Two-Particle Interference of Electron Pairs on a Molecular Level.

We investigate the photodouble ionization of H_{2} molecules with 400 eV photons. We find that the emitted electrons do not show any sign of two-center interference fringes in their angular emission distributions if considered separately. In contrast, the quasiparticle consisting of both electrons (i.e., the "dielectron") does. The work highlights the fact that nonlocal effects are embedded everywhere in nature where many-particle processes are involved.

Transient impulsive electronic Raman redistribution.

Resonant Raman excitation by ultrafast vacuum ultraviolet laser pulses is a powerful means to study electron dynamics in molecules, but experiments must contend with linear background ionization: frequencies high enough to reach resonant core-valence transitions will usually ionize all occupied orbitals as well, and the ionization cross sections are usually dominant. Here we show that attosecond pulses can induce a process, transient impulsive stimulated Raman scattering, which can overwhelm valence ionization. Calculations are performed for atomic sodium, but the principal is valid for many molecular systems. This approach opens the path for high-fidelity multidimensional spectroscopy with attosecond pulses.

Impact of the lateral skeletal stability following bilateral sagittal split ramus osteotomy for mandibular asymmetry.

This study evaluated the stability of bilateral sagittal split ramus osteotomy (BSSRO) associated with positional plagiocephaly and temporal and masseter muscles using posteroanterior cephalogram analysis and three-dimensional computed tomography (3D-CT). This retrospective cohort study included 31 patients who underwent BSSRO for mandibular asymmetry. The cranial vault asymmetry index (CVAI) and the cephalic index were used as indicators of positional plagiocephaly. The distance from the vertical reference line to the menton (Me) was measured on posteroanterior cephalograms immediately and 1 year after surgery, and postoperative stability was assessed. Temporal and masseter muscles were constructed from 3D-CT data and their volumes were measured. Simple regression analysis showed a significant correlation between postoperative changes in the vertical reference line to the Me and the CVAI (R = 0.56, p = 0.001), the amount of surgical movement in the vertical reference line to the Me (R = 0.41, p = 0.023), and the variable temporal muscle volume (R = 0.27, p = 0.028). There was no significant correlation between postoperative changes in the vertical reference line to the Me and the cephalic index (R = 0.093, p = 0.62) and variable masseter muscle volume (R = 0.16, p = 0.38). According to multivariate analysis, CVAI (p = 0.003) and amount of surgical movement in the vertical reference line to the Me (p = 0.014) were significant predictors of postoperative change in the vertical reference line to the Me. Positional plagiocephaly and amount of surgical movement influence lateral skeletal stability following BSSRO for mandibular asymmetry.

Spontaneous regression of malignant lymphoma of the maxillary gingiva following biopsy.

A case of spontaneous regression of malignant lymphoma of the maxillary gingiva following a biopsy is reported. An 84-year-old man was referred to the hospital with chief complaints of swelling of the anterior maxillary gingiva. A non-tender swelling with an ulcer was observed. There was no abnormal bone resorption in the anterior maxillary region and no swelling of the cervical lymph nodes. A biopsy was performed, and the patient was diagnosed with diffuse large B-cell lymphoma. The lesion regressed spontaneously 3 weeks after the initial biopsy. Two years have passed since the spontaneous regression and no recurrence has been observed. If malignant lymphoma regresses on biopsy, observation is considered to be sufficient.

Electron diffraction self-imaging of molecular fragmentation in two-step double ionization of water.

We doubly ionize H(2)O by single photon absorption at 43 eV leading to H(+) + OH(+). A direct double ionization and a sequential process in which single ionization is followed by rapid dissociation into a proton and an autoionizing OH(*) are identified. The angular distribution of this delayed autoionization electron shows a preferred emission in the direction of the emitted proton. From this diffraction feature we obtain internuclear distances of 700 to 1100 a.u. at which the autoionization of the OH(*) occurs. The experimental findings are in line with calculations of the excited potential energy surfaces and their lifetimes.

Analysis of VH gene rearrangement and somatic hypermutation in Sjogren's syndrome and IgG4-related sclerosing sialadenitis.

