[A case of locally recurrent breast cancer difficult to differentiate from nodular fasciitis].

Breast-conserving surgery was performed on a 78-year-old woman for left breast cancer 5 years previously (invasive ductal carcinoma, T1cN2M0, stage IIIA, ER[+], PR[-], HER2[-]). Chemotherapy, radiotherapy, and hormonal therapy were administered. A left subclavian tumor was detected, and an excisional biopsy was performed. Histological examination showed spindle cells, different from primary breast cancer histology, and nodular fasciitis was diagnosed negative cytokeratin and vimentin immunostaining results. After 12 months, a mass had developed in the same region, and reoperation was performed for resection. Similar spindle cells were observed, but they tested positive for cytokeratin. Carcinoma was diagnosed and thought to be locally recurrent breast cancer. Despite postoperative chemotherapy, the patient experienced bone and lung metastasis and a third local recurrence. She died 13 months following the last surgery. Recurrent breast cancer sometimes displays different histology from the initial cancer, and mimics stromal tumors in certain cases.

Ring-shaped Re(I) multinuclear complexes with unique photofunctional properties.

We synthesized for the first time a series of emissive ring-shaped Re(I) complexes (Re-rings) with various numbers of Re(I) units and various lengths of bridge ligands. The photophysical properties of the Re-rings could be varied widely through changes in the size of the central cavity. A smaller central cavity of the Re-rings induced intramolecular π-π interactions between the ligands and consequently caused a stronger emission and a longer lifetime of the excited state. The Re-rings can function as efficient and durable photosensitizers. The combination of a trinuclear Re-ring photosensitizer with fac-[Re(bpy)(CO)3(MeCN)](+) (bpy = 2,2'-bipyridine) as a catalyst photocatalyzed CO2 reduction with the highest quantum yield of 82%.

Synthesis, structure, and optical and redox properties of chlorophyll derivatives directly coordinating ruthenium bisbipyridine at the peripheral ß-diketonate moiety.

The diketonate group of the peripheral position in chlorophyll derivatives 1 and 2 coordinated ruthenium bisbipyridine to give direct linkages 3-5 of the chlorin ring with the Ru(II) complex. Zinc metalation of the central position in the chlorin ring of free base 3 afforded the Ru-Zn binuclear complex 3-Zn. Because the diketonate group at the C3 position of chlorophyll derivatives coordinated to bulky Ru(bpy)2(2+), the plane of the diketonate group was twisted from the chlorin π ring in synthetic 3-5 and 3-Zn to lead to a partial deconjugation and a slight blue shift of the longest wavelength electronic absorption band in dichloromethane. A broad metal-to-ligand charge-transfer absorption band derived from the Ru complex was observed around 500 nm, in addition to visible absorption bands from the chlorophyll moiety. Chlorophyll derivatives 3-5 and 3-Zn directly coordinating the ruthenium complex were less fluorescent in dichloromethane than chlorophyll-diketonate ligands 1, 2, and 1-Zn due to the heavy atom effect of the ruthenium in a molecule. The coordination to the ruthenium complex moiety at the peripheral position shifted the electrochemical reduction of the chlorin part in acetonitrile to a negative potential, and the coordination to zinc at the central position decreased the redox potentials. Chemical modification of the bipyridine and diketonate ligands of the ruthenium complexes greatly affected the redox potentials of Ru(II)/(III) and/or Ru(II)/(I) but minimally the redox properties of the chlorin moiety. Substitution with electron-donating groups shifted the former to a negative potential but only barely shifted the latter. The zinc metalation caused no apparent shifts for the redox potentials of the Ru center.

Immunoelectron microscopic analysis of neurotoxic effect of glutamate in the vestibular end organs during ischemia.

CONCLUSION: The excessive glutamate released from the type I and type II hair cells and the supporting cells injure the bouton-type endings and the nerve chalices in 30 min ischemia, and neuronal damage of glutamate was slight in 10 min ischemia. OBJECTIVE: In the present study, we investigated by means of post-embedding immunoelectron microscopic analysis whether neuronal damage in the vestibular end organs is associated with the change of cellular glutamate concentration during ischemia. METHODS: Transient local anoxia (10 min, 30 min) of guinea pig inner ear was induced by pressing the left labyrinthine artery. The right sides were used as controls. The morphological changes of the vestibular end organs and the areal gold particle densities representing glutamate were compared in the ischemia side and the control side. RESULTS: The areal gold particle densities of the type I and type II hair cells and the supporting cells in the ischemic side were lower than those of the control side. There were no remarkable morphological changes compared to the control side in 10 min ischemia. In 30 min ischemia, the bouton-type endings were swollen and intercellular spaces between the type I hair cells and the nerve chalices were enlarged.

