[Learned helplessness, generalized self-efficacy, and immune function].

Generalized self-efficacy is considered one of important personality traits that determine psychological and physiological stress responses. The present study examined the interaction effects of generalized self-efficacy and controllability of acute stress on salivary secretory immunoglobulin A (s-IgA), task performance, and psychological stress responses in a typical learned helplessness paradigm. Twenty low and 19 high self-efficacy undergraduate women performed two response selection tasks one after another.

Structure-based de novo design of non-nucleoside adenosine deaminase inhibitors.

We searched for non-nucleoside inhibitors of adenosine deaminase by rational structure-based de novo design and succeeded in the discovery of 1-(1-hydroxy-4-phenyl-2-butyl)imidazole-4-carboxamide (FR221647: K(i)=5.9 microM to human ADA) as a novel inhibitor with moderate activity and good pharmacokinetics compared with the known inhibitors pentostatin and EHNA.

A voltage-gated H+ channel is a powerful mechanism for pH homeostasis in murine osteoclasts.

Osteoclasts secrete a large amount of proton (H+) ions and proteolytic enzymes into bone resorption pit to degrade bone matrix. In addition to H+ pumps and exchangers, voltage-gated H+ channels, which are H+ conductive pathways, are expressed in osteoclasts. H+ channels are distinct in their strong H+ extrusion ability, but the functional role is not clear.

Neuropilin-2 is overexpressed in the rat brain after limbic seizures.

Structural rearrangement and synaptic reorganization are known to occur in the brain after seizures. If neuronal rearrangement after seizures always results in abnormal hyperexcitability, it would provide an accurate pathway to the appropriate target and as a result, it may be the mechanism of epileptogenesis. This study examined the mechanism of axon guidance in the mature rat brain after seizures by evaluating the expression of the axonal guidance molecule, neuropilin-2.

Comprehensive allelotyping of well-differentiated human hepatocellular carcinoma with semiquantitative determination of chromosomal gain or loss.

Allelic imbalance (AI), which represents certain chromosomal gains or losses, has been described in human hepatocellular carcinoma (HCC), but the impact of AI on the early stage of hepatocarcinogenesis has not been fully clarified. Moreover, no previous allelotype studies have identified the difference in chromosomal gain and loss that results in AI. To resolve these problems, we examined 18 well-differentiated HCCs with comprehensive allelotyping by using 400 microsatellite markers with semiquantitative assessment of chromosomal gain or loss.

Cell swelling as an intermediate signal leading to activation of a Cl- channel in extracellular calcium-sensing of murine osteoclasts.

Osteoclasts possess extracellular Ca2+-sensing machinery to regulate bone-resorbing activity. In murine osteoclasts, an elevation of the extracellular Ca2+ concentration activated a volume-sensitive outwardly rectifying Cl- (OR(Cl)) channel. Exposure to 40 mM Ca2+ activated the OR(Cl) current in association with an increase in the planar cell area.

Na+ dependence of extracellular Ca2+-sensing mechanisms leading to activation of an outwardly rectifying Cl- channel in murine osteoclasts.

An elevation in the extracellular Ca(2+) concentration ([Ca(2+)](o)) is a key signal for bone remodeling by inhibiting the resorbing activity of osteoclasts. The [Ca(2+)](o)-sensing responses include a variety of morphological and functional changes, but the underlying mechanisms are yet to be defined. This study was aimed at investigating the [Ca(2+)](o)-sensing mechanisms leading to the activation of the Cl(-) channel in murine osteoclasts.

Avidin: a natural bridge for quantum dot-antibody conjugates.

We describe the preparation and characterization of bioinorganic conjugates in which luminescent semiconductor CdSe-ZnS core-shell nanocrystal quantum dots (QDs) were coupled to antibodies through the use of an avidin bridge adsorbed to the nanocrystal surface via electrostatic self-assembly. Avidin, a highly positively charged protein, was found to adsorb tightly to QDs modified with dihydrolipoic acid, which gives their surface a homogeneous negative charge. QD conjugation to biotinylated antibodies subsequently is readily achieved.

Prognostic impact of multiple allelic losses on metastatic recurrence in hepatocellular carcinoma after curative resection.

Loss of heterozygosity (LOH) on chromosomes 13q, 16q and 17p has been associated with the progression of hepatocellular carcinoma (HCC). To investigate the prognostic impact of such LOH, we examined the metastasis-free survival of curatively resected HCC cases, in whom these LOHs were analyzed. Among the 49 HCC patients examined, the frequency of LOHs was 28% on 13q, 33% on 16q and 40% on 17p.

