Combination of CT during arterial portography and double-phase CT hepatic arteriography with multi-detector row helical CT for evaluation of hypervascular hepatocellular carcinoma.

AIM: To evaluate the diagnostic accuracy of the combination of computed tomography (CT) during arterial portography (CTAP) and double-phase CT hepatic arteriography (CTHA) with multidetector-row CT (MDCT) for the evaluation of hepatocellular carcinomas (HCCs) in patients with cirrhosis. MATERIALS AND METHODS: The combination of CTAP and double-phase CTHA was performed on 46 patients with 54 nodular HCCs. Three readers reviewed the images obtained with CTAP alone, first-phase CTHA alone, double-phase CTHA, and the combination of CTAP and double-phase CTHA. The review of the images was conducted on a segment-by-segment basis, with 368 hepatic segments, including 50 segments with 54 HCCs, reviewed for detection of HCCs with the aid of a five-point confidence scale. Diagnostic accuracy was evaluated by comparing the receiver-operating characteristic (ROC) analysis results. RESULTS: The sensitivity for detecting HCCs was significantly higher with either double-phase CTHA or the combination of CTAP and double-phase CTHA than with first-phase CTHA alone (90 and 93 versus 85%, respectively, p<0.01). The specificity for detecting HCCs was significantly higher with the combination of CTAP and double-phase CTHA than with CTAP alone (97 and 94%, respectively, p<0.01). The positive predictive values for detecting HCCs were significantly higher with double-phase CTHA than with first-phase CTHA alone (86 and 82%, respectively, p<0.05). The area under the ROC curve (Az) values were significantly higher with the combination of CTAP and double-phase CTHA (0.983) than with first-phase CTHA alone (0.959; p<0.05). CONCLUSION: The combination of CTAP and double-phase CTHA with MDCT significantly enhances the detection of HCC.

[Temporary placement of inferior vena cava filter prior to transcatheter arterial embolization (TAE) for hepatocellular carcinoma with IVC tumor thrombus--prevention of pulmonary tumor emboli after TAE].

A 66-year-old-man with a right huge hepatocellular carcinoma (HCC) extending into both the right portal vein and the right atrium underwent transcatheter arterial embolization (TAE) via the right hepatic artery. Prior to the TAE, a temporary inferior vena cava (IVC) filter was placed suprarenally for prevention of pulmonary tumor emboli. When we replaced the temporary IVC filter with a new one 7 days after the TAE, the filter which was pulled out of the IVC captured a fragment of the tumor thrombus. A histopathological specimen demonstrated only ghost cells. The patient has been followed at our outpatient clinic without any tumor thrombus or pulmonary infarction for 13 months after this procedure.

Neurilemoma of the renal capsule: MR imaging and pathologic correlation.

We report a case of neurilemoma arising from the renal capsule. Renal neurilemoma is an especially rare tumor, with only 15 cases previously reported. We attempted to correlate MR findings with microscopic components of the tumor. On T2-weighted images the solid part of the tumor was heterogeneous hyperintense. The MR signal intensity on T2-weighted images help estimate microscopic components of the renal neurilemoma.

Effects of corticosteroids on synaptic transmission in rat dorsolateral septal nucleus.

The effects of corticosteroids on synaptic transmission in the rat dorsolateral septal nucleus (DLSN) were examined, in vitro, by using intracellular and voltage-clamp recording methods. Prednisolone (100 microM) increased the amplitude of excitatory postsynaptic potential (EPSP) and depressed both fast and slow inhibitory postsynaptic potentials (IPSP). Under voltage-clamp conditions, prednisolone (100 microM) increased the amplitude of excitatory postsynaptic current (EPSC) and depressed the fast and slow inhibitory postsynaptic currents (IPSCs). Corticosterone (100 microM) mimicked the effects of prednisolone on the postsynaptic currents (PSCs). To examine the direct effects of prednisolone on the EPSC and slow IPSC, the fast IPSC was blocked by bicuculline (20 microM). Under these experimental conditions, prednisolone (100 microM) did not alter the isolated EPSC but depressed slow IPSC by 22 +/- 3% (n = 10). The fast IPSC was isolated by pretreatment with kynurenic acid and CGP55845A, where the EPSC and slow IPSC were blocked. Prednisolone (100 microM) depressed the isolated fast IPSC in DLSN neurons. Prednisolone (100 microM) did not change either the inward current produced by glutamate or the outward current produced by gamma-aminobutyric acid (GABA). The results suggest that corticosteroids facilitate excitatory synaptic transmission in the DLSN by reducing the release of GABA from the presynaptic nerve terminals of interneurons.

