Search PubMed⌕ Search

Biomedical subjects

T Kinouchi

Publications and source records attributed to T Kinouchi.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Results of chemotherapy and salvage surgery for advanced testicular cancer].

Since 1980, 73 patients with advanced testicular cancer have been treated with chemotherapy and 43 patients received post-chemotherapy (salvage) surgery. The median age of all patients was 31 years old, ranging from 17 to 63 years. The histology of the primary testicular tumor was pure seminoma in 23 patients and non-seminoma in 50 patients. According to the Japan Urological Association classification, 38 patients were classified as stage II and 35 patients as stage III. As first-line chamotherapy, 52 patients were treated with PVB regimen (cisplatin, vinblastin, bleomycin), 16 patients with PEB (cisplatin, etoposide, bleomycin) and 5 patients with VAB-6 (vinblastine, actinomycin-D, bleomycin, cisplatin, cyclophosphamide). Thirty (41%) of the 73 patients achieved a complete response (CR) with chemotherapy alone and 63 (86%) achieved no evidence of disease (NED) with salvage treatment. As second-line chemotherapy, 16 patients were treated with PE (cisplatin, etoposide), or VIP (etoposide, ifosfamide, cisplatin) or VeIP (vinblastine, ifosfamide, cisplatin). One of the 16 patients achieved CR and 11 (69%) patients achieved NED. As salvage surgery, retroperitoneal lymphnode dissection (RPLND) was performed in 22 patients, RPLND with thoracotomy in 7 cases and thoracotomy alone in 4 cases. Necrosis was found in surgical specimens of 24 (56%) patients, mature teratoma in 6 (14%) and residual cancer in 13 (30%). Ninety-six percent and 100% of the patients with necrosis and mature teratoma survived with NED, respectively, but only 54% of the patients with residual carcinoma survived despite further treatment. Residual cancer was still found in 8 of the 32 (25%) marker normalized cases. Residual cancer could not reliably be predicted or discriminated from necrosis or mature teratoma by the prognostic criteria. Therefore, salvage surgery remains essential in the treatment of advanced testicular cancer.

Adolescent↗
PubMed1998

The deletion of the C-terminal tail and addition of an endoplasmic reticulum targeting signal to Alzheimer's amyloid precursor protein change its localization, secretion, and intracellular proteolysis.

The metabolic pathway of Alzheimer's amyloid precursor protein (APP) involves restricted intracellular proteolysis by secretases, which leads to the secretion of the N-terminal soluble APP (sAPP) and the generation of a cell-associated C-terminal fragment. The precise cellular sites at which these processes occur remain unknown. In this report, we describe the route of APP sorting and the processing site using novel systems with and without sorting signals on the APP molecule. One system involves the replacement of the C-terminal ten amino acids of APP with Adenoviral E19 protein containing an endoplasmic reticulum (ER) retrieval signal (APPE19); the other involves deleting the last ten amino acids corresponding to the replaced site (APPdeltaC10). APPE19 localized mainly within the cis/medial Golgi compartment and exclusively suppresses the secretion of APP. In contrast, deletion of the C-terminal tail promotes sAPP secretion by a constitutive secretion pathway. Metabolic labeling followed by immunoprecipitation with anti-APP antibody revealed that APPE19 is rapidly degraded within 30 min and that the subsequent intracellular turnover rate is decreased with 40% of the protein retained within the cells even after a chase period a 3 h. In contrast, APPdeltaC10 is rapidly eliminated from the intracellular compartments and secreted into the culture medium. The surface internalization and recycling processes of this protein are relatively impaired compared with wild-type APP. The ratios of the levels of production to secretion of sAPP alpha, the N-terminal, soluble APP fragment released by alpha-secretase, are proportional to the secretion efficiencies among APP species, suggesting the localization of alpha-secretase within a compartment late in the constitutive secretion pathway. These secretion mutants which utilize ER targeting signals are useful tools for analyzing the location of secretases and the intracellular degradation system within a constitutive secretion pathway such as ER quality control.

Adenovirus Early Proteins↗
PubMed1998

Inhibitory effects of citrus fruits on the mutagenicity of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid treated with nitrite in the presence of ethanol.

