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Biomedical subjects

T Kubota

Publications and source records attributed to T Kubota.

At least 19 recordsLinked to original sources

Detailed images of asteroid 25143 Itokawa from Hayabusa.

Rendezvous of the Japanese spacecraft Hayabusa with the near-Earth asteroid 25143 Itokawa took place during the interval September through November 2005. The onboard camera imaged the solid surface of this tiny asteroid (535 meters by 294 meters by 209 meters) with a spatial resolution of 70 centimeters per pixel, revealing diverse surface morphologies. Unlike previously explored asteroids, the surface of Itokawa reveals both rough and smooth terrains. Craters generally show unclear morphologies. Numerous boulders on Itokawa's surface suggest a rubble-pile structure.

Journal Article↗

Touchdown of the Hayabusa spacecraft at the Muses Sea on Itokawa.

After global observations of asteroid 25143 Itokawa by the Hayabusa spacecraft, we selected the smooth terrain of the Muses Sea for two touchdowns carried out on 19 and 25 November 2005 UTC for the first asteroid sample collection with an impact sampling mechanism. Here, we report initial findings about geological features, surface condition, regolith grain size, compositional variation, and constraints on the physical properties of this site by using both scientific and housekeeping data during the descent sequence of the first touchdown. Close-up images revealed the first touchdown site as a regolith field densely filled with size-sorted, millimeter- to centimeter-sized grains.

Journal Article↗

Identification of arginase in human placental villi.

l-Arginine is the common substrate for arginase and nitric oxide synthase (NOS). Arginase converts l-arginine to urea and ornithine, which is the principal precursor for production of polyamines required for cell proliferation. Human placenta expresses endothelial NOS (eNOS) in syncytiotrophoblasts, but the expression of arginase has not been fully elucidated. Our aim was to investigate the expression and distribution patterns of arginase-I (A-I) and arginase-II (A-II) in human placental villi in the first trimester and at term using immunohistochemistry, RT-PCR and Western blot analysis. The arginase enzyme activity in placental villi was also measured. Immunohistochemistry showed different distribution patterns of the arginase isoforms during gestation: A-I was observed only in cytotrophoblasts, while A-II was observed in both cytotrophoblasts and syncytiotrophoblasts. RT-PCR and Western blot analysis showed expression of A-I and A-II in the first trimester and at term in human placental villi. Expression of A-II and arginase activity was greater in the first trimester than at term. Differentiation of cytotrophoblasts into syncytiotrophoblasts may be associated with l-arginine metabolism through modulation of l-arginine availability for eNOS and A-I. And elevated arginase activity in the early gestational period may be responsible for proliferation of trophoblasts by increasing polyamines production. These results suggest that the l-arginine-ornithine-polyamine and l-arginine-nitric oxide pathways play a role in placental growth and development.

Arginase↗

A local GABAergic system within rat trigeminal ganglion cells.

We investigated the GABAergic system within the Sprague-Dawley rat (2-3-weeks old) trigeminal ganglion (TG). Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed expression of glutamate decarboxylase (GAD) 65 and GAD67 mRNAs and mRNAs encoding GABA(A) receptor subunits alpha1-6, beta1-3, gamma1-3, and delta. In situ hybridization revealed that GAD65 and GAD67 mRNAs were expressed in neuronal cell bodies but not satellite cells. Immunohistochemical analysis showed that only GAD65 was expressed in all neuronal cell bodies, and approximately 70% of all neurons exhibited GABA immunoreactivity. Satellite cells were strongly immunopositive for GABA. GABA(A) receptor alpha1, alpha5, beta2/3 and gamma1/2/3 subunit immunoreactivities were observed in the majority of neurons, but no immunoreactivity for alpha2 was observed. Two types of cells were identified in TG based on cell size and morphology, type A and B. The percentage of cells expressing alpha3, alpha4, alpha6, and delta subunits appeared to be dependent on cell size, as delta and alpha6 expression were only observed in small (B-type) neurons. In whole-cell patch clamp experiments, GABA application induced inward Cl- currents in all neurons examined. The EC50 for GABA varied from 5.3 to 240 microm, and the Hill Coefficient (nH) varied between 0.98 and 2.6 at -60 mV. We found that GABA was released from TG cells by increasing extracellular K+ concentration to 100 mm. We speculate that GABA acts as a nonsynaptically released diffusible neurotransmitter, which may modulate somatic inhibition of neurons within the TG.