Interleukin-1beta causes a biphasic response in neurons of rat major pelvic ganglia.

The effect of interleukin-1beta (IL-1beta) on peripheral autonomic neurons was examined with intracellular microelectrodes, in vitro. Recombinant human IL-1beta (6-300 pM) produced a depolarization, associated with decrease in input resistance, followed by a hyperpolarization, associated with increase in input resistance, in neurons of rat major pelvic ganglia (MPG). IL-1beta 163-171 (10-100 pM), the active domain of human IL-1beta, also produced a biphasic response. The IL-1beta-induced responses reversed polarity at the equilibrium potential for Cl-. The IL-1beta-induced responses were blocked by picrotoxin (100 microM) but not by bicuculline (20 microM). Imidazole-4-acetic acid (14AA, 100 microM), a GABA(C) receptor antagonist, reduced the IL-1beta-induced responses. The results suggest that the IL-1beta-induced biphasic response is mediated through GABA(C) receptors in rat MPG neurons.

Role of GABAA and GABAC receptors in the biphasic GABA responses in neurons of the rat major pelvic ganglia.

The role of gamma-aminobutyric acid-A (GABAA) and GABAC receptors in the GABA-induced biphasic response in neurons of the rat major pelvic ganglia (MPG) were examined in vitro. Application of GABA (100 microM) to MPG neurons produced a biphasic response, an initial depolarization (GABAd) followed by a hyperpolarization (GABAh). The input resistance of the MPG neurons was decreased during the GABAd, whereas it was increased during the GABAh. The GABAd could be further separated into the early component (early GABAd) with a duration of 27 +/- 5 s (mean +/- SE; n = 11) and the late component (late GABAd) with a duration of 109 +/- 11 s (n = 11). The duration of the GABAh was 516 +/- 64 s (n = 11). The effects of GABA (5-500 microM) in producing the depolarization and the hyperpolarization were concentration-dependent. GABA (5-30 microM) induced only late depolarizations. The early component of the depolarization appeared when the concentration of GABA was >50 microM. Muscimol produced only early depolarizing responses. Baclofen (100 microM) had no effect on the membrane potential and input resistance of MPG neurons. Bicuculline (60 microM) blocked the early GABAd but not the late GABAd and the GABAh. Application of picrotoxin (100 microM) with bicuculline (60 microM) blocked both the late GABAd and the GABAh. CGP55845A (3 microM), a selective GABAB receptor antagonist, did not affect the GABA-induced responses. cis-4-Aminocrotonic acid (CACA, 1 mM) and trans-4-aminocrotonic acid (TACA, 1 mM), selective GABAC receptor agonists, produced late biphasic responses in the MPG neurons. The duration of the CACA responses was almost the same as those of the late GABAd and GABAh obtained in the presence of bicuculline. Imidazole-4-acetic acid (I4AA, 100 microM), a GABAC receptor antagonist, depressed the late GABAd and the GABAh but not the early GABAd. I4AA (100 microM) and picrotoxin (100 microM) also suppressed the biphasic response to CACA. The early GABAd and the late GABAd were reversed in polarity at -32 +/- 3 mV (n = 7) and -38 +/- 2 mV (n = 4), respectively, in the Krebs solution. The reversal potential of the GABAh was -34 +/- 2 mV (n = 4) in the Krebs solution. The reversal potentials of the late GABAd and the GABAh shifted to -20 +/- 3 mV (n = 5) and -22 +/- 3 mV (n = 5), respectively, in 85 mM Cl- solution. These results indicate that the late GABA(d) and the GABAh are mediated predominantly by bicuculline-insensitive, picrotoxin-sensitive GABA receptors, GABAC (or GABAAOr) receptors, in neurons of the rat MPG.

