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Chyle leaks are attributed to damage to the thoracic duct itself or its tributaries during surgery. Chylothorax after lung cancer surgery can occur due to damaged thoracic duct tributaries; however, little is known of the mechanism involved. A 71‐year‐old female underwent a left upper lobectomy with hilar and mediastinal lymphadenectomy for a 1.8‐cm primary squamous cell carcinoma, and developed a chylothorax a day later. Catheter lymphangiography revealed high‐flow chyle leaks from a damaged thoracic duct tributary, known as a bronchomediastinal lymph trunk, due to a lymphatic reflex from the thoracic duct. Subsequently, catheter embolization of the tributary repaired the chylothorax. The potential for persistent chylothorax after lung cancer surgery and successful lymphatic intervention should be noted., Chylothorax after lung cancer surgery can be associated with lymphatic reflux into the damaged tributary from the thoracic duct. Catheter lymphangiography proved useful in detecting the location and direction of flow of lymphatic leakages as well as that in subsequent embolization.

Treatment for venous thromboembolic conditions differs significantly depending on whether the condition is acute or chronic. Endovenous treatment is now available for treating the most severe cases of acute massive pulmonary thromboembolism, and the goal is rapid central clot removal to relieve life-threatening pulmonary circulation. Endovenous catheter interventions include catheter-directed thrombolysis and catheter-assisted thrombus removal. The latter is divided into aspiration thrombectomy, fragmentation, and rheolytic thrombectomy. Data from cohort studies indicate that the clinical outcome and safety after open surgical treatment and endovenous treatment may be comparable. This paper reviews the current approaches to endovenous treatment for acute massive pulmonary thromboembolism, and presents our study of hybrid treatment using a combination of local fibrinolysis, mechanical fragmentation, and clot aspiration.

When the intercostal and lumbar arteries are occluded by plaque or thrombus, spinal cord perfusion depends on collateral circulation. Some reports have demonstrated collateral circulation to the artery of Adamkiewicz via computed tomography and magnetic resonance angiographies. However, intraspinal collateral circulation to the artery of Adamkiewicz along the spinal cord has not been reported previously. Here, we report two patients with intraspinal collateral circulation to the artery of Adamkiewicz along the spinal cord that was detected with intra-arterial injected computed tomography angiography.

This study investigated the anatomical relationship between the common carotid artery and internal jugular vein during head rotation for the effective performance of percutaneous transjugular procedures. The subjects included 30 volunteers who had never undergone internal jugular vein cannulation. In the supine position, two-dimensional ultrasonographic images of the right internal jugular vein and common carotid artery were obtained, 2 and 4 cm above the clavicle, along the lateral border of the sternal head of the sternocleidomastoid muscle. Ultrasonographic images were examined for head rotation at 0°, 15°, 30°, 45°, 60°, and 75° from the midline to the left. The percentage of overlap of the common carotid artery by the internal jugular vein and the flattening of the internal jugular vein at each head rotation position were measured and evaluated. The overlap of the common carotid artery by the internal jugular vein significantly increased at ≥45° of head rotation 2 cm above the clavicle (P

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related deaths in the world. The Barcelona Clinic Liver Cancer (BCLC) classification has recently emerged as the standard classification system for clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, and percutaneous ablation) can improve survival in HCC patients diagnosed at an early stage and offer potential long-term curative effects. Patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization (TACE), and those diagnosed at an advanced stage receive sorafenib, a multikinase inhibitor, or conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidates for systemic therapy. TACE is often recommended for advanced-stage HCC patients all over the world because these patients desire therapy that is more effective than systemic chemotherapy or conservative treatment. This paper aims to summarize both the published data and important ongoing studies for TACE and to discuss technical improvements in TACE for advanced-stage HCC.

A 61-year-old man was referred with acute type A aortic dissection and underwent emergent hemiarch graft replacement with open stent graft implantation into the distal aortic arch. Atrial and ventricular bipolar temporary epicardial pacing wires (TEPWs) were placed after surgery. On the seventh post-operative day, the TEPWs were cut at the level of the skin, but left in …

Depression has been known to reduce the prefrontal activity associated with the execution of certain cognitive tasks, although whether a temporarily depressed or anxious mood in healthy individuals affects the prefrontal blood oxygen level during cognitive tasks is unknown. Combining the measurement of prefrontal activity with near-infrared spectroscopy (NIRS) and the two cognitive tasks, namely the letter version of the verbal fluency test (VFT-l) and the Stroop test, we measured the effect of a depressed or anxious mood and gender on the changes in the prefrontal oxygenated hemoglobin (Oxy-Hb) levels during those cognitive tests in healthy individuals. Depressed mood or anxious mood was assessed by the Hospital Anxiety and Depression Scale (HADS). Thereby we aimed to explore the possibility of NIRS measurement for detecting the early subclinical manifestation of major depression. Moreover, we examined the possible relationships between prefrontal activation and the functional Val66Met polymorphisms of the brain derived neurotropic factor (BDNF) gene and serum BDNF level. As a result, the increased prefrontal Oxy-Hb levels during cognitive tasks were significantly correlated with the severity of depressed mood in males. The course of the prefrontal Oxy-Hb increase was different depending on the cognitive tasks, i.e., the VFT-l or the Stroop test, in both genders. Correlations of BDNF genotype and serum BDNF level with the prefrontal Oxy-Hb levels during those cognitive tasks were negative. Our results suggest that the early subclinical manifestation of depressed mood in males might be detected by the NIRS measurement, which is not correlated with the individual properties of BDNF.

