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Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 109 records · Page 6Linked to original sources
PubMed2000

In vitro analysis of STAT5 activation by granulocyte-macrophage colony-stimulating factor.

BACKGROUND: The granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor activates multiple and complex signalling pathways in response to GM-CSF stimulation. Biochemical studies suggested that signalling pathways are transmitted through protein/protein interactions, but how these biochemical cascades are initiated and transmitted in response to cytokine stimulation is largely unknown. RESULTS: To investigate these events biochemically, we established an in vitro system leading to the GM-CSF-dependent activation of Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 5 in cell homogenates prepared from BA/F3 cells expressing the GM-CSF receptor. Activation of STAT5 DNA binding ability requires both membrane and cytoplasmic fractions while phosphorylation of JAK2 requires only the membrane fraction. Since the addition of anti-betac or phosphotyrosine antibodies inhibited GM-CSF induced STAT5 DNA binding activity, we examined the role of tyrosine residues of betac for in vitro activation of STAT5. Addition of synthetic tyrosine-phosphorylated peptides derived from betac cytoplasmic tyrosines prior to GM-CSF stimulation inhibited the in vitro activation of STAT5. The association between these tyrosine-phosphorylated peptides and STAT5 was observed by using peptide-coupling beads and BA/F3 lysates. CONCLUSIONS: We established a GM-CSF-dependent in vitro system. In cases of STAT5 activation, each phosphorylated tyrosine residue of betac can act as a docking site and enhance STAT5 activation.

Animals↗
PubMed2000

Temporary use of an accuflex stent for unextractable common bile duct stones.

Endoscopic management has become the main therapeutic approach for the extraction of common bile duct (CBD) stones, and successful removal can be achieved in 80-90% patients using conventional balloon and basket techniques. However, if it is difficult to completely fragment a stone, or to clear the CBD, which may occur for a variety of reasons, the therapeutic problem will remain. When bile duct stones can not be removed, a viable management option is to place a biliary stent to ensure drainage. However, recent studies of long-term biliary stenting, with a plastic stent, showed a relatively high rate of morbidity and mortality. We report an alternative, unique treatment for unextractable common bile duct stones, using the temporal placement of an expandable metallic stent (EMS) to facilitate passage of fragments through the papilla.

Aged↗
PubMed2000

Angiomyomatous hamartoma and associated stromal lesions in the right inguinal lymph node: a case report.

Angiomyomatous hamartoma is a rare disease with a predisposition for the inguinal lymph nodes. A 51-year-old male patient visited a local hospital because of a right inguinal mass, measuring 3 x 4 cm in size, which was resected. The resected specimen showed irregularly distributed thick-walled vessels in the hilum, extending into the medulla and focally into the cortex of the node, eventually becoming more dispersed and associated with smooth muscle cells splaying into sclerotic stroma. These findings are compatible with an angiomyomatous hamartoma. Another tumor-like mass appeared shortly after the resection at the same location, but was not an angiomyomatous hamartoma, rather it was composed of edematous stromal tissue with proliferating smooth muscle cells. The stromal component included thick-walled blood vessels and lymphatics. Although it could not be determined whether these associated changes in the surrounding stroma are a cause or an effect of angiomyomatous hamartoma, they indicate the clinical difficulty in determining an appropriate area of resection and may provide clues to the pathogenesis of angiomyomatous hamartoma.

Actins↗
PubMed2000

The effects of boron neutron capture therapy on liver tumors and normal hepatocytes in mice.

To explore the feasibility of employing boron neutron capture therapy (BNCT) to treat liver tumors, the effects of BNCT were investigated by using liver tumor models and normal hepatocytes in mice. Liver tumor models in C3H mice were developed by intrasplenic injection of SCCVII tumor cells. After borocaptate sodium (BSH) and boronophenylalanine (BPA) administration, (10)B concentrations were measured in tumors and liver and the liver was irradiated with thermal neutrons. The effects of BNCT on the tumor and normal hepatocytes were studied by using colony formation assay and micronucleus assay, respectively. To compare the effects of BSH-BNCT and BPA-BNCT, the compound biological effectiveness (CBE) factor was determined. The CBE factors for BSH on the tumor were 4.22 and 2.29 using D(10) and D(0) as endpoints, respectively. Those for BPA were 9.94 and 5.64. In the case of hepatocytes, the CBE factors for BSH and BPA were 0.94 and 4.25, respectively. Tumor-to-liver ratios of boron concentration following BSH and BPA administration were 0.3 and 2.8, respectively. Considering the accumulation ratios of (10)B, the therapeutic gain factors for BSH and BPA were 0.7 - 1.3 and 3.8 - 6.6, respectively. Therefore, it may be feasible to treat liver tumors with BPA-BNCT.

