Search PubMed⌕ Search

Biomedical subjects

S Sawada

Publications and source records attributed to S Sawada.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effect of rate and inspiratory flow on ventilator-induced lung injury.

BACKGROUND: We examined the effects of decreasing respiratory rate (RR) at variable inspiratory times (It) and reducing inspiratory flow on the development of ventilator-induced lung injury. METHODS: Forty sheep weighing 24.6+/-3.2 kg were ventilated for 6 hours with one of five strategies (FIO2 = 1.0, positive end-expiratory pressure = 5 cm H2O): (1) pressure-controlled ventilation (PCV), RR = 15 breaths/min, peak inspiratory pressure (PIP) = 25 cm H2O, n = 8; (2) PCV, RR = 15 breaths/min, PIP = 50 cm H2O, n = 8; (3) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 6 seconds, n = 8; (4) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 2 seconds, n = 8; and (5) limited inspiratory flow volume-controlled ventilation, RR = 5 breaths/min, pressure-limit = 50 cm H2O, flow = 15 L/min, n = 8. RESULTS: Decreasing RR at conventional flows did not reduce injury. However, limiting inspiratory flow rate (LIFR) maintained compliance and resulted in lower Qs/Qt (HiPIP = 38+/-18%, LIFR = 19+/-6%, p < 0.001), reduced histologic injury (HiPIP = 14+/-0.9, LIFR = 2.2+/-0.9, p < 0.05), decreased intra-alveolar neutrophils (HiPIP = 90+/-49, LIFR = 7.6+/-3.8,p = 0.001), and reduced wet-dry lung weight (HiPIP = 87.3+/-8.5%, LIFR = 40.8+/-17.4%,p < 0.001). CONCLUSIONS: High-pressure ventilation for 6 hours using conventional flow patterns produces severe lung injury, irrespective of RR or It. Reduction of inspiratory flow at similar PIP provides pulmonary protection.

Animals↗
PubMed2000

Dobutamine echocardiography for detection of viable myocardium in ischemic cardiomyopathy.

In patients with ischemic cardiomyopathy, revascularization of hibernating or stunned myocardium can result in improvement in global systolic function and prognosis. The recognition that revascularization can alter the course of ischemic cardiomyopathy has fueled the development of noninvasive methods for detection of viable myocardium. Dobutamine echocardiography has established utility as a method for identifying hibernating and stunned myocardium thereby improving the selection of candidates with ischemic cardiomyopathy for revascularization. This manuscript reviews the rationale and methodology for use of low and high dose dobutamine echocardiography for detection of viable myocardium. The predictive value of the technique is discussed and compared with that of other noninvasive imaging methods.

Cardiotonic Agents↗
PubMed2000

Effect of inotropic stimulation on left atrial appendage function in atrial myopathy of chronic atrial fibrillation.

Atrial fibrillation (AF) leads to remodeling of the left atrium (LA) and left atrial appendage (LAA), resulting in atrial myopathy. Reduced LA and LAA function in chronic AF leads to thrombus formation and spontaneous echo contrast (SEC). The effect of inotropic stimulation on LAA function in patients with chronic AF is unknown. LAA emptying velocity (LAAEV) and maximal LAA area at baseline and after dobutamine were measured by transesophageal echocardiography in 14 subjects in normal sinus rhythm (NSR) and 6 subjects in AF. SEC in the LA was assessed before and after dobutamine. LAAEV increased significantly in both groups. However, the LAAEV at peak dobutamine in patients with AF remained significantly lower than the baseline LAAEV in patients who were in NSR (P = 0.009). Maximal LAA area decreased significantly with dobutamine in both groups, but LAA area at peak dose of dobutamine in patients with AF remained greater than baseline area in those in NSR (P = 0.01). Despite the increase in LAAEV, SEC improved in only two of five patients. We conclude that during AF, the LAA responds to inotropic stimulation with only a modest improvement in function.

Atrial Appendage↗
PubMed2000

Suppression of acute viremia by short-term postexposure prophylaxis of simian/human immunodeficiency virus SHIV-RT-infected monkeys with a novel reverse transcriptase inhibitor (GW420867) allows for development of potent antiviral immune responses resulting in efficient containment of infection.

