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Background and purpose: In patients with rheumatoid arthritis (RA), the serum C‐reactive protein (CRP) level is associated with ischaemic cerebrovascular disease (iCVD). Acute iCVD patients with RA were investigated, assessing changes of clinical characteristics and CRP with progress in RA treatment. Methods: Patients hospitalized for acute iCVD from August 2002 to February 2018 were divided into two groups at February 2010. Patients with RA were retrospectively identified. The incidence of RA, the occurrence of acute exacerbation of inflammation due to causes other than synovitis preceding iCVD (non‐synovitis AEI) and serum CRP were compared. Results: In the first and second periods, 23/1203 patients (1.9%) and 22/1094 patients (2.0%) respectively had acute iCVD with RA. Non‐synovitis AEI was significantly less frequent in the second period (5%, n = 1) than in the first period (35%, n = 8) (P < 0.05). CRP was significantly lower at iCVD onset in the second period [median and interquartile range 2.72 (0.89–4.5) mg/dl vs. 0.34 (0.12–1.19) mg/dl, P < 0.01]. Excluding nine patients with non‐synovitis AEI, CRP was still lower in the second period [1.21 (0.47–2.72) mg/dl vs. 0.33 (0.11–0.98) mg/dl, P < 0.01]. CRP levels before both iCVD and non‐synovitis AEI tended to be lower in the second period [1.53 (0.3–2.78) mg/dl vs. 0.69 (0.06–1.28) mg/dl, P = 0.059]. Two patients using tocilizumab developed iCVD despite persistently low CRP levels. Conclusions: With progress in treatment, RA‐related inflammation was better suppressed and CRP decreased, but the prevalence of RA amongst acute iCVD patients was unchanged. Strategies for tighter control of inflammation are needed, and a new biomarker may be required in patients using tocilizumab. [ABSTRACT FROM AUTHOR]

SUMMARY: For evaluation of defects on extreme ultraviolet (EUV) masks at the blank state of manufacturing, we developed a microcoherent EUV scatterometry microscope (micro‐CSM). The illumination source is coherent EUV light with a 140‐nm focus diameter on the defect using a Fresnel zoneplate. This system directly observes the reflection and diffraction signals from a phase defect. The phase and the intensity image of the defect is reconstructed with the diffraction images using ptychography, which is an algorithm of the coherent diffraction imaging. We observed programmed phase defect on a blank EUV mask. Phase distributions of these programmed defects were well reconstructed quantitatively. We also observed actual defects which were inspected by the ABI tool. Actual amplitude defect and phase defect images were reconstructed with intensity and phase contrast. The reconstructed image indicated the defect type of these defect. The micro‐CSM is very powerful tool to evaluate an EUV phase defect. [ABSTRACT FROM AUTHOR]

Background and Purpose: Prefrontal dopamine release by the combined activation of 5-HT1A and sigma-1 (σ1 ) receptors is enhanced by the GABAA receptor antagonist picrotoxin in mice. Here, we examined whether this neurochemical event was accompanied by behavioural changes.Experimental Approach: Male mice were treated with picrotoxin to decrease GABAA receptor function. Their anhedonic behaviour was measured using the female encounter test. The expression of c-Fos was determined immunohistochemically.Key Results: Picrotoxin caused an anxiogenic effect on three behavioural tests, but it did not affect the immobility time in the forced swim test. Picrotoxin decreased female preference in the female encounter test and attenuated the female encounter-induced increase in c-Fos expression in the nucleus accumbens. Picrotoxin-induced anhedonia was ameliorated by fluvoxamine and S-(+)-fluoxetine, selective serotonin reuptake inhibitors with high affinity for the σ1 receptor. The effect of fluvoxamine was blocked by a 5-HT1A or a σ1 receptor antagonist, and co-administration of the σ1 receptor agonist (+)-SKF-10047 and the 5-HT1A receptor agonist osemozotan mimicked the effect of fluvoxamine. By contrast, desipramine, duloxetine and paroxetine, which have little affinity for the σ1 receptor, did not affect picrotoxin-induced anhedonia. The effect of fluvoxamine was blocked by a dopamine D2/3 receptor antagonist. Methylphenidate, an activator of the prefrontal dopamine system, ameliorated picrotoxin-induced anhedonia.Conclusion and Implications: Picrotoxin-treated mice show anhedonic behaviour that is ameliorated by simultaneous activation of 5-HT1A and σ1 receptors. These findings suggest that the increased prefrontal dopamine release is associated with the anti-anhedonic effect observed in picrotoxin-treated mice. [ABSTRACT FROM AUTHOR]

