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Biomedical subjects

T Kanno

Publications and source records attributed to T Kanno.

At least 181 records · Page 10Linked to original sources

Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro.

The morphogenesis and remodeling of bone depends on the integrated activity of osteoblasts that form bone and osteoclasts that resorb bone. We previously reported the isolation of a new cytokine termed osteoclastogenesis inhibitory factor, OCIF, which specifically inhibits osteoclast development. Here we report the cloning of a complementary DNA of human OCIF. OCIF is identical to osteoprotegerin (OPG), a soluble member of the tumor-necrosis factor receptor family that inhibits osteoclastogenesis. Recombinant human OPG/OCIF specifically acts on bone tissues and increases bone mineral density and bone volume associated with a decrease of active osteoclast number in normal rats. Osteoblasts or bone marrow-derived stromal cells support osteoclastogenesis through cell-to-cell interactions. A single class of high affinity binding sites for OPG/OCIF appears on a mouse stromal cell line, ST2, in response to 1,25-dihydroxyvitamin D3. An anti-OPG/OCIF antibody that blocks the binding abolishes the biological activity of OPG/OCIF. When the sites are blocked with OPG/OCIF, ST2 cells fail to support osteoclastogenesis. These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites.

Amino Acid Sequence↗

Intra- and intercellular Ca2+ signaling in paraneurons and other secretory cells.

Paraneurons are endocrine and sensory cells which share structural, functional, and metabolic features with neurons. They produce identical with or related to neurotransmitters or neurohormones, which are synthesized and secreted by regulated secretion. They are receptoconductile-secretory in function, which is shared by specific proteins distributed at proper regions of cell membrane. A substantial advance has been made in the molecular machinery underlying protein sorting and transport within the endoplasmic reticulum and Golgi apparatus, and the mechanism of targeted membrane fusion by constitutive secretion. Various patterns of [Ca2+]c dynamics play cardinal signaling roles in stimulus-secretion coupling in individual secretory cells. Long-lived recurrent Ca2+ spikes or oscillation may maintain prolonged secretory responses, ATP synthesis in mitochondria, cell growth, differentiation, and division. In the neurons and the paraneurons of neuroectodermal origin, action potentials propagate along a conductile region to the secretory region of each cell and hardly be transmitted to the adjacent cells. In the paraneurons of gut endodermal origin, intracellular signalling including Ca2+ spikes can be propagated to the adjacent cells, and in turn may maintain coordination of individual cells forming a cell society.

Action Potentials↗

Successful resection of arteriovenous malformations in eloquent areas diagnosed by surface anatomy scanning and motor evoked potential.

Successful resection of cerebral arteriovenous malformations (AVMs) involving the sensorimotor cortex was achieved in 17 cases. The theoretical basis for performing resection of AVMs in eloquent areas is the fact that the brain in and around the nidus about 1 mm in thickness is considered not to be functioning. It is also considered that any center of important function, when an AVM is involved, shifts to the near-by cortex from the original site. Nevertheless, it is critically important to recognize the cortex functioning as sensorimotor centers before and during operation. For this purpose, we have used surface anatomy scanning (SAS) in combination with magnetic resonance angiography. SAS is found to be very useful for the recognition of the topographical relationship between the surface anatomy and AVM. During operation, the motor cortex is identified with motor evoked potential. We have found that, in some cases, the motor center has shifted to the accessory motor cortex. With these information, it is possible to start resection of the lesion from dissection of the main feeders and dissection of the nidus from a silent cortex toward the critical area. Apparent neurological improvements were achieved in 15 of 17 patients treated surgically (88%). With this result, we think that AVMs in eloquent areas can be treated successfully when the surgery is well-designed and well-oriented with the combined use of diagnostic imaging and monitoring. As for control of intraoperative bleeding, careful attention to small but important surgical techniques avoids troublesome bleeding during AVM surgery.

Arteriovenous Malformations↗

Treatment and results of partially thrombosed giant aneurysms.

Partially thrombosed giant aneurysms are one of the most difficult diseases in the neurosurgical field. We have had 18 of these cases namely, three in vertebral artery, four in basilar artery, four in internal carotid artery, five in middle cerebral artery, and two in anterior communicating artery. Nine aneurysms were clipped, two aneurysms were removed with anastomosis, two cases were treated interventionally, and five cases were treated conservatively because of serpentine and fusiform types of aneurysms in internal carotid artery bifurcation. These conservatively treated patients died due to infarction. When surgery is selected in the thrombosed giant aneurysms, the approach is the most important to secure the neck. Three-dimensional computed tomography angiography was useful to plan the strategy for surgery. If the neck is big enough for placement of a clip, arterial reconstruction is the choice. The reconstruction must be done including an adequate size of the artery because of the thick wall. If the aneurysm neck is too small to reconstruct, aneurysmectomy with anastomosis is one of the choices.

