Biomedical subjects

K Okamura

Publications and source records attributed to K Okamura.

At least 145 records · Page 8Linked to original sources

PubMed1997

The most primitive vertebrates with jaws possess highly polymorphic MHC class I genes comparable to those of humans.

We report the isolation and extensive analysis of highly polymorphic MHC class I genes from sharks (Triakis scyllia), which belong to the most primitive vertebrate group with jaws, the cartilaginous fish. Predicted complete peptide-binding domains showed retention of the critical amino acid residues that would interact with antigenic peptide termini and revealed extensive allelic polymorphisms comparable to those of classic human MHC class I molecules. Mosaic structures were apparent in these domains, suggesting recombinational mechanisms to create allelic diversity. The present study demonstrates the establishment of the basic strategy for antigen-presentation employed by MHC class I molecules and documents complete divergence of two polymorphic MHC classes at a phylogenetically primitive stage of vertebrate evolution.

Alleles↗

PubMed1997

Immunohistochemical localization of cathepsin D, proliferating cell nuclear antigen and epidermal growth factor receptor in human breast carcinoma analysed by computer image analyser: correlation with histological grade and metastatic behaviour.

AIMS: The purpose of this study is to examine the relationship between immunohistochemical localization of cathepsin D (CD), proliferating cell nuclear antigen (PCNA) and epidermal growth factor receptor (EGF-R) in 65 cases of breast carcinoma in Japanese women and traditional prognostic factors such as histological grade, lymph node status, mitotic rate and clinical stage, in order to possibly identify some indicator(s) that may be specifically associated with prognosis. METHODS AND RESULTS: Serial sections of 5-micron thick were cut from the archival formalin-fixed, paraffin-embedded tissue blocks, and processed for CD, PCNA and EGF-R immunostaining. The results were analysed by computer-based image analysis system. All samples showed a positive immunoreaction for cathepsin D in both the parenchyma and stroma. However, the staining area and intensity varied from cell to cell in the parenchyma and stroma as well as among samples. Subsequently, the evaluation of immunostaining for CD was separately performed in both the parenchyma and stroma (CDpar and CDstr, respectively) and the combination of both components (CDtotal). PCNA and EGF-R showed positive immunostaining almost exclusively in the parenchymal component of the carcinoma tissue specimens. CDtotal significantly correlated with the histological grade, PCNA index (PI), mitotic rate (MR), EGF-R and lymph node metastasis. Significant correlation was also demonstrated between CDpar and the histological grade. EGF-R and lymph node metastasis, or between CDstr and MR, EGF-R and lymph node metastasis. EGF-R correlated highly with the histological grade, MR score, lymph node metastases and recurrence-free survival. CONCLUSIONS: Both the CD parameters and EGF-R are valuable indicators for predicting the biological behaviour of human breast carcinoma.

Breast Neoplasms↗

PubMed1997

No influence of a single bout of exercise on urinary excretion of 8-hydroxy-deoxyguanosine in humans.

We investigated the effect of a single bout of intensive exercise on the excretion of 8-hydroxy-deoxyguanosine in the 24 h urine from healthy non-smokers. We studied three exercise tests in Experiment 1; which consisted of incremental exercise to exhaustion on a treadmill in eleven male long distance runners. Experiment 2; which comprised incremental exercise until reaching exhaustion on a bicycle ergometer in six male untrained subjects. Experiment 3; which consisted of a 20 km run by eleven male long distance runners. No differences in the urinary 8-hydroxy-deoxyguanosine excretion were observed from days 1 to 3 after each respective exercise regimen. However, significant increases in the plasma creatine kinase activity were observed at 24 h or 48 h after exercise, except for Experiment 2. Our results thus suggest that the oxidative stress during a single bout of intensive exercise does not result in an accumulation of oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1997

Endoscopic transvesico-transurethral approach for repair of vesicovaginal fistula: initial case report.

Through an endoscopic transvesico-transurethral approach, we closed a vesicovaginal fistula that occurred after hysterectomy in a patient with uterine leiomyoma. The 3-mm fistula, located in the midportion of retrotrigone, was resected transurethrally and sutured in two layers through two 5-mm suprapubic trocars placed into the bladder and the urethral route under pneumobladder. The patient had no urine leakage from the vagina after surgery.

