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K Kohara

Publications and source records attributed to K Kohara.

At least 19 recordsLinked to original sources
PubMed2004

Brain-derived neurotrophic factor increases inhibitory synapses, revealed in solitary neurons cultured from rat visual cortex.

To elucidate chronic actions of brain-derived neurotrophic factor (BDNF) on GABAergic synapses, we examined effects of a long-term application of BDNF for 10-15 days on autapses (synapses) of solitary GABAergic neurons cultured from rat visual cortex. Solitary neuron preparations were used to exclude a possible contamination of BDNF actions on excitatory neurons in dissociated neuron culture or slice preparations. Neurons were confirmed to be GABAergic pharmacologically with bicuculline, a selective antagonist for GABAA receptors and immunocytochemically with antibody against glutamic acid decarboxylase 65, a GABA synthesizing enzyme. To evaluate GABAergic synaptic function, evoked and/or miniature inhibitory postsynaptic currents (IPSCs) were recorded in the whole-cell voltage-clamp mode. The treatment with BDNF at a concentration of 100 ng/ml enhanced the amplitude of evoked IPSCs and the frequency of miniature IPSCs. In contrast, BDNF did not have a detectable effect on the amplitude of miniature IPSCs and the paired pulse ratio of IPSCs evoked by two, successive activations. To evaluate morphological changes, neurons were immunocytochemically stained with antibodies against microtubule-associated protein 2, to visualize somatodendritic region and synapsin I, to visualize presynaptic sites. The quantitative analysis indicated that BDNF increased the area of soma, the numbers of primary dendrites and dendritic branching points, the total length of dendrites and the number of synaptic sites. Such an action of BDNF was seen in both subgroups of GABAergic neurons, parvalbumin-positive and -negative neurons. To visualize functionally active presynaptic sites, neurons were stained with a styryl dye, FM1-43. BDNF increased the number of stained sites that was correlated with the frequency of miniature IPSCs. These results suggest that the chronic treatment with BDNF promotes dendritic and synaptic development of GABAergic neurons in visual cortex.

Analysis of Variance↗
PubMed2001

Activity-dependent transfer of brain-derived neurotrophic factor to postsynaptic neurons.

Neurotrophins such as brain-derived neurotrophic factor (BDNF) are thought to be transferred from post- to presynaptic neurons and to be involved in the formation and plasticity of neural circuits. However, direct evidence for a transneuronal transfer of BDNF and its relation to neuronal activity remains elusive. We simultaneously injected complementary DNAs of green fluorescent protein (GFP)-tagged BDNF and red fluorescence protein into the nucleus of single neurons and visualized expression, localization, and transport of BDNF in living neurons. Fluorescent puncta representing BDNF moved in axons in the anterograde direction, though some moved retrogradely, and transferred to postsynaptic neurons in an activity-dependent manner.

Animals↗
PubMed2001

An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and common carotid atherosclerosis.

Plasma homocysteine (Hcy) concentration has been shown to be influenced by a mutation in the gene coding methylenetetrahydrofolate reductase (MTHFR). Although plasma Hcy is related to atherosclerotic disorders, conflicting results have been reported about the association between MTHFR gene polymorphism and sclerotic lesions of the common carotid arteries. The effect of age-gene interaction on carotid arterial remodeling was investigated in elderly subjects with several risk factors for atherosclerosis. We evaluated sclerotic lesions of the common carotid arteries by ultrasonography in 326 patients (mean age +/- standard deviation, 73 +/- 12 years) and studied relations among the known risk factors for atherosclerosis, including MTHFR gene polymorphism and its interactions with age and sex. Of the 326 subjects studied, 136 had MTHFR genotype CC, 136 genotype CT, and 54 genotype TT. The three groups did not differ with respect to background factors such as age, history of cigarette smoking, blood pressure, lipids or uric acid, or in the incidence of atherosclerotic diseases. Spearman's rank correlation revealed a significant relationship between gender, age, Brinkman index, systolic blood pressure, triglycerides, HDL-cholesterol (HDL-C), uric acid, and MTHFR gene polymorphism. Multiple regression analysis using intima-media complex thickness (IMT) as a criterion variable and risk factors, including MTHFR gene polymorphism as explanatory variables showed that MTHFR gene polymorphism (P = 0.039) was a significant independent explanatory variable for IMT, along with gender (male) (P < 0.001), age (P < 0.001), systolic blood pressure (SBP) (P = 0.047), total cholesterol (T-C) (P < 0.001), and HDL-C (P < 0.001). Furthermore, a general linear model analysis revealed that interaction between age and MTHFR gene polymorphism was significantly associated with IMT, independently of age, SBP, T-C, and HDL-C in male subjects. However, age-gene interaction was not observed in female subjects. The findings of the present study confirm an association between MTHFR gene polymorphism and common carotid atherosclerosis in the Japanese population and further support the role of risk factor-gene interaction in common carotid atherosclerosis.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2001

