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Biomedical subjects

K Wake

Publications and source records attributed to K Wake.

At least 19 recordsLinked to original sources

Mobile phone use and acoustic neuroma risk in Japan.

OBJECTIVES: The rapid increase of mobile phone use has increased public concern about its possible health effects in Japan, where the mobile phone system is unique in the characteristics of its signal transmission. To examine the relation between mobile phone use and acoustic neuroma, a case-control study was initiated. METHODS: The study followed the common, core protocol of the international collaborative study, INTERPHONE. A prospective case recruitment was done in Japan for 2000-04. One hundred and one acoustic neuroma cases, who were 30-69 years of age and resided in the Tokyo area, and 339 age, sex, and residency matched controls were interviewed using a common computer assisted personal interview system. Education and marital status adjusted odds ratio was calculated with a conditional logistic regression analysis. RESULTS: Fifty one cases (52.6%) and 192 controls (58.2%) were regular mobile phone users on the reference date, which was set as one year before the diagnosis, and no significant increase of acoustic neuroma risk was observed, with the odds ratio (OR) being 0.73 (95% CI 0.43 to 1.23). No exposure related increase in the risk of acoustic neuroma was observed when the cumulative length of use (<4 years, 4-8 years, >8 years) or cumulative call time (<300 hours, 300-900 hours, >900 hours) was used as an exposure index. The OR was 1.09 (95% CI 0.58 to 2.06) when the reference date was set as five years before the diagnosis. Further, laterality of mobile phone use was not associated with tumours. CONCLUSIONS: These results suggest that there is no significant increase in the risk of acoustic neuroma in association with mobile phone use in Japan.

Adult↗

Dosimetry considerations in the head and retina for extremely low frequency electric fields.

Magnetophosphenes are investigated from the viewpoint of electromagnetic dosimetry. Induced current density and internal electric fields at the threshold of perception are estimated by analytical and numerical calculations, assuming different models. Dosimetry for electrophosphenes is also discussed and compared with that for magnetophosphenes. The distribution of current density and internal electric fields is consistent with the experimental observation that flashing sensations reach their greatest intensity at the periphery of the visual field, for both electro and magnetophosphenes. The estimated thresholds in internal electric fields are consistent for magnetophosphenes and for electrophosphenes, respectively. The magnitudes of the thresholds, however, differ by about 10-fold. The thresholds in induced current density are critically dependent on the conductivity of the eye assumed for the calculations. The effect of thin membrane structure is also discussed with regard to the difference between electric field and magnetic field exposures.

Animals↗

Exposure to 2.45 GHz electromagnetic fields induces hsp70 at a high SAR of more than 20 W/kg but not at 5W/kg in human glioma MO54 cells.

PURPOSE: To determine potential hazards from exposure to a high-frequency electromagnetic field (HFEMF) at 2.45 GHz by studies of the expression of heat-shock protein 70 (hsp70) in MO54 cells. METHOD: MO54 cells were exposed to a HFEMF at average specific absorption rates (SAR) of 5, 20, 50 and 100 W/kg, using input powers of 0.8, 3.2, 7.8 and 13 W, at a temperature of up to 39 degrees C. An annular culture dish provided three levels of exposure for a given input power, designated inner, middle and outer rings. Two control groups were used: the first was subjected to sham exposure and the second was a temperature control, used to determine the effect of high temperature using incubation in a conventional incubator at 39 degrees C. Cell survival was determined in intervals up to 24 h. Protein was extracted from MO54 cells in both groups after 2, 4, 8 and 16 h exposure times. Changes in the hsp70 protein levels were analysed by Western blots. RESULTS: Little or no cell death was observed in the sham-exposed cells, nor for incubation at 39 degrees C for up to 16 h. Cell survival decreased to about 30% after exposure to HFEMF for 24 h at an average SAR of 100 W/kg. A slight increase in hsp70 was observed in cells in both the inner and outer rings of the plate after exposure at SAR levels of 25 and 78 W/kg, respectively, for 2 h. With increasing exposure time, hsp70 expression increased except for an SAR of 5 W/kg. In the raised temperature control at 39 degrees C, hsp70 expression also increased as the incubation time increased. However, the expression level of hsp70 for the HFEMF exposure was greater than that for the raised temperature control. CONCLUSION: HFEMF can produce an increased level of hsp70 expression in MO54 cells at SAR levels above 20 W/kg, even when the effect of raised temperature is taken into account.