Effects of interleukin-1 beta on neurons in mammalian pelvic ganglia.

The effects of interleukin-1 beta (IL-1 beta) on the membrane potential and synaptic transmission were examined in neurons of mammalian pelvic ganglia. Bath-application of recombinant human IL-1 beta (6-300 pM) for 10 s-5 min produced a long-lasting hyperpolarization associated with increased input resistance in 11 neurons of rat major pelvic ganglia (MPG). In other 8 neurons, IL-1 beta (300 pM) produced a biphasic response that consists of an initial depolarization followed by a long-lasting hyperpolarization. IL-1 beta 163-171 (10-100 pM), a synthetic nonapeptide analog that contains the active domain of human IL-1 beta, mimicked the effect of IL-1 beta in MPG neurons. gamma-Aminobutyric acid (GABA, 300 microM) produced a depolarization followed by a hyperpolarization that was blocked by picrotoxin (100 microM). Db-cyclic guanosine monophosphate (db-cyclic GMP, 100 microM) also produced an initial depolarization followed by a long-lasting hyperpolarization. These results suggest that the IL-1 beta-induced biphasic response is mediated by a GABA receptor-cyclic GMP pathway. IL-1 beta and IL-1 beta 163-171 caused an initial facilitation followed by a long-lasting depression of the excitatory postsynaptic potential (EPSP) in rabbit VPG. The data suggest that IL-1 beta presynaptically depressed the EPSP by reducing the release of acetylcholine (ACh) from the pelvic nerve terminals.

GABAC receptors mediate slow membrane potentials in neurons of the rat major pelvic ganglia.

Effects of gamma-aminobutyric acid (GABA) on the neuronal membrane of the rat major pelvic ganglia (MPG) were studied using intracellular recording techniques, in vitro. Application of GABA (100 microM) to MPG neurons induced a depolarization (GABAd) associated with a decreased membrane input resistance and a slow hyperpolarization (s-GABAh) associated with an increased membrane input resistance. The GABA depolarization had two phases, a fast depolarization (f-GABAd) and a subsequent slow depolarization (s-GABAd). Bicuculline (60 microM) blocked the f-GABAd but not the s-GABAd and s-GABAh. Picrotoxin (100 microM) blocked all the GABA responses. Imidazole-4-acetic acid (I4AA, 100 microM), a GABAc receptor antagonist, depressed the s-GABAd and s-GABAh, but did not block the f-GABAd. Cis-4-aminocrotonic acid (CACA), a GABAc receptor agonist, produced a depolarization followed by a hyperpolarization in MPG neurons. I4AA (100 microM) depressed the CACA-induced responses. It was concluded that GABAA receptors mediate the f-GABAd and that GABAc receptors mediate the s-GABAd and s-GABAh, in neurons of the rat MPG.

Baclofen reduces GABAA receptor responses in acutely dissociated neurons of bullfrog dorsal root ganglia.

The effect of baclofen on the function of the gamma-aminobutyric acidA (GABAA) receptor was examined in acutely dissociated neurons of bullfrog dorsal root ganaglia (DRG) by using the whole-cell voltage-clamp method. Baclofen (0.1-100 microM) depressed the inward currents produced by GABA (100 microM) and muscimol (100 microM). Baclofen shifted the concentration-response curve for GABA (1 microM-1 mM) downward. Baclofen decreased the maximum response (Vmax) to GABA without changing the apparent dissociation constant (Kd), suggesting a noncompetitive antagonism. The effect of baclofen on the GABA current was blocked by antagonists for the GABAB receptor; the rank order of potency was P-[3-Aminopropyl]-P-diethoxymethylphosphinic acid (CGP 55845A) > > 3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-P- benzyl-phosphinic acid (CGP 35348) > saclofen > > phaclofen. Baclofen produced an irreversible depression of the GABA current in neurons dialyzed with an internal solution containing guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S, 100 microM). Intracellular guanosine 5'-O-(2-thiodiphosphate) (GDP beta S, 100 microM) blocked the inhibitory effect of baclofen on the GABA current. Forskolin (10 microM) and dibutyryl N6, 2'-O-dibutyryladenosine 3':5'-cyclic monophophate (db-cyclic AMP) (200 microM) depressed the GABA current. N-(2-aminoethyl)-5-isoquinolinesulfonamide (H-9, 40 microM) and N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004, 50 microM), protein kinase A (PKA) inhibitors, reduced the depressant effect of baclofen on the GABA current. The baclofen-induced depression of the GABA current was blocked by PKI(5-24), a specific PKA inhibitor, but not by PKC(19-36), a specific protein kinase C (PKC) inhibitor. We suggest that GABAB receptors regulate the GABAA receptor function through a G-protein linked to the adenylyl cyclase-PKA pathway in bullfrog DRG neurons.

