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Biomedical subjects

J Watanabe

Publications and source records attributed to J Watanabe.

At least 55 records · Page 3Linked to original sources

[18F] labeled diacylglycerol analogue as a potential agent to trace myocardial phosphoinositide metabolism.

Phosphoinositide metabolism plays an important role in cardiac pathophysiology. To investigate whether [18F]diacylglycerol could be used to trace myocardial phosphoinositide metabolism, lipids were extracted from rat myocardium after the injection. 1-[8-[18F]fluorooctanoyl]-2-palmitoylglycerol and 1-[8-[18F]fluoropalmitoyl]-2-palmitoylglycerol were predominantly metabolized to phosphatidylethanolamine and triacylglycerol, respectively. The radioactivity incorporated into phosphoinositide metabolism was 51, 44, 32, and 30% 3, 5, 10, and 30 minutes after the injection of 1-[4-[18F]fluorobutyryl]-2-palmitoylglycerol, respectively. 1-[4-[18F]fluorobutyryl]-2-palmitoylglycerol might be a potential tracer to evaluate myocardial phosphoinositide metabolism early after the injection.

Animals↗

Controllable erosion time and profile in poly(ethylene glycol) hydrogels by supramolecular structure of hydrolyzable polyrotaxane.

A series of poly(ethylene glycol) (PEG) hydrogels cross-linked by a hydrolyzable polyrotaxane was prepared and the hydrolytic erosion behavior was characterized. The hydrolyzable polyrotaxane consisting of many alpha-cyclodextrins (alpha-CDs) and a PEG chain capped with bulky end groups via ester linkages was used as a cross-linker in the PEG hydrogels, where alpha-CDs in the polyrotaxane were linked with another PEG chains to form hydrophilic PEG networks. From the result of the erosion study, the time to reach complete gel erosion was found to be prolonged by decreasing the polyrotaxane content and increasing the PEG/alpha-CD ratio. The PEG/alpha-CD ratio, indicating the number of PEG chains linked with one alpha-CD molecule, is considered to make the environment of the polyrotaxane more aqueous and lead to the hydrolysis of ester linkages in the polyrotaxane. However, the higher PEG/alpha-CD ratio prolonged the time of the hydrogel erosion. These results indicate the enhanced stability of ester hydrolysis in the hydrogels with highly water swollen state. Such an anomalous phenomenon may be due to the structural characteristic of the polyrotaxane: ester linkages may be included within the cavity of alpha-CDs, resulting in their enhanced stability. The erosion profile of the hydrogels was changeable by the M(n) of PEG-bisamine, independent of the polyrotaxane content. The hydrogels cross-linked by the polyrotaxane can be new candidates as long-term stable but actually hydrolyzable hydrogels for polymeric scaffolding in tissue engineering.

Cyclodextrins↗

Contribution of Na+/Ca2+ exchanger to the regulation of myogenic tone in isolated rat small arteries.