A nonnucleoside reverse transcriptase (RT) inhibitor, GW420867, was tested for postexposure prophylaxis (PEP) in rhesus macaques experimentally infected with 100 50% tissue culture infective doses of a chimeric simian/human immunodeficiency virus (SHIV) containing the RT gene of HIV-1 (SHIV-RT). Animals were either mock treated, or treated for 4 weeks starting at 8 or 24 h postinfection (p.i.) with GW420867. While such therapy led to undetectable plasma viremia in three of six monkeys, a transient plasma viremia was noted in the other three treated animals at 2 to 4 weeks following cessation of therapy. Following this transient viremia all drug-treated animals showed low or undetectable levels of plasma viremia up to the last sample examined at 90 weeks p.i. Despite low and/or undetectable viremia, virus-specific cytotoxic T lymphocyte and viral Env-specific proliferative responses were seen in the peripheral blood mononuclear cells of both mock- and drug-treated animals as early as 3 weeks p.i. Such virus-specific cellular responses, however, were better maintained in the drug-treated animals than the mock-treated animals. In contrast to the virus-specific cellular response, the magnitude and kinetics of virus specific humoral responses appeared to correlate with the detection of viremia. These data support the view that a short-term PEP with GW420867 permits the generation and maintenance of long-lasting virus-specific cell-mediated immune responses while markedly reducing viral loads to undetectable levels for a prolonged period of time (90 weeks) and leads to long-term disease protection. This model provides a unique means to define mechanisms and correlates of disease protection.

Animals↗
PubMed2000

Effects of bradykinin on prostaglandin I(2) synthesis in human vascular endothelial cells.

The effects of bradykinin on the regulatory mechanisms of prostacyclin synthesis in endothelial cells were investigated in association with intracellular Ca(2+) kinetics, cytosolic phospholipase A(2) (cPLA(2)) activity, and mRNA expression of cPLA(2) and prostaglandin H synthase (PGHS) isoforms. Bradykinin enhanced prostacyclin release from endothelial cells time-dependently, but pretreatment with EGTA H-7 or HOE 140 inhibited bradykinin-induced prostacyclin release. Bradykinin increased both the influx of extracellular Ca(2+) and Ca(2+) release from the intracellular Ca(2+) storage sites. These reactions occurred within 5 minutes after bradykinin stimulation. Within 15 minutes, bradykinin activated cPLA(2) to 1.3-fold the control level. The constitutive expressions of mRNA of cPLA(2), PGHS-1, and PGHS-2 was 87, 562, and 47 amol/microg RNA, respectively. With the stimulation of bradykinin, cPLA(2) mRNA increased to 746 amol/microg RNA in 15 minutes, PGHS-1 mRNA increased to 10 608 amol/microg RNA, and PGHS-2 mRNA increased to 22 400 amol/microg RNA in 180 minutes. Pretreatment with cycloheximide superinduced cPLA(2) and PGHS-2 mRNA expression but almost completely inhibited PGHS-1. Pretreatment with EGTA had effects similar to pretreatment with cycloheximide in the case of cPLA(2) and PGHS-1 but did not affect PGHS-2. These findings suggest that the elevation of cPLA(2) activity caused by the increase of intracellular Ca(2+) concentration is important in the early phase of bradykinin-induced prostacyclin synthesis and that the mechanisms regulating cPLA(2) are different from those regulating PGHS isoforms in endothelial cells.

Bradykinin↗
PubMed2000

Bioavailability assessment of arginine-vasopressin (AVP) using pharmacokinetic-pharmacodynamic (PK-PD) modeling in the rat.

