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Biomedical subjects

N Ogata

Publications and source records attributed to N Ogata.

At least 163 records · Page 9Linked to original sources
PubMed1993

Suppression of chemotactic activity of neutrophils in hyperosmotic conditions comparable to the renal medulla: partial preservation by phosphoenolpyruvate.

Chemotaxis is one of the most important functions of the polymorphonuclear leukocyte (PMN). In the host defense against pyelonephritis, the renal medulla is a site of interaction between bacteria and PMNs. At this site the osmotic pressure is elevated due to a high concentration of NaCl and urea. We evaluated the in vitro chemotactic activity of PMNs under the hyperosmolar conditions created by high concentrations of NaCl and urea. This activity was suppressed by the stimulation of opsonized zymosan and formyl-methionyl-leucyl-phenylalanine. The inhibition of chemotaxis was partially preserved by phosphoenolpyruvic acid (PEP), a precursor of adenosine triphosphate (ATP), in hyperosmolar NaCl but not in urea. The intracellular content of ATP was increased by supplementing the hyperosmolar NaCl with PEP. These observations suggest that inhibition of the chemotactic activity of PMNs is due to differing mechanisms for each NaCl and urea, and that PEP may protect the PMNs against hyperosmolar NaCl by maintaining ATP content.

Adenosine Triphosphate↗
PubMed1993

Effect of recombinant human granulocyte-colony-stimulating factor on renal scarring following infection with MS-piliated bacteria.

Renal scars have been thought to occur only in later stages of chronic pyelonephritis. In our experimental pyelonephritis model, bacteria with mannose-sensitive (MS) pili on its surface promoted renal scarring when inoculated into renal parenchyma. Pretreatment with recombinant human granulocyte-colony-stimulating factor (rhGCSF) inhibited the renal scarring which followed inoculation with MS-piliated bacteria, whereas posttreatment at an early stage of infection had no effect on renal scarring. These findings suggest that rhGCSF may be useful for the prevention of infection without increasing the tissue damage to the renal parenchyma which leads to the renal scarring. Even when rhGCSF is used for treatment of kidney infection, it does not promote increased renal scarring through the increased invasion of leukocytes at the inflammatory site.

Animals↗
PubMed1993

Effect of prednisolone on renal scarring in rats following infection with Serratia marcescens.

Renal scarring is considered a criterion of reflux nephropathy and the end stage of pyelonephritis. Prednisolone, a strong anti-inflammatory drug, at doses of 1 or 2 mg/kg prevented renal scarring in rats following infection with Serratia marcescens. Four or 8 mg/kg of prednisolone, however, did not inhibit renal scar formation. In a time course experiment, renal scarring was prevented when 4-day treatment with prednisolone was initiated 2, 5, or 13 days after infection. These results show that prednisolone is effective in preventing such scarring and suggest the clinical use of this drug for preventing renal scar formation after pyelonephritis and reflux nephropathy.

Animals↗
PubMed1993

[Age-related changes in Bruch's membrane of the senescence accelerated mouse].

We studied pathological changes in Bruch's membrane of Senescence Accelerated Mouse (SAM) P/1. Tannic acid was used to demonstrate collagen fibers and microfibrils in Bruch's membrane. With aging, thickening of Bruch's membrane, especially thickening of the basement membrane of the choriocapillaris, was remarkable. The distance between collagen fibers also became wider, and many more fine fibrils appeared around each collagen fibril with aging. These changes were observed mor in the posterior area than in the periphery.

Aging↗
PubMed1993

[Idiopathic normal pressure hydrocephalus in elderly patients: its pathophysiology and diagnosis].