Adult↗

Identification of alpha- and beta-cells in intact isolated islets of Langerhans by their characteristic cytoplasmic Ca2+ concentration dynamics and immunocytochemical staining.

Ratiometric images of cytoplasmic Ca2+ concentration ([Ca2+]c) in individual cells were recorded simultaneously with a confocal ultraviolet-laser microscope in the Indo-1-loaded islets isolated from mice. After changes in [Ca2+]c in response to glucose or amino acids were recorded, the islet was fixed, permeabilized, and stained by the indirect immunofluorescence method against insulin or glucagon in situ; the individual cells were then identified in the focal plain identical to that used for the [Ca2+]c imaging. Almost all cells identified as insulin-positive (beta-cells) by their distinct immunofluorescence responded to the increase in glucose concentration from 3 to 11 mmol/l with an increase in [Ca2+]c. Major populations of cells (approximately 65%) identified as glucagon-positive (alpha-cells) responded to the addition of arginine (5-10 mmol/l) to 3 mmol/l glucose solution with an increase in [Ca2+]c. About half of the alpha-cells (47.6%) responded to the addition of alanine (5-10 mmol/l) to 3 mmol/l glucose solution with an increase in [Ca2+]c. In contrast, <13% of beta-cells responded to the addition of alanine (5-10 mmol/l) or arginine (5-10 mmol/l) to 3 mol/l glucose with an increase in [Ca2+]c. More than one-fourth of alpha-cells responded with an increase in [Ca2+]c when glucose concentration in perifusion solution was reduced from 11 to 0 mmol/l. These results indicate that [Ca2+]c changes in islet cells stimulated by glucose or amino acid were characteristic of the cell species, at least in the alpha- and beta-cell. This technique provides a useful tool to investigate not only the intracellular signal transduction but also the intercellular signal transmission in the intact islet.

Animals↗

Biochemical properties of human oral polymorphonuclear leukocytes.

Polymorphonuclear leukocytes (PMN) isolated from the oral cavity of healthy human volunteers, spontaneously generated superoxide, nitric oxide (NO) and other reactive oxygen species (ROS) which exhibited strong luminol chemiluminescence (LCL). To understand the physiological roles of oral PMN (OPMN), biochemical properties of the cells were analyzed. Biochemical analysis revealed that OPMN were already primed under physiological conditions. Western blot analysis revealed that they strongly expressed the inducible type of NO synthase (NOS II) and exhibited the activity to catalyze tyrosine phosphorylation of various proteins including a 115 kDa protein (cbl product). OPMN also generated H2O2 and .OH by some superoxide dismutase (SOD)-sensitive mechanism and released myeloperoxidase (MPO). Kinetic analysis using specific inhibitors revealed that OCl- generated by OPMN was predominantly responsible for the enhanced LCL. During the incubation under standard culture conditions, OPMN underwent apoptosis which proceeded more rapidly than that of the circulating PMN (CPMN). Immunochemical analysis revealed that expression of apoptosis-related gene products, such as Bcl-2, Bcl-xL and Bax, was below detectable levels with both cell types. However, caspase-3 but not caspase-1 was markedly activated in OPMN. These results indicate that the primed OPMN spontaneously generate ROS and play an important role in the defense mechanism in the oral cavity and that the generated ROS activate caspase-3 thereby inducing apoptosis of the cells.

Apoptosis↗

Photodynamic stimulation causes sustained increase in intracellular calcium concentration in cells of small cell lung carcinoma.

Photodynamic agents, due to their selective uptake by tumor cells and photon-dependent selective activation, have immense implications for cancer treatment. The present study provided direct evidence that the photon activation of chloro-aluminum phthalocyanine sulphonate (A1PcS4) in the presence of extracellular Ca2+ caused a rapid increase followed by a sustained increase in intracellular concentration of calcium ion ([Ca2+]i) in a small cell lung carcinoma (SCLC) cell line, SBC-3. The [Ca2+]i increase by photodynamic stimulation was completely inhibited by the removal of extracellular Ca2+ and reintroduction of extracellular Ca2+ immediately led to a rapid elevation of [Ca2+]i. However, the increase was not inhibited by application of Ni2+, nifedipine, or SK&F 96365, a receptor-mediated and voltage-dependent Ca2+ entry blocker. The photosensitizer A1PcS4 alone or light alone (4 min) had no effect on [Ca2+]i. Cytotoxicity examination by trypan blue exclusion test, however, suggested photodynamic stimulation-induced cell injury which was observed in both the presence and the absence of extracellular Ca2+. These results indicate that [Ca2+]i increase may not be mandatory for photodynamic stimulation-induced cell injury. Whether [Ca2+]i increase can accelerate, at least in part, cell death under the physiological condition, whether the mechanism(s) of cell death can be different in the presence and the absence of extracellular Ca2+, and whether [Ca2+]i increase can be totally unrelated to cell death await further work.