For near infrared red spectroscopy (NIRS), the debate over the reliability of its absolute value is ongoing, and discussed in this paper with alpha-blocking task. The purpose of the study is step by step clarification on NIRS reliability. The method in this paper is the evaluation with a task that is clinically important and has achieved a wide consensus and a diagnostics of its measurement. From this viewpoint, this paper discussed the NIRS measurement, with the electroencephalography (EEG) measurement of alpha-blocking as the task. Based on the EEG measurement results of alpha-blocking, we investigated the characteristic changes in the NIRS measurements; a correlation between the two measurements was found (0.806), based on alpha-rhythm patterns of EEG and the increasing or decreasing patterns of oxygen metabolism on NIRS. In addition, a correlation was found between complexities in the two measurements (0.677). The variation level of the complexity in the EEG measurements was 7.14 times larger compared with that of NIRS on average which suggests that the EEG measurements included much information than the NIRS measurements for alpha-blocking task. Despite, the correlation results suggest a possibility of NIRS application to alpha-blocking diagnosis. These numericals contribute to step by step clarification on NIRS reliability.

The risk to fall has clinical relevance in prognosis of elderly people. We analyzed aging effects on the physiological properties of the vertical ground reaction force of healthy subjects and examined whether it can be used as an index for postural instability and risk to fall.We analyzed stabilometric data from 1795 healthy volunteers (3 - 93 years old). Vertical acceleration was computed from the load-cell records and underwent frequency analysis. The multiple comparison test was performed by age groups at every frequency within the detected significant band.Variances in vertical acceleration were high in juveniles and elderly people. Both acceleration power at 1.5-2 Hz and power ratio of eye closure to the open eye at 2-6 Hz were markedly high and decreased by 20 years of age. Age groups from 20 to 60 years had low stable power profiles and the age groups over 60 years showed increased power at 5-8 Hz relative to aging.Our findings suggest that the postural instability of young people evoked by eye-closure accounts for 3-Hz vibration and that increased power in elderly subjects around 6.5 Hz has a strong correlation with aging.

Proteomic analysis of developmental toxicity by two-dimensional electrophoresis (2-DE) may detect gender-related toxic effects in embryos without visible gender characteristics. In the present study, we explored sexing of rat embryo stored in frozen 2-DE samples by polymerase chain reaction (PCR) of a male-specific gene sequence, sex determining region Y (Sry). The embryo proper and yolk sac membrane at gestation day 11 from Wistar rats were used for stored embryonic 2-DE samples. The embryonic 2-DE samples were desalted and their total DNA was extracted. The Sry sequence in the extracted DNA was amplified by PCR and the product was analyzed by agarose gel electrophoresis. The embryos with the PCR product of Sry were determined as male, and those without the product were determined as female. It was concluded that stored embryonic 2-DE samples could be used for retrospective examination of gender-related effects in proteomic analysis of developmental toxicity.

Indium, a precious metal classified in group 13 (IIIB) in the periodic table, has been used increasingly in the semiconductor industry. Because indium is a rare metal, technology for indium recycling from transparent conducting films for liquid crystal displays is desired, and its safety evaluation is becoming increasingly necessary. The developmental toxicity of indium in experimental animals was summarized. The intravenous or oral administration of indium to pregnant animals causes growth inhibition and the death of embryos in hamsters, rats, and mice. The intravenous administration of indium to pregnant animals causes embryonic or fetal malformation, mainly involving digit and tail deformities, in hamsters and rats. The oral administration of indium also induces fetal malformation in rats and rabbits, but requires higher doses. No teratogenicity has been observed in mice. Caudal hypoplasia, probably due to excessive cell loss by increased apoptosis in the tailbud, in the early postimplantation stage was considered to account for indium-induced tail malformation as a possible pathogenetic mechanism. Findings from in vitro experiments indicated that the embryotoxicity of indium could have direct effects on the conceptuses. Toxicokinetic studies showed that the embryonic exposure concentration was more critical than the exposure time regarding the embryotoxicity of indium. It is considered from these findings that the risk of the developmental toxicity of indium in humans is low, unless an accidentally high level of exposure or unknown toxic interaction occurs because of possible human exposure routes and levels (i.e. oral, very low-level exposure).

Tamoxifen (Tam) decreased the clearance of L-glutamate (L-Glu) by cultured astrocytes at 1 pM, 1 nM, and 1 μM, but became toxic at 10 μM. When L-Glu transporters were mostly inhibited by threo-β-benzyloxyaspartate (TBOA) (1 mM) or D,L-threo-β-hydroxyaspartate (THA) (1 mM), Tam (1 nM) did not change extracellular L-Glu concentration, confirming that Tam attenuates L-Glu transport through L-Glu transporters. ICI182,780, LY294002, and U0126 inhibited the effect of Tam dose-dependently, suggesting the involvement of estrogen receptors (ERs), the phosphatidylinositol 3-kinase (PI3K) cascade, and the mitogen-activated protein kinase (MAPK) cascade in the effect of Tam. Keywords:: tamoxifen, L-glutamate transporter, astrocyte