Cystoscopy↗

PubMed1997

[Properties of extracellular products produced by group A streptococci isolated from patients with streptococcal toxic shock syndrome].

Extracellular products of group A streptococci isolated from patients with streptococcal toxic shock syndrome (STSS) were examined. The outline of the discussion of the 3 products are as follows; streptolysin O (SLO), proteinase and erythrogenic toxin. SLO and proteinase showed a relatively large amount of products more than erythrogenic toxin. SLO produced by group A streptococci isolated from the patient with STSS had an isoelectric point (pI) of 6.0 and a molecular weight of 64,000 and showed hemolytic activity in the presence of 2-mercaptoethanol (2-ME). Furthermore, the hemolytic activities of all components were inhibited by gamma-globulin and cholesterol. Proteinase had pIs of 8.7 and 8.9, and a molecular weight of 21,000. These data suggest that STSS clinical criteria probably reflects a characteristic of a large amount of products of individual S. pyogenes isolates.

Bacterial Proteins↗

PubMed1997

Effect of amino acid and glucose administration during postexercise recovery on protein kinetics in dogs.

To examine the effect of the timing of amino acids (AA) and glucose (G) administration after exercise on protein kinetics, ten dogs fitted with chronic catheters in the artery and the femoral vein ran on a treadmill for 150 min. They were intraportally infused with a solution containing AA and G either right after (E) or 2 h after (L) the exercise. The protein kinetics were estimated using the arteriovenous difference of phenylalanine (Phe) coupled with the [2H5]Phe dilution method. The net balance of Phe across the hindlimb (HL) was negative after exercise. It became positive in E within 15 min after the start of the infusion, and it remained negative in L until the infusion was initiated. The uptake of Phe by the HL during the second half of the infusion period was higher in E than in L (10.9 +/- 6.6 vs. 5.4 +/- 2.3 nmol.kg-1.min-1, P = 0.049). During the infusion, protein synthesis in the HL was higher in E than in L (29.7 +/- 9.6 vs. 22.0 +/- 10.1 nmol.kg-1.min-1, P = 0.028), whereas proteolysis was comparable (18.7 +/- 5.7 vs. 16.5 +/- 11.1 nmol.kg-1.min-1. These results suggest that the early provision of the nutrients after exercise more effectively enhances protein accretion than nutrients administered later.

Amino Acids↗

PubMed1997

Enlargement glycogen store in rat liver and muscle by fructose-diet intake and exercise training.

This study investigated the effect of long-term intake of a fructose diet and exercise training on glycogen content in liver and skeletal muscle in female rats. Thirty-six rats (8 wk old) were divided into two dietary groups and were fed with a control (chow) diet or fructose diet (containing 20%) fructose) for 12 wk. During this period, one-half of the rats in each dietary group were trained by using a motor-driven treadmill (running speed of 25 m/min and duration of 90 min/day, 5 days/wk). The liver glycogen was increased by intake of a fructose diet and exercise training, and the content was in the following order: control-diet and sedentary rats < fructose-diet and sedentary rats < or = control-diet and trained rats < fructose-diet and trained rats in the ratio of 1:3.4:3.6:5.0. The glycogen content in gastrocnemius muscle showed the same trend as that in liver; the ratio was 1:1.3:1.3:1.6. These results indicate that both long-term intake of the fructose diet and exercise training synergistically increased glycogen in both tissues.

Animals↗

PubMed1997

KF19514, a phosphodieterase 4 and 1 inhibitor, inhibits PAF-induced lung inflammatory responses by inhaled administration in guinea pigs.