A novel method of assessing the extent of oral bioavailability of arginine-vasopressin (AVP) from pharmacological data was presented. After intravascular administration (i.v. bolus or short-term infusion) of AVP to rats, the relationship between blood concentrations and its effect on both mean arterial pressure (hemodynamic effect) and urinary sodium concentration (anti-diuretic effect) was described on the basis of an integrated pharmacokinetic-pharmacodynamic (PK-PD) model. A direct model was used for the hemodynamic response, while an indirect response model, rather than a hypothetical link model was used for the anti-diuretic response. A sigmoid Emax model was applied to describe the drug-receptor interaction. Pharmacological responses after intravascular administration of AVP were reasonably described by the PK-PD model. However, PD parameters estimated by the PK-PD analysis suggested that apparent receptor affinity rather than efficacy in i.v. bolus study was significantly higher than that in the short-term infusion study. This fact indicated that PK-PD relationship was influenced by the intravascular input rate of AVP. We then investigated the relationship between plasma concentration and amount of AVP bound to the V2 receptors in the kidney. The result indicated that the amount of AVP bound to the receptors after i.v. bolus injection was always greater than that after short-term infusion. Since the PK-PD relationship after oral administration was almost identical with that after short-term infusion, the PK-PD model obtained in the short-term infusion study was used to assess the extent of oral bioavailability (EBAPp.o.). The EBAp.o. values, estimated from pharmacological effects (hemodynamic effect and anti-diuretic effect) after oral administration of 5 microg/kg of AVP were 0.68% to 0.93% and were almost identical with the actual EBAPp.o. value (0.81%). From these results, we concluded that oral bioavailability of AVP was reasonably predicted by the PK-PD model, provided that appropriate pharmacological effects and appropriate intravascular dosing rate as a reference formulation are available. The method may be an alternative to methods based on plasma concentrations, when drug concentration cannot be measured and when appropriate pharmacological data are available.

Administration, Oral↗
PubMed2000

Creation of aortic dissection model in swine.

The use of mongrel dogs for experimental purposes was recently restricted and this report presents the experience of creating an aortic dissection model in swine. All the swine in group 1 were anesthetized without pentobarbital and the descending aorta was side-clamped during the creation of the aortic dissection. The false lumen of the completed dissection was patent in the long term despite not having the anchoring suture that the previous canine model required to stabilize the opening of the entry tear. All the swine anesthetized with pentobarbital (ie, group 2) died of heart failure either during cross-clamping of the descending aorta or postoperative aortography. In conclusion, creation of a thoracic aortic dissection is possible in swine, but cross-clamping of the thoracic descending aorta and pentobarbital anesthesia should be avoided.

Aortic Dissection↗
PubMed2000

Abnormal IL-1 receptor antagonist production in patients with polymyositis and dermatomyositis.

OBJECTIVE: To examine the relationship between serum levels of interleukin-1 receptor antagonist (IL-1Ra) and its gene expression in peripheral blood mononuclear cells (PBMC) from patients with polymyositis and dermatomyositis (PM/DM). METHODS: IL-1Ra levels in sera from patients and supernatants of unstimulated monocyte cultures were measured by enzyme-linked immunosorbent assay. Expression of IL-1Ra mRNA was analyzed by Northern blotting, and an 86-base pair variable repeat polymorphism in intron 2 of the IL-1Ra gene was determined by polymerase chain reaction. RESULTS: Serum IL-1Ra was significantly elevated in 27 patients with active-stage PM/DM when compared with levels in 16 patients with inactive-stage PM/DM and 19 normal controls. Serum concentrations of IL-1Ra were correlated with PM/DM disease activity. IL-1Ra mRNA was detected in freshly isolated PBMC from patients with active-stage PM/DM, but not in controls. Moreover, IL-1Ra concentrations were increased significantly in unstimulated monocytes from patients with active-stage PM/DM compared with monocytes from normal controls. However, there were no significant differences in IL-1Ra allele frequencies between patients and normal controls. CONCLUSION: Elevation of both IL-1Ra mRNA and protein in sera of patients with active-stage PM/DM suggest that higher levels of serum IL-1Ra may reflect increased IL-1Ra production in myositis, and that IL-1Ra may regulate IL-1-mediated muscle fiber damage in PM/DM.

Adolescent↗
PubMed2000

Effects of saiko-ka-ryukotsu-borei-to on spontaneous locomotor activity in mice. Oriental Medicine Research Group.

