Search PubMed⌕ Search

Biomedical subjects

T Kinouchi

Publications and source records attributed to T Kinouchi.

At least 127 records · Page 7Linked to original sources
PubMed1993

Membrane cofactor protein (MCP, CD46) in seminal plasma and on spermatozoa in normal and "sterile" subjects.

A sperm protein of molecular mass 43 kDa (the spermatozoa membrane cofactor protein, smMCP) and a seminal plasma protein of 60 kDa (ssMCP) were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting with four monoclonal antibodies (mAb) against membrane cofactor protein (MCP, CD46). These proteins served as factor I cofactors for the cleavage of methylamine-treated C3 (C3ma), the activity of which was blocked by M75, an MCP cofactor-activity-blocking mAb. Thus, these semen proteins are antigenic and functional homologous of MCP. On SDS-PAGE analysis these MCP migrated as single-band proteins which differed from the two-band forms of MCP expressed on other cells. smMCP was N-glycosylated but not O-glycosylated, while ssMCP was O-glycosylated: after deglycosylation of these proteins bands were detected at 38-40 kDa and 43 kDa on SDS-PAGE, respectively. These semen MCP are therefore, structurally different from the conventional MCP. ssMCP in both normal and "sterile" subject groups was determined by sandwich enzyme-linked immunosorbent assay. Seminal plasma in the two groups contained 250-700 ng/ml ssMCP. The difference between the two groups was marginal, although samples from normal subjects tended to show higher concentrations of ssMCP than samples from "sterile" subjects. No molecular difference was observed with ssMCP and smMCP in the two groups by SDS-PAGE/immunoblotting analysis. Immunohistochemical analysis suggested that MCP was positive in glandular epithelial cells and the lumen of the prostate, and in most intra-lumen cells of the testis. Using antibody M177, solubilized prostate and testis were analyzed by immunoblotting and compared with other cell MCP. The major band of MCP in the testis, but not in the prostate, was of 60 kDa, which aligned with ssMCP. No band of testis or prostate MCP, however, aligned with smMCP. ssMCP may be produced in the testis, while the origin of smMCP remains unknown. We hypothesize that ssMCP is important in the survival of spermatozoa, protecting them against local secretion of immunoglobulin and complement in the female genital tract, and that smMCP, which is expressed on acrosome-reacted spermatozoa, plays an essential role in the interaction of spermatozoa with oocytes.

Antigens, CD↗
PubMed1993

Urinary 1-hydroxypyrene as a marker of exposure to polycyclic aromatic hydrocarbons in environment.

The concentrations of pollutants, especially polycyclic aromatic hydrocarbons (PAHs), originating from automobile emissions are high in areas around urban arterial roads. To investigate the possibility of using urinary 1-hydroxypyrene (1-POH) a metabolite of pyrene, as a marker for estimating the amount of human exposure to PAHs, both an animal experiment and an ecological correlation study were conducted. Rats were exposed to one of two sources of PAH: diesel engine emissions containing particulate matter and NO2 at average concentrations of 4.20 mg/m3 and 2.90 ppm, respectively, or, for the control group, air having the respective average concentrations of 0.01 mg/m3 and 0.02 ppm. The concentration of pyrene was 36 ng/mg in the particulate matter in the diluted diesel engine exhaust and 9.0 ng/g in the feed to the rats. Urinary 1-POH levels in the rats of the exposure group increased remarkably over those of the control group, 2.4 times as much by the 2nd week of exposure and 5.6 times by the 4th and 8th weeks. The ecological correlation study was conducted in 1988 and 1989 in two area of Tokyo along arterial roads (Meguro and Itabashi Wards) and in one suburban area (Higashiyamato City) to measure urinary 1-POH levels in elementary school children who lived in those areas. Urinary samples were collected in October in 1988, as well as in January, May, and July in 1989. Throughout the period of investigation, the schoolchildren in the highly NOx-polluted Meguro and Itabashi Wards showed significantly higher urinary 1-POH levels than the children in the less-polluted Higashiyamato City by a factor of 1.1-1.6. These results suggest that the urinary 1-POH level could be used as a good marker for estimating the amount of exposure of residents to PAHs.

