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Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 487 records · Page 27Linked to original sources

Sexual dimorphism of binding sites of testosterone and dihydrotestosterone in rabbit model.

1. Binding sites for testosterone (TR) and dihydrotestosterone (DHTR) were separately detected in various organs of the rabbit. 2. Possibilities obtained were suggested as follows. 3. Sexual dimorphism of TR or DHTR level was present among organs. 4. The responsiveness of TR or DHTR levels to estradiol-17 beta with testosterone, but not estradiol-17 beta alone is different among organs, with sexual minor dimorphism.

Androgens↗

[Serum level of Pseudomonas aeruginosa-specific IgA in patients with chronic lower respiratory tract infection and its clinical significance].

Elevation of the serum IgA level has been observed in many cases of chronic lower respiratory tract infection. To determine the specificity of elevated serum IgA for the pathogen colonizing the respiratory tract of patients, we measured Pseudomonas aeruginosa-specific IgA titers in patients with chronic lower respiratory tract infections by ELISA. Sonicated P. aeruginosa strain BB5746 was used as the coating antigen. Optical density was significantly elevated in sera from patients in whom P. aeruginosa was consistently isolated from sputum cultures, when they were respondent to the antigen, indicating that bacteria-specific IgA is not localized in the respiratory tract surface, but is circulating in the blood stream of these patients. The other two groups, chronic bronchitis patients from whom bacteria other than P. aeruginosa were occasionally isolated from sputum culture, and IgA nephropathy patients, had no detectable specific IgA in their sera as is the case in normal adults. Our results indicate that bacteria-specific serum IgA levels appeared to correlate with duration from the time of bacterial colonization with P. aeruginosa and the degree of bronchial and alveolar destruction seen on chest X-rays. In addition, detection of increased serum P. aeruginosa-specific IgA seems to contribute to the recognition of persistent bacterial colonization of the respiratory tract.

Adult↗

Estrogen and androgen receptors in aorta of the rabbit and regulation by estrogen and androgen.

This study was designed to investigate the sexual and/or regional dimorphism of the effects of estrogens and androgens on the aorta. Estrogen, estradiol-17 beta (E2) and estriol (E3), or androgen, dihydrotestosterone (DHT) and testosterone (T), binding levels, and of effects of E2 and T on their levels were determined in aortas of the male and female rabbits. Priming with E2 affected estrogen binding levels of the male aorta, but the physiological condition with E2 plus T induced the levels of E2 and E3 receptors in the female aorta. DHT receptor level in the male was increased with E2 alone or with T, while a rise in T binding level was seen in the male and female primed with E2 and T. These findings suggest that there is a sexual and/or regional dimorphism in the actions of estrogen and androgen on their receptor synthesis in the aorta.

Androgens↗

[A study on the prediction of long-term prognosis of adulthood epilepsy].

We report results of a study on the relation between the clinical findings 2 years after initiation of the therapy and the long-term prognosis of seizure control, and discuss the possibility of predicting the prognosis in the early stage of therapy. The subjects consisted of 141 patients, observed for 10 to 20 years at Hirosaki University Hospital. Regarding the epilepsy type, the prognosis of temporal lobe epilepsy was unfavorable. In temporal lobe epilepsy, only 21% were in remission (seizure-free for 3 years or more) at the time of the study. Also, the presence of organic brain lesions or neuropsychiatric complications at the early stage of treatment was associated with unfavorable prognosis. We are particularly interested in the possibility of predicting the long-term prognosis from the result of early response to anti-epileptic drug therapy. We found a significant correlation between the early excellent response to drug treatment and the good long-term prognosis. Using discriminant analysis (quantification theory II), we tried to find which factors would influence more to the long-term prognosis. As the result, an importance was found in the following order: (1) epilepsy type, (2) presence or absence of neuropsychiatric complications, (3) age at onset, (4) early response to treatment, (5) presence or absence of organic brain lesions and (6) the interval between the onset and the initiation of drug treatment. Correct identification rate by discriminant analysis was 73%.

Adolescent↗

[Two cases of mediastinitis as a complication of odontogenic infection and tonsillitis].

