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Biomedical subjects

Hiroyuki Koike

Publications and source records attributed to Hiroyuki Koike.

At least 19 recordsLinked to original sources

Acclimation to the growth temperature and thermosensitivity of photosystem II in a mesophilic cyanobacterium, Synechocystis sp. PCC6803.

Differences in the temperature dependence and thermosensitivities of PSII activities in Synechocystis sp. PCC6803 grown at 25 and 35 degrees C were studied. Hill reactions in cells, thylakoid membranes and purified PSII core complexes were measured at high temperatures or at their growth temperatures after high-temperature treatments. In the presence of 2,5-dichloro-p-benzoquinone as an electron acceptor, which can accept electrons directly from Q(A), the temperature dependence of the oxygen-evolving activity was almost the same in thylakoid membranes and in the purified PSII complexes from cells grown at 25 or 35 degrees C. When duroquinone, which accepts electrons only through Q(B) plastoquinone, was used as an electron acceptor, the temperature dependence was the same for purified PSII core complexes but was different between thylakoids isolated from the cells grown at 25 and 35 degrees C. No remarkable difference was observed in protein compositions between thylakoids and between purified PSII complexes from cells grown at 25 or 35 degrees C. However, the fluidity of thylakoids, measured by electron flow to P700, was affected by the growth temperature. These results suggest that one of the major factors which cause the changes in the thermosensitivity of PSII is the change in the fluidity of thylakoid membranes. As for the acclimation of PSII in thylakoids to high temperatures, one of the main causes is the decrease in the high-temperature-induced formation of non-Q(B) PSII due to the decreased fluidity in the cells grown at 35 degrees C.

Acclimatization↗

Molecular mechanism underlying inverse agonist of angiotensin II type 1 receptor.

To delineate the molecular mechanism underlying the inverse agonist activity of olmesartan, a potent angiotensin II type 1 (AT1) receptor antagonist, we performed binding affinity studies and an inositol phosphate production assay. Binding affinity of olmesartan and its related compounds to wild-type and mutant AT1 receptors demonstrated that interactions between olmesartan and Tyr113, Lys199, His256, and Gln257 in the AT1 receptor were important. The inositol phosphate production assay of olmesartan and related compounds using mutant receptors indicated that the inverse agonist activity required two interactions, that between the hydroxyl group of olmesartan and Tyr113 in the receptor and that between the carboxyl group of olmesartan and Lys199 and His256 in the receptor. Gln257 was found to be important for the interaction with olmesartan but not for the inverse agonist activity. Based on these results, we constructed a model for the interaction between olmesartan and the AT1 receptor. Although the activation of G protein-coupled receptors is initiated by anti-clockwise rotation of transmembrane (TM) III and TM VI followed by changes in the conformation of the receptor, in this model, cooperative interactions between the hydroxyl group and Tyr113 in TM III and between the carboxyl group and His256 in TM VI were essential for the potent inverse agonist activity of olmesartan. We speculate that the specific interaction of olmesartan with these two TMs is essential for stabilizing the AT1 receptor in an inactive conformation. A better understanding of the molecular mechanisms of the inverse agonism could be useful for the development of new G protein-coupled receptor antagonists with inverse agonist activity.

Amino Acid Sequence↗

Severity of hyperlipidemia does not affect antiatherosclerotic effect of an angiotensin II receptor antagonist in apolipoprotein E-deficient mice.

The purpose of this study was to clarify whether severity of hyperlipidemia affects the antiatherosclerotic effect of angiotensin II receptor blockers (ARBs). The effect of olmesartan medoxomil, an ARB, on atherosclerotic lesion was examined in apolipoprotein E-deficient (ApoEKO) mice fed a normal diet (ND) or a high-fat-supplemented diet (FD) for 25 weeks. ApoEKO mice have high plasma cholesterol levels, which were further increased by feeding of an FD. Both the atherosclerotic lesion area of the aortic luminal surface and the atherosclerotic lesion thickness in the aortic valves were significantly greater in the FD mice than in the ND mice. Olmesartan medoxomil did not affect the plasma cholesterol levels in either the ND or FD ApoEKO mice; however, it reduced effectively both the atherosclerotic lesion surface area and the lesion thickness even in FD ApoEKO mice. It is concluded that the antiatherosclerotic effect of ARBs is not weakened by the high plasma cholesterol level, suggesting the usefulness of ARBs in the treatment of atherosclerosis, even in a situation in which the plasma cholesterol level is not fully controlled.

