Elevated interleukin 2 levels in serum and cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis.
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Humans↗
Biomedical subjects
A Kaneko
Publications and source records attributed to A Kaneko.
Cat retinal ganglion cells show transient responses to acetylcholine and sustained responses to L-glutamate.
The neuropharmacological basis for the different receptive field properties of cat retinal ganglion cells was investigated using whole cell voltage-clamp recordings from acutely dissociated adult tissue. Subclasses of physiologically characterised ganglion cells were determined on the basis of (i) their soma diameters and (ii) their projection to central visual nuclei (identified by microinjection of fluorescent dyes into the lateral geniculate and/or superior colliculus). The sensitivities of all categories of ganglion cells, prepared from peripheral retina were found to be similar for gamma-amino butyric acid, glycine, acetylcholine and glutamate. The kinetics of desensitisation differed among receptor subtypes, revealing possible physiologically significant molecular specialisations that could be involved in shaping synaptic transmission.
Acetylcholine↗
Intracellular calcium as a second messenger for human hepatocyte growth factor in hepatocytes.
Human hepatocyte growth factor is a newly discovered substance that stimulates DNA synthesis in vitro. In this study, we examined intracellular Ca2+ movement as one of the second messengers for human hepatocyte growth factor in primary-cultured hepatocytes. The addition of hHGF induced Ca2+ oscillation, but the frequency of oscillations varied from cell to cell. We also saw marked intercellular heterogeneity in the initial latent period for the Ca2+ response; the mean latent period was rather longer than those seen with phenylephrine and vasopressin. This difference in the initial latent period may be due to the difference in the pathways of Ca2+ elevation. Duration of culture determined the number of human hepatocyte growth factor-responsive cells; their number peaked at 2 to 5 hours of confluent culture, whereas the peak was earlier in a low-density culture. These changes in responsiveness during culture can be explained by the cell cycle-dependent sensitivity to human hepatocyte growth factor of hepatocytes. The Ca2+ response to human hepatocyte growth factor was dose dependent; 10(-10) mol/L hHGF gave the highest Ca2+ response, similar to the dose-response curve of DNA synthesis. We even observed the Ca2+ response in the Ca(2+)-free buffer, so the increase in Ca2+ was considered due to release from intracellular Ca2+ stores. These results suggest that human hepatocyte growth factor causes the intracellular Ca2+ elevation in the early stage of the cell cycle and that it plays important roles in the signal transduction systems for human hepatocyte growth factor and the proliferation of hepatocytes.
Animals↗
Epidermal growth factor induces dose-dependent calcium oscillations in single fura-2-loaded hepatocytes.
Digital imaging fluorescence microscopy has been used to investigate epidermal growth factor-induced calcium responses of fura-2-loaded hepatocytes in primary culture at the single-cell level. Epidermal growth factor induced oscillations in cytosolic free calcium ([Ca2+]i) consisting of a periodic train of spikes unlike the monophasic elevation in cell suspensions reported previously. In this study, 79% of the cells in the microscopic field responded to 0.1 nmol/L epidermal growth factor, and 78% of the responsive cells displayed oscillations. However, the frequency of oscillations differed considerably from cell to cell. [Ca2+]i measurement in a cell population was simulated using these data, but only a slightly biphasic pattern was obtained, indicating the significance of single-cell measurement of [Ca2+]i. Because considerable heterogeneity existed in the sensitivity to epidermal growth factor between the cells, single hepatocytes were stimulated sequentially with increasing concentrations of epidermal growth factor to investigate the dose dependence of the oscillations. The frequency of the oscillations increased with increasing epidermal growth factor concentration, but the amplitude was similar for all concentrations, suggesting the existence of frequency-encoded information even in the pathway through tyrosine kinase for epidermal growth factor signaling. The pattern of the oscillations with epidermal growth factor, especially the latency, was considerably different from that with phenylephrine, which is known to use the phosphatidylinositol pathway, possibly because of the difference in the pathway toward phosphatidylinositol turnover between these agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
In vitro percutaneous absorption of thiamine disulfide from a mixture of propylene glycol and fatty acid.
