Biomedical subjects

K Yokoyama

Publications and source records attributed to K Yokoyama.

At least 19 recordsLinked to original sources

PubMed2007

Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma: clinical safety.

The curative treatments for hepatocellular carcinoma (HCC), including surgical resection and radiofrequency ablation (RFA), do not prevent tumour recurrence effectively. Dendritic cell (DC)-based immunotherapies are believed to contribute to the eradication of the residual and recurrent tumour cells. The current study was designed to assess the safety and bioactivity of DC infusion into tumour tissues following transcatheter hepatic arterial embolization (TAE) for patients with cirrhosis and HCC. Peripheral blood mononuclear cells (PBMCs) were differentiated into phenotypically confirmed DCs. Ten patients were administered autologous DCs through an arterial catheter during TAE treatment. Shortly thereafter, some HCC nodules were treated additionally to achieve the curative local therapeutic effects. There was no clinical or serological evidence of adverse events, including hepatic failure or autoimmune responses in any patients, in addition to those due to TAE. Following the infusion of (111)Indium-labelled DCs, DCs were detectable inside and around the HCC nodules for up to 17 days, and were associated with lymphocyte and monocyte infiltration. Interestingly, T lymphocyte responses were induced against peptides derived from the tumour antigens, Her-2/neu, MRP3, hTERT and AFP, 4 weeks after the infusion in some patients. The cumulative survival rates were not significantly changed by this strategy. These results demonstrate that transcatheter arterial DC infusion into tumour tissues following TAE treatment is feasible and safe for patients with cirrhosis and HCC. Furthermore, the antigen-non-specific, immature DC infusion may induce immune responses to unprimed tumour antigens, providing a plausible strategy to enhance tumour immunity.

Aged↗

PubMed2006

Value of 123I-MIBG radioactivity in the differential diagnosis of DLB from AD.

OBJECTIVE: To evaluate the diagnostic reliability of cardiac iodine-123 metaiodobenzylguanidine ((123)I-MIBG) radioactivity in discriminating dementia with Lewy bodies (DLB) from Alzheimer disease (AD) regardless of parkinsonism. BACKGROUND: The diagnosis of DLB may be confounded by the absence of parkinsonism. This highlights the need to improve the accuracy of antemortem diagnosis of DLB without parkinsonism. METHODS: Cardiac sympathetic denervation was examined using myocardial (123)I-MIBG scintigraphy in 37 patients with DLB, 42 patients with AD, and 10 normal elderly controls. The DLB patients consisted of seven patients without parkinsonism (DLB/P-) and 30 patients with parkinsonism (DLB/P+) at the time of the study. RESULTS: The heart-to-mediastinum uptake ratio (H/M ratio) of myocardial MIBG uptake was decreased in both the DLB groups vs the AD group (p < 0.0001) and control group (p < 0.0001). The washout rate (WR) was higher in the DLB group than in the control group (p < 0.0001) and AD group (p < 0.0001). No differences were found between the AD and control groups or between the DLB/P+ and DLB/P- groups in either the early or delayed H/M ratio or WR. In discriminating between DLB and AD, regardless of parkinsonism, the delayed H/M ratio had a sensitivity of 100%, a specificity of 100%, and a positive predictive value of 100% at a cutoff value of 1.68. CONCLUSIONS: Our results indicate that dementia with Lewy bodies results in cardiac sympathetic denervation and that iodine-123 metaiodobenzylguanidine myocardial scintigraphy is a sensitive tool for discriminating dementia with Lewy bodies from Alzheimer disease even in patients without parkinsonism.

3-Iodobenzylguanidine↗

PubMed2006

Isothiazoles. Part XV. A mild and efficient synthesis of new antiproliferative 5-sulfanylsubstituted 3-alkylaminoisothiazole 1,1-dioxides.

