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Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 37 records · Page 2Linked to original sources

Percutaneous radiofrequency ablation for unresectable large hepatic tumours during hepatic blood flow occlusion in four patients.

AIM: To evaluate percutaneous radiofrequency (RF) ablation therapy for unresectable large hepatic tumours combined with regional interruption of hepatic blood flow, and to assess the safety and efficacy of this procedure. MATERIALS AND METHODS: Four patients with hepatic tumours were enrolled in this study. Patients were treated by a single session of RF ablation during occlusion of both hepatic artery and hepatic vein. Tumour size ranged from 45-57 mm (mean 50.2 mm). Initial therapeutic efficacy was evaluated with helical computed tomography (CT) performed within 9 days after the treatment. CT or magnetic resonance imaging (MRI) was performed every 2-3 months thereafter. RESULTS: The largest axis of coagulated lesions after the ablation was 50-60 mm (mean 56.5 mm) in diameter. The ablation therapy was considered complete in three patients; after a mean follow-up of 12.7 months, CT and MRI revealed complete destruction of their tumours. One patient required further treatment. No severe complications occurred. CONCLUSION: Although further studies are needed, in this limited clinical trial a local ablation area exceeding 50 mm in diameter was achieved safely.

Aged↗

Development of a tiny neutron probe with an optical fibre for BNCT.

We have developed a tiny neutron probe detector as a monitor of a thermal neutron flux for boron neutron capture therapy. The detector consists of an optical fibre and a small neutron probe. We have used a film-like ZnS(Ag) scintillator and a 6LiF neutron converter for the neutron probe. In order to improve the gamma-neutron discrimination ability, vacuum evaporation of 6LiF onto the ZnS(Ag) film has been done. In order to improve the neutron detection efficiency, we made use of a wavelength-shifting fibre as the probe material. The characteristics of the above two types of fibre probe detector have been evaluated experimentally.

Body Burden↗

Microdosimetry of neutron field for boron neutron capture therapy at Kyoto university reactor.

Microdosimetric single event spectrum in a human body simulated by an acrylic phantom has been measured for the clinical BNCT field at the Kyoto University Reactor (KUR). The recoil particles resulting from the initial reaction and subsequent interactions, namely protons, electrons, alpha particles and carbon nuclei are identified in the microdosimetric spectrum. The relative contributions to the neutron dose from proton, alpha particles and carbon are estimated to be about 0.9, 0.07 and 0.3, respectively, four depths between 5 and 41 mm. We estimate that the dose averaged lineal energy, yD decreased with depth from 64 to 46 keV microm(-1). Relative biological effectiveness (RBE) of this neutron field using a response function for the microdosimetric spectrum was estimated to decrease from 3.6 to 2.9 with increasing depth.

Academic Medical Centers↗

Effectiveness of factor VIII infusions in haemophilia A patients with high responding inhibitors.

We report here the efficacy of factor VIII (FVIII) infusions in two haemophiliacs with inhibitors using clot waveform analysis on the MDA II system, which was possible to detect very low levels of FVIII activity < 1.0 U dL(-1). In the presence of type 1 inhibitors at the level of 6.2 (patient 1) and 14.4 (patient 2) Bethesda Units mL(-1), 3.2 and 6.5 U dL(-1) of FVIII:C remained 30 min after the infusion of FVIII (100 U kg(-1)), respectively. Moreover, 0.9 U dL(-1) of FVIII:C remained 24 h after infusion in patient 2. In both cases, these changes were reflected by qualitative improvement in the aPTT clot waveform and quantitative changes in the minimum value of the second derivative of the aPTT waveform (Min2) that reflects clot acceleration. These results suggest that FVIII infusion may be continued with clinical benefit in some haemophiliacs with high responding inhibitors. Furthermore, the haemostatic response may be monitored accurately and efficiently by clot waveform analysis.

Child↗

Unresponsiveness to factor VIII inhibitor bypassing agents during haemostatic treatment for life-threatening massive bleeding in a patient with haemophilia A and a high responding inhibitor.