The in vitro percutaneous transport of thiamine disulfide (TDS), an oxidized dimer of thiamine, from propylene glycol through excised abdominal rat skin was studied. The application of saturated, long-chain fatty acids [stearic acid (18:0), myristic acid (14:0), and lauric acid (12:0)] as enhancers to the system was also studied. TDS permeated through rat skin from propylene glycol with a flux of 2.5 +/- 0.8 micrograms/cm2/min. The flux was enhanced 31 times by 12:0 and 1.4 times by 14:0 and was suppressed to 80% of its original value by 18:0. The absorption of TDS could not be explained by TDS permeating across a dialysis membrane, but the interaction between TDS and fatty acids may influence the system. The results show the possibility of developing a transdermal thiamine delivery system.
Administration, Cutaneous↗
Sebaceous gland and sweat gland carcinomas of the skin. Clinicopathological study and significance of c-erbB-2 oncoprotein expression.
Thirteen sebaceous gland carcinomas and 10 sweat gland carcinomas were examined to elucidate any important histological parameters influencing their prognosis, and the relationship between immunohistochemical expressions of c-erbB-2 oncoprotein and survival of the patients was analyzed. Sebaceous gland carcinomas with vacuolated cytoplasm in more than 50% of whole tumor area, with necrosis, and without lymphoid cell infiltration in tumor nests and stroma had a higher incidence of tumor recurrence and tumor-related death than tumors with vacuolated cytoplasm in 50% or less of whole tumor area (p < 0.01), without necrosis, and with lymphoid cell infiltration in tumor nest and stroma (p < 0.05). Sweat gland carcinomas of all cases with fatal outcomes demonstrated tubular differentiation in 20% or less of whole tumor area, lymphatic permeation and desmoplastic reaction. Three sebaceous gland carcinomas and three sweat gland carcinomas were positive for c-erbB-2 oncoprotein. Two of three sebaceous gland carcinomas, and all three sweat gland carcinomas developed tumor recurrence and ended in tumor-related deaths. Sweat gland carcinomas with c-erbB-2 expression had significantly shorter survival than those with negative immunostain (p < 0.01). Cytoplasmic appearance, tumor necrosis, and lymphoid cell infiltration in tumor nests and stroma of sebaceous gland carcinoma, and tubular differentiation, lymphatic permeation, and growth patterns of sweat gland carcinoma are considered to closely correlate to the prognosis. Immunohistochemically detected c-erbB-2 oncoprotein may be an indicator of bad prognosis.
Adolescent↗
Voltage-dependent ionic currents in solitary horizontal cells isolated from cat retina.
1. Horizontal cells of the cat retina were isolated by enzymatic dissociation. Two types of horizontal cells were identified: the axonless (A-type) horizontal cell having four to six thick, long (approximately 100 microns) dendrites, and the short-axon (B-type) horizontal cell having many (> 5) fine, short (approximately 30 microns) dendrites. 2. Membrane properties of isolated horizontal cells were analyzed under current-clamp and voltage-clamp conditions. In the A-type cell, the average resting potential was -55 mV and the mean membrane capacitance was 110 pF, whereas values in the B-type cell were -58 mV and 40 pF, respectively. The A-type cell showed long-lasting Ca spikes, but B-type cells had no Ca spikes. 3. Five types of voltage-dependent ionic currents were recorded: a sodium current (INa), a calcium current (ICa), and three types of potassium currents. Potassium currents consisted of potassium current through the inward rectifier (Ianomal), transient outward potassium current (IA), and potassium current through the delayed rectifier (IK(v)). INa was recorded only from A-type cells. Other currents were recorded from both types of cells. 4. INa activated when cells were depolarized from a holding potential (Vh) of -95 mV, and it was maximal at -25 mV. This current was blocked by tetrodotoxin. Approximately half of the A-type cells had INa, but no B-type cell had this current. 5. L-type ICa, an inward-going sustained current, was activated with depolarization more positive than -25 mV. Current amplitude reached a maximal value near 15 mV and became smaller with further depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
In vitro percutaneous absorption of thiamine disulfide through rat skin from a mixture of propylene glycol and fatty acid or its analog.