Antineoplastic Agents↗

The fate of 359 renal allografts harvested from non-heart beating cadaver donors at a single center.

The fates of 359 kidneys harvested from 181 non-heart beating donors (NHBD) at a single center, using a regional in situ cooling technique were retrospectively investigated. 1. Thirty-five kidneys (9.7%) were discarded mainly due to poor arterial perfusion and bacterial contamination. 2. The incidence of primary nonfunction in patients treated with Aza was significantly higher than that in patients receiving CsA or FK (20.5% [8 grafts] vs 6.0% [17 grafts], respectively, p < 0.01). 3. The incidences of immediate and delayed graft function were 16.1% and 77.9%, respectively, among 285 recipients treated with CsA/FK. The average of duration of posttransplant dialysis required in recipients with DGF was 13.7 days and the average lowest serum creatinine level in patients who recovered graft function was 1.58 mg/dl. 4. Patient survival rates in the CsA/FK group were 97.2%, 95.0%, 93.2% and 89.3% at one, 3, 5 and 10 years, respectively, and the graft survival rates at one, 3, 5 and 10 years were 83.3%, 72.0%, 64.7% and 48.6%, respectively. 5. Increasing donor age showed a significant correlation with increased serum creatinine levels as well as with prolonged posttransplant dialysis (p < 0.001 and p < 0.01, respectively). 6. Renal grafts from donors with cerebrovascular disease (CVD) had significantly higher lowest serum creatine levels than grafts from non-CVD donors (p < 0.0001). 7. Renal grafts harvested from NHBD using our in situ cooling technique had excellent renal function when the donor was young or the cause of death was non-CVD. However, when the donor was older (> or = 56 years) and the cause of death was CVD, the grafts were acceptable but the early posttransplant function was often impaired. 8. The current NHBD graft survival rate, the UNOS cadaveric renal graft survival rate and the Japanese living-related donor renal graft survival rate were almost identical at 10 years posttransplant. 9. NHBDs should provide an excellent opportunity to increase organ availability.

Adolescent↗

[Pathophysiological background of transient hyperphosphatasemia].

We studied the relationship between 23 cases with transient hyperphosphatasemia (TH) and viral infection. Many of the patients appeared to be suffering from viral infection. Measurement of antibody in the titer revealed increases in antibody to Echo 22, Entero 71 and Coxsackie B5 in 20.0%, 11.1% and 11.1% of patients, respectively.

Alkaline Phosphatase↗

Ca2+ signaling in the pancreatic acinus.

Change in cytosolic free calcium ion concentration [Ca2+]c, resulting from receptor activation by an appropriate agonist, functions as a cardinal intracellular signaling in the stimulus-secretion coupling in a wide variety of secretory cells including the acini of the pancreas. Ratiometric imaging of [Ca2+]c dynamics by UV-laser scanning confocal microscopy led us to conclude that in the cholecystokinin (CCK)-8-induced recurrent [Ca2+]c, spiking increases initially in the basolateral margin of the acinus and propagates to the luminal margin. [Ca2+]c in this initial cell increased rapidly and uniformly to the maximum level. The decrease in [Ca2+]c in the initial cell coincided with a small increase in [Ca2+]c in the luminal regions of the bilateral neighboring cells followed by uniform maximal increase in [Ca2+]c in these neighboring cells. A series of [Ca2+]c dynamics was repeated to form recurrent Ca2+ spiking. The temporal sequences of [Ca2+]c dynamics recorded during continuous stimulation with CCK-8 at a physiologic concentration in individual acinar cells forming the acinus were displayed on the identical time scale. The figure indicates that the signaling is not synchronous in cells forming an acinus. From these and other results, we proposed a model in which CCK-8 at a low physiologic concentration binds to highly sensitive CCK receptor interacting with heterotrimeric guanosine 5'-triphosphate-binding proteins of the Gq class, generate Ins 1,4,5-P3, and recurrent [Ca2+]c, spiking. The recurrent Ca2+ spiking maintains a sustained secretory response, recurrent exocytosis of zymogen granules, and concomitant secretion of isotonic NaCl.

Animals↗

[Sex and age distribution of patients with macroamylasemia found in the daily isoenzyme analysis].