Animals↗
PubMed2000

A noninvasive dose estimation system for clinical BNCT based on PG-SPECT--conceptual study and fundamental experiments using HPGe and CdTe semiconductor detectors.

A noninvasive method for measuring the absorbed dose distribution during the administration of clinical boron neutron capture therapy (BNCT) using an online three-dimensional (3D) imaging system is presented. This system is designed to provide more accurate information for treatment planning and dosimetry. The single-photon emission computed tomography (SPECT) technique is combined with prompt gamma-ray analysis (PGA) to provide an ideal dose estimation system for BNCT. This system is termed PG-SPECT. The fundamental feasibility of the PG-SPECT system for BNCT is confirmed under the following conditions: (1) a voxel size of 1 x 1 x 1 cm3, comparable to the spatial resolution of our standard dosimetric technique using gold wire activation, where data are available for every 5-10 mm of wire length; (2) a reaction rate of 10B(n,alpha)7Li within the measurement volume is greater than 1.1 x l0(6) interactions/cm3/s, corresponding to a thermal neutron flux of 5 x 10(8) n/cm2/s and a 10B concentration of greater than 10 ppm for the deepest part of the tumor volume under typical BNCT clinical conditions; (3) statistical uncertainty of the count rate for 10B(n,alpha)7Li prompt gamma rays is 10% or less. The desirable characteristics of a detector for the PG-SPECT system were determined by basic experiments using both HPGe and CdTe semiconductor detectors. The CdTe semiconductor detector has the greatest potential for this system because of its compactness and simplicity of maintenance.

Boron Neutron Capture Therapy↗
PubMed2000

Analysis of urgent colonoscopy for lower gastrointestinal tract bleeding.

BACKGROUND: Three hundred and forty-five patients who underwent urgent colonoscopy for acute hematochezia during the past 20 years (from 1976 to 1995) were retrospectively analyzed. METHODS: Urgent colonoscopy was defined as endoscopy performed within 24 h after a bleeding episode. Preparation was initially minimal with a water or glycerine enema. Recently, however, polyethylene glycol is used. RESULTS: The overall diagnostic accuracy for bleeding site detection was 89.1% (307 cases). Successful insertion was made to the ileocecal region in 193 cases (55.9%). The disease most frequently discoverd by urgent colonoscopy was transient ischemic colitis (62 cases). Negative urgent colonoscopy specimens (18 cases) were later diagnosed by other methods as being small intestinal bleeding foci. In 10 cases, initial colonoscopy failed to detect the bleeding foci. Endoscopic hemostasis was performed in 48 cases. Permanent hemostasis succeeded in 32 cases (66.7%). Complications of urgent colonoscopy were fever after the examination (22 cases) and hypotension during endoscopy (7 cases). CONCLUSION: Urgent colonoscopy is considered to be a safe and useful examination for acute lower gastrointestinal bleeding and hemostasis.

Acute Disease↗
PubMed2000

Urokinase cisternal irrigation therapy for prevention of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage: a study of urokinase concentration and the fibrinolytic system.

BACKGROUND AND PURPOSE: Cisternal irrigation therapy with urokinase (UK) was performed in multiple institutions to prevent symptomatic vasospasm. The efficacy and safety of this therapy were evaluated, and the optimal concentration of UK was estimated. METHODS: This therapy was performed in 28 patients who underwent surgery within 72 hours of the onset of severe subarachnoid hemorrhage (Fisher's group 3, CT number [Hounsfield units] >60). After the aneurysm was clipped, irrigation tubes were placed in the Sylvian fissure (inlet) unilaterally and in the prepontine or chiasmatic cistern (outlet). Lactated Ringer's solution with UK (30, 60, or 120 IU/mL) was infused at a rate of 30 mL/h. The presence of symptomatic vasospasm was evaluated by changes in the clinical symptoms and the presence of a new low-density area on CT scan. Drained irrigation fluid and peripheral blood were examined chronologically to evaluate the fibrinolytic system. RESULTS: Symptomatic vasospasm was observed transiently in 3 cases (10.7%) without any low-density area on CT scan. In the 120-IU/mL group, no symptomatic vasospasm occurred. Analysis of drainage fluid suggested that UK 120 IU/mL is effective. The mean values of total drained blood volume for the respective groups were as follows: 58 mL in 30 IU/mL, 106 mL in 60 IU/mL, and 143 mL in 120 IU/mL. No abnormal changes were observed in the coagulative and fibrinolytic systems after UK irrigation. CONCLUSIONS: These results suggest that cisternal irrigation therapy with UK is safe and effective for the prevention of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage.

