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Biomedical subjects

Masanobu Kawakami

Publications and source records attributed to Masanobu Kawakami.

At least 19 recordsLinked to original sources
PubMed2007

Prevention of diabetic retinopathy by intraocular soluble flt-1 gene transfer in a spontaneously diabetic rat model.

The number of patients suffering from diabetes mellitus is constantly rising worldwide, and diabetic retinopathy (DR) has become the most frequent cause of postnatal blindness. Vascular endothelial growth factor (VEGF) is known to play a central role during DR development. Thus, inhibiting the effects of VEGF may hamper the disease progression, and gene transfer of the soluble VEGF receptor sflt-1 is an attractive approach for this purpose. However, the lack of suitable animal models hindered the evaluation of this strategy. Recently, the spontaneously diabetic non-obese Torii (SDT) rat was established and is considered as one of the ideal models for human DR. In this study, we evaluated the efficacy of gene therapy in SDT rats by using adeno-associated viral vectors (AAV-sflt-1) injected into the subretinal space. Thirty weeks later, the progression of DR was assessed by fluorescein angiography using three parameters; the presence of an avascular area, extensive hyperfluorescein and arterial narrowing. These changes were significantly less evident in the 'treated' eyes than in the control. No adverse effects were observed throughout the study. These results indicate that local sflt-1 gene transfer inhibits DR progression in SDT rats and offers powerful therapeutic potential for the management of human DR.

Animals↗
PubMed2006

Effect of topical nipradilol on retinal microvascular leukocyte adhesion in diabetic rats.

BACKGROUND: Retinal leukostasis plays an important role in the pathogenesis of diabetic retinopathy. OBJECTIVES: We studied the effects of nipradilol, a topical antiglaucoma alphabeta-blocker and nitric oxide donor, on the retinal vascular leukocyte adhesion of rats with diabetes. METHODS: Diabetes was induced in seven Brown-Norway rats by one intravenous injection (65 mg/kg) of streptozotocin and confirmed by blood glucose levels >350 mg/dl 48 h after the injection. Nipradilol solution was instilled in the right eye and nipradilol-free base solution in the left eye for 3 weeks, after which the retinal microcirculation was evaluated by acridine orange leukocyte digital fluorography using laser scanning ophthalmoscopy. Leukocytes trapped in the retina were counted around the optic disc in a 5-disc-diameter area and compared between the right and the left eye. RESULTS: The mean retinal leukostasis count in the nipradilol-treated eyes (19 +/- 15 cells) was significantly lower than in the untreated eyes (49 +/- 19 cells; p < 0.0008). The diameter of the retinal artery in the eyes treated with nipradilol significantly increased (111 +/- 13.5%) compared with untreated eyes (p < 0.03). CONCLUSIONS: Topical nipradilol significantly reduced retinal leukostasis in the retinal microcirculation in diabetic rats and may be a prophylactic agent for early diabetic retinopathy through its nitric oxide donor effects on the microcirculation.

Administration, Topical↗
PubMed2006

Increased blood spermine levels decrease the cytotoxic activity of lymphokine-activated killer cells: a novel mechanism of cancer evasion.

Increased blood polyamine levels, often observed in cancer patients, have negative impacts on patient prognosis and are associated with tumor progression. The purpose of our study was to examine the effects of polyamines on cellular immune function. Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were cultured with the human natural polyamines spermine, spermidine, or putrescine, and the effects on immune cell function were examined. The correlation between post-operative changes in blood polyamine levels and lymphokine-activated killer (LAK) activity was also examined in cancer patients. Spermine decreased the adhesion of non-stimulated PBMCs to tissue culture plastic in a dose- and a time-dependent manner without affecting cell viability or activity. This decrease in adhesion capacity was accompanied by a decrease in the number of CD11a bright-positive and CD56 bright-positive cells. Upon stimulation with interleukin 2 to activate LAK cytotoxicity, PBMCs cultured overnight with 100 or 500 microM spermine showed decreased cytotoxic activity against Daudi cells (91.5 +/- 1.7 and 84.9 +/- 3.0%, respectively (n = 6) compared to PBMC cultured without polyamines). In a group of 25 cancer patients, changes in blood spermine levels after surgery were negatively correlated with changes in LAK cytotoxicity after surgery (r = -0.510, P = 0.008: n = 25). Increased blood spermine levels may be an important factor in the suppression of anti-tumor immune cell function.