Air Pollutants↗
PubMed1993

Mutagenicity and antimutagenicity of extracts of three spices and a medicinal plant in Thailand.

Three kinds of spices (caraway, coriander and black pepper seeds) and a medicinal plant called 'tong tak' in Thai (Baliospermum axillar, a species of the spurge family) were fractionated into hot water, methanol and hexane extracts. These extracts were not mutagenic for Salmonella typhimurium strains TA98 and TA100 by the Ames assay. However, when the extracts were treated with nitrite, samples of the water and methanol extracts were mutagenic for strain TA100 without metabolic activation. The mutagenicity of the nitrite-treated methanol and hot water extracts of black pepper was highest (8380 and 22,200 His+ per 0.1 g of spice powder, respectively), and that of the nitrite-treated hot water extracts of caraway and tong tak was moderate. The hot water extracts were examined for their antimutagenic activity against mutagenicity induced by various carcinogens by the Ames assay, using the preincubation technique. The tested samples (equivalent to 1-2 mg of spice powder) reduced the mutagenicity induced by 2.7 nmole (397 ng) of N-methyl-N'-nitro-N-nitrosoguanidine by more than 84%, and that induced by dimethylnitrosamine (1.48 mg) or ICR-170 (10 ng) by 30-60%. However, they did not inhibit the mutagenic activity of 1-nitropyrene, 3-nitrofluoranthene, AF-2, methyl methanesulfonate, N-ethyl-N'-nitro-N-nitrosoguanidine, 2-aminoanthracene, 2-acetylaminofluorene, benzo[a]pyrene or IQ.

Antimutagenic Agents↗
PubMed1993

Mutagenicity of the bile of dogs with an experimental model of an anomalous arrangement of the pancreaticobiliary duct.

To learn the reasons for the high incidence of biliary carcinoma in patients with anomalous arrangement of the pancreaticobiliary duct (APBD) mutagenicity of the bile of APBD-modeled dogs that had received a dorsal pancreatico-cholecystostomy was assayed by the Ames Salmonella mutation test. The bile from two out of 18 APBD dogs was mutagenic for Salmonella typhimurium strain TA98 under the condition of metabolic activation by rat liver S9 fraction, while the bile from 17 normal dogs was not mutagenic. Furthermore, the bile from five APBD dogs i.p. administered 1-nitropyrene (1-NP), which is a typical environmental mutagen, was more mutagenic for strain TA98 than that from 1-NP-treated normal dogs. The bile from the APBD dogs had very high amylase activity, indicating that the bile contained pancreatic juice as a result of the pancreatico-cholecystostomy. When pancreatic juice from a normal dog was added to the bile from 1-NP-treated normal dogs, mutagenicity of the bile increased 1.6- to 2.0-fold. Furthermore, sulfatase increased the mutagenic activity of the bile in the presence of the pancreatic juice. HPLC revealed that the bile from a 1-NP-treated APBD dog contained mutagenic 1-nitro-6/8-hydroxypyrene and 1-nitro-3-hydroxypyrene, while bile from a 1-NP-treated normal dog did not contain these deconjugated products. The pancreatic juice from a normal dog had very high gamma-glutamyltransferase (GGT) and aminopeptidase activities and low sulfatase activity, but it had no beta-glucuronidase activity. In addition, the bacteria that easily infect the biliary duct of APBD dogs, Escherichia coli, Klebsiella, Enterobacter and Proteus, had high beta-glucuronidase activity. In particular, Klebsiella showed a very high sulfatase activity. These results suggest that pancreatic juice enzymes and bacteria infecting the biliary duct deconjugate the detoxified mutagens in the bile and induce mutagenicity of the bile from APBD dogs or APBD patients.

Anastomosis, Surgical↗
PubMed1993

Biological activities of the intestinal microflora in mice treated with antibiotics or untreated and the effects of the microflora on absorption and metabolic activation of orally administered glutathione conjugates of K-region epoxides of 1-nitropyrene.

