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Biomedical subjects

Y Kitamoto

Publications and source records attributed to Y Kitamoto.

At least 19 recordsLinked to original sources
PubMed2005

Mixed magnetic phases in (Ga,Mn)As epilayers.

Two different ferromagnetic-paramagnetic transitions are detected in (Ga,Mn)As/GaAs(001) epilayers from ac susceptibility measurements: transition at a higher temperature results from (Ga,Mn)As cluster phases with [110] uniaxial anisotropy and that at a lower temperature is associated with a ferromagnetic (Ga,Mn)As matrix with 100 cubic anisotropy. A change in the magnetic easy axis from [100] to [110] with increasing temperature can be explained by the reduced contribution of 100 cubic anisotropy to the magnetic properties above the transition temperature of the (Ga,Mn)As matrix.

Journal Article↗
PubMed2003

Asymmetric transport due to spin injection into a Kondo alloy.

Spin injection is found to have a significant effect on the transport properties of the Kondo alloy Cu(Fe). When a spin-polarized electron current flows from Co into Cu(Fe) wires through the Co/Cu(Fe) interface, the resistivity of the Cu(Fe) wire is suppressed near the interface, as distinct from the ordinary logarithmic increase in the resistivity at low temperatures. For the opposite current direction, no significant changes are observed. The asymmetry of the resistivity with respect to the current direction decays with a characteristic length of 1.5+/-0.4 microm at 2.5 K as the distance from the interface is increased. Possible mechanisms for the asymmetry are discussed.

Journal Article↗
PubMed2002

VEGF is an essential molecule for glomerular structuring.

Since glomerular development is regarded as angiogenesis/vasculogenesis, there should be angiogenic cytokines which mediate glomerulogenesis. In the developing kidney, messages of vascular endothelial growth factor (VEGF) and its receptors are expressed in epithelial and endothelial cells of the glomerulus, respectively. In vivo, suppression of VEGF activity by neutralizing antibody seriously interrupts glomerulogenesis. Typically, there are no endothelial cells in the abnormal glomerulus. Structural changes of the glomerulus were clear by observing vascular castings of renal vessels. Although structures of arteries and arterioles were not impaired, the capillary lumen of the glomerulus was completely lost or interrupted halfway through development. It is concluded that VEGF is secreted from the Bowman's capsule, and stimulates endothelial or endothelial progenitor cells in a paracrine fashion to form the glomerulus.

Animals↗
PubMed2001

Randomized phase I study of standard-fractionated or accelerated-hyperfractionated radiotherapy with concurrent cisplatin and vindesine for unresectable non-small cell lung cancer: a report of Japan Clinical Oncology Group Study (JCOG 9601).

BACKGROUND: We attempted dose escalation of standard-fractionated and accelerated-hyperfractionated radiotherapy combined with concurrent cisplatin and vindesine to improve local control and survival in unresectable non-small cell lung cancer. METHODS: Twenty-one patients were enrolled between June 1996 and August 1997. There were 19 males and two females and their median age was 65 years (range 45-74 years). Performance status was 0 in 10 cases and 1 in 11 cases. Disease stage was IIIA in three cases and IIIB in 18 cases. The cases were randomized to a standard-fractionated arm (n = 10) or an accelerated-hyperfractionated radiotherapy arm (n = 11) with two or three cycles of concomitant cisplatin 80 mg/m(2) on day 1 and vindesine 3 mg/m(2) on days 1 and 8 every 4 weeks in both arms. Dose escalation from 60 Gy/30 fractions/6 weeks to 70 Gy/35 fractions/7 weeks was planned in the standard-fractionated radiotherapy group and from 54 Gy/36 fractions/3.6 weeks to 60 Gy/40 fractions/4 weeks and then 66 Gy/44 fractions/4.4 weeks in the accelerated-hyperfractionated radiotherapy group. RESULTS: Grade 3 or 4 hematological toxicities were observed as follows: in the standard-fractionated/accelerated-hyperfractionated radiotherapy group, leukocytopenia 9/10, anemia 2/3 and thrombocytopenia 0/2. Grade 3 non-hematological toxicity consisted of esophagitis 0/3, increased serum total bilirubin 2/0 and hypoxia 0/1. Two patients died of radiation pneumonitis in the standard-fractionated radiotherapy group. Dose-limiting toxicity was observed in four of the 10 and seven of the 11 patients at initial dose level of standard-fractionated radiotherapy, 60 Gy/30 fractions/6 weeks, and of accelerated-hyperfractionated radiotherapy, 54 Gy/36 fractions/3.6 weeks, respectively. Thus, we failed to escalate the dose of radiotherapy in both arms. The overall response rate in the standard-fractionated group and the accelerated-hyperfractionated radiotherapy group was 70 and 73% and the 1-year survival rate was 70 and 64%, respectively. CONCLUSIONS: We concluded that these schedules of radiotherapy with concurrent cisplatin and vindesine were unacceptable for use in patients with unresectable non-small cell lung cancer. Further modifications of the schedule for radiotherapy and evaluation of combination with new chemotherapy are warranted.

