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The human calcium-sensing receptor (CaSR) is a G protein-coupled receptor that maintains extracellular Ca

Combinations of electron-withdrawing and -donating substituents on the 8-hydroxyquinoline ligand of the tris(8-hydroxyquinoline)aluminum (Alq(3)) complexes allow for control of the HOMO and LUMO energies and the HOMO-LUMO gap responsible for emission from the complexes. Here, we present a systematic study on tuning the emission and electroluminescence (EL) from Alq(3) complexes from the green to blue region. In this study, we explored the combination of electron-donating substituents on C4 and C6. Compounds 1-6 displayed the emission tuning between 478 and 526 nm, and fluorescence quantum yield between 0.15 and 0.57. The compounds 2-6 were used as emitters and hosts in organic light-emitting diodes (OLEDs). The highest OLED external quantum efficiency (EQE) observed was 4.6%, which is among the highest observed for Alq(3) complexes. Also, the compounds 3-5 were used as hosts for red phosphorescent dopants to obtain white light-emitting diodes (WOLED). The WOLEDs displayed high efficiency (EQE up to 19%) and high white color purity (color rendering index (CRI≈85).

Immunoglobulin G4 (IgG4)-related systemic disease was first recognized as a clinicopathological entity about 10 years ago, and since then, it has attracted growing attention. It is an autoimmune disease which affects multiple organs including the pancreas, bile duct, salivary glands and retroperitoneum. Further, it was recently reported that it can be manifested as periarteritis, often as inflammatory abdominal aortic aneurysm. We describe the case of a 75-year-old man with autoimmune pancreatitis and parotitis who presented with angina. The serum concentration of IgG4 was significantly increased at 2,510 mg/dl. Coronary angiography showed multiple stenotic lesions and pronounced dilatation of the right coronary artery. Cardiac computed tomography disclosed increased wall thickness of the coronary arteries and focal tumorous lesions surrounding the right coronary artery. Treatment with steroids proved only marginally effective and he underwent surgical resection of the aneurysm and coronary artery bypass grafting. The diagnosis of IgG4-related systemic disease was confirmed by histological examination of the resected mass, which showed a massive infiltration of IgG4-positive plasma cells. This case emphasizes the importance of considering the diagnosis in any patient with abnormally increased wall thickness or ectatic lesions in the coronary arteries.

Background: Studies on patients with hepatitis C virus (HCV) of genotype 1b have suggested that amino acids (aa) 70 and/or 91 of the HCV core protein affect the outcome of interferon (IFN)-α and ribavirin (RBV) therapy, although there are no clear supporting data in vitro. Aims: This study was designed to determine the differences among the antiviral activities of HCV core proteins with various substitutions at aa70 and/or aa91. Methods: The retroviral vectors expressing the HCV core proteins with substitutions of arginine/leucine, arginine/methionine, glutamine/leucine or glutamine/methionine at aa70/aa91 were transiently transfected or stably transducted into an immortalized hepatocyte line (PH5CH8), hepatoma cell lines and an HCV-RNA replicating cell line (sOR) to evaluate antiviral responses to IFN-α or IFN-α/RBV. Sequence analysis was performed using genome-length HCV-RNA replicating cells (OR6 and AH1) to evaluate HCV core mutations during IFN-α treatment. Results: The promoter activity levels of IFN-stimulated genes in the transiently transfected cells or the mRNA levels of 2′-5′-oligoadenylate synthetase in the stably transducted PH5CH8 cells were not associated with the HCV core aa70 and/or aa91 substitutions during IFN-α treatment. Antiviral responses to IFN-α or IFN-α/RBV treatment were enhanced in sOR cells stably transducted with the HCV core, although there were no differences in antiviral responses among the cells expressing different core types. Sequence analysis showed no aa mutations after IFN-α treatment. Conclusions: Antiviral activities were enhanced by HCV core transduction, but they were not associated with the HCV core aa70 and/or aa91 substitutions by in vitro analysis.

