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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 19 recordsLinked to original sources

The biocompatibility and osteoconductivity of a cement containing beta-TCP for use in vertebroplasty.

A new composite bone cement designated "G2B1" was developed for percutaneous transpedicular vertebroplasty. G2B1 contains beta tricalcium phosphate particles and methylmethacrylate-methylacrylate copolymer as the powder components, and methylmethacrylate, urethane dimethacrylate, and tetrahydrofurfuryl methacrylate as the liquid components. Biocompatibility and osteoconductivity were evaluated using scanning electron microscopy, contact microradiography, and Giemsa surface staining 4, 8, 12, 26, and 52 weeks after implantation into rat tibiae. To evaluate osteoconductivity, affinity indices (%) were calculated. Scanning electron microscopy and contact microradiography revealed that bone contact with G2B1 was attained within 4 weeks (affinity index: 50.2 +/- 11.8 at 4 weeks) and at most of the margin within 26 weeks (affinity index: 87.4 +/- 7.2 at 26 weeks). Specifically, G2B1 contacted bone via a wide calcium-phosphate-rich layer, and its degradation started within 8 weeks, mainly in the marginal area. Giemsa surface staining showed that there was almost no inflammatory reaction around the G2B1. These results indicate that G2B1 is a biocompatible and osteoconductive bone cement.

Animals↗

Candida glabrata fungemia in a diabetic patient with neurogenic bladder: successful treatment with micafungin.

A 69-year-old man was transferred to our hospital because of fever and acute renal failure. 5 weeks prior to admission, he was admitted to another hospital and treated with several antibiotics including vancomycin, but fever did not subside and renal dysfunction showed rapid progression. On admission, laboratory findings revealed pyuria, inflammatory changes, acute renal failure, and disseminated intravascular coagulation (DIC). Computed tomography showed left ureteral stone and hydronephrosis. Gallium scintigraphy showed avid uptake in the left kidney. Serum concentration of vancomycin was 57.4 micro/ml. Candida glabrata was isolated from blood, sputum and urine. Under the diagnosis of fungemia and left pyelonephritis, he was treated with micafungin (150 mg/day), gabexate mesilate and insertion of a double-ended pigtail catheter. The above treatment produced regression of systemic inflammation, DIC and acute renal failure. At the last follow-up 3 weeks after discharge, ureteroscopy showed that the ureter stone had already passed but a soft white-yellowish bezoar was detected in the ureter. In this case, neurogenic bladder, poorly controlled diabetes, and long-term antibiotic treatment probably enhanced the development of C. glabrata infection. Antifungal treatment with micafungin is useful in patients with non-albicans Candida infection.

Aged↗

Intraarterial injection of colforsin daropate hydrochloride for the treatment of vasospasm after aneurysmal subarachnoid hemorrhage: preliminary report of two cases.

We describe two patients with symptomatic vasospasms after aneurysmal subarachnoid hemorrhage who were successfully treated with intraarterial injection of colforsin daropate hydrochloride (HCl). Colforsin daropate HCl is capable of directly stimulating adenylate cyclase, which in turn causes vasorelaxation via elevated intracellular concentrations of cyclic adenosine monophosphate. We suggest that colforsin daropate HCl might be a useful therapeutic tool in treating cerebral vasospasm.

Cerebral Angiography↗

Grazing and vigilance by Soay sheep on Lundy island: influence of group size, terrain and the distribution of vegetation.

Animals allocate the time spent on different behaviours according to nutritional requirements, the distribution of food and the risk of predation. When the perceived predation risk is high, animals primarily behave in ways to increase their safety such as regularly scanning their surroundings, forming large groups and feeding in habitats with cover or high visibility. This study investigated which factors Soay sheep (Ovis aries) are most sensitive to in allocating time to different behaviours when the risk of predation is negligible. Continuous focal sampling was used to record the behaviour of the free-ranging Soay sheep on Lundy Island and measures of vegetation, group size and terrain were also recorded. Stepwise multiple regression produced a model of grazing with terrain and range of grass coverage as predictors and a model of vigilance with terrain as a predictor. Sheep grazed for longer on the slopes and as the range of grass cover decreased. They were more vigilant on the slopes. The results support the view that the group size effect largely depends on anti-predatory vigilance and suggest that time-budgets are more sensitive to other factors in the absence of predation.