Aged↗
PubMed2001

Glomerular endothelial cells are maintained by vascular endothelial growth factor in the adult kidney.

Vascular endothelial growth factor (VEGF) is known to maintain endothelial cells of immature vessels and is constitutively expressed in the kidney from the embryo to adult. We tested the hypothesis that VEGF activity is needed to maintain glomerular endothelial cells in the adult. Neutralizing antibody to VEGF165 was intraperitoneally administered to mice for 3 days to strongly suppress its intrinsic activity. On the fourth day, mice were sacrificed and tissues were examined by light and electron microscopies. Vascular casts of renal vessels were observed by a scanning electron microscopy. Distribution of the administered antibody and expressions of VEGF and Flk-1 were examined immunohistochemically. The suppression of endogenous VEGF activity caused swelling and vacuolation of endothelial cells and obstruction of capillaries in the glomerulus. Other tissues were not impaired significantly. The administered antibody was specifically localized to the glomerulus, and was found more predominantly in the juxta-medullary than in the cortical glomerulus. This pattern of antibody deposition was similar to that of Flk-1. VEGF expression in the glomerulus was compensatively elevated by the antibody treatment. These results show that demand for VEGF signaling in the glomerulus is much higher than in other tissues, probably to protect its endothelial cells against high tension for blood filtration. This demand may be fulfilled by enriched signaling through the Flk-1 in the glomerulus.

Animals↗
PubMed2000

[VEGF is an essential molecule for glomerular endothelial cells and its excretion in urine might be a unique marker of glomerular injury].

A glomerulus is a functional unit of the kidney, and endothelial cells in the glomerulus are often exposed to more than 5 times higher pressure than peripheral capillaries. Glomerular development proceeds through angiogenesis and VEGF was shown to mediate the angiogenesis. VEGF is constitutively expressed in the glomerulus from the embryo to adults. When VEGF signal was blocked by the antibody, glomerular endothelial cells were swollen and capillary lumen was interrupted. Changes were more prominent in the juxta-medullary than in the cortical glomerulus. A major VEGF receptor, Flk-1/KDR, is specifically localized to the glomerular endothelial cell among tissues and more predominantly in the juxta-medullary than in the cortical glomerulus. As capillary pressure is higher in the juxta-medullary than in the cortical glomeruli, endothelial cells in the former are exposed to more tension than those in the latter. VEGF might be a protective molecule for endothelial cells against tension. The effect of VEGF on the repair of an impaired glomerulus was evaluated in the rat Thy-1 glomerulonephritis. VEGF inhibited early endothelial injury and accelerated consequent remodeling of the glomerulus. In the patient study, VEGF excretion in the urine was independent from its serum or plasma level, but increased as renal function decreased. VEGF signaling is essential in glomerular development, maintenance and repair. VEGF excreted in the urine might reflect its generation in the kidney and be a unique marker of renal function.

Animals↗
PubMed1999

Interaction between low dose-rate irradiation, mild hyperthermia and low-dose caffeine in a human lung cancer cell line.