Peripheral anorectic hormones, such as glucagon-like peptide (GLP)-1, cholecystokinin (CCK)-8 and leptin, suppress food intake. The newly-identified anorectic neuropeptide, nesfatin-1, is synthesised in both peripheral tissues and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. In the present study, we examined the effects of i.p. administration of GLP-1 and CCK-8 and co-administrations of GLP-1 and leptin at subthreshold doses as confirmed by measurement of food intake, on nesfatin-1-immunoreactive (-IR) neurones in the hypothalamus and brainstem of rats by Fos immunohistochemistry. Intraperitoneal administration of GLP-1 (100 µg/kg) caused significant increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the supraoptic nucleus (SON), the area postrema (AP) and the nucleus tractus solitarii (NTS) but not in the paraventricular nucleus (PVN), the arcuate nucleus (ARC) or the lateral hypothalamic area (LHA). On the other hand, i.p. administration of CCK-8 (50 µg/kg) resulted in marked increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the SON, PVN, AP and NTS but not in the ARC or LHA. No differences in the percentage of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the nuclei of the hypothalamus and brainstem were observed between rats treated with saline, GLP-1 (33 µg/kg) or leptin. However, co-administration of GLP-1 (33 µg/kg) and leptin resulted in significant increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the AP and the NTS. Furthermore, decreased food intake induced by GLP-1, CCK-8 and leptin was attenuated significantly by pretreatment with i.c.v. administration of antisense nesfatin-1. These results indicate that nesfatin-1-expressing neurones in the brainstem may play an important role in sensing peripheral levels of GLP-1 and leptin in addition to CCK-8, and also suppress food intake in rats. [ABSTRACT FROM AUTHOR]

What is known and objective There are no clinical reports that have compared topiroxostat, a selective xanthine oxidase inhibitor, with allopurinol in serum urate-lowering efficacy. The aim of this study was to compare the efficacy and safety of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout. Methods A phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study conducted in Japan. Patients who had inadequate serum urate levels (a gout patient: serum urate level ≥416·4 μmol/L; an asymptomatic hyperuricemic patient with specific complications (urinary lithiasis, hypertension, hyperlipidemia and/or diabetes): serum urate level ≥475·8 μmol/L; and an asymptomatic hyperuricemic patient with no specific complications: serum urate level ≥535·3 μmol/L) were randomized to topiroxostat 120 mg/day or allopurinol 200 mg/day, with an equal allocation ratio, for 16 weeks. To prevent the onset of gouty arthritis by rapid serum urate reduction, these doses were increased in a stepwise manner. The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit. Results and discussion Overall, 206 patients were randomly assigned to topiroxostat and allopurinol. Two hundred and three patients (allopurinol: n = 105, topiroxostat: n = 98) received at least one dose of the study drug and had their serum urate level assessed at least once. The baseline characteristics were comparable between groups. The mean age of patients was 53·0 ± 11·4 years and 99% of patients were male. The primary efficacy endpoint was −34·3 ± 11·1% in the allopurinol group ( n = 105) and −36·3 ± 12·7% in the topiroxostat group ( n = 98). Non-inferiority of the serum urate-lowering efficacy of topiroxostat to allopurinol was proved by the predefined non-inferiority margin (95% confidence interval, −5·3 to 1·3%). The overall incidences of adverse events and adverse drug reactions were similar between both groups. What is new and conclusion Topiroxostat 120 mg/day provides non-inferior serum urate reduction compared with allopurinol 200 mg/day and is well tolerated in Japanese hyperuricemic patients with or without gout. [ABSTRACT FROM AUTHOR]

What is known and objective In Japan, although topiroxostat, a selective xanthine oxidoreductase inhibitor, has been used for the treatment of patients with hyperuricemia including gout, no published randomized controlled studies evaluating the dose-dependent relationship with respect to the serum urate-lowering efficacy have been reported. The aim of this study was to evaluate the dose-dependent relationship with serum urate-lowering efficacy and safety of topiroxostat in Japanese hyperuricemic patients including gout. Methods We conducted an exploratory, phase 2a, multicentre, randomized, double-blind, 8-week, placebo-controlled study in Japanese hyperuricemic patients with or without gout. The study arms were placebo and topiroxostat 40, 60, 80 or 120 mg/day. The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit. Results and discussion One hundred and eighty-seven eligible patients were randomized and 186 received at least one dose of the study drug. The study results demonstrated a dose-dependent serum urate reduction effect ranging from 40 to 120 mg/day ( P < 0·001, Jonckheere-Terpstra test). The mean per cent change in serum urate level from baseline at the final visit was −30·8% in the 120-mg group and 1·6% with placebo, with a between-group difference of −32·4% ([95% confidence interval, −38·9% to −25·9%]; P < 0·001). Incidences of overall adverse events ( AEs) in the topiroxostat groups were comparable to those in the placebo group; however, the incidence of AEs in the 120-mg group was statistically lower than that in the placebo group. The incidences of gouty arthritis were not statistically but numerically higher in the topiroxostat 80- and 120-mg groups. What is new and conclusions A dose-dependent serum urate-lowering efficacy of topiroxostat was observed in Japanese hyperuricemic male patients with or without gout. Further clinical studies aimed at evaluating the long-term safety and clinical efficacy are warranted. [ABSTRACT FROM AUTHOR]

