Single-molecule quantum dot as a Kondo simulator.

Structural flexibility of molecule-based systems is key to realizing the novel functionalities. Tuning the structure in the atomic scale enables us to manipulate the quantum state in the molecule-based system. Here we present the reversible Hamiltonian manipulation in a single-molecule quantum dot consisting of an iron phthalocyanine molecule attached to an Au electrode and a scanning tunnelling microscope tip. We precisely controlled the position of Fe2+ ion in the molecular cage by using the tip, and tuned the Kondo coupling between the molecular spins and the Au electrode. Then, we realized the crossover between the strong-coupling Kondo regime and the weak-coupling regime governed by spin-orbit interaction in the molecule. The results open an avenue to simulate low-energy quantum many-body physics and quantum phase transition through the molecular flexibility.

Accurate ultrasonographic prediction of progesterone concentrations greater than 1 ng/ml in Holstein lactating dairy cows.

To develop an ultrasonographic assay for determining plasma progesterone concentration (P4 ) as < 1 ng/ml or ≥ 1 ng/ml, the corpus luteum (CL) area and P4 were measured in 1094 multiparous Holstein cows. The area-measuring function and frozen images were used to outline and measure CL imaged via ultrasonography, and CL area was estimated as a polygon of a continuation straight line. A significant correlation was found between CL area and P4 (p < 0.001), and this analysis resulted in the following correlation equation: y = -0.35 + 1.02x (r = 0.81). According to the correlation equation, a CL area of 1.3 cm(2) indicated a P4 of 1 ng/ml. Based on this relationship, each animal was categorized into one of six groups, groups differed based on CL area, and the area ranges were as follows: < 1.3 cm(2) (Group A), 1.3-2.2 cm(2) (Group B), 2.3-3.2 cm(2) (Group C), 3.3-4.2 cm(2) (Group D), 4.3-5.2 cm(2) (Group E) and > 5.2 cm(2) (Group F). For each group, the proportion of cows whose P4 was 1 ng/ml or more was 1.5% in Group A, 83.3% in Group B, 76.6% in Group C, 96.6% in Group D, 99.2% in Group E and 100% in Group F. There was a significant difference between Group A and the other five groups, and between Groups B or C and Groups D, E or F (p < 0.005). These results indicate that a functional CL does not exist when the CL area is less than 1.3 cm(2) and that it exists when the CL area is 3.3 cm(2) or more.

Diffuse sclerosing variant of papillary thyroid carcinoma: a study of fine needle aspiration cytology in 20 patients.

BACKGROUND: A diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a rare variant and reports describing the cytological findings are few. PATIENTS AND METHODS: We studied 24 cytological samples from thyroid fine needle aspirates of 20 patients with DSV-PTC. The specimens were taken from 14 non-nodular lesions and 10 nodules. RESULTS: All aspirates taken from both non-nodular lesions and nodules had sufficient cellularity. The carcinoma cells frequently (70-100%) appeared as solid cell balls and hollow balls, and showed a hobnail pattern, squamous differentiation, septate cytoplasmic vacuoles and large unilocular vacuoles. Most of the carcinoma cells seem to be taken from the lumen of dilated lymph vessels. Ground glass nuclear chromatin, intranuclear cytoplasmic inclusions and grooved nuclei were infrequent (50% or less). In the background, a large number of lymphocytes and abundant psammoma bodies were almost always seen. CONCLUSIONS: Cytological findings of DSV-PTC are as follows: (1) solid cell balls and/or hollow balls containing lymphocytes; (2) hobnail cells; (3) septate cytoplasmic vacuoles; (4) large unilocular vacuoles; (5) squamous differentiation; (6) abundant psammoma bodies; (7) lymphocytic background; and (8) the absence or relative lack of characteristic nuclear features of papillary carcinoma. When DSV-PTC is suspected by ultrasound examination, the aspiration cytology from a non-nodular area of the thyroid can led us to the diagnosis of the variant.

Intravenous injection of neural progenitor cells improved depression-like behavior after cerebral ischemia.