Animals↗

Perfusion imaging of meningioma by using continuous arterial spin-labeling: comparison with dynamic susceptibility-weighted contrast-enhanced MR images and histopathologic features.

PURPOSE: The goal of the present study was to determine the utility of continuous arterial spin labeling (CASL) for characterization of meningioma by MR perfusion imaging and to compare these results with those obtained from the T2 dynamic susceptibility contrast (T2DSC) method and from histopathologic examination. METHODS: Twenty-one cases of meningiomas were examined at 1.5T. CASL perfusion imaging was implemented on the basis of multisection single-shot echo-planar imaging with velocity-driven adiabatic spin-inversion preparation. T2DSC perfusion imaging was also performed by using a double-echo spoiled gradient echo sequence in a section containing the tumor. By focusing on the regions of interest, maps of % signal intensity change and cerebral blood flow (CBF) were determined from CASL and cerebral blood volume (CBV). CBF and mean transit time (MTT) were obtained from T2DSC. The microvessel area (MVA) was determined from specimens immunostained with anti-CD31 in 14 cases by measuring the total amount of staining in each histologic section. Linear regression analysis was performed for rCBF values from both perfusion methods and for % signal intensity change and MVA. RESULTS: There was a significant correlation between CBF values determined from both perfusion methods (r(2) = 0.73; P < .001); however, the slope from T2DSC to CASL was less than unity, likely because of the different vascular weighting used for each method. There was also a significant correlation between CASL-% signal intensity change and MVA determined by histopathology (r(2) = 0.91; P < .00001). Perfusion values were the greatest for angiomatous meningioma and lowest for fibrous meningioma when using either perfusion method. CONCLUSIONS: CASL and T2DSC perfusion methods are comparable in the characterization of meningiomas. Further, CASL is of use in assessing tumor microcirculation.

Adult↗

Intracellular Mg2+ influences both open and closed times of a native Ca2+-activated BK channel in cultured human renal proximal tubule cells.

Effects of intracellular Mg2+ on a native Ca(2+)-and voltage-sensitive large-conductance K+ channel in cultured human renal proximal tubule cells were examined with the patch-clamp technique in the inside-out mode. At an intracellular concentration of Ca2+ ([Ca2+](i)) of 10(-5)-10(-4) M, addition of 1-10 mM: Mg2+ increased the open probability (P(o)) of the channel, which shifted the P(o) -membrane potential (V(m)) relationship to the negative voltage direction without causing an appreciable change in the gating charge (Boltzmann constant). However, the Mg(2+)-induced increase in P(o) was suppressed at a relatively low [Ca2+](i) (10(-5.5)-10(-6) M). Dwell-time histograms have revealed that addition of Mg2+ mainly increased P(o) by extending open times at 10(-5) M Ca2+ and extending both open and closed times simultaneously at 10(-5.5) M Ca2+. Since our data showed that raising the [Ca2+](i) from 10(-5) to 10(-4) M increased P(o) mainly by shortening the closed time, extension of the closed time at 10(-5.5) M Ca(2+) would result from the Mg(2+)-inhibited Ca(2+)-dependent activation. At a constant V(m), adding Mg2+ enhanced the sigmoidicity of the P(o)-[Ca2+](i) relationship with an increase in the Hill coefficient. These results suggest that the major action of Mg2+ on this channel is to elevate P(o) by lengthening the open time, while extension of the closed time at a relatively low [Ca2+](i) results from a lowering of the sensitivity to Ca2+ of the channel by Mg2+, which causes the increase in the Hill coefficient.

Calcium↗

Fenofibrate induces apoptotic injury in cultured human hepatocytes by inhibiting phosphorylation of Akt.

Fibric acid derivatives have a potent and effective lipid-lowering action, however, the use of these compounds is sometimes limited due to the occurrence of hepatic injury. In the present study, we characterized cell injury induced by fenofibrate in cultured human hepatocytes. Fenofibrate caused a loss of cell viability and nuclear damage as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling or by DNA electrophoresis, in which caspase activation is involved. The cell injury was accompanied by the shrinkage and the translocation of phosphatidyl serine from inner membrane to the outer membrane as determined by annexin V stain. The mRNA expression for bcl-2 was reduced by fenofibrate. An immunofluorescent stain with antiserum raised against phosphorylated Akt revealed that fenofibrate inhibited insulin-stimulated phosphorylation of Akt. Like fenofibrate, several compounds that inhibit the phosphorylation of Akt, including wortmannin, SH-6 and a high concentration (100 microM) of SB203580, reduced the viability of cultured human hepatocytes. Both nuclear damage and cell injury induced by fenofibrate were reversed by insulin in a concentration-dependent manner. In contrast, bezafibrate or 8(S)-hydroxyeicosatetraenoic acid had no hepatotoxic action. These findings suggest that fenofibrate causes caspase-dependent apoptosis in human hepatocytes by inhibiting phosphorylation of Akt, in which PPARalpha is not involved.