Oxytocin (OXT)-containing neurosecretory cells in the parvocellular divisions of the paraventricular nucleus (PVN), which project to the medulla and spinal cord, are involved in various physiological functions, such as sensory modulation and autonomic processes. In the present study, we examined OXT expression in the hypothalamo-spinal pathway, as well as the hypothalamo-neurohypophysial system, which includes the magnocellular neurosecretory cells in the PVN and the supraoptic nucleus (SON), after s.c. injection of saline or formalin into the hindpaws of transgenic rats that express the OXT and monomeric red fluorescent protein 1 (mRFP1) fusion gene. (i) The numbers of OXT-mRFP1 neurones that expressed Fos-like immunoreactivity (-IR) and OXT-mRFP1 intensity were increased significantly in the magnocellular/parvocellular PVN and SON after s.c. injection of formalin. (ii) OXT-mRFP1 neurones in the anterior parvocellular PVN, which may project to the dorsal horn of the spinal cord, were activated by s.c. injection of formalin, as indicated by a significant increases of Fos-IR and mRFP1 intensity intensity. (iii) Formalin injection caused a significant transient increase in plasma OXT. (iv) OXT, mRFP1 and corticotrophin- releasing hormone mRNAs in the PVN were significantly increased after s.c. injection of formalin. (v) An intrathecal injection of OXT-saporin induced hypersensitivity in conscious rats. Taken together, these results suggest that the hypothalamo-neurohypophysial/-spinal OXTergic pathways may be involved in acute nociceptive responses in rats. [ABSTRACT FROM AUTHOR]

Oxytocin ( OXT) is a well-known neurohypophysial hormone that is synthesised in the paraventricular ( PVN) and supraoptic nuclei ( SON) of the hypothalamus. The projection of magnocellular neurosecretory cells, which synthesise OXT and arginine vasopressin in the PVN and SON, to the posterior pituitary plays an essential role in mammalian labour and lactation through its peripheral action. However, previous studies have shown that parvocellular OXTergic cells in the PVN, which project to the medulla and spinal cord, are involved in various physiological functions (e.g. sensory modulation and autonomic). In the present study, we examined OXT expression in the PVN, SON and spinal cord after chronic inflammation from adjuvant arthritis ( AA). We used transgenic rats that express OXT and the monomeric red fluorescent protein 1 ( mRFP1) fusion gene to visualise both the magnocellular and parvocellular OXTergic pathways. OXT- mRFP1 fluorescence intensity was significantly increased in the PVN, SON, dorsal horn of the spinal cord and posterior pituitary in AA rats. The levels of OXT- mRFP1 mRNA were significantly increased in the PVN and SON of AA rats. These results suggested that OXT was up-regulated in both hypothalamic magnocellular neurosecretory cells and parvocellular cells by chronic inflammation, and also that OXT in the PVN-spinal pathway may be involved in sensory modulation. OXT- mRFP1 transgenic rats are a very useful model for visualising the OXTergic pathways from vesicles in a single cell to terminals in in vitro preparations. [ABSTRACT FROM AUTHOR]

The up-regulation of c- fos gene expression is widely used as a marker of neuronal activation elicited by various stimuli. Anatomically precise observation of c- fos gene products can be achieved at the RNA level by in situ hybridisation or at the protein level by immunocytochemistry. Both of these methods are time and labour intensive. We have developed a novel transgenic rat system that enables the trivial visualisation of c- fos expression using an enhanced green fluorescent protein (e GFP) tag. These rats express a transgene consisting of c- fos gene regulatory sequences that drive the expression of a c- fos-e GFP fusion protein. In c- fos-e GFP transgenic rats, robust nuclear e GFP fluorescence was observed in osmosensitive brain regions 90 min after i.p. administration of hypertonic saline. Nuclear e GFP fluorescence was also observed in the supraoptic nucleus ( SON) and paraventricular nucleus ( PVN) 90 min after i.p. administration of cholecystokinin ( CCK)-8, which selectively activates oxytocin ( OXT)-secreting neurones in the hypothalamus. In double transgenic rats that express c- fos-e GFP and an OXT-monomeric red fluorescent protein 1 (m RFP1) fusion gene, almost all m RFP1-positive neurones in the SON and PVN expressed nuclear e GFP fluorescence 90 min after i.p. administration of CCK-8. It is possible that not only a plane image, but also three-dimensional reconstruction image may identify cytoplasmic vesicles in an activated neurone at the same time. [ABSTRACT FROM AUTHOR]

Background and Purpose: Tenascin-C (TnC) is a multi-domain extracellular matrix glycoprotein that is expressed at a high level during embryogenesis but is almost absent during normal postnatal life. This multi-domain complex molecule is reported to associate with both pro-inflammatory and anti-inflammatory signalling cascades. In this study, we examined how TnC modulated intestinal inflammation.Experimental Approach: TnC pathophysiology was evaluated in cultures of rat intestinal subepithelial myofibroblasts (ISEMF) and intestinal epithelial cells. Wild-type and TnC(-/-) mice were treated with dextran sodium sulfate (DSS) to induce colitis.Key Results: DSS-induced colitis in mice markedly increased TnC in the damaged mucosal areas and up-regulated mRNA for TnC, pro-inflammatory cytokines and growth factors (PDGF-B and TGF-β1). In addition, 2,4,6-trinitrobenzene sulfonic acid-induced colitis and SAMP1/Yit mice, a model of spontaneous Crohn's disease, also exhibited increased mucosal TnC in colon and ilea respectively. PDGF receptor-α (PDGFRα) positive ISEMF were the primary TnC-producing cells in colon tissues. Accordingly, ISEMF collected from the rat colon constitutively expressed both TnC and PDGFRα. PDGF-BB and TGF-β1 up-regulated both TnC mRNA and protein levels in ISEMF. Knock-down of TnC gene increased susceptibility to DSS-induced colitis, compared with TnC(+/+) littermates. TnC(-/-) mice showed marked abrasion of intestinal mucosal barrier and increased inflammatory scores. Moreover, TnC accelerated both trans-well migration and wound healing in epithelial cells.Conclusions and Implications: The pharmacological profiles of PDGF-BB and TGF-β in colitis tissues and ISEMF suggest that increased TnC production during inflammation contributed to epithelial cell migration, remodelling and protection of intestinal barriers. [ABSTRACT FROM AUTHOR]

