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Koichi Kobayashi

Publications and source records attributed to Koichi Kobayashi.

At least 55 records · Page 3Linked to original sources
PubMed2004

Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers.

OBJECTIVE: Circulating endothelial progenitor cells (EPCs) contribute to postnatal angiogenesis. The number of circulating EPCs has an inverse correlation with coronary risk scores. However, the effect of smoking on the number of circulating EPCs is not well-known. METHODS AND RESULTS: We examined the effects of chronic smoking and of smoking cessation on EPC levels. Circulating EPCs were quantified by flow cytometry as CD45lowCD34+CD133+ (progenitor cells [PCs]) or CD45lowCD34+CD133+VEGFR2+ (EPCs) in 14 nonsmokers and in 15 smokers. All smokers quit smoking. Eight quit smoking with nicotine patch and 7 without nicotine patch. PC/EPC levels were inversely correlated with the number of cigarettes smoked. Circulating PCs/EPCs increased rapidly after cessation (P<0.0001) and decreased again after resumption of smoking to the level similar to that before cessation (P=0.0031). The magnitude of increase in EPCs was greater in light smokers than in heavy smokers. CONCLUSIONS: The number of circulating PCs/EPCs was reduced in chronic smokers. Smoking cessation led to a rapid restoration of PC/EPC levels. The recovery of EPC levels was greater in light smokers than in heavy smokers. The decreased number of circulating EPCs would make smokers susceptible to cardiovascular disease, and even short-time cessation of smoking may be an effective means to reduce cardiovascular risk.

AC133 Antigen↗
PubMed2004

The AHNAKs are a class of giant propeller-like proteins that associate with calcium channel proteins of cardiomyocytes and other cells.

To explore the function of the giant AHNAK molecule, first described in 1992 [Shtivelman, E., Cohen, F. E. & Bishop, J. M. (1992) Proc. Natl. Acad. Sci. USA 89, 5472-5476], we created AHNAK null mice by homologous recombination. Homozygous knockouts showed no obvious phenotype, but revealed instead a second AHNAK-like molecule, provisionally designated AHNAK2. Like the original AHNAK, AHNAK2 is a 600-kDa protein composed of a large number of highly conserved repeat segments. Structural predictions suggest that the repeat segments of both AHNAKs may have as their basic framework a series of linked, antiparallel beta-strands similar to those found in beta-propeller proteins. Both AHNAKs appear to localize to Z-band regions of mouse cardiomyocytes and cosediment with membrane vesicles containing the dihydropyridine receptor, which is consistent with earlier reports that the AHNAKs are linked to L-type calcium channels and can be phosphorylated by protein kinase A. The localization of the AHNAKs in close proximity to transverse tubule membranes and Z-band regions of cardiac sarcomeres raise the possibility that they might be involved in regulating excitation/contraction coupling of cardiomyocytes, but other studies indicate that the association of AHNAKs with calcium channel proteins is more widespread. AHNAK2 is predicted to have a PDZ domain within its N-terminal, nonrepeating domain, which may mediate these interactions.

Amino Acid Sequence↗
PubMed2004

Hyperoxia-induced emphysematous changes in subacute phase of endotoxin-induced lung injury in rats.