Percutaneous absorption of thiamine disulfide, (TDS), a lipophilic derivative of thiamine, from a mixture of propylene glycol (PG) and fatty acid (FA) or its analog through rat skin was tested in vitro. Lauric acid (12:0) enhanced the absorption depending on its concentration in PG and showed a maximal enhancement at 10% w/w. At 10% w/v, lauryl alcohol also enhanced the absorption, but less than 12:0, which lauric acid methyl ester suppressed the absorption. The flux of TDS did not depend on the solubility of TDS in the vehicle, but on the permeability coefficient. From these results, it is suggested that FA increases the permeability coefficient not only because FA increases TDS diffusion by disrupting lipid packing in the stratum corneum but also, FA increases TDS partition to lipid phase by interacting with TDS.
Animals↗
Changes in serum human hepatocyte growth factor levels after transcatheter arterial embolization and partial hepatectomy.
We examined the changes in serum human hepatocyte growth factor (hHGF), also called "scatter factor," levels after transcatheter arterial embolization (TAE) and partial hepatectomy (PH) in patients with hepatocellular carcinoma and metastatic liver tumor. In most cases, the serum hHGF levels increased transiently 1-3 days after TAE or PH, and then decreased nearly to the basal levels in 1 wk, suggesting that hHGF may play an important role in liver regeneration in humans. The mean amount of increase in serum hHGF levels after PH was 0.38 ng/ml, which was greater than that after TAE (0.16 ng/ml). In three cases of TAE followed by PH, two showed a greater increase in serum hHGF levels with PH than with TAE, but the third showed the reverse result. Because the rate of increase in serum ALT levels did not affect that of serum hHGF levels, the degree of liver injury induced by TAE or PH does not seem to be a determinant in serum hHGF elevation.
Carcinoma, Hepatocellular↗
Acute intravascular haemolysis in Vanuatu following a single dose of primaquine in individuals with glucose-6-phosphate dehydrogenase deficiency.
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Acute Disease↗
Extrahepatic portal vein aneurysm associated with a tortuous portal vein.
Portal vein aneurysm is rare and its etiology is controversial. A case of extrahepatic portal vein aneurysm associated with an unusually tortuous portal vein is described. Real-time ultrasonography showed anechoic masslike lesions at the porta hepatis communicating with the superior mesenteric vein and intrahepatic portal branches. This suggested the presence of two saccular portal vein aneurysms, 27 x 21 mm and 21 x 13 mm in size. Magnetic resonance imaging and portal venography confirmed the portal vein aneurysms and an unusually tortuous portal vein curving caudally between them. The liver was histologically normal and there was no evidence of portal hypertension. It is speculated that these portal vein aneurysms may have been congenital and that the associated tortuous portal vein might have been secondary to hemodynamic changes in the portal venous system.
Adult↗
Voltage-gated sodium currents in isolated retinal ganglion cells of the cat: relation between the inactivation kinetics and the cell type.
Ganglion cells in the cat retina were retrogradely labeled by injecting a fluorescent dye (DiI) into either the lateral geniculate nucleus (LGN) or the superior colliculus (SC). Cells were then dissociated enzymatically from the retinal tissue. LGN-projecting ganglion cells consisted of 2 different populations, one with small and the other with large somata, which were identified as W and X cells, respectively. SC-projecting cells consisted of a single group of cells with small somata, identified as W cells. The voltage-gated sodium current (INa) was recorded from isolated ganglion cells under the voltage-clamp condition using a patch pipette in the whole cell configuration. INa was identified by reversible tetrodotoxin block. INa was activated by depolarization of the cell from the holding potential (Vh) of -95 mV to membrane voltages (Vm) more positive than -45 mV. The maximum INa was recorded at around -15 mV. INa flowed outward at Vm more positive than +65 mV. The reversal potential of INa became more negative voltages with low extracellular Na concentration ([Na+]o) with a relation of 58 mV for a 10-fold change in [Na+]o. INa was inactivated with a few milliseconds. Once inactivated, INa recovered by holding the cell membrane hyperpolarized. While the voltage dependence of INa activation and steady-state inactivation were constant from cell to cell, the time course of recovery was not. Cells with a large soma showed a rapid recovery, while cells with a small soma showed slow recovery. Thus, the rate of recovery is faster for X cells than for W cells. Perhaps this helps to explain the 'sluggish' firing of the latter cell type.