New light-harvesting molecular systems constructed with a Ru(II) complex and a linear-shaped Re(I) oligomer.

A novel type of light-harvesting complexes was synthesized with a linear-shaped Re(I) oligomer as a photon absorber and a Ru(II) polypyridyl complex as an energy acceptor. The Re(I) oligomer and the Ru(II) complex are connected to each other with a bisdiimine ligand, that is, 1,2-bis[4-(4'-methyl-2,2'-bipyridinyl)]ethane (C2dmb). These Ru(II)-Re(I) multinuclear complexes, [Ru(dmb)(2)(C2dmb)Re(CO)(2){-PP-Re(dmb)(CO)(2)-PP-Re(dmb)(CO)(3)}(2)](PF(6))(7), [Ru(dmb)(2)(C2dmb)Re(CO)(2){-PP-Re(dmb)(CO)(3)}(2)](PF(6))(5), and [Ru(dmb)(2)(C2dmb)Re(CO)(3)-PP-Re(dmb)(CO)(2)-PP-Re(dmb)(CO)(3)](PF(6))(5) (dmb = 4,4'-dimethyl-2,2'-bipyridine; PP = bis(diphenylphosphino)acetylene), can strongly absorb a wide range of UV-vis light and emit mostly from the (3)MLCT excited state of the Ru(II) unit at room temperature in solution even when the Re chain absorbs the light. Comparison of their photophysical properties with those of the corresponding model complexes shows that a highly efficient energy transfer from the Re chain to the Ru(II) unit occurs, and the energy transfer rate constants from each Re(I) unit were determined.

Systematic synthesis, isolation, and photophysical properties of linear-shaped Re(I) oligomers and polymers with 2-20 units.

Systematic synthesis routes have been developed for the linear-shaped rhenium(I) oligomers and polymers bridged with bidentate phosphorus ligands, [Re(N--N)(CO)3-PP-{Re(N--N)(CO)2-PP-}(n)Re(N--N)(CO)3](PF6)(n+2) (N--N = diimine, PP = bidentate phosphine, n = 0-18). These were isolated by size exclusion chromatography (SEC) and identified by (1)H NMR, IR, electrospray ionization Fourier transform mass spectrometry, analytical SEC, and elemental analysis. Crystal structures of [Re(bpy)(CO)3-Ph2PC[triple bond]CPPh2-Re(bpy)(CO)3](PF6)2, [Re(bpy)(CO)3-Ph2PC[triple bond]CPPh2-Re(bpy)(CO)2-Ph2PC[triple bond]CPPh2-Re(bpy)(CO)3](PF6)3 and [Re(bpy)(CO)3-Ph2PC2H4PPh2-{Re(bpy)(CO)2Ph2PC2H4PPh2-}(n)Re(bpy)(CO)3](PF6)(n+2) (bpy = 2,2'-bipyridine, n = 1, 2) were obtained, showing that they have interligand pi-pi interaction between the bpy ligand and the phenyl groups on the phosphorus ligand. All of the oligomers and polymers synthesized were emissive at room temperature in solution. For the dimers, broad emission was observed with a maximum at 523-545 nm, from the (3)MLCT excited-state of the tricarbonyl complex unit, [Re(N--N)(CO)3-PP-]. Emission from the longer oligomers and polymers with > or = 3 Re(I) units was observed at wavelengths 50-60 nm longer than those of the corresponding dimers. This fact and the emission decay results clearly show that energy transfer from the edge unit to the interior unit occurs with a rate constant of (0.9 x 10(8))-(2.5 x 10(8)) s(-1). The efficient energy transfer and the smaller exclusive volume of the longer Re(I) polymers indicated intermolecular aggregation for these polymers in an MeCN solution.

New observations concerning the interpretation of magnetic resonance spectroscopy of meningioma.