The effects of the Japanese Kampo (herbal) medicine, Saiko-ka-ryukotsu-borei-to, on spontaneous locomotor activity were studied in mice. Saiko-ka-ryukotsu-borei-to (60 mg, 150 mg and 300 mg/kg/day) was administered for 14 consecutive days in the drinking water and spontaneous locomotor activity was measured for 60 min by a photocell ambulometer. Saiko-ka-ryukotsu-borei-to (60 mg/kg/day) significantly increased the total activity count on the 11th day after the start of administration when compared to vehicle control, whereas failed to significantly affect the activity on the 2nd, 5th, 8th and 14th days. A similar significant increase was also found with a higher dose (150 mg/kg/day) on the 8th day after the start of administration. However, the highest dose (300 mg/kg/day) did not significantly affect locomotor activity throughout the experimental period. We have previously reported that Saiko-ka-ryukotsu-borei-to, at a dose of 60 mg/kg/day, enhances escape attempts assessed by water-wheel rotations in a mouse model of despair, particularly on the 8th, 11th and 14th days after the start of chronic treatment. However, at higher doses (150 and 300 mg/kg/day), Saiko-ka-ryukotsu-borei-to decreases the escaped attempts on the 5th and 8th days after the treatment. It is therefore concluded that the previously reported changes in escape attempts of mice are not associated with the changes in their spontaneous locomotor activity.

Administration, Oral↗
PubMed2000

Changes in cold-induced vasodilatation, pain and cold sensation in fingers caused by repeated finger cooling in a cool environment.

To examine how repeated cooling of fingers with a rest pause schedule at work affects cold-induced vasodilatation (CIVD), pain and cold sensation in fingers, six healthy men aged 21 to 23 years immersed their left index fingers six times in stirred water at 10 degrees C for 10 minutes. After each cold-water immersion of the fingers, 5-minute rest pause was taken to observe the recovery process of the indicators. This cold-water immersion/rest pause test was carried out in a range of three ambient temperature conditions: 30 degrees C (warm), 25 degrees C (thermoneutral), and 20 degrees C (cool) as experienced in daily life. At the ambient temperatures of 30 degrees C and 25 degrees C, marked CIVD response occurred and the CIVD reactivity did not significantly change upon repetition of cold-water immersion. The lowered finger skin temperature also tended to recover quickly to the pre-immersion level during each post-immersion rest period. At the ambient temperature of 20 degrees C, however, the CIVD response weakened continuously upon repetition of immersion and almost disappeared during the final immersion. The recovery of finger skin temperature during each post-immersion rest was gradually delayed upon repetition of immersion. At every ambient temperature, finger pain and cold sensation induced by each cold-water immersion significantly decreased upon repetition of immersion and completely disappeared during each post-immersion rest period. Oral temperature during the experiment showed no significant change at the ambient temperatures of 25 degrees C and 30 degrees C, but it decreased significantly at the ambient temperature of 20 degrees C. These results suggest that in a cool work environment where the body core temperature is liable to decrease, repeated finger cooling may weaken CIVD reactivity and delay the recovery of finger temperature during post-immersion rest periods. In such lower ambient temperature work conditions, subjective judgements such as the decrease in finger pain and cold sensation during repeated finger cooling and the absence of them during post-immersion rest may not be reliable indicators for monitoring the risk of progressive tissue cooling and frostbite formation.

Adult↗
PubMed2000

Low density lipoproteins develop resistance to oxidative modification due to inhibition of cholesteryl ester transfer protein by a monoclonal antibody.