Phosphodiesterase (PDE) 4 inhibitors are well known for their inhibitory effect on bronchoconstriction and inflammation and may be promising anti-asthma drugs. Platelet-activating factor (PAF) has been proposed as an inflammatory mediator to be relevant to asthma. It causes bronchoconstriction, airway microvascular leakage, inflammatory cell accumulation in the lung and hyperresponsiveness. In this study, we therefore have investigated the anti-asthmatic effects of the inhaled KF19514 [5-phenyl-3'-(3-pyridyl)methyl-3H-imidazo(4,5-c)(1,8) naphthyridin-4(5H)-one], a PDE 4 and 1 inhibitor, on PAF-induced lung inflammatory responses in guinea pigs. The inhaled KF19514 (0.0001-0.01%) significantly inhibited PAF-induced eosinophil and neutrophil accumulation into the airway and hyperresponsiveness in guinea pigs. The IC50 value of KF19514 against eosinophil accumulation was 14.8 microM (0.00063%). Moreover, the effect of KF19514 on the electrical field stimulation-induced bronchial contraction was examined using the main bronchi of guinea pigs in vitro. KF19514 inhibited both cholinergic and tachykininergic contraction and, in particular, produced a potent inhibitory effect on tachykininergic contraction (IC50 = 0.49 microM). The mechanism by which KF19514 inhibited the PAF-induced hyperresponsiveness may in part be the suppression of the tachykinin release. Based on these results, it was demonstrated that the inhaled KF19514 might have a significant potential effect on the inflammatory cell accumulation and hyperresponsiveness induced by PAF.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1997

Synthesis biological evaluation of alkyl, alkoxy, alkylthio, or amino-substituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones.

2,3-Dihydro-1,5-benzothiazepin-4(5H)-ones substituted with an alkyl, alkoxy, alkylthio, hydroxy, or amino group on the fused benzene ring of the 1,5-benzothiazepine skeleton were synthesized and their vasodilating, antihypertensive, and platelet aggregation-inhibitory activities were investigated. (-)-cis-3-Acetoxy-5-[2-(di-methylamino) ethyl]-2,3-dihydro-8-methyl-2-(4-methylphenyl)-1,5-benzothiazepin- 4(5H)-one ((-)-13e) was selected for further studies as a potent inhibitor of platelet aggregation.

Alkylation↗

PubMed1997

In-utero transplantation of fetal hematopoietic cells in the mouse: the effect of donor and recipient gestational maturity.

To investigate the possibility of engrafting fetal liver hematopoietic cells by in utero intraperitoneal transplantation, we transplanted donor cells obtained from mouse fetuses at 13, 15 and 17 days of gestation to mouse fetuses at 15, 16 and 17 days of gestation. Engraftment was assessed by Sry gene amplification of DNA extracted from peripheral blood samples of transplanted mice six weeks after birth. In comparison, we performed an in vitro colony-assay of fetal liver cells at 13, 15, and 17 days of gestation. The incidence of engraftment was significantly higher in cells of 15 days of gestation than in cells of 13 or 17 days of gestation, whereas the colony forming activity decreased gradually from 13 to 15 days of gestation. From these results, we suggest that the 15 day liver contains hematopoietic progenitors which have the specific characteristics required for engraftment by intraperitoneal transplantation.

Animals↗

PubMed1997

Effect of repeated exercise on urinary 8-hydroxy-deoxyguanosine excretion in humans.

The purpose of this study was to investigate the effect of repeated exercise on oxidative damage to DNA in 10 well trained long distance runners who participated in an 8-day training camp. The average running distance during the camp was 30 +/- 3 km/day. The amount of urinary 8-hydroxy-deoxyguanosine (8-OHdG) excretion was used to estimate the oxidative DNA damage. Urine samples were collected for both a 3-day control period as well as throughout the camp. Blood samples were drawn after overnight fasting both before and after the camp. Urinary 8-OHdG excretion was significantly increased during the camp compared to the control period (265.7 +/- 75.5 vs. 335.6 +/- 107.4 pmol/kg/day, P < 0.05). The content of 8-OHdG in the lymphocyte DNA on the day after finishing the camp did not differ from that before the camp. Plasma TBARS, LDH, CK, CK-MB, and myoglobin significantly rose after the camp (P < 0.05). The plasma beta-carotene levels tended to rise after the camp, while the plasma alpha-tocopherol levels increased significantly after the camp (P < 0.05). These results indicate that repeated exercise augments oxidative stress and the DNA is also injured by exercise-induced reactive oxygen species. However, the oxidative damage to DNA is not accumulated by consecutive exercise, although it is sustained as long as the exercise is repeated.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1997

Effect of endurance exercise on the tissue 8-hydroxy-deoxyguanosine content in dogs.