We examined the effects of prolonged hyperoxia (75% O(2)) on lung structure and collagen metabolism in the subacute phase of lung injury induced by continuous infusion of endotoxin (LPS) in a rat model. Experimental groups included control, endotoxin alone, endotoxin plus hyperoxia, and hyperoxia alone. Endotoxin-treated rats received a bolus of LPS (10 mg/kg i.v.) followed by 500 microg.kg(-1).day(-1) in continuous infusion for 10 days. The bronchoalveolar lavage (BAL) fluid/plasma albumin concentration ratio, an index of capillary permeability, and neutrophil and macrophage counts in BAL fluid were highest in the endotoxin plus hyperoxia group. On pathological examination, prolonged hyperoxia exacerbated destruction of the alveolar wall and caused most prominent emphysematous changes in the endotoxin plus hyperoxia group. Lung tissue hydroxyproline concentration was significantly decreased in the hyperoxia group and increased in the endotoxin group. The latent forms of MMP-2 and MMP-9 increased in BAL fluid of the endotoxin- and/or hyperoxia-treated groups, whereas the activities of collagenase and gelatinase, and the active form of MMP-2 were all increased in the hyperoxia-treated groups. Added to endotoxin, prolonged hyperoxia degraded collagen, the major structural component of basement membranes, and caused emphysematous changes associated with activation of collagenase and MMP-2. Our observations suggest that, in the subacute phase of endotoxin-induced lung injury, prolonged hyperoxia causes pulmonary emphysematous changes with persistent injury to the alveolar capillary barrier. Collagenase and MMP-2 activated by hyperoxia, together with MMP-9, may play prominent roles in disruption of the alveolar basement membranes and degradation of collagen lining the alveolar walls.

Animals↗
PubMed2004

Arabidopsis type B monogalactosyldiacylglycerol synthase genes are expressed during pollen tube growth and induced by phosphate starvation.

The galactolipids monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) constitute the major glycolipids of the thylakoid membranes in chloroplasts. In Arabidopsis, the formation of MGDG is catalyzed by a family of three MGDG synthases, which are encoded by two types of genes, namely type A (atMGD1) and type B (atMGD2 and atMGD3). Although the roles of the type A enzyme have been intensively investigated in several plants, little is known about the contribution of type B enzymes to MGDG synthesis in planta. From our previous analyses, unique expression profiles of the three MGDG synthase genes were revealed in various organs and developmental stages. To characterize the expression profiles in more detail, we performed histochemical analysis of these genes using beta-glucuronidase (GUS) assays in Arabidopsis. The expression of atMGD1::GUS was detected highly in all green tissues, whereas the expression of atMGD2::GUS and atMGD3::GUS was observed only in restricted parts, such as leaf tips. In addition, intense staining was detected in pollen grains of all transformants. We also detected GUS activity in the pollen tubes of atMGD2::GUS and atMGD3::GUS transformants grown in wild-type stigmas but not in atMGD1::GUS, suggesting that type B MGDG synthases may have roles during pollen germination and pollen tube growth. GUS analysis also revealed that expression of atMGD2 and atMGD3, but not atMGD1, are strongly induced during phosphate starvation, particularly in roots. Because only DGDG accumulates in roots during phosphate deprivation, type B MGDG synthases may be acting primarily to supply MGDG as a precursor for DGDG synthesis.

Arabidopsis↗
PubMed2004

Lung biopsy with a 12-gauge cutting needle is possible using an insertion sheath in animal models.

RATIONALE AND OBJECTIVES: The volume of lung tumor core biopsy specimens has been restricted because of concerns for complications such as bleeding and air leakage. In this animal experiment, we investigated the possibility of larger bore biopsies through the peripheral lung parenchyma. MATERIALS AND METHODS: Lung biopsy was done in male domestic pigs (n= 4) under thoracotomy. A single biopsy using a 12-gauge cutting biopsy needle was done with sheath (sheath group, eight biopsies) or without sheath (nonsheath group, eight biopsies). After biopsy, bleeding time, bleeding amount, and positive airway pressure causing air leakage from the insertion site was compared between groups (Mann-Whitney U test). To observe long-term effects in closed-chest animals, percutaneous lung biopsy with the use of a sheath was carried out percutaneously in male beagles (n = 9). The animals were observed for 3 weeks. RESULTS: In the pigs (sheath group) after biopsy, bleeding flowed through the sheath and formed a sheath-molded fibrin plug that secured the insertion site. Bleeding time and amount decreased significantly in the sheath group compared with the nonsheath group (115 +/- 108 versus 295 +/- 150 seconds, P = .018, and 37 +/- 41 versus 98 +/- 72 grams, P= .027, respectively). Air leakage pressure was significantly higher in the sheath group compared with the nonsheath group (37 +/- 6 versus 18 +/- 5 cmH2O, P = .001). In the beagles, no complications such as pneumothorax, hemothorax, or airway bleeding was apparent. CONCLUSION: Although we have not evaluated lung tumor biopsy per se, lung tumor biopsy with a 12-gauge cutting needle may be possible with a use of a sheath.