IgG4-related sclerosing sialadenitis is currently considered as an autoimmune disease distinct from Sjogren's syndrome (SS) and responds extremely well to steroid therapy. To further elucidate the characteristics of IgG4-related sclerosing sialadenitis, we analysed VH fragments of IgH genes and their somatic hypermutation in SS (n = 3) and IgG4-related sclerosing sialadenitis (n = 3), using sialolithiasis (n = 3) as a non-autoimmune control. DNA was extracted from the affected inflammatory lesions. After PCR amplification of rearranged IgH genes, at least 50 clones per case (more than 500 clones in total) were sequenced for VH fragments. Monoclonal IgH rearrangement was not detected in any cases examined. When compared with sialolithiasis, there was no VH family or VH fragment specific to SS or IgG4-related sclerosing sialadenitis. However, rates of unmutated VH fragments in SS (30%) and IgG4-related sclerosing sialadenitis (39%) were higher than that in sialolithiasis (14%) with statistical significance (P = 0.0005 and P < 0.0001, respectively). This finding suggests that some autoantibodies encoded by germline or less mutated VH genes may fail to be eliminated and could play a role in the development of SS and IgG4-related sclerosing sialadenitis.

Proliferation and apoptosis of tumour cells before and after neoadjuvant therapy for high-grade extremity sarcomas: divergent associations with tumour response and prognosis.

AIMS: To evaluate proliferation and apoptosis in high-grade sarcomas of the extremities before and after preoperative radio-hyperthermo-chemotherapy (RHC) and to determine the relationship between these parameters and treatment outcomes. METHODS AND RESULTS: Pre- and post-RHC specimens of 41 soft tissue and bone tumours were immunohistochemically stained for minichromosome maintenance protein (MCM) 2 and caspase 3 as proliferation and apoptosis markers, respectively, based on a preliminary study comparing them with conventional markers. Indices were calculated as a percentage of positive cells by counting tumour cells in the most frequently labelled areas. MCM2, caspase 3 and MCM2/caspase 3 (growth) indices were 45.3 +/- 21.9%, 4.1 +/- 7.1% and 82.9 +/- 104.5, respectively, in pre-RHC specimens and 35.4 +/- 30.8%, 39.2 +/- 34.6% and 5.3 +/- 11.7, respectively, in post-RHC specimens. Response scores showed positive correlation with pre-RHC MCM2 and post-RHC caspase 3 indices, inverse correlation with post-RHC MCM2 and post-RHC growth indices and no correlation with prognosis. Multivariate analysis revealed high pre-RHC MCM2 and high post-RHC growth indices as significant unfavourable prognostic factors. CONCLUSIONS: High proliferative activity in untreated sarcoma may predict good response to neoadjuvant therapy, but poor prognosis, whereas a high growth index, i.e. high proliferation:apoptosis ratio in a post-neoadjuvant therapy tumour specimen may indicate poor response and poor prognosis.

Probing ultrafast ππ*/nπ* internal conversion in organic chromophores via K-edge resonant absorption.

Many photoinduced processes including photosynthesis and human vision happen in organic molecules and involve coupled femtosecond dynamics of nuclei and electrons. Organic molecules with heteroatoms often possess an important excited-state relaxation channel from an optically allowed ππ* to a dark nπ* state. The ππ*/nπ* internal conversion is difficult to investigate, as most spectroscopic methods are not exclusively sensitive to changes in the excited-state electronic structure. Here, we report achieving the required sensitivity by exploiting the element and site specificity of near-edge soft X-ray absorption spectroscopy. As a hole forms in the n orbital during ππ*/nπ* internal conversion, the absorption spectrum at the heteroatom K-edge exhibits an additional resonance. We demonstrate the concept using the nucleobase thymine at the oxygen K-edge, and unambiguously show that ππ*/nπ* internal conversion takes place within (60 ± 30) fs. High-level-coupled cluster calculations confirm the method's impressive electronic structure sensitivity for excited-state investigations.Many photo-induced processes such as photosynthesis occur in organic molecules, but their femtosecond excited-state dynamics are difficult to track. Here, the authors exploit the element and site selectivity of soft X-ray absorption to sensitively follow the ultrafast ππ*/nπ* electronic relaxation of hetero-organic molecules.

In vivo activation and nuclear binding of the AtT-20 mouse pituitary tumor cell glucocorticoid receptor.