Biomedical Engineering↗

Increase in hypoxanthine-guanine phosphoribosyl transferase gene mutations by exposure to electric field.

Previously, we reported that exposure to extremely low frequency magnetic field (400 mT) increased in hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene mutations. However, it is unclear these mutations were induced by magnetic field (MF), electric field (EF), or both. To explore this question, a new exposure apparatus for EF was manufactured. We observed an increase in HPRT gene mutations in Chinese hamster ovary (CHO) cells after exposure to EF (10 V/m, 60 Hz) for 10 h. The mutant frequency by EF-exposure was an approximate 2-fold of that by sham-exposure. Our data suggest that the mutations induced by exposure of cells to the variable magnetic field at 400 mT may be, in part, due to the induced EF.

Animals↗

Exaggerated responses to chronic nociceptive stimuli and enhancement of N-methyl-D-aspartate receptor-mediated synaptic transmission in mutant mice lacking D-amino-acid oxidase.

Formalin-induced nociceptive behaviors and N-methyl-D-aspartate (NMDA) subtype glutamate receptor-mediated excitatory synaptic transmission were analyzed in mutant mice lacking D-amino-acid oxidase, which catalyzes the oxidative deamination of D-amino acids. The second phase of the formalin-induced licking response, a part of which is known to be mediated by NMDA receptors in the spinal cord, was significantly augmented in mutant mice. NMDA receptor-mediated excitatory postsynaptic currents recorded from spinal cord dorsal horn neurons by tight-seal whole-cell methods were significantly potentiated in mutant mice. The present observations provide another line of evidence that D-serine functions as an endogenous coagonist at the glycine site of NMDA receptors, and raise the possibility that D-amino-acid oxidase exerts a neuromodulatory function by controlling the concentration of D-serine in the central nervous system.

Animals↗

Cloning and disruption of a phenylalanine ammonia-lyase gene from Ustilago maydis.

The enzyme L-phenylalanine ammonia-lyase (PAL) catalyzes the non-oxidative deamination of L-phenylalanine to form trans-cinnamic acid and ammonia. This enzyme is universally present in higher plants and it catalyzes the starting reaction for a central pathway that generates hundreds of different phenylpropanoid metabolites. Genes encoding PAL have been identified in fungi, but the role of the enzyme has not been determined. We cloned and characterized a gene that encodes PAL from the phytopathogenic fungus Ustilago maydis and we constructed fungal strains carrying a null mutation in the gene. These mutants behaved like wild-type strains in terms of growth, mating, and pathogenicity. These results indicate that PAL does not play a major role in the life cycle of U. maydis under laboratory conditions.

Amino Acid Sequence↗

Nuclear deviation in hepatic parenchymal cells on sinusoidal surfaces in Arctic animals.

In normal rat and human, most of the nuclei of hepatic parenchymal cells are centrally located in the cytoplasm. However, it is reported that the nuclei of hepatic parenchymal cells are situated at a deviated position on sinusoidal surfaces under pathological situations such as chronic hepatitis, hepatocellular carcinoma, adenomatous hyperplasia, or regeneration. During a study on the mechanism of extreme vitamin A-accumulation in hepatic stellate cells of arctic animals including polar bears, arctic foxes, bearded seals, and glaucous gulls, we noticed that these arctic animals displayed the nuclear deviation in hepatic parenchymal cells on sinusoidal surfaces. In this study, we assessed the frequency of hepatic parenchymal cells showing the nuclear deviation on the sinusoidal surfaces in arctic animals. A significantly higher frequency of the nuclear deviation in hepatic parenchymal cells was seen in polar bears (89.8+/-3.4%), arctic foxes (68.6+/-10.5%), bearded seals (63.6+/-8.4%), and glaucous gulls (24.2+/-5.8%), as compared to that of control rat liver (9.8+/-3.5%). However, no pathological abnormality such as fibrosis or necrosis was observed in hepatic parenchymal and nonparenchymal cells of arctic animals, and there were no differences in the intralobular distribution of parenchymal cells displaying the nuclear deviation in the livers from either arctic animals and control rats. The hepatic sinusoidal littoral cells such as stellate cells or extracellular matrix components in the perisinusoidal spaces may influence the nuclear positioning and hence the polarity and intrinsic physiological function of parenchymal cells.

Animals↗

Re-evaluation of the reticulo-endothelial system.