An increased risk of testicular cancer in men with infertility and poor semen quality has been reported. In view of the high cure rates for testicular germ cell tumours, increasing clinical importance is being placed on the protection of fertility. High-dose cytostatic therapy may be expected to cause long-term infertility. Thus, the standard procedure for fertility protection is the cryopreservation of ejaculated spermatozoa or testicular tissue before therapy. Four male patients with azoospermia and two patients with very severe oligozoospermia underwent onco-testicular sperm extraction ( TESE). We attempted onco- TESE in patients with azoospermia and very severe oligozoospermia after orchiectomy. Of the patients with testicular germ cell tumours, four had spermatozoa in their testicular tissues. Sertoli cell-only syndrome was found in one patient, and one patient showed maturation arrest without the detection of spermatozoa. Three of six showed seminomatous germ cell tumour, two of six had nonseminomatous germ cell tumour and one patient showed no malignancy. Two patients achieved clinical pregnancy. Fertility challenges in men with cancer are the most straightforward because of the relative ease of obtaining and cryopreserving sperm. Testicular sperm extraction is a useful technique for obtaining spermatozoa before cytotoxic therapy in azoospermic and very severely oligozoospermic cancer patients. [ABSTRACT FROM AUTHOR]

Comparative field observations of agonistic interactions in juvenile leaf-mimicking Platax orbicularis and Chaetodipterus faber (Ephippidae) were conducted in coastal waters of the Pacific and Atlantic Oceans. Similar agonistic behaviour was observed in the two species, in which individuals stopped displaying their mimetic colouration during encounters with conspecifics, to display conspicuous colours, such as transverse stripes along the body. These events were observed occasionally, almost invariably in individuals of smaller body size. Larger-bodied individuals of both species spent less time in agonistic displays. The absolute size of the fish, however, did not appear to affect the outcome of the encounter, suggesting that dominance is a temporary condition, based on the relative size of the opponents during encounters. [ABSTRACT FROM AUTHOR]

Testicular torsion causes ischaemia-reperfusion (I-R) injury of testis and might lead to male infertility. Its injury initiates a pathophysiological cascade, including an activation of inflammatory cytokines and generation of nitric oxide and other reactive oxygen species. Vascular endothelial growth factor (VEGF) mediates angiogenesis and promotes endothelial cell survival. The aim of our study was to investigate the time course expression of VEGF, VEGF-receptor (R)1, VEGF-R2, nitric oxide synthases (NOS) in experimental I-R injury of rat testis. In torsion side testis, the expression of VEGF protein and mRNA significantly increased in a time-dependent manner ( P < 0.001 and P < 0.001, respectively). Although the expression of VEGF-R1 mRNA was increased in a similar way ( P < 0.001), VEGF-R2 mRNA expression was not detected. In immunohistochemistry, the increase in VEGF protein staining was observed in testicular vascular endothelial cells and germ cells at 24 h after reperfusion. Significant activation of inducible NOS and endothelial NOS was investigated at 12 and 24 h after reperfusion ( P < 0.01 and P < 0.001, respectively). This is the first report to show the time course expression of VEGF in experimental I-R rat testis. [ABSTRACT FROM AUTHOR]

Arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) in the parvocellular neurosecretory cells of the paraventricular nucleus (PVN) play a major role in activating the hypothalamic-pituitary-adrenal axis, which is the main neuroendocrine response against the many kinds of stress. We examined the effects of chronic inflammatory/nociceptive stress on the expression of the AVP-enhanced green fluorescent protein (eGFP) fusion gene in the hypothalamus, using the adjuvant arthritis (AA) model. To induce AA, the AVP-eGFP rats were intracutaneously injected heat-killed Mycobacterium butyricum (1 mg/rat) in paraffin liquid at the base of their tails. We measured AVP, oxytocin and corticosterone levels in plasma and changes in eGFP and CRH mRNA in the hypothalamus during the time course of AA development. Then, we examined eGFP fluorescence in the PVN, the supraoptic nucleus (SON), median eminence (ME) and posterior pituitary gland (PP) when AA was established. The plasma concentrations of AVP, oxytocin and corticosterone were significantly increased on days 15 and 22 in AA rats, without affecting the plasma osmolality and sodium. Although CRH mRNA levels in the PVN were significantly decreased, eGFP mRNA levels in the PVN and the SON were significantly increased on days 15 and 22 in AA rats. The eGFP fluorescence in the SON, the PVN, internal and external layers of the ME and PP was apparently increased in AA compared to control rats. These results suggest that the increases in the concentrations of ACTH and corticosterone in AA rats are induced by hypothalamic AVP, based on data from AVP-eGFP transgenic rats. [ABSTRACT FROM AUTHOR]