To examine whether motor commands of two or more distinct laryngeal motor patterns converge onto a common premotor network, we conducted dual recordings from the laryngeal adductor motoneuron and its premotor neuron within the brainstem respiratory circuitry during fictive breathing, coughing, sneezing, and swallowing in decerebrate paralyzed cats. Expiratory neurons with an augmenting firing pattern (EAUG), whose action potentials evoked monosynaptic IPSPs in the adductor motoneurons, sharply fired during the expulsive phases of fictive coughing and sneezing, during which the adductor motoneurons transiently repolarized. In contrast, these premotor neurons were silent during the swallow-related hyperpolarization in adductor motoneurons. These results show that one class of medullary respiratory neuron, EAUG, is multifunctional and shared among the central pattern generators (CPGs) for breathing, coughing, and sneezing. In addition, although the CPGs underlying these three behaviors and the swallowing CPG do overlap, EAUG neurons are not part of the swallowing CPG and, in contrast to the other three behaviors, are not a source of inhibitory input to adductor motoneurons during swallowing.

Although recent studies have suggested that dentate granule cells play a key role in hippocampal functions, electrophysiological properties in these cells have not been sufficiently explored. In the present study, modification of voltage-gated Ca2+ channels by 4-hydroxynonenal (4HN), a major aldehydic product of membrane lipid peroxidation, in cultured dentate granule cells was examined using the whole-cell patch clamp technique. When whole-cell voltage clamp was applied, the cells exhibited a high-voltage-activated Ca2+ current, which was totally sensitive to 30 microM Cd2+ and partially sensitive to 2 microM nifedipine. 4HN enhanced the Ca2+ current in these cells. When L-type Ca2+ channels were blocked by application of nifedipine, the enhancement was completely canceled, whereas application of omega-conotoxin-GVIA or omega-agatoxin-IVA, blockers of N- and P/Q-type Ca2+ channels, respectively, had no effect. These results suggest that 4HN modulates L-type Ca2+ channels in the dentate granule cells, and thereby plays a role in the physiological and pathophysiological responses of these cells to oxidative stress.

We investigated the effects of estrogen-related compounds including xenoestrogens [17beta-estradiol (E2), 17alpha-ethynylestradiol (EE), diethylstilbestrol (DES), p-nonylphenol (PNP), bisphenol A (BPA) and 17alpha-estradiol (17alpha)] on l-glu uptake by cultured astrocytes via glutamate-aspartate transporter (GLAST). After 24 h treatment, E2 inhibited the l-glu uptake at 1 micro m and higher concentrations. EE and DES also inhibited the l-glu uptake at 1 nm and higher concentrations. The other four compounds had no effect. The effects of E2, EE and DES were completely blocked by 10 nm of ICI182 780 (ICI). beta-Estradiol 17-hemisuccinate : bovine serum albumin (E2-BSA), a membrane-impermeable conjugate of E2, also elicited the inhibition of l-glu uptake at 1 nm and higher concentrations, and the effect was blocked by ICI. 16alpha-Iodo-17beta-estradiol (16alphaIE2), an estrogen receptor alpha (ERalpha) selective ligand, revealed an inhibitory effect at 10 nm, while genistein, an ERbeta selective ligand, failed to reveal such an effect at this concentration. Western blot analysis showed that the predominant ER of cultured astrocytes was ERalpha. The colocalization of ERalpha with GLAST on plasma membranes was immunohistochemically detected in these cells. From these results, we concluded that estrogens down-regulate l-glu uptake activity of astrocytes via membrane ERalpha.

PURPOSE We evaluated usefulness of transcatheter arterial embolization (TAE) for deep renal injury, and investigated whether there is any difference in outcomes for transcatheter arterial embolization (TAE) performed for deep renal injury in a large-sized hospital (university hospital) in comparison with a middle-sized hospital (local hospital). METHODS We retrospectively reviewed the outcomes of 42 patients with renal injury who were transported to the critical care center of Nippon Medical School (NMS) Hospital in Tokyo from April 2001 to April 2011 and 33 patients of renal injury transported to the critical care center of Ohtawara Red Cross (ORC) Hospital in Tochigi prefecture from April 2001 to April 2009. Therefore, a total of 75 patients, which is the sum of the patients presenting to both the hospitals for renal injury were reevaluated according to the guidelines developed by the Japanese Association for the Surgery of Trauma (JAST) and published in 2008. RESULTS Forty-two patients in NMS hospital included 6 women and 36 men who were 16 to 88 years old (mean 41.6), and they were divided into Type I (16), Type II (11), and Type III (15) and were treated with bedrest (30), TAE (7), or laparotomy (5). Five patients died, but no one succumbed solely due to the renal injury. On the other hand, 33 Patients in ORC Hospital included 8 women and 25 men who were 16 to 87 years old (mean 46.6). They were divided into Type I (9). Type II (12), and Type III (12) and were treated with bedrest (24) or TAE (9). Eight patients died, but no one succumbed solely due to the renal injury. Sixteen patients were treated successfully with TAE in the 2 hospitals, and 15 of these 16 patients were divided into type III renal injury. Therefore, we believe that nephrectomy should be avoided in such patients because of the benefits offered by TAE. CONCLUSION TAE was found to be useful for the treatment of type III renal injury in both institutions, irrespective of the size of a hospital.

1.5-Hydroxytryptamine (10 μM) enhanced ionic current mediated through the wild-type P2X2 receptor/channel expressed in Xenopus oocytes.