5-Sulfanyl-3-alkylaminoisothiazole dioxide derivatives have been identified as a new class of potent inhibitors of rat aortic myocite proliferation. They were prepared by applying a simple methodology able to introduce a heteroatom on C-5 of the 3-alkylaminoisothiazole dioxide system. 3-Aminosubstituted-5-chloroisothiazole dioxides react smoothly not only with S-nucleophiles but also with N- and O-nucleophiles affording the corresponding 5-heterosubstituted isothiazole dioxides through an addition-elimination reaction. The behavior of 3-alkylamino-4-bromo-isothiazole 1,1-dioxide with S-, N- and O-nucleophiles affording the same products has also been described. On the contrary, the 3-amino-4,5-unsubstituted isothiazole dioxide system reacts easily only with sulfur nucleophiles affording the corresponding 4,5-dihydro-5-sulfanylderivatives through a simple Michael addition reaction.

Alkyl and Aryl Transferases↗

PubMed2006

Aleukaemic leukaemia cutis as an initial manifestation of myeloid/NK cell precursor acute leukaemia.

Aleukaemic leukaemia cutis is a rare condition characterized by infiltration of leukaemic cells into the skin before they appear in the peripheral blood. We report a case of an aleukaemic leukaemia cutis, which had a history of exposure to atomic bomb radiation. A 57-year-old Japanese woman initially presented with a 20-week history of multiple red papules and plaques mainly over the trunk. Histological examination revealed the infiltration of atypical monocytic cells in the dermis, but no leukaemic cells were detected in the peripheral blood. Twenty-three weeks after the appearance of the eruption, leukaemic cells were detected in the peripheral blood for the first time. The results of immunohistochemistry of the skin biopsy specimen and flow cytometry of the peripheral blood indicated the rare phenotype of myeloid/NK cell precursor acute leukaemia. This is the first case report of myeloid/NK cell precursor acute leukaemia presenting as aleukaemic leukaemia cutis in the English literature, and awareness of this clinical presentation may be important to reach the correct diagnosis.

Fatal Outcome↗

PubMed2006

Radiation myelopathy after radioactive iodine therapy for spine metastasis.

A case of radiation myelopathy after radioactive iodine therapy is reported. This is the first report to describe radiation myelopathy after I-131 therapy. A 62-year-old female with spinal metastasis of T10 received I-131 therapy. She presented with radiation myelopathy 34 months after the irradiation. We need to recognize the possibility of this serious complication even in the case of I-131 therapy. There is a risk of radiation myelopathy even after I-131 therapy, especially in cases with spinal cord compression such as this.

Female↗

PubMed2005

Late preconditioning with isoflurane in cultured rat cortical neurones.

BACKGROUND: We tested the hypothesis that isoflurane induces late preconditioning in cultured rat cortical neurones and preconditioning elicits changes in expression of Kir6.2 (the ion-conducting subunit of the metabolically responsive ATP-sensitive potassium (K(ATP)) channel) and EAAC1 (neuronal glutamate transporter). METHODS: Primary cultures of rat cortical neurones were exposed to non-lethal oxygen-glucose deprivation (OGD), i.e. ischaemic preconditioning, for 30 min, 100 microM of diazoxide, a potent opener of the mitochondrial K(ATP) (mitoK(ATP)) channels, for 60 min or 1.4% isoflurane for 3 h. Lethal OGD was performed for 120 min 24 h after preconditioning stimuli. Neuronal injury was assessed by measurement of lactate dehydrogenase (LDH) efflux into the medium 24 h after lethal OGD, and neural viability was determined by proliferation assay. Gene and protein expression was confirmed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis 24 h after preconditioning stimuli. RESULTS: All preconditioning stimuli resulted in a significant decrease in LDH activity and maintained neuronal viability. These effects were abolished by 5-hydroxydecanoate, a selective inhibitor of the mitoK(ATP) channel. Quantitative RT-PCR and Western blot analysis demonstrated that there was no significant difference between Kir6.2 mRNA and protein levels. All preconditioning stimuli resulted in > or =2-fold increases in EAAC1 mRNA and protein compared with control. CONCLUSIONS: Isoflurane induced late preconditioning in cultured rat cortical neurones. Ischaemic and pharmacological preconditioning with diazoxide and isoflurane induced ischaemic tolerance in the cultured neurones via mitoK(ATP) channels without an increase in Kir6.2 expression, and induced upregulation of EAAC1 expression.