This study was aimed to clarify some ambiguities in the interpretation of proton magnetic resonance spectroscopy (1H-MRS) of meningiomas. The cases of 31 meningioma patients (27 benign and 4 nonbenign meningiomas) that underwent single-voxel 1H-MRS (PRESS sequence, TR/TE = 2,000 ms/68, 136, 272 ms) were retrospectively analyzed. To verify the findings of in-vivo study, phantoms were measured, and pathological sections of 11 patients were reviewed. All meningiomas demonstrated increased choline and decreased creatine, except for a lipomatous meningioma that only displayed a prominent lipid (Lip) peak. Alanine (Ala) and lactate (Lac) coexisted in eight cases, indicating an alternative pathway of energy metabolism in meningiomas. They partially overlapped with each other and demonstrated a triplet-like spectral pattern, which was consistent with phantom study. Glutamine/glutamate (Glx) was helpful for the recognition of meningioma when Ala was absent. N-acetyl compounds(NACs) were observed in nine cases whose voxels were completely limited within the tumors, indicating that meningiomas might have endogenous NACs. Lac was indicative of an aggressive meningioma, although not always a nonbenign one. Lip not only represented micronecrosis in nonbenign meningiomas, but also reflected microcystic changes or fatty degeneration in benign meningiomas. 1H-MRS reflects some distinctive biochemical and pathological changes of meningiomas that might be misinterpreted.

Osteopontin expression in the liver with severe perisinusoidal fibrosis: autopsy case of Down syndrome with transient myeloproliferative disorder.

Down syndrome with transient myeloproliferative disorder (TMD) is often associated with perinatal liver fibrosis. The authors recently encountered an autopsy case of this disease with a characteristic severe perisinusoidal liver fibrosis. Osteopontin (OPN) is a molecule that plays an important role in diverse fibro-inflammatory diseases. The purpose of the present report was to examine the involvement of OPN in development of the Down syndrome-associated liver fibrosis. Histology indicated severe perisinusoidal fibrosis and ductular arrangements of hepatocytes in the liver. Appearance of atypical megakaryocytes in the liver, a feature of TMD associated with Down syndrome, was not evident. On immunohistochemistry expression of OPN was observed in hepatocytes often having ductular arrangements and infiltrating macrophages. In contrast, a small number of transforming growth factor-beta1 (TGF-beta1)-positive mononuclear cells were present in the liver. Numerous activated hepatic stellate cells (HSC) expressing alpha-smooth muscle actin (alpha-SMA) were seen in the perisinusoidal area. A recent report indicated that OPN could directly activate the HSC. Thus, it is suggested that OPN produced by hepatocytes and macrophages induces activation of the HSC, and leads to the development of perisinusoidal liver fibrosis.

Cytoplasmic accumulation of connexin32 protein enhances motility and metastatic ability of human hepatoma cells in vitro and in vivo.

Connexins have long been believed to suppress tumour development during carcinogenesis by exerting gap junctional intercellular communication (GJIC). Although GJIC is abrogated in hepatocellular carcinoma (HCC), connexin32 (Cx32) protein tends to remain expressed in cytoplasm, but not in cell-cell contact areas; thus, it is incapable of forming gap junctions. Hypothesising that cytoplasmic Cx32 protein that has accumulated in HCC should have its proper functions, which are independent of GJIC, we established an inducible expression system of Cx32 in human HuH7 HCC cells, which were unable to support the formation of Cx32-mediated gap junctions, so that Cx32 protein could be overexpressed by doxycycline (Dox) withdrawal. Although the established clone HuH7 Tet-off Cx32 cells exhibited a 4-fold increase in Cx32 expression after Dox withdrawal, none of them were dye-coupled, and Cx32 protein was retained in the Golgi apparatus. However, the proliferation rate of the HuH7 Tet-off Cx32 cells was significantly higher in the Dox-free medium than in the Dox-supplemented one. Transwell assays also revealed that Dox withdrawal enhanced serum-stimulated motility and invasiveness into Matrigel of the HuH7 Tet-off Cx32 cells. Furthermore, when HuH7 Tet-off Cx32 cells were xenografted into the liver of SCID mice, only the mice to which no Dox was administered developed metastatic lesions, indicating that overexpression of cytoplasmic Cx32 protein induced metastasis of HuH7 cells. Our results suggest that, while Cx32-mediated GJIC suppresses the development of HCCs, cytoplasmic Cx32 protein exerts effects favourable for HCC progression, such as invasion and metastasis, once the cells have acquired a malignant phenotype.

Analysis and isolation of cationic rhenium(I) and ruthenium(II) multinuclear complexes using size-exclusion chromatography.

Various cationic rhenium(I) and ruthenium(II) mono- and multinuclear complexes were successfully separated by size-exclusion chromatography (SEC), using a 50:50 (v/v) mixture of methanol and acetonitrile with CH3CO2NH4 as an eluent. The logarithms of the molecular weights were accurately linear in the distribution coefficients: for linear-shaped rhenium(I) multinuclear complexes, log M(W) = -2.86K(SEC) + 5.24 (r = -0.990 and n = 15); for ring-shaped rhenium(I) multinuclear complexes, log M(W) = -2.94K(SEC) + 5.40 (r = -0.999; n = 5); for bimetallic complexes including ruthenium(II), log M(W) = -0.40K(SEC) + 3.37 (r = -0.959; n = 6). This separation method is applicable to the preparative-scale separation of cationic multinuclear complexes from a mixture.