Angiotensin II Type 1 Receptor Blockers↗

The effect of angiotensin II receptor blockade on an end-stage renal failure model of type 2 diabetes.

The effect of olmesartan medoxomil (OLM), an angiotensin II receptor blocker (ARB), on advanced nephropathy and mortality was evaluated in Zucker Diabetic Fatty (ZDF) rats, a type 2 diabetes model. OLM was administered from 36 weeks of age, when the animals developed advanced proteinuria. OLM effectively suppressed the progression of proteinuria. The ZDF rats started to die at 50 weeks of age, which was accompanied by abrupt increase in blood urea nitrogen, suggesting that the cause of death was renal insufficiency. OLM suppressed increases in blood urea nitrogen and increased the survival rate of the ZDF rats. The histological examination revealed that the renal damage was ameliorated by OLM. The macrophage infiltration and monocyte chemoattractant protein-1 (MCP-1) expression was increased in the glomeruli and tubulointerstitium of the ZDF rat kidneys, and the increase was lessened by OLM. In a separate study, albumin increased MCP-1 release from cultured tubular epithelial cells. These results suggest that protein leakage from the glomeruli stimulates MCP-1 production in tubular cells and that MCP-1 released into the interstitial space induces macrophage infiltration and inflammation. It is conceivable that the beneficial actions of ARB on diabetic nephropathy are, at least in part, due to decrease of proteinuria and the subsequent reduction of inflammatory changes in tubular cells.

Angiotensin II Type 1 Receptor Blockers↗

Isolated right ventricular metastasis of uterine cervical carcinoma.

Isolated direct metastasis of uterine cervical carcinoma to the right ventricular endocardium is very rare. A 68-year-old woman was initially diagnosed as having stage IIIb squamous cell carcinoma of the uterine cervix, and was treated with radiation therapy. After 2 years, she developed heart failure and presented with a mass in the right ventricle. The results of further examinations were consistent with a tumor or a thrombus in the right ventricle. She underwent excision of the mass under cardiopulmonary bypass, and histopathologic examination of the resected tissue revealed metastatic squamous cell carcinoma of the uterine cervix. She was discharged 3 weeks after the operation, and underwent chemotherapy. However, she was readmitted with drug-induced interstitial pneumonia and died 5 months after the surgery. Patients with an intracardiac mass and a history of uterine cervical cancer should be suspected of having a myocardial metastasis until it is proven otherwise.

Aged↗

Effect of combined treatment with an angiotensin II receptor antagonist and an HMG-CoA reductase inhibitor on atherosclerosis in genetically hyperlipidemic rabbits.

The purpose of this study was to examine whether coadministration of olmesartan medoxomil (OLM), an AT1 subtype specific angiotensin II receptor blocker (ARB), and pravastatin (PRV), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, could enhance the antiatherogenic effect compared with monotherapy. Vehicle, PRV (25 mg/kg), OLM (0.5 mg/kg), and PRV (25 mg/kg) and OLM (0.5 mg/kg) in combination were administered to Watanabe heritable hyperlipidemic (WHHL) rabbits for 8 months. OLM alone and in combination lowered blood pressure to a similar degree, whereas PRV alone had no effect. PRV alone and in combination lowered blood cholesterol to a similar degree, whereas OLM alone had no effect. The combination of PRV and OLM decreased effectively both surface lesion area and lesional thickness in aortic tissue, producing a greater reduction in aortic cholesterol content than either drug alone. Immunohistological examination of the aorta revealed that PRV reduced macrophage infiltration and lipid deposition and that OLM reduced macrophage infiltration accompanied by reduction in monocyte chemoattractant protein-1 expression and N-(carboxymethyl)lysine protein adduct, an oxidative stress marker. It is concluded that OLM, an ARB, and PRV, an HMG-CoA reductase inhibitor, in combination produce a greater antiatherogenic effect than monotherapy via the combination of the different antiatherosclerotic mechanisms of each drug.

