First Direct Mass Measurements of Nuclides around Z=100 with a Multireflection Time-of-Flight Mass Spectrograph.

The masses of ^{246}Es, ^{251}Fm, and the transfermium nuclei ^{249-252}Md and ^{254}No, produced by hot- and cold-fusion reactions, in the vicinity of the deformed N=152 neutron shell closure, have been directly measured using a multireflection time-of-flight mass spectrograph. The masses of ^{246}Es and ^{249,250,252}Md were measured for the first time. Using the masses of ^{249,250}Md as anchor points for α decay chains, the masses of heavier nuclei, up to ^{261}Bh and ^{266}Mt, were determined. These new masses were compared with theoretical global mass models and demonstrated to be in good agreement with macroscopic-microscopic models in this region. The empirical shell gap parameter δ_{2n} derived from three isotopic masses was updated with the new masses and corroborates the existence of the deformed N=152 neutron shell closure for Md and Lr.

Breakthrough in purification of fossil pollen for dating of sediments by a new large-particle on-chip sorter.

Particle sorting is a fundamental method in various fields of medical and biological research. However, existing sorting applications are not capable for high-throughput sorting of large-size (>100 micrometers) particles. Here, we present a novel on-chip sorting method using traveling vortices generated by on-demand microjet flows, which locally exceed laminar flow condition, allowing for high-throughput sorting (5 kilohertz) with a record-wide sorting area of 520 micrometers. Using an activation system based on fluorescence detection, the method successfully sorted 160-micrometer microbeads and purified fossil pollen (maximum dimension around 170 micrometers) from lake sediments. Radiocarbon dates of sorting-derived fossil pollen concentrates proved accurate, demonstrating the method's ability to enhance building chronologies for paleoenvironmental records from sedimentary archives. The method is capable to cover urgent needs for high-throughput large-particle sorting in genomics, metabolomics, and regenerative medicine and opens up new opportunities for the use of pollen and other microfossils in geochronology, paleoecology, and paleoclimatology.

Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors.

Osteoclasts are terminally differentiated cells derived from hematopoietic stem cells. However, how their precursor cells diverge from macrophagic lineages is not known. We have identified early and late stages of osteoclastogenesis, in which precursor cells sequentially express c-Fms followed by receptor activator of nuclear factor kappaB (RANK), and have demonstrated that RANK expression in early-stage of precursor cells (c-Fms(+)RANK(-)) was stimulated by macrophage colony-stimulating factor (M-CSF). Although M-CSF and RANKL (ligand) induced commitment of late-stage precursor cells (c-Fms(+)RANK(+)) into osteoclasts, even late-stage precursors have the potential to differentiate into macrophages without RANKL. Pretreatment of precursors with M-CSF and delayed addition of RANKL showed that timing of RANK expression and subsequent binding of RANKL are critical for osteoclastogenesis. Thus, the RANK-RANKL system determines the osteoclast differentiation of bipotential precursors in the default pathway of macrophagic differentiation.

Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice.

The cellular components of the hematopoietic stem cell niche have been gradually identified. However, the niche for malignant hematopoiesis remains to be elucidated. Here, using human leukemia cells, which could be transplanted to immunodeficient mice, we studied the in vivo homing, proliferation and survival sites by immunohistopathology, compared with the corresponding sites for cord blood CD34(+) (CBCD34(+)) cells. The human leukemia cells initially localized on the surface of osteoblasts in the epiphysial region, and expanded to the inner vascular and diaphysial regions within 4 weeks. The percentage of CD34(+) leukemia cells in the bone marrow was transiently increased up to 50%. In vivo 5-bromo-2'-deoxyuridine labeling revealed that the epiphysis was the most active site for leukemia cell proliferation. CBCD34(+) cells showed the similar pattern of homing and proliferation to leukemia cells. After high-dose administration of cytosine-1-beta-D-arabinofuranoside, residual leukemia cells were localized in the perivascular endothelium as well as in contact with the trabecular endosteum. These findings suggest that xenotransplantation into immunodeficient mice provides a useful model to study the leukemia niche.