Animals↗
PubMed2004

Metabolism of hemoglobin-vesicles (artificial oxygen carriers) and their influence on organ functions in a rat model.

Phospholipid vesicles encapsulating Hb (Hb-vesicles: HbV) have been developed for use as artificial O(2) carriers (250 nm phi). As one of the safety evaluations, we analyzed the influence of HbV on the organ functions by laboratory tests of plasma on a total of 29 analytes. The HbV suspension ([Hb]=10 g/dl) was intravenously infused into male Wistar rats (20 ml/kg; whole blood = 56 ml/kg). The blood was withdrawn at 8h, and 1, 2, 3, and 7 days after infusion, and the plasma was ultracentrifuged to remove HbV in order to avoid its interference effect on the analytes. Enzyme concentrations, AST, ALT, ALP, and LAP showed significant, but minor changes, and did not show a sign of a deteriorative damage to the liver that was one of the main organs for the HbV entrapment and the succeeding metabolism. The amylase and lipase activities showed reversible changes, however, there was no morphological changes in pancreas. Plasma bilirubin and iron did not increase in spite of the fact that a large amount of Hb was metabolized in the macrophages. Cholesterols, phospholipids, and beta-lipoprotein transiently increased showing the maximum at 1 or 2 days, and returned to the control level at 7 days. They should be derived from the membrane components of HbV that are liberated from macrophages entrapping HbV. Together with the previous report of the prompt metabolism of HbV in the reticuloendothelial system by histopathological examination, it can be concluded that HbV infusion transiently modified the values of the analytes without any irreversible damage to the corresponding organs at the bolus infusion rate of 20 ml/kg.

Animals↗
PubMed2004

Pulmonary metastases from uterine malignancies: results of surgical resection in 133 patients.

OBJECTIVE: The long-term results of the surgical treatment for patients with pulmonary metastases from uterine malignancies were clarified. METHODS: A total of 133 patients who underwent pulmonary metastasectomy for uterine malignancies were enrolled in the Metastatic Lung Tumor Study Group of Japan between March 1984 and February 2002. These patients constituted the study population, and their clinical, pathologic, and prognostic data were retrospectively analyzed. RESULTS: The morbidity and mortality rates related to the operation were minimal (1% and 1%, respectively). The 5- and 10-year survivals after the surgical resection in all cases were 54.6% and 44.9%, respectively. The 5-year survivals for each histologic type were estimated to be 46.8% for squamous cell carcinoma (n = 58), 40.3% for cervical adenocarcinoma (n = 13), 75.7% for endometrial adenocarcinoma (n = 23), 86.5% for choriocarcinoma (n = 16), and 37.9% for leiomyosarcoma (n = 11). In the univariate analysis, the following were shown to be associated with poor survival: primary tumor in the cervix, short disease-free interval (<12 months), large number of resected metastases (> or =4), and large tumor size (> or =3 cm). After mutual adjustment, short disease-free interval (<12 months) alone was related to risk of death (hazard ratio = 2.26, 95% confidence interval = 1.06-4.78) for 105 patients, excluding patients with choriocarcinoma and miscellaneous histologic types. CONCLUSION: Pulmonary metastasectomy for uterine malignancies is a safe and acceptable treatment to improve survival. Patients with a disease-free interval of 12 months or more are good candidates for this treatment if there is adequate control of the primary tumor without extrapulmonary metastasis.

Adenocarcinoma↗
PubMed2004

Nitric oxide signaling during myocardial angiogenesis.