Although numerous studies have investigated the relationship between cholesteryl ester transfer protein (CETP) and high density lipoprotein (HDL) remodeling, the relationship between CETP and low density lipoproteins (LDL) is still not fully understood. In the present study, we examined the effect of the inhibition of CETP on both LDL oxidation and the uptake of the oxidized LDL, which were made from LDL under condition of CETP inhibition, by macrophages using a monoclonal antibody (mAb) to CETP in incubated plasma. The 6-h incubation of plasma derived from healthy, fasting human subjects led to the transfer of cholesteryl ester (CE) from HDL to VLDL and LDL, and of triglycerides (TG) from VLDL to HDL and LDL. These net mass transfers of neutral lipids among the lipoproteins were eliminated by the mAb. The incubation of plasma either with or without the mAb did not affect the phospholipid compositions in any lipoproteins. As a result, the LDL fractionated from the plasma incubated with the mAb contained significantly less CE and TG in comparison to the LDL fractionated from the plasma incubated without the mAb. The percentage of fatty acid composition of LDL did not differ among the unincubated plasma, the plasma incubated with the mAb, and that incubated without the mAb. When LDL were oxidized with CuSO4, the LDL fractionated from the plasma incubated with the mAb were significantly resistant to the oxidative modification determined by measuring the amount of TBARS and by continuously monitoring the formation of the conjugated dienes, in comparison to the LDL fractionated from the plasma incubated without the mAb. The accumulation of cholesteryl ester of oxidized LDL, which had been oxidized for 2 h with CuSO4, in J774.1 cells also decreased significantly in the LDL fractionated from the plasma incubated with mAb in comparison to the LDL fractionated from the plasma incubated without the mAb. These results indicate that CETP inhibition reduces the composition of CE and TG in LDL and makes the LDL resistant to oxidation. In addition, the uptake of the oxidized LDL, which was made from the LDL under condition of CETP inhibition, by macrophages also decreased.

Antibodies, Monoclonal↗
PubMed2000

Loss of heterozygosity on chromosome 6p21.2 as a potential marker for recurrence after radiotherapy of human cervical cancer.

Cervical carcinomas develop as a result of multiple genetic alterations, and specific alterations lead to specific clinical behavior. However, the effect of such alterations on the recurrence of cervical cancer after radiotherapy remains unknown. Chromosome arm 6p is one of those most frequently involved in a loss of heterozygosity (LOH) in patients with cervical carcinoma. The aim of this study was to identify the correlation between the LOH on chromosome 6p21.2 and the recurrence of cervical cancer after radiotherapy. A total of 62 patients with cervical cancer (stage I, 4 patients; stage II, 9 patients; stage III, 37 patients; and stage IV, 12 patients) were included in this study. All patients were treated with definitive radiotherapy. We analyzed specimens from the tumors and venous blood of all patients. Tumors and normal DNA were analyzed by PCR for genetic losses at three polymorphic microsatellite loci (D6S276, D6S1624, and D6S1583). Chromosome 6p21.2 is involved in the LOH in 46.8% (29 of 62) of the informative carcinomas. Ten patients had a local recurrence, 4 had distant metastases, and 13 had both local recurrence and distant metastases after radiotherapy. To evaluate the relationship between the recurrence after radiotherapy and LOH on chromosome 6p21.2, we divided the patients into those with cancer recurrence (n = 27) and those without recurrence (n = 35). LOH on chromosome 6p21.2 was correlated with recurrence after radiotherapy (P = 0.006). The tumors in patients with recurrence were significantly larger than those in patients without recurrence (P = 0.003). However, there was no correlation between the sizes and stages of tumors and the LOH on chromosome 6p21.2. In addition, both overall survival and relapse-free survival were significantly worse for the patients with LOH as compared with those without LOH (P = 0.02 and P = 0.002, respectively). The results of this study suggest that LOH on 6p21.2 is correlated with recurrence of cervical carcinoma after radiotherapy.

Adult↗
PubMed2000

A study of colloidal scintigraphy in alcoholic liver diseases: discordance from asialo-scintigraphic findings.