PURPOSE: To investigate cell killing by means of low dose-rate irradiation (LDRI) combined with concurrent mild hyperthermia and to determine the effect of low-dose caffeine on this combination treatment. MATERIALS AND METHODS: Human lung adenocarcinoma cells, LK87, were treated with LDRI (50 cGy/h) in combination with mild hyperthermia at 41 degrees C and low-dose caffeine (1 mM). Cell survival was estimated by clonogenic assay. Flow-cytometry was performed with PI staining using FACScan. Heat-shock protein (HSP72/73) was measured by the Western blotting method. All treatments were simultaneously performed for up to 48 h (24 Gy). RESULTS: LDRI cytotoxicities were enhanced by hyperthermia at 41 degrees C. D0 calculated from the dose-response curve for LDRI combined with 41 degrees C was 3.46 Gy whereas it was 6.55 Gy for LDRI alone. The survival curve for LDRI +41 degrees C demonstrated no chronic thermotolerance up to 48 h. For LDRI + simultaneous low-dose caffeine, cell killing was also enhanced, where D0 was 3.38 Gy at 37 degrees C. Radiosensitization caused by caffeine was enhanced by combination with simultaneous mild hyperthermia at 41 degrees C, where D0=1.78 Gy. Cell cycle analysis demonstrated remarkable G2 and mild G1 arrest for LDRI alone, but only G1 arrest was observed for LDRI combined with 41 degrees C and for LDRI combined with caffeine. Strong and early G1 arrest was observed in the treatment with LDRI + caffeine at 41 degrees C. The amount of HSP72/73 in the combination of LDRI with caffeine at 41 degrees C was less than that at 41 degrees C alone. CONCLUSION: LDRI cytotoxicity was enhanced by non-lethal hyperthermia. Low dose caffeine produced further cell killing in the combination of LDRI with mild hyperthermia.

Caffeine↗
PubMed1998

Early radiation effects in highly apoptotic murine lymphoma xenografts monitored by 31P magnetic resonance spectroscopy.

PURPOSE: Phosphorus-31 magnetic resonance spectra (31P-MRS) were obtained from highly apoptotic murine lymphoma xenografts before and up to 24 hr following graded doses of radiation ranging from 2 to 30 Gy. Radiation-induced apoptosis was also estimated up to 24 hr by scoring apoptotic cells in tumor tissue. METHODS AND MATERIALS: Highly apoptotic murine lymphoma cells, EL4, were subcutaneously transplanted into C57/BL mice. At 7 days after transplantation, radiation was given to the tumor with a single dose at 3, 10, and 30 Gy. The beta-ATP/Pi, PME/Pi, and beta-ATP/PME values were calculated from the peak area of each spectrum. Radiation-induced apoptosis was scored with counting apoptotic cells on hematoxylin and eosin stained specimens (% apoptosis). RESULTS: The values of % apoptosis 4, 8, and 24 hr after radiation were 21.8, 19.6, and 4.6% at 3 Gy, 35.1, 25.6, and 14.8% at 10 Gy, 38.4, 38.0, and 30.6% at 30 Gy, respectively (cf. 4.4% in control). There was no correlation between early change in beta-ATP/Pi and % apoptosis at 4 hr after radiation when most of the apoptosis occurred. An early decrease in PME/Pi was observed at 4 hr after radiation dose at 30 Gy. For each dose, the values of beta-ATP/Pi 24 hr after radiation were inversely related to radiation dose. CONCLUSION: The increase in beta-ATP/Pi observed by 31P-MRS was linked to the degree of histological recovery from radiation-induced apoptosis.

Adenosine Triphosphate↗
PubMed1997

Vascular endothelial growth factor is an essential molecule for mouse kidney development: glomerulogenesis and nephrogenesis.

Homeostasis of body fluid is maintained by the kidneys, which contain two million glomeruli for blood filtration. A glomerulus is formed by growth of Bowman's capsule harmonized with a capillary during kidney development. The vascular endothelial growth factor (VEGF) is an essential angiogenic cytokine, and VEGF deficiency is known to be fatal in mice in early embryonic stages. As secretions of VEGF from cultured kidneys vary according to developmental stages, the role of VEGF in kidney development was studied in vivo by blocking the endogenous VEGF activity with antibody in newborn mice, in which most organs are already developed but kidneys are still developing. The antibody-treated animals showed normal growth but systemic edema. Vessel formation in the superficial renal cortex was disturbed, nephrogenic areas were diminished, and the number of developing nephrons decreased significantly. Many abnormal glomeruli, lacking capillary tufts, were observed in the antibody-treated mice, and VEGF expression in their Bowman's capsule showed a compensatory increase. These results suggest that VEGF mediates communication between the Bowman's capsule and capillary endothelial cells for developing a glomerulus as well as promoting nephrogenesis. In conclusion, VEGF is likely to be an essential molecule for kidney development, and especially for glomerulogenesis.