This paper describes our experience with a case of inflammatory breast carcinoma with psoas muscle metastasis. The patient was a 56-year-old woman. She underwent standard radical mastectomy for a right inflammatory breast carcinoma on Feburary 27, 1995. After chemotherapy, she was followed on an ambulant basis. In August, 1995, she complained of lumbago and was found to have a tumor by ultrasound. She was admitted to the hospital for examination and treatment. The tumor was diagnosed as neurinoma or sarcoma by ultrasound, computed tomography, magnetic resonance image and angiography. She was operated on October 9, 1995. There was hematoma rather than a tumor of the left psoas muscle and we resected it with psoas muscle. Pathologically, cancer cells infiltrated the psoas muscle and resembled the breast carcinoma cells. The pathological diagnosis was inflammatory breast carcinoma with psoas muscle metastasis. Inflammatory breast carcinoma with psoas muscle metastasis is rare. Only two cases have been reported, to date. Though the diagnosis of retroperitoneal tumor should be made comprehensively with a variety of imagingmodalities, definitive diagnosis relies upon pathological examination. The tumor occasionally has a malignant potential, such that surgical resection is recommended.

1. Block by philanthotoxin-343 (PhTX-343), a neurotoxin from wasps, of ionic currents mediated through neuronal nicotinic acetylcholine (ACh) receptor/channels was characterized in rat phaeochromocytoma PC12 cells, by use of whole cell voltage-clamp techniques. 2. In the cells held at -60 mV, PhTX-343 at 0.1 and 1 microM inhibited an inward current activated by 100 microM ACh. The current inhibition was relieved by depolarizing steps, and augmented at negative potentials, suggesting that PhTX-343 blocks the channel in a voltage-dependent manner. Joro spider toxin-3 (JSTX-3) also exerted voltage-dependent inhibition of ACh-activated currents in a similar concentration range, but argiotoxin636 did not affect the currents. 3. Analysis of the current decay during hyperpolarizing steps indicated that the current inhibition by 100 nM PhTX-343 develops in an order of several hundres of milliseconds. On the other hand, the recovery from the current inhibition during depolarizing steps developed in an order of about 100 ms. 4. The results suggest that PhTX-343 blocks neuronal nicotinic receptor channels in PC12 cells at concentrations lower than those required for channel block in non-mammalian cells, and the block exhibits clear voltage-dependence. Estimated from the voltage-dependence, the binding site of PhTX-343 may be located near the outer mouth of the channel.

The astrocytic L-glutamate (L-Glu) transporter EAAT1 participates in the removal of L-Glu from the synaptic cleft and maintenance of non-toxic concentrations in the extracellular fluid. We have shown that niflumic acid (NFA), a non-steroidal anti-inflammatory drug (NSAIDs), alters L-Glu-induced EAAT1 currents in a voltage-dependent manner using the two-electrode voltage clamp technique in Xenopus oocytes expressing EAAT1. In this study, we characterised the effects of NFA on each type of ion-flux through EAAT1. NFA modulated currents induced by both L-Glu and L-aspartate (L-Asp) in a voltage-dependent manner. Ion-substitution experiments revealed that the activation of additional H(+) conductance was involved in the modulation of currents induced by L-Asp and L-Glu, but Cl(-) was involved only with the L-Asp currents. NFA activated additional currents of EAAT1 in a substrate-dependent manner.

Our aim was to evaluate the long-term efficacy and safety of percutaneous transhepatic obliteration (PTO) alone and combined with balloon-occluded retrograde transvenous obliteration (BRTO) for gastroesophageal varices refractory to BRTO alone. Between July 1999 and December 2010, 13 patients with gastroesophageal varices refractory to BRTO were treated with PTO (n= 6) or a combination of PTO and BRTO (n= 7). We retrospectively investigated the rates of survival, recurrence, or worsening of the varices; hepatic function before and after the procedure; and complications. The procedure achieved complete obliteration or significant reduction of the varices in all 13 patients without major complications. During follow-up, the varices had recurred in 2 patients, of which one had hepatocellular carcinoma, and the other died suddenly from variceal rebleeding 7 years after PTO. The remaining 11 patients did not experience worsening of the varices and showed significant improvements in the serum ammonia levels and prothrombin time. The mean follow-up period was 90 months, and the cumulative survival rate at 1, 3, and 5 years was 92.9%, 85.7%, and 85.7%, respectively. Both PTO and combined PTO and BRTO seem as safe and effective procedures for the treatment of gastroesophageal varices refractory to BRTO alone.

1. Uridine 5'-triphosphate (UTP)-evoked increase in intracellular Ca2+ concentration ([Ca]i) and release of dopamine were investigated in rat phaeochromocytoma PC12 cells. UTP (1-100 microM) evoked an increase in [Ca]i in a concentration-dependent manner. This response was decreased to about 30% by extracellular Ca(2+)-depletion, but not abolished. This [Ca]i rise was mimicked by 100 microM ATP but not by 100 microM 2-methyl-thio-ATP or alpha,beta-methylene-ATP in the absence of external Ca2+, suggesting that the response was mediated by P2U purinoceptors, a subclass of P2-purinoceptors. 2. The UTP-evoked [Ca]i rise consisted of two components; a transient and a sustained one. When external Ca2+ was removed, the sustained component was abolished while the transient component was decreased by about 70% but did not disappear. These results suggest that UTP induces Ca(2+)-mobilization and, subsequently, Ca(2+)-influx. 3. The UTP-evoked increase in [Ca]i was not affected by Cd2+ (100 and 300 microM) or nicardipine (30 microM), inhibitors of voltage-gated calcium channels, but was significantly inhibited by Zn2+ (10-300 microM) in the presence of external Ca2+. Zn2+, however, did not affect the Ca2+ response to UTP in the absence of external Ca2+. 4. UTP (30 microM-1 mM) evoked the release of dopamine from the cells in a concentration-dependent manner. This dopamine release was abolished by Ca(2+)-depletion or Zn2+ but not by Cd2+ or nicardipine. 5. Taken together, the data demonstrate that UTP stimulates P2U-purinoceptors and induces a rise in [Ca]i both by Ca(2+)-mobilization and Ca(2+)-influx in PC12 cells. The dopamine release evoked by UTP requires external Ca2+ which may enter the cells through pathways sensitive to Zn2+ but insensitive to Cd2+ or nicardipine.