It has been shown that the mutagenicity of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCCA), a mutagen precursor in soy sauce treated with nitrite, was strongly increased when it was treated with nitrite in the presence of alcohols. We found that the mutagenicity of MTCCA treated with 50 mM nitrite at pH 3, 37 degrees C for 60 min in the presence of 7.5% ethanol was reduced by the addition of citrus fruits sudachi (Citrus sudachi), lemon (C. limon) and yuzu (C. junos), to the reaction mixture. The mutagenicity-reducing activity per weight of flavedos (outer colored portions of peel) of the citrus fruits was considerably higher than that of the juices. The juices of the other citrus fruits commercially available in Japan also had mutagenicity-reducing activity against the nitrite-treated MTCCA. Among the many components of citrus fruits, dietary fibers lignin and pectin showed strong antimutagenic activity in the reaction mixture, suggesting that the mixed fractions of these components including lignin, pectin, D-limonene, naringin, hesperidin, ascorbic acid and citric acid reduce the mutagenicity of MTCCA in the reaction mixture containing nitrite and ethanol.

Animals↗
PubMed1998

Adjunctive value of cell proliferation but not of apoptosis to interpret pathologic effects on prostatic cancer after neoadjuvant endocrine therapy.

BACKGROUND: The current histological evaluation of the effects of endocrine therapy has difficulty in distinguishing pathologic degeneration caused by androgen ablation from residual poorly differentiated tumor. Therefore, we examined the changes in cell proliferation and apoptosis before and after endocrine therapy and analyzed whether they correlated with pathologic effects and histological differentiation. METHODS: Between January 1986 and December 1995, 52 patients with clinical stage B2 and C prostate cancer underwent radical prostatectomy after neoadjuvant endocrine therapy (median duration 3.8 months). Proliferative and apoptotic activities of pretreatment biopsy specimens and radical prostatectomy specimens were analyzed with MIB-1 monoclonal antibody and in situ end-labeling of fragmented DNA. RESULTS: The mean proliferative index (PI) of radical prostatectomy specimens was significantly lower than that of biopsy specimens (P = 0.000003) and the decrease in PI after endocrine therapy was significantly related to histological differentiation (P = 0.014). There was a weak relationship between the decrease in PI after endocrine therapy and pathologic effects (P = 0.054), while in pathologically effective cases (Grades 2 and 3), three out of 16 (19%) showed a < 50% decrease in PI after endocrine therapy, and may be regarded as having poorly differentiated tumors. The mean apoptotic index (AI) of prostatectomy specimens tended to be higher than that of biopsy specimens (P = 0.054). The increase in AI after endocrine therapy was not related to histological differentiation and pathologic effects. CONCLUSION: Pathologic effects caused by endocrine therapy may be in part misled by routine histopathologic staining and the change in PI may help in recognizing the pathologic effects of endocrine therapy and have adjunctive value for the interpretation of the effects of endocrine therapy.

Aged↗
PubMed1998

Culture supernatants of Lactobacillus acidophilus and Bifidobacterium adolescentis repress ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug by suppressing unbalanced growth of aerobic bacteria and lipid peroxidation.

A nonsteroidal antiinflammatory drug, 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT), induced ileal ulcers in rats after oral administration, while no ulcers were observed after subcutaneous injection. The ileal ulcer formation in BFMeT-treated rats was examined to correlate the administration of cultures of Lactobacillus acidophilus or Bifidobacterium adolescentis with intestinal bacteria in the ileal contents and lipid peroxidation of the small intestinal mucosa. Ileal ulcers were observed in more than 85% of the rats treated with BFMeT at a dose of 1,000 mg/kg when they were given tap water as drinking water. The incidence of ulcer formation was repressed by giving culture supernatants of L. acidophilus or B. adolescentis as drinking water, but not by giving the cell suspension as drinking water. Gram staining of the ileal contents of normal rats revealed that 97% of the stained bacteria were gram-positive rods and only 1.5% were gram-negative rods. The percentage of gram-negative rods 72 hr after BFMeT administration was 49.8% and increased over 30-fold in BFMeT-treated rats. However, the percentage of gram-negative rods was 9.7 % or 16%, respectively, in rats taking culture supernatants of L acidophilus or B. adolescentis. In addition, thiobarbituric acid-reactive substances in the ileal mucosa increased significantly in the rats given tap water for 72 hr after BFMeT treatment, but not in rats given the culture supernatants of L. acidophilus or B. adolescentis. Since BFMeT induced an unbalanced intestinal microflora, the effect of antibiotic treatment on ulcer formation in rats was examined. The magnitude of the ulcer formation in the antibiotic-treated rats was, in decreasing order, metronidazole >none > kanamycin > a mixture (bacitracin, neomycin and streptomycin). These results suggest that the intestinal microflora plays an important role in ulcer formation and that a metabolite(s) of L. acidophilus and B. adolescentis inhibits ileal ulcer formation by repressing changes in the intestinal microflora and lipid peroxidation in BFMeT-treated rats.