Animals↗

Is nitric oxide luteolytic or antiluteolytic?

Nitric oxide (NO) has been reported to be luteolytic based on treatment of cows in vivo with an inhibitor of nitric oxide synthase (NOS-produces NO), which delayed the decline in progesterone by two to three days [Jaroszewki J, Hansel, W. Intraluteal administration of a nitric oxide synthase blocker stimulates progesterone, oxytocin secretion and prolongs the life span of the bovine corpus luteum. Proc Soc Exptl Biol Med 2000;224:50-5; Skarzynski D, Jaroszewki J, Bah, M, et al. Administration of nitric oxide synthase inhibitor counteracts prostaglandin F(2alpha)-induced luteolysis in cattle. Biol Reprod 2003;68:1674-81]. The objective of this experiment was to determine the effect of a long acting NO donor or a NOS inhibitor infused chronically into the interstitial tissue of the ovarian vascular pedicle adjacent to the ovary with a corpus luteum on secretion of progesterone during the ovine estrous cycle. Ewes were treated either with Vehicle (N=5); Diethylenetriamine (DETA-control for DETA-NONOate; N=5); (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl) amino]diazen-1-ium-1,2-diolate (DETA-NONOate-long acting NO donor; N=6); or l-nitro-arginine methyl ester (l-NAME-NOS inhibitor; N=6) every 6 h from 24:00 h (0 h) on day 8 through 18:00 h on day 18 of the estrous cycle. Jugular venous blood was collected every 6h for analysis for progesterone and corpora lutea were collected at 18:00 h on day 18 and weighed. Weights of corpora lutea were heavier (P< or =0.05) in DETA-NONOate-treated ewes when compared to Vehicle, DETA, or l-NAME-treated ewes, which did not differ amongst each other (P> or =0.05). Profiles of progesterone in jugular venous blood on days 8-18 differed (P< or =0.05) in DETA-NONOate-treated ewes when compared to Vehicle, DETA, or l-NAME-treated ewes did not differ (P> or =0.05) amongst each other. It is concluded that NO is not luteolytic during the ovine estrous cycle, but may instead be antiluteolytic and prevent luteolysis.

Animals↗

Bioactive bone cements containing nano-sized titania particles for use as bone substitutes.

Three types of bioactive polymethylmethacrylate (PMMA)-based bone cement containing nano-sized titania (TiO2) particles were prepared, and their mechanical properties and osteoconductivity are evaluated. The three types of bioactive bone cement were T50c, ST50c, and ST60c, which contained 50 wt% TiO2, and 50 and 60 wt% silanized TiO2, respectively. Commercially available PMMA cement (PMMAc) was used as a control. The cements were inserted into rat tibiae and allowed to solidify in situ. After 6 and 12 weeks, tibiae were removed for evaluation of osteoconductivity using scanning electron microscopy (SEM), contact microradiography (CMR), and Giemsa surface staining. SEM revealed that ST60c and ST50c were directly apposed to bone while T50c and PMMAc were not. The osteoconduction of ST60c was significantly better than that of the other cements at each time interval, and the osteoconduction of T50c was no better than that of PMMAc. The compressive strength of ST60c was equivalent to that of PMMAc. These results show that ST60c is a promising material for use as a bone substitute.

Animals↗

Myocardial performance index for assessment of left ventricular outcome in successfully recanalised anterior myocardial infarction.