We experienced two cases of descending necrotizing mediastinitis with different etiology. Case 1: A 59-year-old woman presented with chief complaints of dyspnea and swallowing disturbance. She had been diagnosed as having tonsillitis one week before. She was very pyrexic, and laboratory examination indicated acute inflammation. Chest X-ray and CT-scan showed enlargement of the mediastinum and pleural effusion. We diagnosed the mediastinitis to be a complication of tonsillitis. Case 2: A 54-year-old man had a tooth extracted 3 weeks prior to admission. His chief complaints were craniomandibular disturbance and neck swelling. Laboratory examination disclosed multiple organ failure and DIC. Chest X-ray and CT-scan showed enlargement of the mediastinum and pleural effusion. We diagnosed the mediastinitis in this case to be a consequence of an odontogenic infection following tooth extraction. Both patients received continuous drainage and irrigation of the abscesses and recovered in about 2 months. Case 1 showed an impaired glucose tolerance after recovery from mediastinitis. Although the main causes of mediastinitis are cardiac surgery and esophageal perforation, our cases demonstrate that mediastinitis may occur as a complication of deep neck infection.

Female↗

[Natural course of asymptomatic gallstone disease].

Of 1850 patients with cholelithiasis diagnosed in the past 17 years, 1116 female and 734 male, 598 patients (32.3%) presented with one or more of three major symptoms, i.e., abdominal pain, fever and jaundice, whereas the remainder (67.7%) had none of these symptoms. The proportion of the asymptomatic patients was similar in all age groups, being around 70%. Only 20 per cent of 680 asymptomatic patients, followed for 10 to 17 years (median 13.3 years), developed biliary symptoms. Older patients over 70 years of age had a higher rate of change to the symptomatic group, as compared with younger patients under 70, 29.5% vs. 19.3%, respectively. During this period, carcinoma of the gallbladder developed in one of the asymptomatic patients (0.1%). Oral dissolution therapy was successful in only 4.2 per cent of attempted cases and associated with a recurrence rate of as high as 20%. We conclude that asymptomatic gallstone patients should only be followed up by ultrasound twice a year without any treatment.

Adult↗

[Effect of prostaglandin E2 on the proliferation of cultured guinea pig gastric mucous cells].

To understand the mechanism by which prostaglandins (PGs) preserve gastric mucosal integrity, we established a primary cultured monolayer of guinea pig gastric mucous cells, and by using this culture system, we studied whether endogenously released PGE2 could influence the proliferation of the mucous cells. By the histochemical and morphological analysis at 24h of the culture periods, the cells were recognized to contain PAS-positive mucous granules with only 3% of them being parietal cells. Although the cells which were simultaneously labeled with [3H] arachidonic acid in 0.5% serum-containing medium synthesized and released radiolabeled PGE2, PGI2 and PGA2, the release of PGE2 was more markedly observed and was partially dependent upon arachidonic acid added to the culture medium. By radioimmunoassay of the culture media, the mucous cells were found to release PGE2 in a time-dependent manner in response to 10% serum. Pretreatment of the cells with 10(-4)M indomethacin not only inhibited PGE2 release but also inhibited increase in cell number. However, the addition of PGE2 dose-dependently restored the indomethacin-induced inhibition of cell growth with the maximal increase almost to the control level at 10(-6)M PGE2. These results suggest that PGE2 endogenously released from the cells may exert a proliferative effect on gastric mucous cells.

Animals↗

[Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibody CEA102: experience of 20 cases].

The monoclonal antibody CEA 102 against carcinoembryonic antigen was produced by immunization with purified CEA, and used as a radiotracer for the imaging of colorectal cancer. CEA102 was labeled with 131I by the chloramine-T or the Iodogen method, and administered i.v. to 20 patients with liver metastases, local recurrences, and/or primary tumors. Planar scintigraphy was performed during 5 or 6 postinfusion days. Hypersensitivity reactions such as fever and chill occurred in 4 patients, but no side effects were noted after endotoxin was excluded. Overall sensitivity was 71.4% (primary tumor 4/4, liver metastasis 5/6, lymph node metastasis 1/1, local recurrence 5/10), and no false positive was observed. In the cases of local recurrences, this method was useful to distinguish postoperative fibrosis from local recurrence. These results revealed that radiolabeled CEA102 has a great potential in qualitative diagnosis of colorectal cancer.