Dinuclear lanthanide (Ln=Tb 3+ or Eu 3+ ) complexes (Ln 2 L2 ) of two octadentate macrocyclic polyaminopolycarboxylic ligands connected through a benzophenone (BP) moiety ( L2 ) have been synthesized. Sensitized luminescence properties of Ln 2 L2 in water have been studied in comparison to those of BP-conjugated mononuclear Ln complexes (Ln L1 ). The luminescence intensity of Tb 2 L2 is lower than that of Tb L1 because of lower triplet quantum yield of the BP moiety. In contrast, Eu 2 L2 shows higher intensity than Eu L1 . For both Eu complexes, energy level of triplet excited-state BP ( 3 BP*) is only 3 kJ mol −1 higher than that of 5 D 2 excited-state of Eu 3+ . The 5 D 2 state formed by a triplet-energy transfer (TET) from 3 BP* is therefore deactivated by a back energy transfer (BET) to the ground-state BP, resulting in low luminescence intensity of Eu L1 . In contrast, within Eu 2 L2 , TET from 3 BP* to 5 D 0 state of two Eu 3+ ions is accelerated, thus leading to higher luminescence intensity. Another notable feature of Eu 2 L2 is the luminescence quantum yield independent of its concentration. In contrast, for Eu L1 system, an intermolecular BET occurs from 5 D 2 state of Eu 3+ to the ground-state BP conjugated to another Eu L1 complex, resulting in a yield decrease with the concentration increase.

Sensitized luminescence behavior of lanthanide (Ln=Eu 3+ , Tb 3+ ) macrocyclic cyclen (1,4,7,10-tetraazacyclododecane) complexes bearing one or four benzophenone (BP) moieties as antenna (Ln L1 and Ln L4 ) has been studied in water. Despite higher molar extinction coefficient of Eu L4 owing to four antennae, it shows only one-thirtieth the luminescence intensity of Eu L1 . Energy level of triplet excited–state of BP antenna ( E T ) is only a few kJ mol −1 higher than that of 5 D 2 excited–state of Eu 3+ , thus promoting a back energy transfer (BET) from 5 D 2 of Eu 3+ to ground-state BP antennae. On Eu L4 bearing four antennae, BET occurs more rapidly than that on Eu L1 , thus exhibiting much weaker luminescence. For Tb complexes, the energy gap between E T of BP antenna and 5 D 4 excited state of Tb 3+ is large enough (>13 kJ mol −1 ), such that practically no BET occurs. The luminescence intensity of Tb L4 is, however, lower (two-third) than that of Tb L1 . Time-resolved luminescence measurement reveals that hydration number of Tb 3+ within Tb L4 is twice that within Tb L1 . This is because the structural distortion of ligands on Tb L4 , caused by an intramolecular dipole–dipole interaction among the BP antennae, allows coordination of higher number of H 2 O molecules to Tb 3+ , thus leading to a strong Tb luminescence quenching via O–H oscillators.

Fluorescence behaviors of a triethylenetetramine bearing anthracene (AN) and benzophenone (BP) fragments at the respective ends, L1, have been studied in water, where effects of pH (H+) and metal cations on the emission properties have been studied in detail. L1 behaves as a fluorescent molecular logic gate driven by H+ (Input1) and metal cations (Input2) as input chemicals. The most notable feature of L1 is that this molecule expresses the "either-or" switchable dual logic functions. Operation of L1 with Cu2+ as Input2 expresses the INHIBIT logic function, where a strong AN fluorescence appears only at pH 4 (with H+) without Cu2+ [Input1(1)-Input2(0)]. In contrast, operations of L1 with all other metal cations as Input2 express the TRANSFER logic function, where the presence of H+ allows strong AN fluorescence regardless of whether the metal cation exists or not [Input1(1)-Input2(0); Input1(1)-Input2(1)]. These emission switching behaviors of L1 are driven by the difference in the coordination stability between L1 and metal cations and the photoinduced intramolecular electron and energy transfer processes: (i) a pH-induced electron transfer from unprotonated nitrogen atoms of the polyamine chain to the photoexcited AN [ELT(N--AN*)]; (ii) a pH- and metal coordination-induced electron transfer from the photoexcited AN to the ground-state BP [ELT(AN*--BP)]; and (iii) a Cu2+ coordination-induced energy transfer from the photoexcited AN to Cu2+ [ENT(AN*--Cu2+)].