We described 10 cases of idiopathic normal pressure hydrocephalus (NPH) in elderly patients who had good results after shunting. Retrospective analysis of our cases offers the following results which indicate the pathogenesis and surgical selection of idiopathic NPH. 1) Most of the patients had risk factors of ischemic cerebrovascular disease and had multiple small ischemic lesions such as lacunae. 2) Cerebrospinal fluid (CSF) pressure is below 20mmHg in all cases and its response to acetazolamide loading was suppressed or almost lost in most of cases. 3) The volume of the lateral ventricle was slightly reduced after the effective operation. 4) Some of the patients showed clinical improvement even if they had symptoms for more than 2 years before treatment. Two primary theories exist concerning the cause of NPH. One is extraventricular obstruction to CSF flow at the level of the arachnoid villi or the basal cistern. The other is periventricular white matter ischemic damage which decreases the tensile strength of the ventricular walls and leads to ventricular dilatation. Tangential periventricular shearing force due to ventricular dilatation produces the symptom of NPH. Our results support these descriptions as the causes of idiopathic NPH in elderly patients. We noticed, firstly, involvement of the ischemic risk factor. Other findings implied decreased elasticity or compliance of the brain and the loss of the autoregulatory properties of cerebral circulation which accelerate the ischemic damage to the periventricular white matter. In understanding the etiology, it is important to know the fragility of the aged brain and the mechanical and hemodynamic stress to which it is subjected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Kinetic analysis of two types of Na+ channels in rat dorsal root ganglia.

1. The gating properties of two types of Na+ channels were studied in neurones isolated from rat dorsal root ganglia using the whole cell variation of the patch electrode voltage-clamp technique. 2. Two types of Na+ currents (INa) were identified on the basis of their sensitivity to tetrodotoxin (TTX). One type was insensitive to TTX (up to 0.1 mM), while the other type was blocked by 1 nM of TTX. Whereas they were both insensitive to 50 microM Cd2+, a high concentration (2 mM) of Co2+ selectively inhibited the TTX-insensitive type. 3. The activation thresholds were about -60 and -40 mV for the TTX-sensitive and the TTX-insensitive INa, respectively. Activation of the TTX-sensitive INa developed with a sigmoidal time course which was described by m3 kinetics, whereas the activation of the TTX-insensitive INa was described by a single exponential function. A deactivation process, as measured by the tail current upon repolarization, followed an exponential decay in either type of INa. 4. The rate constant of activation indicated that under comparable membrane potential conditions, the TTX-insensitive channels open 4-5 times slower than the TTX-sensitive ones upon depolarization. Likewise, the rate constant of inactivation indicated that the TTX-insensitive channels inactivate 3-7 times more slowly than the TTX-sensitive ones upon repolarization. 5. The steady-state activation curve for the TTX-insensitive INa was shifted about 20 mV in the positive direction from that for the TTX-sensitive INa. 6. The steady-state inactivation curve for the TTX-insensitive INa as obtained with a 0.5 s prepulse was shifted about 26 mV in the positive direction from that for the TTX-sensitive INa, indicating a greater availability for the TTX-insensitive INa in depolarized membrane. However, on increasing the duration of prepulse, the inactivation curve for the TTX-insensitive INa, but not for the TTX-sensitive INa, shifted in the negative direction due to an extremely slow inactivation process in the TTX-insensitive INa. Consequently, an overlap between the activation and inactivation curves which causes a steady influx of Na+ (window current) became progressively reduce. 7. The time course of INa decay was best described by a single exponential process in either the TTX-sensitive or TTX-insensitive INa, whereas the development of inactivation and the recovery from inactivation, which were measured by a conventional double-pulse protocol, followed a second order process in either channel type.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Regeneration of the rat carotid artery after clipping injury. Part I. A morphological study.

We investigated the natural course of the morphological regeneration of the endothelium and smooth muscle of the rat carotid artery after clipping injury. Vascular damage was produced by clipping the right carotid arteries of Wistar rats. Endothelial regeneration was confirmed by the injection of Evans blue dye and the detection of factor VIII-related antigen. The volume of the smooth muscle cell layer and the luminal size were measured by computer-assisted morphometric analysis. Immediately after arterial injury, Evans blue dye freely permeated the smooth muscle layer, suggesting that complete endothelial denudation had occurred. Endothelial regrowth started within 24 hours and was fastest on the third and fourth days after injury. The endothelial injury was repaired within 5 days. The area of the smooth muscle layer did not change immediately after clipping injury, but it gradually increased within a month. The luminal area of the injured artery increased during the 3-month recovery period. These findings suggest that endothelial regrowth is completed within a week after clipping injury, whereas smooth muscle cell regrowth is slower. In addition, arteriosclerotic luminal narrowing did not occur during recovery of the rat carotid artery from clipping injury.

Animals↗
PubMed1993

Regeneration of the rat carotid artery after clipping injury. Part II. A pharmacological study.