Risk factor-gene interaction in carotid atherosclerosis: effect of gene polymorphisms of renin-angiotensin system.

The risk factor-gene interaction in carotid atherosclerosis was investigated in 205 community-dwelling healthy subjects aged 50 years or more in Japan. The intima-media thickness (IMT) of the common carotid artery was evaluated by ultrasonography with a 7.5-MHz probe. Gene polymorphisms were determined for each subject with angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T, angiotensin II type 1 receptor (AT1R) A1166C, and apolipoprotein E (apoE) genotypes. There was no genotype-specific difference in carotid IMT among any genes examined. Combinations of genotypes did not increase carotid IMT compared with subjects without these genotypes. In the total population, multiple regression analysis showed that age, systolic blood pressure (SBP), sex, and body mass index (BMI) were significantly associated with carotid IMT. However, the association between risk factors and IMT was genotype-specific. Age was significantly associated with IMT in ACE D carriers, but not in subjects with the ACE II genotype. Analysis of covariance adjusted with other risk factors showed that the age-dependent change in IMT was significantly different between subjects with the ACE II genotype and the ACE D carriers (F[1.196] = 4.97; P = 0.027). Similarly, the regression of IMT on SBP was significantly different between AGT TT and AGT MT + MM (F[1.196] = 7.20; P = 0.0079). The regression of IMT on BMI was also significantly different between apo E4 carriers and noncarriers (F[1.196] = 6.78; P = 0.0099). Furthermore, general linear model analysis with risk factors, genotype, and risk factor-genotype interactions revealed that the age*ACE genotype interaction, the SBP*AGT genotype interaction, and the BMI*apoE genotype interaction were significantly associated with IMT. These findings further support the role of risk factor-gene interaction in carotid atherosclerosis.

Aged↗
PubMed2001

Increase in number of functional release sites by cyclic AMP-dependent protein kinase in cultured neurons isolated from hippocampal dentate gyrus.

The enhancement of synaptic exocytosis is one form of long-term potentiation (LTP) of synaptic transmission. As possible mechanisms underlying this enhancement, increases in the release probability and/or the number of release sites are suggested. To obtain direct evidence for the increase in the number of functional release sites induced by protein kinase A (PKA) cascade, we attempted to visualize functional release sites using styryl dyes, FM4-64 and FM1-43, and investigated the effects of PKA on the release sites. A PKA activator FSK increased the number of active release sites by approximately 20-30%. A direct PKA activator, Sp-cAMPS, showed the same effect, which was blocked by a PKA inhibitor, KT5720, suggesting that this effect was mediated by PKA. This PKA-dependent increase in the number of release sites requires Ca(2+) in the bath solution, and Sr(2+) can not be a substitute for Ca(2+). Since the number of functional release sites is approximately half the total number of synaptophysin-immunoreactive sites, the PKA dependent activation of silent release sites of DG neuron terminals is suggested.

Animals↗
PubMed2001

Association between carotid arterial remodeling and plasma concentration of circulating hepatocyte growth factor.