Poststroke depression (PSD) occurs in approximately one-third of stroke survivors and is one of the serious sequelae of stroke. The onset of PSD causes delayed functional recovery by rehabilitation and also increases cognitive impairment. However, appropriate strategies for the therapy against ischemia-induced depression-like behaviors still remain to be developed. Such behaviors have been associated with a reduced level of brain-derived neurotrophic factor (BDNF). In addition, accumulating evidence indicates the ability of stem cells to improve cerebral ischemia-induced brain injuries. However, it remains to be clarified as to the effect of neural progenitor cells (NPCs) on PSD and the association between BDNF level and PSD. Using NPCs, we investigated the effect of intravenous injection of NPCs on PSD. We showed that injection of NPCs improved ischemia-induced depression-like behaviors in the forced-swimming test and sucrose preference test without having any effect on the viable area between vehicle- and NPC-injected ischemic rats. The injection of NPCs prevented the decrease in the level of BDNF in the ipsilateral hemisphere. The levels of phosphorylated CREB, ERK and Akt, which have been implicated in events downstream of BDNF signaling, were also decreased after cerebral ischemia. NPC injection inhibited these decreases in the phosphorylation of CREB and ERK, but not that of Akt. Our findings provide evidence that injection of NPCs may have therapeutic potential for the improvement of depression-like behaviors after cerebral ischemia and that these effects might be associated with restoring BDNF-ERK-CREB signaling.

Preservation of mitochondrial function may contribute to cardioprotective effects of Na+/Ca2+ exchanger inhibitors in ischaemic/reperfused rat hearts.

BACKGROUND AND PURPOSE: Na+/Ca2+ exchanger (NCX) inhibitors are known to attenuate myocardial reperfusion injury. However, the exact mechanisms for the cardioprotection remain unclear. The present study was undertaken to examine the mechanism underlying the cardioprotection by NCX inhibitors against ischaemia/reperfusion injury. EXPERIMENTAL APPROACH: Isolated rat hearts were subjected to 35-min ischaemia/60-min reperfusion or 20-min ischaemia/60-min reperfusion. NCX inhibitors (3-30 microM KB-R7943 (KBR) or 0.3-1 microM SEA0400 (SEA)) were given for 5 min prior to ischaemia (pre-ischaemic treatment) or for 10 min after the onset of reperfusion (post-ischaemic treatment). KEY RESULTS: With 35-min ischaemia/60-min reperfusion, pre- or post-ischaemic treatment with KBR or SEA neither enhanced post-ischaemic contractile recovery nor attenuated ischaemia- or reperfusion-induced Na+ accumulation and damage to mitochondrial respiratory function. With the milder model (20-min ischaemia/reperfusion), pre- or post-ischaemic treatment with 10 microM KBR or 1 microM SEA significantly enhanced the post-ischaemic contractile recovery, associated with reductions in reperfusion-induced Ca2+ accumulation, damage to mitochondrial function, and decrease in myocardial high-energy phosphates. Furthermore, Na+ influx to mitochondria in vitro was enhanced by increased concentrations of NaCl. KBR (10 microM) and 1 microM SEA partially decreased the Na+ influx. CONCLUSIONS AND IMPLICATIONS: The NCX inhibitors exerted cardioprotective effects during relatively mild ischaemia. The mechanism may be attributable to prevention of mitochondrial damage, possibly mediated by attenuation of Na+ overload in cardiac mitochondria during ischaemia and/or Ca2+ overload via the reverse mode of NCX during reperfusion.

Inhibitor of vascular endothelial growth factor receptor tyrosine kinase attenuates cellular proliferation and differentiation to mature neurons in the hippocampal dentate gyrus after transient forebrain ischemia in the adult rat.

Neurogenesis in the adult hippocampal dentate gyrus is promoted by transient forebrain ischemia. The mechanism responsible for this ischemia-induced neurogenesis, however, remains to be determined. It has been suggested that there may be a close relationship between neurogenesis and the expression of vascular endothelial growth factor, an angiogenic factor. The purpose of the present study was to examine the relationship between vascular endothelial growth factor and cell proliferation in the dentate gyrus after transient forebrain ischemia. The mRNA expression of vascular endothelial growth factor was increased in the dentate gyrus on day 1 after ischemia. Immunohistochemical analysis on day 9 after ischemia, when a significant increase in cell proliferation was seen, showed that the cerebral vessel space in the subgranular zone of the dentate gyrus had not been affected by the ischemia. Neither were the vascular densities on days 1 and 3 after ischemia altered compared with those of non-operated naïve control rats. Furthermore, the distance from the center of the proliferative cells to the nearest cerebral vessel of ischemic rats was comparable to that of the sham-operated rats. We demonstrated that transient forebrain ischemia-induced cell proliferation and differentiation to mature neurons in the hippocampal dentate gyrus was attenuated by the i.c.v. administration of a vascular endothelial growth factor receptor tyrosine kinase inhibitor. These results suggest that vascular endothelial growth factor receptor at the early period of reperfusion may contribute to neurogenesis rather than to angiogenesis in the hippocampal dentate gyrus.