To elucidate the effects of the intestinal microflora on absorption and activation of glutathione conjugates of 4,5-epoxy-4,5-dihydro-1-nitropyrene (1-NP 4,5-oxide) and 9,10-epoxy-9,10-dihydro-1-nitropyrene (1-NP 9,10-oxide), we investigated the biological activities of the microflora in specific-pathogen-free (SPF) mice and SPF mice treated with various antibiotics and established the methodology of antibiotic treatment to eliminate the intestinal microflora. Mice were given various kinds of antibiotics by intragastric gavage twice a day for five days. A mixture of antibiotics bacitracin (BC), neomycin (NM) and streptomycin (SM) was the most effective in reducing the various activities of the intestinal microflora. The treatment decreased the bacterial counts and the activities of enzymes of the intestinal contents cysteine conjugate beta-lyase (beta-lyase), beta-glucuronidase and nitroreductase which were derived from the intestinal microflora, but did not affect the activities of gamma-glutamyltransferase and aminopeptidase which were derived from host tissue cells. Furthermore, the treatment did not affect absorption of glucose from the intestinal tract, body weight or liver enzyme activities. The treatment with only an aminoglycoside antibiotic, kanamycin or NM, decreased neither the number of anaerobes in the intestine nor the beta-lyase or nitroreductase activities from the intestinal contents. Glutathione conjugates of [3H]-1-NP oxides were administered to two groups of ICR mice that had been treated with antibiotics (BC, NM, SM) or saline (control group) orally. The radioactivity in the blood increased and reached the maximum level 2 or 3 h after administration of the conjugates in the control group; however, that in the antibiotic-treated group was only slightly increased if at all. Excretion of [3H]-labeled metabolites into the urine was approximately 20% of the total dose in the control group, but it was < 2% in the antibiotic-treated group during 48 h. After 48 h, DNA in the lower intestinal mucosa was extracted and the DNA adducts were analyzed by the 32P-postlabeling method. Three new DNA adducts were detected in the lower intestinal mucosa of the control group but not of the antibiotic-treated group. These results suggest that the intestinal microflora plays an important role in absorption of the metabolites of glutathione conjugates of 1-NP oxides from the intestinal tract and activation of the metabolites in the intestine.

Animals↗
PubMed1993

Amyloid precursor protein is found in lysosomes.

The major component of Alzheimer's disease amyloid is a small polypeptide referred as the amyloid beta protein, which is derived from a larger precursor, amyloid precursor protein (APP). Cell fractionation and immunological studies on the APP molecule indicate that APP is localized either in the neuron and astrocyte and that the molecule is recovered from lysosomal fraction.

Amyloid beta-Protein Precursor↗
PubMed1993

[Neoadjuvant therapy for prostatic cancer].

Neoadjuvant therapy for prostatic cancer might be important to increase cure rates of the disease and preservability of the organs. There were 43 cases in a period of 1975-1990 in which total prostatectomy were performed after neoadjuvant therapy. According to the clinical stage, there were 14 cases in B, 23 in C, 4 in D1 and 2 in D2. The median duration of neoadjuvant therapy was 4 months. Clinical response of the prostate in 37 evaluable cases was as follows; 6 cases were PR (16%), 12 cases were MR (32%) and 19 cases were NC (52%). Histopathological effect was as follows; 5 cases were grade 0a (12%), 12 cases were grade 0b (28%), 16 cases were grade 1 (37%), 8 cases were grade 2 (19%) and 2 cases were grade 3 (5%). In 2 cases with histopathological effect of grade 3, lymph node metastases were thought to have obviously disappeared. Histopathological effect seemed related to clinical response. In cases given neoadjuvant therapy for less than 2 months, no adequate clinicopathological effect was obtained. Cases that could achieve downstaging were 8; 1 in grade 0a, 2 in grade 1, 3 in grade 2 and 2 in grade 3. These results suggest that neoadjuvant therapy plays an important role in advanced prostatic cancer.

Aged↗
PubMed1993

[Successful interferon therapy of renal cell carcinoma with tumor thrombus extending into the inferior vena cava--a case report].

