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Biomedical subjects

K Ando

Publications and source records attributed to K Ando.

At least 235 records · Page 13Linked to original sources

Clinical usefulness of urinary CrossLaps as a sensitive marker of bone metabolism.

CrossLaps peptide [Glu-Lys-Ala-His-Asp-Gly-Gly-Arg], a part of the C-telopeptide of the alpha 1-chain of type I collagen of bone, is a recently developed biochemical marker of bone turnover. In this study, the clinical utility of measurement of urinary CrossLaps was investigated in eleven premenopausal women who received a gonadotropin-releasing hormone (GnRH) agonist for 6 months for treatment of adenomyosis (n = 1) or leiomyomas (n = 10). Along with urinary CrossLaps, the levels of various biochemical markers, and serum estradiol, calcitonin and intact parathyroid hormone (i-PTH) were measured, and lumbar spine bone mineral density (BMD) was also monitored before, during, and at the end of the course of GnRH agonist therapy. Apart from CrossLaps, markers of bone resorption tested were urinary pyridinoline, deoxypyridinoline and hydroxyproline. Markers of bone formation tested were serum osteocalcin and bone-specific alkaline phosphatase (B-ALP). Serum estradiol levels decreased to undetectable levels at 2 months of GnRH agonist therapy. The values for all biochemical markers increased significantly throughout the therapy. The degree of an increase in CrossLaps levels was greater than that in all other markers. Mean lumbar spine (L2-L4) BMD was decreased by 7.2% at 6 months of treatment. The percent change in BMD at 6 months of treatment correlated inversely with the percent change in CrossLaps levels from the baseline to 1, 2, and 5 months of treatment. These results indicate that measurement of urinary CrossLaps might be a useful tool to predict the risk of bone loss caused by hypoestrogenism including GnRH agonist therapy.

Adenomyoma↗

Lymphostin (LK6-A), a novel immunosuppressant from Streptomyces sp. KY11783: taxonomy of the producing organism, fermentation, isolation and biological activities.

In the course of screening for inhibitors of the lymphocyte kinase, Lck (p56lck), aiming at novel immunosuppressants, we isolated a novel alkaloid, lymphostin (LK6-A), from the culture broth of Streptomyces sp. KY11783. Lymphostin was produced in a fermentation medium supplemented with a highly porous polymer resin, which prevented the degradation of this compound in the culture broth. Lymphostin inhibited the kinase activity of Lck with an IC50 value of 0.05 microM, and exhibited potent inhibitory activity against the mixed lymphocyte reaction (MLR) with an IC50 value of 0.009 microM.

Chromatography, High Pressure Liquid↗

MS-681a, b, c and d, new inhibitors of myosin light chain kinase from Myrothecium sp. KY6568. I. Characterization of producing strain and production, isolation and biological activities.

Novel compounds MS-681a, b, c and d were isolated from the culture broth of a fungal strain KY6568. The strain was identified as Myrothecium sp. from its morphological characteristics. MS-681a, b, c and d inhibited the activity of purified smooth muscle myosin light chain kinase with IC50 values of 0.11, 0.29, 0.095 and 0.26 microM, respectively. Cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase and protein kinase C were not inhibited at 100 microM by MS-681 compounds.

Aminoisobutyric Acids↗

Effects of reoxygenation on repair of potentially lethal radiation damage in cultured MG-63 osteosarcoma cells.

