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Biomedical subjects

T Yoshimoto

Publications and source records attributed to T Yoshimoto.

At least 19 recordsLinked to original sources

Horizontal and vertical distribution of estrogenic activities in sediments and waters from Tokyo Bay, Japan.

Endocrine-disrupting chemicals with estrogenic activity (e.g., alkylphenols) have been detected in coastal Japan. We aimed to determine estrogenic activity in extracts of river water, seawater, sediments, and sediment cores from Tokyo Bay by in vitro gene expression assay. Fifty-one of 57 extracts had some estrogenic activity. E2 equivalents (ng E2 equivalents per gram dry weight or per liter above the limit of detection) in river water samples ranged from 0.70 to 4.01 ng/L; in seawater samples from 0.34 to 2.52 ng/L; and in surface sediments from 2.07 to 12.1 ng/g. The relationship between salinity and estrogenic activity in water samples suggested that fresh water is one source of environmental estrogens in Tokyo Bay. Fractionation of sediment extracts showed that the highest estrogenic activity was observed in the midpolar fraction. The observed activities were compared with activities mediated by known concentrations of nonylphenol, bisphenol-A, estrone, and 17beta-estradiol. In sediment collected near the sewage treatment plants, the estrogenic activity of the midpolar fraction could be explained about 34% by nonylphenol and estrone contained in this fraction. Core sediment measurements detected estrogenic activity from as far back as the 1960s. The regulations on the industrial wastewater in early 1970s would be one of the main reasons for the lower estrogenic activity in the upper section of the sediment core. The high estrogenic activities as measured in water and sediment samples from Tokyo might be restricted to certain coastal areas.

Biological Assay↗

Combined therapy of deoxyspergualin and plasmapheresis: a useful treatment for antibody-mediated acute rejection after kidney transplantation.

Antibody-mediated acute rejection (AbAR) is one of the primary causes of graft impairment in kidney transplant recipients. Deoxyspergualin (DSG), which displays an antiproliferative action against antigen-stimulated B cells inhibiting antibody production, may be effective to rescue AbAR in combination with plasmapheresis by suppressing antibody production and elimination. In the present study, we report our experience with DSG/plasmapheresis therapy for the treatment of AbAR. Five kidney transplant patients experienced a steroid-resistant acute rejection requiring dialysis followed by an AbAR that was confirmed by biopsy and flow cytometry crossmatch (FCXM) results. DSG was administration at 3 mg/kg per day for 10 days with plasmapheresis reduce antidonor antibody. Treatment outcome, effectiveness, and adverse events were examined; in two cases sequential FCXM examinations were performed to evaluate antibody status. All five patients received DSG/plasmapheresis therapy. The number of plasmapheresis treatments ranged from 1 to 9 according to treatment outcomes. Four patients recovered graft function following treatment; whereas one showed no response to the treatment, and the graft was lost. No serious side effects or infections were observed during or after treatment. Monitoring of sequential FCXM correlated with the clinical course. AbAR shows a worse prognosis than cellular rejection. It is refractory to conventional antirejection therapy. In the present study, DSG/plasmapheresis therapy was effective in four of five patients (80%) with AbAR. It may be considered the first choice of treatment for cases of acute humoral rejection.

Acute Disease↗

Sequential blood level monitoring of basiliximab during multisession plasmapheresis in a kidney transplant recipient.

Basiliximab, a chimeric monoclonal antibody against the alpha chain of the interleukin-2 receptor (IL-2R) has been used in renal transplant patients. We monitored sequential blood concentrations of basiliximab in a patient who received a kidney transplant with basiliximab-based immunosuppression together with multiple sessions of plasmapheresis. A 34-year-old man received a living-related kidney transplant with induction immunosuppression including tacrolimus, mycophenolate, methylprednisolone, and basiliximab. Severe antibody-mediated acute rejection lead to a requirement for hemodialysis. Deoxyspergualin was administered for 10 days at a daily dose of 5 mg/kg combined with eight sessions of double filtration plasmapheresis (DFPP). After treatment, the serum creatinine returned to 0.95 mg/dL, and there were no major complications or infections. Sequential basiliximab blood levels of the patient were monitored following transplantation. The serum basiliximab concentration decreased by 72.4% after five consecutive DFPPs, and by 87.6% after eight DFPP sessions. The elimination rate of basiliximab (DeltaBLX) was 6.1% before DFPP, but increased over eight DFPPs to 20.5%. Serum basiliximab concentrations declined to 0.16 microg/mL on day 33, which is below the IL-2R saturation concentration (0.2 microg/mL). Multiple sessions of plasmapheresis using DFPP enhanced the elimination of serum basiliximab at an average elimination rate of 19.1%. In the patient reported on here, the serum basiliximab concentration fell to below the IL-2R saturation level (0.2 microg/mL) within 1 month of living-related kidney transplantation. We recommend that additional basiliximab infusions be considered for cases undergoing more than three plasmapheresis sessions.