Ischemic heart disease develops as a consequence of coronary atherosclerotic lesion formation. Coronary collateral vessels and microvascular angiogenesis develop as an adaptive response to myocardial ischemia, which ameliorates the function of the damaged heart. Angiogenesis, the formation of new blood vessels from pre-existing vascular bed, is of paramount importance in the maintenance of vascular integrity both in the repair process of damaged tissue and in the formation of collateral vessels in response to tissue ischemia. Angiogenesis is modulated by a multitude of cytokines/chemokines and growth factors. In this regard, angiogenesis cannot be viewed as a single process. It is likely that different mediators are involved in different phases of angiogenesis. Vascular endothelial cells (ECs) produce nitric oxide (NO), an endothelium-derived labile molecule, which maintains vascular homeostasis and thereby prevents vascular atherosclerotic changes. In patients with ischemic heart disease, the release of endothelium-derived NO is decreased, which plays an important role in the atherosclerotic disease progression. In recent years, endothelium-derived NO has been shown to modulate angiogenesis in vitro and in vivo. In this review, we summarize recent progress in the field of the NO-mediated regulation of postnatal angiogenesis, particularly in response to myocardial ischemia.

Animals↗
PubMed2004

Isoprostanes, prostaglandins and tocopherols in pre-eclampsia, normal pregnancy and non-pregnancy.

This study is designed to evaluate whether oxidative stress and inflammation are involved in severe pre-eclampsia compared to normal pregnancy and non-pregnancy. We have measured plasma and urinary levels of 8-iso-PGF2alpha, a major isoprostane as an indicator of oxidative stress; plasma and urinary 15-keto-dihydro-PGF2alpha, a major metabolite of cyclooxygenase-catalysed PGF2alpha as an indicator of inflammatory response, and plasma -alpha-and -gamma-tocopherol in 18 pre-eclamptic, 19 normal pregnancy and 20 non-pregnant women. Pregnant women had significantly higher levels of 8-iso-PGF2alpha and PGF2alpha metabolite as compared to the non-pregnancy. Levels of 8-iso-PGF2alpha in the pre-eclamptic women did not differ from the normal pregnancy but PGF2alpha metabolite levels were significantly higher in normal pregnancy. On the other hand, gamma-tocopherol levels were significantly lower in pre-eclampsia than normal pregnancy. In contrast, the concentration of alpha-tocopherol was very similar between the groups. alpha-and gamma-tocopherol levels were significantly lower in pregnancy compared to non-pregnancy. Although no direct evidence of oxidative stress and inflammatory response was observed in severe pre-eclampsia, a reduction of gamma-tocopherol suggests the possible precedence of oxidative stress in this condition. Higher levels of isoprostanes and prostaglandin metabolite in late pregnancy suggest the importance of both free radicals and cyclooxygenase-catalysed oxidation products in normal biological processes of pregnancy.

Adult↗
PubMed2004

Hemoglobin-vesicles suspended in recombinant human serum albumin for resuscitation from hemorrhagic shock in anesthetized rats.

OBJECTIVE: Hemoglobin-vesicle (HbV) has been developed to provide oxygen-carrying ability to plasma expanders. Its ability to restore the systemic condition after hemorrhagic shock was evaluated in anesthetized Wistar rats for 6 hrs after resuscitation. The HbV was suspended in 5 g/dL recombinant human serum albumin (HbV/rHSA) at an Hb concentration of 8.6 g/dL. DESIGN: Prospective, randomized, controlled trial. SETTING: Department of Surgery, School of Medicine, Keio University. SUBJECTS: Forty male Wistar rats. INTERVENTIONS: The rats were anesthetized with 1.5% sevoflurane inhalation throughout the experiment. Polyethylene catheters were introduced through the right jugular vein into the right atrium for infusion and into the right common carotid artery for blood withdrawal and mean arterial pressure monitoring. MEASUREMENTS AND MAIN RESULTS: Shock was induced by 50% blood withdrawal. The rats showed hypotension (mean arterial pressure = 32 +/- 10 mm Hg) and significant metabolic acidosis and hyperventilation. After 15 mins, they received HbV/rHSA, shed autologous blood (SAB), washed homologous red blood cells (wRBC) suspended in rHSA (wRBC/rHSA, [Hb] = 8.6 g/dL), or rHSA alone. The HbV/rHSA group restored mean arterial pressure to 93 +/- 8 mm Hg at 1 hr, similar to the SAB group (92 +/- 9 mm Hg), which was significantly higher compared with the rHSA (74 +/- 9 mm Hg) and wRBC/rHSA (79 +/- 8 mm Hg) groups. There was no remarkable difference in the blood gas variables between the resuscitated groups; however, two of eight rats in the rHSA group died before 6 hrs. After 6 hrs, the rHSA group showed significant ischemic changes in the right cerebral hemisphere relating to the ligation of the right carotid artery followed by cannulation, whereas the HbV/rHSA, SAB, and wRBC/rHSA groups showed less changes. CONCLUSIONS: HbV suspended in recombinant human serum albumin provides restoration from hemorrhagic shock that is comparable with that using shed autologous blood.