This study investigated the natural course of functional recovery of the vascular endothelium and smooth muscle after clipping injury of the rat carotid artery. Vascular injury was induced by clipping the right carotid arteries of Wistar rats. The contractile response to KCl, serotonin (5-hydroxytryptamine), and norepinephrine was decreased immediately after arterial injury. The response to KCl and serotonin recovered within 8 weeks, whereas the response to norepinephrine recovered after 12 weeks. Endothelium-dependent relaxation also disappeared immediately after clipping injury, but the recovery of relaxation in response to acetylcholine and adenosine triphosphate was observed within 1 week. Four weeks after clipping injury, higher doses of acetylcholine induced slight arterial contraction. These findings suggest that the recovery of smooth muscle contractility was slower than the process of endothelial regeneration in the rat carotid artery after clipping injury. Endothelium-dependent relaxation recovered within only a week, although the characteristics of the arterial cholinergic receptors may have changed in the chronic recovery stage.

Acetylcholine↗
PubMed1992

Lack of protective immunity against reinfection with hepatitis C virus.

Some individuals infected with hepatitis C virus (HCV) experience multiple episodes of acute hepatitis. It is unclear whether these episodes are due to reinfection with HCV or to reactivation of the original virus infection. Markers of viral replication and host immunity were studied in five chimpanzees sequentially inoculated over a period of 3 years with different HCV strains of proven infectivity. Each rechallenge of a convalescent chimpanzee with the same or a different HCV strain resulted in the reappearance of viremia, which was due to infection with the subsequent challenge virus. The evidence indicates that HCV infection does not elicit protective immunity against reinfection with homologous or heterologous strains, which raises concerns for the development of effective vaccines against HCV.

Acute Disease↗
PubMed1992

The mechanism of GABAB-mediated slowing of the activation phase of high voltage-activated Ca2+ channels in rat sensory neurons.

The mechanism underlying the slowed activation of the high voltage-activated Ca2+ current (HVA-ICa) in the presence of (-)-baclofen was studied in cultured neurons of rat dorsal root ganglia. The decay phase of the baclofen-sensitive component of HVA-ICa was described by a sum of two exponential functions. Although the inhibited portion in the amplitude of the baclofen-sensitive component of HVA-ICa was increased in a concentration-dependent manner, the two decay time constants remained unaffected regardless of the concentration of baclofen. Furthermore, the baclofen-sensitive component of HVA-ICa was largely inactivated by a depolarizing prepulse (-30 mV for 0.5 s). These results support the notion that the slowed activation of the HVA-ICa in the presence of baclofen is due to a preferential inhibition of the inactivating component of HVA-ICa rather than due to voltage-dependent unblocking of a single population of HVA-ICa.

Animals↗
PubMed1992

Use-dependent facilitation of L-like Ca2+ channels counteracts GABAB-mediated inhibition of N-like Ca2+ channels in rat sensory neurons.

Baclofen selectively blocked the inactivating N-like component of the high voltage-activated Ca2+ current (HVA-ICa) without affecting the sustained L-like component of the HVA-ICa in rat sensory neurons. The inhibition of the N-like component by baclofen was reversed by a large depolarizing prepulse to +50 mV as a result of facilitation of the L-like component. These results might indicate that a decrease in influx of Ca2+ through N-like Ca2+ channels due to the baclofen-induced block or due to the voltage-dependent inactivation induced by the depolarizing prepulse can be partially compensated by a rapid Ca2+ influx through extra L-like component facilitated by the depolarizing prepulse. Such a compensation of the Ca2+ influx by the use-dependent facilitation of L-like component may be a significant mechanism for adaptive regulation of Ca2+ channels in response to stimulation with a wide range of amplitude and frequency.

Animals↗
PubMed1992

Ontogenic development of the TTX-sensitive and TTX-insensitive Na+ channels in neurons of the rat dorsal root ganglia.