Action Potentials↗
Membrane currents and pharmacology of retinal bipolar cells: a comparative study on goldfish and mouse.
We obtained solitary bipolar cells using enzymatic (papain) dissociation of the goldfish and mouse (C57BL/6J, adult) retinae and measured the membrane currents of these cells by whole-cell patch clamp. Bipolar cells of these two species showed two main differences. A. Ca current 1. In the mouse, depolarization evoked a transient Ca current that had maximal amplitude at about -30 mV. 2. The Ca conductance was activated by voltage steps to potentials greater than -60 mV and inactivated fully at potentials greater than -20 mV. 3. The mouse Ca current was insensitive to Cd2+ or dihydropyridine. 4. Contrary to mouse, goldfish bipolar cells had a sustained Ca current, which was activated over a more positive potential range (greater than -30 mV), blocked by either 50 microM Cd2+ or 10 microM nifedipine, and markedly augmented by 10 microM Bay K8644. 5. The transient character of the Ca current in mouse bipolar cells may help to shape phasic responses of ganglion cells, while in goldfish the sustained nature of Ca current may contribute to shape tonic responses of ganglion cells. B. Pharmacology 1. We examined the effects of the inhibitory transmitters, glycine and GABA, on bipolar cells. 2. GABA produced strong inhibitory effects on bipolar cells of both goldfish and mouse. 3. The highest GABA sensitivity was found at the bipolar cell axon terminal, the site of reciprocal connection with amacrine cells. 4. GABA increased the Cl conductance. 5. Unlike GABA, glycine was effective only on the mouse bipolar cells. Axon terminals showed the highest glycine sensitivity. 6. Glycine-induced currents were also carried by Cl ions. 7. Since ECl in intact cells is assumed to be -55 mV, both GABA and glycine are thought to generate hyperpolarizing responses in cells maintained at their resting potential (ca. -45 mV). 8. The present study suggests that inhibition from amacrine cells to bipolar cells, found in both species, is mediated by different transmitters.
Animals↗
Injection of RNA from carp retina induces the formation of a membrane potassium channel in Xenopus oocytes.
Total RNA was purified from freshly isolated retinas of adult carp and injected into oocytes of Xenopus laevis (stages 5-6). Two to six days after injection, depolarizing voltage-clamp steps evoked a slowly activated outward current as large as 3 microA. This current inactivated slowly with a single time constant (tau = 3.1 +/- 0.24 S.E.M., for Vm = +30 mV). The current was inhibited by tetraethylammonium (3.8 mM for half-maximal inhibition). In the presence of Co2+ (1 mM) or barium methanesulfonate (40 mM), the current-voltage relationship shifted to slightly more depolarized values (5-10 mV); the maximal value of the current that was sensitive to Co2+ or Ba2+ treatments was only a small fraction (about 10%) of the TEA-sensitive current, and its current-voltage relationship was similar to that for uninjected oocytes. The reversal potential of the membrane current was studied with [K+]0 of 1-77 mM. For [K+]0 greater than 20 mM, the reversal potential changed with a slope of 63 mV (+/- 2 mV S.E.M.) per 10-fold change in [K+]0. The conductance was induced half-maximally at 17 mV (+/- 0.9 mV S.E.M.). The depolarization required for an e-fold increase in conductance was 13 mV (+/- 0.6 mV S.E.M.). From these results, we conclude that the injection of total RNA from carp retinas induces the formation of a membrane K+ channel in Xenopus oocytes. The channel formed has many of the properties reported for the maintained outward current of goldfish horizontal and bipolar cells.