[reaction: see text] A simple-structured molecule (L1) bearing anthracene fragments at both ends of diethylenetriamine chain behaves as a fluorescent molecular switch with pH-controlled absolutely switchable dual-mode fluorescence in water; each mode consists of monomer (pH9) and excimer (pH9) emissions.

N-(9-Anthrylmethyl)-1,4,7,10-tetraazacyclododecane (AC), which acts as an efficient fluorescent chemosensor for detection of pH and metal cations in aqueous solution, was covalently grafted on a Na...

Insomnia is a common problem among patients with obsessive-compulsive disorder (OCD), and patients suffering from acute insomnia with psychiatric comorbidity are more likely to develop chronic insomnia without appropriate intervention. Here we report a case of obsessive-compulsive disorder with acute insomnia, successfully treated with early sleep psychiatric non-pharmacological intervention. The augmentation of medication runs a risk of exacerbating daytime impairment. Clinicians usually prescribe medication, such as antidepressants and hypnotics without reflections for such complaints. However, the use of these sedative agents is often problematic, especially when patients have kept a good QOL activity in daily life. The rapid recovery from acute insomnia in this case suggests that the appropriate use of actigraphy is a favorable non-pharmacological intervention in acute insomnia.

While diuretic drugs are commonly used in patients with congestive heart failure, the efficacy of their long-term use still remains controversial. Recently, a new class of diuretics, vasopressin receptor 2 antagonists, has been launched, and tolvaptan is one such drug. We describe our initial experience with this novel agent. Tolvaptan is potentially useful for treatment of heart failure patients with fluid overload who are refractory to conventional diuretic therapies.

The extraction and separation of transition metals has been investigated using several inorganic adsorbents (silica gel, MCM-41, and aluminum oxide), modified with ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) as chelating ligands. The metal ions in aqueous solution were coordinated successfully by the ligands on the surface of the adsorbents under moderate conditions. Metal−ligand complexes formed on the adsorbents effectively in the region of low pH (1−2) but scarcely formed at pH > 4. Silica gel modified with EDTA (silicaED) was shown to be the most effective adsorbent for the extraction of metals and to form specific metal−EDTA complexes, with stability constants lying in the order Cu2+ > Ni2+ > VO2+ > Zn2+ > Co2+ > Mn2+. The relatively good separation of these six adjacent metals was therefore also carried out using the silicaED. The metals coordinated on the silicaED could be desorbed completely by putting the material into contact with 1 mol/L aqueous HCl solu...

Immunoglobulin G4 (IgG4)-related systemic disease was first recognized as a clinicopathological entity about 10 years ago, and since then, it has attracted growing attention. It is an autoimmune disease which affects multiple organs including the pancreas, bile duct, salivary glands and retroperitoneum. Further, it was recently reported that it can be manifested as periarteritis, often as inflammatory abdominal aortic aneurysm. We describe the case of a 75-year-old man with autoimmune pancreatitis and parotitis who presented with angina. The serum concentration of IgG4 was significantly increased at 2,510 mg/dl. Coronary angiography showed multiple stenotic lesions and pronounced dilatation of the right coronary artery. Cardiac computed tomography disclosed increased wall thickness of the coronary arteries and focal tumorous lesions surrounding the right coronary artery. Treatment with steroids proved only marginally effective and he underwent surgical resection of the aneurysm and coronary artery bypass grafting. The diagnosis of IgG4-related systemic disease was confirmed by histological examination of the resected mass, which showed a massive infiltration of IgG4-positive plasma cells. This case emphasizes the importance of considering the diagnosis in any patient with abnormally increased wall thickness or ectatic lesions in the coronary arteries.