Long-term follow-up study of gastric adenoma/dysplasia.

BACKGROUND AND STUDY AIMS: The natural course of gastric adenoma/dysplasia, regarded as a precancerous lesion, is still uncertain. PATIENTS AND METHODS: From 1976 to 2000, 48 lesions in 43 patients (37 men, six women; mean age 59 years) were diagnosed as having gastric adenoma/dysplasia based on their first biopsies. These lesions were followed for a median of 4.7 years (mean 6 years, range 3-18 years) to evaluate the risk of progression to invasive carcinoma. Retrospectively, histological diagnoses of the biopsy and resected specimens were reclassified according to the Vienna classification of gastrointestinal epithelial neoplasia, and macroscopic changes were evaluated. RESULTS: The diagnosis at first biopsy of the 48 lesions was low-grade adenoma/dysplasia (LGD; category 3) in 38 cases and high-grade adenoma/dysplasia (HGD; category 4) in 10 cases. Ninety-seven percent of the LGD (category 3) lesions (37 of 38) showed no histological changes during the follow-up period; the remaining lesion progressed to noninvasive carcinoma (category 4). Macroscopically, 84 % (32 of 38) of the LGD lesions (category 3) showed no remarkable changes in size, while 11 % (four of 38) shrank and 5 % (two of 38) grew larger. Nine of the 10 HGD lesions (category 4) remained histologically unchanged, while the other progressed to intramucosal carcinoma (category 5). Macroscopically, four of the 10 HGD lesions (category 4) (40 %) showed no remarkable changes in size, while the remaining six (60 %) grew larger. CONCLUSIONS: LGD lesions (category 3) have a quite low risk of progressing to HGD or noninvasive carcinoma (category 4), and were never observed to progress to invasive carcinoma (category 5). HGD lesions (category 4) occasionally progressed to intramucosal carcinoma (category 5), with no instance of invasion into the submucosa or beyond.

[Reoperation for double-outlet right ventricle (SDL type) following the Rastelli procedure: report of a case].

The relationship of the conduit to the sternum is crucial in the Rastelli operation. Right-sided conduits are more greatly affected by sternal compression than left, since the position of the right ventricular infundibulum is more anterior. A 37-year-old woman developed right ventricular outflow tract obstruction, left ventricular outflow tract obstruction, and aortic valve regurgitation secondary to infective endocarditis 15 years after Rastelli repair for double-outlet right ventricle (SDL). We enlarged the ventricular septal defect, performed intraventricular rerouting and aortic valve replacement, and reconstructed the valved conduit using a Carpentier-Edwards conduit. The old conduit was densely adherent to the sternum. Subaortic stenosis was caused by a narrow fibromuscular ridge associated with a bulge of the underlying septal muscle. The patient's recovery was uneventful. She is alive and well without any complaints 1 year after surgery.

NRAMP1 polymorphisms, susceptibility and clinical features of tuberculosis.

OBJECTIVES: To study whether NRAMP1 gene polymorphisms in a Japanese population affect susceptibility to tuberculosis and clinical features of tuberculosis. METHODS: Polymerase chain reaction and restriction fragment-length polymorphism analyses were used to type NRAMP1 polymorphisms in 95 patients with pulmonary tuberculosis and 90 controls. Clinical features of patients also were investigated. RESULTS: No association was seen between susceptibility to tuberculosis and NRAMP1 polymorphisms. Patients with the D543N A allele were significantly more likely than others to develop a cavitary lesion; by logistic regression analysis with adjustment for gender, age, and presence of diabetes, the odds ratio in patients with an A allele was 5.16 (95% confidence interval, 1.30-20.45). CONCLUSIONS: Genetic variation in the human NRAMP1 gene may be associated with cavitation in patients with tuberculosis.

Impairment of cerebral cAMP-mediated signal transduction system and of spatial memory function after microsphere embolism in rats.