The purpose of this study was to investigate the effect of endurance exercise on both the tissue and lymphocyte 8-hydroxy-deoxyguanosine (8-OHdG) content. Six dogs ran on a treadmill for 7 hours. Another six dogs were assigned to a sedentary control group. The exercised dogs were sacrificed immediately after exercise and the counterpart of the sedentary group was also sacrificed at the same time. The brain, lung, liver, spleen, kidney, jejunum, colon, diaphragm, heart, splenius muscle, and the medial and lateral portion of gastrocnemius muscle samples were then collected. Lymphocytes were sampled before and after exercise in the exercised dogs. The 8-OHdG content of lymphocyte DNA was found to significantly decrease after exercise (0.57 +/- 0.19 vs 0.33 +/- 0.10/deoxyguanosine (dG) x 10(5), P < 0.05). The colon was the only tissue which showed a significant decrease in the content (0.83 +/- 0.24 vs 0.54 +/- 0.15/dG x 10(5), P < 0.05). No tissue except for the colon showed any significant changes after exercise. These results therefore indicate that, immediately after endurance exercise, an augmented repair mechanism might thus play a role in the decrease of 8-OHdG in the lymphocytes and the colon, while the 8-OHdG generation might be counterbalanced by its repair in other tissues.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1997

Effect of a single bout of exercise and beta-carotene supplementation on the urinary excretion of 8-hydroxy-deoxyguanosine in humans.

We investigated the effects of acute exhaustive exercise and beta-carotene supplementation on urinary 8-hydroxy-deoxyguanosine (8-OHdG) excretion in healthy nonsmoking men. Fourteen untrained male (19-22 years old) volunteers participated in a double blind design. The subjects were randomly assigned to either the beta-carotene or placebo supplement group. Eight subjects were given 30 mg of beta-carotene per day for 1 month, while six subjects were given a placebo for the same period. All subjects performed incremental exercise to exhaustion on a bicycle ergometer both before and after the 1-month beta-carotene supplementation period. The blood lactate and pyruvate concentrations significantly increased immediately after exercise in both groups. The baseline plasma beta-carotene concentration was significantly 17-fold higher after beta-carotene supplementation. The plasma beta-carotene decreased immediately after both trials of exercise, suggesting that beta-carotene may contribute to the protection of the increasing oxidative stress during exercise. Both plasma hypoxanthine and xanthine increased immediately after exercise before and after supplementation. This thus suggests that both trials of exercise might enhance the oxidative stress. The 24-h urinary excretion of 8-OHdG was unchanged for 3 days after exercise before and after supplementation in both groups. However, the baseline urinary excretion of 8-OHdG before exercise tended to be lower after beta-carotene supplementation. These results thus suggest that a single bout of incremental exercise does not induce the oxidative DNA damage, while beta-carotene supplementation may attenuate it.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1997

TMC-2A, -2B and -2C, new dipeptidyl peptidase IV inhibitors produced by Aspergillus oryzae A374. II. Isolation and structure determination.

New dipeptidyl peptidase IV inhibitors, TMC-2A, -2B, and -2C, were isolated from the fermentation broth of Aspergillus oryzae A374. On the basis of chemical, spectroscopic and X-ray crystallographic analyses, their structures were established to be peptide-like compounds composed of three moieties, L-tryptophan, mono- or dihydroxy-L-leucine and highly substituted isoquinoline.

Amino Acids↗

PubMed1997

M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for poor prognosis patients with urothelial tumors and effect of dose intensity.

