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Koichi Yokono

Publications and source records attributed to Koichi Yokono.

At least 19 recordsLinked to original sources
PubMed2006

Quantification of distension in rat cerebral perforating arteries.

We developed a novel cerebral angiography procedure for rodents using monochromatic synchrotron radiation X-rays and obtained images of rat cerebral perforating arteries for the first time. In normotensive rat, hypercapnia rapidly distended the perforators between 3 and 15 min after induction and major trunk vessels distended more rapidly in 3-6 min. Systemic hypotension made by stepwise hemorrhage distended the perforators up to 158% of control values but constricted most of the large cerebral trunk vessels. In spontaneous hypertensive rats, systemic hypotension-induced distension disappeared in perforators, indicating that perforators with chronic hypertension lose their autoregulatory distensibility.

Animals↗
PubMed2006

In vivo X-ray angiography in the mouse brain using synchrotron radiation.

BACKGROUND AND PURPOSE: We, for the first time, performed in vivo x-ray angiography in the mouse brain using SPring-8, a third-generation synchrotron radiation facility. METHODS: A thin PE-50 tube was placed in the unilateral external carotid artery in adult male C57BL/6J mice. While maintaining the blood flow in the internal carotid artery, 33 muL of contrast agent was injected and then selective angiography of the hemisphere was performed. RESULTS: The average diameters of cerebral artery were as follows: 142.5+/-7.90 microm in middle cerebral artery, 138.3+/-9.35 microm in anterior cerebral artery, 120.5+/-5.53 microm in posterior cerebral artery, and 162.6+/-10.87 microm in internal carotid artery (n=5). To demonstrate the changes in diameter, we induced hypercapnia and detected the dilatation of the vessels between 121% and 124% of the original diameters (n=5). We also repeated angiography in the mice before and after intracarotid injection of vasodilatation drugs papaverine hydrochloride, ATP disodium, and fasudil hydrochloride hydrate and demonstrated the chronological changes in the diameters in each artery at 1, 5, 15, and 30 minutes after injection (n=1 for each drug). CONCLUSIONS: Using only a minimum volume of the contrast agent, synchrotron radiation enables us to study x-ray angiography in the mouse brain. The morphology of the vessels can be clearly observed under physiological conditions. The diameters and their changes can also be successfully studied in vivo.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2006

Suppression of the mTOR-raptor signaling pathway by the inhibitor of heat shock protein 90 geldanamycin.

Heat shock protein 90 (Hsp90) was co-immunoprecipitated with raptor, the binding partner of the mammalian target of rapamycin (mTOR) from HEK293 cells. Hsp90 was detected in the anti-raptor antibody immunoprecipitates prepared from the cell extract by immunoblot analysis using the anti-Hsp90 antibody, and the association of these two proteins was confirmed by immunoprecipitation from the cells co-expressing Hsp90 and raptor as epitope-tagged molecules. Geldanamycin, a potent inhibitor of Hsp90, disrupted the in vivo binding of Hsp90 to raptor without affecting the association of raptor and mTOR, and suppressed the phosphorylation by mTOR of the downstream translational regulators p70 S6 kinase (S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). The protein kinase activity of S6K as well as the phosphorylation of the substrate, 40S ribosomal protein S6, were lowered in the geldanamycin-treated cells. These results indicate that Hsp90 is involved in the regulation of protein translation by facilitating the phosphorylation reaction of 4E-BP1 and S6K catalyzed by the mTOR/raptor complex through the association with raptor, and that the mTOR signaling pathway is a novel target of geldanamycin.

Adaptor Proteins, Signal Transducing↗
PubMed2006

[Group B streptococcal vertebral osteomyelitis following superficial suppurative thrombophlebitis].