Biomarkers↗
PubMed2000

Novel bifunctional polymer with reactivity and temperature sensitivity.

To introduce reactive groups into temperature-responsive polymeric chains of poly(N-isopropylacrylamide) (PIPAAm), IPAAm is copolymerized with other monomer such as acrylic acid (AAc). IPAAm homopolymer exhibited temperature-responsive properties and phase transition at 32 degrees C, however, the lower critical solution temperature (LCST) of the IPAAm-AAc copolymer shifts to a higher temperature and the phase transition becomes insensitive with increasing AAc content. To achieve a useful bifunctional copolymer containing both reactivity and temperature-sensitivity, we assumed that the homopolymer-like structure in the polymer chain would be required to maintain a sensitive temperature response with functional groups. Therefore, we designed a reactive monomer, 2-carboxyisopropylacrylamide (CIPAAm), and investigated its copolymerization with IPAAm. The important characteristic of the poly(IPAAm-co-CIPAAm) structure is that it was composed of the same polymer backbone and isopropylamide groups and some additional carboxyl groups. The transmittance measurement of the polymer aqueous solution revealed that phase transition of IPAAm-co-CIPAAm random copolymer occurred within a very narrow temperature range in pH 6.4, 7.4, and also even 9.0 phosphate buffered solution. These profiles were almost same as that of IPAAm homopolymer. While, under the same conditions, phase transition properties of poly(IPAAm-co-AAc)s solution were considerably influenced by small AAc content. We succeeded with the preparation of bifunctional polymer that possessed reactive functional groups and very sensitive response to temperature change.

Acrylamides↗
PubMed2000

Anthropometric obesity indices in relation to age and gender in Japanese adults.

The body mass index (BMI), waist circumference, waist to hip ratio, waist to height ratio and skinfolds (near-umbilical and iliac areas) in three age groups (35-44, 45-54 and 55-64 years) were compared in 3117 men and 997 women in Tokyo. In both genders, height was significantly shorter, while the waist to hip ratio and waist to height ratio were significantly higher, in the older groups. In the men, there were no significant differences in BMI and waist circumference among the three age groups, but the iliac skinfold was significantly thinner in each older group, and the paraumbilical skinfold was thinner in the group aged 55-64 years. In the women, the paraumbilical skinfold was significantly thicker in each older group, while waist circumference and the iliac skinfold were significantly larger or thicker in the group aged 55-64 years, and BMI was larger in the groups aged 45-54 and 55-64 years. There were age-related discrepancies between BMI and other obesity indices in the different genders, in that only the waist to height ratio and waist to hip ratio increased with age in both genders.

Adult↗
PubMed2000

A cross-sectional study on the relationship between leisure or recreational physical activity and coronary risk factors.

Several researchers have investigated the relationship between physical activity and coronary risk factors. Little is known about the strength of the relationship between physical activity and each coronary risk factor. The aim of this study is to determined the strength of the relationship between leisure or recreational physical activity and selected coronary risk factors. The subjects were 781 male Japanese office workers who underwent an annual physical examination in 1999, including interview about the type and frequency of their leisure or recreational physical activities, other lifestyle questionnaire, and biological measurement, calculated a physical activity index (PAI) for each subject. To investigate the strength of the relationship between PAI and each coronary risk factor, we carried out multiple regression analysis. Smoking habit, log triglycerides, self-rating depression scale (SDS) score, alcohol habit and left ventricular hypertrophy were significantly related to the physical activity (partial R2: 0.031, 0.018, 0.016, 0.0092, 0.0075, respectively). Smoking habit was the strongest determinant of the physical activity. Furthermore, we found the inverse relationship between SDS score and physical activity independently.