Androstadienes↗

Th1-biased humoral immune responses against Wilms tumor gene WT1 product in the patients with hematopoietic malignancies.

The Wilms' tumor gene WT1 is highly expressed in leukemias and myelodysplastic syndrome (MDS), and WT1 expression levels increase along with the disease progression in chronic myeloid leukemia and MDS. We previously reported that IgM and IgG WT1 antibodies were detected with significantly higher detection rate and antibody titers in leukemias and MDS compared to those in healthy volunteers. In this study, whether IgG humoral immune responses against WT1 protein were Th1- or Th2-type were determined by measurement of four subclasses of IgG WT1 antibody, IgG1, IgG2, IgG3, and IgG4. In leukemias and MDS, Th1-type WT1 antibodies such as IgG1, IgG2, and IgG3 were significantly increased in both detection rate and antibody titers compared to those in healthy volunteers, whereas Th2-type WT1 antibody such as IgG4 did not increase. These results showed that Th1-biased humoral immune responses against WT1 protein were generated in leukemias and MDS. These results should allow us to consider that Th1-biased cellular immune responses against WT1 protein, which was essentially needed for cancer immunotherapy targeting WT1, should be elicited in patients with hematopoietic malignancies.

Antibody Formation↗

Single burr hole surgery for the spheno-orbital fibrous dysplasia using intraoperative computed tomography.

Total removal of spheno-orbital fibrous dysplasia was achieved through intraoperative CT-assisted surgery via a burr hole. A 32-year-old man had persistent headache. Radiological studies demonstrated a small osteolytic lesion in the sphenoidal bone underneath the superior orbital fissure. Intraoperative serial CT scans showed the depth and width of the tumor within the complicated structure of the skull base. The lesion was successfully removed by CT-guided minimally invasive surgery.

Adult↗

Salient closed boundary extraction with ratio contour.

We present ratio contour, a novel graph-based method for extracting salient closed boundaries from noisy images. This method operates on a set of boundary fragments that are produced by edge detection. Boundary extraction identifies a subset of these fragments and connects them sequentially to form a closed boundary with the largest saliency. We encode the Gestalt laws of proximity and continuity in a novel boundary-saliency measure based on the relative gap length and average curvature when connecting fragments to form a closed boundary. This new measure attempts to remove a possible bias toward short boundaries. We present a polynomial-time algorithm for finding the most-salient closed boundary. We also present supplementary preprocessing steps that facilitate the application of ratio contour to real images. We compare ratio contour to two closely related methods for extracting closed boundaries: Elder and Zucker's method based on the shortest-path algorithm and Williams and Thornber's method based on spectral analysis and a strongly-connected-components algorithm. This comparison involves both theoretic analysis and experimental evaluation on both synthesized data and real images.

Algorithms↗

Expression of a candidate marker for progenitor cells, Musashi-1, in the proliferative regions of human antrum and its decreased expression in intestinal metaplasia.

AIM: Reliable makers for progenitor cells in the human stomach have not been elucidated. The aim of the present study was to clarify whether Musashi-1 (Msi-1), which has recently been proposed as a stem cell marker in mouse intestine, serves as a marker for progenitor cells in human stomach. METHODS AND RESULTS: Immunohistochemistry revealed that Msi-1+ cells were detected especially in the isthmus/neck region (the putative position of stem cells) of the adult antrum, but were limited to the basal regions of fetal pyloric glands during the early stages of development. These results suggest that Msi-1 expression occurs specifically in the stem cell-containing regions. Msi-1+ cells were intermingled with proliferating cell nuclear antigen (PCNA)+ cells in the isthmus/neck region of the adult antrum, but did not coexpress PCNA or Ki 67. Msi-1 expression overlapped partly with expression of MUC 5 AC and MUC 6, indicating that Msi-1+ cells retain some features of both foveolar and pyloric gland cell differentiation phenotypes. In contrast, Msi-1 expression in gastric glands showing intestinal metaplasia (IM) became weaker than that in the glands without IM. CONCLUSION: The specific expression of Msi-1 within the proliferative regions suggests that Msi-1 is a marker of cells with progenitor characteristics before active proliferation in human antrum.