An 80-year-old woman with type II diabetes mellitus was admitted to hospital with high-grade fever and leg pain for the previous three days. Physical examination revealed marked distention of the peripheral veins in both lower legs and she complained of pain. Spontaneous superficial suppurative thrombophlebitis was diagnosed and transfusion of cefazolin every 8 hours was started immediately after blood cultures. After 48 hours, the distention of the peripheral veins was improved; however, she suffered from a severe back pain thereafter. Two sets of blood culture yielded Group B streptococcus. Therefore the antibiotic was changed to ampicillin every 6 hours. To investigate the cause of back pain, MRI of the lumbar vertebral body was taken. Saggital gadolinium T1-weighted MRI demonstrated a high signal intensity lesion from Th7 to Th11, suggesting vertebral osteomyelitis following Group B streptococcal bacteremia from superficial suppurative thrombophlebitis. One week later, the clinical symptoms mostly disappeared. After six weeks of treatment, she was discharged. Suppurative thrombophlebitis is an inflammation of the vein wall by microorganisms and sometimes causes secondary metastatic abscess. Aging and diabetes are also risk factors for group B streptococcal invasive infection. This case suggests vertebral osteomyelitis should be taken into consideration during the course of group B streptococcal bacteremia in an elderly patient complaining back pain.

Aged↗
PubMed2006

[Possible role of mitochondrial dysfunction in insulin resistance in the elderly].

Both decreased insulin secretion and insulin resistance are two major factors of impaired glucose tolerance (IGT) in the elderly. Up to now, decreased lean body mass and relatively increased fat mass contribute to insulin resistance in the elderly. However, recent reports indicate that muscle mitochondrial function is reduced in aging, and this age-associated decline in mitochondrial function contributes to insulin resistance in the elderly. In addition, exercise intervention to IGT in the elderly is more effective to reduce in the incidence of type 2 diabetes than in younger people. Exercise seems to improve insulin resistance through mitochondrial function by activating AMP-activated protein kinase(AMPK) and PPARgamma coactivator-1alpha (PGC-1alpha).

Adenylate Kinase↗
PubMed2006

[Cognitive dysfunction and dementia associated with elderly diabetes].

Diabetes mellitus and cognitive decline are major public health concerns among the elderly. In diabetic subjects without dementia, certain cognitive domains are impaired, such as memory, attention, and executive/frontal lobe function (diabetic cognitive dysfunction). Recent epidemiological studies have suggested that diabetes increases the risks for vascular dementia as well as Alzheimer's disease. There are accumulating evidences that indicate biological linkage between impaired brain glucose metabolism homeostasis and cognitive decline. Diabetes may cause serious brain damages through several mechanisms and induce a variety of cognitive decline. Most critical issue to be resolved is to identify the mechanism of dementia leading from diabetic cognitive dysfunction. Once elderly diabetics had severe cognitive decline, effective treatment of diabetes were hardly obtained. Thus, diabetic cognitive decline should be considered as an important comorbidity of the elderly diabetes and long-term management of hyperglycemia is required from a view point to sustain healthy brain function. In this short review, we are summarizing the clinical features and current biological findings of diabetic cognitive decline. Also, we introduce the comprehensive treatment of demented diabetic elderly, including therapeutic strategy, nursing and care.

Aged↗
PubMed2006

Impaired response of perforating arteries to hypercapnia in chronic hyperglycemia.

Diabetes mellitus increases the risk of cerebrovascular disease, the effects of hypercapnia on CBF (cerebral blood flow) and cerebrovascular reactivity during diabetes are still inconsistent. Here, we have established a new microangiographic technique using synchrotron radiation (SPring-8, Japan), which enabled us to visualize rat cerebral vessels with high spatial resolution in real time. The goal of the study presented here was to identify the effects of chronic hyperglycemia on hypercapnia-induced vascular responses (endothelium-dependent vasodilatation) and nitric oxide (NO) donor- induced vascular responses (endothelium-independent) of perforating arteries and of the deeply located large cerebral arteries. We found a significant vasodilatation of rat perforating arteries after hypercapnia with a maximum diameter of approximately 140% of baseline in normal Wistar rats. Chronic hyperglycemia impaired vasodilatation of perforating arteries in genetically diabetic GK rats. SNP (sodium nitroprusside) caused a similar vasodilatation of perforating vessels in normal and chronic hyperglycemia, indicating that endothelium-dependent vasodilatation of perforating arteries may be specifically impaired in chronic hyperglycemia. Possible impairment of endothelium-dependent vasodilatation in perforating vessels during chronic hyperglycemia may cause decreased vascular reserve capacity of perforating artery, resulting in the increased ischemic insults and cerebrovascular diseases in diabetes.

