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K Okada

Publications and source records attributed to K Okada.

At least 775 records · Page 43Linked to original sources

Distinct inhibition by non-peptide and peptide arginine vasopressin antagonists of vasopressin-induced activation of mitogen-activated protein kinase in cultured rat vascular smooth muscle cells.

The preincubation of vascular smooth muscle cells (VSMC) with a non-peptide arginine vasopressin (AVP) antagonist (OPC-21268) (0.5 mM) for 10 min completely inhibited the 1 microM AVP-induced activation of mitogen-activated protein (MAP) kinase but did not affect the angiotensin II-, protein kinase C activator- or ionomycin-stimulated MAP kinase. Similar results were obtained with the simultaneous administration of AVP and OPC-21268. This inhibitory effect of OPC-21268 completely disappeared after washing the cells pretreated with OPC-21268. In contrast, the preincubation of VSMC with a peptide AVP antagonist, d(CH2)5Tyr(Me)AVP (1 microM), for 10 min completely blocked the 1 microM AVP-activated MAP kinase but the simultaneous administration of d(CH2)5Tyr(Me)AVP with AVP could inhibit that only by 40%. However, the washing procedure did not affect the inhibitory effect of d(CH2)5Tyr(Me)AVP. These results indicate that OPC-21268 is a specific AVP antagonist to inhibit the AVP-induced activation of MAP kinase. The antagonistic effect of OPC-21268 is also suggested to be relatively weak but prompt as compared to that of a peptide AVP antagonist d(CH2)5Tyr(Me)AVP.

Angiotensin II↗

Bovine leukemia virus induces CD5- B cell lymphoma in sheep despite temporarily increasing CD5+ B cells in asymptomatic stage.

To investigate bovine leukemia virus (BLV)-induced leukemogenesis, we infected sheep with BLV and used flow-cytometric and immunohistological analysis to characterize the phenotypic alterations in lymphocytes from peripheral blood and lymph nodes taken from the animals with lymphoma at various stages. In sheep at the asymptomatic stage, depending on the extent of progression of the disease, the proportions of CD2(+)-, CD4(+)-, CD8(+)-, and gamma delta TCR(+)-T cells that coexpressed CD5 decreased, but CD5+ sIgM+ cells as well as CD5- sIgM+ cells increased for a period. The number of CD5+ B cells, however, rapidly decreased in the lymphoma stage. On the other hand, neoplastic lymphocytes appeared to be a monoclonal population derived from a single cell with surface phenotypes of sIgM+, B-cell-specific molecule B2+, major histocompatibility complex (MHC) class II+, OvCD5-, OvCD2-, OvCD4-, OvCD8-, gamma delta TCR-, which suggests that only CD5- B cells proliferate clonally when the disease proceeds to the lymphoma stage. Thus, rapid decrease of CD5+ B cells may be used as a marker of lymphoma stage. To identify the BLV provirus in the CD5- B and CD5+ B cells throughout the course of disease, each fraction of CD5- B and CD5+ B cell was sorted from the peripheral blood by flow cytometry and nested double polymerase chain reaction was performed. In BLV-infected but healthy sheep, BLV integrated both CD5- B and CD5+ B cells. In lymphoma, however, BLV provirus was detected only in CD5- B cells but not in CD5+ B cells. Therefore it appears that a disappearance of BLV-infected CD5+ cells is one of the critical events leading to CD5- B cell lymphoma in sheep. This is in contrast to the BLV-induced lymphoma in cattle which shows CD5+ phenotype.

Animals↗

Genetic analyses of signalling in flower development using Arabidopsis.

Flower development can be divided into four major steps: phase transition from vegetative to reproductive growth, formation of inflorescence meristem, formation and identity determination of floral organs, and growth and maturation of floral organs. Intercellular and intracellular signalling mechanisms must have important roles in each step of flower development, because it requires cell division, cell growth, and cell differentiation in a concerted fashion. Molecular genetic analysis of the process has started by isolation of a series of mutants with unusual flowering time, with aberrant structure in inflorescence and in flowers, and with no self-fertilization. At present more than 60 genes are identified from Arabidopsis thaliana and some of them have cloned. Although the information is still limited, several types of signalling systems are revealed. In this review, we summarize the present genetic aspects of the signalling network underlying the processes of flower development.

Arabidopsis↗

Genetic complementation of a floral homeotic mutation, apetala3, with an Arabidopsis thaliana gene homologous to DEFICIENS of Antirrhinum majus.

