially purified factor(s) by ion exchange column chromatography had a multimolecular form comprising three active components (80,000, 43,000 and 10,000 daltons) and acidic isoelectric points (pH 4.0, 4.3, and 6.0). The activity was susceptible to heat treatment at 80 degrees C for 10 min, and to trypsin, but the factor was devoid of esteropeptidase activity. Subcellular fractionation located the entire activity in cytosol fraction.
Adenocarcinoma↗
[Bladder carcinoma with sarcomatous changes].
A 78-year-old man underwent surgery to remove a bladder tumor. The bladder contained two solid pedunculated tumors, which existed independently. Histopathologic examination revealed that of most the tumor was composed of spindle-shaped sarcomatous tissue sometimes containing multinucleated giant cells. Transitional cell carcinoma (Grade 3) was also found at the stalk of the tumor with squamous metaplasia. The squamous metaplasia, which gradually changed into sarcomatous tissue, was also found at many parts of the tumor, but no definite transition of the transitional cell carcinoma into sarcomatous tissue was noted. Therefore, the sarcomatous change of carcinoma in our case was brought about by way of squamous metaplasia of transitional cell carcinoma. The tumor could be given the diagnosis of so-called "carcinosarcoma". The pathologic significance of "carcinosarcoma" was briefly discussed.
Aged↗
[Clinical evaluation of Cernilton on benign prostatic hyperplasia].
Twenty-two patients whose average age was 67 years and who had benign prostatic hyperplasia of stage I and II were treated with Cernilton for more than 4 weeks. Subjective symptoms were excellently improved and the improvement rate was over 85% in all of the evaluated symptoms of dysuria. In the overall evaluation, 18 out of 22 patients were rated as moderately improved or better, 2 were slightly improved and 2 remained unaltered. Aggravation of the symptoms was found in none of the patients. Objective findings such as residual urine volume and urinary flow rate were improved in 3 patients, although the shrinkage of the prostate was not observed on rectal palpation, retrograde urethro cystography or transrectal ultrasonography. No adverse reaction was observed during Cernilton therapy. In conclusion, it is suggested that Cernilton may be effective and safe for the conservative treatment of patients with early stage prostatic hyperplasia of non-surgical indication.
Aged↗
[Combination effects of CDDP, ACR and HCFU on progressive urothelial tumors].
Nine patients with progressive urothelial tumors treated with combination chemotherapy were evaluated. The median age of the patients was fifty-four; 6 men and 3 women; 7 of the tumors were of the renal pelvis and/or ureter and at stage C or D at the time of initial chemotherapy. Another of the tumors was triple cancer (bladder, prostate, sigmoid) and the remaining case was of bladder cancer. The stage of the two bladders cancers was T4. All patients were treated with CDDP (cis-platinum), ACR (aclarubicin hydrochloride) and HCFU (carmoful) and given from one to 3 courses repeated at three-week intervals (mean 2.3 courses). Seven patients were evaluable while two had no evaluable lesions. The response with this chemotherapy was 2 cases of PR (28.5%), 4 cases of NC and one case of PD. No severe toxicities such as nephrotoxicity or cardiotoxicity, were revealed with this combination chemotherapy.
Aclarubicin↗
Effect of cryosurgery of the prostate in serum gonadotropin levels in prostatic cancer.
Pituitary gland response to releasing hormone using the LH-RH loading test before and 4 weeks after cryosurgery of the prostate was investigated in eight patients with advanced prostatic carcinoma. In pre- and postoperative comparisons of all patients, there were no significant differences detected before and after surgery. But pituitary response to the releasing hormone was compared before and after the surgery in each of the patients; in one, depression and facilitation of FSH and LH secretion, respectively, were observed and there was a variation in the response of gonadotropin in each patient. Although the number of observable patients is still too low to draw any definite conclusions from the test results, one possible interpretation is that cryosurgery of the prostate may influence hormonal secretion from the pituitary gland.
Adenocarcinoma↗
Humoral immunity following double-freezing of the prostate in patients with prostatic cancer.
In these studies, 10 patients with a confirmed histological diagnosis of stage C and D carcinoma underwent double-freezing of the prostate. The clinical courses in the first group (five patients) were favorable. In the second group (two patients), death by cachexia occurred due to the cancer. In the third group (three patients), death 4 weeks after the second cryosurgery suggests the effects of cryoshock. In the first and second groups, the results of the immunological examinations after the second freezing did not attain the predicted levels. Comparing the results of the third group with those of the first and second groups the primary differences was that the percentages of gamma-globulins and IgE were higher in the third group preoperatively. These findings suggest that patients with high percentages of gamma-globulin and high IgE levels are contraindicated for cryosurgery of the prostate.