AtT-20 mouse pituitary tumor cells were incubated at 25 C with the tritiated glucocorticoids triamcinolone acetonide (9 alpha-fluoro-11 beta, 16 alpha, 17,21-tetrahydroxy-pregna-1, 4-diene-3,20-dione 16,17-acetal with acetone), dexamethasone (9 alpha-fluoro-11 beta, 17,21-trihydroxy-16 alpha-methyl-pregna-1,4-diene-3, 20-dione), prednisolone (11 beta, 17,21-trihydroxypregna-1,4-diene-3,20-dione), and corticosterone (11 beta, 21-hydroxypregn-4-ene-3,20-dione) in order to examine the nuclear binding and glucocorticoid receptor activation produced in vivo. Although the total amounts of intracellular receptor labeled by each steroid were similar, each steroid caused different and characteristic percentages of occupied receptor to be translocated into the nucleus. DEAE chromatography of the nuclear receptor extracted in the presence of sodium molybdate to prevent spontaneous activation showed that, as expected, the nuclear receptor was in the activated form. Activated receptor in the cytosol was determined by DEAE chromatography of cytosol prepared from cells that had been incubated with the various labeled glucocorticoids mentioned above. Total intracellular activated receptor was determined as cytosolic activated receptor plus total nuclear receptor. The results showed that for the four agonists used, the extent of nuclear binding is proportional to the degree of activation and that both of these parameters correlate with steroid-receptor affinity. It was also found that the removal of steroid from the cell incubation medium caused the rapid return of nuclear receptor to the cytosolic compartment in an unactivated form. This reversal was not dependent on protein synthesis. These results are consistent with a model of nuclear binding in which the proportion of steroid-bound receptor that becomes activated is determined by steroid binding affinity. However, the activated receptor partitions between the cytoplasmic and nuclear compartments to the same extent regardless of the steroid used, suggesting that although the percentage of activated receptors is steroid dependent, the nuclear-binding ability of the activated receptor is an intrinsic and constant property of the protein itself.

Hormonal responses to insulin-induced hypoglycemia in man.

Insulin-induced hypoglycemia is a potent stress stimulating ACTH release, but the factors responsible for this ACTH secretion are not known. In this study, several ACTH-stimulating factors, such as CRH, arginine vasopressin (AVP), epinephrine (E), norepinephrine (NE), and dopamine, in addition to ACTH, cortisol, and glucose, were simultaneously measured in plasma before and 15, 30, 60, 90, and 120 min after iv administration of 0.1 U/kg BW regular insulin to seven normal subjects. Insulin administration resulted in significant rises in the mean plasma ACTH level from 4.6 +/- 1.1 (+/- SEM) to 21.6 +/- 4.8 pmol/L at 30 min (P less than 0.01) and in plasma cortisol from 330 +/- 60 to 720 +/- 50 nmol/L at 60 min (P less than 0.01). These increases were preceded by a 41.0 +/- 1.9% (P less than 0.001) fall in blood glucose levels. The mean plasma CRH level rose significantly from 1.0 +/- 0.1 to 1.2 +/- 0.1 pmol/L (P less than 0.01) at 30 min and remained elevated until 120 min. In addition, concomitant and significant rises in plasma AVP levels (basal, 1.5 +/- 0.01; peak, 4.5 +/- 1.1 pmol/L at 30 min; P less than 0.01), E (basal, less than 50; peak, 640 +/- 130 pmol/L at 30 min; P less than 0.01), and NE (basal, 0.07 +/- 0.01; peak, 0.17 +/- 0.03 nmol/L at 60 min; P less than 0.05), but not dopamine, also occurred. These results suggest that multiple ACTH-releasing factors, such as CRH, AVP, E, and NE, are involved in ACTH secretion induced by insulin-induced hypoglycemia in man.

Effect of subcutaneous injection of a long-acting analogue of somatostatin (SMS 201-995) on plasma thyroid-stimulating hormone in normal human subjects.

SMS 201-995 (SMS), a synthetic analogue of somatostatin (SRIF) has been shown to be effective in the treatment of the hypersecretion of hormones such as in acromegaly. However, little is known about the effects of SMS on the secretion of thyroid-stimulating hormone (TSH) in normal subjects. In this study, plasma TSH was determined with a highly sensitive immunoradiometric assay, in addition to the concentration of SMS in plasma and urine with a radioimmunoassay, following subcutaneous injection of 25, 50, 100 micrograms of SMS (4 subjects/dose) or a placebo (6 subjects) to normal male subjects, at 0900 h after an overnight fast. The plasma concentrations of SMS were dose-responsive and the peak levels were 1.61 +/- 0.09, 4.91 +/- 0.30 and 8.52 +/- 1.18 ng/ml, which were observed at 30, 15 and 45 min after the injection of 25, 50 and 100 micrograms of SMS, respectively. Mean plasma disappearance half-time of SMS was estimated to be 110 +/- 3 min. Plasma TSH was suppressed in a dose dependent manner and the suppression lasted for at least 8 hours. At 8 hours after the injection of 25, 50 and 100 micrograms of SMS, the plasma TSH levels were 43.8 +/- 19.4, 33.9 +/- 9.4 and 24.9 +/- 3.2%, respectively, of the basal values. The results suggest that SMS suppresses secretion of TSH from the normal thyrotrophs in man and thus also that attention should be paid to possible hypothyroidism during the long-term treatment of patients such as those with acromegaly with this potent analogue of SRIF.