Previously we reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, inhibited hepatitis C virus (HCV) RNA replication. Furthermore, recent reports revealed that the statins are associated with a reduced risk of hepatocellular carcinoma and lower portal pressure in patients with cirrhosis. The statins exhibited anti-HCV activity by inhibiting geranylgeranylation of host proteins essential for HCV RNA replication. Geranylgeranyl pyrophosphate (GGPP) is a substrate for geranylgeranyltransferase. Therefore, we examined the potential of geranyl compounds with chemical structures similar to those of GGPP to inhibit HCV RNA replication.We tested geranyl compounds [geranylgeraniol, geranylgeranoic acid, vitamin K(2) and teprenone (Selbex)] for their effects on HCV RNA replication using genome-length HCV RNA-replicating cells (the OR6 assay system) and a JFH-1 infection cell culture system. Teprenone is the major component of the anti-ulcer agent, Selbex. We also examined the anti-HCV activities of the geranyl compounds in combination with interferon (IFN)-α or statins.Among the geranyl compounds tested, only teprenone exhibited anti-HCV activity at a clinically achievable concentration. However, other anti-ulcer agents tested had no inhibitory effect on HCV RNA replication. The combination of teprenone and IFN-α exhibited a strong inhibitory effect on HCV RNA replication. Although teprenone alone did not inhibit geranylgeranylation, surprisingly, statins' inhibitory action against geranylgeranylation was enhanced by cotreatment with teprenone.The anti-ulcer agent teprenone inhibited HCV RNA replication and enhanced statins' inhibitory action against geranylgeranylation. This newly discovered function of teprenone may improve the treatment of HCV-associated liver diseases as an adjuvant to statins.

Studies on patients with hepatitis C virus (HCV) of genotype 1b have suggested that amino acids (aa) 70 and/or 91 of the HCV core protein affect the outcome of interferon (IFN)-α and ribavirin (RBV) therapy, although there are no clear supporting data in vitro.This study was designed to determine the differences among the antiviral activities of HCV core proteins with various substitutions at aa70 and/or aa91.The retroviral vectors expressing the HCV core proteins with substitutions of arginine/leucine, arginine/methionine, glutamine/leucine or glutamine/methionine at aa70/aa91 were transiently transfected or stably transducted into an immortalized hepatocyte line (PH5CH8), hepatoma cell lines and an HCV-RNA replicating cell line (sOR) to evaluate antiviral responses to IFN-α or IFN-α/RBV. Sequence analysis was performed using genome-length HCV-RNA replicating cells (OR6 and AH1) to evaluate HCV core mutations during IFN-α treatment.The promoter activity levels of IFN-stimulated genes in the transiently transfected cells or the mRNA levels of 2'-5'-oligoadenylate synthetase in the stably transducted PH5CH8 cells were not associated with the HCV core aa70 and/or aa91 substitutions during IFN-α treatment. Antiviral responses to IFN-α or IFN-α/RBV treatment were enhanced in sOR cells stably transducted with the HCV core, although there were no differences in antiviral responses among the cells expressing different core types. Sequence analysis showed no aa mutations after IFN-α treatment.Antiviral activities were enhanced by HCV core transduction, but they were not associated with the HCV core aa70 and/or aa91 substitutions by in vitro analysis.