The transcription factor cAMP-responsive element binding protein (CREB) has been implicated in synaptic plasticity and memory. The purpose of the present study was to characterize alterations in the cAMP/protein kinase A (PKA)/CREB system after sustained cerebral ischemia. Sustained cerebral ischemia was induced by injection of 900 microspheres (48 microm in diameter) into the right (ipsilateral) hemisphere of rats. Alterations in the CREB, PKA, and cAMP levels in the cerebral cortex and hippocampus were examined up to 7 days after microsphere embolism. Immunoblotting analysis showed a decrease in the immunoreactivity of phosphorylated CREB (pCREB) in the ipsilateral hemisphere on the third day after microsphere embolism, whereas that of the total CREB was not altered. An electrophoretic gel mobility shift assay showed a decrease in the cAMP response element (CRE)-DNA binding activity of CREB in the ischemic region on the third day after the microsphere embolism. Cytosolic PKA C beta in the ipsilateral hemisphere was selectively decreased on the first day after the microsphere embolism, whereas the levels of another catalytic subunit, C alpha, and a regulatory subunit, RII alpha, were not altered. Immunoreactivity of the PKA catalytic subunit C alpha in the nucleus of the ipsilateral hemisphere was decreased on the third day after the embolism. The decreases in the pCREB, CRE-DNA binding activity, and PKA C alpha and C beta levels lasted at least up to 7 days after the operation. A decrease in the cAMP content was also seen in the ipsilateral hemisphere throughout the experiment. Furthermore, microsphere embolized rats showed prolongation of the escape latency in the water maze task determined on the seventh to ninth day after the operation. Our results suggest that sustained cerebral ischemia may impair the phosphorylation and CRE-DNA binding activity of CREB and that these effects may be one of the possible causes for learning and memory dysfunction.

Nonrandom X chromosome inactivation in mouse embryos carrying Searle's T(X;16)16H translocation visualized using X-linked LACZ and GFP transgenes.

Only the morphologically normal X chromosome is inactivated in female mice heterozygous for Searle's X-autosome translocation, T(X;16)16H. Here we performed a visual study of the primary and secondary events that culminate in the completely nonrandom inactivation of the X in female embryos having this translocation. The data we have obtained so far indicate that the initial choice of the future inactive X chromosome is biased, with the degree of skewing somewhere between 70:30% and 90:10% in favor of the morphologically normal X chromosome. The majority of genetically unbalanced cells that inactivate a translocated X chromosome are quickly eliminated from the embryo proper by E8.5, although the survival of such cells is sporadically observed thereafter. The initial nonrandom choice demonstrated in this study supports the contention that the T(X;16)16H translocation disrupts one of the loci involved in the randomness of the choice of the future inactive X chromosome. Although the HMG-LACZ transgene in H253 stock mice is an excellent marker of X chromosome inactivation, the present study suggests that it is infrequently de-repressed on the inactive X chromosome.

The role of X-chromosome inactivation in the manifestation of Rett syndrome.

X-chromosome inactivation (XCI) is random in the majority of patients with classical Rett syndrome (RTT). Preferential inactivation of the X chromosome with the mutated MECP2 gene is found in mildly symptomatic or asymptomatic carrier females. These findings lead to a hypothesis that random XCI is causally involved in the pathogenesis of RTT in heterozygous females. It is the cluster of functionally defective nerve cells lacking fully functional MeCP2 generated by inactivation of normal MECP2 allele that causes the wide spectrum of RTT symptoms. Thus, RTT is a rare human disease manifestation which is triggered most probably by random XCI.

Repair of double-chambered right ventricle: surgical results and long-term follow-up.

BACKGROUND: We reviewed the outcomes of double-chambered right ventricle repair. METHODS: Between 1969 and 1998, 40 patients underwent surgical repair of a double-chamber right ventricle. The patients ranged in age from 3 months to 52 years (mean, 12.8 +/- 11.6 years). Right ventricular outflow tract pressure gradients were from 20 to 170 mm Hg (mean, 65.0 +/- 38.5 mm Hg) An associated ventricular septal defect was present in 27 patients (67.5%). Four patients were older than 30 years of age. RESULTS: There were no hospital or late deaths. Mean postsurgical follow-up was 16.5 +/- 8.9 years (range, 2.5 to 31 years). No patient required further surgery to relieve obstruction of right ventricular outflow tract. CONCLUSIONS: Surgical repair of a double-chambered right ventricle yields excellent hemodynamic and functional results over both the short and long term.

Aneurysmal change in an internal mammary artery-pulmonary artery fistula.

We treated a rare case of aneurysm of the internal mammary artery-pulmonary artery fistula in a 32-year-old woman with unrepaired pulmonary atresia and ventricular septal defect. This aneurysm communicated with the pulmonary artery system through an aortopulmonary collateral. Aneurysmectomy was successful.

A reoperation for anomalous origin of right pulmonary artery: report of a case.

A reoperation to upsize the conduit placed at infancy for the repair of an anomalous origin of the right pulmonary artery (AORPA) was successfully performed in an 8-year-old girl because of an elevated right ventricular pressure and a reduced right pulmonary blood flow. Although primary direct anastomosis is essential for AORPA, one should not hesitate to perform a conduit repair (interposition with a tube prosthesis) on an infant with AORPA whose right pulmonary artery is distant from the main pulmonary artery, because a reoperation can safely be performed even in cases where the conduit is relatively narrow as the patient grows. This is the first report of a reoperation, including a complete replacement of the conduit, after an initial conduit repair for AORPA.