The contribution of the Na+/Ca2+ exchanger to the myogenic vascular tone was examined in rat isolated skeletal muscle small arteries (ASK) with pronounced myogenic tone and mesenteric small arteries (AMS) with little myogenic tone. Myogenic tone was assessed by the vascular inner diameter at transmural pressures of 40 and 100 mmHg. To depress the Na+/Ca2+ exchanger, the extracellular Na+ concentration ([Na+]o) was lowered from 143 to 1.2 mM by substituting choline-Cl for NaCl. The ASK developed significant myogenic tone and constricted further in low [Na+]o. Nifedipine (1 microM) reduced both myogenic tone and low [Na+]o-induced contraction. Because the membrane potential of ASK was not changed by low [Na+]o (-35 +/- 2 mV at 143 mM [Na+]o, -37 +/- 3 mV at 1.2 mM [Na+]o), depolarization-induced Ca2+ influx was not a cause of the low [Na+]o-induced contraction. The AMS did not develop significant myogenic tone. Although low [Na+]o also constricted AMS, the magnitude of constriction was significantly weaker than that in ASK (17 +/- 4 vs. 47 +/- 6%, P < 0.01, at 58 mM Na+). With Bay K 8644, AMS developed myogenic tone, and low [Na+]o-induced constriction was significantly increased. In conclusion, Na+/Ca2+ exchanger may play an important role in regulating myogenic tone, likely via mediating Ca2+-extrusion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Risk factors for severe respiratory syncytial virus-associated lower respiratory tract infection in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract infection that can be a life-threatening disease in infants and children. This study was conducted to look for independent risk factors for severe respiratory syncytial virus-associated lower respiratory tract infection (RSV-LRI) that required oxygen supplementation or mechanical ventilation. METHODS: Medical records of patients younger than 4 years hospitalized with RSV-LRI at Shizuoka Red Cross Hospital from July 1, 1995 to June 30, 1999 were reviewed. The patients were compared using univariate and multivariate logistic regression analysis. RESULTS: A total of 157 patients were hospitalized with RSV-LRI at Shizuoka Red Cross Hospital from the study time period. Of these, 20 patients (12.7%) were diagnosed with severe RSV-LRI. Subjects younger than 3 months of age had an odds ratio (OR) of 59.9 (95% confidence interval (CI) 14.7_244.0) for the dependent variable of severe RSV-LRI (P<0.0001). Subjects with a history of congenital heart disease also had an OR of 99.2 (95% C1 8.5-1160.1) (P<0.0005). CONCLUSIONS: Infants younger than 3 months without any underlying diseases may be at high risk for severe RSV-LRI. Respiratory syncytial virus prophylaxis is needed not only for high-risk patients, but for healthy early infants.

Age Factors↗

Renal pelvic carcinoma of horseshoe kidney caused systemic metastasis by implantation in prostate.

A case is reported of renal pelvic carcinoma of the horseshoe kidney in a 69-year-old man, which showed an interesting metastatic pattern by implantation in the prostate. A few months after transurethral resection of the prostate for benign prostate hyperplasia and extracorporal shock wave lithotripsy for renal stones, the patient complained of severe back pain due to multiple metastatic bone tumors. Autopsy revealed transitional cell carcinoma in the pelvis as well as in the prostate with remarkable vessel invasion. The clinical course and autopsy findings suggested that the systemic expansion of cancer cells from the renal pelvis was caused not only by direct metastasis but also by implantation in the prostate.

Aged↗

Microvolt T wave alternans in human cardiac hypertrophy: electrical instability and abnormal myocardial arrangement.

INTRODUCTION: Although T wave alternans (TWA) is a promising risk marker for myocardial electrical instability, it remains unclear how the presence of TWA is related to myocardial damage. METHODS AND RESULTS: TWA was measured in 28 patients with hypertrophic cardiomyopathy (HCM), 29 patients with hypertensive left ventricular hypertrophy (HLVH), and 15 normal volunteers using a CH2000 system. The amplitude of TWA (Valt) was measured at the lead with the maximum amplitude. Cardiac biopsy was performed in 12 HCM patients, who were divided into two groups (severe and mild) based on histologic findings of myocardial disarray and fibrosis. TWA was positive (Valt > 1.9 microV) in 61% of HCM and 31% of HLVH, despite a nearly identical left ventricular mass index (176 +/- 65 g/m2 vs 175 +/- 39 g/m2). Valt at heart rate = 110 beats/min was significantly greater in HCM with severe disarray and fibrosis than in HCM with mild disarray and in HLVH. CONCLUSION: In HCM patients, a positive TWA test probably is related to abnormal myocardial arrangement (disarray) and/or fibrosis, and it may reflect electrical instability of the myocardium.

Aged↗

Specificity of 17beta-oestradiol and benzo[a]pyrene oxidation by polymorphic human cytochrome P4501B1 variants substituted at residues 48, 119 and 432.