We report a case of haemophilia A with a high responding inhibitor of factor VIII (FVIII) who had a serious retroperitoneal haematoma caused by penetration of a duodenal ulcer. Inhibitor-bypassing therapy was commenced immediately on admission. On the 17th day of treatment with activated prothrombin complex concentrate (APCC; FEIBA, re-bleeding occurred and thrombelastography (TEG) demonstrated resistance to therapy. Treatment was changed to recombinant activated factor VII (rFVIIa; NovoSeven and resulted in clinical improvement together with an improvement in TEG parameters. On the 10th day of continuous infusion with NovoSeven, however, TEG again showed resistance to therapy. FEIBA infusions were re-introduced and TEG results remained satisfactory for 7 days. On day 34, however, further retroperitoneal bleeding was evident and a decline in the haemostatic efficiency of FEIBA was recorded by TEG. NovoSeven was again successfully administered for 7 days. There were no laboratory findings to indicate disseminated intravascular coagulation (DIC), hypercoagulability or abnormal fibrinolysis. The plasma-based clotting tests did not show any additional prolongation on the occasions when the TEG demonstrated unresponsiveness to FEIBA or NovoSeven. These findings suggested that some component of whole blood, other than plasma might have governed the TEG data. The long-term use of APCC such as FEIBA or rFVIIa, requires careful monitoring in terms of FVIII inhibitor bypassing activity as well as the tendency to DIC.

Adolescent↗

A case of secondary hyperparathyroidism whose high turnover bone improved after the direct injection of acetic acid into the parathyroid glands.

A 48-year-old male was admitted to our hospital because of increasing knee pain and thigh muscle weakness. He had been undergoing hemodialysis for 15 years. His serum intact PTH value was 1,600 pg/ml with elevated ALP (387 IU/l) and osteocalcin (400 ng/ml). Ultrasound (US) examination disclosed 2 enlarged parathyroid glands. Because of poor cardiac function, an US-guided acetic acid injection into the enlarged parathyroids (percutaneous acetic acid injection therapy; PAIT) was performed. Soon after the PAIT, his arthralgia disappeared. Serum PTH fell to 220 pg/ml with the regression of bone marker 1 year following the PAIT. The size of his parathyroid glands dramatically regressed and 1 of the enlarged glands finally disappeared. Repeated bone biopsies following double tetracycline labeling showed a significant improvement from osteitis fibrosa to the mild lesion. This is the first known case report of severe secondary hyperparathyroidism whose PTH and high turnover bone was successfully managed by the direct injection of acetic acid into the parathyroid glands. As long as we pay attention to avoiding recurrent nerve palsy induced by acetic acid, US-guided PAIT may be an alternative to percutaneous ethanol injection therapy (PEIT) or surgical parathyroidectomy (PTx).

Acetic Acid↗

Contrast enhancement of the cochlear aqueduct in MR imaging: its frequency and clinical significance.

There have been no previous reports on contrast enhancement of the cochlear aqueduct in magnetic resonance imaging. The purpose of the present study was to evaluate the frequency and significance of this finding. Thirty-one patients (15 men and 16 women; age range 18-81 years) with otologic symptoms (sudden sensorineural hearing loss, vertigo, or tinnitus) were examined using contrast-enhanced imaging on a 1.5-T MR scanner. The normal ear served as the control. Two radiologists evaluated contrast enhancement in the area of the cochlear aqueduct. Forty-eight of 62 ears (77.4%) showed contrast enhancement of the cochlear aqueduct, but no significant differences in the frequency of contrast enhancement were observed between patients with and patients without vertigo, tinnitus, sensorineural hearing loss, cerebellopontine angle tumors, or a high-riding jugular bulb. In addition, no gender- or age-related differences were noted. Contrast enhancement of the cochlear aqueduct was frequently observed, but the frequency of enhancement in symptomatic ears was not significantly higher than in control ears. The results of this study may prove helpful in avoiding unnecessary examinations and potential diagnostic confusion.

Adolescent↗

Boron neutron capture therapy (BNCT) for malignant melanoma with special reference to absorbed doses to the normal skin and tumor.

Twenty-two patients with malignant melanoma were treated with boron neutron capture therapy (BNCT) using 10B-p-boronophenylalanine (BPA). The estimation of absorbed dose and optimization of treatment dose based on the pharmacokinetics of BPA in melanoma patients is described. The doses of gamma-rays were measured using small TLDs of Mg2SiO4 (Tb) and thermal neutron fluence was measured using gold foil and wire. The total absorbed dose to the tissue from BNCT was obtained by summing the primary and capture gamma-ray doses and the high LET radiation doses from 10B(n, alpha)7Li and 14N(n,p)14C reactions. The key point of the dose optimization is that the skin surrounding the tumour is always irradiated to 18 Gy-Eq, which is the maximum tolerable dose to the skin, regardless of the 10B-concentration in the tumor. The neutron fluence was optimized as follows. (1) The 10B concentration in the blood was measured 15-40 min after the start of neutron irradiation. (2) The 10B-concentration in the skin was estimated by multiplying the blood 10B value by a factor of 1.3. (3) The neutron fluence was calculated. Absorbed doses to the skin ranged from 15.7 to 37.1 Gy-Eq. Among the patients, 16 out of 22 patients exhibited tolerable skin damage. Although six patients showed skin damage that exceeded the tolerance level, three of them could be cured within a few months after BNCT and the remaining three developed severe skin damage requiring skin grafts. The absorbed doses to the tumor ranged from 15.7 to 68.5 Gy-Eq and the percentage of complete response was 73% (16/22). When BNCT is used in the treatment of malignant melanoma, based on the pharmacokinetics of BPA and radiobiological considerations, promising clinical results have been obtained, although many problems and issues remain to be solved.