Magnetic domains in nanostructured media studied with M-TXM.

Combining X-ray magnetic circular dichroism (X-MCD) with a transmission X-ray microscope (TXM) allows to image element-specifically magnetic domain structures with 25nm lateral resolution. Both in-plane and out-of-plane systems can be studied in applied magnetic fields. Thus field-dependent parameters, as individual nucleation fields in magnetic nanostructures can be deduced and related to morphology. Images of thermomagnetically written bits in magneto-optical TbFeCo media proof the reliability of the writing process and the importance of an exact thermal design of the systems. Domains observed at corresponding Co L edges proof the chemical sensitivity of M-TXM and its potential to image few monolayer systems.

[Long-term results of Rygg's monocusp ventricular outflow patch for the reconstruction of right ventricular outflow tract in tetralogy of Fallot].

Thirty surviving patients after corrective surgery for tetralogy of Fallot with right ventricular outflow tract reconstruction (RVOTR) using monocusp ventricular outflow patch (MVOP) were reviewed retrospectively to determine the long-term results. The age at operation ranged from 2 to 55 years with a mean of 19 years, and follow-up extended to 18.2 years (cumulative: 345.4 patient-year). There were 4 late deaths (1.2% per patient-year), and the cumulative survival rate was 85.3% at 18 years after the corrective surgery. Eight patients (2.3% per patient-year) required intracardiac reoperations mostly resulted from problems after RVOTR with MVOP, such as recurrent stenosis of right ventricular outflow tract (3 cases) or pulmonary valvular incompetence (4 cases). In addition, one patient underwent balloon angioplasty for the recurrent stenosis located in the distal end of MVOP. Freedom from surgical or catheter reintervention for the MVOP-related complication was 60.6% at 18 years after the corrective surgery. MVOP caused compression of the pulmonary artery at the distal end of the anastomosis and reoperation in a younger patients quite early after the corrective surgery. Like other transannular patches, tissue failure and degeneration of MVOP were inevitable, and resulted in severe pulmonary valvular incompetence that required the valve replacement in 4 patients (1.3% per patient-year). Freedom from pulmonary valve replacement was 71.2% at 18 years after the corrective surgery. As long-term results, our experiences emphasize the need for an innovative transannular patch that possesses significantly better long-term durability.

Control of Xist expression for imprinted and random X chromosome inactivation in mice.

Applying RNA fluorescence in situ hybridization to parthenogenetic embryos with two maternally derived X (X(M)) chromosomes and embryos with X chromosome aneuploidy such as X(P)0 (X(P), paternally derived X chromosome), X(M)X(M)X(P) and X(M)X(M)Y, we studied the control of Xist/Tsix expression for silencing the entire X chromosome in mice. The data show that the paternally derived Xist allele is highly expressed in every cell of the embryo from the 4-cell stage onward, irrespective of the number of X chromosomes in a diploid cell. The high level of Xist transcription is maintained in non-epiblast cells culminating in X(P)-inactivation, whereas in X(P)0 embryos it is terminated by the blastocyst stage, probably as a result of counting the number of X chromosomes in a cell occurring at the morula/blastocyst stage. Xist is also down-regulated in epiblast cells of X(M)X(P) and X(M)X(M)X(P) embryos to make X-inactivation random. In epiblast cells, Xist seems to be up-regulated after counting and random choice of the future inactive X chromosome(s). Although the maternal Xist allele is never activated in fertilized embryos before implantation, some parthenogenetic embryos show Xist up-regulation in a proportion of cells. These and other data reported earlier suggest that imprinted X-inactivation in non-epiblast tissues of rodents had been derived from the random X-inactivation system.

Native valve salvage for post-traumatic tricuspid regurgitation.

We describe two cases of successful management by native valve salvage of an uncommon tricuspid valve regurgitation following blunt chest trauma. The two patients were diagnosed 13 years and six years, respectively, after the trauma. In both cases, tricuspid valvular insufficiency was caused by anterior leaflet prolapse due to chordal and papillary muscle rupture associated with annular dilatation. Operative repair with implantation of artificial chordae, papillary muscle reinsertion and ring annuloplasty resulted in complete recovery. The need for increased awareness of this lesion in patients suffering blunt chest trauma is emphasized, and the relevant literature reviewed.