1. Eight human cytochrome P4501B1 (CYP1B1) allelic variants, namely Arg48 Ala119 Leu432, Arg48 Ala119 Val432 Gly48 Ala119 Leu432, Gly48 Ala119 Val432, Arg48 Ser119 Leu432, Arg48 Ser119 Val432, Gly48 Ser119 Leu432 and Gly48 Ser119 Va1432 (all with Asn453), were expressed in Escherichia coli together with human NADPH-P450 reductase and their catalytic specificities towards oxidation of 17beta-oestradiol and benzo[a]pyrene were determined. 2. All of the CYP1B1 variants expressed in bacterial membranes showed Fe2+.CO versus Fe2+ difference spectra with wavelength maxima at 446 nm and they reacted with antibodies raised against recombinant human CYP1B1 in immunoblots. The ratio of expression of the reductase to CYP1B1 in these eight preparations ranged from 0.2 to 0.5. 3. CYP1B1 Arg48 variants tended to have higher activities for 17beta-oestradiol 4-hydroxylation than Gly48 variants, although there were no significant variations in 17beta-oestradiol 2-hydroxylation activity in these eight CYP1B1 variants. Interestingly, ratios of formation of 17beta-oestradiol 4-hydroxylation to 2-hydroxylation by these CYP1B1 variants were higher in all of the Val432 forms than the corresponding Leu432 forms. 4. In contrast, Leu432 forms of CYP1B1 showed higher rates of oxidation of benzo[a]pyrene (to the 7,8-dihydoxy-7,8-dihydrodiol in the presence of epoxide hydrolase) than did the Val432 forms. 5. These results suggest that polymorphic human CYP1B1 variants may cause some altered catalytic specificity with 17beta-oestradiol and benzo[a]pyrene and may influence susceptibilities of individuals towards endogenous and exogenous carcinogens.

Alleles↗

Successful unrelated cord blood transplantation in Philadelphia chromosome positive acute lymphoblastic leukemia during pulmonary aspergillosis treated by anti-fungal therapy, granulocyte colony-stimulating factor-mobilized granulocytes and surgical resection: case report.

A 3-year-old girl with Philadelphia chromosome positive acute lymphoblastic leukemia developed pulmonary aspergillosis during severe neutropenia by re-induction therapy. She was treated by intravenous fluconazole, oral itraconazole with plasma level monitoring and surgical resection of the focus for 3 months after clinical diagnosis of fungal infection was made. Once she had recovered from surgery we attempted to induce remission with anti-fungal treatment. She developed fever and neutropenia and appeared unlikely to remit with conventional chemotherapy. Unrelated one-antigen-mismatched cord blood (CB) transplantation was performed 2 months after the induction therapy. Her pulmonary aspergillosis was reactivated during subsequent conditioning. Anti-fungal drugs were switched to amphotericin B and granulocyte colony-stimulating factor-mobilized granulocyte concentrates were transfused. She obtained engraftment and has maintained complete hematological and molecular remission without signs of aspergillus infection for 13 months so far after transplantation. Even very high-risk transplantation in pediatric patients could be successfully supported by carefully designed intense comprehensive medical care.

Amphotericin B↗

Base heart rate during sleep in hypertensive and normotensive subjects.