Anesthetics, Inhalation↗

PubMed2005

Assessment of room temperature influence on finger blood flow response induced by short-term grasping of vibrating handle.

OBJECTIVE: To investigate the influence of room temperature on finger blood flow (FBF) change in healthy subjects exposed to short-term grasping of a vibrating handle under different room temperatures. METHODS: FBF was measured using a blood flowmeter in six male subjects on the dorsum of the middle phalanx of third finger in both hands once at the end of every minute for an equal duration of 5 min at pre-exposure, during exposure to grasping of vibrating handle with sinusoidal vibration and after exposure. Vibration was generated with a frequency of 125 Hz and an rms acceleration of 40 m/s(2). Measurements were conducted in four room temperatures of 15+/-1, 20+/-1, 25+/-1 and 30+/-1 degrees C. RESULTS: Compared with the baseline measurements in the exposed hand during grasping of vibrating handle most significant increase in FBF was observed at 15+/-1 degrees C (P<0.001) and least at 30+/-1 degrees C (P<0.05), and after vibration least significant FBF was found at 25+/-1 degrees C (P<0.05). In case of the unexposed hand significant increase in FBF was exhibited at 20+/-1 degrees C (P<0.01) and 30+/-1 degrees C (P<0.01) during vibration, and only at 15+/-1 degrees C (P<0.05) after vibration. CONCLUSIONS: Response in FBF due to grasping of vibrating handle was of different patterns from the baseline measurement under different room temperature conditions in both exposed and unexposed hands and it was influenced by room temperature. Overall, the influence was greater at lower test room temperature, inducing more significant increase in FBF.

Adult↗

PubMed2005

Effect of room temperature on percentage finger systolic blood pressure response to finger cooling.

Percentage finger systolic blood pressure (%FSBP) in response to finger cooling is used to assess vascular components of the hand-arm vibration syndrome and the measurement method is under discussion for standardization. It has been suggested that measurement circumstances including room temperature may affect %FSBP. We investigated the effect of room temperature on %FSBP response to finger cooling in healthy subjects. Six healthy male subjects who were medical students volunteered for the study. Multi-channel plethysmograph was used for simultaneous multi-finger FSBP measurements. The examination room was kept at 21 +/- 1 degrees C and 25 +/- 1 degrees C, and the subjects were randomly assigned. Percentage finger systolic blood pressures for the index, middle, ring and little fingers at 15 degrees C and 10 degrees C cuff-water temperatures were calculated. Four-way analysis of variance was performed to determine the independent effect of subject, room temperature, finger and cuff-water temperature factors on %FSBP. The room temperature as an independent factor affecting %FSBP was statistically significant (P < 0.01). From the results, it can be concluded that %FSBP response to finger cooling in healthy subjects may be affected by room temperature. Therefore, room temperature is expected to be controlled when assessing peripheral vascular components of the upper extremities using %FSBP response to finger cooling.

Adult↗

PubMed2005

Post-irradiation hypoxic incubation of X-irradiated MOLT-4 cells reduces apoptotic cell death by changing the intracellular redox state and modulating SAPK/JNK pathways.

To elucidate radiobiological effects of hypoxia on X-ray-induced apoptosis, MOLT-4 cells were treated under four set of conditions: (1) both X irradiation and incubation under normoxia, (2) X irradiation under hypoxia and subsequent incubation under normoxia, (3) X irradiation under normoxia and subsequent incubation under hypoxia, and (4) both X irradiation and incubation under hypoxia, and the induction of apoptosis was examined by fluorescence microscopy. About 28-33% apoptosis was observed in cells treated under conditions 1 and 2, but this value was significantly reduced to around 18-20% in cells treated under conditions 3 and 4, suggesting that post-irradiation hypoxic incubation rather than hypoxic irradiation mainly caused the reduction of apoptosis. The activation and expression of apoptosis signal-related molecules SAPK/JNK, Fas and caspase-3 were also suppressed by hypoxic incubation. Effects of hypoxic incubation were canceled when cells were treated under conditions 3 and 4 with an oxygen-mimicking hypoxic cell radiosensitizer, whereas the addition of N-acetyl-L-cysteine again reduced the induction of apoptosis. From these results it was concluded that hypoxia reduced the induction of apoptosis by changing the intracellular redox state, followed by the regulation of apoptotic signals in X-irradiated MOLT-4 cells.