Among the homeotic mutants with altered floral organs, two mutants of Arabidopsis thaliana, apetala3 and pistillata, and two mutants of Antirrhinum majus, deficiens and globosa, have a homeotic conversion of the floral organs in whorl 2 and 3, namely petals to sepals and stamens to carpels. We have isolated a homologue of the DEFICIENS gene from A. thaliana wild type and shown complete complementation of apetala3 mutation by introducing the isolated gene using Agrobacterium-mediated transformation. These results show that the APETALA3 is a homologue of DEFICIENS structurally and functionally. The 5'-upstream region of APETALA3 contains three SRE-like sequence, where MADS box-containing proteins are assumed to bind and regulate expression in tissue- and stage-specific manner.

Adaptor Proteins, Signal Transducing↗

Two amidophosphoribosyltransferase genes of Arabidopsis thaliana expressed in different organs.

Amidophosphoribosyltransferase (ATase: EC 2.4.2.14) is a key enzyme in the pathway of purine nucleotide biosynthesis. We have identified several cDNA clones whose amino acid sequences exhibit similarity with the known ATases in a cDNA library of young floral buds of Arabidopsis thaliana. The cDNA clones are derived from two genes homologous with each other. These cDNAs represent the first plant representatives of ATase gene. Structural comparison with ATases of other organisms has revealed that the two genes encode [4Fe-4S] cluster-dependent ATases. Northern blot analysis showed that expression level of the genes is different in three organs; one gene is expressed in flowers and roots, while the other gene is mainly expressed in leaves.

Amidophosphoribosyltransferase↗

Case report 858: Postradiation osteosarcoma of the patella.

A case of postradiation osteosarcoma of the patella in a 54-year-old man was presented. The lesion in the patella was diffuse and highly sclerotic, and was partially radiolucent in radiographs. The whole patella was removed by Miyakawa's method. Diagnostic criteria, clinical features, and radiographic findings of postradiation sarcoma were described. The rarity of osteosarcoma of the patella was emphasized.

Bone Neoplasms↗

Scaphoid megalourethra with multiple urogenital anomalies.

A male infant with scaphoid megalourethra, which is a rare congenital anomaly, is presented. At birth he exhibited a grossly swollen, malformed penis and cryptorchidism. The corpus spongiosum was not palpable. The infant had congenital renal failure. Retrograde urethrography revealed a crescent-shaped dilatation of the anterior urethra, and the diagnosis of scaphoid megalourethra was made. Subsequent uroradiological examinations showed that there were also severe urogenital anomalies, i.e. renal hypoplasia-dysplasia, hydronephrosis, hydroureter and vesicoureteral reflux. This disorder is frequently associated with other urogenital anomalies. Therefore, once the diagnosis is reached, a careful investigation for other associated abnormalities should be undertaken.

Abnormalities, Multiple↗

The efficacy of non-clamping selective cerebral perfusion in distal aortic arch aneurysm repair: report of a case.

Successful repair of a distal aortic arch aneurysm without aortic cross-clamping was carried out in a 74-year-old man, using a combination of special separate cerebral perfusion and retrograde coronary perfusion, termed non-clamping selective cerebral perfusion. We believe that satisfactory results following aortic arch surgery in elderly patients can only be achieved through the prevention of emboli derived from an aortic cross-clamping site, and shortened ischemic time of the vital organs.

Aged↗

Evaluation of bradykinesia induction by SM-9018, a novel 5-HT2 and D2 receptor antagonist, using the mouse pole test.

Induction of bradykinesia by SM-9018, a novel 5-HT2 and D2 antagonist, was compared with that of other neuroleptics using the pole test in mice. Neuroleptics including SM-9018, haloperidol, chlorpromazine, and thioridazine dose dependently induced bradykinesia in the pole-descending behavior of mice with relative potencies consistent with those for catalepsy induction. SM-9018 was about 70 times weaker than haloperidol and twice as weak as thioridazine in inducing bradykinesia. Other CNS drugs such as barbiturates and antidepressants had no effects. Haloperidol-induced bradykinesia was significantly attenuated by a cholinergic muscarinic antagonist (i.e., trihexyphenidyl) and 5-HT2 antagonists (i.e., ritanserin and cyproheptadine) whereas that caused by SM-9018 was relatively resistant to the 5-HT2 antagonists. These findings suggest that SM-9018 is weaker than other neuroleptics in inducing extrapyramidal side effects and that the 5-HT2 blocking activity of SM-9018 may contribute to its atypical neuroleptic property.

Animals↗

Regional cerebral blood flow in the frontal, parietal and occipital cortices increases independently of systemic arterial pressure during slow walking in conscious rats.

