[Molecular biological basis of karyomorphology].
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Animals↗
Biomedical subjects
H Okada
Publications and source records attributed to H Okada.
Nonpeptide angiotensin II type 1 receptor antagonist prevents nephrosclerosis in hypertensive rats.
Angiotensin II (AII) appears essential in remnant kidney models of renal injury in rats, and renal injury was reduced by angiotensin-converting enzyme inhibitor (ACEI). To determine whether this is due to AII blockade or other actions of ACEI, we studied a nonpeptide AII type 1 receptor antagonist and an ACEI in partially nephrectomised spontaneously hypertensive rats (SHR). Thirty SHR underwent surgery and were divided into three equal groups: Control, TCV (0.5 mg/kg/day TCV-116), and CAP (30 mg/kg/day captopril). All SHR received a 5%-NaCl diet. Systolic blood pressure (SBP) and urinary protein were measured at 2-week intervals. Serum total protein, albumin, urea nitrogen, and creatinine were determined at week 8. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured at weeks 4 and 8. Renal injury was evaluated histopathologically. TCV and CAP reduced SBP at week 2 and proteinuria at week 8. GFR and RBF fell in all groups, but decreases were not significant in treated SHR and histopathological changes were significantly ameliorated. All blockade by TCV or CAP reduces renal injury in salt-loaded SHR with partial renal ablation. AII is essential in remnant kidney models of renal injury, and AII blockade is essential in renal protection by ACEI.
Angiotensin Receptor Antagonists↗
Neurtrophil function and pathologic findings in Holstein calves with leukocyte adhesion deficiency.
Leukocyte adhesion deficiency was diagnosed in 4 Holstein calves from 1 to 4 months old. Calves had severe ulcers on oral mucous membranes, gingivitis, severe periodontitis, chronic pneumonia, and stunted growth associated with severe neutrophilia. Neutrophils from affected calves had function defect, characterized by severely decreased adherence, chemotactic movements, phagocytosis, luminol-dependent chemiluminescent response, and O(2-)-producing activities. Deficient CD18 expression (0.1 to 1.7%) on neutrophils was clearly detected by use of flow cytometric analysis. These affected calves were linked to a common ancestral sire that has been documented to be a carrier. Clinical features, leukocyte functional abnormalities, deficient expression of CD18, and mode of inheritance indicated that affected calves had leukocyte adhesion deficiency. In vitro leukocyte functional abnormalities were associated with deficiency in the expression of CD11/CD18. Pathologic findings indicated possible increased susceptibility to infection associated with this disease.
Analysis of Variance↗
[Estimation of medroxyprogesterone acetate (MPA) and etoposide against a human uterine endometrial cancer].
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Animals↗
[Nosocomial respiratory infection caused by Xanthomonas maltophilia in immunocompromised hosts].
Between January 1988 and December 1992, 68 patients admitted to our Department of Internal Medicine with hematological malignancies or solid tumors showed colonization of the respiratory tract with Xanthomonas maltophilia (X. maltophilia). To characterize the significance of respiratory tract colonization by X. maltophilia, we retrospectively reviewed the medical records of the 68 patients colonized with this organism. Twenty-seven of these 68 patients developed pneumonia, with X. maltophilia being implicated in 10 cases. The majority of the 10 patients showed lobular infiltration on chest X-ray. Pleural effusion was observed in 2 (20%) of the 10 patients. All 68 strains of X. maltophilia were resistant to imipenem/cilastatin. Most strains (98.5%) were sensitive to latamoxef, while all strains were sensitive to minocycline. This report describes the clinical features of nosocomial X. maltophilia pneumonia in immunocompromised patients.
Adolescent↗
Anti-bacillus substance in the marine sponge, Hyatella species, produced by an associated Vibrio species bacterium.
The bacterial isolate, M22-1, belonging to the genus Vibrio was obtained from an homogenate of the sponge, Hyatella sp. The bacterium was cultured in marine agar and was found to produce an anti-Bacillus compound. The substance was chemically identified as a peptide antibiotic, an andrimid. The same substance was found in the sponge extract, suggesting that the active component was synthesized by the associated microorganism.
Animals↗
Idiopathic progressive glomerulopathy with extensive subendothelial and mesangial immune deposit formation.
A 32-year-old Japanese male presented with abundant proteinuria, and renal biopsy revealed diffuse subendothelial and mesangial deposits in the glomeruli without hypercellularity or mesangial interposition. There was no clinical or laboratory evidence of systemic conditions such as collagen-vascular disease, paraproteinemia, or infection. Treatment with corticosteroid was ineffective and the patient eventually went into end-stage renal failure. To our knowledge, this is the first report of an idiopathic progressive glomerulopathy characterized by diffuse, global subendothelial and mesangial deposits, which suggests to us a novel insight into glomerular subendothelial/mesangial deposition.