Acetylcysteine↗

PubMed2005

Onychomycosis caused by Fusarium proliferatum.

Fusarium infections in humans are usually opportunistic, but the fungus sometimes infects healthy persons, causing keratomycosis or onychomycosis. Onychomycosis is usually caused by F. solani or F. oxysporum. We report the first two cases of onychomycosis caused by F. proliferatum, and discuss methods of diagnosis and effective treatment. Nail samples from the two patients were examined by direct microscopy, cultured, and identified morphologically and genetically as F. proliferatum. Both patients were treated successfully with oral itraconazole, even though the minimum inhibitory concentration of itraconazole was relatively high in Patient 1. This is the first report of F. proliferatum as an agent of onychomycosis. Itraconazole may be effective in the treatment of onychomycosis caused by F. proliferatum.

Antifungal Agents↗

PubMed2005

Multistep differentiation of GH-producing cells from their immature cells.

In order to study GH cell differentiation, we used the clonal cell lines called MtT/E and MtT/S cells, which were derived from a rat mammotrophic pituitary tumor. Although MtT/E cells are non-hormone-producing ones, Pit-1 protein is present in their nuclei, which suggests that MtT/E cells are progenitor cells of the Pit-1 cell lineage and have the potential to differentiate into hormone-producing cells. On the other hand, MtT/S cells produce GH; however, the responsiveness to GH-releasing hormone (GHRH) is weak and only a small number of secretory granules are present in their cytoplasm, which suggests that MtT/S cells are premature GH cells. In order to differentiate into GH cells from MtT/E cells as a progenitor cell, we examined several differentiation factors and found that retinoic acid (RA) induced the differentiation of MtT/E cells into GH-producing cells. RA-induced GH cells partially matured with the glucocorticoid treatment; however, the responsiveness to GHRH on GH secretion was incomplete. In order to elucidate the mechanism underlying full differentiation of GH cells, we used MtT/S cells. We treated MtT/S cells with glucocorticoid and found that they differentiated into mature GH cells with many secretory granules in their cytoplasm and they responded well to GHRH. These results suggested that MtT/E and MtT/S cells are progenitor or premature GH cells, and show different responses to differentiation factors. Our data also suggested that GH cells differentiate from their progenitor cells through multistep processes.

Animals↗

PubMed2005

The effect of angiotensin receptor blockade ARB on the regression of left ventricular hypertrophy in hemodialysis patients: comparison between patients with D allele and non-D allele ACE gene polymorphism.