By injecting lithium carmine (Lit-car) into living animals, Ribbert (1904) and Kiyono (1914) showed that specific staining occurred in some cells in various organs. Kiyono termed those cells "histiocytes" which consisted of free amoeboid cells and cells of reticulo-endothelium. Aschoff (1924) introduced the concept 'reticulo-endothelial system (RES)' for the collection of cells having in common the property of vital staining. Van Furth (1972) proposed the term "mononuclear phagocyte system (MPS)" advocated that RES be replaced by MPS. As a consequence we presently suffer from a "reticulo-endothelial confusion", based on the delusion that cells other than macrophages are not members of the RES. The point that most clearly illustrates this is the fact that the Lit-car-laden cells in the body are named macrophages in modern textbooks of histology. To clarify the confusion, we re-examined the vital staining at light and electron microscopic levels and analyzed the scavenger cells using biochemical methods. Injected Lit-car was actively endocytosed by sinusoidal endothelial cells in the liver and reticular cells in the sinus of lymph nodes. Of note, uptake of the dye was comparatively much lower in macrophages/monocytes. Our findings indicate the existence of scavenger endothelial cells and reticular cells in blood and lymphatic circulations respectively. We name these two systems "the scavenger RES" collectively.

Animals↗

Studies on the effects of microgravity on the ultrastructure and function of cultured mammalian cells.

Four cultures of monkey kidney cell line, JTC-12, were flown on the Spacelab-J (SL-J) mission during 8 days. The results of the present study showed that the space flight gave no essential effect on morphology, cell cycle, glucose consumption and urokinase production of the mammalian culture cell. However, the cell proliferation slightly decreased under microgravity. Moreover, the lack of gravity induced the trypsin-treated dissociated cells to keep floating in the culture medium. Therefore, the attachment of the cells onto the substratum was delayed, and that caused difficulties in subculturing the cells. The present research also offered some important information on techniques for establishment of cell cultures in space laboratories.

Animals↗

Analysis of induced currents in a rat exposed to 50 Hz linearly and circularly polarized magnetic fields.

This paper presents a numerical analysis of currents induced in a rat by linearly and circularly polarized magnetic fields of 50 Hz. Special focus was placed on pineal gland and retina of rats since these organs were often associated with the changes of melatonin synthesis and concentration. Induced currents in two MRI-based rat models with resolutions of up to 0.125 mm(3) were calculated by using the impedance method. We characterized the induced currents by amplitude and polarization. Calculated induced current densities were extremely small, i.e., < 30 microA/m(2) for both linearly and circularly polarized magnetic fields of 1.41 microT (peak). There were no significant differences in amplitude nor polarization of induced currents in the pineal gland between the linearly and the circularly polarized magnetic fields when the polarization was in a vertical plane. In contrast, the magnetic fields rotating in the horizontal plane produced most circularly polarized currents both in the pineal gland and in the retina.

Animals↗

Cell-cell organization and functions of 'sinusoids' in liver microcirculation system.

Following much controversy through the first three decades in this century structure and function of hepatic sinusoids have been elucidated. The sinusoidal wall consists of endothelial cells, Kupffer cells, dendritic cells, NK cells (pit cells) and stellate cells. Using classic staining methods, immunocytochemistry, fluorescence microscopy, TEM and SEM, cell-cell organizations and functions of sinusoids have been studied. Based on observations, a new definition of the space of Disse was proposed.

Animals↗

[Anesthetic management of a patient with dilated cardiomyopathy under total intravenous anesthesia with propofol and ketamine combined with continuous epidural analgesia].

We report our experience with total intravenous anesthesia (TIVA) with propofol and ketamine combined with continuous epidural analgesia in a 72-year-old-male patient with dilated cardiomyopathy scheduled for a total prostatectomy. After premedication with atropine 0.5 mg and pethidine 35 mg, anesthesia was induced with ketamine 50 mg, fentanyl 0.1 mg and using a step down method of propofol (6-->4-->2 mg.kg-1.hr-1). After hemodynamic parameters had been stabilized, the trachea was intubated. Then, 1.5% lidocaine 6 ml was injected through an epidural catheter, placed at the L 1-2 intervertebral space. Anesthesia was maintained with continuous infusion of propofol 1 mg.kg-1.hr-1 and ketamine 1 mg.kg-1.hr-1, and continuous epidural analgesia with 1.5% lidocaine 2 ml.hr-1. Hemodynamics remained stable throughout the operative procedure. No postoperative complications occurred. TIVA with propofol and ketamine in combination with epidural analgesia is useful for patients with dilated cardiomyopathy in order to maintain stable hemodynamics during anesthesia.