Adult↗
[Therapeutic effectiveness of prednisolone in Mycoplasma pulmonis-infected pneumonia in mice].
The present investigation was designed to analyze the therapeutic efficacy of prednisolone in the development of pulmonary lesions in Mycoplasma pulmonis-infected mice. Mice were treated every day from day 3 to day 9 after M. pulmonis inoculation with minocycline (group M), prednisolone (group P), or with minocycline and prednisolone (group MP) and a control group was left untreated. Mice from each group were sacrificed at days 7, 14, and 21. The macroscopic lung lesion scores of group MP at days 7, 14, 21, and of group M at day 7 were significantly lower (p < 0.05) compared with the control group. Pathological findings in group M and MP showed reduction of the polymorphonuclear leukocyte response in the alveoli compared with the controls. However, infiltration of lymphocytes around the bronchioles and blood vessels of group M was not less than that in group MP. The titer of CF antibody in group MP was the lowest of the four groups. Among the four groups, M. pulmonis was cultured in the joints of group P. These results suggest that combination therapy with minocycline and prednisolone was effective because the mice of group MP had a more marked reduction of infiltration of lymphocytes around the bronchioles and blood vessels as compared with group M. Simultaneously, with prednisolone alone therapy, a risk of dissemination of the mycoplasma organism and diminution of antibody production were suggested.
Animals↗
[Total laparoscopic hysterectomy].
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Female↗
[Metabolism and pharmacokinetics of synthetic estrogens and progestogens].
Synthetic steroids, having delta 4-3-ketone structure, are commonly metabolised to the corresponding tetrahydro-metabolites. The reduction of the 20-ketone group is also essential for pregnan series progestogens. When these metabolic pathways are obstructed in some way, steroids are hydroxylated at proper positions. Hydroxylation of a steroid is primarily directed to form the inactive form, namely, conjugated steroid. However, in some cases, it induces activation or activity change to the original compound. Activation of lynestrenol, as a progestogen and the conversion of norethindrone to ethynylestradiol, are examples. Metabolism of some new steroids and factors affecting the effect of oral contraceptive pills are discussed.
Estradiol Congeners↗
[Regulation of aromatase in human choriocarcinoma cells].
To examine the mechanism regulating trophoblastic aromatase, we studied the effects of various agents on aromatase activity and the aromatase cytochrome P-450 (P-450arom) concentration in human choriocarcinoma JEG-3 cells. Aromatase activity was assessed by radioassay with [1 beta-3H] androstenedione. The P-450arom concentration was determined by an enzyme-linked immunosorbent assay with specific antibodies to P-450arom. Human chorionic gonadotropin (hCG) stimulated aromatase activity and increased the P-450arom concentration in a concentration-dependent (0.1-100 IU/ml) manner. Cholera toxin (CT), an adenylate cyclase activator, stimulated aromatase activity and the P-450arom concentration in a concentration-dependent (0.1-10ng/ml) and a time-dependent (12-72h) manner. 12-O-tetradecanoyl phorbol 13-acetate (TPA) (0.1-100ng/ml), a protein-kinase C activator, also stimulated aromatase activity and increased the P-450arom concentration. On the other hand, Ca2+ ionophore A23187, an agent increasing intracellular Ca2+ accumulation, inhibited aromatase activity and reduced the P-450arom concentration. The effects of CT, TPA and Ca2+ ionophore were additive. Aromatase activity was correlated with the P-450arom concentration. These results suggest that in JEG-3 cells the signal transduction system modulates aromatase activity by changing the P-450arom concentration.
Aromatase↗
Interleukin 4 downregulates cell growth and prostaglandin release of human mesangial cells.
Several clinical studies have proposed that a T cell derived cytokine IL-4 is operative in glomerulonephritis; however, its biological activities on renal cells have not been investigated. To elucidate its possible role in glomerulonephritis, we have examined whether IL-4 has effect on cell growth and prostaglandins synthesis using cultured mesangial cells (MC). IL-4 dose-dependently suppressed DNA synthesis and cell proliferation. IL-4 (10 ng/ml) alone did not affect prostaglandin E2 (PGE2) synthesis by mesangial cells, though, it inhibited IL-1 alpha- and TNF alpha-stimulated PGE2 synthesis by 48% and 81%, respectively. Comparable inhibition was observed on the conversion of exogenous arachidonic acid to PGs by IL-1-stimulated cells, suggesting IL-4 down regulates PG endoperoxide synthase activity. These results demonstrated that IL-4 is antagonistic to inflammatory cytokines upon PG synthesis as well as anti-mitogenic with MC.