OBJECTIVE: Many studies have reported that the resting heart rate (HR) is intimately related to the prognosis of cardiovascular disease. However, HR in the waking state is influenced by psychological and physical activity and has low reproducibility. To measure the base HR (minimum and stable HR during sleep) with ease, we developed a wristwatch-type HR recorder. We then investigated the pathophysiological significance of the base HR. SUBJECTS AND METHODS: The subjects were 158 patients (82 men and 76 women) with essential hypertension (HT) on no medication and 204 normotensive (NT) subjects (105 men and 99 women, matched for age). On the basis of pulse waves from the wristwatch-type photoelectric plethysmograph, using a blue sensor with a wavelength of 450 nm, HR was recorded easily minute by minute during sleep time. In addition, 40 (23 men and 17 women) of the HT patients were hospitalized. Their cardiac index (CI) and stroke volume index (SVI) were measured by means of the cuvette method during waking time and night-time deep sleep when their HR had reached a minimum level. RESULTS: Mean base HR (HRo) in NT subjects was 49+/-4 beats per minute (bpm) and tended to rise with increasing age (r = 0.51, P < 0.01). In HT patients, HR0 was significantly higher: 60+/-7 bpm (P < 0.01). CI of HT patients, measured during night-time deep sleep, maintained a stable value of 2.45+/-0.36 l/min per m2. SVI in patients whose HR0 was above 60 was significantly lower than that in patients whose HR0 was below 60 (37+/-4.5: 45+/-4.8 ml/m2, P < 0.01). Corresponding differences in mean HR and SVI during waking or night-time, became smaller. CONCLUSIONS: These findings suggest that there is a close relation between base HR and cardiac function caused by such conditions as age and hypertension. This relation became indistinct during waking time. Moreover, the wristwatch-type HR recorder appears to be a useful tool for measuring base HR.

Adult↗

Nonselective endothelin receptor antagonist initiated soon after the onset of myocardial infarction may deteriorate 24-hour survival.

To investigate the effects of endothelin blockade initiated immediately after the onset of myocardial infarction on survival and left ventricular remodeling, treatment with the nonselective receptor antagonist TAK-044 (n = 22) or saline (n = 19) for 3 weeks was initiated immediately after coronary ligation in rats. The 24-h survival rate was significantly lower in the TAK-044 group than in the saline group. The systolic blood pressure 24 h after the onset of myocardial infarction was similar in the saline and TAK-044 groups, although it was significantly lower in the TAK-044 group during the 3-week protocol. Heart weight/tibial length was significantly increased in the TAK-044 group compared with the saline group. As all deaths in the TAK-044 group occurred within 24 h after myocardial infarction, we performed additional experiments using a separate group of rats 12-16 h after myocardial infarction. Plasma and myocardial endothelin-1 levels were significantly increased, and a bolus injection of TAK-044 significantly reduced left ventricular dP/dtmax in these rats that had had a myocardial infarction compared with sham-operated rats. Endothelin receptor blockade initiated immediately after the onset of myocardial infarction may deteriorate acute-phase survival and left ventricular remodeling. Inhibition of the positive inotropic action of endothlin-1 may partially explain the increased 24-h mortality.

Animals↗

Posttreatment follow-up of Helicobacter pylori infection using a stool antigen immunoassay.

The Helicobacter pylori stool antigen enzyme immunoassay (HpSA) was evaluated during posttreatment follow-up of patients in a country with a very high prevalence of H. pylori infection. From among 273 dyspeptic individuals (18 to 55 years) initially recruited from a shantytown in Lima, Peru, 238 participants who met the inclusion criteria and were suspected to be H. pylori positive based on (14)C urea breath test (UBT) results underwent endoscopy. Participants with endoscopy-proven infections received standard eradication therapy and were monitored by UBT and HpSA at 1 month following treatment and at 3-month intervals for 9 months posttreatment. A second endoscopy was performed if UBT results showed evidence of treatment failure or H. pylori recurrence. Biopsy results were considered the "gold standard" in all analyses. Among patients who underwent endoscopy, HpSA had a pretreatment sensitivity of 93%. Two-hundred thirty patients completed the treatment regimen, of whom 201 (93%) were considered to have had successful treatment outcomes based on a negative follow-up UBT. Thirty-two patients with UBT-defined treatment failures or H. pylori recurrences at any point during the 9-month follow-up underwent a second endoscopy. In the posttreatment setting, HpSA had an overall sensitivity of 73% and a specificity of 67%. Agreement between UBT and HpSA diminished throughout the follow-up. Among 14 participants in whom HpSA remained positive at 1 month following treatment despite UBT evidence of treatment success, 12 (86%) became HpSA negative within 3 months posttreatment. Although this study confirmed the validity of the HpSA in the initial assessment of dyspeptic patients, the test demonstrated a reduced overall accuracy in the detection of treatment failures and H. pylori recurrences during 9 months of posttreatment follow-up. Furthermore, in some patients it may take up to 3 months after successful eradication for antigen shedding to diminish to levels within the negative HpSA range.