Half of the population of genotype 1 HCV is resistant to current pegylated-interferon-alpha (PEG-IFN-alpha) and ribavirin therapy. The resistance to IFN therapy is an urgent problem, especially in patients with genotype 1 HCV infection. However, sensitivities among HCV strains to anti-HCV reagents including IFNs have not been thoroughly addressed. Here, we established three different subgenomic replicons (1B-4, 1B-5, and KAH5 strains) in addition to our previously established replicon (O strain). We comparatively examined the sensitivities of four replicons to IFN-alpha, IFN-gamma, IFN-lambda, cyclosporine A, and fluvastatin. Among the replicons, the 1B-4 and KAH5 replicons were the most sensitive and resistant, respectively to IFN-lambda (EC(50): 1.50 ng/ml vs. 8.50 ng/ml) and fluvastatin (EC(50): 2.82 microM vs. 7.87 microM), although these replicons possessed similar features in terms of genetic distance from the O strain, HCV RNA expression levels, and sensitivity to IFN-alpha (EC(50): 1.44 IU/ml vs. 1.37 IU/ml) and cyclosporine A (EC(50): 0.71 microg/ml vs. 0.96 microg/ml). These replicons are thus useful tools for examining the mechanism of anti-HCV activity, especially in IFN-lambda and statins.

An azamacrocyclic ligand (L) containing two anthracene (AN) fragments connected through two triethylenetetramine bridges has been synthesized, in which each of the bridges can coordinate with one metal cation. The effects of pH and metal cations (Zn 2+ and Cd 2+ ) on the emission properties of L were studied in water. Without metal cations, L does not show any emission at basic pH values. The addition of Zn 2+ leads to the production of excimer emission, which is due to a static excimer formed by direct excitation of the intramolecular ground-state dimer of the bipolar AN fragments that approach each other by Zn 2+ binding. In contrast, Cd 2+ addition does not result in excimer emission because the Cd 2+ -AN π complex, formed by donation of a π electron of the AN fragments to the adjacent Cd 2+ , suppresses π-stacking interactions of the AN fragments. The most notable feature is the appearance of excimer emission controlled by the input sequence of metal cations: Zn 2+ →Cd 2+ sequential addition (each one equivalent) allows excimer emission, whereas the reverse sequence (Cd 2+ →Zn 2+ ) does not. In the Zn 2+ →Cd 2+ sequence, Cd 2+ coordination is structurally restricted by the first Zn 2+ coordination with the other polyamine bridge, leading to the formation of a weak Cd 2+ -AN π complex. In contrast, for the reverse sequence, the first Cd 2+ coordination forms a stable Cd 2+ -AN π complex, which is not weakened by sequential Zn 2+ coordination, resulting in no excimer emission.

Fluorescence properties of a diethylenetriamine bearing two end pyrene fragments (L) have been studied in water, where effects of adding metal cations (Zn2+, Cd2+, Cu2+, Hg2+, Ag+) on the emission properties of L have been studied. Without metal cations, L shows dual-mode fluorescence consisting of monomer and excimer emissions. The monomer emission intensity (I(M)) is strong at acidic pH but decreases with a pH increase because of an electron transfer (ET) from the unprotonated nitrogen atoms to the excited pyrene fragment. The excimer emission is due to the static excimer formed via a direct photoexcitation of the intramolecular ground-state dimer (GSD) of the end pyrene fragments. The excimer emission intensity (I(E)) is weak at acidic pH but increases with a pH increase because of the GSD stability increase associated with the deprotonation of the polyamine chain. Addition of metal cations leads to I(M) decrease, where chelation-driven I(M) enhancement does not occur even with diamagnetic Zn2+ and Cd2+ at any pH. This is because a pyrene-metal cation pi-complex, formed via a donation of pi-electron of the pyrene fragment to the adjacent metal center, suppresses the monomer photoexcitation. I(E) also decreases upon addition of metal cations because the pyrene-metal cation pi-complex weakens pi-stacking interaction of the end pyrene fragments, leading to GSD stability decrease. The emission properties of L-Zn2+ complexes were studied by means of time-resolved fluorescence decay measurements, and the effects of adding a less-polar organic solvent were also studied to clarify the detailed emission properties.