Macrophage-stimulating protein (MSP) and its receptor, RON, stimulate human osteoclast activity but not proliferation: effect of MSP distinct from that of hepatocyte growth factor.

Stem cell-derived tyrosine kinase (STK) is a member of the hepatocyte growth factor (HGF) receptor family. The ligand for STK, macrophage-stimulating protein (MSP), is a serum protein activated by members of the coagulation cascade. The RON gene is a human homolog of the murine STK. In this study we examined the role of MSP-RON in the signal pathway of human osteoclasts. Using anti-RON antibody, we detected RON expressed in multinucleated osteoclast-like cells (OCLs) formed in cultures of human bone marrow cells. To determine bone resorption, we placed OCLs on thin films of ceramic calcium phosphate formed on quartz plate-coated slides (Millenium Biologix) and measured pit formation. MSP stimulated pit formation by OCLs in a dose-dependent manner. MSP (50 ng/mL) caused a fourfold increase in pit area compared with the control. Furthermore, we examined the effects of MSP and HGF on OCL formation by purified populations of hematopoietic progenitors. OCLs were phenotypically identified by their cross-reactivity with 23c6, a monoclonal antibody that preferentially binds to osteoclasts. HGF (50 ng/mL) stimulated the differentiation of progenitors to 23c6-positive OCLs but did not enhance bone absorption. In contrast, MSP did not affect proliferation of osteoclast precursors but stimulated bone resorption by OCLs. We conclude that the MSP signal transduction pathway plays a role in bone resorption that is distinct from that of HGF.

Presence of dopamine DA-1 receptors in human decidua.

To evaluate the role of dopamine in human parturition, we studied the presence of dopamine receptors in human decidua obtained immediately after delivery, using a radiolabelled receptor assay. [3H]SCH23390, a dopamine DA-1 receptor ligand was used to identify and characterize the DA-1 receptor. Scatchard analysis of our saturation experiments revealed one class of high-affinity binding sites. The equilibrium dissociation constant (Kd) for binding of [3H]SCH23390 to decidual DA-1 receptors was 1.87 +/- 0.16 nM (mean +/- s.d. n = 3) at 30 degrees C. The maximum binding capacity (Bmax) was 79.0 +/- 15.4 fmol/mg protein at 30 degrees C. The specificity of DA-1 receptor binding was inhibited by SCH23390 (a DA-1 antagonist), SKF38393 (a DA-1 agonist) and dopamine with the inhibitory constants (Ki) of 5.82 +/- 2.27 nM (mean +/- s.d., n = 3), 45.6 +/- 30.5 nM (mean +/- s.d. n = 3) and 2.86 +/- 1.02 microM (mean +/- s.d., n = 3) respectively. However, (+/-)-sulpiride (a DA-2 antagonist) and (-)-propranolol (a beta-adrenergic antagonist) were without effect. The specific binding of [3H]spiperone (a DA-2 receptor ligand) was not detected. We previously reported that in vitro the human decidual tissues produce significant amounts of prostaglandins in the presence of dopamine. We postulate that dopamine regulates the production of prostaglandin in human decidua via DA-1 receptors.

Enhanced mucosal expression of interleukin-6 mRNA but not of interleukin-8 mRNA at the margin of gastric ulcer in Helicobacter pylori-positive gastritis.

To elucidate the role of interleukin (IL)-6 and IL-8 in the pathogenesis of gastric ulcer in Helicobacter pylori-positive gastritis, in situ hybridization using digoxigenin-labeled cDNA probes for both cytokines was performed. Immunogold silver staining was added to further improve the sensitivity of this non-radioactive hybridization. The biopsy specimens were taken from eight patients with active gastric ulcer before treatment, in all of whom H. pylori was positive. Macrophages (the putative producers of these cytokines) were determined by immunohistochemistry using anti-CD68 monoclonal antibodies (KP-1). IL-6 mRNA was most abundantly expressed in the epithelium and in the infiltrating cells in tissue adjacent to gastric ulcer. Quantitative analysis disclosed a significant increase in cells positive for IL-6 mRNA near the ulcer margin compared to cells in the surrounding tissue. In contrast, cells positive for IL-8 mRNA were observed in equal proportions and evenly in the epithelium and over the entire layer of the gastric mucosa regardless of the presence of gastric ulcer. The majority of infiltrating cells positive for both IL-6 and IL-8 mRNA were thought to be macrophages because of their morphologic features and their immunohistochemical reactivity to CD68. These findings strongly suggest that IL-6 is overexpressed at the margin of gastric ulcer in H. pylori-positive gastritis.