Salusin-α and -β were recently discovered as bioactive endogenous peptides. In the present study, we investigated the effects of chronic osmotic stimuli on salusin-β-like immunoreactivity (LI) in the rat hypothalamo-neurohypophyseal system. We examined the effects of salusin-β on synaptic inputs to the rat magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) and neurohypophyseal hormone release from both freshly dissociated SONs and neurohypophyses in rats. Immunohistochemical studies revealed that salusin-β-LI neurones and fibres were markedly increased in the SON and the magnocellular division of the paraventricular nucleus after chronic osmotic stimuli resulting from salt loading for 5 days and dehydration for 3 days. Salusin-β-LI fibres and varicosities in the internal zone of the median eminence and the neurohypophysis were also increased after osmotic stimuli. Whole-cell patch-clamp recordings from rat SON slice preparations showed that salusin-β did not cause significant changes in the excitatory and inhibitory postsynaptic currents of the MNCs. In vitro hormone release studies showed that salusin-β evoked both arginine vasopressin (AVP) and oxytocin release from the neurohypophysis, but not the SON. In our hands, in the neurohypophysis, a significant release of AVP and oxytocin was observed only at concentrations from 100 nm and above of salusin-β. Low concentrations below 100 nm were ineffective both on AVP and oxytocin release. We also measured intracellular calcium ([Ca2+]i) increase induced by salusin-β on freshly-isolated single nerve terminals from the neurohypophysis devoid of pars intermedia. Furthermore, this salusin-β-induced [Ca2+]i increase was blocked in the presence of high voltage activated Ca2+channel blockers. Our results suggest that salusin-β may be involved in the regulation of body fluid balance by stimulating neurohypophyseal hormone release from nerve endings by an autocrine/paracrine mechanism. [ABSTRACT FROM AUTHOR]

The effects of intraperitoneal (i.p.) administration of 2-buten-4-olide (2-B4O), an endogenous sugar acid, on the hypothalamo-adenohypophysial system were examined in Lewis rats that were normal and in adjuvant-induced arthritic (AA) rats. In comparison with vehicle-treated rats, the plasma corticosterone and c- fos mRNA levels in the paraventricular nucleus (PVN) of normal rats increased significantly after i.p. administration of 2-B4O. Dual immunostaining revealed that almost all corticotrophin-releasing factor (CRF)-immunopositive neurones in the parvocellular division of the PVN exhibited Fos-like immunoreactivity (LI) 120 min after i.p. administration of 2-B4O (100 mg/kg). In the AA rats, repeated i.p. administration of 2-B4O (100 mg/kg) after immunisation significantly suppressed the expression of clinical symptoms and significantly increased plasma concentrations of corticosterone. Further, repeated i.p. administration of 2-B4O significantly increased CRF mRNA levels in the PVN and pro-opiomelanocortin mRNA levels in the anterior pituitary; however, they did not change arginine vasopressin mRNA levels in the parvocellular division of the PVN. These results suggest that i.p. administration of 2-B4O activates the hypothalamo-pituitary-adrenal (HPA) axis via the activation of CRF neurones in the PVN, and the activation of the HPA axis by i.p. administration of 2-B4O may be associated with the inhibition of AA in rats. [ABSTRACT FROM AUTHOR]

Aim To systematically determine the usefulness of Helicobacter pylori IgG antibody titer decline as a predictor of treatment success after H. pylori eradication in large patient samples. Patients and Methods Serum samples from 258 H. pylori positive patients (52.8 yrs, 65% males) were retrospectively collected from five medical centers, and H. pylori titers were quantitatively determined by ELISA. Serial serum samples were collected at baseline and for up to 4.9 years after treatment. 169 patients underwent successful eradication while 89 remained infected. The median total observation period was 635 days (range, 51 to 1,800 days). Chronological changes in H. pylori titers were analyzed and compared between cured and infection persistent subjects. Results The proportion of infection persistent patients who developed negative H. pylori IgG antibody titers was below 5%. A receiver operating characteristic (ROC) curve for the confirmation of successful eradication according to the percent decline over baseline at each time-point showed that a 60% decline at 1 year or more after eradication treatment strongly correlated with successful eradication (sensitivity = 90% and specificity = 87%). Conclusion A 60% decline in H. pylori IgG titers (HEL-p kit) from baseline to one year or greater is a reliable predictor of successful H. pylori eradication. [ABSTRACT FROM AUTHOR]