The effects of reoxygenation on repair of potentially lethal radiation damage were investigated using MG-63 human osteosarcoma cells in vitro. When exponentially growing MG-63 cells were cultured under hypoxic conditions for 24 h, cells stopped growing and remained at a low density. The hypoxic cells were then reoxygenated by exposure to air and irradiated with a single dose of 3 Gy X rays. The fraction of the reoxygenated cells surviving after 3 Gy increased by a factor of 20.6 when the colony assay was delayed for 24 h. In control cells which were cultured under aerobic conditions before receiving a single dose of 3 Gy, the surviving fraction increased by a factor of 2.5 when the assay was delayed for 24 h. The difference in the magnitude of the repair observed between reoxygenated and aerobic cells was less prominent in confluent cells plated at high density. The enhanced repair after reoxygenation was due mainly to a decrease in the alpha coefficient when the dose-survival curve was fitted to the linear-quadratic model, whereas the most significant change in the fit of the dose-survival curve for the aerobic cells was a decrease in the beta coefficient. The control aerobic cells accumulated at G2/M phase after irradiation, whereas the reoxygenated cells did not show such an accumulation. When the hypoxic cells were irradiated and then reoxygenated, repair of these cells irradiated under hypoxic conditions was also enhanced. This is the first report to show that reoxygenation could increase cell survival after tumor irradiation.

Aerobiosis↗

Response of mouse intestine after single and fractionated irradiation with accelerated carbon ions with a spread-out Bragg peak.

The responses of mouse intestine were examined after irradiation with accelerated carbon ions with a spread-out Bragg peak. The carbon-ion beam (135 MeV/nucleon), accelerated by the RIKEN ring cyclotron facility, was modulated to have a spread-out Bragg peak (SOBP) 3 cm wide. In the SOBP the biological dose (relative physical dose x RBE) was designed in earlier studies to be flat at the 10% survival level of Chinese hamster V79 cells. The numbers of surviving crypt clonogenic cells after single and fractionated irradiation with the carbon-ion beam were obtained by a microcolony assay method. The composite single-dose survival curves for the crypt clonogenic cells were calculated and fitted by a linear-quadratic (LQ) model. An analysis with the LQ model for crypt clonogenic cells showed that the alpha coefficient increased along with increasing LET, and that the beta coefficient was relatively constant, even for high-LET radiations. The biological dose distributions for the crypt clonogenic cells at the 10% survival level were flat in the SOBP. The isoeffective design of the SOBP for the 135 MeV/nucleon carbonion beam, based on biological data from a mammalian in vitro cell system, appears to be applicable to the response of murine intestinal tissue in vivo.

Animals↗

[Complications of thoracoscopic surgery for spontaneous pneumothorax].

We reviewed the cases of 122 patients with primary spontaneous pneumothorax who underwent thoracoscopic surgery at our institution between 1992 and 1995. In 9 cases, thoracotomy became necessary because of severe adhesions (3 cases), large foci (3 cases), and unrecognized foci (3 cases). Complications occurred in 17 cases: collapse in 1 patient after removal of the thoracic drain, persistent air leakage (> 7 days) in 2 patients, and recurrent pneumothorax in 14 patients. There were no significant differences between the recurrent and non-recurrent cases in age, sex location of bullae, past history of pneumothorax, operating time, intraoperative blood loss, or duration of chest tube drainage after surgery. The interval between onset and consult was significantly longer in recurrent cases than in non-recurrent cases, and the number of patients who required chest tube drainage before surgery was significantly higher in recurrent cases. Reoperation was performed in 9 cases. Bullaes that were not detected during the first surgery were found in the 7 of these cases. The recurrent cases in our study were regarded as resulting from a lack of surgical skill that may improved with increasing surgical experience. The Brinkman index was significantly higher in recurrent cases. Smoking and air-leakage before surgery may be risk factors for recurrence following thoracoscopic surgery for spontaneous pneumothorax.

Adolescent↗

[Vasculature in hypertension].

Hypertensive disease causes vascular complications, which are clinically important. Reversely, vascular dysfunction accelerates hypertension and its complication. The structural changes in vasculature alter vascular function but blood vessels, which does not have structural changes, also exhibit abnormal vascular function. Recently, it has been recognized that hemodynamic factors modifis vascular function. Especially, shear stress affects vascular endothelial function to regulate vascular tone, gene expression, and leukocyte adhesion, which intimately related to pathogenesis of hypertensive disease.

Animals↗

Carbohydrate selectin inhibitor CY-1503 reduces neutrophil migration and reperfusion injury in canine pulmonary allografts.