Fluorescence behaviors of a simple-structured molecule (L), a diethylenetriamine bearing two end pyrene fragments, have been investigated in water. Effects of adding a less-polar organic solvent (acetonitrile: MeCN) on the emission behaviors have been studied by means of steady-state and time-resolved fluorescence measurements. L dissolved in water shows dual-mode fluorescence consisting of monomer and excimer emissions. The monomer emission shows an "on-off" intensity profile against the pH window (pH 2-12), whereas the excimer emission shows an "off-on" profile. Upon MeCN addition, the monomer emission maintains the "on-off" profile. In contrast, the "off-on" profile of the excimer emission is drastically changed: L shows two more types of profiles, "off-on-off-on" and "off-on-off", along with the MeCN concentration increase, thus behaving as a multiply configurable fluorescent indicator of the pH window. The MeCN-driven excimer emission switching of L is triggered by (i) the decrease in stability of the intramolecular ground-state dimer (GSD) formed between the end pyrene fragments, which suppresses the direct photoexcitation of GSD (suppression of the "static" excimer formation), leading to a decrease in the excimer emission intensity at basic pH; and (ii) the decrease in polarity of solution, which allows formation of a "dynamic" excimer via a monomer-to-excimer transition, resulting in an enhancement of the excimer emission intensity at acidic-neutral pH.

Modulation of smooth muscle cell (SMC) phenotype plays a central role in neointima formation. We recently demonstrated that Am80, a synthetic retinoic acid receptor α-specific agonist, inhibits the activity of the transcription factor KLF5, which is essential for neointima formation after vascular injury. In the present study, we aimed to further analyze the mechanism by which Am80 inhibits KLF5 and the effects of inhibiting KLF5 on SMCs and vascular lesion formation, as well as to evaluate potential of Am80 for use in the prevention of in-stent neointima formation. We found that Am80 inhibited both the expression and transcriptional function of KLF5. Of particular interest was our finding that KLF5 forms a transcriptionally active complex with unliganded RAR/RXR heterodimer on the PDGF-A promoter; Am80 disrupts this complex, thereby inhibiting KLF5-dependent transcriptional activation. Knocking down KLF5 using small interfering RNA suppressed serum-induced downregulation of SMC differentiation marker gene expression in cultured SMCs, and haploinsufficiency of KLF5 in mice attenuated phenotypic modulation of SMCs after vascular injury, indicating that KLF5 plays a key role in the control of SMC phenotype. Am80 augmented expression of the SMC differentiation marker genes in culture and within the vessel walls, and oral administration of Am80 significantly inhibited in-stent neointima formation in a rabbit stent-placement model. Taken together, these results demonstrate that KLF5 plays an important role in the control of SMC phenotype after vascular injury and suggest the feasibility of using Am80, delivered systemically and/or with a drug eluting stent, to prevent in-stent neointima formation.

Kruppel-like factor 5 (KLF5) is a zinc-finger transcription factor known to play a pivotal role in the pathogenesis of cardiovascular disease. Here, we show that neonatal heterozygous KLF5 knockout mice exhibit a marked deficiency in white adipose tissue development, suggesting that KLF5 is also required for adipogenesis. In 3T3-L1 preadipocytes, KLF5 expression was induced at an early stage of differentiation, and this was followed by expression of PPARgamma2. Constitutive overexpression of dominant-negative KLF5 inhibited adipocyte differentiation, whereas overexpression of wild-type KLF5 induced differentiation even without hormonal stimulation. Moreover, embryonic fibroblasts obtained from KLF5+/- mice showed much attenuated adipocyte differentiation, confirming the key role played by KLF5 in adipocyte differentiation. KLF5 expression is induced by C/EBPbeta and delta. KLF5, in turn, acts in concert with C/EBPbeta/delta to activate the PPARgamma2 promoter. This study establishes KLF5 as a key component of the transcription factor network controlling adipocyte differentiation.

Zeolite modified with octadecyl and diethylenetriamine groups (ZOD), which floats on surface of water, sinks into the water via the formation of metal–ligand complex, owing to the increase in hydrophilicity. The degree of the sinking depends on the metal ions coordinated, allowing selective recovery of ZOD particles loading high concentration of specific metal ion.