1. Effects of 5-hydroxytryptamine (5-HT) on neuronal nicotinic acetylcholine (ACh) receptor channels were investigated by expressing cloned channel subunits in Xenopus oocytes. 2. When channels were expressed with a combination of alpha 3 and beta 4 subunits, 5-HT (10 to 300 microM) reversibly inhibited an inward current activated by 100 microM ACh in a concentration-dependent manner. The inhibition was also observed when alpha 3 subunit was combined with beta 2 subunit instead of beta 4 subunit, or beta 4 subunit was combined with alpha 2 or alpha 4-1 subunit instead of alpha 3 subunit to express channels. 3. Compounds known to antagonize at 5-HT receptors (LY53857, metoclopramide and propranolol) exhibited an agonistic effect: they inhibited the ACh-activated current. 4. The results suggest that 5-HT inhibits recombinant neuronal nicotinic receptor channels through a binding-site distinct from conventional 5-HT receptors. The binding-site may not be attributed to a unique type of channel subunits.

1. The effects of capsaicin on cellular responses evoked by acetylcholine (ACh) and those by adenosine 5'-triphosphate (ATP) were investigated in rat phaeochromocytoma PC12 cells. 2. Capsaicin (1 to 30 microM) suppressed dopamine release and the intracellular Ca2+ increase evoked by 100 microM ACh. The concentration-dependence of the ACh-evoked release of dopamine was not shifted but the maximal response was reduced by capsaicin. Dopamine release evoked by 80 mM KCl was also suppressed by capsaicin (3 and 30 microM), but the extent of suppression was smaller than that of the ACh-evoked release. 3. Under whole-cell voltage-clamp, capsaicin (1 to 30 microM) reversibly inhibited the inward current activated by ACh (30 to 300 microM). The inhibition exhibited dependence on the concentration of ACh, and the current activated by a higher concentration of ACh was less inhibited. Voltage-dependence of block by capsaicin was not observed when it was tested either by applying a ramp pulse during the current activation by ACh or by eliciting the current in cells held at various potentials. 4. High concentrations of capsaicin (30 to 100 microM) enhanced the inward current as well as dopamine release evoked by 30 microM ATP. 5. The results suggest that low concentrations of capsaicin selectively antagonize responses mediated by nicotinic receptor-channels without affecting those mediated by purinoceptor-coupled channels. As the antagonism by capsaicin of the ACh-evoked responses was observed at concentrations as low as 1 microM, the influence on nicotinic receptors should be taken into account when this compound is used as a pharmacological tool to deplete neuropeptides.

Ionic current activated by extracellular ATP was characterized using whole-cell voltage clamp of rat sympathetic neurons isolated from superior cervical ganglia. ATP (10–1000 microM) activated an inward current (IATP) at negative holding potentials in almost all the cells (> 97%). The current was reversed near 0 mV in a quasi-physiological external solution, and the concentration dependence could be fitted by a curve with an EC50 value of 60 microM and a Hill coefficient of 1.8. The relationship between IATP and the current activated by ACh (IACh) was examined. ACh (100 microM) activated an inward current one- to fivefold larger than the current activated by 100 microM ATP. IATP and IACh were not additive; the current activated by simultaneous application of ATP and ACh was only as large as the current activated by ACh alone. During current activation by ATP or ACh, the current activated by the other agonist became smaller, suggesting that these agonists reciprocally inhibit their excitatory responses. The reciprocal inhibition appeared to depend on the extent of channel opening because the reduction of the current elicited by each agonist was relieved when the current elicited by the other agonist had been desensitized. Suramin (100 microM), a purinoceptor antagonist, selectively inhibited IATP whereas two open-channel blockers of nicotinic receptor channels, hexamethonium (10–100 microM) and d- tubocurarine (1–10 microM), inhibited IACh without affecting IATP. When 140 mM glucosamine was used as an external cation, only ATP but not ACh activated a considerable inward current at -150 mV. The ATP-induced glucosamine influx was reduced by simultaneous application of ACh. These results suggest that channel activation by ATP and that by ACh are not independent, and these two excitatory neurotransmitters negatively interact with each other at postsynaptic level in rat sympathetic neurons. The interaction between the ATP- and the ACh- induced conductances was hypothetically explained based upon our previous proposal of “channel overlap”; that is, ATP activates a subpopulation of the nicotinic receptor channels.