Diurnal rhythm of plasma immunoreactive corticotropin-releasing factor in normal subjects.

Plasma corticotropin-releasing factor (CRF), corticotropin (ACTH) and cortisol levels were simultaneously determined by radioimmunoassays at 0600 h, 1200 h, 1800 h and 2200 h in six normal subjects, in order to examine whether the diurnal rhythm in plasma CRF exists and how it correlates to the diurnal rhythm in plasma ACTH and cortisol concentration. The highest CRF level was observed at 0600 h (7.0 +/- 1.2 pg/ml) and significantly lower levels (p less than 0.01) at 1800 h (1.7 +/- 0.2 pg/ml) and 2200 h (1.9 +/- 0.4 pg/ml). A clear diurnal rhythm was demonstrated in plasma ACTH and cortisol levels, with the highest values at 0600 h (44.6 +/- 8.1 pg/ml and 15.9 +/- 2.0 micrograms/dl, respectively) and the lowest at 2200 h (12.3 +/- 2.8 pg/ml and 4.6 +/- 1.0 micrograms/ml, respectively). These results suggest that the diurnal rhythm in ACTH and cortisol is under the regulation, at least in part, of the diurnal rhythm in CRF secretion.

Ultrafast X-ray Auger probing of photoexcited molecular dynamics.

Molecules can efficiently and selectively convert light energy into other degrees of freedom. Disentangling the underlying ultrafast motion of electrons and nuclei of the photoexcited molecule presents a challenge to current spectroscopic approaches. Here we explore the photoexcited dynamics of molecules by an interaction with an ultrafast X-ray pulse creating a highly localized core hole that decays via Auger emission. We discover that the Auger spectrum as a function of photoexcitation--X-ray-probe delay contains valuable information about the nuclear and electronic degrees of freedom from an element-specific point of view. For the nucleobase thymine, the oxygen Auger spectrum shifts towards high kinetic energies, resulting from a particular C-O bond stretch in the ππ* photoexcited state. A subsequent shift of the Auger spectrum towards lower kinetic energies displays the electronic relaxation of the initial photoexcited state within 200 fs. Ab-initio simulations reinforce our interpretation and indicate an electronic decay to the nπ* state.

Classical two-slit interference effects in double photoionization of molecular hydrogen at high energies.

Recent experiments on double photoionization of H2 with photon energies between 160 and 240 eV have revealed body-frame angular distributions that suggest classical two-slit interference effects may be present when one electron carries most of the available energy and the second electron is not observed. We report precise quantum mechanical calculations that reproduce the experimental findings. They reveal that the interpretation in terms of classical diffraction is only appropriate at substantially higher photon energies. At the energies considered in the experiment we offer an alternative explanation based on the mixing of two nondiffractive contributions by circularly polarized light.

The Zrc1 is involved in zinc transport system between vacuole and cytosol in Saccharomyces cerevisiae.

The ZRC1 gene encodes a multicopy suppressor of zinc toxicity in Saccharomyces cerevisiae; however, previously we found that the expression of ZRC1 was induced when the intracellular zinc level was decreased. Zrc1 has six putative transmembrane domains and we determined that a Zrc1-GFP fusion protein was localized to the vacuolar membrane. The steady state level of intracellular zinc in a zrc1Delta mutant cultured in the zinc-abundant medium was lower than that in wild type. No distinct difference was observed in the basal activity of glyoxalase I, which is a cytosolic enzyme requiring zinc for catalytic function and is used here as a marker for cytosolic zinc-availability, between wild type and zrc1Delta mutant, although the activity was decreased much greater extent in the zrc1Delta mutant if the cells were exposed to the metal-limited medium. Similarly, the basal expression level of ZRC1-lacZ reporter gene in zrc1Delta mutant was the same as that in wild type; however, the fold of induction of ZRC1-lacZ expression in zrc1Delta mutant under the zinc-limited conditions was higher than that in the wild type. Based on these results, we present a tentative model for the function of Zrc1 as a mechanism to maintain the zinc homeostasis in yeast.