Reproductive behaviours of the rockhopper blenny Andamia tetradactyla were studied on supralittoral reefs of Kuchierabu-jima Island, southern Japan. Territorial males defended mating nests, which were situated around crevices between rocks and concentrated in the high intertidal zones near the vertical limits of waves. Females occurred in large numbers on algal mats around wave-splashed zones, and approached the nests on both rising and falling tides during daytime. Courtship displays occurred on both rising and falling tides, especially when waves surged and sprayed on the nests. Females spawned eggs in a single layer on air-exposed rock surfaces inside nests. Andamia tetradactyla did not mate in the tidal conditions in which nests were either underwater or completely dried up. Territorial males stayed all day in the nests to guard eggs, even though nests emerged above water for c. 12 h each day. Thermo-hygrometer analysis showed that nests maintained higher humidity than outside. Patterns and sequences of the mating behaviours of fishes do not seem very different from those of underwater blenniid fishes. Thus, A. tetradactyla maintains reproduction out of water, retaining humid habitats on supralittoral reefs, in mating styles that are probably not drastically changed from their ancestral blenniid fishes. [ABSTRACT FROM AUTHOR]

OBJECTIVE. Genetic background and infection have been implicated in the etiology of microscopic polyangiitis (MPA). Killer cell immunoglobulin-like receptors (KIRs) are a diverse family of activating and inhibitory receptors expressed on natural killer (NK) cells and T cells, the genes of which show extreme polymorphism. Some KIRs bind to HLA class I subgroups, and genetic interactions between KIR genes and their ligand HLA have been shown to be associated with several autoimmune and viral diseases. In this study, we examined possible associations of the presence or absence of KIR loci with a genetic predisposition to MPA. METHODS: The presence or absence of 14 KIR loci was determined in 57 myeloperoxidase antineutrophil cytoplasmic antibody-positive Japanese subjects (43 patients with MPA and 239 healthy controls). RESULTS: The carrier frequency of activating KIR2DS3 was significantly decreased among patients with MPA compared with healthy controls (4.7% versus 16.7%; P = 0.038, odds ratio [OR] 0.24, 95% confidence interval [95% CI] 0.06-0.94). When KIRs were analyzed in combination with their HLA ligands, the proportion of individuals carrying inhibitory KIR3DL1 and HLA-Bw4 but not activating receptor KIR3DS1, a combination presumed to be the most inhibitory of all KIR3DS1/3DL1/HLA-B combinations, was significantly increased in the MPA group compared with the control group (46.5% versus 27.0%; P = 0.014, OR 2.35, 95% CI 1.18-4.70). Furthermore, when subjects were classified according to KIR3DL1/3DS1/HLA-B and KIR2DL1/ HLA-C combinations, an increasing trend toward susceptibility was observed as combinations became more inhibitory. CONCLUSION: The decreased activation potential of NK and/or T cells associated with KIR/HLA genotypes may predispose to MPA, possibly through insufficient resistance against infections. [ABSTRACT FROM AUTHOR]

Monitoring the expression of immediate early genes (IEGs) is useful for following stress-induced cellular responses in the neuroendocrine system. We have examined the transcriptional activities of four IEGs (c-fos,junB,NGFI-A andNGFI-B) and of the arginine vasopressin (AVP) gene in the hypothalamic paraventicular (PVN) and supraoptic nuclei (SON) of rats after acute osmotic stimuli, usingin situhybridization histochemistry. After intraperitoneal (i.p.) administration of hypertonic saline (2% body weight, 900 mOsm/kg), the expression levels of all IEG mRNAs were increased significantly both in the PVN and SON at as early as 10 min, peaked at 30 min and remained elevated until 60 min. The expression of AVP heteronuclear (hn)RNA also peaked at 30 min, and remained elevated until 180 min. Thirty min after i.p. administration of hypertonic saline (600 mOsm/kg), the expression levels of all IEG mRNAs in the PVN and SON were significantly increased in comparison with those after i.p. administration of isotonic saline (290 mOsm/kg). Regression analysis revealed that expression levels of the IEG mRNAs and AVP hnRNA were positively correlated with the plasma concentration of sodium, and the rates of increase of the expression levels of all IEG mRNAs were similar. The expression levels of all IEG mRNAs examined are useful markers for following the changes of the AVP gene transcription in the PVN and SON after acute osmotic stimuli in rats. [ABSTRACT FROM AUTHOR]

Fisher C, Folpe A L, Hashimoto H & Weiss S W (2004) Histopathology 45, 245–253 Intra-abdominal synovial sarcoma: a clinicopathological study : To evaluate a series of synovial sarcomas arising in the abdomen, pelvic cavity, or retroperitoneum. Synovial sarcoma is rare within the abdomen. In this location, it can be confused with other biphasic tumours and with other spindle and round cell sarcomas. : Cases were retrieved from archives. There were 11 intra-abdominal tumours among 300 synovial sarcomas in two referral practices (3.7%). Three were pelvic (two midline, one sidewall) and eight were retroperitoneal. They occurred in six males and five females aged from 25 to 75 years (mean 49 years, median 46 years), and ranged in diameter from 65 to 470 mm (mean 210 mm, median 150 mm). Six examples were biphasic, five were monophasic and seven had poorly differentiated areas. Monophasic tumours displayed at least one epithelial marker. One biphasic tumour had a SYT-SSX2 fusion gene. Seven sarcomas were high-grade and four of intermediate grade malignancy. Follow-up data were available in 10 patients. In all but one case, tumour recurred or metastasized within the abdomen. The pelvic sarcomas also metastasized outside the abdomen. Eight of 10 patients (80%) died of disease with survival from 4 to 36 months (mean 17 months, median 18 months). Two patients were alive with disease at 43 and 48 months. : Synovial sarcomas rarely arise within the abdomen and pelvis. They occur mainly in middle age, attain a large size, are difficult to excise and recur locally. Pelvic tumours metastasize distantly. Retroperitoneal tumours remain confined to the abdomen and, unlike synovial sarcomas elsewhere, do not metastasize remotely, although mortality is high. [ABSTRACT FROM AUTHOR]