We experienced a resected case of giant right adrenal adenoma presenting with primary aldosteronism. A 42-year-old woman who had an about 15-year history of hypertension treated at the department of internal medicine on an ambulant basis was admitted to that department for close examination of the disease. It was found that blood aldosterone level was as high as 5698pg/ml, and abdominal ultrasonography, CT, and MRI revealed a tumor in the upper pole of the right kidney. The patient was diagnosed as primary aldosteronism (right adrenal adenoma) and was trransferred to this department of surgery for operation. After abdominal angiography excision of the right adrenal gland by transabdominal approach was performed. The excised adrenal gland was 5.1×4.9×2.0cm in size and 31g in weight. On the 2nd week after the operation aldosterone level remarkably decreased to 51.1pg/ml, however, hypertension still lasted which necessitated antihypertensives. On the 15th postoperative day the patient was again transferred to the department of medicine for controlling hypertension.

We experienced an operated case of gastric cancer with an abnormally high level of serum α-fetoprotein (AFP). A 66-year-old man was admitted to the hospital because of black stool. Close examination indicated that the patient has a gastric cancer. Subtotal gastrectomy was carried out. Preoperative imagings and intraoperative findings disclosed no hepatic metastasis. AFT level once decreased to 41ng/ml on the 60th postoperative day from preoperative level of 6901ng/ml, but thereafter the AFT level rapidly increased. The patient died of liver failure due to hepatic metastasis 4 months after the operation. Immunohistochemical examination confirmed the localization of AFP in moderately differentiated ductal adenocarcinoma cells. In addition the Concanavalin A-reactive rate was as high as 87%, indicating the correlation with hepatic metastasis and revurrence.

We experienced three cases of acute gangrenous cholecystitis following a lower gastrointestinal operation. Case 1: A 76-year-old man developed acute gangrenous cholecystitis after left hemicolectomy for a cancer of the descending colon. Case 2: A 51-year-old man had intractable fistula due to perforation of the small intestine after appendectomy for acute appendicitis, and then developed this disease during a long fasting period. Case 3: A 77-year-old man manifested this disease 5 days after sigmoidectomy for perforation of diverticulum in the sigmoid colon. In all 3 cases laparotomy was carried out within several days after the onset and acalculous gangrenous gallbladder was confirmed. It is supposed that fasting due to lower intestinal operation and following initiation of ingestion can be a probable trigger for this disease.

We recently found that tamoxifen suppresses l-glutamate transport activity of cultured astrocytes. Here, in an attempt to separate the l-glutamate transporter-inhibitory activity from the estrogen receptor-mediated genomic effects, we synthesized several compounds structurally related to tamoxifen. Among them, we identified two compounds, 1 (YAK01) and 3 (YAK037), which potently inhibited l-glutamate transporter activity. The inhibitory effect of 1 was found to be mediated through estrogen receptors and the mitogen-activated protein kinase (MAPK)/phosphatidylinositol 3-kinase (PI3K) pathway, though 1 showed greatly reduced transactivation activity compared with that of 17β-estradiol. On the other hand, compound 3 exerted its inhibitory effect through an estrogen receptor-independent and MAPK-independent, but PI3K-dependent pathway, and showed no transactivation activity. Compound 3 may represent a new platform for developing novel l-glutamate transporter inhibitors with higher brain transfer rates and reduced adverse effects.

We have investigated the effects of Ca2+ on Na+ influx through ATP-activated channels in pheochromocytoma PC12 cells using single channel current recordings. Under cell-attached patch-clamp conditions with 150 mM Na+ and 2 mM Ca2+ in the pipette, the unitary current activity showed an open level of about -4.3 pA at -150 mV. The channel opening was interrupted by flickery noise as well as occasional transition to a subconducting state of about -1.7 pA at -150 mV. The open level was decreased with increased external Ca2+, suggesting that external Ca2+ blocks Na+ permeation. We assessed the block by Ca2+ as the mean amplitude obtained with heavy filtration according to Pietrobon et al. (Pietrobon, D., B. Prod'hom, and P. Hess, 1989. J. Gen. Physiol. 94:1-21). The block was concentration dependent with a Hill coefficient of 1 and a half-maximal concentration of approximately 6 mM. A similar block was observed with other divalent cations, and the order of potency was Cd2+ > Mn2+ > Mg2+ not equal to Ca2+ > Ba2+. High Ca2+, Mg2+ and Ba2+ did not block completely, probably because they can carry current in the channel. The block by external Ca2+ did not exhibit voltage dependence between -100 and -210 mV. In the inside-out patch-clamp configuration, the amplitude of inward channel current obtained with 150 mM external Na+ was reduced by increased internal Ca2+. The reduction was observed at lower concentrations than that by external Ca2+. Internal Ba2+ and Cd2+ induced similar reduction in current amplitude. This inhibitory effect of internal Ca2+ was voltage dependent; the inhibition was relieved with hyperpolarization. The results suggest that both external and internal Ca2+ can block Na+ influx through the ATP-activated channel. A simple one-binding site model with symmetric energy barriers is not sufficient to explain the Ca2+ block from both sides.