Effects of VEGF on Ca(2+)-transient in cultured lymphatic endothelial cells and mechanical activity of isolated lymph vessels.

We investigated the effects of vascular endothelial growth factor (VEGF(165)) on [Ca(2+)](i)-transient in cultured lymphatic endothelial cells (LEC) and mechanical activity of isolated dog thoracic ducts. VEGF (0.1-10 ng/ml) caused a dose-dependent increase of the [Ca(2+)](i) in LEC. Pretreatment with 10(-5) M genistein or 5x10(-6) M herbimycin A produced a significant reduction of the VEGF-induced [Ca(2+)](i)-transient. In the presence of 10(-6) M thapsigargin, VEGF caused no significant effect on the [Ca(2+)](i)-transient. Pretreatment with Ca(2+)-free solution containing 0.1 mM EGTA produced no significant effect on the peak increase of [Ca(2+)](i) induced by 0.1 or 10 ng/ml VEGF, but significantly depressed the sustained part of [Ca(2+)](i) observed at the higher concentration of VEGF. The VEGF (0.1-10 ng/ml) caused a significant dilation of the isolated lymph vessels with intact endothelium, which were precontracted with U46,619. The 10 ng/ml VEGF-induced dilation was significantly reduced by 3 x 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME). The action of L-NAME was inhibited by the simultaneous application of 10(-3) M L-arginine. Mechanical rubbing of the endothelium also caused significant inhibition of the VEGF-induced dilation. The findings suggest that VEGF(165) may activate the receptor-related tyrosine kinase and cause the release of Ca(2+) from the inositol 1,4, 5-triphosphate-sensitive intracellular Ca(2+) stores in LEC. VEGF(165) also produces endothelium-dependent nitric oxide-mediated dilation of the precontracted isolated lymph vessels.

The relation between mercury levels in brain and blood or cerebrospinal fluid (CSF) after mercury exposure.

Rabbits were exposed to elemental mercury (Hg degrees) vapor, methyl mercury (MeHg) and HgCl2 respectively, and the relationship of mercury concentration in brain to that in blood or cerebrospinal fluid (CSF) was investigated after the termination of exposure. At one day post-exposure, the ratio of mercury concentration in brain (microgram Hg/g) to that in blood (microgram Hg/g) was approximately 10.0 in Hg degrees vapor, 0.6 in HgCl2 and 3.0 in MeHg. The ratio for Hg degrees vapor was about 10 times higher than that for HgCl2. In rabbits exposed to Hg degrees vapor, the ratios of mercury concentration in blood to brain or CSF to brain at 1 day and 20 days after the termination of exposure were compared. The blood to brain ratio showed a decrease to about 1/10 after 20 days, and the CSF to brain ratio, a decrease of about 1/2. The results obtained seems to suggest that mercury is eliminated from the blood and CSF more rapidly than from the brain. In the case of rabbits administrated MeHg, the ratio of mercury concentration in blood to that in brain was almost unchanged at both 1 day and 20 days after the termination of exposure. There did not seem to be any differences in the rates of elimination from blood and brain. The elimination of mercury from CSF was more rapid than from brain because the ratio between the mercury concentration of CSF to that of brain showed a decrease to about 1/3 after 20 days.

Excretion of tetramethyllead, trimethyllead, dimethyllead and inorganic lead after injection of tetramethyllead to rabbits.