Anesthesia↗
PubMed2004

[Guide line for the treatment of stage I and stage II non small cell lung cancer].

Evidence based treatment modalities should be established as more than 55,000 patients die of lung cancer every year and its number is increasing. For stage I and stage II non small cell lung cancer (NSCLC), surgery is strongly recommended if there are no contraindications such as impaired pulmonary function and other medical disorders. Although lobectomy (bilobectomy or pneumonectomy) with mediastinal lymphnode dissection is standard operation for stage I and stage II NSCLC, limited operation (segmentectomy or extended segmentectomy) for peripherally located small sized cancer (less than 2 to 3) is now being performed to assess if there is survival difference between standard operation. Also numbers of patients undergoing video-assisted thoracoscopic surgery (VATS) is increasing and studies to compare postoperative survival rate and postoperative quality of life with standard operation is performed. To improve postoperative survival, pre and postoperative treatment such as chemotherapy, radiotherapy or combination of these treatments have been undertaken. Very recently usefulness of postoperative adjuvant chemotherapy with Uracil-Tegafur for stage I adenocecinoma was reported from Japan. For patients with stage I and stage II NSCLS in whom operation is not feasible for medical reasons, radical radiation therapy is recommended.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

26Al incorporation into the brain of suckling rats through maternal milk.

Aluminium inhibits prenatal and postnatal brain development. However, aluminium incorporation into the brain of sucklings through maternal milk has not yet been well clarified because aluminium lacks a suitable isotope for radioactive tracer experiments. Using 26Al (26AlCl(3)) as a tracer, we measured 26Al incorporation into the brain of suckling rats by accelerator mass spectrometry. Lactating rats were subcutaneously injected with 26AlCl(3) from day 1 to day 20 postpartum. Suckling rats were weaned from day 21 postpartum. From day 5 to day 20 postpartum, the amounts of 26Al measured in the cerebrum, cerebellum, spinal cord, liver, and kidneys of suckling rats increased significantly. After weaning, the amounts of 26Al in the liver and kidneys decreased remarkably. Alternatively, in the cerebrum, cerebellum, and spinal cord, as much as 12 to 20% of the 26Al amounts present on day 20 postpartum remained in the tissues on day 730 postpartum. As the life span of rats is about 2 years, we conclude that considerable amounts of the 26Al taken up into the brain of suckling rats through maternal milk remained in their brain throughout their lifetime.

Aluminum↗
PubMed2003

Expression profiles of non-small cell lung cancers on cDNA microarrays: identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs.