It is a fact that there are few effective drugs available except for interferon for that treatment of renal cell carcinoma, and the efficacy rate of interferon is less than 10% even if multiple drug regimens are included. We have experienced a case of renal cell carcinoma in whom interferon therapy was successful in reducing the primary lesion and tumor thrombus extending into the inferior vena cava. A 57-year-old man was admitted to our department with a complaint of macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a right renal tumor and the tumor thrombus. Because of the past history of his myocardial infarction, a radical operation was considered risky. So we started interferon therapy. Four months after the start of interferon therapy, the primary lesion and the tumor thrombus markedly reduced in their size, and the clinical response was evaluated as partial response by response criteria for urological cancer treatment. Therefore, radical nephrectomy and tumor thrombectomy were performed with extracorporeal circulation. Histopathologically, necrosis and lymphocyte infiltration into the cancer cell focus were seen, and these immunologic reactions were considered at the affection of interferon. In some case, interferon therapy is a useful and safe in the treatment of the primary lesion of renal cell carcinoma, and further investigation must be studied.

Carcinoma, Renal Cell↗
PubMed1993

[Tuberculosis of the female urethra: a case report].

A 52-year-old female with the chief complaint of miction pain was referred for the examination of a urethral nodule. Physical inspection revealed the meatus to be reddish and swollen. The painless nodule (1 x 1 x 2 cm) was situated between the urethra and vagina on transvaginal examination. Chest X-ray, drip infusion pyelography (DIP) and urethrocystography (UCG) showed no evidence of tuberculosis. Bladder mucosa was normal on cystoscopy. Mycobacterium tuberculosis was not detected from urine or sputum. The nodule was resected along with a portion of the urethra. Histopathological examination revealed tuberculous granuloma of the urethra.

Drug Therapy, Combination↗
PubMed1992

Decomposition of linear dodecylbenzenesulfonate by simultaneous treatment with ozone and ultraviolet irradiation: rapid disappearance of formed mutagens.

The decomposition products and mutagenic activity in Salmonella typhimurium strains TA98, TA100 and TA104 in the presence and absence of S9 mix of linear dodecylbenzenesulfonate (DBS) in aqueous solution after ozone treatment alone or simultaneous treatment with ozone and ultraviolet (UV) irradiation (ozone/UV treatment) were investigated. The decomposed DBS solutions after these treatments for 4 h were mutagenic for strains TA98, TA100 and TA104 both with and without S9 mix, but this mutagenicity disappeared rapidly during further ozone/UV treatment. Mutagenicity of the decomposed solution of DBS, however, was not substantially decreased by treatment with ozone alone. Formaldehyde and glyoxal were identified as the decomposition products of DBS in water by high-performance liquid chromatography after treatment with 2,4-dinitrophenylhydrazine. Although these two compounds were mutagenic for strain TA104 both with and without S9 mix, they disappeared after further ozone/UV treatment but not after ozone treatment alone. These results indicate that ozone/UV treatment is an effective procedure for purifying drinking water.

Benzenesulfonates↗
PubMed1992

Role of intestinal microflora in metabolism of glutathione conjugates of 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide.

DNA adduct formation in the liver of B6C3F1 mice after administration of 1-nitropyrene (1-NP) was shown by the 32P-postlabeling technique. The major adduct was not N-(deoxyguanosin-8-yl)-1-aminopyrene, which was easily formed in in vitro nitroreduction of 1-NP in the presence of DNA, but the major spots migrated to the same position as the in vitro DNA adduct spots of K-region epoxides of 1-NP (1-NP 4,5- and 9,10-oxide). 1-NP oxides formed by the oxidative activation of 1-NP in the liver were excreted into the bile as detoxified glutathione conjugates which were changed to cysteine conjugates in the upper intestinal tract. The cysteine conjugates were degraded by cysteine conjugate beta-lyase (beta-lyase) of intestinal microflora in the lower intestinal tract. The mutagenicity of cysteine conjugates of 1-NP oxides for Salmonella typhimurium was enhanced by addition of beta-lyase and was decreased by addition of aminooxyacetic acid, a beta-lyase inhibitor. The in vitro binding of the cysteine conjugates to calf thymus DNA was increased by addition of beta-lyase and xanthine oxidase. We administered glutathione conjugates of 1-NP oxides to two groups of mice that had been treated with antibiotics or saline by gavage and analyzed the DNA adducts in the lower intestinal mucosa. The specific DNA adducts were detected in the saline-treated group but not in the antibiotics-treated group. These results suggest that intestinal microflora play an important role in activation of glutathione conjugates of 1-NP oxides.