OBJECTIVE: To investigate whether the myocardial performance index (MPI) can predict left ventricular functional outcome in patients with early recanalisation after anterior acute myocardial infarction (MI) and to determine when the index should be measured. DESIGN: MPI was measured serially by two dimensional Doppler echocardiography after successful percutaneous coronary intervention (PCI). Left ventricular function was evaluated by echocardiography and left ventriculography. To assess coronary microvascular damage, the coronary flow velocity pattern was measured immediately after PCI with a Doppler guidewire. SETTING: Hiroshima City Asa Hospital. PATIENTS: 32 consecutive patients with their first anterior acute MI who had complete occlusion of left anterior descending coronary artery. INTERVENTIONS: Successful PCI within six hours of symptom onset. MAIN OUTCOME MEASURES: Left ventricular anterior wall motion score index (A-WMSI), left ventricular end diastolic pressure (LVEDP), left ventricular ejection fraction (LVEF), and left ventricular end diastolic volume (LVEDV). RESULTS: There was a significant negative correlation between MPI on day 2 and the coronary diastolic deceleration time (r = -0.66, p < 0.002), as well as a significant positive correlation with the coronary diastolic deceleration rate (r = 0.74, p < 0.0001). MPI on day 2 was significantly correlated with the short and long term changes of A-WMSI and with the short term changes of LVEDP. Furthermore, MPI on day 2 was significantly correlated with the short and long term changes of LVEF (r = -0.52, p < 0.003, and r = -0.64, p < 0.0008, respectively) and of LVEDV (r = 0.51, p < 0.003, and r = 0.41, p < 0.05, respectively). CONCLUSIONS: Doppler derived MPI on day 2, representative of the early coronary microvascular state, can predict the left ventricular functional outcome after early successful recanalisation of a patient's first anterior acute MI.

Aged↗

Novel quantitative assessment of myocardial perfusion by harmonic power Doppler imaging during myocardial contrast echocardiography.

OBJECTIVE: To test the hypothesis that the power of the received signal of harmonic power Doppler imaging (HPDI) is proportional to the bubble concentration under conditions of constant applied acoustic pressure, and to determine whether a new quantitative method can overcome the acoustic field inhomogeneity during myocardial contrast echocardiography (MCE) and identify perfusion abnormalities caused by myocardial infarction. METHODS: The relation between Levovist concentration and contrast signal intensity (CI) of HPDI was investigated in vitro under conditions of constant acoustic pressure. MCE was performed during continuous infusion of Levovist with intermittent HPDI every sixth cardiac cycle in 11 healthy subjects and 25 patients with previous myocardial infarction. In the apical views myocardial CI (CI(myo)) was quantified in five myocardial segments. The CI from the left ventricular blood pool adjacent to the segment was also measured in dB and subtracted from the CI(myo) (relative CI (RelCI)). RESULTS: CI had a logarithmic correlation and the calculated signal power a strong linear correlation with Levovist concentration in vitro. Thus, a difference in CI of X dB indicates a microbubble concentration ratio of 10(X/10). In normal control subjects, CI(myo) differed between the five segments (p < 0.0001), with a lower CI(myo) in deeper segments. However, RelCI did not differ significantly between segments (p = 0.083). RelCI was lower (p < 0.0001) in the 39 infarct segments (mean (SD) -18.6 (2.8) dB) than in the 55 normal segments (mean (SD) -15.1 (1.6) dB). RelCI differed more than CI(myo) between groups. CONCLUSIONS: The new quantitative method described can overcome the acoustic field inhomogeneity in evaluation of myocardial perfusion during MCE. RelCI represents the ratio of myocardium to blood microbubble concentrations and may correctly reflect myocardial blood volume fraction.

Adult↗

Inhibition of endotoxin- and antigen-induced airway inflammation by fudosteine, a mucoactive agent.