Administration, Oral↗
PubMed1998

Protective effects of a culture supernatant of Lactobacillus acidophilus and antioxidants on ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug.

Ileal ulcers and thiobarbituric acid (TBA)-reactive substances in the ileal mucosa were induced in rats treated with a nonsteroidal antiinflammatory drug, 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)thiophene (BFMeT), at a dose of 1,000 mg/kg administered with tap water as drinking water. However, the formation of ileal ulcers and TBA-reactive substances in the ileal mucosa was repressed by giving the animals a culture supernatant of Lactobacillus acidophilus as drinking water. We measured the antioxidative activity of the culture supernatant and found that the supernatant inhibited the formation of t-butyl hydroperoxide-induced TBA-reactive substances in erythrocyte membrane ghosts. Therefore, the effects of various known antioxidative compounds on the ileal ulcer formation induced by BFMeT were investigated. While alpha-tocopherol, t-butyl-1,4-hydroxyanisole and allopurinol did not repress ulcer formation after BFMeT treatment, ascorbic acid, dimethyl sulfoxide, glutathione and beta-carotene significantly inhibited formation. Among these compounds, ascorbic acid was the most effective. Accumulation of TBA-reactive substances in the ileal mucosa after BFMeT treatment also decreased significantly in rats treated with ascorbic acid. In addition, the percentage of gram-negative rods in the ileal contents of rats treated with BFMeT and tap water was dramatically increased, but it was not increased in rats treated with BFMeT and these antioxidants. A positive correlation between the percentage of gram-negative rods and the number of ileal ulcers was also observed. These results suggest that lipid peroxidation mediated by oxygen radicals plays an important role in the induction of ileal ulcers by BFMeT in rats, and that lipopolysaccharide-activated neutrophils probably produce highly reactive hypochlorous acid and hydrogen peroxide, which are inactivated by ascorbic acid and glutathione, respectively.

Animals↗
PubMed1998

Crucial role of milk-borne insulin in the development of pancreatic amylase at the onset of weaning in rats.

The development of pancreatic amylase activity was examined in rats fed in regular cages or in special cages, designed so the pups could not reach solid food to prevent weaning. In both groups, the amylase activity in zymogen granules increased in rat pups aged 14 days, peaked at 18 days, and thereafter remained at a 1.6-fold higher level than at 14 days of age. An increase in the plasma concentration of immunoreactive insulin preceded the increase of amylase activity, whereas the plasma concentration of C-peptide, indicating the secretion rate of endogenous insulin, remained unchanged. The administration of insulin at 20 ng/ml (the physiological concentration) in the milk formula caused an increase in the plasma insulin concentration of 17-day-old pups. In addition, increased pancreatic amylase activity was observed in 17-day-old rats raised on milk formula to which insulin was added. We propose that the increase of amylase activity at the beginning of weaning is dependent on the milk-borne insulin and not on the dietary change in rats.

Amylases↗
PubMed1998

Relationship between endothelial function and fibrinolysis in early hypertension.

Abnormalities in fibrinolysis, endothelial function, and glucose and lipid metabolism have been reported in hypertension. This study was conducted to examine the interrelationships between fibrinolytic factors, glucose and lipid metabolism, and endothelial function in hypertension. The effects of administering an angiotensin converting enzyme inhibitor, benazepril, were also examined. Blood levels of the following substances were measured in patients with borderline and mild hypertension (n=50, 51+/-19 years) and in age-matched controls (n=10): total cholesterol, triglycerides, tissue plasminogen activator activity and antigen, and plasminogen activator inhibitor type 1 activity and antigen. Insulin sensitivity was assessed by oral glucose tolerance test, and endothelial function was assessed by evaluating changes in diameter of the brachial artery during reactive hyperemia as observed by ultrasonography. Activities of tissue plasminogen activator and plasminogen activator inhibitor type 1 were both elevated in the hypertensive patients. Stepwise multiple regression analysis showed that plasminogen activator inhibitor type 1 antigen correlated with insulin sensitivity, total cholesterol levels, and triglycerides levels (P<.01). Endothelial function was negatively correlated with tissue plasminogen activator activity and antigen (P<.01). The chronic administration of benazepril (5-10 mg/d) for 20 weeks improved insulin sensitivity, endothelial function (6.6+/-3.4-->9.0+/-2.5%, P<.01), and tissue plasminogen activator activity and antigen. These results indicate that abnormalities in fibrinolysis are associated with endothelial dysfunction as well as disorders of glucose and lipid metabolism in patients with borderline and mild hypertension. The treatment of such patients with benazepril appeared to improve the impairment in fibrinolysis and endothelial dysfunction.