BACKGROUND: Neutrophil adhesion is initiated by the interaction of rapidly expressed endothelial selectins with oligosaccharide structures (sialyl Lewis(x) on polymorphonuclear neutrophils (PMN). The carbohydrate sialyl Lewis X analogue CY-1503 blocks selectin receptors, thereby inhibiting PMN rolling and subsequent firm adhesion and migration. METHODS: We evaluated the inhibitory effect of CY-1503 on PMN migration and reperfusion injury in canine left lung allografts. Donor lungs were flushed with modified Euro-Collins solution (1500 ml, 4 degrees C) and preserved for 21 hours at 1 degree C. Left lung allotransplantation was subsequently performed in 14 mongrel dogs. Immediately after transplantation and allograft reperfusion, the recipient contralateral right pulmonary artery and bronchus were ligated to permit assessment of isolated allograft function during a 6-hour postreperfusion period (FIO2 = 1.0). Allograft gas exchange (q 15 minutes) and hemodynamics (q 60 minutes) were assessed. After sacrifice, allograft bronchoalveolar lavage fluid (BALF) PMN count and allograft tissue myeloperoxidase (MPO) activity were measured. Two groups were studied: In group I (n = 7) CY-1503 was added to the donor lung flush (20 mg/L) and given to the recipient (35 mg/kg intravenous bolus) before reperfusion, followed by a continuous infusion (5.25 mg/kg/h intravenously) during the 6-hour assessment period. Group II animals (n = 7) received no CY-1503. RESULTS: Gas exchange in group I was superior throughout the assessment period (p < 0.01 at 6 hours after reperfusion). BALF PMN count in group I was reduced to 0.57 +/- 0.3 x 10(6) PMN/ml compared with 3.9 +/- 1.3 x 10(6) PMN/ml in group II (p < 0.05). Group I allograft MPO activity was 0.21 +/- 0.06 compared with 0.40 +/- 0.02 delta OD/mg/ min in controls (p < 0.02). Two animals in each group died early after reperfusion as a result of graft failure and were excluded from analysis. CONCLUSIONS: Our observations indicate that selectin inhibition effectively reduces PMN adhesion, migration, and subsequent reperfusion injury in preserved canine lung allografts.

Animals↗

[Clinical aspects of Behçet's disease--epidemiological features and visual prognosis].

Behçet's disease patients who visited the eye clinic of Tokyo University Hospital during the past 20 years were surveyed retrospectively, and their epidemiological features and visual prognosis were demonstrated. We evaluated the number of patients, sex ratio, age of onset, ratio of complete type to incomplete type, and ratio of major symptoms other than the ocular manifestation. The results showed a tendency similar to the results of the nationwide hospital survey in Japan. We also evaluated the visual prognosis of Behçet's disease patients in our clinic by the least square method. In the groups of patients whose visual acuity at the initial visit was over 0.4, the visual prognosis of those who visited from 1984 till 1993 was significantly better than that of those who visited from 1974 till 1983. The use of cyclosporine was presumed to be one of the most important factors in the improved visual prognosis of Behçet's disease patients in our clinic.

Adolescent↗

Purification of a Mycoplasma capricolum MCS4 RNA binding protein and cloning its gene.

MCS4 RNA (125 nt in length) is one of the small stable RNAs found in Mycoplasma capricolum cells. Gel shift assay was performed with the 5' end-32P-labeled MCS4 RNA and the S100 fraction from M. capricolum to identify the RNA binding proteins. Several bands were detected above free MCS4 RNA, indicating that the RNA formed complexes with proteins and/or RNAs. One of the proteins which specifically binds to MCS4 RNA was purified. The amino acid sequence of the N-terminus revealed 60 to 80% identity to those of glyceraldehyde-3-phosphate dehydrogenases (GAPDH) from various sources.

Amino Acid Sequence↗

cDNA cloning, expression and characterization of nitric-oxide synthase from the salivary glands of the blood-sucking insect Rhodnius prolixus.