Animals↗
PubMed2006

Carotid artery occlusion and collateral circulation in C57Black/6J mice detected by synchrotron radiation microangiography.

Using monochromatic synchrotron radiation, we performed microangiography in C57BL/6J mice and investigated their vasculature after unilateral and bilateral carotid artery occlusion. Bilateral occlusion of the carotid artery was made by a ligation of the left common carotid artery followed by a ligation of the right internal carotid artery (ICA) two days later (n=12). Five days after the second surgery, angiography was performed. Unilateral occlusion was made by clipping the right ICA and then angiography was performed immediately (n=5). The control mice did not undergo any occlusion (n=5). We removed the brain of the bilateral occlusion mice after angiography and examined the infarction area. The cerebral microvessels in all animals were clearly visualized. In the control mice, the posterior communicating artery (Pcom) was not visualized. In the unilateral occlusion mice, the anastomosis of the pterygopalatine artery (PPA) and the external carotid artery (ECA) were recognized. The PPA is thus considered to play a role in the collateral vessel between the ICA and the ECA. The Pcom was not visualized. In the bilateral occlusion mice, the Pcom was observed either unilaterally (n=5) or bilaterally (n=5). The Pcom supplied blood flow to the anterior circulation from the vertebrobasilar arteries. The bilateral occlusion mice that had at least one visualized Pcom did not have any infarction. We could successfully visualize the cerebral vasculature of normal mice and carotid artery occluded mice in an in vivo study. Microangiography can demonstrate the development of vasculature and the blood flow dynamics in mice.

Angiography↗
PubMed2005

[Management of hypertension with diabetes mellitus in the elderly].

The number of an elderly patient who has hypertension with diabetes mellitus has been increasing year by year since the life style of people has become Americanized in our country. Metabolic syndrome is characterized by hypertension, dyslipidemia, central adiposity and insulin resistance. It is recently recognized as the high risk for the macrovascular disease such as cerebral infarction and acute myocardial infarction. In diabetic patients, to prevent the life-threatening event or slow complications intensive blood pressure control is as efficacious as good glycemic control. The optimal blood pressure level to reduce hypertension-related morbidity and mortality in diabetic elderly has been proposed 130/80 mmHg in JSH 2004. The blood pressure level in the elderly should be lowered very slowly with careful monitoring of systemic ischemia. Early use of antihypertensive drug combinations is gaining favor. As the first step therapy would be recommended angiotensin receptor blocker, angiotensin-converting enzyme inhibitor and sustained release calcium channel blocker. Especially in the elderly, good control of life-style related diseases would be achieved through a team effort comprising the clinician, psychologist, nurse, pharmacologist, dietitian, other professionals and the patient's family. Comprehensive geriatric assessment can facilitate the maintenance of drug compliance for well control of blood pressure level.

Aged↗
PubMed2005

Neuroprotective effect of D-fructose-1,6-bisphosphate against beta-amyloid induced neurotoxicity in rat hippocampal organotypic slice culture: involvement of PLC and MEK/ERK signaling pathways.

D-fructose-1,6-bisphosphate (FBP) is an endogenous intermediate of glycolytic pathway which has potent neuroprotective effect against various neurotoxic insults. This study examined whether FBP could antagonize the neurotoxicity induced by amyloid beta-peptide (Abeta) in rat hippocampal organotypic slice cultures, and the possible mechanism was also explored. Treatment with FBP (concentration ranges from 1.7 mM to 10 mM) significantly decreased the cell death in hippocampal slices in the presence of Abeta at 24h, 48 h and 72 h, and this neuroprotective effect of FBP against Abeta was not in a dose-dependent manner, FBP 3.5 mM has better neuroprotective effect than that of other FBP concentration groups. Treatment with FBP slightly but significantly increases the ATP levels in hippocampal slices in the presence of Abeta. However, the increment of ATP levels was similar among various FBP concentration groups. Neuroprotective effect of FBP 3.5 mM against Abeta induced neurotoxicity in hippocampal slices was attenuated by addition of phospholipase C (PLC) inhibitor, U73122, mitogen activated extracellular signal protein kinase (MEK) inhibitor, U0126, or extracellular signal activated protein kinase (ERK) inhibitor, PD98059 at 24 h, 48 h and 72 h. However, co-treatment with these three kinds of inhibitors did not change the FBP's effect on ATP levels. Our results suggested FBP has neuroprotective effect against Abeta induced neurotoxicity in hippocampal slice cultures, and FBP plays role not only as an alternative energy source, but also a modulator of PLC and MEK/ERK pathways to regulate the cellular response and survival.