Acute Disease↗

Routine clinical adoption of magnetic resonance imaging was associated with better outcome after surgery in elderly patients with a malignant astrocytic tumour: a retrospective review.

BACKGROUND: There is controversy about extensive surgical treatment for a malignant astrocytic tumour in more elderly patients who may have poorer outcomes and higher complication rates. This retrospective study investigated outcome in elderly patients with malignant astrocytic tumour before and after the adoption of routine clinical use of magnetic resonance (MR) imaging. METHODS: During 1982 through 1999, 88 patients with malignant astrocytic tumour aged 60 years or over were treated in our institute. Thirty-seven patients had an anaplastic astrocytoma and 51 had a glioblastoma. Thirty-seven patients treated from 1982 to 1988 did not have pre-operative evaluation by MR imaging (Group A), 26 patients treated from 1989 to 1995 had preoperative MR imaging evaluation (Group B), and 25 patients treated after 1996 underwent preoperative MR imaging with functional brain mapping and intra-operative navigation system monitoring (Group C). FINDINGS: The median survival time was 8.8 months in Group A, 12.7 months in Group B, and 17.6 months in Group C. Patients with glioblastoma in Group B (11.7 months, n = 15) and Group C (16.0 months, n = 19) had significantly longer median survival time than in Group A (6 months, n = 17) (P = 0.0054 between Groups A and B, P = 0.0024 between Groups A and C). Better preoperative performance status, more thorough surgical resection, and better performance status after the initial treatment was obtained after the introduction of MR imaging, and patients with the optimal indicators showed significantly longer survival time compared with the patients without these factors. INTERPRETATION: Pre-operative MR imaging may contribute to longer survival time by providing an earlier diagnosis in patients with better performance status, by allowing more thorough surgical resection, and resulting in better performance status after the treatment.

Aged↗

Neuromagnetic separation of secondarily bilateral synchronized spike foci: report of three cases.

To demonstrate the high spatiotemporal resolution of magnetoencephalography (MEG), we report three cases with focal epilepsy that exhibited bilateral synchronized spikes on simultaneous scalp EEG and MEG recording. Constant time lags (19.4 +/- 3.0 ms and 20.0 +/- 5.5) between the leading and the following contralateral spikes were noted on MEG and the current dipole sources were localized in the bilateral homotopic regions symmetrically in Cases 1 and 3. In Case 2, MEG indicated leading spikes in the left frontal region, with a time lag of 42.3 +/- 8.4 ms to reach the contralateral frontal and bilateral temporal regions as well. Chronic subdural EEG recording in Cases 1 and 2 confirmed that the leading spike focus in MEG was close to the seizure onset zone in cortical EEG. Spatio-temporal analysis of MEG spikes may be useful to identify the primary epileptic region in patients with synchronized bilateral epileptiform discharges.

Adolescent↗

IL-18 gene therapy develops Th1-type immune responses in Leishmania major-infected BALB/c mice: is the effect mediated by the CpG signaling TLR9?

IL-18 regulates either Th1 or Th2 responses depending on the cytokine microenvironment. Administration of recombinant IL-18 (rIL-18) alone does not promote Th1 response, but rather induces Th2 response and exacerbates Leishmania major infection in susceptible BALB/c mice. Here, we treated BALB/c mice with an IL-18-expressing plasmid by using a gene gun weekly after L. major infection. This gene therapy resulted in improved pathogenic process and preferential induction of Th1 responses by inducing the expression of IL-12 p40, but treatment with rIL-18 did not. Notably, simultaneous administration of rIL-18 with an empty plasmid vector rendered BALB/c mice resistant to the infection, despite the fact that treatment with either rIL-18 alone or the plasmid vector alone did not influence the susceptibility. The synergistic role of the vector with rIL-18 was found to depend on CpG motifs, which enhanced expression of proinflammatory cytokines, especially IL-12, from APCs through Toll-like receptor (TLR) 9 ligation. Treatment with methylated plasmid vector in which CpG was disrupted could no longer prevent the disease development in coadministration with rIL-18. Taken together, IL-18 gene therapy was shown to develop Th1-type protective immunity in L. major-infected BALB/c mice without the requirement of exogenous IL-12, probably via CpG-TLR9 signaling pathway.