6-Ketoprostaglandin F1 alpha↗
[Immunohistochemical determination of endometrial progesterone receptor (PR) content after intrauterine infusion of danazol in rabbits].
Danazol, an isoxazole derivative of 17 alpha-ethinyl-testosterone, has various effects on the female reproductive system. To examine its anti-estrogenic effects through the receptor system and clarify its direct effect on the endometrium in vivo, we applied danazol jelly into the rabbit uterine cavity. Recent studies performed in our laboratory using the ligand-binding assay have shown that danazol administered directly into the uterine cavity is absorbed by the endometrial tissue and exerts its anti-estrogenic effects possibly through progesterone receptors (PR) in the cells. In the present study we examined the variations in endometrial PR content during 7 days after the intrauterine administration of danazol into the rabbit uterine cavity. Immature female white rabbits were used. They were given daily subcutaneous injections of estradiol-17 beta (E2) for 3 days after which their abdomens were opened, and danazol gel was infused into the lumen of the right horn and HPC-jelly was infused into the lumen of the left horn, as the control. Thereafter and until they were killed, the same daily dose of E2 was injected. They were killed 6h, 24h, 3 days, 5 days or 7 days after intrauterine infusion of danazol and PRs were studied immunohistochemically using a specific antireceptor monoclonal antibody (PR-AT 4.14). Six hours after danazol infusion, the PR staining in the glandular epithelium and part of the stroma surrounding the epithelium had declined. On day 3, PR staining declined to its lowest level in the glandular epithelium and stroma. On Day 5, PR staining had been restored in the glandular epithelium but stayed low in the stroma.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Specific IgG autoantibodies are potent inhibitors of autoreactive T cell response to phytohemagglutinin-activated T cells.
PHA-activated human T cells express MHC class II molecules and have been shown to stimulate autoreactive T cells in autologous mixed lymphocyte reaction (T-T AMLR). We now demonstrate that normal human serum can dramatically suppress the proliferative response in T-T AMLR. The inhibitory factor was detected in the IgG fraction, and the activity was found to be mediated through the F(ab')2 portion of the IgG molecule, implying that the inhibitor could be specific. All homologous as well as autologous sera tested contained the inhibitory activity. Human serum was also found to suppress allogenic MLR stimulated by PHA-activated T lymphocytes but not allogenic MLR stimulated by nonactivated PBMC, indicating that the mechanism of inhibition is related to PHA activation of the stimulator cells. Moreover, pretreatment of the PHA-activated T lymphocytes with human serum resulted in a significant inhibition of T-T AMLR, as opposed to pretreatment of nonactivated PBMC, indicating that PHA-activated stimulators are functionally involved in the inhibition. Cytofluorometric analysis revealed that autologous IgG specifically binds to PHA-activated T lymphocytes and not to nonactivated CD3+ T cells. Furthermore, serum absorbed by PHA-activated T lymphocytes substantially lost its inhibitory activity whereas serum absorbed by nonactivated PBMC did not, suggesting that a surface molecule(s) expressed during activation of the stimulator cells is involved in the inhibition. The addition of human serum later in the culture period (> 3 days) resulted in a marked decrease in inhibition, implying that the presence of IgG in the early recognition phase of T-T AMLR is essential for maximum inhibitory effect. These results raise the possibility that natural autoantibodies present in normal human IgG may play an important role in regulating immune response mediated by autoreactive T cells.
Autoantibodies↗
Effects of sustained release formulation of thyrotropin-releasing hormone on learning impairments caused by scopolamine and AF64A in rodents.
The effects of a sustained-release formulation of thyrotropin-releasing hormone (TRH-SR) on learning impairments induced by scopolamine and a cholinergic neurotoxin, ethylcholine aziridinium ion (AF64A), were examined in rodents. Subcutaneous injection of TRH-SR (2.8 mg/kg as free TRH) produced a sustained increase in immunoreactive plasma TRH levels up to about 2 weeks after dosing in rats. TRH-SR (0.56 and 2.8 mg/kg) given subcutaneously 7 days before the acquisition trial markedly ameliorated scopolamine-induced amnesia in mice, as evaluated with a passive avoidance task. Repeated administration of TRH for 7 days at doses of 0.2-5 mg/kg s.c. elicited a dose-dependent recovery from amnesia induced by scopolamine, whereas only the group treated with 5 mg/kg/day showed a significant improvement. The rats with bilateral intracerebroventricular injection of AF64A (3.75 nmol/brain) showed a significant impairment in the water maze task 2 weeks after surgery. TRH-SR (0.56 and 2.8 mg/kg) also exhibited a dose-dependent ameliorating action on the deficit. These findings indicate that TRH-SR ameliorates learning impairments produced by scopolamine and AF64A, and suggest that continuous infusion of TRH may have a potent learning and memory improving action at low doses.