In vitro and in vivo activities of anti-influenza virus compound T-705.

T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has been found to have potent and selective inhibitory activity against influenza virus. In an in vitro plaque reduction assay, T-705 showed potent inhibitory activity against influenza A, B, and C viruses, with 50% inhibitory concentrations (IC(50)s) of 0.013 to 0.

Post-cultured development of basic electrophysiological properties of spinal neurons obtained from rat embryo.

Basic electrical profiles of cultured neurons are modified by multiple factors, such as cell growth, differentiation and cell damage from the isolation procedure. In the present study, we assessed development of electrophysiological properties of rat spinal neurons over the late embryonic and early postnatal period in a neuron-enriched culture. After recovery from acute damage within 2 days after plating, the input conductance and amplitudes of voltage-gated Na(+) and K(+) currents increased parallel to the increase in the cell capacitance.

Molecular cloning of bovine zona pellucida glycoproteins ZPA and ZPB and analysis for sperm-binding component of the zona.

The zona pellucida, a transparent envelope surrounding the mammalian oocyte, comprises three glycoproteins, ZPA, ZPB and ZPC, and plays important roles in fertilization. We have previously reported that apparent relative molecular masses of bovine zona glycoproteins on SDS/PAGE under nonreducing conditions after removal of poly N-acetyllactosamine at the nonreducing portion of sugar chains with endo-beta-galactosidase are 72 000, 58 000 and 45 000 [Noguchi, S., Yonezawa, N.

Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas.

p16, cyclin D1 and retinoblastoma protein (pRB) regulate G1 to S transition and are commonly targeted in various cancers. However, few studies have simultaneously examined all components of the p16/cyclin D1/pRB pathway (RB pathway) in hepatocellular carcinoma (HCC). To clarify the role of the disruption of the RB pathway in HCC, we analyzed p16, pRB and cyclin D1 in 47 HCCs.

Postoperative detection of alpha-fetoprotein mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma.

Background: We tested for the presence of alpha-fetoprotein (AFP) mRNA by using nested RT-PCR in the peripheral blood of hepatocellular carcinoma (HCC) patients who had undergone curative surgery, and investigated the occurrence of intrahepatic and/or extrahepatic metastasis thereafter, to reveal the optimal timing of blood sampling for the prediction of metastatic recurrence.

Methods: Twenty-nine patients with HCC, who had been operated on were analyzed with RT-PCR at several points during the clinical course, and examined for metastatic recurrence for 3-28 months (mean = 18.7 months) after surgery.

Temporal fluctuations of voltage-gated proton currents in rat spinal microglia via pH-dependent and -independent mechanisms.

Voltage-gated proton (H(+)) channels are unique mechanisms to extrude a massive amount of H(+), and are proposed to regulate intracellular pH of microglia during respiratory bursts. Temporal variations of the H(+) current were studied in rat spinal microglia cultivated on the glial cell layer using the voltage-ramp protocol. Repetitive applications of the large and long-lasting depolarization decreased the amplitudes of the H(+) current transiently and reversibly.

The presence of a glycosyl phosphatidylinositol-anchored alpha-mannosidase in boar sperm.

alpha-Mannosidase and beta-galactosidase were released from boar sperm into the medium by treatment with calcium ionophore A23187 or by 0.2% Brij-35/2% acetic acid. About half as much alpha-mannosidase activity as that in the acid extract was recovered by digestion with phosphatidylinositol-specific phospholipase C (PI-PLC), whereas the liberation rate of beta-galactosidase treated with PI-PLC was low.

Potentiation of a voltage-gated proton current in acidosis-induced swelling of rat microglia.

Microglia are equipped with a strong proton (H(+)) extrusion pathway, a voltage-gated H(+) channel, probably to compensate for the large amount of H(+) generated during phagocytosis; however, little is known about how this channel is regulated in pathological states. Because neural damage is often associated with intracellular and extracellular acidosis, we examined the regulatory mechanisms of the H(+) current of rat spinal microglia in acidic environments. More than 90% of round/amoeboid microglia expressed the H(+) current, which was characterized by slow activation kinetics, dependencies on both intracellular and extracellular pH, and blockage by Zn(2+).

Dual CCK-A and CCK-B receptor antagonists (II). Preparation and structure activity relationships of 5-alkyl-9-methyl-1,4-benzodiazepines and discovery of FR208419.