Developmental changes in the sensitivity of neurons to tetrodotoxin (TTX) were studied in relation to the cell size in rat dorsal root ganglia (DRG). Na+ currents were recorded from neurons of various stages of development. Two types of Na+ channels were identified on the basis of their sensitivity to TTX. One type was insensitive to a very high concentration (0.1 mM) of TTX, while the other type was blocked by a low concentration (1 nM) of TTX. These two types of Na+ channels were observed throughout the developmental stages examined from day 17 of gestation and adulthood. Thus, both types of Na+ channels are already established at the early stage of neuronal development and appear to be retained throughout the life-span of the DRG neuron. The concentration-response relationships for the block of TTX-sensitive Na+ current by TTX did not appreciably change during development. Although two types of Na+ channels had strikingly different kinetic properties, the kinetic properties of each channel type were basically similar throughout development. The TTX-sensitive Na+ channels were mainly concentrated in cells with large cell diameters throughout developmental stages examined. These large cells appear to correspond to the 'large-light' cells. On the contrary, the TTX-insensitive Na+ channels were found in smaller diameter cells which may correspond to the 'small-dark' cells. Thus, it is concluded that there are heterogeneous categories of neurons which have Na+ channels with different physiological and pharmacological properties. Since Na+ channels play a pivotal role in the action potential generation, these heterogeneity of DRG neurons appear to be instrumental in integrating the sensory signals.

Animals↗
PubMed1992

Slow inactivation of tetrodotoxin-insensitive Na+ channels in neurons of rat dorsal root ganglia.

Whole-cell patch-clamp experiments were performed with neurons cultured from rat dorsal root ganglia (DRG). Two types of Na+ currents were identified on the basis of sensitivity to tetrodotoxin. One type was blocked by 0.1 nM tetrodotoxin, while the other type was insensitive to 10 microM tetrodotoxin. The peak amplitude of the tetrodotoxin-insensitive Na+ current gradually decreased after depolarization of the membrane. The steady-state value of the peak amplitude was attained several minutes after the change of holding potential. Such a slow inactivation was not observed in tetrodotoxin-sensitive Na+ current. The slow inactivation of the tetrodotoxin-insensitive Na+ current was kinetically distinct from the ordinary short-time "steady-state" inactivation. The voltage dependence of the slow inactivation could be described by a sigmoidal function, and its time course had a double-exponential process. A decrease of external pH partially antagonized the slow inactivation, probably through an increased diffusion potential across the membrane. However, the slow inactivation was not due to change in surface negative charges, since a shift of the kinetic parameters along the voltage axis was not observed during the slow inactivation. Due to the slow inactivation, the inactivation curves for the tetrodotoxin-insensitive Na+ current were shifted in the negative direction as the prepulse duration was increased. Consequently, the window current activated at potentials close to the resting membrane potential was markedly reduced. Thus, the slow inactivation may be involved in the long-term regulation of the excitability of sensory neurons.

Animals↗
PubMed1992

Comparison of two types of Na+ currents with low-voltage-activated T-type Ca2+ current in newborn rat dorsal root ganglia.

Na+ currents and the low-voltage-activated T-type Ca2+ current (T-ICa) were recorded from neurons of rat dorsal root ganglia under similar ionic environments using the whole-cell patch-clamp technique. Two types of Na+ currents were identified on the basis of their sensitivity to tetrodotoxin (TTX) and channel kinetics. One type was blocked by 1 nM TTX and had a faster activation and inactivation time courses (F-INa), while the other type was insensitive to 100 microM TTX and had a much slower channel kinetics (S-INa). Activation thresholds were -60, -40 and -70 mV for F-INa, S-INa and T-ICa, respectively. Peak amplitudes were obtained in respective current/voltage curves at -30 mV (F-INa), 0 mV (S-INa) and -50 mV (T-ICa). The time to peak and the decay time constant measured at potential levels giving peak amplitudes were 0.5 and 1.5 ms for F-INa, 1.4 and 2.9 ms for S-INa and 8.1 and 17 ms for T-ICa, respectively. Cd2+ in a concentration of 50 microM totally blocked T-ICa, whereas it had no effect on either type of Na+ current. T-INa was found in 18 out of 25 cells which possessed F-INs, whereas it was found in only 2 cells among 15 which lacked F-INa. These three types of inward currents having different kinetic and pharmacological properties may mediate diverse functional roles in processing sensory signals.

Animals↗
PubMed1992

GABAB-mediated modulation of the voltage-gated Ca2+ channels.