Adult↗

Alpha 2 integrin +807 polymorphism in drug-induced gingival overgrowth.

Alpha2 integrin on fibroblasts is reported to play an important role in the induction of drug-induced gingival overgrowth, which is characterized by excessive accumulation of type I collagen in gingival connective tissue. Silent polymorphism 807 T/C within the alpha2 integrin gene is associated with high/low alpha2 integrin expression. The aim of this study was to test the hypothesis that expression of alpha2 integrin 807 T/C polymorphism correlates with drug-induced gingival overgrowth. A case-control study comparing 136 subjects taking calcium channel blockers (72 with vs. 64 without drug-induced gingival overgrowth) demonstrated that the frequency of the +807 C allele was significantly higher in the case group than in the controls (odds ratio, 3.61; 95% confidence interval, 2.14 - 6.10; P < 0.05). The present findings suggest that the alpha2 +807 C allele is one of the genetic risk factors for drug-induced gingival overgrowth.

Adolescent↗

Interspecific structural differences in nucleosome as revealed by heteroimmunization in mice with human nucleosome.

Although mounting evidence suggests the association of anti-nucleosome (NS) antibodies with lupus nephropathy in humans, the influence of interspecific differences in NS structure on the diagnosis has not been studied fully. Thus, we investigated the interspecific differences in NS structure by immunizing normal BALB/c mice with human nucleosomes (hNS). We purified hNS and mouse nucleosomes (mNS) from individual established cell lines. Purified NS was of high-pressure liquid chromatography grade and contained less than 1% dinucleosome, if any. Immune responses to NS were tested by an enzyme-linked immunosorbent assay. Of 6 mice, 2 responded to both hNS and mNS. However, antibodies produced in individual mice had higher affinity to mNS than to hNS. IgG response to hNS was IgG1 and IgG2b in subclass, whereas that to mNS was restricted to IgG1. Coincident with this response difference, agarose gel electrophoresis showed a mobility difference between hNS and mNS: the former was slower than the latter. In conclusion, immunodifferentiation in vivo in mice of autologous from heterologous NS together with their mobility difference in agarose gel suggest the presence of interspecific differences in NS. In humans, 2 out of 14 randomly tested patients with systemic lupus erythematosus preferred hNS over mNS; the IgG subclass in one was IgG1, and in the other IgG4. Taken together, interspecific differences in NS will provide a new area of study not only in biochemistry but also in immunology and/or autoimmunity.

Animals↗

Comparison between ultrafiltration and trichloroacetic acid precipitation method for concentration of Staphylococcus aureus enterotoxin in dairy samples.

Staphylococcus aureus enterotoxin that may be contained at low concentrations in milk and dairy products can cause food poisoning. To detect this enterotoxin at low concentrations, samples should be concentrated. We evaluated the performance of centrifugal ultrafiltration method (UF) in comparison with trichloroacetic acid precipitation method (TCA) for the concentration of S. aureus enterotoxin in milk and dairy products. S. aureus enterotoxin A (SEA) were added at various concentrations to ultra high-temperature heating process (UHT) milk, UHT concentrated skim milk, UHT skim milk powder, low heat-treated (LH) skim milk powder, and raw milk. SEA was concentrated by TCA and UF once a day on a total of 3 days by different researchers to prepare test solutions. The fluorescence value (TV) of test solutions was determined using an immunofluorescence autoanalyzer (miniVIDAS), and the linearity and slope of the regression line, relative standard deviation (RSD(RW)) at each added concentration, detection limit (DL), quantification limit (QL), and the recovery rate by each concentration method were obtained according to the guidelines of the International Conference on Harmonization (ICH). The slope of the regression line obtained by UF was steeper than that by TCA for all dairy samples excluding LH (74 degrees C, 20 s) skim milk powder. RSDRW, DL, and QL obtained by UF were comparable to or more excellent than those obtained by TCA. The procedure of UF was simpler than that of TCA. The recovery rate and rapidity were similar between the two methods. The DL and QL of enterotoxins other than SEA in dairy products by UF or TCA were estimated based on the DL and QL of SEA. In this estimation, consideration was given to reactions between each enterotoxin and its antibody, and also to the immunoactivity maintenance rate of each enterotoxin after addition of trichloroacetic acid in TCA. The estimated values were similar to those obtained by experiments using enterotoxin C1 (SEC1). UF using a centrifugal ultrafiltration membrane can be more readily performed and similar to or more reliable than TCA. UF combined with a miniVIDAS can be used for quantitative routine analysis.