In our continuing research for dual CCK-A and -B antagonists, according to our hypothesis that dual CCK-A and -B antagonists should be more efficacious than selective CCK-A antagonists for the treatment of pancreatitis, we have prepared various 5-alkyl-9-methyl-1,4-benzodiazepines. From the compounds prepared, 1-cyclohexyl-carbonylmethyl-5-ethyl-9-methyl-3- (m-tolylureido)-2-oxo-1,4-benzodiazepine, (40) was selected as a candidate for development due to its well-balanced high affinity for both receptors. The R-enantiomer of 40, (R)-40 (FR 208419), had 27-fold higher affinity for the CCK-A receptor and 8-fold more potent CCK-B receptor binding activity than (S)-40.

Disparity of cell swelling and rapid neuronal death by excitotoxic insults in rat hippocampal slice cultures.

The rapidly (< 1 h) developing neuronal death induced by a 15-min-exposure to N-methyl-D-aspartate (NMDA) in rat hippocampal slice cultures is associated with cell swelling. We examined whether the swelling directly leads to neuronal death. The rapid neuronal death assayed by propidium iodide was Cl(-)-dependent, as reported for the cell swelling.

Protection of excitotoxic neuronal death by gluconate through blockade of N-methyl-D-aspartate receptors.

Excitotoxic neuronal death is mediated primarily by the N-methyl-D-aspartate receptor. N-methyl-D-aspartate induces two forms of excitotoxicity in CA1 pyramidal neurons of cultured rat hippocampal slices: the rapidly developing form that depends on external Na+ and Cl-, and the delayed form that requires external Ca2+ but not Cl-. Consistent with this notion, replacement of external Cl- with glucuronate, isethionate or methylsulfate attenuated or delayed selectively the rapid excitotoxicity.

Synergetic activation of outwardly rectifying Cl- currents by hypotonic stress and external Ca2+ in murine osteoclasts.

1. An outwardly rectifying Cl- (ORCl) current of murine osteoclasts was activated by hypotonic stimulation. The current was characterized by rapid activation, little inactivation, strong outward rectification, blockage by DIDS and permeability to organic acids (pyruvate and glutamate).

Effect of FK480, a CCK-A receptor antagonist, on spontaneously developed chronic pancreatitis in WBN/Kob rats.

The effect of FK480, a cholecystokinin-A (CCK-A) selective receptor antagonist, on spontaneously developed chronic pancreatitis was examined in WBN/Kob rats. Animals at age 18 weeks (18w-Control) already had the histologic appearance of chronic pancreatitis as indicated by inflammatory cell infiltration and fibrotic degeneration with interstitial edema. Rats treated with vehicle from 18 to 26 weeks of age (26w-Control) showed further development of pancreatitis as characterized by more extensive appearance of inflammatory cell infiltration and fibrotic changes, with the pancreatic weight significantly decreased.

Augmentation of the inhibitory effect of FK480, a CCK-A receptor antagonist, on pancreatic exocrine secretion by achlorhydria.

The effect of intraluminal acid and cholecystokinin (CCK) receptor blockade on the pancreatic secretory response was examined in rats. Blockade of gastric acid secretion by YM022 (CCK-B receptor antagonist) or famotidine (histamine-2 receptor antagonist) resulted in a significant suppression of casein-stimulated pancreatic exocrine secretion as determined by juice volume and amylase secretion. Ligation of the gastric pylorus, which leads to complete prevention of gastric acid from entering the duodenum, also suppressed pancreatic exocrine secretion.

Strain difference in the induction of T-cell activation-associated, interferon gamma-dependent hepatic injury in mice.

A single intravenous injection of concanavalin A (Con A) induces T-cell activation-associated inflammatory injury selectively in the liver. This study investigated the strain difference in the development of Con A-induced hepatic injury. Normal C57BL/6 and BALB/c spleen cells produced comparable levels of T-cell-derived lymphokines (interferon gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], and interleukin-2 [IL-2]) following in vitro stimulation with Con A.

Differential effect of high extracellular Ca2+ on K+ and Cl- conductances in murine osteoclasts.

Effects of the extracellular Ca2+ concentration ([Ca2+]o) on whole cell membrane currents were examined in mouse osteoclastic cells generated from bone marrow/stromal cell coculture. The major resting conductance in the presence of 1 mm Ca2+ was mediated by a Ba2+-sensitive, inwardly rectifying K+ (IRK) current. A rise in -Ca2+-o (5-40 mM) inhibited the IRK current and activated an 4'4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS)-sensitive, outwardly rectifying Cl- (ORCl) current.