Superconductivity at 52 K in hydrogen-substituted LaFeAsO(1-x)Hx under high pressure.

The 1111-type iron-based superconductor LnFeAsO(1-x)Fx (Ln stands for lanthanide) is the first material with a Tc above 50 K, other than cuprate superconductors. Electron doping into LaFeAsO by H, rather than F, revealed a double-dome-shaped Tc-x diagram, with a first dome (SC1, 0.0550 K observed in RE-1111 compounds (RE: Pr, Sm, and Gd) at ambient pressure is the merging of SC1 and SC2.

Neurotransmitter release from growth cones of rat dorsal root ganglion neurons in culture.

Growing neurites of rat dorsal root ganglion neurons in culture formed growth cones at the tips. Possible release of glutamate from these growth cones was investigated by using a whole-cell patch-clamp recording from an acutely dissociated hippocampal neuron containing glutamate receptors. The hippocampal neuron was placed in contact to various regions of the dorsal root ganglion neurons. Inward currents were recorded from the hippocampal neuron positioned on the growth cones of the dorsal root ganglion neurons (diameter, 12-16 microm) in response to the dorsal root ganglion cell body stimulation. The inward currents were associated with an increase in membrane conductance, and the reversal potential was estimated at -6.5 mV (n=8). The inward currents were blocked by 6-cyano-7-nitroquinoxaline (10 microM), but not blocked by 2-amino-5-phosphonovaleric acid (50 microM) and bicuculline (10 microM). The inward currents were abolished by tetrodotoxin (1 microM), EGTA-buffered Ca2+-free external solution or omega-agatoxin IVA (300 nM), and were inhibited by omega-conotoxin GVIA (3 microM), but were not affected by nicardipine (10 microM). Intracellular calcium ion concentration ([Ca2+]i) in growth cones of the dorsal root ganglion neurons increased in response to dorsal root ganglion cell body stimulation, whereas the elevation of [Ca2+]i was not observed either in the presence of tetrodotoxin (1 microM) or in a Ca2+-free external solution. These results indicate that the inward currents were evoked by glutamate released from the growth cones via a Ca2+-dependent process, and suggest that the growth cones are already endowed with much of the machinery for neurotransmitter release, even before making a structure for synaptic transmission.

Prediction of the chemosensitivity of lung cancer by 99mTc-hexakis-2-methoxyisobutyl isonitrile SPECT.

UNLABELLED: 99mTc-hexakis-2-methoxyisobutyl isonitrile (MIBI) has been reported to accumulate in various tumors and to be a transport substrate for P-glycoprotein (Pgp). The aim of this study was to evaluate the usefulness of 99mTc-MIBI SPECT for in vivo assessment of lung cancer chemosensitivity. Also examined was the relationship between 99mTc-MIBI uptake and Pgp expression. METHODS: Ten lung cancer patients who had undergone surgery were examined. Before surgery, 99mTc-MIBI SPECT was performed 15 and 120 min after injection, and the early uptake (L/Ne), delayed uptake (L/Nd) and washout rate (L/Nwr) of 99mTc-MIBI were calculated by the count ratio of lesion to contralateral normal lung tissue. The results were then compared with chemosensitivity determined by the succinate dehydrogenase inhibition test using six antitumor drugs (doxorubicin, mitomycin C [MMC], vindesine, etoposide [VP-16], cyclophosphamide and cisplatin). Pgp expression was determined by immunohistochemical staining. RESULTS: Sensitivity to MMC correlated significantly with L/Ne (P < 0.01) and L/Nwr (P < 0.05). Sensitivity to VP-16 correlated weakly and insignificantly with L/Nwr. L/Nd showed no correlation with sensitivity to any drug. Neither L/Ne, L/Nd nor L/Nwr was significantly different between the Pgp-positive group (n = 2) and the Pgp-negative group (n = 8). CONCLUSION: The results suggest that 99mTc-MIBI SPECT, a noninvasive in vivo examination, can predict the chemosensitivity of lung cancer to MMC and VP-16 independently of Pgp expression.

Estradiol inhibits Ca2+ and K+ channels in smooth muscle cells from pregnant rat myometrium.