Angiotensin II Type 1 Receptor Blockers↗

Surgical treatment for intrathoracic aneurysm of the innominate artery in an 83-year-old asymptomatic woman.

Aneurysm of the innominate artery is uncommon compared with other peripheral aneurysms, and holds the potential for rupture, embolization, or thrombosis as well as various complications caused by compression to the adjacent structures. The most effective treatment for this condition is surgical resection, but the earlier reports described high mortality rates. We report the case of an 83-year-old asymptomatic woman with an aneurysm in the innominate artery, which was successfully resected and repaired with the use of modern surgical techniques of hypothermic circulatory arrest and selective cerebral perfusion. Aggressive surgical intervention should be employed despite the fact that a patients is asymptomatic.

Aged↗

Antagonizing the angiotensin II subtype 1 receptor: a focus on olmesartan medoxomil.

BACKGROUND: The orally active, nonpeptide antagonists of the angiotensin II subtype 1 (AT1) receptor represent a recent class of antihypertensive drugs that selectively block the renin-angiotensin system. Olmesartan medoxomil is the newest member of this class. OBJECTIVE: This article reviews the renin-angiotensin system and how this system can be pharmacologically inhibited by the selective antagonists of the AT1 receptor, with a main focus on the AT1 receptor antagonist olmesartan. METHODS: Key studies were selected from previous work to illustrate the antihypertensive, cardioprotective, and renoprotective effects of olmesartan, and to compare class effects of AT1 receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors. RESULTS: Olmesartan, the active metabolite of olmesartan medoxomil, is a highly potent antagonist of the AT1 receptor. It inhibits the contractile responses to angiotensin II in guinea pig aorta, inhibits the pressor responses to angiotensin II in rats and dogs, and exhibits dose-dependent antihypertensive effects in spontaneously hypertensive rats. In addition to its antihypertensive effects, olmesartan medoxomil provides protection against cardiac and renal damage in animal models. AT1 receptor antagonists are more specific inhibitors of the renin-angiotensin system compared with ACE inhibitors. They are well tolerated and have an excellent safety profile. Unlike angiotensin-converting enzyme inhibitors, AT1 receptor antagonists lack the nonangiotensin-related side effects such as cough and angioedema. CONCLUSIONS: AT1 receptor antagonists such as olmesartan represent a valid therapeutic option for the treatment of hypertension and other cardiovascular and renal diseases.

Angioedema↗

Deactivation of photosynthetic activities is triggered by loss of a small amount of water in a desiccation-tolerant cyanobacterium, Nostoc commune.

Changes in photosynthetic activities under hypertonic conditions were studied in a terrestrial, highly desiccation-tolerant cyanobacterium, Nostoc commune, and in some desiccation-sensitive cyanobacteria. The amounts of water sustained in the colony matrix outside the N. commune cells and the cellular solute concentration were estimated by measuring the water potential, and the solute concentration was supposed to correspond to around 0.22 M sorbitol. Incubation of the colonies in 0.8 M sorbitol solution inhibited the energy transfer from the phycobilisome (PBS) anchor to PSII core complexes. At higher sorbitol concentrations, light energy absorbed by PSI, PSII, and PBS was dissipated to heat. PSI and cyclic electron flow around PSI was also deactivated by hypertonic treatment. Fv/Fm and (Fm'-F)/Fm' values started to decrease at 0.6 and 0.3 M sorbitol and reached zero at 1.0 and 0.8 M, respectively. Decreases in these two fluorescence parameters corresponded to the decreases in PSII fluorescence (F695) and photosynthetic CO2 fixation, respectively. The intensity of delayed light emission started to decrease at 1.0 M sorbitol and became negligible at 4.0 M. Comparing these changes in N. commune with those in desiccation-sensitive species, we found that N. commune cells actively deactivates photosynthetic systems on sensing water loss.