Expression of ZRC1 coding for suppressor of zinc toxicity is induced by zinc-starvation stress in Zap1-dependent fashion in Saccharomyces cerevisiae.

The ZRC1 gene was cloned as a multicopy suppressor of zinc toxicity in Saccharomyces cerevisiae. Zrc1 belongs to CDF (cation diffusion facilitator) family. The transporters belonging to this family are thought to play an important role in metal detoxification. However, we found that cell growth of zrc1Delta mutant was lowered under the metal-limited conditions, which was restored by zinc. The Zap1 transcription factor is crucial for expression of several genes responsive to zinc-starvation stress. The expression of ZRC1 was induced in Zap1-dependent fashion when the intracellular zinc level was decreased and this induction was repressed by zinc. These results imply an important role of Zrc1 in the zinc-starvation stress.

Two unusual cases of a foreign body in the oral cavity caused by eating raw squid.

Foreign bodies are often encountered by otolaryngologists, but the oral cavity is considered a place where foreign bodies are rare because of its structural and functional features. We here present 2 cases with a foreign body in the oral cavity resulting from eating raw squid. In one of these 2 cases endoscopic examination revealed a gastric foreign body. The foreign bodies in the oral cavity were removed using forceps, together with surrounding mucous membrane. These foreign bodies were identified as sperm bulbs and discharging tube of sogittated calamary (Todarodes pacificus Steenstrup). Larva migrans of anisakiasis are to be differentiated from sperm bulbs; it is important to distinguish between the shape and size of the foreign body in our cases. If sperm bulbs are stuck in the oral cavity, it is necessary to remove them completely to ensure that inflammation is prevented. We stress the importance of checking not only anisakiasis but also sperm bulbs in humans who like eating raw squid.

Correlation of the OSR/ZRCI gene product and the intracellular glutathione levels in Saccharomyces cerevisiae.

The OSR (oxidative-stress-resistance) gene was cloned as the gene which enhances resistance against oxidative stress caused by lipid hydroperoxide in Saccharomyces cerevisiae. The nucleotide sequence of the gene was determined and found to be identical with the zinc-resistance-conferring (ZRCI) gene, which was cloned as the gene enhancing the resistance against zinc and cadmium. A knockout mutant of the OSR gene showed increased sensitivity to lipid hydroperoxide. The intracellular glutathione content in the knockout mutant decreased approx. 40% compared with that of wild-type cells, whereas it increased 3-fold in yeast overexpressing the OSR gene. Therefore the OSR/ZRCI gene product seems to regulate the intracellular glutathione content.

Isolation and characteristics of yeasts able to grow at low concentrations of nutrients.

Seven oligotrophic yeasts, which can grow in a 10(4)-fold dilution of malt-yeast-glucose-peptone medium (10(-4) YM), were mainly isolated from soil. These yeasts belong to the Cryptococcaceae. When inoculated at about 10(2) cells/ml in 10(-4) YM, the isolates grew to 1.4 x 10(3)-2.4 x 10(5) cells/ml after 3 days. Some culture collection yeasts fell into three groups according to their growth characteristics in 10(-4) YM, one group showing characteristics of the oligotrophic yeasts. The half-saturation values of uptake by the five isolated oligotrophic yeasts for D-glucose, L-leucine and L-amino acids were 6.0-25.0, 1.7-43.3 and 3.5-21.6 microM, respectively. The oligotrophic yeasts suspended in 10 mM-phosphate buffer (pH 6.0) had high tolerances for starvation, and remained more than 15% viable after 90 days of starvation.

Oxidative stress response in yeast: purification and characterization of glutathione reductase from Hansenula mrakii.

Glutathione reductase was purified from a yeast. Hansenula mrakii IFO 0895, to approximately 3500-fold with 59% activity yield. The enzyme was homogeneous on polyacrylamide gel electrophoresis. The molecular weight of the enzyme was estimated to be 56 kDa by SDS-polyacrylamide gel electrophoresis, and 123 kDa by gel filtration using a calibrated Sephadex G-150 column. The Km values for glutathione disulfide and NADPH were 21.3 microM and 14.3 microM, respectively. The enzyme was most active at pH 7.5, 55 degrees C. The enzyme was stable up to 40 degrees C, and between pHs 4 and 10. The enzyme was inhibited by p-chloromercuribenzoate and metal ions such as Fe3+, Cd2+, Cu2+, and Zn2+.