The purpose of this study was to investigate the actions of 17beta-estradiol on the electrical activity of pregnant rat myometrium. The longitudinal layer of the myometrium was dissected from pregnant rats (17 to 19 days of gestation), and single cells were isolated by enzymatic digestion. Calcium currents and potassium currents were recorded by the whole-cell voltage-clamp method, and the single calcium-dependent potassium current was recorded by the outside-out patch-clamp method. The effects of 17beta-estradiol on these currents were investigated. When a myometrial cell was held at -50 mV, depolarization to a potential more positive than -30 mV produced an inward current followed by a slowly developing outward current. Application of tetraethylammonium inhibited the outward current while the inward current was completely abolished in a calcium-free solution. Estradiol at high concentrations (> 3 microM) inhibited both inward and outward currents in a voltage-dependent manner. Removal of estradiol restored the amplitude of the outward but not of the inward current. Estradiol (30 microM) also inhibited the activity of single calcium-dependent potassium channels without changing single channel conductance. In conclusion, estradiol at high concentrations inhibited: (1) voltage-dependent calcium, (2) calcium-dependent potassium and (3) voltage-dependent potassium currents. These actions of estradiol would prevent action potential generation and after-hyperpolarizations. Suppression of the after-hyperpolarization might further prevent spike generation due to slowing of the calcium channel's recovery from the inactivated state.

Visualization of calcium channels involved in transmitter release from neuronal growth cones.

Immunocytological localization of omega-agatoxin IVA (omega-aga IVA)-sensitive Ca2+ channels involved in glutamate release from growth cones of cultured rat dorsal root ganglion (DRG) neurons was studied with field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The omega-aga IVA-sensitive Ca2+ channels were visualized by labeling with immuno-gold particles (30 nm). FE-SEM and TEM images showed that immuno-gold particles were present in the area of growth cones as well as somata, and generally absent on neurite stem and fibroblasts. TEM images of vertical ultra-thin sections showed that the immuno-gold particles were present on the surface of the plasma membrane. Since the gold particles indicate the immunological presence of omega-aga IVA-sensitive Ca2+ channels, the Ca2+ channels involved in transmitter release are present on growth cones before making synapse formation.

Synthesis, storage and release of acetylcholine at and from growth cones of rat central cholinergic neurons in culture.

Neurons from the nucleus diagonal band of Broca (DBB) from new born rats protrude neuronal processes and growth cones in culture. Cytochemical observations with the light and electron microscope indicate that growth cones of these neurons take up choline, synthesize acetylcholine (ACh) and store ACh in the vesicles. Electrical stimuli at the soma of DBB neurons evoked inward currents in ACh-sensitive neurons attached to DBB growth cones. These currents were suppressed by TTX, a Ca2+ channel blocker (Cd2+), and an ACh nicotinic antagonist (C6). These results suggest that ACh is synthesized, stored and released from the growth cones of DBB neurons prior to synapse formation.

Estrogen directly acts on osteoclasts via inhibition of inward rectifier K+ channels.

Using the whole-cell patch-clamp technique in freshly isolated rat osteoclasts we examined the effects of estrogen on ionic channels. The predominant current was an inward rectifier K+ current (IKir). In the absence of non-osteoclastic cells, extracellularly applied 17beta-estradiol (>0.1 microM) inhibited IKir, indicating that estrogen acts directly on osteoclasts. Application of 17beta-estradiol (10 microM) for 10 min reduced IKir at the membrane potential of -120 mV to 70 +/- 15% of control. Removal of 17beta-estradiol partially restored the inhibition. The inhibition of IKir was dependent on concentration and application time. Intracellularly applied 17beta-estradiol had no effect on IKir. 17alpha-estradiol also inhibited the IKir, whereas progesterone and testosterone had no effect. The inhibitory action of 17beta-estradiol was not affected by guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS), adenosine 3',5'-cyclic monophosphothioate Rp diastereomer (Rp-cAMPS), okadaic acid, staurosporine and phorbol ester, and was independent of intracellular Ca2+ concentration ([Ca2+]i). With no influence from soluble factors secreted from non-osteoclastic cells, preincubation of the osteoclasts for more than 60 min with much lower concentrations of 17beta-estradiol (1 and 10 nM) caused a reduction of IKir. In current-clamp configuration, application of 17beta-estradiol (10 microM) depolarized the membrane associated with a decrease in a membrane conductance, indicating that 17beta-estradiol inhibits IKir and depolarizes the membrane of osteoclasts. These results suggest that the 17beta-estradiol-induced inhibition of IKir might be mediated via non-genomic mechanisms. This direct action of 17beta-estradiol on osteoclasts may contribute to the regulation of [Ca2+]i and partially account for the protective effects of estrogen against bone loss.