We evaluated the effect of a mucoactive agent (-)-(R)-2-amino-3-(3-hydroxypropylthio) propionic acid (fudosteine), on airway inflammation using endotoxin- and antigen-induced models. Time courses of growth related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) production, neutrophil migration and goblet cell hyperplasia were examined in endotoxin-induced rat airway inflammation. GRO/CINC-1 in bronchoalveolar lavage fluid (BALF) increased in response to intratracheal instillation of endotoxin and peaked within 4 h. Neutrophils in BALF and goblet cells on trachea peaked 24 and 96 h after endotoxin instillation, respectively. Fudosteine significantly inhibited increases in GRO/CINC-1 at 10-100 mg/kg, and neutrophils and goblet cells at 30 and 100 mg/kg. These results suggest that inflammatory events including neutrophil chemoattractant production and neutrophil migration play important roles for goblet cell hyperplasia in endotoxin-induced airway inflammation, and fudosteine inhibits goblet cell hyperplasia by inhibiting GRO/CINC-1 production and/or neutrophil migration. Furthermore, fudosteine (100 mg/kg) inhibited ovalbumin-induced eosinophil infiltration into BALF, suggesting it attenuates asthmatic inflammation.

Animals↗

Multi-institutional phase II trial of irinotecan, cisplatin, and etoposide for sensitive relapsed small-cell lung cancer.

Irinotecan (CPT-11) has been shown to exhibit excellent antitumour activity against small-cell lung cancer (SCLC). A multi-institutional phase II study was therefore conducted to evaluate the efficacy and toxicity of CPT-11 combined with cisplatin (CDDP) and etoposide (ETOP) (PEI regimen) for the treatment of sensitive relapsed SCLC. Patients who responded to first-line chemotherapy but relapsed more than 8 weeks after the completion of first-line therapy (n=40) were treated using the PEI regimen, which consisted of CDDP (25 mg m(-2)) weekly for 9 weeks, ETOP (60 mg m(-2)) for 3 days on weeks 1, 3, 5, 7, and 9, and CPT-11 (90 mg m(-2)) on weeks 2, 4, 6, and 8 with granulocyte colony-stimulating factor support. Five complete responses and 26 partial responses were observed, and the overall response rate was 78% (95% confidence interval 61.5-89.2%). The median survival time was 11.8 months, and the estimated 1-year survival rate was 49%. Grade 3/4 leucocytopenia, neutropenia, and thrombocytopenia were observed in 55, 73, and 33% of the patients, respectively. Nonhaematological toxicities were mild and transient in all patients. In conclusion, the PEI regimen is considered to be highly active and well tolerated for the treatment of sensitive relapsed SCLC.

Adult↗

Daily omega-3 fatty acid intake and depression in Japanese patients with newly diagnosed lung cancer.

The aim of the present study was to examine the association between daily omega-3 fatty acid intake and depression in Japanese cancer patients. Omega-3 fatty acid intake in 771 patients with newly diagnosed primary lung cancer was evaluated using a food-frequency questionnaire, and the prevalence of depression was examined using the cutoff values for the depression subscale included in the Hospital Anxiety and Depression Scale. After adjustment for potential confounding factors, the odds ratio (OR) for depression among patients in the highest quartile of the total eicosapentaenoic acid- (C20:5n-3) and docosapentaenoic acid (C22:6n-3)-intake group compared with patients in the lowest quartile was not significantly different. On the other hand, the OR among the highest quartile of alpha-linolenic acid (C18:3n-3) intake (adjusted OR=0.50, 95% CI: 0.31-0.71, P for trend=0.004) and the highest quartile of total omega-3 fatty acid intake (adjusted OR=0.55, 95% CI: 0.35-0.88, P for trend=0.022) were significantly different. These results suggest that total eicosapentaenoic acid and docosapentaenoic acid intake might not be associated with depression in Japanese patients with newly diagnosed lung cancer, but that alpha-linolenic acid intake and total omega-3 fatty acid intake might be.

Aged↗

Efficacy of droperidol in the prevention of cisplatin-induced delayed emesis: a double-blind, randomised parallel study.