The rockmover wrasse Novaculichthys taeniourus was observed using coral fragments for mound construction on the reefs of Kuchierabu-jima Island, Japan. The wrasse heaped between four and 71 pieces of coral fragments on each sand mound, and dived into the mound just before sunset. Coral fragments may facilitate the retention of sleeping sites under competition with other sand-diving wrasses. [ABSTRACT FROM AUTHOR]

The prototype of the miniature vibrating flow pump (VFP) is developed for the external shunt catheter. The cross-slider mechanism is applied to vibrate the tube, which causes the pumping effect. This mechanism results in successful development of the miniature and lightweight VFP. By the use of the prototype VFP, the experiment of the basic pump performance is made in detail based on the authorized procedure in the research field of fluids engineering. The typical H -Q curve of VFP, which is the relationship between the pump head and the flow rate, can be obtained. This result suggests that the miniature VFP developed here can be expected to be used as the booster pump for the external shunt catheter in clinical applications. [ABSTRACT FROM AUTHOR]

The effect of calcium polycarbophil on the absorption of mycophenolate mofetil, an immunosuppressive agent, was evaluated in healthy subjects. In vitro studies were performed to further evaluate the mechanism of the potential interaction. In the in vitro study, the release of mycophenolate mofetil from a cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, a randomized crossover design with two phases was used. In one phase, 6 male healthy volunteers received 1000 mg of mycophenolate mofetil alone (treatment 1); in the other phase, they received 1000 mg of mycophenolate mofetil and 2400 mg of calcium polycarbophil fine granules concomitantly (treatment 2). They received 30 mg of lansoprazole for 5 days and, on the 6th day, received mycophenolate mofetil and 2400 mg of calcium polycarbophil fine granules concomitantly (treatment 3). The serum concentration of mycophenolic acid was measured by high-performance liquid chromatography. In the in vitro study, the release from a cellulose membrane in the presence of calcium or iron ions was slower than that in the absence of these metal ions. In the in vivo study, the AUC0-12 and C(max) in treatment 2 were less than those in treatment 1. About 50% and 25% decreases in AUC0-12 in treatment 2 and treatment 3 were observed compared with those in treatment 1, respectively. These findings suggest that when mycophenolate mofetil and calcium polycarbophil were coadministered concomitantly, a decrease in mycophenolate mofetil absorption was observed. Therefore, it appears clear that the concomitant administration of mycophenolate mofetil and calcium polycarbophil should be avoided. [ABSTRACT FROM AUTHOR]

Reports on the the discussion during the symposium on the topic related to soft tissue pathology. Criteria for smooth muscle and myofibroblastic differentiation; Role of molecular genetics in soft tissue pathology; Needle biopsy in soft tissue sarcomas.

Amiodarone has pharmacokinetic interactions with various therapeutic agents, including phenytoin, flecainide, and cyclosporine. Mexiletine is metabolized by CYP2D6 and CYP1A2. The objective of this study is to evaluate the effect of amiodarone on the pharmacokinetics of mexiletine through its inhibition of various cytochrome P450 (CYP) subtypes. In a series of 181 inpatients with supraventricular tachyarrhythmias, 26 inpatients received mexiletine and amiodarone therapy (MEX + AMD group), and the others received mexiletine therapy (MEX group). In 10 inpatients of the MEX + AMD group, the mexiletine clearance (CL(MEX)/F) before and after coadministration of amiodarone was compared. CL(MEX)/F was also compared in the MEX and MEX + AMD groups after the start of amiodarone therapy. Serum mexiletine, amiodarone, and desethylamiodarone concentrations were measured by an HPLC method. The CL(MEX)/F was estimated by the Bayesian method using population pharmacokinetic analysis. There was no significant difference in CL(MEX)/F before and after 1-month coadministration of amiodarone in 10 inpatients of the MEX + AMD group. Although serum amiodarone and desethylamiodarone concentrations gradually increased with time after the start of amiodarone therapy in these patients, CL(MEX)/F showed no change at 3 and 5 months after the start of amiodarone therapy. There was no significant difference in CL(MEX)/F of the MEX group and the MEX + AMD group. The results suggest that the pharmacokinetics of mexiletine is not affected by amiodarone in patients with cardiac arrhythmias. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the stereoselective influence of bucolome on the pharmacokinetics and pharmacodynamics of warfarin in Japanese inpatients with heart disease. Thirty patients were administered a fixed-maintenance dose of warfarin alone once a day for at least 7 days. The other 25 patients were concomitantly administered warfarin and a 300 mg dose of bucolome once a day, and blood samples were collected on days 1, 4, 7, 14, or 21 after administration of bucolome. Serum concentration of warfarin enantiomers was measured by a chiral reversed-phase HPLC-ultraviolet detection method. The PT-INR was used as a measure of the pharmacodynamic effect of warfarin. Coadministration of bucolome and warfarin had no effect on serum (R)-warfarin concentration and significantly increased serum (S)-warfarin concentration compared with warfarin alone. The PT-INR of warfarin alone was significantly lower with bucolome cotreatment. These results indicate that the augmented anticoagulant effect of warfarin by bucolome is due to inhibition of (S)-warfarin metabolism in vivo. When bucolome is added to a stabilized regimen of warfarin therapy, the dose of warfarin should be reduced by about 30% to 60%, and caution should be exercised during the first 7 days after coadministration of bucolome. [ABSTRACT FROM AUTHOR]