Rhodnius prolixus, a blood-sucking bug, is a unique insect that is known to produce nitric oxide (NO) in the salivary glands to use as a vasodilator for blood sucking. We report here the cloning of the NO synthase (NOS) cDNA from these salivary glands and its expression in a baculovirus system. This cDNA encodes a protein of 1174 amino acids with a calculated molecular mass of 132,331 Da. The primary structures of mammalian NOS, including the putative cofactor-recognition sites for heme, tetrahydrobiopterin (BH4), calmodulin. FMN, FAD and NADPH are all conserved in salivary-gland NOS. Recombinant salivary-gland NOS differed from nerve NOS and endothelial NOS in that it lacked a large N-terminal domain and an N-terminal myristylation sequence, respectively. Salivary-gland NOS produced in a baculovirus system showed NOS activity and demonstrated that salivary-gland NOS was soluble and was Ca2+ and calmodulin dependent, similarly to mammalian constitutive NOS isoforms. Recombinant salivary-gland NOS was purified to near homogeneity and migrated at 130 kDa on SDS/PAGE.

Amino Acid Sequence↗

Light attenuation by the human eyelid.

Although it has been reported that light treatment during sleep can modify biological rhythms, the amount of light that is transmitted through the human eyelid has not been established. We evaluated eyelid transmission with a visual threshold response. Estimated light transmission through the eyelids was 0.3% for blue, 0.3% for green, and 5.6% for red light. The eyelid was an effective attenuator and acted as a red-pass filter. Illumination intensity and color balance after passing through the eyelid should be considered in evaluating the effects of light treatments during sleep.

Adult↗

Differential induction of carcinogen metabolizing enzymes in a transgenic mouse model of fulminant hepatitis.

The objective of this work is to examine the possible modulation of carcinogen metabolism (activation by cytochrome P450s and detoxification by conjugation via glutathione S-transferases [GST]) in relation to hepatitis B virus (HBV)-associated liver injury. In HBV transgenic mouse lineage 107.5, the hepatitis B surface antigen (HBsAg) is expressed at noncytopathic concentrations but after injection of an HBsAg-specific, major histocompatibility complex (MHC) class I restricted cytotoxic T-lymphocyte (CTL) clone, the mice develop a severe acute necroinflammatory liver disease that reaches maximum severity within 3 days and gradually subsides during the next 2 to 3 weeks. In this model, using immunohistochemical analysis, we observed an increase of P450s (CYP1A and 2A5), both involved in aflatoxin B1, metabolism, but minor changes or no changes for others (2B, 2C, 2E, 3A). There was a fivefold decrease in the total liver P450 microsomal content 3 days' post-CTL injection with the result that the relative proportion of CYP2A5 and 1A compared with other P450s is increased. Individual microsomal P450 enzyme contents estimated by Western blotting; Northern blot analysis of liver CYP messenger RNA (mRNA) levels as well as in vitro metabolism of specific substrates for different P450 isoenzymes were consistent with the immunohistochemical data. Immunohistochemical staining with antibodies to cytosolic pi class GST was increased 1 and 3 days postinjection followed by a progressive decrease at later time points (the same phenomenon was observed to a lesser extent for GST alpha). The activity of hepatic cytosols toward substrates specific for different subclasses of GST (mu, pi, alpha) showed that while GST mu was not changed in the CTL-injected HBV transgenic mice, GST pi and, to a lesser extent, alpha were increased as compared with controls. These results suggest that liver cell injury induced by a process of acute fulminant-like hepatitis can lead to the induction of some carcinogen metabolizing enzymes notably, Cyp 1A, 2A5 and GST pi in the mouse.

Animals↗

Application of interleukin 12 to antitumor cytokine and gene therapy.