Effects of hirsuteine, an indole alkaloid extracted from Uncaria genus, on nicotine and high K-induced responses were investigated in rat pheochromocytoma PC12 cells. Hirsuteine (300 nM-10 μM)inhibited dopamine release evoked by 100 μM nicotine in a concentration-dependent manner. Hirsuteine did not produce a parallel shift of the concentration-response relationship curve for nicotine, but reduced maximal dopamine release. Dopamine release evoked by 60 and 155 mM KCl was also inhibited by hirsuteine, but the concentration necessary for significant inhibition was higher (more than 10 μM). Under whole cell voltage-clamp, hirsuteine reversibly inhibited inward currents activated by 100 μM nicotine. The current inhibition was slightly accelerated by hyperpolarization. The results suggest that hirsuteine non-competitively antagonizes nicotine-evoked dopamine release by blocking ion permeation through nicotinic receptor channel complexes. The blockade of Ca channels, which are activated during nicotine-evoked depolarization, may not play a major role in the antagonism.

1. The effects of reactive blue 2 and brilliant blue G, which have been shown to block extracellular ATP-evoked responses, were investigated to discover whether these compounds act as P2-purinoceptor antagonists in PC12 phaeochromocytoma cells. 2. Reactive blue 2 (10 to 100 microM) suppressed the ATP-stimulated dopamine secretion from PC12 cells in a dose-dependent manner. The concentration-response curve for ATP was shifted to the right and the maximal response was decreased by reactive blue (30 and 100 microM). Brilliant blue G (up to 100 microM) did not significantly affect the secretion. 3. Reactive blue 2 (10 to 100 microM) suppressed the ATP-activated inward current recorded from the voltage-clamped cells in a concentration-dependent manner. Brilliant blue G (up to 100 microM) did not affect the current. 4. The results suggest that reactive blue 2 but not brilliant blue G is a P2-purinoceptor antagonist in PC12 cells. The purinoceptors in these cells may be the same type as those involved in ATP-evoked smooth muscle relaxation, judging from the antagonism by reactive blue 2.

1. The adenosine triphosphate (ATP)-activated inward current was compared to the nicotine-activated inward current in nerve growth factor (NGF)-treated rat phaeochromocytoma PC12 cells. 2. Both ATP and nicotine activated an inward current at negative holding potentials. The concentration of ATP necessary to activate the inward current was about 10-fold higher than that of nicotine; the EC50 was 20.5 microM for ATP and 2.4 microM for nicotine. The maximal responses induced by ATP and nicotine were almost identical in the same cells. The current-voltage relationship for the ATP-activated current was very similar to that for the nicotine-activated current, and both currents reversed around 0 mV in a physiological saline. 3. The ATP-activated current and the nicotine-activated current were not additive; the current activated by a combined administration of ATP (100 microM) and nicotine (10 microM) was only about 20% larger than the current activated by either ATP or nicotine alone. Nicotine (100 microM) did not increase the current activated by 1 microM-ATP. 4. ATP could activate an inward current in the cells even after desensitization to nicotine had developed. 5. Hexamethonium (100 microM) selectively blocked the nicotine-activated current whereas suramin (100 microM), a purinoceptor antagonist, selectively blocked the ATP-activated current. 6. Ionic selectivity was studied by changing compositions of extracellular solutions. When external Na+ was replaced with Cs+, both ATP and nicotine activated inward currents. However, with an extracellular solution containing Tris or glucosamine as a major cation, only ATP, not nicotine, activated an inward current. 7. ATP- and nicotine-activated currents were also recorded from cells bathed in a solution containing 1.8 mM-Ca2+ as the only external cation, suggesting that both pathways are Ca2+ permeable. 8. The results suggest that the ATP-sensitive ionic pathway is not independent of the nicotine-sensitive pathway in these cells. Our working hypothesis is that ATP and nicotine activate the same channels but the binding sites and the open-states of the channels are different between these two agonists.

1. ATP-activated inward current in PC12 pheochromocytoma cells was characterized using the whole-cell voltage-clamp technique. 2. ATP (100 microM) applied extracellular elicited an inward rectifying current with a reversal potential of about +7 mV. The current was desensitized in seconds in spite of continued presence of ATP. 3. A comparison was made of the ability of ATP and its analogues. The order of potency in activating the inward current was ATP greater than ATP gamma S greater than ADP; AMP, adenosine and alpha, beta-methylene ATP were inactive at concentrations up to mM. 4. The ATP-activated current was also observed when external Na+ and Ca2+ were replaced with K+, TEA, Tris or glucosamine. The order of ion selectivity was Na+ greater than K+ greater than TEA not equal to Tris greater than glucosamine. 5. The ATP-activated current was also recorded in extracellular solutions containing Ca2+ as the only external cation. The amplitude increased as the concentration of Ca2+ was increased in the range between 1.8 and 16.2 mM. However, the current amplitude decreased at higher Ca2+ concentrations and the current was not recorded in 110 mM-Ca2+ solution. 6. In the presence of 140 mM-Na+ in the external solution, the current amplitude also decreased as the external Ca2+ concentration was increased (from 1.8 to 16.2 mM). 7. The results indicate that Ca2+ as well as monovalent cations permeate through the ATP-sensitive pathway and that Ca2+ blocks ion permeation, including its own permeation through the pathway. This regulation by extracellular Ca2+ is different to the ATP-activated current in smooth muscle cells.

Acute massive pulmonary thromboembolism is life-threatening and requires vigorous treatment. Anticoagulation is the most traditional treatment for pulmonary thromboembolism, but may not be sufficient for massive thromboemboli. Systemic thrombolytic therapy and surgical thrombectomy are the traditional therapeutic options in this situation. Catheter-directed thrombolysis, percutaneous embolectomy and, more recently, percutaneous thrombus fragmentation techniques using specialized devices are now available to treat the most severe cases of massive pulmonary thromboembolism. The success of these techniques depends on a thorough understanding of the mechanism of action of each of the devices and familiarity with the relevant catheterization techniques. We present a review of currently available equipment and techniques, and describe our work with hybrid treatment using a combination of mechanical fragmentation, localized fibrinolysis and clot aspiration.