Animals↗
High density cAMP-gated channels at the ciliary membrane in the olfactory receptor cell.
Spatial distribution of the cAMP-gated channel was investigated in amphibian olfactory receptor cells. Low doses of cAMP applied to the cytoplasmic side of a membrane patch excised from cilia produced single channel activity of unitary conductance 28pS. Variance analysis showed that the ciliary membrane contained 920 cAMP gated-channels/microns2 in the newt and 2400 channels/microns2 in the toad. In contrast, the membrane of the dendrite and cell body contained only 2 cAMP-gated channels/microns2 (newt) and 6 channels/microns2 (toad). Thus, there is a high density of cAMP-gated channels in the cilia where olfactory transduction is thought to take place.
Animals↗
Studies of the development of optical fiber sensors for biochemical analysis.
An optical fiber sensor utilizing Thymol blue and an ion-exchange resin complex in a cellulose acetate membrane was developed. By monitoring several different chromophores of Thymol blue, the sensor could measure the pH of the solution from 1.0 to 12.0 with good reproducibility. An optical fiber glucose sensor utilizing a cellulose acetate membrane containing glucose oxidase, 2,7-diaminofluorene dihydrochloride, and sodium N-(3-sulfopropyl)-3,3',5,5'-tetramethylbenzidine was developed. Reflectance changes at 580 nm were large enough to trace changes in glucose concentration in physiological saline solution.
Biosensing Techniques↗
Somatic and germinal mutations of tumor-suppressor genes in the development of cancer.
It is generally thought that the germinal mutation of tumor-suppressor genes predisposes the affected children to the development of certain types of hereditary tumors while the somatic mutation of the same genes links to the development of non-hereditary tumors. Retinoblastoma susceptibility gene (RB gene) is a prototype of such genes. We studied the parental origin of new mutation of the RB gene in the sporadic hereditary and non-hereditary retinoblastoma and osteosarcoma. The results showed a preferential involvement of parental genome in the new germinal as well as initial somatic mutations. The male-directed mutagenesis even in the somatic cells has been implicated as a reflection of germinal origin of mutation, even for non-hereditary tumors as a manifestation of mutational mosaicism associated with delayed mutation. The importance of the new mutations occurring as mosaics should be emphasized in the evaluation of cancer risks from parental exposures to radiation and chemicals.
Genes, Retinoblastoma↗
Voltage-gated calcium currents in isolated retinal ganglion cells of the cat.
Voltage-gated calcium current (ICa) was recorded from retinal ganglion cells dissociated from the adult cat under the voltage-clamp condition using a patch pipette in the whole cell configuration. ICa was isolated from the voltage-dependent potassium and sodium currents by ion substitution and selective blockers. ICa was activated by depolarization of the cell from a holding potential (Vh) of -97 mV to more positive voltages than -57 mV. All recorded cells showed similar voltage dependence of ICa activation: 50% activation at about -23 mV. Current-voltage (I-V) relationship of ICa showed a symmetrical bell-shape with a single peak at around -7 mV. The I-V curve recorded with Vh of -57 mV was nearly identical to that obtained with Vh of -97 mV. During a depolarizing command, the amplitude of ICa gradually decreased. Inactivation of ICa depended on Ca influx into the cell. ICa became more sustained either when the extracellular Ca was replaced by Ba, or when the cell was loaded with 30 mM EGTA. Nifedipine (10(-4) M) inhibited ICa reversibly. Effects of Bay K 8644 were bimodal: augmentation at a low concentration (10(-8) M) and suppression at a high concentration (10(-4) M). All these characteristics are identical to the previous findings for the high-threshold (L-type) ICa. The type of ICa recorded from the retinal ganglion cells in the adult cat is different from those in newborn rats.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