Animals↗

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↗

Purification and properties of a novel glycine amino peptidase from Actinomucor elegans and its potential application.

AIMS: To study the properties and show the potential application of a glycine aminopeptidase from Actinomucor elegans. METHODS AND RESULTS: The enzyme was estimated to have molecular mass of 320 kDa by gel filtration and the subunit size of 56.5 kDa by SDS-PAGE. It hydrolysed glycine from substrate more efficiently than other amino acids. The optimal temperature for this enzyme was 40 degrees C and at pH 8.0 it showed its highest activity. The Km and Kcat of the enzyme for glycine-beta-naphthylamine was 0.24 mm and 100.8 s(-1), respectively. Zinc, copper, cadmium and o-phenanthrolin suppressed almost all enzyme activities at the concentration of 1.0 mm. In the process of hydrolysing proteins, it could improve the protease activity considerably. CONCLUSIONS: It was a hexamer metalloenzyme which was specific for the substrates with glycinse residue at the N-terminal and some metal cations were needed to maintain its activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the properties of a novel aminopeptidase and shows its potential application in the process of the food industry.

Aminopeptidases↗

Somatosensory-evoked fields for gingiva, lip, and tongue.

To localize the oral primary somatosensory cortex, we measured somatosensory-evoked fields for the lip, gingiva, and tongue in six healthy subjects. The latency of the first peak of the posterior-oriented current in the contralateral hemisphere was 50.9 +/- 8.3 ms for the gingiva, significantly shorter than those for the lip and tongue peaks. The equivalent current dipole was localized on the central sulcus. The gingival dipole was localized significantly inferior to the lip dipole but not different from the tongue dipole. The moment of the gingival dipole was significantly smaller than that of the lip dipole but not different from that of the tongue dipole. Differences in the above parameters were negligible between the left and right, anterior and posterior, and upper and lower locations within the same organ, except that the dipole location for the anterior upper tongue was significantly inferior to that for the lower tongue.

Adult↗

Intraoperative direct neuroendoscopic observation of the aqueduct in Dandy-Walker malformation.

A 3-month-old female infant with Dandy-Walker malformation manifesting as hydrocephalus was treated successfully by only ventriculoperitoneal shunting. A flexible neuroendoscope was used intraoperatively to confirm the patency of the aqueduct, i.e. communication of the ventricular system and the cyst in the posterior fossa. Direct confirmation of the patency of the aqueduct and cyst communication is valuable to select the shunt procedure in the treatment of Dandy-Walker malformation.

Cerebral Aqueduct↗

Anti-IgM-induced down-regulation of nuclear Thy28 protein expression in Ramos B lymphoma cells.

We recently cloned mouse Thy28 cDNA (mThy28), which is highly conserved among vertebrates and plants. The mThy28 mRNA is highly expressed in testis, liver, kidney, brain, with moderate expression in thymus, spleen, and heart. In the present study, characteristics of mouse Thy28 protein expression were examined using rabbit anti-mThy28 polyclonal antibody (Ab). Levels of mThy28 protein expression were highest in testis, with moderate expression in liver, spleen, and thymus. The Thy28 protein was mainly located in the nucleus, which was revealed by immunofluorescence microscopy and Western blotting using anti-mThy28 Ab, and transient expression of the mThy28/EGFP fusion gene. Engagement of membrane immunoglobulin with anti-IgM induced down-regulation of human Thy28 expression at both mRNA and protein levels, accompanied by induction of apoptosis in Ramos B lymphoma cells. Expression of protein and mRNA and induction of apoptosis were evaluated by flow cytometry/Western blotting, reverse transcription-polymerase chain reaction, and propidium iodide staining, respectively. Anti-IgM also down-regulated the promoter activity of the mThy28 gene, as demonstrated by luciferase assay. Thus, the anti-IgM-induced down-regulation of the nuclear Thy28 expression appears to correlate with the induction of apoptosis in Ramos B lymphoma cells.

Animals↗

Holmium:YAG laser-induced liquid jet dissector: a novel prototype device for dissecting organs without impairing vessels.