Animals↗
PubMed1997

Purification and properties of a new enzyme, D-carnitine dehydrogenase, from Agrobacterium sp. 525a.

A new enzyme, D-carnitine dehydrogenase from Agrobacterium sp. 525a, was purified by DEAE-Toyopearl, ammonium sulfate fractionation, Sephadex G-75, affinity chromatography, and Mono Q and TSK-gel filtration column chromatography. The enzyme had the molecular mass of 89 kDa and consisted of three identical subunits. The optimum pH for the oxidation reaction was 9.3. The Michaelis constants for D-carnitine and NAD+ were 3.1 and 0.07 mM, respectively. The N-terminal 20 amino acids were sequenced.

Alcohol Oxidoreductases↗
PubMed1996

Nicotinamide and pentoxifylline increase human leucocyte filterability: a possible mechanism for reduction of acute hypoxia.

Transient plugging of microcapillaries by leucocytes is a possible reason for the occurrence of acute hypoxia in tumours. We compared the abilities of nicotinamide at 1000 micrograms ml-1 and 150 micrograms ml-1 and pentoxifylline at 300 micrograms ml-1 to increase the filterability of normal and artificially activated human leucocytes through 8 microns pores, as a model for the capillary bed. Using a St George's filtrometer, filterability of treated leucocyte suspensions was compared with control for three to six sequential 60 microliters samples, normalising control values to unity. Pentoxifylline at 300 micrograms ml-1 halved the ratio of treated to control value to 0.47 +/- 0.13 (2 s.e.), P = 0.001 (i.e. an increase in filterability), and nicotinamide at 1000 micrograms ml-1 reduced it to 0.69 +/- 0.22, P = 0.04, but the clinically achievable 150 micrograms ml-1 was ineffective (0.82 +/- 0.25, P = 0.24). Filterability of artificially activated leucocytes was reduced (3.9 +/- 1.20) but was restored to control values of unity by 1000 micrograms ml-1 nicotinamide and 300 micrograms ml-1 pentoxifylline and partially restored by 150 micrograms ml-1 nicotinamide (1.2 mM), which was isoeffective with 100 micrograms ml-1 pentoxifylline (0.37 mM). Pentoxifylline is therefore more effective on a molar basis and was shown to affect both polymorphonuclear leucocytes and lymphocytes, while nicotinamide only affects lymphocytes. The data are consistent with the hypothesis that both agents modify acute hypoxia by increasing leucocyte filterability.

Cell Hypoxia↗
PubMed1995

cDNA sequence and chromosomal localization of human enterokinase, the proteolytic activator of trypsinogen.

Enterokinase is a serine protease of the duodenal brush border membrane that cleaves trypsinogen and produces active trypsin, thereby leading to the activation of many pancreatic digestive enzymes. Overlapping cDNA clones that encode the complete human enterokinase amino acid sequence were isolated from a human intestine cDNA library. Starting from the first ATG codon, the composite 3696 nt cDNA sequence contains an open reading frame of 3057 nt that encodes a 784 amino acid heavy chain followed by a 235 amino acid light chain; the two chains are linked by at least one disulfide bond. The heavy chain contains a potential N-terminal myristoylation site, a potential signal anchor sequence near the amino terminus, and six structural motifs that are found in otherwise unrelated proteins. These domains resemble motifs of the LDL receptor (two copies), complement component Clr (two copies), the metalloprotease meprin (one copy), and the macrophage scavenger receptor (one copy). The enterokinase light chain is homologous to the trypsin-like serine proteinases. These structural features are conserved among human, bovine, and porcine enterokinase. By Northern blotting, a 4.4 kb enterokinase mRNA was detected only in small intestine. The enterokinase gene was localized to human chromosome 21q21 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1994

Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains.