BACKGROUND: Several studies have reported that the circulating concentration of hepatocyte growth factor (HGF) was increased in individuals with clinically overt atherosclerotic disease, including coronary heart disease and peripheral arterial disease. However, whether changes in the circulating concentration of HGF are associated with early atherosclerotic changes in apparently healthy individuals remains to be determined. OBJECTIVE: To investigate the relationship between the plasma concentration of HGF and carotid arterial remodeling. METHODS: Plasma concentrations of HGF were measured in 201 community-dwelling healthy residents free from any medications and signs and history of cardiovascular disease. Carotid intima-media thickness (IMT) and carotid internal diameter were determined by ultrasonography with a 7.5 MHz probe. The study participants were divided into four groups according to the presence or absence of carotid atherosclerosis (presence of plaque, IMT > or = 0.85 mm) and carotid arterial dilatation (diameter > or = 7.0 mm). RESULTS: Carotid arterial remodeling, atherosclerosis or dilatation, or combinations thereof, was associated with significantly greater concentrations of plasma HGF. Among risk factors, plasma HGF was significantly associated with advanced age (> or = 65 years), current smoking and diabetes mellitus, whereas sex, obesity, hypertension and hypercholesterolemia did not affect plasma concentrations of HGF. Multiple regression analysis showed that plasma HGF was independently associated with carotid arterial remodeling (atherosclerosis, dilatation, or both) in addition to age and systolic blood pressure. CONCLUSIONS: These results indicate that the plasma concentration of HGF increases in relation to carotid arterial remodeling, independently of known risk factors for atherosclerosis. These findings further support a possible role of HGF in atherosclerosis.

Aged↗
PubMed2001

[Early treatment with non-invasive positive pressure ventilation a successful case of bulbar type amyotrophic lateral sclerosis].

A 60-year-old man who has suffered dysarthria since 1999. He had noticed twitching of right upper extremity and orbicularis oris muscle since August 2000. The bulbar type of amyotrophic lateral sclerosis was diagnosed. He was admitted for evaluation of sleep disorder with respiratory distress on November 20, 2000. Arterial blood gas analysis on admission showed marked hypercapnea (PaCO2:51.6 Torr). Nocturnal hypoxia index, which was calculated using the nocturnal oximetry monitoring, was elevated. Non-invasive positive pressure ventilation started during sleep at night, although it was earlier than to start for mechanical ventilation. After one week, both hypercapnea and his nocturnal hypoxia index, together with symptoms, improved markedly. Respiratory insufficiency due to progressive fatigue of respiratory muscles, such as diaphragm and intercostal muscles, is a major cause of death in amyotrophic lateral sclerosis. In general mechanical ventilation is introduced when marked hypercapnea and dyspnea become clinically overt. However, the exact time to introduce noninvasive methods of ventilatory support for amyotrophic lateral sclerosis has not been established. Based on the observation in this patient, we would suggest that earlier introduction of non-invasive mechanical support for ventilation (nocturnal hypoxia index > 70) would be useful to improve the symptoms and to prolong the life of patients with ALS. The nocturnal hypoxia index is useful to decide the time of the introduction of non-invasive mechanical support for ventilation.

Amyotrophic Lateral Sclerosis↗
PubMed2001

[Non-operative management of dens fracture in an elderly patient with severe complications].

An 82-year-old woman was diagnosed with hypertension at the age of 50 and had been treated with antihypertensive agents. Proteinuria was detected at age 60 and her renal function subsequently deteriorated. Hemodialysis was started on February 14, 2000. She fell out of the bed and hit her neck in the early morning on February 15. Neck X-ray tomography revealed Anderson type III dens fracture. Since she had several complicating conditions including angina pectoris and arrhythmia, she was treated by external fixation using a halo-vest. The neck pain improved gradually. During her clinical course, she experienced delirium due to immobilization. However, bone union was complete 5 months later. Physicians should be aware of the possibility that even minor injury can cause dens fracture in elderly patients. Conservative management of type III dense fracture should be considered for elderly patients with a compromised condition.

Aged↗
PubMed2000

Helicases and aging.

Studying monogenic hereditary disorders that manifest age-related phenotypes in cells, tissues, and the total organism would be helpful for clarifying the mechanisms of aging. In this context, seven human disorders that manifest age-related phenotypes have been found to be caused by aberrations of five proteins with seven helicase motifs conserved in most of the helicases. These disorders are xeroderma pigmentosum, Cockayne syndrome, trichothiodystrophy, Bloom syndrome, Werner syndrome, X-linked alpha-thalassemia/mental retardation syndrome, and Juberg-Marsidi syndrome. A decline of probably pleiotropic and fundamental function of helicases in these disorders is, therefore, implied to underlie not only the various age-related phenotypes of the disorders but also the pleiotropic and universal nature of ordinary aging. Consistent with this implication, studies of these seven disorders suggest that their various age-related phenotypes are caused by aberrations in multiple processes, especially transcription. Furthermore, a few studies imply some association between aberration of the helicases and phenotypes in ordinary aging.