Adult↗

[Coronary vasodilation during intracoronary injection of papaverine and acetylcholine in syndrome X: evaluation by coronary arteriograms and coronary venous oxygen saturation dynamics].

To evaluate coronary vasodilatory reserve in syndrome X, left coronary arteriography and continuous measurement of coronary venous oxygen saturation (CSO2-Sat) were performed during intracoronary injection of papaverine (PAP) and acetylcholine (ACh) in 11 patients of syndrome X and 13 control subjects. Coronary diameter after PAP increased 10.2% in the control group and 9.8% in the syndrome X group, but after ACh decreased 1.7% in the control group and decreased 2.3% in the syndrome X group. These changes in coronary diameter by PAP and ACh in the two groups were not significantly different. However, coronary vasodilatory responses estimated by CSO2-Sat dynamics to ACh and to ACh/PAP were significantly lower in the syndrome X group than those in the control group (p < 0.05), although coronary response to PAP in the 2 groups was not significantly different. These findings suggest that endothelial-dependent vasodilation of coronary microcirculation is decreased in syndrome X.

Acetylcholine↗

N-acetylaspartylglutamate acts as an agonist upon homomeric NMDA receptor (NMDAR1) expressed in Xenopus oocytes.

The electrophysiological effects of N-acetylaspartylglutamate (NAAG), an endogenous peptide restrictively distributed in the central nervous system, were studied using Xenopus oocytes injected with RNAs transcribed from cloned glutamate receptor cDNAs. NAAG induced an inward current, dose dependently, in oocytes injected with RNA for an N-methyl-D-aspartate receptor subunit (NMDAR1). In contrast, the oocytes injected with RNAs for AMPA-selective glutamate receptors (GluR1, GluR3, GluR1+GluR2 and GluR2+GluR3) scarcely responded to NAAG, and the oocytes injected with RNA for kainate receptor (GluR6) did not respond to NAAG. The half-maximal response (ED50) value of NAAG on expressed NMDAR1 was 185 microM, which shows that NAAG is about 115-times less potent than L-glutamate (Glu), the ED50 of which value was 1.6 microM. The maximal current amplitude induced by NAAG was about 70% of that by Glu. NAAG-induced current in NMDAR1-injected oocytes was potentiated by glycine, dose-dependently antagonized by DL-2-amino-5-phosphonovaleric acid, and blocked by magnesium ions in a voltage-dependent fashion. These results suggest that NAAG is one of the endogenous agonists selective for NMDAR1.

2-Amino-5-phosphonovalerate↗

Comparison of the inhibitory effects of the TXA2 receptor antagonist, vapiprost, and other antiplatelet drugs on arterial thrombosis in rats: possible role of TXA2.

The antithrombotic effect of the thromboxane A2 receptor antagonist, vapiprost, was compared with those of other antiplatelet drugs using an arterial thrombosis model which utilized photochemical reaction in the rat femoral artery. Vapiprost prolonged the time required to occlude the artery with thrombus and inhibited collagen-induced rat platelet aggregation in whole blood ex vivo, in a dose-dependent manner. The potency ranking of antithrombotic effect was vapiprost > ketanserin (serotonin 5-HT2 receptor antagonist) >> ticlopidine (inhibitor of ADP-induced platelet aggregation) = dipyridamole (adenosine uptake inhibitor) > aspirin (cyclooxygenase inhibitor). On the other hand, the ranking of antiplatelet effect was ticlopidine > or = vapiprost > or = aspirin. Ketanserin and dipyridamole were ineffective. Relative to their antiplatelet effect, vapiprost and ketanserin had powerful antithrombotic effects. It is possible that the potent antithrombotic effects of vapiprost and ketanserin in vivo reflect the ability of these drugs to inhibit mediator-induced vascular contractions in addition to platelet aggregation. The results of the present study also suggest that TXA2 may play an important role in thrombogenesis in rats.