BACKGROUND: Our study was undertaken to check the discordance between findings from 99mTc-Sn colloidal reticuloendothelial scintigraphy (RESS) and 99mTc-GSA asialo-scintigraphy (GSA, a technique for evaluation of liver parenchymal cell density and function) and to analyze the discordance in relation to functional disturbances. We compared data between patients with alcoholic liver diseases (ALD) and patients with viral liver diseases (VLD). METHODS: The subjects of this study were 40 patients with chronic liver disease (17 with ALD and 23 with VLD). We used the liver uptake ratio of the tracer of the Sn colloid (SnL15, %), the liver uptake rate (GSAL15, %), and the Rmax (an indicator of total liver receptors) as indices of liver scans. RESULTS: GSAL15 was sometimes nondiscordant from SnL15. The patients were divided into two groups: the nondiscordant group (26 cases where the balance/sum of the two variables was <25%) and the discordant group (14 cases where the balance/sum was > or =25%). SnL15 was 41.6 +/- 16.2% in the nondiscordant group and 42.7 +/- 16.3% in the discordant group (p = 0.80). GSAL15 was 34.3 +/- 12.1% in the nondiscordant group and 21.5 +/- 8.1% in the discordant group (p = 0.001). Rmax was 0.33 +/- 0.17 in the nondiscordant group and 0.113 +/- 0.008 in the discordant group (p = 0.002). Thus, the SnL15, as determined by RESS, did not differ significantly between the nondiscordant and discordant groups, whereas GSAL15 was significantly unfavorable in the discordant group as compared with the nondiscordant group. SnL15 as determined by RESS did not differ significantly between the ALD group (40.4 +/- 18.7%) and the VLD group (43.5 +/- 15.0%) (p = 0.59), whereas Rmax as determined by GSA was significantly improved in the ALD group (0.34 +/- 0.20) compared with the VLD group (0.20 +/- 0.4) (p = 0.02). CONCLUSIONS: Liver cell function was lower in cases that showed discordance between liver cell function and reticuloendothelial function compared with cases without such discordance, although reticuloendothelial function did not differ between discordant and nondiscordant groups. Liver cell function was better in cases of ALD than in cases of VLD, whereas reticuloendothelial function did not differ between the ALD group and the VLD group.

Adult↗
PubMed2000

Determination of p53-mediated transactivational ability in radiation-treated cervical cancer.

To establish a new predictor of human cervical cancer radioresponse, we investigated the transactivational ability of p53 gene in tumor tissue for use as a marker of both pretreatment and postirradiation levels of mRNA of its downstream gene, WAF1. A total of 38 wild-type p53-bearing patients with histologically proved uterine cervical cancer were treated with definitive radiotherapy. Their p53 status was investigated using a single-strand conformation polymorphism analysis, and human papilloma virus 16, 18, 33, and 58 E6 was determined by polymerase chain reaction in pretreatment biopsy specimens. WAF1 mRNA was estimated by reverse transcriptase-polymerase chain reaction in both pretreatment specimens and those obtained after the administration of 10.8 Gy. Undetectable or low pretreatment levels of WAF1 mRNA were associated with complete response in the majority of cases, whereas only a few patients with a high pretreatment WAF1 level responded to treatment (P = .03). The increase in the postirradiation level of WAF1 mRNA positively correlated with better treatment response and long survival (P = .02). Although the human papilloma virus infection did not change the radiation response directly, it decreased the inducibility of WAF1. Consequently, the lower inducibility of WAF1 resulted in a poor treatment response. This is the first clinical report showing that the transactivational ability of p53 may be a determinant of the efficacy of cervical cancer radiotherapy.

Biopsy↗
PubMed2000

Radiofrequency induction heating for the treatment of aortic dissection in an animal model.

BACKGROUND: In this study, radiofrequency (RF) induction heating therapy using a self-expanding Gianturco metallic stent (G-EMS) to treat acute aortic dissection was evaluated. METHODS: We evaluated convergent RF induction heating of G-EMS in pigs. In group A (n=3), an aortic dissection was created to determine the natural course of this lesion. In group B (n=4), 0.40 mm stainless steel bare G-EMSs (2.5 cm, 10 bends) were placed in the aorta 5 to 7 days after dissection, and RF induction heating was performed for 30 (n=2) or 45 (n=2) minutes. In group C (n=6), G-EMSs with 0.10 mm ferro-chrome wire mounted on alternating stent legs were placed in the aorta 1 to 7 days after dissection, and RF induction heating was performed for 10 minutes. RESULTS: In group A, 2 pigs died from rupture of the false lumen. In group B, fusion of the dissection flap was confirmed histologically. However, all of the pigs died. In group C, all of the pigs tolerated the procedure, and fusion of the dissection flap was confirmed in all of the pigs. CONCLUSIONS: This experimental animal study suggested that RF induction heating combined with G-EMS, if properly applied, has a potential to treat acute aortic dissection.

Aortic Dissection↗