Aged↗

Expression of P-selectin on hepatic endothelia and platelets promoting neutrophil removal by liver macrophages.

The role of P-selectin on polymorphonuclear leukocyte (PMN) adhesion-induced PMN elimination in the liver is unclear. Our objectives were to show the expression and distribution of P-selectin in rat liver, as well as to evaluate the changes in the modulation of the expression of P-selectin and its role in the accumulation and sequestration of PMNs. The intravenous administration of endotoxin markedly increased the expression of P-selectin on the venous and sinusoidal endothelial cells, as well as on the platelets trapped in the liver. Its expression peaked at 6 hours postinjection and was associated with a rapid increase in the aggregation and elimination of PMNs in the hepatic sinusoids. Combined treatment with an antibody to P-selectin or with low molecular weight heparin, a P-selectin antagonist, blocked the P-selectin, significantly reduced the arrest of PMNs, and delayed their removal in the liver. Pretreatment with gadolinium chloride inhibited phagocytosis of PMNs by the Kupffer cells, decreased the expression of P-selectin, and limited the hepatic accumulation of PMNs. Thus, P-selectin played a role in accumulation and elimination of PMNs from the liver. Results also suggest that activated Kupffer cells can modulate the expression of P-selectin in the liver and influence the homeostasis of PMNs in the circulation during acute inflammation.

Animals↗

The portal lobule in rat liver fibrosis: a re-evaluation of the liver unit.

We re-evaluated three schemes of liver organization: the classic lobule, the portal lobule, and Rappaport's liver acinus. The lobular angioarchitecture of normal rat liver and the three-dimensional structure of pseudolubules found in rat livers with fibrosis induced by swine serum were compared with the classic lobule of the pig. Normal and fibrotic rat livers and pig livers were perfused, injected with either India ink or 0.75% OsO4 through the portal and/or hepatic vein, and immersionfixed. Whole lobes and hand-cut thick sections were made transparent with a solution of benzyl benzoate and methyl salicylate. The angioarchitecture of normal rat liver differs from pig liver. In the former, terminal portal branches and central veins interdigitate, and in the latter, numerous terminal portal branches that arise from interlobular portal veins establish a vascular basket surrounding one central vein and forming classic lobule. The structure of liver acinus is never found in the pig liver. The terminal portal branch, together with the terminal hepatic artery and bile duct, are present inside each pseudolobule of fibrotic rat livers. Blood from the terminal portal branch flows through inlet venules into radiating sinusoids, and, at the periphery converges into newly formed septal and angular outlet venules; these venules terminate in fibrotic central veins located at each corner. Pseudolobules are not rugby ball-like as Rappaport's liver acini are but are polyhedron in shape. The rat pseudolobules are comparable with the portal lobule; its structure and microcirculation are the reverse of the pig classic lobule. Rat pseudolobules are different from liver acini, as shown by the following: 1) their three-dimensional shape is different; and 2) they have a reverse relationship to classic lobules while acini are defined to subdivide classic lobules. In normal and fibrotic rat livers, the liver unit is the portal lobule with a terminal portal branch as the axial branch and central veins at the periphery. The co-existence of liver acini and classic lobules is doubtful.

Animals↗

Zonal and regional differences identified from precision mapping of vitamin A-storing lipid droplets of the hepatic stellate cells in pig liver: a novel concept of addressing the intralobular area of heterogeneity.