1. The amino acid, gamma-aminobutyric acid (GABA), activates two different receptor types (Bowery et al., 1980; reviewed by Ogata, 1990a). 2. GABAA receptors are bicuculline-sensitive and are coupled to Cl- channels, while activation of bicuculline-insensitive GABAB receptors has been implicated in the modulation of Ca2+ (Dunlap and Fischbach, 1981) and K+ (Gahwiler and Brown, 1985; Inoue et al., 1985a,b; reviewed by Ogata, 1990b) channels. 3. Baclofen is a specific agonist for GABAB receptors (Bowery et al., 1980). In rat sensory neurones, baclofen suppresses the membrane Ca2+ current (ICa) by a mechanism involving a partussis toxin-sensitive G protein (Holz et al., 1986; Scott and Dolphin, 1986). 4. It has been shown that the inhibitory effect of baclofen is more potent on the early portion of ICa than on the later portion and consequently the rate of ICa activation is slowed (Deisz and Lux, 1985; Dolphin and Scott, 1986). 5. The mechanisms underlying these GABAB-mediated modulation of ICa is not fully understood. This article reviews the inhibitory action of baclofen on ICa in sensory neurones.

Animals↗
PubMed1992

Na+ current kinetics are not the determinants of the action potential duration in neurons of the rat ventral tegmental area.

Na+ currents were recorded from two morphological subpopulations of neurons acutely dissociated from the rat ventral tegmental area (VTA). About 45% of 56 VTA cells examined possessed only the ordinary type of Na+ current which was blocked by a low concentration (0.2 microM) of TTX. However, the remaining 55% had the Na+ current which contained a small fraction of the TTX-insensitive component, irrespective of morphological variations and action potential durations of VTA cells. The peak amplitude of the TTX-insensitive component was less than 10% of the peak amplitude of the total Na+ current. The activation and inactivation kinetics of the TTX-insensitive component were much the same as those of the overwhelming TTX-sensitive component of the Na+ current in VTA cells but differed from those of the TTX-insensitive Na+ current reported in peripheral sensory neurons. Thus, it was concluded that the well-known different action potential durations found for subpopulations of VTA cells are not due to multiplicity of Na+ channel kinetics.

Action Potentials↗
PubMed1992

Kinetic analysis of the GABAB-mediated inhibition of the high-threshold Ca2+ current in cultured rat sensory neurones.

1. The action of baclofen on the voltage-gated Ca2+ current (ICa) was studied, using cultured neurones of the newborn rat dorsal root ganglia (DRG). Two major categories of ICa were identified: a small transient current activated positive to -60 mV (low voltage-activated ICa) and a large and slowly inactivating current activated positive to -30 mV (high voltage-activated ICa). 2. Baclofen reversibly blocked the high voltage-activated ICa and slowed the activation phase of the current in a concentration-dependent manner (0.5-50 microM). The half-maximal effective concentration was about 1.5 microM as measured by a peak of ICa. On the contrary, a high concentration of baclofen (100 microM) had no detectable effect on the low voltage-activated ICa. 3. The baclofen-sensitive component of the high voltage-activated ICa was largely inactivated by a depolarized holding potential (Vh) of -40 mV, whereas the baclofen-resistant component was not affected by a change in Vh ranging from -110 to -30 mV. 4. The high voltage-activated ICa had two components of current decay: an inactivating component and a quasi-sustained component, with time constants about 420 and 1220 ms, respectively. The time constant of decay for the inactivating component was not affected by replacement of external Ca2+ with Ba2+, whereas that for the quasi-sustained component was markedly prolonged, suggesting that the decay of this component may be due to Ca(2+)-induced block rather than voltage-dependent inactivation. A high concentration of baclofen (50 microM) selectively blocked the inactivating component. 5. The decay phase of the baclofen-sensitive component of the high voltage-activated ICa was best fitted by a sum of two exponentials, with 29.2 and 481 ms for the fast and slow components, respectively. The time constants of the two components were not affected by an increase in the concentration of baclofen, whereas the amplitudes changed concentration-dependently. 6. The slowed activation of the high voltage-activated ICa by baclofen was partially reversed by a large depolarizing pre-pulse. However, such an acceleration of the current was similarly observed in the control solution. Furthermore, the actual current size increased by the pre-pulse was similar in both the control and baclofen-containing solutions. 7. These results suggest that baclofen selectively blocks the inactivating component of the high voltage-activated ICa which forms a rapid rising phase of this current, thus slowing the activation phase of the total high voltage-activated ICa.

Animals↗