Alcohol Drinking↗
PubMed2000

Molecular structural analysis of HPRT mutations induced by thermal and epithermal neutrons in Chinese hamster ovary cells.

Chinese hamster ovary (CHO) cells were exposed to thermal and epithermal neutrons, and the occurrence of mutations at the HPRT locus was investigated. The Kyoto University Research Reactor (KUR), which has been improved for use in neutron capture therapy, was the neutron source. Neutron energy spectra ranging from nearly pure thermal to epithermal can be chosen using the spectrum shifters and thermal neutron filters. To determine mutant frequency and cell survival, cells were irradiated with thermal and epithermal neutrons under three conditions: thermal neutron mode, mixed mode with thermal and epithermal neutrons, and epithermal neutron mode. The mutagenicity was different among the three irradiation modes, with the epithermal neutrons showing a mutation frequency about 5-fold that of the thermal neutrons and about 1.5-fold that of the mixed mode. In the thermal neutron and mixed mode, boron did not significantly increase the frequency of the mutants at the same dose. Therefore, the effect of boron as used in boron neutron capture therapy (BNCT) is quantitatively minimal in terms of mutation induction. Over 300 independent neutron-induced mutant clones were isolated from 12 experiments. The molecular structure of HPRT mutations was determined by analysis of all nine exons by multiplex polymerase chain reaction. In the thermal neutron and mixed modes, total and partial deletions were dominant and the fraction of total deletions was increased in the presence of boron. In the epithermal neutron mode, more than half of the mutations observed were total deletions. Our results suggest that there are clear differences between thermal and epithermal neutron beams in their mutagenicity and in the structural pattern of the mutants that they induce. Mapping of deletion breakpoints of 173 partial-deletion mutants showed that regions of introns 3-4, 7/8-9 and 9-0 are sensitive to the induction of mutants by neutron irradiation.

Animals↗
PubMed2000

Rapidly progressive polymyositis with elevated antiacetylcholine receptor antibody activity.

We report a 51-year-old woman with polymyositis accompanied by a high titer of antiacetylcholine receptor antibody. The patient presented with weakness of grip strength followed by rapidly progressive dyspnea, which required mechanical ventilation. She was treated with a glucocorticoid and came off the respirator one week later. Antiacetylcholine receptor antibody activity was elevated in the acute phase and decreased during recovery, although other signs of myasthenia gravis were negative. This patient suggested that in cases of rapidly progressive bulbar palsy and limb muscle weakness, it is necessary to include polymyositis associated with elevated antiacetylcholine receptor antibody activity in the differential diagnosis.

Anti-Inflammatory Agents↗
PubMed2000

Effects of "isolating hemodialysis" on prevention of methicillin-resistant Staphylococcus aureus cross-infection in a hemodialysis unit.

AIM: To evaluate the effects of a contact isolation program against methicillin-resistant Staphylococcus aureus (MRSA) cross-infection among patients in a hemodialysis unit. CLINICAL SETTING AND METHODS: In all patients maintaining hemodialysis therapy were tested for MRSA infection and who had MRSA infection, not only inpatients but also outpatients were separated into a designated area (isolating hemodialysis). Clinically isolated MRSA strains were clonotyped with coagulase typing, staphylococcal enterotoxin typing and restriction enzyme analysis of plasmid DNA. RESULTS: The frequency of patients with MRSA infection was 4.5% before starting this protocol and was reduced to 2.9% two and a half years later. At this time, MRSA was isolated from the 8 patients. These 8 clinical strains were differentiated into 6 clonotypes and 3 strains showed the same patterns. Two of 3 were isolated from inpatients and the other was from a patient with community onset MRSA colitis. In this case, most MRSA infections were independent under prophylaxis control and cross-infection was observed only once between hospitalized patients who stayed in a same ward. CONCLUSION: This "isolating hemodialysis" should be useful to prevent cross-infection among patients in end-stage renal disease in a dialysis unit.

Adult↗
PubMed2000

[Autopsied case of an extracranial internal carotid artery dissecting aneurysm].