OBJECTIVE: It is revealed that LVH is one of risk factors for the development of cardiac complications in long-term HD patients. Therefore, maneuvers to reduce hypertrophy of cardium are very important for improving life prognosis. Angiotensin II receptor blockade (ARB) could reduce LVH in general populations without renal failure. However, no conclusive data has been available regarding the clinical consequences of ARB administration on the regression of LVH in HD patients. Furthermore, it has not clearly determined if ACE gene polymorphism has a possible influential effect on it. This study is conducted to clarify these issues. SUBJECTS AND METHOD: 32 hypertensive patients on regular HD (male/female: 21/11, mean age: 60.5 years, mean duration of HD: 52.8 months) were studied. Patients were classified into two groups according to the different type of ACE gene polymorphism: cases with D allele (DD/ID; D group: n = 13) and those without (II; non-D group: n = 19). All patients were administered ARB (losartan 50 - 100 mg/day) and echocardiography (UCG) was performed at 6-month-interval regularly until the end of observation (24 months). RESULTS: Before the commencement of ARB, no differences were found between the two groups, neither in mean blood pressure (MBP: D group/non-D group: 120 +/- 13 vs. 115 +/- 14 mmHg) nor in left ventricular mass index (LVMI: D/non-D: 172 +/- 41 vs. 165 +/- 41 g/m2). During the 24r-month follow-up, there were significant and similar reductions in MBP in both groups. In respect to LVMI, a significant reduction of LVMI was found in the D group after six months (p < 0.01 vs. basal) with a final reduction rate (FRR) -26 +/- 13%, whereas in the non-D group it was found at 24 months (p < 0.01 vs. basal) with FRR -11 +/- 16% (p < 0.01 vs. D group). There were significant differences between the two groups at all points (p < 0.05 at 6, 18 and 24 months, p < 0.005 at 12 months, respectively). CONCLUSION: It is indicated that ARB could insert a regression effect on LVH predominantly in patients with D allele ACE polymorphism, due partly to factor (s) independent of its anti-hypertensive effect.

Alleles↗

PubMed2004

Isolation of eight novel Caenorhabditis elegans small RNAs.

Eight novel small RNAs that were encoded in the regions corresponding to the introns of protein-coding genes were isolated from Caenorhabditis elegans. Seven of them showed a typical snoRNA secondary structure: one C/D snoRNA and six H/ACA snoRNAs. The remaining one RNA did not show any homology to other RNAs in a database. Four of the seven isolated snoRNAs could form base pairings with parts of rRNAs, suggesting that they are potential pseudouridilation sites and methylation sites. The results of our study suggest that there are more as-yet-unidentified small ncRNAs of which genes are located in the intron regions of protein-coding genes in C. elegans.

Animals↗

PubMed2004

Effect of prostaglandin E1 on inflammatory responses and gas exchange in patients undergoing surgery for oesophageal cancer.

BACKGROUND: Oesophageal surgery causes morbidity and mortality from respiratory complications. We tested the possibility that prostaglandin E1 (PGE1) could reduce inflammatory cytokine responses and improve gas exchange after oesophagectomy. METHODS: We randomized 14 patients into two groups. One group received PGE1 20 ng kg(-1) min(-1) i.v. during anaesthesia (PGE1 group) and the other group did not (control group). Anaesthesia was maintained with sevoflurane and epidural anaesthesia. During oesophagectomy, ventilation of one lung was carried out with a double-lumen bronchial tube. The patients were extubated on or after the first postoperative day. Blood samples were taken at induction of anaesthesia, at the end of thoracotomy, at the end of the operation, 2 h after surgery and on the first day after surgery. RESULTS: The groups were similar for ASA physical status, age, FEV1%, operation time, duration of thoracotomy, intraoperative fluid volume and blood loss. The arterial blood gas and arterial pressure during surgery were also similar in the PGE1 and control groups. However, the PaO2/FiO2 ratio on the first day after surgery was significantly greater in the PGE1 group compared with the control group. Serum concentrations of IL-6 and IL-8 increased after surgery in both groups. IL-6 was significantly less in the PGE1 group at the end of the operation and 2 h after the operation. CONCLUSIONS: Intraoperative PGE1 reduced IL-6 production in patients undergoing oesophagectomy and oxygenation was better in the postoperative period.

Aged↗

PubMed2004

Optimal control of ultrafast selection.

Optimal laser control for ultrafast selection of closely lying excited states whose energy separation is smaller than the laser bandwidth is reported on the two-photon transition of atomic cesium; Cs(6S-->7D(J), J=5/2 and 3/2). Selective excitation was carried out by pulse shaping of ultrashort laser pulses which were adaptively modulated in a closed-loop learning system handling eight parameters representing the electric field. Two-color fluorescence from the respective excited states was monitored to measure the selectivity. The fitness used in the learning algorithm was evaluated from the ratio of the fluorescence yields. After fifty generations, a pair of nearly transform-limited pulses were obtained as an optimal pulse shape, proving the effectiveness of the "Ramsey fringes" mechanism. The contrast of the selection ratio was improved by approximately 30% from the simple "Ramsey fringes" experiment.