Cell biology and pathology of liver sinusoidal endothelial cells.

Growing evidence revealed that liver sinusoidal endothelial cells (SEC) play several important roles in physiology and pathology of the liver. It has been well understood that their structural characteristics, such as the membrane sieve and lack of basement membrane, facilitate direct contact of soluble and insoluble serum substances with hepatic parenchymal cells, resulting in enhancement of hepatic metabolic activity. In addition, SEC is now regarded as a member of the scavenger endothelial cells, which have potential to eliminate a variety of macromolecules from the blood circulation by receptor-mediated endocytosis. It is reported that molecules preferentially eliminated by SEC are denatured or modified proteins such as advanced glycation end products, extracellular matrix components including hyaluronic acid, and some lipoproteins. The nature of the scavenger receptors corresponding to these molecules remains to be clarified. Recently, it was noted that SEC has an antigen-presenting function similar to dendritic cells. Taken together, it is suggested that SEC, cooperating with Kupffer cells and hepatic dendritic cells, may partake of immunoregulatory functions in the liver. SEC also plays a pivotal role in the pathological process of ischemia-reperfusion injury following liver surgery and liver transplantation. Thus, it is of importance to elucidate the mechanisms of apoptosis and proliferation of SEC. Recent results on the regulation of growth and apoptotic signaling of SEC are discussed.

Increased expression of H19 non-coding mRNA follows hepatocyte proliferation in the rat and mouse.

BACKGROUND/AIMS: H19 is a paternally imprinted gene that is believed to function as non-coding mRNA. While H19 is only faintly expressed in the normal adult liver, it is abundantly expressed during the fetal period. We explored the possibility that H19 might participate in the regulation of hepatocyte proliferation. METHODS: Adult male rats and mice were subjected to a two-thirds partial hepatectomy, and after various time periods, hepatocytes were isolated and analyzed for H19 gene expression. The expression was also examined in cultured rat hepatocytes. RESULTS: The expression of H19 was dramatically increased after 2 days (rat) and 4 days (mouse), peaked at 3 days (rat) and 6 days (mouse), and then gradually declined. In both species, the increase in H19 gene expression was preceded by the induction of proliferating cell nuclear antigen and DNA synthesis. An allele-specific RT-PCR analysis in the mouse showed that the paternally imprinted status of the gene was maintained after a partial hepatectomy. H19 was strongly induced in spheroid cultures after transient hepatocyte proliferation, but not in conventional monolayer cultures, in which persistent proliferation occurred. CONCLUSIONS: Our results demonstrated that H19 gene expression was dynamically regulated in adult hepatocytes in close association with their proliferation.

Localization of gamma-aminobutyric acid A receptor subunits in the rat spiral ganglion and organ of Corti.

Gamma-aminobutyric acid (GABA) is thought to be the major inhibitory neurotransmitter in the central nervous system. Although it is distributed in the olivo-cochlear bundles, which constitute the mammalian cochlear efferent system, its function in the cochlea is still obscure. In this study, we investigated the localization of GABAa receptor subunits (alpha1-6, beta1-3, gamma) in the rat cochlea in order to determine the role of GABA in the cochlea. Most spiral ganglion cells were intensely immunolabeled with all the anti-GABAa receptor subunit antibodies. In the organ of Corti, punctate immunoreactivities were observed in inner hair cell regions corresponding to the distribution of GABA. These data suggest that GABAa receptor was present in afferent nerve terminals in inner hair cell regions, and that GABA regulated afferent nerve transmission contacting efferent nerve endings by means of the axo-dendritic synapse function.

Construction of molecular wires based on a gold(I) bis-sigma-acetylide building block incorporated into ruthenium(II) polypyridyl complexes.

An Ru(II)-Au(I)-Ru(II) triad has been synthesized from [Ru(bpy)2(3-ethynylphenanthroline)]2+ with Au(tht)Cl and characterized by spectroscopic means such as NMR and ESI-MS; the Ru(II)-Au(I)-Ru(II) triad shows an intense emission at 620 nm upon excitation at 360 nm, which suggests an efficient energy transfer from the Au site to Ru sites via extended pi-conjugation through the ethynyl units.