Regional cerebral blood flow (rCBF) in the frontal, parietal and occipital cortices was measured using laser Doppler flowmetry during walking in conscious rats at moderate speed on a treadmill (4 cm/s) for a 30 s period. During walking rCBF increased in all these three cortices. The rCBF in the parietal cortex started to increase within a few seconds after the start of walking, and continued to increase 42 +/- 16% (mean +/- S.D.) until the end of walking. Within 90 s after walking had ceased, the increased rCBF returned to pre-walking basal levels. The rCBF responses in the frontal and occipital cortices were identical to that in the parietal cortex. Mean arterial pressure (MAP) in a caudal artery of the tail during walking was increased by about 10%. Injection of atropine (5 mg/kg, i.p.), a muscarinic cholinergic receptor antagonist that permeates the blood brain barrier (BBB), reduced the walking-induced increase in cortical rCBF, as determined by measurement of parietal rCBF, from 42 +/- 12% to 28 +/- 15%. However, injection of methylatropine (5 mg/kg, i.p.), a muscarinic cholinergic receptor antagonist that does not permeate the BBB, did not affect the response of rCBF. Neither drug affected the walking-induced response of MAP. Injection of mecamylamine (20 mg/kg, s.c.), a nicotinic cholinergic receptor antagonist that permeates the BBB, reduced the walking-induced increase in cortical rCBF from 47 +/- 12% to 30 +/- 12%. Injection of hexamethonium (20 mg/kg, s.c.), a nicotinic cholinergic receptor antagonist that does not permeate the BBB, did not affect the responses of rCBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Time-dependent effect of chronic UV irradiation on superoxide dismutase and catalase activity in hairless mice skin.

Reactive oxygen species are produced by ultraviolet (UV) exposure and cause oxidative damage. Enzymic antioxidants such as superoxide dismutase (SOD) and catalase (CAT) may play important defensive roles in vivo. The previous studies have focused on the acute effects after single UV irradiation on those enzyme activities. In this study, we investigated the chronic effects of ultraviolet-A (UVA) or ultraviolet-B (UVB) exposure on the skin SOD and CAT activities using hairless mice. Accumulated doses of UVA and UVB after 36-week irradiation conducted 3 times a week were 3240 J/cm2 and 4320 mJ/cm2, respectively. SOD activity was increased by UVB irradiation and gradually returned to control levels, but was unaffected by UVA irradiation. In contrast, CAT activity was suppressed by UVA irradiation, indicating that the skin SOD and CAT activities are not coordinately regulated by long-term UV irradiation. These findings suggest that SOD activity is induced by repeated exposures to UVB in response to chronic photooxidative stress. However, continual cumulative stress may overwhelm the capacity of this system. These time-dependent changes of the cutaneous antioxidant system by chronic UV irradiation should provide us with important information on photooxidative events in cutaneous photoaging.

Animals↗

An immunohistochemical study of an equine B-cell lymphoma.

The tissues of an 8-year-old thoroughbred castrated male horse with equine lymphoma were examined immunohistochemically. Neoplastic masses were observed in the mediastinum, mesenteric lymph nodes, gastric mucosa and serosa, liver capsule, and spleen capsule with associated lymph nodes. Histopathologically, the neoplastic cells were seen to consist predominantly of a mixture of well differentiated small and large types. Immunohistochemically, the small lymphoid cells were MHC class IIlow+ and PanT- and the large lymphoid cells were MHC class IIhigh+ and PanT-. These findings revealed that the neoplastic cells were of B-lymphocyte lineage.

Animals↗

Treatment of adult T-cell leukaemia-lymphoma with irinotecan hydrochloride (CPT-11). CPT-11 Study Group on Hematological Malignancy.

A late phase II study of a new camptothecin analogue, irinotecan hydrochloride (CPT-11), was conducted to evaluate the anti-tumour effect and toxicity in patients with refractory leukaemia and lymphoma including adult T-cell leukaemia (ATL)-lymphoma, in a multi-institutional cooperative study. All the patients with ATL had been previously treated with various conventional combination chemotherapies and were refractory to these therapies or had relapsed. CPT-11 was administered at a dose of 40 mg m-2 day-1 for three consecutive days repeated weekly until evidence of disease progression. One complete remission and four partial remissions were achieved in 13 assessable patients with ATL. The median total dose to achieve remission was 240 mg m-2 and the median duration of response was 31 days. The major toxicities were leucopenia (83%), diarrhoea (62%) and nausea/vomiting (69%). These were relatively severe, but they were generally tolerable and reversible. However, one patient died probably as a result of this therapy. No effective chemotherapy for adult T-cell leukaemia-lymphoma has yet been established, and the prognosis for patients with this disease is very poor. Our results suggest that CPT-11 may be a promising agent for this disease. Further combination therapy with CPT-11 is needed to improve the therapy for ATL.