Journal Article↗

PubMed2004

Properties and applications of microbial transglutaminase.

Some properties and applications of the transglutaminase (TGase) referred to as microbial TGase (MTGase), derived from a variant of Streptomyces mobaraensis (formerly classified as Streptoverticillium mobaraense), are described. MTGase cross-linked most food proteins, such as caseins, soybean globulins, gluten, actin, myosins, and egg proteins, as efficiently as mammalian TGases by forming an epsilon-(gamma-glutamyl)lysine bond. However, unlike many other TGases, MTGase is calcium-independent and has a relatively low molecular weight. Both of these properties are of advantage in industrial applications; a number of studies have illustrated the potential of MTGase in food processing and other areas. The crystal structure of MTGase has been solved. It provides basic structural information on the MTGase and accounts well for its characteristics. Moreover, an efficient method for producing extracellular MTGase has been established using Corynebacterium glutamicum. MTGase may be expected to find many uses in both food and non-food applications.

Coenzymes↗

PubMed2004

Protective effect of keishi-bukuryo-gan and its constituent medicinal plants against nitric oxide donor-induced neuronal death in cultured cerebellar granule cells.

Keishi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan) (KBG) is a traditional Chinese/Japanese medical (Kampo) formulation that has been administered to patients with "Oketsu" (blood stagnation) syndrome. In the process of neuronal cell death induced by brain ischemia, excessive generation of nitric oxide (NO) free radicals is implicated in the neurotoxicity. In the present study, we examined the protective effects of KBG and its constituent medicinal plants against NO donors, sodium nitroprusside (SNP) and 2,2'-(hydroxynitrosohydrazino)bis-ethanamine (NOC18)-induced neuronal death in cultured rat cerebellar granule cells (CGCs). MTT assay showed cell viability to be significantly increased by the addition of KBG extract (KBGE) (100 microg/ml), Cinnamomi Cortex extract (CCE) (3, 10 and 30 microg/ml), Paeoniae Radix extract (PRE) (100 microg/ml) and Moutan Cortex extract (MCE) (10 and 30 microg/ml) compared with exposure to SNP (30 microM, 24 h) only. Also, cell viability was significantly increased by the addition of KBGE (100 and 300 microg/ml), CCE (30 and 100 microg/ml), PRE (100 and 300 microg/ml) and MCE (30 and 100 microg/ml) compared with exposure to NOC 18 (100 microM, 48 h) only. Persicae Semen extract and Hoelen extract did not protect against NO donor-induced neuronal death. These results suggest that KBG has protective effect against NO-mediated neuronal death in cultured CGCs and that it is derived from Cinnamomi Cortex, Paeoniae Radix and Moutan Cortex.

Animals↗

PubMed2004

Optimization of radioimmunotherapy interactions with hyperthermia.

The efficacy of radioimmunotherapy (RIT) employing radiolabelled monoclonal antibodies (MAb) is currently limited in most solid tumours. The combination of local hyperthermia (HT) with RIT has the potential to enhance tumour targeting of MAb; moreover, this approach may add an antitumour effect to radioresistant hypoxic and S-phase cells and may inhibit the cells from repairing sublethal damage or potentially lethal damage caused by ionizing radiation. There are distinct types of protocols in this combination. Hyperthermic temperature and timing relative to RIT administration appear to affect the efficacy of the combination therapy. Responses to heating at any particular condition are not always the same among different tumour types. There are many papers describing influence of HT on the biodistribution of radiolabelled MAb, but only limited information is currently available on 'therapeutic' outcomes regarding the dependency of combination protocols. A previous study suggested that the best therapeutic improvement would be achieved when HT was combined immediately after the administration of MAb, which significantly increases the radiation absorbed dose to tumours and produces a uniform intratumoural dose distribution. Further therapeutic investigation should be required to reach the optimal protocol of combining these two modalities.

Animals↗