Aged↗

Prevalence of atopic dermatitis in Japanese adults.

BACKGROUND: Adult atopic dermatitis (AD) in Japan has become a significant social problem, with as many as one-third of adult patients with severe AD absenting themselves from work or classes due to aggravation of the disease. Reports of such patients have become increasingly common in recent years. Despite the pressing need for epidemiological studies to clarify the prevalence and distribution of AD and to determine its aetiology, no previous research has been carried out on the prevalence of AD within the adult population in Japan. OBJECTIVES: To clarify the prevalence of adult AD in Japan, using the U.K. Working Party's diagnostic criteria. METHODS: The subjects of this study were mostly government officials or their family members visiting the Medical Center of Health Science, Toranomon Hospital in Tokyo for annual health check-ups in the period from September 1997 to August 1998. Questionnaires completed by 10 762 persons (8076 men and 2686 women) aged 30 years or above were analysed. The questionnaire consisted of 14 questions on allergic disease. The U.K. Working Party's diagnostic criteria were used after translation into Japanese. Three types of prevalence were used as indicators of prevalence: point, 1-year and lifetime prevalence. RESULTS: The point prevalence, 1-year prevalence and lifetime prevalence of AD in Japanese adults were 2.9%, 3.0% and 3.3%, respectively. No significant statistical differences were observed between the sexes or among age groups within each sex. The survey indicated that 88.6% of those who had ever had AD were currently affected by active AD, while 93.4% of those who had had at least one episode of AD in the past had experienced an episode over the previous year. CONCLUSIONS: This study gives the first indication of the prevalence of adult AD among the Japanese, based on the U.K. criteria. Both the internal and external validity of this study are believed to be high; it would be safe to conclude that the 1-year prevalence of AD in Japanese adult populations living in urban areas is 3.0%.

Adult↗

Treatment of unruptured cerebral aneurysms--a multi-center study of Japanese national hospitals.

The treatment and natural course of unruptured cerebral aneurysms were analyzed in 427 cases of unruptured cerebral aneurysm registered at five Japanese national hospitals. Of these cerebral aneurysms 295 were treated by craniotomy, and 22 with endovascular coil embolization. Neurological deterioration after treatment occurred in 31 (9.8%) of the 295 craniotomies and 3 (13.6%) of the 22 endovascular treatments. There was no subarachnoid hemorrhage (SAH) reported after the craniotomies whereas one case of SAH was reported after endovascular treatment. For 145 aneurysms in 110 cases, the natural course of the aneurysms was observed without surgical treatment. During the follow up period of in total 2,610 months (217.5 years), seven of these aneurysms ruptured, resulting in a rupture rate of 3.2%/year. Three of these seven aneurysms were less than 10 mm in diameter. The likelihood of an unruptured cerebral aneurysm to rupture was not exceedingly low. Since the risk of rupture and the morbidity related to surgical treatment cannot be predicted by size alone, the morphology, location and condition of the patients should be considered when treating unruptured cerebral aneurysms.

Adult↗

Clinical manifestations, character of aneurysms, and surgical results for unruptured cerebral aneurysms presenting with ophthalmic symptoms.

OBJECTS: Cases with unruptured cerebral aneurysms presenting with visual symptoms were investigated about their site, size, symptom, operative methods and results. MATERIAL: Between 1984 and 1999, 8 cases were treated in Sendai National Hospital. One man and 7 women, mean age 66.4 years. Ophthalmic symptoms were as follows: diplopia in 6, visual acuity deterioration in 2, impaired visual field in 2 and ptosis in 3. Aneurysm location was IC cavernous in 3, IC ophthalmic in 3, ICPC in 1 and Acom in 1. Aneurysms of more than 25 mm numbered 6 cases. RESULTS: Operative methods and results were as follows: Direct clipping 3 cases, parent artery occlusion + EC/IC bypass 4 cases, Aneurysm trapping + EC/IC bypass 1 case. One patient who underwent direct clipping died following intraoperative complication. Of the remaining 7 cases, visual symptoms were improved in 4, remained unchanged in 2 cases, worsened in 1 case. CONCLUSIONS: These results suggest that in cases with unruptured large or giant aneurysms presenting with ophthalmic symptoms, especially in IC cavernous or IC ophthalmic aneurysms, parent artery occlusion + EC/IC bypass is the safest operative procedure.