[Analysis of in-field and marginal relapse in stage I/II non-Hodgkin's lymphoma treated with radiotherapy].

One hundred sixty-three patients with previously untreated stage I/II non-Hodgkin's lymphoma were analyzed as to their in-field and marginal relapse of the irradiated field following treatment with more than 30 Gy of radiotherapy between 1981 and 1995 at Hyogo Medical Center for Adults. Local regrowth in case of partial response was counted as in-field relapse. Complete response was obtained in 94.5% of the cases at the termination of radiotherapy and in 98.8% finally. The ten-year cumulative in-field relapse and marginal relapse rates were 5% and 8.7%, respectively. The cumulative in-field relapse rate (CIFRR) in cases of bulky disease (more than 5 cm in largest diameter of the tumor) was significantly higher than in those of non-bulky disease (26.1% in 8 years vs 2.4% in 10 years, P < 0.01). The radiation dosage delivered (40 Gy = < and 50 Gy > vs 50 Gy < =) a great much difference in cases of bulky disease (23.8% for 8-year CIFRR vs 0% for 1-year CIFRR, respectively), but less difference with non-bulky disease (2.6% vs 2.2%). High LDH and suboptimal dose chemotherapy (three courses and less chemotherapy containing ADM or its derivatives, chemotherapy without ADM or no chemotherapy) had a negative impact on marginal control in aggressive lymphoma. Extended field setting in aggressive lymphoma was not proven to be beneficial in comparison with involved field setting as to marginal field relapse. Thus, it is concluded that (1) higher doses should be given to bulky disease, (2) careful field coverage with enough margin is recommended for aggressive lymphoma with high LDH or treated without optimal dose chemotherapy, and (3) extended field setting is not necessary.

Depletion of glucose causes presynaptic inhibition of neuronal transmission in the rat dorsolateral septal nucleus.

The role of glucose in synaptic transmission was examined in the rat dorsolateral septal nucleus (DLSN) with single-microelectrode voltage-clamp and slice-patch technique. Removal of glucose from the oxygenated Krebs solution caused an outward current associated with an increased membrane conductance. The current-voltage relationship (I-V curve) showed that the hypoglycemia-induced outward current was reversed in polarity at the equilibrium potential for K+. Exposure of DLSN neurons to the glucose-free solution for 5-20 min depressed the excitatory postsynaptic current (EPSC), the inhibitory postsynaptic current (IPSC), and the late hyperpolarizing current (LHC). Replacement of glucose with 2-deoxy-D-glucose (2DG), an antimetabolic substrate, mimicked the deprivation of glucose. Mannoheptulose (10 mM) and dinitrophenol, inhibitors of glucose metabolism, also depressed the PSCs, even in the presence of 10 mM glucose. Glucose-free perfusion did not significantly depress the glutamate-induced inward current, indicating that the inhibition of the EPSC by the glucose-free perfusion was presynaptic. gamma-Aminobutyric acid (GABA)-induced outward currents were depressed by the glucose-free solution. Intracellular dialysis of DLSN neurons with a patch-pipette solution containing 5 mM ATP attenuated the hypoglycemia-induced outward current. Glucose-free superfusion consistently inhibited the IPSC and the LHC without changing the GABA-induced outward current in ATP-treated DLSN neurons. It is suggested that glucose metabolism directly regulates the release of both excitatory amino acids and GABA from the presynaptic nerve terminals.