Carbon Dioxide↗

Inactivation of ycf33 results in an altered cyclic electron transport pathway around photosystem I in Synechocystis sp. PCC6803.

ycf33 encodes a small protein with a molecular mass of 7.5 kDa and is found from cyanobacteria to higher plants. A ycf33 deletion mutant was constructed in Synechocystis sp. PCC6803 and characterized. The mutant showed a higher phycobilisome/chlorophyll ratio than the wild type and a higher photosystem II/photosystem I fluorescence ratio measured at 77 K. Under photoautotrophic conditions, the growth rates were not much different from those of the wild type. Cyclic electron transport activities around photosystem I were not much different between the wild type and the mutant. However, the effects of diphenyleneiodonium, an inhibitor of flavoprotein, on cyclic electron transport in the mutant were different from those in the wild type; it was severely inhibited in the wild type but not much in the mutant. Together with the effects of nitrite, which accepts electrons from ferredoxin via nitrite reductase and those of HgCl2, it was suggested that the pathway of cyclic electron transport is altered in the mutant.

Amino Acid Sequence↗

Synthesis and collateral dilator activity of nitroxyalkylamides having direct or latent sulfhydryl moieties.

To develop an orally active, long-acting nitrate that does not induce tolerance, nitroxyalkyl compounds were prepared and their activities evaluated by the use of carotid collaterals in anesthetized dogs. A compound having a favorable pharmacological profile, that is, long-lasting collateral vasodilatation and little hypotension, and lack of nitrate tolerance, was chosen for further evaluation.

Animals↗

Arrest of chlorophyll synthesis and differential decrease of Photosystems I and II in a cyanobacterial mutant lacking light-independent protochlorophyllide reductase.

The chlL gene encodes one subunit of the light-independent protochlorophyllide reductase. A chlL-lacking mutant of the cyanobacterium Plectonema boryanum is unable to synthesize chlorophyll (Chl) in the dark, causing Chl synthesis to become light-dependent as in angiosperms. When the mutant cells were cultivated heterotrophically in the dark, Chl synthesis was arrested and the Chl content decreased exponentially in reverse profile to cell propagation, indicating that most of the pre-existing Chl was recruited for daughter cells. During this 'etiolating' process the Chl content became less than 0.5% of the original level. In parallel to this there was a decrease in the activity of Photosystem I (PSI), the amount of its core Chl-binding subunits, PsaA/PsaB, and a peripheral subunit, PsaC. Levels of transcripts for these subunits were not significantly changed upon the arrest of Chl synthesis. In contrast, Photosystem II (PSII) was maintained to a significant extent in terms of activity and protein levels of D1 and CP47 until a late stage of the etiolation, implying that PSII is newly synthesized though Chl synthesis was arrested. Low-temperature (77 K) fluorescence spectral analysis supported a selective decrease in Chl associated with PSI. Taken together, it is suggested that the pre-existing Chl molecules in periphery of PSI could be released and re-distributed for PSII biosynthesis in the etiolating cyanobacterial cells.

Bacterial Proteins↗

Anti-hypertensive agents inhibit in vivo the formation of advanced glycation end products and improve renal damage in a type 2 diabetic nephropathy rat model.

Prevention or retardation of diabetic nephropathy (DN) includes anti-hypertensive treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) on the premises that these drugs have an added protective effect beyond their influence on BP. The present study used a strain of spontaneously hypertensive/NIH-corpulent rats [SHR/NDmc-cp (fat/fat)] as a model of type II DN to unravel the renoprotective effects of anti-hypertensive drugs. Olmesartan (1 or 5 mg/kg per d), an ARB, and hydralazine (5mg/kg per d), an anti-hypertensive drug without effect on the renin-angiotensin system (RAS), were given for 20 wk. BP, renal function, glucose and insulin levels, and proteinuria were monitored. Glomerular lesions and kidney pentosidine content were assessed at the end of the study. Olmesartan (1 and 5 mg) significantly reduced BP and kidney pentosidine content and improved histologic renal damage and proteinuria. The changes were dose-dependent. The effect of hydralazine (5 mg) was similar to that of olmesartan (1 mg) but reached statistical significance only for kidney pentosidine content. The similarity of both drugs' effects on kidney damage and proteinuria suggest that renoprotection does not hinge on manipulation of RAS in these rats. By contrast, the inhibition of renal pentosidine formation assessed both by immunohistochemistry and HPLC suggests a critical role of advanced glycation end product (AGE) formation together with hypertension in the genesis of diabetic nephropathy. This view is supported by the correlation found between renal pentosidine content and proteinuria. The unsuspected AGE-lowering effect of hydralazine was further confirmed in vitro and elucidated; it is due to both reactive carbonyl compounds trapping and modifications of the oxidative metabolism. It is concluded that AGE inhibition should be included in the therapeutic strategy of DN.