Adolescent↗

Selective AV nodal vagal stimulation improves hemodynamics during acute atrial fibrillation in dogs.

Although the atrioventricular node (AVN) plays a vital role in blocking many of the atrial impulses from reaching the ventricles during atrial fibrillation (AF), a rapid irregular ventricular rate nevertheless persists. The goals of the present study were to explore the feasibility of novel epicardial selective vagal nerve stimulation for slowing of the ventricular rate during AF and to characterize the hemodynamic benefits in vivo. Electrophysiological-echocardiographic experiments were performed on 11 anesthetized open-chest dogs. Hemodynamic measurements were performed during three distinct periods: 1) sinus rate, 2) AF, and 3) AF with vagal nerve stimulation. AF was associated with significant deterioration of all measured parameters (P < 0.025). The vagal nerve stimulation produced slowing of the ventricular rate, significant reversal of the pressure and contractile indexes (P < 0.025), and a sharp reduction in one-half of the abortive ventricular contractions. The present study provides comprehensive evidence that slowing of the ventricular rate during AF by selective ganglionic stimulation of the vagal nerves that innervate the AVN successfully improved the hemodynamic responses.

Acute Disease↗

Stretch and quick release of rat cardiac trabeculae accelerates Ca2+ waves and triggered propagated contractions.

Rapid shortening of active cardiac muscle [quick release (QR)] dissociates Ca2+ from myofilaments. We studied, using muscle stretches and QR, whether Ca2+ dissociation affects triggered propagated contractions (TPCs) and Ca2+ waves. The intracellular Ca2+ concentration was measured by a SIT camera in right ventricular trabeculae dissected from rat hearts loaded with fura 2 salt, force was measured by a silicon strain gauge, and sarcomere length was measured by laser diffraction while a servomotor controlled muscle length. TPCs (n = 27) were induced at 28 degrees C by stimulus trains (7.5 s at 2.65 +/- 0.13 Hz) at an extracellular Ca2+ concentration ([Ca2+]o) = 2.0 mM or with 10 microM Gd3+ at [Ca2+]o = 5.2 +/- 0.73 mM. QR during twitch relaxation after a 10% stretch for 100-200 ms reduced both the time between the last stimulus and the peak TPC (PeakTPC) and the time between the last stimulus and peak Ca2+ wave (PeakCW) and increased PeakTPC and PeakCW (n = 13) as well as the propagation velocity (Vprop; n = 8). Active force during stretch also increased Vprop (r = 0.84, n = 12, P < 0.01), but Gd3+ had no effect (n = 5). These results suggest that Ca2+ dissociation by QR during relaxation accelerates the initiation and propagation of Ca2+ waves.

Actin Cytoskeleton↗

Declining trend in the in-hospital case-fatality rate from acute myocardial infarction in Miyagi Prefecture from 1980 to 1999.

The case-fatality rate from acute myocardial infarction (AMI) appears to have been declining in recent decades, so the present study reviewed the trend in in-hospital case-fatalities from AMI in Miyagi Prefecture, Japan, 1980-1999. The causes of death and the effects of gender and age on the trend were also analyzed. From the AMI registration database of the Miyagi Study Group for AMI, 12,961 cases of AMI were analyzed. The 30-day in-hospital case-fatality was calculated from the data for 1980-1999: data for causes of death were available for 1980-1997, and the data concerning primary percutaneous transluminal coronary angioplasty (PTCA) for AMI were available for 1997-1999. The in-hospital case-fatality rate declined from 17.0% in the early 80s to 7.3% in the late 90s (approximately 57% reduction). The in-hospital case-fatality rate was higher in female patients. Rhythm failure substantially decreased in the late 1980s. Pump failure is decreasing, but is still the biggest problem. The in-hospital case-fatality rate was significantly lower in patients received PTCA. The declining trend in the in-hospital case-fatality rate suggests the benefits of current therapeutic procedures, including primary PTCA, for AMI. Pump failure is an important target for further decreasing the trend.