Animals↗

Expression of two types of neurofibromatosis type 1 gene transcripts in gastric cancers and comparison of GAP activities.

To understand the molecular mechanism of gastric tumorigenesis, the status of neurofibromatosis type 1 (NF1) gene was analyzed in human gastric cancer cell lines. Although the sequencing of the GTPase activating protein (GAP)-related region of NF1 (NF1-GRD) revealed no apparent mutation, the NF1-GRD transcript (type I) and that containing an additional 63 bp insert in the center of NF1-GRD (type II) were equally expressed in most gastric cancer cells. By contrast, type II was predominantly expressed in normal stomach mucosa. When these two types of NF1-GRD were bacterially expressed and their GAP activities were tested, both types of NF1-GRD similarly stimulated ras GTPase activity. However, arachidonic acid inhibited GAP activities of two types of NF1-GRD to different extents. These results suggest that the increased expression of type I NF1 protein may modulate ras-related signal transduction and it may be related to the control of the gastric cellular proliferation.

Arachidonic Acid↗

Arterial thrombosis model with photochemical reaction in guinea-pig and its property.

We have already developed an arterial thrombosis model in the rat femoral artery which utilized photochemical reaction between systemically injected rose bengal and transillumination of a green light with 540 nm wave length from the outside of the vessel. In the present study, we applied this model to guinea-pigs in order to produce a more suitable thrombus model for evaluation of antithrombotic drugs which act on the prostaglandin cascade. In the guinea-pigs, the irradiated femoral artery was completely occluded in 7 min after the injection of rose bengal (10 mg/kg) in a similar manner to the rats. The processes of primary endothelial injury and the subsequent formation of thrombus during this manipulation were observed by the electron microscopy. Pretreatment with aspirin and Y-20811, a thromboxane synthetase inhibitor, significantly prolonged the time required for occlusion in the guinea-pigs, while these drugs were ineffective in the rats. The antithrombotic effect of vapiprost, a thromboxane A2 receptor antagonist, was more pronounced in the guinea-pigs than the rats. In conclusion, this model in guinea-pigs is more suitable for evaluating antithrombotic drugs, particularly, the action of which is exerted involving the prostaglandin cascade.

Animals↗

p53 gene mutations in human gastric cancer: wild-type p53 but not mutant p53 suppresses growth of human gastric cancer cells.

To further investigate the role of p53 gene inactivation in gastric tumorigenesis, the mutational status of the p53 gene in primary human gastric cancer samples was examined. Reverse transcriptase polymerase chain reaction and subsequent direct sequencing of the p53 gene from gastric cancer samples revealed frequent point mutations of the p53 gene: some of these coincided with those previously identified in gastric cancer cell lines. In addition, both allelic deletion analysis using pYNZ 22 and polymerase chain reaction-restriction fragment length polymorphism analysis demonstrated an allelic deletion of the p53 gene in cancer tissue which contained a point mutation of the p53 gene in the remaining allele. Transfection of the wild-type or mutant p53 genes into gastric cancer cells showed that the wild-type but none of the mutated p53 genes suppressed the colony formation of gastric cancer cells. Furthermore, the incorporation of thymidine into DNA was reduced in cancer cells expressing the wild-type p53 gene. The glutathione S-transferase-wild type p53 fusion protein bound to simian virus 40 large T antigen in COS-1 cell lysate. None of the p53 fusion proteins containing mutations at codons 143, 175, 248, or 273 bound to simian virus 40 large T antigen. By contrast, two different mutant p53 fusion proteins containing mutations specifically observed in gastric cancer bound to simian virus 40 large T antigen. These results indicate that inactivation of the p53 gene through mutations and the allelic deletion may play an important role in gastric tumorigenesis. These mutations may cause a conformational change in the p53 protein resulting in the loss of the suppression by p53 of the growth of gastric cells, partly through disruption of the association of p53 protein with a cellular component.

Antigens, Viral, Tumor↗