We conducted a prospective, randomized, double-blind, parallel study comparing the antiemetic activity and tolerability of treatment with droperidol (2.5 mg d.i.v. twice daily for 5 days) and placebo, both combined with granisetron (3 mg d.i.v. on the first day) and dexamethasone (16 mg d.i.v. on the first day, 8 mg d.i.v. on days 2, 3, and 4 mg d.i.v. on days 4, 5). A total of 180 lung cancer patients receiving high-dose cisplatin (80 mg/m(2))-containing chemotherapy were enrolled in the study, and 171 of them were capable of being evaluated. The clinical characteristics of the patients in the two treatment arms were well balanced. Complete protection from nausea and vomiting was recorded in the acute phase in 97% of patients who treated with droperidol versus 98% of patients who given the placebo (P=0.920), and in 42% versus 38% in the delayed phase (P=0.615). The multiple logistic regression analysis showed that a history of motion sickness was a significant risk factor for cisplatin-induced delayed emesis (odds ratio [OR]=5.98; 95% CI=2.15 to 16.7, P=0.0006). Droperidol-containing treatment was well tolerated by most patients, however, the incidence of sleepiness in the droperidol group was higher than in the placebo group (69% versus 30%, P<0.0001). In conclusion, our data did not support the hypothesis that addition of droperidol to granisetron and dexamethasone reduces the delayed emesis induced by high-dose cisplatin.

Adult↗

Okadaic acid stimulates expression of Fas receptor and Fas ligand by activation of nuclear factor kappa-B in human oral squamous carcinoma cells.

In the present study, we used western blot and RT-PCR analysis to examine the expression of proteins and mRNAs of Fas receptor and Fas ligand in human oral squamous carcinoma SCC-25 cells treated with okadaic acid. Treatment with okadaic acid enhanced the expression of proteins and mRNAs of both Fas receptor and Fas ligand in SCC-25 cells. The amount of IkappaB-alpha in whole cell lysates decreased, while the level of NF-kappaB in nucleus increased, in the okadaic acid-treated cells. Okadaic acid-treatment also alters the cellular localization of NF-kappaB, from cytoplasm to nuclei. To investigate the activation of NF-kappaB in okadaic acid-treated SCC-25 cells, we performed electrophoretic mobility gel shift assay using nuclear extracts and the consensus oligonucleotide for NF-kappaB DNA binding site. The binding of nuclear proteins to the oligonucleotide of NF-kappaB increased when the cells had been treated with 20 nM okadaic acid for 4 h. We transfected the cells with pFLF1, which has the promoter region of Fas receptor gene containing NF-kappaB binding site. A luciferase reporter gene assay demonstrated that the activity in the cells transfected with pFLF1 and treated with 20 nM okadaic acid increased in a time-dependent manner and that the activity was more than three-fold over that in the control cells. Our results suggest that NF-kappaB activated at early stages in the okadaic acid-treated SCC-25 cells stimulated the promoter activity of Fas receptor in the cells leading to the apoptotic death of these cells.

Carcinoma, Squamous Cell↗

A phase II study of cisplatin and docetaxel administered as three consecutive weekly infusions for advanced non-small-cell lung cancer in elderly patients.

BACKGROUND: To evaluate the efficacy and safety of treatments for advanced non-small-cell lung cancer in elderly patients aged 75 years or older, we conducted a phase II study of cisplatin and docetaxel administered in three consecutive weekly infusions. PATIENTS AND METHODS: The eligibility criteria for the study included the presence of chemotherapy-naive advanced non-small-cell lung cancer, age > or =75 years, Eastern Cooperative Oncology Group performance status of 0 or 1, a measurable lesion, adequate organ functions and signed informed consent. The chemotherapy regimen consisted of cisplatin (25 mg/m(2)) and docetaxel (20 mg/m(2)) on days 1, 8 and 15 every 4 weeks. RESULTS: Between February 2000 and March 2002, 34 elderly patients with non-small-cell lung cancer were enrolled in the study and 33 patients were treated. Two complete responses and 15 partial responses were obtained for an objective response rate of 52% in 33 treated patients. The median survival period was 15.8 months, and the 1-year survival rate was 64%. Toxicities were mild with no grade 4 toxicities. Only grade 3 leukopenia (6%), neutropenia (12%), anemia (3%), hyponatremia (3%) and nausea/vomiting (3%) were observed. CONCLUSION: Cisplatin and docetaxel administered in three consecutive weekly infusions was safe and effective for the treatment of elderly patients with chemotherapy-naive non-small-cell lung cancer.