Adult↗
PubMed1998

Activation of 1-nitropyrene by nitroreductase increases the DNA adduct level and mutagenicity.

1-Nitropyrene (1-NP) is a mutagenic nitro compound in the environment. We studied correlations between the mutagenicity of 1-NP for three strains of Salmonella typhimurium, the activity of bacterial nitroreductases and the amount of 1-NP-derived DNA adducts. Bacterial strains used in this study were S. typhimurium strains TA98, nitroreductase-less mutant TA98NR and YG1021 carrying a nitroreductase-producing plasmid. The mutagenicity of 1-NP was measured using the Ames assay, and the nitroreductase activities of these strains were assayed by quantification of 1-aminopyrene produced from 1-NP. The DNA adducts were measured by the 32P-postlabeling method. Among the three bacterial strains, strain YG1021 was the highest in mutagenicity of 1-NP, the nitroreductase activity and the DNA adduct level. However, S. typhimurium strain TA98NR had the lowest values of these three parameters. Nitroreductase activity, DNA adduct level and mutagenicity were strongly correlated with each other. These results indicate that bacterial nitroreductase plays an important role in forming the DNA adducts, and that the higher the adduct level the higher the level of mutagenicity.

DNA Adducts↗
PubMed1998

[Clinical significance of prostate specific antigen (PSA) and PSA density in the detection of T1a and T1b prostate cancer].

The clinical significance of preoperative prostate specific antigen (PSA) and PSA density (PSAD) in distinguishing stage T1a and T1b prostate cancer from benign prostatic hyperplasia (BPH) was studied retrospectively in men who had undergone surgery for BPH. A total of 202 clinically BPH patients underwent transurethral resection of prostate (TURP) or retropubic prostatectomy, and histopathological findings were BPH in 179 patients, T1a cancer in 10 patients and T1b cancer in 13 patients. The T1a cancer group was similar to the BPH group in all parameters. The PSA and PSAD values in the T1b cancer group were significantly higher than those in the BPH group (P < 0.001). Prostate volume and amount of tissue resected in the T1b cancer group were significantly smaller than those in the BPH group (p < 0.001). The cut-off values of PSA and PSAD were examined with T1a and T1b cancer as a positive control and histologically proven BPH as a negative control. When 8.0 ng/ml was used as the PSA cut-off value, the sensitivity was 65% and specificity was 70%. When 0.25 ng/ml/ml was used as the PSAD cut-off value, the sensitivity and specificity were 65% and 75%, respectively. PSAD was useful for improving the specificity. Almost all the cases undetected by using both cut-off values were of T1a cancer. The receiver operating characteristics curve demonstrated that at any point, PSAD was a better detector for distinguishing T1a, T1b cancer from BPH, focusing especially in the range of PSA level between 6.0 and 10.0 ng/ml. These findings suggest that PSA and PSAD are useful parameters in distinguishing T1b cancer from BPH before surgery.

Aged↗
PubMed1998

[Bilateral synchronous adrenal myelolipomas: a case report].

A 70-year-old man, who was diagnosed by computed tomographic scan as having bilateral synchronous adrenal myelolipomas 6 years ago during the follow-up of fatty liver, underwent tumor resection at our Department because of growth of bilateral tumors without any subjective symptoms. Histopathological examination revealed mature adipose tissue cells without atypism and areas of hematopoietic tissue, including the myelotic, lymphotic, erythrocytic, and megakaryocytic cells. The diagnosis of myelolipoma was confirmed. The in vivo doubling time of bilateral tumors was 16.1 months and 31.3 months, respectively.