Cell Adhesion↗
PubMed2006

Age-related changes in carotid artery flow and pressure pulses: possible implications for cerebral microvascular disease.

BACKGROUND AND PURPOSE: We sought to establish the relation between the pulsatile components of pressure and flow waveforms in the carotid artery and their change with age. METHODS: Distention (pressure) and axial flow velocity waveforms were recorded noninvasively and simultaneously from the common carotid artery of 56 healthy subjects aged 20 to 72 years. RESULTS: There was a close relation between the time intervals of pressure and flow waves: from foot to first shoulder or peak, to second shoulder or peak, and to incisura (r=0.97, P<0.0001 for each), which approximated the line of identity. The peak and nadir of flow velocity decreased with age, but late systolic flow augmentation increased substantially (1.6 times in the older group); this can be attributed to earlier wave reflection from the lower body. Pressure augmentation index (PAI) and flow augmentation index (FAI) increased similarly with age (PAI (%) = 0.84 x age - 26.6; FAI (%) = 0.75 x age + 11.9; both P<0.0001). CONCLUSIONS: Arterial stiffening with aging increases carotid flow augmentation and can explain the increasing flow fluctuations in cerebral blood vessels. Measurement of carotid FAI may provide a gauge for risk of cerebral microvascular damage, just as PAI provides a gauge for risk of left ventricular hypertrophy and failure.

Adult↗
PubMed2006

Prospective assessment of proliferative diabetic retinopathy with observations of posterior vitreous detachment.

PURPOSE: To study the relation between posterior vitreous detachment (PVD) and progression of diabetic retinopathy (DR), based on our observation that proliferative DR is rare in patients with complete PVD. METHODS: The medical records of 403 patients with diabetes were reviewed for the relation between progressive DR and the status of PVD and HbA(1c) over 3 years. PVD was classified into none, complete PVD with collapse, complete PVD without collapse, partial PVD with a thickened posterior vitreous cortex, and partial PVD without a thickened posterior vitreous cortex. DR was classified into none, simple, preproliferative, or proliferative. When it became more extensive or when laser treatment or vitreous surgery was performed, the DR was considered progressive. RESULTS: Progression of DR over 3 years occurred in 128/292 (43.8%) eyes with no PVD, 0/14 (0%) eyes with complete PVD with collapse, 2/8 (25%) eyes with complete PVD without collapse, 15/15 (100%) eyes with partial PVD with a thickened posterior vitreous cortex, and 19/74 (25.7%) eyes with partial PVD without a thickened posterior vitreous cortex. Progression of DR occurred significantly more frequently in eyes with partial PVD with a thickened posterior vitreous cortex compared to eyes with complete PVD with collapse (p<0.0001). HbA(1c), did not differ significantly between these two groups (6.9 +/- 0.9% and 7.5 +/- 0.9%, respectively; p = 0.14), although HbA(1c) was significantly higher (p = 0.04) in patients with progressive DR (78 +/- 1.8%) than in patients without progressive DR (7.5 +/- 1.5%). CONCLUSION: Complete PVD is a strong negative risk factor for DR. The PVD status in patients with diabetes should be evaluated.

Diabetic Retinopathy↗
PubMed2006

Possible vascular role of increased plasma arginine vasopressin in congestive heart failure.