Adenocarcinoma↗
Humoral immunity following double freezing of the prostate of patients with prostatic cancer.
In these studies, double freezing of the prostate was applied to 10 patients with a confirmed histologic diagnosis of stage C and D carcinoma. The clinical courses in the first group (five patients) were favorable. In the second group (two patients), death by cachexia occurred due to the cancer. In the third group (three patients), death 4 weeks after the second cryosurgery suggests the effects of Cryoshock. In the first and second groups, the results of immunologic examinations after the second freezing did not attain the predicted levels. Comparing the results of the third group with those of the first and second groups, the primary difference was that the percentages of gamma globulins and IgE were higher in the third group preoperatively. These findings suggest that in patients with high gamma globulin percentages and high IgE levels cryosurgery of the prostate is contraindicated.
Acid Phosphatase↗
Chiral separation of amines by high-performance liquid chromatography after tagging with 4-(N,N-dimethylaminosulphonyl)-7-(2-chloroformylpyrrolidin-1-yl)- 2,1,3-benzoxadiazole.
Chiral tagging reagents, 4-(N,N-dimethylaminosulphonyl)-7-(2-chloroformylpyrrolidin-1 -yl)-2,1,3- benzoxadiazole (R(+)-DBD-Pro-COCl and S(-)-DBD-Pro-COCl), react with mirror image enantiomers of amines to produce corresponding diastereomers in the presence of pyridine as a catalyst. The maximal excitation and emission wavelengths of the resulting diastereomers were ca. 450 nm and 560 nm, respectively. The diastereomers derived from some aliphatic amines were resolved by a reversed-phase chromatography with water-acetonitrile or normal-phase chromatography with n-hexane-ethyl acetate as the eluent. The reactivities of both enantiomers of DBD-Pro-COCl to chiral amines were almost comparable, whereas a slight difference of fluorescence intensity was observed with S(-)-DBD-Pro-COCl. When (S-)-DBD-Pro-COCl was used as the derivatization reagent, amines corresponding to S-configuration were eluted faster than R-configuration. The opposite elution order was obtained with the use of R(+)-DBD-Pro-COCl, instead of S(-)-DBD-Pro-COCl. The Rs values obtained from 1-cyclohexylethylamine (CEA) having aliphatic ring structure was larger than those of amines (1-(1-naphthyl)ethylamine (NEA) and 1-phenylethylamine (PEA)) having aromatic ring structures.
Amines↗
Haplotype structures of the UGT1A gene complex in a Japanese population.
Genetic polymorphisms of UDP-glucuronosyltransferases (UGTs) are involved in individual and ethnic differences in drug metabolism. To reveal co-occurrence of the UGT1A polymorphisms, we first analyzed haplotype structures of the entire UGT1A gene complex using the polymorphisms from 196 Japanese subjects. Based on strong linkage disequilibrium between UGT1A8 and 1A10, among 1A9, 1A7, and 1A6, and between 1A3 and 1A1, the complex was divided into five blocks, Block 8/10, Block 9/6, Block 4, Block 3/1, and Block C, and the haplotypes for each block were subsequently determined/inferred. Second, using pyrosequencing or direct sequencing, additional 105 subjects were genotyped for 41 functionally tagged polymorphisms. The data from 301 subjects confirmed the robustness of block partitioning, but several linkages among the haplotypes with functional changes were found across the blocks. Thus, important haplotypes and their linkages were identified among the UGT1A gene blocks (and segments), which should be considered in pharmacogenetic studies.
Asian People↗
Epidermal growth factor receptor-dependent cytotoxic effect of anti-EGFR antibody-ribonuclease conjugate on human cancer cells.
We have conjugated the murine monoclonal antibody (528) against the human epidermal growth factor receptor (EGFR) to mammalian pancreatic ribonuclease (RNase) via N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolene (2-IT). The conjugate showed dose-dependent cytotoxicity against EGFR-producing squamous cancer cells (A431, TE8, TE5, Ca9-22) and no detectable cytotoxicity against EGFR-deficient small-cell lung cancer cells (H69). The cytotoxicity of the conjugate was positively correlated with the EGFR numbers of each cell line. The addition of excess 528 antibody to the medium protected A431 cells from the conjugate cytotoxicity. This immunoconjugate might be useful for targeted treatment of squamous cell carcinomas hyperexpressing EGFR.
Animals↗