Animals↗

Randomized trial of trigger point injection for renal colic.

BACKGROUND: Many drugs have been utilized for the treatment of renal colic, but to date no drugs that relieve pain quickly and completely have been developed. Thus, we conducted a prospective trial to evaluate the effects of trigger point injection on renal colic. In this study, we used a local injection of lidocaine to the trigger point of patients experiencing renal colic, and evaluated the efficacy in patients using the visual analog scale. METHODS: Sixty patients with renal colic were enrolled in this study and divided into two groups by a simple randomization: (i) the butylscopolamine group (n = 30, intravenous injection of butylscopolamine bromide and sulpyrine); and (ii) the lidocaine group (n = 30, local anesthesia to the trigger point with lidocaine). RESULTS: Renal colic had disappeared completely at the end of the trigger point injection in 15/30 patients and the average time required to produce a 50% improvement in symptoms was 9 min in all patients in the group. In the lidocaine group, only one patient needed an additional anodyne treatment after 60 min and none of the 29 patients whose pain disappeared within 60 min needed further anodyne treatment within 24 h. These results were all significantly superior to those of the conventional treatment. No side-effects and complications were observed. CONCLUSION: Trigger point injection, in our experience, is an easy, safe and effective method for the amelioration of renal colic. It was significantly superior to the combination of intravenous butylscopolamine and sulpyrine.

Adult↗

Recovery of photosynthetic systems during rewetting is quite rapid in a terrestrial cyanobacterium, Nostoc commune.

Recovery processes of photosynthetic systems during rewetting were studied in detail in a terrestrial, highly drought-tolerant cyanobacterium, Nostoc commune. With absorption of water, the weight of N. commune colony increased in three phases with half-increase times of about 1 min, 2 h and 9 h. Fluorescence intensities of phycobiliproteins and photosystem (PS) I complexes were recovered almost completely within 1 min, suggesting that their functional forms were restored very quickly. Energy transfer from allophycocyanin to the core-membrane linker peptide (L(CM)) was recovered within 1 min, but not that from L(CM) to PSII. PSI activity and cyclic electron flow around PSI recovered within 2 min, while the PSII activity recovered in two phases after a time lag of about 5 min, with half times of about 20 min and 2 h. Photosynthetic CO(2) fixation was restored almost in parallel with the first recovery phase of the PSII reaction center activity. Although the amount of absorbed water became more than 20 times the initial dry weight of the N. commune colony in the presence of sufficient water, about twice the initial dry weight was enough for recovery and maintenance of the PSII activity.

Acclimatization↗

Low-molecular-mass polypeptide components of a photosystem II preparation from the thermophilic cyanobacterium Thermosynechococcus vulcanus.

Using a recently introduced electrophoresis system [Kashino et al. (2001) Electrophoresis 22: 1004], components of low-molecular-mass polypeptides were analyzed in detail in photosystem II (PSII) complexes isolated from a thermophilic cyanobacterium, Thermosynechococcus vulcanus (formerly, Synechococcus vulcanus). PsbE, the large subunit polypeptide of cytochrome b(559), showed an apparent molecular mass much lower than the expected one. The unusually large mobility could be attributed to the large intrinsic net electronic charge. All other Coomassie-stained polypeptides were identified by N-terminal sequencing. In addition to the well-known cyanobacterial PSII polypeptides, such as PsbE, F, H, I, L, M, U, V and X, the presence of PsbY, PsbZ and Psb27 was also confirmed in the isolated PSII complexes. Furthermore, the whole amino acid sequence was determined for the polypeptide which was known as PsbN. The whole amino acid sequence revealed that this polypeptide was identical to PsbTc which has been found in higher plants and green algae. These results strongly suggest that PsbN is not a member of the PSII complex. It is also shown that cyanobacteria have cytochrome b(559) in the high potential form as in higher plants.

Amino Acid Sequence↗