Simple polyamines, L1-L3, bearing anthracene and benzophenone units at the respective ends, behave as a fluorescent pH sensor applicable to wide-range pH detection.

Alteration in the differentiated state of smooth muscle cells (SMCs) is known to be integral to vascular development and the pathogenesis of vascular disease. However, it is still largely unknown how environmental cues translate into transcriptional control of SMC genes. We found that deltaEF1 is upregulated during SMC differentiation and selectively transactivates the promoters of SMC differentiation marker genes, SM alpha-actin and SM myosin heavy chain (SM-MHC). DeltaEF1 physically interacts with SRF and Smad3, resulting in a synergistic activation of SM alpha-actin promoter. Chromatin immunoprecipitation assays and knockdown experiments showed that deltaEF1 is involved in the control of the SMC differentiation programs induced by TGF-beta signaling. Overexpression of deltaEF1 inhibited neointima formation and promoted SMC differentiation, whereas heterozygous deltaEF1 knockout mice exhibited exaggerated neointima formation. It thus appears deltaEF1 mediates SMC differentiation via interaction with SRF and Smad3 during development and in vascular disease.

Specimens obtained at autopsy from six neonates with herpes simplex virus (HSV) infections were examined microscopically, electron microscopically, and immunohistochemically. Coagulative necrosis with inclusions was found in the livers and adrenal glands in all cases, as well as in various other organs, including the spleen, bone marrow, lungs, esophagus, tongue, and thymus, in some cases. Distinct hemorrhagic diathesis was found in three cases. No characteristic clinical findings, such as skin rashes or elevated titers of the antibody to HSV, were found, and clinical diagnosis was therefore difficult. In three cases isolation and typing of the causative virus were performed virologically, and type 1 HSV (HSV-1) was identified as the causative virus. Immunohistochemically, the type and distribution of the virus were evaluated in all cases with type-specific antisera to types I and 2 (HSV-2) antigens by the peroxidase-antiperoxidase method. In five cases the infections were found to be due to HSV-1 and in only one case to HSV-2. In the placenta in one case of HSV-2 infection, HSV antigen was demonstrated in the chorionic villi. Electron microscopic study confirmed the existence of viral particles in the placenta in that case and, thus, the possibility of a transplacental route of infection.

A case of intracranial malignant teratoma found in a 27-year-old man was reported. This unique tumor was found in the right frontal lobe separated from the pineal region and revealed various tissue components such as stratified squamous epithelium, glandular tissues, neuron, glia, ependyma, fibromuscular tissue, cartilage, bone, hemangiomatous lesion, melanin-laden cells, and some germ cell components. An immunohistochemical study demonstrated the presence of S-100 protein, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and Factor VIII in some tumourous components. In particular, the distribution of S-100 protein in some germ cells suggested the possibility of the neuroectodermal origin of the germ cells or, alternatively, differentiation to the neuroectoderm.

The methods of fertilizer application tested were as follows: 1) Subsoiling, 2) Broadcasting, 3) Drilling beside planting rows, 4) Drilling between planting rows. With corn and oats, the method of drilling beside planting rows brought the best top growth. With immature soybean and common vetch, it was superior by subsoiling. The yield in each crop was similar in tendency to the top growth, except that of common vetch which decreased owing to lodging caused by excessive growth by the subsoiling method. Drilling between rows brought about the most inferior growth and yields in all the crops. Effects of the difference of the method on the root development were recognized with common vetch and oats as differences in distribution of roots around and beneath the fertilizer placed. Subsoiling application promoted the penetration of roots in common vetch only. It was observed that the roots which distributed around the fertilizer were white and fresh. Though no data about the relation between top growth and root weight were obtained in this investigation, the authors assumed detailed studies of quality or viability of root should be important to elucidate such a relation.