Rabbits were divided to groups of 3, and injected either 9.9 mg of tetramethyllead (Me4Pb)/kg of body weight (7.7 mg Pb/kg) or 39.7 mg/kg (30.8 mg Pb/kg) into the ear vein once only, respectively, and urinary and fecal excretions of lead were studied for chemical species and total lead during the following 7 days. In the group injected 9.9 mg/kg, the urinary total lead excretion was composed of about 73% dimethyllead (Me2Pb2+), about 19% trimethyllead (Me3Pb+), about 6% inorganic lead (Pb2+), and about 2% Me4Pb on the day following the injection, and 100% Me3Pb+ 7 days after the injection. In the group injected 39.7 mg/kg, the urinary total lead excretion was composed of about 67% Me2Pb2+, about 14% Me3Pb+, about 17% Pb2+, and about 2% Me4Pb on the day following the injection, and about 8% Me2Pb2+, about 74% Me3Pb+, about 17% Pb2+, and about 1% Me4Pb 7 days after the injection. In both groups, the fecal total lead excretion during 7 days after the injection was entirely composed of Pb2+. During the 7 days, 1-3% of either administered dose was excreted in the urine, and 7-19% in the feces. The urinary total lead excretion in the rabbits injected Me4Pb was similar to that in the rabbits injected tetraethyllead, but the fecal total lead excretion in the former was extremely smaller. This extremely small fecal excretion of total lead appeared to have resulted from the less elimination of lead into the bile of Me4Pb-injected rabbits.

Blood and urinary levels of metals (Pb, Cr, Cd, Mn, Sb, Co and Cu) in cloisonne workers.

Blood and urine samples from cloisonne ware workers were assayed for Pb, Cr, Cd, Mn, Sb, Co and Cu for biological monitoring. Mean blood Pb levels were 47.8 +/- 27.3 micrograms/dl (111-13.3 micrograms/dl) for 49 cloisonne glaze workers, and 0.97 +/- 0.47 microgram/dl (2.4-0.6 microgram/dl) for 62 normal subjects. There was a distinct difference between the 2 groups, and slight differences (p < 0.01) in mean Cr, Cd and Mn levels. There was a distinct difference in mean urinary Pb level between the 2 groups, and slight differences (p < 0.01) in mean Cr, Cd and Mn levels. The correlation coefficient, r, between blood Pb and Cd levels was 0.631 (p < 0.01) for 132 subjects consisting of cloisonne ware workers and normal subjects. r between blood Pb and blood Cr levels was 0.501 (p < 0.01), and that between blood and urinary Pb levels, 0.794 (p < 0.01). The above assays showed that glaze workers at cloisonne plants suffer severe exposure to lead and slight exposure to Cd and Cr.

Excretion of triethyllead, diethyllead and inorganic lead in rabbits after injection of triethyl neopentoxy lead.

Triethyl neopentoxy lead (TEneoPOL: (C2H5)3Pb [OCH2C(CH3)3] liquid) was administered to rabbits in a single dose of 10 mg/kg body weight (5.4 mg Pb/kg body weight), and the urinary and fecal excretions of lead were measured to determine the fate of this triethyllead derivative. About 4% of the administered amount of was excreted into the urine during the 7 days after the injection; and about 68%, into the feces. In other words, the fecal excretion of total lead was about 17 times as great as the urinary excretion. About 85% of the urinary excretion of total lead was composed of diethyllead (Et2Pb2+), and about 92% of the fecal excretion consisted of inorganic lead (Pb2+). The major chemical species of lead excreted in the urine was Et2Pb2+, while the major species excreted in the feces was Pb2+. These results were similar to those of administration of tetraethyllead (Et4Pb) to rabbits. One of the 7 rabbits died on the day following the injection, and TEneoPOL, a triethyllead derivative, proved to be no less toxic than Et4Pb. However, this compound is immediately hydrolyzed by the ambient moisture to form a white solid compound, so that it is not accompanied by as great a risk of airway exposure as Et4Pb.

[Home hospice care at a clinic].

For the people who want to stay at home until their last day, the primary doctor and clinic where they were diagnosed will be the most reliable supports. We have been operating a 19 bed clinic since 1996. In these three years, we have established what we call a "combination palliative care system." A team composed of two doctors, 13 nurses, 3 care aids, a social worker, and a counselor provides home care services as well as outpatient and inpatient care. From April, 1998 to March, 1999, 59 patients died of cancer. Among them, 25 patients died at home. Their primary cancers were lung (7), colon (3), pancreatic (2), breast (2), ovarian (2), brain (1), stomach (1), hepatoma (1), neck (1) and others. First of all, sufficient consultation with patients and family makes this care successful. Through this, the patient can choose his style of care. The whole staff is involved in this care in turn, so that all of us become acquainted with each patient. Home care includes: 1) medical and nursing service available 24 hours a day, 2) activation of social resources for the support of the patient user, 3) constructive cooperation with relevant institutions, 4) relieving the patient's physical and mental suffering, 5) aroma therapy, oil massage, hair cuts and music therapy, and 6) support by volunteers. In this way, as a neighborhood clinic, the combination palliative care system is valuable.