Adult↗

Therapeutic efficacy of the non-peptide AVP antagonist OPC-31260 in cirrhotic rats.

The present study was undertaken to determine whether a non-peptide arginine vasopressin (AVP) antagonist [5-dimethylamino-1-(4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetra hydro-1H- benzazepine] (OPC-31260) improves the impaired water excretion in rats with experimental liver cirrhosis. Male Wistar rats weighing 200 to 250 g were injected in an equal volume (4 ml/kg) of carbon tetrachloride and olive oil at an interval of seven days for three months, causing liver cirrhosis with ascites. Control rats were injected with only olive oil. Body weight (body wt) and hematocrit (Hct) were lower in the cirrhotic rats than the control rats (body wt 360.7 vs. 238.5 g, P < 0.01; Hct 46.3 vs. 39.2%, P < 0.01). A water loading test (30 ml/kg) was carried out and 20-minute urine collections were made for three hours. The percent of water load excreted was 62.5% in the cirrhotic rats, a value significantly less than that of 102.1% in the control rats. However, its percent increased to 215.1% after the oral administration of 5 mg/kg OPC-31260 (P < 0.01). Minimal urinary osmolality (UOsm) was 185.5 mOsm/kg H2O in the cirrhotic rats receiving the vehicle, a value greater than the control rats of 125.5 mOsm/kg H2O (P < 0.01). The oral administration of 5 mg/kg OPC-31260 reduced minimal UOsm to 85.2 mOsm/kg H2O in the cirrhotic rats (P < 0.01). Urinary excretion of sodium was lower in the cirrhotic rats than the control rats (87.1 vs. 312.4 microEq/3 hr, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Atrial natriuretic peptide and cGMP inhibit Na+/H+ antiporter in vascular smooth muscle cells in culture.

The aim of the present paper was to study the mechanisms of the inhibitory effect of atrial natriuretic peptide (ANP) on the sustained contraction phase of vascular smooth muscle cells (VSMC). Specifically, the potential role of ANP on the Na+/H+ antiporter and Na+ transport systems was investigated. Both ANP and 8-bromo cGMP inhibited 22Na+ uptake and decreased intracellular Na ([Na+]i) in VSMC, an effect that was mimicked by the specific Na+/H+ antiporter inhibitor, hexamethylen amiloride (HMA). The effect of ANP was not additive with HMA, therefore suggesting that both inhibit the same 22Na+ transport pathway. On the other hand, the inhibition of 22Na+ accumulation by ANP was additive with the inhibition by furosemide or bumetanide, thus suggesting that both drugs act on different Na+ exchange systems. In HEPES-buffered medium, ANP, cGMP, and HMA significantly inhibited the AVP-induced intracellular alkalinization, an effect which was associated with significant inhibition of the AVP-induced shape change. In bicarbonate buffered medium, ANP and cGMP decreased the pH level below the baseline after application of AVP, and an inhibition by ANP and cGMP of AVP-induced VSMC shape change was also observed. The recovery of cellular pH after three different types of acid load, namely, ammonium chloride pulse, nigericin clamp and lowering of extracellular pH, was significantly decreased by ANP and cGMP. Taken together, these results indicate that ANP/cGMP inhibit the activity of the Na+/H+ antiporter in VSMC, either in hormone- or pH-stimulated conditions.

Amiloride↗

Effects on tumor induction, growth, metastasis and histology of concurrent administration of putrescine and its metabolizing inhibitor alpha-difluoromethylornithine in nickel tumorigenesis in soft tissue.

The effects of putrescine and the inhibitor of its biosynthesis alpha-difluoromethylornithine (DFMO) on nickel tumorigenesis in soft tissue was studied. Three groups of female F-344 rats were injected i.m. with 10 mg of nickel subsulfide (NiSS) in the right hind leg, after which one group was administered 200 mg/kg body wt of putrescine (i.p.) once a week, and one group was administered 0.2% DFMO in the drinking water for 32 weeks until termination. The DFMO-treated group exhibited longer tumor induction time, lower tumor growth rate and significantly lower metastatic rate, whereas the putrescine-treated group exhibited a temporarily higher tumor growth rate than the NiSS-only group. Histologically, the putrescine-treated group and especially the DFMO-treated group frequently exhibited differentiated sarcomas but the NiSS-only group exhibited anaplastic sarcomas. The present study demonstrated that long-term administration of DFMO has an inhibitory effect on tumors and metastasis, and induces differentiation of tumor cells from anaplastic round cells to well-differentiated pleomorphic cells in NiSS tumorigenesis in soft tissue.

Animals↗