Adult↗

Consumption of hypoallergenic flour prevents gluten-induced airway inflammation in Brown Norway rats.

Brown Norway rats were immunized with gluten, and then fed a diet containing hypoallergenic flour or an amino acid mixture. The rats were then made to inhale a solubilized gluten to induce gluten-specific bronchial asthma. The antibody levels in the serum of rats were measured by ELISA, and cell counts were done on cytospin preparations of bronchoalveolar lavage fluid. Body weight was decreased after allergen challenge in rats fed the amino acid mixture but not in rats fed the hypoallergenic flour. Antibody levels in the serum were significantly lower in rats fed hypoallergenic flour than in those fed the amino acid mixture. Differential cell counts in the bronchoalveolar lavage fluid showed that the numbers of eosinophils, lymphocytes, and neutrophils were significantly lower in rats fed the hypoallergenic flour than in those fed the amino acid mixture. These results suggest that hypoallergenic flour actively suppresses the allergic reactions, probably by inducing oral tolerance.

Animals↗

IgE-reactive 60 kDa glycoprotein occurring in wheat flour.

A new IgE-reactive glycoprotein with a molecular size of 60 kDa was isolated from wheat flour. The N-terminal amino acid sequence of the protein was LDPDESEXVTRYFRIR. The 8th amino acid residue would have been Asn to which the peroxidase-type glycochain was attached. The IgE-binding activity of the glycoprotein was rendered negligible by the enzymatic treatment applied for hypoallergenic flour production.

Amino Acid Sequence↗

A new double cuff sphygmotonometer for accurate blood pressure measurement.

Accurate measurement of blood pressure (BP) is essential in the diagnosis and treatment of hypertension, but neither auscultatory nor oscillometric methods measure intra-arterial BP accurately in all circumstances. Algorithms for automatic BP-measuring devices differ from manufacturer to manufacturer, and no clear authorized algorithm criteria have yet been established. We have devised a double-cuff sphygmotonometer to measure BP on the basis of clear algorithms, and investigated the accuracy of this new method by comparing it with the photo-oscillometric method, which is the most accurate method for non-invasive measurement of intra-arterial BP. In the new method, a small cuff (3x6 cm) replaces the photo-sensor in the brachial cuff (13x24 cm) of the photo-oscillometric device, and BP is determined by means of the oscillation within the small cuff. The comparison based on procedures of AAMI-protocol was performed in 136 hypertensive patients and 54 normotensive subjects. The difference in systolic BP between the photooscillometric and double-cuff methods was -2.26+/-2.31 mmHg (89% under 5 mmHg), and the corresponding difference in diastolic BP was 1.9+/-2.50 mmHg (94% under 5 mmHg). In conclusion, we have devised a new double-cuff method which improves on the photo-oscillometric method, and although it seems to be less accurate than the photo-oscillometric method, the clarity of its algorithm makes it superior to the conventional oscillometric and auscultatory methods employing only one cuff.

Algorithms↗

Surfactant lavage and replacement in meconium aspiration syndrome with pulmonary hemorrhage.

We reported two case studies of meconium aspiration syndrome (MAS) with pulmonary hemorrhage in which we applied surfactant lavage and replacement. Surfactant lavage and replacement of MAS with pulmonary hemorrhage appears to be effective and safe adjunctive therapy. The relatively small replacement doses of surfactant required may be attributed to surfactant lavage followed by surfactant replacement. We suggest that surfactant lavage and replacement of MAS with pulmonary hemorrhage should be further investigated by a randomized controlled trial.

Hemorrhage↗