Adrenal Gland Neoplasms↗
PubMed1998

[Labial adhesion presenting as urinary incontinence and dysuria in a postmenopausal woman: a case report].

A 68-year-old woman admitted to our hospital complaining of urinary incontinence and dysuria. On examination, the labia were found to be fused extensively, with a pinhole opening at the midline. Under spinal anesthesia, the adhesion was clearly separated with the Hegar's dilator. There remains no recurrence in this patient following therapy. The labial adhesion was considered to be an acquired disease caused by infection, trauma in the genitalia, or sexless life, according to hypoestrogenism.

Aged↗
PubMed1997

Effect of intestinal bacteria on formation of azoxymethane-induced aberrant crypt foci in the rat colon.

The effect of intestinal bacteria on formation of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and DNA adducts in the rat colon was investigated. Male Sprague-Dawley rats were administered cultures of Lactobacillus acidophilus, Bifidobacterium adolescentis, Bacteroides fragilis, Escherichia coli and Clostridium perfringens for five weeks and given injections of AOM at 15 mg/kg body weight at the first and second weeks. The number of ACF five weeks after the start of the experiment was decreased in the rats treated with the cultures or culture supernatants of L. acidophilus and C. perfringens. The half-life of O6-methylguanine (O6-meG) in the L. acidophilus group was shorter than that in the GAM broth group. The half-life of 7-methylguanine did not differ among the groups. These results suggest that the metabolite(s) of L. acidophilus and C. perfringens inhibit(s) the ACF formation in rats treated with AOM and that the inhibitory effect of L. acidophilus is due to the enhanced removal of O6-meG from the colon mucosal DNA.

Animals↗
PubMed1997

Effects of dietary bile acids on formation of azoxymethane-induced aberrant crypt foci in F344 rats.

The present study has demonstrated the influence of bile acids (BAs) on the development and growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF). Male F344 rats were treated with two doses of AOM (15 mg/kg) at 7 days apart and fed either basal MF or MF plus 0.4% of cholic (CA), deoxycholic (DCA), chenodeoxycholic (CDCA), lithocholic (LCA) and ursodeoxycholic (UDCA) acid mixed diets for 8 weeks after the first AOM dose. The mean number of ACF/colon of the rats fed CA, DCA, CDCA and LCA were higher than that of MF-fed group and the differences were statistically significant (P < 0.005). But the mean number of ACFs/colon was significantly (P < 0.005) lower in UDCA diet-fed rats compared to MF. UDCA-fed rats also showed a significant decrease in average crypt multiplicity (number of crypts/focus) of ACF compared to MF alone. The mean number of ACF with > or =5 crypts was about 2.5-3.7 times higher in case of CA, DCA, CDCA and LCA and about 8.2 times lower in UDCA compared to the control MF diet group. In a parallel study, feeding for 18 weeks of the same BAs mixed diets without AOM administration did not significantly induce ACF. Therefore, these data suggest that dietary BAs by themselves do not induce ACF in F344 rats but enhance or, in the case of UDCA, suppress the development and growth of AOM-induced ACF.

Animals↗
PubMed1997

Genome analysis of Bacteroides by pulsed-field gel electrophoresis: chromosome sizes and restriction patterns.

The chromosomal DNAs of nine strains of seven Bacteroides species including B. fragilis, the type species of the genus Bacteroides, were digested with rare-cutting restriction enzymes I-Ceu I, Not I, and Asc I and analysed by pulsed-field gel electrophoresis. The genome sizes of B. fragilis, B. distasonis, B. eggerthii, B. ovatus, B. thetaiotaomicron, B. uniformis, and B. vulgatus were determined to be 5.3, 4.8, 4.4, 6.9, 4.8, 4.6, and 5.1 Mbp, respectively. B. distasonis and B. vulgatus, and also B. uniformis and B. eggerthii, showed similar I-Ceu I restriction profiles. I-Ceu I cut B. uniformis and B. eggerthii genomes into four, B. ovatus into five, B. fragilis and B. thetaiotaomicron into six, and B. distasonis and B. vulgatus into seven fragments. On the basis of genome size, restriction profile, and I-Ceu I fragment number, a phylogenetic tree of the Bacteroides species was proposed. This was in overall agreement with the previous phylogenetic tree obtained by 16S rRNA data, with the exceptions of B. distasonis and B. ovatus.

Bacteroides↗