The effects of the M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen, which has been reported to improve the outcome of patients with urothelial cancers, were studied on 41 patients treated at our hospital. The patients were divided into adjuvant (24 patients), neoadjuvant (5 patients), and salvage (12 patients) groups. We investigated the dose intensity, the cause-specific survival, response rate and toxicities in the three groups. Although 36 patients received > or = 95% of the initial doses projected, the mean dose intensity (+/-standard deviation) in the adjuvant, neoadjuvant, and the salvage groups was 77 (+/-11), 73 (+/-4), and 74 (+/-12)%, respectively. The five-year cause-specific survival in the adjuvant group was 69% (95% confidence limit: 50-88%). Only 2 of the 5 patients (40%) in the neoadjuvant group survived 23 months after the initiation of the treatment, and all patients in the salvage group died of cancer or treatment-related toxicity within 33 months. The median survival was 38 months in the adjuvant group, 21 months in the neoadjuvant group, and 7 months in the salvage group. A dose intensity > or = 75% did not improve survival in any group. The overall response rate was 33% in 15 patients with evaluable lesions. A complete response was noted in 1 patient and a partial response was noted in 1 patients. Two patients died of treatment-related complications. Nausea and vomiting were observed in all patients. Leukopenia, thrombocytopenia and anemia > or = WHO grade 3 were observed in 25 (61%), 4 (10%), and 7 (17%) patients, respectively. Thrombocytopenia, anemia, and pyrexia > or = grade 3 were seen relatively more often in the patients receiving a dose intensity < 75%. Stomatitis > or = grade 3 appeared to be more frequent in the patients receiving a dose intensity > or = 75%. Adjuvant M-VAC might be beneficial, while its efficacy was limited in the neoadjuvant and salvage settings. Although dose intensity is considered to be important, it did not appear to be related to survival, the response rate, or the toxicity of M-VAC.

Adult↗

PubMed1997

[A case report of renal cell carcinoma with bilateral adrenal metastases].

A 52-year-old man consulted our hospital with a right abdominal mass. Imaging diagnosis revealed a 10.5-cm right renal tumor and bilateral adrenal masses (7 cm on the left side and 2.5 cm on the right). A radical nephrectomy and bilateral adrenalectomy demonstrated renal cell carcinoma with metastases to bilateral adrenal glands. Despite prophylactic treatment with interferon-alpha, a swollen left cervical lymph node and a left renal mass, which seemed to be metastatic lesions, developed respectively 6 and 33 months postoperative. He is alive with disease at 40 months.

Adrenal Gland Neoplasms↗

PubMed1997

Trigonal splitting is a major complication of endoscopic trigonoplasty at 1-year followup.

PURPOSE: The long-term results of endoscopic trigonoplasty in patients with vesicoureteral reflux were investigated. MATERIALS AND METHODS: We performed endoscopic trigonoplasty in 28 patients with vesicoureteral reflux, including 6 girls 6 to 8 years old. Reflux was grade I in 14 reno-ureteral units, grade II in 15, grade III in 8, grade IV in 1 and grade V in 1. Median followup was 23 months. RESULTS: At a median of 3 months postoperatively vesicoureteral reflux was not apparent in 37 units (95%) and it was downgraded in 1 (3%). At a median of 12 months postoperatively 27 (79%) and 4 (12%) of the 34 ureters had cessation and downgrading, respectively. Of the 13 select patients who underwent cystoscopy 3 had retreating ureteral orifices and 5 had trigonal splitting 6 to 12 months postoperatively. Vesicoureteral reflux was demonstrated in 3 of the 5 patients (4 ureters) with trigonal splitting and in 1 (1 ureter) with retreating ureteral orifices. At a median of 24 months after surgery voiding cystography showed reflux in only 1 of 15 units. No postoperative upper urinary tract dilatation was noted at followup. CONCLUSIONS: Cessation rates of vesicoureteral reflux 12 months after endoscopic trigonoplasty were low with a high incidence of trigonal splitting. These unsatisfactory results mandate technical refinements to avoid trigonal splitting.

Adolescent↗

PubMed1996

Hepatocellular carcinoma associated with anabolic steroid therapy: report of a case and review of the Japanese literature.

We report herein the case of a 35-year-old woman with aplastic anemia who developed hepatocellular carcinoma after long-term therapy with oxymetholone. She was treated with 60 mg/day of oxymetholone for 3 years (total dose 64.8 g). Alpha-fetoprotein, hepatitis B surface antigen, and hepatitis C antibody were all negative, but serum titers of carcinoembryonic antigen and carbohydrate antigen were elevated. Lateral segmentectomy of the liver was performed. The histopathological findings were compatible with those of multiple hepatocellular carcinoma without liver cirrhosis. Three years since the operation, the patient is doing well and no signs of tumor recurrence have been detected. According to our review of Japanese cases of hepatocellular carcinoma associated with anabolic steroid therapy, in all instances the tumors developed after long-term administration of anabolic steroids for hematologic diseases. In patients under long-term anabolic steroid therapy, routine screening of the liver by ultrasonography and computed tomography should be performed to detect liver tumors in the early stages.

Adult↗