Enterokinase is a protease of the intestinal brush border that specifically cleaves the acidic propeptide from trypsinogen to yield active trypsin. This cleavage initiates a cascade of proteolytic reactions leading to the activation of many pancreatic zymogens. The full-length cDNA sequence for bovine enterokinase and partial cDNA sequence for human enterokinase were determined. The deduced amino acid sequences indicate that active two-chain enterokinase is derived from a single-chain precursor. Membrane association may be mediated by a potential signal-anchor sequence near the amino terminus. The amino terminus of bovine enterokinase also meets the known sequence requirements for protein N-myristoylation. The amino-terminal heavy chain contains domains that are homologous to segments of the low density lipoprotein receptor, complement components C1r and C1s, the macrophage scavenger receptor, and a recently described motif shared by the metalloprotease meprin and the Xenopus A5 neuronal recognition protein. The carboxyl-terminal light chain is homologous to the trypsin-like serine proteases. Thus, enterokinase is a mosaic protein with a complex evolutionary history. The amino acid sequence surrounding the amino terminus of the enterokinase light chain is ITPK-IVGG (human) or VSPK-IVGG (bovine), suggesting that single-chain enterokinase is activated by an unidentified trypsin-like protease that cleaves the indicated Lys-Ile bond. Therefore, enterokinase may not be the "first" enzyme of the intestinal digestive hydrolase cascade. The specificity of enterokinase for the DDDDK-I sequence of trypsinogen may be explained by complementary basic-amino acid residues clustered in potential S2-S5 subsites.

Amino Acid Sequence↗
PubMed1993

Effect of blood access on the platelets of azotemic patients initiating dialysis therapy.

The effect of blood access on platelets and clotting factors was investigated in 46 azotemic patients. Arteriovenous fistula was used in 10 patients (AVF group), and polyurethane double-lumen catheters were inserted through the subclavian vein in 6 patients (PUS group) or through the femoral vein in 15 patients (PUF group). Indwelling urokinase-immobilized single-lumen catheters and double-lumen catheters were placed in the femoral vein of 5 patients (UKS group) and 10 patients (UKD group), respectively. Blood cell counts, beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), prothrombin time, and activated partial thromboplastin time were measured before insertion while catheters were indwelling and after catheters were pulled out. Although the platelet count decreased to 83% of the initial value during indwelling in the PUF group and 89% in the PUS group, it did not decrease in the AVF, UKS, and UKD groups. There were no differences between the PUF and PUS groups nor between the UKS and UKD groups. Plasma beta-TG increased in the PUF and UKD groups with indwelling catheters but did not change with the AVF. From these results, we conclude that the AVF did not activate platelets, the urokinase-immobilized catheter activated platelets, and the polyurethane catheter activated and decreased platelets. This might be due to the different surface properties of each blood access. Thus, the urokinase-immobilized catheter seems to be more favorable than the polyurethane catheter for emergency blood access.

Arteriovenous Shunt, Surgical↗
PubMed1993

Differentiation of hematuria using a uniquely shaped red cell.

Although variously shaped urinary red cells have been reported in glomerulonephritic hematuria, no specific shapes with concrete definition have been proposed. This made morphological differentiation of hematuria vague and caused different results among different observers. To solve these problems and improve the diagnostic rate, we employed a uniquely shaped red cell, which only appeared in glomerulonephritic hematuria, as a probe for diagnosis. We studied 182 hematuria cases from 90 glomerulonephritic patients and 95 hematuria cases from 68 urological disease patients. Fresh urine was collected and observed by differential interference microscopy. The red cell, referred to as G1, has a distinctive doughnut-like shape with blebs and was highly specific for glomerulonephritic hematuria. Occurrence of G1 cells increased at lower pH an higher osmolality of urine. A presence of 5% or more G1 cells could be an indicator of glomerulonephritic hematuria. Specificity and sensitivity of this criterion were 100 and 73%. However, when only acidic concentrated urine (pH < or = 6.4, osmolality > or = 400 mosm/kg H2O) was used, the specificity and sensitivity increased to 100 and 99.2%, respectively. Glomerulonephritic and urological hematuria were correctly diagnosed by counting the urinary red cells with doughnut-like shape in acidic and concentrated urine. This method seems to be superior to others in diagnostic rate, simplicity and clarity.

Adolescent↗