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.

Replantation of multi-level fingertip amputation using the pocket principle (palmar pocket method).

Two cases of multi-level fingertip amputation are presented. In each case, replantation was achieved in a two-stage procedure, involving reattachment, de-epithelialisation and insertion into a palmar pocket in stage 1, followed by removal from the palmar pocket 16 days later. The cases are described and the technique is discussed.

Differential diagnosis between thymoma and non-thymoma by dynamic MR imaging.

PURPOSE: To evaluate the usefulness of dynamic MR imaging for differential diagnosis of anterior mediastinal tumors. MATERIAL AND METHODS: Fifty-nine patients with anterior mediastinal tumors were examined. According to histological diagnosis confirmed by surgery or biopsy, 31 had thymomas and 28 had non-thymoma lesions. The patients underwent dynamic MR imaging with gadopentetate dimeglumine administered as a bolus injection. Sequential images were obtained at 30-s intervals for 5 min. Significant differences in the mean peak times of time intensity curves (TICs) were found by histological type, using the Mann-Whitney test. RESULTS: The mean peak time of the TIC was 1.5 min in thymoma and 3.2 min in non-thymoma cases. The difference was statistically significant. Stages I and II of thymoma showed a mean value of 1.3 min, which was significantly shorter than that of 2.5 min in stage III. Differentiation of thymoma/non-thymoma based on the peak time of dynamic MR imaging showed optimal sensitivity (79%) and specificity (84%) when defining thymomas as lesions having peak time appearing earlier than 2 min and non-thymomas later than 2.5 min, with an accuracy of 81%. CONCLUSION: Dynamic MR imaging may improve the differential diagnosis between thymoma and non-thymoma and the staging of thymoma.

Correlation of immunologic status with high-resolution CT and distributions of pulmonary tuberculosis.

PURPOSE: To investigate the correlation of cluster of differentiation (CD)4 lymphocyte counts with high-resolution CT (HRCT) findings and distribution of pulmonary tuberculosis. MATERIAL AND METHODS: Thirty-seven bacteriologically proven pulmonary tuberculosis, clinically non-AIDS, patients underwent HRCT and CD4 lymphocyte counts in peripheral blood cells were obtained within 3 days after the CT examinations. Patients were categorized into four groups according to CD4 lymphocyte counts (A >800; B 800-500; C 500-200; D <200). HRCT findings analyzed were as follows: typical, atypical, and mixed findings of post-primary tuberculosis, common, uncommon, and mixed distribution, and number of lobes involved. RESULTS: CD4 lymphocyte counts correlated with the degree of the mixture of atypical CT findings (rho=0.565, p<0.001) and the degree of the mixture of uncommon distribution (rho=0.431, p<0.01). Number of involved lobes showed no statistically significant correlation (rho=0.209, p=0.21). CONCLUSION: In patients with low CD4 levels, atypical HRCT findings co-exist with typical findings, and uncommon sites are involved in addition to common sites.

The palmar pocket method: an adjunct to the management of zone I and II fingertip amputations.

In 1979 Brent reported a new replantation method, without vascular anastomosis, that used a subcutaneous pocket. Brent chose the contralateral chest wall as a pocket site, but in other clinical reports, the abdominal wall was used. For both sites there were complications such as stiffness in the wrist, elbow, and shoulder joints and anxiety about pulling out the pocketed finger. To overcome these problems, we chose the ipsilateral palm and named this method the palmar pocket method. We used this method in 16 cases in which a digit other than the thumb had been amputated between the tip and lunula. In 13 cases the method was completely successful, and in 3 cases there was a small area of tip necrosis. The palmar pocket method is a simple and reliable operation for fingertip reattachment and more comfortable for patients than pocketing in the chest wall or abdominal wall.

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.

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.

Protein tyrosine kinase inhibitors increase cytosolic calcium and inhibit actin organization as resorbing activity in rat osteoclasts.

Although there is evidence that protein tyrosine kinase inhibitors (PTKIs) suppress bone resorption activity, the mechanism of action of these compounds on osteoclastic bone resorption remains obscure. In the present study, we investigated the effect of PTKIs on cytosolic Ca(2+) concentration ([Ca(2+)](i)) and on the cytoskeleton in rat osteoclasts. The PTKIs, genistein and herbimycin A, reversibly elevated [Ca(2+)](i) measured by fura-2 microfluorimetry. The PTKI-induced increase was abolished by omission of extracellular Ca(2+), but was not attenuated by depletion of Ca(2+) stores. The PTKI-induced increase was inhibited by addition of La(3+) and Ni(2+), but not abolished by dihydropyridine (DHP) Ca(2+) channel blockers. Genistin, an inactive analogue of genistein, had no effect on [Ca(2+)](i). In the cytoskeleton assay, genistein rapidly disrupted the actin ring formation that serves as a marker for the resorbing state of osteoclasts. Disruption of the actin ring formation was also diminished in Ca(2+)-free extracellular solution. These results suggest that PTKIs in rat osteoclasts elevate [Ca(2+)](i) via activation of a DHP-insensitive, nonspecific Ca(2+) entry pathway and disrupt the formation of actin rings, resulting in suppression of bone resorption activity. The regulation of this Ca(2+)-influx by PTKIs is likely to contribute to inhibition of bone resorption by these compounds.

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.

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.

"Crazy paving appearance" on high resolution CT in various diseases.