BACKGROUND: The present study was undertaken to determine the relation of cardiac dysfunction with hormonal release in patients with congestive heart failure. METHODS: Seventy-two patients with congestive heart failure were examined, who were divided into four subgroups classified by the criteria of the New York Heart Association (NYHA). Also, 10 age-matched subjects were served as a control. Plasma arginine vasopressin (AVP), norepinephrine, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined. Cardiac index and pulmonary capillary wedge pressure (PCWP) were measured in 51 of 72 patients. RESULTS: Plasma AVP levels were significantly increased according to the severity of NYHA classes; control: 1.7 +/- 0.2; NYHA I: 4.9 +/- 0.8, NYHA II: 5.5 +/- 0.9, NYHA III: 13.4 +/- 2.6 (p < 0.05), NYHA IV: 26.9 +/- 5.6 pmol/l (p < 0.001). Similar results were obtained with plasma norepinephrine, ANP and BNP. Plasma AVP levels had negative correlation with cardiac index (r = -0.36, p < 0.01), but did not with PCWP and plasma osmolality. Plasma BNP levels positively correlated with PCWP (r = 0.44, p < 0.001), but did not with cardiac index. There was no correlation between plasma AVP and BNP. Intensive therapy profoundly reduced all the hormones according to the improvement of cardiac index in the patients with NYHA class III and IV. The percent decrease in plasma AVP was 60.0%, a value greater than that in plasma BNP. CONCLUSION: The present study indicates that increased AVP may deteriorate cardiac function through V(1a) as well as V(2) action, and that plasma AVP level is also a proper marker for the presence and severity of congestive heart failure.

Adult↗
PubMed2006

Plasma triglyceride and HDL-cholesterol concentrations in Vietnamese girls are affected by lipoprotein lipase, but not apolipoprotein CIII polymorphism.

Lipoprotein lipase (LPL) and apolipoprotein CIII (apoCIII) play an important role in HDL-cholesterol and triglyceride metabolism. This study examined the effects of LPL S447X and apoCIII SstI polymorphisms on the plasma lipid and lipoprotein concentrations in Vietnamese girls. Three hundred and fifty-one Vietnamese girls, from 7 to 9 y of age, were randomly selected from the urban and rural areas of Ho Chi Minh City, Vietnam. The presence of LPL S447X and apoCIII polymorphism was determined using the Invader assay, and the plasma lipid concentrations were measured by an enzymatic method. Dietary intakes and anthropometrics were assessed for each child. The frequencies of LPL 447X (11.9%) and apoCIII S2 (32.6%) polymorphisms in the Vietnamese were similar to those of other Asian populations. The frequency of LPL 447X was the same as that in Caucasians but the frequency of apoCIII S2 was approximately 3.8 times that in Caucasians. Overall, LPL 447X polymorphism was associated with a higher HDL-cholesterol concentration (7.4%, P = 0.007) and a lower triglyceride concentration (-13.6%, P = 0.04) than LPL 447S. The apoCIII S2 polymorphism was not associated with an increase in the plasma triglyceride concentration in Vietnamese girls with a low fat intake. However, due to the high frequency of the apoCIII SstI polymorphism and the increasingly westernized diet in Vietnam, attention should be paid to the interaction of genotype with the Vietnamese diet.

Alleles↗
PubMed2006

Pulse wave analysis and pulse wave velocity: a review of blood pressure interpretation 100 years after Korotkov.

The pulsatile component of blood pressure (ie, pulse pressure) has received considerable attention as an important risk factor for cardiovascular disease. In particular, central blood pressure measurements in the ascending aorta or in the carotid artery are expected to be more useful than conventional brachial pressure measurements for predicting cardiovascular events because central pressure, not the brachial pressure, is the pressure that target organs encounter. Due to wave reflection, the blood pressure in the upper limb does not represent the central blood pressure; therefore, leading researchers have enthusiastically promoted a noninvasive method of measuring central blood pressure and the resulting aortic stiffness. Until now, there has been an increasing body of evidence to support the accuracy and superiority of central blood pressure measurements as well as the assessment of aortic properties over classical brachial pressure measurements. In this review, the information regarding these "central" indices derived from 2 main methods, namely "pulse wave analysis" and "pulse wave velocity", for the application of central blood pressure measurements and arterial stiffness to clinical study and practice, has been summarized.