Acromegaly, diabetes insipidus, and visual loss caused by metastatic growth hormone-releasing hormone-producing malignant pancreatic endocrine tumor in the pituitary gland. Case report.

The case of a 52-year-old woman with acromegaly, diabetes insipidus, and visual impairment caused by a metastatic growth hormone-releasing hormone (GRH)-produced pancreatic tumor is reported. Serum growth hormone (GH) and somatomedin C levels were elevated to 14 ng/ml (normal < 5 ng/ml), and 3.20 U/ml (normal < 1.88 U/ml), respectively. Paradoxical increases were observed in GH levels after glucose tolerance and thyrotropin-releasing hormone-stimulation tests. Biopsy of a pituitary tumor observed on computerized tomography scans and magnetic resonance studies revealed a metastatic cancer. When circulating GRH levels were measured, a marked increase in plasma GRH (1145 pg/ml; normal < 4-1 pg/ml) was observed. The patient died of cachexia due to metastases. Postmortem examination revealed that a primary tumor, a malignant endocrine lesion, was present in the pancreas, with metastatic tumors in the pituitary, lung, liver, and adrenal glands. Synthesis and production of GRH by the tumor was demonstrated by Northern blotting and immunohistochemical analysis. The pituitary gland showed hyperplastic, but not adenomatous changes. The authors stress the importance of both exploration for an ectopic source of GRH and the search for a GH-producing pituitary adenoma when unusual signs and symptoms are seen in patients with acromegaly.

Electrical response to hypotonic NaCl Ringer solution across the dorsal epithelium of the tongue of the frog, Rana catesbeiana.

Stimulation with hypotonic NaCl Ringer solution produced a change in potential across the epithelium, which was not caused by decreased osmotic pressure. The potential profile resembled the receptor potential of frog taste cells and so may be related to water reception.

Electrical response to acid across the dorsal epithelium of the frog tongue.

Acid stimulation produced a change in trans-epithelial potential difference across isolated dorsal epithelium of frog tongue. The responses to acetic acid, tartaric acid and citric acid were significantly greater than those to hydrochloric acid and nitric acid at the same pH. Metabolic inhibitors had no effect on the response, but local anaesthetics reversibly depressed it. The induced response was associated with a decrease in tissue resistance. Positive polarization on the mucosa increased the response, which was decreased or reversed under negative polarization. These responses may be caused by diffusion of H-ions through the tissue, and may influence sour reception in the frog.

Salt-induced electrical epithelial responses of the frog (Rana catesbeiana) tongue and their relation to gustatory nerve activity in vivo.

Stimulation of the frog tongue with various salts produced changes in epithelial potential of the tongue, accompanied by changes in gustatory nerve activity. Both changes varied similarly according to the stimulus. The results indicate that cation transport in the lingual epithelium is involved in gustation.

Sodium permeability of the frog tongue epithelium.

Application of NaCl to the frog tongue produced a sodium influx through the dorsal epithelium. The flux was distinctly faster through those of the palatal epithelium and the skin, and may influence taste reception in frogs.

Relation between translingual potential changes induced by NaCl in the bullfrog tongue and taste nerve activity.

NaCl at various concentrations applied to the dorsal surface of the bullfrog tongue induced slow potential changes across the tongue. They were almost in parallel with changes in impulse discharges simultaneously recorded from the glossopharyngeal nerve.

Resected peripheral small cell carcinoma of the lung: computed tomographic-histologic correlation.