Aging↗
PubMed2000

Association of ACE I/D polymorphism with cardiovascular risk factors.

Since the identification of an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene, the D allele has been recognized to be associated with cardiovascular disease. Moreover, significant associations of this polymorphism with multiple cardiovascular risk factors have been reported, although some studies failed to detect such associations. In the present study, we investigated the association of the ACE gene polymorphism with the parameters of multiple risk factors in 300 Japanese men who participated in a medical check-up. This investigation detected a significant association of the polymorphism with systolic blood pressure (P=0.007) and diastolic blood pressure (P=0.026), with their highest values in DD subjects and lowest values in II subjects. This significant association is consistent with the proposition that the polymorphism influences blood-pressure variability in men. Furthermore, we investigated the association of the polymorphism with four major disorders (obesity, hyperlipidemia, hypertension, diabetes mellitus) correlated with the risk for cardiovascular disease in the same 300 subjects. This investigation failed to detect any significant association of the polymorphism with each disorder. However, there was a trend that all four disorders were more frequent in ID and DD subjects than in II subjects. We therefore analyzed the association between the ACE gene polymorphism and having at least one of the four disorders in the same population. This analysis detected a significant difference: that ID and DD subjects had at least one of the four disorders more frequently than II subjects (P=0.008; odds ratio=1.89, 95% confidence interval= 1.19-2.99). Taken together, the results of this study are compatible with the proposition that the ACE polymorphism is associated with cardiovascular disease partially mediated through the four disorders in our population.

Adult↗
PubMed2000

Increased exocytotic capability of rat cerebellar granule neurons cultured under depolarizing conditions.

To obtain insights into the mechanisms underlying activity-dependent survival of neurons, we surveyed various indices of cellular activity in rat cerebellar granule neurons cultured under conditions advantageous and disadvantageous for survival. Previously, we reported that the turnover of Ca2+ (both influx and efflux) is activated in raised K+-cultures (survival condition), although the cytoplasmic Ca2+ concentration is not affected. We also reported that endocytotic activity was high in the high K+-cultures. In the present study, we used the release of FM1-43 dye [N-(3-triethylammoniumpropyl)-4-(4-dibutylamino)styryl)py ridium bromide] to determine the exocytotic capabilities of neurons cultured in normal K+ (death condition), high K+ (survival condition) and brain-derived neurotrophic factor-supplemented (survival condition) media. The FM1-43 releases triggered by K+-induced depolarization and glutamate exposure were significantly higher in the high K+-cultures than in normal K+-cultures. Interestingly, the neurons whose survival was supported by brain-derived neurotrophic factor did not show high exocytotic capability, indicating that the high exocytotic capability is not a mere result of viability. However, the number of synaptic sites per cell (as monitored by synaptophysin immunopositivity) was unaffected by culture conditions. The present results suggest that an enhanced exocytotic activity supported by a strengthened exocytotic capability may underlie the high viability of rat cerebellar granule neurons cultured under depolarizing conditions.

Animals↗
PubMed2000

Low wall shear stress in carotid arteries in subjects with left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular complications including atherosclerosis. The close linkage between LVH and carotid atherosclerosis has been the focus of much research. However, the underlying mechanism linking the two conditions is not fully understood. Low wall shear stress contributes to intimal thickening and atherosclerosis development as a local mechanism. In the present study, we investigated the relationship between wall shear stress and LVH in subjects with risk factors for atherosclerosis. Eighty subjects with at least one risk factor for atherosclerosis; ie, hypertension, diabetes mellitus, hyperlipidemia, or smoking, were enrolled. Intimal-medial thickness (IMT), number of plaques, internal dimensions, and blood flow velocity in the common carotid artery were evaluated. Wall shear stress was calculated using a Poiseuillean parabolic model of velocity distribution: shear stress = 4 x blood viscosity x central flow velocity/internal dimension. Subjects were divided into two groups; LVH(-) (n = 36) and LVH(+) (n = 44), according to their left ventricular mass index (LVMI). Mean shear stress and systolic peak shear stress were significantly lower in subjects with LVH compared with subjects without LVH. Furthermore, mean shear stress (r = -0.42, P < .0001) and peak shear stress (r = -0.31, P < 0.01) were significantly inversely related to LVMI. Stepwise regression analysis revealed that wall shear stress independently correlated with LVMI as well as IMT. These results indicate that low shear stress could function as a local factor in the development of atherosclerosis in subjects with LVH.