PURPOSE: The purpose of this work was to demonstrate the variety of causes of crazy-paving appearance (CPA) on high resolution CT (HRCT). METHOD: To identify cases exhibiting CPA (ground-glass opacity with superimposed interlobular septal thickening and intralobular interstitial thickening) on HRCT, we prospectively searched for them over a period of 29 months. RESULTS: We identified 10 cases of CPA on HRCT, including 4 Pneumocystis carinii pneumonia, 1 alveolar proteinosis, 1 usual interstitial pneumonia, 1 pulmonary hemorrhage, 1 acute radiation pneumonitis, 1 adult respiratory distress syndrome, and 1 drug-induced pneumonitis. CONCLUSION: CPA can result from a variety of diseases. When we encounter CPA on HRCT, clinical information is necessary for differentiation of these entities.

Augmentation and suppression of action potentials by estradiol in the myometrium of pregnant rat.

The purpose of this study was to investigate the actions of estradiol on spontaneous and evoked action potentials in the isolated longitudinal smooth muscle cells of the pregnant rat. Single cells were obtained by enzymatic digestion from pregnant rat longitudinal myometrium. Action potentials and currents were recorded by whole-cell current-clamp and voltage-clamp methods, respectively. The acute effects of 17beta-estradiol on action potentials and inward and outward currents were investigated. The following results were obtained. The average resting membrane potential of single myometrial cells was -54 mV (n = 40). In many cells, an electrical stimulation evoked a membrane depolarization, and action potentials were superimposed on the depolarization. In some cells, spontaneous action potentials were observed. Estradiol (30 microM) slightly depolarized the membrane (ca. 5 mV) and attenuated the generation of action potentials by reducing the frequency and amplitude of the spikes. Afterhyperpolarization was also attenuated by estradiol (30 microM). On the other hand, in 5 of 35 cells, estradiol increased the first spike amplitude and action potential duration, while frequency of the spike generation and afterhyperpolarization were inhibited. In voltage-clamped muscle cells, estradiol inhibited both inward and outward currents. Acute inhibition or augmentation of spike generation by estradiol is due to the balance of inhibition of inward and outward currents. Inhibition of both currents also prevented afterhyperpolarization, causing potential-dependent block of Ca spikes.

New classification of small pulmonary nodules by margin characteristics on high-resolution CT.

PURPOSE: To analyze margin characteristics of pulmonary nodules on high-resolution CT (HRCT) in order to improve imaging diagnoses. MATERIAL AND METHODS: HRCT images of 193 pulmonary nodules of less than 30 mm maximum diameter (113 primary cancers, 15 metastatic cancers, 55 inflammatory nodules, and 10 benign tumors) were reviewed and classified as to 6 types of margins: round, lobulated, densely spiculated, ragged, tentacle or polygonal and halo. The relationships of these imaging types to the diagnoses, the underlying pathological features, mainly those of tumor growth patterns in 93 neoplasms, and the pathological characteristics of 14 inflammatory nodules were investigated. RESULTS: Eighty-two percent of the lobulated, 97% of the densely spiculated, 93% of the ragged and 100% of the halo nodules were malignant. Eighty percent of the tentacle or polygonal nodules were inflammatory and 66% of the round ones were benign. The 6 types differed statistically as to the nature of the benignity/malignancy (p<0.001). Pathologically, in case of neoplasms, most of the 6 types had a relationship to a particular tumor growth pattern. CONCLUSION: This HRCT classification method is useful for determining the nature of small pulmonary nodules and reflects the underlying pathological characteristics.

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.

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.

Physiological significance of hyperpolarization-activated inward currents (Ih) in smooth muscle cells from the circular layers of pregnant rat myometrium.

The properties of hyperpolarization-activated current in pregnant rat uterus (17-19 days gestation) were investigated using microelectrode and patch-clamp techniques, and isometric tension recording. The resting membrane potentials were -58.4 mV and -48.5 mV in longitudinal and circular muscle cells, respectively. Application of hyperpolarizing current pulses produced a time-dependent anomalous inward rectification of membrane potential only in circular muscle cells. Under voltage-clamp conditions, inward currents (Ih) were activated by long hyperpolarizing pulses below -60 mV in circular but not in longitudinal muscle cells. Application of extracellular but not intracellular Cs+ reduced the amplitude of I(h) in a concentration-dependent manner (an IC50( of 0.15 mM). The reversal potential for Ih was -26.2 mV and the slope conductance was 5 nS/pF. Changes in [K+]o and [Na+]o shifted the reversal potential, and Ih amplitude increased with excess [K+]o and decreased with low [Na+]o. The steady-state activation of Ih was well fitted by a Boltzmann equation with a half-activation potential of -84.3 mV and a slope factor of 9.6 mV. Time courses of activation and deactivation of the current strongly depended on membrane potential, and were well fitted by a single exponential function. The activation time constant of Ih was dependent on temperature. In isometric tension recording, application of extracellular Cs+ to the circular muscles reduced the frequency, but not the amplitude, of spontaneous contractions in a concentration-dependent manner. It is concluded that in pregnant rat uterus Ih channels are predominantly distributed in smooth muscle cells from the circular layer. Since Ih is activated at the resting membrane potential, it is likely that this current contributes to the maintenance of resting membrane potential and spontaneous activity in circular smooth muscle cells of late pregnant rats.

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.

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.

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.

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.