Aorta↗
PubMed2006

Association of hyperadiponectinemia with severity of ventricular dysfunction in congestive heart failure.

BACKGROUND: Adiponectin, which is a collagen-like plasma protein produced by adipose tissue, has anti-atherogenic and anti-inflammatory effects. Plasma adiponectin levels in patients with congestive heart failure (CHF) were determined, as well as relationships between the plasma levels of adiponectin and other hormones. METHODS AND RESULTS: The study group comprised 90 patients with CHF and 20 control subjects, who were divided into 4 subgroups according to New York Heart Association (NYHA) functional class. Plasma levels of adiponectin, tumor necrosis factor (TNF)-alpha and brain natriuretic peptide (BNP) and cardiac hemodynamics were determined. Plasma adiponectin levels were significantly increased according to the severity of NYHA class in the patients with CHF; control: 6.2+/-1.0; NYHA I: 8.5+/-1.9, NYHA II: 12.0+/-2.2, NYHA III: 13.0+/-2.7, NYHA IV: 14.9+/-2.7 microg/ml (p=0.0008). Similarly, plasma BNP levels were significantly increased in accordance with the NYHA class. Plasma adiponectin levels correlated positively with BNP (r=0.40, p=0.0002) and TNF-alpha (r=0.49, p=0.0001), and correlated negatively with cardiac index (r=-0.27, p=0.05). In 24 of 46 patients in the NYHA III and IV subgroups, according to the prompt improvement in cardiac function, levels of both plasma adiponectin and BNP were significantly reduced (p<0.0001). CONCLUSION: Plasma adiponectin levels increased according to the severity of CHF and, moreover, they correlated with the plasma levels of BNP and TNF-alpha. These results indicate that augmented release of adiponectin is involved in the pathogenesis of CHF and further study is needed to elucidate its exact role.

Adiponectin↗
PubMed2006

Close association of regional interleukin-6 levels in the infarct-related culprit coronary artery with restenosis in acute myocardial infarction.

BACKGROUND: The involvement of interleukin (IL)-6 in restenosis of the recanalized coronary artery after the percutaneous coronary intervention (PCI) was examined. METHODS AND RESULTS: There were 40 patients enrolled in the study who had acute myocardial infarction and whose infarct-related coronary arteries were treated by new thrombectomy devices and stenting. Blood samples were collected from the culprit coronary artery before and immediately after the maneuver of the PCI. Restenosis was defined as residual stenosis because it accounted for more than 50% at the follow-up coronary angiography. Plasma IL-6 levels in the infarct-related coronary artery were 12.8 and 13.2 pg/ml before and after the initial maneuver of the PCI, respectively, values that were significantly greater than that of 7.2 pg/ml in the peripheral vein (p<0.0001). The levels of IL-6 in the pre- and the post-stage of PCI were significantly greater in the patients with restenosis than those without restenosis. The plasma IL-6 levels in the post-stage of PCI had significant correlations with late loss and loss index. CONCLUSIONS: The present study findings indicate that plasma IL-6 levels in the culprit coronary artery at the post-stage of PCI are closely associated with the future restenosis of the revasculized coronary artery in acute myocardial infarction.

Acute Disease↗
PubMed2006

Successfully treated massive pulmonary thromboembolism and thrombus in the right atrium due to diffuse malignant lymphoma: a case report.

A 40-year-old man presented with massive pulmonary embolism related to diffuse large B cell lymphoma. His hemodynamic state worsened rapidly to shock after sudden onset of dyspnea. Echocardiography and thoracic computed tomography indicated pulmonary thromboembolism due to deep venous thromboembolism, associated with a mass in the anterior mediastinum and a 5 x 8 cm mass in the left pelvis compressing the left femoral vein. He underwent emergent surgery to remove a huge thrombus from the right atrium through the bilateral pulmonary arteries. Soon after this surgery, his hemodynamic state recovered and excision of the left cervical lymph node revealed diffuse large B cell lymphoma. Venous compression by the lymphoma mass had caused hemostasis and thrombus formation in the present case.