Animals↗
PubMed1992

Carcinogenicity examination of 1-nitropyrene oxides and related chemicals: lack of their tumorigenic effects in a newborn mice assay.

Carcinogenicity of 1-nitropyrene (NP) oxides (1-NP 4, 5-oxide and 1-NP 9, 10-oxide) and related chemicals (1-NP and 1-nitro-6-hydroxypyrene) was examined in the newborn mouse model by i.p. administration at 1, 8, 15 days after birth (each chemical was given at a total dose of 700 nmol per mouse). Low incidences of hepatocellular neoplasms were recognized in male mice exposed to either of these chemicals. However, the incidences were not significantly different from those of animals given solvent alone or of non-treatment. Lymphoma was infrequently seen in female mice given some of tested chemicals. The incidences were also not significantly different from those of mice with the solvent alone or of the controls. The results suggest that although these aromatic hydrocarbons exert genotoxicity or mutagenicity, they may not be potent carcinogens, or the assay with use of newborn mice may be insufficient to monitor carcinogenicity of such chemicals.

Adenoma↗
PubMed1992

[Surveillance after orchiectomy for stage I testicular seminoma].

The results of treatment by orchiectomy and radiotherapy for stage I testicular seminoma are excellent with cure rates exceeding 95% and relapse rates less than 5%. However, after the development of successful surveillance programs for stage I nonseminomatous testicular cancers, the role of radiotherapy has been questioned by some authors and they proposed a "surveillance policy" for these patients. The purpose of this study was to determine the percentage of patients cured by orchiectomy alone, percentage who ultimately required therapy for occult metastases, site of recurrence, and over-all cure rate and treatment morbidity. And these data were compared with those of adjuvant radiotherapy group retrospectively. Twenty seven patients were treated with adjuvant radiotherapy (RT group). Since 1986, 23 patients with stage I testicular seminoma entered the "surveillance only" protocol at our institution (S group) with a follow-up between 14 and 70 months (median 43 months). Informed consent for the policy of surveillance was obtained. Follow up consisted of physical examination, determination of serum tumor markers and chest X-ray bimonthly for 2 years, every 3 months for 1 year, every 6 months for 2 years and annually thereafter to 10 years. CT scans were performed every 4 months for 3 years, every 6 months for 2 years. Two patients in S group (8.7%) relapsed at 4 and 7 months after orchiectomy with nonbulky retroperitoneal disease (less than 5 cm in diameter), whereas only 1 (3.7%) irradiated patients did so after 4 months.

Adult↗
PubMed1992

[Renal cancer specific antitumor activities of a mouse monoclonal antibody K2.7 to human renal cell carcinoma].

We have prepared a mouse monoclonal antibody (mAb) K2.7 (IgG3) by immunizing mice with renal cancer cell (RCC) line OS-RC-2. In a serological analysis by protein A assay, 25 out of 31 RCC lines reacted with the mAb K2.7 but none of the 50 other cell lines from different organs except for 2 cell lines did. In immunohistological analysis by indirect immunoperoxidase assay, 66 out of 72 renal cancer tissues showed positive staining. Metastatic lesions of renal cancers also reacted similarly to the primary lesion. Some restricted normal tissues including tubules of normal kidney showed positive staining. Specific antitumor activities of mAb K2.7 against RCC lines were investigated in vitro by complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC) assays. In CDC assay, all of the 9 RCC lines were killed by mAb K2.7 and normal human serum, and killing activities of mAb K2.7 presumably depend on the number of antibody molecules bound to the cell surface. Sera from 9 patients with renal cancers including low and high stages showed the same killing activities to 3 RCC lines as normal human serum. In the ADCC assay, peripheral leukocytes (PBLs) from 4 healthy donors showed strong killing activities to RCC lines. Killing activity differed with the individual. PBLs from the same 9 patients as in the CDC assay showed significantly positive killing activity against 3 RCC lines. These findings suggest the usefulness of mAb K2.7 for the specific immunotherapy of renal cancer.

Antibodies, Monoclonal↗