In order to clarify the characteristic computed tomographic findings of peripheral small cell lung cancer, the authors investigated 12 patients with surgically resected and histologically proven peripheral small cell lung cancer. Conventional computed tomography was performed on all, and additional high-resolution computed tomographic images were obtained for nine patients. Marginal, internal, and surrounding features of the tumors were analyzed, and these findings were correlated with histologic findings. All 12 tumors appeared as homogenous masses, and eight had well-defined margins. Lobulation was found in seven, marginal ground-glass opacity in three, fine spiculation in two, and both ground-glass opacity and spiculation in one. Cut specimens showed whitish medullary masses without large areas of necrosis, and microscopic specimens showed small areas of necrosis in 11 patients. Marginal ground-glass opacities corresponded to focal edema and hemorrhage in two patients and to intraalveolar invasion in one. Fine spiculation corresponded to vascular/lymphatic invasion in one patient and to irregular intraalveolar spread in another. The authors concluded that a homogenous mass without necrosis is the most characteristic feature of peripheral small cell carcinoma on computed tomography.

Pharmacokinetics of diltiazem in patients with liver cirrhosis.

The pharmacokinetics of diltiazem (DTZ) was investigated in seven control subjects with normal liver function and in seven patients with liver cirrhosis. After long-term oral administration of diltiazem, 30 or 60 mg thrice daily, serum levels of DTZ and its active metabolites, deacetyl DTZ (DAD) and N-demethyl DTZ (DMD), were determined by high performance liquid chromatography. The mean peak serum concentrations (nmol/L) in control patients were 280 for DTZ, 58 for DAD and 101 for DMD. In cirrhotic patients, the serum DTZ tended to increase and the DAD increased (p less than 0.05), while the DMD decreased (p less than 0.05) compared with that of the control (335 for DTZ, 133 for DAD and 77 for DMD, nmol/L). Pharmacokinetic analysis using a one-compartment model revealed no change in the absorption, but a decrease in the elimination for cirrhotic patients (t 1/2; 5.3 to 7.2 h, p less than 0.1). The elimination rate constant correlated with some biochemical indices for hepatocyte function. These results may be explained by the impaired oxidative metabolism of diltiazem in liver cirrhosis.

MODIFIED ETHANOL INJECTION METHOD FOR LIPOSOMES CONTAINING beta-SITOSTEROL beta-D-GLUCOSIDE.

A modified ethanol injection method for liposomes containing soybean phosphatidylcholine (SPC), cholesterol (Ch), beta-sitosterol beta-D-glucoside (Sit-G) and oleic acid (OA) was developed, that can produce homogeneous unilamellar liposomes without the use of sonication and dialysis. In this method, water is poured into a concentrated lipid-ethanol solution and then ethanol is removed in an evaporator. Dilution with water causes spontaneous formation of small and homogenous unilamellar vesicles from micellar aggregate. The size of liposomes can be controlled by the ratio of ethanol to water. OA and Sit-G were distributed at the surface of liposomes and were recognized by Concanavalin A, respectively. This easy and quick method for preparation of liposomes may be applicable in many areas.

High-resolution CT characteristics of poorly differentiated adenocarcinoma of the peripheral lung: comparison with well differentiated adenocarcinoma.

OBJECTIVE: The purpose of this study was to elucidate the characteristic high-resolution CT (HRCT) findings of poorly differentiated adenocarcinoma (PDA) in comparison with those of well differentiated adenocarcinoma (WDA). MATERIALS AND METHODS: We investigated the HRCT features of surgically resected PDAs (n=21) and WDAs (n=31). We analyzed the margin, CT attenuation, and internal architecture of the tumor and findings in the surrounding lung field, comparing them with the corresponding pathologic findings. RESULTS: Smoothness of the greater part (full-1/2 round) of the tumor and solid appearance were more prevalent in PDAs than WDAs (81% vs. 32%, 100% vs. 35%) [p<0.01]. Air-bronchogram was prevalent in WDAs (58%), but was never seen in PDAs [p<0.01]. Ground-glass opacity in PDAs pathologically corresponded to inflammation and edema in the alveolar space. CONCLUSIONS: Smoothness of the tumor margin and solid appearance without air-bronchogram were more commonly found in PDA than in WDA. HRCT may predict the histological differentiation of adenocarcinoma in selected cases in which differentiation is inconclusive by sputum cytology and transbronchial or CT-guided biopsy.