BACKGROUND AND OBJECTIVE: Neurosurgery has long required a method for dissecting brain tissue without damaging principal vessels and adjacent tissue, so as to prevent neurological complications after operation. In this study we fabricated such a prototype device and used it in an attempt to resect an animal liver, which, like the brain, contains many vessels. MATERIALS AND METHODS: The prototype device consisted of a jet nozzle and a suction tube. Pulsed liquid jets at 3 Hz were ejected from the nozzle by a pulsed holmium:YAG (Ho:YAG) laser at an irradiation energy of 230 mJ/pulse. The profile of the liquid jet was observed with a high-speed camera. With this device, liver dissections of anesthetized rabbits were attempted while measuring the local temperature of the target. A histological study of the incised parts was also performed. RESULTS: The liquid jet was emitted straight from the nozzle at an initial velocity of 38 m/sec. The liver parenchyma was cut with the device while preserving the tiny vessels and keeping the operative field clear. The local temperature rose to no more than 314 K (below the heat damage threshold of brain tissue). In the histological findings, there were no signs of hepatic degeneration or necrosis around the dissected margin. CONCLUSIONS: The Ho:YAG laser-induced liquid jet dissector can be applied to neurosurgical operations after incorporating some minor improvements.

Animals↗

Intraoperative thermal artery imaging of an EC-IC bypass in beagles with infrared camera with detectable wave-length band of 7-14 microm: possibilities as novel blood flow monitoring system.

OBJECTIVE: In the past, the usefulness of thermal arterial imaging during coronary bypass surgery using an infrared camera has been reported by several investigators. The goal of this study is to apply this novel imaging system for intraoperative arterial imaging, as well as to develop new utilizations for a neurosurgical procedure. MATERIALS: We have attempted real-time imaging of anastomotic and flow status in an external carotid-internal carotid artery (EC-IC) bypass surgery using a new-generation infrared camera (IRIS IV thermographic imaging system) in beagles. No contrast medium or radiation was used to obtain the images. The detectable wave-length band of the infrared lens was 7-14 microm. After completion of bypass monitoring, an additional teflon tube was inserted into a branch of the STA to inject physiological saline of different temperatures to see the changes in cortical images. RESULTS: Anastomotic and flow status were clearly visualized throughout the operation without local surface cooling, which had been an inevitable procedure in coronary imaging to make a pronounced temperature difference between artery and adjacent tissue. In addition, cortical flow territory was visualized after injection of either cold or warm physiologic saline into the artery from an additionally inserted teflon tube into a branch of STA via bypass artery. CONCLUSION: From the present experience, it is considered that infrared imaging using a detectable wave length band of 7-14 microm may be applicable to a wide variety of near surface lesions, providing a non-invasive functional angiography.

Animals↗

Factors influencing analysis of prolyl endopeptidase in human blood and cerebrospinal fluid: increase in assay sensitivity.

Prolyl endopeptidase (EC 3.4.21.26) (PEP) is present in nearly all investigated mammalian cells and biological fluids and might be involved in the degradation of physiologically important neuropeptides. To be able to investigate the variation of PEP in blood and cerebrospinal fluid (CSF) in human disease, the factors influencing analysis of PEP in these body fluids must be determined. The purpose of the present work was to study the influence of storage conditions, anticoagulation additives, freezing and thawing and substrate solvent on determination of PEP in blood plasma/serum and CSF. It was found that the PEP activity was about 10% higher in plasma (with EDTA and heparinate for anticoagulation) than in serum. Storage at room temperature (20 degrees C) caused a rapid decline in enzyme activity, which was smaller but still considerable at 4 degrees C. Storage at -20 degrees C and -70 degrees C did not decrease the PEP activity. Freezing and thawing of plasma/serum samples showed that the first freeze-thawing cycle produced a 20% reduction in enzyme activity but little further decrease was observed during subsequent cycles of freeze-thawing. In conclusion, PEP activity should preferably be measured within one hour after sampling using EDTA- or heparinate plasma. For long-term storage, samples should be immediately frozen and stored at -20 degrees C or colder. The selection and amount of the organic solvent used to dissolve the fluorogenic substrate strongly influenced the sensitivity of the assay. By developing an optimal solvent system an increase in assay sensitivity of about 400% could be obtained, which for the first time allowed measurement of the PEP activity in CSF.

Adult↗

Neurohypophyseal germinoma histologically misidentified as granulomatous hypophysitis.