Adult↗
PubMed2005

Erythropoietin attenuates cachectic events and decreases production of interleukin-6, a cachexia-inducing cytokine.

In cancer cachexia, erythropoietin often yields beneficial therapeutic effects by improving patient's metabolic and exercise capacity via an increased erythrocyte count. However, erythropoietin also has counter-regulatory effects against pro-inflammatory cytokines, which are postulated to be mediators of cancer cachexia. We investigated the mechanisms by which erythropoietin improves the cachectic condition. In this study, 100 Units/day of erythropoietin were administered intraperitoneally to BALB/c male mice, carrying a subclone of colon 26 adenocarcinoma, beginning on the day after tumor inoculation and continuing until they died. Erythropoietin administration attenuated the decline in body weight, as well as the decline in fat and muscle weights, of tumor-bearing mice, but improved the survival of cachectic mice. Mice receiving erythropoietin had increased erythrocyte and platelet counts, but significantly decreased white blood cell count. In addition, erythropoietin administration significantly decreased interleukin-6 levels, not only in serum but also in the inoculated tumor. These results indicate that the positive therapeutic effects of erythropoietin on cancer cachexia are due, not only to improving metabolic and exercise capacity via an increased erythrocyte count, but also to attenuation of cachectic manifestations by decreased production of the cachexia-inducing cytokine, interleukin-6.

Adenocarcinoma↗
PubMed2005

Relation of atherothrombosis burden and volume detected by intravascular ultrasound to angiographic no-reflow phenomenon during stent implantation in patients with acute myocardial infarction.

This study investigated the mechanism of occurrence of the no-reflow phenomenon during stent implantation in patients with acute myocardial infarction (AMI) using intravascular ultrasound (IVUS) with volumetric analysis. Of 70 patients with AMI who underwent IVUS-guided stent implantation within 24 hours of symptom onset, 12 developed decreased Thrombolysis In Myocardial Infarction flow grade during stent implantation and without subsequent restoration to Thrombolysis In Myocardial Infarction flow grade before stenting. External elastic membrane cross-sectional area and maximum diameter at the culprit lesion as measured by IVUS before stent implantation were significantly larger in the no-reflow group (n = 12) than in the normal reflow group (n = 58; 20.1 +/- 6.5 vs 16.4 +/- 4.3 mm2, p = 0.015 for cross-sectional area and 5.2 +/- 0.9 vs 4.8 +/- 0.6 mm, p = 0.049 for maximum diameter). Plaque volume, volumetric plaque burden (plaque volume/external elastic membrane volume), and change in plaque volume during stent implantation (plaque volume after vs before) were significantly greater in the no-reflow group than in the normal reflow group (239 +/- 142 vs 178 +/- 72 mm3, p = 0.030; 0.76 +/- 0.07 vs 0.71 +/- 0.06, p = 0.010; and -46 +/- 63 vs -11 +/- 37 mm3, p = 0.013, respectively). In conclusion, high atherothrombotic burden and decreased plaque volume as detected by IVUS may be risk factors for development of the no-reflow phenomenon during stent implantation in patients with AMI.

Aged↗
PubMed2005

Alteration in risk factor accumulations of acute myocardial infarction during the last one decade: analysis of patients admitted in Coronary Care Unit.

The present study was undertaken to determine accumulation of risk factors in acute myocardial infarction during two periods of 2002 and 1990-1991. We collected 173 and 153 patients with acute myocardial infarction in 2002 and 1990-1991, respectively, and analyzed the history of multiple risk factors, including diabetes mellitus, impaired glucose tolerance, hyperlipidemia, hypertension and obesity, and laboratory findings. The numbers and their percentages of all the risk factors increased in 2002 compared with 1990-1991. According to plasma glucose level, the patients who had type 2 diabetes mellitus, and impaired fasting glucose or impaired glucose tolerance had increased markedly from 41 to 65%. Multiple accumulation of risk factors had increased during the last one decade, and only one or no risk factor per se was not the case in the patients with acute myocardial infarction. Hyperlipidemia and hypertension became fairly controlled in the patients, but not hyperglycemia in type 2 diabetes mellitus in the period of 2002. These findings may indicate that increased multiple accumulation of risk factors accelerates the occurrence of acute myocardial infarction in 2002 as compared to 1990-1991.