Aged↗

Coding of auditory temporal and pitch information by hippocampal individual cells and cell assemblies in the rat.

This study reports how hippocampal individual cells and cell assemblies cooperate for neural coding of pitch and temporal information in memory processes for auditory stimuli. Each rat performed two tasks, one requiring discrimination of auditory pitch (high or low) and the other requiring discrimination of their duration (long or short). Some CA1 and CA3 complex-spike neurons showed task-related differential activity between the high and low tones in only the pitch-discrimination task. However, without exception, neurons which showed task-related differential activity between the long and short tones in the duration-discrimination task were always task-related neurons in the pitch-discrimination task. These results suggest that temporal information (long or short), in contrast to pitch information (high or low), cannot be coded independently by specific neurons. The results also indicate that the two different behavioral tasks cannot be fully differentiated by the task-related single neurons alone and suggest a model of cell-assembly coding of the tasks. Cross-correlation analysis among activities of simultaneously recorded multiple neurons supported the suggested cell-assembly model.Considering those results, this study concludes that dual coding by hippocampal single neurons and cell assemblies is working in memory processing of pitch and temporal information of auditory stimuli. The single neurons encode both auditory pitches and their temporal lengths and the cell assemblies encode types of tasks (contexts or situations) in which the pitch and the temporal information are processed.

Acoustic Stimulation↗

Microdosimetry of epithermal neutron field at the Kyoto University reactor.

Microdosimetric spectra were measured in order to gain the microdosimetric parameters of some epithermal neutron fields. Changes in dose mean lineal energy YD as a function of depth of heavy water showed a trend of softening with heavy water of the beam. The neutron absorbed dose was obtained by using the frequency mean lineal energy. Results show good agreement with measurements with the activation method using gold foil. This study demonstrated how microdosimetric parameters change in radiation quality as a function of heavy water depth.

Deuterium Oxide↗

Evaluation of apoptosis and micronucleation induced by reactor neutron beams with two different cadmium ratios in total and quiescent cell populations within solid tumors.

PURPOSE: Response of quiescent (Q) and total tumor cells in solid tumors to reactor neutron beam irradiation with two different cadmium (Cd) ratios was examined in terms of micronucleus (MN) frequency and apoptosis frequency, using four different tumor cell lines. METHODS AND MATERIALS: C57BL mice bearing EL4 tumors, C3H/He mice bearing SCC VII or FM3A tumors, and Balb/c mice bearing EMT6/KU tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty min after i.p. injection of sodium borocaptate-10B (BSH), or 3 h after oral administration of p-boronophenylalanine-10B (BPA), the tumors were irradiated with neutron beams. The tumors without 10B-compound administration were irradiated with neutron beams or gamma-rays. This neutron beam irradiation was performed using neutrons with two different Cd ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the MN frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, for apoptosis assay, 6 h after irradiation, tumor cell suspensions obtained in the same manner were fixed, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequencies in total (P + Q) tumor cells were determined from the tumors that were not pretreated with BrdU. RESULTS: Without 10B-compounds, the sensitivity difference between total and Q cells was reduced by neutron beam irradiation. Under our particular neutron beam irradiation condition, relative biological effectiveness (RBE) of neutrons was larger in Q cells than in total cells, and the RBE values were larger for low Cd-ratio than high Cd-ratio neutrons. With 10B-compounds, both frequencies were increased for each cell population, especially for total cells. BPA increased both frequencies for total cells more than BSH did. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that of Q cells treated with BSH. Whether based on the MN frequency or the apoptosis frequency, similar results concerning the sensitivity difference between total and Q cells, the values of RBE, and the enhancement effect by the use of 10B-compound were obtained. CONCLUSION: Apoptosis frequency, as well as the MN frequency, can be applied to our method for measuring the Q cell response to reactor neutron beam irradiation within solid tumor in which the ratio of apoptosis to total cell death is relatively high, as in EL4 tumor. The absolute radiation dose required to achieve the same endpoint for Q cells is much higher than that for total cells when combined with 10B-compound, especially with BPA.

Animals↗

Relation between breastfeeding and the prevalence of asthma : the Tokorozawa Childhood Asthma and Pollinosis Study.