Abstract: A polymorphism in high-affinity receptor of TNF (TNFR2) gene, Met196Arg, was reported to be associated with systemic lupus ery-thematosus (SLE) in Japanese, whereas the association could not be found in Europeans at all and this represents an apparent discrepancy. The association, then, should be tested in other populations to clarify the possible involvement, if any, of the TNFR2 polymorphism in SLE or other related autoimmune diseases. The purposes of this study were to examine the TNFR2 polymorphism in Japanese patients with SLE and to investigate its association with other autoimmune diseases accompanied by vasculitis, mixed connective tissue disease, Buerger's disease, and Takayasu's arteritis. We found no association at all between the TNFR2 polymorphism and any autoimmune diseases including SLE in Japanese. [ABSTRACT FROM AUTHOR]

Aims Primary rhabdoid tumour of the lung is rare, and histological and biological characteristics have not been fully documented. We describe three cases of primary lung rhabdoid tumour, all associated with adenocarcinoma, and investigate the histological features and biological characteristics. Methods and results Three cases were obtained from a total 902 cases of surgically removed primary lung tumours between 1986 and 1998. The rhabdoid cells were found to occupy about 50–90% of each tumour. All of the tumours had nonrhabdoid adenocarcinoma foci in the centre of the tumours. Transition between the adenocarcinomatous and rhabdoid components was demonstrated. Detailed immunohistochemical studies were carried out. The epithelial markers, cytokeratins and epithelial membrane antigen (EMA), were strongly expressed in rhabdoid and adenocarcinomatous components. Furthermore, surfactant apoprotein A was positive in both components in one case, but myoglobin, MyoD and HHF35 were not expressed. Vimentin was strongly and diffusely stained in all cases. The neuroendocrine markers, chromogranin A (all cases), neuron-specific antigen (NSE) (two cases) and CD56 (one case) were occasionally positive in only a small number of the rhabdoid tumour cells. GM-CSF was positively stained in one case, and the dedifferentiated characteristics of the rhabdoid cells was suggested. Proliferative cell nuclear antigen (PCNA) was strongly demonstrated in the rhabdoid tumour cells (all cases). To gain better understanding the highly proliferative characteristics of the tumours, p53 gene (exons 5–8) mutation was examined by DNA sequencing analysis; mutation of the p53 DNA was not detected. Overexpression of p53 protein was also not demonstrated in all cases. HPV6 was demonstrated in one case by PCR method and also non-isotopic in-situ hybridization (NISH). Two cases died in a short period of time (3 years and 4 months, respectively). Conclusion The rhabdoid cells in these... [ABSTRACT FROM AUTHOR]

Aims We report two unusual cases of intrapulmonary small round cell tumour with evidence that they are primitive neuroectodermal tumours. Methods and results The patients were a 25-year-old woman and a 15-year-old man, in whom mass shadows were found by routine chest radiography. Both tumours were located in the pulmonary parenchyma, and there was no evidence of an extrapulmonary involvement by the tumour. The lesions showed morphological and immunophenotypic features consistent with peripheral primitive neuroectodermal tumour (pPNET). These features included a hypercellular diffuse growth pattern of closely packed small round cells occasionally forming abortive Homer–Wright-type rosettes and intense immuroreactivities to neurone-specific enolase and MIC2 gene product (O13). Unusual chondroid foci were present in one of the cases. This diagnosis was further supported by the cytogenetic and reverse transcriptase-polymerase chain reaction (RT-PCR) findings of the characteristic t(11;22) chromosomal translocation and EWS/FLI-1 fusion transcripts, respectively, in one of the cases. Conclusions These morphological and cytogenetic findings substantiate pPNET as a subtype of intrapulmonary small round cell tumours. [ABSTRACT FROM AUTHOR]

A key is provided to both sexes of the four species of Pontomyia; cottoni Womersley, natans Edwards, oceana Tokunaga, pacifica Tokunaga. This genus is widespread in the western Pacific Ocean. Adult females are vermiform. Adult males have normal halteres but reduced wings; they are unusual among Chironomidae in having bare, not plumose antennae. [ABSTRACT FROM AUTHOR]