We studied distributions of sex and age for 102 patients with macroamylasemia found in routine isoenzyme analysis. This study was based on a questionnaire to promote understanding of the clinical significance of macroamylase. More than half of the physicians received our report evaluated the information on macroamylase in the questionnaire. Macroamylasemia found in this study consisted of IgA type immunoglobulin in 92% and mostly had high activities in the serum. The back-ground of these patients with macroamylasemia were 10 cases of hepato-biliary disease, 9 cases of diabetes mellitus, 8 cases of autoimmune disease and so on. The frequency of macroamylasemia in males was double than in females and age distribution was not significant in statistic analysis.

Adolescent↗

Enzyme immunoassay of urinary mevalonic acid and its clinical application.

We have developed an enzyme immunoassay for mevalonic acid (MVA), using a specific monoclonal antibody. The intra- and interassay coefficients of variation calculated on two urine samples were 3.3% and 3.4%, respectively, in the intraassay precision test and 3.5% and 6.9% in the interassay evaluation. Pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, was administered to nine healthy men, and in all cases, their MVA excretion rates then decreased. The more MVA that was excreted in the urine before the pravastatin administration, the greater a reduction of MVA excretion was observed. The daily MVA excretions in healthy men (n = 120) and women (n = 105) were 2.32 micromol/day (SD, 0.82 micromol/day) and 1.85 micromol/day (SD, 0.47 micromol/day), respectively. In streptozotocin-induced diabetic rats (n = 14), the plasma cholesterol concentrations and MVA excretion rates were increased, and a positive correlation was observed between the plasma cholesterol and the urinary MVA concentrations.

Adult↗

Superoxide dismutase-like activity of metal substituted lactoferrin derivatives.

Lactoferrin (LF) is an iron-binding glycoprotein present in various secretions including milk and the specific granules of neutrophils. The main biological properties of this protein are thought to concern the regulation of iron absorption, antimicrobial activity and modulation of neutrophil activity. Copper bound LF (Cu-LF) inhibited the stimulation-dependent reduction of cytochrome c (Cyt. c) in guinea pig peritoneal neutrophils (GPMN) but were without effect on NADPH oxidase activity of the respiratory burst. However, Cu-LF stimulated the stimulation-dependent production of hydrogen peroxide as seen with superoxide dismutase (SOD). Similar but weaker inhibition of Cyt. c reduction than that shown by Cu-LF was observed with manganese-LF (Mn-LF) but not with ferrous-LF (Fe-LF) or apo-LF (Apo-LF). The inhibitory activity was concentration-dependent and the ID50s of Cu-LF and of Mn-LF were 0.1 and 5 microM, respectively. Reactive oxygen species (ROS) detected by luminol chemiluminescence (LCL) of stimulated-GPMN were partially inhibited by Cu-LF. Changes in LCL of stimulated GPMN induced by Cu-LF were similar to those of superoxide dismutase (SOD). Thus, it is concluded that low concentrations of Cu-LF had SOD-like activity and high concentrations of Cu-LF inhibited the stimulation-dependent generation of ROS.

Animals↗

[Effective use of a laboratory database: quality assurance and laboratory workflow applications].

Recent laboratory information systems have usually adopted a client server system. Computing tools which can provide easy access to a database using simple language are now strongly needed. These functions are provided in an End User Computing (EUC) system. An EUC is defined as follows: 1) General end users can easily access the database of the laboraotry system and extract objective data stored in database. 2) The extracted data will be easily converted to files that can be processed by commercially available software. In this paper, we demonstrate the examples how to use the EUC for a quality assurance system and analyses of laboratory workflow. In the case of quality assurance, we demonstrate the setting of reference intervals from stored laboratory data concerning health care examination programs at our university. Secondly, we developed a system of monitoring quality control data, and set parameters for delta checking and actual zone QC method. We can estimate and design an outline of laboratory workflow from extraction of the time currently required for each task. We can measure the turn-around time for laboratory testing and rate of requests for laboratory tests received from physicians via order entry system. Moreover, we can estimate and simulate the waiting time and time required for analyses by outpatient clinics. These time monitoring systems reflect the design of laboratory workflow such as the labor and equipment time required in laboratory work. These uses of laboratory data are currently expanding further and further in the fields of education and laboratory research. We believe that information technology will facilitate future advances of laboratory medicine.

Clinical Laboratory Information Systems↗

Migration activity of microglia and macrophages into rat brain.

We examined the entry of intra-arterially injected microglia and macrophages into the brain using a rat muscle graft model to compare their respective abilities to invade the brain parenchyma. Isolated microglia without any activation treatment entered into the brain with or without the muscle graft, while macrophages activated by phorbol 12-myristate-13-acetate (PMA) entered the brain only in the presence of the muscle graft. These results suggest that microglia have a higher affinity for the brain than macrophages.

Animals↗