Adenosine Triphosphate↗
PubMed2004

Glycolysis regulates the induction of lactate utilization for synaptic potentials after hypoxia in the granule cell of guinea pig hippocampus.

Lactate is considered an alternative substrate that is capable of replacing glucose in maintaining synaptic function in adult neurons. But, we found recently that lactate could be utilized for maintenance of synaptic potentials only after the activation of NMDA and voltage-dependent-calcium channel during glucose deprivation. To clarify more on the relationship between glycolysis and induction of lactate utilization, we tested lower concentration of glucose with hypoxia to induce a relative shortage of anaerobic energy production. Population spikes are not maintained with lactate following hypoxia in 10 mM glucose medium, but are maintained at their original levels with lactate after exposure to hypoxia in lower concentration (5 mM) of glucose. Hypothermia during low glucose-hypoxia, bath application of the NMDA channel blocker and the voltage-sensitive calcium channel blocker, as well as the omission of extracellular calcium prevented the induction of the lactate-supported population spikes. ATP levels in the tissue slices are relatively preserved in the conditions that block the induction of lactate-supported population spikes. From these observations, we propose that the energy source for maintenance of synaptic function in adult neuron changes from adult form (glucose alone) to immature one (glucose and/or lactate) after short of glucose supply.

Action Potentials↗
PubMed2004

Detection of autoreactive T cells in type 1 diabetes using coded autoantigens and an immunoglobulin-free cytokine ELISPOT assay: report from the fourth immunology of diabetes society T cell workshop.

The "gold standard" for evaluation of immunoassays is blinded testing, using coded samples and antigens. Although assays for autoreactive T cells are no exception to this rule, it is nonetheless rarely applied in this context. To facilitate such investigations, we coded a panel of 10 peptides representing T cell epitopes reported to be of relevance to islet autoimmunity. These were deployed in a novel cytokine ELISPOT assay, in which the use of immunoglobulin-free medium reduces background reactivity and thus potentially enhances the specificity and sensitivity of detection of autoreactive T cells. Significant IFN-gamma production against GAD65 (554-575), insulin (B9-23), and IA-2 (709-736) peptides were observed in type 1 diabetic patients, whereas no significant changes from background were detected in healthy controls. These results confirm the utility of the blinded performance of T cell assays as the most robust platform for assessing technologies to T cell autoreactivity.

Adolescent↗
PubMed2004

[Geriatric medicine and long-term care insurance].

Long-term care insurance (LCI) started from April 2000 in Japan. LCI now occupies a central position in the health care of the aged. We reviewed all original papers and reports on LCI published in 1996-2002. At the end of 2002, we searched for papers on LCI in a computer database using the keyword of LCI, and found 3,606 papers. Authors and contents of each paper were categorized using 54 kinds of keywords. Frequent authors were government agencies, care managers, physical therapists, and physicians. When we analyzed these papers according to the places where LCI was used, more than 50% of reports concerned LCI at home. Most frequent keywords were Government/LCI system. Regional health, Physician' assessment and grades for care. Care management, Care manager, and Rehabilitation. Care manager was less observed after the start of LCI. In contrast, the use of keywords including Care service. Dementia, Geriatric syndrome, Nurse, Institutional medicine, Hospital care, Medicine for the aged, Terminal care, Dialysis therapy, Abuse of the aged, and Caregiver burden were increased after LCI. At the beginning of LCI, main concerns are on the new LCI system. However, more individual issues in the care of the aged are now discussed. New issues such as Abuse of the aged and Caregiver burden have been recently raised. From these observations, the role of geriatric medicine seems also to be changing after the induction of LCI. We would now contribute actively to crucial aspects of LCI, such as comprehensive assessment of the aged, functional medical network with care staffs, and new therapeutic approaches to each geriatric syndrome.

Aged↗