Amnesia↗
[The histochemical study of the effects of estrogen on the forebrain cholinergic neurons of fetal female rats transplanted into the anterior eye chamber of adult female rats].
In order to clarify the effects of estrogen on cholinergic basal forebrain neurons, a cholinergic neuron in the diagonal band nucleus of the female fetal rat was implanted into the anterior eye chamber of the female adult rat. Some host rats were treated with 2mg estradiol valerate (E2v) injected every 3 days after ovariectomy while others were not 2 and 4 weeks after transplantation, the growth of cholinergic neurons in the graft was studied using acethylcholinesterase (AChE) histochemistry. At 2 weeks after transplantation, AChE positive neurons and fibers were densely distributed in the grafts of E2v treated rats. Also in grafts without E2v treatment, AChE positive neurons and fibers were found in all the grafts although their density was low. At 4 weeks, AChE staining was dense staining observed in both groups. These results indicate that neurotrophic effect of estrogen on the cholinergic basal forebrain neurons.
Acetylcholinesterase↗
[Metabolism, structure and biological activity of sex steroids].
Recently, the action of steroid hormones are interpreted as the results from the interaction with its proper receptors. However, every steroid hormones and steroid drugs have many biological effects, and if one steroid receptor is enough to result in these multiple effects or not is not well known. On the other hand, our experimental results showed that some steroid drugs are metabolized, in vivo, to form several biologically active compounds. Norethindrone, a representative progestational compound, has also some estrogenic and androgenic effects. It was demonstrated, in our laboratory, that the compound was converted, in vivo, to several androgens and to estrogen, ethynyl estradiol. Since it was demonstrated later that ethynyl estradiol but not norethindrone showed estrogenic activity in vitro, it can be concluded that the estrogenic activity of norethindrone was derived from the metabolite of norethindrone, ethynyl estradiol. Although the chemical structure of norethindrone is far different from that of progesterone, it was demonstrated that the progestational effect of norethindrone was derived from the interaction of norethindrone with progesterone receptor. The binding site of norethindrone with the receptor is identical with that of progesterone. Some steroid drugs, such as lynestrenol are inactive, per se, and the conversion of the compound into norethindrone in liver tissue well explained the progestational activity of the compound. In such cases, the studies on the interaction of original compound with receptor in target tissues will give us poor information on the mechanism of steroid action. Some progestational compounds such as medroxyprogesterone acetate has anticancer effect, but norethindrone and the related compounds have no such an effect. This indicates that the receptor for anticancer effect is different from the receptor for common progestational effect. This was confirmed by many ways and the receptor for anticancer effect was partially characterized. Although dydrogesterone is a potent progestational agent and the endometrial response to this compound is almost identical with that to progesterone, it results in neither the elevation of basal body temperature nor an inhibition of ovulation, which are commonly observed with other progestogens. This also raises a doubt on the identity of progesterone receptors in peripheral and central tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
Binding Sites↗
Increased calcium release from sarcoplasmic reticulum stimulated by inositol trisphosphate in spontaneously hypertensive rat heart cells.
It is known that inositol (1, 4, 5)-trisphosphate (IP3) stimulates Ca2+ release from sarcoplasmic reticulum (SR) in several tissues, but in cardiac myocytes this phenomenon has not been confirmed. The purpose of the present study was to confirm the effect of (1, 4, 5)-IP3 on Ca2+ release from SR in cardiac myocytes. The effect of IP3 on Ca2+ release from SR in hypertrophic cardiac cells was also determined. We examined the effects of IP3 on Ca2+ release from cardiac myocyte SR by the digital-image method in a single cell. We also determined the effect of IP3 on calcium release from isolated SR. SR was prepared from spontaneous hypertensive rat hearts and Wistar kyoto rat hearts. The SR was prelabeled with 45Ca2+, and then incubated with the indicated concentrations of IP3 for 1 min at 37 degrees C. In cardiac myocytes treated with saponin, Ca2+ release stimulated by 10 microM (1, 4, 5)-IP3 was detected by fura-2. In 45Ca2+ prelabeled SR, the maximal Ca2+ release was achieved at 10 microM IP3 incubated for 1 min. The release of Ca2+ was higher in SR of SHR than in the SR of WKY. IP3 stimulates Ca2-release from cardiac SR, and this release is greater in SHR than in WKY. However, it is uncertain whether this phenomenon plays a role in cardiac hypertrophy.
Animals↗