Many risk factors for asthma have been proposed including age, gender (male), smoking, and family history of asthma. The importance of breastfeeding to childhood asthma is a controversial issue. The present study investigated the relation between breastfeeding and the prevalence of asthma among a childhood population. The subjects were 25,767 students, representing all public elementary and junior high schools in Tokorozawa, Japan (age range, 6--15 years). The study population included 2,315 students with asthma and 21,513 controls. Participants' parents completed the Japanese version of the American Thoracic Society and Division of Lung Diseases, National Heart, Lung, and Blood Institute, questionnaire for children adopted by the Japanese Environmental Agency in 1998. The authors added supplementary questions on the parental history of asthma and feeding patterns from the age of 0--3 months. The risk of breastfeeding for asthma was compared with that of artificial feeding. After adjustment for age, gender, parental smoking status, and parental history of asthma, a significantly higher prevalence of asthma was noted among children who had been breastfed (adjusted odds ratio = 1.198; 95% confidence interval: 1.054, 1.363; p for trend < 0.01). The results indicated that breastfeeding in infancy might be related to the higher prevalence of asthma during preadolescence.

Adolescent↗

Development of the polymer micelle carrier system for doxorubicin.

We show the result of pre-clinical study of NK911, a polymeric micelle carrier system for doxorubicin (DOX). The NK911 micelle carrier consists of polyethyleneglycol and conjugated doxorubicin-polyaspartic acid. It has high hydrophobic inner core, and therefore can entrap the sufficient amount of DOX. NK911 has a small particle size of about 40 nm in diameter that accumulates in tumor tissue by EPR effect showing much stronger activity than the free DOX. We plan to perform a clinical trial at National Cancer Center Hospital, Japan from 2001.

Animals↗

Use of highly energetic (116 keV) synchrotron radiation for X-ray fluorescence analysis of trace rare-earth and heavy elements.

This study has revealed the advantages of the use of 116 keV X-rays as an excitation source of X-ray fluorescence (XRF) analyses. This technique is suitable for nondestructive multielemental analyses of heavy elements such as rare-earth elements. The lowest MDL value evaluated for the bulk analysis of a JG-1 standard reference sample (granite rock) was 0.1 ppm for W for a 500 s measurement. The spectrum of standard glass samples of SRM612 demonstrated clearly resolved K-line peaks of more than 30 elements, including all the existing rare-earth elements, at 50 ppm levels. The calibration curve for the determination of a rare-earth element shows a linear relation between the XRF intensity and concentrations from 10 to 0.03 ng. This powerful technique should be useful for nondestructive analyses of rare-earth and heavy elements in geological, geochemical and archaeological samples as well as industrial materials.

Metals, Rare Earth↗

Complete amino acid sequence of kaouthiagin, a novel cobra venom metalloproteinase with two disintegrin-like sequences.

The primary structure of kaouthiagin, a metalloproteinase from the venom of the cobra snake Naja kaouthia which specifically cleaves human von Willebrand factor (VWF), was determined by amino acid sequencing. Kaouthiagin is composed of 401 amino acid residues and one Asn-linked sugar chain. The sequence is highly similar to those of high-molecular mass snake venom metalloproteinases from viperid and crotalid venoms comprised of metalloproteinase, disintegrin-like, and Cys-rich domains. The metalloproteinase domain had a zinc-binding motif (HEXXHXXGXXH), which is highly conserved in the metzincin family. Kaouthiagin had an HDCD sequence in the disintegrin-like domain and uniquely had an RGD sequence in the Cys-rich domain. Metalloproteinase-inactivated kaouthiagin had no effect on VWF-induced platelet aggregation but still had an inhibitory effect on the collagen-induced platelet aggregation with an IC(50) of 0.2 microM, suggesting the presence of disintegrin-like activity in kaouthiagin. To examine the effects of these HDCD and RGD sequences, we prepared synthetic peptides cyclized by an S-S linkage. Both the synthetic cyclized peptides from the disintegrin-like domain and from the Cys-rich domain) had an inhibitory effect on collagen-induced platelet aggregation with IC(50) values of approximately 90 and approximately 4.5 microM, respectively. The linear peptide (RAAKHDCDLPELC) and the cyclized peptide had little effect on collagen-induced platelet aggregation. These results suggest that kaouthiagin not only inhibits VWF-induced platelet aggregation by cleaving VWF but also disturbs the agonist-induced platelet aggregation by both the disintegrin-like domain and the RGD sequence in the Cys-rich domain. Furthermore, our results imply that the corresponding part of the Cys-rich domain in other snake venom metalloproteinases also has a synergistic disturbing effect on platelet aggregation, serving as a second disintegrin-like domain. This is the first report of an elapid venom metalloproteinase with two disintegrin-like sequences.

Amino Acid Motifs↗