Effects of K-7259 on neuronal activity and synaptic transmission in the rat dorsolateral septal nucleus.

K-7259 is a dilazep dihydrochloride derivative that minimizes the damaged area from middle cerebral artery hemiocclusion in the rat (Yamauchi et al. 1992a, b). The effects of K-7259 on the electrophysiological properties of neurons in the rat dorsolateral septal nuclei (DLSN) were examined. K-7259 (100 microM-3 mM) depolarized the membrane with a decrease in input resistance in 36% of the DLSN cells. K-7259 (100 microM) depressed the inhibitory postsynaptic potential (IPSP) and the late hyperpolarizing potential (LHP). The magnitudes of the depressions of the IPSP and LHP with 100 microM K-7259 were 50 +/- 25% (n = 5) and 52 +/- 15% (n = 4), respectively. The amplitudes of the excitatory postsynaptic potentials (EPSPs) were augmented during the inhibition of the IPSP and LHP. However, a voltage-clamp analysis showed that K-7259 did not affect the isolated excitatory postsynaptic current (EPSC). The outward current produced by pressure application of gamma-aminobutyric acid (GABA) to the recording cell was not inhibited by K-7259. These results indicate that K-7259 presynaptically inhibits the IPSP and LHP through a GABAergic pathway.

Patch-clamp analysis of hypoglycemia-induced inhibition of synaptic transmission in the rat dorsolateral septal nucleus.

The role of glucose in neuronal transmission was examined in the rat dorsolateral septal nucleus (DLSN) by using 'slice-patch' techniques. Removal of glucose from the oxygenated Krebs solution produced an outward current associated with an increased K+ conductance. The glucose-depletion depressed the excitatory postsynaptic current (EPSC), the inhibitory postsynaptic current (IPSC) and the late hyperpolarizing current (LHC) produced by stimulation of the fimbria/fornix pathway. It is hypothesized that glucose regulates neurotransmission in the rat DLSN by modulating the release of transmitters from presynaptic nerve terminals.

Intracellular ATP changes the voltage-dependence of delayed rectifier potassium current in bullfrog primary afferent neurons.

Dissociated bullfrog dorsal root ganglion cells were voltage-clamped in the whole-cell configuration to study the steady-state activation and inactivation curves for a delayed rectifier potassium current. The 50%-activation of the current occurred at +15 mV when measured with ATP (5 mM) in the pipette solution as opposed to -11 mV with 5'-adenylylimidodiphosphate (AMP-PNP, 5 mM) and -15 mV with adenosine 5'-O-(3-thiotriphosphate) (5 mM). The 50%-inactivation of the current occurred at -6 mV with ATP but at -31 mM with AMP-PNP. The results suggest that intracellular ATP modulates voltage-dependence of the delayed rectifier in amphibian afferent neurons.

Chemosensitivity of C-cells in bullfrog dorsal root ganglia to substance P and adenosine 5'-triphosphate.

Dissociated bullfrog dorsal root ganglion cells were voltage clamped in the whole-cell configuration. In small C-cells having 20 microns as averaged diameter, substance-P (0.1-1 microM) inhibited an M-type potassium current while ATP (1-10 microM) activated a sodium-potassium current. In large A-cells (approximately 65 microns in diameter) in which ATP has been shown to inhibit M-current, substance P (0.1-1 microM) also inhibited this potassium current without activating the sodium-potassium current. Results provided evidence for the distinction between A- and C-cells in terms of their chemosensitivity.

Slowly inactivating potassium current in cultured bull-frog primary afferent and sympathetic neurones.