Animals↗

Arterioportal shunting as an alternative to microvascular reconstruction after hepatic artery resection.

BACKGROUND: Portal vein and hepatic artery resection and reconstruction may be required in radical surgery for biliary cancer. Microvascular reconstruction requires special equipment and training, and may be difficult to accomplish when the arterial stump is small, when there are multiple vessels or when the stump lies deep within the wound. This study examined the feasibility and safety of arterioportal shunting as an alternative to arterial reconstruction. METHODS: Over 30 months, ten patients with biliary cancer (six bile duct and four gallbladder carcinomas) underwent radical surgery with en bloc resection of the hepatic artery and end-to-side arterioportal reconstruction between the common hepatic or gastroduodenal artery and the portal trunk. RESULTS: No patient died. Complications included bile leakage in two patients and liver abscess in one. Routine angiography performed 1 month after surgery revealed shunt occlusion in three patients. Once the existence of hepatopetal arterial collaterals had been confirmed in the remaining patients, the shunt was occluded by coil embolization. CONCLUSION: Arterioportal shunting appears to be a safe alternative to microvascular reconstruction after hepatic artery resection. However, the safety of the procedure and its potential to increase the cure rate require further assessment in a larger series with a longer follow-up.

Aged↗

Indications for hepatic vein reconstruction in living donor liver transplantation of right liver grafts.

BACKGROUND: To overcome problems arising from a graft of insufficient size, right liver grafts have been used extensively for adult-to-adult living donor liver transplantation (LDLT). However, there are reports of severe congestion in the anterior segment of the graft after transplantation. CASE REPORTS: Right liver transplantation without the middle hepatic vein was performed in six cases. In the second and third cases, the inferior right hepatic vein was reconstructed because it was thick (whereas the middle hepatic vein was not). Abdominal CT revealed congestive infarction of the anterior segment in the second case and of the posterior segment in the third. It was suspected that the former resulted from the lack of an middle hepatic vein, and the latter from obstruction of the reconstructed inferior right hepatic vein. Both patients died without improvement in liver function. Accordingly, in the fifth case, the middle hepatic vein was reconstructed. The postoperative course of this case was uneventful. Doppler ultrasonography showed profuse blood flow in the interposition graft. In the sixth case, the middle hepatic vein was not reconstructed because of technical difficulties. Although abdominal CT showed a congestive area in the anterior segment, the patient recovered uneventfully, probably because the volume of functional graft was sufficient even without the congestive area. CONCLUSION: When the color becomes dark in more than half of the surface of the anterior segment following clamping of middle hepatic vein tributaries and the hepatic artery, the middle hepatic vein should be reconstructed. When the diameter of the inferior right hepatic vein is more than 5 mm, its reconstruction is also recommended.

Adult↗

Usefulness of artificial liver support for pretransplant patients with fulminant hepatic failure.

This study assessed the usefulness of artificial liver support (ALS) for pretransplant patients with fulminant hepatic failure (FHF). Five patients (age 14 to 52 years, 3 men and 2 women) with FHF who were being prepared for living donor liver transplantation (LDLTx) were enrolled in this study. ALS included plasma exchange, using 40 to 50 units of fresh frozen plasma per session, and high-flow hemodiafiltration, using a high-performance polysulfone membrane. Variables such as circulatory and respiratory function, coma grade, and neurologic disorders were evaluated. Although systolic and diastolic blood pressures showed no statistical differences between pre-ALS and post-ALS, the difference in heart rates was statistically significant. After ALS initiation in the pre-LDLTx period, one of the three patients who needed mechanical ventilation was weaned from it. After LDLTx, all patients recovered neurologically; no neurologic disorder was observed. These results suggested that ALS could predict neurologic status after LDLTx. The difference in coma grades also achieved statistical significance. Our study indicates that short-term ALS is useful for improving circulatory and respiratory function prior to liver transplantation, as well as for predicting posttransplantation neurologic status. Although some patients recover by ALS alone, the survival rate of ALS-only patients is less than 50%. ALS prolongs intensive treatment, thus increasing both the risk of infection and the medical costs. Further investigation to determine a precise marker for liver regeneration will be needed to establish a consensus on the indications for long-term ALS. We conclude that ALS is useful to improve circulatory and respiratory functions among pretransplant patients, and to predict neurologic status after LDLTx.

Adolescent↗