Arteriosclerosis↗
PubMed2000

Association between risk factors for atherosclerosis and mechanical forces in carotid artery.

BACKGROUND AND PURPOSE: Mechanical stresses on the arterial wall participate in the pathogenesis of atherosclerosis as local factors. The relationships between local mechanical forces and risk factors for atherosclerosis were investigated. METHODS: Mechanical forces on the arterial wall were evaluated in the carotid artery in 117 patients with risk factors for atherosclerosis including hypertension, dyslipidemia, diabetes mellitus, and smoking, as well as in 20 age- and sex-matched normal controls. Circumferential wall tension and shear stress were evaluated with Laplace's law and a poiseuillean parabolic model of velocity distribution. Circumferential wall strain was also evaluated as carotid mechanical force. RESULTS: Mechanical forces in subjects with risk factors were characterized by low wall shear stress, high circumferential wall tension, and reduced strain. Systolic blood pressure was significantly negatively associated with shear stress and circumferential wall strain. HDL cholesterol showed a significant positive correlation with shear stress and a negative correlation with wall tension. Fasting blood glucose was significantly associated with shear stress, while smoking showed a negative correlation with shear stress and a positive correlation with wall tension. Accumulation of risk factors was associated with further deterioration of mechanical forces. Furthermore, stepwise regression analysis showed that the number of risk factors was significantly associated with mechanical forces independently of carotid intima-media thickness. CONCLUSIONS: These findings suggest that risk factors for atherosclerosis were associated with alteration of mechanical forces. Consequent alteration in mechanical forces could be an underlying local mechanism for the progression of atherosclerosis.

Arteriosclerosis↗
PubMed2000

Deletion polymorphism of ACE gene is associated with higher blood pressure after hospitalization in normotensive subjects.

Blood pressure has been shown to decrease in response to hospital admission. Several parameters including the decline of sympathetic nervous activity and negative sodium balance have been shown to be involved in this phenomenon. We investigated genetic influence on office BP and BP after hospitalization. One hundred and sixty-three men from the general population, free from antihypertensive medication, were enrolled in the present study. They stayed at the hospital for general medical check-up. BP was measured on the day of admission, and again the following day. Mean systolic blood pressure was significantly decreased after hospitalization from 117.3 +/- 9.9 mmHg to 115.3 +/- 12.8 mmHg (p=0.042). Subjects with DD+ID genotype showed a significantly higher systolic blood pressure after hospitalization than that of subjects with genotype II. There were no genotype specific differences in diastolic blood pressure or changes in blood pressure by the administration. In summary, systolic blood pressure after hospitalization was significantly higher in normotensive male subjects who possessed the D allele of ACE I/D polymorphism.

Alleles↗
PubMed2000

[A very elderly autopsy case of cecal cancer with pulmonary lymphangitis carcinomatosa].

A 91-year-old man was admitted with colliquative diarrhea, anorexia and weight loss. He had a history of healed tuberculosis, hypertension and atherosclerotic abdominal aortic aneurysms. On admission, shortness of breath without cough, exertional dyspnea, and ascites were also noticed. His chest X-ray and CT showed almost normal findings in the lung fields except for calcified old pleurisy. Since laboratory tests revealed thrombocytopenia, low fibrinogen, and increased CA19-9. DIC induced by an unknown cancer was diagnosed. He died on the eighth day due to progressive respiratory failure which did not respond to oxygen therapy. Autopsy revealed that he had a poorly differentiated adenocarcinoma in the cecum complicated with pulmonary lymphangitis carcinomatosa. Lymphangitis should be considered in the case of unexplained progressive respiratory failure developing in patient with cancer, even in the absence of X-ray findings.

Adenocarcinoma↗