Blood Glucose↗
PubMed2005

Up-regulated synthesis of mature-type adrenomedullin in coronary circulation immediately after reperfusion in patients with anterior acute myocardial infarction.

OBJECTIVE: Levels of adrenomedullin (AM), a potent vasodilatory peptide, have been shown to increase in the early stage of acute myocardial infarction (AMI). The purpose of this study was to determine whether coronary sinus-aortic step-up of mature forms of AM is accelerated in patients with AMI after reperfusion. METHODS: The subjects were 29 consecutive patients with a first episode of anterior AMI and 10 normal controls. All patients with AMI underwent balloon reperfusion therapy within 24 h after symptom onset. Plasma levels of two molecular forms of AM (an active, mature form [AM-m] and an intermediate, inactive glycine-extended form [AM-Gly]) in the aorta and coronary sinus (CS) were measured by specific immunoradiometric assay after reperfusion. RESULTS: Plasma levels of AM-m and AM-Gly in the aorta and CS were higher in AMI patients than in controls. CS-aortic step-up of AM-m, which is an index of myocardial production of AM-m, was significantly greater in AMI patients than in controls (1.7 +/- 1.4 vs. 0.4 +/- 0.3 pmol/L, P < 0.01). However, there was no significant difference in CS-aortic step-up of AM-Gly (P = 0.30). AMI patients with left ventricular dysfunction (n = 10) had a significantly higher CS-aortic AM-m step-up than AMI patients without left ventricular dysfunction (n = 19). AM-m in the aorta and CS negatively correlated with the left ventricular ejection fraction (r = -0.50, r = -0.48, P < 0.01). CONCLUSIONS: Myocardial synthesis of AM-m is accelerated in patients with reperfused AMI, especially in patients with critical left ventricular dysfunction. Increased myocardial synthesis of active AM may protect against cardiac dysfunction, myocardial remodeling, or both after the onset of AMI.

Adrenomedullin↗
PubMed2005

Spermine, a natural polyamine, suppresses LFA-1 expression on human lymphocyte.

Natural polyamines, spermine, spermidine, and putrescine, play a pivotal role in the regulation of gene expression; therefore, the age-dependent decreases and the disease-dependent increases in polyamine synthesis suggest a possible contribution of polyamines to the age-related and disease-associated changes in cellular function. In this study, we examined the effects of polyamines on the cellular function and the expression of adhesion molecules on human PBMCs from healthy volunteers. Flow cytometry revealed that PBMCs cultured with spermine decreased mean fluorescent intensities (MFIs) of CD11a and CD18 in the lymphocyte light-scattered region, but not in the monocyte region. This suppression was observed in a dose- and time-dependent manner and found nonspecifically on all cell subsets we tested (CD3(+), CD4(+), CD8(+), CD19(+), CD45RA(+), CD45RO(+), CD4(+)CD45RA(+), CD4(+)CD45RO(+), CD8(+)CD45RA(+), CD8(+)CD45RO(+)). The decreases of CD11a and CD18 MFIs were accompanied by the decrease in adherent capacity of PBMCs to HUVECs. Spermine did not hinder cell activities or cell viability. Among 42 healthy volunteers (mean, 49.5 years old; from 26 to 69), blood spermine levels inversely correlated with the CD11a MFIs of cells in the lymphocyte region (r = -0.48; p = 0.001), but not with those in the monocyte region. The effects of spermidine seemed weaker than those of spermine, and blood spermidine levels had no correlation with CD11a MFIs of the lymphocyte region. Putrescine had no effect on the expressions of membrane molecules. Polyamines, especially spermine, decrease LFA-1 (CD11a/CD18) expression on human lymphocyte and adhesion capacity of PBMCs to HUVECs.

CD11a Antigen↗