1. Cultured bull-frog dorsal root ganglion cells were voltage clamped in the whole-cell configuration. The cells were superfused with a nominally calcium-free Ringer solution containing tetrodotoxin (3 microM), magnesium (10 mM), cobalt (1 mM), barium (2 mM), 4-aminopyridine (3 mM) and caesium (2 mM). 2. Step depolarizations (10-40 mV, 100-300 ms) from a holding potential close to the rest (typically -70 mV) evoked an outward current (IK) followed by an outward tail current. The peak amplitude of the current was reduced to less than 10% by tetraethylammonium (30 mM). 3. IK developed to its peak in 200 ms at -30 mV. Tail currents reversed at potentials that changed according to the logarithm of the extracellular potassium concentrations. 4. Tail currents declined to the baseline according to an exponential function of time (tau congruent to 40 ms at -60 mV) and its reciprocal time constant increased e-fold with a 13 mV hyperpolarization. 5. The current inactivated during sustained (1-20 s) depolarizing pulses according to a single exponential function (tau congruent to 3 s). 6. The peak amplitude of IK at -30 mV was progressively increased as the holding potential was made more negative than -70 mV reaching the maximum with step depolarizations from -120 mV. Reversed phenomenon was observed as the holding potential was made less negative than -70 mV. 7. The removal of the steady-state inactivation occurred along with a single exponential function and the time constant was decreased from 70 ms at -70 mV to 10 ms at -120 mV. 8. It is suggested that a slowly inactivating potassium current which we called IK in amphibian sensory neurones could be a class of a 'delayed' rectifier potassium current. A potassium current with properties indistinguishable from those which have been described for the sensory IK also occurred in cultured bull-frog sympathetic neurones. 9. Forskolin (1-30 microM) and 1,9-dideoxy forskolin (10 microM) reduced the amplitude of IK by up to 85% but these actions were not mimicked by any of 8-bromo-cyclic AMP (1 mM), dibutyryl cyclic AMP (1 mM) and 3-isobutyl-1-methylxanthine (1 mM). A hydrophilic forskolin analogue, 7-O-hemisuccinyl-7-deacetyl forskolin (10 microM), was about one-tenth as potent as forskolin (10 microM).

Reduction of the N-type calcium current by noradrenaline in neurones of rabbit vesical parasympathetic ganglia.

1. Intracellular and single-electrode voltage-clamp recordings were made from neurones of vesical parasympathetic ganglia (VPG) isolated from the rabbit urinary bladder. 2. Noradrenaline (NA, 0.5-5 microM) shortened the duration of the action potentials and depressed the amplitudes of both spike after-hyperpolarization and after-current. 3. Voltage-dependent calcium currents (ICa) were recorded by using microelectrodes filled with 2 M-caesium chloride in a superfusing solution containing tetraethylammonium (TEA, 50 mM) and tetrodotoxin (TTX, 500 nM). Noradrenaline (0.5-5 microM) depressed both the ICa and the tail current evoked by depolarizing voltage jumps from -100 to -50 mV to -30 to +20 mV. 4. Substitution of barium for calcium also produced an inward current (IBa) with no obvious tail current. Noradrenaline (1 microM) reduced the magnitude of the IBa without affecting the voltage dependence of the current-voltage relationship for IBa. 5. Yohimbine (1 microM), but not prazosin (1 microM) or propranolol (1 microM), antagonized the NA-induced inhibition of the IBa. UK 14304, a potent alpha 2-adrenoceptor agonist, mimicked NA in depressing the IBa. 6. The transient low-threshold (T), the transient high-threshold (N) and the slowly inactivating high-threshold (L) calcium currents co-existed in VPG neurones. 7. Noradrenaline reduced the IBa evoked at clamp potentials more positive than -20 mV from holding potentials near the resting membrane potential (-70 to -50 mV). Under these conditions, the IBa consisted primarily of N- and L-current components. In contrast, NA had no effect on the isolated T- and L-currents. It is concluded that NA selectively inhibits the N-type calcium channels by an action at alpha 2-adrenoceptors in the rabbit VPG neurones.

Properties of voltage-dependent barium currents in neurons of pelvic parasympathetic ganglia of rabbit.

Properties of voltage-dependent barium current (IBa) were examined in parasympathetic neurons of the rabbit urinary bladder, in vitro. Transient low-threshold IBa was evoked by voltage jump from a holding potential (Vh) of -100 to -50 mV. Additional transient high-threshold IBa appeared at potentials more positive than -30 mV. Long-lasting high-threshold IBa was evoked at 0 to -20 mV. High-threshold currents were blocked by omega-conotoxin but not by dihydropyridines.