Knowledge of hepatic heterogeneity has been strikingly increased, while an accurate means for addressing intralobular positions is still lacking. We examined pig liver preparations of the gold impregnation method for vitamin A-storing lipid droplets in hepatic stellate cells. Droplet morphometry was performed under oil immersion, and the calculated volumes plotted on computerized maps. The heterogeneous results were assessed with five concentric zones and five radial regions; the latter were determined based on midseptum visualized by portal injection. Zonation and regionation thus subdivided lobules into 5-zone/5-region (5Z/5R) compartmentalization. Distribution of values exhibited a distinct zonal gradient, heightened at peripheral zones 1 and 2, decreased over intermediate zone 3 toward centrilobular zones 4 and 5; peak was always found at zone 2. Within a single zone, variations were obvious, forming a regional gradient. Values were significantly higher at periportal than midseptal regions. Digitized mapping showed that low values filled up centrilobular zones, whereas high values concentrated in periportal regions. Along the periphery, inlet venules were quantified, revealing an occurrence rate of 60% at periportal, and 5% at midseptal regions, closely compatible with the regional gradient of vitamin A-storing capacity. The interweaving between zonal and regional gradients results in a vitamin A-low territory, a compound area composed of centrilobular zones plus extensions into midseptal regions. Because the results could account for physiological and pathological events, we regard the 5Z/5R compartmentalization a model worth routine adoption for a precise description of any morphofunctionally demonstrable heterogeneity of the liver lobules.

Adipocytes↗

Uptake of lithium carmine by sinusoidal endothelial and Kupffer cells of the rat liver: new insights into the classical vital staining and the reticulo-endothelial system.

Sinusoidal cells in the rat liver were studied in vivo and in vitro using the original vital staining with lithium carmine, which has contributed much to the development of the concept of the reticulo-endothelial system. Immunohistochemical and electron-microscopic studies revealed that the dye-incorporating cells were sinusoidal endothelial cells, Kupffer cells, and monocytes. The endothelial cells took up much more dye than did the Kupffer cells and bulged largely into the sinusoidal lumen. Electron microscopy revealed that small particles of lithium carmine were associated with coated vesicles of endothelial cells and ruffled membranes of Kupffer cells. In the endothelial cells, these particles were present in various concentrations within vacuolated structures and condensed in the lysosomes forming large aggregates of lithium carmine lumps. These lumps showed crystalline structures, within which the size of the individual particle was up to 30 nm in width and 50 nm in length. A few endothelial cells containing abundant dye underwent degeneration, and some were taken up by Kupffer cells. Liver endothelial cells isolated from lithium carmine-administered rats endocytosed fluorescence-labeled collagen. Isolated endothelial cells from normal rat liver, when cultured with lithium carmine, did not take up any dye, and their endocytosis of formaldehyde-treated albumin was inhibited dose-dependently. We conclude that in the liver, endothelial cells, but not Kupffer cells, predominantly take up lithium carmine. Furthermore, we propose the existence of a generalized cell system based on its vital staining capacity.

Animals↗

Maturation of rat dendritic cells during intrahepatic translocation evaluated using monoclonal antibodies and electron microscopy.

Specific populations of hepatic sinusoidal cells were stained with monoclonal antibodies that recognize monocytes/macrophages (ED1), tissue macrophages (Kupffer cells) (ED2), MHC class II (Ia) antigen (MRC OX6), and dendritic cells/gamma,delta T-cells (MRC OX62) and analyzed by light and electron microscopy. The majority of ED1(+) and/or ED2(+) cells were localized to the hepatic parenchyma, whereas OX6(+) and/or OX62(+) cells were more densely distributed within Glisson's sheath than in the hepatic parenchyma. Double-immunoperoxidase staining of normal liver for ED1, ED2, and OX6 identified dendritic cells (DC) of two different phenotypes, ED1(+)ED2(-)OX6(+) and ED1(-)ED2(-)OX6(+). DC can be classified into three different types based on ultrastructural characteristics. The first type (type I) is characterized by one or more long cytoplasmic processes and a well-developed lysosomal system. The second type (type II) has an inconspicuous lysosomal system, abundant hyaloplasm, and characteristic short cytoplasmic processes. The third type (type I-II) has cytologic features intermediate between those of type I and type II DC. At the electron-microscopic level, these three cell types are found in the sinusoidal lumen, whereas the majority of type II DC are located in the space of Disse and Glisson's sheath. Furthermore, some OX6-labeled elongated DC appeared to traverse the lumen of sinusoids through endothelial pores to enter the space of Disse. One hour after intravenous injection of latex particles (0.81 micrometer in diameter), numerous latex-laden dendritic cells (ED1(+)OX6(+), type I and type I-II) were detected in the lumen of hepatic sinusoids, but not in the space of Disse or Glisson's sheath. These findings suggest that normal rat liver contains resident dendritic cells which downregulate phagocytic activity and mature into potent accessory cells during migration from the portal vein toward the central vein. These DC then traverse the sinusoidal lumen to the hepatic lymph system via the space of Disse.

Animals↗