The effects of phytoestrogens on neuronal nicotinic acetylcholine receptor/channels were examined by expressing recombinant channels in Xenopus oocytes. When functional channels were expressed with human alpha4 and beta2 subunits, daidzein (10 and 100 microM) partially inhibited the ionic current activated by acetylcholine. The current inhibition was also observed when functional channels were expressed with human alpha3 and beta4 subunits or rat homologues. Genistin (100 microM) also inhibited the acetylcholine-activated current. Tamoxifen (100 microM), an antiestrogen did not antagonize the inhibition by daidzein. The results suggest that phytoestrogens, like estrogens and xenoestrogens, block human neuronal acetylcholine receptors through non-genomic mechanisms.

In precollicular decerebrate and paralyzed cats, respiratory nerve activities were recorded during fictive vocalization (FV), which consisted of a distinctive pattern of 1) decreased inspiratory (I) and expiratory (E) phase durations, 2) marked increase of phrenic activity and moderate changes of recurrent laryngeal (RL) and superior laryngeal (SL) I activities, and 3) massive recruitment of laryngeal and abdominal (ABD; lumbar) E activities. FV was produced by electrical stimulation (100 Hz) in the midbrain periaqueductal gray (PAG) or its putative descending pathways in the ventrolateral pons (VLP). Spectral and correlation analyses revealed three types of effect on fast rhythms during FV. 1) I activities: the coherent high-frequency oscillations in I (I-HFO, 60–90 Hz) present in phrenic and RL discharges during the control state did not change qualitatively, but there was an increase of power and a moderate increase (4–10 Hz) of frequency. Sometimes a distinct relatively weak stimulus-locked rhythm appeared. 2) RL and SL activities during E: in recruited discharges, a prominent intrinsic rhythm (coherent E-HFOs at 50–70 Hz) appeared; sometimes a distinct relatively strong stimulus-locked rhythm appeared. 3) ABD activities during E: this recruited activity had no intrinsic rhythm but had an evoked oscillation locked to the stimulus frequency. Thus FV is characterized by 1) appearance of prominent coherent intrinsic rhythms in RL and SL E discharges, which presumably arise as a result of excitation and increased interactions in laryngeal networks; 2) modification of intrinsic rhythmic interactions in inspiratory networks; and 3) evoked rhythms in augmenting-E neuron networks without occurrence of intrinsic rhythms.

Nakazawa, Ken, Min Liu, Kazuhide Inoue, and Yasuo Ohno. Voltage-dependent gating of ATP-activated channels in PC12 cells. J. Neurophysiol. 78: 884–890, 1997. The possibility that P2X receptors exhibit voltage-dependent gating in a similar manner to nicotinic receptors was investigated in rat pheochromocytoma cells with the use of whole cell voltage-clamp techniques. In the presence of extracellular ATP, slowly activating inward currents were elicited by stepping from −50 mV to potentials more negative than −80 mV; these currents had a time constant of ∼60 ms at −120 mV. This slowly activating component (as a fraction of the total ATP-induced current) increased with membrane hyperpolarization from −80 to −100 mV and was much increased when depolarizing prepulses were applied, although the time constant of activation was not altered by depolarizations. The fraction of the slowly activating current and its time constant were decreased as the ATP concentration was increased from 10 to 300 μM. Thus it has been demonstrated that voltage-dependent gating of ATP-activated channels does occur in PC12 cells, and that this gating is modified by agonist concentration. It is possible that such gating may serve as a postsynaptic mechanism to facilitate excitatory neurotransmission by contributing to the inward rectification of the ATP-activated currents.

1. The effects of cadmium ion (Cd2+) on release of dopamine and on an inward current evoked by extracellular ATP were investigated in rat phaeochromocytoma PC12 cells. 2. Cd2+ (100 microM-3 mM) potentiated the dopamine release evoked by 30 microM ATP from the cells. Cd2+ (100 microM) shifted the concentration-response curve of ATP-evoked dopamine release to the left without affecting the maximal response. 3. Suramin (30 microM) completely abolished the dopamine release evoked by 30 microM ATP but only partially inhibited the release evoked by 100 microM ATP consistent with its role as a competitive antagonist. The response evoked by 30 microM ATP in the presence of Cd2+ (300 microM) was comparable to that observed with 100 microM ATP alone; however, only the former was almost completely inhibited by suramin. 4. Cd2+ (100 microM) potentiated an inward current activated by 30 microM ATP alone. A higher concentration of Cd2+ (300 microM) had a smaller effect on amplitude potentiation but significantly prolonged the duration of the current. 5. The time-course of the ATP-evoked dopamine release was investigated using a real-time monitoring system for dopamine release. Although Cd2+ (300 microM) had little effect on the time-course of activation the ATP-evoked dopamine release, it produced a long-lasting dopamine release which slowly returned to the baseline. 6. Taken together, these observations suggest that Cd2+ enhances ATP-evoked dopamine release by affecting P2-purinoceptor/channels. The enhancement may be attributed to a Cd(2+)-dependent increase in sensitivity to ATP.