Aged↗

Dysferlin mutation analysis in a group of Italian patients with limb-girdle muscular dystrophy and Miyoshi myopathy.

Mutations in the dysferlin gene (DYSF) on chromosome 2p13 cause distinct phenotypes of muscular dystrophy: limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), and distal anterior compartment myopathy, which are known by the term 'dysferlinopathy'. We performed mutation analyses of DYSF in 14 Italian patients from 10 unrelated families with a deficiency of dysferlin protein below 20% of the value in normal controls by immunoblotting analysis. We identified 11 different mutations, including eight missense and three deletion mutations. Nine of them were novel mutations. We also identified a unique 6-bp insertion polymorphism within the coding region of DYSF in 15% of Italian population, which was not observed in East Asian populations. The correlation between clinical phenotype and the gene mutations was unclear, which suggested the role of additional genetic and epigenetic factors in modifying clinical symptoms.

Adolescent↗

Heat-stress enhances proliferative potential in rat soleus muscle.

The effects of heat-stress on proliferative potential in vivo were studied in rat skeletal muscle. Male Wistar rats (7-weeks-old) were divided into two groups: control (n=24) and heat-stressed (n=24). Rats in the experimental group were exposed to environmental heat-stress (41 degrees C for 60 min) in a heat chamber without anesthesia. The soleus muscles were dissected 1, 7, and 14 days after the heat exposure. The wet and dry weights of soleus muscle relative to body weight in the heat-stressed group were significantly higher than controls 7 days after the exposure (10.1% and 17.5%, respectively, p <0.05). The distribution of 5-bromo-2'-deoxyuridine and proliferating cell nuclear antigen-positive nuclei, that are the indicators for the cell proliferation, were increased by 2.2 and 5.1 times, respectively 1 day after heating (p <0.05). The expressions of heat shock protein 72 (58.0%) and phosphorylated p70S6 kinase (52.3%) were increased 1 day following heat exposure (p <0.05). These results suggest that heat-stress could promote the cell proliferation and induce muscular hypertrophy.

Adaptation, Physiological↗

Heat stress facilitates the recovery of atrophied soleus muscle in rat.

Effects of heat stress on the recovery of atrophied soleus muscle were studied in rats. Ten-week-old male Wistar rats were randomly divided into cage control (CC) and 5-day hindlimb suspension group (HS). The half of the rats in group HS was exposed to heat stress (41 degrees C for 60 min) in an incubator immediately after the hindlimb suspension (HS-H) and the other group of rats was not heat stressed (HS-C) prior to 10 days of ambulation recovery. One group of cage control rats (CH) was also exposed to heat similarly. The soleus muscles were dissected at four time points, i.e., immediately after the suspension (or heat stress), and 3, 5, and 10 days after the recovery (n=8 per group at each time point). The absolute wet weight and water and protein content of whole soleus muscle in group HS-C were approximately 36, 27, and 8 mg less than CC (p <0.05). Thus, the percentage contribution of water and protein loss to the decrease in muscle weight was 75 and 22%, respectively. Although water content, as well as muscle weight, was elevated within 3 days, the increase of protein was delayed. Heat exposure prior to recovery accelerated the increase in protein content even in the control group. These phenomena were closely associated with 72-kD heat shock protein (HSP72) content. It is suggested that heat stress applied at the end of hindlimb unloading facilitated the recovery of atrophied soleus muscle of rat, through possibly HSP72-related events of protein metabolism. The data also indicated that the combination of heat and mechanical stress evoked larger and long lasting HSP72 response than does heat or mechanical stress alone.

Adaptation, Physiological↗