[Home palliative care of brain tumor patients from our clinic].

This study investigated whether or not home palliative care of brain tumor patients was possible and various ideas for accomplishing this, over the 2 1/2 years since our clinic was opened. There were 22 patients, aged 42-72 years, comprising 7 cases of glioblastoma, 14 cases of metastatic brain tumor, and 1 case of unknown origin. The control of intracranial hypertension and attacks of convulsion was possible with oral medication or suppositories, but not injection. The prognosis of cancer patients which changed home care showed no remarkable changes, and the home care rate was 53%. Malignant brain tumor patients were able to enjoy time with their families at home during the terminal stage, and die with dignity.

In vitro measurement of tissue integrity during saccular aneurysm embolizations for simulator-based training.

In the domain of endovascular neurosurgery, the measurement of tissue integrity is needed for simulator-based training and for the development of new intravascular instruments and treatment techniques. In vitro evaluation of tissue manipulation can be achieved using photoelastic stress analysis and vasculature modeling with photoelastic materials. In this research we constructed two types of vasculature models of saccular aneurysms for differentiation of embolization techniques according to the respect for tissue integrity measurements based on the stress within the blood vessel model wall. In an aneurysm model with 5 mm dome diameter, embolization using MicroPlex 10 (Complex 1D, with 4 mm diameter loops), a maximum area of 3.97 mm² with stress above 1 kPa was measured. This area increased to 5.50 mm² when the dome was touched deliberately with the release mechanism of the coil, and to 4.87 mm² for an embolization using Micrusphere, (Spherical 18 Platinum Coil). In a similar way trans-cell stent-assisted coil embolization was also compared to human blood pressure simulation using a model of a wide-necked saccular aneurysm with 7 mm diameter. The area with stress above 1kPa was below 1 mm² for the pressure simulation and maximized at 3.79 mm² during the trans-cell insertion of the micro-catheter and at 8.92 mm² during the embolization. The presented results show that this measurement system is useful for identifying techniques compromising tissue integrity, comparing and studying coils and embolization techniques for a specific vasculature morphology and comparing their natural stress variations such as that produced by blood pressure.

Photoelastic stress analysis in blood vessel phantoms: three-dimensional visualization and saccular aneurysm with bleb.

BACKGROUND: The photoelastic effect is used for stress measurement during endovascular surgery simulation for quantitative evaluation of catheter trajectory in in vitro environments. By extending the capabilities of this sensing technology, its potential for intravascular tools evaluation will increase. METHODS: In this research the error introduced by stress direction on magnitude measurements was studied, then stress measurements were made in the phantom modelling of a saccular aneurysm with bleb. To visualize three-dimensionally the stress field changes produced by a guide wire in a phantom wall, a scanner and an algorithm relying on maximum likelihood-expectation maximization are proposed. Three-dimensional fields at different pressure level were compared with the stress field surrounding the guide wire. RESULTS: The maximum error in stress magnitude measurements due to stress direction was 2.52%. Stress local maximum was detected in the bleb phantom before rupture. Three-dimensional visualization was obtained in vasculature phantom with average errors of 10.73%, 4.55%, 3.18% for inner pressures of 80, 120, 160 mmHg, respectively. Stress measurement in the neighbourhood of the guide wire is equivalent to applying an inner pressure of 120 mmHg. CONCLUSIONS: For the presented polariscope, the weak influence of stress direction in magnitude measurements was confirmed. In vasculature phantoms, the three-dimensional visualization of stress eliminated birefringence visualization distortion and enabled more comprehensive comparison of stress produced by intravascular tools with stress produced by normal blood pressure.