In vivo administration of interleukin 12 (IL-12) at 2000 U/mouse induced IL-12-activated killer (IL-12AK) cells in parallel with an elevation in serum interferon-gamma (IFN-gamma) activity. Although NK1.1+CD3- natural killer cells are the major precursor of IL-12AK cells, asialoGM1+CD8+ T-cells were also demonstrated to be novel precursors. Such anomalous killer cells may play an important role in the early stages of the host defense mechanisms against tumors. It was also shown that IL-12 is effective in inducing tumor-specific cytotoxic T-lymphocytes. Consistent with these data, IL-12 had marked activity against various kinds of established tumors when given systemically. Mice cured of tumors by IL-12 treatment acquired tumor-specific T-cell immunity. Moreover, we initially demonstrated that IL-12 was effective in preventing and inhibiting the growth of primary tumors induced by the chemical carcinogen methylnitrosourea using c-Ha-ras transgeneic mice. Finally, we investigated the application of IL-12 to antitumor gene therapy. Transfer of the IL-12 gene into A20 B-lymphoma cells resulted in the continuous production of IL-12 and caused abrogation of in vivo tumorigenicity. Tumor cells transfected with the IL-12 gene are potentially a good tool as a tumor vaccine, as they effectively induced IL-12AK cells, IFN-gamma production, and tumor-specific protective immunity. Although B16-BL-6 melanoma cells, which are a highly metastatic subclone of B16 melanoma cells, showed resistance to IL-12 gene therapy, combination therapy with the B7-1 gene and systemic IL-12 administration almost completely inhibited tumor metastasis. Similar results were obtained using B16-BL-6 melanoma cells transfected with both B7-1 and IL-12 genes. These results suggest that IL-12 is a promising cytokine for antitumor cytokine and gene therapy.

Animals↗

Lidocaine reduces reperfusion injury and neutrophil migration in canine lung allografts.

BACKGROUND: Depletion of neutrophils (PMNs) and inhibition of PMN endothelial adhesion ameliorate post-ischemic lung reperfusion injury. Lidocaine reduces PMN adhesion to endothelial surfaces in vivo, and inhibits upregulation of PMN-CD11b/CD18 (Mac-1) in vitro. We evaluated the effect of lidocaine on reperfusion injury, PMN adhesion, and PMN migration in preserved lung allografts. METHODS: Donor lungs were flushed with modified Euro-Collins solution (4 degrees C) after prostaglandin E1 administration (250 micrograms), inflated with 550 mL (inspired oxygen fraction = 1.0), and stored for 24 hours at 1 degree C. Left lung allotransplantation was performed in 13 mongrel dogs. Immediately after reperfusion the recipient right pulmonary artery and bronchus were ligated to permit assessment of allograft function during a 6-hour postreperfusion period. Allograft gas exchange (every 15 minutes) and hemodynamics (every 60 minutes) were assessed. Peripheral blood PMN CD11b expression was determined by flow cytometry. After sacrifice allograft bronchoalveolar lavage fluid PMN count and allograft tissue myeloperoxidase activity were measured. Two groups were studied: In group I (n = 8) lidocaine hydrochloride was added to the donor flush (20 mg/L) solution. In addition lidocaine was given to the recipient at the time of thoracotomy (intravenous bolus of 4 mg/kg) followed by a continuous infusion of 4 mg/kg/h during implantation and the assessment period. Three dogs that did not reach effective lidocaine blood levels at the time of reperfusion (3 to 4 micrograms/mL) were excluded from analysis. Group II animals (n = 5) received no lidocaine. RESULTS: Gas exchange in group I was superior throughout the assessment period (p < 0.05). Bronchoalveolar lavage fluid PMN count in group I was reduced (0.36 x 10(6)PMN/mL versus 6.2 x 10(6) PML/mL; p < 0.03). Group I allograft myeloperoxidase activity was 0.17 U/mg/min compared with 0.28 U/mg/min in group II (p < 0.01). In lidocaine-treated animals PMN CD11b expression was maintained at basal levels 2 hours after reperfusion, compared with group II, in which upregulation of CD11b was observed. Lower lobe wet/dry ratio was not different in the two groups. CONCLUSIONS: Our observations indicate that lidocaine reduces reperfusion injury and inhibits PMN adhesion and subsequent migration to the lung allograft.

Animals↗