We report a case of neurohypophyseal germinoma appearing as predominantly granulomatous reaction in the first histological examination. A 12-year-old boy presented with diabetes insipidus, panhypopituitarism, and bitemporal hemianopsia. Transsphenoidal exploration for the intrasellar mass lesion extending to the suprasellar region was performed in May 1999. Histological examination revealed granulomatous hypophysitis and corticosteroid therapy was initiated. Six months later, the lesion relapsed despite corticosteroid therapy. Subtotal removal of the lesion was performed via an anterior interhemispheric approach in December 1999. Histological examination revealed typical germinoma. Subsequently, the patient underwent irradiation of 20 Gy to the tumour site and 24 Gy to the whole brain. Magnetic resonance imaging confirmed tumour remission. We must consider the possibility of neurohypophyseal germinoma in patients with granulomatous hypophysitis which does not respond to corticosteroid therapy, and perform re-exploration for more specimens to achieve the correct diagnosis.

Adolescent↗

(201)Tl-SPECT, (1)H-MRS, and MIB-1 labeling index of central neurocytomas: three case reports.

BACKGROUND: The proliferative activity and metabolic features of three central neurocytomas were investigated using the findings of thallium-201 single photon emission computed tomography ((201)Tl-SPECT) and proton magnetic resonance spectroscopy ((1)H-MRS), and the MIB-1 labeling index (MIB-1 LI). METHOD: The early and delayed (201)Tl indices were calculated as the ratio of tumour to normal brain tissue uptake by (201)Tl-SPECT. In vivo single-voxel (1)H-MRS was performed with echo time of 272 msec to evaluate the metabolites including choline (Cho), N-acetyl aspartate (NAA) and creatine/phosphocreatine (Cre). An external standard reference was used to semiquantitate each metabolite. MIB-1 LI was determined in the surgical specimens. FINDINGS: The MIB-1 LI was 0.5%, 1.2%, and 7.5% in an atypical central neurocytoma without intraventricular extension. Significant (201)Tl uptake was observed on delayed images in all three central neurocytomas. (1)H-MRS showed the high Cho peaks relative to the NAA and Cre peak. The signal at 3.55 ppm, which may be due to inositol or glycine, was observed in one central neurocytoma. INTERPRETATION: Both (201)Tl-SPECT and (1)H-MRS did not reflect the proliferative potential of central neurocytomas.

Adult↗

A novel method of drug delivery for fibrinolysis with Ho:YAG laser-induced liquid jet.

Two of the problems inherent in the treatment of cerebral emboli are the narrow therapeutic time window and the severe side effects of fibrinolytic drugs. Thus, it is necessary to develop a new method of removing a cerebral thrombus more rapidly and with smaller quantities of fibrinolytics. The behaviour of a bubble formed by holmium (Ho):YAG laser irradiation in a capillary tube filled with pure water was observed at various stand-off distances (L; distance between the end of optical fibre and the capillary exit). Subsequently, a liquid-jet generator was created by insertion of an optical fibre (core diameter: 0.6 mm) into a catheter (6 Fr) filled with pure water, and a pulsed Ho:YAG laser (pulse duration time=350 micros, laser energy=230 mJ/pulse) was used to irradiate the optical fibre. The maximum penetration depth, into a gelatin artificial thrombus, of a liquid jet generated with this device was measured for various stand-off distances. Additionally, the phenomenon and the pressure around the catheter exit were captured via shadowgraph and PVDF needle hydrophone, respectively. The laser-induced bubble in the capillary tube grew rapidly in the direction of propagation and generated a liquid jet. The maximum penetration depth of this liquid jet into an artificial thrombus increased in proportion to L and reached a maximum value (9 mm) when L was around 13 mm. A shock wave whose overpressure at a point 4 mm away from the catheter exit exceeded 12 MPa was captured by shadowgraph. It was concluded that Ho:YAG laser irradiation within a water-filled catheter caused liquid jet formation, which could penetrate straight into an artificial thrombus. Hence, this jet is expected to promote fibrinolysis by means of injecting fibrinolytics deeply into the thrombus. After resolving some problems, this system will be applied to an endovascular therapy for cerebral embolisms in the near future.

Catheterization↗

Mesial temporal lobe epilepsy with lateral temporal lobe abnormalities in magnetoencephalography and glucose metabolism.

Magnetoencephalography (MEG) and positron emission tomography (PET) revealed abnormal findings in the lateral temporal lobe of a 22 year old female with mesial temporal lobe epilepsy. Electroencephalography identified the epileptogenic focus in the left mesial temporal lobe and standard anterior temporal lobectomy resulted in a good surgical outcome. These discrepancies can be explained by the presence of anatomical and functional pathways between the mesial and lateral temporal structures, or pathophysiological abnormalities in both the mesial and lateral temporal lobes. Careful evaluation is necessary for analysis of MEG and PET findings in patients with temporal lobe epilepsy.

Adult↗