To investigate genes involved in pulmonary carcinogenesis and those related to sensitivity of nonsmall cell lung cancers (NSCLCs) to therapeutic drugs, we performed cDNA microarray analysis of 37 NSCLCs after laser-capture microdissection of cancer cells from primary tumors. A clustering algorithm applied to the expression data easily distinguished two major histological types of non-small cell lung cancer, adenocarcinoma and squamous cell carcinoma. Subsequent analysis of the 18 adenocarcinomas identified 40 genes whose expression levels could separate cases with lymph-node metastasis from those without metastasis. In addition, we compared the expression data with measurements of the sensitivity of surgically dissected NSCLC specimens to six anti-cancer drugs (docetaxel, paclitaxel, irinotecan, cisplatin, gemcitabine, and vinorelbine), as measured by the CD-DST (collagen gel droplet embedded culture-drug sensitivity test) method. We found significant associations between expression levels of dozens of genes and chemosensitivity of NSCLCs. Our results provide valuable information for eventually identifying predictive markers and novel therapeutic target molecules for this type of cancer.

Adenocarcinoma↗
PubMed2003

Human serum albumin incorporating synthetic heme: red blood cell substitute without hypertension by nitric oxide scavenging.

The administration of extracellular, hemoglobin-based oxygen carriers often elicits an acute increase in blood pressure by vasoconstriction. This side effect is now recognized to be due to the depletion of nitric oxide (endothelial-derived relaxing factor) by the extravasuated hemoglobins. We have recently found that the administration of a recombinant human serum albumin (rHSA)-based oxygen carrier involving synthetic tetraphenyporphinatoiron(II) derivative (FeP) (rHSA-FeP) does not induce such hypertensive action, because of its low permeability through the vascular endothelium. The heart rate responses after the rHSA-FeP injection were also negligibly small. Visualization of the intestinal microcirculatory changes clearly revealed the widths of the venule and arteriole to be fairly constant. The entirely synthetic rHSA-FeP becomes a promising material as a new type of red blood cell substitute.

Anesthesia↗
PubMed2003

Oxygenation of hypoxic region in solid tumor by administration of human serum albumin incorporating synthetic hemes.

Recombinant human serum albumin incorporating synthetic heme (rHSA-FeP) was tested for its ability to increase O(2) tension in the hypoxia of the solid tumor rat model. By the direct administration of the rHSA-FeP solution (10 mL/kg) via the aorta descendens to the ascites hepatoma LY80 tumor on the right femur, the O(2) tension of the hypoxic region immediately increased to 3.45 +/- 1.43 Torr, which corresponds to a 2.4-fold increase compared to that of the baseline value. These high O(2) levels continued for 300 s after the infusion. The rHSA-FeP solution can be utilized not only as a red blood cell substitute but also as an O(2)-carrying medicine for the effective reoxygenation of the hypoxia solid tumor.

Animals↗
PubMed2003

Contributions of bronchoscopic microsampling in the supplemental diagnosis of small peripheral lung carcinoma.

BACKGROUND: Making a preoperative pathologic diagnosis in patients with small lung nodules remains challenging. We have developed a new, noninvasive bronchoscopic microsampling probe to examine biochemical substances in epithelial lining fluid. We used this probe to measure tumor markers in fluid from tissues surrounding lung nodules less than 30 mm in diameter to test its adjunctive diagnostic utility in lung cancer. METHODS: In 12 patients, epithelial lining fluid was collected in triplicate or duplicate from tissue within 2 cm of small peripheral lung nodules and from the contralateral lung. The diagnosis of adenocarcinoma was surgically confirmed in all patients. Fifteen patients without lung cancer served as controls. Concentrations of carcinoembryonic antigen, cytokeratin fragment 19, and sialyl SSEA-1 were measured in the fluid. RESULTS: Carcinoembryonic antigen and cytokeratin fragment 19 concentrations were significantly higher in fluid near the nodules (median, 8.7 and 87.2 ng/mg, respectively) than on the contralateral sides (median, 1.5 and 3.7 ng/mg, respectively) or in fluid collected from the controls (median, 2.0 and 2.8 ng/mg, respectively). CONCLUSIONS: Measurements of carcinoembryonic antigen and cytokeratin fragment 19 collected by our microsampling probe may be a useful diagnostic adjunct in patients with small peripheral lung nodules.

Adenocarcinoma↗