An autopsy case of extracranial internal carotid artery (ICA) dissecting aneurysm due to atherosclerosis was reported. A 74-year-old man was admitted to our hospital with the chief complaints of hoarseness and a pulsatile mass below the left mandibular angle. Neurological examination showed no obvious deficits except left recurrent laryngeal nerve palsy. Angiography revealed narrowing of the original segment of left ICA with dissection and aneurysmal dilation at the level of C3 vertebra. Seven days after admission, the patient had a sudden onset of consciousness disturbance. The second angiography showed no obvious changes compared with the first findings except slight narrowing in the distal portion above the aneurysmal dilation. The possible mechanism was thought to be recanalization following transient occlusion of the left ICA caused by extension of dissection or intracranial embolism due to a thrombus within the aneurysm. He was managed conservatively, but unfortunately he died of pneumonia. Macroscopic autopsy showed that the aneurysm was fusiform. Histologically, it demonstrated dissection of the hematoma between the media and adventitia layer. Hemorrhage in the atheromatous plaque with disruption of the elastic lamina were observed along with severe degenerative changes of the intima, media and, in part, adventitia layer due to atherosclerosis. In addition, a dissecting aneurysm of the right iliac artery and severe arteriosclerosis were observed in the systemic arteries. On the basis of these findings, the dissecting aneurysm presumably developed after disruption of a weak portion of the atherosclerotic wall, where intraplaque hemorrhage occurred earlier. We suggest that atherosclerosis be regarded as one of the pathogenic factors capable of causing dissecting aneurysm of the extracranial ICA in elderly patients.

Aged↗
PubMed2000

Characterization of antibodies to factor VIII in hemophilia A patients treated by immune tolerance therapy.

The treatment of hemophilia A patients has improved in this decade by production of recombinant factor VIII (FVIII) in mammalian cells, which has significantly reduced contamination by infectious agents. A remaining serious problem in 25-30% of patients with severe hemophilia A is the appearance of antibodies that inactivate FVIII. The present therapy for this condition is frequent treatment with high doses of FVIII to induce tolerance, which is defined as a negative Bethesda assay. Serial plasma samples from 50 evaluable patients in a large study of 72 previously untreated patients were tested to determine whether tolerized patients have actually lost all their anti-FVIII by using a 10 fold more sensitive immunoprecipitation (IP) method of measuring all anti-FVIII antibodies. Six of the 22 patients with inhibitors were given tolerance therapy, and 3 of them were only partially tolerized as determined by IP assay. Seven patients with 1-11 BU/mL lost their inhibitor spontaneously, while 5 non-inhibitor patients with low level immune responses similarly became antibody negative. In a smaller study, a tolerized patient with 0 BU/mL had remaining non-inhibitory antibody levels high enough to reduce the FVIII half-life significantly. Plasmas from 2 patients who were not tolerized, were tested by the IP assay for the A2 and/or C2 domain specificity of the anti-FVIII over time. The antibodies detected were directed against both the heavy and light chains of FVIII, and they increased and decreased at the same rate before and during tolerance therapy.

Antibody Specificity↗
PubMed1999

Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate).

To achieve a combination of spatial specificity in a passive manner with a stimuli-responsive targeting mechanism, a temperature-responsive polymeric micelle is prepared using block copolymers of (poly(N-isopropylacrylamide-b-butylmethacrylate) (PIPAAm-PBMA)). The micelle inner core formed by self-aggregates of PBMA segments successfully loaded with a drug (adriamycin), and the outer shell of PIPAAm chains played a role of stabilization and initiation of micellar thermo-response. Optimum conditions were investigated for the micelle formation and drug loading into the inner cores in a view of micellar stability and function as drug carriers. Outer shell hydrophilicity that prevents inner core interaction with biocomponents and other micelles can be suddenly switched to hydrophobic at a specific site by local temperature increase beyond the LCST (lower critical solution temperature) (32.5 degrees C). These micelles showed reversible structural changes allowing drug release upon heating/cooling thermal fluctuations through the LCST. Polymeric micelles incorporated with adriamycin showed a dramatic thermo-responsive on/off switching behavior for both drug release and in vitro cytotoxicity according to the temperature responsive structural changes of a micellar shell structure. The reversible and sensitive thermo-response of the micelle opens up opportunities to construct a novel drug delivery system in conjunction with localized hyperthermia.

Acrylic Resins↗